U.S. EPA Design for the Environment
              r
Flame Retardants Used in Flexible
Polyurethane Foam: An Alternatives
Assessment Update
&EFA
   United States
   Environmental Protection
   Agency
   June 2014
   EPA 744-D-14-001
 US. ERA*
www.epa.gov/dfe

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                             JUNE 2014 DRAFT REPORT


                              Table of Contents
1   Introduction	1-1
  1.1     The Furniture Flame Retardancy Partnership	1-1
  1.2     Updating the 2005 Furniture Flame Retardancy Report	1-1
  1.3     Alternatives Assessment as a Risk Management Tool	1-4
  1.4     DfE Alternatives Assessment and the Toxic Substances Control Act	1-6
2   Hazard Evaluation Results for Flame Retardants Used in Flexible Polyurethane Foam	2-1
  2.1     Hazard Comparison Table	2-1
  2.2     Hazard and Fate Results by Chemical Group	2-5
  2.3     Hazard and Fate Results by Endpoint	2-6
3   Flexible Polyurethane Foam Flame Retardants and Flammability Standards	3-1
  3.1     Flexible Polyurethane Foam	3-1
  3.2     Flame Retardant Classification and Exposure Considerations	3-1
  3.3     Sources of Data for Identifying Foam Flame Retardants	3-2
  3.4     Notes on Specific Foam Flame Retardants	3-15
  3.5     Standards that Influence the Use of Flame Retardants	3-17
4   Alternative Flame Retardant Solutions not Assessed in This Report	4-1
5   Hazard Evaluation Methodology	5-1
  5.1     Toxicological and Environmental Endpoints	5-1
  5.2     Data Sources and Assessment Methodology	5-8
  5.3     Importance of Physical and Chemical Properties, Environmental Transport, and
  Biodegradation	5-12
  5.4     Evaluating Human Health Endpoints	5-19
  5.5     Evaluating Environmental Toxicity and Fate Endpoints	5-21
  5.6     Endocrine Activity	5-27
6   References	6-1
7   Hazard Evaluations	7-1
  Ammonium polyphosphate (APP)	7-1
  Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester (TBB)	7-20
  Di(2-ethylhexyl) tetrabromophthalate (TBPH)	7-58
  Diethyl bis(2-hydroxyethyl)aminomethylphosphonate	7-101
  Emerald Innovation™ NH-1	7-120
  Expandable graphite	7-204
  Fyrol™HF-5	7-226
  Isopropylated triphenyl phosphate (IPTPP)	7-274
  Melamine	7-335
  Oligomeric ethyl ethylene phosphate	7-379
  Oligomeric phosphonate polyol	7-406
  Tricresyl phosphate (TCP)	7-428
  Triphenyl phosphate (TPP)	7-489
  Tris (l,3-dichloro-2-propyl) phosphate (TDCPP)	7-522
  Tris (2-chloro-l-methylethyl) phosphate (TCPP)	7-579
  Tris (2-chloroethyl) phosphate (TCEP)	7-626
  Tris (p-t-butylphenyl) phosphate (TBPP)	7-678
  V6	7-732
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                 List of Acronyms and Abbreviations

ACR         Acute to chronic ratio
APP         Ammonium polyphosphate
ASTM       American Society for Testing and Materials
BAF         Bioaccumulation factor
BCF         Bioconcentration factor
BEARFTI    Bureau of Electronic and Appliance Repair, Home Furnishings and Thermal
                   Insulation
CASRN      Chemical Abstracts Service Registry Number
CDC         Centers for Disease Control and Prevention
CDR         Chemical Data Reporting
CFR         Code of Federal Regulations
CHO         Chinese hamster ovary cells
ChV         Chronic value
CPSC        Consumer Product Safety Commission
DecaBDE    Decabromodiphenyl ether
DfE         Design for the Environment
DMSO       Dimethyl sulfoxide
             Concentration at which 50% reduction of biomass is observed
             Half maximal effective concentration
ECHA       European Chemicals Agency
ECOSAR    Ecological Structure Activity Relationships
EDSP        Endocrine Disrupter Screening Program
EEC         European Economic Community
EPA         U.S. Environmental Protection Agency
EPI          Estimation Program Interface
ErCso         Concentration at which a 50% inhibition of growth rate is observed
EU          European Union
FFRP        Furniture Flame Retardancy Partnership
FPUF        Flexible polyurethane foam
GD          Gestation day
GHS         Globally Harmonized System of Classification and Labeling of Chemicals
GLP         Good laboratory practice
HPLC        High performance liquid chromatography
HPV         High Production Volume
HPVIS       High Production Volume Information System
HSDB        Hazardous Substances Data Bank
IARC        International Agency for Research on Cancer
IDso         Median ineffective dose
IFR          Inherently flame retardant
IPTPP        Isopropylated triphenyl phosphate
IRIS         Integrated Risk Information System
IUCLID      International Uniform Chemical Information Database
Koc          Sediment/soil adsorption/desorption coefficient
KOW          Octanol/water partition coefficient
                                        in

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                             JUNE 2014 DRAFT REPORT
LbL
LCso
LCA
LD
LD50
LDLo
LFL
LOAEL
LOEC
MF
MITI
MSDS
MW
NAS
NCI
NCP
NES
NFPA
NGO
NICNAS
NOAEC
NOAEL
NOEC
NTP
OECD
OEHHA
OPFR
OPP
OPPT
PBDE
PBT Profiler
PentaBDE
PINFA
PMN
ppm
QSAR
REACH
SAR
SF
SIDS
SMILES
SNUR
TB
TBB
TBPH
Layer-by-layer
Median lethal concentration
Absolute lethal concentration
Life cycle assessment
Lactation day
Median lethal dose
Lethal dose low
Lower limit of flammability
Lowest observed adverse effect level
Lowest observed effect concentration
Molecular formula
Japanese Ministry of International Trade and Industry
Material Safety Datasheet
Molecular weight
National Academy of Sciences
National Cancer Institute
New Chemicals Program
No effects at saturation
National Fire Protection Association
Non-governmental organization
National Industrial Chemicals Notification and Assessment Scheme
No observed adverse effect concentration
No observed adverse effect level
No observed effect concentration
National Toxicology Program
Organisation of Economic Cooperation and Development
California Office of Environmental Health Hazard Assessment
Organophosphate flame retardant
Office of Pesticide Programs
Office of Pollution Prevention and Toxics
Polybrominated diphenyl ether
Persistent, Bioaccumulative, and Toxic Chemical Profiler
Pentabromodiphenyl ether
Phosphorus, Inorganic & Nitrogen Flame Retardants Association
Premanufacture Notification
parts per million
Quantitative Structure Activity Relationship
Registration, Evaluation, Authorisation and Restriction of Chemicals
Structure Activity Relationship
Sustainable Futures
Screening Information Data Set
Simplified Molecular-Input Line-Entry System
Significant New Use Rule
Technical Bulletin
Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester
Di(2-ethylhexyl) tetrabromophthalate
                                         IV

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TBPP        Tris (p-t-butylphenyl) phosphate
TCEP        Tris (2-chloroethyl) phosphate
TCP         Tricresyl phosphate
TCPP        Tris (2-chloro-l-methylethyl) phosphate
TDCPP      Tris (l,3-dichloro-2-propyl) phosphate
TG          Test guidelines
TPP         Triphenyl phosphate
TSCA        Toxic Substances Control Act
UFAC        Upholstered Furniture Action Council
UFL         Upper limit of flammability
V6          Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-
                    chloroethyl) ester
WAF        Water accommodated fraction

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1   Introduction

1.1  The Furniture Flame Retardancy Partnership

The flame retardant pentabromodiphenyl ether (pentaBDE) was widely used as an additive in
furniture foam and in other products to meet flammability requirements in the late 20* century.
In the early 2000s, growing concerns over the possible environmental and public health impacts
of pentaBDE led to a voluntary phase-out of the chemical by the sole U.S. manufacturer. At the
end of 2004, industry voluntarily ceased production of pentaBDE, and U.S. Environmental
Protection Agency (EPA) issued a regulation that prohibited further manufacture of the chemical
without notification of EPA under the Toxic Substances Control Act (TSCA). The substitution
likely to result from the move to alternatives to pentaBDE resulted in the need for evaluating
flame retardants.

In 2003, Design for the Environment (DfE) convened a multi-stakeholder group to undertake an
assessment of viable alternatives to pentaBDE. The Furniture Flame Retardancy Partnership
(FFRP) included chemical manufacturers, furniture manufacturers, governmental  representatives
and environmental non-governmental organizations (NGOs). In 2005, EPA issued a report1
based on the partnership's work assessing the human health and environmental profiles of
alternatives to pentaBDE, indicating that a number of alternatives were available that appeared to
pose a lower level of concern than was associated with pentaBDE.  This DfE Alternatives
Assessment update report identifies and evaluates flame retardants that may be used in flexible
polyurethane foam (FPUF) products (as of 2013) and updates hazard profiles from the previous
report.

Additional actions regarding pentaBDE were outlined in the EPA 2009 Action Plan for
polybrominated diphenyl ethers (PBDEs) (U.S. EPA  2009).

1.2  Updating the 2005 Furniture Flame Retardancy Report

Purpose and Scope of the Updated Report

The goal of the FFRP, as stated in its 2005 report, was to "identify  and assess environmentally
safer chemical alternatives to pentaBDE, and to investigate other technologies for improving
furniture fire safety" (U.S. EPA 2005a). Since the publication of the 2005 FFRP report, the
marketplace for flame retardants used in FPUF has changed significantly, with  some flame
retardant chemicals being withdrawn from the market, and others being introduced. This update
is intended to identify all flame retardants either known to be used, or marketed to be used, in
meeting fire safety requirements for upholstered consumer products containing FPUF. Also, DfE
published updated hazard criteria in 2011 (see "Alternatives Assessment Criteria for Hazard
Evaluation"), and data from the 2005 FFRP report were re-evaluated using the current criteria,
and included in this report. The resulting hazard profiles allow a direct comparison among
substances found in the two DfE alternative assessment reports. It should be noted that, as in all
DfE Alternatives Assessments, the term "alternative" is used to designate any chemical that can
 Available at: http://www.epa.gov/dfe/pubs/flameret/altrep-vl/altrep-vla-coverl.pdf.


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                              JUNE 2014 DRAFT REPORT
be used in the functional category, and does not designate preferability for environmental or
health endpoints.

DfE is publishing the current update for several reasons, in addition to the marketplace changes
and data developments described above. Public and media attention to flame retardants in recent
years has led to new scrutiny of flame retardant chemistry. Also, both the State of California and
the Consumer Product Safety Commission (CPSC) have established or are planning to establish
updated flame retardancy standards for upholstered  furniture (see Section 0 below). The impact
of these changes in terms of flame retardant selection is as yet unknown; therefore, it is
important that the most current information be available to decision makers, which requires an
update of the chemicals and hazard data contained in the 2005 report.  In addition, several
chemicals in this category (notably benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester (TBB),
di(2-ethylhexyl) tetrabromophthalate (TBPH), and tris (2-chloroethyl) phosphate (TCEP)) were
identified by EPA as TSCA Work Plan chemicals for assessment beginning in 2013 (U.S. EPA
2013b). The full list of chemicals for assessment can be found here:
http://www.epa.gov/oppt/existingchemicals/pubs/assessment_chemicals_list.html. Updating the
hazard and use information for these and related chemicals complements other assessment
projects underway at EPA.

This report, by EPA's DfE Program, updates and supplements the previous alternatives
assessment report developed by the FFRP (U.S. EPA 2005a). DfE has identified 16 flame
retardant chemicals, one non-proprietary mixture, and 2 proprietary mixtures to be evaluated in
the updated report.  Additional information on polyurethane foam is available in the 2005 FFRP
report (U.S. EPA 2005a).

The scope of this report has been expanded to include all upholstered  consumer products
containing FPUF (i.e., not just furniture), including  a number of flame retardants that have been
identified in products such as car seats and nursing pillows (Stapleton, Klosterhaus et al.  2011).
These products, like the furniture that was the subject of the 2005 report, are made from FPUF
with a covering fabric, and, when flame retarded, are expected to rely on the same set of flame
retardants. (Some upholstered FPUF products, particularly for babies  and children, are exempt
from flame retardancy requirements, but may still contain flame retarded foam.)

The 2005 report describes alternative methods of improving furniture fire safety; for example,
the use of IFR upholstery, or the use of fire barriers between upholstery and foam. Since the
2005 report was published, one additional technology, known as layer-by-layer (LbL) assembled
flame retardancy, has been in development, but is not yet commercialized. The hazards
associated with this technology are not addressed in this update because it is nanoscale and not
commercially available, and the DfE criteria have not been evaluated  for suitability to assess
nano-sized substances. The current update  addresses the hazards associated with one alternative
technology—expandable graphite (used in graphite impregnated foam), which may be
commercially viable as a replacement for flame retardant chemicals in FPUF for some
applications. All other alternatives are briefly described in Section 4. Because the DfE hazard
criteria are developed for chemical-to-chemical comparison under a specific functional use,
rather than material-to-material comparison,  a life cycle assessment (LCA)  might be a better tool
for evaluating and comparing alternative materials (see Section 1.4).
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How to Use This Report

Audiences for this report include stakeholders interested in chemical hazards and safer
alternatives, including but not limited to chemical manufacturers, component manufacturers,
product manufacturers, retailers, consumers, NGOs, consultants, and state and federal regulators.
Three potential uses of this report include:

Identification of potential substitutes. This report allows stakeholders interested in chemical
substitution to identify functional alternatives for flame retardants used in flexible polyurethane
foam, which is commonly found in furniture. The two lists of potential alternatives includes
chemicals identified by stakeholders as viable, functional alternatives, as well as chemicals that
are not considered functional alternatives, and information on inherently flame retardant (IFR)
polymers. The inclusion of a chemical in this assessment does not indicate environmental- or
health-based preferability. By identifying potential functional alternatives, this report assists
manufacturers in selecting chemicals for additional performance testing, and can identify a need
for alternative approaches to fire safety such as barrier materials, as studied by the CPSC (CPSC
2013b). Although the alternatives identified in this report are additive flame retardants that can
be used in barrier materials, an evaluation of the use of the identified chemicals in these
technologies is outside of the scope of this report.

Selection of alternative chemicals based on comparative chemical hazard assessment. This
report helps decision-makers understand and compare the hazards associated with potential
alternatives to which they can supplement information on performance and cost. Some
alternatives may be associated with hazard concerns similar to those of pentaBDE; others may be
associated with different hazard concerns. Use of the hazard information in Section 5 may help
businesses avoid the cost of repeated substitution. Section 5 contains a robust human health and
environmental profile  for each chemical that is based on empirical data when available, and
enhanced with modeling and expert judgment to fill data gaps. The profiles can help decision-
makers understand which potential alternatives may come under scrutiny in the future, and
choose the safest possible alternative now to reduce future costs. In addition to reading the
hazard comparison table, decision-makers should review the full hazard assessments for each
chemical available in Section 6. The hazard assessments provide more information on hazard
criteria, data interpretation, and information used to assign hazard values in each category, and
ensure a complete understanding of the hazard profiles of each alternative.

Use of hazard information for further analysis and decision-making. The information in this
report can be used to inform further analyses on preferred alternative chemicals, such as risk
assessments or LCA. For example, a decision-maker could identify several functional
alternatives with preferable hazard profiles, and conduct product-specific risk assessments based
on exposure expectations along the product's life-cycle.  A decision-maker could also conduct an
assessment of the (non-hazard) environmental impacts associated with the life cycles of the
alternatives (or any differences in environmental impacts of the product that may result from
choosing one alternative over another). This type of supplementary information may be helpful
in guiding product-specific decision-making. In addition, information in this report can be used
to identify the Very Persistent Very Bioaccumulative chemicals targeted under European
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Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) policy. This
report does not evaluate the relative hazards of alternatives, but GreenScreen®
(www.cleanproduction.org/Greenscreen.php) is one tool that can be used for this purpose. The
criteria used to develop the hazard assessments in this report can also be used to inform Green
Chemistry design.

1.3  Alternatives Assessment as a Risk Management Tool

The DfE Alternatives Assessment process was one of a suite of actions EPA chose to pursue to
manage the potential risks associated with pentaBDE. The Agency chose this tool to inform the
chemical substitution that may occur as an outcome of other risk management activities.

Chemical alternatives assessment compares chemicals within the same functional use group, and
evaluates alternatives across a consistent and comprehensive set of hazard endpoints and
environmental fate parameters. Information about chemical hazards derived from this type of
comparative chemical hazard assessment,  in combination with analyses of cost, performance,
and other factors, can be used by industry  and other decision-makers to select safer alternative
chemicals for a particular use. (For details on DfE's Hazard Assessment criteria, see
"Alternatives Assessment Criteria for Hazard Evaluation," available at
http://www.epa.gov/dfe/alternative_assessments. html.)

Alternatives assessment is most useful in identifying safer substitutes when available alternatives
meet performance requirements and are expected to present lower hazards for human health and
the environment. Alternatives assessments may identify scenarios in which there do not appear to
be any preferable alternatives to the chemical being considered for replacement. In this case, the
resulting information can be used to guide innovation, and the development of safer chemicals
and products.

Functional Use Approach  and Chemical Fate

DfE's "functional use"  approach to alternatives assessment orients chemical  evaluations within a
given product type and  functionality. Under this approach, factors related to exposure scenarios,
such as physical form and route of exposure, can be similar within a given functional use
analysis and will fall out of the comparison, so that a  reduction in hazard is equivalent to a
reduction of risk. When less hazardous alternatives have different physical-chemical profiles or
require different use levels,  it may be appropriate to also conduct an exposure or risk assessment.

DfE Alternatives Assessments consider intrinsic properties of chemical substitutes that affect
exposure potential, including absorption potential, persistence, and bioaccumulation. Under this
approach, the health and environmental hazard profiles in the alternatives assessments become
the key variable and source  of distinguishing characteristics. Information on key properties that
can be used to evaluate significant differences in environmental fate and transport, including
persistence, bioaccumulation, and physical properties, are included in the hazard assessment.
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DfE Alternatives Assessments Scope and Data Sources

As described above, the DfE Alternatives Assessment process is intended to provide useful
hazard and fate data on chemicals within a given functional class; it is not intended to describe
exposure or risk, nor do Alternatives Assessments provide quantitative information on chemical
performance in the product or cost, which are most appropriately conducted by manufacturers
who have hands-on expertise in product cost and performance. DfE Alternatives Assessments
provide complete hazard data according to a uniform set of criteria, in a format amenable to
comparison among chemicals, and in a relatively quick timeframe.  This information can
contribute important information for decision makers, whether chemical manufacturers, product
manufacturers, consumers, orNGOs.

As with other DfE Alternatives Assessments, this report summarizes available data from many
sources, including information from experts on uses of flame retardants, and hazard and fate
information from the scientific literature. Because EPA oversees the TSCA Premanufacture
Notification (PMN) process, DfE also has access to hazard and fate information from
confidential and non-confidential studies submitted to the Agency as part of a PMN chemical
review. Furthermore, when little data are available on a chemical of interest, hazard and fate
information may be derived from data on analog molecules, which  may be confidential. Experts
from DfE, from other groups within EPA's Office of Chemical Safety and Pollution Prevention
(OCSPP), and from DfE's contractors, provide expert judgment on  chemical hazard and fate for
those chemicals.  This report compiles existing data and does not include results of new research
on chemical hazards; EPA did not undertake any testing for this report.

When reporting hazard data on available alternatives, DfE does not recommend specific flame
retardants. It is the role of manufacturers to use the data provided, along with their own expert
knowledge, to choose the safest chemicals possible, while also meeting their requirements for
efficacy, price, and other criteria.

Green Chemistry Principles

The DfE Alternatives Assessment approach is aligned with established green chemistry
principles. Two of these principles are particularly relevant to the DfE approach:

   •   Principle 4:  Design  of safer chemicals - "Chemical products should be designed to affect
       their desired function, while minimizing their toxicity;" and

   •   Principle 10: Design for degradability - "Chemical products should be designed so that
       at the end of their function they break down into innocuous  degradation products and do
       not persist in the environment" (Anastas and Warner 1998).

DfE incorporates these two green chemistry principles in its criteria, and applies them in its
assessment of chemical hazard and fate in the environment. This approach enables identification
of safer substitutes that emphasize greener chemistry, and points the way to innovation in safer
chemical design, where hazard becomes a part of a performance evaluation.
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Alternatives, Life-Cycle, and Risk Assessments

Alternatives assessment, life-cycle assessment (LCA), and risk assessment are tools that can be
used to evaluate and improve the sustainability profiles of chemicals, products, and services.
These tools, which can be complementary to one another, should be selected according to the
ultimate decisions needing to be made, and other regulatory and policy considerations. DfE
Alternatives Assessments establish a foundation that other tools, such as risk assessment and
LCA, can build upon.

Risk assessment and alternatives assessment are both based on the premise that risk is a function
of hazard and exposure. Risk assessment characterizes the nature and magnitude of hazard and
exposure from chemical contaminants and other stressors. A DfE Alternatives Assessment
evaluates and compares the nature of the chemical hazards, and reflects a view that when
exposure is comparable, risk is reduced through the use of less hazardous chemicals. Alternatives
assessment strives to decrease the reliance on exposure controls, thus reducing risk when
exposure controls fail.

An LCA can create a robust picture of a variety of environmental impacts associated with the
material and energy inputs and outputs throughout the life cycle (or part of a life cycle) of a
product or service, and by doing so can identify opportunities for reducing those impacts.
However, an LCA may not assess the inherent hazards of the chemical inputs and outputs for
each life cycle stage. During decision-making, risk assessment or LCA can be applied to the
lower-hazard or potentially preferable alternatives, to further distinguish between preferable
substitutes, or to identify unintended consequences.

1.4   DfE Alternatives Assessment and the Toxic Substances Control Act

EPA's DfE program is administered by the Office of Pollution Prevention and Toxics (OPPT),
which is charged with the implementation of the Toxic Substances Control Act (TSCA) and the
Pollution Prevention Act (PPA).

Central to the administration of TSCA is the management of the TSCA Inventory. Section 8 (b)
of TSCA requires EPA to compile, keep current, and publish a list of each chemical substance
that is manufactured or processed in the United States. Companies are required to verify the
TSCA status of any substance they wish to manufacture or import for a TSCA-related purpose.
For more information, please refer to the TSCA Chemical Substance Inventory website:
http://www.epa.gov/opptintr/existingchemicals/pubs/tscainventory/basic.html.

Substances selected for evaluation in a DfE Alternatives Assessment generally are subject to
TSCA regulations, and therefore must be listed on the TSCA Inventory, or be exempt or
excluded from reporting before being manufactured in or imported to, or otherwise introduced in
commerce in, the United States. For more information see
http://www.epa.gov/oppt/newchems/pubs/whofiles.htm.

To be as inclusive as possible, DfE Alternatives Assessments  may consider substances that may
not have been reviewed yet as new chemicals under TSCA, and therefore may not be listed on
the TSCA Inventory. DfE has worked with stakeholders to identify and include chemicals that
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                              JUNE 2014 DRAFT REPORT
are of interest and likely to be functional alternatives, regardless of their TSCA status. Chemical
identities are gathered from the scientific literature and from stakeholders and, for non-
confidential substances, appropriate TSCA identities are provided.

Persons are advised that substances, including DfE-identified functional alternatives, may not be
introduced into U.S. commerce unless they are in compliance with TSCA. Introducing such
substances without adhering to the TSCA provisions may be a violation of applicable law. Those
who are considering using a substance discussed in this report should check with the
manufacturer or importer  about the substance's TSCA status. If you have questions about the
reportability of substances under TSCA, please contact the OPPT Industrial Chemistry Branch at
202-564-8740.
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                            JUNE 2014 DRAFT REPORT
2   Hazard Evaluation Results for Flame Retardants Used  in
    Flexible Polyurethane Foam

2.1   Hazard Comparison Table

The hazard comparison table is shown below, followed by the results described both by the
chemical groupings found in the hazard comparison table and by type of hazard endpoint.

Other approaches to improving fire safety of upholstered FPUF products exist, including flame
resistant cover fabrics and fire barriers, which could be comprised of chemically treated
materials (e.g., treated cotton-based materials) or inherently flame retardant materials (e.g., wool,
Kevlar), and nanoclay technologies (See Section 3). These alternative technologies are not
assessed for hazard in this report. The DfE Hazard Evaluation Criteria (described in Section
4.1.2) are not amenable to assessing the hazard from the flame resistant cover fabrics and fire
barriers. Additionally, the DfE Hazard Evaluation Criteria have not been evaluated for suitability
to assess nano-sized substances. Further, layer-by-layer nanoclay technologies are currently in
research and development and are not commercially available for use in upholstered FPUF
products.
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                                                        Table 2-1. Screening Level Toxicity Hazard Summary
This table only contains information regarding the inherent hazards of flame retardant chemicals. Evaluation of risk considers both the hazard and exposure associated with each substance
including combustion and degradation by-products. The caveats listed in the legend and footnote sections must be taken into account when interpreting the hazard information in the table.
VL = Very Low hazard L = Low hazard = Moderate hazard H = High hazard VH = Very High hazard — Endpoints in colored text (VL, L, M, H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from predictive models and/or professional judgment.
* This mixture is made up of four components contained in the hazard summary table. Hazard designations in bold and color are based on test data for the mixture, as summarized in the
hazard profiles for the components. Hazard designations in italics are based on the most conservative results from one of the four components.
This component of Firemaster® 550 may be used alone or in other mixtures as an alternative.
¥ Aquatic toxicity: EPA/DfE criteria are based in large part upon water column exposures which may not be adequate for poorly soluble substances such as many flame retardants that may
partition to sediment and particulates.



Chemical
(for full chemical name and relevant
trade names see the individual
profiles in Section 4.8)






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ester (TBB) ¥
Di(2-ethylhexyl) tetrabromophthalate (TBPH) A¥
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L


L
L
H
M

M

L
H
M

M
H
L
H
M

M
H
L
H
M




1VI
M

L
L
L






L
L

L
L
L
L
L

L
L
VL
VH
L

L
VH
VH
VH
L

L
VH
VH
H
H

H

L
H
H

H
H

Chlorinated Phosphorus Alternatives
Tris (2-chloroethyl) phosphate (TCEP)
115-96-8
H
H

JM
XI


L

L
L
H
H

L

Tris (2-chloro-l-methylethyl) phosphate (TCPP)

Tris (l,3-dichloro-2-propyl) phosphate (TDCPP)

Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-
propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester
(V6)
13674-84-5;
6145-73-9
L
M
L
H
H
M

L

L
L

H


13674-87-8
L




L

L

L
L




38051-10-4


L


M


L





H


L


M


L





L


L





H

H




L

L


L

                                                                               2-2

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                                                                 JUNE 2014 DRAFT REPORT
                                                        Table 2-2. Screening Level Toxicity Hazard Summary
This table only contains information regarding the inherent hazards of flame retardant chemicals. Evaluation of risk considers both the hazard and exposure associated with each substance
including combustion and degradation by-products. The caveats listed in the legend and footnote sections must be taken into account when interpreting the hazard information in the table.
VL = Very Low hazard L = Low hazard = Moderate hazard H = High hazard VH = Very High hazard — Endpoints in colored text (VL, L, , H, and VH) were assigned
based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from predictive models and/or professional judgment.
* Expandable graphite commercial formulations are prepared with chemical washes. There are variable hazards from the specific wash chemicals used and, as a result the hazards may
change by manufacturer. One confidential wash has additional hazard concern as follows, based on experimental data: HIGH -Acute Toxicity, Eye Irritation, Dermal irritation. Other
manufacturers may use a wash that contains chromic acid (CASRN 7738-94-5) with additional hazard concerns as follows, based on experimental data: HIGH -Acute Toxicity,
Carcinogenicity, Genotoxicity, Reproductive, Repeated dose, Skin sensitization, Respiratory sensitization, Eye Irritation, Dermal irritation.
d This hazard designation would be assigned MODERATE for a potential for lung overloading if >5% of the particles are in the respirable range as a result of dust forming operations.
¥ Aquatic toxicity: EPA/DfE criteria are based in large part upon water column exposures which may not be adequate for poorly soluble substances such as many flame retardants that may
partition to sediment and particulates. ^





Chemical
(for full chemical name and relevant
trade names see the individual profiles
in Section 4.8)








CASRN
Human Health Effects



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Inorganic/Other Alternatives
Ammonium polyphosphate (APP) ¥
68333-79-9
L
L
L
L
L
L
Ld
L

VL
L
L
L
VH
L

Expandable graphite ¥
12777-87-6
L*
M"
L*
L*
L
L
M"
L*
*
M*
M*
L*
M"
H
L

Melamine
108-78-1



H
M
L
M
L

L
VL
L
M
H
L
                                                                                2-3

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                                                                  JUNE 2014 DRAFT REPORT
                                                   Table 2-2. Screening Level Toxicity Hazard Summary (Continued)
This table only contains information regarding the inherent hazards of flame retardant chemicals. Evaluation of risk considers both the hazard and exposure associated with each substance
including combustion and degradation by-products. The caveats listed in the legend and footnote sections must be taken into account when interpreting the hazard information in the table.
VL = Very Low hazard L = Low hazard = Moderate hazard H = High hazard VH = Very High hazard — Endpoints in colored text (VL, L, M, H, and VH) were assigned
based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from predictive models and/or professional judgment.
§ Based on analogy to experimental data for a structurally similar compound.
d This hazard designation would be assigned MODERATE if >5% of the particles are in the respirable range as a result of dust forming operations.
t This component of Firemaster® 550 may be used alone or in other mixtures as an alternative. It can also be found in Table 2-1 of this report.
* The highest hazard designation of any of the oligomers withMW <1,000.
* Unlike for Firemaster 550, data are available only for the individual components, and not for the mixture. For this mixture, hazard designations are listed in bold and color when there are
measured data for all the components; the designation for the mixture is based on the component with the highest hazard. When measured data are not available for all components, the
designation for the mixture is based on the component with the highest hazard and is an estimation (italics).
Chemical
(for full chemical name and relevant
trade names see the individual profiles
in Section 4. 8)
CASRN
Human Health Effects
Acute Toxicity
Carcinogenicity
Genotoxicity
Reproductive
Developmental
Neurological
Repeated Dose
Skin
Sensitization
Respiratory
Sensitization
Eye Irritation
Dermal
Irritation
Aquatic
Toxicity
1
u
<
Chronic
Environmental
Fate
Persistence
Bioaccumulation
Non-Halogenated Flame Retardant Alternatives continued
Phosphate Alternatives
Triphenyl phosphate (TPP) f

Tricresyl phosphate (TCP) l

Isopropylated triphenyl phosphate (IPTPP) f

Tris (p-t-butylphenyl) phosphate (TBPP)

Diethyl bis(2-
hydroxyethyl)aminomethylphosphonate

Oligomeric ethyl ethylene phosphate

Oligomeric phosphonate polyol
115-86-6
L
M
L
L | L
L
H
L

L
VL
VH
VH
L


1330-78-5

L
L




M

L
L
VH
VH



68937-41-7
L
M
L

H
H

L

L
L
VH
VH

H

78-33-1
L
M
L

L


M

L

VH
VH


2781-11-5
L
M

L
L
M
M
M

L
VL
L
L

184538-58-7
L
L
M
L
M
M
LA
L


L
L
L

363626-50-0
L
M
M
L
M
M
L
L

L
VL
L
L
H

VH

M
H

L

L

L
New-to-Market Proprietary Mixtures
Emerald Innovation™ NH-1 *
Proprietary
H
M
L
M
L

H
~\/f

~\jf
~\jf
VH
VH
M
H

Fyrol™ HF-5 *
Proprietary
L
M*
M
L
M
M§
,|(i
L

M
L
VH
VH
H
rf
 This assessment also includes information for other methylated triphenyl phosphate isomers (phosphoric acid, bis(methylphenyl) phenyl ester (CASRN 26446-73-1) and phosphoric acid,
methylphenyl diphenyl ester (CASRN 26444-49-5)).
                                                                                2-4

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                              JUNE 2014 DRAFT REPORT
2.2  Hazard and Fate Results by Chemical Group

The components of Firemaster® 550, thought to be one of the primary alternatives used since
pentaBDE was phased out, are predicted to have Moderate to High hazards for reproductive,
developmental, neurological and repeated dose toxicities. The phosphate components have
inherently Very High hazard for aquatic toxicity, due to the phosphate ester structure and
molecular weight (MW); all the components have Moderate or High potential to bioaccumulate,
based on parent compound or degradation products. As a whole, the components TBB and TBPH
lack full data characterization necessary to adequately describe hazard and risk.

The chlorinated phosphorus alternatives are TCEP, tris (2-chloro-l-methylethyl) phosphate
(TCPP), tris (l,3-dichloro-2-propyl) phosphate (TDCPP) and phosphoric acid, P,P'-[2,2-
bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester (V6), which are fairly
well characterized with empirical test data. In addition to Firemaster® 550, TDCPP is also
thought to be one of the primary alternatives used to replace pentaBDE in FPUF. The four
chlorinated phosphate substances exhibit several distinguishing characteristics. They have
Moderate to High hazard designations for at least four of the following human health endpoints:
carcinogenicity, genotoxicity, reproductive toxicity, developmental/ neurodevelopmental
toxicity, neurological toxicity, and repeated dose toxicity. TCEP is also acutely toxic. These four
substances also have aquatic toxicity hazards in the Moderate to High range, but lack adequate
characterization of chronic aquatic toxicity. Due to the structure and size of these substances they
are not expected to bioaccumulate, but there is a potential for 'pseudo persistence'.

The non-halogenated alternatives include two inorganics, the nitrogen substance melamine, and a
collection of non-halogenated phosphate esters.

The hazard profiles for the inorganics ammonium polyphosphate (APP) and expandable
graphite indicate lower  levels of concern than the other profiles in this report.  APP is a high MW
polymer. Although APP is not well characterized with test data, based on its structure and very
high MW it is predicted to be Low hazard. While it is not expected to be readily  absorbed due to
its MW, it is predicted to be highly persistent. Expandable graphite is not likely to bioaccumulate
and has potentially Low human health and aquatic toxicity, but there is low confidence in the
hazard profile due to the lack of empirical data, and there is potential for the use of hazardous
chemical washes in the  production process.

The profile for melamine identifies key hazards in human health endpoints including acute
toxicity, carcinogenicity, genotoxicity and reproductive toxicity. Bioaccumulation potential is
low, aquatic toxicity is low-moderate, and persistence is high, but with potential  for degradation.

The phosphorus-based non-halogenated alternatives have varied designations for human
health toxicity; several have Moderate to High hazard for reproductive, developmental,
neurological, and repeated dose toxicity, in addition to insufficient data to characterize the
potential for carcinogenicity. These human health hazards are compounded by the Very High
aquatic toxicity associated with the phosphate esters of this size and structure. Trade-offs can  be
seen within this group: the more degradable (Low persistence) phosphate esters triphenyl
phosphate (TPP), tricresyl phosphate (TCP), isopropylated triphenyl phosphate (IPTPP) and tris
                                          2-5

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                              JUNE 2014 DRAFT REPORT
(p-t-butylphenyl) phosphate (TBPP) have High aquatic toxicity and Moderate to High
bioaccumulation potential, whereas the more persistent substances diethyl bis(2-
hydroxyethyl)aminomethylphosphonate and oligomeric ethyl ethylene phosphate have Low
aquatic toxicity and bioaccumulation designations. Potentially more preferable is the oligomeric
phosphonate polyol, which has Low aquatic toxicity, Moderate persistence, and Low
bioaccumulation potential. Human health and aquatic toxicity designations are Low or Moderate,
but data are limited for these three phosphate alternatives, especially the two oligomers, yielding
conservative Moderate designations for several human health endpoints.  While there is
uncertainty associated with the hazard profiles of diethyl bis(2-hydroxyethyl)-
aminomethylphosphonate, the oligomeric ethyl ethylene phosphate, and the oligomeric
phosphonate polyol due to limited data sets, they have potentially safer profiles than many of the
other alternatives assessed in this report.  The oligomeric phosphonate polyol is a component of
the polyurethane foam, and as such may have no potential for release from the foam during
product use. The combination of Low to Moderate hazard designations and its reaction into the
polyurethane foam make oligomeric phosphonate polyol an alternative anticipated to be safer for
use in upholstered polyurethane foam, when flame retardants are added so the end-use product
meets flammability standards.

Two proprietary mixtures that are new to the market were also reviewed. EPA knows the
chemical identification, but cannot reveal it in this report due to regulations regarding
confidential business information. The two mixtures have one or more components with
measured or predicted hazards associated with several human health endpoints, including
reproductive or developmental toxicity, neurological toxicity, repeated dose toxicity, irritation,
and sensitization, are both Very High hazard for aquatic toxicity, and have the potential to
bioaccumulate.

2.3  Hazard  and Fate Results by Endpoint

The following text describes results by class of endpoint: human health, aquatic toxicity,
persistence, and bioaccumulation potential.

The human health endpoints evaluated in DfE Alternatives Assessments include acute toxicity,
carcinogenicity, genotoxicity, reproductive toxicity, developmental toxicity, neurotoxicity,
repeated  dose toxicity, skin sensitization, respiratory sensitization, eye irritation, and dermal
irritation. Acute mammalian toxicity was Low for all but four of the alternatives: tricresyl
phosphate, melamine, TCEP and Emerald InnovationNH-1. Carcinogenicity and genotoxicity
hazards varied among the alternatives, with many Low or Moderate designations. Two of the
chemicals had High concerns for  carcinogenicity: TCEP and TDCPP. Reproductive,
developmental, neurological, and repeated dose toxicity varied from Low to High across the
chemicals. Irritation and sensitization endpoints were generally not distinguishing, with many
Low or Very Low designations, although a few substances had Moderate designations.

Aquatic toxicity hazards varied significantly, due to the diverse chemistries of the alternatives.
The endpoints evaluated in DfE Alternatives Assessments include acute and chronic aquatic
toxicity based  on water column exposures, which may not be suitable tests for some of the
poorly soluble substances.
                                           2-6

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                              JUNE 2014 DRAFT REPORT
Most flame retardants have High or Very High persistence designations, because they are
expected to be stable by design in order to maintain their flame retardant properties throughout
the lifetime of the product. Several of the flame retardant alternatives in this report were not
designated as highly persistent, including TPP, which is readily biodegradable (low persistence).
Also, TCP, IPTPP, TBPP, and TCEP are inherently biodegradable chemicals that degrade slowly
(Moderate persistence); however, these substances have aquatic toxicity hazards, including
deformities in fish and eutrophication from degradation to inorganic phosphates. There is an
apparent trade-off between persistence and toxicity for diethyl bis(2-hydroxyethyl)-
aminomethylphosphonate and the oligomeric ethyl ethylene phosphate that have High and Very
High persistence but Low to Moderate toxicity.  The oligomeric phosphonate polyol appears to
remove this trade-off with only estimated Moderate persistence and estimated Low - Moderate
toxicity.  Predicting long-term fate in the environment is challenging, so there is an uncertainty
as to how substances will eventually degrade, and whether some substances that are degradable
in standard tests may be 'pseudo persistent,' meaning they are continually present in the
environment due to high production volumes that overwhelm ecosystem degradation rates.

The ability of a chemical to accumulate in living organisms is described by bioconcentration,
bioaccumulation, biomagnification, and/or trophic magnification factors. Some of the
alternatives assessed in this report also have a High potential for bioaccumulation, including  the
New-to-Market mixtures, the brominated alternatives, and some of the phosphate alternatives:
TCP, IPTPP,  and TBPP. The inorganic, chlorinated phosphate and discrete nitrogen-based flame
retardants assessed in this report do not have High potential to bioaccumulate.
                                          2-7

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                             JUNE 2014 DRAFT REPORT
3  Flexible Polyurethane Foam Flame Retardants and
    Flammability Standards

This section provides an overview of flexible polyurethane foam (FPUF), discusses which flame
retardants are used in FPUF, and summarizes the standards that require their use. For more
details about FPUF, its manufacture and exposure potential during the manufacturing processes,
see Chapter 3 of the 2005 FFRP report2.

3.1  Flexible Polyurethane Foam

Numerous types of furniture and other products incorporate FPUF. Rigid polyurethane foams, by
contrast, are used in insulation, construction, and other applications (ISOPA 2005), and are not
assessed in this report update.
                                                        ^
Flexible foam is made either in large slabs ("slabstock") that are cut to shape, or in molds that
have the shape of the finished product. The basic ingredients include polyols, isocyanates,
blowing agents,  and other additives (including flame retardants).  In manufacturing slabstock, the
ingredients are blended in a mixing head and deposited on a conveyor belt, where the
polymerization reactions occur, and the foam is expanded by blowing agents into a large (e.g., 60
foot) "bun." The buns are cured before being cut into shapes for a finished product. In molded
foam, the polymerization reactions occur within the mold, and are heated to accelerate curing.

Furniture and other foam product manufacturers typically receive cured foam and do not directly
handle flame retardant chemicals. Because slabstock is made in very large buns, uses requiring
smaller pieces of foam may consist of off-cuts from larger buns. This may be why smaller
polyurethane foam products may contain flame retardants, even when they are not required to do
so by regulation.

3.2  Flame Retardant Classification and Exposure Considerations

Flame retardants used in FPUF are typically classified as "additive". Additive flame retardants
are blended evenly into the foam, but remain unbound. Additive flame retardants are expected to
be more mobile  during the consumer use phase, for example, by volatilizing from the foam, by
being washed from the foam or from the foam surface, or in dust as the foam itself is
mechanically abraded. Reactive flame retardants are chemically bound to the polymer in the
finished product and are used in rigid PUF; they are not typically used in FPUF.

Additive flame retardants have been widely identified in  air, house dust, and handwipe samples
(Stapleton,  Allen et al. 2008; Dodson, Perovich et al. 2012; Stapleton, Eagle et al. 2012; van der
Veen and de Boer 2012; Carignan, Heiger-Bernays et al.  2013), supporting the idea that additive
flame retardants can  mobilize from a plastic or foam into the local microenvironment.
Furthermore, detection of additive flame retardants in blood and urine samples (Stapleton, Eagle
et al. 2012; Carignan, McClean et  al. 2013) and in vivo studies (Patisaul, Roberts et al.  2012)
demonstrate the bioavailability and absorption of several  additive flame retardants.
: Available at: http://www.epa.gov/dfe/pubs/flameret/altrep-vl/altrep-vla-coverl.pdf.


                                          3-1

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                              JUNE 2014 DRAFT REPORT
Reactive flame retardants, because they are chemically bound to the foam polymer itself, are
expected to have lower mobility, volatility, and bioavailability than additive flame retardants,
especially in the consumer use phase of product life. However, reactive flame retardants may still
be released from furniture, either because they are liberated from the polymer, or the original
polymerization was incomplete (U.S. EPA 2005a). As such, exposure to reactive flame
retardants could occur at all points in the life cycle, including manufacture, use, and disposal.

3.3  Sources of Data for Identifying Foam Flame Retardants

Published Data

Publication of the 2005 FFRP report was one of a set of actions undertaken by EPA and other
stakeholders in response to growing concerns about pentaBDE. After a voluntary phase-out of
pentaBDE by the sole U.S. manufacturer in 2004, EPA issued a Significant New Use Rule
(SNUR), effective August 14, 2006, to ensure that production could not re-commence in the U.S.
without prior notice to EPA.

Recent data suggest that the pentaBDE phase-out has had the desired effect of decreasing the
environmental prevalence of the flame retardant. A study of house dust in 16 California homes
found an overall reduction in median values of pentaBDE components between 2006 and 2011;
the declines in pentaBDE component concentrations were significantly associated with new
(purchased between 2006 and 2011) furniture,  electronics,  and flooring (Dodson, Perovich et al.
2012). However, the changes were not uniform; two homes showed marked increases in
pentaBDE congeners. In another study of 102 FPUF samples from residential couches purchased
across the United States, including 24 percent from California, pentaBDE was identified in 16 of
41 samples purchased between 1985 and 2004, but in only one of the 61  samples dating from
2005 or later (Stapleton, Sharma et al.  2012).

These same studies, along with others, helped confirm the major flame retardants used to replace
pentaBDE. In the study of residential couches, TDCPP was detected in 52 percent of foam
samples dating from 2005 or later (Stapleton, Sharma et al. 2012). Firemaster® 550, identified by
its brominated components, TBB and TBPH, was identified in 18 percent of post-phase-out
samples, while alkylated triphenyl phosphates were identified in another 16 percent of samples.
In only 2 of the 61 post-phase-out samples were flame retardants not identified. The high
detection rate of flame retardants, even in couches purchased outside of California, suggested to
the authors that California's furniture flammability standard 1975 Technical Bulletin (TB) 117
(TB117; see Section 3.5 for more details on the recent update to this standard) "is becoming a de
facto standard across the United States" (Stapleton, Sharma et al. 2012).

Several  other flame retardants were identified in these studies. In a study of foam baby products,
Stapleton et al. (2011) identified a chlorinated  organophosphate flame retardant (OPFR) sold
commercially as V6, previously thought to be used in automobiles; TCPP, a major flame
retardant in FPUF in the United Kingdom, but expected to  have limited use in the United States;
and TCEP. All of these chemicals are included in the current report.
                                          3-2

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                              JUNE 2014 DRAFT REPORT
Stakeholder Information

In the course of developing this report, DfE had conversations with several stakeholders from the
2005 FFRP, other stakeholders in the chemical and furniture industries, and academic
researchers with expertise on flame retardancy. DfE developed a candidate list of chemicals
known to be used in FPUF, including a number of flame retardants for which there was the
possibility of use, but that were ultimately excluded from the report. Discussion of these lists
with various stakeholders provided critical information about flame retardant use, including
valuable information about the limitations of some flame retardants (e.g., that discolor or
"scorch" the foam) that likely limit their use in the marketplace.

Process of Identifying Chemicals for Assessment

Flame retardant chemicals assessed in this update were identified through the following
approach:

       1. Reviewed all chemicals from the 2005 report. Many of the chemicals were identified
       in the original report by proprietary placeholders (i.e., generic names). In some of these
       cases, the chemicals have since been publicly identified either by the manufacturer or by
       another party; for example, the brominated components of Firemaster® 550 were
       identified publicly by Stapleton et al. (2008). In these cases, the publicly available
       chemical names were used. Many of the compounds assessed in the 2005 report are no
       longer sold; manufacturer information as well as direct conversations with manufacturers
       was used to ascertain the current market status of these products.

       2. Identified products advertised for use in FPUF. Website and promotional materials
       from the major U.S. manufacturers, as well as from the trade organization Phosphorus,
       Inorganic & Nitrogen Flame Retardants Association (PINFA), were reviewed.
       Manufacturers of proprietary formulations were also consulted to  ensure that the
       candidate list included  all chemical components.

       3. Examined all PMN chemicals associated with FPUF that were identified by PMN
       submitters as being suitable for flame retardancy. New chemicals are required by TSCA
       to be submitted by the manufacturer through the PMN process before being produced in
       or imported into the United States. In some cases it was possible for these PMNs to be
       associated with trade names, to ascertain whether they were sold for possible use in
       FPUF or limited to other markets (e.g., rigid polyurethane foam).

       4. Added flame retardants identified in furniture and other FPUF applications by
       external researchers. In particular, all flame retardants recently identified in FPUF baby
       products by Stapleton et al. were included.

Chemicals identified through these sources were then grouped into two lists: chemicals known
to be currently used in FPUF, which would therefore be assessed; and chemicals thought not to
be used in FPUF  (see Table 3-1 and Table 3-2, respectively). Stakeholders from the 2005
partnership and other experts were then contacted, and provided with the  proposed lists of
                                          3-3

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                              JUNE 2014 DRAFT REPORT


chemicals to be included and excluded. In some cases, each chemical on the lists was discussed
to receive feedback on whether it was actually in use, or specific reasons its use had been halted.

When chemicals were excluded from the assessment, the reason for exclusion is given on that
list. For example, some flame retardants were identified by manufacturers' promotional materials
as being suitable for polyurethane foam, but were described by experts as suitable only for rigid
polyurethane, lacking the appropriate characteristics for FPUF (e.g., unsuitable viscosity). Other
chemicals had previously been identified as suitable for FPUF, but are no longer sold for that
market.

It is difficult to assess the precise number and volume of flame retardants used in furniture and
other products. Although chemical manufacturers are required to periodically report the amount
of raw chemicals manufactured in or imported into the United States, there is no general
requirement for disclosure of the amount of chemicals contained in manufactured or imported
articles.

As mentioned above, chemical  and FPUF manufacturers consulted for this report identified
issues such as odor and scorch with particular flame retardant chemicals, and suggested that they
are unlikely to be in use in the United States. Flame retardant chemicals phased out by U.S.
manufacturers with odor or scorch issues are unlikely to be used in overseas manufacture as well.
                                          3-4

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                                              JUNE 2014 DRAFT REPORT
Table 3-1. Flame Retardants to be Evaluated in the DfE Furniture Flame Retardancy Update
CASRN
Preferred Chemical Abstract Index Name
Common Names and
Acronyms15
Molecular
Formula (MF)
Structure
Brominated Alternatives
183658-27-7
26040-51-7
Benzoic acid, 2,3,4,5-tetrabromo-,
2-ethylhexyl ester
1,2-Benzenedicarboxylic acid, 3,4,5,
6-tetrabromo-, l,2-bis(2-ethylhexyl) ester
TBB; EH-TBB
TBPH; BEH-TEBP

A
Br
^^^^^^° Br
Br Br
Br — ^ ^ — Br
— v 0 0 X — <^
Halogenated Phosphorus Alternatives
115-96-8
13674-84-5;
6145-73-9
Ethanol, 2-chloro-, phosphate (3:1)
2-Propanol, 1-chloro-, 2,2',2"-phosphate;
1-Propanol, 2-chloro-, 1,1',1 "-phosphate
TCEP; Tris(2-chloroethyl)
phosphate
TCPP; Tris(2-chloro-l-
methylethyl)phosphate;
TCIPP

C9H18Cl304P
cs
— •/->' ^\ ^ '
Cl
ry^^'"''
1
	 / 1
Representative structure
                                                          3-5

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JUNE 2014 DRAFT REPORT
CASRN

13674-87-8




38051-10-4



Preferred Chemical Abstract Index Name

2-Propanol, 1,3-dichloro-, phosphate (3:1)




Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-
1,3 -propanediyl] P,P,P',P'-tetrakis(2-chloroethyl)
ester

Common Names and
Acronyms'5
TDCPP; Tris-(l,3-dichloro-2-
propyl)phosphate; TDCIPP



V6; BCMP-BCEP



Molecular
Formula (MF)
C9H15C1604P




C13H24C1608P2



Structure

Ck
o^^/^'
O-P=OCI
/ \ °^
ci ^ciT
Cl
CI
ci \\
C'X°X°^^o fJ
I 0^°
Inorganic/Other Alternatives
68333-79-9




12777-87-6






Polyphosphoric acids, ammonium salts




Sulfuric acid, compd. with graphite (1:?)






APP; Ammonium
polyphosphate
*
1 V^

Expandable graphite






[NH4P03]n




[C]n[S03H]x






o o
fll 1 II
P-O-f^-P-OH
Q- OH
NH4+
Representative structure
o
H°~^"^xr5^5c °
0 t^^W^^^^-S-OH
I^c^_ °
^^r^
OH
Representative structure
         3-6

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JUNE 2014 DRAFT REPORT
CASRN
108-78-1


Preferred Chemical Abstract Index Name
l,3,5-Triazine-2,4,6-triamine


Common Names and
Acronyms15
Melamine


Molecular
Formula (MF)
C3H6N6


Structure
H2N
NX N)— NH2
>=N
H2N
Phosphate Alternatives
115-86-6

26444-49-5


26446-73-1

Phosphoric acid, triphenyl ester

Phosphoric acid, methylphenyl diphenyl ester


Phosphoric acid, bis(methylphenyl) phenyl ester

TPP; Triphenyl phosphate;
TPHP

Cresyl diphenyl phosphate;
Methylphenyl diphenyl
phosphate; Disflamoll DPK;
MPHDPHP

V
Methylated triphenyl
phosphates;
Bis(methylphenyl) phenyl
phosphate; MPHP

C18H1504P






^ o
O-P-O
\! 	 'J o
O-P-O
(y° tk
Representative structure
O-P-O
0°^
/-^
Representative structure
         3-7

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                                                        JUNE 2014 DRAFT REPORT
CASRN
             Preferred Chemical Abstract Index Name
Common Names and
Acronymsb	
Molecular
Formula (MF)
Structure
1330-78-5
             Phosphoric acid, tris(methylphenyl) ester
Tricresyl phosphate;
Disflamoll TKP; TMPHP
C21H2104P
                                                                                                                          o
                                                                                                                       O-P-Q
                                                                                                                          6
                                                                                                                 Representative structure
68937-41-7
             Phenol, isopropylated, phosphate (3:1)

             Commercial product may include mono-, di-, tri-
             and higher substitutions with appropriate
             CASRNs.
IPPP; ITP; IPTPP;
Isopropylated triphenyl
phosphate; Isopropylated
phenol phosphate; TIPPP
                                                                                      Formula for tri-
                                                                                      propyl
                                                                                      substitution
             Phenol, 4-(l,l-dimethylethyl)-, l,l',l"-phosphate

             Includes mono-, di-, tri-, and higher substitutions
             with appropriate CASPJSfs.
                                    O
                                    M
                                 O-P-Q
                                    6
                                                                                                                 Representative structure
78-33-1
TBPP; tris(4-(tert-
butyl)phenyl phosphate; tert-
butylphenyl diphenyl
phosphate; bis(4-(tert-
butyl)phenyl) phenyl
phosphate; TTBPHP
                                                                                      Formula for tri-
                                                                                      butylated
                                                                                      substitution
                                                                                                                 Representative structure
2781-11-5
             Phosphonic acid, P-[[bis(2-
             hydroxyethyl)amino]methyl]-, diethyl ester
N,N-(bis)-hydroxyethyl-
aminomethane phosphonic
acid diethyl ester; BHEAMP-
DE
                                                                                                                        O
                                                                                                                               OH
                                                                      3-8

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                                                                JUNE 2014 DRAFT REPORT
CASRN
184538-58-7
363626-50-0
Preferred Chemical Abstract Index Name
Phosphoric acid, triethyl ester, polymer with
oxirane and phosphorus oxide (P2O5)
Poly(oxy-l,2-ethanediyl), a,.r^ u
^^5n_]5\_/4_r 1^2-^-4
0'05P2)n
CH5O3P-(C2H4
0)n-(C2H40)n
Structure
[o^ 1 o N
r*.'® ^ M i-i
L J n ^-^^
Representative structure
O
HOj/\ i II r nOH
In T ^n
New-to-Market Proprietary Mixtures
Proprietary
Proprietary
Halogen-free flame retardant
Halogen-free phosphorus-based
Emerald Innovation NH-1
Fyrol HF-5


~
~
a The list of flame retardants for evaluation in the Furniture Flame Retardancy update is based on publicly available information on product availability, public and confidential
information on chemical production, and DfE's conversations with stakeholders. DfE welcomes further input on which flame retardants should be included in the updated report. The
inclusion of these chemicals in the DfE Alternatives Assessment does not denote environmental preference.

b The last acronym listed for each substance is the "practical abbreviation" according to Bergman et al (2012)'s proposed standard approach for making acronyms for organic flame
retardants.  Bergman et al 2012 Environment International 49: 57-82.
                                                                                3-9

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                                                 JUNE 2014 DRAFT REPORT
Table 3-2. Flame Retardants That Will Not be Evaluated in the DfE Furniture Flame Retardancy Update
Flame retardants listed here have been identified as being used in polyurethane or other plastics, but are not thought to be used inflexible
polyurethane foam (FPUF), or are not candidates for DfE's hazard assessment process. DfE welcomes input from stakeholders having additional
information on any production or use of these chemicals in FPUF.
CASRN

Preferred Chemical Abstract Index
Name
Common Names and
Acronyms"
MF

Structure

Reason for
Exclusion15
Brominated Alternatives
77098-07-8;
20566-35-2








125997-20-8










36483-57-5





1,2-Benzenedicarboxylic acid, 3,4,5,6-
tetrabromo-, mixed esters with diethylene
glycol and propylene glycol; 1,2-
Benzenedicarboxylic acid, 3,4,5,6-
tetrabromo-, l-[2-(2-hydroxyethoxy)ethyl] 2-
(2-hydroxypropyl) ester




Phosphoric acid, mixed 3-bromo-2,2-
dimethylpropyl and 2-bromoethyl and 2-
chloroethyl esters








1-Propanol, 2,2-dimethyl-, tribromo deriv.





Diester/ether diol of
tetrabromophthalicanhydride ;
2-(2-Hydroxyethoxy)ethyl 2-
hydroxypropyl
3,4,5,6 -tetrabromophthalate ;
HEEHP-TEBP

^


BBDMP-CDMP-P








•r

Tribromoneopentyl alcohol;
TBNPA




C15H2oBr4O9;
C15H16Br407








C9H18Br2ClO4P
7









CsHgBraO





0 Br
HO ^\ ^\ ^\ Br
^\ ® lr iT'
O^^k^x^x
1^ |^ Br
o


^^
Representative Structure

rBr
J
/
i
	 / i~
^i
s
r ci
Representative Structure

Br


	 \
Br
Representative Structure



Appears to
be used in
rigid
polyurethane
foams only.


Historical FR
for
polystyrene
boards; no
current
production.
Not reported
in Chemical
Data
Reporting
(CDR)°.

Appears to
have been an
unsuccessful
product.

                                                              3-10

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JUNE 2014 DRAFT REPORT
CASRN

632-79-1





1047637-37-5








Preferred Chemical Abstract Index
Name
1 , 3 -Isobenzofurandione, 4,5,6,7 -tetrabromo -





Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-
l,3-propanediyl]P,P,P',P'-tetrakis(2-chloro-
1-methylethyl) ester






Common Names and
Acronyms"
Tetrabromophthalic anhydride;
TEBP-Anh




U-OPFR; BCMP-BCMEP





^


MF
















Structure

O Br
Vi JL BP

o T I
//^f"Br
0 Br
Ck
°W o , 1 o VvCI
\ II / \ II /
o-p-o 1^ o-p-o
^^ o ^' 6 ^~^.
ci y >^ ci
1 1


Reason for
Exclusion15


Advertised
for use in
rigid foams.


Although
identified in
consumer
products,
there is no
evidence of
commercial
production.
Halogenated Phosphorus Alternatives
126-72-7








1-Propanol, 2,3-dibromo-, l,l',l"-phosphate








TDBPP; Tris-(2,3-
dibromopropyl)phosphate







C9H15Br604P








^•^ Br
Br^y
^J
i
Br. 0-P=0
^ 	 / ^

Br
LJ,
Historical FR
identified in
house dust,
but no
evidence of
use in FPUF.
Not reported
listed in
CDRC.
Inorganic/Other Alternatives
21645-51-2






Aluminum hydroxide (A1(OH)3)






ATH; Aluminum trihydrate
J





A1(OH)3








HO. ,OH
Al
i
OH


Inefficient,
requiring
very high
loadings.
Probably not
used in
FPUFd.
         3-11

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JUNE 2014 DRAFT REPORT
CASRN
1318-23-6
1309-42-8

68953-58-2
Preferred Chemical Abstract Index
Name
Boehmite (Al(OH)O)
Magnesium hydroxide (Mg(OH)2)
Nano: layers, clays, mesoporous silicate
Quaternary ammonium compounds,
bis(hydrogenated tallow alkyl)dimethyl, salts
with bentonite
Common Names and
Acronyms"
Aluminum oxide hydroxide
Milk of magnesia
Nano: layers, clays,
mesoporous silicate
Surface treated, Inorganic,
mineral based FR synergist
^
MF
A1(OH)O
Mg(OH)2
7

Structure
^ ^°
*
MQ^
HO OH


Reason for
Exclusion15
Inefficient,
requiring
very high
loadings.
Possible use
in some
niche
applications.
Inefficient,
requiring
very high
loadings.
Probably not
used in
flexible
polyurethane
foamd
Research
product; not
yet
commercially
available.
Vendor
described use
in
thermoplastic
polyurethane;
no other use
data
available.
         3-12

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JUNE 2014 DRAFT REPORT
CASRN

Preferred Chemical Abstract Index
Name
Common Names and
Acronyms"
MF

Structure

Reason for
Exclusion15
Phosphate Alternatives
756-79-6











18755-43-6









78-40-0









Phosphonic acid, P-methyl-, dimethyl ester











Phosphonic acid, P-propyl-, dimethyl ester









Phosphoric acid, triethyl ester









DMMP; Dimethyl methyl
phosphonate










Dimethyl propane phosphonate
DMPP; Levaguard DMPP


m- 4





Triethyl phosphate; Levaguard
TEP-Z


^^

*



C3H9O3P





J





C5H1303P





J



C6H15O4P













O
^P' /
t r\
— o



,




0'
o-p=o
/ 1
\/






\l
o 1
-^ ]p' ,
® O—'



Used in rigid
polyurethane
foams.
PINFA
website lists
as
appropriate
forFPUF;
however, no
evidence of
such use is
available.
Thought to
be used in
rigid but not
flexible
polyurethane
foam;
however, not
reported on
listed on
CDRC.
Used in rigid
but not
flexible
polyurethane
foam. Could
be an
impurity
from other
flame
retardants.
         3-13

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                                                                 JUNE 2014 DRAFT REPORT
CASRN
Preferred Chemical Abstract Index
Name
Common Names and
Acronyms"
MF
Structure
Proprietary Alternatives
~

Antiblaze PR82


Reason for
Exclusion15

For use in
rigid foams.
a The last acronym listed for each substance is the "practical abbreviation" according to Bergman et al (2012)'s proposed standard approach for making acronyms for organic flame
retardants. Bergman et al 2012 Environment International 49: 57-82.
b Flame retardants and use information were identified based on publicly available information on product availability, public and confidential information on chemical production, and
DfE's conversations with stakeholders. DfE welcomes further input on which flame retardants should be included in or excluded from the updated report.
0 The CDR Rule requires manufacturers, including importers, to submit information on the chemical they produce domestically or import into the United States during the principal
reporting year, subject to reporting requirements, http://epa.gov/cdr/ The last two reporting years were 2005 and 2011.
d This substance was assessed in the Alternatives Assessment for Decabromodiphenyl Ether (DecaBDE) Report, available at http://www.epa.gov/dfe/pubs/proiects/decaBDE/about.htm.
                                                                                3-14

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                             JUNE 2014 DRAFT REPORT



3.4  Notes on Specific Foam Flame Retardants

Notes on selected foam flame retardant chemicals included in the report follow.

   •   TDCPP, known to be a major flame retardant in FPUF and produced in a volume
       between 10 and 50 million pounds per year in 2011, was listed by California as a
       Proposition 65 chemical3 in late 2011 for concerns about carcinogenicity (OEHHA 2011;
       U.S. EPA 2013a). The Proposition 65 listing may impact the TDCPP market because it
       requires relabeling products that contain TDCPP for sale in California, though labeling of
       TDCPP products for sale outside of California is not required. TDCPP was identified by
       Stapleton, Sharma et al. (2012) in more than half of couch  samples tested since 2005. In
       2012, the major U.S. manufacturer of TDCPP announced a voluntary phase-out of
       TDCPP production by 2015 (ICL Industrial Products 2012).

   •   There has been recent opposition from consumer and environmental groups to the use of
       halogenated flame retardants, and this opposition may shape the market suitability of
       these flame retardants, regardless of hazard data. Some shift away from halogenated
       flame retardants appears to have already occurred.  While the 2005 FFRP report assessed
       a number of brominated flame retardants, the two brominated components of Firemaster®
       550 (TBB and TBPH) are the only brominated flame retardants included in the current
       update report.

   •   Although TCEP was previously not thought to be used in foam, it has been identified in
       upholstered FPUF products (Stapleton, Klosterhaus et al. 2011). TCEP is a TSCA work
       plan chemical for 2013-14, so the DfE Alternatives Assessment process is a useful
       contribution to other EPA activities on this compound (U.S. EPA 2013b).

   •   TCPP and melamine are the major flame retardants used  in the United Kingdom to meet
       the stringent "Crib 5" standard (BS-5852; UK Parliament 1988), but use of this mixture is
       not known to be common in the United States. However, since TCPP was identified in
       FPUF products by Stapleton et al. (2011), it is included in this report.

   •   The larger molecule "V6" (CASRN 38051-10-4) has been  used in automobile foam, due
       to its lower volatility, but was also identified by Stapleton et  al. (2011) in baby products.
       V6 is a dimer of TCEP, and contains TCEP as an impurity.

   •   Researchers first experimented with the use of expandable graphite in FPUF in the
       1980s, but performance limitations restricted its commercial  adoption (Bhagat 2001).
       These limitations have been overcome (Wolska,  Gozdzikiewicz et al. 2012; Wang, Ge et
       al. 2013), and expandable graphite is now considered viable in FPUF (PINFA 2012).
3 A chemical known to the State of California to cause cancer or reproductive toxicity; businesses are required to
provide a warning (e.g., label consumer products, distribute notices to residents) when exposure to a Proposition 65
chemical may occur.


                                         3-15

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                              JUNE 2014 DRAFT REPORT
   •   A new molecule, "U-OPFR" ("unknown organophosphate flame retardant," BCMP-
       BCMEP), a dimer of TCPP, was identified by Stapleton et al. (2011). This molecule is
       not in EPA's CDR data on the manufacturing, processing, and use of commercial
       chemical substances and mixtures; however, it is possible that whole products with this
       molecule have been imported. Experts consulted by DfE were unfamiliar with this
       molecule, and no references to it beyond the Stapleton paper have been identified. U-
       OPFR was not assessed in this update, because there is no evidence of commercial
       production of this chemical.

Flame Retardants as Mixtures

The assessment of flame retardant hazard properties is complicated by the fact that many flame
retardant products are sold as mixtures. This may be the result of a deliberate mixing of diverse
flame retardant chemicals for performance reasons, or as a natural result of the synthesis of the
flame retardant molecules. For example, a number of flame retardant products now contain
alkylated triphenyl phosphates with a number of different side chains in use (e.g., methyl,
isopropyl, tert-butyl). As a natural result of the synthesis process, these mixtures are likely to
contain the unalkylated TPP itself, along with mixtures  of mono-, di-, tri-, and possibly higher
alkyl substitutions. Each of these  substitutions can also  occur in numerous isomers (e.g., the
substitution might occur on the meta, ortho, or para positions). A single product identified as
IPTPP, therefore, may in fact consist of a large number  of molecules of differing properties,
making evaluation more difficult.

Deliberate mixtures of different molecules are also common. Most notably,  Firemaster® 550 has
been identified as a mixture of TBB, TBPH,  TPP, and IPTPP (Stapleton, Allen et al. 2008);
approximately 50% of the mixture is TBB and TBPH at a ratio of 4:1 by mass, while the
remainder is comprised of the other two molecules. This constitutes a challenge to the DfE
assessment process. Some of the toxicity studies available are of the Firemaster® 550 mixture
itself; others are of the mixture of only the two brominated components (also sold as Firemaster®
BZ-54), while some data exist for each component individually. Therefore, it is not always
possible to attribute effects seen in toxicologic studies to an individual component. (Effects
resulting from additive, synergistic, or antagonistic interactions of a combination  could
complicate the analysis further.) It is likely that the composition of some commercial products
varies from batch to batch. In addition, differential volatilization, degradation, or  absorption may
lead to different exposure patterns to the individual components at various points along the  life
cycle of the product.

DfE attempted to assess hazard profiles of the commercial products, where possible. For
example, since mono- and tri-substituted cresyl triphenyl phosphate are sold as different
products, DfE listed them separately in the list of substances for assessment, but for efficiency
assessed the variety of substitutions of the cresyl phosphate in one profile "tricresyl phosphate."
Similarly, since IPTPP appears to be sold as  a mixture of mono/di/tri-substitutions, that  mixture
was evaluated as a whole. In practical terms, little data are available for each component, and
most available data are associated with a mixture. Where data on individual components do exist,
DfE takes a conservative approach by using the highest  hazard designation for any one
component of the mixture as the hazard designation for  the whole mixture.
                                          3-16

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                              JUNE 2014 DRAFT REPORT
In the case of mixtures of dissimilar molecules, DfE evaluated, as far as possible, both the
components and the complete mixture. Here, again, DfE's criteria were followed in assigning to
each endpoint for the mixture the highest hazard call for a mixture component. (No attempt was
made to assess synergistic or other interactions between component chemicals.)

3.5   Standards that Influence the Use of Flame Retardants

Several regulations currently drive the use of flame retardants in FPUF. As described below,
changes to some of the standards have been proposed or passed. As these changes are
implemented, this report will provide valuable information on available alternatives to enable
informed substitution, should there be a continuing need for flame retardants in FPUF or
upholstery fabric.

California TB117

In 1975, California's Bureau of Electronic and Appliance Repair, Home Furnishings and
Thermal Insulation (BEARHFTI) (then the Bureau of Home Furnishings and Thermal
Insulation) promulgated TB117. Meeting TB117 required a small, candle-sized flame to be
applied directly to the uncovered foam for 12 seconds without igniting a fire (Cal/DCA 2000).
Passing such a test required either an  IFR foam or the use of flame retardants. The  most common
solution was the addition of flame retardants to FPUF (NDRC 2013). Since  manufacturers
generally prefer to make a single product for the U.S. market, the TB117 standard had to some
extent become a national de facto standard. TB117 required labeling of compliant furniture in
California, but labels did not always appear in other states.

In 2010, California amended TB117 to specifically exempt "juvenile furniture":  "strollers, infant
carriers, and nursing pillows" (Cal/DCA 2010). However, as described above, FPUF is
manufactured in large (60-foot) "buns," which are then cut to shape. It is likely that most buns
are made with flame retardants, in anticipation of being used in a mixture of TB117-compliant
and -exempt products. Similarly, the flame retardants in FPUF "pit cubes" identified by
Carignan, Heiger-Bernays, et al. (2013) in a study of gymnast exposure to flame retardants may
have been the result of a manufacturing process that incorporates flame retardants to meet TB117
standards.

In 2013, California enacted changes to the TB117 standard. The new TB117-2013  requires a lit
cigarette to be applied to a miniature assembly of the cover fabrics, barrier materials, and  filling
materials to represent the finished piece of furniture (Cal/DCA 2013). Fabric materials failing the
smolder test can still be used if a fire blocker (inter-liner) layer is added. The new test is based on
the voluntary American Society for Testing and Materials (ASTM) E1353 standard (Cal/DCA
2013). Manufacturers may begin to use the new testing requirements as of January 1, 2014 and
must be fully compliant by January 1, 2015 (California Governor's Office 2013).

The TB117-2013 standard, by testing the combination of fabric and filling material, is
anticipated to lower the requirements for flame retardants in the foam itself. Many  of the more
common thermoplastic fabrics are likely to pass the smolder test, although some fabrics,
primarily cellulosic, are likely to need modification before passing the test (CPSC 2008).
                                         3-17

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                              JUNE 2014 DRAFT REPORT
A number of other localities have passed flammability standards, which are often based on
California standards; for example, the Boston Fire Code incorporates TB133 (Boston Fire
Department 1995). How local standards will change as a result of revisions to TB117 remains an
open question.

California TB133

The more stringent TB133 standard, promulgated in 1991, was designed to increase fire safety in
public spaces. Meeting TB133 requires a large open flame, provided by a gas burner, to be
applied to the assembled piece of furniture for about 80 seconds without igniting a fire. TB133
has been used as the basis for legislation in other localities (TB133 compliance is often voluntary
for sprinklered buildings, in which case TB117 still applies in California (PFA  1992)).

Detailed data on how products meet TB133 are not available, but two general approaches are
possible: the use of flame-retardant fabrics and foams that together provide suitable flame
resistance; alternatively, an intrinsically flame-retardant fire blocker or "inter-liner" layer can be
used between the foam and the cover fabric (PFA 1992). Anecdotal evidence gathered from
manufacturers suggests that the foam components are typically TB117 compliant, and that a
cover fabric back-coated with flame retardant is commonly used. No  public data exist on which
flame retardants are  used in back-coatings.

Consumer Product Safety Commission

In a March 4, 2008,  notice of proposed rulemaking (NPR) published in the Federal Register,
CPSC proposed a national standard addressing the risk of deaths and  injuries associated with
residential upholstered furniture fires4 (CPSC 2008). The proposed rule focused primarily on
fires ignited by  smoldering cigarettes. The standard could be met by either using cover materials
that are sufficiently smolder-resistant to meet a cigarette ignition performance test, or by using
fire barriers (inter-liners) that meet smoldering and open flame resistance tests placed between
the cover fabric and  interior filling materials. In  order to reduce reliance on additive flame
retardants, the proposed rule did not contain performance requirements for filling materials. As
such, CPSC specified a standard foam that did not include any flame  retardant chemicals when
testing cover materials, thereby removing additive flame retardants in the foam from
consideration in order to meet the requirements of the flame resistance test. Technical challenges
with the test methods in this approach prompted CPSC staff to investigate other approaches.
Validation of the test methodology proposed in the NPR showed that furniture constructed with
fire barriers and exposed to a small open flame produced a significantly less intense fire than
furniture constructed without fire  barriers.  CPSC staff believes the fire barrier approach may
have the potential to address nearly all of the upholstered furniture-related fires and save more
lives each year than the 2008 proposed standard.

Subsequently, in 2013, CPSC requested comments on a standard that would cover  a wider range
of ignition sources found in the home (CPSC 2013a).
4 This standard would apply to cushioned, upholstered seating products available for residential, home office, and/or
dormitory use.
                                          3-18

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                              JUNE 2014 DRAFT REPORT
It should be noted that other open flame standards, including the more stringent Crib 5 standard
in the United Kingdom, which tests PUF covered with a standard fire-retarded polyester fabric
but does not allow for the use of fire barriers, are typically met with a combination of additive
flame retardants (NDRC 2013).

Other Standards

The Upholstered Furniture Action Council (UFAC) has developed a voluntary industry standard
for cigarette ignition, which is embodied in the ASTM E-1353 method. The revised California
TB117-2013 follows this method, with modifications. CPSC estimates that 90% of currently
produced furniture meets the voluntary UFAC standard, which does not address open flame
ignitions (CPSC 2008).

In 2013, the New York State Assembly (the lower house of the Legislature) passed a bill
(A06557 in the Assembly, introduced as  S04780 in the  Senate) that would establish an as-yet-
undefined open flame standard for furniture (NY State Assembly 2013). The bill also prohibits
the use of halogenated flame retardants in furniture.

During its July 2013 meeting, the National Fire Protection Association (NFPA) Standards
Council reviewed a request to consider establishing an open flame standard for upholstered
furniture. NFPA is currently accepting public comments on the need for a new standard,
available resources on the issue, individuals who may be interested in participating in the
development of a new standard, and organizations involved in furniture flame retardant standards
(Durso 2013; NFPA 2013).

Other Product Sectors

In addition to furniture,  other products contain upholstered FPUF. Automobile and aircraft
seating is constructed in a manner similar to furniture, with a need for  stringent fire protection, as
well as other requirements. For example, the flame retardant known as "V6" has a higher MW
and lower volatility, and has been identified in automobile applications, where window fogging
is an important problem. Aircraft seating is less cost-sensitive than most consumer products, and
has relied on more expensive flame barriers as well as additive flame retardants, including
expandable graphite. This report includes all flame retardants that DfE identified as being used in
these other sectors; this update does not address the flammability standards for these sectors.

Impacts of Changing Standards

It is difficult to predict the impact of changes to these standards on the use of flame retardants.
The recent changes to TB117, moving from an open flame to a smolder test, will likely lessen
the need for flame retardant additives in foam; however, for some fabrics, this may require flame
retardant coatings or other modifications. An open-flame, performance-based standard from the
CPSC, from New York  State, or from another regulatory body might be met either with flame
retardant inter-liners or with higher loads of flame retardants in foam, a choice made by
individual manufacturers and likely to be driven in many cases by costs.
                                         3-19

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                             JUNE 2014 DRAFT REPORT
4  Alternative Flame Retardant Solutions not Assessed in
    This Report

While the focus of recent public attention has been on additive flame retardant chemicals in
FPUF, other methods can be used to provide increased fire safety. These methods are described
briefly here; however, this update does not attempt to fully characterize these methods. A
rigorous comparison of costs and benefits, particularly over the product life cycle, would require
analysis beyond the scope of this report. More information on alternative methods is available in
the 2005 FFRP report.

Flame Resistant Cover Fabrics

In its 2008 proposal for a national furniture flame retardancy standard, CPSC estimated that
about 14% of fabrics used at that time would fail the proposed smolder test (CPSC 2008); these
fabrics could be coated with a flame retardant to meet a smolder test. Coating fabrics raises the
issue of chemical safety in the coatings used; flame retardant chemicals used for coatings tend to
differ from the flame retardant chemicals used in FPUF. Anecdotal information indicates that
decaBDE, tetrabromobisphenol A, and hexabromocyclododecane - each one the subject of a DfE
Alternatives Assessment (see http://www.epa.gov/dfe/alternative_assessments.html) - have been
used as fabric coatings (Stapleton July 2013, personal communication). The current report does
not attempt to identify or assess flame retardants used in fabric coatings.

Fire Barriers

To meet a more stringent test (e.g., an open flame test), a fire barrier may be used between the
foam and the upholstery fabric. A fire barrier may be IFR (e.g., Kevlar or Nomex), or may be
coated with a flame retardant chemical, possibly including the chemicals identified as
alternatives in this report. Fire barriers have proven highly effective in aircraft seating, even in
extreme fire situations (CPSC 2013b). A suitable fire barrier is likely to be able to achieve
almost any flame retardancy standard; however, costs of such products are likely to be higher.
Mattresses meeting the CPSC 1633 open flame standard most commonly use fire barriers,
although designs  of these barriers vary widely (Nazare, Davis et al. 2012).

Polymers and Reactive Flame Retardants

The current report includes only one polymeric flame retardant (excluding expandable graphite).
While polymers would be expected to have lower mobility, reducing exposures during the
consumer use phase, they are difficult to use in the manufacture of FPUF. Polymeric and reactive
flame retardants typically have high viscosities incompatible with flexible polyurethane, are not
compatible with the extremely small pores used in the blending nozzle, and have difficulty
blending with the polyol. Reactive products are available in other product sectors (e.g., in printed
circuit boards), and there is great interest in the manufacturing industry in finding reactive  flame
retardants for FPUF.
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Nanoclays

There has been recent interest in nanoclay flame retardants, which may slow or prevent the
breakdown of materials and decrease the temperature of the flame, and have been shown to
improve the mechanical properties of polyurethane foam (Betts 2008; Nayani, Gunashekar et al.
2013). Nanoclays can also be combined with other classes of flame retardants to improve their
performance. These materials are currently in the research and development stage, but may
become viable products in the near future. Layer-by-layer (LbL) coatings are nanocomposite
structures assembled by an alternate deposition of anionic and cationic monolayers onto a
substrate (Li, Schulz et al. 2009; Kim, Harris et al. 2012). The LbL deposition technique was
discovered in 1966, and flame retardant LbL coatings have recently gained attention beyond the
areas of academic research and development, with some industrial companies pursuing internal
studies on the effectiveness of LbL coatings as flame retardants in commercial products
(Apaydin, Laachachi et al. 2013). Research has shown that LbL coatings can be effective flame
retardants for a number of different substrates including polyurethane foam (Kim, Harris et al.
2012; Laufer, Kirkland et al. 2012a) and cotton fabric (Li, Schulz et al. 2009; Laufer, Kirkland et
al. 2012b).
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5  Hazard Evaluation Methodology

This section summarizes the lexicological and environmental hazards of Furniture Flame
Retardants (FFRs) and each alternative chemical or proprietary mixture that was identified as a
potential functional substitute for them. Evaluations of chemical formulations may also include
associated substances (e.g., starting materials, byproducts, and impurities) if their presence is
specifically required to allow that alternative to fully function in the assigned role. Otherwise,
pure substances were analyzed in this assessment. Users of the alternative assessments should be
aware of the purity of the trade product they purchase, as the presence of impurities may alter the
assessment of the alternative. This report is a hazard assessment, not a risk assessment. Hazard
assessment as a risk management tool is discussed in more detail in Section 1.4.

Toxicological and environmental endpoints included in the hazard profiles are discussed in
Section 5.1 along with the criteria used to evaluate each hazard endpoint. Data sources and the
review methodology are described in Section 5.2.  The report then offers a detailed description of
the utility of physical-chemical properties in understanding hazard in Section 5.3 and the process
of evaluating human health and environmental endpoints in  Sections 5.4 and 5.5, respectively. A
discussion of the evaluation of endocrine activity is included in Section 5.6. The characteristics
of each chemical included in the alternatives assessment are summarized in the comparative
hazard summary table in Section 2. Lastly, the collected data and hazard profile of each chemical
are presented in Section 6.

5.1  Toxicological and Environmental Endpoints

The assessment of endpoints with the intent to create hazard profiles for a DfE alternatives
assessment follows the guidance of the DfE Alternatives Assessment Criteria for Hazard
Evaluation (U.S. EPA 201 Ib). The definitions for each  endpoint evaluated following these
criteria are outlined in Section 5.1.1 and the criteria by which these endpoints are evaluated are
outlined in Section 5.1.2. Lastly, there are endpoints which DfE characterizes but does not assign
criteria to and these are summarized in Section 5.1.3.

5.1.1   Definitions of Each Endpoint Evaluated Against Criteria
Hazard designations for each chemical discussed in this report were made by direct comparison
of the experimental or estimated data to the DfE Alternatives Assessment Criteria for Hazard
Evaluation (U.S. EPA2011b). Table 5-1 provides brief definitions of human health toxicity,
environmental toxicity and environmental fate endpoints.

Table 5-1: Definitions of Toxicological and Environmental Endpoints for Hazard Assessment
Endpoint
Category
Human Health
Effects
Endpoint
Acute Mammalian Toxicity
Definition
Adverse effects occurring following oral or dermal
administration of a single dose of a substance, or multiple
doses given within 24 hours, or an inhalation exposure of
4 hours.
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Endpoint
Category
Endpoint
Definition
            Carcinogenicity
                                     Capability of a substance to increase the incidence of
                                     malignant neoplasms, reduce their latency, or increase
                                     their severity or multiplicity.
            Mutagenicity/Genotoxicity
                                     Mutagenicity - The ability of an agent to induce
                                     permanent, transmissible changes in the amount, chemical
                                     properties or structure of the genetic material. These
                                     changes may involve a single gene or gene segment, a
                                     block of genes, parts of chromosomes, or whole
                                     chromosomes. Mutagenicity differs from genotoxicity in
                                     that the change in the former case is transmissible to
                                     subsequent cell generations.

                                     Genotoxicity - The ability of an agent or process to alter
                                     the structure, information content, or segregation of DNA,
                                     including those which cause DNA damage by interfering
                                     with normal replication process, or which in a non-
                                     physiological manner (temporarily) alter its replication.
            Reproductive Toxicity
            Developmental Toxicity
            Neurotoxicity
                                     The occurrence of biologically adverse effects on the
                                     reproductive systems of females or males that may result
                                     from exposure to environmental agents. The toxicity may
                                     be expressed as alterations to the female or male
                                     reproductive organs, the related endocrine system, or
                                     pregnancy outcomes. The manifestation of such toxicity
                                     may include, but is not limited to: adverse effects on onset
                                     of puberty, gamete production and transport, reproductive
                                     cycle normality, sexual behavior, fertility, gestation,
                                     parturition, lactation, developmental toxicity, premature
                                     reproductive senescence or modifications in other
                                     functions that were dependent on the integrity of the
                                     reproductive systems.
                                     Adverse effects in the developing organism that may
                                     result from exposure prior to conception (either parent),
                                     during prenatal development, or postnatally to the time of
                                     sexual maturation. Adverse developmental effects may be
                                     detected at any point in the lifespan of the organism. The
                                     major manifestations of developmental toxicity include:
                                     (1) death of the developing organism, (2) structural
                                     abnormality, (3) altered growth, and (4) functional
                                     deficiency.
                                     An adverse change in the structure or function of the
                                     central and/or peripheral nervous system following
                                     exposure to a chemical, physical or biological agent.
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Endpoint
Category

Environmental
Toxicity
Environmental
Fate
Endpoint
Repeated Dose Toxicity
Respiratory Sensitization
Skin Sensitization
Eye Irritation/Corrosivity
Skin Irritation/Corrosion
Definition
Adverse effects (immediate or delayed) that impair
normal physiological function (reversible and irreversible)
of specific target organs or biological systems following
repeated exposure to a chemical substance by any route
relevant to humans. Adverse effects include biologically
significant changes in body and organ weights, changes
that affect the function or morphology of tissues and
organs (gross and microscopic), mortality, and changes in
biochemistry, urinalysis, and hematology parameters that
are relevant for human health; may also include
immunological and neurological effects.
Hypersensitivity of the airways following inhalation of a
substance.
A cell-mediated or antibody -mediated allergic response
characterized by the presence of inflammation that may
result in cell death, following an initial induction exposure
to the same chemical substance, i.e., skin allergy.
Irritation or corrosion to the eye following the application
of a test substance.
Skin irritation- reversible damage to the skin following the
application of a test substance for up to 4 hours. Skin
corrosion- irreversible damage to the skin namely, visible
necrosis through the epidermis and into the dermis
following the application of a test substance for up to 4
hours.
Environmental toxicity refers to adverse effects observed in living organisms that typically
inhabit the wild; the assessment is focused on effects in three groups of surrogate aquatic
organisms (freshwater fish, invertebrates, and algae).
Aquatic Toxicity (Acute)
Aquatic Toxicity (Chronic)
Environmental Persistence
Bioaccumulation
The property of a substance to be injurious to an organism
in a short-term, aquatic exposure to that substance.
The property of a substance to cause adverse effects to
aquatic organisms during aquatic exposures which were
determined in relation to the life-cycle of the organism.
The length of time the chemical exists in the environment,
expressed as a half-life, before it is destroyed (i.e.,
transformed) by natural or chemical processes. For
alternative assessments, the amount of time for complete
assimilation (ultimate removal) is preferred over the initial
step in the transformation (primary removal).
The process in which a chemical substance is absorbed in
an organism by all routes of exposure as occurs in the
natural environment, e.g., dietary and ambient
environment sources. Bioaccumulation is the net result of
competing processes of chemical uptake into the organism
at the respiratory surface and from the diet and chemical
elimination from the organism including respiratory
exchange, fecal egestion, and metabolic biotransformation
of the parent compound and growth dilution.
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The hazard profile for each chemical contains endpoint specific summary statements (see Section
4.8). For each of the endpoints listed in Table 5-1, these summary statements provide the hazard
designation, the type of data (experimental or estimated) and the rationale. The endpoint
summaries may also include explanatory comments, a discussion of confounding factors or an
indication of the confidence in the data to help put the results in perspective.

5.1.2  Criteria

Table 5-2 summarizes the criteria that were used by EPA DfE Program to interpret the data
presented in the hazard evaluations. The DfE Alternatives Assessment Criteria for Hazard
Evaluation underwent internal and public comment, and were finalized in 2011 (U.S. EPA
201 Ib). A hazard  designation  for each human health endpoint was not given for each route of
exposure but rather was based on the exposure route with the highest hazard designation. Data
may have been available for some or all relevant routes of exposure.

The details as to how each endpoint was evaluated are described below and in the DfE full
criteria document, DfE Alternatives Assessment Criteria for Hazard Evaluation, available at:
http://www.epa.gov/dfe/alternatives_assessment_criteria_for_hazard_eval.pdf.

Table 5-2: Criteria Used to Assign Hazard Designations
Endpoint
Very High
High


Very Low
Human Health Effects
Acute mammalian toxicity
Oral median lethal dose
(LD50) (mg/kg)
Dermal LD50 (mg/kg)
Inhalation median lethal
concentration (LC50) -
vapor/gas
(mg/L)
Inhalation LC50 - dust/mist/
fume (mg/L)
<50

<200
<2



<0.5

>50-300

>200-1,000
>2-10



>0.5-1.0

>300-2,000

> 1,000-2,000
>10-20



>l-5

>2,000

>2,000
>20



>5

—

-
—



-

Carcinogenicity





Carcinogenicity





Known or
presumed
human
carcinogen

(equivalent to
Globally
Harmonized
System of
Classification
and Labeling of
Chemicals
(GHS)
Categories 1A
and IB)
Suspected
human
carcinogen








(equivalent to
GHS Category
2)

marginal
evidence of
Carcinogenicity








(And inadequate
evidence in
humans)
Negative studies
or robust
mechanism-
based Structure

Relationship
(SAR)





(As described
above)
-










Mutagenicity/Genotoxicity
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Endpoint
Germ cell mutagenicity
Mutagenicity and
genotoxicity in somatic
cells
Very High
GHS Category
lAorlB:
Substances
known to
induce heritable
mutations or to
be regarded as
if they induce
heritable
mutations in the
germ cells of
humans

High
GHS Category
2: Substances
which cause
concern for
humans owing
to the
possibility that
they may
induce heritable
mutations in the
germ cells of
humans
OR
Evidence of
mutagenicity
supported by
positive results
in in vitro AND
in vivo somatic
cells and/or
germ cells of
humans or
animals

Evidence of
mutagenicity
supported by
positive results
in in vitro OR in
vivo somatic
cells of humans
or animals

Negative for
chromosomal
aberrations and
gene mutations,
or no structural
alerts.
, -
Very Low

Reproductive toxicity
Oral (mg/kg/day)
Dermal (mg/kg/day)
Inhalation - vapor, gas
(mg/L/day)
Inhalation - dust/mist/fume
(mg/L/day)
-
-
-
-
<50
<100
<1
<0.1
50-250
100-500
1-2.5
0.1-0.5
>250-1,000
>500-2,000
>2.5-20
>0.5-5
> 1,000
>2,000
>20
>5
Developmental toxicity
Oral (mg/kg/day)
Dermal (mg/kg/day)
Inhalation - vapor, gas
(mg/L/day)
Inhalation - dust/mist/fume
(mg/L/day)
-
-
-
-
<50
<100
<1
<0.1
50-250
100-500
1-2.5
0.1-0.5
>250-1,000
>500-2,000
>2.5-20
>0.5-5
> 1,000
>2,000
>20
>5
Neurotoxicity
Oral (mg/kg/day) ^
Dermal (mg/kg/day)
Inhalation - vapor, gas
(mg/L/day)
Inhalation - dust/mist/fume
(mg/L/day)
-
-
-
-
<10
<20
<0.2
0.02
10-100
20-200
0.2-1.0
0.02-0.2
>100
>200
>1.0
>0.2
-
-
-
-
Repeated-dose toxicity
Oral (mg/kg/day)
Dermal (mg/kg/day)
-
-
<10
<20
10-100
20-200
>100
>200
-
-
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Endpoint
Inhalation - vapor, gas
(mg/L/day)
Inhalation - dust/mist/fume
(mg/L/day)
Very High
-
-
High
O.2
O.02

0.2-1.0
0.02-0.2

>1.0
>0.2
Very Low
-
-
Sensitization
Skin sensitization
Respiratory sensitization


High frequency
of sensitization
in humans
and/or high
potency in
animals (GHS
Category 1A)
Occurrence in
humans or
evidence of
sensitization in
humans based
on animal or
other tests
(equivalent to
GHS Category
1A and IB)
Low to moderate
frequency of
sensitization in
human and/or
low to moderate
potency in
animals (GHS
Category IB)
Limited
evidence
including the
presence of
structural alerts
Adequate data
available and not
GHS Category
lAorlB
Adequate data
available
indicating lack
of respiratory
sensitization


Irritation/corrosivity ^ ^^^^^^_ ^^
Eye irritation/corrosivity
Skin irritation/corrosivity
Irritation
persists for
>21 days or
corrosive
Corrosive
Clearing in 8-
21 days,
severely
irritating
Severe
irritation at
72 hours
Clearing in
<7 days,
moderately
irritating
Moderate
irritation at
72 hours
Clearing in
<24 hours,
mildly irritating
Mild or slight
irritation at
72 hours
Not irritating
Not irritating
Endocrine activity
Endocrine Activity
For this endpoint, High/Moderate/Low etc. characterizations will not apply. A
qualitative assessment of available data will be prepared.
Environmental Toxicity and Fate
Aquatic toxicity
Acute aquatic toxicity -
LC50 or half maximal
effective concentration
(EC50) (mg/L) ^
Chronic aquatic toxicity -
lowest observed effect
concentration (LOEC) or
chronic value (ChV)
(mg/L)
<1.0
0.1
1-10
0.1-1
>10-100
>1-10
>100orNo
Effects at
Saturation
(NES)
>10orNES


Environmental persistence
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Endpoint
Persistence in water, soil,
or sediment
Persistence in air (half-life
days)
Very High
Half-life
>180 days or
recalcitrant
High

Half-life of 60-
180 days
Half-life <60
but>16 days

Half-life
<16 days OR
passes Ready
Biodegradability
test not
including the
10-day window.
No degradation
products of
concern.
Very Low
Passes Ready
Biodegradability
test with 10-day
window. No
degradation
products of
concern.
For this endpoint, High/Moderate/Low etc. characterizations will not apply. A
qualitative assessment of available data will be prepared.
Bioaccumulation
Bioconcentration Factor
(BCF)/Bioaccumulation
Factor (BAF)
LogBCF/BAF
>5,000
>3.7
5,000-1,000
3.7-3
<1,000-100
<3-2
<100
<2

-
Very High or Very Low designations (if an option for a given endpoint in Table 5-2) were assigned only when there were experimental data
located for the chemical under evaluation. In addition, the experimental data must have been collected from a well conducted study specifically
designed to evaluate the endpoint under review. If the endpoint was estimated using experimental data from a close structural analog, by
professional judgment, or from a computerized model, then the next-level designation was assigned (e.g., use of data from a structural analog
that would yield a designation of very high would result in a designation of high for the chemical in review). One exception is for the estimated
persistence of polymers with an average MW >1,000 daltons, which may result in a Very High designation.


5.1.3   Endpoints Characterized but Not Evaluated


Several additional endpoints were characterized, but not evaluated against hazard criteria. This is

because the endpoints lacked a clear consensus concerning the evaluation criteria (endocrine
activity), data and expert judgment were limited for industrial chemicals (persistence in air,

terrestrial ecotoxicology), or the information was valuable for the interpretation of other toxicity
and fate endpoints (including toxicokinetics and transport in the environment).


Table 5-3: Definitions of Endpoints and Information Characterized but Not Evaluated Against Hazard
Criteria
Toxicological Endpoint
Toxicokinetics
Biomonitoring
Information J
Environmental Transport
Definition
The determination and quantification of the time course of absorption, distribution,
biotransformation, and excretion of chemicals (sometimes referred to as
pharmacokinetics) .
The measured concentration of a chemical in biological tissues where the analysis
samples were obtained from a natural or non-experimental setting.
The potential movement of a chemical, after it is released to the environment, within
and between each of the environmental compartments, air, water, soil, and sediment.
Presented as a qualitative summary in the alternative assessment based on physical-
chemical properties, environmental fate parameters, and simple volatilization models.
Also includes distribution in the environment as estimated from a fugacity model5.
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Toxicological Endpoint
Persistence in Air
Immunotoxicology
Terrestrial Ecotoxicology
Endocrine Activity
Definition
The half -life for destructive removal of a chemical substance in the atmosphere. The
primary chemical reactions considered for atmospheric persistence include hydrolysis,
direct photolysis, and the gas phase reaction with hydroxyl radicals, ozone, or nitrate
radicals. Results are used as input into the environmental transport models.
Adverse effects on the normal structure or function of the immune system caused by
chemical substances (e.g., gross and microscopic changes to immune system organs,
suppression of immuno logical response, autoimmunity, hypersensitivity,
inflammation, and disruption of immunological mechanistic pathways).
Reported experimental values from guideline and nonguideline studies on adverse
effects on the terrestrial environment. Studies on soil, plants, birds, mammals,
invertebrates were also included.
A change in endocrine homeostasis caused by a chemical or other stressor from
human activities (e.g., application of pesticides, the discharge of industrial chemicals
to air, land, or water, or the use of synthetic chemicals in consumer products.)
 A fugacity model predicts partitioning of chemicals among air, soil, sediment, and water under steady state
conditions for a default model "environment" (U.S. EPA 201 le).

5.2  Data Sources and Assessment Methodology

This section explains how data were collected (Section 5.2.1), prioritized and reviewed (Section
5.2.2) for use in the development of hazard profiles. High-quality experimental studies lead to a
thorough understanding of behavior and effects of the chemical in the environment and in living
organisms. Analog approaches and SAR-based estimation methods are also useful tools and are
discussed throughout this section. Information on how polymers  differ from discrete chemicals
in terms of how they are evaluated is presented in Section 5.2.3.

5.2.1   Identifying and Reviewing Measured Data

For each chemical assessed, data were collected in a manner consistent with the High Production
Volume (HPV) Chemical Challenge Program Guidance (U.S. EPA 1999) on searching for
existing chemical information. This process resulted in a comprehensive search of the literature
for available experimental data. For chemicals well characterized by experimental studies this
usually resulted in the collection of recent high-quality reviews or peer-reviewed risk
assessments. These were supplemented by primary searches of scientific literature published
after these secondary sources were released; this is explained in greater detail below. For
chemicals that are not as well characterized, that is, where these secondary sources were not
available or lacked relevant or adequate data, a comprehensive search of the primary scientific
literature was done. Subsequently, these searches led to the collection and review of articles from
the scientific literature, industrial submissions, encyclopedic sources, and  government reports. In
addition, data presented in EPA public databases (e.g., Integrated Risk Information System
(IRIS); the High Production Volume  Information System (HPVIS)) and confidential databases
were obtained for this project. Generally, foreign language (non-English) reports were not used
unless they provided information that was not available from other sources.

Chemical assessments were performed by first searching for experimental data for all endpoints
in Table 5-2. For most alternatives assessed, high quality secondary sources were not available;
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therefore a comprehensive search of the literature was performed to identify experimental data.
In some cases, confidential studies submitted to EPA by chemical manufacturers were also
available to support hazard designations. For those chemicals that were expected to form stable
metabolites, searches were performed to identify relevant fate and toxicity information for the
metabolite or degradation product.

Well Studied Chemicals - Literature Search Strategy

As mentioned above, for chemicals that have been well characterized, the literature review
focused primarily on the use of secondary sources, such as Agency for Toxic Substances and
Disease Registry (ATSDR) Toxicological Profiles or IRIS assessments. Using high-quality
secondary sources maximized available resources and eliminated potential duplication of effort.
However, more than one secondary source was typically used to verify reported values, which
also reduced the potential for presenting a value that was transcribed incorrectly from the
scientific literature. Although other sources might also contain the same experimental value for
an endpoint, effort was not focused on building a comprehensive list of these references, as it
would not have enhanced the ability to reach a conclusion in the assessment. When data for a
selected endpoint could not be located in a secondary source for an otherwise well studied
chemical, the primary literature was searched by endpoint and experimental studies were
assessed for relevant information.

Making Predictions in the Absence of Measured Data

In the absence of primary or secondary data, hazard designations were based on (1) Quantitative
Structure Activity Relationships (QSAR)-based estimations from the EPA New Chemical
Program's predictive methods; (2) analog data; (3) class-based assignments from the EPA
Chemical Categories document and (4) expert judgment by EPA subject matter experts.

For chemicals that lacked experimental information, QSAR assessments were made using either
EPA's Estimation Programs Interface (EPISuite™) for physical-chemical property and
environmental fate endpoints or EPA's Ecological Structure Activity Relationships
(ECOSAR™) QSARs for ecotoxicity.  For the cancer endpoint, estimates were  also obtained
from EPA's OncoLogic expert system. These estimation methods have been automated, and are
available for free (U.S. EPA 2012c). Often analog data were used to support predictions from
models. These approaches were described in the EPA Pollution Prevention (P2) Framework and
Sustainable Futures (SF) program (U.S. EPA 2005b; U.S. EPA 201 le).

For some physical-chemical properties that could not be estimated using EPISuite™,  such as
acid/base dissociation constants, other available methods (e.g., the ACE acidity and basicity
calculator website for dissociation constants) were used (ACE Organic 2013). All estimation
methods employed were limited to those freely available in the public domain.

The methodology and procedures used to assess polymers are described in Section 5.2.3. In
addition, the endpoints for impurities or oligomers with a MW >1,000 daltons were estimated
using professional judgment and the results assessed for inclusion in the overall hazard
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designation. This process is described, as appropriate, under the corresponding endpoints
appearing in Section 5.3.

Although expandable graphite has some structural features in common with carbon-based
nanoparticles, its cross-section diameter is far greater and it would be less likely to pass through
biological membranes.  As a result, available nanoparticle data were not used as analog data in
the evaluation of expandable graphite.

When QSAR models were not available, professional judgment was used to identify hazards for
similar chemicals using the guidance from EPA's New Chemicals Categories (U.S. EPA 2010b).
The categories identify substances that share chemical and toxicological properties and possess
potential health or environmental concerns (U.S. EPA 2010a). In the absence of an identified
category, analogs for which experimental data are available were identified using EPA's Analog
Identification Methodology (AIM) or by substructure searches of confidential EPA databases
(U.S. EPA 2012a). If a hazard designation was still not available,  the expert judgment of
scientists from EPA's New Chemical Program would provide an assessment of the physical-
chemical properties, environmental fate, aquatic toxicity and human health endpoints to fill
remaining data gaps.

Expandable graphite was a unique substance compared to the other alternatives in this report.
Although expandable graphite has some structural features in common with carbon-based
nanoparticles, its cross-section diameter is far greater and it would be less likely to pass through
biological membranes. As a result, it was not considered a nano-sized substance and available
nanoparticle data were not used as analog data in the evaluation. At the time of this report, DfE is
not using the hazard criteria to assess nanoparticles.

5.2.2   Hierarchy of Data Adequacy

Once the studies were  obtained, they were evaluated to establish whether the hazard data were of
sufficient quality to meet the requirements of the assessment process. The adequacy and quality
of the studies identified in the literature review are described in the Data Quality field of the
chemical assessments presented in Section 4.8. The tiered approach described below represents a
general preferred data hierarchy, but the evaluation of toxicological data also requires flexibility
based on expert judgment.

       1.  One or more studies conducted in a manner consistent with established testing
          guidelines
       2.  Experimentally valid but nonguideline studies (i.e., do not follow established testing
          guidelines)
       3.  Reported data without supporting experimental details
       4.  Estimated data using  SAR methods or professional judgment based  on an analog
          approach
       5.  Expert judgment based on mechanistic and structural considerations

In general, data were considered adequate to characterize an endpoint if they were obtained using
the techniques identified in the HPV data adequacy guidelines (U.S. EPA 1999). Studies
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performed according to Harmonized EPA or Organisation for Economic Cooperation and
Development guidelines were reviewed to confirm that the studies followed all required steps.

Experimental studies published in the open literature were reviewed for their scientific rigor and
were also compared and contrasted to guideline studies to identify potential problems arising
from differences in the experimental design.  Data from adequate, well-performed, experimental
studies were used to assign hazard designations in preference to those lacking in sufficient
experimental detail. When multiple adequate studies were available for a given endpoint, any
discrepancies that were identified within the  set of data were examined further and addressed
using a weight-of-evidence approach that was described in the data entry to characterize the
endpoint whenever possible.

When available, experimental data from guideline or well-performed experimental studies were
preferred (Items 1 and 2 in the hierarchy list). Information from secondary sources such as
Material Safety Data Sheets (MSDSs),  or online databases (such as the National Library of
Medicine's Hazardous Substances Data Bank (HSDB), Item 3  in the hierarchy list) was
considered appropriate for some endpoints when it included numerical values for effect levels
that could be compared to the evaluation criteria.

5.2.3   Assessment of Polymers and Oligomers

The methodology and procedures used  to assess polymers were slightly different than those used
for oligomers, discrete compounds and simple mixtures. Although experimental data for
polymers were identified using the literature  search techniques discussed above in Section 5.2.1,
in the absence of experimental data, estimates were performed using professional judgment as
presented in the literature (Boethling and Nabholz 1997). The polymers are a mixture of
molecules with  a distribution of components  (e.g., different chain  lengths) that depend on the
monomers used, their molar ratios, the total number of monomeric units in the polymer chain,
and the manufacturing conditions. To account for this variation, the average MW profile (also
referred to as the number average molecular  weight (MWn)) was used in their assessment as the
individual chains rarely have the same degree of polymerization and weight yet their physical,
chemical, and environmental properties are essentially identical for the purposes of this
assessment. The polymers evaluated as alternatives typically have average MWs ranging from
>1,000 to <100,000 daltons.

For polymers with relatively low average MWs (i.e., those with average MWs generally less than
2,000), the alternative assessment also determined the amount  of oligomers and unchanged
monomers (starting materials) in the MW profile with MWs <1,000 daltons. Special attention
was paid to materials that have a MW <1,000 daltons as these materials often have the highest
hazard (potentially bioavailable substances) in the mixture. This type of assessment was similar
to the evaluation of the hazards of impurities present in discrete chemical products.
Methodological differences between the evaluation of discrete products and polymers are
discussed in Section 5.3. Although the MW of expandable graphite is >1,000, it was not
explicitly evaluated as a polymer. However,  the chemical property and hazard designation
cutoffs associated with polymers and other high MW materials were used in its evaluation.
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For the Alternatives Assessment, there were chemicals that are mixtures of low MW oligomers
comprised of 2 or 3 repeating units. The hazard assessment evaluated all oligomers present.
From all the oligomers, the higher concern material was used to assign the hazard designation.
This process is essentially identical to the evaluation of the hazards associated with impurities or
byproducts present in discrete chemical products. As a result, the alternatives assessment process
determined the amount of oligomers and unchanged monomers (starting materials) present and
considered their potential hazards in the alternatives designation.

5.3   Importance of Physical and Chemical Properties, Environmental Transport, and
      Biodegradation

Physical-chemical properties provide basic information on the characteristics of a chemical
substance and were used throughout the alternatives assessment process. These endpoints
provide information required to assess potential environmental release, exposure, and
partitioning as well as insight into the potential for adverse toxicological effects. The physical-
chemical properties are provided in the individual chemical hazard profiles presented in Section
7. Descriptions of relevant physical-chemical properties and how they contribute to the hazard
assessments are presented below.

Molecular Weight (MW)

MW informs how a chemical behaves in a physical or biological system including bioavailability
and environmental fate. In general, but not strictly, larger compounds tend to be less mobile in
biological and environmental systems. Their large size restricts their transport through biological
membranes and lowers their vapor pressure. Polymers and oligomers evaluated in this
alternatives assessment were mixtures that contain a distribution of components and they may
not have a unique MW (see also Section 5.2.3). To account for variation in these mixtures, the
average MW or MWn, determined experimentally (typically using high pressure liquid
chromatography, viscosity, or light-scattering), was used in the assessment of polymers. The
assessment of polymers also includes oligomers and unchanged monomers (starting materials)
that have MW of <1,000 daltons as these were often the highest concern materials (bioavailable
substances) in the mixture.

Melting Point and Boiling Point

These two properties provide an indication of the physical state of the material at ambient
temperature. Chemicals with a melting point more than 25°C were assessed as a solid.  Those
with a melting point less than 25°C and a boiling point more than 25°C were assessed as a liquid
and those with a boiling point less than 25°C were assessed as a gas. The physical state was used
throughout the assessment, such as in the determination of potential routes of human and
environmental exposure. The melting and boiling points were also useful in determining the
potential environmental fate, ecotoxicity, and human health hazards of a chemical. For example,
organic compounds with high melting points generally have low water solubility and low rates of
dissolution. These properties influence a material's bioavailability and were therefore taken into
account in both the assessment process and the evaluation of experimental studies.  Similarly,
chemicals with a low melting point also have a higher potential to be absorbed through the skin,
gastrointestinal tract, and lungs.
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In the absence of experimental data, the melting point value was not reported and no estimations
were performed. If a chemical decomposes before it melts, this information was included in the
assessment. For boiling point, the maximum value reported in the assessment was 300°C for
high boiling materials including polymers (U.S. EPA 1999). Melting points for polymers and/or
oligomers were not reported as these materials typically reach a softening point and do not
undergo the phase change associated with melting (i.e., solid to liquid).

Vapor Pressure

Vapor pressure is useful in determining the potential for a chemical substance to  volatilize to the
atmosphere from dry surfaces, from storage containers, or during mixing, transfer, or
loading/unloading operations. In the assessment process, chemicals with a vapor pressure less
than 1 x 10~6 mm Hg have a low potential for inhalation exposure resulting from  gases or vapors.
Vapor pressure is also useful for determining the potential environmental fate of a substance.
Substances with a vapor pressure more than 1 x 10~4 mm Hg generally exist in the gas phase in
the  atmosphere. Substances with a vapor pressure between 1 x 10~4 and 1 x 10~8 mm Hg exist as a
                                                                   o
gas/particulate mixture. Substances with a vapor pressure less than 1x10" mm Hg exist as  a
particulate. The potential atmospheric degradation processes described below in the reactivity
section generally occur when a chemical exists in the gas phase. Gases in the atmosphere also
have the potential to travel long  distances from their original point of release. Materials in the
liquid or solid (particulate) phases in the atmosphere generally undergo deposition onto the
Earth's surface.
                                  o
A maximum vapor pressure of 1 x 10"  mm Hg was assigned for chemicals without experimental
data or for those substances that were anticipated by professional judgment to be nonvolatile
(U.S. EPA 1999). The maximum vapor pressure of 1 x  10"8 mm Hg was also the  default value
reported for the vapor pressure of polymers and other high MW materials with a  MW >1,000
daltons (U.S.  EPA 1999).

Water Solubility

The water solubility of a chemical provides an indication of its distribution between
environmental media, potential for environmental exposure through release to aquatic
compartments, and potential for human exposure through ingestion of drinking water. Water
solubility was also used extensively to determine potential  human health and ecotoxicity hazards.
In general, chemicals with water solubility less than 1 x 10"5 g/L indicate a lower concern for
both the expression of adverse effects, and potential aquatic and general population exposure due
to their low bioavailability. However, chemicals with a low bioavailability also tend to be more
environmentally persistent. Low bioavailability is different than no bioavailability, and the two
should not be used interchangeably.

Within the context of this alternatives assessment, the following descriptors were used according
to ranges of water solubility values: more than 10,000 mg/L was considered very soluble; 1,000-
10,000 mg/L  represents soluble; 100-1,000 mg/L represents moderately soluble, 1-100 mg/L
represents slightly soluble, and less than 1 mg/L represents insoluble, noting that these guidelines
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might not match what is used elsewhere within the scientific literature for other disciplines.
Chemicals with higher water solubility were more likely to be transported into groundwater with
runoff during storm events, be absorbed through the gastrointestinal tract or lungs, partition to
aquatic compartments, undergo atmospheric removal by rain washout, and possess a greater
potential for human exposure through the ingestion of contaminated drinking water. Chemicals
with lower water solubility are generally more persistent and have a greater potential to
bioconcentrate.

The water solubility of a substance was also used to evaluate the quality of experimental aquatic
toxicity and oral exposure human health studies as well as the reliability of aquatic toxicity
estimates. If the water solubility of a substance was lower than the reported exposure level in
these experiments, then the study was likely to be regarded as inadequate due to potentially
confounding factors arising from the presence of un-dissolved material. For aquatic toxicity
estimates obtained using SARs, when the estimated toxicity was higher than a chemical's  water
solubility (i.e., the estimated concentration in water at which adverse effects appear cannot be
reached because it was above the material's water solubility), the chemical was described  as
having NES. An NES designation is equivalent to a low aquatic toxicity hazard designation for
that endpoint.

While assessing the water solubility of a chemical substance, its potential to disperse in an
aqueous  solution was also considered. Ideally, a chemicals potential to disperse would be
obtained from the scientific literature. In the absence of experimental data, the potential for
dispersion can be determined from chemical structure and/or comparison to closely related
analogs.  There are two general structural characteristics that lead to the formation of dispersions
in water: (1) chemicals that have both a hydrophilic (polar) head and a hydrophobic (nonpolar)
tail (e.g., surfactants), and (2) molecules that have a large number of repeating polar functional
groups (e.g., polyethylene oxide).

The potential for a chemical to disperse influences potential exposure, environmental fate, and
toxicity.  Dispersible chemicals have greater potential for human  and environmental exposure,
teachability, and aquatic toxicity than what might be anticipated based on the material's water
solubility alone.

Chemicals without experimental  data or chemicals that were anticipated by professional
judgment to be sufficiently insoluble  and thus were not bioavailable were assigned a water
solubility maximum value of 1 x 10~3 mg/L (U.S. EPA 1999). A water solubility of 1 x 10~3 mg/L
is the default value used for discrete organics as well as non-ionic polymers with a MW > 1,000
daltons according to information contained in the literature concerning polymer assessment
(Boethling and Nabholz 1997). This assignment is consistent with an analysis of the chemicals
used in the development of the water solubility estimation program in EPA's EPISuite™
software. The training set for this model included 1,450 chemicals with a MW range 27-628
daltons and experimental water solubility values ranging from miscible to 4 x 10"7 mg/L
(Meylan, Howard et al. 1996; U.S. EPA 201 li). Given that water solubility decreases with MW,
a default value of 1 x 10"3 mg/L is consistent with the limited bioavailability expected for
materials with a MW >1,000 daltons.
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Octanol/Water Partition Coefficient (KoW)

The octanol/water partition coefficient, commonly expressed as its log value (i.e., log Kow) is one
of the most useful properties for performing a hazard assessment. The log Kow indicates the
partitioning of a chemical between octanol and water, where octanol is used to mimic fat and
other hydrophobic components of biological systems. Chemicals with a log Kow less than 1 are
highly soluble in water (hydrophilic), while those with a log Kow more than 4 are not very
soluble in water (hydrophobic). A log Kow more than 8 indicates that the chemical is not readily
bioavailable and is essentially insoluble in water. In addition, a log Kow greater than
approximately 8 may be difficult to obtain experimentally.

The log KOW can be used as a surrogate for the water solubility in a hazard assessment and is
frequently used to estimate the water solubility if an experimental value is not available. It  can
also be used to estimate other properties important to the assessment, including bioconcentration
and soil adsorption, and is a required input for SAR models used to estimate ecotoxicity values.

For chemicals without data, that are not within the domain of EPISuite™ or that were expected
to be insoluble in water (WS <1 x 10~3 mg/L), a minimum value of 10 was assigned for the log
KOW (U.S. EPA 1999). Insoluble chemicals that could be run through EPISuite   software may
use a log KOW >10 if the result appeared to be valid based on expert review.  This assignment is
consistent with an analysis of the chemicals ("training set") used in the development of the
octanol/water partition coefficient estimation program in the EPISuite™ software. The training
set for this model included 10,946 chemicals with a MW range 18-720 daltons and experimental
log Kow values ranging from -3.89 to 8.70 (Meylan and Howard 1995; U.S.  EPA 201 Ih). Given
that log KOW increases with MW, a default value of 10 is consistent with the limited
bioavailability expected for materials with a MW >1,000  daltons. A maximum log Kow of-2 was
used for water soluble materials. For most polymers and other materials that are anticipated to be
insoluble in both water and octanol, the log Kow cannot be measured and was therefore not  listed.

Flammability (Flash Point)

The flash point of a substance is defined as the minimum temperature at which the substance
emits sufficient vapor to form an ignitable mixture with air. Flash point can be used to identify
hazards associated with the handling of volatile chemicals. Substances with a flash point above
37.8°C (100°F) were commonly referred to as non-flammable,  as this is the flammability
definition used in the shipping industry. There are exceptions to this definition such as chemicals
that may form explosive mixtures in the presence of air.

Explosivity

Explosivity refers to the potential for a chemical to form explosive mixtures in air and can be
defined using the limits of flammability. The lower limit of flammability (LFL) is defined as the
minimum concentration of a combustible  substance that is capable of propagating a flame
through a homogenous mixture in the presence of an ignition source. The upper limit of
flammability (UFL) is similarly defined as the highest concentration that can propagate a flame.
LFLs and UFLs are commonly reported as the volume percent or volume fraction of the
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flammable component in air at 25°C. If the ambient air concentration of the gas (or vapor) is
between the upper and lower explosion limit, then the material has the potential to explode if it
comes in contact with an ignition source. Knowledge regarding the explosivity of a given
material in air is also useful in identifying potential hazards associated with the manufacture and
use of that material.

pH

The pH scale measures how acidic or basic a substance is on a range from 0 to 14. A pH of 7 is
neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. This scale is used primarily
to identify potential hazards associated with skin or eye contact with a chemical or its aqueous
solutions. The corrosive nature of chemicals that form either strongly basic (high pH) or strongly
acidic (low pH) solutions are generally likely to result in harm to skin and other biological
membranes. For corrosive chemicals, some experimental studies, such as biodegradation tests,
require additional analysis to determine if the tests were performed at concentrations that cause
harm to microbes in the test (and, therefore, may result in incorrectly identifying a chemical as
persistent in the environment). For chemicals that form moderately basic  or acidic solutions in
water, the pH of the resulting solution can be used in  lieu of a measured dissociation constant.

Dissociation  Constant in Water (pKa)

The dissociation constant determines if a chemical will ionize under environmental conditions.
The dissociation constant in water provides the amount of the dissociated and undissociated
forms of an acid, base, or organic salt in water. Knowledge of the dissociation constant is
required to assess the importance of the other physical-chemical properties used in the hazard
assessment. As the percentage of ionization increases, the water solubility increases while the
vapor pressure, Henry's Law constant, and  octanol/water partition  coefficient decrease. For acids
and bases, the dissociation constant is expressed as the pKA and pKe, respectively.

Henry's  Law Constant

Henry's Law constant is the ratio of a chemical's concentration in the gas phase to that in the
liquid phase (at equilibrium). In environmental assessments, the Henry's Law constant is
typically measured in water at 25°C. The Henry's Law constant provides an indication of a
chemical's volatility from water, which can be used to derive partitioning within environmental
compartments and the amount of material removed by stripping in  a sewage treatment plant.
Henry's Law constant values less than 1 x 10~7 atm-m3/mole indicate slow volatilization from
water to air (the Henry's Law constant for the volatilization of water from water is 1 x 10~7 atm-
m3/mole) and values more than 1  x  10~3 atm-m3/mole indicate rapid volatilization from water to
air. To aid in  determining the importance of volatilization, the assessment uses two models based
on the Henry's Law constant. These models determine the half-life for volatilization from a
                                                      O       Q
model river and a model lake. A maximum value of 1 x 10" atm-m /mole for the Henry's Law
constant was  assigned for chemicals without experimental data or for those that were anticipated
by professional judgment to be nonvolatile.
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Sediment/Soil Adsorption/Desorption Coefficient (KoC)

The soil adsorption coefficient provides a measure of a chemical's ability to adsorb to the
organic portion of soil and sediment. This provides an indication of the potential for the chemical
to leach through soil and be introduced into groundwater, which may lead to environmental
exposures to wildlife or humans through the ingestion of drinking water drawn from
underground sources. Chemicals with high soil adsorption coefficients are expected to be
strongly adsorbed to soil and are unlikely to leach into ground water. The soil adsorption
coefficient also describes the potential for a chemical to partition from environmental waters to
suspended solids and sediment. The higher the Koc the more strongly a chemical is adsorbed to
soil. Strong adsorption may impact other fate processes,  such as the rate of biodegradation, by
making the chemical less bioavailable.

The soil adsorption coefficient, Koc, is normalized with respect to the organic carbon content of
the soil to account for geographic differences. The assignments for the degree that a chemical is
adsorbed to soil within the context of the assessment were described qualitatively as very strong
(above 30,000), strong (above 3,000), moderate (above 300), low (above 30), and negligible
(above 3). When determining the potential for a chemical to adsorb to soil and suspended organic
matter, the potential for a chemical to form  chemical bonds with humic acids and attach to  soil
also needs to be considered, although this process is generally limited to a small number of
chemical classes.

A maximum value of 30,000 for the Koc was assigned for chemicals without experimental data or
for those that were anticipated by professional judgment to be strongly absorbed to soil (U.S.
EPA 2005b). A default Koc of 30,000 was used for polymers and other high MW materials  with a
MW>l,OOOdaltons.

Reactivity

The potential for a substance to undergo irreversible chemical reactions in the environment can
be used in the assessment of persistence. The primary chemical reactions considered in an
environmental fate assessment are: hydrolysis, photolysis, and the gas phase reaction with
hydroxyl radicals, ozone or nitrate radicals. The most important reaction considered in the hazard
assessment of organic compounds is hydrolysis, or the reaction of a chemical  substance with
water. Because the rate of hydrolysis reactions can change substantially as a function of pH,
studies performed in the pH range typically found in the environment (pH 5-9) were considered.
The second reaction considered in the assessment is photolysis, the reaction of a chemical with
sunlight.  Both hydrolysis and photolysis occur in air, water, and soil, while only hydrolysis was
considered in sediment. The half-lives for reactive processes, if faster than removal via
biodegradation, were used to assign the hazard designation by direct comparison to the DfE
persistence criteria.

For the atmospheric compartment, persistence also includes the evaluation of oxidative gas-
phase processes.  These processes include the reaction with ozone, hydroxyl radicals, and nitrate
radicals.  Since the average concentration of these oxidative species in the atmosphere has been
measured, the experimental or estimated rate constants were converted to, and reported as,  a
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half-life in the assessment using standard pseudo first-order kinetics (U.S. EPA 201 If; U.S. EPA
20 lid).

For inorganic compounds, an additional chemical process was considered, the potential to be
reduced or oxidized (undergo a redox reaction) under environmental conditions. Redox reactions
change the oxidation state of the species through the transfer of electrons to form another
compound (such as the reduction of Cr(VI) to Cr(III)). A change in the oxidation state of a metal
or inorganic species can result in significant changes in the material's hazard designation. In this
example, going from Cr(VI) to Cr(III) makes the compound less toxic.

Environmental Transport

The persistence of a chemical substance is based on determining the importance of removal
processes that may occur once a chemical enters the environment. As noted in Section 5.3,
chemicals with a half-life of less than 60 days are expected to be at most a Moderate hazard
designation for persistence. Persistence does not directly address the pathways in which a
chemical substance might enter the environment (e.g., volatilization or  disposal in a landfill) and
focuses instead on the  removal processes that are expected to occur once it is released into air,
water, soil, or sediment. Similarly, the persistence assessment does not  address what might
happen to a chemical substance throughout its life cycle, such as disposal during incineration of
consumer or commercial products. Understanding the environmental transport of a chemical
substance can help identify processes relevant to environmental assessment. For example, if a
chemical is toxic to benthic organisms and partitions primarily to sediment, its potential release
to water should be carefully considered in the selection of alternatives.

Biodegradation

In the absence of rapid hydrolysis or other chemical reactions, biodegradation is typically the
primary environmental degradation process for organic compounds. Determining the importance
of biodegradation is, therefore, an important component of the assessment. Biodegradation
processes are divided into two types. The first is primary biodegradation, in which a chemical
substance is  converted to another substance. The second is ultimate biodegradation, in which a
chemical is completely mineralized to small building-block components (e.g., CC>2 and water).
DfE persistence criteria use data that are reported as percent of theoretical ultimate degradation
in the guideline Ready Biodegradability test or as a half-life in other experimental studies; both
of these measurements can be compared directly to the DfE criteria in 5.1.2. When considering
primary degradation, the assessment process includes an evaluation of the potential for the
formation of metabolites that were more persistent than the parent materials. Chemical
substances that undergo rapid primary degradation but only slow ultimate biodegradation were
considered to have stable metabolites. In the absence of measured data  on the substance of
interest, DfE evaluated the potential for biodegradation for chemicals with a MW <1,000 daltons
using the EPA EPISuite™ models. EPISuite™ estimates the probability for ready biodegradation
as well as the potential for primary and ultimate removal, as described in Section 5.3. A default
Very High persistence hazard designation was assigned for polymers and other high MW
materials with a MW >1,000 daltons according to information contained in the literature
concerning polymer assessment (Boethling and Nabholz 1997).
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5.4  Evaluating Human Health Endpoints

After data collection and analysis of the physical-chemical properties for the chemicals being
assessed the comparison of the data against the hazard criteria can begin. Section 5.4.1 discusses
how measured data are used to make hazard designations for human health endpoints and
Section 5.4.2 presents the approach for filling in data gaps to make these hazard designations.

5.4.1  Endpoints Characterized  and Evaluated Against Criteria Based on Measured Data

This section provides a short description of how measured data were used to designate the level
of hazard for each endpoint. As a reminder, the criteria for the hazard designations are in Table
5-2.

For acute mammalian toxicity the median lethal doses or concentrations were used to assign the
hazard designation. Four levels of hazard designation have been defined ranging from Low to
Very High.

For cancer the hazard designation was contingent on the level of evidence for increased
incidence of cancer, and not potency. The definitions applied in DfE criteria are based on
International Agency for Research  on Cancer (IARC) levels of evidence (International Agency
for Research on Cancer 2006). For example,  a designation of Very High concern requires that
the substance be characterized as a "known or presumed human carcinogen", whereas a
designation of Low concern requires either negative studies or robust SAR conclusions. A
designation of Moderate was applied as a default value when there was an absence of data
suggesting High carcinogenicity, and an absence of data supporting Low carcinogenicity (i.e.,  a
lack of negative studies or weak SAR conclusions).

Similarly,  the hazard designation for mutagenicity/genotoxicity was also based on the level of
evidence rather than potency. Complete data requirements for this endpoint were both gene
mutation and chromosomal aberration assays. For instances of incomplete or inadequate
mutagenicity/genotoxicity data, a Low hazard designation cannot be given.

For chronic endpoints, such as reproductive,  developmental, neurological and repeated dose
toxicity, the hazard designation was based  on potency. The evaluation considers both lowest
observed adverse effect levels (LOAELs) and identification of no observed adverse effect levels
(NOAELs) when available. The LOAEL and the NOAEL are experimental dose levels, and their
reliability is dictated by the study design. In studies for which the lowest dose tested resulted in
an adverse effect (and therefore a NOAEL was not established), and in studies for which the
highest dose tested was a NOAEL, a conservative approach using professional judgment was
used to address uncertainty regarding the lowest dose or exposure level that might be expected to
cause a particular adverse effect. For example, in the absence of an  established a NOAEL, an
identified LOAEL might fall within the range of a Moderate hazard; however, it is uncertain if a
lower dose, such as one that falls within the range of High hazard exists because no lower doses
were tested. In such cases, professional judgment was applied to assign a hazard designation
when possible. Some degree of uncertainty was evident in results from studies in which a
NOAEL may fall within one hazard range (e.g., Moderate hazard) and the identified LOAEL
falls within a different hazard range (e.g., Low hazard) because the true LOAEL may fall in
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either category, but there were not enough experimental data points to determine the true
LOAEL. Professional judgment was also applied to these cases to assign a hazard descriptor
when possible and the rationale used was described in the assessment. Developmental
neurotoxicity was considered and was evaluated using the developmental toxicity criteria, which
are more stringent than the criteria for neurotoxicity, and thus designed to be more protective
(U.S. EPA 201 Ib).

The criteria for skin and respiratory sensitization, which are immune-based responses, consider
the frequency and potency of the reactions. For skin sensitization, categories were based on the
weight of evidence6 from traditional animal bioassays, but in vitro alternative studies were also
considered. At this time, there are no standard test methods for respiratory sensitization; as a
result there was often no designation for this endpoint.

The evaluation of skin and eye irritation and corrosivity were based on the time to recovery.

5.4.2  SAR - Application of SAR and Expert Judgment to Endpoint Criteria

If measured data pertaining to human health criteria were not available, potential adverse effects
were estimated with SAR analysis. To make these estimates, DfE relied on the expertise of
scientists in EPA's New Chemicals Program (NCP) who have reviewed thousands of chemicals
and associated data using these methods.  SAR uses the molecular structure of a chemical to infer
a physicochemical property that can be related to specific effects on human health. These
correlations may be qualitative ("simple SAR") or quantitative (QSAR). Information on EPA's
use of SAR analysis has been published by U.S. EPA (1994). Public access to free validated
quantitative SAR models for human health endpoints is far more limited than physical-chemical
properties, environmental fate parameters, or ecotoxicology.  Carcinogenicity was assessed using
the OncoLogic expert system that provides a qualitative result directly applicable to the DfE
criteria. For other endpoints that required SAR approaches, an analog approach using expert
judgment was used as discussed in Section 5.2. All estimates obtained in this project were
reviewed by EPA scientists having subject matter expertise. Estimates for the other human health
endpoints were based on expert judgment using an  analog approach and not through the use of
computerized SAR methodologies.

Carcinogenicity

The potential for a chemical to cause cancer in humans was estimated using OncoLogic expert
system. This program uses a decision tree based on the known Carcinogenicity of chemicals with
similar chemical structures, information on mechanisms of action, short-term predictive tests,
epidemiological studies, and expert judgment.

Polymer Assessment

Estimates for polymers were obtained using information contained in the literature concerning
polymer assessment based on the MW profile (Boethling and Nabholz 1997). Those polymers
6 Generally, weight of evidence is defined as the process for characterizing the extent to which the available data
support a hypothesis that an agent causes a particular effect (U.S. EPA 1999; U.S. EPA 2002; U.S. EPA 2005b).


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with MW >1,000 were assessed using an appropriate representative structure that has a MW less
than or equal to the average MW. For polymers with an average MW >1,000 daltons and a
significant amount of low MW material <1,000 daltons, the low MW components were also
assessed for their environmental fate and potential toxicity in order to identify any possible
hazards for the most bioavailable fraction. Similarly, the presence of unreacted monomers
requires that the assessment consider these components for polymers of any MW range. The
properties for polymers with an average MW >1,000 with no low MW components were
generally evaluated as a single high MW material for each of the properties described below. In
general, polymers with an average MW > 1,000 were not amenable to the available SAR
estimation methods and based on the SF guidance are assumed to have low to no bioavailability.
Polymers with MW >1,000 that were not degradable or reactive are also typically not
bioavailable. Polymers with an average MW >10,000 have potential for adverse  effects due to
lung overloading when respirable particles are present (less than ten microns). There may be
exceptions to the rules of thumb  outlined above and as  such this guidance should not be held as
absolute thresholds.

Polymers and oligomers with MWs < 1,000 were assessed using a representative  structure for all
the MW species anticipated to be present in the mixture. The procedures were essentially
identical to those employed for the evaluation of impurities or byproducts in discrete chemicals,
although in this case the oligomer with the highest concern was used to drive the hazard
designation. Unreacted monomers, if present, were also assessed and considered in the hazard
evaluation.

5.5  Evaluating Environmental Toxicity and Fate Endpoints

As with endpoints previously mentioned, the preferred  method for the evaluation of
environmental endpoints is the use of experimental data. In their absence, the alternatives
assessment uses computerized QSAR models developed by EPA for the evaluation of
environmental endpoints that can be directly compared to the DfE criteria. When measured data
were unavailable, the hazard designation for aquatic toxicity was estimated using EPA's
ECOSAR™ software and the persistence designation was estimated using models in EPA's
EPISuite™ software. As a direct result of the design of these models and their direct application
to DfE criteria, the evaluation of environmental endpoints using experimental or estimated data
was discussed together in the following subsections.

5.5.1  Aquatic Toxicity

For ecological toxicity,  the alternatives assessment focused on the hazard  designations for acute
and chronic studies on freshwater species of algae, invertebrates, and fish, (often referred to as
the "three surrogate species"). Aquatic toxicity values were reported in the assessment as
follows:

   •  Acute (estimated or experimental) - LCso in mg/L
   •  Chronic (experimental) - No observed effect concentration (NOEC) in mg/L
   •  Chronic (estimated) -  ChV, or the geometric mean between the NOEC and the LOEC, in
       mg/L
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Experimental data reported in the alternatives assessment also included information on the
species tested. Test data on other organisms (e.g., worms) were included in the assessment if data
were readily available. These data would be evaluated using professional judgment to support
hazard designations assigned using the three surrogate species; however, they were not used by
themselves to assign a hazard designation as DfE criteria are not available. Poorly soluble
substances for which the water column exposures may not be adequate to describe sediment and
particulate exposures will be identified by a footnote.

If an experimental or estimated effect level exceeded the known water solubility of a chemical
substance, or if the log Kow exceeded the estimated ECOSAR™ cut-off values for acute and
chronic endpoints (which are class specific), NES were predicted for the aquatic toxicity
endpoints. NES indicates that at the highest concentration achievable, the limit of a chemical's
water solubility, no adverse effects were observed (or would be expected). In these cases, a Low
hazard designation was assigned. In the cases where both an estimated water solubility and
ECOSAR1  estimate were used, then an additional factor of ten was applied to the water
solubility before a NES designation was assigned to account for the combined uncertainty in the
model estimates.

In the case where an experimental aquatic toxicity value was significantly higher than the
chemical's water solubility, it was likely the result of a poorly conducted study. In this
circumstance, which is generally more frequent for formulated products or mixtures, additional
details were provided in the data quality section to describe why the reported values could not be
used to assign a hazard designation.

EPA's ECOSAR™ estimation program uses chemical structure to estimate toxicity of a chemical
substance  using class-specific QSARs. ECOSAR™ automatically determines all  of the classes
that a chemical substance may belong to and, therefore, may provide a number of different
ecotoxicity estimates for some or all of the species and durations estimated. Modeled results are
dependent on the functional groups present on the molecule as well as the diversity of chemicals
with experimental data that were used to build the models. The hazard profiles report every
estimated value returned from ECOSAR™. Narcosis classes (neutral organics) are only provided
for comparative purposes if class-specific QSARs are available; the latter will be used
preferentially. If multiple class-specific QSARs are available,  the hazard designation was based
on the most conservative ECOSAR™ estimate, unless expert judgment suggested that an
individual substance was better represented by a specific class based on analysis of the operative
mechanism of action.  However, if the chemical substance is not anticipated to lie within the
domain of the class-specific estimates provided by ECOSAR,  or to undergo the same mode of
action of the chemicals that appear in their training sets, then the narcosis (baseline toxicity)
associated with the neutral organic class will be used. Experimental log Kow values were used
preferentially as input into ECOSAR™. In their absence, estimated log Kowvalues from
        TA r ^      A             i-™ ,                              *"-'
EPISuite  were used. ECOSAR  is maintained and developed as a stand-alone program, but is
also accessible through the EPA EPISuite™ program after it is installed; therefore, the
Estimations Program Interface (EPI) program was cited for the ECOSAR™ values in this report.

The QSARs for ECOSAR™ were built using experimental  data for several chemical classes. For
a chemical class to be defined within ECOSAR™, sufficient acute experimental data were
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required to build a QSAR for all three species included in the model. The equations in ECOSAR
are derived from surrogate species offish, zooplankton, and phytoplankton. While these
surrogate species can comprise several genera as well as families, the equations are not intended
to be species-specific, but rather estimates of toxicity to the general trophic levels they represent
(fish, aquatic invertebrates, and aquatic plants). There were instances, however, where sufficient
experimental data are not available to build a chronic QSAR for some of the three surrogate
species. When ECOSAR™ did not provide chronic estimates, the acute value (experimental or
estimated) was divided by an acute to chronic ratio (ACR) to arrive at the ChV. ACRs of 10
were used for fish and daphnid and an ACR of 4 was used for algae (Mayo-Bean, Nabholz et al.
2011).

An estimate  of NES is the default value used for organics, oligomers, or non-ionic polymers with
a MW >1,000 daltons in the assignment of aquatic toxicity hazard. In EPA's New Chemical
program, aquatic toxicity is not predicted for chemicals with a MW >1,000 daltons as uptake has
been found to decrease exponentially with MWs >600 daltons (Nabholz, Clements et al. 1993)
due to a decrease in passive absorption through respiratory membranes (Mayo-Bean, Nabholz et
al. 2011). This methodology was also used in the evaluation of expandable graphite, a large,
insoluble material with a MW >1,000 daltons.

5.5.2   Bioaccumulation

Bioaccumulation is a process in which a chemical substance  is absorbed in an organism by all
routes of exposure as occurs in the natural environment, e.g., from dietary and ambient
environment sources. Bioaccumulation is the net result of the competing processes; this includes
uptake, metabolism and elimination of a chemical in an organism. Bioaccumulation can be
evaluated using the BAF, the steady state ratio of a chemical in an organism  relative to its
concentration in the ambient environment, where the organism is exposed through ingestion and
direct contact. Experimental BAFs have not been widely available in the scientific literature and,
as a result, experimental BCFs are more commonly used to evaluate the bioaccumulation hazard.
BCFs are defined as the ratio of the concentration of a chemical  in an organism to the
concentration of the chemical in the organism's surroundings; BCFs are typically measured for
fish (in water) using guideline studies.

Experimental BAF  or BCF values can be compared directly to the DfE criteria for this endpoint
to assign a hazard designation. The BCF/BAF designations range from <100 for a Low
designation to >5,000 for a Very High designation (see Section 5.1.2). If experimental values
were available for both of these endpoints, and the BCF and BAF were >100 (i.e., above the Low
designation), the largest factor was used to assign hazard designation. If experimental BCFs
<100 were available, the estimated upper trophic BAF from EPISuite™ was used preferentially
if its use resulted in a more conservative hazard designation and if the potential  for metabolism
was accurately accounted for within the model estimates.

In the absence of experimental data, evaluation of bioaccumulation potential can be done using
the log KOW and the log octanol/air partition coefficient Koa as estimated by EPISuite™.
However, analysis using Koa requires the use of metabolism data for higher trophic, air breathing
organisms, which can be difficult  to obtain from the scientific literature and cannot be readily
estimated. BAFs and BCFs from EPISuite™ were, therefore, typically used for the
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bioaccumulation hazard designation when experimental data were lacking. These values can be
compared directly to DfE criteria and the most conservative result was used for the hazard
designation. For chemicals that had estimated bioaccumulation data, available experimental
monitoring data were used to provide insight into the reliability of the model results. For
example, an estimated Low bioaccumulation potential may be increased to a Moderate
designation if a chemical was routinely identified in samples from higher trophic levels, or a
High designation if the chemical was routinely measured in animals at the top of the food chain.

An estimate of Low is the default value used for discrete organics with a MW >1,000 daltons in
the assignment of bioaccumulation hazard. This assignment is consistent with an analysis of the
chemicals used in the development of the bioconcentration and bioaccumulation estimation
programs in the EPISuite™ software (U.S. EPA 201 Ig). The training sets for these models
included 527 and 421 chemicals, respectively, with a MW range 68-992 daltons (959 daltons for
BAF). Given that BCF and BAF reach a maximum and then decrease with increasing log Kow, a
default value of Low is, in general, consistent with the limited bioavailability expected for
materials with a MW >1,000 daltons. DfE will use all available well-conducted studies when
evaluating bioaccumulation potential for materials with a MW >1,000, including environmental
biomonitoring data on higher trophic levels.

In general, for polymers and other materials with a MW >1,000 daltons, the default
bioaccumulation designation of Low was assigned, arising from their predicted limited
bioavailability (Boethling and Nabholz 1997). A more detailed analysis was performed for
compounds at  or near this bright line cutoff as well as for polymers with components where
residuals <1,000 had the potential to be present.

5.5.3   Environmental Persistence

A chemical's persistence in the environment is evaluated by determining the type and rate of
potential removal processes. These removal processes were generally divided into two
categories: chemical and biological. Of the chemical degradation processes, an evaluation of
environmental persistence includes the reaction of a chemical with water, also known as
hydrolysis, because water is ubiquitous in the environment.  Hydrolysis rate constants can be
obtained from  the literature or estimated, and the resulting half-lives can be compared directly to
DfE criteria. For commercial chemicals, hydrolysis tends to be a slower  environmental removal
process than biodegradation. Direct and indirect photolysis also represents other potential
chemical degradation processes that are considered in the alternative assessment, and they are
discussed later in this section.

Biodegradation, the most prevalent biological removal process, was divided into two types. The
first is primary biodegradation, in which a chemical substance is converted to another substance
through a single transformation. The second is ultimate biodegradation, in which a chemical is
completely degraded to CO2, water, and mineral oxides (such as phosphates for chemicals
containing phosphorus). DfE criteria utilize ultimate biodegradation preferentially for the
persistence hazard designation, although primary removal rates were informative in assigning
hazard designations particularly for materials that were transformed slowly, and to a lesser extent
for those that are transformed rapidly.
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If ultimate biodegradation data were not available, primary removal data were used in some
cases. For primary removal processes, the potential for the formation of degradation products
that are more persistent than the parent compounds must be considered in the hazard designation.
When present, the persistent degradation products should be evaluated for fate and toxicity. Half-
life data on the persistent degradation products, if available, were used to determine the
assignment for the persistence designation. In the absence of persistent degradation products,
primary biodegradation half-life data were compared directly to the DfE criteria to assign a
hazard designation.

Biodegradation processes can be classified as either aerobic or anaerobic. Aerobic
biodegradation is an oxidative process that occurs in the presence of oxygen. Anaerobic
biodegradation is a reductive process that occurs only in the absence of oxygen. Aerobic
biodegradation is typically assessed for soil and water, while anaerobic biodegradation is
generally assessed in sediment. For determining the persistence hazard, the importance of both
aerobic and anaerobic biodegradation as well as partitioning and transport in the environment
were considered  to determine what removal processes were most likely to occur. Anaerobic
degradation may use any of several electron acceptors depending on their availability in a given
environment and the prevailing redox potential (Eh). The biodegradative populations that are
dominant in a given environment vary with the conditions and so do their biodegradative
capabilities.

One aspect of the assessment is to  determine the potential for removal of a chemical substance,
and especially removal attributable to biodegradation within a sewage treatment plant and other
environments. In this assessment, the term "ready biodegradability" refers to a chemical's
potential to undergo ultimate degradation in guideline laboratory studies. A positive result in a
test for ready biodegradability can be considered as indicative of rapid and ultimate  degradation
in most environments including biological sewage treatment plants. Ready tests typically include
a 10-day window, beginning when the biodegradation parameter (e.g., disappearance of
dissolved organic carbon from test substance, or theoretical  oxygen demand) reaches 10%. The
10-day window must occur within the 28-day length of the test. If the pass level of the test (60%
for oxygen demand and CO2 production; 70% for dissolved organic carbon disappearance) is
met in the 10-day window, the chemical received a Very Low hazard designation. Those that did
not pass the 10-day window criterion but met the pass level  in 28 days received a Low hazard
designation. If ready biodegradability test data were available  but the chemical did not meet the
pass level, the chemical was evaluated based on measured data using the DfE half-life criteria
(Table 5-1). These half-life criteria were  also used to assign a hazard designation for non-
guideline ultimate biodegradation  studies reported in the scientific literature.

In the absence of a reported half-life, experimental data were also used to approximate half-life
as appropriate. For example, a chemical that undergoes <5% removal in 30 days would be
expected to have a half-life >60 days and would be assigned a High persistence concern.

When experimental data on the biodegradation of a chemical substance were not available, the
potential of that substance to undergo this removal process was assessed from the results of the
EPISuite™ models. These models fall into one of four classes: Rapid biodegradation models
based on linear and non-linear regressions that estimate the probability that a chemical substance
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will degrade fast; expert survey models that estimated the rate of ultimate and primary
biodegradation using semi-quantitative methods; probability of ready biodegradability in the
OECD 301C test; and probability of rapid biodegradation under methanogenic anaerobic
conditions. Each of these is discussed in the following paragraphs.

The first models (Biowin 5 and 6) used in the screening assessment estimated ready
biodegradability in the OECD 301C test and are also known as Japanese Ministry of
International Trade and Industry (MITI) models. These models provided the probability that a
material passes this standardized test. Those chemicals that were estimated to pass the ready
biodegradability test received a Low persistence designation. If a chemical was not estimated to
pass the MITI test, the results of the other EPISuite1  biodegradation models were used.

The rapid biodegradation potential models within EPISuite™ (Biowin 1 and  2) were useful for
determining if a chemical substance was expected to biodegrade quickly in the environment. If a
chemical was likely to biodegrade quickly, it was generally assigned a Low hazard designation
for persistence. The results of the estimates from these models may be used in concert with the
semi-quantitative output from a second set of models, which include ultimate and primary
biodegradation survey models (Biowin 3  and 4) for evaluating persistence. These models
provided a numeric result, ranging from 1 to 5, which relates to the amount of time required for
complete ultimate degradation (Biowin 3) and removal of the parent substance by primary
degradation  (Biowin 4) of the test compound. The numeric result from Biowin 3 was converted
to an estimated half-life for removal that can be compared directly to DfE criteria. If results from
different models (other than the MITI models) led to a different hazard designation, then the
ultimate biodegradation model results were used preferentially. If the transport properties
indicate the potential for the material to partition to sediment, an anoxic compartment, then the
results of the anaerobic probability model (Biowin 7) will also be evaluated.

Half-lives  for hydrolysis from experimental studies or EPISuite™ estimates were used in
preference to biodegradation data when they suggested that hydrolysis is a more rapid removal
process. Hydrolysis half-lives were compared directly to DfE criteria to assign the persistence
designation. Similar to primary biodegradation, breakdown products resulting from hydrolysis
were evaluated for fate and toxicity when they were expected to be more persistent than the
parent compound.

Photolysis may also be an important environmental removal process. In general, environmental
removal rates from photolysis do not compete with biodegradation or hydrolysis although there
are exceptions such as iodides. Photolysis may  be an important removal process for chemicals
that were not bioavailable because of their limited water solubility. Estimation methods  for
photolysis rates were not available using computerized SAR tools.  If experimental or suitable
analog data were available, the rate of photolysis was evaluated relative to other removal
processes.

When evaluating the environmental persistence designation, it should be noted that chemicals
with a High  or Very High designation can degrade over time, although this process may occur at
a very slow rate. As a result, a Very High designation may have been assigned if persistent
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degradates were expected to be produced, even at a very slow rate, in the absence of
experimental biodegradation data for the parent substance.

Chemicals that contain a metal were assigned a High persistence designation in the assessment,
as these inorganic moieties are recalcitrant. In this instance, an 'R' footnote was added to the
hazard summary table to indicate that the persistence potential was based on the presence of a
recalcitrant inorganic moiety. The assessment process also included the evaluation of the
potential chemical reactions of metal-containing and inorganic moieties to determine if they were
potentially transformed to more or less hazardous forms. However, no alternatives that contain
metals were evaluated in this updated assessment.

Polymers with a MW >1,000 generally received a Very High persistence designation due to their
lack of bioavailability.

5.6   Endocrine Activity

Chemicals included in DfE alternatives assessments were screened for potential endocrine
activity, consistent with the DfE Alternatives Assessment Criteria. Endocrine activity refers to a
change in endocrine homeostasis caused by a chemical or other stressor. An endocrine
disrupter is an external agent that interferes in some way with the role of natural hormones in
the body, in a manner causing adverse effects. Relevant data are summarized in the hazard
assessments for each chemical, located in Section 6. Data on endocrine activity were available
for twelve of the chemicals included in this report. For chemicals without available data on
endocrine activity, this was acknowledged with a "no data located" statement. When endocrine
activity data were available, the data are summarized as a narrative. A unique hazard designation
of Low, Moderate or High is not provided for this endpoint in Table 5-2, for reasons discussed
below.

The document Special Report  on Environmental Endocrine Disruption: An Effects Assessment
and Analysis describes EPA's  activities regarding the evaluation of endocrine disruption (U.S.
EPA 1997). This report was requested by the Science Policy Council and prepared by EPA's
Risk Assessment Forum. This report states that "Based on the current state of the science, the
Agency does not consider endocrine disruption to be an adverse endpoint per se, but rather to be
a mode or mechanism of action potentially leading to other outcomes, for example, carcinogenic,
reproductive or developmental effects, routinely considered in reaching regulatory decisions"
(U.S.  EPA 1997). The report also states that "Evidence of endocrine disruption alone can
influence priority  setting for further testing and the assessment of results of this testing could
lead to regulatory action if adverse effects are shown to occur" (U.S. EPA  1997).

The 1996 Food Quality Protection Act (FQPA) directed EPA to develop a  scientifically validated
screening program to determine whether certain substances may cause hormonal effects in
humans. In response, EPA established the Endocrine Disrupter Screening Program (EDSP) (U.S.
EPA 2012b). The EDSP is developing requirements for the screening and testing of thousands of
chemicals for their potential to affect the endocrine system. When complete, EPA will use these
screening and testing approaches to set priorities and conduct further testing when warranted.
The science related to measuring and demonstrating endocrine disruption is relatively new, and
validated testing methods at EPA are still being developed.
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The EDSP proposes a two-tiered approach that includes initial screening followed by more in-
depth testing when warranted (U.S. EPA 201 la). The Tier 1 screening battery is intended to
identify chemicals with the potential to interact with the estrogen, androgen, or thyroid hormone
systems through any of several recognized modes of action. Positive findings for Tier 1 tests
identify the potential for an interaction with endocrine systems, but do not fully characterize the
nature of possible effects in whole animals. Tier 2 testing is intended to  confirm, characterize,
and quantify the effects for chemicals that interact with estrogen, androgen, and thyroid hormone
systems. These test methods must undergo a four-stage validation process (protocol
development, optimization/prevalidation, validation, and peer-review) prior to regulatory
acceptance and implementation. Validation is ongoing for Tier 1 and Tier 2 methods7. Once
validated test methods have been established for screening and testing of potential endocrine
disrupters, guidance must be developed for interpretation of these test results using an overall
weight-of-evidence characterization.

To assess the data on endocrine activity, DfE applies the weight of evidence approach developed
by the EDSP (U.S. EPA 201 Ic). This process integrates and evaluates data, and always relies on
professional judgment (U.S. EPA 201 Ic). To evaluate endocrine activity with this weight of
evidence approach, DfE examined multiple lines of evidence (when available) and considered
the nature of the effects within and across studies, including number, type, and
severity/magnitude of effects, conditions under which effects occurred (e.g., dose, route,
duration), consistency, pattern, range, and interrelationships of effects observed within and
among studies, species, strains, and sexes, strengths and limitations of the in vitro and in vivo
information, and biological plausibility of the potential for an interaction with the endocrine,
androgen, or thyroid hormonal pathways.

Most test data for chemicals in this report consist of in vitro assays, but results of in vitro assays
alone were not generally expected to provide a sufficient basis to support a hazard designation
for endocrine disruption. EPA expects that in vivo evidence would typically be given greater
overall influence in the weight of evidence evaluation than in vitro findings because of the
inherent limitations of such assays. Although in vitro assays can provide insight into the mode of
action, they have limited ability to account for normal metabolic activation and clearance of the
compound, as well as  normal intact physiological conditions (e.g.,  the ability of an animal to
compensate for endocrine alterations).

As described in the DfE Alternatives  Assessment Criteria, endocrine activity was summarized in
a narrative, rather than by High, Moderate or Low hazard designation. The endocrine activity
summaries can be found in the hazard profiles. This is an appropriate approach because there is
no consensus on what constitutes high, moderate or low concern for this endpoint. The summary
of endocrine activity largely relies on representative studies and expert review summaries.
7 Information on the status of assay development and validation efforts for each assay in EPA's EDSP can be found
at: http://www.epa.gov/oscpmont/oscpendo/pubs/assavvalidation/status.htm
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       mattresses: a review." Fire Science Reviews 1(2).

NDRC. (2013). "Memo to CPSC regarding Upholstered Furniture Fire Safety Technology. July
       1, 2013." from http://www.regulations.gov/#!documentDetail:D=CPSC-2008-0005-0049.

NFPA (2013). "New Projects and Documents."

NY State Assembly. (2013). "Bill No. A06557." from
       http://assemblv.state.ny.us/leg/7default fld=&bn=A06557&term=2013&Summary=Y&A
       ctions=Y&Votes=Y&Memo=Y&Text=Y.

OEHHA. (2011). "Chemicals Known to the State to Cause Cancer or Reproductive Toxicity.
       October 28, 2011. "from
       http://oehha.ca.gov/prop65/prop65 list/files/P65singlel02811.pdf.

Patisaul, H. B., S. C. Roberts, et al.  (2012). "Accumulation and Endocrine Disrupting Effects of
       the Flame Retardant Mixture Firemaster® 550 in Rats: An Exploratory Assessment."
       Journal of Biochemical and Molecular Toxicology 27(2):  124-136.

PFA (1992). "Information on Flexible Polyurethane Foam: California Technical Bulletin 133
       (TB 133) and Furniture Fire Safety."  In Touch 2(2).

PINFA. (2012). "Product selector: Expandable graphite." from
       http://www.pinfa.org/component/chronocontact/? chronoformname=product_selector_det
       ails&product selector=98.

Stapleton, H. M. (July 2013). Personal Communication.
                                         6-3

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                             JUNE 2014 DRAFT REPORT
Stapleton, H. M., J. G. Allen, et al. (2008). "Alternate and New Brominated Flame Retardants
       Detected in U.S. House Dust." Environ Sci Technol 42: 6910-6916.

Stapleton, H. M., S. Eagle, et al. (2012). "Serum PBDEs in a North Carolina Toddler Cohort:
       Associations with Handwipes, House Dust, and Socioeconomic Variables." Environ.
       Health Perspect. 120(7): 1049-1054.

Stapleton, H. M., S. Klosterhaus, et al. (2011). "Identification of Flame Retardants in
       Polyurethane Foam Collected from Baby Products." Environ. Sci. Technol. 45(12): 5323-
       5331.

Stapleton, H. M., S. Sharma, et al. (2012). "Novel and High Volume Use Flame Retardants in
       US Couches Reflective of the 2005 PentaBDE Phase Out." Environ. Sci. Technol.
       46(24): 13432-13439.
                                                        ^
U.S. EPA. (1994). "Joint Project on the Evaluation of (Quantitative) Structure Activity
       Relationships."  Retrieved November 18, 2013, from
       http://www.epa. gov/oppt/newchems/pub s/ene4147. pdf

U.S. EPA. (1997). "Special Report on Environmental Endocrine Disruption: An Effects
       Assessment and Analysis."  Retrieved November 18, 2013, from
       http://www.epa.gov/raf/publications/pdfs/ENDOCRINE.PDF.

U.S. EPA. (1999). "High Production Volume (HPV) Challenge: Determining the Adequacy of
       Existing Data."  Retrieved November 18, 2013, from
       http://www.epa.gov/hpv/pubs/general/datadfm.htm.

U.S. EPA. (2005a). "Furniture Flame Retardancy Partnership: Environmental Profiles of
       Chemical Flame-Retardant Alternatives for Low-Density Polyurethane Foam (EPA 742-
       R-05-002A)."  Retrieved November 18, 2013, from
       http://www.epa. gov/dfe/pub s/flameret/ffr-alt. htm.

U.S. EPA. (2005b). "Pollution Prevention (P2) Framework."   Retrieved November 18, 2013,
       from http://www.epa.gov/opptintr/newchems/pubs/sustainable/p2frame-june05a2.pdf

U.S. EPA. (2009). "Polybrominated Diphenyl Ethers (PBDEs) Action Plan." from
       http://www.epa.gov/oppt/existingchemical s/pubs/actionplans/pbdes_ap_2009_1230_fmal
       .pdf

U.S. EPA. (2010a). "Chemical  Categories Report."  Retrieved April 17, 2012, from
       http://www.epa.gov/opptintr/newchems/pubs/chemcat.htm.

U.S. EPA (2010b). TSCANew Chemicals Program (NCP) Chemical Categories. Office of
       Pollution Prevention and Toxics. Washington, DC.

U.S. EPA. (201 la). "Assay Development."  Retrieved April 17, 2012, from
       http://www.epa.gov/oscpmont/oscpendo/pubs/assayvalidation/index.htm.
                                         6-4

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                              JUNE 2014 DRAFT REPORT
U.S. EPA. (201 Ib). "Design for the Environment Program Alternatives Assessment Criteria for
       Hazard Evaluation (version 2.0)."  Retrieved November 18, 2013, from
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       http://www.regulations. gov/#! documentDetail:D=EPA-HQ-OPPT-2010-0877-0021.

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       http://www.epa. gov/oppt/exposure/pub s/epi suite, htm.

U.S. EPA. (201 le). "Interpretive Assistance Document for Assessment of Discrete Organic
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       http://www.epa. gov/oppt/exposure/pub s/epi suite, htm.

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       http://www.epa.gov/oppt/exposure/pubs/episuite.htm.

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       http ://www. epa. gov/oppt/sf/tool s/methods .htm.

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       http://www.epa.gov/oppt/existingchemicals/pubs/workplans.html.

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       environmental occurrence, toxicity and analysis." Chemosphere 88(10): 1119-1153.
                                          6-5

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                              JUNE 2014 DRAFT REPORT
Wang, C.-Q., F.-Y. Ge, et al. (2013). "Effects of expandable graphite and dimethyl
      methylphosphonate on mechanical, thermal, and flame-retardant properties of flexible
      polyurethane foams." Journal of Applied Polymer Science 130(2): 916-926.

Wolska, A., M. Gozdzikiewicz, et al. (2012). "Influence of graphite and wood-based fillers on
      the flammability of flexible polyurethane foams." Journal of Materials Science 47(15):
      5693-5700.
                                          6-6

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                                                           JUNE 2014 DRAFT REPORT
        7   Hazard Evaluations

              Ammonium polyphosphate (APP)
                                                  Screening Level Toxicology Hazard Summary

This table only contains information regarding the inherent hazards of flame retardant chemicals. Evaluation of risk considers both the hazard and exposure associated with the
substance including combustion and degradation by-products. The caveats listed in the legend and footnote sections must be taken into account when interpreting the hazard
information in the table.
VL = Very Low hazard L = Low hazard   = Moderate hazard   = High hazard VH = Very High hazard - Endpoints in colored text (VL, L,   , H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].

d This hazard designation would be assigned MODERATE for a potential for lung overloading if >5% of the particles are in the respirable range as a result of dust forming
operations.










Chemical










CASRN
Human Health Effects


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                                                         JUNE 2014 DRAFT REPORT
                                       HO
                                                O

                                                P,
o
P—OH
OH
                                             NH4+
                                                   CASRN: 68333-79-9
                                                   MW: -100,000
                                                   MF: (NH4)k-H(n+2.k)PnO(3n+i) (NAS,
                                                   2000)
                                                                                                             Physical Forms:
                                                                                                             Neat: Solid
                                                   Use: Flame retardant
SMILES: This polymer inorganic salt with MW >1,000 and no low MW components is not amenable to SMILES notation.
Synonyms: Polyphosphoric acids, ammonium salts; Ammonium polyphosphate; Ammonium polyphosphates; Polymetaphosphoric acid, ammonium salt,
Polyphosphoric acid, ammonium salt APP; APP I; APP II
Trade names: AP 422, AP 462, APP (fireproofing agent), APP 422, Albaplas AP 95, Amgard CL, Amgard MC, Amgard TR Antiblaze MC, Antiblaze MCM, Budit
3076, Budit 3076DC, Budit 3077, Budit 365, DFP-I, EINECS 269- 789-9, Exolit 462, Exolit 263, Exolit 422, Exolit 442, Exolit 454, Exolit 455, Exolit 462, Exolit
470, Exolit AP 422, Exolit AP 423, Exolit AP 462, FR-Cros 480, FR-Cros 484,Fire-Trol LCG-R Flameguard PT 8, Hostaflam 423, Hostaflam AP 420, Hostaflam AP
422, Hostaflam AP 462, Hostaflam AP 464, Hostaflam TP-AP 751, Hostaflam TP-AP 752, Novawhite, Phos-Chek P 30, Phos-Chek P 40, Phos-Chek P 60, Poly-N
10-34-0, Poly-N 11-37-0, Sumisafe, Taien A, Taien H
Chemical Considerations: High-MW ammonium polyphosphate (n>50) with a minimum of water-soluble fractions are being used to an increasing extent in flame
retardants (Gard, 2005, Schrodter et al., 2005). These insoluble ammonium polyphosphates are long chain, ionic phosphate polymers with the following MF:
(NH4)k-H(n+2-k)PnO(3n+i), where n typically can range from 70 (Wanjie International Co., 2007) to >1,000 (PINFA, 2010) and k represents the degree of replacement of
hydrogen ions with ammonium ions. MWs can be as high as 100,000 g/mole and oligomers with a MW <1,000 are not expected. The high MW inorganic polymer
was assessed as a non-bioavailable material. Prior assessments for similar polyphosphates evaluated the lower, water soluble moieties, which also have application as
aflame retardant (Professional judgment; SinoHarvest, 2013).
Polymeric: Yes
Oligomeric: Not applicable
Metabolites, Degradates and Transformation Products: Ammonia; phosphate (Leisewitz et al., 2000)
Analog: None
Endpoint(s) using analog values: Not applicable
Analog Structure: Not applicable
Structural Alerts: Not applicable
Risk Phrases: This substance is not classified in the Annex 1 of Directive 67/548/EEC (ESIS, 2012).
Hazard and Risk Assessments: The Maine Department of Environmental Protection (MDEP) Safer Alternative Assessment for Decabromodiphenyl Ether Flame
Retardant in Plastic Pallets includes a GreenScreen Assessment of Ammonium Polyphosphate although these were performed on lower MW materials (MDEP, 2007).
                                                                      7-2

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JUNE 2014 DRAFT REPORT
Ammonium polyphosphate CASRN 68333-79-9
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
PHYSICAL/CHEMICAL PROPERTIES
Melting Point (°C)
Boiling Point (°C)
Vapor Pressure (mm Hg)
Water Solubility (mg/L)
Decomposes at > 275°C (Measured)
Decomposes at 300°C for long chain
ammonium polyphosphate (Measured)
Decomposes at approx. 150°C for short
chain ammonium polyphosphate
(Measured)
>275
decomposition with evolution of
ammonia and phosphoric acid
(Measured)
<10-8at25°C
(Estimated)
<0.75 at 20°C
reported as < 1 hPa (Measured)
\
0.5 % (w/w) at 25 °C in 10% suspension
(Measured)
0.05-0.5% max at 25 °C in 10%
suspension (Measured)
J
10,000 (Measured)
Reported as approximately 10 g/L at
25°CandatpH5.5
IUCLID, 2000
OECD-SIDS, 2007
OECD-SIDS, 2007
Clariant, 2011
Professional judgment;
Boethling and Nabholz, 1997
IUCLID, 2000; OECD-SIDS,
2007
Clariant, 2011
Wanjie International Co, 2007
IUCLID, 2000
Consistent with values reported in
other secondary sources.
Consistent with values reported in
other secondary sources.
Reported for the low MW
ammonium polyphosphate.
Reported in chemical datasheet,
consistent with the high melting
point expected for this chemical.
Cutoff value for large high MW
polymers.
Ammonium polyphosphate will have
negligible vapor pressure as an
inorganic salt. Any measurable
vapor pressure is due to
decomposition and the release of
ammonia gas.
Reported in chemical datasheet.
Inadequate. This value likely
represents a dispersion and is not an
indication of the material's true
water solubility.
This value is not consistent with the
other secondary sources; the value is
most likely for the low MW
ammonium polyphosphate.
         7-3

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JUNE 2014 DRAFT REPORT
Ammonium polyphosphate CASRN 68333-79-9
PROPERTY/ENDPOINT

Log Kow
Flammability (Flash Point)
Explosivity
Pyrolysis
pH
pKa
DATA
Reported as 100% at 25 °C; considered to
be miscible. (Measured)

Not flammable (Measured)
Not explosive (Measured)

5.5-7.5
At 25 °C in 10% suspension (Measured)

REFERENCE
OECD-SIDS, 2007
^^^
OECD-SIDS, 2007
OECD-SIDS, 2007

Clariant, 2011

DATA QUALITY
This value is not consistent with the
other secondary sources; it is likely
for the low MW ammonium
polyphosphate.
No data located; polymers with a
MW > 1,000 are outside the domain
of the available estimation methods.
Reported in chemical datasheet.
Reported in chemical datasheet.
No data located.
Measured by chemical supplier. Data
are likely for the formulated material
in water, and would be dependent on
the ammonium/polyphosphate ratios.
No data located.
HUMAN HEALTH EFFECTS
Toxicokinetics
Dermal Absorption in vitro
Absorption,
Distribution,
Metabolism &
Excretion
Oral, Dermal or Inhaled
Other
Absorption is not expected for any route of exposure. This inorganic polymer moiety is large with a MW
>1,000. Based on professional judgment, it is expected to have limited bioavailability and therefore is not
expected to be readily absorbed, distributed or metabolized in the body.

Gastrointestinal absorption of higher
polyphosphates following ingestion is
probably low; they are most likely
hydrolyzed by stomach acids to
phosphate and ammonium ions.
No absorption is expected for all routes
of exposure if insoluble in water.
(Estimated)

NAS, 2000
Professional judgment
No data located.
Limited study details reported in a
secondary source.
Estimated based on
physical/chemical properties and
limited bioavailability.
         7-4

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JUNE 2014 DRAFT REPORT
Ammonium polyphosphate CASRN 68333-79-9
PROPERTY/ENDPOINT
Acute Mammalian Toxicity
Acute Lethality
Oral
Dermal
Inhalation
DATA
REFERENCE
DATA QUALITY
LOW: This polymer is large, with a MW >1,000. It is expected to have limited bioavailability and therefore
is of low potential for acute mammalian toxicity. This low hazard designation is also supported by a rat
oral LD50 of >2,000 mg/kg, a rat dermal LD50 of >2,000 mg/kg, and a 4-hour rat LC50 of >5.09 mg/L.
Rat oral LD50 >2,000 mg/kg
Rat oral LD50 = 4,740 mg/kg
Rabbit oral LD50 >2,000 mg/kg
Rat dermal LD50 >5,000 mg/kg
^^ i^
Rat dermal LD50 >2,000 mg/kg
Rat Inhalation 4-hour LC50 >5.09 mg/L
(nose-only exposure, aerosol)
OECD-SIDS, 2007
IUCLID, 2000; Clariant, 2009
^^ '
OECD-SIDS, 2007
IUCLID, 2000; NAS, 2000;
OECD-SIDS, 2007
OECD-SIDS, 2007
NAS, 2000; OECD-SIDS, 2007
Limited study details reported in a
secondary source.
Although limited study details were
reported in a secondary source,
results indicated that LD50 values
were greater than the high dosages
tested; data for commercial mixture
Exolit 422 (purity not specified).
Although limited study details were
reported in a secondary source,
results indicated that LD50 values
were greater than the high dosages
tested.
Although limited study details were
reported in a secondary source,
results indicated that LD50 values
were greater than the high dosages
tested; data for commercial mixture
Exolit 456 (90% ammonium
polyphosphate and 10%
monoammonium phosphate).
Although limited study details were
reported in a secondary source,
results indicated that LD50 values
were greater than the high dosages
tested.
Although limited study details were
reported in a secondary source,
results indicate that LC50 values are
         7-5

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JUNE 2014 DRAFT REPORT
Ammonium polyphosphate CASRN 68333-79-9
PROPERTY/ENDPOINT


Carcinogenicity

OncoLogic Results
Carcinogenicity (Rat and
Mouse)
Combined Chronic
Toxicity/Carcinogenicity
Other
Genotoxicity

Gene Mutation in vitro
Gene Mutation in vivo
Chromosomal Aberrations in
vitro
DATA

REFERENCE

DATA QUALITY
greater than the highest
concentration tested; it is unspecified
if the inhaled substance is a
vapor/gas or dust/mist/fume.
LOW: This polymer is large, with a MW >1,000. It is expected to have few to no residual monomers.
Additionally, crosslinking, swellability, dispersability, reactive functional groups, inhalation potential, and
hindered amine groups are not expected. Therefore, there is low potential for Carcinogenicity based on
professional judgment. No data located.



Limited bioavailability expected;
crosslinking swellability, dispersability,
reactive functional groups, inhalation
potential, and hindered amine groups are
not expected.
(Estimated)



Professional judgment;
Boethling and Nabholz, 1997
No data located.
No data located.
No data located.
Based on cutoff value for large high
MW polymers.
LOW: This polymer is large, with a MW >1,000. It is expected to have limited bioavailability and therefore
has low potential for genotoxicity.
Limited bioavailability expected
(Estimated)
Negative, Ames assay, Salmonella
Typhimurium TA98. TA100, TA1535,
TA1537, TA1538, and E. coli WP2uvrA;
with and without metabolic activation


Professional judgment;
Boethling and Nabholz, 1997
IUCLID, 2000; NAS, 2000


Based on cutoff value for large high
MW polymers.
Reported in a secondary source,
study details and test conditions
were not provided.
No data located.
No data located.
         7-6

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JUNE 2014 DRAFT REPORT
Ammonium polyphosphate CASRN 68333-79-9
PROPERTY/ENDPOINT

Chromosomal Aberrations in
vivo
DNA Damage and Repair
Other
Reproductive Effects

Reproduction/Developmental
Toxicity Screen
Combined Repeated Dose
with Reproduction/
Developmental Toxicity
Screen
Reproduction and Fertility
Effects
Other
Developmental Effects

Reproduction/
Developmental Toxicity
Screen
Combined Repeated Dose
with Reproduction/
Developmental Toxicity
Screen ^B
Prenatal Development
Postnatal Development
Prenatal and Postnatal
Development
DATA



REFERENCE



DATA QUALITY
No data located.
No data located.
No data located.
LOW: This polymer is large, with a MW >1,000. It is expected to have limited bioavailability and therefore
has low potential for reproductive effects based on professional judgment and the polymer assessment
literature. No data located.



Limited bioavailability expected



Professional judgment;
Boethling and Nabholz, 1997
No data located.
No data located.
No data located.
Based on cutoff value for large high
MW polymers.
LOW: This polymer is large, with a MW >1,000. It is expected to have limited bioavailability and therefore
has low potential for developmental effects based on professional judgment and polymer assessment
literature. No data located.
^+









No data located.
No data located.
No data located.
No data located.
No data located.
         7-7

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JUNE 2014 DRAFT REPORT
Ammonium polyphosphate CASRN 68333-79-9
PROPERTY/ENDPOINT

Developmental Neurotoxicity
Other
Neurotoxicity

Neurotoxicity Screening
Battery (Adult)
Other
Repeated Dose Effects


Skin Sensitization

Skin Sensitization
Respiratory Sensitization
(Respiratory Sensitization ^|
DATA

Limited bioavailability expected
REFERENCE

Professional judgment;
Boethling and Nabholz, 1997
DATA QUALITY
No data located.
Based on cutoff value for large high
MW polymers.
LOW: This polymer is large, with a MW >1,000. It is expected to have limited bioavailability and therefore
has low potential for neurotoxicity based on professional judgment and the polymer assessment literature.
No data located.

Limited bioavailability expected
(Estimated)

Professional judgment;
Boethling and Nabholz, 1997
No data located.
Based on cutoff value for large high
MW polymers.
LOW: This polymer is large, with a MW >1,000. It is expected to have limited bioavailability; however,
because the MWn is >10,000, there is the possibility of lung overloading if >5% of the particles are in the
respirable range as a result of dust forming operations. No experimental data located.
Limited bioavailability expected
(Estimated) ^r^^
This polymer MWn is > 10,000; There is
uncertain potential for lung effects from
lung overload if respirable particles are
inhaled; Polymers with a MW > 10,000
have the potential for irreversible lung
damage as a result of lung overloading.
(Estimated)
Professional judgment;
Boethling and Nabholz, 1997
Professional judgment;
Boethling and Nabholz, 1997
Based on cutoff value for large high
MW polymers.
Based on cutoff value for large high
MW polymers.
LOW: Not a skin sensitizer in guinea pigs.
Not a skin sensitizer, guinea pigs
SafePharm Labs, 1993; NAS,
2000
Reported in chemical data sheet;
adequate study details provided.
No data located.

[No data located.
         7-8

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JUNE 2014 DRAFT REPORT
Ammonium polyphosphate CASRN 68333-79-9
PROPERTY/ENDPOINT
Eye Irritation

Eye Irritation
Dermal Irritation

Dermal Irritation
DATA
REFERENCE
DATA QUALITY
VERY LOW: Mixtures containing primarily ammonium polyphosphate were not irritating to rabbit eyes.
Not irritating, rabbits
Not irritating, rabbits
OECD-SIDS, 2007
^^^
IUCLID, 2000
^^^
Reported in secondary source; study
details and test conditions were not
provided; data for commercial
mixture (70% ammonium
polyphosphate and 30%
monoammonium phosphate).
Reported in a secondary source;
study details and test conditions
were not provided; data for
commercial mixture Exolit 456
(90% ammonium polyphosphate and
10% monoammonium phosphate).
Study in accordance with OECD 405
guideline.
LOW: Mixtures containing primarily ammonium polyphosphate were not irritating to slightly irritating to
skin.
Not irritating, rabbits 4-hour occlusion
^^ fr
Slightly irritating, rabbits; 24-hour
occlusive patch test
Not irritating
OECD-SIDS, 2007
IUCLID, 2000
IUCLID, 2000
Reported in a secondary source;
study details and test conditions
were not provided; data for
commercial mixture (70%
ammonium polyphosphate and 30%
monoammonium phosphate).
Reported in a secondary source;
study details and test conditions
were not provided; data for
commercial mixture Exolit 422
(purity not specified).
Reported in a secondary source;
study details and test conditions
were not provided; data for
commercial mixture Exolit 456
         7-9

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JUNE 2014 DRAFT REPORT
Ammonium polyphosphate CASRN 68333-79-9
PROPERTY/ENDPOINT


Endocrine Activity

Immunotoxicity

Immune System Effects
DATA

Not irritating, rabbits. Very slight
erythema in 2/3 animals 1 -hour after
exposure to AMGARD LR4; however,
no skin reaction was observed after 24
and 72 hours.
Not irritating, rabbits exposed 5 times
(23 hours for each exposure) to fabric
treated with LR2
Not irritating, human volunteers.
*^^ \
REFERENCE

NAS, 2000
^^^
NAS, 2000
NAS, 2000
DATA QUALITY
(90% ammonium polyphosphate and
10% monoammonium phosphate).
Study in accordance with OECD 404
guideline.
Limited study details reported in a
secondary source. Study was
conducted using AMGARD LR2
(liquid containing test substance,
urea and water) and AMGARD L4
(powder).
Limited study details reported in a
secondary source. Study was
conducted using AMGARD LR2
(liquid containing test substance,
urea and water).
Limited study details reported in a
secondary source. Study was
conducted using AMGARD LR2
(liquid containing test substance,
urea and water).
This polymer is large, with a MW >1,000. It is not expected to have endocrine activity due to its poor
bioavailability and inability to be readily metabolized in the body based on professional judgment.
Limited bioavailability expected
Professional judgment;
Boethling and Nabholz, 1997
Based on cutoff value for large high
MW polymers.
This polymer is large, with a MW >1,000. It is expected to have limited bioavailability and therefore has
low potential for immunotoxicity based on professional judgment and the polymer assessment literature.
No data located.
Limited bioavailability expected
Professional judgment;
Boethling and Nabholz, 1997
Based on cutoff value for large high
MW polymers.
         7-10

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JUNE 2014 DRAFT REPORT
Ammonium polyphosphate CASRN 68333-79-9
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
ECOTOXICITY
ECOSAR Class
Acute Aquatic Toxicity
Fish LC50
Not applicable
LOW: Water insoluble polymers with a MW >1,000 that do not contain reactive functional groups and are
comprised of minimal low MW oligomers are estimated to have no effects at saturation (NES). These
polymers have NES because the amount dissolved in water is not anticipated to reach a concentration at
which adverse effects may be expressed. Based on professional judgment, guidance for the assessment of
aquatic toxicity hazard leads to a low concern for those materials that display NES. Experimental data are
also consistent with this hazard designation.
NES
(Estimated)
Oncorhynchus mykiss 96-hour LC50 >101
mg/L
(Experimental)
Danio rerio 96-hour LC50 = 100 - 1,000
mg/L
(Experimental)
Brachydanio rerio 96-hour LC50 >500
mg/L
(Experimental)
Freshwater fish (Oncorhynchus mykiss)
96-hour LC50 = 123,000 - 1,326,000
(jg/L (123 -1326 mg/L)
(Experimental)
Freshwater fish (Oncorhynchus
tshawytschd) 96-hour LC50 = 685-1 195
mg/L
(Experimental)
Professional judgment
IUCLID, 2000; OECD-SIDS,
2007
Clariant, 2009
IUCLID, 2000
EPA, 2013
Buhl and Hamilton, 1998
The large MW, limited
bioavailability and low water
solubility suggest there will be NES.
Inadequate; limited study details
reported in a secondary source and
value is much greater than the
anticipated water solubility.
Inadequate; limited study details
reported in a secondary source and
value is much greater than the
anticipated water solubility.
Guideline study red in a secondary
source with limited study details;
OECD 203. Test substance: Exolit
456 (90% ammonium polyphosphate
and 10% of ammonium phosphate).
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source. Study conducted
with Fire-Trol LCG-R (composed
primarily of liquid ammonium
         7-11

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JUNE 2014 DRAFT REPORT
Ammonium polyphosphate CASRN 68333-79-9
PROPERTY/ENDPOINT

Daphnid LC50
DATA

Freshwater fish (Oncorhynchus mykiss)
LC50 = 872-> 1 0,000 mg/L
(Experimental)
Freshwater fish (Oncorhynchus mykiss)
96-hour LC50 = 1,006,000 - 10,000,000
(jg/L( 1,006 -10,000 mg/L
(Experimental)
Freshwater fish (Pimephales promelas)
96-hour LC50 = 5 19,000 - 2,3 17,000
(jg/L(519-1080mg/L)
(Experimental)
Hyalella azteca 96-hour LC50 = 73 mg/L
(Experimental)
Daphnia magna 48-hour EC50 = 90,890
(jg/L (90.89 mg/L)
(Experimental)
Daphnia magna 48-hour EC50 = 848,000
- 1,036,000 (jg/L (848 - 1,036 mg/L)
(Experimental)
Daphnia magna 24-hour EC50 =
1,007,000 (jg/L (1,007 mg/L)
Range = 780,000 - 1,300,000 ng/L
(780 -1,300 mg/L)
REFERENCE

Gaikowski et al., 1996
^^^
EPA, 2013
EPA, 2013
McDonald et al., 1997
EPA, 2013
EPA, 2013
EPA, 2013
DATA QUALITY
polyphosphate with attapulgite clay,
a corrosion inhibitor and iron oxide).
Limited study details reported in a
secondary source. Study conducted
with Fire-Trol LCG-R (composed
primarily of liquid ammonium
polyphosphate with attapulgite clay,
a corrosion inhibitor and iron oxide).
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source. Study conducted
with Fire-Trol LCG-R (composed
primarily of liquid ammonium
polyphosphate with attapulgite clay,
a corrosion inhibitor and iron oxide).
Limited study details provided in a
secondary source.
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source.
         7-12

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JUNE 2014 DRAFT REPORT
Ammonium polyphosphate CASRN 68333-79-9
PROPERTY/ENDPOINT

Green Algae EC50
Chronic Aquatic Toxicity
Fish ChV
Daphnid ChV
Green Algae ChV
DATA
(Experimental)
NES
(Estimated)
NES
(Estimated)
REFERENCE

Professional judgment
Professional judgment
DATA QUALITY

The large MW, limited
bioavailability and low water
solubility suggest there will be NES.
The large MW, limited
bioavailability and low water
solubility suggest there will be NES.
LOW: Water insoluble polymers with a MW >1,000 that do not contain reactive functional groups and are
comprised of minimal low MW oligomers are estimated to have NES. These polymers have NES because
the amount dissolved in water is not anticipated to reach a concentration at which adverse effects may be
expressed. Based on professional judgment, guidance for the assessment of aquatic toxicity hazard leads to
a low potential for those materials that display NES.
NES
(Estimated)
NES
(Estimated)
NES
(Estimated)
Professional judgment
Professional judgment
Professional judgment
The large MW, limited
bioavailability and low water
solubility suggest there will be NES.
The large MW, limited
bioavailability and low water
solubility suggest there will be NES.
The large MW, limited
bioavailability and low water
solubility suggest there will be NES.
ENVIRONMENTAL FATE
Transport
Henry's Law Constant (atm-
m3/mole)
Sediment/Soil
Adsorption/Desorption - Koc
The estimated negligible water solubility and estimated negligible vapor pressure indicate that this ionic
polymer is anticipated to partition predominantly to soil and sediment. The estimated Henry's Law
Constant of <10~8 atm-m3/mole indicates that it is not expected to volatilize from water to the atmosphere.
The estimated Koc of >30,000 indicates that it is not anticipated to migrate from soil into groundwater and
also has the potential to adsorb to sediment.
<10"8 (Estimated)
>30,000 (Estimated)
Professional judgment;
Boethling and Nabholz, 1997
Professional judgment;
Boethling and Nabholz, 1997
Cutoff value for large high MW
polymers.
High MW polymers are expected to
adsorb strongly to soil and sediment.
         7-13

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JUNE 2014 DRAFT REPORT
Ammonium polyphosphate CASRN 68333-79-9
PROPERTY/ENDPOINT

Level III Fugacity Model
Persistence
Water
Soil
Aerobic Biodegradation
Volatilization Half-life for
Model River
Volatilization Half-life for
Model Lake
Aerobic Biodegradation
DATA

REFERENCE

DATA QUALITY
This substance is not amenable to
the model.
VERY HIGH: This polymer is large, with a MW >1,000. It is expected to have negligible water solubility
and poor bioavailability to microorganisms indicating that biodegradation is not expected to be an
important removal process in the environment. Hydrolysis is expected for ammonium polyphosphates,
mainly via end-clipping of a monophosphate unit to form monoammonium phosphate. Hydrolysis rates
increase with increasing chain lengths, but reach a limit when n>50. Qualitative statements from
manufacturers indicate hydrolysis is slow, but increases with prolonged exposure to water and elevated
temperatures. Therefore, hydrolysis is not expected to occur at a rate that would greatly reduce the
polymeric chain. Furthermore, long-chain ammonium polyphosphates produced for flame retardant
applications may be formulated with melamine or other stabilizers that impede hydrolysis. Evaluation of
these values suggest that APP polymer size will be reduced by primary degradation but ultimate
degradation of the HMW polymer is >180 days.
Recalcitrant (Estimated)
>1 year (Estimated)
>1 year (Estimated)
The half-life values ranged from 5.2-8.7
days in soil under aerobic conditions for
liquid ammonium polyphosphate. Liquid
ammonium polyphosphate hydrolyzed
faster than solid ammonium
polyphosphate and anaerobic conditions,
caused by subsequent flooding,
accelerated hydrolysis. (Measured)
Ammonium polyphosphate breaks down
to ammonia and phosphate rapidly in soil
and sewage sludge. (Measured)
Professional judgment;
Boethling and Nabholz, 1997
Professional judgment
Professional judgment
OECD-SIDS, 2007
Leisewitz et al, 2000
Cutoff value for large high MW
polymers.
Based on the magnitude of the
estimated Henry's Law Constant.
Based on the magnitude of the
estimated Henry's Law Constant.
Not applicable; this non-guideline
study is for the low MW, liquid form
of ammonium polyphosphate.
Not applicable; biodegradation data
is expected for the more soluble low
MW ammonium polyphosphate.
Reported in a secondary source.
         7-14

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JUNE 2014 DRAFT REPORT
Ammonium polyphosphate CASRN 68333-79-9
PROPERTY/ENDPOINT

Air
Reactivity
Anaerobic Biodegradation
Soil Biodegradation with
Product Identification
Sediment/Water
Biodegradation
Atmospheric Half-life
Photolysis
Hydrolysis
DATA
Recalcitrant
Study results: 50%/1.6 days
Test method: Field Test
The half-life values ranged from 1.6-2.0
days in soil under anaerobic soil
conditions for liquid ammonium
polyphosphate. Liquid ammonium
polyphosphate hydrolyzed faster than
solid ammonium polyphosphate and
anaerobic conditions, caused by flooding,
accelerated hydrolysis. (Measured)


Not a significant fate process (Estimated)
Not a significant fate process (Estimated)
7
Not a significant fate process (Estimated)
REFERENCE
Professional judgment
OECD-SIDS, 2007
^^


Professional judgment
Professional judgment; Mill,
2010
Professional judgment; Gard,
2005; Wanjie International Co,
2007; PINFA, 2010; EFRA,
2011
DATA QUALITY
The substance has a MW >1,000 and
is not anticipated to be assimilated
by microbial populations; therefore,
biodegradation is not expected.
Not applicable; this nonguideline
study is for the liquid form of
ammonium polyphosphate.
No data located.
No data located.
This substance is expected to exist
entirely in particulate form in air and
is not anticipated to undergo gas-
phase chemical reactions.
The substance does not contain
functional groups that would be
expected to absorb light at
environmentally significant
wavelengths.
Hydrolysis is expected, mainly via
end-clipping of a monophosphate
unit to form monoammonium
phosphate. Qualitative statements
from manufacturers indicate
         7-15

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JUNE 2014 DRAFT REPORT
Ammonium polyphosphate CASRN 68333-79-9
PROPERTY/ENDPOINT


Environmental Half-life
Bioaccumulation

Fish BCF
Other BCF
DATA

Chemical hydrolysis of polyphosphates
proceeds slowly in sterile, neutral
solutions at room temperature.
Solubility is pH dependent: at pH > 7 the
substance will completely hydrolyze to
HPO42" and at pH 4-7 the substance will
completely hydrolyze to H2PO4".
(Measured)
> 180 days (Estimated)
-VI V
^^ fr
LOW: This ionic polymer is large, with
poor bioavailability indicating that it wi
judgment.
<100 (Estimated)

REFERENCE

OECD-SIDS, 2007
^^
Professional judgment
DATA QUALITY
hydrolysis is slow, but increases
with prolonged exposure to water
and elevated temperatures.
Hydrolysis is not expected to occur
at a rate that would greatly reduce
the polymeric chain to a MW < 1,000
g/mole.
Consistent with values reported in
other secondary sources.
The substance has a MW >1,000 and
is not anticipated to be assimilated
by microorganisms. Therefore,
biodegradation is not expected to be
an important removal process. It is
also not expected to be removed by
other degradative processes under
environmental conditions because of
limited water solubility and limited
partitioning to air.
a MW >1,000. It is expected to have negligible water solubility and
11 have low potential for bioaccumulation based on professional
Professional judgment

The substance has a MW >1,000 and
is not anticipated to be assimilated
by aquatic organisms; therefore,
bioconcentration is not expected.
No data located.
         7-16

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                                                    JUNE 2014 DRAFT REPORT
                                              Ammonium polyphosphate CASRN 68333-79-9
          PROPERTY/ENDPOINT
              DATA
REFERENCE
DATA QUALITY
                BAF
                                                            No data located.
                Metabolism in Fish
                                                            No data located.
                                      ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring
No data located.
Ecological Biomonitoring
No data located.
Human Biomonitoring
This chemical was not included in the NHANES biomonitoring report (CDC, 2013).
                                                                7-17

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                                                  JUNE 2014 DRAFT REPORT


Boethling RS, Nabholz, JV (1997) Environmental assessment of polymers under the U.S. Toxic Substances Control Act. In: Hamilton, JD,
Sutcliffe R, eds. Ecological assessment of polymers strategies for product stewardship and regulatory programs. Van Nostrand Reinhold, 187-234.

Buhl KJ, Hamilton SJ (1998) Acute toxicity of fire-retardant and foam-suppressant chemicals to early life stages of Chinook salmon
(Oncorhynchus Tshawytschd). Environ Toxicol Chem 17(8): 1589-1599.

CDC (2013) Fourth national report on human exposure to environmental chemicals, updated tables, March 2013. Centers for Disease Control and
Prevention, http://www.cdc.gov/exposurereport/pdf/FourthReport_UpdatedTables_Mar2013.pdf. Accessed May 10, 2013.

Clariant (2009) Exolit AP 422 safety data sheet. ec.europa.eu/environment/waste/stakeholders/individual_bus/clariant/att_4a.pdf

Clariant (2011) Product data sheet- flame retardants Exolit AP 422 ammonium polyphosphate.
http://www.additives.clariant.com/bu/additives/PDS_Additives.nsf/www/DS-OSTS-7SHDAQ?open.

EFRA (2011) Flame retardant fact sheet. Ammonium polyphosphate (APP). European Flame Retardants Association. http://www.cefic-
efra. com/image s/storie s/factsheet/6 APPFactSheetAB -1  00 .pdf.

EPA (2013) ECOTOX database, http ://cfpub. epa. gov/ecotox/quick  query .htm.

ESIS (2012) European chemical Substances Information System. European Commission, http://esis.jrc.ec.europa.eu/.

Gaikowski MP, Hamilton SJ, Buhl KJ, et al. (1996) Acute toxicity of three fire-retardant and two fire-suppressant foam formulations to the early
life stages of rainbow trout (Oncorhynchus Mykiss). Environ Toxicol Chem 15(8):1365-1374.

Gard DR (2005) Phosphoric acids and phosphates. Kirk-Othmer encyclopedia of chemical technology. Wiley-Interscience.
http://onlinelibrarv.wilev.com/book/10.1002/0471238961.

IUCLID (2000) Phosphoric acids, ammonium salts. IUCLID data set. European Commission, European Chemicals Bureau.

Leisewitz A, Kruse H,  Schramm E (2000) Substituting  environmentally relevant flame retardants: Assessment fundamentals Volume 1: Results
and summary overview. Berlin: Federal Environmental Agency.

MDEP (2007) Decabromodiphenyl ether flame retardant in plastic pallets. A safer alternatives assessment. Appendices. Maine Department of
Environmental Protection. Prepared by Pure Strategies, Inc.,  Gloucester, MA.
                                                              7-18

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                                                 JUNE 2014 DRAFT REPORT


McDonald SF, Hamilton SJ, Buhl KJ, et al. (1997) Acute toxicity of fire-retardant and foam-suppressant chemicals to Hyalella Azteca (Saussure).
Environ Toxicol Chem 16(7): 1370-1376.

Mill T (2000) Photoreactions in surface waters. In: Boethling R Mackay D, eds. Handbook of property estimation methods for chemicals,
environmental health sciences. Boca Raton: Lewis Publishers, 355-381.

NAS (2000) Toxicological risks of selected flame-retardant chemicals. National Academy of Sciences. Washington, DC: The National Academies
Press, http://www.nap.edu/catalog.php?record_id=9841.

OECD-SIDS (2007) SIDS dossier. CAS No. 68333-79-9. Ammonium polyphosphate. Organisation for Economic Co-operation and Development.
http://webnet.oecd.org/Hpv/UFSIDS Details.aspx?id=7AA7AAF3-3CDE-4F63-8A36-DAA7E786855F.
                                                                          ^^^\           r
PFNFA (2010) Human health and environmental fact sheet ammonium polyphosphate. Phosphorus, Inorganic & Nitrogen Flame Retardants
Association, www.pinfa.eu/uploads/Documents/Exolit_AP.pdf.

SafePharm Laboratories (1993) Acute toxicity to rainbow trout (Amgard TDCP). Derby, England: SafePharm Laboratories.

Schrodter K, Betterman G, Staffel T, et al. (2005) Phosphoric acid and phosphates. Ullmann's encyclopedia of industrial chemistry.
http://onlinelibrarv.wilev.com/book/10.1002/14356007. July 15, 2005.

SinoHarvest (2013) Ammonium polyphosphate. http://www.sinoharvest.com/products/Ammonium-polyphosphate.html.

Wanjie International Co (2007) Product fact sheet for ammonium polyphosphate.
http://www.wuzhouchem.com/cataloged/indu/ammonium_polyphosphate.htm. February 16,2011.
                                                             7-19

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                                                          JUNE 2014 DRAFT REPORT
              Benzole acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester (TBB)
                                                  Screening Level Toxicology Hazard Summary

This table only contains information regarding the inherent hazards of flame retardant chemicals. Evaluation of risk considers both the hazard and exposure associated with the
substance including combustion and degradation by-products. The caveats listed in the legend and footnote sections must be taken into account when interpreting the hazard
information in the table.	^B	
VL = Very Low hazard L = Low hazard   = Moderate hazard H = High hazard VH = Very  High hazard - Endpoints in colored text (VL, L,  , H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].
             Chemical
  CASRN
                                                                          Human Health Effects
y
Tox
Acu
y
Carcinogen
ox
Ge
duc
Re
Developmen
ogica
Neu
Repeated Do
Skin Sensitization
ry
io
Respirato
Sensitization
on
Eye
                                                                                                                  _o
                                                                                                                  -*^
                                                                                                                  sS
                                                        0)
                                                       p
                                                                                   Aquatic
                                                                                  Toxicity*
                                                                                                                         u
Chronic
                                                                         Environmental
                                                                              Fate
ence
Per
Bioaccumulation
Benzoic acid, 2,3,4,5-tetrabromo-, 2-
ethylhexyl ester (TBB)
183658-27-7
M
M
M
M
M
M
H
H
**Aquatic toxicity: EPA/DfE criteria are based in large part upon water column exposures which may not be adequate for poorly soluble substances such as many
flame retardants that may partition to sediment and particulates.
                                                                       7-20

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JUNE 2014 DRAFT REPORT
Br
Br 0
SMILES : O=C(c 1 c(Br)c(Br)c(Br)c(Br)c 1 )OCC(CCCC)CC
CASRN: 183658-27-7
MW: 549.9
MF: C15H18Br4O2
Physical Forms: Liquid
Neat: Liquid
Use: Flame retardant

Synonyms: Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester; TBB; EH-TBB. Related trade names: this chemical is one of the components of the commercial
products BZ-54, CN-2065 and Firemaster 550 (FM550).
Chemical Considerations: This is a discrete organic chemical with a MW below 1,000. EPI v4. 1 1 was used to estimate physical/chemical and environmental fate
values where adequate experimental data were lacking.
Polymeric: No
Oligomeric: Not applicable
Metabolites, Degradates and Transformation Products: 2,3,4,5-tetrabromobenzoic acid (TBBA CASRN 27581-13-1) (and the corresponding 2-ethylhexanol 104-
76-7) by metabolism and hydrolysis (Estimated); 2,3,4,5-tetrabromomethylbenzoate by metabolism di- and tri-brominated analogs by anaerobic biodegradation
(Estimated) and photodegradation (Davis and Stapleton, 2009; Bearr et al., 2012; Roberts et al., 2012; Patisaul et al., 2013).
Analog: Confidential analogs Analog Structure: Not applicable
Endpoint(s) using analog values: Reproductive, developmental,
repeated dose effects, carcinogenicity, eye irritation and dermal
irritation
Structural Alerts: Polyhalogenated aromatic hydrocarbons, immunotoxicity (EPA, 2012).
Risk Phrases: Not classified by Annex VI Regulation (EC) No 1272/2008 (ESIS, 2012).
Hazard and Risk Assessments: None identified.
         7-21

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JUNE 2014 DRAFT REPORT
Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
PHYSICAL/CHEMICAL PROPERTIES
Melting Point (°C)
Boiling Point (°C)
Vapor Pressure (mm Hg)
Water Solubility (mg/L)
Log Kow
Flamm ability (Flash Point)
Explosivity
Pyrolysis
pH
pKa

>300
(Estimated)
<10-8at25°C
(Estimated)
0.000011 (Estimated)
8.8
(Estimated) k
Flash Point: 2 15°C
Performed according to EEC Methods,
Directive 92/69/EEC (OJ No. L383A,
29. 12.92), Part A, Method A9, flash
point (Measured)
Not expected to form explosive mixtures
with air (Estimated)

Not applicable (Estimated)
J
Not applicable (Estimated)

EPIv4.11;EPA, 1999
EPIv4.11;EPA, 1999
EPIv4.11;EPA, 1999
EPIv4.11
Chemtura, 2013
Professional judgment

Professional judgment
Professional judgment
No data located.
Cutoff value for high boiling point
compounds according to HPV
assessment guidance.
Cutoff value for nonvolatile
compounds according to HPV
assessment guidance.
Estimated value is less than the cutoff
value, <0.001 mg/L, for non-soluble
compounds according to HPV
assessment guidance.

Adequate guideline study.
No experimental data located; based
on its use as a flame retardant.
No data located.
Does not contain functional groups
that are expected to ionize under
environmental conditions.
Does not contain functional groups
that are expected to ionize under
environmental conditions.
         7-22

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                                                        JUNE 2014 DRAFT REPORT
                                     Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
           PROPERTY/ENDPOINT
                                           DATA
                                          REFERENCE
                                  DATA QUALITY
                                                        HUMAN HEALTH EFFECTS
Toxicokinetics
                             TBB is estimated to have poor absorption by all routes of exposure based on analogy to a structurally
                             similar confidential analog; however, experimental data for Firemaster 550 (a mixture made up of a sum
                             total of TBB and TBPH of 50%) indicate that absorption of TBB can occur in rats following oral
                             exposure from gestation through lactation. TBB was detected in tissues of exposed dams and the pups
                             following exposure to FM550. The primary metabolite of TBB (TBBA) was also detected in dam livers.
                             TBB from a BZ-54 (TBB and TBPH mixture) was shown to be metabolized by hepatic subcellular
                             fractions in fathead minnow, carp, and mouse. The final metabolite is tetrabromobenzoic acid TBBA
                             (27581-13-1). This was confirmed in vitro using liver and intestinal subcellular fraction. In all
                             experiments, TBB was consistently metabolized to TBBA via cleavage of the 2-ethylhexyl chain without
                             requiring added cofactors. No phase II metabolites of TBBA were detected. The metabolism of TBB in
                             humans has not been evaluated.
Dermal Absorption in vitro
                                                                                           No data located.
Absorption,
Distribution,
Metabolism &
Excretion
Oral, Dermal or Inhaled
Pregnant rats were administered 0, 0.1 or
1 mg/kg-day of FM550 in the diet across
gestation and through lactation
(Gestation day (GD) 8 - PND 21)
FM550 components including TBPH
was detected in adipose, liver, and
muscle tissues in Dams at PND 21 with
the highest concentration in the adipose
tissue (768 ng/g w.w. in high dose, 29.6
ng/g w.w. in low dose, <  7.0 ng/g w.w.
in controls). The primary metabolite of
TBB (TBBA) was also detected in liver
tissue of dams on PND 21.
TBB was detected in pooled PND21 pup
adipose tissue. TBB was not detected in
pooled pup adipose tissue by PND220.
Patisauletal., 2013
Non guideline study indicates that
absorption of this compound can
occur in rats through oral exposure;
the test substance identified as
FM550 is a mixture made up of
TBB, TBPH (sum total of TBB
and TBPH is approximately 50%),
TPP and IPTPP; it is unclear if
absorption in pups occurred due to
gestational exposure or through
lactation.
                                                                    7-23

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                                              JUNE 2014 DRAFT REPORT
                           Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT
               DATA
       REFERENCE
        DATA QUALITY
      Other
In vitro metabolism experiments with
liver and intestinal subcellular fractions
following exposure to TBB. TBB was
rapidly metabolized to 2,3,4,5-
tetrabromobenzoic acid (TBBA) via
cleavage of the 2-ethylhexyl chain
without requiring added cofactors. The
Km and Vmax values for TBB
metabolism was estimated to be 11.1 ±
3.9 \M and 0.644 ± 0.144 nmol min-1
mg protein-1, respectively in human
microsomes.  No phase II metabolites of
TBBA were detected. The metabolism
of TBB in humans has not been
evaluated.
Roberts etal., 2012
Adequate study details reported.
                                    Metabolism was measured in the fat
                                    head minnow, common carp, mouse, and
                                    snapping turtle by measuring the loss of
                                    the parent compound (TBB and TBPH)
                                    in hepatic subcellular fractions
                                    Metabolic loss of TBB was observed for
                                    all species with the exception of
                                    snapping turtles; metabolism rates of
                                    TBB were similar between the
                                    subcellular fractions in the fathead
                                    minnow and carp. There were
                                    differences in the rated of metabolism
                                    between the subcellular fraction in mice
                                    with greater metabolism in microsomal
                                    fractions than in cytosolic or S9
                                    fractions. Observed metabolites,
                                    including 2,3,4,5-
                                    tetrabromomethylbenzoate (TBMB),
                                    Bearr etal., 2012
                            Test substance identified as
                            Firemaster BZ-54 (TBB and TBPH
                            in approximate 3:1 ratio).
                                                           7-24

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                                                        JUNE 2014 DRAFT REPORT
                                      Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
           PROPERTY/ENDPOINT
                                            DATA
                                          REFERENCE
                                   DATA QUALITY
                                               appeared to be derived from TBB. It was
                                               concluded by the authors that some
                                               species can metabolize TBB and TBPH
                                               to form varying metabolites.
                                               Estimated to have poor absorption by all
                                               routes of exposure.
                                                                 Professional judgment
                                                              Based on a closely related
                                                              confidential analog and professional
                                                              judgment.
Acute Mammalian Toxicity
                             LOW: Based on a rat oral LD50 >2,000 mg/kg. Acute toxicity values are estimated to be a Low hazard
                             for components of a commercial mixture containing TBB and TBPH (Firemaster 550).
Acute Lethality
Oral
                 Dermal
Rat oral LD50 >2,000 mg/kg
                                               Rat oral LD50 > 5,000 mg/kg
                                               (Estimated based on analogy)
                                               Rat oral LD50 > 5,000 mg/kg
                                               (Estimated)
                             Rabbit dermal LD50 > 2,000 mg/kg
                             (Estimated based on analogy)
Submitted confidential study
                                                                 Chemtura, 2006
                                                                 Chemtura, 2006
                                   Chemtura, 2006
Confidential study submitted to EPA;
test substance purity: 99.7%;
conducted according to 92/69/EEC
guideline consistent with OECD
guideline 401.
                                                              No study details reported in an
                                                              MSDS; estimated based on analogy
                                                              to a similar compound to a
                                                              component of Firemaster 550
                                                              (commercial mixture containing TBB
                                                              and TBPH); it is not certain if this
                                                              component contains TBB.
                                                              No study details reported in an
                                                              MSDS; estimated based on one
                                                              component of Firemaster 550
                                                              (commercial mixture containing TBB
                                                              and TBPH); it is not certain if this
                                                              component contains TBB.
                           No study details reported in an
                           MSDS; estimated based on analogy
                           to a similar compound to a
                           component of Firemaster 550
                           (commercial mixture containing TBB
                                                                    7-25

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JUNE 2014 DRAFT REPORT
Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT


Inhalation
Carcinogenicity

OncoLogic Results
Carcinogenicity (Rat and
Mouse)
Combined Chronic
Toxicity/Carcinogenicity
Other
DATA

Rabbit dermal LD50 > 2,000 mg/kg
(Estimated)
Rat 1-hr inhalation LC50 > 200 mg/L
(Estimated based on analogy)
REFERENCE

Chemtura, 2006
^
Chemtura, 2006
DATA QUALITY
and TBPH); it is not certain if this
component contains TBB.
No study details reported in an
MSDS; estimated based on one
component of Firemaster 550
(commercial mixture containing TBB
and TBPH); it is not certain if this
component contains TBB.
No study details reported in an
MSDS; estimated based on analogy
to a similar compound to a
component of Firemaster 550
(commercial mixture containing TBB
and TBPH); it is not certain if this
component contains TBB.
MODERATE: There is uncertainty due to lack of data for this substance. TBB is estimated to have
uncertain potential for Carcinogenicity based on analogy to a closely related confidential analog and
professional judgment; carcinogenic effects cannot be ruled out.



Estimated to have uncertain potential for
Carcinogenicity.



Professional judgment
No data located.
No data located.
No data located.
Based on analogy to closely related
chemical classes and professional
judgment.
(Estimated by analogy)
         7-26

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JUNE 2014 DRAFT REPORT
Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT
Genotoxicity

Gene Mutation in vitro
Gene Mutation in vivo
Chromosomal Aberrations in
vitro
Chromosomal Aberrations in
vivo
DNA Damage and Repair
Other
DATA
REFERENCE
DATA QUALITY
LOW: Estimated based on negative results for mutagenicity in bacteria and chromosomal aberrations in
clastogenicity assays for a component of Firemaster 550 (a commercial mixture containing TBB and
TBPH).
Negative; an unspecified component of a
commercial mixture was not mutagenic
in Salmonella typhimurium or
Escherichia coli when tested in dimethyl
sulphoxide.
(Estimated)

Negative; an unspecified component of a
commercial mixture showed no evidence
of clastogenicity in an in vitro cytogenic
test.
(Estimated)
Negative; a similar compound to an
unspecified component of a commercial
mixture did not induce chromosome
aberrations in human peripheral blood
lymphocytes with and without metabolic
activation.
(Estimated based on analogy)
J


Chemtura, 2006
^

Chemtura, 2006
Chemtura, 2006



No study details reported in an
MSDS; estimated based on one
component of Firemaster 550
(commercial mixture containing TBB
and TBPH); it is not certain if this
component contains TBB.
No data located.
No study details reported in an
MSDS; estimated based on one
component of Firemaster 550
(commercial mixture containing TBB
and TBPH); it is not certain if this
component contains TBB.
Limited study details reported in an
MSDS; estimated based on analogy
to a similar compound to a
component of Firemaster 550
(commercial mixture containing TBB
and TBPH); it is not certain if this
component contains TBB; study
conducted according to OECD 422.
No data located.
No data located.
No data located.
         7-27

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                                                         JUNE 2014 DRAFT REPORT
                                      Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
            PROPERTY/ENDPOINT
               DATA
       REFERENCE
        DATA QUALITY
Reproductive Effects
MODERATE: No reproductive effects were reported in a 2-generation oral (gavage) reproductive
toxicity study in rats at doses up to 165 mg/kg-day (highest dose tested) of Firemaster BZ 54 (commercial
mixture of TBB and TBPH) with a larger constituent of TBB. The NOAEL of 165 mg/kg-day falls within
the Moderate hazard criteria range; it is possible that effects driven by either component may occur
within the Moderate hazard range if tested at a higher dose. It is not clear which component or
components of the commercial mixture caused the reported developmental effects. Data from a
reproductive/developmental toxicity screen in rats exposed to a similar compound to a component of
Firemaster 550 (commercial mixture containing TBB and TBPH) indicated histopathological effects in
female reproductive organs at doses > 25 mg/kg-day (lowest dose tested; a NOAEL was not identified). It
is uncertain if the commercial mixture contained TBB.
                 Reproduction/Developmental
                 Toxicity Screen
Estimated to have moderate potential for
reproductive effects.
(Estimated by analogy)
                                               2-generation oral (gavage) reproductive
                                               toxicity study in rats administered 15,
                                               50, or 165 mg/kg-day; FO generation
                                               was treated 10 weeks prior to pairing
                                               through the mating period. Males were
                                               treated until termination; females were
                                               treated through gestation and lactation,
                                               and until termination on PND 21; pup
                                               selected (30/sex/dose) to continue as Fl
                                               parental generation began treatment on
                                               PND 22 and continued treatment similar
                                               to the FO generation.
                                               No adverse effects on reproductive
                                               performance or fertility in rats.

                                               NOAEL:  165 mg/kg-day (highest dose
                                               tested)
                                               LOAEL: Not established
                                               (Estimated)
Professional judgment
Estimated based on a closely related
confidential analog and professional
judgment.
                                    MPI Research, 2008a
                           Test substance: Firemaster BZ 54
                           (commercial mixture of TBB and
                           TBPH) with a larger constituent of
                           TBB; it is not clear which component
                           or components of the mixture are
                           driving the reported developmental
                           effects.
                                                                     7-28

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JUNE 2014 DRAFT REPORT
Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT


























Combined Repeated Dose with
Reproduction/ Developmental
Toxicity Screen















Reproduction and Fertility
Effects
Other





DATA
Reproductive/developmental toxicity
screen in rats orally administered 0, 25,
100, 400 mg/kg-day of a similar
compound to an unspecified component
of a commercial mixture.
Reduced number of successful
pregnancies and viable offspring at
doses of 100 and 400 mg/kg-day;
histopathological effects reported in
thymus and male reproductive organs
(testes and epididymides) at 400 mg/kg-
day; histopathological effects in female
reproductive organs and adrenals at
doses of > 25 mg/kg-day.
NOAEL: Not established
LOAEL: 25 mg/kg-day (lowest dose
tested)
(Estimated based on analogy)


Potential for reproductive effects
following long-term exposure to BZ-54
HP
(Estimated)
7

REFERENCE
Chemtura, 2006




^



^^^S. T










Chemtura, 2008





DATA QUALITY
Limited study details reported in an
MSDS; estimated based on analogy
to a similar compound to a
component of Firemaster 550
(commercial mixture containing TBB
and TBPH); it is not certain if this
component contains TBB; study
conducted according to OECD 422.










No data located.

No study details reported in an
MSDS; Estimated based on BZ-54
HP (commercial mixture containing
TBB and TBPH); it is not clear
which component is driving repeated
dose effects.
         7-29

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                                                         JUNE 2014 DRAFT REPORT
                                      Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
           PROPERTY/ENDPOINT
               DATA
       REFERENCE
        DATA QUALITY
Developmental Effects
MODERATE: Developmental effects were reported in a 2-generation reproductive toxicity study in rats
and a prenatal study in rats exposed to CN-2065 (a commercial mixture of TBB and TBPH with the
predominant constituent being TBB). Developmental effects were reported at doses of 165 mg/kg-day
and 100 mg/kg-day in the 2-generation and prenatal studies, respectively. Both studies had a NOAEL of
50 mg/kg-day which falls within the Moderate hazard criteria range. It is not clear which component or
components of the commercial mixture caused the reported developmental effects.
Development/neurodevelopmental effects were reported in a study in pregnant Wistar rats administered
a FM550 mixture (sum total of TBB  and TBPH approximately 50%) during gestation though lactation
(GD8 - PND21); developmental effects  included early female puberty, weight gain, altered exploratory
behavior, and increased male left ventricle thickness (LOAEL = 1 mg/kg-day, NOAEL = 0.1 mg/kg-day).
It is uncertain which component or components of the FM 550 mixture is driving the reported
developmental effects. While the FM 550 mixture data indicates a High hazard potential, it may be the
other components driving the reported toxicity. Experimental data indicated no effects on embryonic
survival or development in exposed zebrafish embryos.
                 Reproduction/ Developmental
                 Toxicity Screen
2-generation oral (gavage) reproductive
toxicity study in rats administered 15,
50, or 165 mg/kg-day; FO generation
was treated 10 weeks prior to pairing
through the mating period. Males were
treated until termination; females were
treated through gestation and lactation,
and until termination on PND 21; pup
selected (30/sex/dose) to continue as Fl
parental generation began treatment on
PND 22 and continued treatment similar
to the FO generation.
Parental toxicity: lower body weights
and body weight gains during premating
period in parental and F1 females at
highest dose; Lower body weights in the
premating period in Fl males; body
weight gains were not affected in males
Developmental toxicity: at highest dose,
MPI Research, 2008a
Study details reported in an
unpublished report; test substance:
Firemaster BZ 54 (CN-2065)
(commercial mixture of TBB and
TBPH) with the predominant
constituent being TBB; it is not clear
which component or components of
the mixture are driving the reported
developmental effects.
                                                                     7-30

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JUNE 2014 DRAFT REPORT
Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT









































Combined Repeated Dose with
Reproduction/ Developmental
Toxicity Screen
DATA
lower body weights at birth and
throughout lactation was reported in
both generations of offspring (Fl and
F2); this resulted in lower premating
body weights of the first female
generation. Decreased spleen weights at
lactation day (LD) 21 in Fl male pups
and F2 male and female pups.
Parental toxicity:
NOAEL: 50 mg/kg-day
LOAEL: 165 mg/kg-day
Developmental toxicity:
NOAEL: 50 mg/kg-day
LOAEL: 165 mg/kg-day
(Estimated)
Estimated to have moderate potential for
developmental/ neurodevelopmental
effects.
(Estimated by analogy)



REFERENCE





^


^^^S. J


^^



Professional judgment






DATA QUALITY















Estimated based on a closely related
confidential analog and professional
judgment.

No data located.


         7-31

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JUNE 2014 DRAFT REPORT
Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT
































Prenatal Development




























Postnatal Development
Prenatal and Postnatal
Development
DATA
Prenatal study in rats exposed to 0, 50,
100, 300 mg/kg-d Firemaster BZ54
(CN-2065)onGD6-19.
Maternal toxicity: increased incidence of
animals with sparse hair in abdominal
region, lower gestation body weights
and body weight gain, and lower
gestation food consumption at doses >
100 mg/kg-day.
Developmental toxicity: decreased fetal
weight at 100 mg/kg-day; increased
incidence of fused cervical vertebral
neural arches (litter incidence of 8%) in
fetuses at 300 mg/kg-day; increased
litter incidence of fetal ossification
variations involving additional
ossification centers to the cervical
vertebral neural arches, incomplete
ossified skull bones (jugal, parietal, and
squamosal), and unossified sternebrae.
Maternal toxicity:
NOAEL: 50 mg/kg-day
LOAEL: 100 mg/kg-day

Developmental toxicity:
NOAEL: 50 mg/kg-day
LOAEL (developmental): 100 mg/kg-
day based on decreased fetal weight
(Estimated)

Pregnant Wistar rats were administered
0, 0.1 or 1 mg/kg-day of FM550 in the
REFERENCE
MPI Research, 2008b




^



^^^S. r




















Patisauletal., 2013

DATA QUALITY
Study details reported in an
unpublished report; test substance:
Firemaster BZ54 (CN-2065);
commercial mixture of TBB and
TBPH with the predominant
constituent being TBB; it is not clear
which component or components of
the mixture are driving the reported
developmental effects.




















No data located.
Estimated based on data for FM550
mixture; non guideline study; the test
         7-32

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                                              JUNE 2014 DRAFT REPORT
                           Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                    diet during gestation and through
                                    lactation (GD8-PND 21);
                                    Maternal toxicity: Increased serum
                                    thyroxine (T4) levels in the high dose
                                    dams compared to controls was reported.
                                    There was no significant change in
                                    triiodothyronine (T3) levels in dam
                                    serum. Decreased hepatic
                                    carboxylesterease activity was also
                                    reported in dams in the high dose group.
                                    Developmental toxicity: female
                                    offspring in the high dose group
                                    displayed a significantly earlier vaginal
                                    opening when compared to controls. A
                                    statistically significant increase in
                                    weight was reported in both males and
                                    females in the high dose group at PND
                                    120. This effect persisted through PND
                                    180 to PND 220 with high dose males
                                    and females having significantly higher
                                    weights than same sex controls. A dose-
                                    dependent decrease in the number of rats
                                    to enter with open arms, (indicating
                                    anxiety), was reported in both male and
                                    female offspring. Increased blood
                                    glucose levels were reported in male
                                    offspring in the high-dose group
                                    compared to controls. There was no
                                    statistically significant difference in
                                    heart weight of male or female offspring.
                                    Left ventricular (LV) free wall thickness
                                    was significantly increased in male
                                    offspring in the high dose group; there
                                    were no changes in LV thickness in
                                                  substance identified as FM550 is a
                                                  mixture made up of TBB, TBPH
                                                  (sum total of TBB and TBPH is
                                                  approximately 50%), TPP and
                                                  IPTPP; it is not clear which
                                                  component or components of the
                                                  mixture are driving the reported
                                                  developmental effects.
                                                           7-33

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                                             JUNE 2014 DRAFT REPORT
                          Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT
               DATA
       REFERENCE
        DATA QUALITY
                                    females at any dose.

                                    Maternal Toxicity:
                                    NOAEL: 0.1 mg/kg-day
                                    LOAEL: 1 mg/kg-day

                                    Developmental toxicity:
                                    NOAEL: 0.1 mg/kg-day
                                    LOAEL: 1 mg/kg-day (based on early
                                    vaginal opening in females, increased
                                    weight in males and females, decreased
                                    open arm behavior, increased blood
                                    glucose levels in males and increased
                                    LV thickness in males)
                                    (Estimated)
      Developmental Neurotoxicity
      Other
Potential for developmental effects
following long-term exposure to BZ-54
HP
(Estimated)
Chemtura, 2008
                                    Zebrafish embryos were exposed under
                                    static conditions to purified TBB at
                                    concentrations up to 10 uM from 5.25 -
                                    96 hours post fertilization (hpf);
                                    There were no effects on embryonic
                                    survival or development.

                                    NOAEL: Not established
                                    LOAEL: Not established
                                    McGeeetal., 2013
                                                               No data located.
No study details reported in an
MSDS; Estimated based on BZ-54
HP (commercial mixture containing
TBB and TBPH); it is not clear
which component is driving repeated
dose effects.
                           Zebrafish is a nonstandard species;
                           current DfE criteria for this endpoint
                           are based on gestational and/or
                           postnatal exposure to mammalian
                           species. Thus, this study cannot be
                           used to assign a hazard designation
                           for the developmental endpoint.
                                                          7-34

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                                                         JUNE 2014 DRAFT REPORT
                                      Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
            PROPERTY/ENDPOINT
               DATA
       REFERENCE
        DATA QUALITY
Neurotoxicity
MODERATE: Estimated based on analogy to a similar compound to a component of Firemaster 550
(commercial mixture containing TBB and TBPH). There is potential for neurological effects after
breathing or swallowing large amounts or after long-term exposure to this analog. There were no
neurotoxic effects reported in a 28-day oral toxicity study in rats treated with the analog.
                 Neurotoxicity Screening
                 Battery (Adult)
                 Other
Potential for neurological effects
following long-term exposure to BZ-54
HP
(Estimated)
                                               Potential for neurological effects after
                                               breathing or swallowing large quantities
                                               or repeated exposure over a prolonged
                                               period of time is possible for a similar
                                               compound to an unspecified component
                                               of the commercial mixture.
                                               (Estimated based on analogy)
                                               28-day sub-chronic oral toxicity study in
                                               rats treated with 0, 160, 400, 1,000
                                               mg/kg-day;
                                               No neurotoxicity effects were reported.

                                               NOAEL: 1,000 mg/kg-day (highest dose
                                               tested)
                                               LOAEL: Not established (Estimated)
                                                               No data located.
Chemtura, 2008
                                    Chemtura, 2006
                                    Chemtura, 2006
No study details reported in an
MSDS; Estimated based on BZ-54
HP (commercial mixture containing
TBB and TBPH); it is not clear
which component is driving repeated
dose effects.
                           No study details reported in an
                           MSDS; estimated based on analogy
                           to a similar compound to a
                           component of Firemaster 550
                           (commercial mixture containing TBB
                           and TBPH); it is not certain if this
                           component contains TBB.
                           Limited study details reported in an
                           MSDS; neurotoxicity was evaluated
                           in this study; estimated based on one
                           component of Firemaster 550
                           (commercial mixture containing TBB
                           and TBPH); it is not certain if this
                           component contains TBB.
                                                                     7-35

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                                                         JUNE 2014 DRAFT REPORT
                                      Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
           PROPERTY/ENDPOINT
               DATA
REFERENCE
DATA QUALITY
Repeated Dose Effects
MODERATE: Estimated based on an increased incidence of sparse hair in abdominal region, reduced
body weight, and reduced food consumption in dams during gestation in a prenatal study in rats exposed
to CN-2065 (commercial mixture of TBB and TBPH with the predominant constituent being TBB) on
GD 6-19 at doses > 100 mg/kg-day (NOAEL = 50 mg/kg-day). Reduced body weight and body weight
gain during the premating period in parental FO and Fl female rats treated with 165 mg/kg-day CN-
2065 (NOAEL = 50 mg/kg-day) was also reported in a 2-generation oral reproductive toxicity in rats. In
addition, TBB is Estimated to have a moderate potential for liver effects and cerebral hemorrhages
based on a closely related confidential analog and professional judgment and is estimated to have
kidney, liver, adrenal, thymus, developmental, reproductive, and neurological effects following long-
term exposure to commercial mixtures that included TBB.
                                               In a prenatal study in rats exposed to 0,
                                               50, 100, 300 mg/kg-d on GD 6-19; dams
                                               experienced increased incidence of
                                               animals with sparse hair in abdominal
                                               region, lower gestation body weights
                                               and body weight gain, and lower
                                               gestation food consumption at doses >
                                               100 mg/kg-day.

                                               NOAEL: 50 mg/kg-day
                                               LOAEL (maternal):  100 mg/kg-day
                                               (Estimated)
                                               2-generation oral (gavage) reproductive
                                               toxicity study in rats administered 15,
                                               50, or 165 mg/kg-day; FO generation
                                               was treated  10 weeks prior to pairing
                                               through the  mating period. Males were
                                               treated until termination; females were
                                               treated through gestation and lactation,
                                               and until termination on PND 21; pup
                                               selected (30/sex/dose) to continue as Fl
                                               parental generation began treatment on
                                               PND 22 and continued treatment similar
                                    MPI Research, 2008b
                                    MPI Research, 2008a
                    Study details reported in an
                    unpublished report Test substance:
                    Firemaster BZ54 (CN-2065);
                    commercial mixture of TBB and
                    TBPH with the predominant
                    constituent being TBB; it is not clear
                    which component or components of
                    the mixture are driving the reported
                    effects.
                    Study details reported in an
                    unpublished report; test substance:
                    Firemaster BZ 54 (CN-2065)
                    commercial mixture of TBB and
                    TBPH with the predominant
                    constituent being TBB; it is not clear
                    which component or components of
                    the mixture are driving the reported
                    developmental effects.
                                                                     7-36

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JUNE 2014 DRAFT REPORT
Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT


DATA
to the FO generation
Parental toxicity: lower body weights
and body weight gains during premating
period in parental and Fl females at
highest dose; Lower body weights in the
premating period in Fl males; body
weight gains were not affected in males
Parental toxicity:
NOAEL: 50 mg/kg-day
LOAEL: 165 mg/kg-day (reduced body
weight and body weight gain)
(Estimated)
Estimated to have moderate potential for
liver effects and concern for cerebral
hemorrhages.
(Estimated by analogy)
28-day sub-chronic oral toxicity study in
rats treated with 0, 160, 400, 1,000
mg/kg-day;
Kidney effects were only reported at
1,000 mg/kg-day.
No systemic effects were reported at 160
mg/kg-day (NOEL).
NOEL: 160 mg/kg-day
NOAEL: 400 mg/kg-day
LOAEL: 1,000 mg/kg-day based on
kidney effects
(Estimated)
Potential for neurological effects after
breathing or swallowing large quantities
or repeated exposure over a prolonged
REFERENCE
^
^^^S. J
Professional judgment
Chemtura, 2006
Chemtura, 2006
DATA QUALITY

Estimated based on a closely related
confidential analog and professional
judgment.
Limited study details reported in an
MSDS; neurotoxicity was evaluated
in this study; estimated based on one
component of Firemaster 550
(commercial mixture containing TBB
and TBPH); it is not certain if this
component contains TBB. The
NOAEL of 400 mg/kg is assumed
based on the information in the
report.
No study details reported in an
MSDS; estimated based on analogy
to a similar compound to a
         7-37

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                                                         JUNE 2014 DRAFT REPORT
                                      Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
           PROPERTY/ENDPOINT
               DATA
       REFERENCE
        DATA QUALITY
                                               period of time is possible for a similar
                                               compound to an unspecified component
                                               of the commercial mixture
                                               (Estimated based on analogy)
                                                               component of Firemaster 550
                                                               (commercial mixture containing TBB
                                                               and TBPH); it is not certain if this
                                                               component contains TBB.
                                               Potential for kidney and liver effects
                                               following long-term exposure to BZ-54
                                               HP
                                               (Estimated)
                                    Chemtura, 2008
                           No study details reported in an
                           MSDS; Estimated based on BZ-54
                           HP (commercial mixture containing
                           TBB and TBPH); it is not clear
                           which component is driving repeated
                           dose effects.
Skin Sensitization
MODERATE: Estimated based on positive results for skin sensitization following exposure to
components of commercial mixtures containing TBB. It is not certain which component or components
caused the reported effects.
                 Skin Sensitization
The commercial mixture Firemaster BZ
54 is a skin sensitizer.
(Estimated)
                                               An unspecified component of the
                                               commercial mixture was not sensitizing
                                               in a Buehler test.
                                               (Estimated)
                                               An unspecified component of the
                                               commercial mixture was reported to be a
                                               sensitizer in a M&K sensitization assay.
                                               (Estimated)
Chemtura, 2013
                                    Chemtura, 2006
                                    Chemtura, 2006
Limited study details reported in an
MSDS; Test substance: Firemaster
BZ 54 (commercial mixture of TBB
and TBPH) with a larger constituent
of TBB; it is not clear which
component or components of the
mixture are driving the reported
effects.
                           No study details reported in an
                           MSDS; estimated based on one
                           component of Firemaster 550
                           (commercial mixture containing TBB
                           and TBPH); it is not certain if this
                           component contains TBB.
                           No study details reported in an
                           MSDS; estimated based on one
                           component of Firemaster 550
                           (commercial mixture containing TBB
                           and TBPH); it is not certain if this
                           component contains TBB.
                                                                     7-38

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JUNE 2014 DRAFT REPORT
Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT
Respiratory Sensitization
[Respiratory Sensitization
Eye Irritation

Eye Irritation
DATA
REFERENCE
DATA QUALITY
No data located.


No data located.
LOW: Estimated to have mild eye irritation based on a closely related confidential analog, experimental
data reporting mild irritation to components of a commercial mixture, and professional judgment.
Mild eye irritation in rabbits
(Estimated by analogy)
The commercial mixture Firemaster BZ
54 is a slight eye irritant.
(Estimated)
An unspecified component of the
commercial mixture was reported to be a
slight eye irritant in rabbits.
(Estimated)
No eye irritation was reported in rabbits
for a similar compound to an unspecified
component of the commercial mixture.
(Estimated based on analogy)
Professional judgment
Chemtura, 2013
^^^S. J
Chemtura, 2006
Chemtura, 2006
Estimated based on a closely related
confidential analog and professional
judgment.
Limited study details reported in an
MSDS; Test substance: Firemaster
BZ 54 (commercial mixture of TBB
and TBPH) with a larger constituent
of TBB; it is not clear which
component or components of the
mixture are driving the reported
effects.
No study details reported in an
MSDS; estimated based on one
component of Firemaster 550
(commercial mixture containing TBB
and TBPH); it is not certain if this
component contains TBB.
No study details reported in an
MSDS; estimated based on analogy
to a similar compound to a
component of Firemaster 550
(commercial mixture containing TBB
and TBPH); it is not certain if this
component contains TBB.
         7-39

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                                                         JUNE 2014 DRAFT REPORT
                                      Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
            PROPERTY/ENDPOINT
               DATA
       REFERENCE
        DATA QUALITY
Dermal Irritation
LOW: Estimated to have mild skin irritation based on a closely related confidential analog, experimental
data reporting mild irritation to components of a commercial mixture, and professional judgment.
                 Dermal Irritation
Mild skin irritation in rabbits
(Estimated based on analogy)
                                               The commercial mixture Firemaster BZ
                                               54 is a mild skin irritant.
                                               (Estimated)
                                               No skin irritation was reported in rabbits
                                               for a similar compound to an unspecified
                                               component of the commercial mixture.
                                               (Estimated based on analogy)
                                               An unspecified component of the
                                               commercial mixture was reported to be a
                                               slight skin irritant in rabbits.
                                               (Estimated)
Professional judgment
Estimated based on a closely related
confidential analog and professional
judgment.
                                    Chemtura, 2013
                                    Chemtura, 2006
                                    Chemtura, 2006
                           Limited study details reported in an
                           MSDS; Test substance: Firemaster
                           BZ 54 (commercial mixture of TBB
                           and TBPH) with a larger constituent
                           of TBB; it is not clear which
                           component or components of the
                           mixture are driving the reported
                           effects.
                           No study details reported in an
                           MSDS; estimated based on analogy
                           to a similar compound to a
                           component of Firemaster 550
                           (commercial mixture containing TBB
                           and TBPH); it is not certain if this
                           component contains TBB.
                           No study details reported in an
                           MSDS; estimated based on one
                           component of Firemaster 550
                           (commercial mixture containing TBB
                           and TBPH); it is not certain if this
                           component contains TBB.
                                                                     7-40

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                                                         JUNE 2014 DRAFT REPORT
                                      Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
           PROPERTY/ENDPOINT
               DATA
REFERENCE
DATA QUALITY
Endocrine Activity
Increased serum thyroxine (T4) levels were reported in the serum of dams following oral administration
to FM550 (mixture of 50% sum total of TBB and TBPH); other components of the mixture were not
identified. It is unclear which component or components of the mixture are driving the endocrine
activity effects. There was no experimental data located specifically for the TBB compound.
                                               Potential for adrenal effects following
                                               long-term exposure to BZ-54 HP
                                               (Estimated)
                                               Pregnant Wistar rats were administered
                                               0, 0.1 or 1 mg/kg-day of FM550 in the
                                               diet during gestation and through
                                               lactation (GD8-PND 21);
                                               Increased serum thyroxine (T4) levels
                                               (increase of 65%) in the high dose dams
                                               compared to controls was  reported.
                                               There was no significant change in
                                               triiodothyronine (T3) levels in dam
                                               serum. There was no reported
                                               statistically significant change in T4 or
                                               T3 levels in pup serum on PND 21 when
                                               compared to controls.
                                               (Estimated)
                                               Reproductive/developmental toxicity
                                               screen in rats orally administered 0, 25,
                                               100, 400 mg/kg-day of a similar
                                               compound to an unspecified component
                                               of a commercial mixture.
                                               Reduced number of successful
                                               pregnancies and viable offspring at
                                               doses of 100 and 400 mg/kg-day;
                                               histopathological effects reported in
                                    Chemtura, 2008
                                    Patisauletal., 2013
                                    Chemtura, 2006
                    No study details reported in an
                    MSDS; Estimated based on BZ-54
                    HP (commercial mixture containing
                    TBB and TBPH); it is not clear
                    which component is driving repeated
                    dose effects.
                    Estimated based on data for FM550
                    mixture; non guideline study; test
                    substance identified as FM550 is a
                    mixture made up of TBB, TBPH
                    (sum total of TBB and TBPH is
                    approximately 50%), TPP and
                    IPTPP; it is not clear which
                    component or components of the
                    mixture are driving the reported
                    endocrine activity effects.
                    Limited study details reported in an
                    MSDS; estimated based on analogy
                    to a similar compound to a
                    component of Firemaster 550
                    (commercial mixture containing TBB
                    and TBPH); it is not certain if this
                    component contains TBB; study
                    conducted according to OECD 422.
                                                                     7-41

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JUNE 2014 DRAFT REPORT
Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT

Immunotoxicity

Immune System Effects
DATA
thymus and male reproductive organs
(testes and epididymides) at 400 mg/kg-
day; histopathological effects in female
reproductive organs and adrenals at
doses of 25 mg/kg-day.
NOAEL: Not established
LOAEL: 25 mg/kg-day (lowest dose
tested)
(Estimated based on analogy) ^^^i
REFERENCE
^
DATA QUALITY

Estimated to have potential for immunotoxicity based on a structural alert for polyhalogenated aromatic
hydrocarbons.
Potential for thymus effects following
long-term exposure to BZ-54 HP
(Estimated)
Potential for immunotoxicity based on
structural alert for polyhalogenated
aromatic hydrocarbons
(Estimated) ^^^^^^^
Chemtura, 2008
Professional judgment; EPA,
2012
No study details reported in an
MSDS; Estimated based on BZ-54
HP (commercial mixture containing
TBB and TBPH); it is not clear
which component is driving repeated
dose effects.
Estimated based on structural alert
for polyhalogenated aromatic
hydrocarbons and professional
judgment.
ECOTOXICITY
ECOSAR Class
Acute Aquatic Toxicity
Fish LC50
Esters
LOW: Based on an estimated log Kow of 8.8 and the fact that the experimental effect levels in fish,
daphnia, and algae were well above the estimated water solubility (0.00001 mg/L), NES are predicted for
this endpoint.
Fish 96-hour LC50 = No effects at
saturation (NES)
(Experimental)
Oncorhynchus mykiss rainbow trout 96-
Submitted confidential study
Chemtura, 2006
No study details reported in a
submitted confidential study report.
Species, test conditions, and toxicity
values not specified.
No study details reported in an
         7-42

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                                             JUNE 2014 DRAFT REPORT
                          Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT
DATA
       REFERENCE
        DATA QUALITY
                                   hour LC50 =1.6 mg/L
                                   (Estimated by analogy)
                                                MSDS; estimated based on analogy
                                                to a similar compound to a
                                                component of Firemaster 550
                                                (commercial mixture containing TBB
                                                and TBPH); it is not certain if this
                                                component contains TBB. Based on
                                                log Kow of 8.8 and the reported effect
                                                level was above the estimated water
                                                solubility (0.000011 mg/L), NFS are
                                                predicted for this endpoint.
                                   Fathead minnow 96-hour LC50 =10.8
                                   mg/L
                                   (Estimated by analogy)
                     Chemtura, 2006
                           No study details reported in an
                           MSDS; estimated based on analogy
                           to a similar compound to a
                           component of Firemaster 550
                           (commercial mixture containing TBB
                           and TBPH); it is not certain if this
                           component contains TBB. Based on
                           log Kow of 8.8 and the reported effect
                           level was above the estimated water
                           solubility (0.000011 mg/L), NFS are
                           predicted for this endpoint.
                                    Oncorhynchus mykiss rainbow trout 96-
                                    hour LC50> 12 mg/L
                                    (Estimated)
                     Chemtura, 2006, 2013
                           No study details reported in an
                           MSDS; estimated based on one
                           component of Firemaster 550 and for
                           Firemaster BZ-54 (commercial
                           mixtures containing TBB and
                           TBPH);  Based on log Kow of 8.8 and
                           the reported effect level was above
                           the estimated water solubility
                           (0.000011 mg/L), NFS are predicted
                           for this endpoint.
                                   Fish 96-hour LC5C
                                   (Estimated)
  = 0.008 mg/L
ECOSARvl.ll
NFS: The estimated log Kow of 8.8
for this chemical exceeds the SAR
                                                         7-43

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                                                         JUNE 2014 DRAFT REPORT
                                      Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
           PROPERTY/ENDPOINT
               DATA
       REFERENCE
        DATA QUALITY
                                               ECOSAR: Esters
                                                               limitation for log Kow of 5.0; NES are
                                                               predicted for these endpoints.
                                               Fish 96-hour LC50 = 0.0004 mg/L
                                               (Estimated)
                                               ECOSAR: Neutral organics
                                    ECOSAR v 1.11
                           NES: The estimated log Kow of 8.8
                           for this chemical exceeds the SAR
                           limitation for log Kow of 5.0; NES are
                           predicted for these endpoints.
                           Narcosis classes (neutral organics)
                           are provided for comparative
                           purposes; DfE assessment
                           methodology will use the lowest
                           estimated toxicity value provided by
                           ECOSAR classes that have a more
                           specific mode of action relative to
                           narcosis.
Daphnid LC50
Daphnia magna 48-hour EC50 = 0.42
mg/L.
(Experimental)
Chemtura, 2006, 2013
No study details reported in an
MSDS; estimated based on one
component of Firemaster 550 and for
Firemaster BZ-54 (commercial
mixture containing TBB and TBPH);
Based on log Kow of 8.8 and the
reported effect level was above the
estimated water solubility (0.000011
mg/L), NES are predicted for this
endpoint.
                                               Daphnia magna 24-hour EC50 =1.2
                                               mg/L.
                                               (Experimental)
                                    Chemtura, 2006, 2013

                           No study details reported in an
                           MSDS; estimated based on one
                           component of Firemaster 550 and for
                           Firemaster BZ-54 (commercial
                           mixtures containing TBB and
                           TBPH); Based on log Kow of 8.8 and
                           the reported effect level was above
                           the estimated water solubility
                           (0.000011 mg/L), NES are predicted
                                                                     7-44

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JUNE 2014 DRAFT REPORT
Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT

Green Algae EC50
DATA

Daphnia magna 48-hour LC50 = 2.44
mg/L
(Estimated by analogy)
Daphnia 48-hour LC50 = 0.008 mg/L
(Estimated)
ECOSAR: Esters
Daphnia 48-hour LC50 = 0.0004 mg/L
(Estimated)
ECOSAR: Neutral organics
^
7
Green algae 96 hour LC50 = No effects at
saturation (NES).
(Experimental)
Green algae 96-hour EC50 = 0.0012
mg/L
REFERENCE

Chemtura, 2006
^
^^^S. J
ECOSAR v 1.11
ECOSAR v 1.11
Submitted confidential study
ECOSAR v 1.11
DATA QUALITY
for this endpoint.
No study details reported in an
MSDS; estimated based on analogy
to a similar compound to a
component of Firemaster 550
(commercial mixture containing TBB
and TBPH); it is not certain if this
component contains TBB. Based on
log Kow of 8.8 and the reported effect
level was above the estimated water
solubility (0.00001 1 mg/L), NES are
predicted for this endpoint.
NES: The estimated log Kow of 8.8
for this chemical exceeds the SAR
limitation for log Kow of 5.0; NES are
predicted for these endpoints.
NES: The estimated log Kow of 8.8
for this chemical exceeds the SAR
limitation for log Kow of 5.0; NES are
predicted for these endpoints.
Narcosis classes (neutral organics)
are provided for comparative
purposes; DfE assessment
methodology will use the lowest
estimated toxicity value provided by
ECOSAR classes that have a more
specific mode of action relative to
narcosis.
Limited study details reported in
submitted confidential study report.
NES: The estimated log Kow of 8.8
for this chemical exceeds the SAR
         7-45

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                                             JUNE 2014 DRAFT REPORT
                          Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                    (Estimated)
                                    ECOSAR: Esters
                                                limitation for log Kow of 6.4; NES are
                                                predicted for these endpoints.
                                    Green algae 72-hour NOAEC = 0.31
                                    mg/L
                                    96-hour NOAEC =1.3 mg/L
                                    (Estimated by analogy)
                     Chemtura, 2006
                    No study details reported in an
                    MSDS; estimated based on analogy
                    to a similar compound to a
                    component of Firemaster 550
                    (commercial mixture containing TBB
                    and TBPH); it is not certain if this
                    component contains TBB. Based on
                    log Kow of 8.8 and the reported effect
                    level was above the estimated water
                    solubility (0.000011 mg/L), NES are
                    predicted for this endpoint.
                                    Selenastrum capricornutum 96-hour
                                    EC50>5.1mg/L
                                    (Estimated)
                     Chemtura, 2006, 2013
                    No study details reported in an
                    MSDS; estimated based on one
                    component of Firemaster 550 and for
                    Firemaster BZ-54 (commercial
                    mixture containing TBB and TBPH);
                    based on log Kow of 8.8 and the
                    reported effect level was above the
                    estimated water solubility (0.000011
                    mg/L), NES are predicted for this
                    endpoint.
                                    Green algae 96-hour EC50 = 0.0004
                                    mg/L
                                    (Estimated)
                                    ECOSAR: Neutral organics
                     ECOSAR v 1.11

                    NES: The estimated log Kow of 8.8
                    for this chemical exceeds the SAR
                    limitation for log Kow of 5.0; NES are
                    predicted for these endpoints.
                    Narcosis classes (neutral organics)
                    are provided for comparative
                    purposes; DfE assessment
                    methodology will use the lowest
                    estimated toxicity value provided by
                    ECOSAR classes that have a more
                                                          7-46

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JUNE 2014 DRAFT REPORT
Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT

Chronic Aquatic Toxicity
Fish ChV
Daphnid ChV
DATA

REFERENCE

DATA QUALITY
specific mode of action relative to
narcosis.
LOW: Based on estimated chronic toxicity values for fish, daphnid, and algae that indicate no effects at
saturation (NES).
Fish ChV = 0.0001 5 mg/L
(Estimated)
ECOSAR: Esters
Green algae 96-hour EC50 = 0.0004
mg/L
(Estimated)
ECOSAR: Neutral organics
^\ V
Daphnia ChV = 0.00083 mg/L
(Estimated)
ECOSAR: Esters
^+
ECOSAR v 1.11
ECOSAR v 1.11
ECOSAR v 1.11
NES: The estimated log Kow of 8.8
for this chemical exceeds the SAR
limitation for log Kow of 8.0; NES are
predicted for these endpoints.
NES: The estimated log Kow of 8.8
for this chemical exceeds the SAR
limitation for log Kow of 5.0; NES are
predicted for these endpoints.
Narcosis classes (neutral organics)
are provided for comparative
purposes; DfE assessment
methodology will use the lowest
estimated toxicity value provided by
ECOSAR classes that have a more
specific mode of action relative to
narcosis.
NES: The estimated log Kow of 8.8
for this chemical exceeds the SAR
limitation for log Kow of 8.0; NES are
predicted for these endpoints.
         7-47

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JUNE 2014 DRAFT REPORT
Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT

Green Algae ChV
DATA
Daphnia ChV = 0.0002 mg/L
(Estimated)
ECOSAR: Neutral organics
Green algae ChV = 0.003
(Estimated)
ECOSAR: Esters
Green algae ChV = 0.004
(Estimated)
ECOSAR: Neutral organics
^
7
REFERENCE
ECOSAR v 1.11
^
^^^S. r
ECOSAR v 1.11
ECOSAR v 1.11
DATA QUALITY
NES: The estimated log Kow of 8.8
for this chemical exceeds the SAR
limitation for log Kow of 8.0; NES are
predicted for these endpoints.
Narcosis classes (neutral organics)
are provided for comparative
purposes; DfE assessment
methodology will use the lowest
estimated toxicity value provided by
ECOSAR classes that have a more
specific mode of action relative to
narcosis.
NES: The estimated log Kow of 8.8
for this chemical exceeds the SAR
limitation for log Kow of 8.0; NES are
predicted for these endpoints.
NES: The estimated log Kow of 8.8
for this chemical exceeds the SAR
limitation for log Kow of 8.0; NES are
predicted for these endpoints.
Narcosis classes (neutral organics)
are provided for comparative
purposes; DfE assessment
methodology will use the lowest
estimated toxicity value provided by
ECOSAR classes that have a more
specific mode of action relative to
narcosis.
ENVIRONMENTAL FATE
         7-48

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JUNE 2014 DRAFT REPORT
Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT
Transport

Henry's Law Constant (atm-
m3/mole)
Sediment/Soil
Adsorption/Desorption - Koc
Level III Fugacity Model
DATA
REFERENCE
DATA QUALITY
Level III fugacity models incorporating available physical and chemical property data indicate that at
steady state, TBB is expected to be found primarily in soil and to a lesser extent, water. Hydrolysis of
TBB is not expected to occur at a significant rate at environmentally-relevant pH conditions. TBB is
expected to have low mobility in soil based on its measured K0o Therefore, leaching of TBB through soil
to groundwater is not expected to be an important transport mechanism. Estimated volatilization half-
lives indicate that it will be slightly volatile from surface water. In the atmosphere, TBB is expected to
exist in the particulate phase, based on its estimated vapor pressure. Particulates will be removed from
air by wet or dry deposition.
7. IxlO'6 (Estimated)
>28840 (Measured)
Air = 0.3%
Water = 12%
Soil = 87%
Sediment =1% (Estimated)
EPIv4.11
^ *
Submitted confidential study
EPIv4.11
Estimated by the HENRYWIN
Group SAR Method with no
measured chemical property inputs.
Limited study details available; the
degree of precision reported is
atypical for this type of study.
This estimation was obtained using
the Level III Fugacity model based
on the equal emissions distribution
assumption with no measured
chemical property inputs.
         7-49

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JUNE 2014 DRAFT REPORT
Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT
Persistence
Water
Aerobic Biodegradation
Volatilization Half-life for
Model River
DATA
REFERENCE
DATA QUALITY
HIGH: The persistence hazard designation for TBB is based on estimated rates of removal in soil and
the persistence of degradation products. Confidential experimental biodegradation studies reported half-
lives of 3.5 days in water and 8.5 days in sediment with a shake flask die-away test and 6% degradation
after 28 days in a closed bottle test. TBB has an estimated half-life of 120 days in soil where fugacity
models indicate that it is expected to partition. Although TBB may undergo hydrolysis under basic
conditions, the resulting hydrolysis products are expected to have high persistence. TBB has the
potential to undergo photodegradation, under laboratory conditions when dissolved in organic solvents,
however the importance of this process under environmental conditions cannot be determined. The
vapor phase reaction half-life of TBB with atmospheric hydroxyl radicals is estimated at < 1 day,
although it is expected to exist primarily in the particulate phase in air.
Passes Ready Test: No
Test method: OECD TG 301D: Closed
Bottle Test
6% biodegradation after 28 days
(Measured) r^^J
Study results: 50% in 3.5 days
Test method: Shake Flask
Shake flask die-away test (Measured)
Weeks-months (Primary Survey Model)
Months (Ultimate Survey Model)
(Estimated for degradation product)
Study results: 50% in 8.5 days
Test method: Shake Flask
Performed in water with suspended
sediment (Measured)
8 days (Estimated)
Submitted confidential study
Submitted confidential study
EPIv4.11
Submitted confidential study
EPIv4.11
Adequate guideline study.
Adequate guideline study. Although
limited experimental data were
available, the anticipated degradation
product, 2,3,4,5-tetrabromobenzoic
acid, is anticipated to be resistant to
degradation under the test conditions.
Estimated for the degradation product
2,3,4,5-tetrabromobenzoic acid
(CASRN 27581-13-1).
Adequate guideline study. Although
limited experimental data were
available, the anticipated degradation
product, 2,3,4,5-tetrabromobenzoic
acid, is anticipated to be resistant to
degradation under the test conditions.
Based on the magnitude of the
estimated Henry's Law constant.
         7-50

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JUNE 2014 DRAFT REPORT
Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT

Soil
Air
Reactivity
Volatilization Half-life for
Model Lake
Aerobic Biodegradation
Anaerobic Biodegradation
Soil Biodegradation with
Product Identification
Sediment/Water
Biodegradation
Atmospheric Half-life
Photolysis
Hydrolysis
DATA
98 days (Estimated)

Not probable


1 day Based on a 12-hour day.
(Estimated)
Half-life = 95 min. in methanol
Half-life = 86 min. in tetrahydrofuran
Half-life = 162 min. in toluene
Di- and tri-brominated analogues were
identified by electron capture negative
ion/mass spectrometry ECNI/MS as the
most dominant photodegradation
products (Measured)
Half-life of 3.4 days at pH 8; 34 days at
pH 7 (Estimated)
50%/>1 year at pH 4, 7, and 9
(Measured)
REFERENCE
EPIv4.11

Holliger et al., 2004; EPI
v4.11
^


EPIv4.11
Davis and Stapleton, 2009
EPIv4.11
Submitted confidential study
DATA QUALITY
Based on the magnitude of the
estimated Henry's Law constant.
No data located.
The estimated value addresses the
potential for ultimate biodegradation.
However, there is potential for
primary anaerobic biodegradation of
haloaromatic compounds by
reductive dehalogenation.
No data located.
No data located.

The half-life and rate data are not
relevant to removal rates in the
environment as the test substance
was dissolved in organic solvents.
However, the results demonstrate the
potential for some debromination.
Hydrolysis rates are expected to be
pH-dependent and may be limited the
by low water solubility of this
compound.
Limited study details available. Data
indicate the resistance of the material
to hydrolysis under environmental
conditions.
         7-51

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JUNE 2014 DRAFT REPORT
Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT
Environmental Half-life
Bioaccumulation

Fish BCF
Other BCF
BAF
DATA
Aquatic mesocosm study; a controlled
source of TBB was applied and analyzed
by GC-MS over the course of the study
TBB was detected in both the particulate
and sediment compartment samples.
Degradation products were detected but
not identified (Measured)
120 days Soil (Estimated)
REFERENCE
de Jourdan et al., 2013
^
PBT Profiler
^ *
DATA QUALITY
This field study provides data about
the partitioning and fate/persistence
of this compound under
environmental conditions.
Half-life estimated for the
predominant compartment, oil, as
determined by EPI methodology.
HIGH: The bioaccumulation hazard designation is estimated based on the estimated BAF and
monitoring data reporting detections in many different species including those higher on the food chain.
In addition, the stable metabolite and degradation product of TBB is expected to have a moderate
Bioaccumulation designation based on an estimated BAF value.
6.2 Reported as a range: 1.7 - 6.2
(Measured)
10 for tetrabromobenzoic acid (TBBA),
an expected metabolite and hydrolysis
product of TBB (Estimated for
metabolite) ^^^^^^^^_

2100 (Estimated)
Fish were orally exposed to commercial
flame retardant formulations including
Firemaster BZ-54®, containing TBB for
56 days and depurated (e.g., fed clean
food) for 22 days. Homogenized fish
tissues were extracted and analyzed on
day 0 and day 56 using gas
chromatography electron-capture
negative ion mass spectrometry
Submitted confidential study
EPIv4.11

EPIv4.11
Bearretal., 2010
Adequate guideline study.
Estimations run with using the
SMILES:
O=C(c 1 c(Br)c(Br)c(Br)c(Br)c 1 )O .
No data located.

BAFs were not calculated. Non
guideline study indicates that
absorption of this compound can
occur in fish through dietary
exposure.
         7-52

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JUNE 2014 DRAFT REPORT
Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT


Metabolism in Fish
DATA
(GC/ECNI-MS). TBB and TBPH, were
detected in tissues at approximately 1%
of daily dosage along with brominated
metabolites. (Measured)
TBB was detected in adipose, liver, and
muscle tissues in rat dams and rat pup
adipose tissue. The primary metabolite
of TBB (TBBA) was also detected in
liver tissue of rat dams. The pregnant
rats were administered 0, 0.1 or 1
mg/kg-day of FM550 by oral gavage
across gestation and through lactation
(GD8-PND 21). (Measured)
835 for tetrabromobenzoic acid (TBBA),
an expected metabolite and hydrolysis
product of TBB (Estimated for
metabolite)

REFERENCE

Patisaul et al., 2013
^^^S. r
EPIv4.11

DATA QUALITY

BAFs were not calculated. Non
guideline study indicates that
absorption of this compound can
occur in rats through oral exposure;
the test substance identified as
FM550 is a mixture made up of TBB,
TBPH (CASRN 26040-51-7), IPTPP
(CASRN 68937-41-7) and TPP
(CASRN 115-86-6).
Estimations run with using the
SMILES:
O=C(clc(Br)c(Br)c(Br)c(Br)cl)O.
No data located.
ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring
Ecological Biomonitoring
Human Biomonitoring
TBB was detected in gas and particle -phase air samples collected from Denmark, near the shores of the Great
Lakes, Norway and Sweden. TBB was detected in the marine atmosphere near Antarctica, the Arctic, East Asia
and Southeast Asia. TBB was detected in sediment samples from Denmark, the Faroe Islands, Finland,
Norway, Sweden and Yadkin River in North Carolina. TBB was detected in dust from Bavaria, Belgium,
Canada, Kuwait, New Zealand, Pakistan, Sweden, United States, airplanes and a UK daycare (Stapleton et al.,
2008, 2009; Ali et al., 201 1, 2012, 2013; Covaci et al., 2012; Dodson et al., 2012; EFSA, 2012; Kopp et al.,
2012; LaGuardia et al., 2012; Ma et al., 2012; Moller et al., 2012a, 2012b; Sahlstrom et al., 2012; Shoeib et al.,
2012; Xiao et al., 2012; Allen et al., 2013).
TBB was detected in bivalve (Corbicula fluminea); fmless porpoise; gastropod (Elimia proximo); fish; ring-
billed gulls; Black-legged kittiwake; Brimnich's guillemot; Capelin; Common eider; gastropod (Elimia
proximo); polar bear; ringed seal; egg; pet cat and dog hair; artic fox (EPA, 2009; Lam et al., 2009; Sagerup et
al., 2010; Zhou et al., 2010; Gentes et al., 2012; LaGuardia et al., 2012).
This chemical was not included in the NF£ANES biomonitoring report (CDC, 2013).
         7-53

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                                                 JUNE 2014 DRAFT REPORT


Ali N, Ali L, Mehdi T, et al. (2013) Levels and profiles of organochlorines and flame retardants in car and house dust from Kuwait and Pakistan:
Implication for human exposure via dust ingestion. Environ Int 55:62-70.

Ali N, Dirtu AC, Van den Eede N, et al. (2012) Occurrence of alternative flame retardants in indoor dust from New Zealand: indoor sources and
human exposure assessment. Chemosphere 88(11): 1276-82.

Ali N, Harrad S, Goosey E, et al. (2011)  "Novel" brominated flame retardants in Belgian and UK indoor dust: Implications for human exposure.
Chemosphere 83(10): 1360-1365.

Allen JG, Stapleton HM, Vallarino J, et al. (2013) Exposure to flame retardant chemicals on commercial airplanes. Environ Health 12:17.

Bearr JS, Mitchelmore CL, Roberts SC, et al. (2012) Species specific differences in the in vitro metabolism of the flame retardant mixture,
Firemaster(R) BZ-54. Aquat Toxicol 124-125:41-47.

Bearr JS, Stapleton HM, Mitchelmore CL (2010) Accumulation and DNA damage in fathead minnows (Pimephales promelas) exposed to 2
brominated flame-retardant mixtures, Firemaster 550 and Firemaster BZ-54. Environ Toxicol Chem 29(3):722-729.

CDC (2013) Fourth national report on human exposure to environmental chemicals, updated tables, March 2013. Centers for Disease Control and
Prevention. http://www.cdc.gov/exposurereport/pdf/FourthReport UpdatedTables Mar2013 .pdf. Accessed May 10, 2013.

Chemtura (2006) Material Safety Data Sheet FIREMASTER 550. Chemtura Product Safety Group.

Chemtura (2008) Material Safety Data Sheet FIREMASTER BZ-54 HP.

Chemtura (2013) Material Safety Data Sheet for Firemaster BZ-54. Chemtura Corporation.

Covaci A, lonas AC, van den Eede N, et al. (2012) Characterization of flame retardants in home indoor dust from California, USA.
Organohalogen Compounds 74:1506-1509, 1504 pp.

Davis EF and Stapleton HM (2009) Photodegradation pathways of nonabrominated diphenyl ethers, 2-ethylhexyltetrabromobenzoate and di(2-
ethylhexyl)tetrabromophthalate: identifying potential markers of photodegradation. Environ Sci Technol 43(15):5739-5746.

de Jourdan BP, Hanson ML, Muir DC, et al. (2013) Environmental fate  of three novel brominated flame  retardants in aquatic mesocosms. Environ
Toxicol Chem 32(5): 1060-1068.
                                                             7-54

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                                                  JUNE 2014 DRAFT REPORT


Dodson RE, Perovich LJ, Covaci A, et al. (2012) After the PBDE phase-out: a broad suite of flame retardants in repeat house dust samples from
California. Environ Sci Technol 46(24): 13056-13066.

ECOSAR (Ecological Structure Activity  Relationship), Version 1.11. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/oppt/newchems/tools/21ecosar.htm.

EFSA (2012) Scientific Opinion on Emerging and Novel Brominated Flame Retardants (BFRs) in Food. European Food Safety Authority. EFSA
Journal 10(10):2908.

EPA (1999) Determining the adequacy of existing data. Washington, DC: U.S. Environmental Protection Agency.
http: //www .epa. gov/hpv/pubs/general/datadeqfn .pdf.

EPA (2009) Screening-level hazard characterization for Phosphonic acid, P-[[bis(2-hydroxyethyl)amino]methyl]-, diethyl ester (Fyrol 6, CASRN
2781-11-5). U.S. Environmental Protection Agency, http://www.epa.gov/hpvis/hazchar/2781115 Fyrol%206 Sept2009.pdf.EPA (2012) Using
noncancer screening within the SF initiative. Washington, DC: U.S. Environmental Protection Agency, http://www.epa.gov/oppt/sf/pubs/noncan-
screen.htm.

EPI Estimation Programs Interface (EPI) Suite, Version 4.11. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm.
                                        ^P                               7
ESIS (2012) European chemical Substances Information System. European Commission, http://esis.jrc.ec.europa.eu/.

Gentes M, Letcher RJ, Caron-Beaudoin E, et al. (2012) Novel flame retardants in urban-feeding ring-billed gulls from the St. Lawrence River,
Canada. Environ Sci Technol 46(17):9735-9744.

Holliger C, Regeard C, Diekert G (2004) Dehalogenation by anaerobic bacteria. In: Haggblom MM, Bossert ID, eds. Dehalogenation: Microbial
processes and environmental applications. Kluwer Academic Publishers. 115-157.

Kopp EK, Fromme H, Volkel W (2012) Analysis of common and emerging brominated flame retardants in house dust using ultrasonic assisted
solvent extraction and on-line sample preparation via column switching with liquid chromatography-mass spectrometry. J Chromatogr A 1241:28-
36.

La Guardia MJ, Hale RC, Harvey E, et al. (2012) In situ accumulation of HBCD, PBDEs, and several alternative flame-retardants in the bivalve
(Corbiculafluminea) and gastropod (Elimiaproximo). Environ Sci Technol 46(11):5798-5805.
                                                               7-55

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                                                  JUNE 2014 DRAFT REPORT


Lam JC, Lau RK, Murphy MB, et al. (2009) Temporal trends of hexabromocyclododecanes (HBCDs) and polybrominated diphenyl ethers
(PBDEs) and detection of two novel flame retardants in marine mammals from Hong Kong, South China. Environ Sci Technol 43(18):6944-6949.

Ma Y, Venier M, Hites RA (2012) 2-Ethylhexyl tetrabromobenzoate and bis(2-ethylhexyl) tetrabromophthalate flame retardants in the Great
Lakes atmosphere. Environ Sci Technol 46(1):204-208.

McGee SP and Konstantinov A Stapleton HM, et al. (2013) Aryl phosphate esters within a major pentaBDE replacement product induce
cardiotoxicity in developing zebrafish embryos: Potential role of the aryl hydrocarbon receptor. Toxicol Sci 133(1): 144-156.

Moller A, Xie Z, Cai M, et al. (2012a) Brominated flame retardants and dechlorane plus in the marine atmosphere from Southeast Asia toward
Antarctica. Environ Sci Technol 46:3141-3148.

Moller A, Xie Z, Cai M, et al. (2012b) Polybrominated diphenyl ethers vs alternate brominated flame retardants and dechloranes from East Asia to
the Arctic. Environ Sci Technol 45(16)6793-6799.

MPI Research (2008a) CN-2065: An oral two-generation reproduction and fertility study in rats. MPI Research Inc.

MPI Research (2008b) CN-2065: Prenatal developmental toxicity study in rats. MPI Research Inc.

Patisaul HB, Roberts SC, Mabrey N, et al. (2013) Accumulation and endocrine disrupting effects of the flame retardant mixture Firemaster 550 in
rats:  an exploratory assessment. J Biochem Mol Toxicol 27(2): 124-36.

PBT Profiler. Persistent (P), Bioaccumulative (B), and Toxic (T) Chemical (PBT) Profiler, Version 1.301. Washington, DC: U.S. Environmental
Protection Agency, www.pbtprofiler.net.

Roberts SC, Macaulay LJ, Stapleton HM (2012) In vitro metabolism of the brominated flame retardants 2-ethylhexyl-2,3,4,5-tetrabromobenzoate
(TBB) and bis(2-ethylhexyl) 2,3,4,5-tetrabromophthalate (TBPH) in human and rat tissues. Chem Res Toxicol 25(7): 1435-1441.

Sagerup K, Herzke D, Harju M, et al. (2010) New brominated flame retardants in Arctic biota. Statlig program for forurensningsovervaking.
http://www.klif.no/publikasjoner/2630/ta2630.pdf.

Sahlstrom L, Sellstrom U, DeWit CA (2012) Clean-up method for determination of established and emerging brominated flame retardants in dust.
Anal Bioanal Chem 404(2):459-466.
                                                              7-56

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                                                  JUNE 2014 DRAFT REPORT


Shoeib M, Harner T, Webster GM, et al. (2012) Legacy and current-use flame retardants in house dust from Vancouver, Canada. Environ Pollut
(Oxford, United Kingdom) 169:175-182.

Stapleton HM, Allen JG, Kelly SM, et al. (2008) Alternate and new brominated flame retardants detected in U.S. house dust. Environ Sci Technol
42(18):6910-6916.

Stapleton HM, Klosterhaus S, Eagle S, et al. (2009) Detection of organophosphate flame retardants in furniture foam and U.S. house dust. Environ
Sci Technol 43 (19): 7490-7495.

Xiao H, Shen L, Su Y, et al. (2012) Atmospheric concentrations of halogenated flame retardants at two remote locations: the Canadian High
Arctic and the Tibetan Plateau. Environ Pollut 161:154-161.

Zhou SN, Reiner EJ, Marvin C, et al. (2010) Liquid chromatography-atmospheric pressure photoionization tandem mass spectrometry for analysis
of 36 halogenated flame retardants in fish. J Chromatogr A 1217(5):633-641.
                                                              7-57

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                                                           JUNE 2014 DRAFT REPORT
              Di(2-ethylhexyl) tetrabromophthalate (TBPH)
                                                  Screening Level Toxicology Hazard Summary

This table only contains information regarding the inherent hazards of flame retardant chemicals. Evaluation of risk considers both the hazard and exposure associated with the
substance including combustion and degradation by-products. The caveats listed in the legend and footnote sections must be taken into account when interpreting the hazard
information in the table.	^B	
VL = Very Low hazard L = Low hazard   = Moderate hazard H = High hazard VH = Very High hazard - Endpoints in colored text (VL, L,  , H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].
             Chemical
CASRN
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Di(2-ethylhexyl) tetrabromophthalate   |   26040-51-7
                                M    M
                                                                                          H
 Aquatic toxicity: EPA/DfE criteria are based in large part upon water column exposures which may not be adequate for poorly soluble substances such as many
flame retardants that may partition to sediment and particulates.
                                                                        7-58

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                                                         JUNE 2014 DRAFT REPORT
                                                                                                              CASRN: 26040-51-7
                                                                                                              MW: 706.14
                                                                                                              MF:
                                                                                                              Physical Forms: Liquid
                                                                                                              Neat: Liquid
                                                                                                              Use: Flame retardant
SMILES: O=C(OCC(CCCC)CC)clc(c(c(c(clBr)Br)Br)Br)C(=O)OCC(CCCC)CC
Synonyms: 1,2-Benzenedicarboxylic acid, 3,4,5,6-tetrabromo-, l,2-bis(2-ethylhexyl) ester; TBPH; BEH-TEBP. Related trade names: Uniplex FRP-45; this chemical
is one of the components of the commercial products BZ-54, CN-2065 and Firemaster 550 (FM550).
Chemical Considerations: This is a discrete organic chemical with a MW below 1,000. EPI v4.11 was used to estimate physical/chemical and environmental fate
values where experimental data were lacking.
Polymeric: No
Oligomeric: Not applicable
Metabolites, Degradates and Transformation Products: Mono(2-ethylhexyl) tetrabromophthalate (TBMEFiP) by in vitro metabolism (and the corresponding 2-
ethylhexanol 104-76-7) or hydrolysis (Estimated); di- and tri-brominated analogs of TBPH by anaerobic biodegradation (Estimated) and photodegradation (Davis and
Stapleton, 2009; Bearr et al., 2012; Roberts et al., 2012; Patisaul et al., 2013).
Analog: Confidential analogs
Endpoint(s) using analog values: Carcinogenicity, reproductive,
developmental effects and repeated dose effects
Analog Structure: Not applicable
Structural Alerts: Polyhalogenated aromatic hydrocarbons, immunotoxicity (EPA, 2012).
Risk Phrases: Not classified by Annex VI Regulation (EC) No 1272/2008 (ESIS, 2012).
Hazard and Risk Assessments: Di(2-ethylhexyl) tetrabromophthalate is part of the HPV Data Summary and Test Plan (ACC, 2004).
                                                                     7-59

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JUNE 2014 DRAFT REPORT
Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
PHYSICAL/CHEMICAL PROPERTIES
Melting Point (°C)
Boiling Point (°C)
Vapor Pressure (mm Hg)
Water Solubility (mg/L)
Log Kow
Flammability (Flash Point)
Explosivity
Pyrolysis
pH
pKa
-20
Freezing point approximately -20°C
(Measured)
>300
(Estimated)
<10-8at25°C
(Estimated)
2xlO"9 (Estimated)
12
(Estimated)
Flash Point: >265°C (Measured)
Not expected to form explosive
mixtures with air (Estimated)

Not applicable (Estimated)
Not applicable (Estimated)
Unitex Chemical
Corporation, 2006
EPIv4.11;EPA, 1999
EPIv4.11;EPA, 1999
^^^N. T
EPIv4.11;EPA, 1999
EPIv4.11;EPA, 1999
Unitex Chemical
Corporation, 2006
Professional judgment

Professional judgment
Professional judgment
No study details obtained from a
material safety data sheet (MSDS).
Cutoff value for high boiling point
compounds according to FiPV
assessment guidance.
Cutoff value for nonvolatile
compounds according to FiPV
assessment guidance.
Estimated value is less than the cutoff
value, <0.001 mg/L, for nonsoluble
compounds according to FiPV
assessment guidance.
Estimated value is greater than the
cutoff value, >10, according to
methodology based on HPV
assessment guidance.
Test substance identified as Uniplex
FRP-45 (TBPH >99.5% purity).
No experimental data located; based on
its use as a flame retardant.
No data located.
Does not contain functional groups that
are expected to ionize under
environmental conditions.
Does not contain functional groups that
are expected to ionize under
environmental conditions.
         7-60

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                                                     JUNE 2014 DRAFT REPORT
                                          Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
          PROPERTY/ENDPOINT
                                             DATA
                                      REFERENCE
                                  DATA QUALITY
                                                      HUMAN HEALTH EFFECTS
Toxicokinetics
                                TBPH is estimated to have poor absorption by all routes of exposure based on analogy to a
                                structurally similar confidential analog; however, experimental data for the FM550 (a mixture made
                                up of a sum total of TBB and TBPH of 50%) indicate that absorption of TBPH can occur in rats
                                following oral exposure from gestation through lactation. TBPH was detected in liver tissues of dams
                                following exposure to FM550, but not in any evaluated tissues in the offspring. The monoester,
                                mono(2-ethylhexyl)tetrabromophthalate (TBMEHP 61776-60-1) was identified as the primary
                                metabolite when tested in vitro. There were no metabolites of TBPH detected  in human or rat
                                subcellular fractions; however, in the presence of purified porcine carboxylesterase, the formation of
                                TBMEHP was detected at a rate of 1.08 mol min ' mg protein"1. No phase II metabolites of TBMEHP
                                were detected. TBPH in humans has  not been evaluated. TBPH was also found to be metabolized in
                                vitro in hepatic subcellular fractions  of fathead minnow, common carp, wild-type mice, and snapping
                                turtle. There were no data located regarding toxicokinetic properties of the pure TBPH compound
                                following oral, dermal or inhaled routes of exposure.
Dermal Absorption in vitro
                                                                                         No data located.
Absorption,
Distribution,
Metabolism
& Excretion
Oral, Dermal or Inhaled
Estimated to have poor absorption
by all routes of exposure.
Professional judgment
Based on a closely related confidential
analog and professional judgment.
                                  •egnant rats (3/dose group) were
                                administered 0, 0.1 or 1 mg/kg-day
                                of FM550 in the diet across
                                gestation and through lactation
                                (GD8-PND21).
                                FM500 components including
                                TBPH were detected in the liver
                                tissues in Dams at PND 21 (596
                                ng/g w.w. in high dose, 80.6 ng/g
                                w.w. in low dose, < 18.0 ng/g w.w.
                                in controls). TBPH was not detected
                                in adipose or muscle tissue of dams.
                                The primary metabolite of TBPH
                                (TBMEHP) was not detected in any
                                tissues in dams on PND 21.
                                TBPH was not detected in any pup
                                Patisauletal., 2013
                          Nonguideline study indicates that
                          absorption of this compound can occur
                          in rats through oral exposure; the test
                          substance identified as FM550 is a
                          mixture made up of TBB and TBPH
                          (sum total of the TBB and TBPH
                          components is approximately 50%) and
                          other compounds including IPTPP
                          (CASRN 68937-41-7) and TPP
                          (CASRN 115-86-6); it is unclear if
                          TBPH absorption in pups occurred due
                          to gestational exposure or through
                          lactation; this study was a non-
                          guideline exploratory assessment and
                          used a small number of animals per
                          dose group.
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                                            JUNE 2014 DRAFT REPORT
                                Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
             DATA
      REFERENCE
         DATA QUALITY
                                   adipose tissue.
                                   (Estimated)
  Other
In vitro metabolism experiments
with liver and intestinal subcellular
fractions following exposure to
TBPH identified monoester,
mono(2-
ethylhexyl)tetrabromophthalate
(TBMEHP 61776-60-1) as the
primary metabolite when tested in
vitro. There were no metabolites of
TBPH detected in human or rat
subcellular fractions; however, in
the presence of purified porcine
carboxylesterase, the formation of
TBMEHP was detected at a rate of
1.08 mol min-1 mg protein-1. No
phase II metabolites of TBMEHP
were detected. TBPH in humans has
not been evaluated.
Roberts etal., 2012
TBPH appears to be more recalcitrant
to metabolism than TBB, and may
have a longer half-life after absorption
in vivo which may influence potential
toxicity. The metabolism of TBPH to
TBMEHP may also influence the
toxicity of TBPH, but metabolism may
not occur quickly enough to influence
the bioaccumulation of TBPH.
                                   TBPH was metabolized to
                                   TBMEHP at a rate of 89
                                   pmol/hr/mg esterase in vitro in the
                                   presence of hepatic porcine esterase.
                                Springer etal., 2012
                          Adequate.
                                   In vitro metabolism was measured
                                   in hepatic subcellular fractions in fat
                                   head minnow, common carp, wild-
                                   type mice, and snapping turtle
                                   exposed to by measuring the loss of
                                   the parent compound (TBB and
                                   TBPH) from the Firemaster BZ-54
                                   mixture.
                                   Metabolic loss of TBPH was
                                Bearretal.,2012
                          Test substance identified as Firemaster
                          BZ-54 (TBB and TBPH in
                          approximate 3:1 ratio).
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JUNE 2014 DRAFT REPORT
Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT


Acute Mammalian Toxicity
Acute
Lethality
Oral
Dermal
DATA
observed for all species; metabolism
of TBPH was generally at a lower
rate than TBB in the fathead
minnow, common carp and mouse;
however, TBPH was metabolized in
the snapping turtle while TBB was
not. TBPH metabolism was
significant for all species and cell
fractions. It was concluded by the
authors that some species can
metabolize TBB and TBPH to form
varying metabolites.
REFERENCE
k^^
DATA QUALITY

LOW: Based on oral and dermal LD50 values of > 2,000 mg/kg in rats and rabbits, respectively. And
an inhalation LC50 > 200 mg/L.
Rat oral LD50 = 2,000 mg/kg
Rat oral LD50 > 5,000 mg/kg
Rabbit dermal LD50 > 3,090 mg/kg
J
Rabbit dermal LD50 > 2,000 mg/kg
(Estimated based on analogy)
Bradford et al., 1996
ACC, 2004; Chemtura, 2006
ACC, 2004
Chemtura, 2006
Procedure appears consistent with
OECD methods for acute oral toxicity
testing. Purity: 99.7%.
Study details reported in a secondary
source; also reported in an MSDS;
estimated based on one component of
Firemaster 550 (commercial mixture
containing TBB and TBPH); it is not
certain if this component contains
TBPH.
Study details reported in a secondary
source. Test material was RC9927; FR-
45B; CASRN 26040-51-7 (Purity >
95%).
No study details reported in an MSDS;
estimated based on analogy to a similar
compound to a component of
Firemaster 550 (commercial mixture
containing TBB and TBPH); it is not
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JUNE 2014 DRAFT REPORT
Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT


Inhalation
Carcinogenicity

OncoLogic Results
Carcinogenicity (Rat and Mouse)
Combined Chronic
Toxicity/Carcinogenicity
Other
Genotoxicity

Gene Mutation in vitro
DATA

Rabbit dermal LD50 > 2,000 mg/kg
(Estimated)
Rat 1-hr inhalation LC50 > 200 mg/L
(Estimated based on analogy)
REFERENCE

Chemtura, 2006
Chemtura, 2006
^/
DATA QUALITY
certain if this component contains
TBPH.
No study details reported in an MSDS;
estimated based on one component of
Firemaster 550 (commercial mixture
containing TBB and TBPH); it is not
certain if this component contains
TBPH.
No study details reported in an MSDS;
estimated based on analogy to a similar
compound to a component of
Firemaster 550 (commercial mixture
containing TBB and TBPH); it is not
certain if this component contains
TBPH.
MODERATE: There is uncertainty due to lack of data for this substance. EPA does not expect this
substance to be carcinogenic; however, such effects cannot be ruled out. TBPH is estimated to have
uncertain potential for Carcinogenicity based on analogy to a closely related confidential analog and
professional judgment.



Estimated to have uncertain
potential for Carcinogenicity.
(Estimated by analogy)



Professional judgment
No data located.
No data located.
No data located.
Based on analogy to closely related
chemical classes and professional
judgment.
MODERATE: There was a weakly positive result for chromosome aberrations in human
lymphocytes. There were negative results in 2 other in vitro chromosomal aberration assays using a
component of Firemaster 550 (a commercial mixture containing TBB and TBPH). TBPH did not
cause gene mutations in bacteria or chromosomal aberrations in an in vivo mouse micronucleus
assay.
Negative for gene mutation in
ACC, 2004 (Study details reported in a secondary
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JUNE 2014 DRAFT REPORT
Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT


Gene Mutation in vivo
Chromosomal Aberrations in vitro
Chromosomal Aberrations in vivo
DATA
Salmonella typhimurium TA98,
TA100, TA1535, TA1537, TA1538
with and without metabolic
activation.
Negative; an unspecified component
of a commercial mixture was not
mutagenic in Salmonella
typhimurium or Escherichia coll
when tested in dimethyl sulphoxide.
(Estimated)

Weakly positive for chromosome
aberrations in human lymphocytes
with and without metabolic
activation.
Negative; a similar compound to an
unspecified component of a
commercial mixture did not induce
chromosome aberrations in human
peripheral blood lymphocytes with
and without metabolic activation.
(Estimated based on analogy)
Negative; an unspecified component
of a commercial mixture showed no
evidence of clastogenicity in an in
vitro cytogenic test.
(Estimated)
Negative for clastogenic effects in
an in vivo mouse micronucleus
assay.
REFERENCE

Chemtura, 2006
^^^N. T

ACC, 2004
Chemtura, 2006
Chemtura, 2006
ACC, 2004
DATA QUALITY
source. Test material was RC9927; FR-
45B; CASRN 26040-51-7 (Purity >
95%).
No study details reported in an MSDS;
estimated based on one component of
Firemaster 550 (commercial mixture
containing TBB and TBPH); it is not
certain if this component contains
TBPH.
No data located.
Study details reported in a secondary
source. Test material was RC9927; FR-
45B; CASRN 26040-51-7 (Purity >
95%).
Limited study details reported in an
MSDS; estimated based on analogy to
a similar compound to a component of
Firemaster 550 (commercial mixture
containing TBB and TBPH); it is not
certain if this component contains
TBPH; study conducted according to
OECD 422.
No study details reported in an MSDS;
estimated based on one component of
Firemaster 550 (commercial mixture
containing TBB and TBPH); it is not
certain if this component contains
TBPH.
Study details reported in a secondary
source. Test material was RC9927; FR-
45B; CASRN 26040-51-7 (Purity >
         7-65

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                                                      JUNE 2014 DRAFT REPORT
                                          Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
          PROPERTY/ENDPOINT
             DATA
      REFERENCE
         DATA QUALITY
                                                                                                      95%).
            DNA Damage and Repair
                                                         No data located.
            Other
                                                         No data located.
Reproductive Effects
MODERATE: No reproductive effects were reported in a 2-generation oral (gavage) reproductive
toxicity study in rats at doses up to 165 mg/kg-day (highest dose tested) of Firemaster BZ 54
(commercial mixture of TBB and TBPH) with a larger constituent of TBB. The NOAEL of 165
mg/kg-day falls within the Moderate hazard criteria range; it is possible that effects driven by either
component may occur within the Moderate hazard range if tested at a higher dose. Exposure to
TBPH did not cause adverse changes in testes or ovary weights in a 28-day repeat dose study in rats;
however, while reproductive organs and tissues were examined, other reproductive parameters were
not reported to have been examined. Data from a reproductive/developmental toxicity screen in rats
exposed to a similar compound to a component of Firemaster 550 (commercial mixture containing
TBB and TBPH) indicated histopathological effects in female reproductive organs at doses > 25
mg/kg-day (lowest dose tested; a NOAEL was not identified). It is uncertain if the commercial
mixture contained TBPH.
            Reproduction/Developmental
            Toxicity Screen
Reproductive/developmental
toxicity screen in rats orally
administered 0, 25, 100, 400 mg/kg-
day of a similar compound to an
unspecified component of a
commercial mixture.
Reduced number of successful
pregnancies and viable offspring at
doses of 100  and 400 mg/kg-day;
histopathological effects reported in
thymus and male reproductive
organs (testes and epididymides) at
400 mg/kg-day; histopathological
effects in female reproductive
organs and adrenals at doses of > 25
mg/kg-day.

NOAEL: Not established
Chemtura, 2006
Limited study details reported in an
MSDS; estimated based on analogy to
a similar compound to a component of
Firemaster 550 (commercial mixture
containing TBB and TBPH); it is not
certain if this component contains
TBPH; study conducted according to
OECD 422.
                                                                  7-66

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Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT






































Combined Repeated Dose with
Reproduction/ Developmental
Toxicity Screen


















Reproduction and Fertility Effects




DATA
LOAEL: 25 mg/kg-day (lowest dose
tested)
(Estimated based on analogy)
Estimated to have moderate
potential for reproductive effects.
(Estimated by analogy)
2-generation oral (gavage)
reproductive toxicity study in rats
administered 15, 50, or 165 mg/kg-
day Firemaster BZ54; FO generation
was treated 10 weeks prior to
pairing through the mating period.
Males were treated until
termination; females were treated
through gestation and lactation, and
until termination on PND 2 1 ; pup
selected (30/sex/dose) to continue as
Fl parental generation began
treatment on PND 22 and continued
treatment similar to the FO
generation.
No adverse effects on reproductive
performance or fertility in rats.
NOAEL: 165 mg/kg-day (highest
dose tested)
LOAEL: Not established
(Estimated)
Rat, 28-day repeat dose dietary
toxicity study; 0, 200, 2,000, and
20,000 ppm in diet (~0, 21.1, 211,
2,1 10 mg/kg-day); There were no
adverse effects on a full
REFERENCE



Professional judgment


MPI Research, 2008a

P^



^/














ACC, 2004




DATA QUALITY



Estimated based on a closely related
confidential analog and professional
judgment.
Test substance: Firemaster BZ 54
(commercial mixture of TBB and
TBPH) with a larger constituent of
TBB; it is not clear which component
or components of the mixture are
driving the reported developmental
effects.














Study details reported in a secondary
source. Test material was RC9927; FR-
45B; CASRN 26040-51-7 (Purity >
95%). It is reported that a full
complement of male and female
         7-67

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Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT


Other
Developmental Effects
[Reproduction/ Developmental
DATA
complement of male and female
reproductive organs and tissues
examined by gross necropsy and
histopathology; No changes in testes
and ovary weights.
NOAEL: 2,000 ppm (2,1 10 mg/kg-
day - highest dose tested)
LOAEL: Not established ^^^
Potential for reproductive effects
following long-term exposure to
BZ-54 HP
(Estimated)
REFERENCE
^
Chemtura, 2008
^/
DATA QUALITY
reproductive tissues and organs were
evaluated, however, the list of tissues
and organs is unspecified. While
reproductive organs and tissues were
examined, other reproductive
parameters were not reported to be
examined.
No study details reported in an MSDS;
Estimated based on BZ-54 HP
(commercial mixture containing TBB
and TBPH); it is not clear which
component is driving repeated dose
effects.
MODERATE: Developmental effects were reported in a 2-generation reproductive toxicity study in
rats and a prenatal study in rats exposed to CN-2065 (a commercial mixture of TBB and TBPH with
the predominant constituent being TBB). Developmental effects were reported at doses of 165 mg/kg-
day and 100 mg/kg-day in the 2-generation and prenatal studies, respectively. Both studies had a
NOAEL of 50 mg/kg-day which falls within the Moderate hazard criteria range. It is not clear which
component or components of the commercial mixture caused the reported developmental effects.
Development/neurodevelopmental effects were reported in a study in pregnant Wistar rats
administered a FM550 mixture (sum total of TBB and TBPH approximately 50%) during gestation
though lactation (GD8 - PND21); developmental effects included early female puberty, weight gain,
altered exploratory behavior, and increased male left ventricle thickness (LOAEL = 1 mg/kg-day,
NOAEL = 0.1 mg/kg-day). It is uncertain which component or components of the FM 550 mixture is
driving the reported developmental effects. While the FM 550 mixture data indicates a High hazard
potential, it may be the other components driving the reported toxicity. Gestational exposure to the
TBPH monoester metabolite TBMEHP at a dose of 200 mg/kg-day resulted in an increased number
of altered seminiferous cords (MNGs) per cord area in male fetuses from exposed rat dams.
Experimental data indicated no effects on embryonic survival or development in exposed zebrafish
embryos.
Estimated to have moderate [Professional judgment
Estimated based on a closely related
         7-68

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                                             JUNE 2014 DRAFT REPORT
                                Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
             DATA
      REFERENCE
         DATA QUALITY
  Toxicity Screen
potential for developmental effects.
(Estimated by analogy)
                           confidential analog and professional
                           judgment.
  Combined Repeated Dose with
  Reproduction/ Developmental
  Toxicity Screen
2-generation oral (gavage)
reproductive toxicity study in rats
administered 15, 50, or 165 mg/kg-
day; FO generation was treated 10
weeks prior to pairing through the
mating period. Males were treated
until termination; females were
treated through gestation and
lactation, and until termination on
PND 21; pup selected (30/sex/dose)
to continue as Fl parental
generation began treatment on PND
22 and continued treatment similar
to the FO generation.
Parental toxicity: lower body
weights and body weight gains
during  premating period in parental
and Fl females at highest dose;
Lower body weights in the
premating period in Fl males; body
weight gains were not affected in
males.
Developmental toxicity: at highest
dose, lower body weights at birth
and throughout lactation were
reported in both generations of
offspring (Fl and F2); this resulted
in lower premating body weights of
the first female generation.
Decreased spleen weights at
lactation day 21 in Fl male pups
MPI Research, 2008a
Study details reported in an
unpublished report; test substance:
Firemaster BZ 54 (CN-2065)
commercial mixture of TBB and TBPH
with the predominant constituent being
TBB; it is not clear which component
or components of the mixture are
driving the reported developmental
effects.
                                                         7-69

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                                        JUNE 2014 DRAFT REPORT
                             Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                               and F2 male and female pups.

                               Parental toxicity:
                               NOAEL: 50 mg/kg-day
                               LOAEL: 165 mg/kg-day

                               Developmental toxicity:
                               NOAEL: 50 mg/kg-day
                               LOAEL: 165 mg/kg-day
                                                   7-70

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                                            JUNE 2014 DRAFT REPORT
                                Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
             DATA
      REFERENCE
         DATA QUALITY
  Prenatal Development
Prenatal study in rats exposed to 0,
50, 100, 300 mg/kg-d Firemaster
BZ54 (CN-2065) on GD 6-19.
Maternal toxicity: increased
incidence of animals with sparse
hair in abdominal region, lower
gestation body weights and body
weight gain, and lower gestation
food consumption at doses > 100
mg/kg-day.
Developmental toxicity:  decreased
fetal weight at 100 mg/kg-day;
increased incidence of fused
cervical vertebral neural arches
(litter incidence of 8%) in fetuses at
300 mg/kg-day; increased litter
incidence of fetal ossification
variations involving additional
ossification centers to the cervical
vertebral neural arches, incomplete
ossified skull bones (jugal, parietal,
and squamosal), and unossified
sternebrae.
MPI Research, 2008b
                                   Maternal toxicity:
                                   NOAEL
                                   LOAEL:
         50 mg/kg-day
         100 mg/kg-day
                                   Developmental toxicity:
                                   NOAEL: 50 mg/kg-day
                                   LOAEL: 100 mg/kg-day based on
                                   decreased fetal weight
                                   (Estimated)
Study details reported in an
unpublished report Test substance:
Firemaster BZ54 (CN-2065);
commercial mixture of TBB and TBPH
with the predominant constituent being
TBB; it is not clear which component
or components of the mixture are
driving the reported developmental
effects.
                                                         7-71

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                                             JUNE 2014 DRAFT REPORT
                                 Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   Fischer Rats were administered the
                                   TBPH metabolite TBMEHP at 0,
                                   200, and 500 mg/kg-day by oral
                                   gavage on GDs 18 and 19.

                                   Maternal toxicity: There were no
                                   treatment related effects on liver,
                                   kidney, adrenal gland, or ovary
                                   weights at any dose. At the highest
                                   dose, there was a significantly
                                   decreased level of the liver enzyme
                                   alkaline phosphatase and a
                                   decreased level of alanine
                                   transaminase. Decreased serum
                                   calcium levels and increased blood
                                   urea nitrogen levels were also
                                   reported at the highest dose. There
                                   was a dose-dependent decrease in
                                   cholesterol levels and serum T3
                                   levels; there was no  effect on serum
                                   T4 levels.
                                   There were no abnormalities in the
                                   kidneys or thyroids following
                                   treatment; however,  there were
                                   effects (increased hepatocytes with
                                   mitotic spindles and increased
                                   hepatocytes with dense
                                   hypereosinophilic cytoplasm and
                                   condensed, fragmented nuclei)
                                   reported. These effects are
                                   indications of proliferation and
                                   apoptosis.

                                   Developmental toxicity: The
                    Springer etal., 2012
                    Estimated based on the assumption of
                    total conversion of TBPH to
                    TBMEHP; the test substance is
                    identified as the TBPH metabolite
                    TBMEHP; The doses reported are
                    based on TBMEHP; though TBPH is
                    expected to metabolize to TBMEHP, it
                    is uncertain if these effects would
                    occur or at what dose effects might
                    occur following TBPH exposure.
                                                         7-72

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Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT











Postnatal Development Jl
Prenatal and Postnatal
Development
Developmental Neurotoxicity
Other
DATA
number of manifestation of altered
seminiferous cords (MNGs) per
cord area were significantly
increased in fetuses from exposed
dams. There were no reported
significant changes in fetal
testosterone production.
Maternal toxicity:
NOAEL: 200 mg/kg-day
LOAEL: 500 mg/kg-day (liver
effects)
Developmental toxicity:
NOAEL: Not established
LOAEL: 200 mg/kg-day (increased
number of fetal MNGs)
(Estimated)




Potential for developmental effects
following long-term exposure to
BZ-54 HP
(Estimated)
Pregnant Wistar rats were
administered 0, 0.1 or 1 mg/kg-day
of FM550 in the diet during
gestation and through lactation
REFERENCE

^^^
k^^
^/





Chemtura, 2008
Patisauletal., 2013
DATA QUALITY





No data located.
No data located.

No data located.
No study details reported in an MSDS;
Estimated based on BZ-54 HP
(commercial mixture containing TBB
and TBPH); it is not clear which
component is driving repeated dose
effects.
Estimated based on data for FM550
mixture; non guideline study; the test
substance is a mixture made up of TBB
and TBPH (sum total of TBB and
         7-73

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                                             JUNE 2014 DRAFT REPORT
                                Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   (GD8-PND21);
                                   Maternal toxicity: Increased serum
                                   thyroxine (T4) levels in the high
                                   dose dams compared to controls was
                                   reported. There was no significant
                                   change in triiodothyronine (T3)
                                   levels in dam serum. Decreased
                                   hepatic carboxylesterease activity
                                   was also reported in dams in the
                                   high dose group.
                                   Developmental toxicity: female
                                   offspring in the high dose group
                                   displayed a significantly earlier
                                   vaginal opening when compared to
                                   controls. A statistically significant
                                   increase in weight was reported in
                                   both males and females in the high
                                   dose group at PND 120. This effect
                                   persisted through PND 180 to PND
                                   220 with high dose males and
                                   females having significantly higher
                                   weights than same sex controls. A
                                   dose-dependent decrease in the
                                   number of rats to enter with open
                                   arms, (indicating anxiety), was
                                   reported in both male and female
                                   offspring. Increased blood glucose
                                   levels were reported in male
                                   offspring in the high-dose group
                                   compared to controls. There was no
                                   statistically significant difference in
                                   heart weight of male or female
                                   offspring. Left ventricular (LV) free
                                   wall thickness was significantly
                                              TBPH approximately 50%) and other
                                              compounds including IPTPP (CASRN
                                              68937-41-7) and TPP (CASRN 115-
                                              86-6); it is not clear which component
                                              or components of the mixture are
                                              driving the reported developmental
                                              effects.
                                                         7-74

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                                                       JUNE 2014 DRAFT REPORT
                                           Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
           PROPERTY/ENDPOINT
             DATA
      REFERENCE
         DATA QUALITY
                                             increased in male offspring in the
                                             high dose group; there were no
                                             changes in LV thickness in females
                                             at any dose.

                                             Maternal Toxicity:
                                             NOAEL: 0.1 mg/kg-day
                                             LOAEL: 1 mg/kg-day

                                             Developmental toxicity:
                                             NOAEL: 0.1 mg/kg-day
                                             LOAEL: 1 mg/kg-day (based on
                                             early vaginal opening in females,
                                             increased weight in males and
                                             females, decreased open arm
                                             behavior, increased blood glucose
                                             levels in males and increased LV
                                             thickness in males)
                                             (Estimated)
                                             Zebrafish embryos were exposed
                                             under static conditions to purified
                                             TBPH at concentrations up to 10
                                             uM from 5.25 -96 hours post
                                             fertilization (hpf).
                                             There were no effects on embryonic
                                             survival or development.
                                McGeeetal., 2013
                          Zebrafish is a nonstandard species;
                          current DfE criteria for this endpoint
                          are based on gestational and/or
                          postnatal exposure to mammalian
                          species. Thus, this study cannot be
                          used to assign a hazard designation for
                          the developmental endpoint.
Neurotoxicity
MODERATE: Estimated based on analogy to a similar compound to a component of Firemaster 550
(commercial mixture containing TBB and TBPH). There is potential for neurological effects after
breathing or swallowing large amounts or after long-term exposure to this analog. There were no
neurotoxic effects reported in a 28-day oral toxicity study in rats treated with the analog.
            Neurotoxicity Screening Battery
            (Adult)
28-day sub-chronic oral toxicity
study in rats treated with 0, 160,
400, 1,000 mg/kg-day;
Chemtura, 2006
Limited study details reported in an
MSDS; neurotoxicity was evaluated in
this study; estimated based on one
                                                                   7-75

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                                           JUNE 2014 DRAFT REPORT
                                Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
             DATA
      REFERENCE
         DATA QUALITY
                                  No neurotoxicity effects were
                                  reported.

                                  NOAEL: 1,000 mg/kg-day (highest
                                  dose tested)
                                  LOAEL: Not established
                                  (Estimated)
                                                          component of Firemaster 550
                                                          (commercial mixture containing TBB
                                                          and TBPH); it is not certain if this
                                                          component contains TBPH.
  Other
Potential for neurological effects
following long-term exposure to
BZ-54 HP
(Estimated)
Chemtura, 2008
                                  Potential for neurological effects
                                  after breathing or swallowing large
                                  quantities or repeated exposure over
                                  a prolonged period of time is
                                  possible for a similar compound to
                                  an unspecified component of the
                                  commercial mixture.
                                  (Estimated based on analogy)
                                Chemtura, 2006
No study details reported in an MSDS;
Estimated based on BZ-54 HP
(commercial mixture containing TBB
and TBPH); it is not clear which
component is driving repeated dose
effects.
                          No study details reported in an MSDS;
                          estimated based on analogy to a similar
                          compound to a component of
                          Firemaster 550 (commercial mixture
                          containing TBB and TBPH); it is not
                          certain if this component contains
                          TBPH.
                                                        7-76

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                                                      JUNE 2014 DRAFT REPORT
                                          Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
          PROPERTY/ENDPOINT
             DATA
REFERENCE
DATA QUALITY
Repeated Dose Effects
MODERATE: There was a slight decrease in body weight along with decreased calcium and
phosphorus levels in female rats with a LOAEL= 20,000 ppm (2,110 mg/kg-day). While this effect is
known to occur at values that fall within the hazard criteria range for a LOW hazard designation,
the NOAEL is identified as 2,000 ppm (211 mg/kg-day). The hazard criteria values are based on 90-
day studies; therefore, the hazard criteria values are tripled for chemicals evaluated in 28-day
studies. The LOAEL of 2,110 mg/kg-day remains in the Low hazard category, while the NOAEL of
211 mg/kg-day falls within the Moderate hazard designation (30 - 300 mg/kg-day). There is
uncertainty as to where effects may occur. A Moderate hazard was designated as a conservative
approach. TBPH is also estimated to have a Moderate potential for liver effects cerebral
hemorrhages based on a closely related confidential analog and professional judgment and is
estimated to have kidney, liver, adrenal, thymus, developmental, reproductive, and neurological
effects following long-term exposure to commercial mixtures that included TBPH. There was an
increased incidence of sparse hair in abdominal region, reduced body weight, and reduced food
consumption in dams during gestation in  a prenatal study in rats exposed to CN-2065 (commercial
mixture of TBB and TBPH with the predominant constituent being TBB) on GD 6-19 at doses > 100
mg/kg-day (NOAEL = 50 mg/kg-day). Reduced body weight and body weight gain during the
premating period in parental FO and Fl female rats treated with 165 mg/kg-day CN-2065 (NOAEL =
50 mg/kg-day) was also reported in a 2-generation oral reproductive toxicity in rats.
                                             Rat, 28-day dietary toxicity study; 0,
                                             200, 2,000, and 20,000 ppm in diet
                                             (~0, 21.1, 211, 2,110 mg/kg-day);
                                             There was no mortality, clinical
                                             signs of toxicity, or adverse effects
                                             on examined organs or tissues;
                                             There was a slight decrease in body
                                             weight along with decreased
                                             calcium and phosphorus levels in
                                             females in the 20,000 ppm (2,110
                                             mg/kg-day) group.

                                             NOAEL: 2,000 ppm (211 mg/kg-
                                             day)
                                             LOAEL: 20,000 ppm (2,110 mg/kg-
                                ACC, 2004
                    Study details reported in a secondary
                    source. Test material was RC9927; FR-
                    45B; CASRN 26040-51-7 (Purity >
                    95%). Doses were reported as ppm in
                    the diet but were converted to
                    mg/kg/day using EPA 1988 reference
                    values for body weight and food
                    consumption. The hazard criteria for
                    repeat dose toxicity is based on 90 day
                    studies; the hazard criteria values are
                    tripled for chemicals evaluated in 28-
                    day studies. The LOAEL of 2,110
                    mg/kg-day remains in the Low hazard
                    category, while the NOAEL of 211
                    mg/kg-day falls within the Moderate
                                                                  7-77

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                                             JUNE 2014 DRAFT REPORT
                                Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   day) based on slightly decreased
                                   body weight and decreased calcium
                                   and phosphorus levels (females)
                                              hazard designation (30-300 mg/kg-
                                              day). There is uncertainty as to where
                                              effects may occur.
                                   Estimated to have moderate
                                   potential for liver effects and
                                   concern for cerebral hemorrhages.
                                   (Estimated by analogy)
                    Professional judgment
                    Estimated based on a closely related
                    confidential analog and professional
                    judgment.
                                   Potential for neurological effects
                                   after breathing or swallowing large
                                   quantities or repeated exposure over
                                   a prolonged period of time is
                                   possible for a similar compound to
                                   an unspecified component of the
                                   commercial mixture
                                   (Estimated  based on analogy)
                    Chemtura, 2006
                    No study details reported in an MSDS;
                    estimated based on analogy to a similar
                    compound to a component of
                    Firemaster 550 (commercial mixture
                    containing TBB and TBPH); it is not
                    certain if this component contains
                    TBPH.
                                   Potential for kidney and liver effects
                                   following long-term exposure to
                                   BZ-54 HP
                                   (Estimated)
                    Chemtura, 2008
                    No study details reported in an MSDS;
                    Estimated based on BZ-54 HP
                    (commercial mixture containing TBB
                    and TBPH); it is not clear which
                    component is driving repeated dose
                    effects.
                                   2-generation oral (gavage)
                                   reproductive toxicity study in rats
                                   administered 15, 50, or 165 mg/kg-
                                   day; FO generation was treated 10
                                   weeks prior to pairing through the
                                   mating period. Males were treated
                                   until termination; females were
                                   treated through gestation and
                                   lactation, and until termination on
                                   PND 21; pup selected (30/sex/dose)
                                   to continue as Fl parental
                                   generation began treatment on PND
                    MPI Research, 2008a
                    Study details reported in an
                    unpublished report; test substance:
                    Firemaster BZ 54 (CN-2065)
                    commercial mixture of TBB and TBPH
                    with the predominant constituent being
                    TBB; it is not clear which component
                    or components of the mixture are
                    driving the reported developmental
                    effects.
                                                         7-78

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                                            JUNE 2014 DRAFT REPORT
                                Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   22 and continued treatment similar
                                   to the FO generation.
                                   Parental toxicity: lower body
                                   weights and body weight gains
                                   during premating period in parental
                                   and Fl females at highest dose;
                                   Lower body weights in the
                                   premating period in Fl males; body
                                   weight gains were not affected in
                                   males.

                                   Parental toxicity:
                                   NOAEL: 50 mg/kg-day
                                   LOAEL: 165 mg/kg-day (reduced
                                   body weight and body weight gain)
                                   (Estimated)
                                   In a prenatal study in rats exposed to
                                   0, 50, 100, 300 mg/kg-d on GD 6-
                                   19; dams experienced increased
                                   incidence of animals with sparse
                                   hair in abdominal region, lower
                                   gestation body weights and body
                                   weight gain, and lower gestation
                                   food consumption at doses > 100
                                   mg/kg-day.

                                   NOAEL: 50 mg/kg-day
                                   LOAEL (maternal):  100 mg/kg-day
                                   (Estimated)
                   MPI Research, 2008b
                    Study details reported in an
                    unpublished report Test substance:
                    Firemaster BZ54 (CN-2065);
                    commercial mixture of TBB and TBPH
                    with the predominant constituent being
                    TBB; it is not clear which component
                    or components of the mixture are
                    driving the reported developmental
                    effects.
                                   28-day sub-chronic oral toxicity
                                   study in rats treated with 0, 160,
                                   400, 1,000 mg/kg-day;
                                   Kidney effects were reported.
                   Chemtura, 2006
                    Limited study details reported in an
                    MSDS; neurotoxicity was evaluated in
                    this study; estimated based on one
                    component of Firemaster 550
                                                        7-79

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                                                      JUNE 2014 DRAFT REPORT
                                          Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
          PROPERTY/ENDPOINT
             DATA
      REFERENCE
         DATA QUALITY
                                             NOAEL: 160mg/kg-day
                                             LOAEL: 1,000 mg/kg-day based on
                                             kidney effects
                                             (Estimated)
                                                          (commercial mixture containing TBB
                                                          and TBPH); it is not certain if this
                                                          component contains TBPH.
Skin Sensitization
LOW: TBPH is not a skin sensitizer in guinea pigs. There were positive results for skin sensitization
following exposure to components of commercial mixtures containing TBPH. It is not certain which
component or components caused the reported effects.
            Skin Sensitization
Negative for skin sensitization in
guinea pigs
                                             The commercial mixture Firemaster
                                             BZ 54 is a skin sensitizer.
                                             (Estimated)
                                             An unspecified component of the
                                             commercial mixture was reported to
                                             be a sensitizer in a M&K
                                             sensitization assay.
                                             (Estimated)
                                             An unspecified component of the
                                             commercial mixture was not
                                             sensitizing in a Buehler test.
                                             (Estimated)
ACC, 2004
                                Chemtura, 2013
                                Chemtura, 2006
                                Chemtura, 2006
Study details reported in a secondary
source. Test material was RC9927; FR-
45B; CASRN 26040-51-7 (Purity >
95%).
                          Limited study details reported in an
                          MSDS; Test substance: Firemaster BZ
                          54 (commercial mixture of TBB and
                          TBPH) with a larger constituent of
                          TBB; it is not clear which component
                          or components of the mixture are
                          driving the reported effects.
                          No study details reported in an MSDS;
                          estimated based on one component of
                          Firemaster 550 (commercial mixture
                          containing TBB and TBPH); it is not
                          certain if this component contains
                          TBPH.
                          No study details reported in an MSDS;
                          estimated based on one component of
                          Firemaster 550 (commercial mixture
                          containing TBB and TBPH); it is not
                          certain if this component contains
                          TBPH.
                                                                  7-80

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JUNE 2014 DRAFT REPORT
Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
Respiratory Sensitization
[Respiratory Sensitization
Eye Irritation

Eye Irritation
Dermal Irritation

Dermal Irritation
DATA
REFERENCE
DATA QUALITY
No data located.

|No data located.
LOW: TBPH is a slight eye irritant in rabbits. Experimental studies reported mild irritation to
components of a commercial mixture.
Slight eye irritant in rabbits
The commercial mixture Firemaster
BZ 54 is a slight eye irritant.
(Estimated)
An unspecified component of the
commercial mixture was reported to
be a slight eye irritant in rabbits.
(Estimated)
No eye irritation was reported in
rabbits for a similar compound to an
unspecified component of the
commercial mixture.
(Estimated based on analogy)
ACC, 2004
Chemtura, 2013
^/
Chemtura, 2006
Chemtura, 2006
Study details reported in a secondary
source. Test material was RC9927; FR-
45B; CASRN 26040-51-7 (Purity >
95%).
Limited study details reported in an
MSDS; Test substance: Firemaster BZ
54 (commercial mixture of TBB and
TBPH) with a larger constituent of
TBB; it is not clear which component
or components of the mixture are
driving the reported effects.
No study details reported in an MSDS;
estimated based on one component of
Firemaster 550 (commercial mixture
containing TBB and TBPH); it is not
certain if this component contains
TBPH.
No study details reported in an MSDS;
estimated based on analogy to a similar
compound to a component of
Firemaster 550 (commercial mixture
containing TBB and TBPH); it is not
certain if this component contains
TBPH.
LOW: TBPH is a slight skin irritant in rabbits. Experimental data reported mild irritation from
components of a commercial mixture.
Slight skin irritant in rabbits
ACC, 2004
Study details reported in a secondary
source. Test material was RC9927; FR-
         7-81

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                                                      JUNE 2014 DRAFT REPORT
                                          Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
          PROPERTY/ENDPOINT
             DATA
REFERENCE
DATA QUALITY
                                                                                                      45B; CASRN 26040-51-7 (Purity >
                                                                                                      95%).
                                            No skin irritation was reported in
                                            rabbits for a similar compound to an
                                            unspecified component of the
                                            commercial mixture.
                                            (Estimated based on analogy)
                                Chemtura, 2006
                    No study details reported in an MSDS;
                    estimated based on analogy to a similar
                    compound to a component of
                    Firemaster 550 (commercial mixture
                    containing TBB and TBPH); it is not
                    certain if this component contains
                    TBPH.
                                             An unspecified component of the
                                             commercial mixture was reported to
                                             be a slight skin irritant in rabbits.
                                             (Estimated)
                                Chemtura, 2006
                    No study details reported in an MSDS;
                    estimated based on one component of
                    Firemaster 550 (commercial mixture
                    containing TBB and TBPH); it is not
                    certain if this component contains
                    TBPH.
                                             The commercial mixture Firemaster
                                             BZ 54 is a mild skin irritant.
                                             (Estimated)
                                Chemtura, 2013
                    Limited study details reported in an
                    MSDS; Test substance: Firemaster BZ
                    54 (commercial mixture of TBB and
                    TBPH) with a larger constituent of
                    TBB; it is not clear which component
                    or components of the mixture are
                    driving the reported effects.
Endocrine Activity
One study indicated that TBPH does not cause changes in estrogenic and androgenic activity in yeast
reporter-gene assays. Increased serum thyroxine (T4) levels were reported in the serum of dams
following oral administration to FM500 (mixture of 50% sum total of TBB and TBPH); other
components of the mixture are TPP and IPTPP. It is unclear which component or components of the
mixture are driving the endocrine activity effects.
                                             Potential for adrenal effects
                                             following long-term exposure to
                                             BZ-54 HP
                                             (Estimated)
                                Chemtura, 2008
                    No study details reported in an MSDS;
                    Estimated based on BZ-54 HP
                    (commercial mixture containing TBB
                    and TBPH); it is not clear which
                    component is driving repeated dose
                    effects.
                                                                  7-82

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                                            JUNE 2014 DRAFT REPORT
                                Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   Negative for estrogenic and
                                   androgenic activity in yeast
                                   reporter-gene assays (Beta-
                                   galactosidase assay and
                                   bioluminescent estrogen and
                                   androgen screens using
                                   Saccharomyces cerevisiae).
                   Ezechias et al., 2012
                    Test substance purity: 99.5%
                                   Pregnant Wistar rats were
                                   administered 0, 0.1 or 1 mg/kg-day
                                   of FM550 in the diet during
                                   gestation and through lactation
                                   (GD8-PND21);
                                   Increased serum thyroxine (T4)
                                   levels (increase of 65%) in the high
                                   dose dams compared to controls was
                                   reported. There was no significant
                                   change in triiodothyronine (T3)
                                   levels in dam serum. There was no
                                   reported statistically significant
                                   change in T4 or T3 levels in pup
                                   serum on PND 21 when compared
                                   to controls.
                                   (Estimated)
                   Patisaul et al., 2013
                                   Reproductive/developmental
                                   toxicity screen in rats orally
                                   administered 0, 25, 100, 400 mg/kg-
                                   day of a similar compound to an
                                   unspecified component of a
                                   commercial mixture. Reduced
                                   number of successful pregnancies
                                   and viable offspring at doses of 100
                                   and 400 mg/kg-day;
                                   histopathological effects reported in
                    Chemtura, 2006
                    Estimated based on data for FM550
                    mixture; non guideline study; the test
                    substance identified as FM550 is a
                    mixture made up of TBB, TBPH
                    (sum total of TBB and TBPH is
                    approximately 50%), TPP and
                    IPTPP; it is not clear which
                    component or components of the
                    mixture are driving the reported
                    endocrine activity effects.
                    Limited study details reported in an
                    MSDS; estimated based on analogy to
                    a similar compound to a component of
                    Firemaster 550 (commercial mixture
                    containing TBB and TBPH); it is not
                    certain if this component contains
                    TBPH; study conducted according to
                    OECD 422.
                                                         7-83

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JUNE 2014 DRAFT REPORT
Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT

Immunotoxicity

Immune System Effects
DATA
thymus and male reproductive
organs (testes and epididymides) at
400 mg/kg-day; histopathological
effects in female reproductive
organs and adrenals at doses of 25
mg/kg-day.
NOAEL: Not established
LOAEL: 25 mg/kg-day (lowest dose
tested)
(Estimated based on analogy)
REFERENCE
k^^
DATA QUALITY

No data located. There is potential for immunotoxicity based on the structural alert for
polyhalogenated aromatic hydrocarbons and professional judgment.
Potential for thymus effects
following long-term exposure to
BZ-54 HP
(Estimated)
Potential for immunotoxicity based
on the structural alert for
polyhalogenated aromatic
hydrocarbons
(Estimated)
Chemtura, 2008
7
Professional judgment
No study details reported in an MSDS;
Estimated based on BZ-54 HP
(commercial mixture containing TBB
and TBPH); it is not clear which
component is driving repeated dose
effects.
Estimated based on a structural alert
for polyhalogenated aromatic
hydrocarbons and professional
judgment.
ECOTOXICITY
ECOSAR Class
Acute Aquatic Toxicity
Fish LC50
Esters
LOW: Based on an estimated Log Kow of 12 and the fact that the experimental effect levels in fish,
daphnia, and algae were above the estimated water solubility (1.98 E-9 mg/L), NES are predicted for
this endpoint.
Fish 96-hour LD50 = No effects at
saturation (NES)
(Experimental)
Submitted confidential study
Study details reported in a submitted
confidential study.
         7-84

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                                           JUNE 2014 DRAFT REPORT
                                Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
DATA
      REFERENCE
         DATA QUALITY
                                  Oncorhynchus mykiss rainbow trout
                                  96-hour LC50> 12 mg/L
                                  (Estimated)
                   Chemtura, 2006,2013
                                  Oncorhynchus mykiss rainbow trout
                                  96-hour LC50 =1.6 mg/L
                                  (Estimated by analogy)
                   Chemtura, 2006
                                  Fathead minnow 96-hour LC50
                                  10.8 mg/L
                                  (Estimated by analogy)
                   Chemtura, 2006
                                  Fish 96-hour LC5C
                                  (Estimated)
   = 0.00015 mg/L
ECOSARvl.ll
                          No study details reported in an MSDS;
                          estimated based on one component of
                          Firemaster 550 and for Firemaster BZ-
                          54 (commercial mixtures containing
                          TBB and TBPH); Based on log Kow of
                          12 and the reported effect level was
                          above the estimated water solubility
                          (1.983 x 10'9 mg/L), NES are predicted
                          for this endpoint.
                          No study details reported in an MSDS;
                          estimated based on analogy to a similar
                          compound to a component of
                          Firemaster 550 (commercial mixture
                          containing TBB and TBPH); it is not
                          certain if this component contains
                          TBPH. Based on log Kow of 12 and the
                          reported effect level was above the
                          estimated water solubility (1.983 x 10"9
                          mg/L), NES are predicted for this
                          endpoint.
                          No study details reported in an MSDS;
                          estimated based on analogy to a similar
                          compound to a component of
                          Firemaster 550 (commercial mixture
                          containing TBB and TBPH); it is not
                          certain if this component contains
                          TBPH. Based on log Kow of 12 and the
                          reported effect level was above the
                          estimated water solubility (1.983 x 10"9
                          mg/L), NES are predicted for this
                          endpoint.
NES: The estimated log Kow of 12 for
this chemical exceeds the SAR
                                                        7-85

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                                                      JUNE 2014 DRAFT REPORT
                                          Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
          PROPERTY/ENDPOINT
             DATA
      REFERENCE
         DATA QUALITY
                                             ECOSAR: Esters
                                                          limitation for log Kow of 5.0; NES are
                                                          predicted for these endpoints.
                                             Fish 96-hour LC50 = 6.7x10"7 mg/L
                                             (Estimated)
                                             ECOSAR: Neutral organics
                                ECOSAR vl. 11
                          NES: The estimated log Kow of 12 for
                          this chemical exceeds the SAR
                          limitation for log Kow of 5.0; NES are
                          predicted for these endpoints.

                          Narcosis classes (neutral organics) are
                          provided for comparative purposes;
                          DfE assessment methodology will use
                          the lowest estimated toxicity value
                          provided by ECOSAR classes that
                          have a more specific  mode of action
                          relative to narcosis.
Daphnid LC50
Daphnia magna 48- hour EC50=
0.30 mg/L (immobility)
(Experimental)
ACC, 2004
                                             Daphnia magna 48-hour LC50:
                                             2.44 mg/L
                                             (Estimated by analogy)
                                Chemtura, 2006

Study details reported in a secondary
source. Test material was RC9927; FR-
45B; CASRN 26040-51-7 (Purity >
95%). Based on an estimated log Kow
of 12 and the fact that the experimental
effect levels in Daphnia were above the
estimated water solubility (1.983 x 10"9
mg/L), NES are predicted for this
endpoint.
                          No study details reported in an MSDS;
                          estimated based on analogy to a similar
                          compound to a component of
                          Firemaster 550 (commercial mixture
                          containing TBB and TBPH); it is not
                          certain if this component contains
                          TBPH. Based on log Kow of 12 and the
                          reported effect level was above the
                          estimated water solubility (1.983 x 10"9
                          mg/L), NES are predicted for this
                                                                  7-86

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                                            JUNE 2014 DRAFT REPORT
                                Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                                                                             endpoint.
                                  Daphnia magna 48-hour EC50 =
                                  0.42 mg/L
                                  (Estimated)
                   Submitted confidential study;
                   Chemtura, 2006, 2013
                    Study details reported in an
                    unpublished study submitted to EPA.
                    Limited study details were also
                    reported in an MSDS; estimated based
                    on one component of Firemaster 550
                    and for Firemaster BZ-54  (commercial
                    mixture containing TBB and TBPH);
                    Based on log Kow of 12 and the
                    reported effect level was above the
                    estimated water solubility (1.983 x 10"9
                    mg/L), NES are predicted for this
                    endpoint.
                                  Daphnia magna 24-hour EC50 =1.2
                                  mg/L
                                  (Estimated)
                   Submitted confidential study
                    Study details reported in an
                    unpublished study submitted to EPA;
                    Limited study details were also
                    reported in an MSDS; estimated based
                    on one component of Firemaster 550
                    and for Firemaster BZ-54  (commercial
                    mixtures containing TBB  and TBPFi);
                    Based on log Kow of 12 and the
                    reported effect level was above the
                    estimated water solubility.
                                   Daphnia 48-hour LC50 = 0.0001
                                   mg/L
                                   (Estimated)
                                   ECOSAR: Esters
                   ECOSARvl.ll
                    NES: The estimated log Kow of 12 for
                    this chemical exceeds the SAR
                    limitation for log Kow of 5.0; NES are
                    predicted for these endpoints.
                                   Daphnid 48-hour LC50 = 9.53xlO"7
                                   mg/L
                                   (Estimated)
                                   ECOSAR: Neutral organics
                   ECOSARvl.ll
                    NES: The estimated log Kow of 12 for
                    this chemical exceeds the SAR
                    limitation for log Kow of 5.0; NES are
                    predicted for these endpoints.

                    Narcosis classes (neutral organics) are
                                                        7-87

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                                                      JUNE 2014 DRAFT REPORT
                                          Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
          PROPERTY/ENDPOINT
             DATA
      REFERENCE
         DATA QUALITY
                                                                                                       provided for comparative purposes;
                                                                                                       DfE assessment methodology will use
                                                                                                       the lowest estimated toxicity value
                                                                                                       provided by ECOSAR classes that
                                                                                                       have a more specific mode of action
                                                                                                       relative to narcosis.
Green Algae EC50
Green algae 96-hour LC50 = No
effects at saturation (NES)
(Experimental)
Submitted confidential study
                                             Green algae 72-hour NOAEC = 0.31
                                             mg/L
                                             96-hour NOAEC =1.3 mg/L
                                             (Estimated by analogy)
                                Chemtura, 2006
                                             Green algae 96-hour EC50 =
                                             0.0000092 mg/L
                                             (Estimated)
                                             ECOSAR: Esters
                                ECOSAR vl. 11
                                             Green algae 96-hour EC50 =
                                             3.17xlO-5mg/L
                                             (Estimated)
                                             ECOSAR: Neutral organics
                                ECOSAR vl. 11

Study details reported in an
unpublished study submitted to EPA.
                          No study details reported in an MSDS;
                          estimated based on analogy to a similar
                          compound to a component of
                          Firemaster 550 (commercial mixture
                          containing TBB and TBPH); it is not
                          certain if this component contains
                          TBPH. Based on log Kow of 12 and the
                          reported effect level was above the
                          estimated water solubility (1.983 x 10"9
                          mg/L), NES are predicted for this
                          endpoint.
                          NES: The estimated log Kow of 12 for
                          this chemical exceeds the SAR
                          limitation for log Kow of 6.4; NES are
                          predicted for these endpoints.
                          NES: The estimated log Kow of 12 for
                          this chemical exceeds the SAR
                          limitation for log Kow of 6.4; NES are
                          predicted for these endpoints.

                          Narcosis classes (neutral organics) are
                          provided for comparative purposes;
                          DfE assessment methodology will use
                          the lowest estimated toxicity value
                                                                  7-88

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JUNE 2014 DRAFT REPORT
Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT

Chronic Aquatic Toxicity
Fish ChV
Daphnid ChV
DATA

Selenastrum capricornutum 96-hour
EC50>5.1mg/L
(Estimated)
REFERENCE

Chemtura, 2006,2013
^^^N. T
DATA QUALITY
provided by ECOSAR classes that
have a more specific mode of action
relative to narcosis.
No study details reported in an MSDS;
estimated based on one component of
Firemaster 550 and for Firemaster BZ-
54 (commercial mixture containing
TBB and TBPH); based on log Kow of
12 and the reported effect level was
above the estimated water solubility
(0.00001 1 mg/L), NES are predicted
for this endpoint.
LOW: Based on estimated chronic toxicity values for fish, daphnid, and algae that suggest no effects
at saturation (NES).
Fish ChV = 0.0000014 mg/L
(Estimated)
ECOSAR: Esters
Fish ChV =1.93xlQ-7 mg/L
(Estimated)
ECOSAR: Neutral organics
^
7
Daphnia ChV = 0.000004 Img/L
(Estimated)
ECOSAR vl. 11
7
ECOSAR vl. 11
ECOSAR vl. 11
NES: The estimated log Kow of 12 for
this chemical exceeds the SAR
limitation for log Kow of 8.0; NES are
predicted for these endpoints.
NES: The estimated log Kow of 12 for
this chemical exceeds the SAR
limitation for log Kow of 8.0; NES are
predicted for these endpoints.
Narcosis classes (neutral organics) are
provided for comparative purposes;
DfE assessment methodology will use
the lowest estimated toxicity value
provided by ECOSAR classes that
have a more specific mode of action
relative to narcosis.
NES: The estimated log Kow of 12 for
this chemical exceeds the SAR
         7-89

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                                                      JUNE 2014 DRAFT REPORT
                                          Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
          PROPERTY/ENDPOINT
             DATA
      REFERENCE
         DATA QUALITY
                                             ECOSAR: Esters
                                                          limitation for log Kow of 8.0; NES are
                                                          predicted for these endpoints.
                                             Daphnid ChV = 1.2xl(Tmg/L
                                             (Estimated)
                                             ECOSAR: Neutral organics
                                ECOSAR vl. 11
                          NES: The estimated log Kow of 12 for
                          this chemical exceeds the SAR
                          limitation for log Kow of 8.0; NES are
                          predicted for these endpoints.

                          Narcosis classes (neutral organics) are
                          provided for comparative purposes;
                          DfE assessment methodology will use
                          the lowest estimated toxicity value
                          provided by ECOSAR classes that
                          have a more specific  mode of action
                          relative to narcosis.
Green Algae ChV
Green algae ChV = 0.00006 mg/L
(Estimated)
ECOSAR: Esters
ECOSAR vl. 11
                                             Green algae ChV = 6.43 x!0"3mg/L
                                             (Estimated)
                                             ECOSAR: Neutral organics
                                ECOSAR vl. 11
NES: The estimated log Kow of 12 for
this chemical exceeds the SAR
limitation for log Kow of 8.0; NES are
predicted for these endpoints.
                          NES: The estimated log Kow of 12 for
                          this chemical exceeds the SAR
                          limitation for log Kow of 8.0; NES are
                          predicted for these endpoints.

                          Narcosis classes (neutral organics) are
                          provided for comparative purposes;
                          DfE assessment methodology will use
                          the lowest estimated toxicity value
                          provided by ECOSAR classes that
                          have a more specific  mode of action
                          relative to narcosis.
                                                                  7-90

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JUNE 2014 DRAFT REPORT
Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
ENVIRONMENTAL FATE
Transport

Henry's Law Constant (atm-
m3/mole)
Sediment/Soil
Adsorption/Desorption - Koc
Level III Fugacity Model
Level III fugacity models incorporating available physical and chemical property data indicate that
at steady state, TBPH is expected to be found primarily in soil and to a lesser extent, water.
Hydrolysis of TBPH is not expected to occur at a significant rate at environmentally-relevant pH
conditions. TBPH is expected to have low mobility in soil based on its measured Koc value. Leaching
of TBPH through soil to groundwater is not expected to be an important transport mechanism.
Estimated volatilization half-lives indicate that it will be non-volatile from surface water. In the
atmosphere, TBPH is expected to exist in the particulate phase, based on its estimated vapor
pressure. Particulates will be removed from air by wet or dry deposition.
3xlO"7 (Estimated)
>28,840 (Measured)
>30,000 (Estimated)
Air = 0.2%
Water = 12%
Soil = 88%
Sediment = 0.01% (Estimated)
EPIv4.11
Submitted confidential study
EPIv4.11
EPIv4.11
Estimated by the HENRYWIN Group
SAR Method with no measured
chemical property inputs.
Limited study details available; the
degree of precision reported is atypical
for this type of study and expected to
be beyond the capabilities of known
test methods.
Cutoff value for non-mobile
compounds.
This estimation was obtained using the
Level III Fugacity model based on the
equal emissions distribution
assumption with no measured chemical
property inputs.
         7-91

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                                                      JUNE 2014 DRAFT REPORT
                                          Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
          PROPERTY/ENDPOINT
                                             DATA
                                      REFERENCE
                                   DATA QUALITY
Persistence
                                 HIGH: The primary removal processes of TBPH produce persistent metabolites and degradation
                                 products resulting in a high persistence designation. TBPH was reported to have a half-life of 3.5
                                 days in water and 8.5 days in sediment in a confidential shake flask die-away test. In two closed
                                 bottle tests <4 or 2% of theoretical oxygen demand in a Closed Bottle test was reported after 28 days.
                                 TBPH has an estimated half-life of 120 days in soil where it is mainly expected to partition. TBPH is
                                 not expected to undergo hydrolysis at appreciable rates. Hydrolysis rates are expected to be pH-
                                 dependent and may be limited the by low water solubility of this compound. TBPH has the potential
                                 to undergo photodegradation, in an experimental study, half-lives of 147 to 220 minutes were
                                 obtained in the presence of organic solvents. The vapor phase reaction half-life of TBPH with
                                 atmospheric hydroxyl radicals is estimated at <1 day, although it is expected to exist primarily in the
                                 particulate phase in air.
Water
Aerobic Biodegradation
Passes Ready Test: No
Test method: OECD TG 30ID:
Closed Bottle Test

<4%ThOD after 10 days
(Measured)
                                             Passes Ready Test: No
                                             Test method: OECD TG 30IB:
                                             Evolution Test
                                                            CO2
                                             2% degradation as measured by CO2
                                             production after 28 days using the
                                             modified Sturm (OECD 30IB) test
                                             (Measured)
                                             Study results: 50%/8.5 days
                                             Test method: Shake Flask

                                             Performed in water with suspended
                                             sediment (Measured)
                                             Study results: 50%/3.5 days
Health & Environmental
Horizons Ltd, 2003
                                                                 ACC, 2004
                                                                 Submitted confidential study
                                                                 Submitted confidential study
Adequate guideline study.
                                                          Adequate guideline studies.
                                                          Adequate guideline study. Although
                                                          limited experimental data were
                                                          available, the anticipated degradation
                                                          product, mono(2-ethylhexyl)
                                                          tetrabromophthalate, is anticipated to
                                                          be resistant to degradation under the
                                                          test conditions.
                                                          Adequate guideline study. Although
                                                                  7-92

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JUNE 2014 DRAFT REPORT
Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT

Soil
Air
Reactivity

Volatilization Half-life for Model
River
Volatilization Half-life for Model
Lake
Aerobic Biodegradation
Anaerobic Biodegradation
Soil Biodegradation with Product
Identification ^^^^^^J
Sediment/Water Biodegradation
Atmospheric Half-life
Photolysis
DATA
Test method: Die-Away
Shake flask die away test
(Measured)
Weeks (Primary Survey Model)
Months (Ultimate Survey Model)
(Estimated for degradation product)
210 days (Estimated)
>1 year (Estimated)

Not probable
{%


0.5 days Based on a 12-hour day.
(Estimated)
Half-life = 220 min. in methanol
Half-life = 169 min. in
tetrahydrofuran
Half-life = 147 min. in toluene
Di and tribrominated analogues of
TBPH (most of which were also
REFERENCE

EPIv4.11
EPIv4.11
EPIv4.11

EPIv4.11;Holligeretal.,
2004


EPIv4.11
Davis and Stapleton, 2009
DATA QUALITY
limited experimental data were
available, the anticipated degradation
product, mono(2-ethylhexyl)
tetrabromophthalate, is anticipated to
be resistant to degradation under the
test conditions.
Estimated for the degradation product
mono(2-ethylhexyl)
tetrabromophthalate .
Based on the magnitude of the
estimated Henry's Law constant.
Based on the magnitude of the
estimated Henry's Law constant.
No data located.
The estimated value addresses the
potential for ultimate biodegradation.
However, there is potential for primary
anaerobic biodegradation of
haloaromatic compounds by reductive
dehalogenation.
No data located.
No data located.

The half-life and rate data are not
relevant to removal rates in the
environment as the test substance was
dissolved in organic solvents.
However, the results demonstrate the
potential for some debromination.
         7-93

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JUNE 2014 DRAFT REPORT
Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT


Hydrolysis
Environmental Half-life
Bioaccumulation

Fish BCF
DATA
missing both alkane branches) were
identified by electron capture
negative ion/mass spectrometry
ECNI/MS as the most dominant
photodegradation products
(Measured)
Half-life of 29 days at pH 7; 3 days
at pH 8 (Estimated)
50%/>1 year at pH 4, 7, and 9
(Measured)
Aquatic mesocosm study; a
controlled source of TBPHwas
applied and analyzed by GC-MS
over the course of the study
TBPH was detected in both the
particulate and sediment
compartment samples (Measured)
120 days in soil (Estimated)
REFERENCE

EPIv4.11
Submitted confidential study
de Jourdan et al., 2013
7
PBT Profiler
DATA QUALITY

Hydrolysis rates are expected to be pH-
dependent and may be limited the by
low water solubility of this compound.
Limited study details. Data indicate the
resistance of the material to hydrolysis
under environmental conditions.
This field study provides data about the
partitioning and fate/persistence of this
compound under environmental
conditions.
Half-life estimated for the predominant
compartment (soil), as determined by
EPI methodology.
HIGH: The bioaccumulation hazard designation is estimated based on TBPH monitoring data
reporting detections in many different species including those higher on the food chain. In addition, a
stable metabolite and degradation product of TBPH is expected to have a moderate bioaccumulation
designation based on an estimated BAF value. Although the experimental BAF is low, the persistence
of TBPH and its detection in many species from different habitats and trophic levels indicates
potential for a high bioaccumulation designation in aquatic or terrestrial species.
6.2 Reported as a range: 1.7 - 6.2
(Measured)
56 (Estimated for metabolite)
Submitted confidential study
EPIv4.11
Adequate guideline study.
Estimations run for mono(2-
         7-94

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                                           JUNE 2014 DRAFT REPORT
                               Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
             DATA
      REFERENCE
DATA QUALITY
                                                                                            ethylhexyl) tetrabromophthalate, with a
                                                                                            SMILES:
                                                                                            O=C(OCC(CC)CCCC)c(c(c(c(clBr)
                                                                                            Br)Br)C(=O)O)clBr.
  Other BCF
                                                         No data located.
  BAF
2.4 (Estimated)
EPIv4.11
                                  Fish were orally exposed to
                                  commercial flame retardant
                                  formulations including Firemaster
                                  BZ-54®, containing TBPH, for 56
                                  days and depurated (e.g., fed clean
                                  food) for 22 days; homogenized fish
                                  tissues were extracted and analyzed
                                  on day 0 and day 56 using gas
                                  chromatography electron-capture
                                  negative ion mass spectrometry
                                  (GC/ECNI-MS).

                                  2,3,4,5-tetrabromo-
                                  ethylhexylbenzoate (TBB) and
                                  TBPH, were detected in tissues at
                                  approximately 1% of daily dosage
                                  along with brominated metabolites
                                  (Measured)
                                Bearretal.,2010
                          BAFs were not calculated. Non
                          guideline study indicates that
                          absorption of this compound can occur
                          in fish following dietary exposure.
                                  TBPH was detected in liver tissues
                                  in rat dams. The pregnant rats were
                                  administered 0, 0.1 or 1 mg/kg-day
                                  of FM550 by oral gavage across
                                  gestation and through lactation
                                  (GD8-PND 21).  (Measured)
                                Patisauletal., 2013
                          BAFs were not calculated. Non
                          guideline study indicates that
                          absorption of this compound can occur
                          in rats through oral exposure; the test
                          substance identified as FM550 is a
                          mixture made up of TBPH, TBB
                          (CASRN 183658-27-7), IPTPP
                          (CASRN 68937-41-7) and TPP
                          (CASRN 115-86-6).
                                                       7-95

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JUNE 2014 DRAFT REPORT
Di(2-ethylhexyl) tetrabromophthalate
PROPERTY/ENDPOINT


Metabolism in Fish
DATA
169
Upper trophic Log BAF = 2.23
Mid trophic Log BAF = 3.17
Lower trophic Log BAF = 3.78
(Estimated for metabolite)

CASRN 26040-51-7
REFERENCE
EPIv4.11


DATA QUALITY
Estimations run for mono(2-
ethylhexyl) tetrabromophthalate, with a
SMILES:
O=C(OCC(CC)CCCC)c(c(c(c(clBr)
Br)Br)C(=O)O)clBr.
No data located.
ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring
Ecological Biomonitoring
Human Biomonitoring
TBPH was detected in particle -phase air samples collected from the Canadian Fiigh Arctic, near the shores
of the Great Lakes, Thailand, and the Tibetan Plateau. TBPH was detected in the marine atmosphere from
the East Indian Archipelago toward the Indian Ocean and further toward Antarctica. TBPH was detected in
seawater from the European Arctic. TBPH was detected in sediment samples from the Yadkin River in
North Carolina. TBPH was detected in dust from Belgian, Canada, Kuwait, New Zealand, Pakistan,
Sweden, Eastern Romania, United States and airplanes (Stapleton et al., 2008; Harju et al., 2009; Ali et al.,
2011, 2012, 2013; Moller etal, 2011, 2012; Covaci etal., 2012; Dodsonet al., 2012; EFSA, 2012;
LaGuardia et al., 2012; Ma et al., 2012; Sahlstrom et al., 2012; Shoeib et al., 2012; Xiao et al., 2012; Allen
etal., 2013).
TBPH was detected in bivalve (Corbiculafluminea); fmless porpoise; gastropod (Elimia proximo); fish;
ring-billed gulls; cod liver oil supplement; Elvers; humpback dolphin (Hoh et al., 2009; Lam et al., 2009;
EFSA, 2012; Gentes et al., 2012; LaGuardia et al., 2012; Sagerup et al., 2010; Suhring et al., 2013).
This compound was detected human serum samples. This chemical
biomonitoring report (CDC, 2013; He et al., 2013).
was not included in the NHANES
         7-96

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                                                 JUNE 2014 DRAFT REPORT


ACC (2004) High Production Volume (HPV) Challenge Program. Test plan for phthalic acid tetrabromo bis 2-ethylhexyl ester (CAS# 26040-51-
7). Robust summaries & test plans: Diisopropyl ether. American Chemistry Council. Submitted under the HPV Challenge Program.
http://www.epa.gov/HPV/pubs/summaries/phthacid/cl5484tp.pdf.

Ali N, Ali L, Mehdi T, et al. (2013) Levels and profiles of organochlorines and flame retardants in car and house dust from Kuwait and Pakistan:
Implication for human exposure via dust ingestion. Environ Int 55:62-70.

Ali N, Dirtu AC, Van den Eede N, et al. (2012) Occurrence of alternative flame retardants in indoor dust from New Zealand: indoor sources and
human exposure assessment. Chemosphere 88(11): 1276-82.

Ali N, Harrad S, Goosey E, et al. (2011)  "Novel" brominated flame retardants in Belgian and UK indoor dust: Implications for human exposure.
Chemosphere 83(10): 1360-1365.

Allen JG, Stapleton HM, Vallarino J, et al. (2013) Exposure to flame retardant chemicals on commercial airplanes. Environ Health 12:17.

Bearr JS, Mitchelmore CL, Roberts SC, et al. (2012) Species specific differences in the in vitro metabolism of the flame retardant mixture,
Firemaster(R) BZ-54. Aquatic Toxicology 124-125:41-47.

Bearr JS, Stapleton HM, Mitchelmore CL (2010) Accumulation and DNA damage in fathead minnows (Pimephales promelas) exposed to 2
brominated flame-retardant mixtures, Firemaster 550 and Firemaster BZ-54. Environ Toxicol Chem 29(3):722-729.

Bradford L, Pinzoni E, Wuestenenk J (1996) The Effect of Fogging of Common FR Additives in Flexible Foam. Proceedings of the Polyurethane
Foam Association, October 17 & 18,  1996. Akzo Nobel Central Research, http://www.pfa.org/abstracts/ab96.html.

CDC (2013) Fourth national report on human exposure to environmental chemicals, updated tables, March 2013. Centers for Disease Control and
Prevention. http://www.cdc.gov/exposurereport/pdf/FourthReport UpdatedTables Mar2013 .pdf. Accessed May 10, 2013.

Chemtura (2006) Material Safety Data Sheet FIREMASTER 550. Chemtura Product Safety Group.

Chemtura (2008) Material Safety Data Sheet FIREMASTER BZ-54 HP.

Chemtura (2013) Material Safety Data Sheet for Firemaster BZ-54. Chemtura Corporation.

Covaci A, lonas AC, van den Eede N, et al. (2012) Characterization of flame retardants in home indoor dust from California, USA.
Organohalogen Compounds 74:1506-1509, 1504 pp.



                                                             7-97

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                                                  JUNE 2014 DRAFT REPORT


Davis EF, Stapleton HM (2009) Photodegradation pathways of nonabrominated diphenyl ethers, 2-ethylhexyltetrabromobenzoate and di(2-
ethylhexyl)tetrabromophthalate: identifying potential markers of photodegradation. Environ Sci Technol 43(15):5739-5746.

de Jourdan BP, Hanson ML, Muir DC, et al. (2013) Environmental fate of three novel brominated flame retardants in aquatic mesocosms. Environ
Toxicol Chem 32(5): 1060-1068.

Dodson RE, Perovich LJ, Covaci A, et al. (2012) After the PBDE phase-out: a broad suite of flame retardants in repeat house dust samples from
California. Environ Sci Technol 46(24): 13056-13066.

ECOSAR (Ecological Structure Activity Relationship), Version 1.11. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/oppt/newchems/tools/21ecosar.htm.

EPA (1999) Determining the adequacy of existing data. Washington, DC: U.S.  Environmental Protection Agency.
http: //www. epa. gov/hpv/pubs/general/datadeqfn .pdf.

EPA. 2004. The pollution prevention (P2) framework, October 2003 version updated in January 2004. Office of Pollution Prevention and Toxics
7403M, Washington, DC: U.S. Environmental Protection Agency, EPA-748-B-03-001.
http: //www .epa. gov/opptintr/newchems/pubs/sustainable/p2frame -j une 05 a2 .pdf.

EPA (2012) Using noncancer screening within the SF initiative. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/oppt/sf/pubs/noncan-screen.htm.

EPI Estimation Programs Interface (EPI) Suite, Version 4.11. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm.

ESIS (2012) European chemical Substances Information System. European Commission, http://esis.jrc.ec.europa.eu/.

EFSA (2012)  European Food Safety Authority. EFSA Journal 10(10):2908.

Ezechias  M, Svobodova K, Cajthaml T (2012) Hormonal activities of new brominated flame retardants. Chemosphere 87(7):820-824.

Gentes M, Letcher RJ, Caron-Beaudoin E, et al. (2012) Novel flame retardants in urban-feeding ring-billed gulls from the St. Lawrence River,
Canada. Environ Sci Technol 46(17):9735-9744.
                                                               7-98

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                                                  JUNE 2014 DRAFT REPORT


Harju M, Heimstad E, Herzke D, et al. (2009) Current state of knowledge and monitoring requirements - Emerging "new" brominated flame
retardants in flame retarded products and the environment (TA-2462/2008). Oslo, Norway: Norwegian Pollution Control Authority.
http://www.klif.no/publikasjoner/2462/ta2462.pdf.

He S, Li M, Jin J, et al. (2013) Concentrations and trends of halogenated flame retardants in the pooled serum of residents of Laizhou Bay, China.
Chemosphere 32(6): 1242-1247.

Health & Environmental Horizons Ltd (2003) IUCLID data set phthalic acid tetrabromo ester.

Hoh E, Lehotay SJ, Mastovska K, et al. (2009) Capabilities of direct sample introduction- Comprehensive two-dimensional gas chromatography-
Time-of-flight mass spectrometry to analyze organic chemicals of interest in fish oils. Environ Sci Technol43:3240-3247.

Holliger C, Regeard C, Diekert G (2004) Dehalogenation by anaerobic bacteria. In: Haggblom MM, Bossert ID, eds. Dehalogenation: Microbial
processes and environmental applications. Kluwer Academic Publishers,  115-157.

La Guardia MJ, Hale RC, Harvey E, et al. (2012) In situ accumulation of HBCD, PBDEs, and several alternative flame-retardants in the bivalve
(Corbiculafluminea) and gastropod (Elimiaproximo). Environ Sci Technol 46(11):5798-5805.

Lam JC, Lau RK, Murphy MB, et al. (2009) Temporal trends of hexabromocyclododecanes (HBCDs) and polybrominated diphenyl ethers
(PBDEs) and detection of two novel flame retardants in marine mammals from Hong Kong, South China. Environ Sci Technol 43(18):6944-6949.

Ma Y, Venier M, Kites RA (2012) 2-Ethylhexyl tetrabromobenzoate and  bis(2-ethylhexyl) tetrabromophthalate flame retardants in the Great
Lakes atmosphere. Environ Sci Technol 46(1):204-208.

McGee SP, Konstantinov A, Stapleton HM, et al. (2013) Aryl phosphate esters within a major pentaBDE replacement product induce
cardiotoxicity in developing zebrafish embryos: Potential role of the aryl hydrocarbon receptor. Toxicol Sci 133(1): 144-156.

Moller A, Xie Z, Cai M, et al. (2012) Polybrominated diphenyl ethers vs alternate brominated flame retardants and dechloranes from East Asia to
the Arctic. Environ Sci Technol 45(16):6793-6799.

Moller A, Xie Z, Sturm R et al. (2011) Polybrominated diphenyl ethers (PBDEs) and alternative brominated flame retardants in air and seawater
of the European Arctic.  Environ Pollut 159(6): 1577-1583.

MPI Research (2008a) CN-2065: An oral two-generation reproduction  and fertility study in rats. MPI Research Inc.
                                                              7-99

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                                                  JUNE 2014 DRAFT REPORT


MPI Research (2008b) CN-2065: Prenatal developmental toxicity study in rats. MPI Research Inc.

PBT Profiler. Persistent (P), Bioaccumulative (B), and Toxic (T)  Chemical (PBT) Profiler, Version 1.301. Washington, DC: U.S. Environmental
Protection Agency, www.pbtprofiler.net.

Patisaul HB, Roberts SC, Mabrey N, et al. (2013) Accumulation and endocrine disrupting effects of the flame retardant mixture Firemaster 550 in
rats: an exploratory assessment. J Biochem Mol Toxicol 27(2): 124-36.

Roberts SC, Macaulay LJ, Stapleton HM (2012) In vitro metabolism of the brominated flame retardants 2-ethylhexyl-2,3,4,5-tetrabromobenzoate
(TBB) and bis(2-ethylhexyl) 2,3,4,5-tetrabromophthalate (TBPH) in human and rat tissues. Chem Res Toxicol 25(7): 1435-1441.

Sagerup K, Herzke D, Harju M, et al. (2010) New brominated flame retardants in Arctic biota. Statlig program for forurensningsovervaking.
http://www.klif.no/publikasjoner/2630/ta2630.pdf.

Sahlstrom L, Sellstrom U, DeWit CA (2012) Clean-up method for determination of established and emerging brominated flame retardants in dust.
Anal Bioanal Chem 404(2): 45 9-466.

Shoeib M, Harner T, Webster GM, et al. (2012) Legacy and current-use flame retardants in house dust  from Vancouver, Canada.  Environ Pollut
169:175-182.

Springer C, Dere E, Hall SJ, et al. (2012) Rodent thyroid, liver, and fetal testis toxicity of the monoester metabolite of bis-(2-ethylhexyl)
tetrabromophthalate (TBPH), a novel brominated flame retardant present in indoor dust. Environ Health Perspect 120(12): 1711-1719.

Stapleton HM, Allen JG, Kelly SM, et al. (2008) Alternate and new brominated flame retardants detected in U.S. house dust. Environ Sci Technol
42(18):6910-6916.

Suhring R, Moller A, Freese M, et al. (2013) Brominated flame retardants and dechloranes in eels from German rivers. Chemosphere 90:118-124.

Unitex Chemical Corporation (2006) Material safety data sheet. Product name: Uniplex FRP-45.  Greensboro, NC: Unitex  Chemical Corporation.
http://www.unitexchemical.com/MSDS  CURR/UPLXFRP45  MSDS.pdf.

Xiao H, Shen L, Su Y, et al. (2012) Atmospheric concentrations of halogenated flame retardants at two remote locations: the Canadian High
Arctic and the Tibetan Plateau. Environ Pollut 161:154-161.
                                                              7-100

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                                                           JUNE 2014 DRAFT REPORT
             Diethyl bis(2-hydroxyethyl)aminomethylphosphonate
                                                  Screening Level Toxicology Hazard Summary

This table only contains information regarding the inherent hazards of flame retardant chemicals. Evaluation of risk considers both the hazard and exposure associated with the
substance including combustion and degradation by-products. The caveats listed in the legend and footnote sections must be taken into account when interpreting the hazard
information in the table.
VL = Very Low hazard L = Low hazard   = Moderate hazard H = High hazard VH = Very High hazard - Endpoints in colored text (VL, L,   , H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].







Chemical







CASRN
Human Health Effects

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2781-11-5^
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                                                                       7-101

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                                                         JUNE 2014 DRAFT REPORT
                                                                                                               CASRN:2781-ll-5
                                                                                                               MW: 255.25
                                                                                                               MF: C9H22NO5P
                                                                                                               Physical Forms: Liquid
                                                                                                               Neat: Liquid
                                                                                                               Use: Flame retardant
SMILES: O=P(OCC)(OCC)CN(CCO)CCO
Synonyms: Diethyl bis(2-hydroxyethyl)aminomethylphosphonate; Phosphonic acid, ((bis(2-hydroxyethyl)amino)methyl)-, diethyl ester; Diethyl ((N,N-bis(2-
hydroxyethyl)amino)methyl)phosphonate; O,O-DiethylN,N-bis(2-hydroxyethyl)aminomethyl phosphonate
Tradenames: Fyrol 6; LEVAGARD 4090 N; ADEKA FC 450
Chemical Considerations: The substance is a discrete chemical, but is sold at 70-90% purity. The substance, Phosphonic acid, P-[[bis(2-
hydroxyethyl)amino]methyl]-, diethyl ester, reacts into the polymer during curing. The major impurities are most likely residual starting materials diethylphosphite,
diethanolamine and formaldehyde. EPI v4.11 was employed to estimate physical/chemical and environmental fate values due to an absence of experimental data
(Supresta, 2006).
Polymeric: No
Oligomeric: Not applicable
Metabolites, Degradates and Transformation Products: Hydrolysis products are diethylphosphite (762-04-9) and the diethanolamine/formaldehyde reaction
product (72624-00-1); this latter substance can further degrade to form diethanolamine (111-42-2) and formaldehyde (50-00-0) (Sturtz et al., 1977; Professional
judgment).
Analog: Phosphonic acid, 4-morpholinyl-, dimethyl ester
(DMMPA; CASRN 597-25-1), phosphonic acid, P-methyl-,
dimethyl ester (DMMP; CASRN 756-79-6) and phosphonic
acid, dimethyl ester (DMP; CASRN 868-85-9)
Endpoint(s) using analog values: Carcinogenicity
Analog Structure:
O 	
Vrv^° \j_0 \_i_o
^ \ H \
Phosphonic acid, 4-morpholmyl-, dimethyl ester Phosphonic acid, P-methyl-, dimethyl ester Phosphonic acid dimethyl ester
(CASRN 597-25-1) (CASRN 756-79-6) (CASRN 868-85-9)
                                                                     7-102

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                                                       JUNE 2014 DRAFT REPORT
Structural Alerts: Organophosphates, Neurotoxicity; Amines, Kidney Toxicity (EPA, 2012).
Risk Phrases: Not classified by Annex VI Regulation (EC) No 1272/2008 (ESIS, 2012).
Hazard and Risk Assessments: Hazard Characterization by EPA in September 2009 (EPA, 2009).
                                                                  7-103

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JUNE 2014 DRAFT REPORT
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate CASRN 2781-11-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
PHYSICAL/CHEMICAL PROPERTIES
Melting Point (°C)
Boiling Point (°C)
Vapor Pressure (mm Hg)
Water Solubility (mg/L)
-43
(Measured)
>170 Decomposes
Results from a thermo gravimetric(TG) study run from 100-
700°C. (Measured)
>300
(Estimated)
^
196
OECD 103 and EPA OPPTS 830.7220 test guidelines
(Measured)
3.3xlO-7at25°C
(Estimated) ^^b^
0.43 at 20°C
OECD 104 test guideline study employing the Isoteniscopic
method. (Measured)
900,000 (Measured)
OECD 105 test guideline study, flask method.
LANXESS,
2012
Kettrup et al.,
1990
J
EPIv4.11;
EPA, 1999
Supresta, 2006;
Professional
judgment
EPIv4.11
Supresta, 2006;
Professional
judgment
Supresta, 2006
Nonguideline study, sufficient details
were not available to assess the quality
of this study.
Adequate, value obtained from peer-
reviewed primary source. The study
showed that vaporization and
decomposition occur simultaneously,
and that 88% degradation had taken
place by 700°C.
Cutoff value for high boiling compounds
according to HPV assessment guidance;
decomposition likely occurs before the
boiling point is reached.
Adequate, decomposition occurs upon
boiling as described in additional
sources, above. The data are for the
commercial mixture, reported as 85%
purity. It is possible that this measured
boiling point reflects vaporization of
these impurities as well as vaporization
of the test substance.

Inadequate, the data is for the
commercial mixture, which is reported to
have only 70-90% purity. The results are
likely due to volatile impurities in the
substance.
Adequate, guideline study. The data are
for the commercial mixture, reported as
70-90% purity.
         7-104

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JUNE 2014 DRAFT REPORT
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate CASRN 2781-11-5
PROPERTY/ENDPOINT

Log Kow
Flammability (Flash Point)
Explosivity
Pyrolysis
pH
pKa
DATA
1,000,000 (Estimated)
-0.72
OECD 105 test guideline study. (Measured)
86.5 EG A 9/DIN EN ISO 2719 method (Measured)
Not flammable (Estimated)
Not expected to form explosive mixtures with air.
(Estimated)

8 (Measured)
^^^k \ ^
pKb for nitrogen = 5.2 (Estimated)
pKb for nitrogen = 5.6 (Estimated)
REFERENCE
EPIv4.11
Supresta, 2006
LANXESS,
2012
Professional
judgment
Professional
judgment

LANXESS,
2012
ACE, 2013
HSDB, 2005
DATA QUALITY
The estimated value is close to the
measured value of 900,000 mg/L.
Adequate, guideline study. The data are
for the commercial mixture, with 70-
90% purity.
Sfonguideline study, sufficient details
were not available to assess the quality
of this study.
Mo experimental data located; based on
its use as a flame retardant.
Mo experimental data located; based on
its use as a flame retardant.
No data located.
Sfonguideline study, sufficient details
were not available to assess the quality
of this study, which was carried out on a
10% solution in water.
Adequate, indicates that in solution this
substance is a weak base.
Adequate, indicates that in solution this
substance is a weak base. Value obtained
from peer-reviewed secondary source.
HUMAN HEALTH EFFECTS
Toxicokinetics
Dermal Absorption in vitro
Absorption, Oral, Dermal or Inhaled
Distribution, Other
Metabolism
& Excretion
No data were located






^o data located.
No data located.
^o data located.
         7-105

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JUNE 2014 DRAFT REPORT
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate CASRN 2781-11-5
PROPERTY/ENDPOINT
Acute Mammalian Toxicity
Acute
Lethality
Oral
Dermal
Inhalation
Carcinogenicity

OncoLogic Results
Carcinogenicity (Rat and
Mouse)
DATA
REFERENCE
DATA QUALITY
LOW: Based on an oral LD50 > 5000 mg/kg bw in rats and a dermal LD50 > 2,000 mg/kg bw in rabbits. No data
were located for the inhalation route of exposure.
Rat 14-day oral LD50 >5,000 mg/kg bw
Test conditions: 10 rats per sex; gavage (in corn oil) at 5,000
mg/kg bw; 14-day observation
Results: clinical signs; all animals appeared normal by day 2
Rabbit 14-day dermal LD50 >2,000 mg/kg bw
Test conditions: 5 rabbits per sex; 24-hour dermal application
at 2,000 mg/kg bw; 14-day observation Results: Clinical
signs, dermal irritation; no deaths; all animals appeared
normal by day 2

Supresta, 2006;
EPA, 2009
Supresta, 2006;
EPA, 2009

Adequate; guideline study (EPA
guidelines for pesticide registration; Fed.
Reg. 43:163, 37336-37402 [1978];
OECD [1981]) Summarized in reliable
secondary sources; Test substance: Fyrol
6; purity not specified.
Adequate; guideline study (EPA
guidelines for pesticide registration; Fed.
Reg. 43:163, 37336-37402 [1978];
OECD [1981]) Summarized in reliable
secondary sources. Test substance: Fyrol
6; purity not specified.
No data located.
MODERATE: Data for three structurally similar analogs indicate evidence of Carcinogenicity in laboratory
animals. Rats exposed orally to DMP, DMMP or DMMPA had increased incidence of lung tumors, leukemia, or
kidney tumors but mice exposed orally to DMP or DMMPA did not have increased tumor incidence. While there
is no evidence to indicate this compound is a suspected human carcinogen, the evidence of Carcinogenicity in
laboratory animals for the analogs and the uncertainty based on lack of studies on this compound warrants a
Moderate hazard designation.

Rats (F344) were orally administered 0, 100, 200 mg/kg-
day (male) and 0, 50, and 100 mg/kg-day (female) of the
analog DMP for 103 weeks.
There is evidence of Carcinogenicity in males following
exposure (increased incidence of squamous cell
carcinoma in lung and alveolar/bronchial cell adenoma
or carcinoma)
Equivocal evidence was reported for female rats.
(Estimated by analogy)

OECD SIDS,
2004
^o data located.
istimated based on analogy to
)hosphonic acid, dimethyl ester
(CASRN 868-85-9); data reported in
a secondary source.
         7-106

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                                              JUNE 2014 DRAFT REPORT
                             Diethyl bis(2-hydroxyethyl)aminomethylphosphonate CASRN 2781-11-5
PROPERTY/ENDPOINT
                      DATA
REFERENCE
         DATA QUALITY
                              Mice (B6C3F1) were orally administered 0, 100, 200
                              mg/kg-day of the analog DMP.
                              There was no evidence of carcinogenicity in male or
                              female mice.

                              Estimated by analogy)
                                                  OECD STDS,
                                                  2004
               stimated based on analogy to
             Dhosphonic acid, dimethyl ester
              CASRN 868-85-9); data reported in
               secondary source.
                              IARC classification: The analog DMP "is not
                              lassifiable as to its carcinogenicity to humans (group
                              3)".

                              Estimated by analogy)
                                                  IARC, 1999
               stimated based on analogy to
             Dhosphonic acid, dimethyl ester
              CASRN 868-85-9); IARC
             dassification; estimated based on
             malaogy to phosphonic acid,
             dimethyl ester (CASRN 868-85-9);
             data reported in a secondary source.
    Combined Chronic
    Toxicity/Carcinogenicity
In a 2-year toxicology and carcinogenicity study,
"344/N rats were orally administered the analog
DMMPA at a dose of 0, 150, 300, 600 mg/kg-day for
[03 weeks.
There was some evidence of carcinogenicity for male
and female rats (increased incidence of mononuclear cell
eukemia).

^Estimated by analogy)
NTP, 1986
Estimated based on analogy to
Jhosphonic acid, 4-morpholinyl-,
dimethyl ester (CASRN 597-25-1).
                              In a 2-year toxicology and carcinogenicity study,
                              B6C3F1 mice were orally administered the analog
                              DMMPA at a dose of 0, 150, 300, 600 mg/kg-day for
                              [03 weeks.
                              There was no evidence of carcinogenicity for male or
                              'emale rats.

                              Estimated by analogy)
                                                  NTP, 1986
             Estimated based on analogy to
             Phosphonic acid, 4-morpholinyl-,
             dimethyl ester (CASRN 597-25-1).
                                                         7-107

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JUNE 2014 DRAFT REPORT
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate CASRN 2781-11-5
PROPERTY/ENDPOINT


Other
Genotoxicity

Gene Mutation in vitro
Gene Mutation in vivo
DATA
n a 2-year toxicology and carcinogen! city study,
"344/N rats were orally administered the analog Fyrol
DMMP at a dose of 0, 500, or 1,000 mg/kg-day for 2
years.
There was some evidence of carcinogenic activity in
male rats (increased incidences of tubular cell
lyperplasia, tubular cell adenocarcinomas, hyperplasia
of the transitional cell epithelium, and transitional cell
)apillomas of the kidney). There was also increased
ncidence of mononuclear cell leukemia in male rats at
the highest dose.
Mo evidence of carcinogenic activity for female rats was
reported.
(Estimated by analogy) - ^^^^^^^

REFERENCE
NTP, 1987
J

DATA QUALITY
istimated based on analogy to
)hosphonic acid, P-methyl-, dimethyl
ester (CASRN 756-79-6).
No data located.
MODERATE: Based on weight of evidence from multiple studies. Diethyl bis(2-
tiydroxyethyl)aminomethylphosphonate produced chromosomal aberrations and gene mutations in mammalian
cells in vitro. In contrast, negative results were obtained in gene mutation tests in bacteria and no cell
transformation was evident in mammalian cells. No in vivo studies were located.
Positive; Fyrol 6 (purity not specified) was weakly mutagenic
to mouse lymphoma cell line (L5 178Y) with and without
metabolic activation
Negative; Fyrol 6 (purity not specified) was not mutagenic in
S. cerevisiae strain D4 with or without metabolic activation
Negative; Fyrol 6 (purity not specified) was not mutagenic in
S. typhimurium strains TA98, TA100, TA1535, TA1537,
TA1538 with or without metabolic activation

Supresta, 2006;
EPA, 2009
Supresta, 2006;
EPA, 2009
Supresta, 2006;
EPA, 2009

Adequate studies summarized in reliable
secondary sources.
Adequate study summarized in reliable
secondary sources.
Adequate study summarized in reliable
secondary sources.
No data located.
         7-108

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JUNE 2014 DRAFT REPORT
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate CASRN 2781-11-5
PROPERTY/ENDPOINT

Chromosomal Aberrations in
vitro
Chromosomal Aberrations in
vivo
DNA Damage and Repair
Other
Reproductive Effects

Reproduction/Developmental
Toxicity Screen
Combined Repeated Dose
with Reproduction/
Developmental Toxicity
Screen
Reproduction and Fertility
Effects
DATA
Positive; Fyrol 6 (purity not specified) caused increased
chromosomal aberrations in mouse lymphoma cells
(L5 178Y) with and without metabolic activation


Negative; Fyrol 6 (purity not specified) did not cause cell
transformation in BALB/3T3 cells with or without metabolic
activation
REFERENCE
Supresta, 2006;
EPA, 2009


Supresta, 2006
DATA QUALITY
Adequate study summarized in reliable
secondary sources.
No data located.
^o data located.
Adequate study summarized in reliable
secondary sources.
LOW: Based on a NOAEL of 750 mg/kg-day (LOAEL not established) in a combined
reproductive/developmental toxicity screen in rats. No significant reproductive effects were observed.
Combined reproductive/developmental toxicity screen in
Sprague-Dawley rats (12/sex/dose)
Fyrol 6 (purity 85%) administered by gavage at 50, 250, or
750 mg/kg-day for 2 weeks prior to mating, during mating,
gestation, lactation (females) Results: No effects on clinical
signs, mortality, parental body weights, food consumption,
reproductive or developmental indices, histopathology.
Systemic toxicity:
NOAEL: 750 mg/kg-day (highest dose tested)
LOAEL: Not established
Reproductive toxicity:
NOAEL: 750 mg/kg-day (highest dose tested)
LOAEL: Not established


Supresta, 2006;
EPA, 2009


Adequate; guideline study (OECD 421)
summarized in reliable secondary
sources; True NOAELs may be > 750
mg/kg-day; No LOAELs were
established in the study.
No data located.
^o data located.
         7-109

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JUNE 2014 DRAFT REPORT
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate CASRN 2781-11-5
PROPERTY/ENDPOINT

Other
Developmental Effects

Reproduction/
Developmental Toxicity
Screen
Combined Repeated Dose
with Reproduction/
Developmental Toxicity
Screen W
Prenatal Development
Postnatal Development
Prenatal and Postnatal
Development
Developmental Neurotoxicity
Other
DATA

REFERENCEI DATA QUALITY
^^ |No data located.
LOW: Based on a NOAEL of 750 mg/kg-day (LOAEL not established) in a combined
reproductive/developmental toxicity screen in rats. No significant developmental effects were observed.
Combined reproductive/developmental toxicity screen in
Sprague-Dawley rats (12/sex/dose) Fyrol 6 (purity 85%)
administered by gavage at 50, 250, or 750 mg/kg-day for 2
weeks prior to mating, during mating, gestation, lactation
(females)
Results: No effects on clinical signs, mortality, parental body
weights, food consumption, reproductive or developmental
indices, histopathology.
Maternal toxicity:
NOAEL: 750 mg/kg-day (highest dose tested)
LOAEL: Not established
Developmental toxicity:
NOAEL: 750 mg/kg-day (highest dose tested)
LOAEL: Not established






Supresta, 2006;
EPA, 2009
J






Adequate; guideline study (OECD 421)
summarized in reliable secondary
sources; true NOAELs may be > 750
mg/kg-day; No LOAELs were
established in this study.
^o data located.
No data located.
^o data located.
No data located.
^o data located.
No data located.
         7-110

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JUNE 2014 DRAFT REPORT
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate CASRN 2781-11-5
PROPERTY/ENDPOINT
Neurotoxicity

Neurotoxicity Screening
Battery (Adult)
Other
Repeated Dose Effects


Skin Sensitization

Skin Sensitization
Respiratory Sensitization
[Respiratory Sensitization
DATA
REFERENCE
DATA QUALITY
MODERATE: There is potential for neurotoxicity based on a structural alert for organophosphates. No
experimental data was located.
Potential for neurotoxicity based on a structural alert for
organophosphates
(Estimated)

Professional
judgment

Estimated based on a structural alert for
organophosphates and professional
ludgment.
^o data located.
MODERATE: There is potential for kidney effects based on a structural alert for amines. No adverse effects
were reported in a 13-week oral gavage study in rats at doses as high as 500 mg/kg-day (highest dose tested);
however, only quantitative data for liver and kidney weight, and cross-sectional area of liver cells were reported.
The experimental data are insufficient to rule out kidney toxicity; therefore, a conservative approach was
applied and an estimated Moderate hazard was designated.
Potential for kidney toxicity based on a structural alert for
amines
(Estimated)
Sprague-Dawley rats (22/sex/dose) administered Fyrol 6
(purity 90.7%) by gavage (in corn oil) at 0, 20, 100, or 500
mg/kg-day for 13 weeks.
Results: No Fyrol 6 treatment-related adverse effects;
increased liver weight, hepatocellular hypertrophy,
eosinophilia of centrilobular hepatocytes considered adaptive
effect in absence of histopathological evidence of hepatic
necrosis or clinical evidence of liver dysfunction.
NOAEL: 500 mg/kg-day (highest dose tested)
LOAEL: Not established
Professional
judgment
Supresta, 2006;
EPA, 2009
Estimated based on a structural alert for
amines and professional judgment.
Study summarized in reliable secondary
sources; only quantitative data was
reported and only reported data for liver
and kidney weight, and cross-sectional
area of liver cells; no LOAEL was
identified in the study.
MODERATE: There is uncertain potential for skin Sensitization due to lack of data; Skin Sensitization cannot be
ruled out. A moderate hazard designation is applied conservatively.
There is uncertain potential for skin Sensitization due to lack
of data.
(Estimated)
Professional
judgment
No data located.
No data were located

|No data located.
         7-111

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JUNE 2014 DRAFT REPORT
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate CASRN 2781-11-5
PROPERTY/ENDPOINT
Eye Irritation

Eye Irritation
Dermal Irritation

Dermal Irritation
Endocrine Activity

Immunotoxicity

Immune System Effects
DATA
LOW: Diethyl bis(2-hydroxyethyl)aminomethylphosphons
within 72-hours post-instillation.
Rabbit (9 of mixed sex); mild conjunct val irritation at 0.01
mL in 6 rabbits with unwashed eyes at 24 hours
postinstillation, no effects in 3 rabbits with washed eyes;
irritation cleared by 72-hours postinstillation.
REFERENCE
DATA QUALITY

ite produced mild irritation in rabbits which cleared
Supresta, 2006;
EPA, 2009
Guideline study (EPA guidelines for
pesticide registration; Fed. Reg. 43:163,
37336-37402 [1978]; OECD [1981])
summarized in secondary sources; Test
substance: Fyrol 6; purity not specified.
VERY LOW: Diethyl bis(2-hydroxyethyl)aminomethylphosphonate was not irritating to rabbit skin.
Rabbit (6 of mixed sex); nonirritating when applied at 0.5 mL
for 4 hours and observed at 4 and 48 hours post-
administration.
Supresta, 2006;
EPA, 2009
Study that followed DOT Fed. Reg. Title
49, Part 173 Appendix II (10/01/1977)
summarized in secondary sources. Test
substance: Fyrol 6; purity not specified.
No data were located

|No data located.
No data were located

|No data located.
ECOTOXICITY
ECOSAR Class
Acute Aquatic Toxicity
Fish LC50

LOW: Based on experimental and estimated values for fish, daphnia and green algae.
Oncorhynchus mykiss (rainbow trout; aka Salmo gairdnerf)
96-hr LC50> 1 0,000 mg/L.
Test substance: Fyrol 6; purity not given Static test; Test
substance concentrations: 1,000, 1,800, 3,200, 5,600, 10,000
mg/L (nominal); There was 20% mortality at 3200 mg/L but
none at higher concentrations.
(Experimental)
Freshwater fish 96-hour LC50 = 3,000 mg/L
(Estimated)
ECOSAR: Aliphatic amines
Freshwater fish 96-hour LC50 = 58,000 mg/L
(Estimated)
Supresta, 2006;
EPA, 2009
ECOSAR
vl.ll
ECOSAR
vl.ll
Guideline study (OECD 203) according
to reliable secondary sources. Purity not
given, but apparently in the range of 70-
90% based on reported purity of batches
used for selected physical -chemical
properties endpoints.

ECOSAR also provided results for the
Esters, and Esters (phosphate) classes;
         7-112

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                                                         JUNE 2014 DRAFT REPORT
                                      Diethyl bis(2-hydroxyethyl)aminomethylphosphonate CASRN 2781-11-5
        PROPERTY/ENDPOINT
                       DATA
REFERENCE
         DATA QUALITY
                                       ECOSAR: Neutral organics
                                                                   however, professional judgment
                                                                   indicates that this compound is not
                                                                   currently well represented in ECOSAR
                                                                   vl. 11. Narcosis classes (neutral
                                                                   organics) are provided for comparative
                                                                   purposes; DfE assessment methodology
                                                                   will use the lowest estimated toxicity
                                                                   value provided by ECOSAR classes that
                                                                   have a more specific mode of action
                                                                   relative to narcosis.
Daphnid LC50
Daphnia magna (water flea) 48-hour EC50 > 86 mg/L
Test substance: Fyrol 6; purity 84.5%
Flow-through test
Test substance concentrations: 63, 125, 250, 500, and 1,000
mg/L (nominal); 936 mg/L (measured at nominal of 1,000
mg/L)
(Experimental)
Supresta, 2006;
EPA, 2009
Guideline study (OECD 202; EPA
OPPTS 850.1010) according to reliable
secondary sources.
                                       Daphnia magna 48-hour LC50 = 260 mg/L
                                       (Estimated)
                                       ECOSAR: Aliphatic amines
                                                     ECOSAR
                                                     vl.ll
                                       Daphnia magna 48-hour LC50 = 26,000 mg/L
                                       (Estimated)
                                       ECOSAR: Neutral organics
                                                     ECOSAR
                                                     vl.ll
              ECOSAR also provided results for the
              Esters, and Esters (phosphate) classes;
              however, professional judgment
              indicates that this compound is not
              currently well represented in ECOSAR
              vl.ll. Narcosis classes (neutral
              organics) are provided for comparative
              purposes; DfE assessment methodology
              will use the lowest estimated toxicity
              value provided by ECOSAR classes that
              have a more specific mode of action
              relative to narcosis.
                                                                    7-113

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JUNE 2014 DRAFT REPORT
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate CASRN 2781-11-5
PROPERTY/ENDPOINT
Green Algae EC50
Chronic Aquatic Toxicity
Fish ChV
DATA
Green algae (Pseudokirchneriella subcapitatd) 96-hour EC50
>86 mg/L;
Test substance: Fyrol 6; purity 84.5%
Static test
Test substance concentrations: 7.5, 15, 30, 60, and 120 mg/L
(nominal); 86 mg/L (measured at 120 mg/L nominal)
(Experimental)
Green algae 96-hour EC50 = 400 mg/L
(Estimated)
ECOSAR: Aliphatic amines
Green algae 96-hour EC50 = 6,800 mg/L
(Estimated)
ECOSAR: Neutral organics
,^\ X
^^ fr
REFERENCE
Supresta, 2006;
EPA, 2009
ECOSAR
vl.ll
ECOSAR
vl.ll
DATA QUALITY
Study details reported in a secondary
source.

ECOSAR also provided results for the
Esters, and Esters (phosphate) classes;
however, professional judgment
indicates that this compound is not
currently well represented in ECOSAR
vl.ll. Narcosis classes (neutral
organics) are provided for comparative
purposes; DfE assessment methodology
will use the lowest estimated toxicity
value provided by ECOSAR classes that
have a more specific mode of action
relative to narcosis.
LOW: Based a NOEC of 86 mg/L in green algae and estimated values for fish, daphnia and algae.
Freshwater fish ChV = 460 mg/L
(Estimated)
ECOSAR: Aliphatic amines
Freshwater fish ChV = 4,200 mg/L
(Estimated)
ECOSAR: Neutral organics
r
ECOSAR
vl.ll
ECOSAR
vl.ll

ECOSAR also provided results for the
Esters, and Esters (phosphate) classes;
however, professional judgment
indicates that this compound is not
currently well represented in ECOSAR
vl.ll. Narcosis classes (neutral
organics) are provided for comparative
         7-114

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JUNE 2014 DRAFT REPORT
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate CASRN 2781-11-5
PROPERTY/ENDPOINT

Daphnid ChV
Green Algae ChV
DATA

Daphnia magna ChV =16 mg/L
(Estimated)
ECOSAR: Aliphatic amines ^^^
Daphnia magna ChV = 1 ,200 mg/L
(Estimated)
ECOSAR: Neutral organics
,^\ X
Green algae (Pseudokirchneriella subcapitatd) 96-hour
NOEC = 86 mg/L
(Experimental)
Green algae ChV =110 mg/L
(Estimated)
ECOSAR: Aliphatic amines
Green algae ChV = 1,000 mg/L
(Estimated)
ECOSAR: Neutral organics
r
REFERENCE

ECOSAR
vl.ll
ECOSAR
vl.ll
Supresta, 2006
ECOSAR
vl.ll
ECOSAR
vl.ll
DATA QUALITY
purposes; DfE assessment methodology
will use the lowest estimated toxicity
value provided by ECOSAR classes that
have a more specific mode of action
relative to narcosis.

ECOSAR also provided results for the
Esters, and Esters (phosphate) classes;
however, professional judgment
indicates that this compound is not
currently well represented in ECOSAR
vl.ll. Narcosis classes (neutral
organics) are provided for comparative
purposes; DfE assessment methodology
will use the lowest estimated toxicity
value provided by ECOSAR classes that
have a more specific mode of action
relative to narcosis.
Study details reported in a secondary
source.

ECOSAR also provided results for the
Esters, and Esters (phosphate) classes;
however, professional judgment
indicates that this compound is not
currently well represented in ECOSAR
vl.ll. Narcosis classes (neutral
organics) are provided for comparative
         7-115

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JUNE 2014 DRAFT REPORT
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate CASRN 2781-11-5
PROPERTY/ENDPOINT

DATA

REFERENCE

DATA QUALITY
purposes; DfE assessment methodology
will use the lowest estimated toxicity
value provided by ECOSAR classes that
have a more specific mode of action
relative to narcosis.
ENVIRONMENTAL FATE
Transport

Henry's Law Constant (atm-
m3/mole)
Sediment/Soil
Adsorption/Desorption - Koc
Level III Fugacity Model
Level III fugacity models incorporating available physical and chemical property data indicate that at steady
state, diethyl bis(2-hydroxyethyl)aminomethylphosphonate is expected to be found primarily in soil and to a
lesser extent, water. Diethyl bis(2-hydroxyethyl)aminomethylphosphonate is expected to exist in both neutral and
cationic forms at environmentally-relevant pH, based on the estimated pKb values. The neutral form of diethyl
bis(2-hydroxyethyl)aminomethylphosphonate is expected to have high mobility in soil based on its estimated Koc.
The cationic form may have less mobility, as cations bind more strongly to organic carbon and clay due to their
positive charge. Estimated volatilization half-lives indicate that the substance will be nonvolatile from surface
water. In the atmosphere, diethyl bis(2-hydroxyethyl)aminomethylphosphonate is expected to exist in both vapor
and particulate phases, based on its estimated vapor pressure. Particulates will be removed from air by wet or
dry deposition. Vapor-phase diethyl bis(2-hydroxyethyl)aminomethylphosphonate will be susceptible to
atmospheric degradation processes.
<10'8 (Estimated)
10 (Estimated)
Air = 0%
Water = 35%
Soil = 65%
Sediment = 0% (Estimated)
EPIv4.11;
Professional
judgment
EPIv4.11
EPIv4.11
Cutoff value for non-volatile
compounds.


         7-116

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JUNE 2014 DRAFT REPORT
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate CASRN 2781-11-5
PROPERTY/ENDPOINT
Persistence
Water
Soil
Air
Aerobic Biodegradation
Volatilization Half-life for
Model River
Volatilization Half-life for
Model Lake
Aerobic Biodegradation
Anaerobic Biodegradation
Soil Biodegradation with
Product Identification
Sediment/Water
Biodegradation
Atmospheric Half-life
DATA
REFERENCE
DATA QUALITY
HIGH: Experimental studies on the commercial product, which is estimated to contain approximately 85%
diethyl bis(2-hydroxyethyl)aminomethylphosphonate, determined the substance to be not readily biodegradable
using a modified Sturm test (OECD TG 301B), as only 15-19% biodegradation occurred over 28 days using
activated sewage sludge as the inoculum. Diethyl bis(2-hydroxyethyl)aminomethylphosphonate undergoes
hydrolysis under alkaline conditions, with a half-life of 14 hours at pH 9; it is relatively stable to hydrolysis
under neutral and acidic conditions, with half-lives of 26 days at pH 7 and 179 days at pH 4. Diethyl bis(2-
hydroxyethyl)aminomethylphosphonate is not expected to be susceptible to direct photolysis by sunlight, since it
does not absorb light at wavelengths >290 nm. The atmospheric half-life of vapor phase diethyl bis(2-
hydroxyethyl)aminomethylphosphonate is estimated to be 0.9 hours, although it is expected to exist primarily in
the particulate phase in air.
Passes Ready Test: No
Test method: OECD TG 30 IB: Modified Sturm test
19% degradation over 28 days for 20 mg/L substance; 15%
degradation over 28 days for 10 mg/L substance. Purity of
test substance not reported, but is most likely ca. 85%.
Activated sludge from municipal sewage treatment plant
employed. (Measured)
Days-weeks (Primary survey model)
Weeks-Months (Ultimate survey model) (Estimated)
>1 year (Estimated)
>1 year (Estimated)
^+

Probable (Anaerobic-methanogenic biodegradation
probability model)

*
0.075 days (Estimated)
Supresta, 2006

EPIv4.11
EPIv4.11




EPIv4.11
Adequate, guideline study.



^o data located.

^o data located.
^o data located.

         7-117

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JUNE 2014 DRAFT REPORT
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate CASRN 2781-11-5
PROPERTY/ENDPOINT
Reactivity
Photolysis
Hydrolysis
Environmental Half-life
Bioaccumulation

Fish BCF
Other BCF
BAF
Metabolism in Fish
DATA
Not a significant fate process (Estimated)
Half-life at pH 4 =179 days;
Half-life at pH 7 = 26 days;
Half-life at pH 9 = 14 hours,
All values at 25 °C as measured using the OECD 111 test
guideline and EPA OPPTS 835.2100 test method (Measured)

REFERENCE
Professional
judgment; Mill,
2000
Supresta, 2006

DATA QUALITY
The substance does not contain
functional groups that would be expected
to absorb light at wavelengths >290 nm.
Adequate, valid guideline study. The
purity of the substance was reported to
be 85%.
^o data located.
LOW: Both the estimated BCF and BAF for fish are less than 100.
3.2 (Estimated)

1 (Estimated) ^^F

EPIv4.11

EPIv4.11


No data located.

^o data located.
ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring
Ecological Biomonitoring
Human Biomonitoring
No data located.
No data located.
No data located.
         7-118

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                                                  JUNE 2014 DRAFT REPORT


ACE (2013) ACE Acidity and Basicity Calculator. http://aceorganic.pearsoncmg.eom/epoch-plugin/ppublic/pKa.jsp.

ECOSAR Ecological Structure Activity Relationship (ECOSAR), Version 1.11. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/oppt/newchems/tools/21ecosar.htm.

EPA (1999) High Production Volume (HPV) Challenge. Determining the adequacy of existing data. Washington, DC: U.S. Environmental
Protection Agency, http://www.epa.gov/hpv/pubs/general/datadfin.htm.

EPA (2009) Screening-level hazard characterization for phosphonic acid, P-[[bis(2-hydroxyethyl)amino]methyl]-, diethyl ester (Fyrol 6, CASRN
2781-11-5)  U.S. Environmental Protection Agency, http://www.epa.gov/hpvis/hazchar/2781115_Fyrol%206_Sept2009.pdf.

EPA (2012) Using noncancer screening within the SF initiative. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/oppt/sf/pubs/noncan-screen.htm.

EPI Estimation Programs Interface (EPI) Suite, Version 4.11. Washington, DC:  U.S. Environmental Protection Agency.
http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm.

ESIS (2012) European chemical Substances Information System. European Commission, http://esis.jrc.ec.europa.eu/.

HSDB (2005) Diethyl ((diethanolamino) methyl) phosphonate. Hazardous Substances Data Bank. National Library of Medicine.
http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen7HSDB.

Kettrup A, Ohrbach K, Matuschek G, et al. (1990) Thermal analysis-mass spectrometry and thermogravimetric adsorption on fire retardants.
Thermochimica Acta 166:41-52.

LANXESS  (2012) Material Safety Data Sheet for LEVAGARD 4090 N.

Mill T (2000) Photoreactions in surface waters. In: Boethling R Mackay D, eds. Handbook of Property Estimation Methods for Chemicals,
Environmental Health Sciences. Boca Raton: Lewis Publishers, 355-381.

Sturtz GL, Lecolier SL, Clement JC, et al. (1977) Diol-phosphonates US Patent 4,052,487.

Supresta (2006) HPV Robust Summary for Fyrol 6.
                                                              7-119

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                                                              JUNE 2014 DRAFT REPORT
               Emerald Innovation™ NH-1
                                                     Screening Level Toxicology Hazard Summary

This table only contains information regarding the inherent hazards of flame retardant chemicals. Evaluation of risk considers both the hazard and exposure associated with the
substance including combustion and degradation by-products. The caveats listed in the legend and footnote sections must be taken into account when interpreting the hazard
information in the table.
VL = Very Low hazard L = Low hazard    = Moderate hazard   = High hazard VH = Very High hazard - Endpoints in colored text (VL, L,   , H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].

* Unlike for Firemaster 550, data are not available for this mixture, only for the individual components. For this mixture, hazard designations are listed in bold and color when there
are measured data for all the components; the designation for the mixture is based on the component with the highest hazard. When measured data are not available for all
components, the designation for the mixture is based on the component with the highest hazard and is an estimation (italics).




Chemical




CASRN
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Emerald Innovation™ NH-1*
Confidential C
Confidential D
Confidential E
Confidential
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                                                                           7-120

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                                                         JUNE 2014 DRAFT REPORT
                                                                                                             CASRN: Confidential
                                                                                                             MW: Confidential
                                                                                                             MF: Confidential
                                                                                                             Physical Forms: Liquid
                                                                                                             Neat:
                                                                                                             Use: Flame retardant
SMILES: Confidential
Synonyms: Emerald Innovation™ NH-1; Halogen-free flame retardant
Chemical Considerations: This alternative is a mixture. EPI v4.11 was used to estimate physical/chemical and environmental fate values due to an absence of
experimental data. Measured values from experimental studies were incorporated into the estimations.
Polymeric: No
Oligomeric: Not applicable
Metabolites, Degradates and Transformation Products: None identified; although there is potential for other confidential substances to be formed (Professional
judgment).
Analog: Not applicable
Endpoint(s) using analog values: Not applicable
Analog Structure: Not applicable
Structural Alerts: Organophosphates; Neurotoxicity (EPA, 2012).
Risk Phrases: One component is listed as R50/53: Very toxic to aquatic organisms. May cause long-term adverse effects in the aquatic environment (OECD-SIDS,
2002).
Hazard and Risk Assessments: None identified.
                                                                     7-121

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JUNE 2014 DRAFT REPORT
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
PHYSICAL/CHEMICAL PROPERTIES
Melting Point (°C)
Boiling Point (°C)
Vapor Pressure (mm Hg)
Confidential C: -70
(Measured)
Confidential D: 50.5
(Measured)
Confidential D: 49
Reported as 49-50°C (Measured)
Confidential C: 200 at 4 mmHg
Reported as 200-230°C at 5.0-5.3 hPa
(Measured)
Confidential C: 215 at 4 mmHg
Reported as 215-228°C at 4 mmHg
(Measured)
Confidential C: 225 at 4 mmHg
Reported as 225-228°C at 4 mmHg
(Measured)
Confidential D and E: >300
(Estimated)
Confidential D: 245
Reported at 1 1 mm Hg (Measured)
Confidential D: 220
Reported at 5 mm Hg (Measured)
Confidential C: 0.03 at 150°C
(Measured)
Confidential C: 2. 17x10 7 at25°C
Reported as 2.8xlO'7 hPa at 25 °C
(Measured)
Confidential C: 0.01 at 20°C
Confidential study (as cited in
ATSDR2012)
Lide, 2008
EC, 2000
Confidential study
ATSDR2012
Confidential study
EPIv4.11;EPA, 1999
O'Neil et al., 2006
EC, 2000
ATSDR2012
Confidential study
Confidential study
Reported in peer reviewed secondary
sources.
Reported in a primary source.
Reported in a secondary source;
consistent with value reported in
primary source.
Reported in a peer reviewed
secondary source at a reduced
pressure.
Reported in a peer reviewed
secondary source.
Secondary source. No study details
provided.
Cutoff value for high boiling point
compounds according to HPV
assessment guidance.
Reported in a primary source.
Reported in a secondary source;
consistent with value reported in
primary source.
Reported in a peer reviewed
secondary source.
Reported in secondary source. No
study details were provided.
Secondary source. No study details
         7-122

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JUNE 2014 DRAFT REPORT
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT

Water Solubility (mg/L)
Log Kow
DATA
(Measured)
Confidential D: 6.28x10 6 at 25°C
(Extrapolated)
Confidential D: 1.5x1 06
(Measured)
Confidential E: 2.1x10 8 at 25°C
(Estimated)
Confidential C: 1,100 (Measured)
Reported as 1 . 1 g/L at 25 °C
Confidential C: 1,100 (Measured)
Reported as 1.1-1.3 g/L at 20°C
Confidential D: 1.9 (Measured)
Reported at 25 °C
Confidential D: 0.75 (Measured)
OECD Guideline 105
Confidential E: 7.7xlO"7 (Estimated)
Confidential D: 0.025 (Measured)
Confidential C: 3. 75
(Measured)
Confidential C: 3.65
Reported as Kow = 4,500 (Measured)
Confidential D: 4.59
(Measured)
Confidential D: 4.76
(Measured)
REFERENCE

Confidential study
EC, 2000
EPIv4.11
ATSDR2012
Confidential study
Confidential study
EC, 2000
EPA, 1999;EPIv4.11
EC, 2000
HSDB, 2003; ATSDR 2012;
PhysProp, 2012
Confidential study
Hanschetal., 1995
OECD-SIDS, 2002
DATA QUALITY
provided.
Reported in a secondary source.
Reported in a secondary source.

Reported in a peer reviewed
secondary source.
Reported in peer reviewed secondary
source.
Reported in a secondary source.
Guideline study reported in a
secondary source.
Estimated value is less than the cutoff
value, <0.001 mg/L, for insoluble
compounds according to HPV
assessment guidance.
Reported in a secondary source; not
consistent with other measured
values.
Valid guideline study. Reported in
peer reviewed secondary sources.
Secondary source. No study details
provided.
Reported in a primary source.
Reported in a secondary source;
consistent with value reported in
primary source.
         7-123

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JUNE 2014 DRAFT REPORT
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT

Flammability (Flash Point)
Explosivity
Pyrolysis
pH
pKa
DATA
Confidential E: 11 (Estimated)
Flash Point: 258°C Cleveland Open
Cup method (Measured)
Confidential C, D & E: Not expected
to form explosive mixtures with air
(Estimated)

Confidential C: Neutral for 1 g/L
water at 20°C (Measured)
Confidential D & E: Not applicable
(Estimated)
Confidential D & E: Not applicable
(Estimated)
REFERENCE
EPIv4.11;EPA, 1999
Chemtura, 2013
Professional judgment

Confidential study
Professional judgment
Professional judgment
DATA QUALITY
Estimated value is greater than the
cutoff value, >10, according to
methodology based on HPV
assessment guidance.
Reported in the product literature for
commercial mixture.
No experimental data located; based
on its use as a flame retardant.
No data located.
Reported in peer reviewed secondary
source.
Does not contain functional groups
that are expected to ionize under
environmental conditions.
Does not contain functional groups
hat are expected to ionize under
snvironmental conditions.
         7-124

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JUNE 2014 DRAFT REPORT
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
HUMAN HEALTH EFFECTS
Toxicokinetics
Dermal Absorption in vitro
Absorption,
Distribution,
Metabolism
& Excretion
Oral, Dermal or Inhaled
Confidential C was found to absorb into the hepatic portal circulation following dietary exposure;
metabolism is likely to occur in the liver. Confidential D is hydrolyzed in the liver to produce a primary
metabolite. Confidential D can be detected in human breast milk.

Confidential C: Rats were fed diets
containing 03, 0.3 or 3.0%
Confidential C for 5 or 14 weeks or
0.25 or 0.5 ml/kg for 18 weeks.
Confidential C was absorbed into the
hepatic portal circulation. The site of
metabolism is likely to be the liver,
which was the only target organ for
toxicity in this study
Confidential D: Pregnant rats were
administered 0, 0.1 or 1 mg/kg-day of
confidential product in the diet across
gestation and through lactation (GD8
-PND21)
Components of a confidential product
were detected in adipose, liver, and
muscle tissues in Dams at PND 21
with the highest concentration in the
adipose tissue (768 ng/g w.w. in high
dose, 29.6 ng/g w.w. in low dose,
<7.0 ng/g w.w. in controls). The
primary metabolite was also detected
in liver tissue of dams on PND 2 1 .
Confidential D: Confidential D is
hydrolyzed in rat liver homogenate to
produce metabolites.

ECHA, 2013
^^^N. T
^f
Confidential study
7
OECD-SIDS, 2002; ECHA, 2012
^o data located.
Sufficient study details in a secondary
source.
Non guideline study indicates that
absorption of this compound can
occur in rats through oral exposure;
the test substance is confidential
sroduct.
Reported in a secondary source.
         7-125

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JUNE 2014 DRAFT REPORT
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT

Other
Acute Mammalian Toxicity
Acute
Lethality
Oral
DATA
Confidential D: Confidential D
concentrations in milk were analyzed
n a human cohort study conducted
jetween 1997 and 2007. Median
concentration across all subjects was
8.5 ng/g (min-max values: 3.2 - 1 1
ng/g).
REFERENCE
ECHA, 2012
DATA QUALITY
Limited study details reported in a
secondary source.
HIGH: Based on a 4-hour inhalation LC50 < 5.03 mg/L in rats following exposure to Confidential C. The
LC50 value of 5.03 mg/L is in the Moderate hazard criteria range, the actual LC50 could possibly be < 1.0
mg/L; therefore, a conservative hazard designation is assigned. Confidential C is of LOW concern for acute
toxicity via the oral and dermal routes of exposure. Acute toxicity is LOW for Confidential D and E.
Confidential C: Rat oral LD50 >2,000
mg/kg
Confidential C: Rat oral LD50 =
3,000 mg/kg
Confidential C: Guinea pig oral LD50
= 3,000 mg/kg
Confidential C: Rat oral LD50 =
4,700 mg/kg
Confidential C: Rat oral LD50 =
9,490 mg/kg
Confidential D: Rat, mouse, oral
LD50 >5,000 mg/kg
Confidential D: Rat oral LD50 >6,400
mg/kg
Confidential D: Rat oral LD50
>20,000 mg/kg
Confidential D: Rat oral LD50 =
10,800 mg/kg
Confidential D: Rat oral LD50 =
ECHA, 2013
Confidential study
ECETOC, 1992
Confidential study
ECETOC, 1992
OECD-SIDS, 2002
ATSDR 2009
OECD-SIDS, 2002
OECD-SIDS, 2002
OECD-SIDS, 2002
Sufficient study details in secondary
source. Conducted in accordance with
OECD Guideline 401.
No study details reported in a
secondary source.
No study details reported in a
secondary source.
No study details reported in a
secondary source.
No study details reported in a
secondary source.
Reported in a secondary source.
Reported in a secondary source.
Study reported in a secondary source.
Study reported in a secondary source;
number of animals not reported.
Study reported in a secondary source.
         7-126

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JUNE 2014 DRAFT REPORT
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT


Dermal
DATA
3,500 mg/kg
Confidential E: Rabbit dermal LD50
>2,000 mg/kg
Confidential E: Rat or LD50 4,700
mg/kg (females); >5,000 mg/kg
(males) ^^1
Confidential E: Rat oral LD50 >5,000
mg/kg
Confidential E: Rat oral LD50 =
20,000 mg/kg
Confidential E: Rat oral LD50 > 30
ml/kg (-32,490 mg/kg based on a
density of 1.083 g/cm3)
Confidential C: Rabbit dermal LD50
>2 mL/kg (-2,040 mg/kg bw)
Confidential C: Rabbit dermal LD50
>4,640 mg/kg
Confidential C: Rabbit dermal LD50
>5,000 mg/kg ^T
Confidential C: Rabbit dermal LD50
> 10,000 mg/kg
Confidential D: Rabbit dermal LD50
>7,900 mg/kg
Confidential D: Rabbit dermal LD50
> 10,000 mg/kg
Confidential E: Rabbit dermal LD50
REFERENCE

ECHA, 2013
ECHA, 2013
ECHA, 2013
Confidential study
Confidential study
ECHA, 2013
ECHA, 2013
ECHA, 2013
Confidential study
ATSDR 2009
OECD-SIDS, 2002
Confidential study
DATA QUALITY
Dose range and number of animals is
not provided.
Adequate study reported in a
secondary source. Four studies; test
substance is confidential product.
Adequate study reported in a
secondary source. Test substance is
confidential product.
Adequate study reported in a
secondary source. Three studies; test
substance is confidential product.
Adequate primary source. Test
substance is confidential product.
Adequate primary source.
Sufficient details in a secondary
source. Equivalent or similar to
OECD Guideline 402.
Sufficient details reported in a
secondary source. No information on
substance purity.
Sufficient details reported in a
secondary source.
No details reported in a secondary
source.
Reported in a secondary source.
Reported in a secondary source.
Adequate primary source. Test
         7-127

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JUNE 2014 DRAFT REPORT
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT


Inhalation
Carcinogenicity
DATA
> 10,000 mg/kg
Confidential E: Rabbit dermal LD50
>10 ml/kg (-10,830 mg/kg based on a
density of 1.083 g/cm3)
Confidential C: Rat 4-hour
inhalation LC50 <5.03 mg/L
During the first 4-hours post exposure
2/5 female rats died. During the 14-
day observation period 4/5 males and
all female rats died.
Confidential C: Rat 4-hour
inhalation LC50 >0.52 mg/L.
Confidential C: Rat 4-hour
inhalation LC50 >4.43 mg/L.
Confidential C: Rat 4-hour nose-only
inhalation LC50 >6.4 mg/L
Confidential D: Rat 1-hour LC50 >
200 mg/L
Confidential E: Rat 6-hour inhalation
(vapor) LC50 >0.4 mg/L
Confidential E: Rat 1 -hour inhalation
LC50 >200 mg/L
REFERENCE

Confidential study
ECHA, 2013
^^^N. T
ECHA, 2013
ECHA, 2013
ECHA, 2013
OECD-SIDS, 2002; ATSDR 2009
ECHA, 2013
Confidential study
DATA QUALITY
substance is confidential product.
Adequate primary source.
Sufficient details reported in a
secondary source. However, only a
single concentration was tested; test
substance was in aerosol form.
Sufficient details reported in a
secondary source. However, only a
single concentration was tested.
Sufficient details reported in a
secondary source. No data on test
substance purity.
Sufficient details reported in a
secondary source. Conducted in
accordance with OECD Guideline
403. No data on test purity.
Reported in a secondary source.
Insufficient exposure time ( 1 hour),
no data on method or GLP.
Adequate study reported in a
secondary source. Test material is a
confidential product.
Adequate primary source. Test
material is defined as confidential
product.
MODERATE: There is uncertainty due to lack of data for Confidential C and E. Carcinogenic effects cannot
be ruled out. OncoLogic modeling indicates a marginal to low potential for carcinogenicity for Confidential
D. No long-term carcinogenicity assays were found.
         7-128

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JUNE 2014 DRAFT REPORT
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT

OncoLogic Results
Carcinogenicity (Rat and
Mouse)
Combined Chronic
Toxicity/Carcinogenicity
Other
Genotoxicity

Gene Mutation in vitro
DATA
Confidential D: Marginal; likely to
lave equivocal carcinogenic activity.
Confidential D: Mouse lung adenoma
test: Male A/St mice (20/group)
received i.p. injections of either 20
mg/kg (18/6 weeks); 40 mg/kg (3/1
week); or 80 mg/kg. No significant
ncrease in incidence of adenoma
compared to negative controls, and
positive control (urethane) produced
[9.6 tumors/mouse with 100%
survival.


REFERENCE
OncoLogic, 2008
OECD-SIDS, 2002
^^^
^^^N. T


DATA QUALITY
No data located.
^o data located.
No data located.
No data located.
LOW: Based on negative results for in vitro and in vivo studies.
Confidential C: Negative, HGPRT
assay in Chinese hamster ovary
^CHO) cells, with and without
metabolic activation.
Confidential C: Negative, mouse
ymphoma L5 178Y cells with and
without metabolic activation. Positive
controls responded as expected.
Confidential C: Negative,
Salmonella typhimurium strains
TA1535, TA1537, TA98 and TA100
with and without metabolic activation.
Positive controls responded as
expected.
ECHA, 2013; Confidential study
ECHA, 2013
Confidential study
Limited data reported in a secondary
source. Study report was not available
although data have been peer-
reviewed in reference work. No
information available regarding use of
positive controls.
Sufficient details reported in a
secondary source. Conducted in
accordance with OECD Guideline
476.
Sufficient details in a secondary
source.
         7-129

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                                                JUNE 2014 DRAFT REPORT
                                                 Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  Confidential C: Negative,
                                  Salmonella typhimurium strains TA98
                                  and TA100 with and without
                                  metabolic activation. Positive controls
                                  responded as expected.
                    Confidential study
                        Sufficient study details reported in a
                        primary source.
                                  Confidential C: Negative,
                                  Salmonella typhimurium strains
                                  TA98, TA100, TA1535, TA1537,
                                  TA1538 with and without metabolic
                                  activation. Positive controls
                                  responded as expected.
                    ECHA, 2013
                        Sufficient details in summaries of
                        three similar studies reported in a
                        secondary source. No data on test
                        substance purity.
                                  Confidential C: Negative,
                                  Salmonella typhimurium strains
                                  TA1535, TA1537, TA98 and TA100
                                  with and without metabolic activation.
                    ECHA, 2013
                       Adequate study reported in a
                       secondary source. Study protocol in
                       line with Guideline for gene point
                       mutation assay in bacterial cells.
                                  Confidential C: Negative,
                                  Salmonella typhimurium strains
                                  TA98, TA100, TA1535, TA1537,
                                  TA1538 with and without metabolic
                                  activation.
                                  Cytotoxicity was evident in strain
                                  TA100 at >/= 0.29 microliters per
                                  plate.
                    ECHA, 2013
                       Adequate study reported in a
                       secondary source. The test method is
                       comparable to current protocols using
                       bacterial strains standard at the date in
                       which the study was conducted.
                                  Confidential C: Negative, E. coll
                                  strain pol A+ and pol A- with and
                                  without metabolic activation.
                                  No cytotoxicity, tested up to
                                  precipitating concentrations. Positive
                                  controls responded as expected.
                    ECHA, 2013
                        Sufficient study details reported in a
                        secondary source. Acceptable
                        scientific method. No data on test
                        substance purity.
                                  Confidential D: Negative, Ames
                                  assay in Salmonella typhimurium
                                  strains TA98, TA100, TA1537,
                                  TA1538 with and without metabolic
                    ATSDR 2009; ECHA, 2013
                       Reported in a secondary source.
                                                            7-130

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JUNE 2014 DRAFT REPORT
 Emerald Innovation™ NH-1
PROPERTY/ENDPOINT


Gene Mutation in vivo
DATA
activation
Confidential D: Negative, forward
mutation assay in mouse lymphoma
L5178Y cells
Confidential E: Negative, cell
transformation assay in BALB/3T3
cells without metabolic activation.
Test concentrations: 0.00125,
0.00250, 0.005, 0.01 and 0.02 pi/ml
Confidential E: Negative, mouse
lymphoma L5 178Y cells with and
without metabolic activation.
Test concentrations: 0.013, 0.025,
0.038, 0.05, and 0.1 nl/ml
Confidential E: Negative, mouse
lymphoma L5 178Y cells with and
without metabolic activation.
Test concentrations: 0.975, 15.6, 31.3,
62.5, and 125 nl/ml. The
concentration of 125 nl/ml was highly
toxic and insufficient survivors were
obtained at 250 nl/ml to perform the
assay.
Confidential E: Negative,
Salmonella typhimurium strains
TA1535, TA1537, TA1538, TA98
and TA100 and Saccharomyces
cerevisiae D4 with and without
metabolic activation.
Test concentrations: 0.01, 0.1, 1.0,
5.0, and 10 (J/plate

REFERENCE

OECD-SIDS, 2002; ECHA, 2013
ECHA, 2013
ECHA, 2013
^^
ECHA, 2013
7
ECHA, 2013

DATA QUALITY

Reported in a secondary source.
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
No data located.
          7-131

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                                                JUNE 2014 DRAFT REPORT
                                                 Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
             DATA
          REFERENCE
        DATA QUALITY
    Chromosomal Aberrations in
    vitro
 onfidential D: Negative in
chromosome aberration test in Chinese
lamster V79 cells; with and without
metabolic activation.
ECHA, 2013
Reported in a secondary source.
                                   onfidential E: Negative, sister
                                  ;hromatid exchanges (SCEs) and
                                  chromosome aberrations in mouse
                                  ymphoma L5178Y cells with and
                                  without metabolic activation.
                                  Test concentrations:  - S9 mix:
                                  D.000625, 0.00125, 0.00250, 0.00500
                                  and 0.01000 nl/ml; +S9 mix: 0.00125,
                                  D.00250, 0.00500, 0.01000 and
                                  D.02000 nl/ml
                                  ECHA, 2013
                                 Adequate study reported in a
                                 secondary source. Test material is
                                 defined as confidential product.
    Chromosomal Aberrations in
    vivo
Confidential C: Negative,
micronucleus assay in NMRI mice
(5/sex/dose) administered
 onfidential C via oral gavage at a
dose of 1,800 mg/kg. Positive controls
responded as expected.
ECHA, 2013
Sufficient details reported in a
secondary source. Conducted in
accordance with OECD Guideline
474. No data on test substance purity.
    DNA Damage and Repair
Confidential C: Negative, DNA
damage and/or repair assay in Syrian
lamster kidney cells with and without
metabolic activation. Positive controls
responded as expected.
ECHA, 2013
                                  Confidential D: Negative,
                                  unscheduled DNA synthesis in
                                  lamster fibroblast cells
                                  OECD-SIDS, 2002
Sufficient details reported in a
 econdary source. No data on purity
of test substance.
                                 Reported in a secondary source.
    Other
 onfidential D: Negative, mitotic
gene conversion assay in
Saccharomyces cerevisiae with and
without activation
OECD-SIDS, 2002
Reported in a secondary source.
                                                           7-132

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                                                         JUNE 2014 DRAFT REPORT
                                                          Emerald Innovation™ NH-1
          PROPERTY/ENDPOINT
              DATA
          REFERENCE
        DATA QUALITY
Reproductive Effects
MODERATE: No adverse effects were observed on fetal viability, post-implantation loss, total implantations
or the incidence of fetal malformations at doses up to 1,500 mg/kg-day (LOAEL not established) following
gestational oral exposure to Confidential C in rats. Although no reproductive effects were observed in this
study, there is a lack of data on reproductive parameters as measured in fertility or multigenerational
studies and no data were available for other routes of exposure. It is uncertain if effects would occur in more
definitive studies or via other routes; a Moderate hazard has been designated based on this uncertainty.
Reproductive toxicity is LOW for Confidential D and E.
             Reproduction/Developmental
             Toxicity Screen
Confidential C: Confidential C was
administered by gavage in corn oil to
three groups of 25 mated Charles
River CD female  rats at dose levels of
0 (corn oil), 250,  500 or 1,500 mg/kg-
day on days 6 to 15 of gestation. The
treatment had no effect at any dose
level on fetal resorption, fetal
viability, post-implantation loss, total
implantations or the incidence of fetal
malformations.

NOAEL: 1,500 mg/kg-day (highest
dose tested)
LOAEL: Not established
Confidential study
Sufficient details reported in a
secondary source.
                                                                     7-133

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                                                JUNE 2014 DRAFT REPORT
                                                 Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
              DATA
          REFERENCE
         DATA QUALITY
    Combined Repeated Dose with
    Reproduction/ Developmental
    Toxicity Screen
 onfidential D:
Reproductive/developmental dietary
study; Confidential D was
idministered in the diet for 91  days at
concentrations of 0, 0.25, 0.50, 0.75,
  1.0% (~0, 166, 341,516 or 690
-ng/kg-day, respectively). At the
completion of this study, females were
nated with males from the same
jroup. All remained on the same diet
is in the subchronic study until day 20
}f gestation when dams were
sacrificed. No signs of parental
oxicity, no reproductive effects
number pregnant, corpora lutea,
mplantations, implantation efficiency,
"esorptions).

SfOAEL: 690 mg/kg-day (highest dose
ested)
 GAEL: Not established
OECD-SIDS, 2002; ATSDR, 2009   Reported in a secondary source
    Reproduction and Fertility
    Effects
Confidential D: Rabbits, dermal
clipped, intact), 5x/week, 3 weeks,
50% solution in ethanol; no effect on
he reproductive organs reported up to
he highest dose tested (1,000 mg/kg-
iay)

SfOAEL: 1,000 mg/kg-day (highest
iose tested)
OECD-SIDS, 2002
Reported in a secondary source.
Organs examined by histopathology;
here were no effects at the highest
dose tested; dermal repeated-dose
study.
                                   Confidential E: Sprague-Dawley rats
                                   12/sex/dose) were orally gavaged
                                  mth 50, 250, 1,000 mg/kg-day
                                  ECHA, 2013
                                 Adequate study reported in a
                                 secondary source. Test material is
                                 defined as confidential product.
                                                            7-134

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                                                JUNE 2014 DRAFT REPORT
                                                  Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   'onfidential E. Exposure was 2 weeks
                                   prior to mating, during mating period
                                   up to 2 weeks, males and females)
                                   and during gestation, lactation and
                                   antil post-partum day 4 (females).

                                   No mortality or overt signs of parental
                                   oxicity. No effect was seen on body
                                   weight and food consumption. Gross
                                   necropsy and organ weight data and
                                   listopathology of the  reproductive
                                   Drgans revealed no adverse findings.
                                   Mean litter size and mean number of
                                   ive pups was comparable between the
                                   reatment groups. No effects on litter
                                   weights. Percent post-implantation
                                   oss was higher in 250 and 1,000
                                   mg/kg-day groups (not statistically
                                   significant). Subsequently, a
                                   statistically significant increase in the
                                   absolute number of stillbirths in the
                                   250 and 1,000 mg/kg-day groups was
                                   noted. However, overall a similar
                                   number of pup deaths were observed
                                   across all groups. Overall, pup
                                   survival from day 0 to 4 was lower in
                                   he 250 mg/kg-day group (due to 10
                                   deaths in one litter), higher in the 50
                                   mg/kg-day group and approximately
                                   he same as control in the  1,000
                                   mg/kg-day group.

                                   NOAEL: 1,000 mg/kg-day (highest
                                   lose tested)
                                                            7-135

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                                               JUNE 2014 DRAFT REPORT
                                                 Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
             DATA
          REFERENCE
        DATA QUALITY
                                  ,OAEL: Not established
    Other
 onfidential D: Men living in
lomes with higher amounts of
Confidential D in house dust had
•educed sperm count and altered
lormone levels related to fertility
md thyroid function. Each
nterquartile range (IQR)
 'onfidential D increase in house
iust samples was associated with a
 9% decrease in sperm
concentrations and a 10% increase
n prolactin levels.
Confidential study
The actual exposure to Confidential
D is unknown; it is not known if
 onfidential D or other substances
found in the household dust caused
or contributed to the reported
oxicity.
                                                           7-136

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                                                         JUNE 2014 DRAFT REPORT
                                                          Emerald Innovation™ NH-1
         PROPERTY/ENDPOINT
             DATA
          REFERENCE
        DATA QUALITY
Developmental Effects
LOW: Based on a rat oral reproductive/developmental NOAEL = 690 mg/kg-day for fetal effects (highest
dose tested) following exposure to Confidential D. Developmental toxicity is also LOW for Confidential E
(based on a NOAEL and LOAEL of 400 and 1,000 mg/kg-day, respectively) and VERY LOW for
 onfidential C (based on a NOAEL of 2,000 mg/kg-day).

There were no data located for the developmental neurotoxicity endpoint. Decreased cholinesterase activity
n pregnant lab animals has been shown to have a negative impact on fetal brain development. As a result,
;here is uncertain potential for developmental neurotoxicity for this substance.
             Reproduction/ Developmental
             Toxicity Screen
 onfidential D:
Reproductive/developmental dietary
study; Confidential D was
idministered in the diet for 91 days at
concentrations of 0, 0.25, 0.50, 0.75,
  1.0% (~0, 166, 341,516 or 690
rig/kg-day, respectively). At the
completion of this study, females were
nated with males from the same
jroup. All remained on the same diet
is in the subchronic study until day 20
}f gestation when dams were sacrifice.
Mo effects on fetal endpoints
viability, early or late deaths, fetal
weight, length or distribution) or
skeletal anomalies.

Developmental effects:
SfOAEL: 690 mg/kg-day (highest dose
ested)
 GAEL: Not established
OECD-SIDS, 2002; ATSDR, 2009;
ECHA, 2012
  LOAEL was not identified; there
were no effects at the highest dose
ested.
             Combined Repeated Dose with
             Reproduction/ Developmental
             Toxicity Screen
                                                                  No data located.
                                                                    7-137

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JUNE 2014 DRAFT REPORT
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT































Prenatal Development






























DATA
Confidential C: In a range-finding
developmental toxicity study,
Confidential C was administered by
gavage in corn oil to groups of 5
mated Charles River CD female rats
at dose levels of 0, 25, 250, 500
1,000, and 2,000 mg/kg-day on days 6
to 15 of gestation. At doses up to
1,000 mg/kg-day, all rats survived.
Two animals died or were sacrificed
in the high dose group. Maternal
toxicity (reduced righting reflex,
hypoactivity, lethargy, ataxia and
stained anogenital haircoat) was
observed in the animals receiving 500
mg/kg-day or greater. Maternal
weight gain was normal in animals
receiving 1,000 mg/kg-day or less.
The treatment had no effect at any
dose level on fetal resorption, fetal
viability, postimplantation loss and
total implantations.
Maternal Toxicity:
NOAEL: 250 mg/kg-day
LOAEL: 500 mg/kg-day
Developmental toxicity:
NOAEL: 2,000 mg/kg-day (highest
dose tested)
LOAEL: Not established
Confidential C: In a developmental
toxicity study, Confidential C was
REFERENCE
ECHA, 2013




^^^

^L

^^^N. T



^f



T











ECHA, 2013; Confidential study

DATA QUALITY
Adequate study reported in a
secondary source. Conforms to
Guidelines for a range finding
teratology study, but some data
missing. No data on when sacrifices
were conducted. No data on whether
fetal examinations were conducted.






















Sufficient study details reported in
secondary sources. No data on test
         7-138

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                                                JUNE 2014 DRAFT REPORT
                                                 Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  administered by gavage in corn oil to
                                  three groups of 25 mated Charles
                                  River CD female rats at dose levels of
                                  250, 500 and 1,500 mg/kg-day on
                                  days 6 to 15 of gestation. Sacrifices
                                  were conducted on Gd 20. Maternal
                                  weight gain was depressed only in the
                                  high-dose group. The treatment had
                                  no effect at any dose level on fetal
                                  resorption, fetal viability,
                                  postimplantation loss, total
                                  implantations or incidence of fetal
                                  malformations.

                                  Maternal Toxicity:
                                  NOAEL: 500 mg/kg-day
                                  LOAEL: 1,500 mg/kg-day

                                  Developmental toxicity:
                                  NOAEL: 1,500 mg/kg-day (highest
                                  dose tested)
                                  LOAEL: Not established
                                                      substance purity in secondary sources.
                                  Confidential D: Pregnant Wistar rats
                                  were administered 0, 0.1 or 1 mg/kg-
                                  day of the confidential analog in the
                                  diet during gestation and through
                                  lactation (GD8 - PND 21); Maternal
                                  toxicity: Increased serum thyroxine
                                  (T4) levels in the high dose dams
                                  compared to controls was reported.
                                  There was no significant change in
                                  triiodothyronine (T3) levels in dam
                                  serum. Decreased hepatic
                    Confidential study
                        Estimated based on data for
                        confidential mixture; non guideline
                        study.
                                                            7-139

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                                                 JUNE 2014 DRAFT REPORT
                                                  Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  carboxylesterease activity was also
                                  reported in dams in the high dose
                                  group. Developmental toxicity:
                                  female offspring in the high dose
                                  group displayed a significantly earlier
                                  vaginal opening when compared to
                                  controls. A statistically significant
                                  increase in weight was reported in
                                  both males and females in the high
                                  dose group at PND 120. This effect
                                  persisted through PND 180 to PND
                                  220 with high dose males and females
                                  having significantly higher weights
                                  than same sex controls. A dose-
                                  dependent decrease in the number of
                                  rats to enter with open arms,
                                  (indicating anxiety), was reported in
                                  both male and female offspring.
                                  Increased blood glucose levels were
                                  reported in male offspring in the high-
                                  dose group compared to controls.
                                  There was no statistically significant
                                  difference in heart weight of male or
                                  female offspring. Left ventricular
                                  (LV) free wall thickness was
                                  significantly increased in male
                                  offspring in the high dose group; there
                                  were no changes in LV thickness in
                                  females at any dose.

                                  Maternal Toxicity:
                                  NOAEL: O.lmg/kg-day
                                  LOAEL: 1 mg/kg-day
                                                             7-140

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                                                JUNE 2014 DRAFT REPORT
                                                 Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  Developmental toxicity:
                                  NOAEL: O.lmg/kg-day
                                  LOAEL: 1 mg/kg-day (based on early
                                  vaginal opening in females, increased
                                  weight in males and females,
                                  decreased open arm behavior,
                                  increased blood glucose levels in
                                  males and increased LV thickness in
                                  males)
                                  Confidential E: Sprague-Dawley rats
                                  (7 females/group) were administered
                                  Confidential E via oral gavage at
                                  doses on 100, 400, 1,000 mg/kg-day
                                  on GD 6-20.

                                  Reduced food consumption on GD 6-
                                  9 (1,000 mg/kg-day). Increased body
                                  weight gain (400 and 1,000 mg/kg-
                                  day). Increased absolute and relative
                                  liver weight in all treatment groups
                                  (not considered by study authors to be
                                  treatment-related). Embryo- or feto-
                                  toxicity as indicated by a reduction in
                                  fetal body weight (1,000 mg/kg-day).
                                  Craniofacial malformations in 3
                                  fetuses (1,000 mg/kg-day). Increased
                                  maternal body weight gain was
                                  reported on GDO-6 for the  100 and
                                  400 mg/kg-day dose groups and on
                                  GDI6-21 for the 400 mg/kg-day dose
                                  group; absolute and relative liver
                                  weights were increased in all
                                  treatment groups.
                    ECHA, 2013
                       Adequate study reported in a
                       secondary source. Test material is
                       defined as confidential product.
                                                            7-141

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                                                JUNE 2014 DRAFT REPORT
                                                 Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  Maternal toxicity:
                                  NOAEL: Not established
                                  LOAEL: 100 mg/kg-day (lowest dose
                                  tested)

                                  Developmental toxicity:
                                  NOAEL: 400 mg/kg-day
                                  LOAEL: 1,000 mg/kg-day
                                  Confidential E: Charles River rats
                                  (25 females) were administered
                                  Confidential E via oral gavage at
                                  doses of 0, 300, 1,000, 3,000 mg/kg-
                                  day once daily on GD 6-19.

                                  Clinical signs  of toxicity in all groups,
                                  including controls. Decrease in mean
                                  number of early resorptions and mean
                                  postimplantation loss (mid dose),
                                  which was attributed by study authors
                                  to a random occurrence. Slight
                                  increase in number of litters with
                                  malformations (high dose), but was
                                  not considered biologically significant
                                  by study authors (single incidences).

                                  NOAEL (maternal and
                                  developmental): 3,000 mg/kg-day
                                  (highest dose tested)
                                  LOAEL: Not established
                    ECHA, 2013
                       Adequate study reported in a
                       secondary source. Test material is
                       defined as confidential product.
                                  Confidential E: Charles River rats (5
                                  females/group) were administered
                                  Confidential E at doses of 250, 500,
                    ECHA, 2013
                       Adequate study reported in a
                       secondary source. Test material is
                       defined as confidential product.
                                                            7-142

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JUNE 2014 DRAFT REPORT
 Emerald Innovation™ NH-1
PROPERTY/ENDPOINT

















































Postnatal Development
Prenatal and Postnatal
Development
Developmental Neurotoxicity





DATA
1,000, 2,500, 5,000 mg/kg-day once
daily on GD 6-19.
No mortality or behavioral effects
were observed. Anogenital staining
and/or matting in all treatment groups.
Red and/or brown matter around the
nose, mouth and forelimbs (5,000
mg/kg-day). Slight reduction in body
weight gain (1,000 and 2,500 mg/kg-
day); severe reduction in mean
maternal body weight gain (5,000
mg/kg-day). Increase in
postimplantation loss, decrease in
viable fetuses (5,000 mg/kg-day).
Maternal toxicity:
NOAEL: 2,500 mg/kg-day
LOAEL: 5,000 mg/kg-day
Developmental toxicity:
NOAEL: 5,000 mg/kg-day
LOAEL: Not established



Confidential C: There were no data
located for the developmental
neurotoxicity endpoint. As a result,
there is uncertain potential for
developmental neurotoxicity for this
substance.
REFERENCE




^^^

A^ ^A

^^^N. T



^f


7







Professional judgment





DATA QUALITY




















No data located.
^o data located.

No data located.





          7-143

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                                                          JUNE 2014 DRAFT REPORT
                                                           Emerald Innovation™ NH-1
          PROPERTY/ENDPOINT
              DATA
          REFERENCE
        DATA QUALITY
                                            Confidential D: There were no data
                                            located for the developmental
                                            neurotoxicity endpoint. Decreased
                                            cholinesterase activity in pregnant lab
                                            animals has been shown to have a
                                            negative impact on fetal brain
                                            development. As a result, there is
                                            uncertain potential for developmental
                                            neurotoxicity for this substance.
                                  Professional judgment
                                 No data located.
                                            Confidential E: Uncertain concern
                                            for developmental neurotoxicity based
                                            on the potential for Cholinesterase
                                            (ChE) inhibition in dams that may
                                            result in alterations of fetal
                                            neurodevelopment.

                                            (Estimated)
                                  Professional judgment
                                 Estimated based on a structural alert
                                 for organophosphates for the
                                 tieurotoxicity endpoint.
              Other
                                                                       data located.
Neurotoxicity
MODERATE: Neurotoxic effects following exposure to Confidential C included morphological changes to
the sciatic nerve, reduction in caudal nerve response and increases in absolute and relative refractory
periods at a dose of 255 mg/kg-day in rats (lowest dose tested). These studies indicated that there is some
potential for neurotoxicity at higher doses. In addition, there is potential for neurotoxic effects based on a
structural alert. A NOAEL and LOAEL of- 10 and ~ 100 mg/kg-day, respectively were established in
rabbits following dermal exposure to Confidential E. Adverse effects included decreased brain
cholinesterase. The  potential for neurotoxic effects following exposure to Confidential D is LOW.
              Neurotoxicity Screening
              Battery (Adult)
Confidential C: Sprague-Dawley rats
(12/sex/dose), received Confidential C
daily via oral gavage at doses of 0.25
or 0.50 g/kg-day for 18 weeks. (255
or 510 mg/kg-day). Adverse
neurological signs were evident in
almost all exposed rats in the second
half of the study. Nerve conduction
ECHA, 2013; Confidential study
Sufficient study details study reported
in a secondary source. Study limited
by not establishing a NOAEL.
                                                                      7-144

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                                                JUNE 2014 DRAFT REPORT
                                                 Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  measurements were made with all rats
                                  at the end of the 6th, 12th, and 18th
                                  week.
                                  No differences in body weights
                                  throughout the study. Breathing
                                  difficulty and ataxia were observed.
                                  Tremors at high dose. Significantly
                                  reduced conduction velocity in the
                                  caudal nerve in both treatment groups.
                                  Increased absolute (18 weeks) and
                                  relative refractory periods (12 and 18
                                  weeks). Morphological changes
                                  (axonal degeneration and
                                  demyelination) in both treated groups,
                                  with a greater incidence in the high
                                  dose animals. Both myelinated and
                                  unmyelinated nerves were adversely
                                  affected. The gradual development of
                                  neurotoxicity after several weeks of
                                  treatment confirms the progressive
                                  nature of this form of toxicity, and
                                  suggests that repeated exposure is
                                  necessary to elicit a neurotoxic
                                  response.
                                                       ^+
                                  NOAEL: Not established
                                  LOAEL: 255 mg/kg-day
                                                            7-145

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                                                JUNE 2014 DRAFT REPORT
                                                 Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  Confidential D: 4-month dietary
                                  study, 10 rats/dose, 0.25, 0.5, 0.75 or
                                  1% test concentration (161, 345, 517
                                  or 711 mg/kg-day, respectively), no
                                  neurobehavioral effects (open field,
                                  accelerating rotarod, forelimb grip
                                  strength and negative geotaxis
                                  examinations).

                                  NOAEL: 711 mg/kg-day (highest
                                  dose tested)
                                  LOAEL: Not established
                    ATSDR 2009
                        Reported in a secondary source.
                                  Confidential C: Single oral
                                  administration of Confidential C to
                                  rats (1,000 - 3,200 mg/kg for females,
                                  1,000 - 9,000 mg/kg for males)
                                  (20/sex/group). Three weeks after
                                  administration, measurements of
                                  nerve conduction velocity (NCV),
                                  relative refractory period (RRP) and
                                  absolute refractory period (ARP) were
                                  conducted in the caudal nerve.
                                  Dose related reductions in caudal
                                  NCV in both sexes and a significant
                                  increase in refractory period (both
                                  RRP and ARP) recorded in the two
                                  highest dosed male groups. No
                                  morphological changes in the sciatic
                                  nerves of low dose rats. At higher
                                  doses some changes were recorded,
                                  including sciatic nerve section
                                  degenerative changes in some
                                  myelinated and unmyelinated fibers.
                    ECHA, 2013; Confidential study
                        Sufficient study details reported in
                        secondary sources.
                                                            7-146

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                                                JUNE 2014 DRAFT REPORT
                                                 Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  NOAEL: 1,500 mg/kg
                                  LOAEL: 3,200 mg/kg for males and
                                  1750 mg/kg for females
                                  Confidential C: Sprague-Dawley rats
                                  (20/sex/group) administered
                                  Confidential C in the diet at
                                  concentrations of 0, 300, 3,000 and
                                  10,000 ppm (approximately 20.4, 204,
                                  or 612 mg/kg-day) for 18-weeks
                                  followed by an 8-week recovery
                                  period.
                                  No effect on bodyweight; no gross
                                  signs of neurotoxicity; no significant
                                  alterations in NCV, ARP, or RRP
                                  except for significant reductions in
                                  NCV in high-dose females; no
                                  microscopic morphological changes
                                  in central and peripheral nervous
                                  tissues.

                                  NOAEL: 204 mg/kg-day
                                  LOAEL: 612 mg/kg-day
                    ECHA, 2013
                       Sufficient study details reported in a
                       secondary source.
                                  Confidential E: White leghorn hens
                                  were administered Confidential E via
                                  oral gavage at an oral dose of 11,700
                                  mg/kg-day for 6 weeks. Significant
                                  inhibition of plasma cholinesterase
                                  was found, but no significant
                                  inhibition of brain neurotoxic
                                  esterase.

                                  NOAEL: > 11,700 mg/kg-day
                    ECHA, 2013
                       Adequate study reported in a
                       secondary source. Test material is
                       defined as confidential product.
                                                           7-147

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                                                JUNE 2014 DRAFT REPORT
                                                 Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
              DATA
          REFERENCE
        DATA QUALITY
                                  LOAEL: Not established
                                  Confidential E: White leghorn
                                  chickens were administered
                                  Confidential E via oral gavage at an
                                  oral dose of 0, 240, 300, 360 and 420
                                  mg/kg-day for 5 consecutive days and
                                  were observed for 30 days. No
                                  behavioral signs of delayed
                                  neurotoxicity were observed. Gross
                                  pathological examination revealed no
                                  lesions attributable to ingestion of the
                                  test substance.

                                  NOAEL: >420 mg/kg-day
                                  LOAEL: Not established
                                  Confidential study
                                 Adequate primary source. Test
                                 material is defined as confidential
                                 product.
                                  Confidential E: White leghorn hens
                                  were administered Confidential E via
                                  oral gavage at a single dose of 11,830
                                  mg/kg. No adverse effects.

                                  NOAEL: 11,830 mg/kg
                                  LOAEL: Not established
                                  ECHA, 2013
                                 Adequate study reported in a
                                 secondary source. Test material is
                                 defined as confidential product.
    Other
Confidential C: There is potential for
neurotoxic effects based on a
structural alert for organophosphates.
(Estimated)
Professional judgment
Estimated based on a structural alert
and professional judgment.
                                  Confidential C: In a 14-day gavage
                                  study in rats (20/sex/group), at doses
                                  of 0.8 and 1.12 ml/kg-day (814 and
                                  1142 mg/kg-day) for females and at
                                  0.8 and 2.24 ml/kg-day (814 and 2285
                                  mg/kg-day) for males, no clinical
                                  signs of neurotoxicity were reported.
                                  ECHA, 2013; Confidential study
                                 Sufficient study details in secondary
                                 source.
                                                            7-148

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                                                JUNE 2014 DRAFT REPORT
                                                 Emerald Innovation™  NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  Significant reduction in caudal nerve
                                  conduction velocity was observed in
                                  high dose females and dose-related
                                  increases of refractory (relative and
                                  absolute) periods were also observed
                                  in all animals immediately after
                                  cessation of exposure. After 15 days
                                  recovery increases in ARP and RRP
                                  remained only in high dose females.

                                  NOAEL: 814 mg/kg-day
                                  LOAEL: 1,142 mg/kg-day (based on
                                  electrophysiological changes still
                                  present after the recovery period)
                                  Confidential C: Twenty hens were
                                  tested with two doses of 5,000 mg/kg
                                  Confidential C administered in a
                                  gelatin capsule or dermally 21-days
                                  apart and were killed 21 days after the
                                  second dose.
                                  Esterase inhibition studies (NTE,
                                  brain AChE and plasma BuChE) were
                                  conducted following a single oral
                                  dose of Confidential C to groups of 5
                                  hens. Positive and negative controls
                                  were also evaluated for comparison.
                                  All 20 hens dosed with 2 x 5,000
                                  mg/kg Confidential C survived. No
                                  treatment-related findings of
                                  neurotoxicity were observed in
                                  Confidential C-treated hens dosed
                                  orally or dermally. NTE activity in the
                                  brain following Confidential C
                     ECHA, 2013; Confidential study
                        Sufficient study details reported in
                        secondary sources.
                                                            7-149

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                                                JUNE 2014 DRAFT REPORT
                                                 Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  exposure was within normal limits;
                                  brain AChE was inhibited by 45%
                                  with no evidence of associated
                                  clinical signs or cholinergic toxicity
                                  and plasma BuChE activity was also
                                  inhibited.
                                  Exposure to Confidential C does not
                                  induce delayed neurotoxicity in hens
                                  and no neurologic deficits nor
                                  histopathological changes
                                  characteristic of OPIDN were
                                  observed.

                                  NOAEL: >5,000 mg/kg
                                  LOAEL: Not established
                                  Confidential D: There is potential for
                                  neurotoxic effects based on a
                                  structural alert for organophosphates
                                  (Estimated)
                    Professional judgment
                        Estimated based on a structural alert
                        for organophosphates and
                        professional judgment.
                                  Confidential D: Two female
                                  hens/dose in delayed neurotoxicity
                                  test, gavage, 2,000, 3,000, 5,000,
                                  8,000, or 12,500 mg/kg, no signs of
                                  toxicity in4ife or at necropsy

                                  NOAEL >12,500 mg/kg; highest dose
                                  tested
                                  LOAEL: Not established
                    OECD-SIDS, 2002
                        Reported in a secondary source. No
                        data on test substance purity.
                                  Confidential D: Several acute oral
                                  studies in hens, administered doses up
                                  to 12,500 mg/kg, generally found no
                                  signs of paralysis, histopathological
                                  changes in examined nerve tissues, or
                    OECD-SIDS, 2002
                        Reported in a secondary source. No
                        data on test substance purity.
                                                            7-150

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                                                JUNE 2014 DRAFT REPORT
                                                 Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
   DATA
REFERENCE
DATA QUALITY
                                  behavior immediately after or during
                                  observation periods of up to 36 days.
                                  However, blood cholinesterase was
                                  decreased by up to 87% in studies
                                  where it was measured.

                                  NOAEL: > 12,500 mg/kg; highest
                                  dose tested
                                  LOAEL: Not established
                                  Confidential E: Rabbits
                                  (10/sex/dose) were dermally exposed
                                  to Confidential E at doses of 0, 10,
                                  100, and 1,000 mg/kg 6 hours/ days, 5
                                  days/week for 23 days.

                                  No treatment-related  deaths. Edema,
                                  atonia, desquamation and fissuring.
                                  Increased mean terminal blood urea
                                  nitrogen values (high dose). Dose
                                  response depression of RBC and brain
                                  cholinesterase (mid and high dose).
                                  No effect on body weights,
                                  hematology and clinical chemistry
                                  data, organ weights and organ/body
                                  weight ratios. No treatment-related
                                  gross or microscopic  changes.
                        ECHA, 2013
                       Adequate study reported in a
                       secondary source. Test material is
                       defined as confidential product.
                                  NOAEL:
                                  LOAEL:
10 mg/kg-day;
100 mg/kg-day
                                  Confidential E: There is potential for
                                  neurotoxic effects based on a
                                  structural alert for organophosphates
                                  (Estimated)
                        Professional judgment
                       Estimated based on a structural alert
                       and professional judgment.
                                                           7-151

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                                                         JUNE 2014 DRAFT REPORT
                                                          Emerald Innovation™ NH-1
         PROPERTY/ENDPOINT
             DATA
REFERENCE
DATA QUALITY
Repeated Dose Effects
HIGH: Based on weight of evidence including reduced body weight in male rats administered Confidential D
in the diet for 28-days. The NOAEL of 23.5 mg/kg-day and the LOAEL of 161.4 mg/kg-day span across the
High and Moderate hazard designation ranges (DfE criteria are for 90-day repeated dose studies; criteria
values are tripled for chemicals evaluated in 28-day studies making the High hazard range < 30 mg/kg-day
and the Moderate hazard range between 30 and 300 mg/kg-day). Repeated dose toxicity is of MODERATE
concern for Confidential E (based on a NOAEL and LOAEL of ~ 10 and ~ 100 mg/kg-day, respectively in a
dermal study in rabbits) and of LOW concern for Confidential C (based on a NOAEL and LOAEL value of
100 mg/kg-day and > 200 mg/kg-day, respectively, in rats following oral exposure).
                                           Confidential C: Sprague Dawley rats
                                           (10/sex/dose) were administered
                                           Confidential C via oral gavage at
                                           doses of 0, 1, 10 and 100 mg/kg once
                                           per day for 14 days. Confidential C
                                           did not have any effect on body
                                           weight gain or organ weights in either
                                           sex or at any dose level. There were
                                           no treatment-related hematological
                                           abnormalities or gross/microscopic
                                           changes detected in major tissues and
                                           organs following dosing with
                                           Confidential C.

                                           NOAEL: > 100 mg/kg-day (highest
                                           dose tested)
                                           LOAEL: Not established
                                           Confidential C: In a 4-week study,
                                           Sprague-Dawley rats were fed diets
                                           containing 0, 500, 2,000, 7,500 or
                                           15,000 mg Confidential C/kg
                                           (approximately 25, 100, 375, or 750
                                           mg/kg-bw/day). No signs of toxicity
                                           were in males; slight decrease in body
                                           weight and food consumption in
                                  ECHA, 2013: Confidential study
                                  Confidential study
                       Sufficient study details reported in
                       secondary sources. Study limited by
                       inability to establish a LOAEL.
                       Limited study details in secondary
                       sources.
                                                                    7-152

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                                                JUNE 2014 DRAFT REPORT
                                                 Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  females (7,500 or 15,000 mg/kg). No
                                  compound-related changes were
                                  observed at necropsy.

                                  Toxicity in males:
                                  NOAEL: >750 mg/kg-day (highest
                                  dose tested)
                                  LOAEL: Not established

                                  Toxicity in females:
                                  NOAEL: 100 mg/kg-day
                                  LOAEL: 375 mg/kg-day
                                  Confidential C: Sprague Dawley rats
                                  (12/sex/dose) were administered
                                  Confidential C via oral gavage at
                                  doses of 0.25 and 0.5 mL/kg (255 and
                                  510 mg/kg-day, based on a density of
                                  1.018 g/cm3), 5 days/week for 18
                                  weeks.
                                  Reduced activity in all rats, clinical
                                  signs of toxicity (difficulties in
                                  breathing, piloerection, lacrimation,
                                  increased urination) at high dose. No
                                  hematological changes. Dose-related
                                  decrease in red cell AChE and
                                  reduction in GPT (high dose only).
                                  Significant increase in both liver and
                                  kidney weights (high dose females), a
                                  significant increase in liver weight in
                                  low dose females and similar increase
                                  for high dose males when expressed
                                  as percent body weight. Cardiac
                                  lesions (males in both treated groups).
                    ECHA, 2013; Confidential study
                        Sufficient study details in secondary
                        sources. Limitations include inability
                        to determine a NOAEL.
                                                            7-153

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                                                JUNE 2014 DRAFT REPORT
                                                 Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  NOAEL: Not established
                                  LOAEL: 0.25 mL/kg (255 mg/kg-
                                  day) based on increased liver weight
                                  in females and decrease in red blood
                                  cell AChE plus cardiac lesions in
                                  males
                                  Confidential C: Confidential C was
                                  administered to four groups of
                                  Sprague-Dawley rats (20/sex/group)
                                  at target dietary concentrations of 0,
                                  300, 3,000 and 10,000 ppm for 18-
                                  weeks. Dietary analyses verified the
                                  following average inclusion rates of
                                  Confidential C in the diets: 280 ppm
                                  (low); 3,000 ppm (intermediate);
                                  9,900 ppm (high dose).
                                  No ophthalmic lesions attributable to
                                  Confidential C. All treatment group
                                  rats gained weight. Reduced food
                                  consumption during the first week in
                                  high and intermediate dose groups.
                                  Throughout the remaining period all
                                  treatment groups consumed amounts
                                  of diet similar to the controls.
                                  Hematological and clinical chemistry
                                  parameters were equivalent in dosed
                                  and control rats with the following
                                  exceptions: increased platelet counts
                                  (10,000 ppm both sexes) and
                                  increased serum gamma glutamyl
                                  transpeptidase and a depressed plasma
                                  cholinesterase in the 3,000 and 10,000
                    ECHA, 2013; Confidential study
                        Sufficient study details reported in
                        secondary sources. Conducted in
                        accordance with OECD Guideline
                        408.
                                                            7-154

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                                                JUNE 2014 DRAFT REPORT
                                                 Emerald Innovation™ NH-1
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DATA QUALITY
                                  ppm groups. Increased liver weight
                                  (absolute and relative) at the high
                                  dose (10,000 ppm). Microscopic
                                  examination revealed mild periportal
                                  hepatocellular hypertrophy and
                                  periportal vacuolization in males only
                                  at 3,000 and 10,000 ppm.

                                  NOAEL: 300 ppm Confidential C in
                                  the diet (equivalent to approximately
                                  20.4 mg/kg-day), for both sexes
                                  LOAEL: 3,000 ppm (approximately
                                  204 mg/kg-bw/day) for periportal
                                  vacuolization and hypertrophy in
                                  males
                                  Confidential C: New Zealand white
                                  rabbits (6/sex/dose) were dermally
                                  exposed to Confidential C at doses of
                                  0, 10, 100 or 1,000 mg/kg-day, 5
                                  days/week for 21 days.
                                  There were no deaths and no adverse
                                  clinical signs of toxicity were
                                  observed in treated rabbits. No
                                  adverse systemic toxicity was
                                  observed following dosing at 1,000
                                  mg/kg-day. Local irritation (minimal
                                  to moderate erythema, edema, atonia
                                  and desquamation) occurred in a
                                  dose-related manner and severity and
                                  increased with time. Microscopic
                                  observations of treated skin from high
                                  dose animals included squamous cell
                                  hyperplasia, hyperkeratosis, hair
                    ECHA, 2013; Confidential study
                        Sufficient study details reported in
                        secondary sources. Conducted in
                        accordance with OECD Guideline
                        410.
                                                            7-155

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                                                 JUNE 2014 DRAFT REPORT
                                                  Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   follicles distended with keratin and
                                   surface accumulation of keratin and
                                   erosions/ulcers. No such observations
                                   were seen in control males and only
                                   infrequently in control females.
                                   A no effect level (NOEL) for skin
                                   irritation was not established in this
                                   study, but irritation at the low dose
                                   was minimal.

                                   NOAEL: 1,000 mg/kg-day (for
                                   systemic toxicity; highest dose tested)
                                   LOAEL: Not established
                                   Confidential C: Wistar rats
                                   (15/sex/group) were fed a diet
                                   containing 0.03, 0.3 or 3.0%
                                   Confidential C for 5 or 14 weeks.
                                   Body weight gain was suppressed in
                                   all rats in the top dose groups (3.0%).
                                   Serum cholinesterase activity was
                                   significantly decreased in both sexes
                                   in the  0.3 and 3.0% groups and serum
                                   gamma glutamyl transferase was
                                   significantly increased in both sexes
                                   in the top dose group after both 5 and
                                   14-weeks of exposure. Serum amylase
                                   levels were also increased in males
                                   (0.3 and 3.0 % groups) and in females
                                   (3%). Absolute and relative liver
                                   weights in  both sexes were
                                   significantly increased in the top dose
                                   group (3.0%) after both 5 and 14-
                                   weeks of treatment. Histopathological
                     ECHA, 2013; Confidential study
                        English abstract only provides
                        qualitative data; therefore, magnitude
                        of the effects described cannot be
                        ascertained. NOAEL and LOAEL
                        derived by the authors are unreliable.
                                                             7-156

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                                               JUNE 2014 DRAFT REPORT
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PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  examination showed that only male
                                  rats in the top dose group (3.0%)
                                  exhibited moderate periportal
                                  hepatocyte swelling after 14-weeks.

                                  NOEL: 0.03 % diet (male rat: 20
                                  mg/kg-day; female rat: 22 mg/kg-day)
                                  LOAEL: 0.3% (-210 mg/kg-day for
                                  males and 250 mg/kg-day for
                                  females)
                                  Confidential D: 28-day repeated dose
                                  dietary study, rats were fed test
                                  substance at concentrations of 0, 250,
                                  1,000 and 4,000 ppm. Effects on body
                                  weights were observed.

                                  NOAEL (male): 250 ppm (23.5
                                  mg/kg-day)
                                  LOAEL (male): 1,000 ppm (161.4
                                  mg/kg-day)
                    ECHA, 2012
                       Reported in secondary source. DfE
                       criteria are for 90-day repeated dose
                       studies. Criteria values are tripled for
                       chemicals evaluated in 28-day studies.
                                  Confidential D: 35-day repeated-
                                  dose oral (dietary) study, 5 male
                                  rats/group, test compound
                                  concentrations of 0, 0.5, and 5.0%
                                  (~0, 350, and 3,500 mg/kg-day,
                                  respectively), with a 0.1% (-70
                                  mg/kg-day) dose replacing the high
                                  dose group after 3 days. Slight
                                  reduction in body weight gain and
                                  increase in liver weight in 350 mg/kg-
                                  day dose group.

                                  NOAEL: 70 mg/kg-day
                    OECD-SIDS, 2002
                       Reported in a secondary source.
                       Limited study details provided.
                                                           7-157

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                                               JUNE 2014 DRAFT REPORT
                                                Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  LOAEL: 350 mg/kg-day
                                  Confidential D: 4-month repeated-
                                  dose dietary study, Sprague-Dawley
                                  rats (10 rats/dose) were fed 0.25, 0.5,
                                  0.75 or 1% test concentration (161,
                                  345, 517 or 711 mg/kg-day,
                                  respectively). Reduced body weight
                                  gain (11%) at 345 mg/kg-day.

                                  NOAEL: 161 mg/kg-day
                                  LOAEL: 345 mg/kg-day
                    OECD-SIDS, 2002; ATSDR 2009
                       Reported in a secondary source.
                                  Confidential D: 21-day repeated-
                                  dose dermal study, rabbits
                                  (10/sex/group) were exposed to test
                                  compound concentrations of 0, 100,
                                  and 1,000 mg/kg-day. No mortality,
                                  clinical symptoms, or changes in body
                                  weight, hematology, clinical
                                  chemistry, necropsy, organ weights
                                  and histopathology reported; only
                                  decreased acetyl cholinesterase levels
                                  in plasma, erythrocytes and brain
                                  were reported and not considered to
                                  be of toxicological relevance as there
                                  was no clinical or histological
                                  correlation.

                                  NOAEL:  1,000 mg/kg-day; highest
                                  dose tested
                                  LOAEL: Not established
                    OECD-SIDS, 2002
                       Reported in a secondary source.
                       Treatment period only 21 days.
                                  Confidential D: In a 3-month study,
                                  rats were orally gavaged with test
                                  substances at 0, 380 and 1,900 mg/kg-
                    ATSDR 2009
                       Limited study details reported in a
                       secondary source. Primary source is
                       an abstract with few experimental
                                                           7-158

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                                                JUNE 2014 DRAFT REPORT
                                                 Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
   DATA
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DATA QUALITY
                                  day. No toxic effects were observed.

                                  NOEL: 1,900 mg/kg-day; highest
                                  dose tested
                                  LOEL: Not established
                                                         details.
                                  Confidential E: Rabbits
                                  (10/sex/dose) were dermally exposed
                                  to Confidential E at doses of 0, 10,
                                  100, and 1,000 mg/kg 6 hours/ days, 5
                                  days/week for 23 days.

                                  No treatment-related deaths. Edema,
                                  atonia, desquamation and fissuring.
                                  Increased mean terminal blood urea
                                  nitrogen values (high dose). Dose
                                  response depression of RBC and brain
                                  cholinesterase (mid and high dose).
                                  No effect on body weights,
                                  hematology and clinical chemistry
                                  data, organ weights and organ/body
                                  weight ratios. No treatment-related
                                  gross or microscopic changes.
                        ECHA, 2013
                       Adequate study reported in a
                       secondary source. Test material is
                       defined as confidential product.
                                  NOAEL:
                                  LOAEL: ;
10 mg/kg-day;
100 mg/kg-day
                                  Confidential E: Rabbits
                                  (10/sex/dose) were dermally exposed
                                  to Confidential E at doses of 100 and
                                  1,000 mg/kg 6 hours/ days, 5
                                  days/week for 3 weeks.

                                  No deaths. No clinical signs of
                                  toxicity. The test material was mildly
                        ECHA, 2013
                       Adequate study reported in a
                       secondary source. Test material is
                       defined as confidential product.
                                                            7-159

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                                                JUNE 2014 DRAFT REPORT
                                                 Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
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DATA QUALITY
                                  to moderately irritating to the skin. A
                                  dose-correlated body weight effect
                                  was noted. Significant inhibition of
                                  plasma, erythrocyte and brain
                                  cholinesterase activity. No significant
                                  gross or microscopic pathologic
                                  alterations except for the local skin
                                  lesions.

                                  LOAEL: ~ 100 mg/kg-day
                                  NOAEL: 1,000 mg/kg-day
                                  Confidential E: Male and female rats
                                  (15/sex/group) were fed Confidential
                                  E in the diet at doses of 100, 300,
                                  1,000 ppm (7.5, 21.4, 71.6 mg/kg-
                                  day, males; 9.0, 26.5, 86.2 mg/kg-day,
                                  females) for 90 days.
                                  No adverse effects related to test
                                  article treatment in any of the dosage
                                  groups.

                                  NOAEL: 1,000 ppm (71.6 mg/kg-day
                                  for males, 86.2 mg/kg-day for
                                  females; highest dose tested)
                                  LOAEL: Not established
                    ECHA, 2013
                        Adequate study reported in a
                        secondary source. Test material is
                        defined as confidential product.
                                  Confidential E: Confidential E was
                                  administered to Sprague-Dawley rats
                                  (20/sex/dose) at concentrations of 0,
                                  100, 400 and 1,600 ppm by diet for 90
                                  days.

                                  Confidential E: No treatment related
                                  mortality and clinical signs.
                    ECHA, 2013
                        Adequate study reported in a
                        secondary source. Test material is
                        defined as confidential product.
                                                            7-160

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                                                 JUNE 2014 DRAFT REPORT
                                                  Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
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DATA QUALITY
                                   Statistically significant differences in
                                   hematology and clinical chemistry
                                   values and in red blood cell, plasma
                                   and brain cholinesterase activities
                                   between control and treated animals
                                   were minimal, inconsistent and
                                   considered not to be of biological
                                   significance. A biologically
                                   significant increase in liver and
                                   adrenal weights (only females) was
                                   noted in the high-dose groups, but this
                                   was not regarded as a toxic and
                                   therefore not an adverse effect.

                                   NOAEL: 1,600 ppm (107.5 mg/kg-
                                   day for males and 124.8 mg/kg-day
                                   for females; highest dose tested)
                                   LOAEL: Not established
                                   Confidential E: Sprague-Dawley rats
                                   (10/sex/dose) were fed Confidential E
                                   in the diet at doses of 0, 250, 500,
                                   750, 1,000 and 2,000 mg/kg-day for 1
                                   month.

                                   No deaths or toxicologically
                                   significant clinical signs. Hepatic
                                   enlargement and mahogany red livers
                                   at all doses (significant at >500
                                   mg/kg-day). Rounding of hepatic
                                   edges and diffuse green-tan
                                   discoloration of kidneys (>500 mg/kg-
                                   day).
                     ECHA, 2013
                        Adequate study reported in a
                        secondary source. Test material is
                        defined as confidential product.
                                                             7-161

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                                                JUNE 2014 DRAFT REPORT
                                                 Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  NOAEL: 250 mg/kg-day
                                  LOAEL: >500 mg/kg-day
                                  Confidential E: Charles River rats
                                  (15/sex/dose) were exposed via
                                  whole-body inhalation to Confidential
                                  E aerosol at concentrations of 0, 10.1
                                  or 101.1 mg/m3 (0, 0.0101, or 0.1011
                                  mg/L), or 6 hours/day, 5 days/week
                                  for a total of 62 exposures over 90
                                  days.

                                  No deaths attributed to test material.
                                  Ruffed, discolored fur and ptosis
                                  (both doses); rhinitis, sneezing,
                                  wheezing and hemorrhagic
                                  conjunctivitis (high dose). No
                                  difference in body weights,
                                  hematology parameters, clinical
                                  chemistry values and urinalysis
                                  parameters. Gross necropsy showed
                                  no adverse effects. Increased liver
                                  weight in high-dose males. No
                                  treatment related histopathological
                                  effects.

                                  NOAEL: 101.1 mg/m3 (0.1011 mg/L)
                                  LOAEL: Not established
                    ECHA, 2013
                       Adequate study reported in a
                       secondary source. Test material is
                       defined as confidential product.
                                                            7-162

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                                                          JUNE 2014 DRAFT REPORT
                                                           Emerald Innovation™  NH-1
          PROPERTY/ENDPOINT
              DATA
                                            REFERENCE
        DATA QUALITY
Skin Sensitization
MODERATE: Confidential C and E produced positive responses in a
did not produce sensitization in a modified Buehler test in guinea pigs
volunteers. Confidential D was not a skin sensitizer in guinea pigs.
                                                                 local lymph node assays in mice but
                                                                 or in repeated patch tests in human
              Skin Sensitization
Confidential C: Sensitizing, mouse
local lymph node assay (LLNA).
The test item solutions were applied
on the dorsal surface of ears of
experimental animals (25 (iL/ear) for
three consecutive days. A significant
lymphoproliferative response was
noted.
                                            Confidential C: Not sensitizing,
                                            guinea pigs, modified Buehler test
                                            There were no signs of irritation at
                                            any of the test sites during induction
                                            or at challenge. No data provided
                                            regarding positive controls.
                                            Confidential C: Not sensitizing,
                                            repeated human insult patch test in
                                            209 volunteers.
                                            3-week induction period, 4
                                            applications of 0.2 mL per week for
                                            24 hours to occluded skin. During the
                                            fourth week, 4 similar applications
                                            were made to previously untreated
                                            sites. There was no dermal reaction to
                                            challenge applications.
                                            Confidential D: Several human case
                                            studies have reported allergic
                                            dermatitis; 15 of 23,192 (0.065%)
                                            human volunteers patch tested from
                                            1950 to 1962 had positive reactions to
                                            cellulose acetate film containing 7-
                                  ECHA, 2013
                                   ECHA, 2013
                                   Confidential study
                                   OECD-SIDS, 2002
Sufficient study details reported in a
secondary source. Conducted
according to OECD Guideline 429.
                                                                    The lack of positive controls
                                                                    diminishes reliability of the results.
                                                                    Sufficient information reported in a
                                                                    secondary source.
                                                                    Reported in a secondary source.
                                                                    Limited study details provided; patch
                                                                    testes conducted with mixtures;
                                                                    unclear which component of mixture
                                                                    caused low incidence of sensitization.
                                                                      7-163

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PROPERTY/ENDPOINT


Respiratory Sensitization
[Respiratory Sensitization
DATA
10% Confidential D and 3-4%
phthalic esters
Confidential D: A confidential skin
Sensitization study with negative
results in guinea pigs
Confidential D: None of the patients
tested in two separate studies of 343
and 174 patients, respectively, had
Sensitization reactions to triphenyl
phosphate
Confidential D: Not sensitizing,
guinea pig maximization test
Confidential E: Sensitizing, Mouse
local lymph node assay (LLNA).
Confidential E: Not sensitizing,
patch test, human volunteers
REFERENCE

Submitted confidential study
OECD-SIDS, 2002
^^^N. r
OECD-SIDS, 2002
ECHA, 2013
ECHA, 2013
DATA QUALITY

Reported in a confidential study.
Reported in a secondary source.
Limited study details provided.
Study reported in a secondary source;
conducted according to OECD Guide-
line 406.
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
No data were located.

|No data located.
         7-164

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                                                           JUNE 2014 DRAFT REPORT
                                                            Emerald Innovation™ NH-1
          PROPERTY/ENDPOINT
              DATA
          REFERENCE
        DATA QUALITY
Eye Irritation
MODERATE: Confidential C produced slight irritation in rabbits
animals. Confidential D is mildly irritating to the eyes with effects
did not produce eye irritation in rabbits.
                            which persisted up to 72 hours in some
                            clearing within 72 hours. Confidential E
              Eye Irritation
Confidential C: Slightly irritating,
rabbits.
Undiluted 0.1 mL was applied; the
eye was washed 24 hours later. One
hour up to 72 hours, the treated
conjunctiva showed beefy-red blood
vessels and slight to moderate
swelling. From 24 to 48 hours, the iris
of one animal was reddened. Diffuse
translucent areas of the cornea were
observed one hour after
administration in two animals,
persisting to72 hours in one animal.
Clear colorless discharge was
observed in all animals, persisting to
48 hours in one animal. All signs of
irritation had resolved at 7 days.
                                             Confidential C: Slightly irritating,
                                             rabbits (3/sex).
                                             Undiluted 0.1 mL was applied. All
                                             dosed rabbits displayed excessive
                                             blinking and rubbing on instillation.
                                             No corneal opacity or iritis.
                                             Conjunctival redness, chemosis and
                                             discharge in all rabbits at 1 -h post-
                                             exposure and redness persisted in 1/6
                                             rabbits through 48-h. Slight to
                                             obvious swelling with partial eversion
                                             of the eyelids and slight discharge was
                                             observed in all rabbits at 1 -h post-
ECHA, 2013
                                   ECHA, 2013
Sufficient study details reported in a
secondary source. Conducted in
accordance with OECD Guideline
405.
                                  Sufficient study details reported in a
                                  secondary source.
                                                                       7-165

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PROPERTY/ENDPOINT


DATA
instillation. All ocular lesions had
resolved at 72-h.
Confidential C: Slightly irritating,
rabbits (3/sex).
Confidential C: No corneal opacity.
Iritis (grade 1) in one female rabbit.
Conjunct val irritation (grade 1 or 2)
in all test animals at Ihour post-
instillation, in 4 rabbits at 24 hours,
persisting to 72 hours in one rabbit.
Confidential C: Slightly irritating,
rabbits.
Undiluted 0.1 mL was applied. 3/6
rabbits exhibited moderate
conjunctival erythema and iritis which
resolved within 48-h.
Confidential C: In four studies
Confidential C was non-irritating to
the eyes of albino rabbits.
Confidential D: Not irritating, rabbits
Confidential D: Mild irritation in
rabbit eyes, clearing within 72 hours
Confidential E: Not irritating, rabbits
Confidential E: Not irritating,
rabbits;
No irritation in the washed and
unwashed eyes after 24, 48, 72 hours
and 4 days.
REFERENCE

ECHA, 2013
^^^
^^^N. T
ECHA, 2013
^^
Confidential study
OECD-SIDS, 2002
OECD-SIDS, 2002
Confidential study
ECHA, 2013
DATA QUALITY

Sufficient study details reported in a
secondary source.
Limited study details reported in a
secondary source.
No details provided in a secondary
source.
Study reported in a secondary source;
conducted according to OECD Guide-
line 405.
Study reported in a secondary source
Adequate primary source. Test
material is defined as confidential
product.
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
         7-166

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                                                          JUNE 2014 DRAFT REPORT
                                                           Emerald Innovation™ NH-1
          PROPERTY/ENDPOINT
              DATA
          REFERENCE
        DATA QUALITY
                                            Confidential E: Not irritating,
                                            rabbits;
                                            No irritation in the washed and
                                            unwashed eyes after 1 hour or up to 4
                                            days.
                                  ECHA, 2013
                                 Adequate study reported in a
                                 secondary source. Test material is
                                 defined as confidential product.
                                            Confidential E: Not irritating,
                                            rabbits;
                                            No irritation in the washed and
                                            unwashed eyes after 24, 48, 72 hours
                                            and 4 and 7 days.
                                  ECHA, 2013
                                 Adequate study reported in a
                                 secondary source. Two studies, test
                                 material is a confidential product.
Dermal Irritation
MODERATE: Based on weight of evidence. Confidential C produced moderate irritation in rabbits which
persisted up to 72 hours in some animals. Confidential E initially produced moderate to severe irritation in
rabbits with mild to moderate irritation and erythema persisting 72 hours post-administration. Confidential
D is not a skin irritant in rabbits.
              Dermal Irritation
Confidential C: Moderately
irritating, three rabbits.
Undiluted 0.5 mL applied for 4 hours;
semi occlusive. Well-defined to
severe erythema up to 72 hours in 2
rabbits. Same rabbits showed very
slight to slight edema, with roughness
and scaling of the skin up to 7 days.
All effects were reversible within 14
days.
                                            Confidential C: Moderately
                                            irritating, six rabbits.
                                            Undiluted 0.5 mL was applied.
                                            Erythema was more severe in abraded
                                            than intact sites at both 24- and 72-
                                            hours. Effects were not fully
                                            reversible within 72-hours.
                                            Confidential C: Slightly irritating,
                                            six rabbits
ECHA, 2013
                                  ECHA, 2013
                                  ECHA, 2013
Sufficient details reported in a
secondary source. Conducted in
accordance with OECD Guideline
404.
                                 Sufficient study details reported in a
                                 secondary source.
                                 Sufficient study details reported in a
                                 secondary source.
                                                                      7-167

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                                                 JUNE 2014 DRAFT REPORT
                                                  Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   Undiluted 0.5 mL was applied to
                                   intact skin of rabbits under occlusion
                                   for 4-hour induced a slight transient
                                   irritation response.
                                   Confidential C: Slightly irritating,
                                   six rabbits.
                                   Undiluted 0.5 mL applied for 2 hours;
                                   occlusive. At 24-hour post exposure
                                   rabbits had slight erythema at the
                                   intact site with incidence and severity
                                   of irritation increasing at 72-hour to
                                   well-defined erythema. At the abraded
                                   sites, the incidence and severity of
                                   irritation remained the same over both
                                   time periods. No edema or corrosive
                                   effect was observed in any treated
                                   rabbit at any site. Effects were no
                                   fully reversible within 72 hours.
                     ECHA, 2013
                        Sufficient study details reported in a
                        secondary source.
                                   Confidential C: Irritating, rabbits
                                   (6/sex/group), 21-day dermal study.
                                   Rabbits received 10, 100, or 1,000
                                   mg/kg on unabraded skin followed by
                                   occlusion for 6 hours. Slight to
                                   moderate erythema. Microscopic
                                   observations showed squamous cell
                                   hyperplasia, hyperkeratosis, hair
                                   follicles distended with keratin and
                                   surface accumulation of keratin and
                                   cellular debris, erosions ulcers,
                                   acute/subacute inflammation and
                                   congestion and hemorrhages in
                                   various combinations. Dose-related
                                   effects with increasing severity over
                     Confidential study
                        Sufficient study details reported in a
                        secondary source.
                                                              7-168

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DATA
time.
Confidential C: Not irritating, six
rabbits.
Undiluted 0.5 mL applied for 24
hours; occlusive. Irritation consisted
of very slight erythema (scores of
0.33 at 24-hour and 0.17 at 72-h).
Confidential D: Not irritating,
rabbits; semi -occlusive or occlusive
conditions for 4, 24 or 72 hours
Confidential D: Non-irritant, rabbit
Confidential E: Irritating, rabbits;
Moderate to severe erythema in intact
and abraded skin of 6 rabbits after 4
hours. By 24 hours, irritation
decreased to mild erythema in two
rabbits. At 72 hours, 5 rabbits had
mild to moderate erythema and
irritation cleared in 1 rabbit.
Confidential E: Irritating, rabbits;
Mild erythema and edema 24 hours
after exposure (4 rabbits). At the 72
hour observation, irritation decreased
and included mild erythema in one of
the six rabbits. Primary Irritant Score
= 0.46.
Confidential E: Not irritating, rabbits
Confidential E: Not irritating,
rabbits;
No effects in intact and abraded skin
REFERENCE

ECHA, 2013
^^^
OECD-SIDS, 2002
^^^N. T
ATSDR, 2009
ECHA, 2013
7
ECHA, 2013
Confidential study
ECHA, 2013
DATA QUALITY

Sufficient study details reported in a
secondary source.
Study reported in secondary source;
conducted according to OECD Guide-
line 404
Reported in a secondary source.
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
Adequate primary source. Test
material is defined as confidential
product.
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
         7-169

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Emerald Innovation™ NH-1
PROPERTY/ENDPOINT


Endocrine Activity

DATA
following a 24 hour exposure.
Confidential E: Not irritating,
rabbits;
Mild erythema was noted at the 24
hour observation period in 2/6
animals. All scores were 0 by 72
hours.
REFERENCE

ECHA, 2013
^^^
DATA QUALITY

Adequate study reported in a
secondary source. Test material is
defined as confidential product.
Confidential C is listed in one study in the top 20 EOCs (endocrine disrupting chemicals) in U.S. stream
waters. It inhibited the luciferase expression induced by dihydrotestosterone and 1713-estradiol and increased
both 17 beta-estradiol (E2) and testosterone (T) concentrations in H295R cells. Confidential C was negative
for estrogenic activity in a yeast two-hybrid assay and did not act as an estrogen receptor agonist or
adversely affect sex hormones of zebrafish.
Confidential D was found to be inactive in estrogen-receptor binding assays; however, it was shown to be a
moderate androgen-receptor (AR) binder in a competitive binding assay. Confidential D was shown to
inhibit human AR in the absence of agonist and to inhibit testosterone-induced AR activity. In addition,
Confidential D significantly impaired reproduction in zebrafish and was correlated with decreased sperm
count and altered hormone levels in men. Increased serum thyroxine (T4) levels were reported in the serum
of dams following oral administration to a confidential product containing Confidential D; other components
of the mixture were not identified. It is unclear which component or components of the mixture are driving
the endocrine activity effects.
No data were available for Confidential E. By analogy, rats exposed to a mixture containing Confidential E
had significantly prolonged diestrus, hypertrophy and cholesteryl lipidosis of adrenocortical and ovarian
interstitial cells and minimal degeneration in the adrenal cortex and ovary. No effect on the testes was noted.
Confidential C: Ranked as atop 20
EOC (endocrine disrupting chemical)
in U.S. stream water
Confidential C: Confidential C
inhibited the luciferase expression
induced by dihydrotestosterone (10~9
M). The IC50 value was 4.7 x 10"5 -
6.0 x 10'4 M. Confidential C also
Confidential study
Confidential study

Adequate primary source; Japanese
with English abstract.
         7-170

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JUNE 2014 DRAFT REPORT
 Emerald Innovation™ NH-1
PROPERTY/ENDPOINT

































DATA
inhibited the luciferase expression
induced by 17B-estradiol (3 x 10~10
M). The IC50 value was 3.3 x 10~5 -
2.3xl(r4M.
Confidential C: Endocrine disrupting
potential investigated using human
cell lines as well as zebrafish (Danio
rerio). Sex hormone synthesis and
steroidogenic gene transcriptions were
measured using H295R cells. With
MVLN cells, estrogen receptor
binding activities of OPFRs were
evaluated. In zebrafish, sex hormones
and related gene transcriptions were
determined for each sex after 14 days
of exposure. Confidential C increased
both 17 beta-estradiol (E2) and
testosterone (T) concentrations in
H295R cells. In MVLN cells.
Transcription of SULT1E1 and
SULT2A1 genes was down-regulated
when the cells were exposed to 10
mg/L Confidential C. Confidential C
did not act as an estrogen receptor
agonist and had no adverse effects on
sex hormones of zebrafish.
Confidential C: Negative for
estrogenic activity in a yeast two-
hybrid assay.
REC10 (M) = >1 x 10"4 (concentration
showing 10% relative activity of 10"7
M 17 beta-estradiol)
Confidential D: 21 -day reproduction
REFERENCE




Confidential study
^^^



^^^N. r



^f



T








Confidential study





Confidential study
DATA QUALITY




Adequate primary source.





















Adequate primary source.





Adequate primary source.
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                                                 JUNE 2014 DRAFT REPORT
                                                  Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   study in zebrafish. Significant
                                   decrease in fecundity, significant
                                   increases of plasma 17B-estradiol
                                   (E2) concentrations, vitellogenin
                                   (VTG) levels, and E2/testosterone (T)
                                   and E2/11-ketotestosterone (11-KT)
                                   ratios. Sex-dependent changes in
                                   transcriptional profiles of several
                                   genes of the hypothalamus-pituitary-
                                   gonad (HPG) axis.
                                   Confidential D: Study conducted to
                                   determine effects of triaryl phosphates
                                   on mouse and human nuclear
                                   receptors. Mouse constitutively active
                                   receptor (CAR) was activated by 1.3-
                                   fold following exposure to
                                   Confidential D. Testosterone-induced
                                   AR-dependent activity was lowered
                                   by 30-40%.
                     Confidential study
                        Adequate primary source.
                                   Confidential D: Exposure to
                                   Confidential D in zebrafish resulted in
                                   severe pericardial edema and blocked
                                   looping of the atrium and ventricle.
                                   Confidential D-induced cardiotoxicity
                                   in zebrafish embryos is mediated
                                   through an AHR independent
                                   pathway.
                     Confidential study
                        Adequate primary source.
                                   Confidential D: In a luciferase
                                   reporter-gene assay using cultured
                                   cells, Confidential D inhibited the
                                   luciferase expression induced by
                                   dihydrotestosterone (10~9 M).
                     Confidential study
                        Primary source in Japanese with
                        English abstract.
                                                             7-172

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                                                JUNE 2014 DRAFT REPORT
                                                 Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  IC50 for antiandrogenic activity :
                                  0.000047 - 0.0006 M
                                  Confidential D: Endocrine disrupting
                                  potential was investigated using
                                  human cells lines (H295R, MVLN)
                                  and zebrafish plasma. Confidential D
                                  was cytotoxic to H295R cells
                                  (showing <80% cell viability at > 10
                                  mg/L) and significantly increased E2
                                  and T production. Transcription of
                                  CYP19A1 was significantly up-
                                  regulated and transcription of
                                  SULT1E1 gene was down-regulated.
                                  No binding affinity to E2 receptor in
                                  MVLN cells, but binding of E2 to ER
                                  was reduced in a dose-dependent
                                  manner. Plasma E2 was significantly
                                  increased in fish plasma and T and
                                  11-KT were decreased (1 mg/L).
                                  Changes in transcription of
                                  steroidogenic genes and vitellogenin
                                  gene were observed.
                     Confidential study
                        Adequate, primary source.
                                  Confidential D: Men living in homes
                                  with higher amounts of Confidential
                                  D in house dust had reduced sperm
                                  count and altered hormone levels
                                  related to fertility and thyroid
                                  function. Each interquartile range
                                  (IQR) Confidential D increase in
                                  house dust samples was associated
                                  with a 19% decrease in sperm
                                  concentrations and a 10% increase in
                                  prolactin levels.
                     Confidential study
                        The actual exposure to Confidential D
                        is unknown; it is not known if
                        Confidential D or other substances
                        found in the household dust caused or
                        contributed to the reported toxicity.
                                                            7-173

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                                                JUNE 2014 DRAFT REPORT
                                                 Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  Confidential D: Pregnant Wistar rats
                                  were administered 0, 0.1 or 1 mg/kg-
                                  day of the analog confidential product
                                  in the diet during gestation and
                                  through lactation (GD8 - PND 21);
                                  Increased serum thyroxine (T4) levels
                                  (increase of 65%) in the high dose
                                  dams compared to controls was
                                  reported. There was no significant
                                  change in triiodothyronine (T3) levels
                                  in dam serum. There was no reported
                                  statistically significant change in T4
                                  or T3 levels in pup serum on PND 21
                                  when compared to controls.
                    Confidential study
                        Estimated based on experimental data
                        for a confidential product.
                                  Confidential D: Inhibited AR activity
                                  in COS-1 cells transfected with
                                  human AR both in the absence of
                                  agonist, as well as inhibited
                                  testosterone-induced AR activity by
                                  30 40%. (Measured)
                    ATSDR 2009
                        Reported in a secondary source.
                                  Confidential D: Moderate binding in
                                  a competitive androgen-receptor (AR)
                                  binding assay using recombinant rat
                                  protein expressed in Escherichia coli.
                    ATSDR 2009
                        Reported in a secondary source.
                                  Confidential D: Inactive in a binding
                                  assay with the rat uteri estrogen
                                  receptor from ovariectomized
                                  Sprague-Dawley rats
                    ATSDR 2009
                        Reported in a secondary source
                                  Confidential E: In an oral study,
                                  male and female rats were
                                  administered Confidential E at doses
                                  of 0 or 1.7 g/kg-day (0 or 1700
                                  mg/kg-day) via gavage in sesame oil
                    Confidential study
                        Estimated based on analogy. Data are
                        for a confidential mixture.
                                                            7-174

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                                                 JUNE 2014 DRAFT REPORT
                                                  Emerald Innovation™  NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   or 2.8 g/kg (2,800 mg/kg) neat
                                   Confidential E for 20, 40 and 60 days.
                                   Hypertrophy and cholesteryl lipidosis
                                   of adrenocortical and ovarian
                                   interstitial cells; minimal degeneration
                                   in the adrenal  cortex and ovary. No
                                   decreased testicular weight or
                                   degeneration of seminiferous tubules.
                                   (Estimated by analogy)
                                   Confidential E: In an oral study,
                                   groups of intact and ovariectomized
                                   female rats were administered
                                   Confidential E at doses of 0 or 1.7
                                   g/kg-day (0 or 1,700 mg/kg-day) via
                                   oral gavage in sesame oil vehicle or as
                                   neat Confidential E for 20, 40 or 60
                                   days. Cholesteryl lipidosis in AC and
                                   OI cells; elevated estradiol levels
                                   (14.5 times greaterthan controls). No
                                   effect on serum concentrations of
                                   androstenedione and corticosterone.
                                   Abnormal reproductive cycles in
                                   treated females that were significantly
                                   prolonged in diestrus. Increased liver
                                   weights (134% that of controls) and
                                   P-450 enzymes (3 times greaterthan
                                   controls)
                                   (Estimated by analogy)
                     Confidential study
                        Estimated based on analogy. Data are
                        for a confidential mixture.
                                                             7-175

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                                                         JUNE 2014 DRAFT REPORT
                                                          Emerald Innovation™ NH-1
          PROPERTY/ENDPOINT
              DATA
         REFERENCE
DATA QUALITY
Immunotoxicity
Confidential C produced weak inhibition of mouse lymphocyte mitogenesis for T-cells; no inhibition was
observed in B-cells. Oral exposure of rats to Confidential D for 4 months and dermal exposure of rabbits for
3 weeks produced no effects on immune function parameters.
             Immune System Effects
Confidential C: Immunotoxicity
evaluation using the mouse splenic
lymphocyte mitogenesis test. No
inhibition for lymphocyte mitogenesis
in B-cells; weak inhibition for
lymphocyte mitogenesis for T cells.
                                           Confidential D: 120-day dietary
                                           study, rats, 0, 0.25, 0.5, 0.75, and 1%
                                           of Confidential D(~0, 161, 345, 517
                                           and 711 mg/kg-day); initial,
                                           secondary, and tertiary immunizations
                                           with sheep red blood cells performed
                                           at 60, 81, and 102  days, respectively.
                                           No significant effects were reported
                                           on the weight and histopathology of
                                           the spleen, thymus and lymph nodes,
                                           and no significant changes to the
                                           humoral response were reported.
                                           Confidential D: Rabbits, up to 1,000
                                           mg/kg-day, applied 5 days/week for 3
                                           weeks to intact or abraded skin had no
                                           gross or microscopic effects on the
                                           spleen, thymus, or lymph nodes.
Confidential study
                                  ATSDR 2009
                                  ATSDR 2009
                                 Reported in a secondary source.
                                 Reported in a secondary source.
                                                                     7-176

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JUNE 2014 DRAFT REPORT
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
ECOTOXICITY
ECOSAR Class
Acute Aquatic Toxicity
Fish LC50

VERY HIGH: Based on experimental fish 96-hour LC50 values < 1.0 mg/L for Confidential D and E and a
48-hour EC50 of 0.343 mg/L in daphnia for Confidential E. Acute aquatic toxicity is of HIGH concern for
Confidential C based in an experimental 48-hour LC50 of 6.8 mg/L in fish.
Confidential C: Freshwater fish
(Oryzias latipes) 48-hour LC50 = 6.8
mg/L (mortality 30°C), 27 mg/L
(mortality 20°C) and 44 mg/L
(mortality 10°C)
Static conditions. The acute toxicity
of Confidential C to the killifish is
increased with an increase in
temperature.
(Experimental)
Confidential C: Freshwater fish
(Carassius auratus) 96-hour LC50 > 5
mg/L
(Experimental) V ^^
Confidential C: Freshwater fish
(Pimephales promelas} 96-hour LC50
= 11. 2 mg/L
Flow-through conditions; nominal
concentrations of 6.29, 9.68, 14.9,
22.9 and 35. 2 mg/L.
(Experimental)
Confidential C: Freshwater fish
{Pimephales promelas} 96-hour LC50
= 16 mg/L
(Experimental)
Confidential C: Freshwater fish
(Oncorhynchus mykiss} 96-hour LC50
ECHA, 2013; Confidential study
^^^N. T
^f
Confidential study
ECHA, 2013
Confidential study
ECHA, 2013; Confidential study
Adequate study reported in Japanese
with English summary and tables.
Adequate study reported in a
secondary source.
Adequate study reported in a
secondary source.
Adequate study reported in a
secondary source
Adequate study reported in a
secondary source. No monitoring of
         7-177

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Emerald Innovation™ NH-1
PROPERTY/ENDPOINT

DATA
= 24 mg/L
Nominal concentrations of 0 (control,
dechlorinated tap water), 10, 18, 32,
56, 100 mg/L under static conditions
(Experimental)
Confidential C: Freshwater fish 96-
hour LC50 = 8.8 mg/L
(Estimated)
ECOSAR: Neutral organics
Confidential D: Freshwater fish
(Oncorhynchus mykiss) 96-hour LC50
= 0.4 mg/L
(Experimental) ^ "^
Confidential D: Freshwater fish
(Oncorhynchus mykiss) 96-hour LC50
= 0.85 mg/L
(Experimental) ^1 ^_
Confidential D: Freshwater fish
(Lepomis macrochirus) 964iour LC50
= 290 mg/L
(Experimental)
^
Confidential D: Fish 96-hour LC50 =
1.62 mg/L
(Estimated)
ECOSAR: Neutral organics
Confidential E: Freshwater fish
REFERENCE

ECOSAR vl. 11
^^^\ r
OECD-SIDS, 2002
OECD-SIDS, 2002
OECD-SIDS, 2002
ECOSAR vl. 11
ECHA, 2013
DATA QUALITY
physico-chemical conditions.
ECOSAR also provided results for the
Esters, and Esters (phosphate) classes;
however, professional judgment
indicates that this compound is not
currently well represented in
ECOSAR vl. 11.
Reported in a secondary source.
Reported in a secondary source.
Guideline study.
Limited study details reported in a
secondary source. The study does not
meet important criteria for standard
methods (e.g., test substance
concentration at solubility threshold
in water).
ECOSAR also provided results for the
Esters, and Esters (phosphate) classes;
however, professional judgment
indicates that this compound is not
currently well represented in
ECOSAR vl. 11.
Adequate study reported in a
         7-178

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                                               JUNE 2014 DRAFT REPORT
                                                Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  (Ictalurus punctatus)
                                  96-hour LC50 = 0.8 mg/L (static);
                                  Nominal concentrations: 0.06, 0.12,
                                  0.25, 0.5 and 1.0 mg/L
                                  (Experimental)
                                                     secondary source. Test material is a
                                                     confidential product.
                                  Confidential E: Freshwater fish
                                  (Oncorhynchus mykiss)
                                  96-hour LC50 = 2 mg/L (static);
                                  24-hour LC50 = 26 mg/L;
                                  48-hour LC50= 13 mg/L;
                                  Confidential E: 96-hour NOEC =
                                  0.56 mg/L;
                                  nominal concentrations: 0.56, 0.75,
                                  1.0, 1.4, 1.8, 2.4, 3.2, 4.2, 5.6, 7.5, 10,
                    ECHA, 2013
                       Adequate study reported in a
                       secondary source. Test material is a
                       confidential product.
                                  14, 18, 24, 32 and 49 mg/L
                                  (Experimental)
                                  Confidential E: Freshwater fish
                                  (Oncorhynchus mykiss)
                                  96-hour LC50 = 2 mg/L (static)
                                  (Experimental)
                    ECHA, 2013
                                  Confidential E: Freshwater fish
                                  (Pimephales promelas)
                                  96-hour LC50 = 2.3 mg/L (static)
                                  (Experimental)
                    ECHA, 2013
                                  Confidential E: Freshwater fish
                                  (Oncorhynchus mykiss)
                                  96-hour LC50= 2.37 mg/L (static);
                                  24-hour LC50 = 7.1 mg/L;
                                  48-hour LC50= 3.77 mg/L;
                                  96-hour NOEC =1 mg/L;
                                  nominal concentrations: 1.0, 1.8, 3.2,
                                  5.6 and 10.0 mg/L
                                  (Experimental)
                    ECHA, 2013
                       Adequate study reported in a
                       secondary source. Test material is a
                       confidential product.
                       Adequate study reported in a
                       secondary source. Test material is a
                       confidential product.
                       Adequate study reported in a
                       secondary source. Test material is a
                       confidential product.
                                                           7-179

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Emerald Innovation™ NH-1
PROPERTY/ENDPOINT

DATA
Confidential E: Saltwater fish
(Cyprinodon variegatus}
96-hour LC50 = 3 mg/L (static);
96-hour NOEC=1. 8 mg/L;
(Experimental)
Confidential E: Freshwater fish
(Lepomis macrochirus)
96-hour LC50 = 3.1 mg/L (static)
(Experimental)
Confidential E: Freshwater fish
(Pimephales promelas)
96-hour LC50 = 3.4 mg/L (static)
(Experimental)
Confidential E: Freshwater fish
(Oncorhynchus mykiss)
96-hour LC50 = 3.9 mg/L (flow-
through);
24-hour LC50 = 10.4 mg/L;
48-hour LC50 = 4.9 mg/L;
72-hour LC50 = 4.2 mg/L;
96-hour NOEC = 2.5 mg/L
(Experimental)
Confidential E: Freshwater fish
(Oncorhynchus mykiss)
96-hour LC50 = 5.4 mg/L (static)
24-hour LC50 = 30.3 mg/L;
48-hour LC50 =15.2 mg/L;
96-hour NOEC = 3.2 mg/L;
nominal concentrations: 3. 2, 5.6, 10.0,
18.0 and 32.0 mg/L
(Experimental)
Confidential E: Saltwater fish
REFERENCE
ECHA, 2013
ECHA, 2013
^^^N. T
ECHA, 2013
^^
ECHA, 2013
7
ECHA, 2013
ECHA, 2013
DATA QUALITY
Adequate study reported in a
secondary source. Test material is a
confidential product.
Adequate study reported in a
secondary source. Test material is a
confidential product.
Adequate study reported in a
secondary source. Test material is a
confidential product.
Adequate study reported in a
secondary source. Test material is a
confidential product.
Adequate study reported in a
secondary source. Test material is a
confidential product.
Adequate study reported in a
         7-180

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                                               JUNE 2014 DRAFT REPORT
                                                Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  (Cyprinodon variegatus)
                                  96-hour LC50 > 0.27 mg/L (semi-
                                  static);
                                  96-hour NOEC = 0.27 mg/L;
                                  nominal concentrations: 0.13, 0.22,
                                  0.36, 0.6 and 1.0 mg/L
                                  (Experimental)
                                                     secondary source. Test material is a
                                                     confidential product.
                                  Confidential E: Saltwater fish
                                  (Cyprinodon variegatus)
                                  96-hour LC50 > 1.3 mg/L (semi-
                                  static);
                                  96-hour NOEC =1.3 mg/L
                                  nominal concentrations: 0.13, 0.22,
                                  0.36, 0.60 and  1.0 mg/L
                                  measured (mean) concentrations:
                                  0.19, 0.33, 0.38, 0.83 and 1.3 mg/L
                                  (Experimental)
                    ECHA, 2013
                                  Confidential E: Freshwater fish 96-
                                  hour LC50 = 0.0000087 mg/L
                                  (Estimated)
                                  ECOSAR: Neutral organics
                    ECOSARvl.ll
                       Adequate study reported in a
                       secondary source. Test material is a
                       confidential product.
                       NES: The log Kow of 11 for this
                       chemical exceeds the SAR limitation
                       for the log Kow of 5.0; NES are
                       predicted for these endpoints.
                       ECOSAR also provided results for the
                       Esters, and Esters (phosphate) classes;
                       however, professional judgment
                       indicates that this compound is not
                       currently well represented in
                       ECOSARvl.ll.
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JUNE 2014 DRAFT REPORT
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
Daphnid LC50
DATA
Confidential C: Daphnia magna 48-
hour EC50 = 53 mg/L
48-hour NOEC = 4.6 mg/L
Nominal concentrations: 2.2, 4.6, 10,
22, 46 and 100 mg/L; Measured
concentrations: 4.44-8.33-22.2-46.0-
100 mg/L (initial)
(Experimental)
Confidential C: Daphnia magna 48-
hour EC50 = 75 mg/L;
24-hour LC50 = 84 mg/L;
NOEC = 32 mg/L
(Experimental)
Confidential C: Daphnia magna 48-
hour LC50 = 5.9 mg/L
(Estimated)
ECOSAR: Neutral organics
Confidential D: Daphnid 48-hour
LC50= 1.28 mg/L
(Experimental)
Confidential D: Daphnid 48-hour
EC50= 1.35 mg/L
Static
(Experimental)
Confidential D: Daphnid 48-hour
LC50= 1.0 mg/L
(Experimental)
Confidential D: Daphnid 48-hour
LC50= 1.28 mg/L
(Estimated)
REFERENCE
ECHA, 2013
^^^
Confidential study
^ r
ECOSAR vl. 11
7
Confidential study
OECD-SIDS, 2002
Confidential study
ECOSAR vl. 11
DATA QUALITY
Adequate study reported in a
secondary source. Conducted in
accordance with OECD Guideline
202.
Adequate study reported in a
secondary source.
ECOSAR also provided results for the
Esters, and Esters (phosphate) classes;
however, professional judgment
indicates that this compound is not
currently well represented in
ECOSAR vl. 11.
Sufficient study details reported.
Study reported in a secondary source;
conducted according to US EPA
660/3-75-009.
Sufficient study details reported.
ECOSAR also provided results for the
Esters, and Esters (phosphate) classes;
however, professional judgment
         7-182

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                                                        JUNE 2014 DRAFT REPORT
                                                         Emerald Innovation™ NH-1
         PROPERTY/ENDPOINT
             DATA
         REFERENCE
        DATA QUALITY
                                           ECOSAR: Neutral organics
                                                                  indicates that this compound is not
                                                                  currently well represented in
                                                                  ECOSAR vl. 11.
                                           Confidential E: Daphnia magna 48-
                                           hour EC50 = 0.34 mg/L (static)
                                           (Experimental)
                                 ECHA, 2013
                                Adequate study reported in a
                                secondary source. Test material is a
                                confidential product.
                                           Confidential E: Daphnia magna 48-
                                           hour EC50 = 2.9 mg/L (static)
                                           Test concentrations not specified
                                           (Experimental)
                                 ECHA, 2013
                                Adequate study reported in a
                                secondary source. Test material is a
                                confidential product.
                                           Confidential E: Daphnia magna 48-
                                           hour EC50 = 5 mg/L (static)
                                           Test concentrations not specified
                                           (Experimental)
                                 ECHA, 2013
                                           Confidential E: Daphnia magna 48-
                                           hour LC50 = 0.000011 mg/L
                                           (Estimated)
                                           ECOSAR: Neutral organics
                                 ECOSAR vl. 11
                                Adequate study reported in a
                                secondary source. Test material is a
                                confidential product.
                                NES: The log Kow of 11 for this
                                chemical exceeds the SAR limitation
                                for the log Kow of 5.0; NES are
                                predicted for these endpoints.
                                ECOSAR also provided results for the
                                Esters, and Esters (phosphate) classes;
                                however, professional judgment
                                indicates that this compound is not
                                currently well represented in
                                ECOSAR vl. 11.
Green Algae EC50
Confidential C: Green algae
(Pseudokirchneriella subcapitatd) 72-
hour EC50 = 61 mg/L (growth rate);
72-hour NOEC = 4.6 mg/L
Static conditions; nominal
concentrations: 0, 0.32, 1.0, 3.2, 10,
32, 100 mg/L
(Experimental)
ECHA, 2013
Adequate study reported in a
secondary source. Conducted in
accordance with OECD Guideline
201.
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                                               JUNE 2014 DRAFT REPORT
                                                Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                 Confidential C: Green algae 96-hour
                                 EC5o = 8.5 mg/L
                                 (Estimated)
                                 ECOSAR: Neutral organics
                    ECOSARvl.ll
                       ECOSAR also provided results for the
                       Esters, and Esters (phosphate) classes;
                       however, professional judgment
                       indicates that this compound is not
                       currently well represented in
                       ECOSARvl.ll.
                                 Confidential D: Green algae
                                 (Selenastrum capricornutum) 96-
                                 hour EC50 = 2.0 mg/L
                                 (Experimental)
                    OECD-SIDS, 2002
                       Reported in a secondary source.
                                 Confidential D: Green algae 96-hour
                                 EC50 = 2.0 mg/L
                                 (Experimental)
                    Confidential study
                                 Confidential D: Green algae
                                 (Scenedesmus subspicatus) 72-hour
                                 LOEC = 0.5-5 mg/L
                                 NOEC = 0.25 - 2.5 mg/L
                                 (Experimental)
                    OECD-SIDS, 2002
                                 Confidential D: Green algae 96-hour
                                 EC50= 1.59 mg/L
                                 (Estimated)
                                 ECOSAR: Neutral organics
                    ECOSARvl.ll
                                 Confidential E: Green algae
                                 (Pseudokirchneriella subcapitatd) 14-
                                 day LOEC (biomass) = 0.1 mg/L
                                 (static);
                                 14-day EC100 (93% growth inhibition)
                                 = 10.0 mg/L
                                 nominal concentrations: 0.1 mg/L, 1
                                 mg/L, 10.0 mg/L and 100 mg/L
                                 (Experimental)
                    ECHA, 2013
                       Sufficient study details reported.
                       Study reported in secondary source;
                       conducted according to OECD
                       guideline 201.
                       ECOSAR also provided results for the
                       Esters, and Esters (phosphate) classes;
                       however, professional judgment
                       indicates that this compound is not
                       currently well represented in
                       ECOSARvl.ll.
                       Adequate study reported in a
                       secondary source. Test material is a
                       confidential product.
                                                          7-184

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                                                        JUNE 2014 DRAFT REPORT
                                                         Emerald Innovation™ NH-1
         PROPERTY/ENDPOINT
             DATA
         REFERENCE
        DATA QUALITY
                                          Confidential E: Green algae
                                          (Pseudokirchneriella subcapitatd) 96-
                                          hour EC50 = 2.6 mg/L (growth rate)
                                          (static) nominal concentrations: 0.6
                                          mg/L, 1.0 mg/L, 3.2 mg/L, 5.6 mg/L
                                          and 10 mg/L
                                          (Experimental)
                                 ECHA, 2013
                                Adequate study reported in a
                                secondary source. Test material is a
                                confidential product.
                                          Confidential E: Green algae 96-hour
                                          EC50 = 0.00021 mg/L
                                          (Estimated)
                                          ECOSAR: Neutral organics
                                 ECOSARvl.ll
                                NES: The log Kow of 11 for this
                                chemical exceeds the SAR limitation
                                for the log Kow of 6.4; NES are
                                predicted for these endpoints.
                                ECOSAR also provided results for the
                                Esters, and Esters (phosphate) classes;
                                however, professional judgment
                                indicates that this compound is not
                                currently well represented in
                                ECOSARvl.ll.
Chronic Aquatic Toxicity
VERY HIGH: Based on an experimental fish 30-day LOEC = 0.037 mg/L for Confidential D and
experimental data in fish and daphnia for Confidential E. No chronic experimental data were available for
algae. Chronic aquatic toxicity is of HIGH concern for Confidential C based on estimated ChV values for
fish, daphnia and algae using the ECOSAR Neutral organics class.
Fish ChV
Confidential C: Freshwater fish ChV
= 1.0 mg/L
(Estimated)
ECOSAR: Neutral organics
                                          Confidential D: Freshwater fish
                                          (Oncorhynchus mykiss} 30-day LOEC
                                          = 0.037 mg/L
                                          (Experimental)
ECOSARvl.ll
                                 ECHA, 2013
ECOSAR also provided results for the
Esters, and Esters (phosphate) classes;
however, professional judgment
indicates that this compound is not
currently well represented in
ECOSARvl.ll.
                                Reported in a secondary source.
                                                                   7-185

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                                               JUNE 2014 DRAFT REPORT
                                                Emerald Innovation™  NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                 Confidential D: Fish (Pimephales
                                 promelas) 30-day LOEC = 0.23 mg/L
                                 NOEC = 0.087 mg/L
                                 There were no changes in hatchability
                                 of eggs, mean total length, and
                                 average we weight of fry. There was
                                 reduced percentage survival of fry
                                 through 30 days post-exposure at 0.23
                                 mg/L. Severe scoliosis was reported
                                 in several fry and erratic swimming
                                 was reported in all fry at 0.23 mg/L.
                                 (Experimental)
                    OECD-SIDS, 2002
                       Sufficient study details reported.
                                 Confidential D: Fish ChV = 0.15
                                 mg/L
                                 (Estimated)
                                 ECOSAR: Neutral organics
                    ECOSARvl.ll
                                 Confidential E: Freshwater fish
                                 {Pimephales promelas} 90-day NOEC
                                 = 0.093 mg/L (flow-through);
                                 nominal concentrations: 0.06, 0.12,
                                 0.25, 0.5 and 1.0 mg/L
                                 measured (mean) concentrations:
                                 0.022, 0.040, 0.093, 0.194 and 0.496
                                 mg/L
                                 (Experimental)
                    ECHA, 2013
                       ECOSAR also provided results for the
                       Esters, and Esters (phosphate) classes;
                       however, professional judgment
                       indicates that this compound is not
                       currently well represented in
                       ECOSARvl.ll.
                       Adequate study reported in a
                       secondary source. Test material is a
                       confidential product.
                                                           7-186

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                                               JUNE 2014 DRAFT REPORT
                                                Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                 Confidential E: Freshwater fish
                                 (Pimephales promelas} 30-day NOEC
                                 (growth, reproduction) = 0.14 mg/L
                                 (flow-through);
                                 30-day LOEC (reproduction) = 0.25
                                 mg/L;
                                 30-day NOEC (mortality) = 0.25
                                 mg/L;
                                 measured concentrations: 60, 140,
                                 250, 410 and 1340 (jg/1 (0.06, 0.14,
                                 0.25,0.41, 1.34 mg/L)
                                 (Experimental)
                    ECHA, 2013
                       Adequate study reported in a
                       secondary source. Test material is a
                       confidential product.
                                 Confidential E: Freshwater fish
                                 {Pimephales promelas} 30-day LC50 >
                                 1 < 2 mg/L (flow-through);
                                 nominal concentrations: 0.125, 0.25,
                                 0.5, 1.0 and 2.0 mg/L
                                 (Experimental)
                    ECHA, 2013
                                 Confidential E: Freshwater fish ChV
                                 = 0.0000022 mg/L
                                 (Estimated)
                                 ECOSAR: Neutral organics
                    ECOSARvl.ll
                       Adequate study reported in a
                       secondary source. Test material is a
                       confidential product.
                       NES: The log Kow of 11 for this
                       chemical exceeds the SAR limitation
                       for the log Kow of 8.0; NES are
                       predicted for these endpoints.
                       ECOSAR also provided results for the
                       Esters, and Esters (phosphate) classes;
                       however, professional judgment
                       indicates that this compound is not
                       currently well represented in
                       ECOSARvl.ll.
                                                          7-187

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                                                        JUNE 2014 DRAFT REPORT
                                                         Emerald Innovation™  NH-1
         PROPERTY/ENDPOINT
             DATA
         REFERENCE
        DATA QUALITY
Daphnid ChV
Confidential C: Daphnia magna
ChV = 0.90 mg/L
(Estimated)
ECOSAR: Neutral organics
ECOSARvl.ll
ECOSAR also provided results for the
Esters, and Esters (phosphate) classes;
however, professional judgment
indicates that this compound is not
currently well represented in
ECOSARvl.ll.
                                           Confidential D: Daphnid ChV
                                           0.186 mg/L
                                           (Estimated)
                                           ECOSAR: Neutral organics
                                 ECOSARvl.ll
                                           Confidential E: Daphnia magna 21-
                                           day NOEC (reproduction) = 0.015 -
                                           0.02 mg/L (flow-through);
                                           21-day NOEC (mortality) = 0.03 -
                                           0.06 mg/L;
                                           21-day EC50 (immobilization) = 0.028
                                           mg/L;
                                           5 concentrations were used, but these
                                           are not specified in the report.
                                           (Experimental)
                                 ECHA, 2013
                                           Confidential E: Daphnia magna 21-
                                           day NOEC (mortality) = 0.03 - 0.07
                                           mg/L (flow-through);
                                           21-day NOEC (reproduction) > 0.026
                                           mg/L;
                                           21-day EC50 (immobilization) = 0.023
                                           mg/L;
                                           5 concentrations were used, but these
                                           are not specified in the report.
                                           (Experimental)
                                 ECHA, 2013
                                ECOSAR also provided results for the
                                Esters, and Esters (phosphate) classes;
                                however, professional judgment
                                indicates that this compound is not
                                currently well represented in
                                ECOSARvl.ll.
                                Adequate study reported in a
                                secondary source. Test material is a
                                confidential product.
                                Adequate study reported in a
                                secondary source. Test material is a
                                confidential product.
                                                                    7-188

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                                               JUNE 2014 DRAFT REPORT
                                                Emerald Innovation™  NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                 Confidential E: Daphnia magna 21-
                                 day NOEC (reproduction) = 0.032
                                 mg/L (flow-through);
                                 nominal concentrations: 0, 0.032,
                                 0.096, 0.256, 0.352 mg/L)
                                 (Experimental)
                    ECHA, 2013
                       Adequate study reported in a
                       secondary source. Test material is a
                       confidential product.
                                 Confidential E: Daphnia magna 21-
                                 day NOEC (reproduction/survival) =
                                 0.0399 mg/L (Flow through);
                                 21-day LOEC (reproduction/survival)
                                 = 0.0933 mg/L;
                                 21-day NOEC (mortality) = 0.04
                                 mg/L; nominal (t=0): 20.025, 0.075,
                                 0.225, 0.675 and 1 mg/L measured
                                 (t=0) sediment pond: 0.068, 0.116,
                                 0.411, 0.980 mg/L measured (t=2)
                                 sediment pond: 0.029, 0.059, 0.202,
                                 0.504 and 0.789 mg/L
                                 (Experimental)
                    ECHA, 2013
                       Adequate study reported in a
                       secondary source. Test material is a
                       confidential product.
                                 Confidential E: Daphnia magna 21-
                                 day NOEC (mortality, reproduction) =
                                 0.040 mg/L (flow-through);
                                 21-day LOEC (mortality,
                                 reproduction) = 0.1 mg/L
                                 nominal concentrations: 0.01, 0.20,
                                 0.40, 0.80, 0.16 mg/L
                                 (Experimental)
                    ECHA, 2013
                       Adequate study reported in a
                       secondary source. Test material is a
                       confidential product.
                                                           7-189

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                                                        JUNE 2014 DRAFT REPORT
                                                         Emerald Innovation™ NH-1
         PROPERTY/ENDPOINT
             DATA
         REFERENCE
        DATA QUALITY
                                           Confidential E: Daphnia magna
                                           ChV = 0.0000095 mg/L
                                           (Estimated)
                                           ECOSAR: Neutral organics
                                 ECOSARvl.ll
                                NES: The log Kow of 11 for this
                                chemical exceeds the SAR limitation
                                for the log Kow of 8.0; NES are
                                predicted for these endpoints.
                                ECOSAR also provided results for the
                                Esters, and Esters (phosphate) classes;
                                however, professional judgment
                                indicates that this compound is not
                                currently well represented in
                                ECOSARvl.ll.
Green Algae ChV
Confidential C: Green algae ChV =
3.2 mg/L
(Estimated)
ECOSARvl.ll
                                           Confidential D: Green algae ChV =
                                           0.925 mg/L
                                           (Estimated)
                                           ECOSAR: Neutral organics
                                 ECOSARvl.ll
                                           Confidential E: Green algae ChV =
                                           0.00032 mg/L
                                           (Estimated)
                                           ECOSAR: Neutral organics
                                 ECOSARvl.ll
ECOSAR also provided results for the
Esters, and Esters (phosphate) classes;
however, professional judgment
indicates that this compound is not
currently well represented in
ECOSARvl.ll.
                                ECOSAR also provided results for the
                                Esters, and Esters (phosphate) classes;
                                however, professional judgment
                                indicates that this compound is not
                                currently well represented in
                                ECOSARvl.ll.
                                NES: The log Kow of 11 for this
                                chemical exceeds the SAR limitation
                                for the log Kow of 8.0; NES are
                                predicted for these endpoints.
                                ECOSAR also provided results for the
                                Esters, and Esters (phosphate) classes;
                                however, professional judgment
                                indicates that this compound is not
                                currently well represented in
                                ECOSARvl.ll.
                                                                   7-190

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JUNE 2014 DRAFT REPORT
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
ENVIRONMENTAL FATE
Transport

Henry's Law Constant (atm-
m3/mole)
Sediment/Soil
Adsorption/Desorption - Koc
Level III Fugacity Model
Level III fugacity models incorporating available physical and chemical property data indicate that at steady
state, the components of this mixture are expected to be found primarily in soil and to a lesser extent, water.
Confidential C and D are expected to have moderate mobility in soil, based on measured Koc values in silty
clay, loamy sand and silt loam and estimates. Confidential E is expected to have negligible mobility in soil.
Leaching through soil to groundwater may occur, though it is not expected to be an important transport
mechanism. Confidential D may volatilize from moist soil and water surfaces based on its Henry's Law
constant. Volatilization from dry surface is not expected based on its vapor pressure. In the atmosphere,
Confidential D is expected to exist in both the vapor phase and particulate phase; Confidential C and E are
expected to exist in the particulate phase. Particulates may be removed from air by wet or dry deposition.
Confidential C: <10"8 (Estimated)
Confidential D: 1.2x10 5 (Measured)
Confidential E: 6.9xlO"7 (Estimated)
Confidential C: 1,300 (Estimated)
Confidential D: 2,514 Reported for
silty clay. (Measured)
Confidential D: 2,736 Reported for
silt loam (Measured)
Confidential D: 3,561 Reported for
loamy sand. (Measured)
Confidential E: >3 0,000 (Estimated)
J
Confidential C: Air = 0.1%
Water = 22.4%
Soil = 76.8%
Sediment = 0.7% (Estimated)
Confidential D: Air = 0.7%
Water = 14.5%
EPIv4.11
Confidential study
EPIv4.11
EPIv4.11
Confidential study
Confidential study
Confidential study
EPIv4.11;EPA, 2005
EPIv4.11
EPIv4.11
Estimated using measured water
solubility and vapor pressure values.
Reported in a primary source.
Using HENRYWIN v3.20 Bond
method results.
MCI Method
Reported in a primary source.
Reported in a primary source.
Reported in a primary source.
Estimated value is greater than the
cutoff value, >30,000, for non-mobile
compounds.

Reported in a Level III Fugacity
model. Experimental data is
         7-191

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JUNE 2014 DRAFT REPORT
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT


Persistence
Water
Aerobic Biodegradation
DATA
Soil = 75. 8%
Sediment = 9.02% (Estimated)
Confidential E: Air = 0.2%
Water =11. 3%
Soil = 85.1%
Sediment = 3.5% (Estimated)
REFERENCE

EPIv4.11
DATA QUALITY
consistent with partitioning to
sediment.

MODERATE: Based on primary and ultimate biodegradation data that suggest a half-life for ultimate
degradation of >16 days and <60 days for Confidential E based on a close structural analog. Biodegradation
studies for an analog to Confidential E reported 100% primary degradation after approximately 11 days in a
river die-away study and 93% primary degradation after 9 weeks in a SCAS test using activated sludge
inoculum under aerobic conditions. The analog to Confidential E was found to have primary half-lives of 4.2
and 8.4 days in pond and river sediment, respectively, and showed mineralization of 1.7-37.2% after 8 weeks
in water-sediment microcosms. However, DfE criteria are based on ultimate biodegradation and the above
results are consistent with a MODERATE designation. Other components of the commercial mixture were
found to degrade more rapidly. Confidential C was found to be readily biodegradable with activated sludge
inoculum and the modified Sturm test. Confidential D was found to be readily biodegradable in a Japanese
MITI ready biodegradability test, OECD 301C and 93.8% removal of Confidential D as dissolved organic
carbon (DOC) occurred over 20 days in an OECD 303A guideline study. The biodegradation results for
Confidential C and D are consistent with a Low persistence designation. The mixture contains phosphate
esters; these components are expected to be generally resistant to hydrolysis in neutral or acidic waters, but
may be hydrolyzed slowly in alkaline waters. Photolysis is not expected to be an important fate process since
this mixture does not contain compounds with functional groups that would be expected to absorb light in
the environment.
Confidential C: Passes Ready Test:
Yes
Test method: OECD TG 30 IB: CO2
Evolution Test
87% degradation after 28 days
(Measured)
Confidential C: Passes Ready Test:
No
Test method: OECD TG 301C:
Confidential study
Confidential study
Valid guideline study.
Valid guideline study.
         7-192

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                                               JUNE 2014 DRAFT REPORT
                                                Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  Modified MITI Test (I)

                                  0% degradation after 4 weeks using
                                  an activated sludge inoculum.
                                  (Measured)
                                  Confidential C: Study results:
                                  88%/28d
                                  Test method: 302A: Inherent -
                                  Modified SCAS Test

                                  Primary degradation (Measured)
                    Confidential study
                       Valid guideline study.
                                  Confidential C: Study results:
                                  51%/28d
                                  Test method: Shake Flask

                                  Ultimate biodegradation (Measured)
                    Confidential study
                                  Confidential C: Study results:
                                  Test method: Die-Away

                                  Slight degradation (-0-10%) after 30
                                  days using river water inoculum and
                                  four river die-away tests. During two
                                  river die-away tests from the same
                                  study, the test substance achieved
                                  20% degradation after 30 days and
                                  100% degradation after 22 days.
                                  (Measured)
                    Confidential study
                                  Confidential C: Study results:
                                  100%/14d
                                  Test method: Other

                                  100% degradation after 14 days using
                                  river water inoculum after an
                    Confidential study
                       Valid non-guideline study. Monsanto
                       shake flask procedure.
                       Valid non-guideline study; study
                       details could not be determined as the
                       source paper was written in Japanese.
                       Reported in peer reviewed secondary
                       source. Limited study details were
                       provided.
                                                           7-193

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                                               JUNE 2014 DRAFT REPORT
                                                Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                 acclimatization period of several days
                                 and a molybdenum blue colorimetric
                                 method. (Measured)
                                 Confidential C: Study results:
                                 Test method: Other

                                 17.6 and 100% degradation after 14^
                                 days using seawater inoculum after an
                                 acclimatization period of several days
                                 and a molybdenum blue colorimetric
                                 method. (Measured)
                    Confidential study
                       Reported in peer reviewed secondary
                       source. Limited study details were
                       provided.
                                 Confidential D: Passes Ready Test:
                                 Yes
                                 Test method: OECD TG 301C:
                                 Modified MITI Test (I)

                                 83-94% biodegradation after 28 days
                                 at 100 mg/L of test substance.
                                 (Measured)
                    OECD-SIDS, 2002
                       Reported in a guideline study.
                                 Confidential D: Study results:
                                 100%/3 days
                                 Test method: Die-Away

                                 Reported as inherently biodegradable
                                 in a river water/river die-away test
                                 (Measured)
                    OECD-SIDS, 2002
                       Reported in a secondary source.
                                 Confidential E: Study results: 93%/9
                                 weeks
                                 Test method: Biological Treatment
                                 Simulation

                                 SCAS test. 93% primary degradation
                                 after 9 weeks in domestic activated
                    Confidential study
                       Nonguideline study for confidential
                       analog.
                                                          7-194

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JUNE 2014 DRAFT REPORT
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT

Soil

Volatilization Half-life for
Model River
Volatilization Half-life for
Model Lake
Aerobic Biodegradation
DATA
sludge at a test substance addition rate
of 3 mg/L every 24 hours. (Estimated
?y analogy)
Confidential E: Study results:
100%/lldays
Test method: Die-Away
Complete primary degradation
occurred after about 1 1 days in a river
water die-away study. (Estimated by
analogy)
Confidential C: >1 year (Estimated)
Confidential D: 4 days (Estimated)
Confidential E: 79 days (Estimated)
Confidential C: >1 year (Estimated)
Confidential D: 47 days (Estimated)
Confidential E: >1 year (Estimated)
Confidential D: Study results:
93.8%/20days
Test method: 303A: Activated Sludge
Units - Simulation Test
Removal as DOC, using initial
concentration of 5 mg/L with activated
sludge. Reported as inherently
)iodegradable. (Measured)
REFERENCE

Confidential study
^^^
^^^N. r
EPIv4.11
EPIv4.11
EPIv4.11
EPIv4.11
EPIv4.11
EPIv4.11
EC, 2000; OECD-SIDS, 2002
DATA QUALITY

Nonguideline study for confidential
analog.

Reported in the volatilization from
water model.


Reported in the volatilization from
water model.

Reported in a guideline study.
         7-195

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                                               JUNE 2014 DRAFT REPORT
                                                Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
             DATA
         REFERENCE
DATA QUALITY
                                   onfidential D: Study results:
                                  77%/28 days
                                  Test method: Other
                                  Reported as ultimately biodegradable.
                                  VIonsanto Shake Flask Procedure
                                  precursor to Closed bottle test).
                                  Measured)
                                 OECD-SIDS, 2002
                                 Reported in a secondary source.
                                   onfidential D: Study results:
                                  32%/28 days
                                  rest method: CO2 Evolution
                                  Modified Sturm test. Reported as
                                  altimately biodegradable. Measured in
                                  iomestic, adapted activated sludge
                                  Measured)
                                 OECD-SIDS, 2002
                                 Reported in a secondary source.
                                   onfidential D:
                                  Study results: 93%/49 days
                                  Test method: 302A: Inherent -
                                  Modified SCAS Test
                                  Reported as inherently biodegradable.
                                  Measured)
                                 OECD-SIDS, 2002
                                 Reported in a guideline study.
    Anaerobic Biodegradation
 onfidential C & E: Not probable
Anaerobic-methanogenic
Biodegradation probability model)
EPIv4.11
                                   onfidential D:
                                  Study results: 89.7%/40 days
                                  Test method: CO2 Evolution Test
                                  Primary degradation: 31.1% after 3
                                  days, 89.7% after 40 days in river
                                  sediment. CO2 evolution: 0.8% after 3
                                  days, and 21.9% after 40 days.
                                  Measured)
                                 OECD-SIDS, 2002
                                 Reported in a secondary source.
                                                           7-196

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JUNE 2014 DRAFT REPORT
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT

Air
Reactivity
Soil Biodegradation with
Product Identification
Sediment/Water
Biodegradation
Atmospheric Half-life
Photolysis
DATA

Confidential D: 86.9%/40 days
'rimary degradation in river sediment.
43. 3% after 3 days
86.9% after 40 days (Measured)
Confidential E: Mineralization of the
est substance (2 mg) ranged from 1.7
o 37.2% after 8 weeks in microcosms
containing sediment and water from
acustrine, riverine, and estuarine
scosystems. The rate of degradation
was related to the nutrient level and
contaminant.
Estimated by analogy)
Confidential E: 50%/4.2 days at 25°C
n pond sediment; 50%/8.4 days at
25 °C in river sediment.
Test substance was subject to static
river and pond sediment-water
ncubations in respirometer flasks at
emperatures and redox conditions
ypical of aquatic environments.
Estimated by analogy)
Confidential C: 0.08 days
(Estimated)
Confidential D: 1 day (Estimated)
Confidential E: 0.43 days
^Estimated)
Confidential C, D and E: Not
expected to be a significant fate
REFERENCE

OECD-SIDS, 2002
^^^
Confidential study
^^
Confidential study
EPIv4.11
EPIv4.11
EPIv4.11
Mill, 2000; Professional judgment
DATA QUALITY
No data located.
Reported in a secondary source.
vfonguideline study for confidential
analog.
vfonguideline study for confidential
analog.



This compound does not contain
functional groups that would be
         7-197

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JUNE 2014 DRAFT REPORT
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT


Hydrolysis
DATA
process. (Estimated)
Confidential D: A 0.1 mg/L solution
(with acetone) was exposed to a
mercury lamp to examine the effect of
UV light on the degradation of
Confidential D.
High pressure lamp (100W): 100%/20
minutes
Low pressure lamp (15W): 100%/1
hour
(Measured)
Confidential C: Phosphate esters, are
generally resistant to hydrolysis in
neutral or acidic waters, but may be
hydrolyzed in alkaline waters.
(Measured)
Confidential C: Half-lives:
95 days at pH 5, 6, 7, and 8
93 days at pH 9
75 days at pH 10 (Estimated)
Confidential D: 50%/>28 days
Reported at 25 °C; pH 5 (Measured)
Confidential D: 50%/19 days
Reported at 25 °C; pH 7 (Measured)
Confidential D: 50%/3 days
Reported at 25 °C; pH 9 (Measured)
Confidential D: 50%/7.5 days
Reported at pH 8.2 in river/lake water
(Measured)
Confidential D: 50%/1.3 days
Reported at pH 9.5 in river/lake water
REFERENCE

EC, 2000
^^^
^^^N. T
Confidential study; ATSDR, 2012
EPIv4.11
EC, 2000; OECD-SIDS, 2002
OECD-SIDS, 2002
EC, 2000; OECD-SIDS, 2002
EC, 2000
EC, 2000
DATA QUALITY
expected to absorb light of
wavelengths >290 nm.
Reported in a secondary source under
laboratory conditions.
Reported in several secondary
sources. No quantitative rate data
were located.

Reported in a secondary source.
Reported in a secondary source.
Reported in a secondary source.
Reported in a secondary source.
Reported in a secondary source.
         7-198

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JUNE 2014 DRAFT REPORT
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT


Environmental Half-life
DATA
(Measured)
Confidential D: 100%/10 minutes at
pH 13 (Measured)
Confidential E: Half-lives:
460 years atpH 5;
46 years at pH 6;
4.6 years at pH 7;
1 70 days at pH 8;
17daysatpH9;
1.7 days at pH 10 (Estimated)
Confidential C: 17 days (Estimated)
Confidential D: 75 days (Estimated)
Confidential D: In loamy sand,
observed half-lives of 37 days
(aerobic) and 21 days (anaerobic)
(Measured)
Confidential E: 120 days (Estimated)
REFERENCE

ECHA, 2013
EPIv4.11
^^^
^^^N. T
PBT Profiler
PBT Profiler
7
OECD-SIDS, 2002
PBT Profiler
DATA QUALITY

Reported in secondary source.
Documentation of study details was
not sufficient to assess its reliability.

Half-life estimated for the
predominant compartment, soil, as
determined by EPI methodology.
Half-life estimated for the
predominant compartment, soil, as
determined by EPI and the PBT
Profiler methodology.
Reported in a secondary source.
Half-life estimated for the
predominant compartment, soil, as
determined by EPI methodology.
         7-199

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JUNE 2014 DRAFT REPORT
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
Bioaccumulation

Fish BCF
DATA
REFERENCE
DATA QUALITY
HIGH: The bioaccumulation designation is based on an estimated BAF value for Confidential E; this value is
>1,000. The estimated low BCF value is consistent with the limited water solubility estimates. The
bioaccumulation designations for the other components, Confidential C and D, are LOW and MODERATE,
respectively.
Confidential C: 4.1
Reported as <0.6 to 4.1 in Carp.
Substance concentration: 0.2 mg/L.
(Measured)
Confidential C:<5. 8
in Carp
Substance concentration: 0.02 mg/L
(Measured)
Confidential D: 132-364 (Rainbow
trout) (Measured)
Confidential D: 271
Rainbow trout (Measured)
Confidential D: 364
Reported as 132-364 in rainbow trout
(Measured) ^^
Confidential D: 193
Reported as 84-193 in Medaka
(Measured)
Confidential D: 160
Reported as 68-160 in Fathead
minnow (Measured)
Confidential D: 144
Medaka (Measured)
Confidential D: 110
Goldfish (Measured)
Confidential E: 37 (Estimated)
HSDB, 2003
^^^
HSDB, 2003
Confidential study
EC, 2000
OECD-SIDS, 2002
EC, 2000
EC, 2000
OECD-SIDS, 2002
OECD-SIDS, 2002
EPIv4.11
Guideline study reported in a peer
reviewed secondary source.
Guideline study reported in a peer
reviewed secondary source.
Adequate.
Reported in a secondary source.
Insufficient study details to assess the
quality of the reported values.
Reported in a secondary source.
Reported in a secondary source.
Reported in a secondary source.
Reported in a secondary source.
Estimated using the representative
structure.
         7-200

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JUNE 2014 DRAFT REPORT
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT

Other BCF
BAF
Metabolism in Fish
DATA

Confidential C: 54 (Estimated)
Confidential D: 73 (Estimated)
Confidential E: 18,000 (Estimated)

REFERENCE

EPIv4.11
EPIv4.11
EPIv4.11

DATA QUALITY
No data located.


Estimated using the representative
structure.
^o data located.
ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring
Ecological Biomonitoring
Human Biomonitoring
Confidential C was detected in river water, drinking water and wastewater effluent. It was detected in indoor air
and dust in offices and homes. It has been detected globally in the atmosphere. It was detected in sediment samples.
Confidential D has been detected in drinking water, household dust, sediment, river water, seawater, rainwater,
snow, wastewater effluent, ambient air, and indoor air (Confidential references).
Confidential C was detected in herring gull eggs and fish. Confidential D has been detected in fish tissues,
bottlenose dolphin blubber (Confidential references).
Confidential C has been detected in human adipose tissue. Confidential D was detected in human milk, adipose
tissue and human plasma. Confidential C, D and E were not included in the NHANES biomonitoring report (CDC,
2013; Confidential references).
         7-201

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                                                  JUNE 2014 DRAFT REPORT


ATSDR (2009) Atlanta, GA: U.S. Department of Health and Human Services, Agency for Toxic Substances and Disease Registry.

ATSDR (2012) Atlanta, GA: U.S. Department of Health and Human Services, Agency for Toxic Substances and Disease Registry.

CDC (2013) Fourth national report on human exposure to environmental chemicals, updated tables, March 2013. Centers for Disease Control and
Prevention, http://www.cdc.gov/exposurereport/pdf/FourthReport_UpdatedTables_Mar2013.pdf. Accessed May 10, 2013.

EC (2000) IUCLID dataset.
                                                                           ^^^
ECHA (2012) Registered substances. European Chemicals Agency.

ECHA (2013) Registered substances. European Chemicals Agency.

ECOSAR (Ecological Structure Activity Relationship), Version 1.11. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/oppt/newchems/tools/21ecosar.htm.

EPA (1999) Determining the adequacy of existing data. Washington, DC: U.S. Environmental Protection Agency.
http: //www .epa. gov/hpv/pubs/general/datadeqfn .pdf.

EPA (2005) Pollution prevention (P2) framework. Washington, DC: U.S. Environmental Protection Agency, Office of Pollution Prevention and
Toxics, http://www.epa.gov/opptintr/newchems/pubs/sustainable/p2frame-june05a2.pdf.

EPA (2012) Using noncancer screening within the SF initiative. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/oppt/sf/pubs/noncan-screen.htm.

EPI Estimation Programs Interface (EPI)  Suite, Version 4.11. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm.

Hansch C, Leo A, Hoekman D (1995) Exploring QSAR - hydrophobic, electronic, and steric constants. Washington, DC: American Chemical
Society.

HSDB (2003) Hazardous Substances Data Bank. National Library of Medicine. http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen7HSDB.

Lide  DR (2008) CRC Handbook of chemistry and physics. 88th ed. Boca Raton, FL: CRC Press, Taylor and Francis Group, 3-512.

Mill T (2000) Photoreactions in surface waters. In: Boethling R Mackay D, eds. Handbook of Property Estimation Methods for Chemicals,
Environmental Health Sciences. Boca Raton: Lewis Publishers, 355-381.
                                                              7-202

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                                                  JUNE 2014 DRAFT REPORT


OncoLogic (2008) U.S. EPA and LogiChem, Inc. 2005, Version 7.0. 2008.

O'Neil MJ, et al., eds (2006) The Merck index: An Encyclopedia of Chemicals, Drugs, and Biologicals. 14th ed. Whitehouse Station, N.J: Merck.

PBT Profiler. Persistent (P),Bioaccumulative (B), and Toxic (T) Chemical (PBT) Profiler, Version 1.301. Washington, DC: U.S. Environmental
Protection Agency, www.pbtprofiler.net.

PhysProp (2012) Physical properties database. Estimation Programs Interface Suite, Version 4.10. Washington, DC: U.S. Environmental
Protection Agency, http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm.
                                                              7-203

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                                                             JUNE 2014 DRAFT REPORT
               Expandable graphite
                                                    Screening Level Toxicology Hazard Summary

This table only contains information regarding the inherent hazards of flame retardant chemicals. Evaluation of risk considers both the hazard and exposure associated with the
substance including combustion and degradation by-products. The caveats listed in the legend and footnote sections must be taken into account when interpreting the hazard
information in the table.
VL = Very Low hazard L = Low hazard   = Moderate hazard H = High hazard VH = Very High hazard - Endpoints in colored text (VL, L,   , H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].

* Expandable graphite commercial formulations are prepared with chemical washes. There are variable hazards from the specific wash chemicals used and, as a result the hazards
may change by manufacturer. One confidential wash has additional hazard concern as follows, based on experimental data: HIGH-Acute Toxicity, Eye Irritation, Dermal irritation.
Other manufacturers may use a wash that contains chromic acid (CASRN 7738-94-5) with additional hazard concerns as follows, based on experimental data: HIGH-Acute Toxicity,
Carcinogenicity, Genotoxicity, Reproductive, Repeated dose, Skin sensitization, Respiratory sensitization, Eye Irritation, Dermal irritation.	





Chemical





CASRN
Human Health Effects

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                                                        *
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 Aquatic toxicity: EPA/DfE criteria are based in large part upon water column exposures which may not be adequate for poorly soluble substances such as many
flame retardants that may partition to sediment and particulates.
                                                                          7-204

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JUNE 2014 DRAFT REPORT
° r-5T
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structure
CASRN: 12777-87-6
MW: > 1,000 (Estimated)
MF: [C]n[S03H]x
Physical Forms: Solid
Neat:
Use: Flame retardant
SMILES: Not applicable
Synonyms: Sulfuric acid, compd. with graphite; Sulfuric acid, compd. With graphite (1:?); Expandable graphite; exfoliated graphite; sulfuric acid, compound with
graphite; graphite hydrogen sulfate (CASRN 12689-13-3); graphite bisulfate (CASRN 12689-13-3); graphite intercalation compounds
Chemical Considerations: Expandable graphite is manufactured by a process where the carbon sheets of graphite are modified by oxidative chemical treatment. The
oxidation of graphite causes an increase in the distance between graphite crystal lattice planes and an increase in the specific volume of the graphite particles by a
factor of 200 to 400. There are different hazards that result from the specific wash chemicals used and, as a result, the hazards may change by manufacturer.
Commercial expandable graphite products may contain 0.1-3.0% free silica or quartz (CASRN 14808-60-7) as residuals from graphite. Synthetic and natural graphite
may be mixtures that contain deliberate additives such as cristobalite, clay, coal, and petroleum products. Also, natural graphite is usually found associated with
impurities such as mica, iron oxide, granite and free silica in 2-25%. Expandable graphite is typically 85-98% carbon (CASRN 7782-42-5); the other components of
the commercial products are the expansion agents (i.e., sulfuric acid CASRN 7664-93-9) and other formulation specific confidential additives. Nanoscale components
are not expected to be present and were not included in this assessment. Expandable graphite particle sizes reported in product documentation are typically >200(jm x
30 (jm, outside of the nanoscale range (Jager et al., 2010; MSDS, 2012; AvTech Industries, 2013; GrafTech, 2013; IPCS, 2013; Professional judgment).
Polymeric: No
Oligomeric: Not applicable
Metabolites, Degradates and Transformation Products: Products
Analog: Graphite (CASRN 7782-42-5)
Endpoint(s) using analog values: Carcinogenicity
of combustion are carbon dioxide; carbon monoxide; sulfuric acid; sulfur dioxide (MSDS, 2012).
Analog Structure: Not applicable
Structural Alerts: Respirable, Poorly Soluble Particulates (EPA, 2012).
Risk Phrases: Not classified by Annex VI Regulation (EC) No 1272/2008 (ESIS, 2012).
Hazard and Risk Assessments: None identified
         7-205

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JUNE 2014 DRAFT REPORT
Expandable graphite CASRN 12777-87-6
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
PHYSICAL/CHEMICAL PROPERTIES
Melting Point (°C)
Boiling Point (°C)
Vapor Pressure (mm Hg)
Water Solubility (mg/L)
Log Kow
Flammability (Flash Point)
Explosivity
4,489
(Estimated by analogy)
3,825
sublimes (Estimated by analogy)
Triple point: graphite -liquid-gas 4492°C
at 101.325 kPa (Estimated by analogy)
<10-8at25°C
(Estimated)
<0.001 (Estimated by analogy)
Graphite (CASRN 7782-42-5) is reported
as insoluble in water
Soluble sulfur content in expandable
natural graphite samples was determined
by ICP-MS: 614, 635 and 641 mg/L;
corresponds to 0.764, 0.755 and 0.789 %
soluble sulfur respectively (Measured)
Using preliminary visual experiments the
water solubility is <1 1 mg/L according to
OECD Guideline 105 and EU Method
A. 6. The concentration of the test item
was determined using ICP-OES method.
(Measured)


Not expected to form explosive mixtures
in air (Estimated)
HSDB, 2009b
HSDB, 2009b
HSDB, 2009a
EPA, 1999
^r*
HSDB, 2009b
ECHA, 2013b
ECHA, 2013b


Professional judgment
Reported for Graphite (CASRN
7782-42-5).
Reported for Graphite (CASRN
7782-42-5).
Reported for Graphite (CASRN
7782-42-5).
Cutoff value for nonvolatile
compounds according to HPV
assessment guidance.
Cutoff value for non-soluble
compounds.
This nonguideline study provides
supporting information about the
solubility of the sulfur component of
this sample.
It was not possible to determine the
water solubility of the complete test
item.
No data located; this chemical is
outside the estimation domain of
EPI.
No data located.
No experimental data located; based
on its use as a flame retardant.
         7-206

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JUNE 2014 DRAFT REPORT
Expandable graphite CASRN 12777-87-6
PROPERTY/ENDPOINT
Pyrolysis
pH
pKa
DATA

2 at 20°C; according to CIPAC Handbook
Volume L, 2005; MT 191 Acidity or
Alkalinity of Formulations (Measured)
Not applicable (Estimated)
REFERENCE

ECHA, 2013b
Professional judgment
DATA QUALITY
No data located.
Reported in a secondary source.
Not applicable; this substance
contains compounds that are outside
the estimation domain of SPARC.
HUMAN HEALTH EFFECTS
Toxicokinetics
Dermal Absorption in vitro
Absorption,
Distribution,
Metabolism &
Excretion
Oral, Dermal or Inhaled
Other
No experimental data were located on the absorption, distribution, metabolism or excretion of expandable
graphite. An IPCS reported that graphite (CASRN 7782-42-5) may be absorbed into the body following
inhalation exposure; however, the report does not indicate what the data is based on and was not reported
in any other source. Absorption is not expected for the oral and dermal routes of exposure based on
analogy to graphite; nano-scale components are not expected to be present and data for the nanoscale
graphite were not included in this assessment.

Graphite can be absorbed into the body
via the inhalation route
^^ fr


IPCS, 2013

No data located.
Very Limited data reported in a
secondary source for Graphite
(CASRN 7782-42-5), though there
is no indication what the data is
based on; this information was not
reported in any other source.
No data located.
         7-207

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                                                         JUNE 2014 DRAFT REPORT
                                                    Expandable graphite CASRN 12777-87-6
           PROPERTY/ENDPOINT
                                          DATA
                                            REFERENCE
                                    DATA QUALITY
Acute Mammalian Toxicity
                           LOW: Expandable graphite is not acutely toxic via the oral or dermal routes in rats. No adequate
                           experimental data were located for the inhalation route; however, graphite dust may be irritating to the
                           respiratory tract.
                           Expandable graphite commercial formulations are prepared with chemical washes. There are variable
                           hazards from the specific wash chemicals used and, as a result the hazards may change by manufacturer.
                           A High hazard concern for acute toxicity is estimated for formulations containing one confidential wash
                           and also for washes containing chromic acid (CASRN 7738-94-5).
Acute Lethality
Oral
                  Dermal
                  Inhalation
Rat oral LD50 > 2,000 mg/kg bw
All animals survived until the end of the
study without showing any signs of
toxicity.
                           Rat dermal LD50
                           > 2,000 mg/kg bw
                           semi-occlusive conditions
                           Graphite dust is irritating to the
                           respiratory tract
                                             Inhalation LC50 = not determined;
                                             All attempts to generate an atmosphere
                                             using the test substance as received were
                                             unsuccessful.
ECHA, 2013b
                                     ECHA, 2013b
                                     REACH, 2006
                                                                ECHA, 2013b
Data are for Expandable Natural
Graphite (sulfuric acid, compound
with graphite), Purity > 93 %. Study
was conducted according to OECD
Guideline 423 and GLP.
                             Data are for Expandable Natural
                             Graphite (sulfuric acid, compound
                             with graphite), Purity > 93 %. Study
                             was conducted according to OECD
                             Guideline 402 and GLP.
                             Data are for Graphite (CASRN
                             7782-42-5); limited data reported in
                             a secondary source.
                                                                  Data are for Expandable Natural
                                                                  Graphite (sulfuric acid, compound
                                                                  with graphite), Purity > 93 %. Study
                                                                  was conducted according to OECD
                                                                  Guideline 403 and GLP. The overall
                                                                  results of the pre-test trials indicate
                                                                  that the physical properties of the
                                                                  test substance prevented the
                                                                  achievement of the required testing
                                                                  concentration.
                                                                    7-208

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JUNE 2014 DRAFT REPORT
Expandable graphite CASRN 12777-87-6
PROPERTY/ENDPOINT
Carcinogenicity

OncoLogic Results
Carcinogenicity (Rat and
Mouse)
Combined Chronic
Toxicity/Carcinogenicity
Other
DATA
REFERENCE
DATA QUALITY
MODERATE: No experimental data were located for expandable graphite. Graphite (CASRN 7782-42-5)
is classified as a Group 1 carcinogen by IARC and a suspected carcinogen by NTP. These classifications
are based on quartz as an impurity, and do not apply to graphite that is completely free of quartz.
However, there is no evidence of graphite on the market in pure form. In order to remain conservative, a
MODERATE hazard is designated by analogy to graphite.
Expandable graphite commercial formulations are prepared with chemical washes. There are variable
hazards from the specific wash chemicals used and, as a result the hazards may change by manufacturer.
A High hazard concern for Carcinogenicity is estimated for formulations containing chromic acid (CASRN
7738-94-5).



Graphite is classified as a Group 1
carcinogen and suspected carcinogen by
IARC and NTP, respectively. The
classifications are a result of quartz as an
impurity, and do not apply to graphite that
is completely free of quartz. However,
there is no evidence of graphite on the
market in pure form.



GrafTech, 2013
No data located.
No data located.
No data located.
Data are for Graphite (CASRN
7782-42-5).
         7-209

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JUNE 2014 DRAFT REPORT
Expandable graphite CASRN 12777-87-6
PROPERTY/ENDPOINT
Genotoxicity

Gene Mutation in vitro
Gene Mutation in vivo
Chromosomal Aberrations in
vitro
Chromosomal Aberrations in
vivo
DNA Damage and Repair
Other
DATA
REFERENCE
DATA QUALITY
LOW: Based on negative results in in vitro gene mutation and chromosomal aberration studies. The size of
expandable graphite particles are much larger than the nanoscale graphite used in an in vitro
micronucleus test in human bronchial epithelial cells using graphite nanofibers (95%; outer diameter 80-
200 nm, inner diameter 30-50 nm, length 5-20 um) which had positive results. Toxicity was most likely a
result from the impurity quartz rather than from graphite itself.
Expandable graphite commercial formulations are prepared with chemical washes. There are variable
hazards from the specific wash chemicals used and, as a result the hazards may change by manufacturer.
A High hazard concern for genotoxicity is estimated for formulations containing chromic acid (CASRN
7738-94-5).
Negative, (Salmonella typhimurium)
strains TA 98, TA 100, TA 1535, TA
1537 and TA 102 with and without
metabolic activation

Positive, In vitro micronucleus test in
human bronchial epithelial BEAS 2B cells
without metabolic activation; continuous
treatment for 48 and 72 hours. Treatment
for 24 hours produced negative results
Negative, in vitro mammalian cell
micronucleus test in human lymphocytes,
with and without metabolic activation



ECHA, 2013b

CCRIS, 2013
ECHA, 201 3b



Data are for Expandable Natural
Graphite (sulfuric acid, compound
with graphite), Purity > 93 %. Study
was conducted in accordance with
OECD Guideline 471 and GLP
No data located.
Data are for Graphite (CASRN
7782-42-5); test material was
graphite nanofibers (95%; outer
diameter 80-200 nm, inner diameter
30-50 nm, length 5-20 \m\)
Data are for Expandable Natural
Graphite (sulfuric acid, compound
with graphite), Purity > 93 %. Study
was conducted in accordance with
OECD Guidelines and GLP
No data located.
No data located.
No data located.
         7-210

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                                                         JUNE 2014 DRAFT REPORT
                                                     Expandable graphite CASRN 12777-87-6
           PROPERTY/ENDPOINT
               DATA
        REFERENCE
       DATA QUALITY
Reproductive Effects
LOW: No experimental data were located for expandable graphite. There were no adverse reproductive
effects in rats at doses up to 1,159 mg/kg-day in an oral combined repeated dose
reproduction/developmental toxicity screening study using graphite (CASRN 7782-42-5).
Expandable graphite commercial formulations are prepared with chemical washes. There are variable
hazards from the specific wash chemicals used and, as a result the hazards may change by manufacturer.
A High hazard concern for reproductive toxicity is estimated for formulations containing chromic acid
(CASRN 7738-94-5).
                  Reproduction/Developmental
                  Toxicity Screen
                  Combined Repeated Dose
                  with Reproduction/
                  Developmental Toxicity
                  Screen
In a combined repeated dose toxicity
study with reproduction/developmental
toxicity screening, male and female
Wistar rats (10/sex/group) were fed
expanded graphite powder in the diet at
concentrations of 0, 91, 261, 813 mg/kg-
day (for males), 0, 120, 343, 1,067 mg/kg-
day (for females in premating period), 0,
106, 309, 930 mg/kg-day (for females
during gestation) and 0, 111, 370, 1,159
mg/kg-day (for females during lactation).
Mating was insufficient in all treatment
groups and control; it was reported that
the reason for insufficient mating was
unclear. No adverse effects on precoital
time or fertility, number of implantation
sites or number of live born pups. No
effect on litter size, pup survival, or pup
body weight. Sporadically observed
clinical findings in pups and controls
(reduced size of testes and epidydimides)
were not considered to be related to the
test substance.
                                                                  No data located.
ECHA, 2013b
Data are for Expanded graphite
powder (CASRN 7782-42-5). Study
was conducted in accordance with
OECD Guideline 422 and GLP.
                                                                     7-211

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JUNE 2014 DRAFT REPORT
Expandable graphite CASRN 12777-87-6
PROPERTY/ENDPOINT


Reproduction and Fertility
Effects
Other
Developmental Effects

Reproduction/
Developmental Toxicity
Screen
DATA
NOAEL (parental, reproductive and
developmental): 12,000 mg/kg diet (target
high limit, corresponding to 813 mg/kg-
day for males and 1,067, 930 and 1,159
mg/kg-day for females during premating,
gestation and lactation, respectively);
highest doses tested
LOAEL: Not established


REFERENCE
^^
^^^

DATA QUALITY

No data located.
No data located.
LOW: No experimental data were located for expandable graphite. There were no adverse developmental
effects in rats at doses up to 1,159 mg/kg-day in an oral combined repeated dose
reproduction/developmental toxicity screening study using graphite (CASRN 7782-42-5). Sporadically
observed clinical findings in pups and controls (reduced size of testes and epidydimides) were not
considered to be related to the test substance.
\

No data located.
         7-212

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JUNE 2014 DRAFT REPORT
Expandable graphite CASRN 12777-87-6
PROPERTY/ENDPOINT
































Combined Repeated Dose
with Reproduction/
Developmental Toxicity
Screen



























Prenatal Development
DATA
In a combined repeated dose toxicity
study with reproduction/developmental
toxicity screening, male and female
Wistar rats (10/sex/group) were fed
expanded graphite powder in the diet at
concentrations of 0, 91, 261, 813 mg/kg-
day (for males), 0, 120, 343, 1,067 mg/kg-
t/day (for females in premating period), 0,
106, 309, 930 mg/kg-day (for females
during gestation) and 0, 111, 370, 1,159
mg/kg-day (for females during lactation).
Mating was insufficient in all treatment
groups and control; it was reported that
the reason for insufficient mating was
unclear. No adverse effects on precoital
time or fertility, number of implantation
sites or number of live born pups. No
effect on litter size, pup survival, or pup
body weight. Sporadically observed
clinical findings in pups and controls
(reduced size of testes and epidydimides)
were not considered to be related to the
test substance.
NOAEL (parental, reproductive and
developmental): 12,000 mg/kg-day diet
(target high limit, corresponding to 813
mg/kg-day for males and 1,067, 930 and
1,159 mg/kg-day for females during
premating, gestation and lactation,
respectively); highest doses tested
LOAEL: Not established

REFERENCE
ECHA, 2013b




^^



^^*






















DATA QUALITY
Data are for Expanded graphite
powder (CASRN 7782-42-5). Study
was conducted in accordance with
OECD Guideline 422 and GLP.



























No data located.
         7-213

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JUNE 2014 DRAFT REPORT
Expandable graphite CASRN 12777-87-6
PROPERTY/ENDPOINT





Postnatal Development
Prenatal and Postnatal
Development
Developmental Neurotoxicity
Other
Neurotoxicity

























Neurotoxicity Screening
Battery (Adult)



















Other
DATA





REFERENCE





DATA QUALITY
No data located.
No data located.

No data located.
No data located.
LOW: No experimental data were located for expandable graphite. There were no adverse neurological
effects in rats at doses up to 1159 mg/kg-day in a combined repeated dose reproduction/developmental
toxicity screening study using graphite (CASRN 7782-42-5). Functional Observational Battery tests were
normal.
In a combined repeated dose toxicity
study with reproduction/developmental
toxicity screening, male and female
Wistar rats (10/sex/group) were fed
expanded graphite powder in the diet at
concentrations of 0, 91, 261, 813 mg/kg-
day (for males), 0, 120, 343, 1067 mg/kg-
day (for females in premating period), 0,
106, 309, 930 mg/kg-day (for females
during gestation) and 0, 1 1 1, 370, 1 159
mg/kg-day (for females during lactation).
No effects on locomotor activity or any of
the investigated endpoints of the
Functional Observational Battery.
NOAEL: 12,000 mg/kg-day diet (target
high limit, corresponding to 813 mg/kg-
day for males and 1067, 930 and 1 159
mg/kg-day for females during premating,
gestation and lactation, respectively);
highest doses tested
LOAEL: Not established

ECHA, 2013b





















Data are for Expanded graphite
powder (CASRN 7782-42-5). Study
was conducted in accordance with
OECD Guideline 422 and GLP.

















No data located.
         7-214

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                                                       JUNE 2014 DRAFT REPORT
                                                   Expandable graphite CASRN 12777-87-6
          PROPERTY/ENDPOINT
               DATA
REFERENCE
DATA QUALITY
Repeated Dose Effects
MODERATE: No experimental data were located for expandable graphite. There were no adverse effects
in rats at doses up to 1159 mg/kg-day in an oral combined repeated dose reproduction/developmental
toxicity screening study using graphite (CASRN 7782-42-5). Repeated inhalation of graphite fumes or dust
over a prolonged period of time may increase the risk of developing lung diseases. Prolonged and repeated
overexposure to graphite dust can lead to pneumoconiosis and may increase the risks of developing
respiratory cancer. It should be noted that the potential for fibrotic disease is a result of exposure to
quartz as an impurity, and not to pure graphite.
Expandable graphite commercial formulations are prepared with chemical washes. There are variable
hazards from the specific wash chemicals used and, as a result the hazards may change by manufacturer.
A High hazard concern for repeated dose toxicity is estimated for formulations containing chromic acid
(CASRN 7738-94-5).
                                                                  7-215

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                                               JUNE 2014 DRAFT REPORT
                                          Expandable graphite CASRN 12777-87-6
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   In a combined repeated dose toxicity
                                   study with reproduction/developmental
                                   toxicity screening, male and female
                                   Wistar rats (10/sex/group) were fed
                                   expanded graphite powder in the diet at
                                   concentrations of 0, 91, 261, 813 mg/kg
                                   body weight/day (for males), 0, 120, 343,
                                   1,067 mg/kg-day (for females in
                                   premating period), 0, 106, 309, 930
                                   mg/kg-day (for females during gestation)
                                   and 0, 111, 370, 1,159 mg/kg-day (for~
                                   females during lactation).
                                   No adverse effects on body weight gain or
                                   food consumption; no effect on
                                   hematology or clinical chemistry NOAEL
                                   (parental, reproductive and
                                   developmental): 12,000 mg/kg-day diet
                                   (target high limit, corresponding to 813
                                   mg/kg-day for males and 1067, 930 and
                                   1,159 mg/kg-day for females during
                                   premating, gestation and lactation,
                                   respectively); highest doses tested
                                   LOAEL: Not established
                      ECHA, 2013b
                      Data are for Expanded graphite
                      powder (CASRN 7782-42-5). Study
                      was conducted in accordance with
                      OECD Guideline 422 and GLP.
                                   Male Wistar rats were exposed via
                                   inhalation (head/nose) to target
                                   concentrations of 0.5, 2.5, or 10 mg/m3
                                   graphene or graphite nanoplatelets 6
                                   hours/day for 5 days. No adverse clinical
                                   signs or alterations in body weight.
                                   Increases in lavage markers indicative for
                                   inflammatory processes following
                                   exposure to 10 mg/m
                                   graphene. The calculated volumetric load
                      Ma-Hock etal., 2013
                      Study details reported in a primary
                      source; study conducted in
                      accordance with OECD Guideline
                      412 and GLP
                                                           7-216

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                                                         JUNE 2014 DRAFT REPORT
                                                     Expandable graphite CASRN 12777-87-6
           PROPERTY/ENDPOINT
               DATA
        REFERENCE
       DATA QUALITY
                                              did not correlate to toxicity, nor did the
                                              particle surface burden of the lung. No
                                              adverse effects following exposure to
                                              graphite nanoplatelets.
                                              Repeated inhalation of fumes or dust over
                                              a prolonged period of time increases the
                                              risk of developing lung diseases.
                                              Prolonged and repeated overexposure to
                                              dust can lead to pneumoconiosis.
                                              Repeated exposure to high concentrations
                                              of dust may adversely affect the lungs and
                                              increase the risks of developing
                                              respiratory cancer.
                                     REACH, 2006; GrafTech, 2013
                             Limited details in a secondary
                             source. The potential for fibrotic
                             disease is a result of exposure to
                             quartz as an impurity, not graphite.
                                              There are over 600 cases of graphite
                                              pneumoconiosis reported in literature; 14
                                              cases had relatively complete
                                              documentation as to details about dust
                                              exposure and only 1 completely
                                              documented case suggests that nearly pure
                                              graphite may cause pneumoconiosis.
                                     HSDB, 2009b
                             Data are for Graphite (CASRN
                             7782-42-5). Study details reported
                             in a secondary source
Skin Sensitization
LOW: No experimental data for expandable graphite were located. Graphite (CASRN 7782-42-5) was not
a dermal sensitizer in mice.
Expandable graphite commercial formulations are prepared with chemical washes. There are variable
hazards from the specific wash chemicals used and, as a result the hazards may change by manufacturer.
A High hazard concern for skin sensitization is estimated for formulations containing chromic acid
(CASRN 7738-94-5).
                  Skin Sensitization
Not a skin sensitizer in mice.
Test item: 0.5%, 1%, 2.5%, 5% and 10%
graphite in acetone:olive oil (5:1). 10%
graphite was the maximum achievable
dose.
ECHA, 2013a
Data are for Expanded graphite
powder (CASRN 7782-42-5). Study
was conducted in accordance with
OECD Guideline 429 and GLP.
                                                                     7-217

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JUNE 2014 DRAFT REPORT
Expandable graphite CASRN 12777-87-6
PROPERTY/ENDPOINT
Respiratory Sensitization
[Respiratory Sensitization
Eye Irritation

Eye Irritation
Dermal Irritation

Dermal Irritation
DATA
REFERENCE
DATA QUALITY
No data were located; however, expandable graphite commercial formulations are prepared with chemical
washes. There are variable hazards from the specific wash chemicals used and, as a result the hazards may
change by manufacturer. A High hazard concern for respiratory Sensitization is estimated for
formulations containing chromic acid (CASRN 7738-94-5).


No data located.
MODERATE: Expandable graphite produced slight irritation to rabbits, which was fully reversible within
6-10 days. Expandable graphite dust may cause irritation.
Expandable graphite commercial formulations are prepared with chemical washes. There are variable
hazards from the specific wash chemicals used and, as a result the hazards may change by manufacturer.
A High hazard concern for eye irritation is estimated for formulations containing one confidential wash
and also for washes containing chromic acid (CASRN 7738-94-5).
Dust may irritate the eyes
Test substance was instilled into one eye
for 24 hours. Slight irritation to rabbits
which was fully reversible within 6-10
days. Conjunctival discharge, redness and
chemosis, but no corrosive ocular effects.
REACH, 2006; GrafTech, 2013
ECHA, 2013b
Limited details in a secondary
source
Data are for Expandable Natural
Graphite. Study was conducted
according to OECD Guideline 405
and GLP.
MODERATE: Expandable graphite was not a primary skin irritant in rats; however graphite dust may
irritate the skin causing eczema-like skin disorders. Prolonged contact with graphite may cause redness,
irritation and dry skin.
Expandable graphite commercial formulations are prepared with chemical washes. There are variable
hazards from the specific wash chemicals used and, as a result the hazards may change by manufacturer.
A High hazard concern for dermal irritation is estimated for formulations containing one confidential
wash and also for washes containing chromic acid (CASRN 7738-94-5).
Dust may irritate skin. May cause
eczema-like skin disorders (dermatitis).
Prolonged skin contact may cause
redness, irritation and dry skin.
Test substance was applied to
approximately 10% of total body surface
of rats and was covered for 24 hours. Not
REACH, 2006; GrafTech, 2013
ECHA, 201 3b
Limited details in a secondary
source.
Data are for Expandable Natural
Graphite. Study was conducted
according to OECD Guideline 402
         7-218

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JUNE 2014 DRAFT REPORT
Expandable graphite CASRN 12777-87-6
PROPERTY/ENDPOINT


Endocrine Activity

Immunotoxicity

Immune System Effects
DATA
a primary skin irritant in rats
REFERENCE

DATA QUALITY
and GLP.
No data were located


No data located.
No experimental data were located for expandable graphite. Rats gavaged with graphite powder (CASRN
7782-42-5) suspended in physiological saline had a dose-dependent increase in LDH, B-glucuronidase and
total protein and Polymorphonuclear levels were 12.2% and 27.3% for the low and high dose, respectively.
The inflammatory response was dose-related, with slight recovery after 14 days.
Female Wistar rats (5/group) gavaged
with 0.5 and 3 mg graphite suspended in
0.3 mL physiological saline. No
mortalities or systemic effects. Dose-
dependent increase in LDH, B-
glucuronidase and total protein.
Polymorphonuclear levels were 12.2%
and 27.3% on day 3 at the low- and high
dose, respectively. Slight inflammatory
effect at the low dose and moderate effect
at the high dose. Slight recovery after 14
days; however, polymorphonuclear levels
remained statistically increased.
ECHA, 2013a
J r
Data are for Expanded graphite
powder (CASRN 7782-42-5).
ECOTOXICITY
ECOSAR Class
Acute Aquatic Toxicity
Fish LC50

LOW: Based on experimental LD/LC50 values > 100 mg/L in fish daphnia and algae. It should be noted
that expandable graphite may contain soluble surface acidity or alkalinity, which may be hazardous to
aquatic organisms.
Freshwater fish (Oncorhynchus mykiss)
96-hour LC50> 100 mg/L
Static conditions; 100 mg/L test item
(nominal concentration)
(Experimental)
Expandable graphite may contain soluble
surface acidity or alkalinity, which is
ECHA, 201 3b
MSDS, 2012
Data are for Expandable Natural
Graphite (sulfuric acid, compound
with graphite), Purity > 93 %. Study
was conducted in accordance with
OECD Guideline 203 and GLP
Limited details in an MSDS. Data
for Expandable flake graphite, 85-
         7-219

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JUNE 2014 DRAFT REPORT
Expandable graphite CASRN 12777-87-6
PROPERTY/ENDPOINT

Daphnid LC50
Green Algae EC50
Chronic Aquatic Toxicity
Fish ChV
Daphnid ChV
Green Algae ChV
DATA
expected to be hazardous to aquatic
organisms.
(Experimental)
Daphnia magna 48-hour EC50 > 100 mg/L
Static conditions; 100 mg/L (nominal
concentration)
(Experimental)
Green algae (Pseudokirchneriella
subcapitata ) 72-hour EC50 > 100 mg/L
Static conditions; 100 mg/L (nominal
concentration)
(Estimated by Analogy)
Expandable graphite may contain soluble
surface acidity or alkalinity, which is
expected to be hazardous to aquatic
organisms.
(Experimental)
REFERENCE

ECHA, 2013b
^^
ECHA, 201 3b
MSDS, 2012
DATA QUALITY
98% carbon (CASRN 12777-87-6),
manufactured by Ashbury Carbons.
Data are for Expandable Natural
Graphite (sulfuric acid, compound
with graphite), Purity > 93 %. Study
was conducted in accordance with
OECD Guideline 202 and GLP
Data are for Expanded Graphite
Powder. Study was conducted
according to OECD Guideline 20 1
and GLP.
Limited details in an MSDS. Data
for Expandable flake graphite, 85-
98% carbon (CASRN 12777-87-6),
manufactured by Ashbury Carbons.
MODERATE: No data were located. Based on lack of data for this endpoint, chronic aquatic toxicity
cannot be ruled out. It should be noted that expandable graphite may contain soluble surface acidity or
alkalinity, which may be hazardous to aquatic organisms. This compound is not amenable to available
estimation methods.






No data located.
No data located.
No data located.
         7-220

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JUNE 2014 DRAFT REPORT
Expandable graphite CASRN 12777-87-6
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
ENVIRONMENTAL FATE
Transport

Henry's Law Constant (atm-
m3/mole)
Sediment/Soil
Adsorption/Desorption - Koc
Level III Fugacity Model
Persistence
Water
Soil
Air
Aerobic Biodegradation
Volatilization Half-life for
Model River ^^^^
Volatilization Half-life for
Model Lake
Aerobic Biodegradation
Anaerobic Biodegradation
Soil Biodegradation with
Product Identification ^J
Sediment/Water
Biodegradation
Atmospheric Half-life
The transport evaluation is based on available analog data for graphite (CASRN 7782-42-5) and
professional judgment. The negligible water solubility, and negligible vapor pressure of the naturally
occurring, major component of this material would suggest that it will be relatively immobile in the
environment.
<10"8 (Estimated)
>3 0,000 (Estimated)

Professional judgment
^^ 7
Professional judgment; EPA,
2005
Professional judgment
Cutoff value for nonvolatile
compounds based on professional
judgment. No data located; this
chemical is outside the estimation
domain of EPI.
Cutoff value fornonmobile
compounds.
No data located; this chemical is
outside the estimation domain of
EPI.
HIGH: Expandable graphite is estimated to display high persistence in the environment. The major
component of this chemical, graphite, is a naturally occurring material and is nonreactive under typical
environmental conditions.







Not applicable (Estimated)







Professional judgment
No data located.
No data located.
No data located.
No data located.
No data located.
No data located.
No data located.
No data located. Substance contains
naturally occurring material that is
         7-221

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JUNE 2014 DRAFT REPORT
Expandable graphite CASRN 12777-87-6
PROPERTY/ENDPOINT

Reactivity

Photolysis
Hydrolysis
Environmental Half-life
Bioaccumulation

Fish BCF
Other BCF
BAF
Metabolism in Fish
DATA

Not a significant fate process. (Estimated)
Not a significant fate process. (Estimated)

REFERENCE

Professional judgment; Mill,
2000
^K 7
Professional judgment

DATA QUALITY
not amenable to atmospheric
degradation processes. The
negligible vapor pressure of the
major component of this material
suggests that partitioning to air is
unlikely.
No data located. The substance does
not contain functional groups that
would be expected to absorb light at
environmentally significant
wavelengths.
No data located; hydrolysis is not
anticipated to be an environmental
removal process due to the lack of
functional groups that hydrolyze
under environmental conditions.
Not all input parameters for this
model were available to run the
estimation software (EPI).
LOW: This chemical is not expected to be bioaccumulative based on its negligible water solubility, large
MW, large cross sectional diameter and professional judgment.
<100 (Estimated)
^

<100 (Estimated)

Professional judgment

Professional judgment

This chemical has negligible water
solubility. This chemical is a large
solid which is unlikely to pass
through biological membranes.
No data located.
No data located; this chemical is
outside the estimation domain of
EPI.
No data located.
         7-222

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                                                    JUNE 2014 DRAFT REPORT
                                                Expandable graphite CASRN 12777-87-6
          PROPERTY/ENDPOINT
              DATA
REFERENCE
DATA QUALITY
                                      ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring
Graphite (CASRN 7782-42-5) is found as a naturally occurring material and is mined in open-pit and
underground mines (HSDB, 2009b).
Ecological Biomonitoring
No data located.
Human Biomonitoring
No data located.
                                                               7-223

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                                                 JUNE 2014 DRAFT REPORT


AvTech Industries (2013) MSDS (Material Safety Data Sheet) FR Eco-Additive 20TM.

CCRIS (2013) Graphite Chemical Carcinogenesis Research Information System.

ECHA (2013a) Graphite. Registered substances. European Chemicals Agency. http://apps.echa.europa.eu/registered/data/dossiers/DISS-9e9d7fl6-
96ef-5932-e044-00144f67d031/AGGR-bbd4665b-6e31-46e4-8a3c-Ocl308670910  DISS-9e9d7fl6-96ef-5932-e044-00144f67d031.html#AGGR-
bbd4665b-6e31-46e4-8a3c-0cl308670910.

ECHA (2013b) Sulphuric acid, compound with graphite. Registered substances. European Chemicals Agency.
http://apps.echa.europa.eu/registered/data/dossiers/DISS-9e9fal9d-efcf-29ab-e044-00144f67d031/DISS-9e9fal9d-efcf-29ab-e044-
00144f67d031  DISS-9e9fal9d-efcf-29ab-e044-00144f67d031.html.

EPA (1999) Determining the adequacy of existing data. Washington, DC:  U.S. Environmental Protection Agency.
http: //www .epa. gov/hpv/pubs/general/datadeqfn .pdf.

EPA (2005) Pollution prevention (P2) framework. Washington, DC: U.S. Environmental Protection Agency, Office of Pollution Prevention and
Toxics, http://www.epa.gov/opptintr/newchems/pubs/sustainable/p2frame-june05a2.pdf.

EPA (2012) TSCA New Chemicals Program (NCP) chemical categories, http://www.epa.gov/oppt/newchems/pubs/npcchemicalcategories.pdf.

ESIS (2012) European chemical Substances Information System. European Commission, http://esis.jrc.ec.europa.eu/.

GrafTech (2013) Material Safety Data Sheet GRAFGUARD.

HSDB (2009a) Carbon. Hazardous Substances Data Bank. National Library of Medicine. http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen7HSDB.

HSDB (2009b) Graphite. Hazardous Substances Data Bank. National Library of Medicine. http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen7HSDB.

IPCS (2013) Graphite (Natural).

Jager H, Frohs W, Banek M, et al. (2010) Carbon 4. Industrial carbons. Ullmann's encyclopedia of industrial chemistry.
http://onlinelibrary.wilev.com/doi/10.1002/14356007.n05 n03/full#n05 n03-sec 1-0012.

MSDS (2012) Expandable flake graphite. Material Safety Data Sheet.
                                                             7-224

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                                                 JUNE 2014 DRAFT REPORT


Ma-Hock L, Strauss V, Treumann S, et al. (2013) Comparative inhalation toxicity of multi-wall carbon nanotubes, graphene, graphite
nonoplatelets and low surface carbon black. Part and Fibre Toxicol 52(1):23-41.

Mill T (2000) Photoreactions in surface waters. In: Boethling R, Mackay D, eds. Handbook of Property Estimation Methods for Chemicals,
Environmental Health Sciences. Boca Raton: Lewis Publishers, 355-381.

REACH (2006) Review of Annex IV of the regulation no. 1907/2006 (REACH) evaluation of existing entries Appendix 2.
                                                             7-225

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                                                              JUNE 2014 DRAFT REPORT
               Fyrol™ HF-5
                                                     Screening Level Toxicology Hazard Summary

This table only contains information regarding the inherent hazards of flame retardant chemicals. Evaluation of risk considers both the hazard and exposure associated with the
substance including combustion and degradation by-products. The caveats listed in the legend and footnote sections must be taken into account when interpreting the hazard
information in the table.
VL = Very Low hazard L = Low hazard   = Moderate hazard H = High hazard VH = Very High hazard - Endpoints in colored text (VL, L,   , H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].

* Unlike for Firemaster 550, data are not available for this mixture, only for the individual components. For this mixture, hazard designations are listed in bold and color when there
are measured data for all the components; the designation for the mixture is based on the component with the highest hazard. When measured data are not available for all
components, the designation for the mixture is based on the component with the highest hazard and is an estimation (italics).
d This hazard designation would be assigned MODERATE for a potential for lung overloading if >5% of the particles are in the respirable range as a result of dust forming
operations.
§ Based on analogy to experimental data for a structurally similar compound.
* The highest hazard designation of any of the oligomers withMW <1,000.	^^r	








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Fyrol™ HF-5*
Confidential A
Confidential B
Confidential
Confidential
Confidential
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                                                                           7-226

-------
                                                         JUNE 2014 DRAFT REPORT
                                                                                                             CASRN: Confidential
                                                                                                             MW: Confidential
                                                                                                             MF: Confidential
                                                                                                             Physical Forms: Liquid
                                                                                                             Neat:
                                                                                                             Use: Flame retardant
SMILES: Confidential
Synonyms: Confidential
Chemical Considerations: This alternative is a mixture that contains polymeric components. Residual monomers, unreacted starting material and low MW oligomers
are expected to be present at a level requiring their assessment. The oligomers that have a MW > 1,000 are assessed using the available polymer assessment literature.
The lower MW components and oligomers with a MW <1,000 are assessed with EPI v4.11 and ECOSAR vl. 11 estimates due to an absence of publically available
experimental data (Boethling and Nabholz, 1997).
Polymeric: Yes
Oligomeric: Confidential oligomers
Metabolites, Degradates and Transformation Products: None identified; although biodegradation or hydrolysis pathways may yield confidential substances
(Professional judgment)
Analog: Aryl phosphates and other confidential analogs
Endpoint(s) using analog values: Carcinogenicity and
Neurotoxicity
Analog Structure: Not applicable
Structural Alerts: Organophosphates, neurotoxicity (EPA, 2012).
Risk Phrases: Not classified by Annex VI Regulation (EC) No 1272/2008 (ESIS, 2012).
Hazard and Risk Assessments: None identified.
                                                                     7-227

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JUNE 2014 DRAFT REPORT
Fyrol™ HF-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
PHYSICAL/CHEMICAL PROPERTIES
Melting Point (°C)
Boiling Point (°C)
Vapor Pressure (mm Hg)
Confidential B: -12
(Measured)
Confidential B: -13
(Measured)
Confidential B: -16.7
(Measured)
Confidential A: >300
(Estimated)
Confidential B: 300
(Measured)
Confidential B: >300
(Measured)
Confidential B: 370 Decomposes
(Measured)
Confidential B: > 400 Decomposes
(Measured)
Confidential B: 38
at 138 Pa (Measured)
Confidential A: 3.6x10 6 for n=l
2.1xlO-8forn=2-5
(Estimated)
Confidential A: <108
(Estimated)
Confidential study
Confidential study
Confidential study
^^^N. r
EPI v4. 11; Professional
judgment; EPA, 1999
Confidential study
Confidential study
Confidential study
Confidential study
Confidential study
EPIv4.11
Professional judgment;
Boethling and Nabholz, 1997
The reported values are for the pour point
of the commercial polymeric mixture,
which is a liquid at room temperatures.
The reported values are for the pour point
of the commercial polymeric mixture,
which is a liquid at room temperatures.
The reported values are for the pour point
of the commercial polymeric mixture,
which is a liquid at room temperatures.
Estimate based on representative oligomers
where with MW < 1,000. Also estimated
for oligomers with MWs >1,000. Cutoff
value according to HPV assessment
guidance and cutoff value used for large,
high MW solids.
Decomposition may occur before the
boiling point is reached.
Decomposition may occur before the
boiling point is reached.
Decomposition may occur before the
boiling point is reached.
Decomposition may occur before the
boiling point is reached.
Decomposition may occur before the
boiling point is reached.
Estimates based on representative
oligomers.
Cutoff value for large, high MW polymers.
         7-228

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JUNE 2014 DRAFT REPORT
Fyrol™ HF-5
PROPERTY/ENDPOINT

Water Solubility (mg/L)
Log Kow
DATA
Confidential B: 1.9x10 5 at 20°C
(Measured)
Confidential B: 0.007 at 38°C
(Measured)
Confidential B: 0.28
(Measured)
Confidential B: <0.075 at 38°C
(Measured) ^^^
Confidential A:
3,375 mg/L for n=l
933 mg/L for n=2
233 mg/L for n=3
1 mg/L for n=6 (Estimated) ^^
Confidential A: Soluble (Measured)
Confidential A: Miscible
(Measured)
Confidential B: 1.05 (Measured)
at 20°C
Confidential A: -0.58
(Measured)
Confidential A: 0.42 for n=l
-0.03 for n=2
-0.48 for n=3
-1.33 for n=6
(Estimated)
Confidential A: <-l
(Measured)
REFERENCE
EPA, 2010
Confidential study
Confidential study
IUCLID, 2001
EPIv4.11
^^
Confidential study
Submitted confidential study
EPA, 2010
Submitted confidential study
EPIv4.11
Confidential study
DATA QUALITY
The reported experimental data is for the
commercial polymeric mixture.
The reported experimental data is for the
commercial polymeric mixture.
The reported experimental data is for the
commercial polymeric mixture.
The reported experimental data is for the
commercial polymeric mixture.
Estimates based on representative
oligomers.
Non-quantitative value from a MSDS for a
confidential commercial product
containing 95-100% pure material.
Non-quantitative value with limited details
reported.
The reported experimental data is for the
commercial polymeric mixture.
Limited study details provided in a
confidential source.
Estimates based on representative
oligomers
From a MSDS for a confidential
commercial product containing 95-100%
pure material.
         7-229

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JUNE 2014 DRAFT REPORT
Fyrol™ HF-5
PROPERTY/ENDPOINT

Flammability (Flash Point)
Explosivity
Pyrolysis
pH
pKa
DATA
Confidential B: 4.93
(Measured)
Confidential B: 4.9
(Measured)
Confidential A: Not flammable
(Measured)
Confidential B: 302°C (Measured)
Confidential B: >240°C (Measured)
Confidential B: >230°C (Measured)
Confidential A: Not explosive
(Measured)
Confidential B: Not explosive
(Measured)

Confidential A & B: Not applicable
(Estimated)
Confidential A & B: Not applicable
(Estimated) ^^^JB^^
REFERENCE
EPA, 2010; Confidential study
Confidential study
Confidential study
Confidential study
Confidential study
Confidential study
Confidential study
IUCLID, 2001; Confidential
study

Professional judgment
Professional judgment
DATA QUALITY
The reported experimental data is for the
commercial polymeric mixture.
The reported experimental data is for the
commercial polymeric mixture
From a MSDS for a confidential
commercial product containing 95-100%
pure material.
Adequate.
Adequate.
Adequate.
From a MSDS for a confidential
commercial product containing 95-100%
pure material.
Insufficient study details to assess the
quality of this value.
Mo data located.
Does not contain functional groups that are
expected to ionize.
Does not contain functional groups that are
expected to ionize.
         7-230

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                                                         JUNE 2014 DRAFT REPORT
                                                                  Fyrol™ HF-5
          PROPERTY/ENDPOINT
                                             DATA
                                        REFERENCE
                                       DATA QUALITY
                                                          HUMAN HEALTH EFFECTS
Toxicokinetics
                                Confidential B is readily absorbed via the oral route and was absorbed to a lesser extent following dermal
                                xposure. Metabolism was extensive with metabolites excreted in feces, urine, and in expired air as CO2.
                                Absorption is expected to be low for all routes for Confidential A.
Dermal Absorption in vitro
                                                                                            No data located.
Absorption,
Distribution,
Metabolism
& Excretion
Oral, Dermal or Inhaled
  onfidential B: Studies were
conducted on rats, mice and monkeys
bllowing exposure to Confidential B
purity: 99%) via intravenous
njection, oral, inhalation, and dermal
•outes of exposure.

Blood, urine and feces were collected
br approximately 7 days and
metabolites were isolated and
characterized; the brain, mesenteric
at, kidneys, liver, lungs, tests/ovaries
and spleen were collected from rats at
ime of necropsy

Confidential B was absorbed and was
xtensively metabolized; Metabolism
vas consistent between species,
sexes, and individual animals;
ixcretion occurred primarily in the
feces and then urine
Confidential study
Non-guideline study.
                                                                     7-231

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                                               JUNE 2014 DRAFT REPORT
                                                       Fyrol™ HF-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  Confidential B: Rats were exposed
                                  to radiolabeled Confidential B
                                  (purity: 99%) via a single oral gavage
                                  dose of 100 mg/kg

                                  83% of the administered dose of
                                  Confidential B was absorbed; 80% of
                                  the absorbed radiolabelled dose was
                                  excreted in the feces as metabolites,
                                  7% was excreted in the urine and 5%
                                  was excreted as CO2 in expired air.

                                  Un-metabolized Confidential B was
                                  found in the feces following oral
                                  exposure, indicating that some of the
                                  administered oral dose was not
                                  absorbed through the gastrointestinal
                                  route.
                    Confidential study
                    Non-guideline study.
                                                          7-232

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                                                JUNE 2014 DRAFT REPORT
                                                        Fyrol™ HF-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                    onfidential B: Rats and monkeys
                                   were administered a dermal dose of
                                   100 mg/kg radiolabelled 14C-
                                    bnfidential B (purity: 99%) for 6
                                   tiours

                                   20% of Confidential B was absorbed
                                   n the systemic circulation in rats
                                   bllowing the six-hour exposure and <
                                   10% was absorbed in monkeys. 7
                                   lays post-exposure, rats eliminated 7,
                                   32, and 1% of administered dose in
                                   he urine, feces, and expired air,
                                   •espectively.

                                   1% of the administered dose was
                                   sliminated in expired air in monkeys
                                   after 7 days; the remaining absorbed
                                   lose was excreted by day 28.
                    Confidential study
                     Non-guideline study.
                                   Confidential B: Rats were exposed
                                   ;o Confidential B via nose-only
                                   nhalation for 6 hours at a target
                                   delivered dose of 100 mg/kg 60% of
                                   Confidential B was excreted in the
                                   feces in males and  52% in females
                                   bllowing exposure.

                                   [0% in males and 7% in females was
                                   sxcreted in the urine.
                    Confidential study
                     Non-guideline study; doses are not reported
                     in standard mg/L units; the authors state
                     that actual retained dose in the lung cannot
                     3e measured accurately for the inhalation
                     study.
                                                            7-233

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                                                JUNE 2014 DRAFT REPORT
                                                        Fyrol™ HF-5
PROPERTY/ENDPOINT
             DATA
       REFERENCE
           DATA QUALITY
   Other
Confidential A: For low MW
components (n < 6), absorption is
expected to be low for all routes
based on confidential analogs. For
high MW components, no absorption
is expected through the skin and
gastrointestinal tract. Poor absorption
is expected in the lungs because the
polymer is dispersible due to its
physical chemical properties.
(Estimated)
Professional judgment
Estimated based on analogy to a
confidential analog, physical chemical
properties, and professional judgment.
                                   Confidential B: Rats and mice were
                                   administered a single intravenous
                                   dose of 100 mg/kg Confidential B
                                   (purity: 99%)

                                   In rats, 13%, 45 %, and 7% of the
                                   administered intravenous dose was
                                   excreted in urine, feces, and expired
                                   air (as CO2), respectively, 7 days
                                   after exposure

                                   In monkeys, 24% and 26% was
                                   excreted in urine and feces,
                                   respectively; expired air was not
                                   measured
                                                   *

                                   There were no data reported for mice
                                   following intravenous exposure.
                                  Confidential study
                            Non-guideline study.
                                                            7-234

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JUNE 2014 DRAFT REPORT
Fyrol™ HF-5
PROPERTY/ENDPOINT
Acute Mammalian Toxicity
Acute
Lethality
Oral
Dermal
Inhalation
Carcinogenicity
DATA
REFERENCE
DATA QUALITY
LOW: Based on oral and dermal LD50 values >2,000 mg/kg.
Confidential A: Rat oral LD50 =
5,000 mg/kg
Confidential B: Rat Oral LD50
>5,000 mg/kg-bw
Confidential A: Rabbit dermal LD50
>2,000 mg/kg
Confidential B: Rat Dermal LD50
>2,000 mg/kg-bw
Confidential B: Rat Inhalation
(aerosol, nose-only) LC50 >4.14 mg/L
'^^ X
^^ WT
Submitted confidential study
EPA, 2010
Submitted confidential study
^^^\ r
EPA, 2010
EPA, 2010
7
Data reported in a confidential study
submitted to EPA for the polymeric
mixture that included LMW components.
Guideline study reported in a secondary
source. Data are for the commercial
polymeric mixture.
Data reported in a confidential study
submitted to EPA for the polymeric
mixture that included LMW components.
Guideline study reported in a secondary
source. Data are for the commercial
polymeric mixture.
The study is a quality guideline study
reported in a secondary source; It cannot be
used to determine a hazard designation
jecause there were no effects at the highest
concentrations tested (4.14 mg/L); From
this data, it cannot be determined if effects
happened at 4. 15 mg/L (MODERATE) or
at a concentration that can be considered
^OW; therefore, this study cannot be used
to determine a hazard designation.
MODERATE: Confidential B is estimated to have uncertain potential for carcinogenicity based on analogy
to related chemicals and professional judgment. Confidential A is estimated to have low potential for
carcinogenicity.
         7-235

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JUNE 2014 DRAFT REPORT
Fyrol™ HF-5
PROPERTY/ENDPOINT

OncoLogic Results
Carcinogenicity (Rat and Mouse)
Combined Chronic
Toxicity/Carcinogenicity
Other
Genotoxicity

Gene Mutation in vitro
DATA
Confidential A: Based on estimates
considering that the residual
monomers do not contain substituted
terminal double bonds; the low MW
species do not contain reactive-
functional-group-bearing side chains;
the polymer is cross-linked, is not *
linear, and has a MW of less than
100,000 ^^
Confidential B:
Confidential B: Uncertain potential
for oncogenicity (Estimated by
analogy)


REFERENCE
OncoLogic, 2008
OncoLogic, 2008
Professional judgment


DATA QUALITY
Estimated for the polymer containing lower
MW components.
Structure could not be evaluated by
OncoLogic.
Estimated by analogy.
No data located.
Mo data located.
MODERATE: There is uncertain concern for mutagenicity of Confidential A. This substance did not cause
gene mutations in bacteria; however, there is uncertainty due to the lack of experimental data for this
endpoint. Complete data requirements for this endpoint are both gene mutation and chromosomal
aberration assays. For instances of incomplete or inadequate mutagenicity/genotoxicity data, a Low hazard
designation cannot be given. The genotoxicity hazard of Confidential B is LOW based on negative results in
in vitro and in vivo studies.
Confidential A: Uncertain concern
for mutagenicity
(Estimated)
Confidential A: Negative for gene
mutation in an Ames test in S.
typhimurium andE. coli.
Professional judgment
Submitted confidential study
Estimated for the low MW component due
to ethyl substituted phosphate.
Data reported in a submitted confidential
study.
         7-236

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JUNE 2014 DRAFT REPORT
Fyrol™ HF-5
PROPERTY/ENDPOINT


Gene Mutation in vivo
Chromosomal Aberrations in
vitro
Chromosomal Aberrations in
vivo
DNA Damage and Repair
Other
DATA
Confidential B: Negative in
Salmonella typhimurium (strains not
indicated) with and without
metabolic activation at
concentrations up to 5,000 (jg/plate.
Mo cytotoxicity was evident.
Confidential B: Negative in
Escherichia coll (strains not
indicated) with and without
metabolic activation at
concentrations up to 5,000 (jg/plate.
Mo cytotoxicity was evident.

Confidential B: Negative in
chromosomal aberration test (cultured
luman lymphocytes) with and
without metabolic activation at
concentrations up to 625 (ig/mL.
Cytotoxicity data not indicated.
Confidential B: Negative in
mammalian erythrocyte micronucleus
test (Swiss mice) following a single
oral dose of 5,000 mg/kg-bw
Confidential B: Negative in
mammalian erythrocyte micronucleus
test (mice) following single oral dose
of 5 00 mg/kg-bw


REFERENCE
EPA, 2010; Confidential study
EPA, 2010; Confidential study
^^^

EPA, 2010; Confidential study
7
EPA, 2010; Confidential study



DATA QUALITY
Guideline study. Data are for the
commercial polymeric mixture.
Guideline study. Data are for the
commercial polymeric mixture.
No data located.
Guideline study. Data are for the
commercial polymeric mixture.
Guideline study. Data are for the
commercial polymeric mixture.
Reported in a submitted confidential study;
Study was conducted in accordance with
GLP and OECD Guideline 474.
Mo data located.
No data located.
         7-237

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                                                          JUNE 2014 DRAFT REPORT
                                                                  Fyrol™ HF-5
          PROPERTY/ENDPOINT
             DATA
       REFERENCE
           DATA QUALITY
Reproductive Effects
LOW: Experimental data for Confidential B indicate no adverse effects on reproductive performance or
'ertility parameters at doses up to 1,000 mg/kg-day (highest dose tested) in a two generation dietary study
n rats. There may be potential for reproductive toxicity based on analogy to a confidential analog.
Confidential A is also estimated to have a LOW potential for reproductive effects based on expert judgment
and a lack of structural alert for this endpoint.
             Reproduction/Developmental
             Toxicity Screen
                                                             No data located.
              Combined Repeated Dose with
              Reproduction/ Developmental
              Toxicity Screen
                                                             No data located.
             Reproduction and Fertility
             Effects
 onfidential B: Two generation
iietary reproduction study in rats.
Sprague-Dawley rats (30/sex/dose)
  re fed 0, 50, 500, or 1,000 mg/kg-
iay Confidential B in the diet for 10
EPA, 2010; Confidential study
                                             Sfo clinical signs of toxicity. No
                                             effects on litter survival. No adverse
                                             effects on any reproductive or fertility
                                             Darameter measured. No treatment-
                                             "elated lesions in any reproductive
                                             urgan.

                                             SfOAEL (parental systemic and
                                             "eproductive toxicity) ~ 1,000 mg/kg-
                                             iay
                                              GAEL: not established
Study details reported in a secondary
source. Data are for the commercial
polymeric mixture.
                                                                     7-238

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JUNE 2014 DRAFT REPORT
Fyrol™ HF-5
PROPERTY/ENDPOINT


Other
Developmental Effects

Reproduction/ Developmental
Toxicity Screen 4
DATA
Confidential B: Potential for
reproductive toxicity; no pregnancies
1,000 mg/kg-day); reduced litter size
and weight (250 mg/kg-day)
NOEL: 50 mg/kg-day
LOEL: 205 mg/kg-day
Estimated by analogy)
Confidential A: There is low
potential for reproductive effects
^Estimated)
REFERENCE
Professional judgment;
Submitted confidential study
Expert j udgment
^^^N. T
DATA QUALITY
Estimated by analogy to confidential
analog.
Estimated based on expert judgment and
the lack of structural alerts.
MODERATE: Based on a NOAEL of 50 mg/kg bw-day in a two generation dietary reproduction study in
rats fed Confidential B. Adverse effects included delayed vaginal opening and preputial separation at a
dose of 500 mg/kg bw-day. No adverse developmental effects were observed in rabbits following oral
administration of Confidential B at doses up to 1,000 mg/kg bw-day. Confidential A is estimated to have a
ow potential for developmental effects based on expert judgment and a lack of structural alert for this
endpoint.
There were no data located for the developmental neurotoxicity endpoint.


No data located.
         7-239

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                                               JUNE 2014 DRAFT REPORT
                                                       Fyrol™ HF-5
PROPERTY/ENDPOINT
             DATA
       REFERENCE
           DATA QUALITY
   Combined Repeated Dose with
   Reproduction/ Developmental
   Toxicity Screen
 onfidential B: Two generation
dietary reproduction study in rats.
Sprague-Dawley rats (30/sex/dose)
were fed 0, 50, 500, or 1,000 mg/kg-
iay Confidential B in the diet for 10
EPA, 2010; Confidential study
                                  Vaginal opening and preputial
                                  separation were delayed at 500 and
                                  1,000 mg/kg-day. This effect was
                                  considered by study authors to be
                                  secondary to reduction of body
                                  weight in FI generation during week
                                  [ (treated animals had decreased body
                                  weights compared to controls during
                                  week 1, reportedly due to an initial
                                  aversion to taste of diet).

                                  NOAEL: 50 mg/kg bw-day (for
                                  vaginal opening and preputial
                                  separation) LOAEL: 500 mg/kg bw-
                                  iay
Guideline study. Data are for the
 ;ommercial polymeric mixture.
                                                          7-240

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                                               JUNE 2014 DRAFT REPORT
                                                       Fyrol™ HF-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                    onfidential B: Developmental oral
                                   javage study in rabbits. Pregnant
                                   Mew Zealand white rabbits
                                   27/group) were dosed with 0, 50,
                                   200 or 1,000 mg/kg-day Confidential
                                    by oral gavage on GD 6-28.

                                   Mo clinical signs of toxicity. No^
                                   idverse effects on maternal  food
                                   consumption, body weight gain or
                                   urgan weights. No adverse effects on
                                   etal body weights, viability, or any
                                   ievelopmental endpoint measured.

                                   SfOAEL (maternal and developmental
                                   oxicity): 1,000 mg/kg-day
                                    GAEL: not established as highest
                                   concentration tested did not produce
                                   idverse effects
                    EPA, 2010
                     Guideline study reported in a secondary
                     ource. Data are for the commercial
                     polymeric mixture.
                                                          7-241

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JUNE 2014 DRAFT REPORT
Fyrol™ HF-5
PROPERTY/ENDPOINT

Prenatal Development
Postnatal Development
Prenatal and Postnatal
Development
Developmental Neurotoxicity
Other
Neurotoxicity

Neurotoxicity Screening Battery
(Adult)
DATA
Confidential B: Pregnant rabbits;
oral gavage; GD 6-23; 0, 50, 200 or
,000 mg/kg-day test material
No deaths or clinical signs of toxicity.
^o significant effect on body weight,
)ody weight gain, food consumption
or organ weight.
No significant effect on litter weight
or pup viability. No gross external,
skeletal or soft tissues malformations
or anomalies.
NOAEL: 1,000 mg/kg-day (highest
dose tested)
LOAEL = Not established



Confidential A: There is low
potential for developmental effects
^Estimated)
REFERENCE
Confidential study
^^S
^^



Expert j udgment
DATA QUALITY
Study details reported in a secondary
source; Study conducted according to GLP.
No data located.
No data located.
No data located.
Estimated based on expert judgment and
the lack of structural alerts.
MODERATE: Based on a 28-day inhalation LOAEL of 0.5 mg/L for inhibition of plasma ChE in rats
NOAEL = 0.1 mg/L) following exposure to Confidential B; criteria values are tripled for chemicals
evaluated in 28-day studies; the LOAEL of 0.5 mg/kg-day falls within the Moderate hazard criteria (0.06 -
0.6 mg/L). Confidential A is estimated to have uncertain potential for neurotoxic effects based on a
structural alert and professional judgment.
Confidential B: 28-day oral (gavage)
study NOAEL: l,000mg/kg
Estimated by analogy)
Professional judgment;
Submitted confidential study
Estimated based on analogy to a
confidential analog.
         7-242

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JUNE 2014 DRAFT REPORT
Fyrol™ HF-5
PROPERTY/ENDPOINT


Other
DATA
Confidential B: 28-day inhalation
study in rats; 0, 0.1, 0.5 and 2.0 mg/L
aerosol)
Significant inhibition of plasma ChE
0.5 and 2.0 mg/L). No clinical signs
suggestive of neurotoxic effect and
ChE was not affected after study
ermination
NOAEL: 0.1 mg/L
LOAEL: 0.5 mg/L (plasma ChE
nhibition)
Confidential B: 28-day oral (gavage)
study in mice; 0, 500, 1,500, 5,000
tng/kg
Dose-related decrease in plasma ChE
compared to controls, which was no
onger apparent after the 60 day
recovery period.
No NOAEL/LOAEL determined
Confidential A: There is potential
x>r neurotoxic effects based on a
structural alert for organophosphates.
(Estimated)
Confidential A: Uncertain concern
x>r neurotoxicity (Estimated)
REFERENCE
Confidential study; EPA, 2010
^^S
Confidential study
7
Professional judgment
Professional judgment
DATA QUALITY
Study details reported in a secondary
source; study was not designed to assess all
neurological parameters; criteria values are
tripled for chemicals evaluated in 28-day
studies; the LOAEL of 0.5 mg/kg-day falls
within the Moderate hazard criteria (0.06 -
0.6 mg/L).
Study details reported in a secondary
source; study was not designed to assess all
neurological parameters; cannot rule out all
neurotoxicity.
Estimated based on a structural alert and
professional judgment.
Estimated for the low MW component due
to ethyl substituted phosphate.
         7-243

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                                                         JUNE 2014 DRAFT REPORT
                                                                  Fyrol™ HF-5
          PROPERTY/ENDPOINT
             DATA
REFERENCE
DATA QUALITY
Repeated Dose Effects
MODERATE: Experimental data reported alveolar histiocytosis in rats following a 4-week inhalation
exposure to 0.5 mg/L Confidential B aerosol (NOAEL = 0.1 mg/L). The criteria threshold for a low hazard
designation is 0.2 mg/L for mists based on 90-day repeated dose studies; guidance values are tripled for 28-
day study evaluations making the MODERATE hazard range from 0.06 - 0.6 mg/L No other exposure-
related gross or microscopic pathology was identified in any organ. There is also potential for liver toxicity
based on a confidential analog, though no effects occurred at 300 mg/kg-day for that analog (higher than
the criteria threshold for a low hazard designation). Confidential A is estimated to have low potential for
repeated dose effects based on expert judgment.
                                             Confidential A: Estimated to have
                                             low potential for repeated dose
                                             effects for the low MW components
                                             of this substance.
                                             This substance may contain polymer
                                             components with a MW > 1,000. In
                                             this case, it is expected to have
                                             limited bioavailability; however,
                                             there is the possibility of lung
                                             overloading.
                                             (Estimated)
                                             Confidential B: 28-day oral study,
                                             rats
                                             Potential for liver toxicity.
                                             NOEL: 300 mg/kg-day
                                             (Estimated based on analogy)
                                 Professional judgment
                                 Submitted confidential study;
                                 Professional judgment
                     Estimated based on professional judgment.
                     Estimated based on analogy to confidential
                     analog.
                                                                     7-244

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                                               JUNE 2014 DRAFT REPORT
                                                        Fyrol™ HF-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   Confidential B: In a 28 day
                                   inhalation study Sprague-Dawley rats
                                   (10/sex/group) were exposed
                                   (aerosol, nose only) to 0, 100, 500 or
                                   2,000 mg/m3 (0, 0.1,  0.5, or 2 mg/L)
                                   Confidential B.

                                   No deaths or clinical  signs of
                                   toxicity. Decreased body weight and
                                   food consumption in  males and
                                   significant inhibition of plasma
                                   cholinesterase in females at 2,000
                                   mg/m3. White foci in the lungs at
                                   2,000 mg/m3 and alveolar
                                   histiocytosis at 500 and 2,000 mg/m3.
                                   Although lung changes are relevant,
                                   they were not considered to be a
                                   reflection of a specific toxic response
                                   to Confidential B; these changes are
                                   characteristic of exposure to non-
                                   cytotoxic water-insoluble materials.
                                   No other gross or microscopic
                                   pathology in any organ.

                                   NOAEC: 100 mg/m3 (0.1 mg/L)
                                   LOAEC: 500 mg/m3  (0.5 mg/L)
                                   based on alveolar histiocytosis)
                    EPA, 2010; Confidential study
                     Guideline study reported in a secondary
                     source. Data are for the commercial
                     polymeric mixture.
                                                           7-245

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                                                JUNE 2014 DRAFT REPORT
                                                        Fyrol™ HF-5
PROPERTY/ENDPOINT
              DATA
       REFERENCE
           DATA QUALITY
   Immune System Effects
Confidential B: Oral gavage study
in mice. Female B6C3F1 mice
(50/group) were exposed via oral
gavage to 0, 500, 1,500, or 5,000
mg/kg-day Confidential B for 28
days.
No deaths, clinical signs of toxicity,
or effects on body or organ weights.
No adverse histopathological
changes or necropsy findings. No
treatment-related changes in
peritoneal cell numbers or cell types,
peritoneal macrophage phagocytic
activity or host susceptibility to
infection. No adverse effect on
splenic natural killer cell activity,
lymphocyte blastogenesis, or
antibody-forming cell function.

There were significant decreases in
erythrocyte cholinesterase activity
and plasma pseudocholinesterase
activity in all dose groups, but both
enzyme activities returned to control
levels at the end of the 60 day
recovery period.
                *
NOAEL: 5,000 mg/kg-day (highest
dose tested)
LOAEL: Not established
EPA, 2010
Guideline study reported in a secondary
source. Data are for the commercial
polymeric mixture.
                                                            7-246

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JUNE 2014 DRAFT REPORT
Fyrol™ HF-5
PROPERTY/ENDPOINT
Skin Sensitization

Skin Sensitization
Respiratory Sensitization
(Respiratory Sensitization
Eye Irritation

Eye Irritation
Dermal Irritation

Dermal Irritation
DATA
REFERENCE
DATA QUALITY
LOW: Confidential A and B are estimated to have low potential for skin Sensitization based on expert
judgment. There was no experimental data located.
Confidential A: There is low
potential for skin Sensitization
(Estimated)
Confidential B: No potential for
skin Sensitization (Estimated)
Expert j udgment
Expert j udgment
Estimated based on expert judgment.
Estimated by expert judgment.
No data located.


No data located.
MODERATE: Confidential A was moderately to slightly irritating to rabbit eyes. Confidential B produced
mild irritation in rabbit eyes; however, clearing occurred within 24 hours.
Confidential A: Moderate to slight
eye irritation in rabbits; conjunctival
irritation with redness and discharge;
cleared within 96 hours.
Confidential B: Rabbit, minimally
irritating. 0.1 ml instilled into the left
eyes of 3 rabbits produced slight
conjunctival redness and chemosis
that was reversible by 24 hours.
Submitted confidential study
EPA, 2010
Data reported in a confidential study
submitted to EPA.
Guideline study reported in a secondary
source. Data are for the commercial
polymeric mixture.
LOW: Confidential A is slightly irritating to rabbit skin with irritation clearing within 3 days. Confidential
B is not a dermal irritant in rabbits.
Confidential A: Slightly irritating to
rabbit skin
Confidential A: Mild and transient
dermal irritation in rabbits; cleared
within 3 days.
Confidential B: Rabbit, not irritating
Submitted confidential study
Submitted confidential study
EPA, 2010
Data reported in a confidential study
submitted to EPA
Data reported in a confidential study
submitted to EPA.
Guideline study reported in a secondary
source. Data are for the commercial
polymeric mixture.
         7-247

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                                                          JUNE 2014 DRAFT REPORT
                                                                   Fyrol™ HF-5
          PROPERTY/ENDPOINT
             DATA
REFERENCE
DATA QUALITY
Endocrine Activity
 onfidential B caused delayed vaginal opening and preputial separation at a dose of 500 mg/kg bw-day
 NOAEL: 50 mg/kg bw-day) in a two generation dietary reproduction study in rats. A metabolite of the test
substance is listed as a suspected endocrine disruptor by the EU. The potential for endocrine activity for
 onfidential A is uncertain.
                                               'onfidential B: Listed as a potential
                                              endocrine disruptor on the EU
                                              Priority List of Suspected Endocrine
                                              Disrupters.
                                 European Commission, 2012
                                               onfidential B: Two generation
                                              iietary reproduction study in rats.
                                              Sprague-Dawley rats (30/sex/dose)
                                              were fed 0, 50, 500, or 1,000 mg/kg-
                                              iay Confidential B in the diet for 10
                                              weeks.

                                              Vaginal opening and preputial
                                              separation were delayed at 500 and
                                              1,000 mg/kg-day. This effect was
                                              considered by study authors to be
                                              secondary to reduction of body
                                              weight in FI generation during week
                                               (treated animals had decreased body
                                              weights compared to controls during
                                              week 1, reportedly due to an initial
                                              iversion to taste of diet).

                                              SfOAEL: 50 mg/kg bw-day (for
                                               aginal opening and preputial
                                              separation)
                                               GAEL: 500 mg/kg bw-day
                                 EPA, 2010; Confidential study
                     Potential for endocrine disruption. In vitro
                     data indicating potential for endocrine
                     disruption in intact organisms. Also
                     included effects in vivo that may, or may
                     not, be endocrine disruption-mediated. May
                     include structural analyses and metabolic
                     considerations".
                     Guideline study. Data are for the
                     commercial polymeric mixture.
                                                                      7-248

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JUNE 2014 DRAFT REPORT
Fyrol™ HF-5
PROPERTY/ENDPOINT
Immunotoxicity

Immune System Effects
DATA
REFERENCE
DATA QUALITY
Confidential B had no effect on immunological parameters at doses up to 5,000 mg/kg-day (highest dose
tested) in an oral gavage study in mice. Confidential A is estimated to have a low potential for immunotoxic
effects based on expert judgment.
Confidential A: There is low
potential for immunotoxic effects
(Estimated)
Expert judgment
Estimated based on expert judgment.
         7-249

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                                                JUNE 2014 DRAFT REPORT
                                                         Fyrol™ HF-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   Confidential B: Negative, oral
                                   gavage study in mice. Female
                                   B6C3F1 mice (50/group) were
                                   exposed via oral gavage to 0, 500,
                                   1,500, or 5,000 mg/kg-day
                                   Confidential B for 28 days.
                                   No deaths, clinical signs of toxicity,
                                   or effects on body or organ weights.
                                   No adverse histopathological
                                   changes or necropsy findings. No
                                   treatment-related changes in
                                   peritoneal cell numbers or cell types,
                                   peritoneal macrophage phagocytic
                                   activity or host susceptibility to
                                   infection. No adverse effect on
                                   splenic natural killer cell activity,
                                   lymphocyte blastogenesis, or
                                   antibody-forming cell function.
                                   There were significant decreases in
                                   erythrocyte cholinesterase activity
                                   and plasma pseudocholinesterase
                                   activity in all dose groups, but both
                                   enzyme activities returned to control
                                   levels at the end of the 60 day
                                   recovery period.
                                   NOAEL: 5,000 mg/kg-day
                                   LOAEL: not established, as highest
                                   dose tested did not produced adverse
                                   effects.
                    EPA, 2010
                     Guideline study reported in a secondary
                     source. Data are for the commercial
                     polymeric mixture.
                                                            7-250

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                                                         JUNE 2014 DRAFT REPORT
                                                                 Fyrol™ HF-5
          PROPERTY/ENDPOINT
             DATA
       REFERENCE
          DATA QUALITY
ECOSAR Class
                                                               ECOTOXICITY
Acute Aquatic Toxicity
VERY HIGH: Based on measured EC50 values for daphnia following exposure to Confidential B. Measured
values for fish and algae are higher than the water solubility limit, suggesting no effects at saturation
(NES). Acute aquatic toxicity is expected to be LOW for Confidential A.
Fish LC50
Confidential A: Danio rerio
(Zebrafish) 96-hour LC50 >1,000
mg/L according to OECD 203
(Experimental)
                                            Confidential A: Freshwater fish 96-
                                            hour LC50 = 7,200 mg/L
                                            (Estimated)
                                            ECOSAR: Neutral organics
                                            Confidential A: Freshwater fish 96-
                                            hour LC50 (Estimated)
                                            ECOSAR: Neutral organics
Clariant, 2011
Data reported in a confidential study
submitted to EPA; the toxicity value is well
above the water solubility for this
substance; therefore NES is predicted.
                                 ECOSAR vl. 11
                                 ECOSAR vl. 11
                            Estimates based on representative oligomer
                            where n=l. The effect level exceeds the
                            water solubility of 3,375 mg/L; NES are
                            predicted for these endpoints. ECOSAR
                            also provided results for the Esters, and
                            Esters (phosphate) classes; however,
                            professional judgment indicates that this
                            compound is not currently well represented
                            inECOSARvl.il.
                            Estimates based on representative oligomer
                            where n=2. The effect level exceeds the
                            water solubility of 932.9 mg/L; NES are
                            predicted for these endpoints. ECOSAR
                            also provided results for the Esters, and
                            Esters (phosphate) classes; however,
                            professional judgment indicates that this
                            compound is not currently well represented
                            inECOSARvl.il.
                                                                    7-251

-------
                                              JUNE 2014 DRAFT REPORT
                                                       Fyrol™ HF-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  Confidential A: Freshwater fish 96-
                                  hour LC50 = 89,000 mg/L
                                  (Estimated)
                                  ECOSAR: Neutral organics
                    ECOSARvl.ll
                                  Confidential A: Freshwater fish 96-
                                  hour LC50 = 280,000 mg/L
                                  (Estimated)
                                  ECOSAR: Neutral organics
                    ECOSARvl.ll
                                  Confidential A: Freshwater fish 96-
                                  hour LC50 = 300,000 mg/L
                                  (Estimated)
                                  ECOSAR: Neutral organics
                    ECOSARvl.ll
                     Estimates based on representative oligomer
                     where n=3. The effect level exceeds the
                     water solubility of 232.7 mg/L; NES are
                     predicted for these endpoints. ECOSAR
                     also provided results for the Esters, and
                     Esters (phosphate) classes; however,
                     professional judgment indicates that this
                     compound is not currently well represented
                     inECOSARvl.il.
                     Estimates based on representative oligomer
                     where n=4. The effect level exceeds the
                     water solubility of 54.73 mg/L; NES are
                     predicted for these endpoints. ECOSAR
                     also provided results for the Esters, and
                     Esters (phosphate) classes; however,
                     professional judgment indicates that this
                     compound is not currently well represented
                     inECOSARvl.il.
                     Estimates based on representative oligomer
                     where n=5. The effect level exceeds the
                     water solubility of 4.716 mg/L; NES are
                     predicted for these endpoints. ECOSAR
                     also provided results for the Esters, and
                     Esters (phosphate) classes; however,
                     professional judgment indicates that this
                     compound is not currently well represented
                     inECOSARvl.il.
                                                          7-252

-------
                                                         JUNE 2014 DRAFT REPORT
                                                                 Fyrol™ HF-5
          PROPERTY/ENDPOINT
             DATA
       REFERENCE
          DATA QUALITY
                                            Confidential A: Freshwater fish 96-
                                            hour LC50 = 880,000 mg/L
                                            (Estimated)
                                            ECOSAR: Neutral organics
                                 ECOSARvl.ll
                                            Confidential B: Brachydanio rerio
                                            96-hour LC50 =12.3 mg/L
                                            (Experimental)
                                 EPA, 2010
                                            Confidential B: Fish 96-hour LC50
                                            NES
                                            (Estimated)
                                            ECOSAR: Neutral organics
                                 ECOSARvl.ll
                            Estimates based on representative oligomer
                            where n=6. The effect level exceeds the
                            water solubility of 1.041 mg/L; NES are
                            predicted for these endpoints. ECOSAR
                            also provided results for the Esters, and
                            Esters (phosphate) classes; however,
                            professional judgment indicates that this
                            compound is not currently well represented
                            inECOSARvl.il.
                            Guideline study reported in a secondary
                            source (OECD Guide-line 203). Data are
                            for the commercial polymeric mixture.
                            Given that the reported value is greater
                            than the water solubility, NES were
                            observed for this endpoint.
                            Estimates were performed on oligomers of
                            the polymeric mixture that have a MW
                            < 1,000; NES are estimated for the n=l and
                            higher oligomers. ECOSAR also provided
                            results for the Esters, and Esters
                            (phosphate) classes; however, professional
                            judgment indicates that this compound is
                            not currently well represented in ECOSAR
                            vl.ll.
Daphnid LC50
Confidential A: Daphnia magna 48-
hour LC50 = 3,500 mg/L
(Estimated)
ECOSAR: Neutral organics
ECOSARvl.ll
Estimates based on representative oligomer
where n=l. The effect level exceeds the
water solubility of 3,375 mg/L; NES are
predicted for these endpoints. ECOSAR
also provided results for the Esters, and
Esters (phosphate) classes; however,
professional judgment indicates that this
compound is not currently well represented
inECOSARvl.il.
                                                                    7-253

-------
                                              JUNE 2014 DRAFT REPORT
                                                      Fyrol™ HF-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  Confidential A: Daphnia magna 48-
                                  hour LC50= 13,OOOmg/L
                                  (Estimated)
                                  ECOSAR: Neutral organics
                    ECOSARvl.ll
                                  Confidential A: Daphnia magna 48-
                                  hour LC50 = 40,000 mg/L
                                  (Estimated)
                                  ECOSAR: Neutral organics
                    ECOSARvl.ll
                                  Confidential A: Daphnia magna 48-
                                  hour LC50 = 120,000 mg/L
                                  (Estimated)
                                  ECOSAR: Neutral organics
                    ECOSARvl.ll
                     Estimates based on representative oligomer
                     where n=2. The effect level exceeds the
                     water solubility of 932.9 mg/L; NES are
                     predicted for these endpoints. ECOSAR
                     also provided results for the Esters, and
                     Esters (phosphate) classes; however,
                     professional judgment indicates that this
                     compound is not currently well represented
                     inECOSARvl.il.
                     Estimates based on representative oligomer
                     where n=3. The effect level exceeds the
                     water solubility of 232.7 mg/L; NES are
                     predicted for these endpoints. ECOSAR
                     also provided results for the Esters, and
                     Esters (phosphate) classes; however,
                     professional judgment indicates that this
                     compound is not currently well represented
                     inECOSARvl.il.
                     Estimates based on representative oligomer
                     where n=4. The effect level exceeds the
                     water solubility of 54.73 mg/L; NES are
                     predicted for these endpoints. ECOSAR
                     also provided results for the Esters, and
                     Esters (phosphate) classes; however,
                     professional judgment indicates that this
                     compound is not currently well represented
                     inECOSARvl.il.
                                                          7-254

-------
                                              JUNE 2014 DRAFT REPORT
                                                      Fyrol™ HF-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  Confidential A: Daphnia magna 48-
                                  hour LC50 < 130,000 mg/L
                                  (Estimated)
                                  ECOSAR: Neutral organics
                   ECOSARvl.ll
                                  Confidential A: Daphnia magna 48-
                                  hour LC50 = 370,000 mg/L
                                  (Estimated)
                                  ECOSAR: Neutral organics
                   ECOSARvl.ll
                                  Confidential B: Daphnia magna 48-
                                  hour EC50 = 0.7 mg/L
                                  (Experimental)
                   EPA, 2010
                                  Confidential B: Daphnia magna 48-
                                  hour LC50 = NES
                                  (Experimental)
                                  ECOSAR: Neutral organics
                   ECOSARvl.ll
                    Estimates based on representative oligomer
                    where n=5. The effect exceeds the water
                    solubility of 4.716 mg/L; NES are
                    predicted for these endpoints. ECOSAR
                    also provided results for the Esters, and
                    Esters (phosphate) classes; however,
                    professional judgment indicates that this
                    compound is not currently well represented
                    inECOSARvl.il.
                    Estimates based on representative oligomer
                    where n=6. The effect level exceeds the
                    water solubility of 1.041 mg/L; NES are
                    predicted for these endpoints. ECOSAR
                    also provided results for the Esters, and
                    Esters (phosphate) classes; however,
                    professional judgment indicates that this
                    compound is not currently well represented
                    inECOSARvl.il.
                    Guideline study reported in a secondary
                    source (U.S. EPA OPPTS 850.1010). Data
                    are for the commercial polymeric mixture.
                    Estimates were performed on oligomers of
                    the polymeric mixture that have a MW
                    < 1,000; NES are estimated for the n=l and
                    higher oligomers. ECOSAR also provided
                    results for the Esters, and Esters
                    (phosphate) classes; however, professional
                    judgment indicates that this compound is
                    not currently well represented in ECOSAR
                    vl.ll.
                                                          7-255

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                                                         JUNE 2014 DRAFT REPORT
                                                                 Fyrol™ HF-5
          PROPERTY/ENDPOINT
             DATA
       REFERENCE
          DATA QUALITY
Green Algae EC50
Confidential A: Green algae 96-hour
EC50 = 1,400 mg/L
(Estimated)
ECOSAR: Neutral organics
ECOSARvl.ll
Estimates based on representative oligomer
where n=l. ECOSAR also provided results
for the Esters, and Esters (phosphate)
classes; however, professional judgment
indicates that this compound is not
currently well represented in ECOSAR
vl.ll.
                                            Confidential A: Green algae 96-hour
                                            EC50 = 4,300 mg/L
                                            (Estimated)
                                 ECOSARvl.ll
                                            Confidential A: Green algae 96-hour
                                            EC50 = 12,000 mg/L
                                            (Estimated)
                                            ECOSAR: Neutral organics
                                 ECOSARvl.ll
                            Estimates based on representative oligomer
                            where n=2. The effect level exceeds the
                            water solubility of 932.9 mg/L; NES are
                            predicted for these endpoints. ECOSAR
                            also provided results for the Esters, and
                            Esters (phosphate) classes; however,
                            professional judgment indicates that this
                            compound is not currently well represented
                            inECOSARvl.il.
                            Estimates based on representative oligomer
                            where n=3. The effect level exceeds the
                            water solubility of 232.7 mg/L; NES are
                            predicted for these endpoints. ECOSAR
                            also provided results for the Esters, and
                            Esters (phosphate) classes; however,
                            professional judgment indicates that this
                            compound is not currently well represented
                            inECOSARvl.il.
                                                                    7-256

-------
                                               JUNE 2014 DRAFT REPORT
                                                       Fyrol™ HF-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   Confidential A: Green algae 96-hour
                                   EC50 = 30,000 mg/L
                                   (Estimated)
                                   ECOSAR: Neutral organics
                    ECOSARvl.ll
                                   Confidential A: Green algae 96-hour
                                   EC50 = 32,000 mg/L
                                   (Estimated)
                                   ECOSAR: Neutral organics
                    ECOSARvl.ll
                                   Confidential A: Green algae 96-hour
                                   EC50 = 77,000 mg/L
                                   (Estimated)
                                   ECOSAR: Neutral organics
                    ECOSARvl.ll
                                   Confidential B: Pseudokirchneriella
                                   subcapitata 72-hour EC50 = 48.6
                                   mg/L
                                   (Experimental)
                    EPA, 2010
                     Estimates based on representative oligomer
                     where n=4. The effect level exceeds the
                     water solubility of 54.73 mg/L; NES are
                     predicted for these endpoints. ECOSAR
                     also provided results for the Esters, and
                     Esters (phosphate) classes; however,
                     professional judgment indicates that this
                     compound is not currently well represented
                     inECOSARvl.il.
                     Estimates based on representative oligomer
                     where n=5. The effect level exceeds the
                     water solubility of 4.716 mg/L; NES are
                     predicted for these endpoints. ECOSAR
                     also provided results for the Esters, and
                     Esters (phosphate) classes; however,
                     professional judgment indicates that this
                     compound is not currently well represented
                     inECOSARvl.il.
                     Estimates based on representative oligomer
                     where n=6. The effect level exceeds the
                     water solubility of 1.041 mg/L; NES are
                     predicted for these endpoints. ECOSAR
                     also provided results for the Esters, and
                     Esters (phosphate) classes; however,
                     professional judgment indicates that this
                     compound is not currently well represented
                     inECOSARvl.il.
                     Guideline study reported in a secondary
                     source (OECD 201). Data are for the
                     commercial polymeric mixture.
                     Given that the reported value is greater
                     than the water solubility, NES was
                     observed for this endpoint.
                                                           7-257

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                                                        JUNE 2014 DRAFT REPORT
                                                                Fyrol™ HF-5
          PROPERTY/ENDPOINT
             DATA
       REFERENCE
          DATA QUALITY
                                            Confidential B: Pseudokirchneriella
                                            subcapitata 72-hour NOEC =10
                                            mg/L (WAF) 72-hour LOEC = 100
                                            mg/L (WAF)
                                            (Experimental)
                                Confidential study
                           Study details reported in a secondary
                           source. Study conducted according to GLP
                           and OECD guideline 201.
                                            Confidential B: Green algae 96-hour
                                            EC50 = NES
                                            (Estimated)
                                            ECOSAR: Neutral organics
                                ECOSARvl.ll
                           Estimates were performed on oligomers of
                           the polymeric mixture that have a MW
                           < 1,000; NES are estimated for the n=l and
                           higher oligomers. ECOSAR also provided
                           results for the Esters, and Esters
                           (phosphate) classes; however, professional
                           judgment indicates that this compound is
                           not currently well represented in ECOSAR
                           vl.ll.
Chronic Aquatic Toxicity
VERY HIGH: Based on an experimental 21-day NOEC = 0.021 mg/L in Daphnia magna following exposure
to Confidential B. No effects at Saturation (NES) are predicted for Confidential A based on estimated
chronic aquatic toxicity values for representative oligomers.
Fish ChV
Confidential A: Freshwater fish
ChV = 590 mg/L
(Estimated)
ECOSAR: Neutral organics
                                            Confidential A: Freshwater fish
                                            ChV = 2,100 mg/L
                                            (Estimated)
                                            ECOSAR: Neutral organics
ECOSARvl.ll
Estimates based on representative oligomer
where n=l. ECOSAR also provided results
for the Esters, and Esters (phosphate)
classes; however, professional judgment
indicates that this compound is not
currently well represented in ECOSAR
vl.ll.
                                ECOSARvl.ll
                           Estimates based on representative oligomer
                           where n=2. The effect level exceeds the
                           water solubility of 932.9 mg/L; NES are
                           predicted for these endpoints. ECOSAR
                           also provided results for the Esters, and
                           Esters (phosphate) classes; however,
                           professional judgment indicates that this
                           compound is not currently well represented
                           inECOSARvl.il.
                                                                    7-258

-------
                                              JUNE 2014 DRAFT REPORT
                                                       Fyrol™ HF-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  Confidential A: Freshwater fish
                                  ChV = 6,700 mg/L
                                  (Estimated)
                                  ECOSAR: Neutral organics
                    ECOSARvl.ll
                                  Confidential A: Freshwater fish
                                  ChV = 20,000 mg/L
                                  (Estimated)
                                  ECOSAR: Neutral organics
                    ECOSARvl.ll
                                  Confidential A: Freshwater fish
                                  ChV = 21,000 mg/L
                                  (Estimated)
                                  ECOSAR: Neutral organics
                    ECOSARvl.ll
                     Estimates based on representative oligomer
                     where n=3. The effect level exceeds the
                     water solubility of 232.7 mg/L; NES are
                     predicted for these endpoints. ECOSAR
                     also provided results for the Esters, and
                     Esters (phosphate) classes; however,
                     professional judgment indicates that this
                     compound is not currently well represented
                     inECOSARvl.il.
                     Estimates based on representative oligomer
                     where n=4. The effect level exceeds the
                     water solubility of 54.73 mg/L; NES are
                     predicted for these endpoints. ECOSAR
                     also provided results for the Esters, and
                     Esters (phosphate) classes; however,
                     professional judgment indicates that this
                     compound is not currently well represented
                     inECOSARvl.il.
                     Estimates based on representative oligomer
                     where n=5. The effect level exceeds the
                     water solubility of 4.716 mg/L; NES are
                     predicted for these endpoints. ECOSAR
                     also provided results for the Esters, and
                     Esters (phosphate) classes; however,
                     professional judgment indicates that this
                     compound is not currently well represented
                     inECOSARvl.il.
                                                          7-259

-------
                                                        JUNE 2014 DRAFT REPORT
                                                                Fyrol™ HF-5
          PROPERTY/ENDPOINT
             DATA
       REFERENCE
          DATA QUALITY
                                            Confidential A: Freshwater fish
                                            ChV = 60,000 mg/L
                                            (Estimated)
                                            ECOSAR: Neutral organics
                                ECOSARvl.ll
                                            Confidential B: ChV = NES
                                            (Estimated)
                                            ECOSAR: Neutral organics
                                ECOSARvl.ll
                           Estimates based on representative oligomer
                           where n=6. The effect level exceeds the
                           water solubility of 1.041mg/L; NES are
                           predicted for these endpoints. ECOSAR
                           also provided results for the Esters, and
                           Esters (phosphate) classes; however,
                           professional judgment indicates that this
                           compound is not currently well represented
                           inECOSARvl.il.
                           Estimates were performed on oligomers of
                           the polymeric mixture that have a MW
                           < 1,000; NES are estimated for the n=l and
                           higher oligomers. ECOSAR also provided
                           results for the Esters, and Esters
                           (phosphate) classes; however, professional
                           judgment indicates that this compound is
                           not currently well represented in ECOSAR
                           vl.ll.
Daphnid ChV
Confidential A: Daphnia magna
ChV = 230 mg/L
(Estimated)
ECOSAR: Neutral organics
ECOSARvl.ll
                                            Confidential A: Daphnia magna
                                            ChV = 730 mg/L
                                            (Estimated)
                                            ECOSAR: Neutral organics
                                ECOSARvl.ll
Estimates based on representative oligomer
where n=l. ECOSAR also provided results
for the Esters, and Esters (phosphate)
classes; however, professional judgment
indicates that this compound is not
currently well represented in ECOSAR
vl.ll.
                           Estimates based on representative oligomer
                           where n=2. ECOSAR also provided results
                           for the Esters, and Esters (phosphate)
                           classes; however, professional judgment
                           indicates that this compound is not
                           currently well represented in ECOSAR
                           vl.ll.
                                                                   7-260

-------
                                              JUNE 2014 DRAFT REPORT
                                                      Fyrol™ HF-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  Confidential A: Daphnia magna
                                  ChV = 2,100mg/L
                                  (Estimated)
                                  ECOSAR: Neutral organics
                    ECOSARvl.ll
                                  Confidential A: Daphnia magna
                                  ChV = 5,600 mg/L
                                  (Estimated)
                                  ECOSAR: Neutral organics
                    ECOSARvl.ll
                                  Confidential A: Daphnia magna
                                  ChV = 6,000 mg/L
                                  (Estimated)
                                  ECOSAR: Neutral organics
                    ECOSARvl.ll
                     Estimates based on representative oligomer
                     where n=3. The effect level exceeds the
                     water solubility of 232.7 mg/L; NES are
                     predicted for these endpoints. ECOSAR
                     also provided results for the Esters, and
                     Esters (phosphate) classes; however,
                     professional judgment indicates that this
                     compound is not currently well represented
                     inECOSARvl.il.
                     Estimates based on representative oligomer
                     where n=4. The effect level exceeds the
                     water solubility of 54.73 mg/L; NES are
                     predicted for these endpoints. ECOSAR
                     also provided results for the Esters, and
                     Esters (phosphate) classes; however,
                     professional judgment indicates that this
                     compound is not currently well represented
                     inECOSARvl.il.
                     Estimates based on representative oligomer
                     where n=5. The effect level exceeds the
                     water solubility of 4.716 mg/L; NES are
                     predicted for these endpoints. ECOSAR
                     also provided results for the Esters, and
                     Esters (phosphate) classes; however,
                     professional judgment indicates that this
                     compound is not currently well represented
                     inECOSARvl.il.
                                                          7-261

-------
                                                        JUNE 2014 DRAFT REPORT
                                                                Fyrol™ HF-5
          PROPERTY/ENDPOINT
             DATA
       REFERENCE
          DATA QUALITY
                                            Confidential A: Daphnia magna
                                            ChV = 15,000 mg/L
                                            (Estimated)
                                            ECOSAR: Neutral organics
                                ECOSARvl.ll
                           Estimates based on representative oligomer
                           where n=6. The effect level exceeds the
                           water solubility of 1.041 mg/L; NES are
                           predicted for these endpoints. ECOSAR
                           also provided results for the Esters, and
                           Esters (phosphate) classes; however,
                           professional judgment indicates that this
                           compound is not currently well represented
                           inECOSARvl.il.
                                            Confidential B: Daphnia magna
                                            21-day NOEC = 0.021 mg/L
                                            21-day EC50 = 0.037 mg/L Semi-
                                            static
                                            (Experimental)
                                Submitted confidential study
                                            Confidential B: 21-day ChV = NES
                                            (Estimated)
                                            ECOSAR: Neutral organics
                                ECOSARvl.ll
                           Reported in a submitted confidential study;
                           Study conducted according to GLP and
                           OECD guideline 211.
                           Estimates were performed on oligomers of
                           the polymeric mixture that have a MW
                           < 1,000; NES are estimated for the n=l and
                           higher oligomers. ECOSAR also provided
                           results for the Esters, and Esters
                           (phosphate) classes; however, professional
                           judgment indicates that this compound is
                           not currently well represented in ECOSAR
                           vl.ll.
Green Algae ChV
Confidential A: Green algae ChV =
270 mg/L
(Estimated)
ECOSAR: Neutral organics
ECOSARvl.ll
Estimates based on representative oligomer
where n=l. ECOSAR also provided results
for the Esters, and Esters (phosphate)
classes; however, professional judgment
indicates that this compound is not
currently well represented in ECOSAR
vl.ll.
                                                                   7-262

-------
                                              JUNE 2014 DRAFT REPORT
                                                      Fyrol™ HF-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  Confidential A: Green algae ChV =
                                  740 mg/L
                                  (Estimated)
                    ECOSARvl.ll
                     Estimates based on representative oligomer
                     where n=2. ECOSAR also provided results
                     for the Esters, and Esters (phosphate)
                     classes; however, professional judgment
                     indicates that this compound is not
                     currently well represented in ECOSAR
                     vl.ll.
                                  Confidential A: Green algae ChV
                                  1,800 mg/L
                                  (Estimated)
                                  ECOSAR: Neutral organics
                    ECOSARvl.ll
                                  Confidential A: Green algae ChV
                                  4,200 mg/L
                                  (Estimated)
                                  ECOSAR: Neutral organics
                    ECOSARvl.ll
                     Estimates based on representative oligomer
                     where n=3. The effect level exceeds the
                     water solubility of 232.7 mg/L; NES are
                     predicted for these endpoints. ECOSAR
                     also provided results for the Esters, and
                     Esters (phosphate) classes; however,
                     professional judgment indicates that this
                     compound is not currently well represented
                     inECOSARvl.il.
                     Estimates based on representative oligomer
                     where n=4. The effect level exceeds the
                     water solubility of 54.73 mg/L; NES are
                     predicted for these endpoints. ECOSAR
                     also provided results for the Esters, and
                     Esters (phosphate) classes; however,
                     professional judgment indicates that this
                     compound is not currently well represented
                     inECOSARvl.il.
                                                          7-263

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                                              JUNE 2014 DRAFT REPORT
                                                      Fyrol™ HF-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  Confidential A: Green algae ChV =
                                  4,700 mg/L
                                  (Estimated)
                                  ECOSAR: Neutral organics
                   ECOSARvl.ll
                                  Confidential A: Green algae ChV =
                                  10,000 mg/L
                                  (Estimated)
                                  ECOSAR: Neutral organics
                   ECOSARvl.ll
                                  Confidential B: ChV = NES
                                  (Estimated)
                                  ECOSAR: Neutral organics
                   ECOSARvl.ll
                    Estimates based on representative oligomer
                    where n=5. The effect level exceeds the
                    water solubility of 4.716 mg/L; NES are
                    predicted for these endpoints. ECOSAR
                    also provided results for the Esters, and
                    Esters (phosphate) classes; however,
                    professional judgment indicates that this
                    compound is not currently well represented
                    inECOSARvl.il.
                    Estimates based on representative oligomer
                    where n=6. The effect level exceeds the
                    water solubility of 1.041 mg/L; NES are
                    predicted for these endpoints. ECOSAR
                    also provided results for the Esters, and
                    Esters (phosphate) classes; however,
                    professional judgment indicates that this
                    compound is not currently well represented
                    inECOSARvl.il.
                    Estimates were performed on oligomers of
                    the polymeric mixture that have a MW
                    < 1,000; NES are estimated for the n=l and
                    higher oligomers. ECOSAR also provided
                    results for the Esters, and Esters
                    (phosphate) classes; however, professional
                    judgment indicates that this compound is
                    not currently well represented in ECOSAR
                    vl.ll.
                                               ENVIRONMENTAL FATE
                                                         7-264

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                                                        JUNE 2014 DRAFT REPORT
                                                                Fyrol™ HF-5
          PROPERTY/ENDPOINT
             DATA
       REFERENCE
          DATA QUALITY
Transport
The environmental fate for the lower MW oligomers; with MW<1,000 is based on the estimated moderate
water solubility and low vapor pressure indicating that the lower MW oligomers are anticipated to
partition predominantly to soil. The higher MW oligomers where with MW>1,000 are expected to have
negligible water solubility and negligible vapor pressure indicating that the higher MW oligomers are
anticipated to partition predominantly to soil and sediment. The components of the mixture are expected to
be immobile in soil based on the estimated Koc values. Leaching through soil to groundwater is not expected
to be an important transport mechanism. Estimated volatilization half-lives indicate that the components
will be non-volatile from surface water. Volatilization from dry surface is also not expected based on its
vapor pressure. In the atmosphere, the mixture components are expected to exist solely in the particulate
phase, based on its estimated vapor pressure. Particulates may be removed from air by wet or dry
deposition.
             Henry's Law Constant (atm-
             m3/mole)
Confidential A: <10 8 for n>l
(Estimated)
EPI v4.11 ; Professional
judgment; Boethling and
Nabholz, 1997
                                            Confidential B:<108 forn>l
                                            (Estimated)
Estimates based on representative
oligomers; cutoff values for nonvolatile
compounds. Estimated by the
HENRYWIN Group SAR Method with no
measured chemical property inputs. High
MW polymers are expected to have low
vapor pressure and are not expected to
undergo volatilization.
                                 EPIv4.11
                            Cutoff value for nonvolatile compounds.
                            Higher MW components are also expected
                            to have Henry's Law Constant values
                            below this cutoff.
             Sediment/Soil
             Adsorption/Desorption - Koc
Confidential A: 11,000 forn=l;
>30,000forn>2
(Estimated)
EPI v4.11; Professional
judgment
Using MCI Method KOCWIN v2.00,
estimate based on representative oligomers.
Also estimated for oligomers with MWs
>1,000 based on professional judgment.
                                            Confidential B: >30,000 for n>l
                                            (Estimated)
                                 EPI v4.11: EPA, 2005
                            Cutoff value fornonmobile compounds
                            according to HPV assessment guidance.
                            Higher MW components are also expected
                            to have Koc values above this cutoff.
                                                                    7-265

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                                           JUNE 2014 DRAFT REPORT
                                                   Fyrol™ HF-5
PROPERTY/ENDPOINT
            DATA
       REFERENCE
          DATA QUALITY
   Level III Fugacity Model
Confidential A:
Air = 0%
Water =15%
Soil = 80%
Sediment = 4.8% (Estimated)
EPIv4.11
                                Confidential B:
                                Air=l%
                                Water =1%
                                Soil = 40%
                                Sediment = 59% (Estimated for n
                                1)
                               EPIv4.11
Estimate based on representative oligomer
where n=l.
                          Estimates were performed on
                          representative components of the polymer.
                                                      7-266

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                                                        JUNE 2014 DRAFT REPORT
                                                                Fyrol™ HF-5
          PROPERTY/ENDPOINT
                                            DATA
                                       REFERENCE
                                     DATA QUALITY
Persistence
                               VERY HIGH: The persistence designation is based on the higher MW components (MW >1,000). The
                               lower MW oligomers (MW <1,000) are expected to have lower persistence because of their higher water
                               solubility and increased bioavailability to microorganisms. The higher MW components are expected to
                               have higher persistence because of their low water solubility and poor bioavailability, indicating that
                               neither biodegradation nor hydrolysis are expected to be important environmental fate processes. A ready
                               test using the OECD guideline 301D demonstrated 0% biodegradation occurred after 28 days and 2%
                               biodegradation was achieved after 140 days. In a nonguideline study with limited details, slow hydrolysis
                               was reported for a confidential commercial product at normal temperatures in acidic and alkaline aqueous
                               solutions. Additionally, this mixture does not contain components with functional groups that would be
                               expected to absorb light at environmentally significant wavelengths. Experimental values for commercial
                               products and evaluation of the higher MW components of this polymer suggest an environmental half-life
                               of >180 days. Moderate persistence is expected for Confidential B based on experimental biodegradation
                               studies.
Water
Aerobic Biodegradation
Confidential A:
Passes Ready Test: No
Test method: OECD TG 301D:
Closed Bottle Test

This commercial product
biodegraded 0% at day 28 and 2% at
day 140 (Measured)
                                            Confidential A: Hours-days
                                            (Primary Survey Model)
                                            Confidential A: Weeks (Ultimate
                                            Survey Model) (Estimated)
Confidential study
From a MSDS for a confidential
commercial product containing 95-100%
pure material.
                                                               EPIv4.11
                                                            Estimate based on representative oligomers
                                                            where n=l-2.
                                                                    7-267

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JUNE 2014 DRAFT REPORT
Fyrol™ HF-5
PROPERTY/ENDPOINT

Soil

Volatilization Half-life for Model
River
Volatilization Half-life for Model
Lake
Aerobic Biodegradation
Anaerobic Biodegradation
Soil Biodegradation with Product
Identification
Sediment/Water Biodegradation
DATA
Confidential B:
Study results: 37%/28 days
Test method: Other
37% degradation after 28 days;
66% degradation after 56 days
Using Directive 84/449/EEC, C.6
(Measured) inherent biodegradation,
2.7 mg/L of compound in activated
sludge (Measured)
Confidential A: >1 year for n>l
(Estimated)
Confidential B: >1 year for n=l and
n=2 (Estimated)
Confidential A: >1 year for n>l
(Estimated)
Confidential B: >1 year for n=l and
n=2 (Estimated)

Confidential A: Probable
(Anaerobic-methanogenic
biodegradation probability model)
Confidential B: Not probable;
according to the anaerobic-
methanogenic biodegradation
probability model


REFERENCE
IUCLID, 2001
EPIv4.11
EPIv4.11
EPIv4.11
EPIv4.11

EPIv4.11
EPIv4.11


DATA QUALITY
The data is for the commercial product.
Estimate based on representative
oligomers.
Based on the magnitude of the estimated
Henry's Law Constant.
Estimate based on representative
oligomers.
Based on the magnitude of the estimated
Henry's Law Constant.
Mo data located.
Estimate based on representative oligomers
where n=l.
Estimated for the n>l components.
No data located.
No data located.
         7-268

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                                                         JUNE 2014 DRAFT REPORT
                                                                 Fyrol™ HF-5
          PROPERTY/ENDPOINT
                                            DATA
                                        REFERENCE
                                      DATA QUALITY
Air
Atmospheric Half-life
Confidential A:
0.086 days for n=l
0.056 days for n=2
0.042 days for n=3
0.025 days for n=6
(Estimated)
EPIv4.11
Estimate based on representative
oligomers.
                                             Confidential B: 0.5 days or 6 hours
                                             (Estimated for n=l)

                                             0.3 days or 4 hours (Estimated for
                                             n=2)
                                                                EPIv4.11
Reactivity
Photolysis
Confidential A & B: Not a
significant fate process (Estimated)
Professional judgment; Mill,
2000
The substance does not contain functional
groups that would be expected to absorb
light at wavelengths >290 nm.
             Hydrolysis
                               Confidential A: Hydrolyzes slowly
                               at normal temperatures in acidic or
                               alkaline aqueous solutions
                               (Measured)
                                 Confidential study
                                             Confidential A:

                                             50%/3.3yearsatpH5-8
                                             50%/3yearsatpH9
                                             forn=l (Estimated)
                                                                EPIv4.11
                            Non-quantitative value from a MSDS for a
                            confidential commercial product
                            containing 95-100% pure material.
                                                            Estimate based on representative oligomer.
                                                                     7-269

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                                                JUNE 2014 DRAFT REPORT
                                                        Fyrol™ HF-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   Confidential A:
                                   Linear phosphoric acids are strongly
                                   hygroscopic. These substances
                                   undergo viscosity changes and
                                   hydrolysis to less complex forms
                                   when exposed to moist air.
                                   Hydrolytic degradation to phosphoric
                                   acid occurs upon dissolution in
                                   water. The rate of hydrolysis
                                   temperature dependent; at 25 °C, the
                                   half-life is several days and at 100°C,
                                   the half-life is minutes.
                    Confidential study
                     Supporting information about this related
                     class of compounds.
                                   Confidential B:
                                   Half-life = 320 days at pH 7
                                   Half-life = 32 days at pH 8
                                   Half-life = 3 days pH 9
                                   (forn=l)
                                   Half-life = 240-320 days at pH 7
                                   Half-life = 24-32 days  at pH 8
                                   Half-life = 2-3 days pH 9
                                   (for n=2) (Estimated)
                    EPIv4.11
                                   Confidential B:
                                   Half-life = 11 days (20°C; pH 4)
                                   Half-life = 17 days (20°C; pH 7)
                                   Half-life = 21 days (20°C; pH 9)
                                   OECD 111 (Measured)
                    IUCLID, 2001
                     Hydrolysis rates are expected to be pH-
                     dependent and may be limited by the low
                     water solubility of this compound. Under
                     basic conditions, sequential
                     dephosphorylation reactions may occur.
                     Inadequate. Although reported as a
                     guideline study, phosphate esters as a
                     chemical class have been observed to
                     hydrolyze more rapidly under basic pHs
                     then under neutral or acidic conditions. The
                     reported half-lives do not follow this trend,
                     and are therefore suspect. Under basic
                     conditions, sequential dephosphorylation
                     reactions may occur.
                                                            7-270

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JUNE 2014 DRAFT REPORT
Fyrol™ HF-5
PROPERTY/ENDPOINT
Environmental Half-life
Bioaccumulation

Fish BCF
Other BCF
DATA
Confidential A: >180 days
(Estimated)
Confidential A: 30
(Estimated)
Confidential B: >180 days
HIGH: Based on the estimated BCF
hazard designation criteria indicatii
>1,000 are expected to have limited
bioaccumulative.
Confidential A: 3.2 (Estimated)
Confidential A: <100 oligomers
(Estimated)
7
Confidential B: 1,300 for n=l
5 9 for n=2 (Estimated)

REFERENCE
Professional judgment
PBT Profiler
PBT Profiler
DATA QUALITY
The oligomers with a MW > 1,000 are not
anticipated to be assimilated by
microorganisms. Therefore, biodegradation
is not expected to be an important removal
process. The higher MW oligomers are
also not expected to be removed by other
degradation processes under environmental
conditions because of limited water
solubility and limited partitioning to air.
Half-life estimated for the predominant
compartment, soil, for the oligomer where
n=l, as determined by EPI and the PBT
Profiler methodology.
Half-life estimated for the predominant
compartment, soil, as determined by EPI
and the PBT Profiler methodology.
value for the lower MW components (MW<1,000); it is above the High
ig a high potential for bioaccumulation. The oligomers with a MW
water solubility, poor bioavailability and are not expected to be
EPIv4.11
Professional judgment
EPIv4.11

Estimate based on representative oligomers
with a MW< 1,000.
The substance has a MW >1,000 and is not
anticipated to be taken up by aquatic
organisms; therefore, bioconcentration is
not expected.

No data located.
         7-271

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JUNE 2014 DRAFT REPORT
Fyrol™ HF-5
PROPERTY/ENDPOINT

BAF
Metabolism in Fish
DATA
Confidential A:
0.94 for n=l
0.91 for n=2
0.90forn=3-5
(Estimated)
Confidential A: n>6 oligomers
(Estimated)
Confidential B: 81 for n=l
7 for n=2 (Estimated)

REFERENCE
EPIv4.11
Professional judgment
EPIv4.11

DATA QUALITY
Estimate based on representative oligomers
with a MW< 1,000.
No data located for MW >1,000 oligomers.

No data located.
ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring
Ecological Biomonitoring
Human Biomonitoring
No data located.
No data located.
This chemical was not included in the NHANES biomonitoring report (CDC, 2013).
         7-272

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                                                  JUNE 2014 DRAFT REPORT


Boethling RS, Nabholz JV (1997) Environmental assessment of polymers under the U.S. Toxic Substances Control Act. Washington, DC: U.S.
Environmental Protection Agency.

CDC (2013) Fourth national report on human exposure to environmental chemicals, updated tables, March 2013. Centers for Disease Control and
Prevention. http://www.cdc.gov/exposurereport/pdf/FourthReport UpdatedTables  Mar2013 .pdf. Accessed May 10, 2013.

ECOSAR (Ecological Structure Activity Relationship), Version 1.11. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/oppt/newchems/tools/21ecosar.htm.

EPA (1999) Determining the adequacy of existing data. Washington, DC: U.S. Environmental Protection Agency.
http: //www .epa. gov/hpv/pubs/general/datadeqfn .pdf.

EPA (2005) Pollution prevention (P2) framework. Washington, DC: U.S. Environmental Protection Agency, Office of Pollution Prevention and
Toxics, http://www.epa.gov/opptintr/newchems/pubs/sustainable/p2frame-june05a2.pdf.

EPA (2012) Using noncancer screening within the SF initiative. Washington, DC: U.S. Environmental Protection Agency.
http: //www .epa. gov/oppt/sf/pubs/noncan-screen .htm.

EPI Estimation Programs Interface (EPI) Suite, Version 4.11. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm.

ESIS (2012) European chemical Substances Information System. European Commission,  http://esis.jrc.ec.europa.eu/.

European Commission (2012) EU priority list of suspected endocrine disrupters.

Mill T (2000) Photoreactions in surface waters. In: Boethling R Mackay D, eds. Handbook of Property Estimation Methods for Chemicals,
Environmental Health Sciences. Boca Raton:  Lewis Publishers, 355-381.

OncoLogic (2008) U.S. EPA and LogiChem,  Inc. 2005, Version 7.0. 2008.

PBT Profiler Persistent (P), Bioaccumulative  (B), and Toxic (T) Chemical (PBT) Profiler, Version 1.301. Washington, DC: U.S. Environmental
Protection Agency, www.pbtprofiler.net.
                                                              7-273

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                                                           JUNE 2014 DRAFT REPORT
              Isopropylated triphenyl phosphate (IPTPP)
                                                   Screening Level Toxicology Hazard Summary

This table only contains information regarding the inherent hazards of flame retardant chemicals. Evaluation of risk considers both the hazard and exposure associated with the
substance including combustion and degradation by-products. The caveats listed in the legend and footnote sections must be taken into account when interpreting the hazard
information in the table.
VL = Very Low hazard L = Low hazard   = Moderate hazard H = High hazard VH = Very High hazard - Endpoints in colored text (VL, L,   , H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].






Chemical






CASRN
Human Health Effects

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Isopropylated triphenyl phosphate
(IPTPP)
68937-41-7
L
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                                                                        7-274

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                                                          JUNE 2014 DRAFT REPORT
                                            -n          .   _                                                    Use: Flame retardant
                                            Representative Structure
                                                                                                               CASRN: 68937-41-7
                                                                                                               MW: 452
                                                                                                               MF: C27
                                                                                                               Physical Forms: Liquid
                                                                                                               Neat:
SMILES: O=P(Oc2ccc(cc2)C(C)C)(Oc3ccc(cc3)C(C)C)Oclccc(ccl)C(C)C (Representative structure for tris(isopropylphenyl) phosphate)
cl(C(C)C)ccc(OP(=O)(Oc3ccc(C(C)C)cc3)Oc2ccccc2)ccl (Representative structure for di(isopropylphenyl) phenyl phosphate)
cl(C(C)C)ccc(OP(=O)(Oc3ccccc3)Oc2ccccc2)ccl (Representative structure for isopropylphenyl diphenyl phosphate)
Synonyms: Phenol, isopropylated, phosphate (3:1); IPPP; ITP; IPTPP; TIPPP; Isopropylated triphenyl phosphate; Isopropylated phenol phosphate
Chemical Considerations: The alternative, isopropylated triphenyl phosphate, may contain a mixture consisting of isopropylated triphenyl phosphates, with an
unspecified amount of isopropylation. Mono- to nona- isopropylphenyl phosphate have been found, for example tris[2,4,6-tri(propan-2-yl)phenyl] phosphate. The
majority of isomers contain isopropyl substitution at the ortho- and para- position although meta isomers may be present to a lesser extent. The isopropyl groups are
typically distributed between the three phenyl rings however di- and tri- alkylation may be present on a single phenyl ring (for example, diisopropylphenyl diphenyl
phosphate (CASRN 58570-87-9)). Isomers expected to be present will be discussed in this report as appropriate when determining hazard designations. A description
of the test sample and isomer content is included in the data entries when available. However test substance composition was not consistently reported in the literature.
Chemical, fate, and toxicity data for components of the mixture represented by other CASRN were collected in the preparation of this AA and are listed below:

  Phenol, isopropylated, phosphate (3:1) (CASRN 68937-41-7)
  Triphenyl phosphate, TPP (CASRN 115-86-6)
  4-isopropylphenyl diphenyl phosphate (CASRN 55864-04-5)
  2-isopropylphenyl diphenyl phosphate (CASRN 64532-94-1)
  Isopropyl phenyl diphenyl phosphate (CASRN 28108-99-8); (CASRN 101299-37-0)
  2-(l-Methylethyl)phenyldiphenyl ester phosphoric acid mixture w/triphenyl phosphate (CASRN 96300-97-9); (CASRN 66797-44-2)
  Di(isopropylphenyl)phenylphosphate (CASRN 28109-00-4)
  Di(2-isopropylphenyl)phenylphosphate (CASRN 69500-29-4)
  Tri(3-isopropylphenyl)phosphate (CASRN 72668-27-0)
  Tri(isopropylphenyl)phosphate (CASRN 26967-76-0)
  Tri(4-isopropylphenyl)phosphate (CASRN 2502-15-0)
  3,4-bis(l-methylethyl)phenyl diphenyl ester (CASRN 68155-51-1)
Estimated values using representative structures as indicated in the SMILES section of this assessment will be used to fill assessment data gaps. EPI v4.11 was used to
estimate physical/chemical and environmental fate values due to an absence of experimental data (Weil, 2001; ECHA, 2013b).
                                                                      7-275

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JUNE 2014 DRAFT REPORT
Polymeric: No
Oligomeric: Not applicable
Metabolites, Degradates and Transformation Products: Phenol (CASRN 108-95-2), isopropylphenol (CASRN 25168-06-3); diphenyl phosphate (CASRN 838-85-
7); 2-isopropyl phenol (CASRN 88-69-7), 4-isopropyl phenol (CASRN 99-89-8), 3 -isopropylphenol (CASRN 618-45-1) and diisopropyl phenols (CASRN 27923-56-
4) along with the corresponding mono and diphenyl phosphates by hydrolysis. Cyclic metabolites of isopropylated phenyl phosphates by metabolism in rabbit bile;
diphenyl phosphate in fish (Nobile et al, 1980; Huckins and Petty, 1983; Muir et al., 1989; Yang et al., 1990).
Analog: Tris(isopropylphenyl) phosphate isomers and other
isopropyl substituted phenyl phosphate esters anticipated to be
present in the commercial product were considered in the evaluation,
as indicated in the chemical considerations section; orthocresyl
phosphate
Endpoint(s) using analog values: Neurotoxicity
Structural Alerts: Organophosphates; Neurotoxicity (EPA, 2012).
Analog Structure: Not applicable
^^^

Risk Phrases: R48/22 - harmful: danger of serious damage to health by prolonged exposure if swallowed; R62 - possible risk of impaired fertility; R63
of harm to the unborn child;
R50/R53 - Very toxic to aquatic organisms. May cause long-term adverse effects in the aquatic environment.
There is currently no classification of "dangerous to the environment" for isopropylated triphenyl phosphate, itself. The commercial products containing
triphenyl phosphate are generally classified based on the triphenyl phosphate content of the product (Environment Agency, 2009; ECHA, 2013b).
- possible risk
isopropylated
Hazard and Risk Assessments: An Environmental Risk Evaluation report for isopropylated triphenyl phosphate was published in August 2009. This substance is
part of EPA's HPV Challenge and is a registered substance with the European Chemicals Agency (Great Lakes Chemical Corporation, 2001; Environment Agency,
2009; ECHA, 2013a, 2013b).
         7-276

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JUNE 2014 DRAFT REPORT
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
PHYSICAL/CHEMICAL PROPERTIES
Melting Point (°C)
Boiling Point (°C)
<-20
Pour point; OECD Guideline 102
(Measured)
-26
Reported as a range -12 to -26°C
(Measured)
-26
Reported as a melting/pour point
(Measured)
>300 Decomposes
(Measured)
>300 Decomposes
(Measured)
>400 at 735 mmHg
No boiling point observed up to 400°C;
OECD Guideline 103 (Measured)
>175°C at 0.05 mm Hg for o-
isopropylphenyl diphenyl phosphate;
180°C at 0.2 mm Hg m-isopropylphenyl
diphenyl phosphate;
185°C at 0.05 mm Hg p-isopropylphenyl
diphenyl phosphate (Measured)
>220 at 1 mmHg
ECHA, 2013b
IUCLID, 2001
^^^
Muir, 1984
Environment Agency, 2009
Environment Agency, 2009
ECHA, 201 3b
Wightman and Malaiyandi, 1983 (as
cited in Environment Agency, 2009)
Muir, 1984; Boethling and Cooper,
Test material identified as phenol,
isopropylated, phosphate (3:1).
Reported in a secondary source for
isopropylated triphenyl phosphates.
The broad melting point range is
consistent with a mixture.
Reported in a secondary source for
isopropylphenyl diphenyl
phosphate.
Reported in a secondary source for
a commercial isopropylphenyl
diphenyl phosphate product,
Reofos 50.
Data are for a commercial
triisopropylphenyl phosphate
product, Durad 3 10M; reported in a
secondary source.
Data for a commercial product,
Reofos 65; reported in a secondary
source.
Data are for pure isomers at
reduced pressures; reported in a
secondary source. The
diisopropylated phenyl phosphate
and higher alkylated isomers are
expected to boil at higher
temperatures.
Reported in a secondary source for
         7-277

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JUNE 2014 DRAFT REPORT
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT

Vapor Pressure (mm Hg)
DATA
Reported as 220-23 0°C at 1 mm Hg for
commercial isopropylphenyl diphenyl
phosphate (Measured)
>220 at 4 mmHg
Reported as 220-270° at 5.32 hPa
(Measured)
2.8xlO-7at30°C
(Measured)
5.8xlO-6at70°C
Reported for triphenyl phosphates with a
relatively high degree of alkylation
(such as tris(isopropylphenyl)
phosphate) (Measured)
2.3xlO'5 at 70°C
Reported for triphenyl phosphates with a
relatively low degree of alkylation (such
as isopropylphenyl diphenyl phosphate)
(Measured)
<0.026 at 150°C
Reported as 0.0346 hPa at 150°C
(Measured)
3.4at20°C
OECD Guideline 104; additional study
4.4 mm Hg at 25 °C (Measured)
4xlO-8at25°C
(Estimated)
REFERENCE
1985
IUCLID, 2001
Environment Agency, 2009
Environment Agency, 2009
^^
Environment Agency, 2009
IUCLID, 2001
ECHA, 2013b
EPIv4.11
DATA QUALITY
a commercial isopropylphenyl
diphenyl phosphate product, at
reduced pressure.
Data are for commercial products
Reofos and Durad; reported in a
secondary source.
Reported in a secondary source for
a commercial isopropylphenyl
diphenyl phosphate.
Reported in a secondary source.
Reported in a secondary source.
Reported in a secondary source for
commercial products, Reofos and
Durad.
Reported in a secondary source for
commercial product, Reofos 65.
Based on a representative structure
for a component of the mixture,
with one isopropyl substituent
         7-278

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JUNE 2014 DRAFT REPORT
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT

Water Solubility (mg/L)
DATA

<2xl(r8at250C
(Estimated)
0.026 (Estimated)
0.00083 (diisopropylated triphenyl
phosphate isomer);
2.6xlO"5 (triisopropylated triphenyl
phosphate isomer) (Estimated)
<2.2 (Measured)
Shake flask method
<2 (Measured)
*
Reported as 0.7 to 2 mg/L in water
considered insoluble in water
0.33 (Measured)
OECD 105; analyzed using GC/MS
REFERENCE

EPIv4.11
EPIv4.11
EPIv4.11;EPA, 1999
^^
Saeger et al., 1979 (as cited in
Environment Agency, 2009)
IUCLID, 2001
ECHA, 2013b
DATA QUALITY
group.
Based on representative structures
for components of the mixture,
with two or more isopropyl
substituent groups.
Based on a representative structure
for a component of the mixture,
with one isopropyl substituent
group.
Estimated value is less than the
cutoff value, <0.001 mg/L, for non-
soluble compounds according to
HPV assessment guidance. Based
on representative structures for
components of the mixture, with
two or more isopropyl substituent
groups.
Reported in a secondary source for
Kronitex 1000, consisting of
isopropylphenyl diphenyl
phosphate along with triphenyl
phosphate and
bis(isopropylphenyl) phenyl
phosphate.
Reported in a secondary source for
commercial products Reofos and
Durad.
Reported in a secondary source for
a commercial product Reofos 65.
         7-279

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                                                          JUNE 2014 DRAFT REPORT
                                               Isopropylated triphenyl phosphate CASRN 68937-41-7
          PROPERTY/ENDPOINT
               DATA
         REFERENCE
       DATA QUALITY
Log Kow
6.2 (monoisopropylated triphenyl
phosphate);
7.6 (diisopropylated triphenyl
phosphate);
9.1 (triisopropylated triphenyl
phosphate);
(Estimated)
EPIv4.11
Estimated using representative
structures indicated in the SMILES
section for isopropylated phenyl
phosphate with one, two and three
isopropyl substituent groups
respectively.
                                             <5.44
                                             (Measured)
                                    IUCLID, 2001
                                 Inadequate. Reported in a
                                 secondary source for commercial
                                 product Reofos and Durad. The
                                 components of this mixture are
                                 expected to have a range of Kow
                                 values not represented in the study
                                 result.
                                             5.3
                                             Modified shake flask method
                                             (Measured)
                                     Saeger et al., 1979 (as cited in
                                     Environment Agency, 2009)
                                 Inadequate since the study was
                                 performed on a commercial
                                 product, Kronitex 1000, consisting
                                 of isopropylphenyl diphenyl
                                 phosphate along with triphenyl
                                 phosphate and
                                 bis(isopropylphenyl) phenyl
                                 phosphate. The components of this
                                 mixture are expected to have a
                                 range of Kow values not represented
                                 in the study result.
                                             <6.57

                                             3.23 (for triphenyl phosphate) and 4.30,
                                             5.40 and 6.57 (for three other
                                             components of the isopropylphenyl
                                             diphenyl phosphate mixture); the mean
                                             value obtained for all components was
                                             5.99
                                    Renberg et al., 1980 (as cited in
                                    Environment Agency, 2009)
                                 Inadequate, reported in a secondary
                                 source for a commercial product,
                                 Kronitex 1000. The components of
                                 this mixture are expected to have a
                                 range of Kow values.
                                                                      7-280

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JUNE 2014 DRAFT REPORT
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT

Flammability (Flash Point)
Explosivity
Pyrolysis
pH
pKa
DATA
High performance thin layer
chromatography (HPTLC) method for a
commercial product (Measured)
Flash points: >220°C, 200°C, 199°C
Reported for commercial products,
Reofos 50, Durad 310M, and for
isopropylated triphenyl phosphates,
respectively (Measured)
Auto ignition temperatures: 585°C,
5650Cand551°Cat 101.3 Pa reported
for commercial products Reofos 50;
Durad 3 10M and isopropylated triphenyl
phosphates, respectively (Measured)
Not expected to form explosive mixtures
with air (Estimated)

Not applicable (Estimated)
Not applicable (Estimated)
REFERENCE

IUCLID, 2001 (as cited in
Environment Agency, 2009)
IUCLID, 2001 (as cited in
Environment Agency, 2009)
^^
Professional judgment

Professional judgment
Professional judgment
DATA QUALITY

Reported in a secondary source for
commercial products.
Reported in a secondary source for
commercial products.
No experimental data located;
aased on its use as a flame
retardant.
No data located.
Does not contain functional groups
that are expected to ionize under
environmental conditions.
Does not contain functional groups
that are expected to ionize under
environmental conditions.
         7-281

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                                                         JUNE 2014 DRAFT REPORT
                                              Isopropylated triphenyl phosphate CASRN 68937-41-7
          PROPERTY/ENDPOINT
                                          DATA
                                             REFERENCE
                                       DATA QUALITY
                                                         HUMAN HEALTH EFFECTS
Toxicokinetics
                           No data were available on the absorption, distribution or metabolism of isopropylated triphenyl phosphates
                           in experimental animals or humans. Isopropylated phenyl phosphates, R3 (tri-(o-iso-propylphenyl
                           phosphate)) and Reolube HYD 46, were metabolized within 24 hours and detected in the bile of rabbits
                           following oral administration. Dermal absorption rates in human epidermis studies for IPTPP component
                           TPP were 0.67 and 0.9 ug/cm2/h for Reolube HYD 46 and Reofos 50, respectively. Absorption rates for
                           IPTPP component 2-IDPP were 0.54 and 3.32 ug/cm2/h, for Reolube HYD 46 and Reofos 50, respectively.
                           Steady state was achieved within one hour. Experimental data for the FM550 (a mixture made up of a sum
                           total of TBB and TBPH of 50% with other components identified as IPTPP and TPP) indicate that
                           absorption of TBB can occur in rats following oral exposure from gestation through lactation. At least one
                           component of the mixture was detected in tissues of exposed dams and the pups following exposure to
                           FM550.
Dermal Absorption in vitro
                           Two in vitro studies using the human
                           epidermis to investigate absorption rates
                           of IPTPP commercial formulations
                           Reolube HYD 46 and Reofos 50.
                           Absorption rates for IPTPP component
                           TPP were 0.67 and 0.9 (jg/cm2/h for
                           Reolube HYD 46 and Reofos 50,
                           respectively. Absorption rates for IPTPP
                           component 2-IDPP were 0.54 and 3.32
                           (jg/cm2/h, for Reolube HYD 46 and
                           Reofos 50, respectively. Steady state
                           was achieved within one hour.
                                   IUCLID, 2000; Environment
                                   Agency, 2009
                                Limited study details reported in a
                                secondary source. Study was
                                conducted on commercial products
                                Reolube HYD 46 and Reofos 50
                                (concentrations not specified)
Absorption,
Distribution,
Metabolism &
Excretion
Oral, Dermal or Inhaled
Rabbits were administered single oral
doses of isopropylated phenyl
phosphates via gavage. Cyclic
metabolites of isopropylated phenyl
phosphates were detected in the bile
collected from the rabbits for up to 24
hours post-administration.
Yangetal., 1990
Reliable primary source. Study was
conducted using Isopropylated
phenyl phosphates, including R3
(tri-(o-iso-propylphenyl
phosphate)) and Reolube Hyd 46
                                            Pregnant rats were administered 0, 0.1
                                            or 1 mg/kg-day of FM550 in the diet
                                                               Patisauletal., 2013
                                                                   Non guideline study indicates that
                                                                   absorption of this compound can
                                                                    7-282

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JUNE 2014 DRAFT REPORT
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT


Other
Acute Mammalian Toxicity
Acute Lethality
Oral
DATA
across gestation and through lactation
(GD8-PND21).
FM550 components including TBPH
was detected in adipose, liver, and
muscle tissues in Dams at PND 2 1 with
the highest concentration in the adipose
tissue (768 ng/g w.w. in high dose, 29.6
ng/g w.w. in low dose, < 7.0 ng/g w.w.
in controls). The primary metabolite of
TBB (TBBA) was also detected in liver
tissue of dams on PND 2 1 .
TBB was detected in pooled PND2 1 pup
adipose tissue. TBB was not detected in
pooled pup adipose tissue by PND220.

REFERENCE
^^^
k^

DATA QUALITY
occur in rats through oral exposure;
the test substance identified as
FM550 is a mixture made up of
TBB, TBPH (sum total of TBB
and TBPH is approximately
50%), TPP and IPTPP; it is
unclear if absorption in pups
occurred due to gestational
exposure or through lactation.
^o data located.
LOW: Based on the weight of evidence for multiple studies. The test substance was not acutely toxic to rats,
rabbits, and Chinese hamsters via the oral route and rats and rabbits via the dermal route of exposure.
Acute inhalation data were inadequate to assess hazard. Oral and dermal LD50 values ranged from >2,000
to >20,000 mg/kg. Adequate data for the inhalation route were not located.
Rabbit oral lethal dose low (LDLo) = 3.2
mL/kg (-3,520 mg/kg)
^
7
Rat oral LD50 >5,000 mg/kg
Rat Oral LD50 <20,000 mg/kg (females);
>20,000 mg/kg (males)
FMC Corporation, 1990
EPA, 2010
IUCLID, 2000, 2001
Sufficient study details reported in
a primary source. Study was
conducted using Durad 1 10 (100%
phenol, isopropylated phosphate
(3:1)); limit test using 3 rats/sex.
The LDLo value was converted to
mg/kg using a density of 1 . 108
g/cm3.
Limited study details reported in a
secondary source. Study was
conducted using Durad 300 or
Reofos 50.
Limited study details reported in a
secondary source. Study was
         7-283

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JUNE 2014 DRAFT REPORT
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT


Dermal
Inhalation
Carcinogenicity

OncoLogic Results
Carcinogenicity (Rat and
Mouse)
Combined Chronic
Toxicity/Carcinogenicity ^(
DATA
Reofos 50 and Reofos 65: 0/5 deaths in
males and 4/5 deaths in females
Reofos 95 and Durad 300: no deaths
Chinese hamster oral LD0 >5,000 mg/kg
Rabbit Dermal LDLo = 2.5 mL/kg (~
2,750 mg/kg)
Rat Dermal LD50 >2,000 mg/kg
Rabbit Dermal LD50 > 10,000 mg/kg
Rat Inhalation 1 -hour LC50 >200 mg/L
\
REFERENCE

IUCLID, 2000
ChemID, 2013
k^
IUCLID, 2000
IUCLID, 2000
IUCLID, 2001
DATA QUALITY
conducted using Reofos 50, Reofos
65, Reofos 95 or Durad 300.
Limited study details reported in a
secondary source. Study was
conducted using Reofos 50.
Limited study details reported in a
secondary source. The LDLo value
was converted to mg/kg using a
density of 1.1 08 g/cm3.
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source. This study was
classified as "invalid" in the
IUCLID document.
MODERATE: No adequate Carcinogenicity studies were located. The OncoLogic program estimates
marginal risk for Carcinogenicity; In addition, there is uncertainty regarding the Carcinogenicity of
Isopropylated triphenyl phosphate due to the lack of data for this substance. Carcinogenic effects cannot be
completely ruled out.
Marginal
J

OncoLogic, 2008



No data located.
No data located.
         7-284

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                                                          JUNE 2014 DRAFT REPORT
                                               Isopropylated triphenyl phosphate CASRN 68937-41-7
          PROPERTY/ENDPOINT
               DATA
         REFERENCE
       DATA QUALITY
                 Other
3 days of exposure to [Formulation 7],
tested at concentrations between 0.04
and 5.0 g/mL, did not induce cell
transformation in cultured Balb/c-3T3
cells (with or without metabolic
activation)
Submitted confidential study
Data are inadequate as described in
an robust summary not yet
validated; test substance undefined
and identified only as formulation
7; data are intended to support any
adequate carcinogenicity data.
Genotoxicity
LOW: Based on weight of evidence that includes negative results in gene mutation tests (in vitro and in vivo)
and no evidence of chromosomal aberrations (in vivo) in mice. One chromosomal aberration test in
hamsters resulted in positive results; however, based on weight of evidence, it seems the potential for
genotoxicity is Low. All studies were conducted  using commercial mixtures of Reofos 50 and/or Reolube
HYD 46 (composition not specified).
                 Gene Mutation in vitro
Negative, gene mutations in cultured
L5178Y mouse lymphoma cells with
and without metabolic activation.
                                             Negative, gene mutations in Balb/3T3
                                             mouse embryo fibroblasts with and
                                             without metabolic activation
                                             Negative, multiple studies using several
                                             strains of Salmonella typhimurium with
                                             and without metabolic activation.
                                             Negative, Salmonella typhimurium (5
                                             strains, unspecified) with and without
IUCLID, 2000
                                    IUCLID, 2000
                                    IUCLID, 2000, 2001
                                    IUCLID, 2001
Limited study details reported in a
secondary source. Study was
conducted using commercial
mixture Reofos 50 (30% TPP, 70%
IPTPP). GLP-compliant.
                                 Limited study details reported in a
                                 secondary source. Studies were
                                 conducted using commercial
                                 mixtures Reofos 50 (30% TPP,
                                 70% IPTPP) and Reolube HYD 46
                                 (composition not specified).
                                 Limited study details in secondary
                                 sources; commercial mixtures
                                 tested included: Reofos 50 (30%
                                 TPP, 70% IPTPP), Reofos 65 (20%
                                 TPP, 80% IPTPP), Reofos 95 (9%
                                 TPP, 91% IPTPP), Durad 300 (5%
                                 TPP, 95% IPTPP) and Reolube
                                 FTYD 46 (composition not
                                 specified).
                                 Limited study details reported in a
                                 secondary source. This study is
                                                                      7-285

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JUNE 2014 DRAFT REPORT
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT


Gene Mutation in vivo
Chromosomal Aberrations in
vitro
Chromosomal Aberrations in
vivo
DATA
metabolic activation
Negative, dominant lethal mutations in
mature germ cells of male Drosophila
melanogaster

Negative, sister chromatid exchanges
(SCEs) in male and female Chinese
hamsters (single oral gavage)
Negative, micronuclei induction in
NMRI female mice (single oral gavage)
Negative, chromosomal aberrations in
bone marrow from male and female
Chinese hamsters administered Reofos
50 or Reolube HYD 46 by gavage at
5000 mg/kg.
Positive, significantly increased
incidence of anomalies of nuclei in bone
REFERENCE

IUCLID, 2000
^^^

IUCLID, 2000
^^
IUCLID, 2000
IUCLID, 2000
IUCLID, 2000
DATA QUALITY
classified as "not assignable" in the
IUCLID document.
Limited study details reported in a
secondary source. Studies were
conducted using commercial
mixture Reofos 50 (30% TPP, 70%
IPTPP). GLP-compliant.
^o data located.
Limited study details reported in a
secondary source. Studies were
conducted using commercial
mixtures Reofos 50 (30% TPP,
70% IPTPP) and Reolube HYD 46
(composition not specified). Non-
GLP.
Limited study details reported in a
secondary source. Study was
conducted using commercial
mixture Reolube HYD 46
(composition not specified). Non-
GLP, non-guideline.
Limited study details reported in a
secondary source. Studies were
conducted using commercial
mixtures Reofos 50 (30% TPP,
70% IPTPP and Reolube HYD 46
^composition not specified). GLP-
compliant, according to OECD
guideline 475.
Limited study details reported in a
secondary source. Studies were
         7-286

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JUNE 2014 DRAFT REPORT
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT


DNA Damage and Repair
Other
Reproductive Effects

Reproduction/Developmental
Toxicity Screen ^
DATA
marrow cells from male and female
Chinese hamsters administered Reofos
50 or Reolube HYD 46 by single gavage
at doses up to 5,000-6,000 mg/kg
Negative, DNA damage and repair in
cultured rat hepatocytes with and
without metabolic activation

REFERENCE

Environment Agency, 2009
k^

DATA QUALITY
conducted using commercial
mixtures Reofos 50 (30% TPP,
70% IPTPP) and Reolube HYD 46
(composition not specified). GLP-
compliant, non-guideline.
Limited study details reported in a
secondary source. Studies were
conducted using commercial
mixtures Reofos 50 (30% TPP,
70% IPTPP) and Reolube HYD 46
^composition not specified). Non-
GLP.
No data located.
HIGH: Based on a LOAEL of 25 mg/kg-day in a combined subchronic reproductive/developmental toxicity
screening test in rats. Effects included changes in ovarian and epididymal weights (25 and 100 mg/kg-day,
respectively) and reduced fertility (100 and 400 mg/kg-day); the final study results were not available and
the formulation of the test substance was not specified. In addition, this substance has been assigned the risk
phrase R62 - possible risk of impaired fertility. In a dermal study with Reolube HYD (components not
specified) in rats, reduced absolute and relative testicular weights and slight testicular tubular atrophy were
observed at 1,000 mg/kg-day.

|No data located.
         7-287

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JUNE 2014 DRAFT REPORT
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT























Combined Repeated Dose
with Reproduction/
Developmental Toxicity
Screen

















Reproduction and Fertility
Effects
DATA
In a combined repeated dose
reproductive/developmental toxicity
screening study, male and female rats
were orally gavaged with 0, 25, 100 or
400 mg/kg-day test substance
(isopropylated triphenyl phosphate;
specific formulation confidential) for 14
days premating, during mating for a total
of at least 28 days of treatment of males,
and during gestation and up to 4 days
postpartum for a total of up to 53 days of
treatment of females.
Results: Limited to summary statements
that indicated decreased fertility at mid-
and high-dose levels, decreased litter
size and pup survival at least at high
dose, and treatment-related changes in
selected organ weights at all dose levels.
NOAEL: Not established
LOAEL: 25 mg/kg-day (treatment-
related organ weight changes)


REFERENCE
Submitted confidential study; Great
Lakes Chemical Corporation, 2004a,
2004b


^^^



k^^ '



^^



7





DATA QUALITY
Results from 2 combined repeated
dose reproduction/developmental
toxicity screening tests of
isopropylated triphenyl phosphate
(formulation confidential).
















^o data located.

         7-288

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                                                        JUNE 2014 DRAFT REPORT
                                              Isopropylated triphenyl phosphate CASRN 68937-41-7
          PROPERTY/ENDPOINT
              DATA
         REFERENCE
       DATA QUALITY
                 Other
In a dermal study in rats, test substance
was applied to shaved skin at 0, 40, 200
or 1,000 mg/kg for 6 hours/day, 5
days/week for 4 weeks. Reduced
absolute and relative testicular weights
(1,000 mg/kg-day); slight testicular
tubular atrophy (control and high-dose
males). No associated microscopic
findings).
NOAEL: 200 mg/kg-day
LOAEL: 1,000 mg/kg-day
IUCLID, 2000
Limited study details reported in a
secondary source. Study conducted
using commercial mixture Reolube
HYD (components not specified).
Developmental Effects
HIGH: Estimated based on analogy to Kronitex TCP (1330-78-5). Reduced fetal body weight was reported
at 20 mg/kg-day (NOAEL not established; lowest dose tested) in a developmental study in rats orally
exposed to the analog. In addition, increased skeletal variations were reported at 750 mg/kg-day for the
analog. A LOAEL of 400 mg/kg-day (NOAEL = 100 mg/kg-day) was reported following exposure to
Isopropylated triphenyl phosphate in a combined subchronic reproductive/developmental toxicity screening
test in rats. Effects included reduced pre- and post-natal survival; the final study results were not available
and the formulation of the test substance was not specified. Development effects were reported in a study in
pregnant Wistar rats administered a FM550 mixture (sum total of TBB and TBPH approximately 50%
with additional  components identified as IPTPP and TPP) during gestation though lactation (GD8 -
PND21); developmental effects included early female puberty, weight gain, altered exploratory behavior,
and increased male left ventricle thickness (LOAEL = 1 mg/kg-day, NOAEL = 0.1 mg/kg-day). It is
uncertain which component or components of the FM 550 mixture is driving the reported developmental
effects. This substance has been assigned the risk phrase R63 - possible risk of harm to the unborn child.
There were no experimental data for the neurodevelopmental toxicity endpoint located; There is uncertain
concern for developmental neurotoxicity based on the potential for Cholinesterase (ChE) inhibition in dams
that may result  in alterations of fetal neurodevelopment.
                 Reproduction/
                 Developmental Toxicity
                 Screen
                                                                      data located.
                                                                    7-289

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                                                JUNE 2014 DRAFT REPORT
                                     Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
               DATA
         REFERENCE
       DATA QUALITY
       Combined Repeated Dose
       with Reproduction/
       Developmental Toxicity
       Screen
In a combined repeat
dose/reproductive/developmental
toxicity screening study, male and
female rats were orally gavaged with 0,
25, 100 or 400 mg/kg-day test substance
(isopropylated triphenyl phosphate;
specific formulation confidential) for 14
days premating, during mating for a total
of at least 28 days of treatment for
males, and during gestation and up to 4
days postpartum for a total of up to 53
days of treatment for females.

Results: Limited to  summary statements
that indicated decreased fertility at mid-
and high-dose levels, decreased litter
size and pup survival at least at high
dose, and treatment-related changes in
selected organ weights at all dose levels.

NOAEL (maternal): Not established
LOAEL (maternal): 25 mg/kg-day
(treatment-related organ weight
changes)

NOAEL (developmental): 100 mg/kg-
day
LOAEL (developmental): 400 mg/kg-
day (decreased litter size and pup
survival)
Submitted confidential study; Great
Lakes Chemical Corporation, 2004b
Results from 2 combined repeated
dose reproduction/developmental
toxicity screening tests of
isopropylated triphenyl phosphate
(formulation confidential).
                                                            7-290

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JUNE 2014 DRAFT REPORT
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT































Prenatal Development























Postnatal Development ^
Prenatal and Postnatal
Development




DATA
In a developmental study, female rats
were orally gavaged with 0, 20, 100,
400, and 750 mg/kg-day of the analog
tricresyl phosphate (TCP) on GD 0-19.
Maternal toxicity was evident at > 100
mg/kg-day and included increased
frequency of salivation, hair loss, and
unkempt appearance. Reduced body
weight and body weight gain was
observed at 400 and 750 mg/kg-day.
There were no maternal macroscopic
findings.
Fetal body weight was reduced at all
dose levels and there was an increase in
skeletal variations (indicating delayed
fetal ossification) at 750 mg/kg-day.
Maternal toxicity:
NOAEL: 20 mg/kg-day
LOAEL: 100 mg/kg-day
Developmental toxicity:
NOAEL: Not established
LOAEL: 20 mg/kg-day (lowest dose
tested)
(Estimated by analogy)

Pregnant Wistar rats were administered
0, 0.1 or 1 mg/kg-day of the analog
FM550 in the diet during gestation and
through lactation (GD8 - PND 21);
Maternal toxicity: Increased serum
thyroxine (T4) levels in the high dose
REFERENCE
ECHA, 2013a




^^^



^^*



^^


7








Patisauletal., 2013





DATA QUALITY
Estimated based on analogy; study
was conducted using Kronitex TCP
^tris (methylphenyl) phosphate;
CASRN 1330-78-5).




















No data located.
Estimated based on data for
FM550 mixture; non guideline
study; the test substance identified
as FM550 is a mixture made up of
TBB, TBPH (sum total of TBB
and TBPH is approximately
         7-291

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                                                JUNE 2014 DRAFT REPORT
                                     Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   dams compared to controls was
                                   reported. There was no significant
                                   change in triiodothyronine (T3) levels in
                                   dam serum. Decreased hepatic
                                   carboxylesterease activity was also
                                   reported in dams in the high dose group.
                                   Developmental toxicity: female
                                   offspring in the high dose group
                                   displayed a significantly earlier vaginal
                                   opening when compared to controls. A
                                   statistically significant increase in
                                   weight was reported in both males and
                                   females in the high dose group at PND
                                   120. This effect persisted through PND
                                   180 to PND 220 with high dose males
                                   and females having  significantly higher
                                   weights than same sex controls. A dose-
                                   dependent decrease  in the number of rats
                                   to enter with open arms, (indicating
                                   anxiety), was reported in both male and
                                   female offspring.  Increased blood
                                   glucose levels were  reported in male
                                   offspring in the high-dose group
                                   compared to controls.  There was no
                                   statistically significant difference in
                                   heart weight of male or female
                                   offspring. Left ventricular (LV) free
                                   wall thickness was significantly
                                   increased in male offspring in the high
                                   dose group; there  were no changes in
                                   LV thickness in females at any dose.

                                   Maternal Toxicity:
                                   NOAEL: 0.1 mg/kg-day
                                                       50%), TPP and IPTPP; it is not
                                                       clear which component or
                                                       components of the mixture are
                                                       driving the reported developmental
                                                       effects.
                                                            7-292

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JUNE 2014 DRAFT REPORT
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT


Developmental Neurotoxicity
Other
DATA
LOAEL: 1 mg/kg-day
Developmental toxicity:
NOAEL: 0.1 mg/kg-day
LOAEL: 1 mg/kg-day (based on early
vaginal opening in females, increased
weight in males and females, decreased
open arm behavior, increased blood
glucose levels in males and increased
LV thickness in males)
Uncertain concern for developmental
neurotoxicity based on the potential for
Cholinesterase (ChE) inhibition in dams
that may result in alterations of fetal
neurodevelopment

REFERENCE
^^^
Professional judgment
^^

DATA QUALITY

Estimated based on a structural
alert for organophosphates for the
neurotoxicity endpoint.
No data located.
         7-293

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                                                          JUNE 2014 DRAFT REPORT
                                               Isopropylated triphenyl phosphate CASRN 68937-41-7
          PROPERTY/ENDPOINT
               DATA
         REFERENCE
       DATA QUALITY
Neurotoxicity
HIGH: Based on analogy to ortho-cresyl phosphate; IPTPP has the potential to undergo a similar
mechanism of action as ortho-cresyl phosphate with the formation of an intermolecular intermediate that
effects the nervous system. Significant inhibition of brain ChE and NTE activity was observed in rats
following single oral gavage with 2,000 mg/kg of commercial mixture Reofos 54. Inhibition of ChE was also
seen in rats following dermal exposure with 500 and 1,000 mg/kg of commercial mixtures Kronitex 50 and
Reolube HYD, respectively. There is potential for neurotoxicity based on a structural alert for
organophosphates.
                 Neurotoxicity Screening
                 Battery (Adult)
                 Other
Male rats (5/group) were administered
2,000 mg/kg Reofos 65 via single oral
gavage. No clinical signs of toxicity in
treated animals; positive control animals
gavaged with tri-o-cresyl phosphate
(TCOP) displayed lacrimation, tremors,
staining and had lowered body
temperatures. Significant inhibition of
brain cholinesterase and neuropathy
target esterase activity (35 and 50% less
than controls, respectively) in treated
animals. Serum cholinesterase activity in
treated animals was 87% less than that
of controls, compared to 94% less in
positive control (TOCP-treated) animals.
                                             Rats were exposed (head only) for 20
                                             minutes to an unspecified concentration
                                             of smoke and decomposition gases from
                                             foam containing equal proportions of the
                                             test substance; There were no convulsive
                                             seizures or characteristic of exposure to
                                             toxic bicyclic phosphites or phosphates
                                             observed.
In a dermal study in rats, test substance
IUCLID, 2000
                                     Submitted confidential study
IUCLID, 2000
Limited study details reported in a
secondary source. Study conducted
using commercial mixture Reofos
65 (20% TPP, 80% IPTPP).
                                 Study was not conducted according
                                 to standard guidelines; study
                                 evaluated neurotoxicity of test
                                 substance. Test substance
                                 identified as combustion products
                                 of an isopropylated triaryl
                                 phosphates/ triphenyl phosphate
                                 mixture in the presence of cyclic
                                 phosphonate compounds; exposure
                                 concentration not specified.
Limited study details reported in a
                                                                      7-294

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                                                JUNE 2014 DRAFT REPORT
                                     Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   was applied to shaved skin at 0, 40, 200
                                   or 1,000 mg/kg for 6 hours/day, 5
                                   days/week for 4 weeks. Slightly
                                   depressed plasma ChE activity (females
                                   at l,000mg/kg-day)

                                   NOAEL: 200 mg/kg-day
                                   LOAEL: 1,000 mg/kg-day
                                                      secondary source. Study conducted
                                                      using commercial mixture Reolube
                                                      HYD (components not specified)
                                   In a dermal study in rats (5/sex/group),
                                   Kronitex 50 was applied to shaved skin
                                   at 0, 100, 500 or 2,000 mg/kg 6
                                   hours/day, 5 days/week for 4 weeks.
                                   Decreased plasma cholinesterase (ChE)
                                   activity (females at 500 and 2,000
                                   mg/kg-day); decreased erythrocyte ChE
                                   activity (males, 2,000 mg/kg-day)

                                   NOAEL: 100 mg/kg-day
                                   LOAEL: 500 mg/kg-day
                      IUCLID, 2000
                                   There is potential for neurotoxicity
                                   based on the presence of the
                                   organophosphates structural alert.
                                   (Estimated)
                      Professional judgment
                                   Numerous studies assessed the potential
                                   for commercial isopropylated phenyl
                                   phosphate test substances (e.g., Reofos
                                   50, Reofos 65, Reofos 95, Reofos 120,
                                   Reolube HYD 46) to cause delayed
                                   neuropathy in hens. Ataxia and axonal
                                   degeneration could be elicited by single
                                   dosing at 2,000 mg/kg or higher and by
                                   repeated dosing at 90 mg/kg-day or
                                   higher. One study employed the
                      IUCLID, 2000
                       Limited study details reported in a
                       secondary source. Study conducted
                       using commercial mixture
                       Kronitex 50 (components not
                       specified). Limited number of
                       endpoints assessed.
                       Estimated based on structural alert
                       for organophosphates.
                       Sufficient evidence that
                       commercial isopropylated phenyl
                       phosphate formulations cause
                       delayed neuropathy in hens.
                       IUCLID (2000) summarized
                       results from a number of
                       unpublished studies.
                                                            7-295

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                                                JUNE 2014 DRAFT REPORT
                                     Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   inhalation exposure route and reported
                                   ataxia and degenerative neurological
                                   effects following single 8-hour exposure
                                   to aerosols of Reofos 50 at 2.4 mg/L (no
                                   effects at 0.62 mg/L).
                                   Potential for neurological effects; this
                                   substance has the potential to undergo a
                                   similar mechanism of action as ortho-
                                   cresyl phosphate with the formation of
                                   an intermolecular intermediate that
                                   effects the nervous system.
                                   (Estimated by analogy)
                     Professional judgment
                       Estimated based on analogy to
                       ortho-cresyl phosphate and
                       professional judgment.
                                                            7-296

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                                                          JUNE 2014 DRAFT REPORT
                                               Isopropylated triphenyl phosphate CASRN 68937-41-7
          PROPERTY/ENDPOINT
               DATA
REFERENCE
DATA QUALITY
Repeated Dose Effects
HIGH: Based on a combined repeated dose with reproductive/developmental toxicity screen test in rats; a
LOAEL of 25 mg/kg-day (lowest dose tested) was determined for changes in organ weights (NOAEL was
not established); final study results were not available and the test substance formulation was not specified.
A LOAEL of 460 mg/kg-day in rats following 28 days of dietary exposure to commercial mixture Kronitex-
100 (composition not specified). Dermal NOAELs were 100 and 200 mg/kg-day in rats following 4 weeks of
exposure to commercial mixtures Kronitex 50 and Reolube HYD, respectively. In addition, there may be
some potential for repeated dose effects based on analogy to TPP, a component of the commercial mixture.
                                             In a combined repeated dose
                                             reproductive/developmental toxicity
                                             screening study, male and female rats
                                             were orally gavaged with 0, 25, 100 or
                                             400 mg/kg-day test substance
                                             (isopropylated triphenyl phosphate;
                                             specific formulation confidential) for 14
                                             days premating, during mating for a total
                                             of at least 28 days of treatment of males,
                                             and during gestation and up to 4 days
                                             postpartum for a total of up to 53 days of
                                             treatment of females.
                                             Treatment-related changes in selected
                                             organ weights at all dose levels

                                             NOAEL: Not established
                                             LOAEL: 25 mg/kg-day (based on
                                             changes in organ weights)
                                             Sprague-Dawley rats (10/sex) were
                                             exposed to Kronitex 100 in the diet at
                                             concentrations of 0, 0.1, 0.5, or 1.0%
                                             (~0, 91, 460, or 910 mg/kg-day) for 28
                                             days; Mortalities included 12 rats (1
                                             control, 4 low-dose, 4 mid-dose, and 3
                                             high-dose) that were determined not to
                                             be treatment related; there were no
                                    Submitted confidential study; Great
                                    Lakes Chemical Corporation, 2004a,
                                    2004b
                       Limited study results reported in
                       study summary statements;
                       screening tests of isopropylated
                       triphenyl phosphate (formulation
                       confidential).
                                    Submitted confidential study:
                                    IUCLID, 2000, 2001
                       Limited study details provided in a
                       secondary source. Study was
                       conducted using commercial
                       mixture Kronitex K-100 (purity,
                       composition not specified). Doses
                       were reported as % in the diet but
                       were converted by SRC, Inc. to
                       mg/kg bw-day using EPA 1988
                                                                     7-297

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                                                JUNE 2014 DRAFT REPORT
                                     Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   effects on urinalysis results or incidence
                                   of gross lesions at necropsy. Reduced
                                   feed consumption was observed in the
                                   mid-dose group in both sexes and
                                   reduced body weight gain was noted in
                                   high-dose females. Abnormalities (not
                                   specified) were observed in clinical
                                   chemistry measurements in mid- and
                                   high-dose groups and in hematology
                                   parameters at the high dose. Relative
                                   liver weights were elevated in all treated
                                   groups. There were no indications of
                                   treatment-related histopathologic lesions
                                   in livers or kidneys of high-dose groups.

                                   NOAEL: 0.1% (-91 mg/kg-day)
                                   LOAEL: 0.5% (-460 mg/kg-day) based
                                   on unspecified abnormalities in clinical
                                   chemistry
                                                      reference values for body weight
                                                      and food consumption.
                                   In a dermal study in rats (5/sex/group),
                                   Kronitex 50 was applied to shaved skin
                                   at 0, 100, 500 or 2,000 mg/kg 6
                                   hours/day, 5 days/week for 4 weeks.
                                   Decreased plasma cholinesterase (ChE)
                                   activity (females at 500 and 2,000
                                   mg/kg-day); decreased erythrocyte ChE
                                   activity (males, 2,000 mg/kg-day);
                                   increased adrenal weights and slight
                                   fatty change of the adrenal cortex (males
                                   at 500 and 2,000 mg/kg-day

                                   NOAEL: 100 mg/kg-day
                                   LOAEL: 500 mg/kg-day
                     IUCLID, 2000
                       Limited study details reported in a
                       secondary source. Study conducted
                       using commercial mixture
                       Kronitex 50 (components not
                       specified). Limited number of
                       endpoints assessed.
                                                            7-298

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JUNE 2014 DRAFT REPORT
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT




























Skin Sensitization







Skin Sensitization






Respiratory Sensitization
(Respiratory Sensitization
DATA
In a dermal study in rats, test substance
was applied to shaved skin at 0, 40, 200
or 1,000 mg/kg for 6 hours/day, 5
days/week for 4 weeks. Slightly
depressed plasma ChE activity (females
at 1,000 mg/kg -day); reduced absolute
and relative testicular weights (1,000
mg/kg-day); slight testicular tubular
atrophy (control and high-dose males);
slightly increased absolute and relative
adrenal weights (no associated
microscopic findings).
NOAEL: 200 mg/kg-day
LOAEL: 1,000 mg/kg-day
REFERENCE
IUCLID, 2000




^^^



^^*


^^

DATA QUALITY
Limited study details reported in a
secondary source. Study conducted
using commercial mixture Reolube
HYD (components not specified)










LOW: The commercial mixtures Reofos 50 and Reolube HYD 46 were not sensitizing to guinea pigs
Not sensitizing to guinea pig skin
following intracutaneous injection and
challenge treatment using Reofos 50 and
Reolube HYD 46.



IUCLID, 2000






Limited study details reported in a
secondary source. Study was
conducted using commercial
mixtures Reofos 50 (30% TPP,
70% IPTPP) and Reolube HYD 46
(components not specified in
secondary source)
No data located

|No data located.
         7-299

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                                                            JUNE 2014 DRAFT REPORT
                                                Isopropylated triphenyl phosphate CASRN 68937-41-7
           PROPERTY/ENDPOINT
               DATA
          REFERENCE
       DATA QUALITY
Eye Irritation
LOW: Based on no irritation to slight ocular irritation that cleared within 10 days postinstillation.
                  Eye Irritation
In a number of acute eye irritation tests
using a variety of commercial
isopropylated phenyl phosphate
formulations, Reofos 50 was determined
to be nonirritating (1 study) to slightly
irritating (2 studies); Reolube HYD 46
was slightly irritating (slight-to-
moderate redness that cleared in  10
days); Reofos 65, Refos 95, and Durad
300 were nonirritating.
                                              Slight conjuctival erythema in rabbits;
                                              cleared within 48 hours; characterized as
                                              "practically non-irritating" based on a
                                              maximum irritation score of 1.3/110 at
                                              24 hours; no conjunctival discharge or
                                              effects on the cornea or iris were
                                              reported.
                                              non-irritating in rabbits; there were no
                                              signs of eye irritation observed at
                                              1,24,48, or 72 hours
IUCLID, 2000, 2001
Weight of evidence indicates that
commercial isopropylated phenyl
phosphate is not a primary eye
irritant
                                     Submitted confidential study
                                     Submitted confidential study
                                  Study is inadequate to determine if
                                  this substance is an eye irritant
                                  because data are on an undefined
                                  chemical composition; rabbit eyes
                                  were instilled with 0.01 mL of a
                                  test substance identified as a
                                  mixture of isopropylated triaryl
                                  phosphates and triphenyl
                                  phosphate  [formulation 1].
                                  Study is inadequate to determine if
                                  this substance is an eye irritant
                                  because data are on an undefined
                                  chemical composition; rabbit eyes
                                  were instilled with 0.01 mL of a
                                  test substance identified as a
                                  mixture of isopropylated triaryl
                                  phosphates and triphenyl
                                  phosphate  [formulation 2].
                                                                        7-300

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                                                           JUNE 2014 DRAFT REPORT
                                                Isopropylated triphenyl phosphate CASRN 68937-41-7
          PROPERTY/ENDPOINT
               DATA
          REFERENCE
       DATA QUALITY
Dermal Irritation
LOW: Based on no evidence of irritation in rabbit skin. Two of the studies were conducted using mixtures
of isopropylated triaryl phosphates and triphenyl phosphate with undefined chemical compositions. The
data may not be suitable to determine the potential for skin irritancy.
                 Dermal Irritation
In a number of acute dermal irritation
tests using a variety of commercial
isopropylated phenyl phosphate
formulations, Reofos 50 was
nonirritating;  Reolube HYD 46 was
slightly irritating (slight erythema for up
to 72 hours); Refos 95 and Durad 300
were nonirritating.
                                              Not irritating to rabbit skin following
                                              dermal exposure for 4 hours on two
                                              occluded test sites (0.5 mL per site);
                                              there was no sign of irritation at 4.5, 24,
                                              48, or 72 hours following exposure;
                                              irritation scores were 0/8.0 at all time
                                              points.
                                              Not irritating to rabbit skin following
                                              dermal exposure for 4 hours on two
                                              occluded test sites (0.5 mL per site);
                                              there was no sign of irritation at 4.5, 24,
                                              48, or 72 hours following exposure;
                                              irritation scores were 0/8.0 at all time
                                              points.
IUCLID, 2000; IUCLID, 2001
Weight of evidence indicates that
commercial isopropylated phenyl
phosphate is not a primary dermal
irritant.
                                     Submitted confidential study
                                     Submitted confidential study
                                 Study is inadequate to determine if
                                 this substance is skin irritant
                                 because data are on an undefined
                                 chemical composition; test
                                 substance identified as a mixture of
                                 isopropylated triaryl phosphates
                                 and triphenyl phosphate
                                 [formulation 2].
                                 Study is inadequate to determine if
                                 this substance is skin irritant
                                 because data are on an undefined
                                 chemical composition; test
                                 substance identified as a mixture of
                                 isopropylated triaryl phosphates
                                 and triphenyl phosphate
                                 [formulation 1].
                                                                       7-301

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                                                          JUNE 2014 DRAFT REPORT
                                               Isopropylated triphenyl phosphate CASRN 68937-41-7
          PROPERTY/ENDPOINT
               DATA
REFERENCE
DATA QUALITY
Endocrine Activity
No data were available for this test substance. Effects to the adrenal glands were reported following dermal
application of the commercial mixture Kronitex 50 to shaved rat skin. Changes to adrenal weights and
testicular weights were also reported following exposure to a commercial mixture of Kronitex 50
(Components not specified); these changes may be indicative of endocrine activity. Increased serum
thyroxine (T4) levels were reported in the serum of dams following oral administration to the analog FM550
(mixture of 50% sum total of TBB and TBPH and additional components identified as IPTPP and TPP). It
is unclear which component or components of the mixture are driving the endocrine activity effects.
                                             Male and female rats (5/sex/group), the
                                             analog Kronitex 50 was applied to
                                             shaved skin at 0, 100, 500 or 2,000
                                             mg/kg bw 6 hours/day, 5 days/week for
                                             4 weeks.
                                             Increased adrenal weights and slight
                                             fatty change of the adrenal cortex (males
                                             at 500 and 2,000 mg/kg-bw

                                             NOAEL =  100 mg/kg bw
                                             LOAEL = 500 mg/kg bw (adrenal
                                             weights)
                                             (Estimated by analogy)
                                             In a dermal study in rats, test substance
                                             was applied to shaved skin at 0, 40, 200
                                             or 1,000 mg/kg for 6 hours/day, 5
                                             days/week for 4 weeks.
                                             Reduced absolute and relative testicular
                                             weights (1,000 mg/kg-day);  slight
                                             testicular tubular atrophy (control and
                                             high-dose males); slightly increased
                                             absolute and relative adrenal weights (no
                                             associated microscopic findings).
                                             Pregnant Wistar rats were administered
                                             0, 0.1 or 1 mg/kg-day of the analog
                                             FM550 in the diet during gestation and
                                    IUCLID, 2000
                                    IUCLID, 2000
                                    Patisauletal., 2013
                       Limited study details reported in a
                       secondary source. Study conducted
                       using commercial mixture
                       Kronitex 50 (components not
                       specified). Limited number of
                       endpoints assessed.
                       Limited study details reported in a
                       secondary source. Study conducted
                       using commercial mixture Reolube
                       HYD (components not specified);
                       these effects may be indicative of
                       endocrine activity.
                       Estimated based on experimental
                       data for the FM550 mixture; non
                       guideline study; the test substance
                                                                     7-302

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JUNE 2014 DRAFT REPORT
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT

Immunotoxicity
Immune System Effects
DATA
through lactation (GD8 - PND 21);
Increased serum thyroxine (T4) levels
(increase of 65%) in the high dose dams
compared to controls was reported.
There was no significant change in
triiodothyronine (T3) levels in dam
serum. There was no reported
statistically significant change in T4 or
T3 levels in pup serum on PND 2 1 when
compared to controls.
REFERENCE
^^^
DATA QUALITY
identified as FM550 is a mixture
made up of TBB and TBPH (sum
total of TBB and TBPH is
approximately 50%) and other
compounds including TPP and
IPTPP; it is not clear which
component or components of the
mixture are driving the reported
endocrine activity effects.
No data located.

|No data located.
ECOTOXICITY
ECOSAR Class
Acute Aquatic Toxicity

VERY HIGH: Based on experimental LC50 values of <0.3 mg/L in fish (conducted using commercial
mixture Phosflex [28-30% triphenyl phosphate, along with isomers of isopropylphenyl diphenyl phosphate,
isomers of diisopropylphenyl diphenyl phosphate and tri-substituted phenol phosphates]) and 0.25 mg/L in
daphnia (conducted using isopropyl phenyl diphenyl phosphate [composition not specified]). The reported
water solubility values from studies on commercial mixtures may not adequately represent all components
of the mixture. The tris(isopropylphenyl) phosphate isomers and other isopropyl substituted phenyl
phosphate ester components anticipated to be present in the commercial product are expected to have a
range of water solubility values. Therefore NES may be predicted for some components but not others.
Estimated data using the ECOSAR program predicted no effects at saturation (NES) for these organisms.
Two experimental studies were available for green algae which determined a 14-day NOEC and LOEC of
0.1 mg/L for Kronitex 200 and Phosflex 31P (major components triphenyl phosphate and 2-isopropylphenyl
diphenyl phosphate), respectively. Estimated data based on the monoisopropyl diphenyl phosphate predict
Very High hazard for algae; however, estimated data using other isomers predicted no effects at saturation
(NES). In addition, this substance has been assigned the risk phrase R50/R53 - Very toxic to aquatic
organisms. May cause long-term adverse effects in the aquatic environment.
         7-303

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                                                          JUNE 2014 DRAFT REPORT
                                               Isopropylated triphenyl phosphate CASRN 68937-41-7
          PROPERTY/ENDPOINT
               DATA
         REFERENCE
       DATA QUALITY
Fish LC50
Fish (Ictalurus punctatus) 96-hour LC50
<0.3 mg/L
The test was performed under static test
conditions using acetone as solvent; test
substance concentrations were nominal
(Experimental)
Cleveland et al., 1986
Adequate, primary source. Study
was conducted using the
commercial mixture Phosflex 3 IP
(28-30% triphenyl phosphate,
along with isomers of
isopropylphenyl diphenyl
phosphate, isomers of
diisopropylphenyl diphenyl
phosphate and tri-substituted
phenol phosphates); water
solubility of the commercial
mixture tested was not reported.
                                             Fish (Ictalurus punctatus) 96-hour LC50
                                             = 43 mg/L
                                             The test was performed under static test
                                             conditions using acetone as solvent; test
                                             substance concentrations were nominal.
                                             (Experimental)
                                    Environment Agency, 2009
                                 Adequate study reported in a
                                 secondary source. Study was
                                 conducted using commercial
                                 product Houghto-Safe 1120
                                 (isopropylphenyl diphenyl
                                 phosphate as the principal
                                 component); the LC50> value of 43
                                 is sufficiently above the water
                                 solubility for the principal
                                 component; NES is predicted.
                                             Fish (Ictalurus punctatus) 96-hour LC50
                                             = 15 mg/L
                                             30-day LC50 = 4.5 mg/L
                                             The test was performed under flow-
                                             through test conditions using acetone as
                                             solvent; test substance concentrations
                                             were nominal.
                                             (Experimental)
                                    Environment Agency, 2009
                                 Adequate study reported in a
                                 secondary source. Study was
                                 conducted using commercial
                                 product, Houghto-Safe 1120 (with
                                 isopropylphenyl diphenyl
                                 phosphate as the principal
                                 component).
                                             Fish (Oncorhynchus mykiss) 96-hour
                                             LC50 = 0.65 mg/L
                                             8-day LC50 = 0.59 mg/L
                                    Environment Agency, 2009
                                 Adequate study reported in a
                                 secondary source. Study was
                                 conducted using commercial
                                                                      7-304

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                                               JUNE 2014 DRAFT REPORT
                                     Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   The test was performed under flow-
                                   through test conditions using acetone as
                                   solvent; test substance concentrations
                                   were nominal.
                                   (Experimental)
                                                      product, Houghto-Safe 1120 (with
                                                      isopropylphenyl diphenyl
                                                      phosphate as the principal
                                                      component).
                                   Fish (Oncorhynchus mykiss) 96-hour
                                   LC50 = 0.9 mg/L
                                   The test was performed under static test
                                   conditions using acetone as solvent; test
                                   substance concentrations were nominal
                                   (Experimental)
                     Cleveland et al., 1986
                       Adequate primary source. Study
                       was conducted using the
                       commercial mixture Phosflex 3 IP
                       (28-30% triphenyl phosphate,
                       along with isomers of
                       isopropylphenyl diphenyl
                       phosphate, isomers of
                       diisopropylphenyl diphenyl
                       phosphate and tri-substituted
                       phenol phosphates).
                                   Fish (Oncorhynchus mykiss) 96-hour
                                   LC50= 1.15 mg/L
                                   NOEC: 0.4 mg/L
                                   LOEC: 0.74 mg/L Test was performed
                                   under semi-static test conditions; not
                                   stated whether the effect level values
                                   were nominal or measured
                                   concentrations.
                                   (Experimental)
                     IUCLID, 2000
                       Limited study details reported in a
                       secondary source. Study was
                       conducted using commercial
                       product Reofos 50 (30% TPP, 70%
                       IPTPP). Reliability of this study
                       was not specified in the IUCLID.
                                   Fish (Oncorhynchus mykiss) 96-hour
                                   LC50 =1.7 mg/L
                                   The test was performed under static test
                                   conditions; test substance concentrations
                                   were nominal; at least 8 concentrations
                                   tested.
                                   (Experimental)
                     IUCLID, 2001; Environment
                     Agency, 2009
                       Adequate study reported in a
                       secondary source. Study was
                       conducted using commercial
                       product Houghto-Safe 1120
                       (isopropylphenyl diphenyl
                       phosphate as the principal
                       component).
                                   Fish (Oncorhynchus mykiss) 96-hour
                                   LC5o = 4.5 mg/L
                     Environment Agency, 2009
                       Adequate study reported in a
                       secondary source. Study was
                                                           7-305

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                                                JUNE 2014 DRAFT REPORT
                                     Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   (Experimental)
                                                      conducted using the commercial
                                                      mixture Kronitex 200 (4-6%
                                                      triphenyl phosphate, 7-10% 2-
                                                      isopropylphenyl diphenyl
                                                      phosphate, 20-25% 4-
                                                      isopropylphenyl diphenyl
                                                      phosphate, along with bis-(2-
                                                      isopropylphenyl) phenyl phosphate
                                                      and minor amounts of di-, tri- and
                                                      tetraisopropyl-substituted triphenyl
                                                      phosphates).
                                   Fish (Lepomis macrochirus) 96-hour
                                   LC5o = 2.6 mg/L
                                   The test was performed under static test
                                   conditions using acetone as solvent; test
                                   substance concentrations were nominal.
                                   (Experimental)
                      Cleveland et al., 1986
                       Adequate study reported in a
                       secondary source. Study was
                       conducted using the commercial
                       mixture Phosflex 3 IP (28-30%
                       triphenyl phosphate, along with
                       isomers of isopropylphenyl
                       diphenyl phosphate, isomers of
                       diisopropylphenyl diphenyl
                       phosphate and tri-substituted
                       phenol phosphates).
                                   Fish (Lepomis macrochirus) 96-hour
                                   LC50 =11 mg/L
                                   17-day LC50 = 5.0 mg/L
                                   The test was performed under flow-
                                   through test conditions using acetone as
                                   solvent; test substance concentrations
                                   were nominal.
                                   (Experimental)
                     Environment Agency, 2009
                       Adequate study reported in a
                       secondary source. Study was
                       conducted using commercial
                       product, Houghto-Safe 1120 (with
                       isopropylphenyl diphenyl
                       phosphate as the principal
                       component).
                                   Fish (Lepomis macrochirus) 96-hour
                                   LC50 =12 mg/L
                                   The test was performed under static test
                                   conditions using acetone as solvent; test
                     Environment Agency, 2009
                       Adequate study reported in a
                       secondary source. Study was
                       conducted using commercial
                       product Houghto-Safe 1120
                                                            7-306

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                                                JUNE 2014 DRAFT REPORT
                                     Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   substance concentrations were nominal
                                   and at least 8 concentrations were tested.
                                   (Experimental)
                                                       (isopropylphenyl diphenyl
                                                       phosphate as the principal
                                                       component).
                                   Fish (Lepomis macrochirus) 96-hour
                                   LC5o = 29 mg/L
                                   The test was performed under static test
                                   conditions using acetone as solvent; test
                                   substance concentrations were nominal
                                   (Experimental)
                      Cleveland et al., 1986
                                   Fish (Pimephales promelas) 96-hour
                                   LC50 =1.7 mg/L
                                   The test was performed under static test
                                   conditions using acetone as solvent; test
                                   substance concentrations were nominal.
                                   (Experimental)
                      Cleveland et al., 1986
                                   Fish (Pimephales promelas) 96-hour
                                   LC50 =10.8 mg/L
                                   NOEC = 3.2mg/L
                                   The test was performed under static test
                                   conditions using acetone as solvent; test
                      IUCLID, 2000, 2001
                       Adequate study reported in a
                       secondary source. Study was
                       conducted using the commercial
                       mixture Kronitex 200 (4-6%
                       triphenyl phosphate, 7-10% 2-
                       isopropylphenyl diphenyl
                       phosphate, 20-25% 4-
                       isopropylphenyl diphenyl
                       phosphate, along with bis-(2-
                       isopropylphenyl) phenyl phosphate
                       and minor amounts of di-, tri- and
                       tetraisopropyl-substituted triphenyl
                       phosphates); The value is well
                       above the water solubility of the
                       test substance.
                       Adequate study reported in a
                       secondary source. Study was
                       conducted using the commercial
                       mixture Phosflex 3 IP (28-30%
                       triphenyl phosphate, along with
                       isomers of isopropylphenyl
                       diphenyl phosphate, isomers of
                       diisopropylphenyl diphenyl
                       phosphate and tri-substituted
                       phenol phosphates).
                        Limited study details reported in a
                        secondary source. Study was
                        conducted using commercial
                        product Reofos 50 (30% TPP, 70%
                        IPTPP).
                                                            7-307

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                                                JUNE 2014 DRAFT REPORT
                                     Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   substance concentrations were nominal
                                   (Experimental)
                                   Fish (Pimephales promelas) 96-hour
                                   LC50 = 17 mg/L
                                   20-dayLC50 = 8.5mg/L
                                   The test was performed under static test
                                   conditions using acetone as solvent; test
                                   substance concentrations were nominal
                                   (Experimental)
                      Environment Agency, 2009
                       Limited study reported in a
                       secondary source. Study was
                       conducted using commercial
                       product, Houghto-Safe 1120 (with
                       isopropylphenyl diphenyl
                       phosphate as the principal
                       component).
                                   Fish (Pimephales promelas) 96-hour
                                   LC50 = 35 mg/L
                                   The test was performed under static test
                                   conditions using acetone as solvent; test
                                   substance concentrations were nominal.
                                   (Experimental)
                      Environment Agency, 2009
                                   Fish (Pimephales promelas) 96-hour
                                   LC50 =14.9 mg/L
                                   The test was performed under static test
                                   conditions using acetone as solvent; test
                                   substance concentrations were nominal.
                                   (Experimental)
                      IUCLID, 2000
                                   Fish (Pimephales promelas) 96-hour
                                   LC50 = 50.1mg/L
                                   The test was performed under static test
                                   conditions using acetone as solvent; test
                                   substance concentrations were nominal.
                                   (Experimental)
                      IUCLID, 2001
                                   Fish (Oncorhynchus mykiss) 96-hour
                      IUCLID, 2000, 2001
                       Adequate study reported in a
                       secondary source. Study was
                       conducted using commercial
                       product Houghto-Safe 1120
                       (isopropylphenyl diphenyl
                       phosphate as the principal
                       component); the value is well
                       above the water solubility of the
                       test substance.
                       Limited study details reported in a
                       secondary source. Study was
                       conducted using commercial
                       product Reofos 65 (components
                       not specified). The value is well
                       above the water solubility of the
                       test substance.
                       Limited study details reported in a
                       secondary source. Study was
                       conducted using commercial
                       product Reofos 65 (20% TPP, 80%
                       IPTPP). The value is well above
                       the water solubility of the test
                       substance.
                       Limited study details reported in a
                                                            7-308

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                                                JUNE 2014 DRAFT REPORT
                                     Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   LC50=1.6mg/L
                                   NOEC <1 mg/L
                                   The test was performed under static test
                                   conditions using acetone as solvent; test
                                   substance concentrations were nominal.
                                   (Experimental)
                                                      secondary source. Two studies
                                                      conducted using commercial
                                                      product Reofos 50 (30% TPP, 70%
                                                      IPTPP) and Kronitex 50.
                                   Fish (Oncorhynchus mykiss) 96-hour
                                   LC50 = 2.4 mg/L
                                   NOEC <1 mg/L
                                   The test was performed under static test
                                   conditions with nominal test
                                   concentrations (1.0, 1.8, 3.2, 5.6, 10.0
                                   mg/L)
                                   (Experimental)
                     IUCLID, 2001
                                   Fish (Oncorhynchus mykiss) 96-hour
                                   LC50 = 4.46 mg/L
                                   NOEC <0.56 mg/L
                                   The test was performed under static test
                                   conditions with nominal test
                                   concentrations
                                   (Experimental)
                     IUCLID, 2001
                                   Fish (Brachydanio rerio) 96-hour LC50
                                   > 1,000 mg/L
                                   The study was conducted using nominal
                                   test conditions; test chamber conditions
                                   (static, flow-through, etc.) not specified
                                   (Experimental)
                     IUCLID, 2000
                       Limited study details reported in a
                       secondary source. Study was
                       conducted using commercial
                       mixture K-100 (composition not
                       specified).
                       Limited study details reported in a
                       secondary source. Study was
                       conducted using commercial
                       mixture K-200 (composition not
                       specified).
                       Limited study details reported in a
                       secondary source. Study was
                       conducted using commercial
                       product Reolube HYD 46
                       (components not specified). This
                       was a water accommodated
                       fraction (WAF) test. The test
                       substance was reported as being
                       mixed with lecithin using
                       ultrasonication to form an
                       emulsion, which resulted in turbid
                       test solutions. The results cannot be
                                                           7-309

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                                               JUNE 2014 DRAFT REPORT
                                    Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                                                                                       considered valid.
                                  Fish 96-hour LC50 = 0.00017 mg/L
                                  (Estimated)
                                  ECOSAR: Neutral organics
                     ECOSARvl.ll
                                  Fish 96-hour LC50 = 0.003 mg/L
                                  (Estimated)
                                  ECOSAR: Neutral organics
                     ECOSARvl.ll
                                  Fish 96-hour LC50 = 0.056 mg/L
                                  (Estimated)
                                  ECOSAR: Neutral organics
                     ECOSARvl.ll
                       Estimations for triisopropyl phenyl
                       phosphate; the log Kow of 9.1 for
                       this chemical exceeds the SAR
                       limitation for log Kow of 5.0; NES
                       are predicted for these endpoints.
                       ECOSAR also provided results for
                       the Esters, and Esters (phosphate)
                       classes; however, professional
                       judgment indicates that this
                       compound is not currently well
                       represented in ECOSAR v 1.11.
                       Estimations for diisopropyl phenyl
                       phosphate; the log Kow of 7.6 for
                       this chemical exceeds the SAR
                       limitation for log Kow of 5.0; NES
                       are predicted for these endpoints.
                       ECOSAR also provided results for
                       the Esters, and Esters (phosphate)
                       classes; however, professional
                       judgment indicates that this
                       compound is not currently well
                       represented in ECOSAR v 1.11.
                       Estimations for monoisopropyl
                       phenyl phosphate; the log Kow of
                       6.2 for this chemical exceeds the
                       SAR limitation for log Kow of 5.0;
                       NES are predicted for these
                       endpoints. ECOSAR also provided
                       results for the Esters, and Esters
                       (phosphate) classes; however,
                       professional judgment indicates
                       that this compound is not currently
                                                           7-310

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                                                         JUNE 2014 DRAFT REPORT
                                               Isopropylated triphenyl phosphate CASRN 68937-41-7
          PROPERTY/ENDPOINT
               DATA
         REFERENCE
       DATA QUALITY
                                                                                                                 well represented in ECOSAR
                                                                                                                 vl.ll.
Daphnid LC50
Daphnia magna 48-hour LC50 = 0.25
mg/L
The test was performed under static test
conditions
(Experimental)
Environment Agency, 2009
Adequate study reported in a
secondary source. Study was
conducted using isopropyl phenyl
diphenyl phosphate (purity not
given).
                                            Daphnia magna 4 8-hour EC50 = 0.83
                                            mg/L
                                            NOEC = 0.32 mg/L
                                            The test was performed under static test
                                            conditions; test substance concentrations
                                            were nominal.
                                            (Experimental)
                                    IUCLID, 2001
                                            Daphnia magna 4 8-hour EC50 =1.5
                                            mg/L NOEC = 1 mg/L
                                            The test was performed under static test
                                            conditions using a cosolvent; test
                                            substance concentrations were nominal.
                                            (Experimental)
                                    IUCLID, 2001
                                            Daphnia magna 48-hour EC50 = 2.44
                                            mg/L NOEC = 0.56 mg/L
                                            The test was performed under static test
                                            conditions; test substance concentrations
                                            were nominal.
                                            (Experimental)
                                    IUCLID, 2001
                                            Daphnia magna 48-hour EC50 = 3.2
                                            mg/L
                                            The test was performed under static test
                                            conditions using an acetone solvent; test
                                            substance concentrations were nominal.
                                            (Experimental)
                                    Sanders et al., 1985
                                Limited study details reported in a
                                secondary source. Study was
                                conducted using Kronitex-100
                                (components not specified).
                                Limited study details reported in a
                                secondary source. Study was
                                conducted using Kronitex-200
                                (components not specified).
                                Limited study details reported in a
                                secondary source. Study was
                                conducted using Kronitex-5
                                (components not specified).
                                Adequate guideline study. Study
                                was conducted using the
                                commercial mixture Kronitex 200
                                (major components: triphenyl
                                phosphate and 2-isopropylphenyl
                                diphenyl phosphate).
                                                                     7-311

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                                               JUNE 2014 DRAFT REPORT
                                    Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  Daphnia magna 48-hour EC50 = 6.8
                                  mg/L
                                  The test was performed under static test
                                  conditions; test substance concentrations
                                  were nominal.
                                  (Experimental)
                     Sanders et al., 1985
                       Adequate study reported in a
                       secondary source. Study was
                       conducted using the commercial
                       mixture Phosflex 3 IP (major
                       components being triphenyl
                       phosphate and 2-isopropylphenyl
                       diphenyl phosphate).
                                  Daphnia magna 4 8-hour EC50 =14
                                  mg/L
                                  48-hour NOEC = 0.3 mg/L
                                  Test substance concentrations were
                                  nominal; 13 concentrations tested
                                  between 0.14 and 167 mg/L.
                                  (Experimental)
                     IUCLID, 2000
                       Adequate study reported in a
                       secondary source. Study was
                       conducted using commercial
                       product Reolube HYD 46
                       (components not specified). The
                       substance was reported to have
                       been tested as an emulsion using
                       lecithin and ultrasonic dispersion.
                       The results of the study are
                       questionable.
                                  Daphnia magna 4 8-hour EC50 = 31.3
                                  mg/L
                                  (Experimental)
                     IUCLID, 2000
                       Adequate study reported in a
                       secondary source. Study was
                       conducted using commercial
                       product Reofos 50 (components
                       not specified); the value is well
                       above the water solubility of the
                       test substance.
                                  Daphnia magna 48-hour EC50 > 1,000
                                  mg/L (as WAF)
                                  semi-static test conditions (renewal
                                  every 24 hours);
                                  (Experimental)
                     Environment Agency, 2009
                       Limited study details reported in a
                       secondary source. Study was
                       conducted using a commercial
                       tris(isopropyl phenyl) phosphate
                       product; Durad 310M (5% dodecyl
                       phosphate, 4% triphenyl
                       phosphate, with the remainder
                       made up of isopropylated triaryl
                       phosphates). There were
                                                           7-312

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                                               JUNE 2014 DRAFT REPORT
                                     Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                                                                                       uncertainties in the results that
                                                                                                       included possible presence of some
                                                                                                       test substance in the control water
                                                                                                       and adherence of test substance to
                                                                                                       daphnids. The test substance was
                                                                                                       not acutely toxic to daphnia at
                                                                                                       concentrations up to the solubility
                                                                                                       limit (0.77 mg/L).
                                  Daphnid 48-hour LC50= 0.00018 mg/L
                                  (Estimated)
                                  ECOSAR: Neutral organics
                     ECOSARvl.ll
                                  Daphnid 48-hour LC50 = 0.003 mg/L
                                  (Estimated)
                                  ECOSAR: Neutral organics
                     ECOSARvl.ll
                                  Daphnid 48-hour LC50 = 0.047 mg/L
                                  (Estimated)
                                  ECOSAR: Neutral organics
                     ECOSARvl.ll
                       Estimations for triisopropyl phenyl
                       phosphate; the log Kow of 9.1 for
                       this chemical exceeds the SAR
                       limitation for log Kow of 5.0; NES
                       are predicted for these endpoints.
                       ECOSAR also provided results for
                       the Esters, and Esters (phosphate)
                       classes; however, professional
                       judgment indicates that this
                       compound is not currently well
                       represented in ECOSAR v 1.11.
                       Estimations for diisopropyl phenyl
                       phosphate; the log Kow of 7.6 for
                       this chemical exceeds the SAR
                       limitation for log Kow of 5.0; NES
                       are predicted for these endpoints.
                       ECOSAR also provided results for
                       the Esters, and Esters (phosphate)
                       classes; however, professional
                       judgment indicates that this
                       compound is not currently well
                       represented in ECOSAR v 1.11.
                       Estimations for monoisopropyl
                       phenyl phosphate; the log Kow of
                       6.2 for this chemical exceeds the
                                                           7-313

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                                                         JUNE 2014 DRAFT REPORT
                                               Isopropylated triphenyl phosphate CASRN 68937-41-7
          PROPERTY/ENDPOINT
               DATA
         REFERENCE
       DATA QUALITY
                                                                                                                 SAR limitation for log Kow of 5.0;
                                                                                                                 NES are predicted for these
                                                                                                                 endpoints. ECOSAR also provided
                                                                                                                 results for the Esters, and Esters
                                                                                                                 (phosphate) classes; however,
                                                                                                                 professional judgment indicates
                                                                                                                 that this compound is not currently
                                                                                                                 well represented in ECOSAR
                                                                                                                 vl.ll.
Green Algae EC50
Green algae (Selenastrum
capricornutum ) 14-day LOEC = 0.1
mg/L (lowest concentration tested)
50% growth inhibition between 1.0 and
10.0 mg/L
(Experimental)
Sanders et al., 1985
                                             Green algae (Selenastrum
                                             capricornutum ) 14-day NOEC = 0.1
                                             mg/L
                                             The test substance concentrations were
                                             nominal using an acetone solvent.
                                             Nominal exposure level of 100 mg/L
                                             resulted in 53% growth inhibition
                                             (Experimental)
                                    Sanders et al., 1985
                                             Green algae 96-hour EC50 = 0.002 mg/L
                                             (Estimated)
                                             ECOSAR: Neutral organics
                                    ECOSAR vl.ll
Adequate primary source. Study
was conducted using commercial
mixture Phosflex 3 IP (major
components triphenyl phosphate
and 2-isopropylphenyl diphenyl
phosphate).
                                Adequate primary source. Study
                                was conducted using commercial
                                mixture Kronitex 200 (major
                                components: triphenyl phosphate
                                and 2-isopropylphenyl diphenyl
                                phosphate).
                                Estimations for triisopropyl phenyl
                                phosphate; the log Kow of 9.1 for
                                this chemical exceeds the SAR
                                limitation for log Kow of 6.4; NES
                                are predicted for these endpoints.
                                ECOSAR also provided results for
                                the Esters, and Esters (phosphate)
                                classes; however, professional
                                judgment indicates that this
                                compound is not currently well
                                                                     7-314

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                                               JUNE 2014 DRAFT REPORT
                                    Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                                                                                     represented in ECOSAR v 1.11.
                                  Green algae 96-hour EC50 = 0.019 mg/L
                                  (Estimated)
                                  ECOSAR: Neutral organics
                     ECOSAR vl. 11
                                  Green algae 96-hour EC50 = 0.17 mg/L
                                  (Estimated)
                                  ECOSAR: Neutral organics
                     ECOSAR vl. 11
                       Estimations for diisopropyl phenyl
                       phosphate; the log Kow of 7.6 for
                       this chemical exceeds the SAR
                       limitation for log Kow of 6.4; NES
                       are predicted for these endpoints.
                       ECOSAR also provided results for
                       the Esters, and Esters (phosphate)
                       classes; however, professional
                       judgment indicates that this
                       compound is not currently well
                       represented in ECOSAR v 1.11.
                       Estimations for monoisopropyl
                       phenyl phosphate; the log Kow of
                       9.1 for this chemical exceeds the
                       SAR limitation for log Kow of 6.4;
                       NES are predicted for these
                       endpoints. ECOSAR also provided
                       results for the Esters, and Esters
                       (phosphate) classes; however,
                       professional judgment indicates
                       that this compound is not currently
                       well represented in ECOSAR
                       vl.ll.
                                                          7-315

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                                                        JUNE 2014 DRAFT REPORT
                                              Isopropylated triphenyl phosphate CASRN 68937-41-7
          PROPERTY/ENDPOINT
              DATA
         REFERENCE
       DATA QUALITY
Chronic Aquatic Toxicity
VERY HIGH: Based on experimental LOECs < 0.1 mg/L in fish and daphnia using commercial mixtures
Kronitex 200 and Phosflex 31. The reported water solubility values from studies on commercial mixtures
may not adequately represent all components of the mixture. The tris(isopropylphenyl) phosphate isomers
and other isopropyl substituted phenyl phosphate ester components anticipated to be present in the
commercial product are expected to have a range of water solubility values. Therefore NES may be
predicted for some components but not others. No chronic experimental data were available for algae.
Estimated data using the ECOSAR program and monoisopropyl class predict very high hazard for fish,
daphnia and algae; however, estimated data using other isomers predict no effects at saturation (NES) for
all organisms. In addition, this substance has been assigned the risk phrase R50/R53 - Very toxic to aquatic
organisms. May cause long-term adverse effects in the aquatic environment.
Fish ChV
Fish (Pimephales promelas) 30-, 60- and
90-day NOEC (growth) = 0.5 mg/L
(nominal)
LOEC (mortality) = 1.0 mg/L (nominal)
The study was conducted using flow-
through test conditions. Measurements
of test substance at 2-week intervals
only evaluated levels of triphenyl
phosphate (28-30% of the composition
of Phosflex 3 IP) and isodecyl diphenyl
phosphate (percentage composition of
Phosflex 3 IP not stated). Triphenyl
phosphate and isodecyl  diphenyl
phosphate accounted for 5.8-20.5% of
the nominal test substance
concentration.
(Experimental)
                                            Fish (Pimephalespromelas) 30-day
                                            NOEC (growth) = 0.5 mg/L (nominal)
                                            60 and 90 day NOEC (growth) = 1.0
                                            mg/L (nominal)
                                            The study was conducted using flow-
                                            through test conditions. Measurements
Cleveland et al., 1986
                                   Cleveland et al., 1986
Study was conducted using the
commercial mixture Phosflex 3 IP
(28-30% triphenyl phosphate,
along with isomers of
isopropylphenyl diphenyl
phosphate, isomers of
diisopropylphenyl diphenyl
phosphate and tri-substituted
phenol phosphates).
                                Study was conducted using
                                commercial mixture Kronitex 200
                                (4-6% triphenyl phosphate, 7-10%
                                2-isopropylphenyl diphenyl
                                phosphate, 20-25% 4-
                                isopropylphenyl diphenyl
                                                                    7-316

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                                               JUNE 2014 DRAFT REPORT
                                    Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  of test substance at 2-week intervals
                                  only evaluated levels of triphenyl
                                  phosphate and isodecyl diphenyl
                                  phosphate which comprised 31-41% of
                                  the test substance and the sum of these
                                  components only accounted for 4.8-
                                  8.8% of the nominal test substance
                                  concentration.
                                  (Experimental)
                                  Fish ChV = 0.009 mg/L
                                  (Estimated)
                                  ECOSAR: Neutral organics
                     ECOSARvl.ll
                                  Fish ChV = 0.000035 mg/L
                                  (Estimated)
                                  ECOSAR: Neutral organics
                     ECOSARvl.ll
                                  Fish ChV = 0.00055 mg/L
                                  (Estimated)
                                  ECOSAR: Esters
                     ECOSARvl.ll
                                                      phosphate, along with bis-(2-
                                                      isopropylphenyl) phenyl phosphate
                                                      and minor amounts of di-, tri- and
                                                      tetraisopropyl-substituted triphenyl
                                                      phosphates). The 60- and 90-day
                                                      NOEC is greater than the 30-day
                                                      NOEC which indicates that the
                                                      decreased growth at 30 days  may
                                                      be a spurious result.
                       Estimations for monoisopropyl
                       phenyl phosphate. ECOSAR also
                       provided results for the Esters, and
                       Esters (phosphate) classes;
                       however, professional judgment
                       indicates that this compound is not
                       currently well represented in
                       ECOSARvl.ll.
                       Estimations for triisopropyl phenyl
                       phosphate; The log Kow of 9.1 for
                       this chemical exceeds the SAR
                       limitation for log Kow of 8.0; NES
                       are predicted for these endpoints.
                       ECOSAR also provided results for
                       the Esters, and Esters (phosphate)
                       classes; however, professional
                       judgment indicates that this
                       compound is not currently well
                       represented in ECOSAR v 1.11.
                       Estimations for diisopropyl phenyl
                       phosphate. ECOSAR also provided
                       results for the Esters, and Esters
                       (phosphate) classes; however,
                       professional judgment indicates
                                                           7-317

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                                                         JUNE 2014 DRAFT REPORT
                                              Isopropylated triphenyl phosphate CASRN 68937-41-7
          PROPERTY/ENDPOINT
               DATA
         REFERENCE
       DATA QUALITY
                                                                                                                that this compound is not currently
                                                                                                                well represented in ECOSAR
                                                                                                                vl.ll.
Daphnid ChV
Daphnia magna 21-day LOEC
(reproduction) = 0.027 mg/L
21-day NOEC (reproduction) = 0.006
mg/L
21-day NOEC (survival) = 0.027 mg/L
The study was conducted under flow-
through test conditions; test
concentrations: 0, 0.006, 0.027, 0.072,
0.154 mg/L (100% mortality at 0.072
and 0.154 mg/L)
(Experimental)
Sanders et al., 1985
Study was conducted using the
commercial mixture Kronitex 200
(major components: triphenyl
phosphate and 2-isopropylphenyl
diphenyl phosphate).
                                            Daphnia magna 21-day LOEC
                                            (reproduction) = 0.056 mg/L
                                            21-day NOEC (reproduction) = 0.028
                                            mg/L
                                            21-day NOEC (survival) = 0.028 mg/L
                                            The study was conducted under flow-
                                            through test conditions; test
                                            concentrations were nominal (0.00085-
                                            0.056 mg/L)
                                            (Experimental)
                                    Sanders et al., 1985
                                            Daphnid ChV = 0.00011 mg/L
                                            (Estimated)
                                            ECOSAR: Neutral organics
                                    ECOSAR vl.ll
                                Study was conducted using the
                                commercial mixture Phosflex 3 IP
                                (major components: triphenyl
                                phosphate and 2-isopropylphenyl
                                diphenyl phosphate).
                                Estimations for triisopropyl phenyl
                                phosphate; The log Kow of 9.1 for
                                this chemical exceeds the SAR
                                limitation for log Kow of 8.0; NES
                                are predicted for these endpoints.
                                ECOSAR also provided results for
                                the Esters, and Esters (phosphate)
                                classes; however, professional
                                judgment indicates that this
                                                                    7-318

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                                                        JUNE 2014 DRAFT REPORT
                                              Isopropylated triphenyl phosphate CASRN 68937-41-7
          PROPERTY/ENDPOINT
              DATA
         REFERENCE
       DATA QUALITY
                                                                                                               compound is not currently well
                                                                                                               represented in ECOSAR v 1.11.
                                            Daphnid ChV = 0.0012 mg/L
                                            (Estimated)
                                            ECOSAR: Neutral organics
                                   ECOSAR vl. 11
                                Estimations for diisopropyl phenyl
                                phosphate; ECOSAR also provided
                                results for the Esters, and Esters
                                (phosphate) classes; however,
                                professional judgment indicates
                                that this compound is not currently
                                well represented in ECOSAR
                                vl.ll.
                                            Daphnid ChV = 0.013 mg/L
                                            (Estimated)
                                            ECOSAR: Neutral organics
                                   ECOSAR vl.ll
                                Estimations for monoisopropyl
                                phenyl phosphate. ECOSAR also
                                provided results for the Esters, and
                                Esters (phosphate) classes;
                                however, professional judgment
                                indicates that this compound is not
                                currently well represented in
                                ECOSAR vl.ll.
Green Algae ChV
Green algae ChV = 0.002 mg/L
(Estimated)
ECOSAR: Neutral organics
ECOSAR vl.ll
                                            Green algae ChV = 0.015 mg/L
                                            (Estimated)
                                            ECOSAR: Neutral organics
                                   ECOSAR vl.ll
Estimations for triisopropyl phenyl
phosphate; The log Kow of 9.1 for
this chemical exceeds the SAR
limitation for log Kow of 8.0; NES
are predicted for these endpoints.
ECOSAR also provided results for
the Esters, and Esters (phosphate)
classes; however, professional
judgment indicates that this
compound is not currently well
represented in ECOSAR vl.ll.
                                Estimations for diisopropyl phenyl
                                phosphate. The estimated effect
                                exceeds the water solubility by
                                lOx. NES are predicted for these
                                                                    7-319

-------
                                                        JUNE 2014 DRAFT REPORT
                                              Isopropylated triphenyl phosphate CASRN 68937-41-7
          PROPERTY/ENDPOINT
              DATA
REFERENCE
DATA QUALITY
                                                                                                               endpoints. ECOSAR also provided
                                                                                                               results for the Esters, and Esters
                                                                                                               (phosphate) classes; however,
                                                                                                               professional judgment indicates
                                                                                                               that this compound is not currently
                                                                                                               well represented in ECOSAR
                                                                                                               vl.ll.
                                            Green algae ChV = 0.11 mg/L
                                            (Estimated)
                                            ECOSAR: Neutral organics
                                   ECOSAR vl.ll
                       Estimations for monoisopropyl
                       phenyl phosphate. The effect level
                       exceeds the water solubility of
                       0.02647 mg/L, but not by lOx as
                       required to be considered NES by
                       ECOSAR. ECOSAR also provided
                       results for the Esters, and Esters
                       (phosphate) classes; however,
                       professional judgment indicates
                       that this compound is not currently
                       well represented in ECOSAR
                       vl.ll.
                                                          ENVIRONMENTAL FATE
Transport
Level III fugacity models incorporating available physical and chemical property data indicate that at
steady state, isopropylated triphenyl phosphate is expected to be found primarily in soil and to a lesser
extent, sediment and water. Isopropylated triphenyl phosphate is expected to have low mobility in soil,
based on estimated Koc values of the components. Leaching through soil to groundwater may occur, though
it is not expected to be an important transport mechanism. Estimated volatilization half-lives indicate that
the components of this mixture will be non-volatile from surface water. Volatilization from dry surface is
also not expected based on its vapor pressure. In the atmosphere, isopropylated triphenyl phosphate is
expected to exist in both the vapor phase and particulate phase, based on its vapor pressure. Vapor phase
isopropylated triphenyl phosphate will be degraded in the atmosphere by reaction with photochemically-
produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 0.7 days. Particulates may
be removed from air by wet or dry deposition.
                                                                    7-320

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Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT

Henry's Law Constant (atm-
m3/mole)
Sediment/Soil
Adsorption/Desorption - Koc
Level III Fugacity Model
DATA
7.7xlO~8 for the monoisopropylated
triphenyl phosphate;
1.5xlO"7 for the diisopropylated
triphenyl phosphate;
2.9xlO~7 for the diisopropylated
triphenyl phosphate isomer
Bond estimate (Estimated)
0.000012 for TPP (CASRN 115-86-6) a
possible mixture component (Estimated
by analogy)
>30,000 for the mono, di and tri-
isopropylated phenyl phosphates
(Estimated)
2,514-3,561 in silty clay, loamy sand
and silt loam; for TPP (CASRN 1 15-86-
6) a possible component of the mixture
(Estimated by analogy)
Air = 0.2%
Water = 9.3%
Soil = 76%
Sediment = 14% (Estimated)
REFERENCE
EPIv4.11
Mayer et al., 1981; Huckins et al.,
1991
EPIv4.11;EPA, 2005
Anderson et al., 1993
EPIv4.11
DATA QUALITY
Based on representative structures
for components of the mixture
using the HENRYWIN (v3.20)
Program.
Reported for triphenyl phosphate
(CASRN 115-86-6).
Estimated using the representative
structures indicated in the SMILES
section.
Reported for triphenyl phosphate
(CASRN 1 15-86-6) a component
of the mixture. Cutoff value for
nonmobile compounds.
Based on a representative structure
for a component of the mixture, tri-
IPTPP.
         7-321

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                                                        JUNE 2014 DRAFT REPORT
                                              Isopropylated triphenyl phosphate CASRN 68937-41-7
          PROPERTY/ENDPOINT
                                         DATA
                                            REFERENCE
                                      DATA QUALITY
Persistence
                           MODERATE: The environmental half-life of the isopropylated triphenyl phosphate is expected to be >16
                           days based on experiments using commercial mixtures of this alternative. Commercial isopropylated
                           triphenyl phosphate mixtures passed some ready biodegradable tests, but not all (17.9% degradation in 28
                           days using a closed bottle test, OECD 301D). Substantial degradation seen over extended time periods
                           indicates that the substance can be considered to be inherently biodegradable. Ultimate degradation is
                           expected based on studies with mixed microbial populations from sludge acclimated to the test substance in
                           a semi-continuous activated sludge system (SCAS), a modified Sturm method experiment and a die-away
                           test. Some degradation under anaerobic conditions of the triaryl phosphate isomers mixture is also expected
                           based on an anaerobic sediment study. The isopropylated triphenyl phosphate mixture components will
                           undergo hydrolysis under alkaline conditions, with estimated hydrolysis half-lives of <13 days at pH 9. The
                           mixture is expected to be relatively stable to hydrolysis under neutral and acidic conditions, with estimated
                           half-lives of >2 years at pH 7. Isopropylated triphenyl phosphate mixture components are not expected to
                           be susceptible to direct photolysis by sunlight, since they do not absorb light at wavelengths >290 nm. The
                           atmospheric half-live of vapor-phase isopropylated triphenyl phosphate mixture components is estimated to
                           be <12 hours.
Water
Aerobic Biodegradation
Passes Ready Test: No
Test method: OECD TG 30ID: Closed
Bottle Test

17.9 % after 28 days in activated sludge
from a domestic waste water treatment
plant (Measured)
                                            Passes Ready Test: No
                                            Test method: OECD TG 30IB: CO2
                                            Evolution Test

                                            21% and 13% biodegradation after 28
                                            days using activated sludge from a
                                            sewage treatment plant (with 10.6 mg/L
                                            and 21.5 mg/L, respectively) (Measured)
                                            Passes Ready Test: No
                                            Test method: OECD TG 30IB: CO2
                                            Evolution Test
ECHA, 2013b
Reported in a secondary source for
a commercial product Reofos 65.
                                                              IUCLID, 2001 (as cited in
                                                              Environment Agency, 2009)
                                                              IUCLID, 2001 (as cited in
                                                              Environment Agency, 2009)
                                                                   Reported in a secondary source for
                                                                   a commercial product, Reofos 120.
                                                                   Reported in a secondary source for
                                                                   a commercial product Reolube
                                                                   HYD46.
                                                                    7-322

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                                              JUNE 2014 DRAFT REPORT
                                   Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
         REFERENCE
       DATA QUALITY
                                 29% and 40% degradation based on CO2
                                 evolution (with 10 mg/L and 20 mg/L,
                                 respectively) (Measured)
                                 Passes Ready Test: Yes
                                 Test method: OECD TG 30IB: CO2
                                 Evolution Test

                                 74% at 10 mg/L and 80% at 20 mg/L
                                 using an activated sludge inoculum after
                                 28 days (Measured)
                     IUCLID, 2001 (as cited in
                     Environment Agency, 2009)
                               Reported in a secondary source for
                               a commercial product, Reofos 50.
                                 Passes Ready Test: No
                                 Test method: OECD TG 30IF:
                                 Manometric Respirometry Test

                                 47% degradation after 28 days and 60%
                                 degradation after 68 days (Measured)
                     Sherren, 2003 (as cited in
                     Environment Agency, 2009)
                               Reported in a secondary source for
                               a commercial product, Reofos 120.
                                 Passes Ready Test: Yes
                                 Test method: OECD TG 301 A:
                                 Die-Away Test
            DOC
IUCLID, 2001 (as cited in
Environment Agency, 2009)
Reported in a secondary source for
a commercial product, Reofos 50.
                                 94% degradation after 26 days; the test
                                 protocol was not followed (Measured)
                                 Passes Ready Test: No
                                 Test method: OECD TG 30IF:
                                 Manometric Respirometry Test

                                 46% ThOD after 28 days (Measured)
                     Environment Agency, 2009
                               This study is not sufficient to fully
                               characterize the aerobic
                               biodegradation under
                               environmental conditions.
                                 Passes Ready Test: Yes
                                 Test method: OECD TG 301 A: DOC
                                 Die-Away Test

                                 86% degradation was seen after 31 days
                     IUCLID, 2001 (as cited in
                     Environment Agency, 2009)
                               Reported in a secondary source for
                               a commercial product Reolube
                               HYD 46. Results should be
                               considered with caution as the Die-
                               Away test is not currently
                                                         7-323

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                                                JUNE 2014 DRAFT REPORT
                                     Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
              DATA
         REFERENCE
       DATA QUALITY
                                   using an activated sludge inoculum and
                                   a test concentration of 32.6 mg/L.
                                   (Measured)
                                                                    recommended for substances of
                                                                    low water solubility (below 100
                                                                    mg/L).
                                   Study results: 80%/28 days
                                   Test method: Die-Away

                                   Using settled Mississippi River water; 1
                                   mg/L commercial product Kronitex
                                   1000 (Measured)
                                    Saeger et al., 1979 (as cited in
                                    Environment Agency, 2009)
                                 Reported in a secondary source
                                 using a commercial product,
                                 Kronitex 1000.
                                   Study results: Inherently
                                   Test method: Other

                                   Inherently biodegradable based on study
                                   based on the modified Sturm method
                                   using acclimated bacteria; CO2 evolved
                                   from the test substance (expressed as a
                                   percentage of the maximum theoretical
                                   amount): 9% after seven days, 49% after
                                   28 days and 62% after 48 days
                                   (Measured)
                                    Saeger et al., 1979 (as cited in
                                    Environment Agency, 2009)
                                 Reported in a secondary source
                                 using a commercial product,
                                 Kronitex 1000.
                                   Study results: 49%
                                   Test method: Other

                                   An equilibrium removal rate of 49 ± 8%
                                   at 3 mg/L and 35 ± 11% at 13 mg/L
                                   using a semi-continuous activated
                                   sludge (SCAS) unit (Measured)
                                    Saeger et al., 1979 (as cited in
                                    Environment Agency, 2009)
                                 Reported in a secondary source
                                 using a commercial product,
                                 Kronitex 1000.
       Volatilization Half-life for
       Model River
177 days (Estimated)
EPIv4.11
Based on a representative structure
for a component of the mixture,
with three isopropyl substituent
groups.
                                   >1 year (Estimated)
                                    EPIv4.11
                                 Based on a representative structure
                                 for a component of the mixture,
                                                           7-324

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Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT

Soil

Volatilization Half-life for
Model Lake
Aerobic Biodegradation
Anaerobic Biodegradation
Soil Biodegradation with
Product Identification
Sediment/Water
Biodegradation
DATA

>1 year (Estimated)
>1 year (Estimated)
Study results: 50%/50-60 days
Test method: Other
under aerobic conditions in hydrosoil
from a small pond;
TPP (CASRN 115-86-6) initial
concentration of 0.05 ppm; major
product is diphenyl phosphate
(Estimated by analogy)
Not probable (Anaerobic -methanogenic
biodegradation probability model)

7.3% mineralization after 28 days; 14C-
labeled isopropylphenyl diphenyl
phosphate at 22°C, pH 7. 1-7.7 in 10 g
(wet weight) of sediment and 90 ml of
water taken from the littoral zone of a
slightly eutrophic reservoir. (Measured)
8.4%/28 days 7. l%-8.4% mineralization
after 28 days by 14C -labeled isopropyl
phenyl diphenyl phosphate at 22°C, pH
7.1-7.7 in 10 g (wet weight) of sediment
REFERENCE

EPIv4.11
EPIv4.11
k^
Muiretal., 1989
^^
7
EPIv4.11

Heitkamp et al., 1984 (as cited in
Environment Agency, 2009)
Heitkamp et al., 1984 (as cited in
Environment Agency, 2009)
DATA QUALITY
with one isopropyl substituent
group.
Based on a representative structure
for a component of the mixture,
with three isopropyl substituent
groups.
Based on a representative structure
for a component of the mixture,
with one isopropyl substituent
group.
Sfonguideline study for a
component, TPP (CASRN 115-86-
6) of the mixture.

No data located.
Reported in a secondary source for
a component of the mixture,
isopropylphenyl diphenyl
phosphate.
Reported in a secondary source.
         7-325

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JUNE 2014 DRAFT REPORT
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT

Air
Reactivity

Atmospheric Half-life
Photolysis
Hydrolysis
DATA
and 90 ml of water taken from the
littoral zone of a slightly eutrophic
reservoir (Measured)
0.8 days (Estimated)
0.5 days (Estimated)
Not a significant fate process
(Estimated)
50%/3.5yearsatpH7;
50%/13 days at pH 9 (Estimated)
50%/1.7yearsatpH7;
50%/6.2 days at pH 9 (Estimated)
50%/18.5 days at pH 7, 25°C
50%/43daysatpH7, 15°C;
50%/16.5 days atpH 9, 15°C;
50%/6.1daysatpH9,25°C;
stable at pH 4
7
In accordance with the OECD 111 using
GC/MS analysis (Measured)
Samples of Kronitex 100 and Kronitex
50 were refluxed under basic conditions
for several hours
The solutions were acidified and
REFERENCE

EPIv4.11
EPIv4.11
Professional judgment; Mill, 2000
EPIv4.11
EPIv4.11
ECHA, 2013b
Nobileetal., 1980
DATA QUALITY

Based on a representative structure,
monoisopropylated triphenyl
phosphate isomer.
Based on a representative structure,
triisopropylated triphenyl
phosphate isomer.
The components of this mixture do
not contain functional groups that
would be expected to absorb light
of wavelengths >290 nm.
Based on a representative structure,
with three isopropyl substituent
groups.
Based on a representative structure,
with one isopropyl substituent
groups.
Guideline study reported in a
secondary source based on a
commercial product, Reofos 65 .
Nonguideline study reported for
commercial products.
         7-326

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                                                        JUNE 2014 DRAFT REPORT
                                              Isopropylated triphenyl phosphate CASRN 68937-41-7
          PROPERTY/ENDPOINT
              DATA
         REFERENCE
       DATA QUALITY
                                            extracted; hydrolysis products (phenol,
                                            2-isopropyl phenol, 4-isopropyl phenol,
                                            3-isopropylphenol and diisopropyl
                                            phenols) were identified by infrared
                                            spectrometry (IR), gas liquid
                                            chromatograph-mass spectrometry
                                            (GLC-MS) and nuclear magnetic
                                            resonance (NMR) (Measured)
Environmental Half-life
120 days in Soil (Estimated)
EPIv4.11;PBT Profiler
Half-life estimated for the
predominant compartment, as
determined by EPI and the PBT
Profiler methodology; using a
representative structure for a
component of the mixture, with
three isopropyl substituent groups.
Bioaccumulation
HIGH: The bioaccumulation designation is based on the estimated BAF values for the isopropylated
triphenyl phosphate compounds; these values are >1,000. Measured BCF of <9,250, are available for a
commercial mixture containing isopropylated triphenyl phosphate. However, there is lower confidence in
the experimental BCF values because they are not consistent with the limited water solubility of this
chemical, and because the studies were performed on a mixture of unquantified components. Toxicokinetic
and fish metabolism studies determined that in some species, isopropylated phenyl phosphate is likely to be
bioavailable and undergo metabolism and elimination. Additional, lower BCF values were reported from
studies with the isomer isopropylphenyl diphenyl phosphate that would result  in a Moderate designation.
The BAF was used preferentially as the removal rate of isopropylated triphenyl phosphates in some species
of fish may not compete with the rate of uptake.
                 Fish BCF
<9,250 Pimephalespromelas flow-
through system; fish were exposed to
five concentrations of the test substance,
samples taken at 30, 60 and 90 days of
exposure and analyzed for both
isopropylphenyl diphenyl phosphates
and triphenyl phosphate (Measured)
                                            495 Pimephales promelas flow-through
Cleveland et al., 1986 (as cited in
Environment Agency, 2009)
                                   Environment Agency, 2009
Reported in a secondary source for
commercial products, Kronitex 200
andPhosflexSlP.
                                Adequate, nonguideline study
                                                                    7-327

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                                               JUNE 2014 DRAFT REPORT
                                    Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
               DATA
         REFERENCE
       DATA QUALITY
       Other BCF
       BAF
                                               14 f
                                  system; using "C-labelled
                                  isopropylphenyl diphenyl phosphate, at
                                  a concentration of 2.5 (jg/1 for 28 days
                                  (Measured)
                                                                    using labeled components of the
                                                                    mixture.
                                  440-550; in fathead minnows using
                                    Huckins and Petty, 1983
                                  deuterium and  C labeled 2-
                                  isopropyldiphenyl phosphate
                                  (Measured)
                                Adequate, nonguideline study
                                using labeled components of the
                                mixture.
                                  998 (Estimated)
                                    EPIv4.11
                                  570 (Estimated)
                                    EPIv4.11
                                   193 (Estimated)
                                    EPIv4.11
TBB was detected in adipose, liver, and
muscle tissues in rat dams and rat pup
adipose tissue. The primary metabolite
of TBB (TBBA) was also detected in
liver tissue of rat dams. The pregnant
rats were administered 0, 0.1 or 1
mg/kg-day of FM550 by oral gavage
across gestation and through lactation
(GD8 - PND 21).  This study did not
analyze the samples for the presence of
IPTPP. (Estimated by analogy)
Patisauletal., 2013
                                 Based on a representative structure
                                 for a component of the mixture,
                                 with two isopropyl substituent
                                 groups.
                                Based on a representative structure
                                for a component of the mixture,
                                   th one isopropyl substituent
                                group.
                                 Based on a representative structure
                                 for a component of the mixture,
                                 with three isopropyl substituent
                                 groups.
                                                                    No data located.
BAFs were not calculated. Non
guideline study indicates that
absorption of TBB can occur in
rats through oral exposure; the test
substance identified as FM550 is a
mixture made up of TBB, TBPH
(CASRN 26040-51-7), IPTPP
(CASRN 68937-41-7) and TPP
(CASRN 115-86-6).
                                                           7-328

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                                                JUNE 2014 DRAFT REPORT
                                     Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
               DATA
         REFERENCE
       DATA QUALITY
       Metabolism in Fish
                                   320,000 (Estimated)
                                    EPIv4.11
                                 Based on a representative structure
                                 for a component of the mixture,
                                 with three isopropyl substituent
                                 groups.
                                   69,000 (Estimated)
                                    EPIv4.11
                                 Based on a representative structure
                                 for a component of the mixture,
                                 with two isopropyl substituent
                                 groups.
                                   700 (Estimated)
                                    EPIv4.11
                                 Based on a representative structure
                                 for a component of the mixture,
                                 with one isopropyl substituent
                                 group.
                                   1,300-1,900 for Trixylenyl phosphate;
                                   400 for Tricresyl phosphate
                                   Based on whole fish wet-weight,
                                   equilibrium in the fish was not reached
                                   for these compounds (Estimated by
                                   analogy)
                                    Bengtsson et al., 1986
                                 Non-guideline study using
                                 commercial mixtures.
Fathead minnows were exposed to 14C-
2-isopropylphenyl diphenyl phosphate
for 28 days followed by a 14 day
elimination phase
Labeled diphenyl phosphate was
identified as a major metabolite in whole
body fish samples; additional 14C-
residues were associated with lipid and
protein materials (Measured)
Huckins and Petty, 1983 (as cited in
Environment Agency, 2009)
Adequate, nonguideline study.
                                   The major route of metabolism of
                                   isopropylphenyl diphenyl phosphate in
                                   rainbow trout (Oncorhynchus mykiss) is
                                   O-dearylation to yield diphenyl
                                   phosphate; the diphenyl phosphate is
                                   then eliminated either as the compound
                                    Muir, 1984 (as cited in Environment
                                    Agency, 2009); Boethling and
                                    Cooper, 1985
                                 Adequate, nonguideline study.
                                                            7-329

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JUNE 2014 DRAFT REPORT
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT



DATA REFERENCE
itself or as a conjugate (Measured) ^^^
ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring
Ecological Biomonitoring
Human Biomonitoring
DATA QUALITY


Isopropylated triphenyl phosphate was detected in Beale AFB soils; air, water, sediment and soil in the US
(Boethling and Cooper, 1985; David and Seiber, 1999; Environment Agency, 2009; Salamova et al., 2014).
Isopropylphenyl diphenyl phosphate was found in vegetation in the US (Boethling and Cooper, 1985 (as cited in
Environment Agency, 2009)).
Isopropylated triphenyl phosphate was not included in the NHANES biomonitoring report (CDC, 2013).
         7-330

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                                                  JUNE 2014 DRAFT REPORT


Anderson C, Wischer D, Schmieder A, et al. (1993) Fate of triphenyl phosphate in soil. Chemosphere 27(5):869-879.

Bengtsson BE, Tarkpea M, Sletten T, et al. (1986) Bioaccumulation and effects of some technical triaryl phosphate products in fish and nitocra-
spinipes. Environ Toxicol Chem 5(9):853-861.

Boethling RS, Cooper JC (1985) Environmental fate and effects of triaryl and tralkyl/aryl phosphate esters. Residue Rev 94:49-99.

CDC (2013) Fourth national report on human exposure to environmental chemicals, updated tables, March 2013. Centers for Disease Control and
Prevention. http://www.cdc.gov/exposurereport/pdf/FourthReport UpdatedTables Mar2013 .pdf. Accessed May 10, 2013.

ChemID (2013) Phenol, isopropylated, phosphate (3:1). ChemID plus. National Library of Medicine, http://chem.sis.nlm.nih.gov/chemidplus/.

Cleveland L, Mayer FL, Buckler DR, et al. (1986) Toxicity of five alkyl-aryl phosphate ester chemicals to four species of freshwater fish. Environ
Toxicol Chem 5(3):273-282.

David MD, Seiber JN (1999) Analysis of Organophosphate Hydraulic Fluids in U.S. Air Force Base Soils. Arch Environ Contam Toxicol
36(3):235-241.

ECF£A (2013a) Isopropylated triaryl phosphate. Classification & labelling inventory. European Chemicals Agency. http://clp-
inventory.echa.europa.eu/SummaryOfClassAndLabelling.aspx?SubstanceID=18683&HarmOnly=no?fc=true&lang=en.

ECFiA (2013b) Phenol, isopropylated, phosphate (3:1). Registered substances. European Chemicals Agency.
http://apps.echa.europa.eu/registered/data/dossiers/DISS-9c7ba203-61eO-4c46-e044-00144f67d249/DISS-9c7ba203-61eO-4c46-e044-
00144f67d249  PISS-9c7ba203-61 eO-4c46-e044-00144f67d249.html.

ECOSAR (Ecological Structure Activity Relationship), Version 1.11. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/oppt/newchems/tools/21ecosar.htm.
                                                      J
Environment Agency (2009) Environmental risk evaluation report: Isopropylated triphenyl phosphate (CAS nos. 28108-99-8, 26967-76-0 &
68937-41-7). UK.

EPA (1999) Determining the adequacy of existing data. Washington, DC: U.S. Environmental Protection Agency.
http: //www .epa. gov/hpv/pubs/general/datadeqfn .pdf.
                                                              7-331

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                                                  JUNE 2014 DRAFT REPORT


EPA (2005) Pollution prevention (P2) framework. Washington, DC: U.S. Environmental Protection Agency, Office of Pollution Prevention and
Toxics, http://www.epa.gov/opptintr/newchems/pubs/sustainable/p2frame-june05a2.pdf.

EPA (2010) Screening hazard characterization sponsored chemical Isopropylated triphenyl phosphate. Supporting chemical trixylyl phosphate.

EPA (2012) Using noncancer screening within the SF initiative. Washington, DC: U.S. Environmental Protection Agency.
http: //www .epa. gov/oppt/sf/pubs/noncan-screen .htm.

EPI Estimation Programs Interface (EPI) Suite, Version 4.11. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm.

FMC Corporation (1990) Durad 110 non-definitive acute oral toxicity study in rats with cover letter dated 102590 and attachments. FMC
Corporation. Submitted to the U.S. Environmental Protection Agency under TSCA.

Great Lakes Chemical Corporation (2001) HPV test plan and robust summaries for isopropylated triphenyl phosphate.

Great Lakes Chemical Corporation (2004a) Submission of reproductive and fetal survival effects in the rat via an OECD 421 guideline screening
study on a research and development material of phenol, isopropylated phosphate.

Great Lakes Chemical Corporation (2004b) Submission of reproductive and fetal survival effects in the rat via an OECD 422 guideline screening
study of phenol, isopropylated phosphate.

Heitkamp MA, Huckins JN, Petty JD, et al. (1984) Fate and metabolism of isopropylphenyl diphenyl phosphate in freshwater sediments. Environ
SciTechnol 18(6):434-439.

Huckins JN, Petty JD (1983) Dynamics of isopropylphenyldiphenyl phosphate in fathead minnows (Pimephales promelas). Chemosphere
12(6):799-808.
                                                      J
Huckins JN, Fairchild JF, Boyle TP (1991) Role of exposure mode in the bioavailability of triphenyl phosphate to aquatic organisms. Arch
Environ Contam Toxicol 21:481-485.

IUCLID (2000) Phenol, isopropylated, phosphate. IUCLID data set.

IUCLID (2001) Isopropylated triphenyl phosphate. IUCLID data set. Great Lakes Chemical Corp.
                                                              7-332

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                                                  JUNE 2014 DRAFT REPORT


Mayer F, Adams WJ, Finley MT, et al. (1981) Phosphate ester hydraulic fluids: An aquatic environmental assessment of pydrauls 50E and 1 15E.
In: Branson DR Dickson KL, eds. American Society for Testing and Materials STP 737: 103-123.

Mill T (2000) Photoreactions in surface waters. In: Boethling R Mackay D, eds. Handbook of Property Estimation Methods for Chemicals,
Environmental Health Sciences. Boca Raton: Lewis Publishers, 355-381.

Muir CG, Yarechewski AL, Grift NP (1989) Biodegradation of four triaryl/alkyl phosphate esters in sediment under various temperature and redox
conditions. Toxicol Environ Chem 18(4):269-286.

Muir DCG (1984) Phosphate esters. Handbook of Environmental Chemistry Anthropogenic Substances. Berlin, Germany: Springer-Berlag, 41-66.

Nobile ER Page SW, Lombardo P (1980) Characterization of 4 commercial flame retardant aryl phosphates. Bull Environ Contam Toxicol
25(5):755-761.

OncoLogic (2008) U.S. EPA and LogiChem, Inc. 2005, Version 7.0. 2008.

PBT Profiler Persistent (P), Bioaccumulative (B), and Toxic  (T) Chemical (PBT) Profiler, Version 1.301. Washington, DC: U.S. Environmental
Protection Agency, www.pbtprofiler.net.

Patisaul HB, Roberts SC, Mabrey N, et al. (2013) Accumulation and endocrine disrupting effects of the flame retardant mixture Firemaster 550 in
rats: an exploratory assessment. J Biochem Mol Toxicol 27(2): 124-36.

Renberg et al (1980) As reported  in environmental risk evaluation report: Isopropylated triphenyl phosphate.

Saeger VW, Hicks O, Kaley RG,  et al. (1979) Environmental fate of selected phosphate esters. Environ Sci Technol 13(7):840-844.

Salamova A, Ma Y, Venier M, et al.  (2014) High levels of organophosphate flame retardants in the Great Lakes atmosphere. Environ Sci Technol
Sanders HO, Hunn JB, Robinson-Wilson E, et al. (1985) Toxicity of seven potential polychlorinated biphenyl substitutes to algae and aquatic
invertebrates. Environ Toxicol Chem 4(2): 149-154.

Sherren (2003) As reported in environmental risk evaluation report: Isopropylated triphenyl phosphate.
                                      *
Weil ED (2001) Flame retardants, phosphorus. Kirk-Othmer's Encyclopedia of Chemical Technology. Wiley-Interscience, 484-510.



                                                              7-333

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                                                JUNE 2014 DRAFT REPORT


Wightman RH, Malaiyandi M (1983) Physical properties of some synthetic trialkyl/aryl phosphates commonly found in environmental samples.
Environ Sci Technol 17(5): 25 6-261.

Yang SM, Thieme RA, Von Meyerinck L, et al. (1990) Identification of cyclic metabolites of isopropylated phenyl phosphates in rabbit bile.
Biomed Environ Mass Spectrom 19(9): 5 73-5 76.
                                                            7-334

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              Melamine
                                                   Screening Level Toxicology Hazard Summary

This table only contains information regarding the inherent hazards of flame retardant chemicals. Evaluation of risk considers both the hazard and exposure associated with the
substance including combustion and degradation by-products. The caveats listed in the legend and footnote sections must be taken into account when interpreting the hazard
information in the table.
VL = Very Low hazard L = Low hazard   = Moderate hazard H = High hazard VH = Very High hazard - Endpoints in colored text (VL, L,   , H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].






Chemical






CASRN
Human Health Effects

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Melamine
108-78-1


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                                                                        7-335

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                                                         JUNE 2014 DRAFT REPORT
H2N^

  N'   >-NH2

H,N
                                                                                                              CASRN: 108-78-1
                                                                                                              MW: 126.13
                                                                                                              MF: C3H6N6
                                                                                                              Physical Forms: Solid
                                                                                                              Neat: Solid
                                                                                                              Use: Flame retardant
SMILES: nlc(N)nc(N)ncl(N)
Synonyms: l,3,5-triazine-2,4,6-triamine; Cyanuramide; Cyanurotriamide; Cymel, Isomelamine; Melamine; 2,4,6-triamino-S-triazine; S-Triazinetriamine; 1,3,5-
triazine-2,4,6(lH,3H,5H)-triimine
Chemical Considerations: This is a discrete organic chemical with a MW below 1,000. EPI v4.11 was used to estimate physical/chemical and environmental fate
values in the absence of experimental data. Measured values from experimental studies were incorporated into the estimations.
Polymeric: No
Oligomeric: Not applicable
Metabolites, Degradates and Transformation Products: Hydrolysis products: ammeline, ammelide and cyanuric acid; Metabolites: cyanuric acid; Pyrolysis:
ammonia, melem, melone (OECD-SIDS, 1998; Crews et al., 2006; Liu et al., 2010; Zheng et al., 2013).
Analog: None
Endpoint(s) using analog values: Not applicable
          Analog Structure: Not applicable
Structural Alerts: Substituted triazines, aquatic toxicity; toxicity to the respiratory system, basic amines; systemic effects, amine groups; potential nephrotoxins,
amines; genetic toxicity, aromatic amines; developmental toxicity, aromatic amines (EPA, 2010, 2012).
Risk Phrases: None identified (ESIS, 2012).
Hazard and Risk Assessments: Melamine was assessed under the Screening information data set (SIDS) for HPV chemicals (OECD-SIDS, 1998).
                                                                     7-336

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JUNE 2014 DRAFT REPORT
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
PHYSICAL/CHEMICAL PROPERTIES
Melting Point (°C)
Boiling Point (°C)
Vapor Pressure (mm Hg)
Water Solubility (mg/L)
350
Decomposes and sublimes; ammonia
will be split off at >300°C and
possibly cyanuric acid at >600°C
which burns in the open flame
(Measured)
361
using the DSC method; using 99.9%
pure melamine (Measured)
345
(Measured) ^^^K
354
Decomposes at >280°C forming
ammonia (Measured)
>280 Decomposes
Sublimes; Heat of sublimation: -121
kJ/mol at 25 °C (Measured)
3.59xl(r10 at 20°C (Extrapolated)
3.52xlO-10at20°C
Reported as 4.7xlO'8 Pa at 20°C;
Dynamic method with N2 or NH3
(Extrapolated)
3,480 (Measured)
using OECD 105
OECD-SIDS, 1998; ECHA, 2013
^^^
ECHA, 2013
PhysProp, 2012
OECD-SIDS, 1998
OECD-SIDS, 1998; ECHA, 2013
PhysProp, 2012
OECD-SIDS, 1998; ECHA, 2013
ECHA, 2013
This substance sublimes
according to results reported in
secondary source.
Guideline study reported in
secondary source.
Reported in a secondary source.
Reported in a secondary source.
This substance sublimes
according to results reported in
secondary source. Also indicated
in the melting point entry above.
Consistent with other reported
extrapolated values.
Nonguideline study reported in
secondary source.
Guideline study reported in a
secondary source.
         7-337

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JUNE 2014 DRAFT REPORT
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT

Log Kow
Flammability (Flash Point)
Explosivity
DATA
3,200 (Measured)
at 20°C; pH 7-8
3,000 (Measured)
at 20°C;pH 8.4-8.9 ^
-1.14
at 25°C; OECD 107 Shake flask
method (Measured) ™
-1.22
OECD 107 Shake flask method
(Measured)
-1.37
(Measured)
Not flammable (Measured)
Flash point: >280°C (Measured)
Not explosive according to Directive
84/449/EEC, A. 10 (Measured)
Weakly explosive according to
Method VDI 3673 (Measured)
REFERENCE
OECD-SIDS, 1998
OECD-SIDS, 1998
OECD-SIDS, 1998
b^^s '
ECHA, 2013
PhysProp, 2012
OECD-SIDS, 1998
ECHA, 2013
OECD-SIDS, 1998
OECD-SIDS, 1998
DATA QUALITY
Reported in a secondary source.
Reported in a secondary source.
Guideline study reported in a
secondary source.
Guideline study reported in a
secondary source.
Reported in secondary source.
Reported in a secondary source.
Reported in a secondary source;
study details not provided.
Guideline study reported in a
secondary source.
Reported in a secondary source.
         7-338

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JUNE 2014 DRAFT REPORT
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
Pyrolysis
pH
pKa
DATA
Deammoniation and condensation lead
to compounds with higher molecular
mass when melamine is heated above
300°C (in the absence of ammonia or
at low ammonia partial pressure).
Thermal degradation starts with the
release of ammonia and the formation
of melem (CASRN 1502-47-2).
Heating to 600°C yields more
ammonia and melone (CASRN 325 18-
77-7) (Measured) ^
7.5 and 9.5;
Test substance: 100 g/L of melamine
(99.8%) in 10% aqueous suspension;
Borealis internal test method No. 210
(Measured) ^^
8 (Measured)
pKbl = 7.3;
pKb2=11.4
according to OECD 112 (Measured)
pKbl = 9
There are several amino groups that
result in basic properties. (Measured)
pKbl = 9
pKb2 = 14
Kbi= l.lxlO'9
Kb2 = l.OxlO-14 at 25°C (Measured)
Considered a weak base
REFERENCE
Crews et al., 2006
^^^
b^^s '
ECHA, 2013
OECD-SIDS, 1998
ECHA, 2013
Baynes et al., 2008
Crews et al., 2006
OECD-SIDS, 1998
DATA QUALITY
Supporting information provided.
Reported in a secondary source.
Approximate value reported in a
secondary source. No study
details provided.
Guideline study reported in a
secondary source.
Reported from a nonguideline
study.
Study details were not available.
Supporting information provided
in a secondary source.
         7-339

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JUNE 2014 DRAFT REPORT
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT

DATA
Neutral at pH values of 6 to 13;
Cation formation at the triazine ring
nitrogen at pH values of 1 to 4
(Measured)
5 (Measured)
REFERENCE

Weber, 1970; HSDB, 2008
DATA QUALITY

Reported in a secondary source.
         7-340

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JUNE 2014 DRAFT REPORT
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
HUMAN HEALTH EFFECTS
Toxicokinetics
Dermal Absorption in vitro
Absorption,
Distribution,
Metabolism &
Excretion
Oral, Dermal or Inhaled
Melamine was rapidly absorbed, distributed to body fluids, cleared from plasma and excreted mainly via
urine in monkeys. In rats, melamine was distributed to the stomach, small intestine, cecum, and large
intestine, and found in blood and urine. Following a single oral exposure to pregnant rats, melamine was
detected in the maternal serum, breast milk, whole foetus, amniotic fluid, neonatal serum and neonatal
kidney. There is evidence that Melamine passed through the placenta, reached the fetus and
accumulated in the lactating mammary gland. Excretion occurred through the placenta of the fetus and
the kidneys of neonates and was later excreted into amniotic fluid. Melamine was transferred quickly to
fetal circulation in studies where placentas from mothers following caesarean section or normal delivery
were perfused with melamine. Melamine was readily cleared by the kidney in pigs administered
melamine intravenously; distribution may be limited to the extracellular fluid compartment. There was
no concern for binding in tissues. The half-life was reported as 4.04 hours. In monkeys, the half-life in
plasma was ~4.41 hours. Other data for the melamine indicate an elimination phase half-life of 2.7 hours
from plasma and 3 hours for urine.

Rhesus monkeys were orally
administered melamine at a single
dose of 1.4 mg/kg bw. Melamine was
rapidly absorbed, distributed to body
fluids, rapidly cleared from plasma and
excreted mainly via urine. The half-life
in plasma was -4.41 hours. There was
no correlation (concentration-time
curve in plasma and urine) between
melamine and cyanuric acid,
suggesting that melamine may not be
metabolized to cyanuric acid in vivo.
Pregnant Sprague-Dawley rats were
administered a single oral dose of
melamine (-6-7 mg in <2 ml water) on
GD 17. Melamine was also
administered to neonates at postnatal
day 14 ((~0.3-0.6mg in <0.2 mL in

Liu etal., 2010
Chuetal., 2010
No data located.
Adequate, primary source
Adequate primary source
         7-341

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JUNE 2014 DRAFT REPORT
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT


Other
DATA
water).
Melamine was detected in the maternal
serum, breast milk, whole foetus,
amniotic fluid, neonatal serum and
neonatal kidney. This is evidence that
Melamine passed through the placenta,
reached the fetus and accumulated in
the lactating mammary gland.
Excretion occurred through the
placenta of the fetus and the kidneys of
neonates and was later excreted into
amniotic fluid.
Distributed to stomach, small intestine,
cecum, and large intestine, and found
in blood and urine of rats.
The elimination phase half-life
calculated from plasma data was 2.7
hours, and the urinary half-life was 3.0
hours. The renal clearance was
determined to be 2.5 mL/min.
Pigs (5 weanling) were administered
Melamine intravenously at a dose of
6.13 mg/kg.
Melamine is readily cleared by the
kidney; distribution may be limited to
the extracellular fluid compartment.
No concern for binding in tissues.
Half-life: 4.04 hours; clearance: 0.11
L/h/kg; volume distribution: 0.61 L/kg.
Placentas from mothers following
caesarean section or normal delivery
were perfused with 0 mM or 1 mM
melamine, or 10 mM melamine with
REFERENCE
^^^
b^^s '
ECHA, 2013
Mastetal., 1983
Baynes et al., 2008
Partanen et al., 2012
DATA QUALITY

Study details reported in a
secondary source.
Adequate, non-guideline study.
Adequate primary source
Adequate, primary study
         7-342

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JUNE 2014 DRAFT REPORT
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT


Acute Mammalian Toxicity
Acute Lethality
Oral
Dermal
Inhalation
DATA
10 nM cyanuric acid (CYA).
Melamine (34-45%) was transferred
quickly to fetal circulation (0.12-
1.34% within 5 minutes, 34% within 4
hours); addition of CYA had no effect.
Functionality of the placental tissue
was not affected. Viability of BeWo
cells was decreased. It is concluded
that melamine may be fetotoxic.
REFERENCE
^^^
DATA QUALITY

MODERATE: Based on an inhalation LC50 of 3.25 mg/L, a dermal LD50 of > 1,000 mg/kg, and a
structural alert for basic amines. Oral LD50 values were > 2,000 mg/kg.
Rat LD50 = 3,160 mg/kg (male), 3,850
mg/kg (female)
Rat LD50 = 3,161 mg/kg (male), 3,828
mg/kg (female)
Rat LD50 >6,400 mg/kg
Mouse LD50 = 3,296 mg/kg (male),
7,0 14 mg/kg (female)
Mouse LD50 = 4,550 mg/kg
LD50 ~ 4,800 mg/kg
Rabbit LD50 > 1,000 mg/kg
RatLC50=3.248mg/L
Trochimowicz et al., 2001
NTP, 1983; Melnick et al., 1984
BASF, 1969
NTP, 1983; Melnick et al., 1984
American Cyanamid Company,
1955; May, 1979; Trochimowicz et
al., 2001
Hoechst, 1963
Unknown, 1990; ECHA, 2013
Ubaidullajev, 1993
Sufficient study details were not
reported.
Sufficient study details reported.
Sufficient study details were not
available.
Sufficient study details reported.
Sufficient study details were not
available. Reported in secondary
sources.
Sufficient study details were not
available.
Sufficient study details were not
available. Study was not
conducted according to any
specific guideline; insufficient
description of the method.
The study details, if present, were
not translated into English.
         7-343

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                                                          JUNE 2014 DRAFT REPORT
                                                           Melamine CASRN 108-78-1
            PROPERTY/ENDPOINT
              DATA
         REFERENCE
       DATA QUALITY
                                                Rat inhalation 4-hour LC50 >5.19 mg/L
                                                (nose only)
                                   ECHA, 2013
                                Adequate study reported in a
                                secondary source. Study was
                                conducted according to OECD
                                Guideline 403 and GLP.
                                                Potential for toxicity to the respiratory
                                                system based on a structural alert for
                                                basic amines.
                                   Professional judgment
                                Estimated based on a structural
                                alert for basic amines and
                                professional judgment.
Carcinogenicity
MODERATE: The carcinogenicity hazard potential for melamine is based on evidence that oral
exposure to melamine causes cancer in experimental animals. However, there is no evidence for
carcinogenicity to humans. In addition, OncoLogic estimated a marginal concern that is consistent with
DfE Moderate hazard criteria. Tumor formation in animals appeared to be due to mechanical irritation
by bladder calculi/stones. IARC classifies melamine as Group 3: not classifiable as to its carcinogenicity to
humans.
                 OncoLogic Results
Marginal
                 Carcinogenicity (Rat and
                 Mouse)
Group 3: melamine is not classifiable
as to its carcinogenicity to humans;
there is inadequate evidence in humans
for the carcinogenicity of melamine,
and there is sufficient evidence in
experimental animals for the
carcinogenicity of melamine under
conditions in which it produces
bladder calculi.
                                                Significant formation of transitional
                                                cell carcinomas in the urinary bladder
                                                of dosed male rats and significant
                                                chronic inflammation in the kidney of
                                                dosed female rats were observed
                                                following exposure in the feed for up
                                                to 103 weeks. Carcinoma formation
                                                was significantly correlated with the
                                                incidence of bladder stones. A
                                                transitional-cell papilloma was
OncoLogic, 2005
IARC, 1999
                                   NTP, 1983; Huff, 1984; Melnick et
                                   al., 1984
IARC classification statement.
                                Sufficient study details reported.
                                                                     7-344

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                                               JUNE 2014 DRAFT REPORT
                                                Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                    observed in the urinary bladder of a
                                    single high dose male rat, and
                                    compound related lesions were
                                    observed in the urinary tract of dosed
                                    animals. Based on the mechanical
                                    nature of tumor formation, FDA and
                                    EPA considered melamine
                                    noncarcinogenic.
                                    Increased incidence of acute and
                                    chronic inflammation and epithelial
                                    hyperplasia of the urinary bladder was
                                    observed in male mice following oral
                                    (feed) exposure for up to 103 weeks.
                                    Bladder stones and compound related
                                    lesions were observed in the urinary
                                    tract of test animals. There was no
                                    evidence of bladder tumor
                                    development. Melamine was not
                                    considered carcinogenic.
                     NTP, 1983; Melnick et al., 1984
                       Sufficient study details reported.
                                    Melamine-induced proliferative
                                    lesions of the rat urinary tract were
                                    directly due to the irritant stimulation
                                    of calculi, and not to molecular
                                    interactions between melamine or its
                                    metabolites with the bladder
                                    epithelium.
                     Okumura et al., 1999
                       Sufficient study details reported.
                                    Water intake, used as an index of
                                    urinary output, was increased by NaCl
                                    treatment. Calculus formation resulting
                                    from melamine administration was
                                    suppressed dose-dependently by the
                                    simultaneous NaCl treatment. The
                                    main constituents of calculi were
                     Ogasawara et al., 1995
                       Sufficient study details reported.
                                                           7-345

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                                               JUNE 2014 DRAFT REPORT
                                                 Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                     melamine and uric acid (total contents
                                     61.1-81.2%).  The results indicate that
                                     melamine-induced proliferative lesions
                                     of the urinary tract of rats were
                                     directly due to the irritation induced-
                                     stimulation of calculi, and not
                                     molecular interactions between
                                     melamine itself or its metabolites with
                                     the bladder epithelium.
                                     Melamine: As an initiator, melamine
                                     caused no significant increase in
                                     papillomas per mouse when compared
                                     to controls.
                     Perrella and Boutwell, 1983
                        Sufficient study details reported;
                        non-guideline study.
                                     Diffuse papillary hyperplasia of the
                                     bladder epithelium and bladder calculi
                                     were observed in all melamine treated
                                     rats. Elevated spermidine/spermine
                                     Nl-acetyltransferase (SAT) activity
                                     following melamine treatment was
                                     considered to be an indicator of cell
                                     proliferation.
                     Matsui-Yuasi et al., 1992
                        Sufficient study details reported;
                        non-guideline study.
                                     Decreased antitumor activity was
                                     correlated with increasing
                                     demethylation; melamine was
                                     considered inactive as an antitumor
                                     drug.
                     Rutty and Connors, 1977
                        Sufficient study details were not
                        available.
                                     In an in vitro cytotoxicity study in
                                     cultured ADJ/PC6 plasmacytoma
                                     ascites tumor cells the ID50 (median
                                     ineffective dose) was 470 (ig/mL after
                                     72 hours of treatment.
                     Rutty and Abel, 1980
                        Sufficient study details were not
                        available.
                                                            7-346

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JUNE 2014 DRAFT REPORT
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT

Combined Chronic
Toxicity/Carcinogenicity
Other
Genotoxicity

Gene Mutation in vitro
DATA
No effects were observed in rats fed
1,000 ppm of melamine. Four of the
10 rats fed 10,000 ppm of melamine
had bladder stones associated with the
development of benign papillomas.
Increased incidence of urinary bladder
stones (6/20 rats) was noted in the
10,000 ppm dose group, and was
associated with an increase in benign
papillomata. The NOAEL was
determined to be 1,000 ppm (67
mg/kg).

REFERENCE
American Cyanamid Company,
1958
American Cyanamid Company,
1955
b^S

DATA QUALITY
Sufficient study details were not
available.
Sufficient study details were not
available.
No data located.
MODERATE: Based a weight of evidence from multiple studies. Results were positive for chromosomal
aberrations and sister chromatid exchange in vivo in mice exposed to melamine. There were also positive
results in vitro for DNA synthesis-inhibition in Hela S3 cell and genetic toxicity in Escherichia coli WP2s
in a microscreen assay following exposure to melamine. In addition, there is estimated potential for
genotoxicity based on a structural alert for aromatic amines.
Bacterial forward mutation assay:
Negative with and without liver
activation
Bacterial forward mutation assay:
Negative
Bacterial reverse mutation assay:
Negative with and without liver
activation
Bacterial reverse mutation assay:
Negative with and without unspecified
metabolic activation
In vitro mouse lymphoma test:
Negative with and without liver
activation
Haworth et al., 1983; NCI/NTP,
2007
Seiler, 1973
Lusbyetal., 1979
Mastetal., 1982b
McGregor etal., 1988
Sufficient study details reported
Sufficient study details were not
available.
Sufficient study details were not
available.
Sufficient study details were not
available.
Sufficient study details reported.
         7-347

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JUNE 2014 DRAFT REPORT
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT


Gene Mutation in vivo
Chromosomal Aberrations in
vitro
Chromosomal Aberrations in
vivo
DATA
CHO/HGPRT forward mutation assay:
Negative with and without liver
activation

In vitro chromosomal aberrations test:
Negative in CHO with and without
liver activation
In vitro sister chromatid exchange
assay: Negative in CHO with and
without liver activation
In vitro sister chromatid exchange
assay: Negative in CHO with and
without liver activation
In vivo mouse micronucleus test: The
initial test gave a positive trend (P =
0.003) for chromosomal damage;
however, both peripheral blood smears
and the repeat bone marrow test were
negative. The overall conclusion was
that melamine does not induce
chromosomal damage.
In vivo mouse micronucleus test:
Negative without activation
In vivo chromosome aberrations test in
mice: Positive
In vivo sister chromatid exchange
assay in mice: Positive
REFERENCE
Mastetal., 1982b

Galloway et al, 1987; NCI/NTP,
2007
Mastetal., 1982b
^^^
Galloway et al., 1987; NCI/NTP,
2007
NTP, 1983; Shelby etal., 1993
Mastetal., 1982b
NCI/NTP, 2007
NCI/NTP, 2007
DATA QUALITY
Sufficient study details were not
available.
No data located.
Sufficient study details reported.
Sufficient study details were not
available.
Sufficient study details reported.
Sufficient study details reported.
Sufficient study details were not
available.
Sufficient study details reported.
Sufficient study details reported.
         7-348

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JUNE 2014 DRAFT REPORT
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT

DNA Damage and Repair
Other
DATA
In vivo and in vitro unscheduled DNA
synthesis (UDS) test: None of the
tested chemicals, including melamine,
were genotoxic hepatocarcinogens in
the in vivo assay, and melamine was
negative for UDS in the in vitro assay
SQS/umu test: Negative for its ability
to result in DNA damage and induce
the expression of the umu operon
DNA synthesis-inhibition test in Hela
S3 cells: Inhibits DNA synthesis by
50% (DI50) at >300 (M
Potential for genotoxicity based on a
structural alert for aromatic amines
Sex-linked recessive lethal mutations
were not induced in Drosophila
melanogaster .
Drosophila Muller-5 test: Negative for
mutagenicity ^^^^^^
Drosophila melanogaster Sex-linked
recessive lethal: No mutagenic effects
were observed.
In vitro flow cytometric DNA repair
assay: Negative for genotoxic effects
Microscreen assay: Positive for genetic
toxicity in E. coli WP2s
Growth and genotoxic effects to
bacteria (Salmonella typhimurium) and
yeast (Saccharomyces cerevisiae):
Non-mutagenic in S. typhimurium with
REFERENCE
Mirsalis et al., 1983
Heil and Reifferscheid, 1992
^^^
Heil and Reifferscheid, 1992
Professional judgment
IARC, 1986; OECD-SIDS, 1998
Rohrborn, 1959
Luers and Rohrborn, 1963
Seldenetal., 1994
Rossman et al., 1991
Sugitaetal., 1991
DATA QUALITY
In vivo and in vitro unscheduled
DNA synthesis (UDS) test: None
of the tested chemicals, including
melamine, were genotoxic
hepatocarcinogens in the in vivo
assay, and melamine was negative
for UDS in the in vitro assay
Non-guideline study.
Sufficient study details were not
available.
Estimated based on a structural
alert for aromatic amines and
professional judgment.
Secondary source; sufficient
study details were not available.
Sufficient study details were not
available.
Sufficient study details were not
available.
Non-guideline study.
Non-guideline study.
Sufficient study details were not
available.
         7-349

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                                                        JUNE 2014 DRAFT REPORT
                                                          Melamine CASRN 108-78-1
           PROPERTY/ENDPOINT
              DATA
         REFERENCE
      DATA QUALITY
                                              or without S-9 mix. The growth of
                                              eight out of nine strains tested was
                                              delayed by 10 mM melamine during
                                              24-hour cultivation. S. cerevisiae strain
                                              was tested, and did not recover its
                                              growth following 48-hour cultivation.
Reproductive Effects
HIGH: Based on a NOAEL = 10 mg/kg-day (LOAEL of 50 mg/kg-day) for increased apoptotic index of
spermatogenic cells in male mice orally administered melamine for 5 days. In addition, altered
epididymal sperm morphology and damage of testicular DNA were reported at a dietary dose of 412
mg/kg-day (lowest dose tested).
                 Reproduction/Developmental
                 Toxicity Screen
                 Combined Repeated Dose with
                 Reproduction/ Developmental
                 Toxicity Screen
                 Reproduction and Fertility
                 Effects
In a 5-day study, male mice (8/group)
were orally administered melamine
only at doses of 0, 2,  10 and 50 mg/kg-
day or melamine in combination with
cyanuric acid at doses of 0, 1,5 and 25
mg/kg-day.
Sperm abnormalities were evaluated in
a separate select group of mice
(8/group), which were fed melamine
only at doses of 0, 412, 824, and 1648
mg/kg-day, or melamine in
combination with cyanuric acid at
doses of 0, 206, 412, or 824 mg/kg-
day.
No deaths in mice fed 2,  10 and 50
mg/kg-day melamine or 1 and 5
mg/kg-day melamine and cyanuric
acid; 3 deaths in co-administration
Yin etal., 2013
                                                                  Mo data located.
                                                                 No data located.
Adequate, primary study
                                                                    7-350

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JUNE 2014 DRAFT REPORT
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
















DATA
group fed 25 mg/kg/day.
Grossly enlarged, pale yellow kidneys
in all mice that survived. Increase in
apoptotic index of spermatogenic cells
in mice fed 50 mg/kg-day melamine-
only; more severe apoptosis in co-
administered mice at 5 and 25 mg/kg-
day.
NOAEL: 10 mg/kg-day
LOAEL: 50 mg/kg-day (increased
apoptotic index of spermatogenic
cells)
Sperm abnormality group: no deaths in
mice administered melamine-only; all
co-administered mice died before day
6 and exhibited anorexia, decreased
activity and hunched posture. Altered
epididymal sperm morphology
(particularly the head abnormality) and
damage of testicular DNA in all
melamine-only treatment groups.
NOAEL: not established
LOAEL: 412 mg/kg-day (altered
epididymal sperm morphology;
damage of testicular DNA)
There were no treatment-related
macroscopic or microscopic effects on
mammary glands, ovaries, prostate,
seminal vesicles, testes and uterus in
rats and mice in a 13 -week study.
REFERENCE

^^^
b^^s '

w



OECD-SIDS, 1999
DATA QUALITY








Study details, including
administered dose information,
were not provided.
         7-351

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JUNE 2014 DRAFT REPORT
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT

Other
Developmental Effects





























Reproduction/ Developmental
Toxicity Screen
Combined Repeated Dose with
Reproduction/ Developmental
Toxicity Screen
Prenatal Development




















Postnatal Development
DATA

REFERENCE

DATA QUALITY
No data located.
MODERATE: Estimated based on a structural alert for aromatic amines. Limited experimental data
indicated no developmental effects in rats exposed during gestation to doses up to 1,060 mg/kg-day. This
experimental data is insufficient to determine a hazard designation for this endpoint.





Melamine was administered to
pregnant female Wistar rats in the diet
at concentrations of 1,500 ; 4,500 and
15,000 ppm on day 6 through day 16
post coitum (136, 400, and 1060
mg/kg-day) Signs of maternal toxicity
at 136 mg/kg-day included decreased
body weight and feed consumption,
hematuria (23/25 rats), indrawn flanks
(7/25 rats), and piloerection (1/25
rats). No adverse effects on gestational
parameters and no signs of
developmental toxicity were noted.
Maternal toxicity:
NOAEL: 400
LOAEL: 1,060 mg/kg-day (decreased
body weight and feed consumption)
Developmental toxicity:
NOAEL > 1,060 mg/kg-day; highest
dose tested
LOAEL: Not established






Hellwig et al., 1996; ECHA, 2013






w














Mo data located.

No data located.


Limited study details reported in a
secondary source; test material as
cited in study report: Melamine
(mixture of Melamine from
Agrolinz and BASF at a ratio of
1:1); analytical purity: about
100%.














No data located.
         7-352

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JUNE 2014 DRAFT REPORT
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT

Prenatal and Postnatal
Development
Developmental Neurotoxicity
Other
Neurotoxicity

Neurotoxicity Screening
Battery (Adult)
Other
DATA


Potential for developmental toxicity
based on a structural alert for aromatic
amines.
(Estimated)
REFERENCE


Professional judgment
^^^
DATA QUALITY
No data located.
Mo data located.
Estimated based on a structural
alert for aromatic amines and
professional judgment.
LOW: Potential for neurotoxicity is expected to be low.

Potential for neurotoxicity is expected
to be low (Estimated)

Expert j udgment
Mo data located.
Estimated based on expert
judgment.
         7-353

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                                                         JUNE 2014 DRAFT REPORT
                                                           Melamine CASRN 108-78-1
           PROPERTY/ENDPOINT
              DATA
REFERENCE
DATA QUALITY
Repeated Dose Effects
MODERATE: Based on repeated oral exposure to melamine in rats. Bladder stones were reported at a
dose of 72 mg/kg-day in a 90-day dietary study in rats. In addition, decreased body weight gain and feed
consumption was reported. NOAELs of 167.5 and 140 mg/kg bw-day were reported in 7 day and 14 day
oral studies in rats, respectively. A NOAEL of 0.0005 mg/L was reported in a 4-month inhalation study
in rats based on no general toxic or gonadotoxic symptoms. Nephrotoxicity was noted in a 3-month oral
study in monkeys at 200 mg/kg-day (NOAEL = 60 mg/kg-day). The formation of calculi, hyperactive
regeneration of renal tubular epithelium, tubular cell debris, crystal deposition, bladder ulcers and
bladder stones, epithelial cell atypia, hyperplasia of the urinary bladder, clinical signs, changes in clinical
chemistry, and decreased body weight gain were reported in laboratory animals following repeated oral
doses > 100 mg/kg-day. In addition, there is estimated potential for systemic effects based on a structural
alert for amine groups and an estimated potential for nephrotoxicity based on a structural alert for
amines.
                                               Rat 90-day dietary toxicity study: One
                                               male rat receiving  18,000 ppm and two
                                               males receiving 6,000 ppm died. Mean
                                               body weight gain and feed
                                               consumption were  reduced. Stones and
                                               diffuse epithelial hyperplasia in the
                                               urinary bladders were observed in
                                               male rats of all treatment groups. Focal
                                               epithelial hyperplasia was observed in
                                               only 1 male. A second and third 13-
                                               week repeated dose toxicity study was
                                               conducted in rats at a dose range of
                                               750 to 18,000 ppm; bladder stones
                                               were observed at all dose levels. At
                                               18,000 ppm, stones occurred in diets
                                               with and without the addition of
                                               ammonium chloride to drinking water.

                                               NOAEL: Not established
                                               LOAEL: 750 ppm  (72 mg/kg-day;
                                               bladder stones ); lowest dose tested
                                  NTP, 1983; Melnick et al., 1984
                       Sufficient study details reported.
                                                                     7-354

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                                               JUNE 2014 DRAFT REPORT
                                                Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                    In a 7-day oral study, male and female
                                    F344 rats were fed melamine and
                                    cyanuric acid (co-exposure) in the diet
                                    at concentrations of 0, 7, 23, 69, 229,
                                    or 694 ppm (0, 0.9, 2.8, 8.6,  17.6, or
                                    29.8 mg/kg-day). Rats were also  fed
                                    Melamine or cyanuric acid alone at a
                                    concentration of 1388 ppm (167.5
                                    mg/kg-day).
                                    Histopathological alterations
                                    consistent with nephrotoxicity at 229
                                    and 694 ppm (co-exposure); renal
                                    injury as evidenced by alterations in
                                    the expression of KIM-1, TIMP1,
                                    clusterin, osteopontin, and NGAL
                                    genes in kidney tissue. There were no
                                    statistically significant gene expression
                                    changes in rats fed melamine or
                                    cyanuric acid only. Crystals were
                                    present in the renal tubules in 5/12 rats
                                    fed melamine only.

                                    NOAEL: 1388 ppm (167.5 mg/kg-day;
                                    only dose tested)
                                    LOAEL: Not established
                     Camacho et al., 2011; Jacob et al.,
                     2011
                       Study details reported in a
                       primary source. Toxicity was a
                       result of co-exposure of melamine
                       and cyanuric acid. No toxicity
                       was evident in rats fed melamine
                       in the absence  of cyanuric acid;
                       only one melamine-only dose
                       tested.
                                    Rat 28-day dietary toxicity study:
                                    Incidence and size of bladder stones
                                    were directly related to the amount of
                                    substance administered. The larger
                                    stones were found to be unchanged
                                    melamine in a matrix of protein, uric
                                    acid and phosphate.
                     American Cyanamid Company,
                     1984
                       Sufficient study details were not
                       available.
                                                           7-355

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                                               JUNE 2014 DRAFT REPORT
                                                Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                     Lowest effect dose (LED): 1,500 ppm
                                     (-125 mg/kg-day) in males.
                                     In a 3-month oral study, monkeys were
                                     administered melamine via nasal-
                                     gastric gavage at doses of 0, 60, 200 or
                                     700 mg/kg-day. Effects at 700 mg/kg-
                                     day included turbid and whitish urine,
                                     urine crystals,  red blood cell changes,
                                     increased serum alanine
                                     aminotransferase and kidney and/or
                                     liver weights, nephrotoxicity,
                                     pericarditis and increased
                                     hematopoiesis. Nephrotoxicity was
                                     also evident at 200 mg/kg-day.

                                     NOAEL: 60 mg/kg-day
                                     LOAEL: 200 mg/kg-day
                                     (nephrotoxicity)
                     Early etal., 2013
                        Study details reported in a
                        primary source.
                                     Rat 28-day dietary toxicity study:
                                     Clinical signs included a dose-related
                                     increase in pilo-erection, lethargy,
                                     bloody urine spots in the cage and on
                                     the pelage of animals, and
                                     chromodacryorrhea. The incidence of
                                     urinary bladder calculi and urinary
                                     bladder hyperplasia in treated animals
                                     was dose dependent, with a significant
                                     relationship between the calculi and
                                     hyperplasia. Calculi composition
                                     indicated the presence of an organic
                                     matrix containing melamine,
                                     phosphorus, sulfur, potassium, and
                                     chloride. Crystals of dimelamine
                     RTI, 1983
                        Sufficient study details reported
                                                           7-356

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                                              JUNE 2014 DRAFT REPORT
                                                Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                    monophosphate were identified in the
                                    urine.

                                    NOAEL: 2,000 ppm (240 mg/kg-day),
                                    excluding the observed increase in
                                    water consumption and the incidence
                                    of crystalluria.
                                    LOAEL: 4,000 ppm (475 mg/kg-day)
                                    based on the formation of calculi.
                                    In a 14-day oral study, rats were
                                    administered melamine at doses of 0,
                                    140, 700, and 1,400 mg/kg-day
                                    (lowered to 1,000 mg/kg-day
                                    subsequently due to mortality). A 5-
                                    day study was also conducted with
                                    genomic biomarkers on kidney tissues.
                                    Doses were 0, 350 and 1,050 mg/kg-
                                    day.
                                    Effects (14-day study) at 700 mg/kg-
                                    day included clinical signs of toxicity
                                    (red urine), decreased body weight,
                                    changes in clinical chemistry
                                    parameters (increased serum urea
                                    nitrogen and creatinine), and kidney
                                    effects (renal tubular cell debris,
                                    crystal deposition, and hyperactive
                                    regeneration of renal tubular
                                    epithelium)
                                    Systemic effects from the 5-day study
                                    were similar to the 14-day study.
                                    Significant up-regulation of Kim-1,
                                    Clu, Sppl, A2m, Lcn2, Tcfrsfl2a,
                                    Gpnmb, and CD44 and significant
                     Early etal., 2013
                       Study details reported in a
                       primary source.
                                                          7-357

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                                               JUNE 2014 DRAFT REPORT
                                                 Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                     down-regulation of Tff3.

                                     NOAEL: 140mg/kg-day
                                     LOAEL: 700 mg/kg-day (clinical
                                     signs, changes in clinical chemistry,
                                     tubular cell debris, crystal deposition,
                                     and hyperactive regeneration of renal
                                     tubular epithelium)
                                     Mouse 90-day dietary toxicity study: a
                                     single female mouse died after
                                     receiving 9,000 ppm. Mean body
                                     weight gain relative to controls was
                                     depressed. The incidence of mice with
                                     bladder stones was dose-related and
                                     was greater in males than in females.
                                     Sixty percent of mice having bladder
                                     ulcers also had urinary bladder stones.
                                     Bladder ulcers were multifocal or
                                     associated with inflammation
                                     (cystitis). Epithelial hyperplasia and
                                     bladder stones were observed together
                                     in 2 mice. Also, epithelial cell atypia
                                     was seen.

                                     NOAEL:  6,000 ppm (600 mg/kg-day).
                                     LOAEL:  9,000 ppm (900 mg/kg-day;
                                     decreased body weight gain, bladder
                                     ulcers and bladder stones, epithelial
                                     cell atypia)
                     NTP, 1983; Melnick et al., 1984
                        Sufficient study details reported.
                                     Increased incidence of acute and
                                     chronic inflammation and epithelial
                                     hyperplasia of the urinary bladder was
                                     observed in mice following oral (feed)
                     NTP, 1983
                        Repeated dose effects reported in
                        a carcinogenicity bioassay study.
                                                           7-358

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JUNE 2014 DRAFT REPORT
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT


DATA
exposure for up to 103 weeks to 2,250
or 4,500 ppm. There was also
increased incidence of bladder stones
in male mice.
NOAEL: Not established
LOAEL: 2,250 ppm in the diet (lowest
concentration tested; hyperplasia of the
urinary bladder, bladder stones in
males) ^^
Rat 24- to 30-month dietary toxicity
study: A dose related trend for dilated
glands in glandular gastric mucosa and
inflammation in non glandular gastric
mucosa was observed. Urinary bladder
calculi formation was not observed.
Rat 30-month dietary toxicity study:
Neither accumulation of calculi nor
any treatment-related urinary bladder
lesions were found.
Rabbit and dog 2 8 -day dietary toxicity
study: no significant rise in the body
temperature of rabbits was noted.
Gross histological examination of the
heart, lung, liver, spleen, thyroid,
pancreas, intestines, kidneys and
bladder did not show pathological
changes. A zone of fat was found in
the inner part of the renal cortex in two
dogs, but also in the kidneys of 3
control dogs.
Dog 1-year dietary toxicity study:
crystalluria started 60 to 90 days into
REFERENCE
^^^
Wolkowski, 1983
Mastetal., 1982a
Lipshitz and Stokey, 1945
American Cyanamid Company,
1955
DATA QUALITY

Sufficient study details were not
available.
Sufficient study details were not
available.
Sufficient study details were not
available.
Sufficient study details were not
available.
         7-359

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                                              JUNE 2014 DRAFT REPORT
                                                Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                    treatment, and persisted during the
                                    study period. No other effects
                                    attributable to melamine were
                                    observed.
                                    Melamine may cause kidney stone
                                    formation when ingested chronically in
                                    dogs. In addition, pediatric patients
                                    may be at increased risk for stone
                                    formation when melamine is combined
                                    with cyanuric acid in formula.
                     Skinner etal., 2010
                       Study details reported in a
                       primary source.
                                    In a 42-day study, Broiler hens
                                    (20/group) were fed diets containing
                                    melamine only, melamine in
                                    combination with cyanuric acid (CYA)
                                    or CYA only. Group 1: control; group
                                    II: 10 mg/kg MEL and 3.3 mg/kg
                                    CYA; group III: 30 mg/kg MEL and
                                    10 mg/kg CYA; group IV:  100 mg/kg
                                    MEL and 33.3 mg/kg CYA; group V:
                                    100 mg/kg MEL only; group VI: 33.3
                                    mg/kg CYA only.
                                    No clinical signs of toxicity. Melamine
                                    alone had no effect on growth, but co-
                                    administration and CYA alone had
                                    adverse effects. Average daily weight
                                    gain of group II was reduced and food
                                    consumption was decreased in group
                                    III. No pathological changes in the
                                    livers of hens in group II. Swelling of
                                    some hepatic cells and granular
                                    degeneration in hens co-administered
                                    melamine and CYA (severity
                                    increased with dose). Lesions in the
                     Ding etal., 2012
                       Study details reported in a
                       primary source. It appears that
                       effects from melamine-only
                       exposures are minimal and that
                       toxicity is a result of co-
                       administration with cyanuric acid.
                                                          7-360

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JUNE 2014 DRAFT REPORT
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT


Skin Sensitization

Skin Sensitization
Respiratory Sensitization
[Respiratory Sensitization
DATA
kidney were similar and correlated
with dose. Increased rate of renal
apoptosis in the melamine-only group
on day 42; rate was increased for
CYA-only group on days 21 and 42.
In a 4 -month study, male rats were
exposed via inhalation to melamine at
concentrations of 0, 0.011, 0.058 and
0.50 mg/m3. No general toxic or
gonadotoxic symptoms.
NOAEL: 0.50 mg/mg3 (0.0005 mg/L);
highest concentration tested
LOAEL: Not established
Potential for nephrotoxicity based on a
structural alert for amines
Potential for systemic toxicity based
on a structural alert for amine groups
REFERENCE

ECHA, 2013
b^S
Professional judgment
Professional judgment
DATA QUALITY

Insufficient description of the
study. It is not clear if a vapor,
dust or aerosol was applied. The
study is not considered to be
reliable.
Estimated based on a structural
alert for amine groups and
professional judgment.
Estimated based on a structural
alert for amine groups and
professional judgment.
LOW: Melamine is not a skin sensitizer to guinea pigs.
Non-sensitizing to guinea pigs
Non-sensitizing to guinea pigs
ECHA, 2013
Fasset and Roudabush, 1963;
Trochimowicz et al., 2001
Adequate study reported in a
secondary source. Study was
conducted in accordance with
OECD Guideline 406 and GLP.
Sufficient study details were not
available.
No data located.


No data located.
         7-361

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JUNE 2014 DRAFT REPORT
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
Eye Irritation

Eye Irritation
Dermal Irritation

Dermal Irritation
Endocrine Activity

DATA
REFERENCE
DATA QUALITY
LOW: Melamine was mildly irritating to rabbit eyes.
Non-irritating to rabbit eyes
Non-irritating to rabbit eyes following
0.5 mL of 10% melamine
Mild irritant to rabbit eyes following
exposure to 30 mg of dry powder
Slightly irritating to rabbit eyes
BASF, 1969
American Cyanamid Company,
1955; Trochimowicz et al., 2001
American Cyanamid Company,
1955; Trochimowicz et al., 2001
Marhold, 1972
Sufficient study details were not
available.
Sufficient study details were not
available.
Sufficient study details were not
available.
Sufficient study details were not
available.
VERY LOW: Melamine was not irritating to rabbit skin.
Not irritating to rabbit skin
Not irritating to rabbit skin
Not irritating to rabbit skin
Not irritating to rabbit skin
Rijcken, 1995
BASF, 1969
American Cyanamid Company,
1955; Trochimowicz et al., 2001
Fasset and Roudabush, 1963;
Trochimowicz et al., 2001
OECD 404 guideline study.
Sufficient study details were not
available.
Sufficient study details were not
available.
Sufficient study details were not
available.
There was limited data located for the endocrine endpoint. Melamine showed no estrogenic activity (no
change in B-galactosidase activity) in an in vitro yeast two-hybrid assay in Saccharomyces cerevisiae Y
190.
Showed no estrogenic activity (no
change in B-galactosidase activity) in
an in vitro yeast two-hybrid assay in
Saccharomyces cerevisiae Y 190.
ECHA, 2011
Reported in a secondary source.
Non-guideline study.
         7-362

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JUNE 2014 DRAFT REPORT
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
Immunotoxicity
Immune System Effects
DATA
REFERENCE
DATA QUALITY
There was limited data located for the immunotoxicity endpoint. Melamine did not inhibit the
mitogenesis of B- and T- lymphocytes in an in vitro mouse lymphocyte mitogenesis test. It is unclear how
well a mitogenesis test assesses immunotoxicity of chemicals. The available data are not sufficient to
determine the hazard potential for this endpoint.
Did not inhibit the mitogenesis of B-
and T- lymphocytes in an in vitro
mouse lymphocyte mitogenesis test.
ECHA, 2011
^^^
Reported in a secondary source.
Unclear how well mitogenesis test
assesses immunotoxicity of
chemicals.
ECOTOXICITY
ECOSAR Class
Acute Aquatic Toxicity
Fish LC50
Melamines
LOW: Based on experimental acute aquatic values > 100 mg/L in fish, daphnia, and algae. Estimated
toxicity values indicate No Effects at Saturation (NES).
Oryzias latipes 48-hour LC50 = 1,000
mg/L
(Experimental) ^^^^
Freshwater fish (Leuciscus idus
melanotus) 48-hour LC50 >500 mg/L
(Experimental)
Poecilia reticulata 96-hour LC50
>3,000 mg/L
(Experimental)
Freshwater fish (Oncorhynchus
mykiss) 96-hour LC50 >3,000 mg/L
NOEC = 3,000 mg/L
semi-static; 0, 750, 1,500 and 3,000
ppm (nominal)
(Experimental)
Poecilia reticulata 4,400 mg/L dose
lethal to < 10%
(Experimental)
OECD-SIDS, 1999
OECD-SIDS, 1999; ECHA, 2013
OECD-SIDS, 1999; ECHA, 2013
ECHA, 2013
OECD-SIDS, 1999; ECHA, 2013
Study details reported in a
secondary source.
Study details reported in a
secondary source.
Study details reported in a
secondary source.
Adequate study reported in a
secondary source. Study was
conducted in accordance to a
method similar to present
guidelines; non-GLP.
Study details reported in a
secondary source.
         7-363

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                                                        JUNE 2014 DRAFT REPORT
                                                          Melamine CASRN 108-78-1
           PROPERTY/ENDPOINT
              DATA
         REFERENCE
      DATA QUALITY
                                              Freshwater fish 96-hour LC50:
                                              16,500 mg/L (ECOSAR class:
                                              Anilines, amino-meta);

                                              1,560 mg/L (ECOSAR class:
                                              Melamines);

                                              110,000 mg/L (ECOSAR class:
                                              Neutral organics)
                                              (Estimated)
                                  ECOSAR vl. 11
                               The estimated effect levels for the
                               ECOSAR Anilines, amino-meta
                               and Neutral organics classes
                               exceed the water solubility of
                               3,230 mg/L. NES are predicted
                               for these endpoints.

                               Narcosis classes (neutral
                               organics) are provided for
                               comparative purposes; DfE
                               assessment methodology will use
                               the lowest estimated toxicity
                               value provided by ECOSAR
                               classes that have a more specific
                               mode of action relative to
                               narcosis.
Daphnid LC50
Daphnia magna 48-hour LC50 > 1,000
mg/L
48-hour EC50 (mobility and behavior)
= 200 mg/L
static test conditions;
0, 56, 100, 180, 320, 560, and 1,000
mg/L (nominal)
(Experimental)
ECHA, 2013
                                              Daphnia magna 48-hour LC50 >2,000
                                              mg/L
                                              48-hour EC50(behavior) < 180 mg/L
                                              static test conditions;
                                              180, 320, 560, 1,000, 1,800 and 2,000
                                              mg/L (nominal)
                                              (Experimental)
                                  ECHA, 2013
                                              Daphnia magna 48-hour LC50:
                                              17 mg/L
                                  ECOSAR vl. 11
Adequate study reported in a
secondary source. Study was
conducted according to EPA
Office of Pesticide Programs
(OPP) 72-2, EU Method C.2 and
GLP.
                               Adequate study reported in a
                               secondary source. Study was
                               conducted according to EPA OPP
                               72-2, EU Method C.2 and GLP.
                               The estimated effect level for the
                               ECOSAR Neutral organics class
                                                                   7-364

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                                                        JUNE 2014 DRAFT REPORT
                                                          Melamine CASRN 108-78-1
           PROPERTY/ENDPOINT
              DATA
         REFERENCE
      DATA QUALITY
                                               (ECOSAR class: Anilines, amino-
                                               meta);

                                               510mg/L
                                               (ECOSAR class: Melamines);

                                               46,000 mg/L
                                               (ECOSAR class: Neutral organics)
                                               (Estimated)
                                                                  exceeds the water solubility of
                                                                  3,230 mg/L. NES are predicted
                                                                  for these endpoints.

                                                                  Narcosis classes (neutral
                                                                  organics) are provided for
                                                                  comparative purposes; DfE
                                                                  assessment methodology will use
                                                                  the lowest estimated toxicity
                                                                  value provided by ECOSAR
                                                                  classes that have  a more specific
                                                                  mode of action relative to
                                                                  narcosis.
Green Algae EC50
Green algae (Selenastrum
capricornutum) 96-hour EC50 = 325
mg/L
NOEC = 98 mg/L
static test conditions;
0, 10, 32, 100, 320 and  1,000 ppm
(nominal)
(Experimental)
ECHA, 2013
Study details reported in a
secondary source. Study was
conducted in accordance with
guideline PRO/FT Algae-AC090-
6 and GLP.
                                               Green algae (Scenedesmus
                                               pannonicus) 4-day EC50 = 940 mg/L
                                               4-day NOEC = 320 mg/L
                                               static test conditions;
                                               0, 10, 32, 100, 320, 560, 1,000 and
                                               2,000 mg/L (nominal)
                                               (Experimental)
                                  OECD-SIDS, 1999; ECHA, 2013
                                Study details reported in a
                                secondary source. Study was
                                conducted in accordance with
                                Dutch draft Standard Method
                                NEN 6506, 1979.
                                               Green algae 96-hour EC50:
                                               6.1 mg/L (ECOSAR class: Anilines,
                                               amino-meta);

                                               1,400 mg/L (ECOSAR class:
                                  ECOSAR vl. 11
                                NES are predicted for these
                                endpoints.

                                Narcosis classes (neutral
                                organics) are provided for
                                                                    7-365

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                                                        JUNE 2014 DRAFT REPORT
                                                         Melamine CASRN 108-78-1
           PROPERTY/ENDPOINT
              DATA
         REFERENCE
      DATA QUALITY
                                              Melamines);

                                              9,400 mg/L (ECOSAR class: Neutral
                                              organics)
                                              (Estimated)
                                                                 comparative purposes; DfE
                                                                 assessment methodology will use
                                                                 the lowest estimated toxicity
                                                                 value provided by ECOSAR
                                                                 classes that have a more specific
                                                                 mode of action relative to
                                                                 narcosis.
Chronic Aquatic Toxicity
MODERATE: Based on an estimated chronic aquatic ChV of 1.3 m
amino-meta) in green algae. Experimental data in fish and daphnia
toxicity hazard. Estimated data for fish (ECOSAR classes Anilines,
organics) indicate NES, while estimated data for daphnia indicate a
Anilines, amino-meta).
                           g/L (ECOSAR class: Anilines,
                           indicate a Low chronic aquatic
                           amino-meta, Melamines, and Neutral
                           Moderate hazard (ECOSAR class:
Fish ChV
Salmo gairdneri NOEC (macroscopic)
= 500 mg/L;
NOEC (microscopic) <125 mg/L
(Experimental)
                                              Jordanella floridae 35-day NOEC >
                                              1,000 mg/L
                                              (Experimental)
                                              Freshwater fish ChV:
                                              1,500 mg/L (ECOSAR class: Anilines,
                                              amino-meta);

                                              7,700 mg/L (ECOSAR class:
                                              Melamines);

                                              7,500 mg/L (ECOSAR class: Neutral
                                              organics)
                                              (Estimated)
OECD-SIDS, 1999
                                  OECD-SIDS, 1999
                                 ECOSAR vl. 11
Study details reported in a
secondary source, study details
and test conditions were not
provided.
                               Study details reported in a
                               secondary source, study details
                               and test conditions were not
                               provided.
                               The estimated effect levels for the
                               ECOSAR Melamines and Neutral
                               organics classes exceed the water
                               solubility of 3,230 mg/L. NES are
                               predicted for these endpoints.
                               The toxicity value for the
                               ECOSAR Anilines, amino-meta
                               class was estimated through
                               application of acute-to-chronic
                               ratios per methods outlined in the
                               ECOSAR Methodology
                               Document.
                                                                   7-366

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                                                        JUNE 2014 DRAFT REPORT
                                                          Melamine CASRN 108-78-1
           PROPERTY/ENDPOINT
              DATA
         REFERENCE
      DATA QUALITY
                                                                                                               Narcosis classes (neutral
                                                                                                               organics) are provided for
                                                                                                               comparative purposes; DfE
                                                                                                               assessment methodology will use
                                                                                                               the lowest estimated toxicity
                                                                                                               value provided by ECOSAR
                                                                                                               classes that have a more specific
                                                                                                               mode of action relative to
                                                                                                               narcosis.
Daphnid ChV
Daphnia magna 21-day LC50 = 32-56
mg/L, 21-day LCioo = 56 mg/L, 21-day
NOEC= 18 mg/L
(Experimental)
OECD-SIDS, 1999; ECHA, 2013
                                              Daphnia magna ChV:
                                              0.16 mg/L (ECOSAR class: Anilines,
                                              amino-meta);

                                              56 mg/L (ECOSAR class: Melamines);

                                              1,900 mg/L (ECOSAR class: Neutral
                                              organics)
                                              (Estimated)
                                  ECOSAR vl. 11
Study details reported in a
secondary source, study details
and test conditions were not
provided.
                               The toxicity value for the
                               ECOSAR Melamines class was
                               estimated through application of
                               acute-to-chronic ratios per
                               methods outlined in the ECOSAR
                               Methodology Document.

                               Narcosis classes (neutral
                               organics) are provided for
                               comparative purposes; DfE
                               assessment methodology will use
                               the lowest estimated toxicity
                               value provided by ECOSAR
                               classes that have a more specific
                               mode of action relative to
                               narcosis.
                                                                   7-367

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JUNE 2014 DRAFT REPORT
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
Green Algae ChV
DATA
Green algae ChV:
1.3 mg/L (ECOSAR class: Anilines,
amino-meta);
270 mg/L (ECOSAR class:
Melamines);
1,200 mg/L (ECOSAR class: Neutral
organics)
(Estimated)
REFERENCE
ECOSAR vl. 11
^^^
b^S
DATA QUALITY
The toxicity values for the
ECOSAR Anilines, amino-meta
and Melamines classes were
estimated through application of
acute-to-chronic ratios per
methods outlined in the ECOSAR
Methodology Document.
Narcosis classes (neutral
organics) are provided for
comparative purposes; DfE
assessment methodology will use
the lowest estimated toxicity
value provided by ECOSAR
classes that have a more specific
mode of action relative to
narcosis.
ENVIRONMENTAL FATE
Transport

Henry's Law Constant (atm-
m3/mole)
Sediment/Soil
Adsorption/Desorption - Koc
Level III Fugacity Model
Level III fugacity models incorporating available physical and chemical property data indicate that at
steady state, melamine is expected to be found primarily in soil and to a lesser extent, water. Melamine is
expected to have high mobility in the soil, based on its calculated Koc. Melamine will not volatilize from
moist soil and water surfaces based on its Henry's Law constant. Volatilization from dry surfaces is not
expected based on its vapor pressure. In the atmosphere, melamine is expected to exist almost entirely in
the particulate phase. Particulates may be removed from air by wet or dry deposition.
<10'8 at 20°C (Estimated)
J
32 (Estimated)
Air = 0.01%
Water = 25%
Soil = 74.9%
EPIv4.11
EPIv4.11
EPIv4.11
Estimated from experimental
water solubility and vapor
pressure.


         7-368

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                                                        JUNE 2014 DRAFT REPORT
                                                         Melamine CASRN 108-78-1
           PROPERTY/ENDPOINT
                                           DATA
                                          REFERENCE
                                      DATA QUALITY
                                              Sediment = 0.1% (Estimated)
Persistence
                             HIGH: Experimental data indicate melamine undergoes slow degradation under stringent guideline
                             conditions, although melamine is readily degraded in acclimated treatment systems. Pure culture studies
                             have shown biodegradation of melamine by enzymatic hydrolytic deamination in less than 10 days.
                             However, an original MITI test detected less than 30% degradation after 14 days and two separate
                             guideline OECD 302B studies observed no degradation after 28 days and 16% degradation after 20 days.
                             The environmental persistence half-life of melamine is therefore expected to be between 60  and 180 days
                             based on the guideline biodegradation studies, consistent with a High hazard designation. Melamine was
                             found to hydrolyze in strong alkaline and acidic solutions but hydrolysis is not expected under neutral
                             conditions. Melamine is not expected to be susceptible to direct photolysis by sunlight. The atmospheric
                             half-life of vapor-phase melamine is estimated to be 16 days.
Water
Aerobic Biodegradation
Passes Ready Test: No
Test method: Original MITI test

<30% after 14 days (Measured)
                                              Study results: 16%/20days
                                              Test method: 302B: Inherent - Zahn-
                                              Wellens/EMPA Test

                                              Elimination of 10% after 14 days; not
                                              inherently degradable (Measured)
                                              Study results: 0%/28 days
                                              Test method: 302B: Inherent - Zahn-
                                              Wellens/EMPA Test

                                              (Measured)
                                              Study results: 14±10% /100 days
                                              Test method: Activated sludge
                                              treatment systems

                                              Local municipal WWTP; 100 day
                                              adaptation; average melamine removal
                                              14±10% with the Modified Ludzack-
OECD-SIDS, 1998
Guideline study reported in a
secondary source.
                                                               OECD-SIDS, 1998
                                                                 Guideline study reported in a
                                                                 secondary source.
                                                               OECD-SIDS, 1998
                                                               Xuetal.,2013
                                                                 Guideline study reported in a
                                                                 secondary source.
                                                                   7-369

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JUNE 2014 DRAFT REPORT
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT

Soil

Volatilization Half-life for
Model River
Volatilization Half-life for
Model Lake
Aerobic Biodegradation
Anaerobic Biodegradation
DATA
Ettinger process and 20±15% with the
continuous stirred tank reactor
(Measured)
Study results: 100%/<10days
Test method: Other: Pure culture study
Bacterium, Nocardioides sp. strain
ATD6 rapidly degraded melamine and
accumulated cyanuric acid and
ammonium, via the intermediates
ammeline and ammelide. (Measured)
>1 year (Estimated)
>1 year (Estimated)
Study results: 100%/4 days
Test method: Other: Pure culture study
Bacterium, A. citrulli strain B-12227
rapidly degraded melamine and
accumulated cyanuric acid, ammeline
and ammelide, via the intermediates
ammeline and ammelide. (Measured)
A set of soil bacteria has been
identified whose members rapidly
metabolize melamine as their source of
nitrogen to support growth; these
bacteria contain an enzyme which
hydrolytically deaminate melamine
(Measured)
Not probable (Anaerobic-
methanogenic biodegradation
probability model)
REFERENCE

Takagietal., 2012
^^^
b^S
EPIv4.11
EPIv4.11
Shiomi and Ako, 2012
Cook and Hutter, 1981, 1984
EPIv4.11
DATA QUALITY

Melamine degradation was found
to occur in species specific
biodegradation studies.


Melamine degradation was found
to occur in species specific
biodegradation studies.
Melamine degradation was found
to occur in species specific
biodegradation studies.

         7-370

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JUNE 2014 DRAFT REPORT
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT

Air
Reactivity
Soil Biodegradation with
Product Identification
Sediment/Water
Biodegradation
Atmospheric Half-life
Photolysis
Hydrolysis
Environmental Half-life
DATA


16 days (Estimated)

Melamine hydrolysis proceeds
stepwise, with loss of one to three
amino groups; hydrolysis occurs by
reaction with mineral acid or inorganic
alkali; Hydrolysis products include
ammeline (CASRN 645-92-1),
ammelide (CASRN 645-93-2) and
cyanuric acid (CASRN 108-80-5)
(Measured)
Melamine is hydrolyzed in strong
alkaline and acidic solutions.
The rate constants at 100°C:
k(s'1) = 3.8E-6[OIT]
k(s-l)= 1.25E10-4[H+].
Hydrolysis products are ammeline,
ammelide and cyanuric acid.
(Measured)
2-3 years in soil (Measured)
75 days (Estimated)
REFERENCE


EPIv4.11

OECD-SIDS, 1998
b^^s '
OECD-SIDS, 1998
OECD-SIDS, 1998
PBT Profiler
DATA QUALITY
No data located.
Mo data located.

Mo data located.
Reported in a secondary source.
Reported in a secondary source.
Study was conducted in the
extreme pH ranges at high
temperatures. This study is not
relevant for environmental
conditions.
Reported in a secondary source.
Half-life estimated for the
predominant compartment (soil),
as determined by EPI
methodology.
         7-371

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JUNE 2014 DRAFT REPORT
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
Bioaccumulation

Fish BCF
Other BCF
BAF
Metabolism in Fish
DATA
REFERENCE
DATA QUALITY
LOW: Measured BCF and estimated BAF values are below 100, the Low bioaccumulation designation
criteria.
<3.8 Cyprinus carpio for 0.2 mg/L
<0. 3 8 for 2 mg/L; according to OECD
305C (Measured)

0.9 (Estimated)

OECD-SIDS, 1998

EPIv4.11

Guideline study reported in a
secondary source.
Mo data located.

Mo data located.
ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring
Ecological Biomonitoring
Human Biomonitoring
Melamine has been detected in river water and sediments in Japan (ECHA, 2013).
Melamine has been reported in fish in Japan (ECHA, 2013).
Melamine was not included in the NHANES biomonitoring report (CDC, 2009).
         7-372

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                                                JUNE 2014 DRAFT REPORT


American Cyanamid Company (1955) Melamine: Acute and chronic toxicity Report 55-21 Unpublished study.

American Cyanamid Company (1958) AERO melamine, in-house publication (As cited in TSCA Section 8(e) Substantial risk notice U.S. EPA,
8EHQ-0192-1995 (1992).

American Cyanamid Company (1984) Summary of company study.

BASF (1969) BASF AG, Department of Toxicology (XFX5), unpublished data (As cited in Melamine OECD SIDS document and melamine
IUCLID document).

Baynes RE, Smith G, Mason SE, et al. (2008) Pharmacokinetics of melamine in pigs following intravenous administration. Food Chem Toxicol
46:1196-1200.

CDC (2009) Fourth national report on human exposure to environmental chemicals. Atlanta, GA: Centers for Disease Control and Prevention.
http: //www .cdc. gov/exposurereport/pdf/FourthReport .pdf.

Camacho L, Kelly KP, Beland FA, et al. (2011) Gene expression of biomarkers of nephrotoxicity in F344 rats co-exposed to melamine and
cyanuric acid for seven days. Toxicol Lett 206(2): 166-171.

Chu CY, Chu KO, Chan JY, et al. (2010) Distribution of melamine in rat foetuses and neonates. Toxicol Lett 199(3):398-402.

Cook AM, Hutter R (1981) s-Triazines as nitrogen sources for bacteria. J Agric Food Chem 29:1135-1143.

Cook AM, Hutter R (1984) Deethylsimazine: Bacterial dechlorination, deamination, and complete degradation. J Agric Food Chem 32:581-585.

Crews, GM, Ripperger W, et al. (2006) Melamine and guanamines. Ullmann's Encyclopedia of Industrial Chemistry, Vol 22. New York: John
Wiley & Sons, Inc.
                                                    7
Ding XM, Zhang KY, Wang L, et al. (2012) Toxicity of melamine and cyanuric acid in broilers and residues in tissues. Hum Exp Toxicol
31(2):174-184.

Early RJ, Yu H, Mu XP, et al. (2013) Repeat oral dose toxicity studies of melamine in rats and monkeys. Arch Toxicol 87(3):517-527.
                                                            7-373

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                                                  JUNE 2014 DRAFT REPORT


ECHA (2011) Melamine cyanurate. Registered substances. European Chemicals Agency.
http://apps.echa.europa.eu/registered/data/dossiers/DISS-9eb230bf-9edO-1955-e044-00144f67d031/AGGR-a3a77856-6622-456f-8995-
5483f815f4a4 DISS-9eb230bf-9edO-1955-e044-00144f67d031.html.

ECHA (2013) Melamine. Registered substances. European Chemicals Agency. http://apps.echa.europa.eu/registered/data/dossiers/DISS-
9c8039ea-8496-674c-e044-00144f67d249/AGGR-2F9a90f3-6e35-4292-937a-99dOf4cf998a_DISS-9c8039ea-8496-674c-e044-
00144f67d249 .html#AGGR-2f9a90f3 -6e3 5 -4292-93 7a-99dOf4cf998a.

ECOSAR (Ecological Structure Activity Relationship), Version 1.11. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/oppt/newchems/tools/21ecosar.htm.

EPA (2010) TSCA new chemicals program (NCP) chemical categories. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/oppt/newchems/pubs/npcchemicalcategories.pdf.

EPA (2012) Using noncancer screening within the SF initiative. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/oppt/sf/pubs/noncan-screen.htm.

EPI Estimation Programs Interface (EPI) Suite, Version 4.11. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm.
                                         ^P                              7
ESIS (2012) European chemical Substances Information System. European Commission, http://esis.jrc.ec.europa.eu/.

Fasset DW, Roudabush RL (1963) Unpublished data (Unpublished data referenced by melamine OECD SIDS document and Trochimowicz,
2001).

Galloway SM, Armstrong MJ, Reuben C, et al. (1987) Chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells:
evaluations of 108 chemicals. Environ Mol Mutagen 10(Suppl  10): 1-175.

HSDB  (2008) Melamine. Hazardous Substances Data Bank. National Library of Medicine. http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen7HSDB.

Haworth S, Lawlor T, Mortelmans K, et al. (1983) Salmonella mutagenicity test results for 250 chemicals. Environ Mutagen 1:3-142.

Heil J,  Reifferscheid G (1992) Detection of mammalian carcinogens with an immunological DNA synthesis-inhibition test. Carcinogenesis
13(12):2389-2394.
                                                              7-374

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                                                  JUNE 2014 DRAFT REPORT


Hellwig J, Gembrandt C, Hildebrandt B (1996) Prenatal toxicity in Wistar rats after oral administration (diet) Project Number 32R0242/94007.

Hoechst AG (1963) (Cited in melamine IUCLID document). Unveroffentl Unters Bericht 5(7)

Huff JE (1984) Carcinogenesis results on seven amines, two phenols, and one diisocyanate used in plastics and synthetic elastomers. Industrial
hazardous plastics and synthetic elastomers.

IARC (1986) Melamine. IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans vol 39. International Agency for
Research on Cancer World Health Organization, 333-346.

IARC (1999) Melamine. IARC monographs on the evaluation of carcinogenic risks to humans vol 73. International Agency for Research on
Cancer World Health Organization, 329-338.

Jacob CC, Reimschuessel R Von Tungeln LS, et al. (2011) Dose-response assessment of nephrotoxicity from a 7-day combined exposure to
melamine and cyanuric acid in F344 rats. Toxicol Sci 119(2):391-397.

Lipshitz WL, Stokey E (1945) The mode of action of three diuretics: Melamine, adenine and formoguanamine. J Pharmacol Exp Ther 83:235-249.

Liu G, Li S, Jia J, et al. (2010) Pharmacokinetic study of melamine in rhesus monkey after a single oral administration of a tolerable daily intake
dose. Regul Toxicol Pharmacol 56(2): 193-196.

Luers H, Rohrborn G (1963) The mutagenic activity of ethylenimine derivatives with different numbers of reactive groups. Genetic Today 1:64-
65.

Lusby AF, Simmons Z, McGuire PM (1979) Variation in mutagenicity of s-Triazine compounds tested on four salmonella strains. Environ
Mutagen 1:287-290.

Marhold JV (1972) [Sbornik vysledku toxixologickeho vysetreni latek a pripravku (Czechoslovakian).: 153.

Mast RW, Boyson BG, Giesler PJ  (1982a) Evaluation of the chronic toxicity of melamine in a 30-month Fischer 344 rat feeding study.
Toxicologist.

Mast RW, Jeffcoat AR Sadler BM, et al. (1983) Metabolism, disposition and excretion of [14C]melamine in male Fischer 344 rats. Food Chem
Toxicol 21(6):807-810.
                                                              7-375

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                                                 JUNE 2014 DRAFT REPORT


Mast RW, Naismith RW, Friedman MA (1982b) Mouse micronucleus assay of melamine. Environ Mutagen 4:340-341.

Matsui-Yuasa I, Otani S, Yano Y, et al. (1992) Spermidine/spermine Nl-acetyltransferase, a new biochemical marker for epithelial proliferation in
rat bladder. Jpn J Cancer Res 83:1037-1040.

May DR (1979) Cyanamids. In: Kirk-Othmer Encyclopedia of Chemical Technology, Vol 7 New York: John Wiley & Sons, 291-306.

McGregor DB, Brown A, Cattanach P, et al. (1988) Responses of the L5178Y tk+/tk- mouse lymphoma cell forward mutation assay: III. 72 coded
chemicals. Environ Mol Mutagen 12:85-154.

Melnick RL, Boorman GA, Haseman JK, et al. (1984) Urolithiasis and bladder carcinogenicity of melamine in rodents. Toxicol Appl Pharmacol
72(2):292-303.

Mirsalis J, Tyson K, Beck J, et al. (1983) Induction of unscheduled DNA synthesis (UDS) in hepatocytes following in vitro and in vivo treatment.
Environ Mutagen 5(482):344.

NCI/NTP (2007) Carcinogenesis Technical Report Series: Melamine. National Cancer Institute/National Toxicology Program.
http://ntpapps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=l 08-78-1.

NTP (1983) Carcinogenesis Bioassay of Melamine (CAS No. 108-78-1) in F344/N Rats and B6C3F1 Mice (Feed Study). National Toxicology
Program Technical Report  Series 245:1-171.

OECD-SIDS (1998) Screening information data set - SIDS - for high production volume chemicals - Volume 7, Parts 1, 2 and 3- Melamine.
United Nations Environment Programme, Case postale 356(1) Organisation for Economic Co-operation and Development, 3.

OECD-SIDS (1999) Full SIDS dossier on the HPV phase 2 chemical melamine. http://www.chem.unep.ch/irptc/sids/OECDSIDS/108781 .pdf.

Ogasawara H, Imaida K, Ishiwata H, et al. (1995) Urinary bladder Carcinogenesis induced by melamine in F344 male rats: correlation between
carcinogenicity and urolith formation. Carcinogenesis 16(ll):2773-2777.

Okumura M, Hasegawa R, Shirai T, et al. (1999) Relationship between calculus formation and Carcinogenesis in the urinary bladder of rats
administered the non-genotoxic agents, thymine or melamine. Carcinogenesis 13(6): 1043-1045.

OncoLogic (2005) Version 6.0. U.S. EPA and LogiChem, Inc.
                                                             7-376

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                                                  JUNE 2014 DRAFT REPORT


PBT Profiler Persistent (P), Bioaccumulative (B), and Toxic (T) Chemical (PBT) Profiler, Version 1.301. Washington, DC: U.S. Environmental
Protection Agency, www.pbtprofiler.net.

Partanen H, Vahakangas K, Woo CS, et al. (2012) Transplacental transfer of melamine. Placenta 33(l):60-66.

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assay and a comparison with S.  typhimurium mutagenicity and rodent carcinogenicity assays. Mutat Res 260:349-367.

Rutty CJ, Abel G (1980) In vitro cytotoxicity of the methylmelamines. Chem Biol Interact 29(2):235-246.

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                                                              7-377

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                                                  JUNE 2014 DRAFT REPORT


Skinner CG, Thomas JD, Osterloh JD (2010) Melamine toxicity. J Med Toxicol 6(l):50-55.

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Yin RH, Wang XZ, Bai WL, et al. (2013) The reproductive toxicity of melamine in the absence and presence of cyanuric acid in male mice. Res
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Zheng X, Zhao A, Xie G, et al. (2013) Melamine-induced renal toxicity is mediated by the gut microbiota.  Sci Transl Med 5(172): 122.
                                                             7-378

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                                                            JUNE 2014 DRAFT REPORT
              Oligomeric ethyl ethylene phosphate
                                                   Screening Level Toxicology Hazard Summary

This table only contains information regarding the inherent hazards of flame retardant chemicals. Evaluation of risk considers both the hazard and exposure associated with the
substance including combustion and degradation by-products. The caveats listed in the legend and footnote sections must be taken into account when interpreting the hazard
information in the table.
VL = Very Low hazard L = Low hazard    = Moderate hazard H = High hazard VH = Very High hazard - Endpoints in colored text (VL, L, M, H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].

d This hazard designation would be assigned MODERATE for a potential for lung overloading if >5% of the particles are in the respirable range as a result of dust forming
operations.






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CASRN
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Oligomeric ethyl ethylene phosphate  |  184538-58-7  |      |z,|M|z,|M|M|z,d|z,|      |      |L|z,|l,|   Kg|    L
                                                                         7-379

-------
                                                          JUNE 2014 DRAFT REPORT
                                               Representative structure
                                                                                                                 CASRN: 184538-58-7
                                                                                                                 MW: Product MWN range from 300
                                                                                                                       to 4,000
                                                    MF: (C6H1504P •
                                                                                                                                        O5P2)n
                                                                                                                 Physical Forms: Liquid
                                                                                                                 Neat:
                                                                                                                 Use: Flame retardant
SMILES: C(COP(=O)(OCC)OCC)OP(=O)(OCC)OCC (Representative structure used for n=l estimations)
The polymeric components with MW > 1,000 oligomers (n>6) are not amenable to SMILES notation.
Synonyms: Phosphoric acid, triethyl ester, polymer with oxirane and phosphorus oxide (P2O5); Oxirane, polymer with phosphorus oxide (P2O5) and triethyl
phosphate; Phosphorus oxide (P2O5), polymer with oxirane and triethyl phosphate; Alkylphosphate oligomer; Oligomeric ethyl ethylene phosphate
Trade names: Fyrol PNX; Fyrol PNX-LE; Modified oligomeric ethyl ethylene phosphate; Exolit 550;
Chemical Considerations: This alternative is a polymer consisting of oligomers with MWs above and below 1,000 daltons according to publicly available patents
and commercial product literature. A typical phosphorus content of 19% was reported from these sources. Residual monomers, unreacted starting material (triethyl
phosphate) and low MW oligomers are expected to be present at a level requiring their assessment. The n>6, oligomers have a MW > 1,000 and are assessed using the
available polymer assessment literature. The n<5 oligomers are those with a MW <1,000 and are assessed with EPI v4.11 and ECOSAR vl. 11 estimates due to an
absence of publically available experimental physical/chemical, environmental fate and aquatic toxicity values (Hardy and Jaffe, 1983; Boethling and Nabholz, 1997;
Akzo Nobel and Wuestenenk, 2005).
Polymeric: Yes
Oligomeric: The oligomers are produced by reacting phosphorus pentoxide with triethyl phosphate to form a polyphosphate ester that is in turn reacted with ethylene
oxide. The repeating phosphate ester units, represented between the brackets where n = 2 to 20 units, although n=500 has been reported in one patent. Both linear and
cross-linked polymers may be formed during polymerization. The polymers may be terminated with either an ethyl or hydroxyl ethyl group (Hardy and Jaffe, 1983;
Akzo Nobel and Wuestenenk, 2005; Professional judgment).
Metabolites, Degradates and Transformation Products: None identified; although biodegradation or hydrolysis pathways may yield diethyl phosphate, ethyl
phosphate, ethanol, phosphate and ethylene glycol (Professional judgment)
Analog: None
Endpoint(s) using analog values: Not applicable
Analog Structure: Not applicable
Structural Alerts: Organophosphates, neurotoxicity (EPA, 2012).
Risk Phrases: Not classified by Annex VI Regulation (EC) No 1272/2008 (ESIS, 2012).
Hazard and Risk Assessments: None identified.
                                                                      7-380

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JUNE 2014 DRAFT REPORT
Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
PHYSICAL/CHEMICAL PROPERTIES
Melting Point (°C)
Boiling Point (°C)
Vapor Pressure (mm Hg)
Water Solubility (mg/L)
Log Kow

>300
forn>l (Estimated)
3.6xl(r6at250C
for n=l
2.1xlO-8forn=2-5
(Estimated)
6 oligomers (Estimated)
3375 mg/L for n=l
93 3 mg/L for n=2
23 3 mg/L for n=3
1 mg/L for n=6 (Estimated)
Soluble (Measured)
^
Miscible (Measured)
-0.58
(Measured)
0.42 for n=l
-0.03 for n=2
-0.48 for n=3

EPIv4.11;
Professional
judgment; EPA,
1999
EPIv4.11
Professional
judgment; Boethling
andNabholz, 1997
EPIv4.11
ICL, 2010
Submitted
confidential study
Submitted
confidential study
EPIv4.11
No data located.
Estimate based on representative
oligomers where n=l-5 with MW <
1,000. Also estimated for oligomers
where n>6 with MWs > 1,000.
Cutoff value according to HPV
assessment guidance and cutoff
value used for large, high MW
solids.
Estimates based on representative
oligomers where n=l-5.
Cutoff value for large, high MW
polymers.
Estimates based on representative
oligomers where n=l-6.
Non-quantitative value from a
MSDS for the commercial product
Fyrol PNX LE containing 95-100%
pure material.
Non-quantitative value with limited
details reported.
Limited study details provided in a
confidential source.
Estimates based on representative
oligomers where n=l-6.
         7-381

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JUNE 2014 DRAFT REPORT
Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
PROPERTY/ENDPOINT

Flammability (Flash Point)
Explosivity
Pyrolysis
pH
pKa
DATA
-1.33 for n=6
(Estimated)
<-l
(Measured)
Not flammable (Measured)
Not explosive (Measured)

Not applicable (Estimated)
Not applicable (Estimated)
REFERENCE

ICL, 2010
ICL, 2010
ICL, 2010

Professional
judgment
Professional
judgment
DATA QUALITY

From a MSDS for the commercial
product Fyrol PNX LE containing
95-100% pure material.
From a MSDS for the commercial
product Fyrol PNX LE containing
95-100% pure material.
From a MSDS for the commercial
product Fyrol PNX LE containing
95-100% pure material.
No data located.
Does not contain functional groups
that are expected to ionize under
environmental conditions.
Does not contain functional groups
that are expected to ionize under
environmental conditions.
HUMAN HEALTH EFFECTS
Toxicokinetics
Dermal Absorption in vitro
Absorption,
Distribution,
Metabolism &
Excretion
Oral, Dermal or Inhaled
Other
For low MW components (n < 6), absorption is estimated to be low for all routes based on confidential analogs.
For high MW components, no absorption is expected through the skin and gastrointestinal tract. Poor
absorption is estimated in the lungs because the polymer is dispersible due to its physical chemical properties.


For low MW components (n < 6), absorption is expected to
be low for all routes based on confidential analogs. For
high MW components, no absorption is expected through
the skin and gastrointestinal tract. Poor absorption is
expected in the lungs because the polymer is dispersible
due to its physical chemical properties.
(Estimated)


Professional
judgment
No data located.
No data located.
Estimated based on analogy to a
confidential analog, physical
chemical properties, and
professional judgment.
         7-382

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JUNE 2014 DRAFT REPORT
Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
PROPERTY/ENDPOINT
Acute Mammalian Toxicity
Acute
Lethality
Oral
Dermal
Inhalation
Carcinogenicity

OncoLogic Results
Carcinogenicity (Rat and
Mouse)
Combined Chronic
Toxicity/Carcinogenicity
Other
DATA
REFERENCE
DATA QUALITY
LOW: Based on oral and dermal LD50 values > 2,000 mg/kg for the polymeric mixture that included LMW
components. No data were located for the inhalation route of exposure.
The higher MW components of this polymer (MW >1,000) are expected to have limited bioavailability and have
low potential for acute toxicity.
Rat oral LD50 = 5,000 mg/kg
Rabbit dermal LD50 > 2,000 mg/kg

Submitted
confidential study
Submitted
confidential study

Data reported in a confidential study
submitted to EPA for the polymeric
mixture that included LMW
components.
Data reported in a confidential study
submitted to EPA for the polymeric
mixture that included LMW
components.
No data located.
LOW: Estimated based on predictions for the polymer containing lower MW components. The risk for
Carcinogenicity is estimated to be low considering that the residual monomers do not contain substituted
terminal double bonds, and reactive-functional-group-bearing side chains. The higher MW components of this
polymer (MW >1,000) are expected to have limited bioavailability and have low potential for Carcinogenicity.
No experimental data were located.
Based on estimates considering that the residual monomers
do not contain substituted terminal double bonds; the low
MW species do not contain reactive-functional-group-
bearing side chains; the polymer is cross-linked, is not
linear, and has a MW of less than 100,000.
^k 7


OncoLogic, 2008



Estimated for the polymer
containing lower MW components.
No data located.
No data located.
No data located.
         7-383

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JUNE 2014 DRAFT REPORT
Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
PROPERTY/ENDPOINT
Genotoxicity

Gene Mutation in vitro
Gene Mutation in vivo
Chromosomal Aberrations in
vitro
Chromosomal Aberrations in
vivo
DNA Damage and Repair
Other
Reproductive Effects

Reproduction/Developmental
Toxicity Screen
Combined Repeated Dose
with Reproduction/
Developmental Toxicity
Screen
Reproduction and Fertility
Effects
DATA
REFERENCE
DATA QUALITY
MODERATE: There is uncertain concern for mutagenicity based on the structure, ethyl substituted phosphate.
This substance did not cause gene mutations in bacteria; however, there is uncertainty due to the lack of
experimental data for this endpoint. Complete data requirements for this endpoint are both gene mutation and
chromosomal aberration assays. For instances of incomplete or inadequate mutagenicity/genotoxicity data, a
Low hazard designation cannot be given. The higher MW components of this polymer (MW >1,000) are
expected to have limited bioavailability and have low potential for genotoxicity.
Uncertain concern for mutagenicity
(Estimated)
Negative for gene mutation in an Ames test in
S.typhimurium andE. coll.





Professional
judgment
Submitted
confidential study





Estimated for the low MW
component due to ethyl substituted
phosphate.
Data reported in a submitted
confidential study.
No data located.
No data located.
No data located.
No data located.
No data located.
LOW: Estimated to have a low potential for reproductive effects based on expert judgment and a lack of
structural alert for this endpoint. No experimental data were located. The higher MW components of this
polymer (MW >1,000) are expected to have limited bioavailability and have low potential for reproductive
toxicity.






No data located.
No data located.
No data located.
         7-384

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JUNE 2014 DRAFT REPORT
Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
PROPERTY/ENDPOINT

Other
Developmental Effects

Reproduction/
Developmental Toxicity
Screen
Combined Repeated Dose
with Reproduction/
Developmental Toxicity
Screen
Prenatal Development
Postnatal Development
Prenatal and Postnatal
Development
Developmental Neurotoxicity
Other
DATA
There is low potential for reproductive effects
(Estimated)
REFERENCE
Expert judgment
DATA QUALITY
Estimated based on expert judgment
and the lack of structural alerts.
MODERATE: There were no experimental data for the developmental toxicity endpoint. There were no
structural alerts identified for this endpoint. The higher MW components of this polymer (MW >1,000) are
expected to have limited bioavailability and have low potential for developmental toxicity.
There were also no experimental data located for the developmental neurotoxicity endpoint. There is uncertain
potential for developmental neurotoxicity for this substance based on a structural alert for organophosphates
for the neurotoxicity endpoint; decreased cholinesterase activity in pregnant lab animals has been shown to
have a negative impact on fetal brain development. As a result, an estimated Moderate designation is assigned.

k _ ^T ^^



Uncertain concern for developmental neurotoxicity based
on the potential for Cholinesterase (ChE) inhibition in dams
that may result in alterations of fetal neurodevelopment.
(Estimated) \ *
There is low potential for developmental effects
(Estimated) f





Professional
judgment
Expert j udgment
No data located.
No data located.
No data located.
No data located.
No data located.
Estimated based on a structural alert
for organophosphates for the
neurotoxicity endpoint.
Estimated based on expert judgment
and the lack of structural alerts.
         7-385

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JUNE 2014 DRAFT REPORT
Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
PROPERTY/ENDPOINT
Neurotoxicity

Neurotoxicity Screening
Battery (Adult)
Other
Repeated Dose Effects


Skin Sensitization

Skin Sensitization
Respiratory Sensitization
[Respiratory Sensitization
DATA
REFERENCE
DATA QUALITY
MODERATE: Estimated to have uncertain potential for neurotoxic effects based on a structural alert and
professional judgment. No data were located. In the absence of experimental data, a Moderate hazard
designation is assigned. The higher MW components of this polymer (MW >1,000) are expected to have limited
bioavailability and have low potential for acute toxicity.

There is potential for neurotoxic effects based on a
structural alert for organophosphates.
(Estimated)
Uncertain concern for neurotoxicity (Estimated)

Professional
judgment
Professional
judgment
No data located.
Estimated based on a structural alert
and professional judgment.
Estimated for the low MW
component due to ethyl substituted
phosphate.
LOW: Estimated to have low potential for repeated dose effects for the low MW components of this substance
based on expert judgment. This substance may contain polymer components with a MW >1,000. In this case, it
is expected to have limited bioavailability; however, there is the possibility of lung overloading. No
experimental data were located.
Estimated to have low potential for repeated dose effects
for the low MW components of this substance.
This substance may contain polymer components with a
MW >1,000. In this case, it is expected to have limited
bioavailability; however, there is the possibility of lung
overloading.
(Estimated)
Professional
judgment
Estimated based on professional
judgment.
LOW: Estimated to have low potential for skin Sensitization based on expert judgment. There were no
experimental data located.
There is low potential for skin Sensitization
(Estimated) W
Expert judgment
Estimated based on expert
judgment.
No data located.


No data located.
         7-386

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JUNE 2014 DRAFT REPORT
Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
PROPERTY/ENDPOINT
Eye Irritation

Eye Irritation
Dermal Irritation

Dermal Irritation
Endocrine Activity

Immunotoxicity

Immune System Effects
DATA
REFERENCE
DATA QUALITY
MODERATE: This substance was moderately to slightly irritating to rabbit eyes.
Moderate to slight eye irritation in rabbits; conjunctival
irritation with redness and discharge; cleared within 96
hours.
Submitted
confidential study
Data reported in a confidential study
submitted to EPA.
LOW: This substance is slightly irritating to rabbit skin with irritation clearing within 3 days.
Slightly irritating to rabbit skin
Mild and transient dermal irritation in rabbits; cleared
within 3 days.
Submitted
confidential study
Submitted
confidential study
Data reported in a confidential study
submitted to EPA
Data reported in a confidential study
submitted to EPA.
The potential for endocrine activity for the low MW components of this substance is uncertain.
The higher MW components of this polymer (MW >1,000) are expected to have limited bioavailability and have
low potential for endocrine activity.


No data located.
Estimated to have a low potential for immunotoxic effects based on expert judgment. The higher MW
components of this polymer (MW >1,000) are expected to have limited bioavailability and have low potential
for immunotoxicity.
There is low potential for immunotoxic effects
(Estimated)
Expert j udgment
Estimated based on expert
judgment.
ECOTOXICITY
ECOSAR Class
Acute Aquatic Toxicity
Fish LC50

LOW: Based on estimated acute aquatic toxicity values for representative oligomers that predict No Effects at
Saturation (NES). Experimental data in fish also indicate a Low hazard though experimental data was not
located for daphnia or algae.
Danio rerio (Zebrafish) 96-hour LC50 > 1,000 mg/L
according to OECD 203
(Experimental)
Freshwater fish 96-hour LC50 = 7,200 mg/L
(Estimated)
ECOSAR: Neutral organics
Clariant, 2011
ECOSAR vl. 11
Data reported in a confidential study
submitted to EPA; the toxicity value
is well above the water solubility
for this substance; therefore NES is
predicted.
Estimates based on representative
oligomer where n=l. The effect
level exceeds the water solubility of
         7-387

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                                                JUNE 2014 DRAFT REPORT
                                     Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                                                                                       3375 mg/L; NES are predicted for
                                                                                                       these endpoints. ECOSARalso
                                                                                                       provided results for the Esters, and
                                                                                                       Esters (phosphate) classes;
                                                                                                       however, professional judgment
                                                                                                       indicates that this compound is not
                                                                                                       currently well represented in
                                                                                                       ECOSARvl.ll.
                                 Freshwater fish 96-hour LC50 = 27,000 (Estimated)
                                 ECOSAR: Neutral organics
                             ECOSARvl.ll
                Estimates based on representative
                oligomer where n=2. The effect
                level exceeds the water solubility of
                932.9 mg/L; NES are predicted for
                these endpoints. ECOSARalso
                provided results for the Esters, and
                Esters (phosphate) classes;
                however, professional judgment
                indicates that this compound is not
                currently well represented in
                ECOSARvl.ll.
                                 Freshwater fish 96-hour LC50 = 89,000 mg/L
                                 (Estimated)
                                 ECOSAR: Neutral organics
                             ECOSARvl.ll
                Estimates based on representative
                oligomer where n=3. The effect
                level exceeds the water solubility of
                232.7 mg/L; NES are predicted for
                these endpoints. ECOSARalso
                provided results for the Esters, and
                Esters (phosphate) classes;
                however, professional judgment
                indicates that this compound is not
                currently well represented in
                ECOSARvl.ll.
                                 Freshwater fish 96-hour LC50 = 280,000 mg/L
                                 (Estimated)
                                 ECOSAR: Neutral organics
                             ECOSARvl.ll
                Estimates based on representative
                oligomer where n=4. The effect
                level exceeds the water solubility of
                                                            7-388

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                                                JUNE 2014 DRAFT REPORT
                                     Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                                                                                       54.73 mg/L; NES are predicted for
                                                                                                       these endpoints. ECOSARalso
                                                                                                       provided results for the Esters, and
                                                                                                       Esters (phosphate) classes;
                                                                                                       however, professional judgment
                                                                                                       indicates that this compound is not
                                                                                                       currently well represented in
                                                                                                       ECOSARvl.ll.
                                 Freshwater fish 96-hour LC50 = 300,000 mg/L
                                 (Estimated)
                                 ECOSAR: Neutral organics
                             ECOSARvl.ll
                Estimates based on representative
                oligomer where n=5. The effect
                level exceeds the water solubility of
                4.716 mg/L; NES are predicted for
                these endpoints. ECOSARalso
                provided results for the Esters, and
                Esters (phosphate) classes;
                however, professional judgment
                indicates that this compound is not
                currently well represented in
                ECOSARvl.ll.
                                 Freshwater fish 96-hour LC50 = 880,000 mg/L
                                 (Estimated)
                                 ECOSAR: Neutral organics
                             ECOSARvl.ll
                Estimates based on representative
                oligomer where n=6. The effect
                level exceeds the water solubility of
                1.041 mg/L; NES are predicted for
                these endpoints. ECOSARalso
                provided results for the Esters, and
                Esters (phosphate) classes;
                however, professional judgment
                indicates that this compound is not
                currently well represented in
                ECOSARvl.ll.
                                                            7-389

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                                                         JUNE 2014 DRAFT REPORT
                                             Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
        PROPERTY/ENDPOINT
                       DATA
  REFERENCE
       DATA QUALITY
Daphnid LC50
Daphnia magna 48-hour LC50 = 3,500 mg/L
(Estimated)
ECOSAR: Neutral organics
ECOSARvl.ll
Estimates based on representative
oligomer where n=l. The effect
level exceeds the water solubility of
3,375 mg/L; NES are predicted for
these endpoints. ECOSAR also
provided results for the Esters, and
Esters (phosphate) classes;
however, professional judgment
indicates that this compound is not
currently well represented in
ECOSARvl.ll.
                                         Daphnia magna 48-hour LC50 = 13,000 mg/L
                                         (Estimated)
                                         ECOSAR: Neutral organics
                                                    ECOSARvl.ll
                  Estimates based on representative
                  oligomer where n=2. The effect
                  level exceeds the water solubility of
                  932.9 mg/L; NES are predicted for
                  these endpoints. ECOSAR also
                  provided results for the Esters, and
                  Esters (phosphate) classes;
                  however, professional judgment
                  indicates that this compound is not
                  currently well represented in
                  ECOSARvl.ll.
                                         Daphnia magna 48-hour LC50 = 40,000 mg/L
                                         (Estimated)
                                         ECOSAR: Neutral organics
                                                    ECOSARvl.ll
                  Estimates based on representative
                  oligomer where n=3. The effect
                  level exceeds the water solubility of
                  232.7 mg/L; NES are predicted for
                  these endpoints. ECOSAR also
                  provided results for the Esters, and
                  Esters (phosphate) classes;
                  however, professional judgment
                  indicates that this compound is not
                  currently well represented in
                  ECOSARvl.ll.
                                                                    7-390

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                                                JUNE 2014 DRAFT REPORT
                                    Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                 Daphnia magna 48-hour LC50 = 120,000 mg/L
                                 (Estimated)
                                 ECOSAR: Neutral organics
                             ECOSARvl.ll
                Estimates based on representative
                oligomer where n=4. The effect
                level exceeds the water solubility of
                54.73 mg/L; NES are predicted for
                these endpoints. ECOSAR also
                provided results for the Esters, and
                Esters (phosphate) classes;
                however, professional judgment
                indicates that this compound is not
                currently well represented in
                ECOSARvl.ll.
                                 Daphnia magna 48-hour LC50 = 130,000 mg/L
                                 (Estimated)
                                 ECOSAR: Neutral organics
                             ECOSARvl.ll
                Estimates based on representative
                oligomer where n=5. The effect
                exceeds the water solubility of
                4.716 mg/L; NES are predicted for
                these endpoints. ECOSAR also
                provided results for the Esters, and
                Esters (phosphate) classes;
                however, professional judgment
                indicates that this compound is not
                currently well represented in
                ECOSARvl.ll.
                                 Daphnia magna 48-hour LC50 = 370,000 mg/L
                                 (Estimated)
                                 ECOSAR: Neutral organics
                             ECOSARvl.ll
                Estimates based on representative
                oligomer where n=6. The effect
                level exceeds the water solubility of
                1.041 mg/L; NES are predicted for
                these endpoints. ECOSAR also
                provided results for the Esters, and
                Esters (phosphate) classes;
                however, professional judgment
                indicates that this compound is not
                currently well represented in
                ECOSARvl.ll.
                                                            7-391

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                                                         JUNE 2014 DRAFT REPORT
                                             Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
        PROPERTY/ENDPOINT
                       DATA
  REFERENCE
       DATA QUALITY
Green Algae EC50
Green algae 96-hour EC50 = 1,400 mg/L
(Estimated)
ECOSAR: Neutral organics
ECOSARvl.ll
Estimates based on representative
oligomer where n=l. ECOSAR also
provided results for the Esters, and
Esters (phosphate) classes;
however, professional judgment
indicates that this compound is not
currently well represented in
ECOSARvl.ll.
                                         Green algae 96-hour EC50 = 4,300 mg/L
                                         (Estimated)
                                                    ECOSARvl.ll
                  Estimates based on representative
                  oligomer where n=2. The effect
                  level exceeds the water solubility of
                  932.9 mg/L; NES are predicted for
                  these endpoints. ECOSAR also
                  provided results for the Esters, and
                  Esters (phosphate) classes;
                  however, professional judgment
                  indicates that this compound is not
                  currently well represented in
                  ECOSARvl.ll.
                                         Green algae 96-hour EC50 = 12,000 mg/L
                                         (Estimated)
                                         ECOSAR: Neutral organics
                                                    ECOSARvl.ll
                  Estimates based on representative
                  oligomer where n=3. The effect
                  level exceeds the water solubility of
                  232.7 mg/L; NES are predicted for
                  these endpoints. ECOSAR also
                  provided results for the Esters, and
                  Esters (phosphate) classes;
                  however, professional judgment
                  indicates that this compound is not
                  currently well represented in
                  ECOSARvl.ll.
                                         Green algae 96-hour EC50 = 30,000 mg/L
                                         (Estimated)
                                         ECOSAR: Neutral organics
                                                    ECOSARvl.ll
                  Estimates based on representative
                  oligomer where n=4. The effect
                  level exceeds the water solubility of
                                                                    7-392

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                                                 JUNE 2014 DRAFT REPORT
                                     Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                                                                                       54.73 mg/L; NES are predicted for
                                                                                                       these endpoints. ECOSARalso
                                                                                                       provided results for the Esters, and
                                                                                                       Esters (phosphate) classes;
                                                                                                       however, professional judgment
                                                                                                       indicates that this compound is not
                                                                                                       currently well represented in
                                                                                                       ECOSARvl.ll.
                                 Green algae 96-hour EC50 = 32,000 mg/L
                                 (Estimated)
                                 ECOSAR: Neutral organics
                             ECOSARvl.ll
                Estimates based on representative
                oligomer where n=5. The effect
                level exceeds the water solubility of
                4.716 mg/L; NES are predicted for
                these endpoints. ECOSARalso
                provided results for the Esters, and
                Esters (phosphate) classes;
                however, professional judgment
                indicates that this compound is not
                currently well represented in
                ECOSARvl.ll.
                                 Green algae 96-hour EC50 = 77,000 mg/L
                                 (Estimated)
                                 ECOSAR: Neutral organics
                             ECOSARvl.ll
                Estimates based on representative
                oligomer where n=6. The effect
                level exceeds the water solubility of
                1.041 mg/L; NES are predicted for
                these endpoints. ECOSARalso
                provided results for the Esters, and
                Esters (phosphate) classes;
                however, professional judgment
                indicates that this compound is not
                currently well represented in
                ECOSARvl.ll.
                                                            7-393

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                                                        JUNE 2014 DRAFT REPORT
                                             Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
        PROPERTY/ENDPOINT
                      DATA
  REFERENCE
       DATA QUALITY
Chronic Aquatic Toxicity
LOW: Based on estimated chronic aquatic toxicity values for representative oligomers that predict No Effects
at Saturation (NES).
Fish ChV
Freshwater fish ChV = 590 mg/L
(Estimated)
ECOSAR: Neutral organics
                                         Freshwater fish ChV = 2,100 mg/L
                                         (Estimated)
                                         ECOSAR: Neutral organics
                                         Freshwater fish ChV = 6,700 mg/L
                                         (Estimated)
                                         ECOSAR: Neutral organics
                                         Freshwater fish ChV = 20,000 mg/L
ECOSAR vl. 11
Estimates based on representative
oligomer where n=l. ECOSAR also
provided results for the Esters, and
Esters (phosphate) classes;
however, professional judgment
indicates that this compound is not
currently well represented in
ECOSAR vl.ll.
                                                   ECOSAR vl. 11
                                                   ECOSAR vl.ll
                                                   ECOSAR vl.ll
                  Estimates based on representative
                  oligomer where n=2. The effect
                  level exceeds the water solubility of
                  932.9 mg/L; NES are predicted for
                  these endpoints. ECOSAR also
                  provided results for the Esters, and
                  Esters (phosphate) classes;
                  however, professional judgment
                  indicates that this compound is not
                  currently well represented in
                  ECOSAR vl.ll.
                  Estimates based on representative
                  oligomer where n=3. The effect
                  level exceeds the water solubility of
                  232.7 mg/L; NES are predicted for
                  these endpoints. ECOSAR also
                  provided results for the Esters, and
                  Esters (phosphate) classes;
                  however, professional judgment
                  indicates that this compound is not
                  currently well represented in
                  ECOSAR vl.ll.
                  Estimates based on representative
                                                                    7-394

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                                                JUNE 2014 DRAFT REPORT
                                     Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                 (Estimated)
                                 ECOSAR: Neutral organics
                                                oligomer where n=4. The effect
                                                level exceeds the water solubility of
                                                54.73 mg/L; NES are predicted for
                                                these endpoints. ECOSAR also
                                                provided results for the Esters, and
                                                Esters (phosphate) classes;
                                                however, professional judgment
                                                indicates that this compound is not
                                                currently well represented in
                                                ECOSAR vl.ll.
                                 Freshwater fish ChV = 21,000 mg/L
                                 (Estimated)
                                 ECOSAR: Neutral organics
                             ECOSAR vl.ll
                Estimates based on representative
                oligomer where n=5. The effect
                level exceeds the water solubility of
                4.716 mg/L; NES are predicted for
                these endpoints. ECOSAR also
                provided results for the Esters, and
                Esters (phosphate) classes;
                however, professional judgment
                indicates that this compound is not
                currently well represented in
                ECOSAR vl.ll.
                                 Freshwater fish ChV = 60,000 mg/L
                                 (Estimated)
                                 ECOSAR: Neutral organics
                             ECOSAR vl.ll
                Estimates based on representative
                oligomer where n=6. The effect
                level exceeds the water solubility of
                1.041 mg/L; NES are predicted for
                these endpoints. ECOSAR also
                provided results for the Esters, and
                Esters (phosphate) classes;
                however, professional judgment
                indicates that this compound is not
                currently well represented in
                ECOSAR vl.ll.
                                                            7-395

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                                                        JUNE 2014 DRAFT REPORT
                                            Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
        PROPERTY/ENDPOINT
                      DATA
  REFERENCE
       DATA QUALITY
Daphnid ChV
Daphnia magna ChV = 230 mg/L
(Estimated)
ECOSAR: Neutral organics
ECOSARvl.ll
Estimates based on representative
oligomer where n=l. ECOSAR also
provided results for the Esters, and
Esters (phosphate) classes;
however, professional judgment
indicates that this compound is not
currently well represented in
ECOSARvl.ll.
                                         Daphnia magna ChV = 730 mg/L
                                         (Estimated)
                                         ECOSAR: Neutral organics
                                                   ECOSARvl.ll
                  Estimates based on representative
                  oligomer where n=2. ECOSAR also
                  provided results for the Esters, and
                  Esters (phosphate) classes;
                  however, professional judgment
                  indicates that this compound is not
                  currently well represented in
                  ECOSARvl.ll.
                                         Daphnia magna ChV = 2,100 mg/L
                                         (Estimated)
                                         ECOSAR: Neutral organics
                                                   ECOSARvl.ll
                  Estimates based on representative
                  oligomer where n=3. The effect
                  level exceeds the water solubility of
                  232.7 mg/L; NES are predicted for
                  these endpoints. ECOSAR also
                  provided results for the Esters, and
                  Esters (phosphate) classes;
                  however, professional judgment
                  indicates that this compound is not
                  currently well represented in
                  ECOSARvl.ll.
                                         Daphnia magna ChV = 5,600 mg/L
                                         (Estimated)
                                         ECOSAR: Neutral organics
                                                   ECOSARvl.ll
                  Estimates based on representative
                  oligomer where n=4. The effect
                  level exceeds the water solubility of
                  54.73 mg/L; NES are predicted for
                  these endpoints. ECOSAR also
                  provided results for the Esters, and
                                                                    7-396

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                                                JUNE 2014 DRAFT REPORT
                                    Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                                                                                      Esters (phosphate) classes;
                                                                                                      however, professional judgment
                                                                                                      indicates that this compound is not
                                                                                                      currently well represented in
                                                                                                      ECOSARvl.ll.
                                Daphnia magna ChV = 6,000 mg/L
                                (Estimated)
                                ECOSAR: Neutral organics
                             ECOSARvl.ll
                Estimates based on representative
                oligomer where n=5. The effect
                level exceeds the water solubility of
                4.716 mg/L; NES are predicted for
                these endpoints. ECOSAR also
                provided results for the Esters, and
                Esters (phosphate) classes;
                however, professional judgment
                indicates that this compound is not
                currently well represented in
                ECOSARvl.ll.
                                Daphnia magna ChV = 15,000 mg/L
                                (Estimated)
                                ECOSAR: Neutral organics
                             ECOSARvl.ll
                Estimates based on representative
                oligomer where n=6. The effect
                level exceeds the water solubility of
                1.041 mg/L; NES are predicted for
                these endpoints. ECOSAR also
                provided results for the Esters, and
                Esters (phosphate) classes;
                however, professional judgment
                indicates that this compound is not
                currently well represented in
                ECOSARvl.ll.
                                                            7-397

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                                                         JUNE 2014 DRAFT REPORT
                                             Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
        PROPERTY/ENDPOINT
                      DATA
  REFERENCE
       DATA QUALITY
Green Algae ChV
Green algae ChV = 270 mg/L
(Estimated)
ECOSAR: Neutral organics
ECOSARvl.ll
Estimates based on representative
oligomer where n=l. ECOSAR also
provided results for the Esters, and
Esters (phosphate) classes;
however, professional judgment
indicates that this compound is not
currently well represented in
ECOSARvl.ll.
                                         Green algae ChV = 740 mg/L
                                         (Estimated)
                                                    ECOSARvl.ll
                  Estimates based on representative
                  oligomer where n=2. ECOSAR also
                  provided results for the Esters, and
                  Esters (phosphate) classes;
                  however, professional judgment
                  indicates that this compound is not
                  currently well represented in
                  ECOSARvl.ll.
                                         Green algae ChV = 1,800 mg/L
                                         (Estimated)
                                         ECOSAR: Neutral organics
                                                    ECOSARvl.ll
                  Estimates based on representative
                  oligomer where n=3.  The effect
                  level exceeds the water solubility of
                  232.7 mg/L; NES are predicted for
                  these endpoints. ECOSAR also
                  provided results for the Esters, and
                  Esters (phosphate) classes;
                  however, professional judgment
                  indicates that this compound is not
                  currently well represented in
                  ECOSARvl.ll.
                                         Green algae ChV = 4,200 mg/L
                                         (Estimated)
                                         ECOSAR: Neutral organics
                                                    ECOSARvl.ll
                  Estimates based on representative
                  oligomer where n=4. The effect
                  level exceeds the water solubility of
                  54.73 mg/L; NES are predicted for
                  these endpoints. ECOSAR also
                  provided results for the Esters, and
                                                                    7-398

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                                                JUNE 2014 DRAFT REPORT
                                    Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                                                                                      Esters (phosphate) classes;
                                                                                                      however, professional judgment
                                                                                                      indicates that this compound is not
                                                                                                      currently well represented in
                                                                                                      ECOSARvl.ll.
                                Green algae ChV = 4,700 mg/L
                                (Estimated)
                                ECOSAR: Neutral organics
                             ECOSARvl.ll
                Estimates based on representative
                oligomer where n=5. The effect
                level exceeds the water solubility of
                4.716 mg/L; NES are predicted for
                these endpoints. ECOSAR also
                provided results for the Esters, and
                Esters (phosphate) classes;
                however, professional judgment
                indicates that this compound is not
                currently well represented in
                ECOSARvl.ll.
                                Green algae ChV = 10,000 mg/L
                                (Estimated)
                                ECOSAR: Neutral organics
                             ECOSARvl.ll
                Estimates based on representative
                oligomer where n=6. The effect
                level exceeds the water solubility of
                1.041 mg/L; NES are predicted for
                these endpoints. ECOSAR also
                provided results for the Esters, and
                Esters (phosphate) classes;
                however, professional judgment
                indicates that this compound is not
                currently well represented in
                ECOSARvl.ll.
                                                 ENVIRONMENTAL FATE
                                                            7-399

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                                                        JUNE 2014 DRAFT REPORT
                                            Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
        PROPERTY/ENDPOINT
                      DATA
  REFERENCE
       DATA QUALITY
Transport
The environmental fate for the lower MW oligomers where n is 1-5, with MW<1,000 are based on the estimated
moderate water solubility and low vapor pressure indicating that the lower MW oligomers are anticipated to
partition predominantly to soil. The higher MW oligomers where n>6, with MW>1,000 are expected to have
negligible water solubility and negligible vapor pressure indicating that the higher MW oligomers are
anticipated to partition predominantly to soil and sediment. The estimated Henry's Law Constant of <10~8 atm-
m3/mole indicates that the lower MW and higher MW oligomers are not expected to volatilize from  water to the
atmosphere. The estimated K0c of >11,000 indicates that the lower MW and higher MW oligomers  are not
anticipated to migrate through soil to groundwater and also have the potential to adsorb to sediment.
             Henry's Law Constant (atm-
             m3/mole)
<1(T forn>l (Estimated)
EPIv4.11;
Professional
judgment; Boethling
andNabholz, 1997
Estimates based on representative
oligomers where n=l-5; cutoff
values for nonvolatile compounds.
Estimated by the HENRYWIN
Group SAR Method with no
measured chemical property inputs.
Estimates based on representative
oligomers where n>6; cutoff value
used for large, high MW polymers.
High MW polymers are expected to
have low vapor pressure and are not
expected to undergo volatilization.
             Sediment/Soil
             Adsorption/Desorption - Koc
ll,000forn=l
>3 0,000 for n>2
(Estimated)
EPIv4.11;
Professional
judgment
Using MCI Method KOCWIN
v2.00, estimate based on
representative oligomers where
n=l-5. Also estimated for oligomers
where n>6 with MWs > 1,000 based
on professional judgment.
             Level III Fugacity Model
Air = 0%
Water = 0.55%
Soil = 52%
Sediment = 47% (Estimated)
EPIv4.11
Estimate based on representative
oligomer where n=6.
                                        Air = 0%
                                        Water =15%
                                        Soil = 80%
                                                   EPIv4.11
                  Estimate based on representative
                  oligomer where n=l.
                                                                    7-400

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JUNE 2014 DRAFT REPORT
Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
PROPERTY/ENDPOINT


Persistence
Water
Soil
Aerobic Biodegradation
Volatilization Half-life for
Model River
Volatilization Half-life for
Model Lake
Aerobic Biodegradation
Anaerobic Biodegradation
Soil Biodegradation with
Product Identification
Sediment/Water
Biodegradation
DATA
Sediment = 4.8% (Estimated)
REFERENCE

DATA QUALITY

VERY HIGH: The persistence designation for this polymer is based on its higher MW components (MW
>1,000). The lower MW oligomers (MW <1,000; n < 5) of this polymer are expected to have lower persistence
because of their higher water solubility and increased bioavailability to microorganisms. The higher MW
components are expected to have higher persistence because of their low water solubility and poor
bioavailability, indicating that neither biodegradation nor hydrolysis are expected to be important
environmental fate processes. This is supported by experimental studies with the commercial product. In a
ready test using the OECD guideline 301D, 0% biodegradation occurred after 28 days and 2% biodegradation
was achieved after 140 days. In a nonguideline study with limited details, slow hydrolysis was reported for the
commercial product at normal temperatures in acidic and alkaline aqueous solutions. Additionally, this
polymer does not contain functional groups that would be expected to absorb light at environmentally
significant wavelengths. Experimental values for commercial products and evaluation of the higher MW
components of this polymer suggest an environmental half-life of >180 days.
Passes Ready Test: No
Test method: OECD TG 30 ID: Closed Bottle Test
This commercial product biodegraded 0% at day 28 and 2%
at day 140 (Measured)
Hours-days (Primary Survey Model)
Weeks (Ultimate Survey Model) (Estimated)
>1 year for n>l (Estimated)
>1 year for n>l (Estimated)

Probable (Anaerobic-methanogenic biodegradation
probability model)

*
ICL, 2010
EPIv4.11
EPIv4.11
EPIv4.11

EPIv4.11


From a MSDS for the commercial
product Fyrol PNX LE containing
95-100% pure material.
Estimate based on representative
oligomers where n=l-2.
Estimate based on representative
oligomers where n=l-6.
Estimate based on representative
oligomers where n=l-6.
No data located.
Estimate based on representative
oligomers where n=l.
No data located.
No data located.
         7-401

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JUNE 2014 DRAFT REPORT
Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
PROPERTY/ENDPOINT
Air
Reactivity
Atmospheric Half-life
Photolysis
Hydrolysis
Environmental Half-life
DATA
0.086 days for n=l
0.056 days for n=2
0.042 days for n=3
0.025 days for n=6
(Estimated)
Not a significant fate process (Estimated)
Hydrolyzes slowly at normal temperatures in acidic or
alkaline aqueous solutions (Measured)
50%/340daysatpH5-8
50%/320daysatpH9
for n=6 (Estimated) ^f ^^^tr
50%/3.3yearsatpH5-8
50%/3 years at pH 9
forn=l (Estimated)
> 180 days (Estimated)
^
S
30 (Estimated)
REFERENCE
EPIv4.11
Professional
judgment; Mill,
2000
ICL, 2010
EPIv4.11
EPIv4.11
Professional
judgment
EPIv4.11;PBT
Profiler
DATA QUALITY
Estimate based on representative
oligomers where n=l-6.
The substance does not contain
functional groups that would be
expected to absorb light at
wavelengths >290 nm.
Non-quantitative value from a
MSDS for the commercial product
Fyrol PNX LE containing 95-100%
pure material.
Estimate based on representative
oligomer where n=6.
Estimate based on representative
oligomer where n=l .
The n>6 oligomers with a MW
> 1,000 are not anticipated to be
assimilated by microorganisms.
Therefore, biodegradation is not
expected to be an important removal
process. The higher MW oligomers
are also not expected to be removed
by other degradation processes
under environmental conditions
because of limited water solubility
and limited partitioning to air.
Half-life estimated for the
predominant compartment (Soil) for
         7-402

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JUNE 2014 DRAFT REPORT
Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
PROPERTY/ENDPOINT

Bioaccumulation

Fish BCF
Other BCF
BAF
Metabolism in Fish
DATA

REFERENCE

DATA QUALITY
the oligomer where n=l, as
determined by EPI and the PBT
Profiler methodology.
LOW: Both the higher MW and lower MW oligomers are estimated to have Low potential for
bioaccumulation. The representative oligomers with lower MW, where n=l-5, have estimated BCF values of 3.2
and estimated BAF values below 1. The high MW oligomers, where n>6 (MW >1,000) are expected to have
limited water solubility, poor bioavailability and are not expected to be bioaccumulative.
3.2 for n= 1-5 (Estimated)
<100 for the n>6 oligomers (Estimated)

0.94 for n=l
0.90 for n=2-5
(Estimated)
n>6 oligomers (Estimated)

EPIv4.11
Professional
judgment

EPIv4.11
Professional
judgment

Estimate based on representative
oligomers where n=l-5.
The substance has a MW >1,000
and is not anticipated to be taken up
by aquatic organisms; therefore,
bioconcentration is not expected.
No data located.
Estimate based on representative
oligomers where n=l-5.
No data located for MW >1,000
oligomers where n>6.
No data located.
ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring
Ecological Biomonitoring
Human Biomonitoring
No data located.
No data located.
This chemical was not included in the NHANES biomonitoring report (CDC, 2013).
         7-403

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                                                  JUNE 2014 DRAFT REPORT


Akzo Nobel NV, Wuestenenk JA (2005) Flame-retardant soot-containing polyurethane foams.

Boethling RS, Nabholz JV (1997) Environmental assessment of polymers under the U.S. Toxic Substances Control Act. Washington, DC: U.S.
Environmental Protection Agency.

CDC (2013) Fourth national report on human exposure to environmental chemicals, updated tables, March 2013. Centers for Disease Control and
Prevention. http://www.cdc.gov/exposurereport/pdf/FourthReport UpdatedTables  Mar2013 .pdf. Accessed May 10, 2013.

Clariant (2011) Safety data sheet in accordance with regulation (EU) No. 453/2010 Exolit OP 550 (LV).

ECOSAR (Ecological Structure Activity Relationship), Version 1.11. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/oppt/newchems/tools/21ecosar.htm.

EPA (1999) Determining the adequacy of existing data. Washington, DC: U.S. Environmental Protection Agency.
http: //www .epa. gov/hpv/pubs/general/datadeqfn .pdf.

EPA (2012) Using noncancer screening within the SF initiative. Washington, DC: U.S. Environmental Protection Agency.
http: //www .epa. gov/oppt/sf/pubs/noncan-screen .htm.

EPI Estimation Programs Interface (EPI) Suite, Version 4.11. Washington,  DC: U.S. Environmental Protection Agency.
http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm.

ESIS (2012) European chemical Substances Information System. European Commission, http://esis.jrc.ec.europa.eu/.

Gard DR (2005) Phosphoric acids and phosphates. Kirk-Othmer encyclopedia of chemical technology. Wiley-Interscience.
http://onlinelibrarv.wilev.com/book/10.1002/0471238961.

Hardy TA, Jaffe F (1983) Method of preparing oligomeric phosphate esters US 4382042. http://www.google .com/patents/US43 82042.

ICL (2010) Material Safety Data Sheet for phosphoric acid, triethyl ester, polymer with oxirane and phosphorus oxide. ICL Industrial Products.

Mill  T (2000) Photoreactions in surface waters. In: Boethling R Mackay D, eds. Handbook of Property Estimation Methods for Chemicals,
Environmental Health Sciences. Boca Raton:  Lewis  Publishers, 355-381.
                                       T
OncoLogic (2008) U.S. EPA and LogiChem,  Inc., Version 7.0. 2008.


                                                              7-404

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                                                JUNE 2014 DRAFT REPORT


PBT Profiler Persistent (P), Bioaccumulative (B), and Toxic (T) Chemical (PBT) Profiler, Version 1.301. Washington, DC: U.S. Environmental
Protection Agency, www.pbtprofiler.net.
                                                           7-405

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                                                           JUNE 2014 DRAFT REPORT
              Oligomeric phosphonate polyol
                                                  Screening Level Toxicology Hazard Summary
This table only contains information regarding the inherent hazards of flame retardant chemicals. Evaluation of risk considers both the hazard and exposure associated with the

substance including combustion and degradation by-products. The caveats listed in the legend and footnote sections must be taken into account when interpreting the hazard

information in the table.	^B	

VL = Very Low hazard L = Low hazard   = Moderate hazard H = High hazard VH = Very High hazard - Endpoints in colored text (VL, L, M, H, and VH) were

assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment

[(Quantitative) Structure Activity Relationships "(Q)SAR"].
            Chemical
  CASRN
                                                                        Human Health Effects
£>
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I
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                                                           O
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U
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O
                                   u

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                                                          JUNE 2014 DRAFT REPORT
                                                                                                                CASRN: 363626-50-0
                                                                                                                MW:<1,000;MWN311
                                                                                                                MF:
                                                                                                                Physical Forms: Liquid
                                                                                                                Neat: Liquid
                                                                                                                Use: Reactive flame retardant
SMILES: C(O)COP(C)(=O)OCCO (Representative structure where n=l; MW = 184)
Synonyms: Poly(oxy-l,2-ethanediyl), a,a'-(methylphosphinylidene)bis[co-hydroxy-; Bis(polyoxyethylene) methylphosphonate; Polyethylene glycol
methylphosphonate
Trade Names: Exolit OP 560
Chemical Considerations: : This alternative is a phosphonate polyol with an average MW of 311 daltons and a typical phosphorus content of 10-13% according to
publicly available product literature Representative monomers and oligomers were assessed with EPI v4.11 and ECOSAR 1.11 estimates due to an absence of publicly
available experimental physical/chemical, environmental fate and aquatic toxicity values.

This alternative is a reactive flame retardant designed for use in the production of polyurethane foams. It is incorporated into a polymer backbone (i.e. polyurethane)
by chemically bonding with raw materials during the polymerization process. Although not all reactive flame retardants have reactive functional groups, all reactive
flame retardants are irreversibly incorporated into a polymer during manufacture to improve flame retardancy.  Once a reactive flame retardant is incorporated into a
polymer, it is unlikely to be released. Additive flame retardants, in contrast, are not reacted or chemically bonded with the manufactured product and have potential to
be released under certain conditions (Clariant, 2012;  Clariant, 2013).
Polymeric: Yes
Oligomeric: This alternative is a polymer consisting of methylphosphonate substituted with polyethylene glycol.
Metabolites, Degradates and Transformation Products: None identified.
Analog: None
 Endpoint(s) using analog values: Not applicable
Analog Structure: Not applicable
Structural Alerts: Organophosphates - neurotoxicity (EPA, 2012).
Risk Phrases: Not classified by Annex VI Regulation (EC) No 1272/2008 (ESIS, 2012).
Hazard and Risk Assessments: None identified.
                                                                      7-407

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JUNE 2014 DRAFT REPORT
Oligomeric phosphonate polyol CASRN 363626-50-0
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
PHYSICAL/CHEMICAL PROPERTIES
Melting Point (°C)
Boiling Point (°C)
Vapor Pressure (mm Hg)
Water Solubility (mg/L)
<-30 (Measured)
>150 at 0.76 mm Hg decomposes; using
differential thermal analysis (DTA)
(Measured)
>300
for n= 1-7 (Estimated)
n=l: 6.9X10'6
n=2: 3.6xlO'8
<10-8at25°Cforn>3-7
(Estimated)
Slow hydrolysis in the presence of water
(Measured)
IxlO6 for n=l-7 (Estimated)
Clariant, 2012
Clariant, 2012
EPIv4.11;EPA, 1999
^K
EPIv4.11;EPA, 1999
7
Clariant, 2012; Clariant, 2013
EPIv4.11
Cutoff value reported in a Safety
Data Sheet with no study details.
Cutoff value reported in a Safety
Data Sheet with no study details.
Estimate based on representative
structures where n=l-7. Cutoff value
for high boiling point compounds
according to HPV assessment
guidance; decomposition likely
occurs before the boiling point is
reached.
Estimates based on representative
structures where n=l-7. Cutoff value
for nonvolatile compounds for n=3-
7 oligomers according to HPV
assessment guidance.
No study details and no indication of
measured hydrolysis rates were
reported in the Safety Data Sheet;
rates are expected to be pH
dependent.
Estimates based on representative
structures where n=l-7. Slow
hydrolysis expected in the presence
of water based on Safety Data Sheet.
         7-408

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JUNE 2014 DRAFT REPORT
Oligomeric phosphonate polyol CASRN 363626-50-0
PROPERTY/ENDPOINT
Log Kow
Flammability (Flash Point)
Explosivity
Pyrolysis
pH
pKa
Particle Size
DATA
<-2
for n= 1-7
(Estimated)
Flashpoint: 196°C
According to Cleveland DIN 51376; open
cup (Estimated)
Not flammable (Estimated)
Not expected to form explosive mixtures
with air (Estimated)

4.5 at 10 g/L (Estimated)


REFERENCE
EPIv4.11
Clariant, 2012
^^
Professional judgment
Professional judgment

Clariant, 2012; Clariant, 2013


DATA QUALITY
Estimated values based on
representative structures where n=l-
7, indicate high estimated water
solubility.
Reported in a product datasheet.
No experimental data located; based
on its use as a flame retardant.
No experimental data located; based
on its use as a flame retardant.
No data located.
Reported in a Safety Data Sheet.
No data located.
No data located.
         7-409

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JUNE 2014 DRAFT REPORT
Oligomeric phosphonate polyol CASRN 363626-50-0
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
HUMAN HEALTH EFFECTS
Toxicokinetics


Dermal Absorption in vitro
Absorption,
Distribution,
Metabolism &
Excretion









Oral, Dermal or Inhaled
Other











Acute Mammalian Toxicity
Acute Lethality




Oral


Dermal
Inhalation
There were no experimental data located for any route of exposure. There is potential for absorption from
the lungs and poor absorption is expected from the skin and gastrointestinal tract. This substance may
undergo metabolic oxidation to form a carboxylic acid.


There is potential for absorption via
inhalation. Absorption is expected to be
poor from the skin and gastrointestinal
tract.
The most relevant route of exposure is
inhalation due to potential worker
exposure and because greater
bioavailability is expected via the
inhalation route of exposure compared to
the oral route.
This substance may undergo metabolic
oxidation to form a carboxylic acid


Professional judgment
^^^^. r


*








No data located.
Based on these physical chemical
properties and professional
judgment.









LOW: Based on an oral LD50 value >2,000 mg/kg. No data were located for the dermal and inhalation
routes of exposure.
Rat oral LD50 >2,000 mg/kg




Clariant, 2012; Submitted
confidential study



Limited study details reported in a
Safety Data Sheet and in a submitted
confidential study.
No data located.
No data located.
         7-410

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JUNE 2014 DRAFT REPORT
Oligomeric phosphonate polyol CASRN 363626-50-0
PROPERTY/ENDPOINT
Carcinogenicity

OncoLogic Results
Carcinogenicity (Rat and
Mouse)
Combined Chronic
Toxicity/Carcinogenicity
Other
Genotoxicity

Gene Mutation in vitro
Gene Mutation in vivo
Chromosomal Aberrations in
vitro
Chromosomal Aberrations in
vivo
DNA Damage and Repair
Other
Reproductive Effects

Reproduction/Developmental
Toxicity Screen
DATA
REFERENCE
DATA QUALITY
MODERATE: There is uncertainty due to lack of experimental data for this substance; carcinogenic
effects cannot be ruled out.








Structure could not be evaluated by
OncoLogic.
No data located.
No data located.
No data located.
MODERATE: There is uncertainty due to the lack of experimental data for this endpoint. This substance
was not a mutagen in bacteria in one study. DfE criteria for this endpoint require both gene mutation and
chromosomal aberration assays. For instances of incomplete or inadequate mutagenicity/genotoxicity data,
a Low hazard designation cannot be assigned.
Negative for gene mutation in an Ames
test.





Clariant, 2012; Submitted
confidential study





Limited study details reported in a
Safety Data Sheet and in a submitted
confidential study.
No data located.
No data located.
No data located.
No data located.
No data located.
LOW: Estimated based on expert judgment and lack of structural alerts for reproductive toxicity
identified for this substance. No experimental data were located.


No data located.
         7-411

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JUNE 2014 DRAFT REPORT
Oligomeric phosphonate polyol CASRN 363626-50-0
PROPERTY/ENDPOINT

Combined Repeated Dose
with Reproduction/
Developmental Toxicity
Screen
Reproduction and Fertility
Effects
Other
Developmental Effects

Reproduction/
Developmental Toxicity
Screen
Combined Repeated Dose
with Reproduction/
Developmental Toxicity
Screen
Prenatal Development
Postnatal Development
Prenatal and Postnatal
Development ^J
DATA


There is low potential for reproductive
effects
(Estimated)
REFERENCE

^^
Expert judgment
DATA QUALITY
No data located.
No data located.
Estimated based on expert judgment
and the lack of structural alerts.
MODERATE: There were no experimental data for the developmental toxicity endpoint. There were no
structural alerts identified for this endpoint.
There were also no experimental data located for the developmental neurotoxicity endpoint. There is
uncertain potential for developmental neurotoxicity for this substance based on a structural alert for
organophosphates for the neurotoxicity endpoint; decreased cholinesterase activity in pregnant lab
animals has been shown to have a negative impact on fetal brain development. As a result, an estimated
Moderate designation is assigned.










No data located.
No data located.
No data located.
No data located.
No data located.
         7-412

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JUNE 2014 DRAFT REPORT
Oligomeric phosphonate polyol CASRN 363626-50-0
PROPERTY/ENDPOINT

Developmental Neurotoxicity
Other
Neurotoxicity

Neurotoxicity Screening
Battery (Adult)
Other
Repeated Dose Effects


DATA
Uncertain concern for developmental
neurotoxicity based on the potential for
Cholinesterase (ChE) inhibition in dams
that may result in alterations of fetal
neurodevelopment.
(Estimated)
There is low potential for developmental
effects (Estimated)
REFERENCE
Professional judgment
Expert j udgment
DATA QUALITY
Estimated based on a structural alert
for organophosphates for the
neurotoxicity endpoint.
Estimated based on expert judgment
and the lack of structural alerts.
MODERATE: Estimated to have uncertain potential for neurotoxic effects based on a structural alert for
organophosphates and professional judgment. Neurotoxicity is generally decreased for phosphonates
compared to phosphate esters and for structures without good leaving groups. However, there were no
experimental data located, particularly for the most relevant route of exposure (inhalation). Due to the
lack of data, the concern for the structural alert could not be ruled out; therefore, a conservative
designation of Moderate is assigned.

There is potential for neurotoxic effects
based on a structural alert for
organophosphates
(Estimated)
^
7

Professional judgment
No data located.
Estimated based on a structural alert
for organophosphates and
professional judgment.
Neurotoxicity is generally decreased
for phosphonates when compared to
phosphate esters and for structures
that lack "good" leaving groups;
alcohols are not considered "good"
leaving groups.
LOW: Estimated based on expert judgment and lack of structural alerts for repeated dose toxicity
identified for this substance. No experimental data were located.
Estimated to have low potential for
repeated dose effects
(Estimated)
Expert j udgment
Estimated based on expert judgment
and absence of structural alerts.
         7-413

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JUNE 2014 DRAFT REPORT
Oligomeric phosphonate polyol CASRN 363626-50-0
PROPERTY/ENDPOINT
Skin Sensitization

Skin Sensitization
Respiratory Sensitization

Respiratory Sensitization
Eye Irritation

Eye Irritation
Dermal Irritation

Dermal Irritation
Endocrine Activity

Immunotoxicity

Immune System Effects
DATA
REFERENCE
DATA QUALITY
LOW: Estimated based on expert judgment and lack of structural alerts for skin Sensitization identified
for this substance. No experimental data were located.
There is low potential for skin
Sensitization
(Estimated)
Expert judgment
Estimated based on expert judgment
and the absence of structural alerts.
No data located.


No data located.
LOW: No eye irritation to slight eye irritation was reported.
Slight eye irritation
Not an eye irritant in rabbits.
Professional judgment;
Submitted confidential study
Clariant, 2012
Data reported in a confidential study
submitted to EPA.
Limited study details reported in a
Safety Data Sheet; conducted
according to OECD 405.
VERY LOW: This substance is not a skin irritant.
Not a skin irritant; 4-hour exposure to
rabbits.
Clariant, 2012; Submitted
confidential study
Limited study details reported in a
Safety Data Sheet and a submitted
confidential study; conducted
according to OECD 404.
No experimental data were located.


No data located.
There were no immunotoxicity structural alerts identified for substance. There were no experimental data
located.
There is low potential for immunotoxic
effects
(Estimated)
Expert judgment
Estimated based on expert judgment
and the absence of structural alerts.
         7-414

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                                                        JUNE 2014 DRAFT REPORT
                                               Oligomeric phosphonate polyol CASRN 363626-50-0
          PROPERTY/ENDPOINT
               DATA
       REFERENCE
       DATA QUALITY
                                                               ECOTOXICITY
ECOSAR Class
Acute Aquatic Toxicity
LOW: Based on estimated acute aquatic toxicity values for representative oligomers (n=l through n=7).
Estimated values were all >100 mg/L. Estimated values were predicted to have No Effects at Saturation
(NES) for the n=3 through n=7 oligomers for fish and daphnia and for n=4 through n=7 for algae.
Experimental data in fish also indicate a Low hazard; experimental data were not located for daphnia or
algae.
Fish LC50
Brachydanio rerio (Zebrafish) 96-hour
LC50> 100 mg/L
(Experimental)
                                             Freshwater fish 96-hour LC50 =
                                             n=l-7:> 100 mg/L

                                             (Estimated)
                                             ECOSAR: Neutral organics
Clariant, 2012; Submitted
confidential study
                                    ECOSAR vl. 11
Limited study details reported in a
Safety Data Sheet and in a submitted
confidential study; conducted
according to OECD 203.
                             Estimates based on representative
                             oligomers where n=l through n = 7.

                             The estimated effect for n=2 (3.50 x
                             106mg/L) exceeds the water
                             solubility of 1x106 mg/L, but not by
                             lOx as required to be considered
                             NES by ECOSAR The chemical
                             may not be soluble enough to
                             measure the predicted effect.

                             The corresponding estimated effects
                             for n=3 through n=7 exceed the
                             water solubility of IxlO6 mg/L by
                             more than lOx. NES are predicted
                             for these endpoints.

                             Narcosis classes (neutral organics)
                             are provided for comparative
                             purposes; DfE assessment
                             methodology will use the lowest
                                                                   7-415

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                                                        JUNE 2014 DRAFT REPORT
                                               Oligomeric phosphonate polyol CASRN 363626-50-0
          PROPERTY/ENDPOINT
               DATA
       REFERENCE
       DATA QUALITY
                                                                                                              estimated toxicity value provided by
                                                                                                              ECOSAR classes that have a more
                                                                                                              specific mode of action relative to
                                                                                                              narcosis.

                                                                                                              ECOSAR also provided results for
                                                                                                              the Esters, and Esters (phosphate)
                                                                                                              classes; however, professional
                                                                                                              judgment indicates that this
                                                                                                              compound is not currently well
                                                                                                              represented in ECOSAR v 1.11.
Daphnid LC50
Daphnia magnet 48-hour LC50 =
n=l-7:  > 100 mg/L

(Estimated)
ECOSAR: Neutral organics
ECOSAR vl. 11
Estimates based on representative
oligomers where n=l through n=7.

The estimated effects for n=2 (1.3 x
106 mg/L) and n=3 (5.1 x 106 mg/L)
exceed the water solubility of IxlO6
mg/L, but not by lOx as required to
be considered NES by ECOSAR.
The chemical may not be soluble
enough to measure the predicted
effect.

The corresponding estimated effects
for n=4 through n=7 exceed the
water solubilities (IxlO6 mg/L) by
more than lOx. NES are predicted
for these oligomers.

Narcosis classes (neutral organics)
are provided for comparative
purposes; DfE assessment
methodology will use the lowest
                                                                    7-416

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                                                        JUNE 2014 DRAFT REPORT
                                               Oligomeric phosphonate polyol CASRN 363626-50-0
          PROPERTY/ENDPOINT
               DATA
       REFERENCE
       DATA QUALITY
                                                                                                              estimated toxicity value provided by
                                                                                                              ECOSAR classes that have a more
                                                                                                              specific mode of action relative to
                                                                                                              narcosis.

                                                                                                              ECOSAR also provided results for
                                                                                                              the Esters, and Esters (phosphate)
                                                                                                              classes; however, professional
                                                                                                              judgment indicates that this
                                                                                                              compound is not currently well
                                                                                                              represented in ECOSAR v 1.11.
Green Algae EC50
Green algae 96-hour EC50 =
n=l-7:> lOOmg/L

(Estimated)
ECOSAR: Neutral organics
ECOSAR vl. 11
Estimates based on representative
oligomers where n=l through n=7.

The estimated effects for n=4 (1.50x
106mg/L) and n=5 (4.40 x 106mg/L)
exceed the water solubility of IxlO6
mg/L, but not by lOx as required to
be considered NES by ECOSAR.
The chemical may not be soluble
enough to measure the predicted
effect.

The corresponding estimated effects
for n=6 and n=7 exceed the water
solubilities (IxlO6 mg/L) by more
than lOx. NES are predicted for
these oligomers.

Narcosis classes (neutral organics)
are provided  for comparative
purposes; DfE assessment
methodology will use the lowest
                                                                    7-417

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                                            JUNE 2014 DRAFT REPORT
                                   Oligomeric phosphonate polyol CASRN 363626-50-0
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                                                                                estimated toxicity value provided by
                                                                                                ECOSAR classes that have a more
                                                                                                specific mode of action relative to
                                                                                                narcosis.

                                                                                                ECOSAR also provided results for
                                                                                                the Esters, and Esters (phosphate)
                                                                                                classes; however, professional
                                                                                                judgment indicates that this
                                                                                                compound is not currently well
                                                                                                represented in ECOSAR v 1.11.
                                                        7-418

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JUNE 2014 DRAFT REPORT
Oligomeric phosphonate polyol CASRN 363626-50-0
PROPERTY/ENDPOINT
Chronic Aquatic Toxicity
DATA
REFERENCE
DATA QUALITY
LOW: Based on estimated chronic aquatic toxicity values for representative oligomers (n=l and n= 7).
Estimated values for all oligomer were >10 mg/L. Estimated values for the n=4 through n=7 oligomers for
fish, n=5 through n=7 oligomers for daphnia, and n=7 oligomer for algae were predicted to have No
Effects at Saturation (NES). There were no experimental data located.
         7-419

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                                                         JUNE 2014 DRAFT REPORT
                                               Oligomeric phosphonate polyol CASRN 363626-50-0
          PROPERTY/ENDPOINT
               DATA
       REFERENCE
       DATA QUALITY
Fish ChV
Freshwater fish ChV =
n=l-7:  > 100 mg/L

(Estimated)
ECOSAR: Neutral organics
ECOSARvl.ll
Estimates based on representative
oligomers where n=l through n=7.

The estimated effect for n=4 (2.90 x
106 mg/L) exceeds the water
solubility of 1x106 mg/L, but not by
lOx as required to be considered
NES by ECOSAR. The chemical
may not be soluble enough to
measure the predicted effect. The
corresponding estimated effects for
n=5 through n=7 exceed the water
solubilities (IxlO6 mg/L) by more
than lOx. NES are predicted for
these oligomers.

Narcosis classes (neutral organics)
are provided for comparative
purposes; DfE assessment
methodology will use the lowest
estimated toxicity value provided by
ECOSAR classes that have a more
specific mode of action relative to
narcosis.

ECOSAR also provided results for
the Esters, and Esters (phosphate)
classes; however, professional
judgment indicates that this
compound is not currently well
represented  in ECOSAR v 1.11.
                                                                    7-420

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                                                        JUNE 2014 DRAFT REPORT
                                               Oligomeric phosphonate polyol CASRN 363626-50-0
          PROPERTY/ENDPOINT
               DATA
       REFERENCE
       DATA QUALITY
Daphnid ChV
Daphnia magna ChV =
n=l-7: > 100 mg/L

(Estimated)
ECOSAR: Neutral organics
ECOSARvl.ll
Estimates based on representative
oligomers where n=l through n=7.
The estimated effects for n=5 (1.30
x 106 mg/L) and n=6 (3.80 x 106
mg/L) exceeds the water solubility
of 1x106 mg/L,  but not by lOx as
required to be considered NES by
ECOSAR. The  chemical may not be
soluble enough  to measure the
predicted effect. The estimated
effect for n=7 exceeds the water
solubility (IxlO6 mg/L) by more
than lOx. NES are predicted for this
oligomer.

Narcosis classes (neutral organics)
are provided for comparative
purposes; DfE assessment
methodology will use the lowest
estimated toxicity value provided by
ECOSAR classes that have  a more
specific mode of action relative to
narcosis.

ECOSAR also provided results for
the Esters, and Esters (phosphate)
classes; however, professional
judgment indicates that this
compound is not currently well
represented in ECOSAR vl. 11
                                                                    7-421

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JUNE 2014 DRAFT REPORT
Oligomeric phosphonate polyol CASRN 363626-50-0
PROPERTY/ENDPOINT
Green Algae ChV






















DATA
Green algae ChV =
n=l-7:> lOOmg/L
(Estimated)
ECOSAR: Neutral organics





^



^ ...
\J
-VI V
^^ §r


^

7

REFERENCE
ECOSAR vl. 11



^^


^^^







w







DATA QUALITY
Estimates based on representative
oligomers where n=l through n=7.

The estimated effect for n=7 (1.90 x
106 mg/L) exceeds the water
solubility of 1x1 06 mg/L, but not by
lOx as required to be considered
NES by ECOSAR. The chemical
may not be soluble enough to
measure the predicted effect.
Narcosis classes (neutral organics)
are provided for comparative
purposes; DfE assessment
methodology will use the lowest
estimated toxicity value provided by
ECOSAR classes that have a more
specific mode of action relative to
narcosis.
ECOSAR also provided results for
the Esters, and Esters (phosphate)
classes; however, professional
judgment indicates that this
compound is not currently well
represented in ECOSAR v 1 . 1 1 .
ENVIRONMENTAL FATE
         7-422

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                                                        JUNE 2014 DRAFT REPORT
                                              Oligomeric phosphonate polyol CASRN 363626-50-0
          PROPERTY/ENDPOINT
               DATA
       REFERENCE
       DATA QUALITY
Transport
Level III fugacity models incorporating available physical and chemical property data indicate that at
steady state, the polymer is anticipated to be found predominantly in soil, and to a lesser extent, water.
The estimated Henry's Law Constant of <10"8 atm-m3/mole based on an estimated high water solubility
and low vapor pressure indicates that the polymer is not expected to volatilize from water to the
atmosphere. The estimated Koc values in the range of 10-260 indicate that components of the polymer are
anticipated to migrate through soil to groundwater.
                  Henry's Law Constant (atm-
                  m3/mole)
<1(T for n= 1-7 (Estimated)
EPI v4.11; Professional
judgment
                  Sediment/Soil
                  Adsorption/Desorption - Koc
n=l-6: 10
n=7: 260 (Estimated)
                  Level III Fugacity Model
Air = 0%
Water = 12%
Soil = 88%
Sediment = 0% (Estimated)
n=7
                                            Air = 0%
                                            Water = 31%
                                            Soil = 69%
                                            Sediment = 0% (Estimated)
                                            n=l
EPIv4.11
EPIv4.11
                                    EPIv4.11
Estimates based on representative
structures where n=l-7. Cutoff
values for non-volatile compounds.
Estimated by the HENRYWIN
Bond SAR Method with no
measured chemical property inputs.
Using MCI Method KOCWIN v
2.00, estimates based on
representative structures where n=l-
7.
Estimate based on a representative
structure where n=7.
                            Estimate based on a representative
                            structure where n=l.
                                                                   7-423

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JUNE 2014 DRAFT REPORT
Oligomeric phosphonate polyol CASRN 363626-50-0
PROPERTY/ENDPOINT
Persistence
Water
Aerobic Biodegradation
Volatilization Half-life for
Model River
DATA
REFERENCE
DATA QUALITY
MODERATE: Biodegradation is expected to be an important mechanism of removal. Phosphonates occur
naturally in the environment where many strains of bacteria have been isolated that metabolize
phosphonates. Although no experimental biodegradation studies were located, estimates using
representative components of the polymer indicate that the lower MW components (where n<2) are
expected to have ultimate persistence with a half-life >16-<60 days, equivalent to a Moderate hazard
designation using a conservative approach. The larger representative oligomers, outside the domain of the
biodegradation estimation methods, are anticipated to behave similarly based on the chemical properties.
Hydrolysis was reported in a Safety Data Sheet for this polymer. The available study details did not
provide key information of the rate of hydrolysis and important test conditions, such as pH. This
polymeric mixture does not contain functional groups that would be expected to absorb light at
environmentally significant wavelengths; therefore degradation by direct photolysis is not expected.
n=l: Days (Primary Survey Model)
Weeks (Ultimate Survey Model)
(Estimated)
n=7: Weeks (Primary Survey Model)
Months (Ultimate Survey Model)
(Estimated)
In nature, phosphonates are found in cell
membranes of plants and animals.
Bacterial metabolism of phosphonates
with the C-P lyase enzyme plays a major
role in biodegradation of phosphonates
and the phosphorus cycle in the
environment. The C-P lyase enzyme,
converts alkylphosphonates to the
corresponding alkane and inorganic
phosphate and is found in many strains of
bacteria with broad specificity.
Phosphonates are considered to be
inherently biodegradable. (Estimated)
>1 year for n=l-7 (Estimated)
EPIv4.11
EPIv4.11
Ghisalba et al., 1987; Nowack,
2003
EPIv4.11
Estimate based on a representative
structure where n=l.
The higher MW oligomer where
n=7 is outside the domain of the
available estimation methods.
Supporting information about the
bacterial biodegradation of this class
of compounds.
Estimates based on representative
structures where n=l-7.
         7-424

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JUNE 2014 DRAFT REPORT
Oligomeric phosphonate polyol CASRN 363626-50-0
PROPERTY/ENDPOINT

Soil
Air
Reactivity
Volatilization Half-life for
Model Lake
Aerobic Biodegradation
Anaerobic Biodegradation
Soil Biodegradation with
Product Identification
Sediment/Water
Biodegradation
Atmospheric Half-life
Photolysis
Hydrolysis
Environmental Half-life
DATA
>1 year for n=l-7 (Estimated)

Probable (Anaerobic -methanogenic
biodegradation probability model)


n=l: 0.19
n=2: 0.13
n=3: 0.10
n=7: 0.05
(Estimated)
Not a significant fate process (Estimated)
Slow hydrolysis in the presence of water
(Measured)
n=l-7: >1 year at pH 5 to 9 (Estimated)
30 (Estimated)
REFERENCE
EPIv4.11

EPIv4.11
^^


EPIv4.11
7
Professional judgment; Mill,
2000
Clariant, 2012; Clariant, 2013
EPIv4.11
PBT Profiler vl.301; EPI v4. 1 1
DATA QUALITY
Estimates based on representative
structures where n=l-7.
No data located.
Estimate based on representative
structure where n=l-2. Estimates
indicate anaerobic biodegradation is
not probable for representative
structures where n=3-7.
No data located.
No data located.
Estimates based on representative
structures where n=l-7. The
substance is expected to have
limited volatility; therefore, this is
not expected to be an important
removal pathway.
The substance does not contain
functional groups that would be
expected to absorb light at
wavelengths >290 nm.
No study details and no indication of
hydrolysis rate were reported in the
Safety Data Sheet; rates are
expected to be pH dependent.
Estimates based on representative
structures where for n=l-7.
Half-life estimated for the
predominant compartment (Soil) for
a representative structure where
         7-425

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JUNE 2014 DRAFT REPORT
Oligomeric phosphonate polyol CASRN 363626-50-0
PROPERTY/ENDPOINT

Bioaccumulation

Fish BCF
Other BCF
BAF
Metabolism in Fish
DATA

>75 days (Estimated)
REFERENCE

PBT Profiler vl.301; EPI v4. 1 1
^^
DATA QUALITY
n>l-2, as determined by EPI and the
PBT Profiler methodology.
The higher MW oligomers where
n=3-7, are outside the domain of the
available estimation methods; the
half-life estimated for the
predominant compartment is
anticipated to be shorter than the
estimated output.
LOW: Estimated based on BCF values of 3.2 and BAF values of <1 for the representative structures of the
polymeric mixture.
n=l-7: 3. 2 (Estimated)

n= 1-7: 0.9 (Estimated)

EPIv4.11

EPIv4.11

Estimates based on representative
structures where n=l-7.
No data located.
Estimates based on representative
structures where n=l-7.
No data located.
ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring
Ecological Biomonitoring ^^H
Human Biomonitoring
No data located.
No data located.
This chemical was not included in the NHANES biomonitoring report. (CDC, 2013).
         7-426

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                                                  JUNE 2014 DRAFT REPORT


CDC (2013) Fourth national report on human exposure to environmental chemicals, updated tables, March 2013.
http://www.cdc.gov/exposurereport/pdf/FourthReport_UpdatedTables_Mar2013 .pdf.

Clariant (2012) Safety data sheet in accordance with Regulation (EU) No.453/2010: EXOLIT OP 560. Clariant.

Clariant (2013) Product data sheet - Flame retardants: Exolit OP 560: Phosphorus polyols. Clariant.
http://www.clariant.com/bu/additives/PDS_Additives.nsf/www/DS-OSTS-7SHC6G?open.

ECOSAR Ecological Structure Activity Relationship (ECOSAR). Estimation Programs Interface (EPI) Suite for Windows, Version 1.11.
Washington, DC: EPPvVIN/EPISUITE. U.S. Environmental Protection Agency, http://www.epa.gov/oppt/newchems/tools/21ecosar.htm.

EPA (1999) Determining the adequacy of existing data. High Production Volume (HPV) Challenge. Washington, DC: U.S. Environmental
Protection Agency, http://www.epa.gov/hpv/pubs/general/datadeqfn.pdf.

EPA (2012) Using noncancer screening within the SF initiative. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/oppt/sf/pubs/noncan-screen.htm.

EPI Estimation Programs Interface (EPI) Suite, Version 4.11. Washington, DC: EPPvVIN/EPISUITE. U.S. Environmental Protection Agency.
http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm.

ESIS (2012) European chemical Substances Information  System. European Commission, http://esis.jrc.ec.europa.eu/.

Ghisalba O, Kueenzi M, Ramostombo GM, et al. (1987) Microbial degradation and utilization of selected organophosphorus compounds
Strategies and applications. 41:206-214.

Mill T (2000) Photoreactions in surface waters. In: Boethling R Mackay D, eds. Handbook of Property Estimation Methods for Chemicals,
Environmental Health Sciences. Boca Raton:  Lewis Publishers.:355-381.

PBT Profiler Persistent (P), Bioaccumulative  (B), and Toxic (T) Chemical (PBT) Profiler, Version 1.301. Washington, DC: U.S. Environmental
Protection Agency, www.pbtprofiler.net.
                                                              7-427

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                                                          JUNE 2014 DRAFT REPORT
              Tricresyl phosphate (TCP)
Screening Level Toxicology Hazard Summary
This table only contains information regarding the inherent hazards of flame retardant chemicals. Evaluation of risk considers both the hazard and exposure associated with the
substance including combustion and degradation by-products. The caveats listed in the legend and footnote sections must be taken into account when interpreting the hazard
information in the table.
VL = Very Low hazard L = Low hazard = Moderate hazard = High hazard VH = Very High hazard - Endpoints in colored text (VL, L, , H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].








Chemical








CASRN
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1330-78-5

L
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L
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VH
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M
H
 This assessment also includes information for other methylated triphenyl phosphate isomers (phosphoric acid, bis(methylphenyl) phenyl ester (CASRN 26446-73-1) and
phosphoric acid, methylphenyl diphenyl ester (CASRN 26444-49-5)).
                                                                      7-428

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                                                          JUNE 2014 DRAFT REPORT
                                             Representative Structure
                                                                                                               CASRN: 1330-78-5; 26446-73-1;
                                                                                                               26444-49-5
                                                                                                               MW: 368.37
                                                                                                               MF: C21H21O4P
                                                                                                               Physical Forms: Liquid
                                                                                                               Neat:
                                                                                                               Use: Flame retardant
SMILES: O=P(Oclccc(C)ccl)(Oc2ccc(C)cc2)Oc3ccc(C)cc3 (Representative structure for tricresyl phosphate)
O=P(Oclccc(C)ccl)(Oc2ccc(C)cc2)Oc3ccccc3 (Representative structure for dicresyl phenyl phosphate)
O=P(Oclcccccl)(Oc2ccccc2)Oc3ccccc3C (Representative structure for monocresyl diphenyl phosphate)
Synonyms: TCP; Phosphoric acid, tris(methylphenyl) ester; Tritolyl phosphate; Phosphoric acid, tritolyl ester; Tri(methylphenyl) phosphate
Chemical Considerations: The alternative, tricresyl phosphate, may contain a mixture of methylated triphenyl phosphate isomers with an unspecified amount of
methyl substitution. The composition will be dependent on the manufacturing, purification and processing of the compound. Mono-o-ere syl and di-o-cresyl isomers
have well documented toxicity concerns. Efforts are made to minimize the amount of ortho-isomer present in commercial products, to amounts typically less than
0.4% (Weiner and Jortner, 1999). Therefore, preparations will consist mainly of meta- and para-substituted isomers (HSDB, 2013d). The isomers and components
expected to be present will be discussed in this report as appropriate when determining hazard designations. Test substance composition was not consistently reported
in the literature however a description of the test sample and isomer content is included in the data entries when available. Chemical, fate, and toxicity data for
components of the mixture represented by other CASRN were collected in the preparation of this AA and are listed below:
  Phosphoric acid, tris(methylphenyl) ester (CASRN 1330-78-5)
  tri-o-cresyl phosphate (CASRN 78-30-8)
  tri-m-cresyl phosphate (CASRN 563-04-2)
  tri-p-cresyl phosphate (CASRN 78-32-0)
  phosphoric acid, bis(methylphenyl) phenyl ester (CASRN 26446-73-1)
  p-cresyl diphenyl phosphate (CASRN 78-31-9)
  2-methylphenyl diphenyl phosphate (CASRN 5254-12-6)
  phenyl di(p-tolyl) phosphate (CASRN 34909-69-8)
  phosphoric acid, 3-methylphenyl diphenyl ester (CASRN 69500-28-3)
  (2,4-dimethylphenyl) diphenyl phosphate (CASRN 86864-87-1)
  (2,3-dimethylphenyl) diphenyl phosphate (CASRN 25155-24-2)
  diphenyl xylyl phosphate (CASRN 29660-68-2)
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  (2,5-dimethylphenyl) diphenyl phosphate (CASRN 73179-40-5)
  diphenyl 2,4,6-trimethylphenyl ester (CASRN 73179-43-8)
  phosphoric acid, methylphenyl diphenyl ester (CASRN 26444-49-5)
Estimated values using representative structures as indicated in the SMILES section of this assessment, will be used to fill assessment data gaps. EPI v4.11 was used
to estimate physical/chemical and environmental fate values due to an absence of experimental data (Weiner and Jortner, 1999; EPA, 2010; van der Veen and de Boer.
2012; HSDB, 2013d).
Polymeric: No
Oligomeric: Not applicable
Metabolites, Degradates and Transformation Products: Degradates include orthophosphate and phenolic moieties; phenol; p-cresyl p-carboxyphenyl phosphate; p-
hydroxybenzoic acid; di-p-cresyl phosphate; oxidized triesters di-p-cresyl p-carboxyphenyl phosphate and p-cresyl di-p-carboxyphenyl phosphate; p-hydroxybenzoic
acid; dicresylphosphate and cresol.
Metabolites: p-cresyl p-carboxyphenyl phosphate; p-hydroxybenzoic acid; di-p-cresyl phosphate; p-cresyl p-carboxyphenyl phosphate and the oxidized triesters; 2-(2-
cresyl)-4h-l-3-2-benzodioxaphosphorin-2-one (CASRN 1222-87-3) (Kurebayashi et al., 1985; WHO, 1990; NTP, 1994; Great Lakes Chemical Corporation, 2001;
van der Veen and de Boer, 2012; Schindler et al., 2013).
Analog: Tricresyl phosphate isomers and methyl substituted
phenyl phosphate esters anticipated to be present in the
commercial product were considered in this evaluation, as
described in the chemical considerations section.
Endpoint(s) using analog values: Not applicable
Analog Structure: Not applicable
Structural Alerts: Organophosphates; Neurotoxicity (EPA, 2012).
Risk Phrases: Not classified by Annex VI Regulation (EC) No 1272/2008 (ESIS, 2012).
Hazard and Risk Assessments: This alternative was included in a risk assessment prepared for phosphate ester flame retardants by the Agency for Toxic Substances
and Disease Registry. A screening level hazard characterization was prepared for tricresyl phosphate by EPA. HPV Data Summary, Test Plan, SIDS Initial
Assessment Profile and SIAM were completed for Diphenyl Cresyl Phosphate (OECD, 1998; Great Lakes Chemical Corporation, 2001; OECD-SIDS, 2002; EPA,
2010; ATSDR 2012).
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Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
PHYSICAL/CHEMICAL PROPERTIES
Melting Point (°C)
Boiling Point (°C)
-33
(Measured)
-35
Crystallizing point (Measured)
-38
(Measured)
<-10
(Measured)
25.5
(Measured)
11
(Measured)
77
(Measured)
420
(Measured)
439
(Measured)
410
(Measured) ^^r
390
(Measured)
265
(Measured)
265 at 10 mmHg
(Measured)
PhysProp, 2012
HSDB, 2013d
van der Veen and de Boer, 2012
OECD-SIDS, 2002
HSDB, 2013b
PhysProp, 2012
van der Veen and de Boer, 2012
HSDB, 2013d
van der Veen and de Boer, 2012
PhysProp, 2012
HSDB, 2013a
PhysProp, 2012
Aldrich, 1994
Reported in a secondary source.
Reported in a secondary source with
limited study details.
Reported in a secondary source for
cresyl diphenyl phosphate (CASRN
26444-49-5); purity not stated.
Reported for cresyl diphenyl
phosphate (CASRN 26444-49-5).
Reported for tri-m-cresyl phosphate
(CASRN 563-04-2).
Reported for tri-o-cresyl phosphate
(CASRN 78-30-8).
Limited study details and test method
not stated; inconsistent with other
values reported.
Reported in a secondary source, with
limited study details.
Reported in a secondary source; test
method not stated.
Reported for tri-o-cresyl phosphate
(CASRN 78-30-8).
Reported for cresyl diphenyl
phosphate (CASRN 26444-49-5).
Reported in a secondary source.
Similar values reported in other
sources at a reduced pressure.
Reported for a 90% mixture of
isomers at a reduced pressure.
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Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT

Vapor Pressure (mm Hg)
Water Solubility (mg/L)
DATA
260 at 15 mmHg
(Measured)
241
Reported as a range 24 1-25 5 °C at 0.533
hPa (Measured)
245
(Measured)
235
(Measured)
6xlO-7at25°C
(Extrapolated)
4.7xlO-6at25°C
(Measured)
1.46xlO-5at25°C
(Extrapolated)
<9xlO-7at25°C
Reported as <1.2xlQ-4 Pa; OECD TG 104
Dynamic method (Measured)
0.003 at 150°C
Reported as 0.0044 hPa at 150°C
(Measured)
0.36 (Measured)
at 25 °C
0.24 (Measured)
REFERENCE
HSDB, 2013b
Great Lakes Chemical
Corporation, 2001
OECD-SIDS, 2002
van der Veen and de Boer, 2012
PhysProp, 2012
PhysProp, 2012; van der Veen
and de Boer, 2012
PhysProp, 2012
OECD-SIDS, 2002
Great Lakes Chemical
Corporation, 2001
Saeger et al., 1979 (as cited in
EPA, 2010; PhysProp, 2012;
HSDB, 2013d); van der Veen
and de Boer, 2012
PhysProp, 2012; van der Veen
and de Boer, 2012
DATA QUALITY
Reported for tri-m-cresyl phosphate
(CASRN 563-04-2) at a reduced
pressure.
Reported for tricresyl phosphate
(CASRN 1330-78-5) at a reduced
pressure.
Reported for cresyl diphenyl
phosphate (CASRN 26444-49-5).
Reported in a secondary source for
cresyl diphenyl phosphate (CASRN
26444-49-5) purity not stated.
Reported in a secondary source with
limited study details.
Reported in a secondary source for
cresyl diphenyl phosphate (CASRN
26444-49-5); purity not stated.
Reported for tri-o-cresyl phosphate
(CASRN 78-30-8).
Guideline study reported in a
secondary source for cresyl diphenyl
phosphate (CASRN 26444-49-5);
purity of test substance not indicated.
Reported in a secondary source at an
elevated temperature.
Nonguideline study reported for a
mixture of isomers; purity not stated.
Reported in a secondary source for
cresyl diphenyl phosphate (CASRN
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Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT

Log Kow
DATA

0.15 (Measured)
0.1 (Measured)
at 25 °C
2.4 (Measured)
Test method OECD TG 105; at 25 °C
2.6 (Measured)
Reported as 0.0026 g/L at 25 °C
5.11
(Measured)
5.9
(Measured)
4.51
(Measured)
^+
3.7
Test method OECD TG 1 17; at 25°C
(Measured)
5.3
monocresyl diphenyl phosphate;
5.8
for dicresyl phenyl phosphate;
REFERENCE

PhysProp, 2012
HSDB, 2013d
OECD-SIDS, 2002
^^^\ T
OECD-SIDS, 2002; HSDB,
2013a
Saeger et al., 1979 (as cited in
PhysProp, 2012; HSDB, 2013d);
van der Veen and de Boer, 2012
HSDB, 20 13d; Great Lakes
Chemical Corporation, 2001
Saeger et al., 1979 (as cited in
PhysProp, 2012; HSDB, 2013a);
van der Veen and de Boer, 2012
OECD-SIDS, 2002
EPIv4.11
DATA QUALITY
26444-49-5); purity not stated.
Reported for bis(methylphenyl)
phenyl phosphate (CASRN 26446-
73-1).
Reported in a secondary source;
purity and test method not stated.
Guideline study reported in a
secondary source for cresyl diphenyl
phosphate (CASRN 26444-49-5).
Purity of test substance not indicated.
Reported for cresyl diphenyl
phosphate (CASRN 26444-49-5); test
method and purity of substance not
indicated.
Nonguideline study on a mixture of
isomers, purity not stated.
Reported in a secondary source;
purity and test method not stated.
Reported in a secondary source for
cresyl diphenyl phosphate (CASRN
26444-49-5) for the commercial
product mixture Santicizer 140.
Guideline study reported in a
secondary source for cresyl diphenyl
phosphate (CASRN 26444-49-5);
purity of test substance not indicated.
Estimated using representative
structures indicated in the SMILES
section for methylated phenyl
phosphate with one, two and three
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Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT

Flammability (Flash Point)
Explosivity
Pyrolysis
pH
pKa
DATA
6.3
fortricresyl phosphate (Estimated)
Flash point: 212°C (Measured)
Flash point: 232°C (Measured)
Auto flammability: 607°C (Measured)
Flash point: 225 °C closed cup (Measured)
Flash point: 242°C open cup (Measured)
Flash point: 240°C open cup (Measured)
Not expected to form explosive mixtures
with air (Estimated)

Not applicable (Estimated)
Not applicable (Estimated)
REFERENCE

van der Veen and de Boer, 2012
van der Veen and de Boer, 2012
Great Lakes Chemical
Corporation, 200 1
Great Lakes Chemical
Corporation, 200 1
OECD-SIDS, 2002
OECD-SIDS, 2002
Professional judgment

Professional judgment
Professional judgment
DATA QUALITY
methyl substituent groups
respectively.
Reported in a secondary source for
cresyl diphenyl phosphate (CASRN
26444-49-5) with limited details.
Reported in a secondary source with
limited details.
Reported fortricresyl phosphate.
Reported fortricresyl phosphate.
Reported for cresyl diphenyl
phosphate (CASRN 26444-49-5).
Reported for cresyl diphenyl
phosphate (CASRN 26444-49-5).
No experimental data located; based
on its use as a flame retardant.
No data located.
Does not contain functional groups
that are expected to ionize under
environmental conditions.
Does not contain functional groups
that are expected to ionize under
environmental conditions.
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                                                          JUNE 2014 DRAFT REPORT
                                                       Tricresyl phosphate CASRN 1330-78-5
          PROPERTY/ENDPOINT
                                             DATA
                                              REFERENCE
                                      DATA QUALITY
                                                           HUMAN HEALTH EFFECTS
Toxicokinetics
                             Available information indicates that all three isomers of tricresyl phosphate are well absorbed following oral
                             and dermal exposure. TCP is widely distributed in tissues with highest concentrations in adipose tissue,
                             liver, kidneys, intestine, and stomach. Tri-p-cresyl metabolites were identified in blood, urine, feces, and
                             tissues of the rats up to 72 hours following oral administration. Oxidation that occurred in the liver and
                             hydrolysis in the intestine resulted in urinary metabolites that included hydroxybenzoic acid, di-p-cresyl
                             phosphate, and p-cresyl p-carboxyphenyl phosphate. Major metabolites found in the bile were dip-cresyl
                             phosphate, p-cresyl p-carboxyphenyl phosphate, and the oxidized triesters di-p-cresyl p-carboxyphenyl
                             phosphate and p-cresyl di-p-carboxyphenyl phosphate. The main fecal compound was the parent compound
                             (tri-p-cresyl phosphate). Elimination occurs through urine, feces and expiration. No information was located
                             regarding absorption, distribution, or excretion of inhaled tricresyl phosphate.
Dermal Absorption in vitro
                                                                                                 No data located.
Absorption,
Distribution,
Metabolism &
Excretion
Oral, Dermal or Inhaled
Available information indicates that all
three isomers of tricresyl phosphate were
well absorbed following oral
administration to rats. Dermal application
of radiolabeled (14C)-tri-o-cresyl
phosphate to cats resulted in 28% and 20%
of the applied radioactivity being
recovered in urine  and feces, respectively,
during 10 days post application; it was
stated that based on similarity of structure
and physical properties, other isomeric
tricresyl phosphate esters would likely
also be absorbed through the skin.
Following gavage  administration of
radiolabeled (14C)-tri-p-cresyl phosphate
to rats, radioactivity was widely
distributed in the tissues at 24 hours with
highest concentrations in adipose tissue,
liver, kidneys, intestine, and stomach. At
72 hours, total internal radioactivity was
only 25% that observed at 24 hours.
Kurebayashi et al., 1985; NTP,
1994
Study details reported in reliable data
sources; Toxicokinetic data for
tricresyl phosphate (CASRN 1330-
78-5) mainly include results for the
tri-ortho isomer (CASRN 78-30-8)
and tri-para isomer (CASRN 78-32-
0), although limited information is
also available for the tri-meta isomer
(CASRN 563-04-2).
                                                                      7-435

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   JUNE 2014 DRAFT REPORT
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT



























































Other
DATA
Parent compound and p-cresyl p-
carboxyphenyl phosphate (a metabolite)
were present in liver at 24 hours post
dosing. Parent compound was also
detected in adipose tissue at 24 and 72
hours post dosing and at trace amounts in
the kidney at 72 hours post dosing. Tri-p-
cresyl metabolites were identified in
blood, urine, feces, and tissues of the rats
up to 72 hours following oral
administration; oxidation occurred in the
liver and hydrolysis in the intestine,
resulting in urinary metabolites that
included p-hydroxybenzoic acid, di-p-
cresyl phosphate, and p-cresyl p-
carboxyphenyl phosphate. Major
metabolites found in the bile were di-p-
cresyl phosphate, p-cresyl p-
carboxyphenyl phosphate, and the
oxidized triesters di-p-cresyl p-
carboxyphenyl phosphate and p-cresyl di-
p-carboxyphenyl phosphate. The main
fecal compound was the parent compound
(tri -p-cresyl phosphate). For 3 days post
dosing, expiratory excretion of 14CO2
amounted to 18% of the total radioactivity.
No information was located regarding
absorption, distribution, or excretion of
inhaled tricresyl phosphate.

REFERENCE





^^^



^^^N. T







*












DATA QUALITY





























No data located.
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JUNE 2014 DRAFT REPORT
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
Acute Mammalian Toxicity
Acute Lethality
Oral
DATA
REFERENCE
DATA QUALITY
MODERATE: Based on an oral LD50 of 1,160 mg/kg in rats exposed to tri-o-cresyl phosphate (CASRN 78-
30-8). Acute toxicity values for the dermal and inhalation routes of exposure indicate a LOW hazard
concern.
Rat oral LD50 =1,160 mg/kg bw
Rabbit oral LD50 >3,000 mg/kg bw
Rabbit oral LD50 >3,000 mg/kg bw
Mouse oral LD50 = 3,900 mg/kg bw
\
Rat oral LD50 >4,640 mg/kg/bw
Rat oral LD50 = 5,190 mg/kg bw
J
Rat oral LD50 = 6,400 mg/kg bw
Rat oral LD50 = 8,400 mg/kg bw
WHO, 1990
^^^
WHO, 1990
^^^\ T
WHO, 1990
WHO, 1990
WHO, 1990
WHO, 1990
OECD-SIDS, 2002
Johannsen et al., 1977
Limited study details reported in a
secondary source; test substance: Tri-
o-cresyl phosphate (CASRN 78-30-
8).
Limited study details reported in a
secondary source; test substance: Tri-
p-cresyl phosphate (CASRN 78-32-
0).
Limited study details reported in a
secondary source; test substance: Tri-
m-cresyl phosphate (CASRN 563-04-
2).
Limited study details reported in a
secondary source; test substance:
Tricresyl phosphate (mixed isomers);
CASRN 1330-78-5.
Limited study details reported in a
secondary source; Test substance:
Tricresyl phosphate (mixed isomers);
CASRN 1330-78-5).
Limited study details reported in a
secondary source; Test substance:
tricresyl phosphate (mixed isomers);
CASRN 1330-78-5.
Limited study details reported in a
secondary source; test substance:
Diphenyl cresyl phosphate (CASRN
26444-49-5).
Limited study details reported in a
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                                                JUNE 2014 DRAFT REPORT
                                            Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
               DATA
        REFERENCE
        DATA QUALITY
     Dermal
     Inhalation
                                  Single gavage dose (in corn oil) followed
                                  by 14-day observation
                                                                   primary source; test substance: Tri-o-
                                                                   cresyl phosphate (CASRN 78-30-8).
                                  Rat oral LD50 = 10,400 mg/kg bw
                                      Johannsen et al., 1977
                             Limited study details reported in a
                             primary source; test substance: Cresyl
                             diphenyl phosphate (CASRN 26444-
                             49-5).
                                  Rat oral LD50 range 15,750-31,320 mg/kg
                                  bw
                                  Single gavage dose; 14-day observation
                                      Great Lakes Chemical
                                      Corporation, 2001; EPA, 2010;
                                      ATSDR2012
                             Results summarized in reliable
                             secondary sources; Test substance:
                             Phosphoric acid,
                             tris(methylphenyl)ester (CASRN
                             1330-78-5).
Rabbit dermal LD50 = 3,700 mg/kg bw
24-hour occluded dermal application
followed by rinsing and  14-day
observation
Johannsen et al., 1977
Limited study details reported in a
primary source; test substance: Tri-o-
cresyl phosphate (CASRN 78-30-8).
                                  Dermal LD50 >5,000 and <20,000 mg/kg
                                  Single dermal application followed by 14-
                                  day observation period
                                      Great Lakes Chemical
                                      Corporation, 2001; EPA, 2010;
                                      ATSDR2012
                             Limited study details reported in a
                             secondary sources; Test substance:
                             Phosphoric acid,
                             tris(methylphenyl)ester (CASRN
                             1330-78-5).
                                  Rabbit dermal LD50 >5,000 mg/kg bw
                                  Single 24-hour occluded application
                                  followed by rinsing and 14-day
                                  observation
                                      Johannsen et al., 1977
                             Limited study details reported in a
                             primary source; test substance: Cresyl
                             diphenyl phosphate (CASRN 26444-
                             49-5).
                                  Rabbit dermal LD50 >7,900 mg/kg bw
                                  Single gavage dose (in corn oil) followed
                                  by 14-day observation period
                                      Johannsen et al., 1977
                             Limited study details reported in a
                             primary source; test substance:
                             Tricresyl phosphate (mixed isomers);
                             CASRN 1330-78-5.
Rat 4-hour LC50 >5.2 mg/L
Ten rats/sex exposed to tricresyl
phosphate aerosol at 5.2 mg/L for 4 hours,
observed for 14 days post exposure
Great Lakes Chemical
Corporation, 2001; EPA, 2010
Study considered valid without
restriction by secondary source; test
substance: Tricresyl phosphate
(CASRN 1330-78-5).
                                                           7-438

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Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT


Carcinogenicity

OncoLogic Results
Carcinogenicity (Rat and
Mouse)
Combined Chronic
Toxicity/Carcinogenicity
DATA
No deaths
Rats, mice, guinea pigs; no deaths
Test conditions: 6-hour exposure to 3,530
mg/m3 vapors followed by 14-day
observation period
LC50>3.5mg/L
REFERENCE

ATSDR2012
DATA QUALITY

Limited study details reported in a
reliable secondary source; Test
substance: Phosphoric acid,
tris(methylphenyl)ester (CASRN
1330-78-5).
LOW: Based on no evidence of Carcinogenicity in rats or mice following dietary exposure to a commercial
mixture of tricresyl phosphate for 2-years.


2-Year dietary study in Fischer 344/N rats
(95/sex/concentration)
Test substance concentrations: 0, 75, 150,
300 ppm (approximately 0, 3, 6, and 13
mg/kg bw-day for males and 0, 4, 7, and
15 mg/kg bw-day for females)
Chronic toxicity: NOAEL =13 mg/kg bw-
day (males); 4 mg/kg bw-day for females
LOAEL = 26 mg/kg bw-day (males) and 7
mg/kg bw-day (females) for cytoplasmic
vacuolization of adrenal cortex
No evidence of carcinogenic activity
2-Year dietary study in B6C3F1 mice
(95/sex/concentration)
Test substance concentrations: 0, 60, 125,
250 ppm (approximately 0, 7, 13, and 27
mg/kg bw-day for males and 0, 8, 18, and
37 mg/kg bw-day for females)
chronic toxicity NOAEL =18 mg/kg bw-
day for females, not established for males


NTP, 1994
NTP, 1994
No data located.
No data located.
Study details reported in a reliable
primary source; test substance:
Tricresyl phosphate (CASRN 1330-
78-5) as a commercial product
comprised of 18% dicresyl phosphate
esters (unconfirmed isomeric
composition) and 79% tricresyl
phosphate esters (21% confirmed as
tri-m-cresyl phosphate, 4% as tri-p-
cresyl phosphate, and no detectable
tri-o-cresyl phosphate [<0.1%]).
Study details reported in a reliable
primary source; test substance:
Tricresyl phosphate (CASRN 1330-
78-5) as a commercial product
comprised of 18% dicresyl phosphate
esters (unconfirmed isomeric
composition) and 79% tricresyl
phosphate esters (21% confirmed as
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JUNE 2014 DRAFT REPORT
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT


Other
Genotoxicity

Gene Mutation in vitro
Gene Mutation in vivo
DATA
LOAEL: 7 mg/kg bw-day (males) and 37
mg/kg bw-day (females) for ceroid
pigmentation of adrenal cortex
No evidence of carcinogenic activity

REFERENCE


DATA QUALITY
tri-m-cresyl phosphate, 4% as tri-p-
cresyl phosphate, and no detectable
tri-o-cresyl phosphate [<0.1%]).
No data located.
LOW: Based on negative results for gene mutations in bacteria after treatment with mixed isomers of cresyl
diphenyl phosphate or a commercial formulation of tricresyl phosphate and negative results for
chromosomal aberrations in CHO cells in vitro after treatment with tricresyl phosphate as a commercial
formulation. Negative results were also reported in a micronucleus test in Crj:BDFl mice treated with
commercial diphenyl cresyl phosphate by gavage.
Salmonella typhimurium strains TA98,
TA100, TA1535, TA1537 treated with or
without metabolic activation
Test substance concentrations: 100-10,000
micrograms/plate
Negative- test substance not mutagenic
with or without metabolic activation
Salmonella typhimurium strains TA98,
TA100, TA1535, TA1537 treated with or
without metabolic activation
Test substance concentrations: 100-10,000
micrograms/plate
Negative; test substance not mutagenic
with or without metabolic activation
J

Zeigeretal., 1987
NTP, 1994

Study details reported in a reliable
primary source; test substance: Cresyl
diphenyl phosphate (CASRN 26444-
49-5; mixed isomers).
Study details reported in a reliable
primary source; test substance:
Tricresyl phosphate (CASRN 1330-
78-5) as a commercial product
comprised of 18% dicresyl phosphate
esters (unconfirmed isomeric
composition) and 79% tricresyl
phosphate esters (21% confirmed as
tri-m-cresyl phosphate, 4% as tri-p-
cresyl phosphate, and no detectable
tri-o-cresyl phosphate [<0.1%]).
No data located.
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                                                JUNE 2014 DRAFT REPORT
                                            Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
                DATA
        REFERENCE
        DATA QUALITY
     Chromosomal Aberrations in
     vitro
CHO cells treated with or without
metabolic activation
Test substance concentrations: 50-5,000
micrograms/mL
Negative; test substance did not cause
chromosomal aberrations
NTP, 1994
                                  CHO cells treated with or without
                                  metabolic activation
                                  Test substance concentrations: 0.05-16
                                  micrograms/mL
                                  Negative; test substance did not cause
                                  sister chromatid exchanges
                                      NTP, 1994
     Chromosomal Aberrations in
     vivo
     DNA Damage and Repair
     Other
Micronucleus test in Crj:BDFl mice
(5/sex) treated by single gavage
Test substance concentrations: 0, 312.5,
625, 1250 mg/kg bw (in olive oil)
Negative- test substance did not cause
micronucleated polychromatic
erythrocytes in bone marrow
OECD-SIDS, 2002
Study details reported in a reliable
primary source; test substance:
Tricresyl phosphate (CASRN 1330-
78-5) as a commercial product
comprised of 18% dicresyl phosphate
esters (unconfirmed isomeric
composition) and 79% tricresyl
phosphate esters (21% confirmed as
tri-m-cresyl phosphate, 4% as tri-p-
cresyl phosphate, and no detectable
tri-o-cresyl phosphate [<0.1%]).
                             Study details reported in a reliable
                             primary source; test substance:
                             Tricresyl phosphate (CASRN 1330-
                             78-5) as a commercial product
                             comprised of 18% dicresyl phosphate
                             esters (unconfirmed isomeric
                             composition) and 79% tricresyl
                             phosphate esters (21% confirmed as
                             tri-m-cresyl phosphate, 4% as tri-p-
                             cresyl phosphate, and no detectable
                             tri-o-cresyl phosphate [<0.1%]).
                                                                   No data located.
                                                                   No data located.
Study details reported in a secondary
source; conducted according to
OECD Test Guideline 474; test
substance: Commercial diphenyl
cresyl phosphate (CASRN 26444-49-
5; purity 41.
                                                            7-441

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                                                         JUNE 2014 DRAFT REPORT
                                                      Tricresyl phosphate CASRN 1330-78-5
          PROPERTY/ENDPOINT
               DATA
        REFERENCE
        DATA QUALITY
Reproductive Effects
HIGH: Based on a LOAEL of 7 mg/kg-day for ovarian interstitial cell hyperplasia (NOAEL = 4 mg/kg-day)
in female rats following a 2-year dietary exposure to tricresyl phosphate as a commercial mixture. A 13-
week oral (gavage) exposure to the same tricresyl phosphate mixture resulted in ovarian interstitial cell
vacuolization in both rats and mice at a dose of 50 mg/kg-day. Thirteen weeks of dietary exposure to the
tricresyl phosphate commercial mixture caused an increased incidence of interstitial cell hypertrophy in rats
at 55 mg/kg-day, and ovarian interstitial cell vacuolization in mice at 530 mg/kg-day.
Decreased sperm motility was reported in Fl mice that consumed a commercial tricresyl phosphate mixture
from the diet at an estimated dose of 62.5 mg/kg-day and whose parents had been exposed at the same
estimated dose during mating, gestation, and lactation in a continuous breeding dietary study; cross-over
matings at an estimated dose of 250 mg/kg-day revealed decreased numbers of live pups per litter from
matings of treated females to control males and treated males to control females. In a 1-generation study of
rats, abnormal sperm morphology was also noted following gavage dosing of commercial tricresyl phosphate
at 100 mg/kg-day).
Decreased fertility was reported in rats following gavage administration of a commercial diphenyl cresyl
phosphate mixture at 300 mg/kg-day (NOAEL = 60 mg/kg-day) during  premating, mating, gestation, and
parturition. Decreased testicular and epididymal weights and increased ovarian weights were observed in
rats administered a hydraulic fluid (tricresyl phosphate being the major component) at 400 mg/kg-day from
7 days prior to breeding and throughout 63 days of continuous breeding and 28 days post breeding.
               Reproduction/Developmental
               Toxicity Screen
               Combined Repeated Dose with
               Reproduction/ Developmental
               Toxicity Screen
               Reproduction and Fertility
               Effects
Continuous breeding protocol using
dietary exposure of CD-I mice (40
breeding pairs in control group, 20
breeding pairs in treatment group)
Test substance concentrations: 0, 0.05,
0.1, and 0.2% tricresyl phosphate by
weight (continuous breeding phase doses
estimated to have been 0, 62.5, 124, and
250 mg/kg-day, respectively); control and
0.2% dose level used for cross-over
                                                                  No data located.
                                                                  No data located.
Chapinetal., 1988
Well-designed study that followed a
continuous breeding protocol; test
substance: Tricresyl phosphate
(CASRN 1330-78-5); composed of
74.9% tricresyl phosphate (consisting
of mixed isomers and 20.6% pure m-
cresyl, 3.9% pure para-cresyl, and
<0.1% pure o-cresyl isomers), with
the remainder composed of dicresyl
phenyl and di- and tricresylxylyl
                                                                     7-442

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JUNE 2014 DRAFT REPORT
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT


































































DATA
mating phase
Test substance treatment period:
Continuous breeding phase included 98
days (7 days prior to breeding); cross-over
mating phase included 7 days prior to
breeding; an additional 7 days of
cohabitation treatment (males and
females) and throughout gestation
(females); last Fl litter of mice continued
on treatment of their parents until sexual
maturity (postpartum day 74), throughout
a 1-week cohabitation period with mice of
the same dose group, and necropsied 3
weeks later for assessment of litters and
treatment-related gross and
histopathological effects
Continuous breeding phase results:
Significantly decreased fertility at 124 and
250 mg/kg-day; decreased sperm motility
in Fl males at 62.5 mg/kg-day
Cross-over mating phase results:
Significantly decreased numbers of live
pups per litter in treated male X control
female and treated female X control male
groups; significantly decreased proportion
of pups born alive in control male X
treated female group

NOAEL: Not established
LOAEL: 62.5 mg/kg-day (based on
decreased sperm motility in Fl males)
One -generation oral (gavage) reproductive
toxicity study in Long -Evans rats (12
REFERENCE





^^^



^^^N. T







*













Carlton et al., 1987

DATA QUALITY
phosphates;
Tricresyl phosphate doses were
estimated for the FO parental mice;
the LOAEL of 62.5 mg/kg bw-day
for decreased sperm motility in Fl
males assumes that the dose to the
growing and mating Fl males was the
same as that of their parents. EPAHC,
2010 reported a LOAEL of 62.5
mg/kg bw-day for significantly
decreased number of litters/pair in the
continuous breeding phase; however,
the study report noted significantly
"increased" number of litters/pair
(5.06 versus 4.87 in controls). The
LOAEL for the continuous breeding
phase should be the mid-dose level
(124 mg/kg bw-day) based on
significantly increased numbers of
dead pups in the 4th and 5th litters
and decreased live pup body weight;
a NOAEL of 62.5 mg/kg bw-day was
identified for the continuous breeding
phase of the study.







Study details reported in a primary
source; test substance: Tricresyl
         7-443

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                                               JUNE 2014 DRAFT REPORT
                                            Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  males/dose, 24 females/dose)
                                  Test substance doses (in corn oil): 0, 100,
                                  200 mg/kg/day for males; 0, 200, 400
                                  mg/kg-day for females
                                  Dosing period: 56 days prior to mating
                                  and during 10 days of mating for males;
                                  14 days prior to mating and through 10
                                  days of mating, gestation, and lactation for
                                  females
                                  Significantly increased percent abnormal
                                  sperm in 100 and 200 mg/kg-day males;
                                  decreased sperm concentration, motility
                                  and progressive movement and minimal-
                                  to-mild significantly increased
                                  histopathologic lesions in testes and
                                  epididymides of 200 mg/kg-day males;
                                  dose-related severely decreased litter size
                                  in both groups of dosed females

                                  NOAEL: Not established
                                  LOAEL: lOOmg/kgbw-day based on
                                  abnormal sperm morphology
                                                   phosphate (CASRN 1330-78-5);
                                                   composition: <9% tri-o-cresyl
                                                   phosphate and remainder a mixture of
                                                   tri-p-, and tri-m-cresyl phosphate and
                                                   other tri-cresyl isomers.
                                  Repeated-dose gavage study of male and
                                  female Crj:CD (SD) rats (10/group)
                                  administered commercial diphenyl cresyl
                                  phosphate (CASRN 26444-49-5; purity
                                  41.9%) for approximately 45 consecutive
                                  days (14 days premating, mating,
                                  gestation, until postpartum day 3).
                                  Dose levels: 0, 12, 60, 300 mg/kg bw-day

                                  NOAEL: 60 mg/kg bw-day
                                  LOAEL: 300 mg/kg bw-day for decreased
                      OECD, 1998; OECD-SIDS,
                      2002
                     Study details reported in a secondary
                     source; conducted according to
                     OECD guidelines for a Combined
                     Repeated Dose and
                     Reproductive/Developmental
                     Screening Toxicity Test; test
                     substance: commercial diphenyl
                     cresyl phosphate (CASRN 26444-49-
                     5; purity 41.
                                                           7-444

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                                                 JUNE 2014 DRAFT REPORT
                                             Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   fertility
                                   Modified continuous breeding protocol
                                   using gavage treatment in F344 rats (40
                                   breeding pairs in control group, 20
                                   breeding pairs in treatment group)
                                   Test substance concentrations: 0, 400
                                   mg/kg-day (served as positive control for
                                   a butylated triphenyl phosphate-containing
                                   hydraulic fluid)
                                   Treatment period: 98 days including 7
                                   days prior to breeding period, 63-day
                                   breeding period, 28-day postbreeding
                                   period; a second phase (cross-over mating)
                                   included a 28-day treatment period
                                   Severely decreased numbers of test
                                   substance-treated breeding pairs delivering
                                   litters (9/20, 0/20, and 0/20 pairs
                                   delivering litters  1, 2, and 3, respectively,
                                   compared to 40/40, 39/40, and 28/40
                                   control pairs) Cross-over mating trials
                                   resulted in 0% fertility among the test-
                                   substance-treated males, but no apparent
                                   effect on test substance-treated females
                                   Test substance-treated rats exhibited
                                   significantly decreased testicular and
                                   epididymal weights and increased ovarian
                                   weights

                                   NOAEL: Not established
                                   LOAEL: 400 mg/kg bw-day (only dose
                                   tested) based on severely decreased
                                   numbers of breeding pairs delivering
                                   litters, decreased testicular and epididymal
                       Latendresse et al., 1994
                      Study details reported in a primary
                      source; only one dose tested; test
                      substance: A mixture of compounds
                      in a hydraulic fluid of which tricresyl
                      phosphate (CASRN 1330-78-5) was a
                      major component; the test substance
                      was composed of mostly p- and o-
                      tricresyl phosphate isomers (62% by
                      weight), cresyl-xylyl (18% by
                      weight), and cresyl-ethyl-phenyl
                      phosphates (18% by weight).
                                                             7-445

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                                               JUNE 2014 DRAFT REPORT
                                            Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
               DATA
        REFERENCE
        DATA QUALITY
     Other
                                  weights, increased ovarian weight
2-Year dietary study in Fischer 344/N rats
(95/sex/concentration)
Test substance concentrations: 0, 75, 150,
300 ppm (approximately 0, 3, 6, and 13
mg/kg bw-day for males and 0, 4, 7, and
15 mg/kg bw-day for females)

NOAEL: 4 mg/kg bw-day (females)
LOAEL: 7 mg/kg bw-day for ovarian
interstitial cell hyperplasia
NTP, 1994
                                  13-Week gavage study in B6C3F1 mice
                                  (10/sex/dose)
                                  Test substance concentrations: 0, 50, 100,
                                  200, 400, 800 mg/kg bw-day (in corn oil)
                                  Dosing frequency: Ix/d, 5d/w

                                  NOAEL: not established
                                  LOAEL: 50 mg/kg bw-day for ovarian
                                  interstitial cell vacuolization
                                     NTP, 1994
                                  13-Week gavage study in Fischer 344/N
                                  rats (10/sex/dose)
                                  Test substance concentrations: 0, 50, 100,
                                  200, 400, 800 mg/kg bw-d (in corn oil)
                                  Dosing frequency: Ix/d, 5d/w

                                  NOAEL: not established
                                  LOAEL: 50 mg/kg bw-day for ovarian
                                  interstitial cell vacuolization
                                     NTP, 1994
                                  13-Week dietary study in Fischer 344/N
                                  rats (10/sex/dose)
                                     NTP, 1994
Reliable NTP study; test substance:
Tricresyl phosphate (CASRN 1330-
78-5) as a commercial product
comprised of 18% dicresyl phosphate
esters (unconfirmed isomeric
composition) and 79% tricresyl
phosphate esters (21% confirmed as
tri-m-cresyl phosphate, 4% as tri-p-
cresyl phosphate, and no detectable
tri-o-cresyl phosphate [<0.1%]).
                             Reliable NTP study; test substance:
                             Tricresyl phosphate (CASRN 1330-
                             78-5) as a commercial product
                             comprised of 18% dicresyl phosphate
                             esters (unconfirmed isomeric
                             composition) and 79% tricresyl
                             phosphate esters (21% confirmed as
                             tri-m-cresyl phosphate, 4% as tri-p-
                             cresyl phosphate, and no detectable
                             tri-o-cresyl phosphate [<0.1%]).
                             Reliable NTP study; test substance:
                             Tricresyl phosphate (CASRN 1330-
                             78-5) as a commercial product
                             comprised of 18% dicresyl phosphate
                             esters (unconfirmed isomeric
                             composition) and 79% tricresyl
                             phosphate esters (21% confirmed as
                             tri-m-cresyl phosphate, 4% as tri-p-
                             cresyl phosphate, and no detectable
                             tri-o-cresyl phosphate [<0.1%]).
                             Reliable NTP study; test substance:
                             Tricresyl phosphate (CASRN 1330-
                                                           7-446

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                                                        JUNE 2014 DRAFT REPORT
                                                     Tricresyl phosphate CASRN 1330-78-5
          PROPERTY/ENDPOINT
               DATA
REFERENCE
DATA QUALITY
                                           Test substance concentrations: 0, 900,
                                           1700, 3300, 6600, 13,000 ppm
                                           (approximately 0, 55, 120, 220, 430, and
                                           750 mg/kg bw-day for males and 0, 65,
                                           120, 230, 430, and 770 mg/kg bw-day for
                                           females)

                                           NOAEL:  not established
                                           LOAEL:  55 mg/kg bw-day for ovarian
                                           interstitial cell hypertrophy
                                                                 78-5) as a commercial product
                                                                 comprised of 18% dicresyl phosphate
                                                                 esters (unconfirmed isomeric
                                                                 composition) and 79% tricresyl
                                                                 phosphate esters (21% confirmed as
                                                                 tri-m-cresyl phosphate, 4% as tri-p-
                                                                 cresyl phosphate, and no detectable
                                                                 tri-o-cresyl phosphate [<0.1%]).
                                           13-Week dietary study in B6C3F1 mice
                                           (10/sex/concentration)
                                           Test substance concentrations: 0, 250,
                                           500, 1,000, 2,100, 4,200 ppm
                                           (approximately 0, 45, 110, 180, 380, and
                                           900 mg/kg bw-day for males and 0, 65,
                                           130, 230, 530, and  1,050 mg/kg bw-day
                                           for females)

                                           NOAEL: 230 mg/kg bw-day
                                           LOAEL: 530 mg/kg bw-day for ovarian
                                           interstitial cell vacuolization
                                     NTP, 1994
                     Reliable NTP study; test substance:
                     Tricresyl phosphate (CASRN 1330-
                     78-5) as a commercial product
                     comprised of 18% dicresyl phosphate
                     esters (unconfirmed isomeric
                     composition) and 79% tricresyl
                     phosphate esters (21% confirmed as
                     tri-m-cresyl phosphate, 4% as tri-p-
                     cresyl phosphate, and no detectable
                     tri-o-cresyl phosphate [<0.1%]).
Developmental Effects
MODERATE: Based on increased numbers of dead Fl pups per litter were reported among CD-I mice
receiving commercial tricresyl phosphate from the diet at an estimated dose of 124 mg/kg-day (NOAEL =
62.5 mg/kg-day) in a continuous breeding protocol. Decreases in litter size and postnatal pup survival were
also reported in a one-generation reproductive toxicity study of rats gavaged at 200 mg/kg-day (lowest dose
tested) during premating and mating (males and females) and gestation and lactation (females).
There were no data located for the developmental neurotoxicity endpoint.
               Reproduction/ Developmental
               Toxicity Screen
               Combined Repeated Dose with
               Reproduction/ Developmental
               Toxicity Screen
                                                                 No data located.
                                                                 No data located.
                                                                    7-447

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                                                 JUNE 2014 DRAFT REPORT
                                             Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
                DATA
        REFERENCE
        DATA QUALITY
     Prenatal Development
Continuous breeding protocol using
dietary exposure of CD-I mice (40
breeding pairs in control group, 20
breeding pairs in treatment group)
Test substance concentrations: 0, 0.05,
0.1, and 0.2% tricresyl phosphate by
weight (continuous breeding phase doses
estimated to have been 0, 62.5, 124, and
250 mg/kg-day, respectively); control and
0.2% dose level used for cross-over
mating phase
Test substance treatment period:
Continuous breeding phase included 98
days (7 days prior to breeding); cross-over
mating phase included 7 days prior to
breeding; an additional 7 days of
cohabitation treatment (males and
females) and throughout gestation
(females); last Fl litter of mice continued
on treatment of their parents until sexual
maturity (postpartum day 74), throughout
a 1-week cohabitation period with mice of
the same dose group, and necropsied 3
weeks later for assessment of litters and
treatment-related gross and
histopathological effects
Continuous breeding phase results:
Significantly decreased fertility at 124 and
250 mg/kg bw-day
Cross-over mating phase results:
Significantly decreased numbers of live
pups per litter in treated male X control
female and treated female  X control male
groups; significantly decreased proportion
Chapinetal., 1988
Well-designed study that followed a
continuous breeding protocol; test
substance: Tricresyl phosphate
(CASRN 1330-78-5); composed of
74.9% tricresyl phosphate (consisting
of mixed isomers and 20.6% pure m-
cresyl, 3.9% pure para-cresyl, and
<0.1% pure o-cresyl isomers), with
the remainder composed of dicresyl
phenyl and di- and tricresylxylyl
phosphates; Tricresyl phosphate
doses were estimated for the FO
parental mice; the LOAEL of 62.5
mg/kg bw-day for decreased sperm
motility in F1 males assumes that the
dose to the growing and mating Fl
males was the same as that of their
parents. EPAHC, 2010 reported a
LOAEL of 62.5 mg/kg bw-day for
significantly decreased number of
litters/pair in the continuous breeding
phase; however, the study report
noted significantly "increased"
number of litters/pair (5.06 versus
4.87 in controls). The LOAEL for the
continuous breeding phase should be
the mid-dose level (124 mg/kg bw-
day) based on significantly increased
numbers of dead pups in the 4th and
5th litters and decreased live pup
body weight; a NOAEL of 62.5
mg/kg bw-day was  identified for the
continuous breeding phase of the
study.
                                                             7-448

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                                                JUNE 2014 DRAFT REPORT
                                             Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   of pups born alive in control male X
                                   treated female group

                                   NOAEL: 62.5 mg/kg bw-day
                                   LOAEL: 124 mg/kg bw-day based on
                                   increased number of dead Fl pups/litter
                                   One-generation oral (gavage) reproductive
                                   toxicity study in Long-Evans rats (12
                                   males/dose, 24 females/dose)
                                   Test substance doses (in corn oil): 0, 100,
                                   200 mg/kg-day for males; 0, 200, 400
                                   mg/kg-day for females
                                   Dosing period: 56 days prior to mating
                                   and during 10 days of mating for males;
                                   14 days prior to mating and through 10
                                   days of mating, gestation, and lactation for
                                   females
                                   Dose-related severely decreased litter size
                                   and decreased postnatal pup viability in
                                   both groups of dosed females

                                   NOAEL: Not established
                                   LOAEL: 200 mg/kg bw-day based on
                                   decreased litter size and postnatal pup
                                   viability (lowest dose tested)
                      Carlton et al., 1987
                      Study details reported in a primary
                      source; test substance: Tricresyl
                      phosphate (CASRN 1330-78-5);
                      composition: <9% tri-o-cresyl
                      phosphate and remainder a mixture of
                      tri-p-, and tri-m-cresyl phosphate and
                      other tri-cresyl isomers.
                                   Modified continuous breeding protocol
                                   using gavage treatment in F344 rats (40
                                   breeding pairs in control group, 20
                                   breeding pairs in treatment group)
                                   Test substance concentrations: 0, 400
                                   mg/kg-day (served as positive control for
                                   a butylated triphenyl phosphate-containing
                                   hydraulic fluid)
                      Latendresse et al., 1994
                      Study details reported in a primary
                      source; only one dose tested; Test
                      substance: A mixture of compounds
                      in a hydraulic fluid of which tricresyl
                      phosphate (CASRN 1330-78-5) was a
                      major component; the test substance
                      was composed of mostly p- and o-
                      tricresyl phosphate isomers (62% by
                                                            7-449

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JUNE 2014 DRAFT REPORT
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT


Postnatal Development
Prenatal and Postnatal
Development
Developmental Neurotoxicity
Other
DATA
Treatment period: 98 days including 7
days prior to breeding period, 63-day
breeding period, 28-day postbreeding
period; a second phase (cross-over mating)
included a 28-day treatment period
Severely decreased numbers of test
substance-treated breeding pairs delivering
litters (9/20, 0/20, and 0/20 pairs
delivering litters 1, 2, and 3, respectively,
compared to 40/40, 39/40, and 28/40
control pairs)
NOAEL: Not established
LOAEL: 400 mg/kg bw-day (only dose
tested) based on reduced number of live
pups/litter


Uncertain concern for developmental
neurotoxicity based on the potential for
Cholinesterase (ChE) inhibition in dams
that may result in alterations of fetal
neurodevelopment (Estimated)

REFERENCE
^^^
^^^N. T


Professional judgment

DATA QUALITY
weight), cresyl-xylyl (18% by
weight), and cresyl-ethyl-phenyl
phosphates (18% by weight).
No data located.
No data located.
Estimated based on a structural alert
for organophosphates for the
neurotoxicity endpoint.
No data located.
         7-450

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                                                         JUNE 2014 DRAFT REPORT
                                                     Tricresyl phosphate CASRN 1330-78-5
          PROPERTY/ENDPOINT
               DATA
        REFERENCE
        DATA QUALITY
Neurotoxicity
MODERATE: Multifocal axonal degeneration was observed in spinal nerve preparations from female mice
administered commercial tricresyl phosphate by gavage once per day, 5 days/week for 13 weeks at 100
mg/kg-day; at a dose level of 200 mg/kg-day, male and female rats exhibited decreased grip strength and
degenerative effects in spinal cord and sciatic nerve preparations. NOAELs of 100 and 50 mg/kg-day were
identified for neurotoxicity of males and females, respectively. Similar effects were reported following a 13-
week dietary study with the same commercial product in mice and rats, albeit at dietary concentrations
resulting in higher estimated oral doses (>750 mg/kg-day for rats and >380 mg/kg-day for mice)
Tri-o-cresyl phosphate and other organophosphorus compounds cause a delayed neuropathy that has been
termed organophosphate-induced  delayed neurotoxicity (OPIDN). Neurological symptoms are typically
delayed by 1-3 weeks after initial exposure and begin to be expressed as ataxia and progressive development
of paralysis of hind limbs; partial recovery may follow. Chickens and cats are particularly sensitive to
organophosphate-induced OPIDN.
Tri-o-cresyl phosphate occurs as a contaminant in commercial tricresyl phosphate mixtures, but usually in
concentrations of <1%.
               Neurotoxicity Screening
               Battery (Adult)
               Other
13-Week gavage study in B6C3F1 mice
(10/sex/dose)
Test substance concentrations: 0, 50, 100,
200, 400, 800 mg/kg bw-day (in corn oil)
Dosing frequency: Ix/d, 5d/w

NOAEL (males):  100 mg/kg bw-day
LOAEL (males): 200 mg/kg bw-day for
decreased fore- and hind limb grip
strength and degeneration in spinal cord
and sciatic nerve

NOAEL (females): 50 mg/kg bw-day
LOAEL (females): 100 mg/kg bw-day for
multifocal axonal degeneration in spinal
cord
NTP, 1994
                                                                  No data located.
Reliable study, although not designed
to comprehensively assess
neurological endpoints; test
substance: Tricresyl phosphate
(CASRN 1330-78-5)  as a commercial
product comprised of 18% dicresyl
phosphate esters (unconfirmed
isomeric composition) and 79%
tricresyl phosphate esters (21%
confirmed as tri-m-cresyl phosphate,
4% as tri-p-cresyl phosphate, and no
detectable tri-o-cresyl phosphate
[<0.1%]). In addition to the identified
LOAEL of 100 mg/kg bw-day for
multifocal axonal degeneration in the
spinal cord of female mice,
significantly decreased grip strength
                                                                    7-451

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                                                JUNE 2014 DRAFT REPORT
                                            Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                                                                                     was observed at doses > 200 mg/kg
                                                                                                     bw-day as well. Degeneration in
                                                                                                     spinal cord and sciatic nerve
                                                                                                     preparations was noted in male and
                                                                                                     female mice at doses > 200 mg/kg
                                                                                                     bw-day.
                                  13-Week dietary study in Fischer 344/N
                                  rats (10/sex/dose)
                                  Test substance concentrations: 0, 900,
                                  1700, 3300, 6600, 13,000 ppm
                                  (approximately 0, 55, 120, 220, 430, and
                                  750 mg/kg bw-day for males and 0, 65,
                                  120, 230, 430, and 770 mg/kg bw-day for
                                  females)

                                  NOAEL (males): 430 mg/kg bw-day
                                  LOAEL (males): 750 mg/kg bw-day for
                                  reduced hind limb grip strength

                                  NOAEL (females): 770 mg/kg bw-day
                                  (highest dose tested)
                                  LOAEL (females): Not established
                      NTP, 1994
                                  13-Week dietary study in B6C3F1 mice
                                  (10/sex/concentration)
                                  Test substance concentrations: 0, 250,
                                  500, 1,000, 2,100, 4,200 ppm
                                  (approximately 0, 45, 110, 180, 380, and
                                  900 mg/kg bw-day for males and 0, 65,
                                  130, 230, 530, and 1,050 mg/kg bw-day
                                  for females)

                                  NOAEL (males): 180 mg/kg bw-day
                                  (males)
                      NTP, 1994
                     Reliable study, although not designed
                     to comprehensively assess
                     neurological endpoints; test
                     substance: Tricresyl phosphate
                     (CASRN 1330-78-5) as a commercial
                     product comprised of 18% dicresyl
                     phosphate esters (unconfirmed
                     isomeric composition) and 79%
                     tricresyl phosphate esters (21%
                     confirmed as tri-m-cresyl phosphate,
                     4% as tri-p-cresyl phosphate, and no
                     detectable tri-o-cresyl phosphate
                     [<0.1%]). Histopathologic
                     evaluations of spinal cord and sciatic
                     nerve preparations revealed no signs
                     of degenerative effects at any dose.
                     Reliable study, although not designed
                     to comprehensively assess
                     neurological endpoints; test
                     substance: Tricresyl phosphate
                     (CASRN 1330-78-5) as a commercial
                     product comprised of 18% dicresyl
                     phosphate esters (unconfirmed
                     isomeric composition) and 79%
                     tricresyl phosphate esters (21%
                     confirmed as tri-m-cresyl phosphate,
                     4% as tri-p-cresyl phosphate, and no
                                                           7-452

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                                                JUNE 2014 DRAFT REPORT
                                             Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   LOAEL (males): 380 mg/kg bw-day for
                                   reduced forelimb grip strength

                                   NOAEL (females): 230 mg/kg bw-day
                                   LOAEL (females): 530 mg/kg bw-day for
                                   reduced fore- and hind limb grip strength
                                                    detectable tri-o-cresyl phosphate
                                                    [<0.1%]). Histopathologic evaluation
                                                    of spinal cord and sciatic nerve
                                                    preparations revealed degenerative
                                                    effects at 530 and 1,050 mg/kg bw-
                                                    day in females and 900 mg/kg bw-
                                                    day in males.
                                   13-Week gavage study in Fischer 344/N
                                   rats (10/sex/dose)
                                   Test substance concentrations: 0, 50, 100,
                                   200, 400, 800 mg/kg bw-day (in corn oil)
                                   Dosing frequency: Ix/d, 5d/w
                                   Neurological endpoints included fore- and
                                   hind limb grip strength and
                                   histopathological evaluations of spinal
                                   cord and sciatic nerve

                                   NOAEL: 800 mg/kg bw-day (highest dose
                                   tested)
                                   LOAEL: Not established
                      NTP, 1994
                      Reliable study, although not designed
                      to comprehensively assess
                      neurological endpoints; test
                      substance: Tricresyl phosphate
                      (CASRN 1330-78-5)  as a commercial
                      product comprised of 18% dicresyl
                      phosphate esters (unconfirmed
                      isomeric composition) and 79%
                      tricresyl phosphate esters (21%
                      confirmed as tri-m-cresyl phosphate,
                      4% as tri-p-cresyl phosphate, and no
                      detectable tri-o-cresyl phosphate
                      [<0.1%]). There were no effects on
                      grip strength or histopathology of
                      spinal cord or sciatic  nerve of treated
                      male rats. Reported decreased hind
                      limb grip strength in female rats at
                      400- and 800 mg/kg bw-day was of
                      small magnitude (12 and 14% less,
                      respectively, than controls).
                      Furthermore, the 800 mg/kg bw-day
                      group of female rats exhibited
                      significantly lower grip strength than
                      the controls (10% less) at
                      examination prior to the initiation of
                      glutaraldehyde treatment. The 400
                                                            7-453

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                                                JUNE 2014 DRAFT REPORT
                                             Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   Tri-o-cresyl phosphate and other
                                   organophosphorus compounds cause a
                                   delayed neuropathy that has been termed
                                   organophosphate-induced delayed
                                   neurotoxicity (OPIDN). Neurological
                                   symptoms are typically delayed by 1 -3
                                   weeks after initial exposure and begin to
                                   be expressed as ataxia and progressive
                                   development of paralysis of hind limbs;
                                   partial recovery may follow. Chickens and
                                   cats are particularly sensitive to
                                   organophosphate-induced OPIDN.
                                   Neuropathologically, degeneration of
                                   spinal cord and peripheral nerve fibers is
                                   observed.
                                   OPIDN has been elicited in rats as well,
                                   but at relatively high repeated oral doses
                                   (>840mg/kgbw-day).
                                   Tri-o-cresyl phosphate occurs as a
                                   contaminant in commercial tricresyl
                                   phosphate mixtures, but usually in
                                   concentrations of <1%.
                                   Ingestion of preparations contaminated by
                                   TOCP by humans may be followed
                      WHO, 1990
                                                                                                      mg/kg bw-day group of female rats
                                                                                                      also exhibited 10% less hind limb
                                                                                                      grip strength than controls (not
                                                                                                      statistically significant) prior to the
                                                                                                      initiation of glutaraldehyde treatment.
                                                                                                      Therefore, the 800 mg/kg bw-day
                                                                                                      dose level should be considered a
                                                                                                      NOAEL for neurological effects in
                                                                                                      the female rats as well.
                      Summary of Tri-o-cresyl phosphate
                      neurological effects.
                                                            7-454

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                                                JUNE 2014 DRAFT REPORT
                                             Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   polyneuropathy. Delayed neurotoxic
                                   symptoms include pain and paraesthesia in
                                   the lower extremities. Muscle weakness
                                   can quickly progress to paralysis of the
                                   lower extremities and may or may not
                                   involve the upper extremities. Axonal
                                   degeneration has been reported following
                                   histopathological examination. There is
                                   variation between individuals both in
                                   response to TCP and recovery from the
                                   toxic effects of TOCP. Severe symptoms
                                   have been reported following the ingestion
                                   of 0.15 g of TCP, while other individuals
                                   failed to show any toxic effect after
                                   ingesting 1-2 g. Some patients show
                                   complete recovery while others do not.
                                   2-Year dietary study in B6C3F1 mice
                                   (95/sex/concentration)
                                   Test substance concentrations: 0, 60, 125,
                                   250 ppm (approximately 0, 7, 13, and 27
                                   mg/kg bw-day for males and 0, 8, 18, and
                                   37 mg/kg bw-day for females)
                                   Neurological endpoints assessed included
                                   grip strength testing and histopathological
                                   evaluation of spinal cord and sciatic
                                   preparations

                                   NOAEL (males): 27 mg/kg bw-day
                                   (highest dose tested)
                                   LOAEL (males): Not established

                                   NOAEL (females): 37 mg/kg bw-day
                                   (highest dose tested)
                      NTP, 1994
                      Reliable study, although not designed
                      to comprehensively assess
                      neurological endpoints; test
                      substance: Tricresyl phosphate
                      (CASRN 1330.78-5) as a commercial
                      product comprised of 18% dicresyl
                      phosphate esters (unconfirmed
                      isomeric composition) and 79%
                      tricresyl phosphate esters (21%
                      confirmed as tri-m-cresyl phosphate,
                      4% as tri-p-cresyl phosphate, and no
                      detectable tri-o-cresyl phosphate
                      [<0.1%]). Neurobehavioral
                      evaluations were performed on 15
                      mice/sex from each exposure group.
                      At 3-month interim evaluation,
                      significantly decreased hind limb grip
                                                            7-455

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                                                JUNE 2014 DRAFT REPORT
                                             Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   LOAEL (females): Not established
                                   2-Year dietary study in Fischer 344/N rats
                                   (95/sex/concentration)
                                   Test substance concentrations: 0, 75, 150,
                                   300 ppm (approximately 0, 3, 6, and 13
                                   mg/kg bw-day for males and 0, 4, 7, and
                                   15 mg/kg bw-day for females)
                                   Neurological endpoints assessed included
                                   grip strength testing and histopathological
                      NTP, 1994
                                                    strength was observed in female mice
                                                    of the highest treatment level (250
                                                    ppm; ca. 7% lower than controls);
                                                    there was no significant change in
                                                    grip strength at 9- and 15-month
                                                    interim evaluations. There was no
                                                    histopathological evidence of
                                                    treatment related effects on sciatic
                                                    nerve or spinal cord. Note: Grip
                                                    strength was not decreased in male or
                                                    female mice in 13-week gavage and
                                                    dietary studies at much higher dose
                                                    levels; the 13-week studies were
                                                    performed using the same strains of
                                                    mice, the same formulation of
                                                    glutaraldehyde, and the same
                                                    laboratory as the 2-year dietary study.
                                                    These results suggest that the finding
                                                                  OO               O
                                                    of decreased hind limb grip strength
                                                    at the 3-month interim evaluation in
                                                    the  2-year dietary study are spurious.
                                                    In that case, the 2-year dietary study
                                                    identified NOAELs of 27 and 37
                                                    mg/kg-day for neurological effects in
                                                    male and female mice, respectively.
                      Reliable study, although not designed
                      to comprehensively assess
                      neurological endpoints; test
                      substance: Tricresyl phosphate
                      (CASRN 1330-78-5) as a commercial
                      product comprised of 18% dicresyl
                      phosphate esters (unconfirmed
                      isomeric composition) and 79%
                                                            7-456

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                                                JUNE 2014 DRAFT REPORT
                                             Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   evaluation of spinal cord and sciatic
                                   preparations

                                   NOAEL (males): 13 mg/kg bw-day
                                   (highest dose tested)
                                   LOAEL (males): Not established

                                   NOAEL (females):  15 mg/kg bw-day
                                   (highest dose tested)
                                   LOAEL (females): Not established
                                                    tricresyl phosphate esters (21%
                                                    confirmed as tri-m-cresyl phosphate,
                                                    4% as tri-p-cresyl phosphate, and no
                                                    detectable tri-o-cresyl phosphate
                                                    [<0.1%]). Neurobehavioral
                                                    evaluations were performed on 15
                                                    rats/sex from each exposure group. At
                                                    3-month interim evaluation,
                                                    significantly decreased hind limb grip
                                                    strength was reported for male rats at
                                                    the two highest treatment levels (300
                                                    and 600 ppm; ca.  11% lower than
                                                    controls) and female rats at the
                                                    highest treatment level (600 ppm; ca.
                                                    7% lower than controls); there was no
                                                    significant treatment-related effect on
                                                    grip strength at 9- and 15-month
                                                    interim evaluations. There was no
                                                    histopathological evidence of
                                                    treatment-related effects on spinal
                                                    cord or sciatic nerve. Note: Grip
                                                    strength was not decreased in male or
                                                    female rats in 13-week gavage and
                                                    dietary studies at much higher dose
                                                    levels; the 13-week studies were
                                                    performed using the same strains of
                                                    rats, the same formulation of
                                                    glutaraldehyde, and the  same
                                                    laboratory as the 2-year dietary study.
                                                    These results suggest that the finding
                                                    of decreased hind limb grip strength
                                                    at the 3-month interim evaluation in
                                                    the 2-year dietary study are spurious.
                                                    In that case, the 2-year dietary study
                                                            7-457

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                                                         JUNE 2014 DRAFT REPORT
                                                      Tricresyl phosphate CASRN 1330-78-5
          PROPERTY/ENDPOINT
               DATA
REFERENCE
DATA QUALITY
                                                                                                               identified NOAELs of 13 and 15
                                                                                                               mg/kg-day for neurological effects in
                                                                                                               male and female rats, respectively.
                                            Potential for neurotoxic effects based on a
                                            structural alert for organophosphates
                                            (Estimated by analogy)
                                     Professional judgment
                     Estimated based on a structural alert
                     for organophosphates and
                     professional judgment.
Repeated Dose Effects
HIGH: In addition to the neurotoxicity effects described above, increased incidence of liver lesions was
reported in a 2-year dietary study in mice fed commercial tricresyl phosphate at a dose of 13 mg/kg bw-day
(NOAEL = 7 mg/kg bw-day); cytoplasmic vacuolization of the adrenal cortex and ovarian interstitial cell
hypertrophy were noted at 26 mg/kg bw-day (NOAEL = 13 mg/kg bw-day). Similar effects were reported
following a 13-week dietary study with the same commercial product in mice and rats at 50 mg/kg bw-day
(lowest dose tested). Furthermore, TCP is immunotoxic in the range of high hazard (see immunotoxicity
section).
                                            2-Year dietary study in B6C3F1 mice
                                            (95/sex/concentration)
                                            Test substance concentrations: 0, 60, 125,
                                            250 ppm (approximately 0, 7, 13, and 27
                                            mg/kg bw-day for males and 0, 8, 18, and
                                            37 mg/kg bw-day for females)

                                            NOAEL:  7 mg/kg bw-day (males); 37
                                            mg/kg bw-day (females; highest dose
                                            tested)
                                            LOAEL:  13 mg/kg bw-day for males
                                            based on increased incidences of liver
                                            lesions (ceroid pigmentation, clear cell
                                            foci, fatty change)
                                     NTP, 1994
                                            2-Year dietary study in Fischer 344/N rats
                                            (95/sex/concentration)
                                            Test substance concentrations: 0, 75,  150,
                                            300 ppm (approximately 0, 3, 6, and 13
                                            mg/kg bw-day for males and 0, 4, 7, and
                                            15 mg/kg bw-day for females)
                                     NTP, 1994
                      Study details reported in a primary
                      source; test substance: Tricresyl
                      phosphate (CASRN 1330.78-5) as a
                      commercial product comprised of
                      18% dicresyl phosphate esters
                      (unconfirmed isomeric composition)
                      and 79% tricresyl phosphate esters
                      (21% confirmed as tri-m-cresyl
                      phosphate, 4% as tri-p-cresyl
                      phosphate, and no detectable tri-o-
                      cresyl phosphate [<0.1%]).
                      Study details reported in a primary
                      source; test substance: Tricresyl
                      phosphate (CASRN 1330-78-5) as a
                      commercial product comprised of
                      18% dicresyl phosphate esters
                      (unconfirmed isomeric composition)
                                                                     7-458

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                                               JUNE 2014 DRAFT REPORT
                                            Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  NOAEL:  13 mg/kg bw-day (males); 7
                                  mg/kg bw-day (females)
                                  LOAEL: 26 mg/kg bw-day (males) and 15
                                  mg/kg bw-day (females) for cytoplasmic
                                  vacuolization of adrenal cortex at 3-month
                                  interim evaluation
                                                   and 79% tricresyl phosphate esters
                                                   (21% confirmed as tri-m-cresyl
                                                   phosphate, 4% as tri-p-cresyl
                                                   phosphate, and no detectable tri-o-
                                                   cresyl phosphate [<0.1%]).
                                  13-Week gavage study in B6C3F1 mice
                                  (10/sex/dose)
                                  Test substance concentrations: 0, 50, 100,
                                  200, 400, 800 mg/kg bw-day (in corn oil)
                                  Dosing frequency:  Ix/d, 5d/w

                                  NOAEL: not established
                                  LOAEL: 50 mg/kg bw-day for
                                  cytoplasmic vacuolization of the adrenal
                                  cortex (males and females), ovarian
                                  interstitial cell hypertrophy
                      NTP, 1994
                                  13-Week gavage study in Fischer 344/N
                                  rats (10/sex/dose)
                                  Test substance concentrations: 0, 50, 100,
                                  200, 400, 800 mg/kg bw-day (in corn oil)
                                  Dosing frequency:  Ix/d, 5d/w

                                  NOAEL: not established
                                  LOAEL: 50 mg/kg bw-day for
                                  cytoplasmic vacuolization of the adrenal
                      NTP, 1994
                     Study details reported in a primary
                     source; test substance: Tricresyl
                     phosphate (CASRN 1330-78-5) as a
                     commercial product comprised of
                     18% dicresyl phosphate esters
                     (unconfirmed isomeric composition)
                     and 79% tricresyl phosphate esters
                     (21% confirmed as tri-m-cresyl
                     phosphate, 4% as tri-p-cresyl
                     phosphate, and no detectable tri-o-
                     cresyl phosphate [<0.1%]); EPA HC
                     (2010) suggested that relatively wide
                     range of NOAEL values among less-
                     than-lifetime repeated-dose oral
                     studies may be related to variations in
                     isomeric composition of CASRN
                     1330-78-5.
                     Study details reported in a primary
                     source; test substance: Tricresyl
                     phosphate (CASRN 1330-78-5) as a
                     commercial product comprised of
                     18% dicresyl phosphate esters
                     (unconfirmed isomeric composition)
                     and 79% tricresyl phosphate esters
                     (21% confirmed as tri-m-cresyl
                     phosphate, 4% as tri-p-cresyl
                                                           7-459

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                                               JUNE 2014 DRAFT REPORT
                                            Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  cortex (males and females)
                                                   phosphate, and no detectable tri-o-
                                                   cresyl phosphate [<0.1%]); EPA HC
                                                   (2010) suggested that relatively wide
                                                   range of NOAEL values among less-
                                                   than-lifetime repeated-dose oral
                                                   studies may be related to variations in
                                                   isomeric composition of CASRN
                                                   1330-78-5.
                                  13-Week dietary study in Fischer 344/N
                                  rats (10/sex/dose)
                                  Test substance concentrations: 0, 900,
                                  1700, 3300, 6600, 13,000 ppm
                                  (approximately 0, 55, 120, 220, 430, and
                                  750 mg/kg bw-day for males and 0, 65,
                                  120, 230, 430, and 770 mg/kg bw-day for
                                  females)

                                  NOAEL: not established
                                  LOAEL: 55 mg/kg bw-day (males) for
                                  cytoplasmic vacuolization of the  adrenal
                                  cortex, 65 mg/kg bw-day (females) for
                                  cytoplasmic vacuolization of the  adrenal
                                  cortex and ovarian interstitial cell
                                  hypertrophy
                      NTP, 1994
                                  Repeated-dose gavage study of male and
                                  female Crj:CD (SD) rats (10/group)
                                  administered commercial diphenyl cresyl
                                  phosphate (CASRN 26444-49-5; purity
                                  41.9%) for approximately 45 consecutive
                                  days (14 days premating, mating,
                                  gestation, until postpartum day 3).
                                  Dose levels: 0, 12, 60, 300 mg/kg bw-day
                      OECD-SIDS, 2002
                     Study details reported in a primary
                     source; test substance: Tricresyl
                     phosphate (CASRN 1330-78-5) as a
                     commercial product comprised of
                     18% dicresyl phosphate esters
                     (unconfirmed isomeric composition)
                     and 79% tricresyl phosphate esters
                     (21% confirmed as tri-m-cresyl
                     phosphate, 4% as tri-p-cresyl
                     phosphate, and no detectable tri-o-
                     cresyl phosphate [<0.1%]); EPA HC
                     (2010) suggested that relatively wide
                     range of NOAEL values among less-
                     than-lifetime repeated-dose oral
                     studies may be related to variations in
                     isomeric composition of CASRN
                     1330-78-5.
                     Secondary source indicated the study
                     followed OECD guidelines for a
                     Combined Repeated Dose and
                     Reproductive/Developmental
                     Screening Toxicity Test; test
                     substance: commercial diphenyl
                     cresyl phosphate (CASRN 26444-49-
                     5; purity 41.
                                                           7-460

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                                               JUNE 2014 DRAFT REPORT
                                            Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  NOAEL: 12 mg/kg bw-day
                                  LOAEL: 60 mg/kg bw-day for
                                  enlargement and vacuolization of adrenal
                                  cortex
                                  13-Week dietary study in B6C3F1 mice
                                  (10/sex/concentration)
                                  Test substance concentrations: 0, 250,
                                  500, 1,000, 2,100, 4,200 ppm
                                  (approximately 0, 45, 110, 180, 380, and
                                  900 mg/kg bw-day for males and 0, 65,
                                  130, 230, 530, and 1,050 mg/kg bw-day
                                  for females)

                                  NOAEL: 45 mg/kg bw-day (males); not
                                  established for females
                                  LOAEL: 110 mg/kg bw-day (males) and
                                  65 mg/kg bw-day (females) for
                                  cytoplasmic vacuolization of the adrenal
                                  cortex
                      NTP, 1994
                     Study details reported in a primary
                     source; test substance: Tricresyl
                     phosphate (CASRN 1330-78-5) as a
                     commercial product comprised of
                     18% dicresyl phosphate esters
                     (unconfirmed isomeric composition)
                     and 79% tricresyl phosphate esters
                     (21% confirmed as tri-m-cresyl
                     phosphate, 4% as tri-p-cresyl
                     phosphate, and no detectable tri-o-
                     cresyl phosphate [<0.1%]); EPA HC
                     (2010) suggested that relatively wide
                     range of NOAEL values among less-
                     than-lifetime repeated-dose oral
                     studies may be related to variations in
                     isomeric composition of CASRN
                     1330-78-5.
                                  3-Month gavage study in Sprague-Dawley
                                  rats (5/sex/dose)
                                  Test substance concentrations: 30, 100,
                                  300, 1,000 mg/kg bw-day
                                  Dosing frequency: Ix/d, 6d/w

                                  NOAEL: 300 mg/kg bw-day
                                  LOAEL: 1,000 mg/kg bw-day for
                                  decreased body weight in males and
                                  hypertrophy of the adrenal cortex in both
                                  sexes
                      WHO, 1990; Great Lakes
                      Chemical Corporation, 2001;
                      EPA, 2010
                     Small group numbers (5
                     rats/sex/dose); study considered valid
                     with restrictions by secondary source;
                     test substance: Tricresyl phosphate
                     (CASRN 1330-78-5) in 5% gum
                     arabic; test substance purity: 100%;
                     EPA HC (2010) suggested that
                     relatively wide range of NOAEL
                     values among less-than-lifetime
                     repeated-dose oral studies may be
                     related to variations in isomeric
                                                           7-461

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JUNE 2014 DRAFT REPORT
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT










































Skin Sensitization





Skin Sensitization



Respiratory Sensitization
[Respiratory Sensitization
DATA

2 8 -Day dietary study in Sprague-Dawley
rats (10/sex/dose)
Test substance concentrations: 0, 0.1, 0.5,
1.0% (males: 0, 236, 1,281, 1,551 mg/kg
bw-day; females: 0, 250, 1,229, 2,130
mg/kg bw-day)

NOAEL: 236 mg/kg bw-day (males); 250
mg/kg bw-day (females)
LOAEL: 1,281 mg/kg bw-day (males) for
mortality; 1,229 mg/kg bw-day (females)
for mortality


k _ ^7

.^^^ \
y^L 1


REFERENCE

FMC, 1976



^^^



^^^\ T







7



DATA QUALITY
composition of CASRN 1330-78-5.
Guideline not specified, but appears
to follow OECD test guideline 407;
test substance: Tricresyl phosphate
(CASRN 1330-78-5); this study was
summarized in ATSDR 2012; Great
Lakes Chemical Corporation, 2001;
and EPA HC, 2010. However, the
estimated low- and mid-dose levels
provided by these secondary sources
are much lower than the doses
calculated using reported body weight
and compound consumption data in
the primary report (i.e., estimated
doses reported in EPAHC (2010)
were 0, 50, 250, and 500 mg/kg-day
and estimated doses reported in
ATSDR (2012) were 0, 140, 938, and
2647 mg/kg-day for the males, and 0,
120, 745, and 2258 mg/kg-day for the
females)
MODERATE: There is uncertain potential for skin Sensitization based on a protein binding alert for this
compound and professional judgment.
There is uncertain potential for skin
Sensitization based on a protein binding
alert for this compound. (Estimated)

Professional judgment



Estimated based on a protein binding
alert (nucleophilic substitution on
)hosphonates) and professional
udgment.
No data located.

|No data located.
         7-462

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JUNE 2014 DRAFT REPORT
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
Eye Irritation

Eye Irritation
Dermal Irritation

Dermal Irritation
DATA
REFERENCE
DATA QUALITY
LOW: Tricresyl phosphate caused conjuctival effects in 2/6 rabbits that cleared within 48 hours.
Eye irritation study in rabbits (n=9)
Treated eye of 3/9 rabbits rinsed 4 seconds
post application
Conjunctival effects at 24 hours in 2/6
rabbits with unrinsed eyes which cleared
by 48 hours; no effects in rinsed eyes;
results considered to indicate that test
substance was not an eye irritant
Great Lakes Chemical
Corporation, 2001; EPA, 2010
^^^
Study details reported in secondary
sources; considered valid; test
substance: undiluted phosphoric acid,
tris(methylphenyl)ester (CASRN
1330-78-5).
LOW: Tricresyl phosphate caused erythema in 1/6 rabbits that cleared within 72 hours.
Skin irritation study in rabbits (n=6)
Test substance applied to shaved and
intact and abraded sites on the back of
each rabbit under semi occlusive
conditions for 24 hours and observed for
up to 7 days post application
Erythema on abraded skin of 1/6 rabbits at
24 hours resolved by 72 hours; no edema
at any site; results indicated that test
substance did not cause skin irritation
Great Lakes Chemical
Corporation, 2001; EPA, 2010
Study details reported in secondary
sources; considered valid; test
substance: undiluted phosphoric acid,
tris(methylphenyl)ester (CASRN
1330-78-5).
         7-463

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JUNE 2014 DRAFT REPORT
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
Endocrine Activity
































DATA
REFERENCE
DATA QUALITY
Dose-related increasing severity of cytoplasmic vacuolization of the adrenal glands were noted in rats and
mice exposed to receiving commercial tricresyl phosphate by repeated gavage dosing or continuously via the
diet for 13 weeks at doses in the range of 50-800 mg/kg bw-day. Cytoplasmic vacuolization of the adrenal
cortex in male rats at the highest dose level (13 mg/kg bw-day) and female rats at all dose levels (4, 7, and 15
mg/kg bw-day) was observed in a 2-year dietary study, but primarily in the 7 mg/kg bw-day group at the 9-
and 15-month interim sacrifice and terminal sacrifice. Ceroid pigmentation of the adrenal cortex occurred
in all groups of mice (test substance doses 7-37 mg/kg bw-day) throughout most of the 2-year study.
Thirteen-week oral (gavage) and feeding
studies and 2-year feeding studies in
F344/N rats and B6C3F1 mice. Results of
13 -week studies: Rats and mice exposed
to test substance by repeated gavage
dosing or continuously via the diet at test
substance doses in the range of 50-800
mg/kg bw-day to male and female rats and
mice exhibited dose-related increasing
severity of cytoplasmic vacuolization of
the adrenal glands. Results of 2-year
studies: Cytoplasmic vacuolization of the
adrenal cortex was noted in male rats at
the highest dose level (13 mg/kg bw-day)
and female rats at all dose levels (4, 7, and
15 mg/kg bw-day); primarily in the 7
mg/kg bw-day group of female rats at 9-
and 15 -month interim sacrifice and
terminal sacrifice. Ceroid pigmentation of
the adrenal cortex occurred in all groups
of mice (test substance doses 7-37 mg/kg
bw-day) throughout most of the 2-year
study, with markedly increased severity in
the high-dose females (37 mg/kg bw-day).
3 -Month gavage study in Sprague-Dawley
rats (5/sex/dose) Test substance
NTP, 1994

^^^N. T





















WHO, 1990; Great Lakes
Chemical Corporation, 2001;
Study details reported in a reliable
primary source; test substance:
Tricresyl phosphate (CASRN 1330-
78-5) as a commercial product
comprised of 18% dicresyl phosphate
esters (unconfirmed isomeric
composition) and 79% tricresyl
phosphate esters (21% confirmed as
tri-m-cresyl phosphate, 4% as tri-p-
cresyl phosphate, and no detectable
tri-o-cresyl phosphate [<0.1%]).













Small group numbers (5
rats/sex/dose); study considered valid
         7-464

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                                                         JUNE 2014 DRAFT REPORT
                                                      Tricresyl phosphate CASRN 1330-78-5
          PROPERTY/ENDPOINT
               DATA
        REFERENCE
        DATA QUALITY
                                            concentrations: 30, 100, 300, 1,000 mg/kg
                                            bw-day Dosing frequency: Ix/d, 6d/w

                                            NOAEL: 300 mg/kg bw-day
                                            LOAEL: 1,000 mg/kg bw-day for
                                            decreased body weight in males and
                                            hypertrophy of the adrenal cortex in both
                                            sexes
                                     EPA, 2010
                             with restrictions by secondary source;
                             test substance: Tricresyl phosphate
                             (CASRN 1330-78-5) in 5% gum
                             arabic; test substance purity: 100%;
                             EPA HC (2010) suggested that
                             relatively wide range of NOAEL
                             values among less-than-lifetime
                             repeated-dose oral studies may be
                             related to variations in isomeric
                             composition of CASRN 1330-78-5.
Immunotoxicity
Decreased immune response to tetanus antigen significantly reduced at low doses in rats fed technical-grade
tricresyl phosphate for 6 weeks. Significant changes in gross immune organ weights and histology were
reported at high doses. Significantly decreased thymus weight was noted in male and female mice and rats
administered commercial tricresyl phosphate by repeated gavage for 16 days at doses > 1450 mg/kg-day.
Other effects seen at 2900 mg/kg bw-day included necrosis of mandibular lymph nodes and spleen and
lymphoid depletion in spleen and/or thymus.
               Immune System Effects
Rats fed diets containing 0, 20, 50, or 100
ppm tricresyl phosphate and immunized
with tetanus toxoid 25 days following
initiation of exposure
After 6 weeks of treatment, doses of 6
mg/kg bw-day and higher resulted in
reduced antibody titer to tetanus toxoid
and significantly reduced cell-mediated
immune response (at 12 mg/kg bw-day,
serum IgM and IgG were significantly
reduced).
No effects were reported at 2.4 mg/kg bw-
day
                                            16-day gavage study in mice
                                            Test substance concentrations: 0, 360,
                                            730, 1450, or 2900 mg/kg bw-day (in corn
                                            oil), 5800 mg/kg bw-day (neat); 5
ATSDR2012
Study details reported in a secondary
source; test substance: Technical-
grade (90% purity) tricresyl
phosphate (CASRN 1330-78-5);
unspecified mixture of ortho, meta,
and para isomers.
                                     NTP, 1994
                             Study details reported in a primary
                             source; test substance: Tricresyl
                             phosphate (CASRN 1330-78-5) as a
                             commercial product comprised of
                                                                     7-465

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                                               JUNE 2014 DRAFT REPORT
                                           Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  days/week
                                  Significantly decreased thymus weight in
                                  males and females at doses of 1450 mg/kg
                                  bw-day or more; necrosis of mandibular
                                  lymph node and lymphoid depletion in the
                                  spleen of males and females at 2900
                                  mg/kg bw-day (but not at 5800 mg/kg bw-
                                  day); lymphoid depletion in the thymus of
                                  males at 2900 mg/kg bw-day or more; and
                                  necrosis and lymphoid depletion in the
                                  thymus of females at 2900 mg/kg bw-day
                                  (but not at 5800 mg/kg bw-day)
                                                   18% dicresyl phosphate esters
                                                   (unconfirmed isomeric composition)
                                                   and 79% tricresyl phosphate esters
                                                   (21% confirmed as tri-m-cresyl
                                                   phosphate, 4% as tri-p-cresyl
                                                   phosphate, and no detectable tri-o-
                                                   cresyl phosphate [<0.1%]).
                                  16-day gavage study in F344/N rats
                                  Test substance concentrations: 0, 360,
                                  730, 1450, or 2900 mg/kg bw-day (in corn
                                  oil), 5800 mg/kg bw-day (neat); 5
                                  days/week
                                  Significantly decreased thymus weight in
                                  males and females at doses of 1450 mg/kg
                                  bw-day or more; necrosis of mandibular
                                  lymph node in males at 2,900 mg/kg bw-
                                  day (but not at 5800 mg/kg bw-day);
                                  necrosis of spleen in males at 2900 and
                                  5800 mg/kg bw-day and females at 2900
                                  mg/kg bw-day (but not at 5800 mg/kg bw-
                                  day); necrosis and lymphoid depletion in
                                  thymus of males and females at 2900
                                  mg/kg bw-day (but not at 5800 mg/kg bw-
                                  day).
                      NTP, 1994
                     Study details reported in a primary
                     source; test substance: Tricresyl
                     phosphate (CASRN 1330-78-5) as a
                     commercial product comprised of
                     18% dicresyl phosphate esters
                     (unconfirmed isomeric composition)
                     and 79% tricresyl phosphate esters
                     (21% confirmed as tri-m-cresyl
                     phosphate, 4% as tri-p-cresyl
                     phosphate, and no detectable tri-o-
                     cresyl phosphate [<0.1%]).
                                                          7-466

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JUNE 2014 DRAFT REPORT
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
ECOTOXICITY
ECOSAR Class
Acute Aquatic Toxicity
Fish LC50

VERY HIGH: Based on experimental acute aquatic toxicity values < 1.0 mg/L in fish, daphnia, and algae.
Estimated aquatic toxicity values are also consistent with a Very High hazard designation. Both
experimental and estimated toxicity values are at or near the water solubility limit of this compound.
Lepomis macrochirus (bluegill) 96-hour
LC50 = 0.26 mg/L at water hardness 44
mg/L; 0.061 mg/L at water hardness 314
mg/L
Flow -through test conditions
(Experimental)
Oncorhynchus mykiss (rainbow trout) 96-
hour LC50 range 0.26-0.4 mg/L
Flow -through test conditions
(Experimental)
Danio rerio (Zebra Danio) 96-hour LC50
range 0.4-5.9 mg/L
Renewal test conditions
Solvent: sulfinyl bis(methane)
(Experimental)
Oncorhynchus mykiss (rainbow trout;
Salmo gairdneri); 10/group 96-hour LC50
= 0.75 mg/L (95% CL 0.54-1.04 mg/L)
Static test conditions with solvent controls
(solvent not specified)
Test substance concentrations: 0.56, 1.00,
1.80, 3.20, 5.60 mg/L (nominal)
(Experimental)
Oryzias latipes (Japanese Medaka) 96-
hour LC50 =1.3 mg/L
Test substance concentrations: 0.29-3.09
EPA, 2013
^^^N. T
EPA, 2013
EPA, 2013
Great Lakes Chemical
Corporation, 2001; EPA, 2010
OECD, 1998; OECD-SIDS,
2002
Limited study details reported in a
secondary source; test substance:
Phosphoric acid,
tris(methylphenyl)ester (CASRN
1330-78-5).
Limited study details reported in a
secondary source; test substance:
Phosphoric acid,
tris(methylphenyl)ester (CASRN
1330-78-5).
Limited study details reported in a
secondary source; test substance:
Phosphoric acid,
tris(methylphenyl)ester (CASRN
1330-78-5).
Limited study details reported in a
secondary source which did not
specify a reliability code; test
substance: Phosphoric acid,
tris(methylphenyl)ester (CASRN
1330-78-5); purity 100%.
Limited details reported in a
secondary source that indicated the
study followed OECD Test Guideline
         7-467

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                                                JUNE 2014 DRAFT REPORT
                                            Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  mg/L (nominal); solvent: methanol
                                  Semi-static open-system test conditions
                                  (Experimental)
                                  Oryzias latipes (Japanese Medaka) 96-
                                  hour LC50 >3.2 <10 mg/L
                                  Renewal test conditions
                                  (Experimental)
                      EPA, 2013
                                  Lepomis macrochirus (bluegill) 96-hour
                                  LC50 range 29-7,000 mg/L
                                  Static test conditions
                                  (Experimental)
                      EPA, 2013
                                  Pimephalespromelas (fathead minnow);
                                  10/group 96-hour LC50 >100 mg/L
                                  Static test conditions
                                  Test substance concentrations: 10, 18, 32,
                                  56, and 100 mg/L (nominal)
                                  (Experimental)
                      Great Lakes Chemical
                      Corporation, 2001
                                  Brachydanio rerio (Zebrafish) 96-hour
                                  LC0 = 8.1 mg/L (not specified whether
                                  nominal or analytical)
                                  96-hour LC90 = 11.5 mg/L (not specified
                                  whether nominal or analytical)
                                  Test conditions not specified
                                  (Experimental)
                      OECD-SIDS, 2002
                                  Fish 96-hour LC50: 0.34 mg/L
                                  (Estimated)
                                  ECOSAR: Neutral organics
                      ECOSARvl.ll
                                                   203; test substance: Diphenyl cresyl
                                                   phosphate (CASRN 26444-49-5);
                                                   Purity: stated as "phenol, m-cresol, p-
                                                   cresol = 59%, 22%, 12%".
                      Limited study details reported in a
                      secondary source; test substance:
                      Phosphoric acid,
                      tris(methylphenyl)ester (CASRN
                      1330-78-5).
                      Limited study details reported in
                      secondary sources; test substance:
                      Phosphoric acid,
                      tris(methylphenyl)ester (CASRN
                      1330-78-5).
                      Limited study details reported in a
                      secondary source which considered
                      the study valid with restrictions; test
                      substance: Phosphoric acid,
                      tris(methylphenyl)ester (CASRN
                      1330-78-5); purity  100%'
                      Limited details reported in a
                      secondary source; test substance:
                      Diphenyl cresyl phosphate (CASRN
                      26444-49-5); purity not specified.
                      Estimations for monocresyl diphenyl
                      phosphate The estimated log Kow of
                      5.2 for this chemical exceeds the
                      SAR limitation for log Kow of 5.0;
                      NES are predicted for these
                      endpoints. Dicresyl phenyl phosphate
                                                           7-468

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                                                         JUNE 2014 DRAFT REPORT
                                                      Tricresyl phosphate CASRN 1330-78-5
          PROPERTY/ENDPOINT
                DATA
        REFERENCE
        DATA QUALITY
                                                                                                               and higher alkylated isomers have
                                                                                                               higher estimated log Kow values;
                                                                                                               therefore NES are predicted for the
                                                                                                               higher alkylated isomers also.
                                                                                                               ECOSAR also provided results for
                                                                                                               the Esters, and Esters (phosphate)
                                                                                                               classes; however, professional
                                                                                                               judgment indicates that this
                                                                                                               compound is not currently well
                                                                                                               represented in ECOSAR vl. 11.
Daphnid LC50
Daphnia magna (water flea) 4 8-hour LC50
= 0.27 mg/L
Static test conditions Test substance
concentrations: 0.06, 0.1, 0.18, 0.32, 0.56
mg/L (nominal)
Solvent: Acetone NOEC: 0.1 mg/L
(nominal)
(Experimental)
Great Lakes Chemical
Corporation, 2001; EPA, 2010
                                            Daphnia magna (water flea) 4 8-hour LC50
                                            = 5.6 mg/L
                                            Flow-through test conditions
                                            (Experimental)
                                      WHO, 1990
                                            Daphnid 48-hour LC50:
                                            0.26 mg/L
                                            (Estimated)
                                            ECOSAR: Neutral organics
                                      ECOSAR vl. 11
Great Lakes Chemical Corporation
considered the study valid with
restrictions; test substance:
Phosphoric acid,
tris(methylphenyl)ester (CASRN
1330-78-5).
                             Limited study details in secondary
                             source; test substance: Phosphoric
                             acid, tritolyl ester (CASRN 1330-78-
                             5).
                             Estimations for monocresyl diphenyl
                             phosphate The estimated log Kow of
                             5.2 for this chemical exceeds the
                             SAR limitation for log Kow of 5.0;
                             NES are predicted for these
                             endpoints. Dicresyl phenyl phosphate
                             and higher alkylated isomers have
                             higher estimated log Kow values;
                             therefore NES are predicted for the
                             higher alkylated isomers also.
                             ECOSAR also provided results for
                                                                     7-469

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                                                         JUNE 2014 DRAFT REPORT
                                                      Tricresyl phosphate CASRN 1330-78-5
          PROPERTY/ENDPOINT
               DATA
        REFERENCE
        DATA QUALITY
                                                                                                              the Esters, and Esters (phosphate)
                                                                                                              classes; however, professional
                                                                                                              judgment indicates that this
                                                                                                              compound is not currently well
                                                                                                              represented in ECOSAR vl. 11.
Green Algae EC50
Scenedesmus pannonicus (green algae)
96-hour EC50 = 0.56 mg/L (growth rate)
(Experimental)
EPA, 2010
Limited study details summarized in
reliable secondary source, test
substance: Phosphoric acid,
tris(methylphenyl)ester (CASRN:
1330-78-5).
                                            Pseudokirchneriella subcapitata (formerly
                                            Selenastrum capricornutum ; green algae)
                                            72-hour EC50 = 0.99 mg/L (nominal)
                                            72-hour NOEC = 0.55 mg/L (nominal)
                                            Test substance concentrations:  0.31-3.24
                                            mg/L (nominal); solvent: methanol
                                            (Experimental)
                                     OECD, 1998; OECD-SIDS,
                                     2002
                             Limited study details reported in
                             secondary source that indicated the
                             study followed OECD Test Guideline
                             201; Test substance: Diphenyl cresyl
                             phosphate (CASRN 26444-49-5);
                             purity: stated as "phenol, m-cresol, p-
                             cresol = 59%, 22%, 12%".
                                            Green algae 96-hour EC50 range 1.3-3.8
                                            mg/L (growth)
                                            Static test conditions
                                            (Experimental)
                                     WHO, 1990; EPA, 2013
                             Limited study details reported in
                             secondary sources; test substance:
                             Phosphoric acid,
                             tris(methylphenyl)ester (CASRN
                             1330-78-5).
                                            Green algae 96-hour EC50 = 0.13 mg/L
                                            (Estimated)
                                            ECOSAR: Neutral organics
                                     ECOSAR vl. 11
                             Estimation for tricresyl phenyl
                             phosphate. ECOSAR also provided
                             results for the Esters, and Esters
                             (phosphate) classes; however,
                             professional judgment indicates that
                             this compound is not currently well
                             represented in ECOSAR vl. 11.
                                            Green algae 96-hour EC50 = 0.29 mg/L
                                            (Estimated)
                                            ECOSAR: Neutral organics
                                     ECOSAR vl. 11
                             Estimation for dicresyl phenyl
                             phosphate. ECOSAR also provided
                             results for the Esters, and Esters
                             (phosphate) classes; however,
                                                                     7-470

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                                                        JUNE 2014 DRAFT REPORT
                                                     Tricresyl phosphate CASRN 1330-78-5
          PROPERTY/ENDPOINT
               DATA
        REFERENCE
        DATA QUALITY
                                                                                                            professional judgment indicates that
                                                                                                            this compound is not currently well
                                                                                                            represented in ECOSAR vl. 11.
                                           Green algae 96-hour EC50 = 0.67 mg/L
                                           (Estimated)
                                           ECOSAR: Neutral organics
                                     ECOSAR vl. 11
                             Estimation for monocresyl diphenyl
                             phosphate. ECOSAR also provided
                             results for the Esters, and Esters
                             (phosphate) classes; however,
                             professional judgment indicates that
                             this compound is not currently well
                             represented in ECOSAR vl. 11.
Chronic Aquatic Toxicity
VERY HIGH: Based on estimated chronic aquatic toxicity values < 0.1 mg/L in fish, daphnia, and algae. The
only experimental studies located were for Daphnia magna and indicated a High hazard designation with
toxicity values within the 0.1 - 1 mg/L range. No experimental chronic studies were located for fish or algae.
Fish ChV
Fish ChV = 0.006 mg/L
(Estimated)
ECOSAR: Neutral organics
                                           Fish ChV = 0.017 mg/L
                                           (Estimated)
                                           ECOSAR: Neutral organics
                                           Fish ChV = 0.047 mg/L
                                           (Estimated)
                                           ECOSAR: Neutral organics
ECOSAR vl. 11
                                     ECOSAR vl. 11
                                     ECOSAR vl. 11
ECOSAR also provided results for
the Esters, and Esters (phosphate)
classes; however, professional
judgment indicates that this
compound is not currently well
represented in ECOSAR vl. 11.
                             ECOSAR also provided results for
                             the Esters, and Esters (phosphate)
                             classes; however, professional
                             judgment indicates that this
                             compound is not currently well
                             represented in ECOSAR vl. 11.
                             ECOSAR also provided results for
                             the Esters, and Esters (phosphate)
                             classes; however, professional
                             judgment indicates that this
                             compound is not currently well
                             represented in ECOSAR vl. 11.
                                                                    7-471

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                                                        JUNE 2014 DRAFT REPORT
                                                     Tricresyl phosphate CASRN 1330-78-5
          PROPERTY/ENDPOINT
               DATA
        REFERENCE
        DATA QUALITY
Daphnid ChV
Daphnia magna (water flea) 21-day LC50
= 0.35 mg/L (mortality)
21-day EC50 = 0.31 mg/L (reproduction)
21-day NOEC = 0.12 mg/L (reproduction)
Test substance concentrations: 0.038-3.8
mg/L (nominal); solvent: dimethyl
sulfoxide (DMSO)
Semi-static open-system test conditions
(Experimental)
OECD, 1998; OECD-SIDS,
2002
                                           Daphnia magna (water flea) 21-day EC 50
                                           range 0.1-1.0
                                           Renewal test conditions
                                           (Experimental)
                                     EPA, 2010, 2013
                                           Daphnid ChV = 0.010 mg/L
                                           (Estimated)
                                           ECOSAR: Neutral organics
                                     ECOSARvl.ll
                                           Daphnid ChV = 0.024 mg/L
                                           (Estimated)
                                           ECOSAR: Neutral organics
                                     ECOSARvl.ll
                                           Daphnid ChV = 0.058 mg/L
                                           (Estimated)
                                           ECOSAR: Neutral organics
                                     ECOSARvl.ll
Secondary source indicated the study
followed OECD Test Guideline 202;
test substance: Diphenyl cresyl
phosphate (CASRN 26444-49-5)
Purity: stated as "phenol, m-cresol, p-
cresol = 59%, 22%, 12%".
                             Limited study details reported in
                             secondary sources; test substance:
                             Phosphoric acid,
                             tris(methylphenyl)ester (CASRN
                             1330-78-5).
                             Estimation for tricresyl phenyl
                             phosphate. ECOSAR also provided
                             results for the Esters, and Esters
                             (phosphate) classes; however,
                             professional judgment indicates that
                             this compound is not currently well
                             represented in ECOSAR vl. 11.
                             Estimation for dicresyl phenyl
                             phosphate. ECOSAR also provided
                             results for the Esters, and Esters
                             (phosphate) classes; however,
                             professional judgment indicates that
                             this compound is not currently well
                             represented in ECOSAR vl. 11.
                             Estimation for monocresyl diphenyl
                             phosphate. ECOSAR also provided
                             results for the Esters, and Esters
                             (phosphate) classes; however,
                             professional judgment indicates that
                                                                    7-472

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                                                        JUNE 2014 DRAFT REPORT
                                                     Tricresyl phosphate CASRN 1330-78-5
          PROPERTY/ENDPOINT
               DATA
       REFERENCE
        DATA QUALITY
                                                                                                            this compound is not currently well
                                                                                                            represented in ECOSAR vl. 11.
Green Algae ChV
Green algae ChV = 0.081 mg/L
(Estimated)
ECOSAR: Neutral organics
ECOSAR vl. 11
                                           Green algae ChV = 0.17 mg/L
                                           (Estimated)
                                           ECOSAR: Neutral organics
                                     ECOSAR vl. 11
                                           Green algae ChV = 0.34 mg/L
                                           (Estimated)
                                           ECOSAR: Neutral organics
                                     ECOSAR vl. 11
Estimation for tricresyl phenyl
phosphate. ECOSAR also provided
results for the Esters, and Esters
(phosphate) classes; however,
professional judgment indicates that
this compound is not currently well
represented in ECOSAR vl. 11.
                            Estimation for dicresyl phenyl
                            phosphate. ECOSAR also provided
                            results for the Esters, and Esters
                            (phosphate) classes; however,
                            professional judgment indicates that
                            this compound is not currently well
                            represented in ECOSAR vl. 11.
                            Estimation for monocresyl diphenyl
                            phosphate. ECOSAR also provided
                            results for the Esters, and Esters
                            (phosphate) classes; however,
                            professional judgment indicates that
                            this compound is not currently well
                            represented in ECOSAR vl. 11.
                                                                   7-473

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JUNE 2014 DRAFT REPORT
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
ENVIRONMENTAL FATE
Transport

Henry's Law Constant (atm-
m3/mole)
Sediment/Soil
Adsorption/Desorption - Koc
Level III fugacity models incorporating available physical and chemical property data indicate that at
steady state, tricresyl phosphate is expected to be found primarily in soil and to a lesser extent, sediment.
Tricresyl phosphate is expected to have negligible to moderate mobility in soil based on both measured and
estimated K0c values. Leaching of tricresyl phosphate through soil to groundwater is not expected to be an
important transport mechanism. There is slight potential for volatilization from moist soil surfaces based
upon the measured Henry's Law constant; however adsorption to soil is expected to attenuate this process.
In the atmosphere, tricresyl phosphate is expected to exist in the vapor and particulate phase. Vapor phase
tricresyl phosphate will be degraded in the atmosphere by reaction with photochemically-produced
hydroxyl radicals; the half-life for this reaction in air is estimated to be 0.8 days. Particulate phase tricresyl
phosphate will be removed from air by wet or dry deposition.
8xlO"7 (Measured)
8.3xlO"5 (Measured)
4xlO~8 for monocresyl diphenyl phosphate;
5x1 0~8 for dicresyl phenyl phosphate and
tricresyl phosphate
Bond method (Estimated)
Reported as the adsorption coefficient per
gram of clay minerals.
Kaolin: 0.236 (236 L/kg)
Alumina: 0.177 (177 L/kg)
Montmorillonite: 4.614 (4614 L/kg)
(Measured)
Reported as the adsorption coefficient per
gram of clay minerals.
Kaolin: 0.196 (196 L/kg)
Alumina: 0.144 (144 L/kg)
PhysProp, 2012
EPA, 2010
EPIv4.11
Takimoto et al., 1998
Takimoto et al., 1998
Reported in s a secondary source with
limited details.
Reported for tri-m-cresyl phosphate
(CASRN 563-04-2); purity and test
method not stated.
Estimated using representative
structures indicated in the SMILES
section for methylated phenyl
phosphate with one, two and three
methyl substituent groups
respectively.
Nonguideline, well-documented
study for reagent grade tri-p-cresyl
phosphate (CASRN 78-32-0).
Nonguideline, well-documented
study for reagent grade tri-m-cresyl
phosphate (CASRN 563-04-2).
         7-474

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JUNE 2014 DRAFT REPORT
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT


Level III Fugacity Model
DATA
Montmorillonite: 1.361 (1361 L/kg)
(Measured)
Reported as the adsorption coefficient per
gram of clay minerals.
Kaolin: 0.158 (158 L/kg)
Alumina: 0.118 (118 L/kg)
Montmorillonite: 1.550 (1550 L/kg)
(Measured)
18,000 for monocresyl diphenyl
phosphate;
28,000 for dicresyl phenyl phosphate
MCI method (Estimated)
>30,000 MCI method (Estimated)
Air = 0.3%
Water = 9.9%
Soil = 64%
Sediment = 26% (Estimated)
REFERENCE

Takimoto et al., 1998
^^^
EPIv4.11
EPIv4.11;EPA, 2005
EPIv4.11
DATA QUALITY

Nonguideline, well-documented
study for reagent grade tri-o-cresyl
phosphate (CASRN 78-30-8).
Estimated using a representative
structure
Estimated using a representative
structure fortricresyl phosphate.
Cutoff value fornonmobile
compounds.
Estimated using a representative
structure fortricresyl phosphate.
         7-475

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                                                        JUNE 2014 DRAFT REPORT
                                                    Tricresyl phosphate CASRN 1330-78-5
          PROPERTY/ENDPOINT
                                           DATA
                                            REFERENCE
                                    DATA QUALITY
Persistence
                            MODERATE: Based on nonguideline studies that have demonstrated primary and ultimate biodegradation
                            of tricresylphosphate and related components under aerobic conditions. There is evidence of biodegradation
                            resulting in a half-life less than 60 days but greater than 16 days. Both CASRN 563-04-2 and 26444-49-5 did
                            not pass ready biodegradability OECD 301C tests, however some degradation, <43.1%, was observed after
                            28 days. Other biodegradation tests, including OECD 302A, 302C, CO2 Evolution and a Die Away test
                            indicated some degradation by this pathway. Experimental data for the direct photolysis of CASRN 26444-
                            49-5 reported a half-life of 4.86 years; therefore, direct photolysis of tricresyl phosphate is not expected to be
                            an important fate process. Experimental half-lives of 27 to 87 minutes for tricresyl phosphate and 2
                            individual isomers, demonstrate removal by hydrolysis under alkaline conditions.
Water
Aerobic Biodegradation
Passes Ready Test: No
Test method: OECD TG 301C: Modified
MITI Test (I)

30.8 and 43.1% degradation in 28 days
(Measured)
                                           Passes Ready Test: No
                                           Test method: OECD TG 301C: Modified
                                           MITI Test (I)

                                           Reported as 0, 0, and 0% after 28 days
                                           from BOD; 11, 5 and 5% after 28 days
                                           from high performance liquid
                                           chromatography (HPLC); using GLP
                                           (Measured)
                                           Passes Ready Test: No
                                           Test method: OECD TG 301C: Modified
                                           MITI Test (I)

                                           Using OECD Test Guideline 301C (100
                                           mg/L concentration of test substance),
                                           diphenyl cresyl phosphate had a 0%
                                           theoretical BOD after 28 days of
                                           incubation. (Measured)
EPA, 2010
                                                                 OECD-SIDS, 2002
                                                                HSDB, 2013a
Reported for tri-m-cresyl phosphate
(CASRN 563-04-2); purity not stated.
                                                                 Guideline study in a secondary source
                                                                 for cresyl diphenyl phosphate
                                                                 (CASRN 26444-49-5).
                                                                 Reported for diphenyl cresyl
                                                                 phosphate (CASRN 26444-49-5)
                                                                 purity not stated. This study used an
                                                                 initial concentration of compound
                                                                 that was more than 40 times greater
                                                                 than the water solubility.
                                                                   7-476

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                                               JUNE 2014 DRAFT REPORT
                                            Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  Study results: 78.6%/7 days
                                  Test method: CO2 Evolution

                                  In a modified Sturm test ultimate
                                  degradation was measured. At 26.4 mg/L
                                  tricresyl phosphate achieved 78.6% of its
                                  theoretical CO2 in 7 days and 82% in 8
                                  days. (Measured)
                      WHO, 1990; HSDB, 2013d
                     Nonguideline study reported in
                     secondary sources; purity not
                     indicated.
                                  Study results: 100%/28 days
                                  Test method: 302C: Inherent - Modified
                                  MITI Test (II)

                                  (Measured)
                      EPA, 2010
                                  Study results: 65.7%/28 days
                                  Test method: 302C: Inherent - Modified
                                  MITI Test (II)

                                  Inherently biodegradable (Measured)
                      EPA, 2010
                                  Study results: 82%/22 weeks
                                  Test method: 302A: Inherent - Modified
                                  SCAS Test

                                  Primary degradation measured; influent
                                  concentrations of 3 mg/L/day (Measured)
                      HSDB, 2013a
                                  Study results: 100%/4 days
                                  Test method: Die-Away

                                  River water; complete degradation in 4
                                  days (Measured)
                      HSDB, 2013a
                                  Study results: 75-100%/29 days
                                  Test method: Die-Away

                                  In die-away tests in Japanese river water
                      HSDB, 2013d
                     Reported in a secondary source with
                     limited study details for tri-p-cresyl
                     phosphate (CASRN 78-32-0); purity
                     not stated.
                     Reported in a secondary source with
                     limited study details for tri-o-cresyl
                     phosphate (CASRN 78-30-8).
                     Reported in a secondary source for
                     diphenyl cresyl phosphate (CASRN
                     26444-49-5).
                     Reported for diphenyl cresyl
                     phosphate (CASRN 26444-49-5);
                     purity not stated.
                     Nonguideline study reported in
                     secondary sources; purity not
                     indicated.
                                                           7-477

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                                               JUNE 2014 DRAFT REPORT
                                            Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  and Japanese bay water tricresyl
                                  phosphate achieved 100% primary
                                  degradation after 4 days at 26°C; 75-100%
                                  degradation was observed after 29 days at
                                  7°C, a lag-phase of 1-3 days was
                                  observed. (Measured)
                                  Study results: 82%/28 days
                                  Test method: Die-Away

                                  In a river die-away test, at a test
                                  concentration of 26 mg/L, CO2 evolution
                                  was 79% after 7 days, 82% after 28 days
                                  and 86% after 48 days. (Measured)
                      HSDB, 2013c
                     Reported for tri-o-cresyl phosphate
                     (CASRN 78-30-8) purity and study
                     details not stated.
                                  Study results: >97%/4 weeks
                                  Test method: Die-Away

                                  In a semi-continuous activated sludge test
                                  using influent concentrations of 3 and 13
                                  mg/L/day tricresyl phosphate was shown
                                  to undergo 97% and >99% primary
                                  degradation, respectively, after 4 weeks.
                                  (Measured)
                      Saeger et al., 1979 (as cited in
                      EPA, 2010; HSDB, 2013d)
                     Nonguideline study reported for a
                     commercial grade mixture of isomers;
                     purity not indicated.
                                  Study results: 100%/4 days
                                  Test method: Die-Away

                                  In a river die-away test in water from the
                                  Mississippi river St. Louis, MO. Complete
                                  primary degradation of tricresyl phosphate
                                  was achieved after 4 days following an
                                  initial lag-phase of 2 days with 8%
                                  degradation.  Rapid degradation attributed
                                  to microbial adaptation. (Measured)
                      EPA, 2010; HSDB, 2013d
                     Nonguideline study reported in a
                     secondary source for a commercial
                     grade mixture of isomers; purity not
                     indicated.
                                  A die-away study using Lake Ontario
                      Howard and Deo, 1979 (as cited
                     Reported for individual isomers.
                                                           7-478

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                                                JUNE 2014 DRAFT REPORT
                                            Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  water from Oswego, NY found that the
                                  individual isomers exhibited a two-day lag
                                  period before degrading rapidly; the ortho-
                                  and meta-isomers were completely
                                  degraded within 4 days while about half of
                                  the para-isomer was degraded in 5 days.
                                  (Measured)
                      in EPA, 2010; HSDB, 2013a,
                      2013c)
                                  Study results: 82.1%/28 days
                                  Test method: Screening Test

                                  Inherently biodegradable. After 7, 28, and
                                  48 days 78.6, 82.1, and 86.3% theoretical
                                  CO2 evolution was achieved in acclimated
                                  bacterial inoculum, respectively. There
                                  was a 14-day acclimation period noted.
                                  (Measured)
                      Saeger et al., 1979 (as cited in
                      EPA, 2010)
                      Reported for a commercial grade
                      sample; mixture of isomers purity not
                      stated.
                                  Study results: 97%/4 weeks
                                  Test method: Other

                                  99% after 7 weeks; activated sludge
                                  inoculum and a test substance addition
                                  rate of 3 and 13 mg/L per 24 hours.
                                  (Measured)
                      HSDB, 2013c
                                  Study results: 53.2%/7 days
                                  Test method: Other

                                  At test concentrations of 23.1 mg/L, this
                                  chemical achieved 53.2, 84.5 and 91.3%
                                  of its theoretical CO2 evolution in
                                  activated sludge after 7, 28, and 48 days,
                                  respectively. (Measured)
                      HSDB, 2013a
                                  Study results: 50%/7.5 hours
                                  Test method: Other
                      Great Lakes Chemical
                      Corporation, 2001
                      Reported for tri-o-cresyl phosphate
                      (CASRN 78-30-8); purity and test
                      method not stated.
                      Reported for diphenyl cresyl
                      phosphate (CASRN 26444-49-5)
                      purity and test method not stated.
                      Reported for tri-p-cresyl phosphate
                      (CASRN 78-32-0).
                                                           7-479

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                                                JUNE 2014 DRAFT REPORT
                                            Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   1 (jg/ml of 14C-tri-p-cresyl phosphate
                                   achieved 70-80% degradation after 24
                                   hours in sewage sludge at 21°C.
                                   Degradation was determined by liquid
                                   scintillation counting, gas
                                   chromatography, and thin layer
                                   chromatography. The remaining test
                                   material was associated with the sludge
                                   solids. The major metabolite was p-
                                   hydroxybenzoic acid. (Measured)
                                   Study results: 40-60%/48 hour
                                   Test method: Other

                                   Rapid biodegradation was observed in
                                   activated sludge. 40-60% degradation of
                                   tricresyl phosphate was achieved in a 48-
                                   hour wastewater treatment simulation test.
                                   (Measured)
                      HSDB, 2013d
                                  Biodegradable in tests using activated
                                  sludge seed. (Measured)
                      HSDB, 2013b
                                  Performed in sediment-water incubation
                                  systems; Pond sediment half-life: 3.2, 4.1,
                                  and 16.3 days at 25, 10, and 2°C,
                                  respectively;
                                  River sediment half-life: 10.1 days at
                                  25 °C. (Measured)
                      HSDB, 2013b
                                   Study results: 50%/10 days
                                   Test method: Field Test

                                   Biodegradation in river water and bottom
                                   sediment followed first-order kinetics. The
                      HSDB, 2013c
                      Nonguideline study reported in a
                      secondary source. Purity of test
                      substance and test details not stated.
                      Reported for tri-m-cresyl phosphate
                      (CASRN 563-04-2) purity and test
                      method not stated.
                      Reported for tri-m-cresyl phosphate
                      (CASRN 563-04-2) purity not stated.
                      Reported for tri-o-cresyl phosphate
                      (CASRN 78-30-8); purity not stated.
                                                            7-480

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JUNE 2014 DRAFT REPORT
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT

Soil
Air

Volatilization Half-life for
Model River
Volatilization Half-life for
Model Lake
Aerobic Biodegradation
Anaerobic Biodegradation
Soil Biodegradation with
Product Identification
Sediment/Water
Biodegradation
Atmospheric Half-life
DATA
first-order rate constant in river water
ranged from approximately 0.0022 per
hour at 14°C to 0.0030 per hour at 25°C;
this corresponds to a half-life of about 13
days at 14°C and 10 days at 25°C
(Measured)
Study results: 0%/8 weeks
Test method: Screening Test
The meta isomer of tricresyl phosphate did
not degrade in 1:10 dilutions of primary
anaerobic sludge after 8 weeks.
(Measured)
River water half-life:
approx. 13 days at 14°C;
2.9daysat20°C
Bottom sediment half-life:
approx. 8 days at 14°C;
5.4 days at 25°C (Measured)
58 days (Estimated)
>1 year (Estimated)

Not probable (Anaerobic -methanogenic
biodegradation probability model)


0.91 days for monocresyl diphenyl
REFERENCE

HSDB, 2013d
^^^N. T
HSDB, 2013b
7
EPIv4.11
EPIv4.11

EPIv4.11


EPIv4.11
DATA QUALITY

Nonguideline study reported in a
secondary source for tri-m-cresyl
phosphate (CASRN 563-04-2); purity
not stated.
Reported for tri-m-cresyl phosphate
(CASRN 563-04-2) purity not stated.
River water and bottom sediment
biodegradation followed first-order
kinetics.
Estimated using a representative
structure for tricresyl phosphate.
Estimated using a representative
structure for tricresyl phosphate.
No data located.
Tricresyl phosphate (CASRN 1330-
78-5); estimated from representative
structure : tri-ortho-cresyl -phosphate .
No data located.
No data located.
Estimated using representative
         7-481

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JUNE 2014 DRAFT REPORT
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT

Reactivity

Photolysis
Hydrolysis
Environmental Half-life
DATA
phosphate;
0.84 for dicresyl phenyl phosphate:
0.78 fortricresyl phosphate
(Estimated)
50%/4. 86 years
Test performed in water using direct
sunlight. Concentration: 5xlO"5M;
Spectrum: Epsilon = 8.17xl03 at 300 nm
Degradation rate: 2.26xlO"13 mol/l/s
Quantum yield = 0.01 (Measured)
50%/47 days at pH 7; 25°C
50%/5. 10 days at pH 9 and 25°C
(Measured)
50%/27 minutes in 0.03 M NaBO3 at pH
10.3 (Measured)
50%/70 minutes in 0.03 M NaBO3 at pH
10.3 (Measured)
50%/87 minutes in 0.03 M NaBO3 at pH
10.3 (Measured)
In alkaline medium hydrolysis to
dicresylphosphate and cresol occurs;
stable in neutral and acidic media.
(Measured)
75 (Estimated)
REFERENCE

OECD-SIDS, 2002
^^^N. T
OECD-SIDS, 2002
David and Seiber, 1999
David and Seiber, 1999
David and Seiber, 1999
van der Veen and de Boer, 2012
PBT Profiler
DATA QUALITY
structures indicated in the SMILES
section for methylated phenyl
phosphate with one, two and three
methyl substituent groups
respectively.
Nonguideline study reported in a
secondary source for cresyl diphenyl
phosphate (CASRN 26444-49-5)
purity of test substance and test
method not stated.
Reported in a secondary source for
cresyl diphenyl phosphate (CASRN
26444-49-5).
Reported for tri-p-cresyl phosphate
(CASRN 78-32-0).
Reported for tricresyl phosphate
(CASRN 1330-78-5) mixed isomers.
Reported for tri-o-cresyl phosphate
(CASRN 78-30-8).
Supporting information reported in a
secondary source.
Estimation for tricresyl phenyl
phosphate, dicresyl phenyl phosphate
and monocresyl phenyl phosphate.
Half-life estimated for the
predominant compartment, as
determined by EPI and the PBT
Profiler methodology.
         7-482

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JUNE 2014 DRAFT REPORT
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
Bioaccumulation

Fish BCF
DATA
REFERENCE
DATA QUALITY
HIGH: Multiple experimental BCF and estimated BAF values are above 1,000, the high bioaccumulation
designation criteria.
165 in fathead minnows; flow -through test
with 32 day exposure period (Measured)
169 in Rainbow trout; flow-through test;
BCF of 10 for white muscle and 169 for
gut and adipose tissue (Measured)
700 in Zebra fish; flow-through test with
14 day exposure period (Measured)
928 in fathead minnow; 24-hour static test
measured a BCF range of 596-928 based
on total 14C; since the 14C measurements
include tricresyl phosphate metabolites,
the observed BCF values indicate a worse-
case estimate only. (Measured)
980 (Measured)
1,420 in rainbow trout; 24-hour static test
measured a BCF range of 784-1420 based
on total 14C; since the 14C measurements
include tricresyl phosphate metabolites,
the observed BCF values indicate a worse-
case estimate only. (Measured)
1,711 (Measured)
3,700 in Gambusia fish; reported as an
ecological magnification factor; static test
using a model ecosystem. Tri-p-cresyl
HSDB, 2013d
HSDB, 2013d
^^^
HSDB, 2013d
HSDB, 2013d
OECD-SIDS, 2002
HSDB, 2013d
van der Veen and de Boer, 2012
Boethling and Cooper, 1985 (as
cited in HSDB, 2013d)
Reported in a secondary source, test
method not stated.
Reported in a secondary source for a
commercial mixture (IMOL S-140)
75% tricresyl phosphate and 18%
trixylyl phosphate (CASRN 25155-
23-1).
Reported in a secondary source, test
method not stated.
Reported in a secondary source with
meta- and para-isomers specified,
although percent composition of the
components and purity not stated.
Reported in a secondary source for
cresyl triphenyl phosphate (CASRN
26444-49-5); test method not stated.
Reported in a secondary source with
meta- and para-isomers specified,
although percent composition of the
components and purity not stated.
Reported in a secondary source for
cresyl diphenyl phosphate (CASRN
26444-49-5); purity not stated.
Reported in a secondary source.
         7-483

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JUNE 2014 DRAFT REPORT
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT


Other BCF
BAF
Metabolism in Fish
DATA
phosphate was found to accumulate and
persist in all aquatic test systems studied.
(Measured)

1381 (Estimated)
1422 (Estimated)
214 (Estimated)

REFERENCE


EPIv4.11
^^^
EPIv4.11
^^^N. T
EPIv4.11

DATA QUALITY

No data located.
Estimated using the Arnot-Gobas
method with a representative
structure for tricresyl phosphate.
Estimated using the Arnot-Gobas
method with a representative
structure for dicresyl phenyl
phosphate.
Estimated using the Arnot-Gobas
method with a representative
structure for monocresyl phenyl
phosphate.
No data located.
ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring
Ecological Biomonitoring "^^
Human Biomonitoring
Tricresyl phosphate has been detected in areas of Japan, Canada, US, UK, Italy, Norway, Sweden, Germany, and
Austria in river water, drinking water, rain water and snow, sediments, sea sediment and soil samples. Cresyl
diphenyl phosphate was detected in coastal marine sediments in the UK. Tricresyl phosphate has been detected in
atmospheric samples, indoor air of theaters, offices, electronic stores, an electronics dismantling facility and
airplanes. It has also been detected in fly ash and stack emissions, and various effluents, in dust samples/wipe
samples from automobile interiors, aircraft and vegetation samples. In one study, tricresyl phosphate isomers, m-
TCP and o-TCP were detected in atmospheric samples, while the para isomer was scarcely detected (Takimoto et
al., 1999; OECD-SIDS, 2002; Bacaloni et al., 2008; Takigami et al., 2009; Ibbotson and Ibhadon, 2010; Solbu et
al., 2011; HSDB, 2013d; Salamova et al., 2014).
Tricresyl phosphate has been detected in fish (HSDB, 2013d).
Human biomonitoring found small amounts of metabolites of tri-m- and tri-p cresyl phosphates in the urine of
aircraft crews. Metabolites of tri-o-cresyl phosphates were not detected above the LOD of the study (Schindler et
al., 2013).
         7-484

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                                                  JUNE 2014 DRAFT REPORT


ATSDR (2012) Toxicological profile for phosphate ester flame retardants. U.S. Department of Health and Human Services, Agency for Toxic
Substances and Disease Registry.

Aldrich (1994) Catalog handbook of fine chemicals 1994-1995. Milwaukee, WI: Aldrich Chemical Company, Inc.

Bacaloni A, Cucci F, Guarino C, et al. (2008) Occurrence of organophosphorus flame retardant and plasticizers in three volcanic lakes of central
Italy. Environ Sci Technol 42(6): 1898-1903.

Boethling RS, Cooper JC (1985) Environmental fate and effects of triaryl and tralkyl/aryl phosphate esters. Residue Rev 94:49-99.

Carlton BD, Basaran AH, Mezza LE, et al. (1987) Examination of the reproductive effects of tricresyl phosphate administered to Long-Evans rats.
Toxicology 46(3):321-328.

Chapin RE, George JD, Lamb JC (1988) Reproductive toxicity of tricresyl phosphate in a continuous breeding protocol in Swiss (CD-I) mice.
Fundam Appl Toxicol  10(2):344-354.

David MD, Seiber JN (1999) Accelerated hydrolysis of industrial organophosphates in water and soil using sodium perborate. Environ Pollut
ECOSAR (Ecological Structure Activity Relationship), Version 1.11. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/oppt/newchems/tools/21ecosar.htm.

EPA (2005) Pollution prevention (P2) framework. Washington, DC: U.S. Environmental Protection Agency, Office of Pollution Prevention and
Toxics, http://www.epa.gov/opptintr/newchems/pubs/sustainable/p2frame-june05a2.pdf

EPA (2010) Screening level hazard characterization phosphoric acid tris(methylphenyl) ester (Tricresyl phosphate, CASRN 1330-78-5).

EPA (2012) Using noncancer screening within the SF initiative. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/oppt/sf/pubs/noncan-screen.htm.

EPA (2013) ECOTOX database. http://cfpub.epa.gov/ecotox/quick_query.htm.

EPI Estimation Programs Interface (EPI) Suite, Version 4.1 1. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm.
                                                              7-485

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                                                  JUNE 2014 DRAFT REPORT


ESIS (2012) European chemical Substances Information System. European Commission, http://esis.jrc.ec.europa.eu/.

FMC (1976) Acute and subacute toxicity tests Kronitex TCP: Tricresyl phosphate (Report No ICD/T-76-030).

Great Lakes Chemical Corporation (2001) IUCLID data set. Phosphoric acid, tris(methylphenyl) ester

HSDB (2013a) Diphenyl cresyl phosphate. Hazardous Substances Data Base. National Library of Medicine, http://toxnet.nlm.nih.gov/cgi-
bin/sis/htmlgen?HSDB.

HSDB (2013b) Tri-M-cresyl phosphate. Hazardous Substances Data Bank. National Library of Medicine, http://toxnet.nlm.nih.gov/cgi-
bin/sis/htmlgen?HSDB.

HSDB (2013c) Tri-o-cresyl phosphate. Hazardous Substances Data Bank. National Library of Medicine, http://toxnet.nlm.nih.gov/cgi-
bin/sis/htmlgen?HSDB.

HSDB (2013d) Tricresyl phosphate. Hazardous Substances Data Base. National Library of Medicine, http://toxnet.nlm.nih.gov/cgi-
bin/sis/htmlgen?HSDB.

Howard PH, Deo PG (1979) Degradation of aryl phosphates in aquatic environments. Bull Environ Contam Toxicol 22(3):337-344.

Ibbotson J, Ibhadon AO (2010) Origin and analysis of aliphatic and cyclic hydrocarbons in northeast United Kingdom coastal marine sediments.
Mar Pollut Bull 60(7): 1136-1141.

Johannsen FR, Wright PL, Gordon DE, et al. (1977) Evaluation of delayed neurotoxicity and dose-response relationships of phosphate esters in the
adult hen. Toxicol Appl Pharmacol 41:291-304.

Kurebayashi H, Tanaka A, Yahama T (1985) Metabolism and disposition of the flame retardant plasticizer, tri-p-cresyl phosphate, in the rat.
Toxicol Appl Pharmacol 77:395-404.

Latendresse JR Brooks CL, Flemming CD, et al. (1994) Reproductive toxicity of butylated triphenyl phosphate and tricresyl phosphate  fluids in
F344 rats.  Fundam Appl Toxicol 22(3):392-399.

NTP (1994) NTP technical report on the toxicology and carcinogenesis studies of tricresyl phosphate in F344/N rats and B6C3F1 mice (Gavage
and feed studies).
                                                              7-486

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                                                  JUNE 2014 DRAFT REPORT


OECD (1998) SIDS initial assessment profile for diphenyl cresyl phosphate. SIAM 7, 25-27.

OECD-SIDS (2002) Diphenyl cresyl phosphate: CAS No: 26444-49-5. SIDS Initial Assessment Profile. Organization for Economic Cooperation
and Development, Screening Information Data Set (SIDS), United Nations Environment Programme.
http://www.chem.unep.ch/irptc/sids/OECDSIDS/26444495.pdf

PBT Profiler Persistent (P), Bioaccumulative (B), and Toxic (T)  Chemical (PBT) Profiler, Version 1.301. Washington, DC: U.S. Environmental
Protection Agency, www.pbtprofiler.net.

PhysProp (2012) Physical properties database. Estimation Programs Interface Suite, Version 4.10. Washington, DC: U.S. Environmental
Protection Agency, http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm.

Saeger VW, Hicks O, Kaley RG, et al. (1979) Environmental fate of selected phosphate esters. Environ Sci Technol 13(7):840-844.

Salamova A, Ma Y, Venier M, et al. (2014) High levels of organophosphate flame retardants in the Great Lakes atmosphere. Environ Sci Technol
Schindler BK, Weiss T, Schutze A, et al. (2013) Occupational exposure of air crews to tricresyl phosphate isomers and organophosphate flame
retardants after fume events. Arch Toxicol 87(4):645-648.

Solbu K, Daae Hanne L, Olsen R et al. (201 1) Organophosphates in aircraft cabin and cockpit air-method development and measurements of
contaminants. J Environ Monit 13(5): 1393-1403.

Takigami H, Suzuki G, Hirai Y, et al. (2009) Flame retardants in indoor dust and air of a hotel in Japan. Environ Int 35(4):688-693.

Takimoto K, Hirakawa T, Ito K, et al. (1999) Source and transport of tricresyl phosphate (TCP) isomers in Kurose river basin. Atmos Environ
33(19):3191-3200.
                                                     J
Takimoto K, Ito K, Mukai T, et al. (1998) Effect of linear-dodecylbenzenesulfonate and humic acid on the adsorption of tricresyl phosphate
isomers onto clay materials. Environ Sci Technol 32(24):3907-3912.

WHO (1990) Tricresyl phosphate. Environmental Health Criteria 110(1990)

Weiner ML, Jortner BS (1999) Organophosphate -induced delayed neurotoxicity of triarylphosphates. Neurotoxicology 20(4):653-674.
                                                              7-487

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                                                 JUNE 2014 DRAFT REPORT


Zeiger E, Anderson B, Haworth S, et al. (1987) Salmonella mutagenicity tests III. Results from the testing of 255 chemicals. Environ Mutagen
9(Suppl. 9): 1-110.

van der Veen I, de Boer J (2012) Phosphorus flame retardants: Properties, production, environmental occurrence, toxicity and analysis.
Chemosphere  88(10): 1119-1153.
                                                             7-488

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                                                           JUNE 2014 DRAFT REPORT
              Triphenyl phosphate (TPP)
                                                  Screening Level Toxicology Hazard Summary

This table only contains information regarding the inherent hazards of flame retardant chemicals. Evaluation of risk considers both the hazard and exposure associated with the
substance including combustion and degradation by-products. The caveats listed in the legend and footnote sections must be taken into account when interpreting the hazard
information in the table.
VL = Very Low hazard L = Low hazard   = Moderate hazard H = High hazard VH = Very High hazard - Endpoints in colored text (VL, L,  , H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].






Chemical






CASRN
Human Health Effects

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Triphenyl phosphate (TPP)
I    115-86-6   |       |  M  |      |      |      |   L  |   H   |  L   |      |  L   |  VL  |  VH  |  VH  |   L    |
                                                                        7-489

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                                                        JUNE 2014 DRAFT REPORT
                                                                                                           CASRN: 115-86-6
                                                                                                           MW: 326.29
                                                                                                           MF: C18H15O4P
                                                                                                           Physical Forms:
                                                                                                           Neat: Solid
                                                                                                           Use: Flame retardant
SMILES: O=P(Oc 1 ccccc 1 )(Oc 1 ccccc 1 )Oc 1 ccccc 1
Synonyms: Phosphoric acid, triphenyl ester; O,O,O-Triphenyl phosphate; TPP
Chemical Considerations: This is a discrete organic chemical with a MW below 1,000. EPI v4.11 was used to estimate physical/chemical and environmental fate
values due to an absence of experimental data. Measured values from experimental studies were incorporated into the estimations.
Polymeric: No
Oligomeric: Not applicable
Metabolites, Degradates and Transformation Products: Diphenyl phosphate (CASRN 838-85-7) and phenol (CASRN 108-95-2) (OECD-SIDS, 2002)
Analog: No analog
Endpoint(s) using analog values: Not applicable
Analog Structure: Not applicable
Structural Alerts: Organophosphates; Neurotoxicity (EPA, 2012).
Risk Phrases: R50/53: Very toxic to aquatic organisms. May cause long-term adverse effects in the aquatic environment (OECD-SIDS, 2002).
Hazard and Risk Assessments: DfE Alternatives Assessment for Furniture Flame Retardancy Partnership and Flame Retardant Alternatives for DecaBDE
Partnership; Toxicological Profile for Phosphate Ester Flame Retardants, September, 2012; OECD SIDS Initial Assessment Report, October 2002 (OECD-SIDS,
2002; EPA, 2005, 2012; ATSDR, 2009).
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JUNE 2014 DRAFT REPORT
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
PHYSICAL/CHEMICAL PROPERTIES
Melting Point (°C)
Boiling Point (°C)
Vapor Pressure (mm Hg)
Water Solubility (mg/L)
Log Kow
Flammability (Flash Point)
50.5
(Measured)
49
Reported as 49-5 0°C (Measured)
>300
(Estimated)
245
Reported at 1 1 mm Hg (Measured)
220
Reported at 5 mm Hg (Measured)
6.28xlO-6at25°C
(Extrapolated)
l.SxlO'6
(Measured)
1.9 (Measured)
Reported at 25 °C
0.75 (Measured)
OECD Guideline 105
0.025 (Measured)
4.59
(Measured)
4.76
(Measured)
220°C (Measured)
Lide, 2008
EC, 2000
EPIv4.11;EPA, 1999
OTSfeil et al., 2006
EC, 2000
Dobry and Keller, 1957
EC, 2000
Saegeretal, 1979
EC, 2000
EC, 2000
Hanschetal., 1995
OECD-SIDS, 2002
Lewis, 2007
Reported in a primary source.
Reported in a secondary source;
consistent with value reported in
primary source.
Cutoff value for high boiling
point compounds according to
HPV assessment guidance.
Reported in a primary source.
Reported in a secondary source;
consistent with value reported in
primary source.
Reported in a secondary source.
Reported in a secondary source.
Reported in a secondary source.
Guideline study reported in a
secondary source.
Reported in a secondary source;
not consistent with other
measured values.
Reported in a primary source.
Reported in a secondary source;
consistent with value reported in
primary source.
No study details reported.
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JUNE 2014 DRAFT REPORT
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
Explosivity
Pyrolysis
pH
pKa
DATA
Not expected to form explosive
mixtures with air (Estimated)

Not applicable (Estimated)
Not applicable (Estimated)
REFERENCE
Professional judgment

Professional judgment
Professional judgment
DATA QUALITY
No experimental data located;
aased on its use as a flame
retardant.
No data located.
Does not contain functional
groups that are expected to
ionize under environmental
conditions.
Does not contain functional
groups that are expected to
ionize under environmental
conditions.
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JUNE 2014 DRAFT REPORT
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
HUMAN HEALTH EFFECTS
Toxicokinetics





Dermal Absorption in vitro
Absorption,
Distribution,
Metabolism &
Excretion
















Oral, Dermal or Inhaled



















Triphenyl phosphate is hydrolyzed in the liver to produce diphenyl phosphate as the primary
metabolite. TPP can be detected in human breast milk. Experimental data for the FM550 (a
mixture made up of a sum total of TBB and TBPH of 50% with additional components identified as
IPTPP and TPP) indicate that absorption of at least one component (TBB) can occur in rats
following oral exposure from gestation through lactation. TBB was detected in tissues of exposed
dams and the pups following exposure to FM550.

Pregnant rats were administered 0, 0. 1
or 1 mg/kg-day of FM550 in the diet
across gestation and through lactation
(GD8-PND21)
FM550 components including TBPH
was detected in adipose, liver, and
muscle tissues in Dams at PND 2 1 with
the highest concentration in the adipose
tissue (768 ng/g w.w. in high dose,
29.6 ng/g w.w. in low dose, < 7.0 ng/g
w.w. in controls). The primary
metabolite of TBB (TBBA) was also
detected in liver tissue of dams on
PND 21.
TBB was detected in pooled PND21
pup adipose tissue. TBB was not
detected in pooled pup adipose tissue
by PND220.
Triphenyl phosphate is hydrolyzed in
rat liver homogenate to produce the
metabolite diphenyl phosphate

Patisauletal., 2013



^^A












OECD-SIDS, 2002; ECHA,
2012

^o data located.
Sfon guideline study indicates
that absorption of this compound
can occur in rats through oral
exposure; the test substance
identified as FM550 is a mixture
made up of TBB, TBPH (sum
total of TBB and TBPH is
approximately 50%), TPP and
IPTPP; it is unclear if
absorption in pups occurred due
to gestational exposure or
through lactation.






Reported in a secondary source.


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JUNE 2014 DRAFT REPORT
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT

Other
Acute Mammalian Toxicity
Acute Lethality
Oral
Dermal
Inhalation
Carcinogenicity

OncoLogic Results
Carcinogenicity (Rat and Mouse)
DATA
TPP concentrations in milk were
analyzed in a human cohort study
conducted between 1997 and 2007.
Median concentration across all
subjects was 8.5 ng/g (min-max values:
3.2-llng/g).
REFERENCE
ECHA, 2012
DATA QUALITY
Limited study details reported in
a secondary source
LOW: Oral LD50 in rats and mice is >5,000 mg/kg and the dermal LD50 in rabbits is >7,900 mg/kg.
No adequate data were located to assess the toxicity of inhalation exposure.
Rat, mouse, oral LD50 >5,000 mg/kg
Rat oral LD50 >6,400 mg/kg
Rat oral LD50 >20,000 mg/kg
Rat oral LD50 = 10,800 mg/kg
Rat oral LD50 = 3,500 mg/kg
Rabbit dermal LD50 >7,900 mg/kg
Rabbit dermal LD50 > 10,000 mg/kg
Rat 1-hour LC50 >200 mg/L
OECD-SIDS, 2002
ATSDR, 2009
OECD-SIDS, 2002
OECD-SIDS, 2002
OECD-SIDS, 2002
ATSDR, 2009
OECD-SIDS, 2002
OECD-SIDS, 2002; ATSDR,
2009
Reported in a secondary source.
Reported in a secondary source.
Study reported in a secondary
source.
Study reported in a secondary
source; number of animals not
reported.
Study reported in a secondary
source. Dose range and number
of animals is not provided.
Reported in a secondary source.
Reported in a secondary source.
Reported in a secondary source.
Insufficient exposure time ( 1
hour), no data on method or
GLP.
MODERATE: OncoLogic modeling indicates a marginal to low potential for Carcinogenicity. No
long-term Carcinogenicity assays were found.
Marginal; likely to have equivocal
carcinogenic activity.
Mouse lung adenoma test: Male A/St
mice (20/group) received i.p. injections
of either 20 mg/kg (18/6 weeks); 40
OncoLogic, 2008
OECD-SIDS, 2002

Reported in a secondary source.
Nonstandard study, limited
histopathology and short-
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JUNE 2014 DRAFT REPORT
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT


Combined Chronic
Toxicity/Carcinogenicity
Other
Genotoxicity

Gene Mutation in vitro
Gene Mutation in vivo
Chromosomal Aberrations in vitro
Chromosomal Aberrations in vivo
DNA Damage and Repair
Other
DATA
mg/kg (3/1 week); or 80 mg/kg. No
significant increase in incidence of
adenoma compared to negative
controls, and positive control
(urethane) produced 19.6
tumors/mouse with 100% survival.


REFERENCE



DATA QUALITY
duration.
No data located.
""Jo data located.
LOW: Triphenyl phosphate was not mutagenic in bacteria or mammalian cells in vitro and did not
cause chromosomal aberrations in vitro. In addition, triphenyl phosphate did not result in DNA
damage in hamster fibroblast cells.
Negative, Ames assay in Salmonella
typhimurium strains TA98, TA100,
TA1537, TA1538 with and without
metabolic activation
Negative, forward mutation assay in
mouse lymphoma L5 178Y cells

Negative in chromosome aberration
test in Chinese hamster V79 cells; with
and without metabolic activation.

Negative, unscheduled DNA synthesis
in hamster fibroblast cells
Negative, mitotic gene conversion
assay in Saccharomyces cerevisiae
with and without activation
ATSDR, 2009; ECHA, 2013
OECD-SIDS, 2002; ECHA,
2013

ECHA, 2013

OECD-SIDS, 2002
OECD-SIDS, 2002
Reported in a secondary source.
Reported in a secondary source.
""Jo data located.
Reported in a secondary source.
No data located.
Reported in a secondary source.
Reported in a secondary source.
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                                                         JUNE 2014 DRAFT REPORT
                                                      Triphenyl phosphate CASRN 115-86-6
              PROPERTY/ENDPOINT
              DATA
       REFERENCE
      DATA QUALITY
Reproductive Effects
LOW: Based on a rat oral reproductive/developmental NOAEL = 690 mg/kg-day for reproductive
effects (highest dose tested). In addition, no histopathological effects on reproductive organs were
reported following 3 weeks of dermal exposure in rabbits. Correlation of TPP in house dust and
decreased sperm counts in humans has been reported, however rat  studies did not measure the
same endpoint, so there is an insufficient data for this effect.
                 Reproduction/Developmental
                 Toxicity Screen
                 Combined Repeated Dose with
                 Reproduction/ Developmental
                 Toxicity Screen
Reproductive/developmental dietary
study; TPP was administered in the
diet for 91 days at concentrations of 0,
0.25, 0.50, 0.75, or 1.0% (~0, 166, 341,
516 or 690 mg/kg-day, respectively).
At the completion of this study,
females were mated with males from
the same group. All remained on the
same diet as in the subchronic study
until day 20 of gestation when dams
were sacrificed. No  signs of parental
toxicity, no reproductive effects
(number pregnant, corpora lutea,
implantations, implantation efficiency,
resorptions).

NOAEL:  690 mg/kg-day (highest dose
tested)
LOAEL: Not established
                 Reproduction and Fertility Effects
Rabbits, dermal (clipped, intact),
5x/week, 3 weeks, 50% solution in
ethanol; no effect on the reproductive
organs reported up to the highest dose
tested (1,000 mg/kg-day)

NOAEL: 1,000 mg/kg-day
OECD-SIDS, 2002; ATSDR,
2009
OECD-SIDS, 2002
                                                                  data located.
Reported in a secondary source.
Reported in a secondary source.
Organs examined by
tiistopathology; there were no
sffects at the highest dose tested;
dermal repeated-dose study.
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JUNE 2014 DRAFT REPORT
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT

Other
Developmental Effects

Reproduction/ Developmental
Toxicity Screen ^^^
DATA
Men living in homes with higher
amounts of TPP in house dust had
reduced sperm count and altered
hormone levels related to fertility and
thyroid function. Each interquartile
range (IQR) TPP increase in house
dust samples was associated with a
19% decrease in sperm concentrations
and a 10% increase in prolactin levels.
REFERENCE
Berts, 2010; Meeker and
Stapleton, 2010
DATA QUALITY
The actual exposure to TPP is
unknown; it is not known if TPP
or other substances found in the
household dust caused or
contributed to the reported
toxicity.
LOW: Based on a rat oral reproductive/developmental NOAEL = 690 mg/kg-day for fetal effects
(highest dose tested). Developmental effects were reported in a study in pregnant Wistar rats
administered the analog mixture FM550 (sum total of TBB and TBPH approximately 50%) during
gestation though lactation (GD8 - PND21); developmental effects included early female puberty,
weight gain, altered exploratory behavior, and increased male left ventricle thickness (LOAEL = 1
mg/kg-day, NOAEL = 0.1 mg/kg-day). It is uncertain which component or components of the FM
550 mixture is driving the reported developmental effects. While the FM 550 mixture data indicates
a High hazard potential, it may be the other components driving the reported toxicity.
There were no data located for the developmental neurotoxicity endpoint. Decreased cholinesterase
activity in pregnant lab animals has been shown to have a negative impact on fetal brain
development. As a result, there is uncertain potential for developmental neurotoxicity for this
substance.


No data located.
         7-497

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JUNE 2014 DRAFT REPORT
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT





























Combined Repeated Dose with
Reproduction/ Developmental
Toxicity Screen















Prenatal Development '"^^
Postnatal Development
Prenatal and Postnatal Development







r
DATA
Reproductive/developmental dietary
study; TPP was administered in the
diet for 9 1 days at concentrations of 0,
0.25, 0.50, 0.75, or 1.0% (~0, 166, 341,
516 or 690 mg/kg-day, respectively).
At the completion of this study,
females were mated with males from
the same group. All remained on the
same diet as in the subchronic study
until day 20 of gestation when dams
were sacrifice. No effects on fetal
endpoints (viability, early or late
deaths, fetal weight, length or
distribution) or skeletal anomalies.
Developmental effects:
NOAEL: 690 mg/kg-day (highest dose
tested)
LOAEL: Not established


Pregnant Wistar rats were administered
0, 0.1 or 1 mg/kg-day of the analog
FM550 in the diet during gestation and
through lactation (GD8 - PND 21);
Maternal toxicity: Increased serum
thyroxine (T4) levels in the high dose
dams compared to controls was
reported. There was no significant
change in triiodothyronine (T3) levels
in dam serum. Decreased hepatic
carboxylesterease activity was also
reported in dams in the high dose
REFERENCE
OECD-SIDS, 2002; ATSDR,
2009; ECHA, 2012







^










Patisauletal., 2013








DATA QUALITY
A LOAEL was not identified;
there were no effects at the
lighest dose tested.















^o data located.
No data located.
Estimated based on data for
FM550 mixture; non guideline
study; the test substance
identified as FM550 is a mixture
made up of TBB, TBPH (sum
total of TBB and TBPH is
approximately 50%), TPP and
IPTPP; it is not clear which
component or components of the
mixture are driving the reported
developmental effects.
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                                            JUNE 2014 DRAFT REPORT
                                         Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                       group.
                                       Developmental toxicity: female
                                       offspring in the high dose group
                                       displayed a significantly earlier vaginal
                                       opening when compared to controls. A
                                       statistically significant increase in
                                       weight was reported in both males and
                                       females in the high dose group at PND
                                       120. This effect persisted through PND
                                       180 to PND 220 with high dose males
                                       and females having significantly higher
                                       weights than same sex controls. A
                                       dose-dependent decrease in the number
                                       of rats to enter with open arms,
                                       (indicating anxiety), was reported in
                                       both male and female offspring.
                                       Increased blood glucose levels were
                                       reported in male offspring in the high-
                                       dose group compared to controls.
                                       There was no statistically significant
                                       difference in heart weight of male or
                                       female offspring. Left ventricular (LV)
                                       free wall thickness was significantly
                                       increased in male offspring in the high
                                       dose group; there were no changes in
                                       LV thickness in females at any dose.
                                               J
                                       Maternal Toxicity:
                                       NOAEL: O.lmg/kg-day
                                       LOAEL: 1  mg/kg-day

                                       Developmental toxicity:
                                       NOAEL: O.lmg/kg-day
                                       LOAEL: 1  mg/kg-day (based on early
                                                        7-499

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JUNE 2014 DRAFT REPORT
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT


Developmental Neurotoxicity
Other
Neurotoxicity

Neurotoxicity Screening Battery
(Adult)
Other
J
DATA
vaginal opening in females, increased
weight in males and females, decreased
open arm behavior, increased blood
glucose levels in males and increased
LV thickness in males)
There were no data located for the
developmental neurotoxicity endpoint.
Decreased cholinesterase activity in
pregnant lab animals has been shown
to have a negative impact on fetal brain
development. As a result, there is
uncertain potential for developmental
neurotoxicity for this substance

REFERENCE

Professional judgment
K 7

DATA QUALITY

Mo data located.
^o data located.
LOW: Based on an adult rat neurotoxicity screening battery NOAEL = 711 mg/kg-day; all other
experimental results are consistent with this hazard designation.
4-month dietary study, 10 rats/dose,
0.25, 0.5, 0.75 or 1% test concentration
(161, 345, 517 or 711 mg/kg-day,
respectively), no neurobehavioral
effects (open field, accelerating
rotarod, forelimb grip strength and
negative geotaxis examinations)
NOAEL: 711 mg/kg-day (highest dose
tested)
LOAEL: Not established
There is potential for neurotoxic effects
based on a structural alert for
organophosphates
(Estimated)
Two female hens/dose in delayed
ATSDR, 2009
Professional judgment
OECD-SIDS, 2002
Reported in a secondary source.
Estimated based on a structural
alert for organophosphates and
professional judgment.
Reported in a secondary source.
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                                            JUNE 2014 DRAFT REPORT
                                         Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                       neurotoxicity test, gavage, 2,000,
                                       3,000, 5,000, 8,000, or 12,500 mg/kg,
                                       no signs of toxicity in-life or at
                                       necropsy

                                       NOAEL > 12,500 mg/kg; highest dose
                                       tested
                                       LOAEL: Not established
                                                  No data on test substance purity.
                                       Several acute oral studies in hens,
                                       administered doses up to 12,500
                                       mg/kg, generally found no signs of
                                       paralysis, histopathological changes in
                                       examined nerve tissues, or behavior
                                       immediately after or during
                                       observation periods of up to 36 days.
                                       However, blood cholinesterase was
                                       decreased by up to 87% in studies
                                       where it was measured.

                                       NOAEL > 12,500 mg/kg; highest dose
                                       tested
                                       LOAEL: Not established
                     OECD-SIDS, 2002
                     Reported in a secondary source.
                     No data on test substance purity.
                                       15-day repeated dose dermal study,
                                       rabbits (10/sex/group) were exposed to
                                       test compound concentrations of 0,
                                       100, and 1,000 mg/kg-day. No
                                       mortality, clinical symptoms, or
                                       changes in body weight, hematology,
                                       clinical chemistry, necropsy, organ
                                       weights and histopathology reported;
                                       only decreased acetyl cholinesterase
                                       levels in plasma, erythrocytes and
                                       brain were reported and not considered
                     OECD-SIDS, 2002
                     Reported in a secondary source.
                     Treatment period only 15 days;
                     quantitative data, effect levels,
                     and test substance purity were
                     not presented in the study report.
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JUNE 2014 DRAFT REPORT
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT


Repeated Dose Effects

J
DATA
to be of toxicological relevance as
there was no clinical or histological
correlation.
REFERENCE

DATA QUALITY

HIGH: Based on weight of evidence including reduced body weight in male rats administered
triphenyl phosphate in the diet for 28-days. The NOAEL of 23.5 mg/kg-day and the LOAEL of
161.4 mg/kg-day span across the High and Moderate hazard designation ranges (DfE criteria are
for 90-day repeated dose studies; criteria values are tripled for chemicals evaluated in 28-day
studies making the High hazard range < 30 mg/kg-day and the Moderate hazard range between 30
and 300 mg/kg-day).
28-day repeated dose dietary study,
rats were fed test substance at
concentrations of 0, 250, 1,000 and
4,000 ppm. Effects on body weights
were observed.
NOAEL (male): 250 ppm (23.5 mg/kg-
day)
LOAEL (male): 1,000 ppm (161.4
mg/kg-day)
3 5 -day repeated-dose oral (dietary)
study, 5 male rats/group, test
compound concentrations of 0, 0.5, and
5.0% (~0, 350, and 3,500 mg/kg-day,
respectively), with a 0.1% (-70 mg/kg-
day) dose replacing the high dose
group after 3 days. Slight reduction in
body weight gain and increase in liver
weight in 350 mg/kg-day dose group.
NOAEL: 70 mg/kg-day
LOAEL: 350 mg/kg-day
4-month repeated-dose dietary study,
Sprague-Dawley rats (10 rats/dose)
ECHA, 2012
OECD-SIDS, 2002
OECD-SIDS, 2002; ATSDR,
2009
Reported in secondary source.
DfE criteria are for 90-day
repeated dose studies. Criteria
values are tripled for chemicals
evaluated in 28-day studies.
Reported in a secondary source.
Limited study details provided.
Reported in a secondary source.
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Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT


Immune System Effects
J
DATA
were fed 0.25, 0.5, 0.75 or l%test
concentration (161, 345, 517 or 711
mg/kg-day, respectively). Reduced
body weight gain (1 1%) at 345 mg/kg-
day.
NOAEL: 161 mg/kg-day
LOAEL: 345 mg/kg-day
15 day repeated-dose dermal study,
rabbits (10/sex/group) were exposed to
test compound concentrations of 0,
100, and 1,000 mg/kg-day. No
mortality, clinical symptoms, or
changes in body weight, hematology,
clinical chemistry, necropsy, organ
weights and histopathology reported;
only decreased acetyl cholinesterase
levels in plasma, erythrocytes and
brain were reported and not considered
to be of toxicological relevance as
there was no clinical or histological
correlation.
In a 3 -month study, rats were orally
gavaged with test substances at 0, 380
and 1,900 mg/kg-day. No toxic effects
were observed.
NOEL: 1,900 mg/kg-day; highest dose
tested
LOEL: Not established
120-day dietary study, rats, 0, 0.25,
0.5, 0.75, and 1% of triphenyl
phosphate (~0, 161, 345, 517 and 711
REFERENCE

OECD-SIDS, 2002
ATSDR, 2009
ATSDR, 2009
DATA QUALITY

Reported in a secondary source.
Treatment period only 15 days;
quantitative data, effect levels,
and test substance purity were
not presented in the study report.
Limited study details reported in
a secondary source. Primary
source is an abstract with few
experimental details.
Reported in a secondary source.
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JUNE 2014 DRAFT REPORT
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT


Skin Sensitization

Skin Sensitization
J
DATA
mg/kg-day); initial, secondary, and
tertiary immunizations with sheep red
blood cells performed at 60, 81, and
102 days, respectively. No significant
effects were reported on the weight and
histopathology of the spleen, thymus
and lymph nodes, and no significant
changes to the humoral response were
reported.
NOAEL: 711 mg/kg-day (highest dose
tested)
Rabbits, up to 1,000 mg/kg-day,
applied 5 days/week for 3 weeks to
intact or abraded skin had no gross or
microscopic effects on the spleen,
thymus, or lymph nodes.
NOAEL: 1,000 mg/kg-day (highest
dose tested)
REFERENCE
K 7
ATSDR, 2009
DATA QUALITY

Reported in a secondary source.
LOW: Based on an experimental study in guinea pigs indicating that triphenyl phosphate is not a
skin sensitizer.
Several human case studies have
reported allergic dermatitis; 15 of
23,192 (0.065%) human volunteers
patch tested from 1950 to 1962 had
positive reactions to cellulose acetate
film containing 7-10% triphenyl
phosphate and 3-4% phthalic esters
A confidential skin Sensitization study
with negative results in guinea pigs
None of the patients tested in two
separate studies of 343 and 174
OECD-SIDS, 2002
Submitted confidential study
OECD-SIDS, 2002
Reported in a secondary source.
Limited study details provided;
patch tests conducted with
mixtures; unclear which
component of mixture caused
low incidence of Sensitization.
Reported in a confidential study.
Reported in a secondary source.
Limited study details provided.
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JUNE 2014 DRAFT REPORT
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT


Respiratory Sensitization
[Respiratory Sensitization
Eye Irritation

Eye Irritation
Dermal Irritation

Dermal Irritation
DATA
patients, respectively, had Sensitization
reactions to triphenyl phosphate
Not sensitizing, guinea pig
maximization test
REFERENCE

OECD-SIDS, 2002
DATA QUALITY

Study reported in a secondary
source; conducted according to
OECD Guide-line 406
No data located.

|No data located.
LOW: Triphenyl phosphate is mildly irritating to the eyes with effects clearing within 72 hours.
Not irritating, rabbits
Mild irritation in rabbit eyes, clearing
within 72 hours
OECD-SIDS, 2002
OECD-SIDS, 2002
Study reported in a secondary
source; conducted according to
OECD Guide-line 405
Study reported in a secondary
source
VERY LOW: Triphenyl Phosphate is not a skin irritant in rabbits
Not irritating, rabbits; semi-occlusive
or occlusive conditions for 4, 24 or 72
hours
Non-irritant, rabbit ^^^
OECD-SIDS, 2002
ATSDR, 2009
Study reported in secondary
source; conducted according to
OECD Guide-line 404
Reported in a secondary source.
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                                                         JUNE 2014 DRAFT REPORT
                                                      Triphenyl phosphate CASRN 115-86-6
              PROPERTY/ENDPOINT
              DATA
REFERENCE
DATA QUALITY
Endocrine Activity
Triphenyl phosphate was found to be inactive in estrogen-receptor binding assays; however, it was
shown to be a moderate androgen-receptor (AR) binder in a competitive binding assay. Triphenyl
phosphate was shown to inhibit human AR in the absence of agonist and to inhibit testosterone-
induced AR activity. In addition, Triphenyl phosphate significantly impaired reproduction in
zebrafish and was correlated with decreased sperm count and altered hormone levels in men.
Increased serum thyroxine (T4) levels were reported in the serum of dams following oral
administration to FM550 (mixture of 50% sum total of TBB and TBPH with additional components
identified as IPTPP and TPP). It is unclear which component or components of the mixture are
driving the endocrine activity effects.
                                                    21-day reproduction study in zebrafish.
                                                    Significant decrease in fecundity,
                                                    significant increases of plasma 17B-
                                                    estradiol (E2) concentrations,
                                                    vitellogenin (VTG) levels, and
                                                    E2/testosterone (T) and E2/11-
                                                    ketotestosterone (11-KT) ratios. Sex-
                                                    dependent changes in transcriptional
                                                    profiles of several genes of the
                                                    hypothalamus-pituitary-gonad (HPG)
                                                    axis.
                                                    Study conducted to determine effects
                                                    of triaryl phosphates on mouse and
                                                    human nuclear receptors. Mouse
                                                    constitutively active receptor (CAR)
                                                        activated by 1.3-fold following
                                                    exposure to TPP. Testosterone-induced
                                                    AR-dependent activity was lowered by
                                                    30-40%.
r
exp<
                                                    Exposure to TPP in zebrafish resulted
                                                    in severe pericardial edema and
                                                    blocked looping of the atrium and
                                                    ventricle. TPP-induced cardiotoxicity
                                                    in zebrafish embryos is mediated
                                   Liu etal., 2013
                                   Honkakoski et al., 2004
                                   McGee etal., 2013
                     Adequate primary source
                     Adequate primary source
                     Adequate primary source
                                                                     7-506

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                                            JUNE 2014 DRAFT REPORT
                                         Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                       through an AHR independent pathway.
                                       In a luciferase reporter-gene assay
                                       using cultured cells, TPP inhibited the
                                       luciferase expression induced by
                                       dihydrotestosterone (10~9 M).

                                       IC50 for antiandrogenic activity =
                                       0.000047 - 0.0006 M
                     Ohyama et al., 2006
                     Primary source in Japanese with
                     English abstract
                                       Endocrine disrupting potential was
                                       investigated using human cells lines
                                       (H295R, MVLN) and zebrafish
                                       plasma. TPP was cytotoxic to H295R
                                       cells (showing <80% cell viability at >
                                       10 mg/L) and significantly increased
                                       E2 and T production. Transcription of
                                       CYP19A1 was significantly up-
                                       regulated and transcription of
                                       SULT1E1 gene was down-regulated.
                                       No binding affinity to E2 receptor in
                                       MVLN cells, but binding of E2 to ER
                                       was reduced in a dose-dependent
                                       manner. Plasma E2 was significantly
                                       increased in fish plasma and T and 11-
                                       KT were decreased (1 mg/L). Changes
                                       in transcription of steroidogenic genes
                                       and vitellogenin gene were observed.
                     Liu etal., 2012
                     Adequate, primary source
                                       Men living in homes with higher
                                       amounts of TPP in house dust had
                                       reduced sperm count and altered
                                       hormone levels related to fertility and
                                       thyroid function. Each interquartile
                                       range (IQR) TPP increase in house
                                       dust samples was associated with a
                     Berts, 2010; Meeker and
                     Stapleton, 2010
                     The actual exposure to TPP is
                     unknown; it is not known if TPP
                     or other substances found in the
                     household dust caused or
                     contributed to the reported
                     toxicity.
                                                        7-507

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Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT

DATA
19% decrease in sperm concentrations
and a 10% increase in prolactin levels.
Pregnant Wistar rats were administered
0, 0.1 or 1 mg/kg-day of the analog
FM550 in the diet during gestation and
through lactation (GD8 - PND 21);
Increased serum thyroxine (T4) levels
(increase of 65%) in the high dose
dams compared to controls was
reported. There was no significant
change in triiodothyronine (T3) levels
in dam serum. There was no reported
statistically significant change in T4 or
T3 levels in pup serum on PND 2 1
when compared to controls.
Inhibited AR activity in COS-1 cells
transfected with human AR both in the
absence of agonist, as well as inhibited
testosterone-induced AR activity by 30
40%. (Measured) ^f
Moderate binding in a competitive
androgen-receptor (AR) binding assay
using recombinant rat protein
expressed in Escherichia coli.
Inactive in a binding assay with the rat
uteri estrogen receptor from
ovariectomized Sprague-Dawley rats
REFERENCE

Patisauletal., 2013
K 7
ATSDR 2009
ATSDR 2009
ATSDR 2009
DATA QUALITY

Estimated based on data for
FM550 mixture; non guideline
study; the test substance
identified as FM550 is a mixture
made up of TBB, TBPH (sum
total of TBB and TBPH is
approximately 50%), TPP and
IPTPP; it is not clear which
component or components of the
mixture are driving the reported
endocrine activity effects.
Reported in a secondary source.
Reported in a secondary source.
Reported in a secondary source
         7-508

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JUNE 2014 DRAFT REPORT
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
Immunotoxicity

Immune System Effects
DATA
REFERENCE
DATA QUALITY
Oral exposure of rats to triphenyl phosphate for 4 months and dermal exposure of rabbits for 3
weeks produced no effects on immune function parameters.
120-day dietary study, rats, 0, 0.25,
0.5, 0.75, and 1% of triphenyl
phosphate (~0, 161, 345, 517 and 711
mg/kg-day); initial, secondary, and
tertiary immunizations with sheep red
blood cells performed at 60, 81, and
102 days, respectively. No significant
effects were reported on the weight and
histopathology of the spleen, thymus
and lymph nodes, and no significant
changes to the humoral response were
reported.
Rabbits, up to 1,000 mg/kg-day,
applied 5 days/week for 3 weeks to
intact or abraded skin had no gross or
microscopic effects on the spleen,
thymus, or lymph nodes.
ATSDR, 2009
K 7
ATSDR, 2009
Reported in a secondary source.
Reported in a secondary source.
ECOTOXICITY
ECOSAR Class
Acute Aquatic Toxicity
Fish LC50
j

VERY HIGH: Based on experimental fish 96-hour LC50 values of 0.4 and 0.85 mg/L.
Freshwater fish (Oncorhynchus mykiss)
96-hour LC50 = 0.4 mg/L
(Experimental)
Freshwater fish (Oncorhynchus mykiss)
96-hour LC50 = 0.85 mg/L
(Experimental)
Freshwater fish (Lepomis macrochirus)
96-hour LC50 = 290 mg/L
(Experimental)
OECD-SIDS, 2002
OECD-SIDS, 2002
OECD-SIDS, 2002
Reported in a secondary source
Reported in a secondary source.
Guideline study.
Limited study details reported in
a secondary source. The study
does not meet important criteria
for standard methods (e.g., test
         7-509

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JUNE 2014 DRAFT REPORT
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT

Daphnid LC50
Other Freshwater Invertebrate LC50
Green Algae EC50
j
DATA

Fish 96-hour LC50 = 1.62 mg/L
(Estimated)
ECOSAR: Neutral organics
Daphnid 48-hour LC50 = 1.28 mg/L
(Experimental)
Daphnid 48-hour EC50 = 1.35 mg/L
Static
(Experimental)
Daphnid 48-hour LC50 =1.0 mg/L
(Experimental) ^^^
Daphnid 48-hour LC50 = 1.28 mg/L
(Estimated)
ECOSAR: Neutral organics
Mysidopsis bahia 96-hour LC50 >0.18 -
0.32 mg/L
(Experimental)
Green algae (Selenastrum
capricornutum ) 96-hour EC50 = 2.0
mg/L
(Experimental)
Green algae 96-hour EC50 = 2.0 mg/L
(Experimental)
REFERENCE

ECOSAR v 1.11
FMC, 1979
OECD-SIDS, 2002
Mayer et al., 1981
ECOSAR v 1.11
OECD-SIDS, 2002
OECD-SIDS, 2002
Mayer et al., 1981
DATA QUALITY
substance concentration at
solubility threshold in water).
ECOSAR also provided results
for the Esters, and Esters
(phosphate) classes; however,
professional judgment indicates
that this compound is not
currently well represented in
ECOSAR vl. 11.
Sufficient study details reported.
Study reported in a secondary
source; conducted according to
US EPA 660/3-75-009.
Sufficient study details reported.
ECOSAR also provided results
for the Esters, and Esters
(phosphate) classes; however,
professional judgment indicates
that this compound is not
currently well represented in
ECOSAR vl. 11.
Reported in a secondary source.
Reported in a secondary source.
Sufficient study details reported.
         7-510

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JUNE 2014 DRAFT REPORT
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT

Chronic Aquatic Toxicity
Fish ChV
J
DATA
Green algae (Scenedesmus
subspicatus) 72-hour LOEC = 0.5-5
mg/L
NOEC = 0.25 - 2.5 mg/L
(Experimental)
Green algae 96-hour EC50 = 1.59 mg/L
(Estimated)
ECOSAR: Neutral organics
REFERENCE
OECD-SIDS, 2002
ECOSAR v 1.11
K 7
DATA QUALITY
Study reported in secondary
source; conducted according to
OECD guideline 201.
ECOSAR also provided results
for the Esters, and Esters
(phosphate) classes; however,
professional judgment indicates
that this compound is not
currently well represented in
ECOSAR vl. 11.
VERY HIGH: Based on an experimental fish 30-day LOEC = 0.037 mg/L. No chronic experimental
data were available for daphnia or algae.
Freshwater fish (Oncorhynchus mykiss)
30-day LOEC = 0.037 mg/L
(Experimental)
Fish (Pimephales promelas) 30-day
LOEC = 0.23 mg/L
NOEC = 0.087 mg/L
There were no changes in hatchability
of eggs, mean total length, and average
we weight of fry. There was reduced
percentage survival of fry through 30
days post-exposure at 0.23 mg/L.
Severe scoliosis was reported in
several fry and erratic swimming was
reported in all fry at 0.23 mg/L.
(Experimental)
Fish ChV = 0.1 5 mg/L
(Estimated)
ECOSAR: Neutral organics
ECHA, 2013
OECD-SIDS, 2002
ECOSAR v 1.11
Reported in a secondary source.
Sufficient study details reported.
ECOSAR also provided results
for the Esters, and Esters
(phosphate) classes; however,
professional judgment indicates
         7-511

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JUNE 2014 DRAFT REPORT
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT

Daphnid ChV
Green Algae ChV
DATA

Daphnid ChV = 0.186 mg/L
(Estimated)
ECOSAR: Neutral organics
Green algae ChV = 0.925 mg/L
(Estimated)
ECOSAR: Neutral organics
REFERENCE

ECOSAR v 1.11
ECOSAR v 1.11
^^A
DATA QUALITY
that this compound is not
currently well represented in
ECOSAR vl. 11.
ECOSAR also provided results
for the Esters, and Esters
(phosphate) classes; however,
professional judgment indicates
that this compound is not
currently well represented in
ECOSAR vl. 11.
ECOSAR also provided results
for the Esters, and Esters
(phosphate) classes; however,
professional judgment indicates
that this compound is not
currently well represented in
ECOSAR vl. 11.
ENVIRONMENTAL FATE
Transport
Henry's Law Constant (atm-m3/mole)
Sediment/Soil Adsorption/Desorption
- KOC
J
Level III fugacity models incorporating available physical and chemical property data indicate that
at steady state, TPP is expected to be found primarily in soil and to a lesser extent, water. Triphenyl
phosphate is expected to have moderate mobility in soil, based on measured Koc values in silty clay,
loamy sand and silt loam. Leaching through soil to groundwater may occur, though it is not
expected to be an important transport mechanism. Triphenyl phosphate may volatilize from moist
soil and water surfaces based on its Henry's Law constant. Volatilization from dry surface is not
expected based on its vapor pressure. In the atmosphere, triphenyl phosphate is expected to exist in
both the vapor phase and particulate phase. Particulates may be removed from air by wet or dry
deposition.
1.2xlO"5 (Measured)
2,5 14 Reported for silty clay
(Measured)
2,736 Reported for silt loam
(Measured)
Huckins et al., 1991
Anderson et al., 1993
Anderson et al., 1993
Reported in a primary source.
Reported in a primary source.
Reported in a primary source.
         7-512

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                                                        JUNE 2014 DRAFT REPORT
                                                     Triphenyl phosphate CASRN 115-86-6
              PROPERTY/ENDPOINT
                                                DATA
                                         REFERENCE
                                  DATA QUALITY
                 Level III Fugacity Model
                                                   3,561 Reported for loamy sand.
                                                   (Measured)
                                                                     Anderson et al., 1993
                                                              Reported in a primary source.
                                   Air = 0.7%
                                   Water = 14.5%
                                   Soil = 75.8%
                                   Sediment = 9.02% (Estimated)
                                  EPIv4.11
                            Reported in a Level III Fugacity
                            model. Experimental data is
                            consistent with partitioning to
                            sediment.
Persistence
                                   LOW: The persistence of triphenyl phosphate is based on experimental data. Under aerobic
                                   conditions in a Japanese MITI ready biodegradability test (OECD Test Guidelines (TG) 301C),
                                   90% biodegradation of triphenyl phosphate occurred after 28 days, and 93.8% triphenyl phosphate
                                   removal as dissolved organic carbon (DOC) occurred over 20 days in an OECD 303A guideline
                                   study. TPP does not meet the criteria for very low persistence because the percent removal in the
                                   criteria does not occur within a 10-day window. In loamy sand, a half-life of 37 days was observed
                                   under aerobic conditions. Triphenyl phosphate was determined to be inherently biodegradable in a
                                   river die-away test, after degrading 100% over 3 days in river water. Triphenyl phosphate may
                                   degrade under anaerobic conditions, with primary degradation of 31.1% after 3 days (89.7% after
                                   40 days) in river sediment. However, removal under anaerobic conditions is not anticipated to be an
                                   important fate process. Triphenyl phosphate will undergo hydrolysis under alkaline conditions,
                                   with half-lives of 3 days at pH 9; it is relatively stable to hydrolysis under neutral and acidic
                                   conditions, with half-lives of 28 days at pH 5 and 19 days at pH 7. Triphenyl phosphate is not
                                   expected to be susceptible to direct photolysis by sunlight, since it does not absorb light at
                                   wavelengths >290 nm. The atmospheric half-live of vapor-phase triphenyl phosphate is estimated to
                                   be 12 hours.
Water
Aerobic Biodegradation
Passes Ready Test: Yes
Test method: OECD TG 301C:
   idified MITI Test (I)
                                                    les
                                                   Mo
                                                   83-94% biodegradation after 28 days at
                                                   100 mg/L of test substance.
                                                   (Measured)
                                                   Study results: 100%/3 days
                                                   Test method: Die-Away

                                                   Reported as inherently biodegradable
OECD-SIDS, 2002
                                                                     OECD-SIDS, 2002
Reported in a guideline study.
                                                              Reported in a secondary source.
                                                                    7-513

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                                                         JUNE 2014 DRAFT REPORT
                                                      Triphenyl phosphate CASRN 115-86-6
              PROPERTY/ENDPOINT
                                                 DATA
                                          REFERENCE
                                  DATA QUALITY
                                                    in a river water/river die-away test
                                                    (Measured)
                 Volatilization Half-life for Model
                 River
                                   4 days (Estimated)
                                   EPIv4.11
                            Reported in the volatilization
                            from water model.
                 Volatilization Half-life for Model
                 Lake
                                   47 days (Estimated)
                                   EPIv4.11
                            Reported in the volatilization
                            from water model.
Soil
Aerobic Biodegradation
Study results: 93.8%/20 days
Test method: 303A: Activated Sludge
Units - Simulation Test
Removal as DOC, using initial
concentration of 5 mg/L with activated
sludge. Reported as inherently
biodegradable. (Measured)
EC, 2000; OECD-SIDS, 2002
Reported in a guideline study.
                                                    Study results: 77%/28 days
                                                    Test method: Other
                                                    Reported as ultimately biodegradable.
                                                    Monsanto Shake Flask Procedure
                                                    (precursor to Closed bottle test).
                                                    (Measured)
                                                                      OECD-SIDS, 2002
                                                               Reported in a secondary source.
                                                    Study results: 82%/28 days
                                                    Test method: CO2 Evolution
                                                    Modified Sturm test. Reported as
                                                    ultimately biodegradable. Measured in
                                                    domestic, adapted activated sludge
                                                    (Measured)
                                                                      OECD-SIDS, 2002
                                                               Reported in a secondary source.
                                                    Study results: 93%/49 days
                                                    Test method: 302A: Inherent -
                                                    Modified SCAS Test
                                                    Reported as inherently biodegradable.
                                                    (Measured)
                                                                      OECD-SIDS, 2002
                                                               Reported in a guideline study.
                                                                     7-514

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JUNE 2014 DRAFT REPORT
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT

Air
Reactivity
Anaerobic Biodegradation
Soil Biodegradation with Product
Identification
Sediment/Water Biodegradation
Atmospheric Half-life
Photolysis
Hydrolysis
J
DATA
Study results: 89.7%/40 days
Test method: CO2 Evolution Test
Primary degradation: 31.1% after 3
days, 89.7% after 40 days in river
sediment. CO2 evolution: 0.8% after 3
days, and 21.9% after 40 days.
(Measured)

86.9%/40 days
Primary degradation in river sediment.
43. 3% after 3 days
86.9% after 40 days (Measured)
1 day (Estimated)
Not a significant fate process
(Estimated)
A 0. 1 mg/L solution (with acetone)
was exposed to a mercury lamp to
examine the effect of UV light on the
degradation of TPP.
High pressure lamp (100W): 100%/20
mins
Low pressure lamp (15W): 100%/1
hour
(Measured)
50%/>28 days
Reported at 25°C; pH 5 (Measured)
50%/19 days
Reported at 25°C; pH 7 (Measured)
REFERENCE
OECD-SIDS, 2002

OECD-SIDS, 2002
EPIv4.11
Mill, 2000; Professional
judgment
EC, 2000
EC, 2000; OECD-SIDS, 2002
OECD-SIDS, 2002
DATA QUALITY
Reported in a secondary source.
^o data located.
Reported in a secondary source.

Triphenyl phosphate does not
contain functional groups that
would be expected to absorb
light of wavelengths >290 nm.
Reported in a secondary source
under laboratory conditions.
Reported in a secondary source.
Reported in a secondary source.
         7-515

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JUNE 2014 DRAFT REPORT
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT


Environmental Half-life
Bioaccumulation

Fish BCF
J
DATA
50%/3 days
Reported at 25°C; pH 9 (Measured)
50%/7.5 days
Reported at pH 8.2 in river/lake water
(Measured)
50%/1.3days
Reported at pH 9.5 in river/lake water
(Measured)
100%/10 minutes atpH 13 (Measured)
75 days (Estimated)
In loamy sand, observed half-lives of
37 days (aerobic) and 21 days
(anaerobic) (Measured)
REFERENCE
EC, 2000; OECD-SIDS, 2002
EC, 2000
EC, 2000
ECHA, 2013
PBT Profiler
OECD-SIDS, 2002
DATA QUALITY
Reported in a secondary source.
Reported in a secondary source.
Reported in a secondary source.
Reported in secondary source.
Documentation of study details
was not sufficient to assess its
reliability.
Half-life estimated for the
predominant compartment, as
determined by the PBT Profiler
methodology.
Reported in a secondary source.
MODERATE: There is moderate potential for bioaccumulation based on experimental BCF values.
132-364 (Rainbow trout) (Measured)
271
Rainbow trout (Measured)
364
Reported as 132-364 in rainbow trout
(Measured)
193
Reported as 84-193 in Medaka
(Measured)
160
Reported as 68-160 in Fathead minnow
Mayer etal., 1981
EC, 2000
OECD-SIDS, 2002
EC, 2000
EC, 2000
Adequate.
Reported in a secondary source.
Insufficient study details to
assess the quality of the reported
values.
Reported in a secondary source.
Reported in a secondary source.
         7-516

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JUNE 2014 DRAFT REPORT
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT


Other BCF
BAF
Metabolism in Fish
DATA
(Measured)
144
Medaka (Measured)
110
Goldfish (Measured)

The pregnant rats were administered 0,
0.1 or 1 mg/kg-day of FM550 by oral
gavage across gestation and through
lactation (GD8-PND 21).
(Estimated by analogy)
73 (Estimated)

REFERENCE

OECD-SIDS, 2002
OECD-SIDS, 2002

Patisaul et al., 2013
^ r
^^b
EPIv4.11

DATA QUALITY

Reported in a secondary source.
Reported in a secondary source.
^o data located.
BAFs were not calculated. This
study did not analyze the
samples for the presence of TPP.
Non guideline study. The test
substance identified as FM550 is
a mixture made up of TBB,
TBPH (CASRN 26040-51-7),
IPTPP (CASRN 68937-41-7)
and TPP (CASRN 1 15-86-6).

^o data located.
ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring
Ecological Biomonitoring
Human Biomonitoring
Triphenyl phosphate has been detected in drinking water in samples collected by the USGS. It has also
been detected in household dust in the United States (at concentrations of (<173-1,798,100 ng/g),
Pakistan, New Zealand, Belgium, Spain and Japan. Triphenyl phosphate has been detected in sediment
from Taihu Lake in China at concentrations ranging from 0.41-5.54 (Jg/kg and in sediment in the U.S. It
has also been detected in river water, seawater, rainwater, snow, wastewater effluent, ambient air, and
indoor air (OECD-SIDS, 2002; Stiles et al., 2008; Stapleton et al., 2009; Berts, 2010; Ali et al., 2012; Cao
et al., 2012; van der Veen and de Boer, 2012; HSDB, 2013; Salamova et al., 2014).
Triphenyl phosphate has been detected in fish tissues. It has also been detected in the blubber of
bottlenose dolphins collected from the Gulf of Mexico (Kuehl and Haebler, 1995; Campone et al., 2010).
Triphenyl phosphate was detected in human milk, adipose tissue and human plasma. This chemical was
not included in the NHANES biomonitoring report (Shah et al., 2006; ECHA, 2012; CDC, 2013).
         7-517

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                                                  JUNE 2014 DRAFT REPORT
ATSDR (2009) Toxicological profile for phosphate ester flame retardants. Atlanta, GA: Agency for Toxic Substances and Disease Registry.

Ali N, Van den Eede N, Dirtu AC, et al. (2012) Assessment of human exposure to indoor organic contaminants via dust ingestion in Pakistan.
Indoor Air 22(3):200-211.

Anderson C, Wischer D, Schmieder A, et al. (1993) Fate of triphenyl phosphate in soil. Chemosphere 27(5):869-879.

Berts KS (2010) Endocrine damper? Flame retardants linked to male hormone, sperm count changes. Environ Health Perspect 118(3):A 130.

CDC (2013) Fourth national report on human exposure to environmental chemicals, updated tables, March 2013. Centers for Disease Control and
Prevention, http://www.cdc.gov/exposurereport/pdf/FourthReport_UpdatedTables_Mar2013.pdf Accessed May 10, 2013.

Campone L, Piccinelli AL, Ostman C, et al. (2010) Determination of organophosphorus flame retardants in fish tissues by matrix solid-phase
dispersion and gas chromatography. Anal Bioanal Chem 397(2):799-806.

Cao S, Zeng X, Song H, et al. (2012) Levels and distributions of organophosphate flame retardants and plasticizers in sediment from Taihu Lake,
China. Environ Toxicol Chem 31(7): 1478-1484.

Dobry A, Keller R (1957) Vapor pressures of some phosphate and phosphonate esters. J Phys Chem 61(10): 1448-1449.

EC (2000) IUCLID dataset triphenyl phosphate. http://esis.jrc.ec.europa.eu/doc/IUCLID/data  sheets/115866.pdf

ECFiA (2012) Triphenyl phosphate. Registered substances. European Chemicals Agency.
http://apps.echa.europa.eu/registered/data/dossiers/DISS-9c823fa6-50fe-Ob74-e044-00144f67d249/AGGR-25e8a69c-b7a3-48f4-8aa3-
df36bOa9735f DISS-9c823fa6-50fe-Ob74-e044-00144f67d249.html#section 1.1.

ECFiA (2013) Triphenyl phosphate. Registered substances. European Chemicals Agency.
http://apps.echa.europa.eu/registered/data/dossiers/DISS-9c823fa6-50fe-Ob74-e044-00144f67d249/DISS-9c823fa6-50fe-Ob74-e044-
00144f67d249 DISS-9c823fa6-50fe-Ob74-e044-00144f67d249.html.

ECOSAR (Ecological Structure Activity Relationship), Version 1.11. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/oppt/newchems/tools/21ecosar.htm.
                                                             7-518

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                                                  JUNE 2014 DRAFT REPORT


EPA (1999) Determining the adequacy of existing data. Washington, DC: U.S. Environmental Protection Agency.
http: //www .epa. gov/hpv/pubs/general/datadeqfn .pdf.

EPA (2005) Furniture flame retardancy partnership/ Design for the Environment (DfE). http://www.epa.gov/dfe/pubs/projects/flameret/index.htm.

EPA (2012) An alternatives assessment for the flame retardant decabromodiphenyl ether (DecaBDE) Draft report.

EPA (2012) Using noncancer screening within the SF initiative. Washington, DC: U.S. Environmental Protection Agency.
http: //www .epa. gov/oppt/sf/pubs/noncan-screen .htm.

EPI Estimation Programs Interface (EPI) Suite, Version 4.11. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm.

FMC (1979) Acute aquatic toxicity of triphenyl phosphate. FMC Industrial Chemical Division.

HSDB (2013) Triphenyl phosphate. Hazardous Substances Data Bank. National Library of Medicine, http://toxnet.nlm.nih.gov/cgi-
bin/sis/htmlgen?HSDB.

Hansch C, Leo A, Hoekman D (1995) Exploring QSAR - hydrophobic, electronic, and steric constants. Washington, DC: American Chemical
Society.

Honkakoski P, Palvimo Jorma J, et al. (2004) Effects of triaryl phosphates on mouse and human nuclear receptors. Biochem Pharmacol 67(1):97-
106.

Huckins JN, Fairchild JF, Boyle TP (1991) Role of exposure mode in the bioavailability of triphenyl phosphate to aquatic organisms. Arch
Environ Contam Toxicol 21:481-485.

Kuehl DW, Haebler R (1995) Organochlorine, organobromine, metal, and selenium residues in bottlenose dolphins (Tursiops truncatus) collected
during an unusual mortality event in the Gulf of Mexico, 1990. Arch Environ Contam Toxicol 28:494-499.

Lewis RJ (2007) Hawley's Condensed Chemical Dictionary. 14 ed. New York: Wiley-Interscience.

Lide  DR (2008) Tris(2-chloroethyl) phosphate. CRC Handbook of chemistry and physics. 88th ed. Boca Raton, FL: CRC Press, Taylor and
Francis Group, 3-512.
                                                              7-519

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                                                  JUNE 2014 DRAFT REPORT


Liu X, Ji K, Choi K (2012) Endocrine disruption potentials of organophosphate flame retardants and related mechanisms in H295R and MVLN
cell lines and in zebrafish. Aquat Toxicol 114-115:173-181.

Liu X, Ji K, Jo A, et al. (2013) Effects of TDCPP or TPP on gene transcriptions and hormones of HPG axis, and their consequences on
reproduction in adult zebrafish (Danio rerio). Aquat Toxicol 134-135:104-111.

Mayer F, Adams WJ, Finley MT, et al. (1981) Phosphate ester hydraulic fluids: An aquatic environmental assessment of pydrauls 50E and 115E.
In: Branson DR Dickson KL, eds. American Society for Testing and Materials STP 737:103-123.

McGee SP, Konstantinov A, Stapleton FIM, et al. (2013) Aryl phosphate esters within a major pentaBDE replacement product induce
cardiotoxicity in developing zebrafish embryos: Potential role of the aryl hydrocarbon receptor. Toxicol Sci 133(1): 144-156.

Meeker JD, Stapleton HM (2010) House dust concentrations of organophosphate flame retardants in relation to hormone levels and semen quality
parameters. Environ Health Perspect 118(3):318-323.

Mill T (2000)  Photoreactions in surface waters. In: Boethling R Mackay D, eds. Handbook of Property Estimation Methods for Chemicals,
Environmental Health Sciences.  Boca Raton: Lewis Publishers, 355-381.

O'Neil MJ, et al., eds (2006) The Merck index: an encyclopedia of chemicals, drugs, and biologicals.  14th ed. Whitehouse Station, N.J: Merck.

OECD-SIDS (2002) Triphenyl phosphate. CAS No: 115-86-6. Screening Information DataSet (SIDS). Organisation for Economic Co-operation
and Development, http://www.inchem.org/documents/sids/sids/115 866 .pdf.

Ohyama K, Nagata S, Hosogoe N, et al. (2006) Hormonal effects of organic phosphate triesters study by the reporter gene assay. Tokyo-to Kenko
Anzen Kenkyu Senta Kenkyu Nenpo 56:333-338.

OncoLogic (2008) U.S. EPA and LogiChem, Inc. 2005, Version 7.0.  2008.

Patisaul HB, Roberts SC, Mabrey N, et al. (2013) Accumulation and  endocrine disrupting effects of the flame retardant mixture Firemaster 550 in
rats: an exploratory assessment. J Biochem Mol Toxicol 27(2): 124-36.

PBT Profiler Persistent (P),Bioaccumulative (B),  and Toxic (T) Chemical (PBT) Profiler, Version 1.301. Washington, DC: U.S. Environmental
Protection Agency, www.pbtprofiler.net.
                                                             7-520

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                                                  JUNE 2014 DRAFT REPORT


Saeger VW, Hicks O, Kaley RG, et al. (1979) Environmental fate of selected phosphate esters. Environ Sci Technol 13(7):840-844.

Salamova A, Ma Y, Venier M, et al. (2014) High levels of organophosphate flame retardants in the Great Lakes atmosphere. Environ Sci Technol
Shah M, Meija J, Cabovska B, et al. (2006) Determination of phosphoric acid triesters in human plasma using solid-phase microextraction and gas
chromatography coupled to inductively coupled plasma mass spectrometry. J Chromatogr A 1 103(2):329-336.

Stapleton HM, Klosterhaus S, Eagle S, et al. (2009) Detection of organophosphate flame retardants in furniture foam and U.S. house dust. Environ
Sci Technol 43 (19): 7490-7495.

Stiles R Yang I, Lippincott RL, et al. (2008) Measurement of drinking water contaminants by solid phase microextraction initially quantified in
source water samples by the USGS. Environ Sci Technol 42(8):2976-2981.van der Veen I, de Boer J (2012) Phosphorus flame retardants:
Properties, production, environmental occurrence, toxicity and analysis. Chemosphere 88(10): 1 1 19-1 153.
                                                             7-521

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                                     JUNE 2014 DRAFT REPORT
Tris (l,3-dichloro-2-propyl) phosphate (TDCPP)
Screening Level Toxicology Hazard Summary
This table only contains information regarding the inherent hazards of flame retardant chemicals. Evaluation of risk considers both the hazard and exposure associated with the
substance including combustion and degradation by-products. The caveats listed in the legend and footnote sections must be taken into account when interpreting the hazard
information in the table.
VL = Very Low hazard L = Low hazard = Moderate hazard = High hazard VH = Very High hazard - Endpoints in colored text (VL, L, , H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].









Chemical









CASRN
Human Health Effects



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Tris (l,3-dichloro-2-propyl) phosphate
(TDCPP)
13674-87-8

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                                              7-522

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JUNE 2014 DRAFT REPORT
C11
CI^AO
ci-"V
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                                                           JUNE 2014 DRAFT REPORT
Polymeric: No
Oligomeric: Not applicable
Metabolites, Degradates and Transformation Products: Metabolites: Bis(l,3-dichloroisopropyl) hydrogen phosphate; bis(l,3-dichloro-2-propyl) phosphate, 1,3-
dichloro-2-propanediol, l,3-dichloro-2-propanol; an unidentified glutathione conjugate; l,3-dichloro-2-propyl, l-chloro-2-propanol phosphate; unidentified diester
metabolites; dimethyl derivative of l,3-dichloro-2-propyl phosphate; bis(l,3-dichloro-2-propyl) l-chloro-2-propanol phosphate;  l-chloro-2-propanol phosphate;
bis( 1,3-dichloro-2-propyl), 1 -carboxy-3-cloro-2-propyl phosphate.

Thermal Degradation products: carbon monoxide, carbon dioxide, hydrochloric acid, chloromethane, chloroethane, vinyl chloride, 1,2-dichloroethane,
chloropropenes, dichloropropenes, 1,2,3-trichloropropane, 2-chloroethanol, l,3-dichloro-2-propanol, acetaldehyde, acrolein, chloroacetone (Lynn etal., 1981; Nomeir
et al.,  1981; Sasaki et al., 1984; NICNAS, 2001; BASF, 2007; EU, 2008; Van den Fade et al., 2013).
Analog: No analogs
Endpoint(s) using analog values: Not applicable
Analog Structure: Not applicable
Structural Alerts: Organophosphates, neurotoxicity. This chemical appears on the List of Chemicals Known to the State to Cause Cancer for the State of California:
California Proposition 65 cancer (EPA, 2012; California EPA, 2013).
Risk Phrases: R40 - limited evidence of a carcinogenic effect. R51/53 - toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment
(ECHA, 2012).
Hazard and Risk Assessments: A risk assessment for this chemical was completed by the European Union (EU) in 2008. This chemical was part of the HPV Data
Summary and Test Plan (Akzo Nobel, 2001; EU, 2008).
                                                                       7-524

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JUNE 2014 DRAFT REPORT
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
PHYSICAL/CHEMICAL PROPERTIES
Melting Point (°C)
Boiling Point (°C)
x^
J
-58
Using differential scanning
calorimetry with a method compliant
with OECD Guideline 102. Freezing
point reported as -40°C. (Measured)
<-20
GLP study in accordance with
Directive 92/69/EC (Measured)
26.66
(Measured)
27
This substance exists as a
supercooled liquid and can crystallize
at temperatures below 27°C.
(Measured)
326
GLP study in accordance with
Sective 92/69/EC. Decomposition
> observed. (Measured)
236 at 5 mmHg
Reported as 236-237 at 5 mm Hg
(Measured)
200 at 4 mmHg
Reported as 200 at 4 mmHg
Akzo Nobel, 2001; EU, 2008
Cuthbert and Mullee, 2002; EU,
2008
Akzo Nobel, 2003; EU, 2008
CERI, 1999
Cuthbert and Mullee, 2002 (as
cited in EU, 2008)
WHO, 1998; Budavari, 2001
Akzo Nobel, 2003 (as cited in
EU, 2008)
Adequate OECD guideline study
reported in a secondary source.
Adequate guideline study
reported in a secondary source.
Sufficient details were not
available to assess the quality of
this study.
Sufficient details were not
available to assess the quality of
this study.
Guideline study reported in a
secondary source.
This value was measured at
lowered pressure.
This value was measured at
lowered pressure.
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JUNE 2014 DRAFT REPORT
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT

Vapor Pressure (mm Hg)
Water Solubility (mg/L)
J
DATA
(Measured)
200 at 4 mmHg Decomposes
Reported as 200 at 4 mmHg
(Measured)
200 Decomposes
Reported as gradual decomposition
above 200°C (Measured)
4.2xlO-8at25°C
Reported as 5.6xlO"6 Pa; GLP study
in accordance with Directive
92/69/EC vapor pressure balance
method. (Measured)
0.01at30°C
Results reported ranged from 0.01
mmHg at 30°C to 0.09 mmHg 20°C.
(Measured)
0.01at30°C
(Measured) ^^^
18.1 (Measured)
Reported as 18.1 ± 1.1 mg/L at 20°C,
GLP study in accordance with
Directive 92/69/EC
42 (Measured)
OECD Guideline 105: Shake-flask
method
100 (Measured)
REFERENCE

WHO, 1998
HSDB, 2003
Tremain, 2002 (as cited in EU,
2008)
^^A
EU, 2008
WHO, 1998; Akzo Nobel, 2001
Cuthbert and Mullee, 2002 (as
cited in EU, 2008)
Akzo Nobel, 2001 (as cited in
EU, 2008)
Eldefrawi et al, 1977 (as cited
DATA QUALITY

Decomposition may occur before
the boiling point is reached. This
value was measured at lowered
pressure.
Decomposition may occur before
the boiling point is reached.
Adequate OECD guideline study
reported in a secondary source.
Values are higher than might be
expected for the main component.
This measured vapor pressure is
high relative to the boiling points
reported for this chemical.
Adequate guideline study
reported in a secondary source.
Adequate OECD guideline study
reported in a secondary source.
Adequate guideline study
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Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT

Log Kow
Flammability (Flash Point)
J
DATA

7 (Measured)
Study performed at 24°C
110 (Measured)
3.69
Using the GLP study in accordance
with 92/69/EC, HPLC method.
Reported as 3.69 ± 0.36 at 20°C.
(Measured)
3.75
Using shake-flask method
(Measured)
3.65
(Measured)
3.8
(Measured)
Auto ignition temperature: 512.77°C
(Measured)
>107.22°C Study performed using
Seta closed cup method (Measured)
252°C Study performed using
Cleveland open cup method
(Measured)
REFERENCE
in WHO, 1998; Budavari, 2001;
EU, 2008)
Hollifield, 1979 (as cited in
Aston etal., 1996; EU, 2008)
CERI, 1999 (as cited in EU,
2008)
Submitted confidential study (as
cited in EU, 2008)
Sasaki et al, 1981 (as cited in
EU, 2008)
HSDB, 2003 (as cited in EU,
2008)
WHO, 1998 (as cited in EU,
2008)
Akzo Nobel, 2003 (as cited in
EU, 2008)
Akzo Nobel, 2003 (as cited in
EU, 2008)
WHO, 1998; NAS, 2000;
HSDB, 2003; EU, 2008
DATA QUALITY
reported in a secondary source.
Sufficient details were not
available to assess the quality of
this study.
Sufficient details were not
available to assess the quality of
this study.
Adequate guideline study
reported in a secondary source.
Consistent value reported in a
secondary source.
Sufficient details were not
available to assess the quality of
this study.
Sufficient details were not
available to assess the quality of
this study.
Sufficient details were not
available to assess the quality of
this study.
Adequate standardized method
reported in a secondary source.
Adequate standardized method
reported in a secondary source.
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Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
Explosivity
Pyrolysis
pH
pKa
DATA
Not expected to form explosive
mixtures with air. (Estimated)
When heated to decomposition, it
emits toxic fumes of Cl+ and Pox
(Measured)
Thermal oxidative degradation in air
at 370°C: Hydrogen halides,
halogenated C2 and C3 species,
acrolein (Measured)
0.1 mole TDCPP heated at 250-
260°C under reduced pressure, 3 mm
Hg, results in an overall yield of 60
wt%. Pyrolysis products identified:
trans-l,3-dichloropropene 26.7%; cis-
1,3-dichloropropene 36.0%; 1,2,3-
trichloropropane 34.4%; l-chloro-2-
propene 2.9% (Measured)
Not applicable (Estimated)
Not applicable (Estimated)
REFERENCE
Professional judgment
Lewis, 2000
HSDB, 2003
^s S
Choudhry and Hutzinger, 1982
Professional judgment
Professional judgment
DATA QUALITY
No experimental data located;
based on its use as a flame
retardant.
Limited study details provided.
Limited study details provided.
Semi -quantitative description of
the pyrolysis products. No
oxygenated or phosphorus-
containing compounds as
pyrolysis products. This study
does not provide a complete
profile of the pyrolysis.
Does not contain functional
groups that are expected to ionize
under environmental conditions.
Does not contain functional
groups that are expected to ionize
under environmental conditions.
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                                                         JUNE 2014 DRAFT REPORT
                                             Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
              PROPERTY/ENDPOINT
                                                DATA
                                         REFERENCE
                                   DATA QUALITY
                                                         HUMAN HEALTH EFFECTS
Toxicokinetics
                                   TDCPP is readily absorbed (100% assumed) by the oral route of exposure. Absorption through
                                   human skin membranes in vitro was calculated to be 6.0 -15.4% of the applied dose. TDCPP is
                                   distributed primarily to the liver, kidney and lung following oral, dermal, and intravenous
                                   exposure. Once in the tissues, the parent compound and metabolites are rapidly excreted. TDCPP is
                                   quickly and extensively metabolized by oxidation to its metabolite, bis (l,3-dichloro-2-propyl)
                                   phosphate (BDCP). Phase I metabolites included BDCPP, bis(l,3-dichloro-2-propyl) l-chloro-2-
                                   propanol phosphate, l,3-dichloro-2-propyl, l-chloro-2-propanol phosphate, a product of two
                                   oxidative dechlorination reactions, and bis(l,3-dichloro-2-propyl),l-carboxy-3-cloro-2-propyl
                                   phosphate. A substitution of a chlorine atom by glutathione was the only phase II metabolite
                                   detected in this study. Excretion occurred primarily via the urine (50%), but also through feces and
                                   expired air. No accumulation in the body is expected due to rapid elimination of the compound.
Dermal Absorption in vitro
                                   In vitro absorption of TCDP in
                                   acetone through skin of adult hairless
                                   mice.
                                   Dermal loading rate: 0.013 - 0.067 -
                                   0.13 (jg/cm
                                   Absorption rate (SD%): 57-45-39
                                   (7.3-11-13)
                                   % Absorption vs. dermal loading:
                                   Inverse, as dose increases percent
                                   absorbed decreases
                                 Buist et al., 2009
                            Adequate study details reported in
                            a secondary source.
Absorption,
Distribution,
Metabolism &
Excretion
Oral, Dermal or Inhaled
Radiolabelled TDCPP was orally
administered to male Sprague-
Dawley rats at a single dose of 0.2, 2,
and 20 (jmol/kg (~ 86 (jg/kg, 860
Mg/kg, and8.6mg/kg);
There was > 90% absorption from the
GI tract within 24 hours; TDCPP was
then distributed in the body to the
kidney > liver > lung > blood >
muscle.
Nomeir et al., 1981 (as cited in
ECHA, 2012)
Study details reported in a
secondary source; Test substance
identified as Fyrol FR-2; test
substance purity not reported;
                                                    TDCPP is readily absorbed by the
                                                                    EU, 2008
                                                              Summary of toxicokinetic studies
                                                                     7-529

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                                            JUNE 2014 DRAFT REPORT
                               Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                       oral route of exposure with 100%
                                       absorption assumed based on animal
                                       studies. Absorption through human
                                       skin membrane in vitro was
                                       calculated to be 15.4, 10.69, and
                                       6.0% for doses of 0.003, 0.01, and
                                       0.12 mg/m3, respectively. TDCPP is
                                       distributed preferentially to the liver,
                                       kidney and lung following oral,
                                       dermal, and intravenous exposure.
                                       Once in the tissues, the parent
                                       compound and metabolites were
                                       rapidly excreted resulting in low
                                       concentration levels in the tissues.
                                       TDCPP is quickly and extensively
                                       metabolized by oxidation to its
                                       metabolite bis (l,3-dichloro-2-propyl)
                                       phosphate (BDCP). Excretion
                                       occurred primarily through the urine
                                       (50%), but also through feces and
                                       expired air. No accumulation in the
                                       body is expected because of rapid
                                       elimination of the compound.
                                                 reviewed in secondary source.
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                                           JUNE 2014 DRAFT REPORT
                               Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
             DATA
       REFERENCE
       DATA QUALITY
   Other
Male Sprague-Dawley rats were
administered an unspecified dose of
14C-TDCPP by intravenous jugular
vein catheters; TDCPP was quickly
distributed from plasma to tissues.
Administered TDCPP was detected in
all tissues after 5 and 30 minutes, but
was only detected in fat after 8 hours.
TDCPP could not be detected in any
tissues 24 hours after administration;
In the tissues, the highest
concentration of TDCPP was in the
kidney (6.75 nmoles/g), liver (2.75
nmoles/g), small intestine (1.98
nmoles/g), and  blood (1.84
nmoles/g);
In rats, BDCP is reported to be the
major metabolite of TDCPP;
Following intravenous administration
of TDCPP, only 19% could be
recovered in the body within a half
hour; 82% of TDCPP remained in the
body, while <0.1% was detected in
the urine and feces after 30 minutes.
The primary route of elimination of
TDCPP is due to its metabolism to
BDCP which is mainly excreted in
the urine and feces.
Lynn et al., 1981 (as cited in
ECHA, 2012)
Study details reported in a
secondary source; Test substance
purity not reported.
                                      Incubation experiments using 1.0
                                      mg/mL HLM or S9 proteins, 50
                                      TBOEP or TCEP, or TCPP, or 20
                                      TPHP or TDCPP and NADPH
                                      regenerating solution in 1 mM total
                                 Van den Bade et al., 2013
                             Study details reported in an
                             abstract.
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Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT








































Acute Mammalian Toxicity
Acute Lethality











Oral









J

DATA
volume were conducted for 1 hour.
There was a 46% and 68% clearance
of the compound in the HLM and S9
incubations, respectively.
Phase I metabolites included the
oxidative dechlorination products of
TDCPP and the hydrolysis product
BDCPP, (Ml), bis(l,3-dichloro-2-
propyl) l-chloro-2-propanol
phosphate (M2), l,3-dichloro-2-
propyl, l-chloro-2-propanol
phosphate (M3), a product of two
oxidative dechlorination reactions
(M4), and bis(l,3-dichloro-2-
propyl), 1 -carboxy-3 -cloro-2-propyl
phosphate (M5).
A substitution of a chlorine atom by
glutathione (M6), was the only phase
II metabolite detected; this adduct
was the primary metabolite present.
REFERENCE









^\










DATA QUALITY




















LOW: TDCPP is not acutely toxic via the oral, dermal and inhalation routes of exposure.
Rat oral LD50 of >2,000 mg/kg;
clinical signs observed during the
first 5 days after dosing included
hypokinesia, piloerection, soiled
coats, ataxia, chromodacryorrhea,
rhinorrhea, and salivation.
Mouse oral LD50 = 2,250 mg/kg
(female): LD50 = 2,670 mg/kg (male);
Treated animals exhibited ataxic gait,
hyperactivity, convulsion and death.
No mortality was observed in
controls or in males at 2,210 mg/kg
Cuthbert, 1989b; WHO, 1998





Kamataetal., 1989





Test substance identified as
Tolgard TDCP MK1; Other
studies available only in
secondary sources reported
similar results.

No body weight or gross necropsy
examination.




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Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT


Dermal
Inhalation
DATA
or females at 1,890 mg/kg.
Rat oral LD50 = 2,830 mg/kg
Rat oral LD50 = 3,160 mg/kg:
No effects at 1,000 mg/kg. Dose-
related depression at or above 2,160
mg/kg; survivors appeared normal by
day 5. No gross lesions in survivors;
fatalities had congestion of heart,
lung, and liver
Rabbit oral LD50 = 6,800 mg/kg;
Clinical signs shortly after dosing
included ataxia, weakness, and
diarrhea; survivors normal by day 9.
Necropsy revealed no abnormalities.
Rat dermal LD50 > 2,000;
No deaths and no clinical signs were
noted 24 hours after treatment.
Rabbit dermal LD50 >4,650 mg/kg;
24-hour method, occluded.
Mortality after 14 days = 0/4. No
overt signs of toxicity and no gross
necropsy findings.
Rat inhalation LC50 >9.8 mg/L;
No mortality after 14 days; initial
REFERENCE

Eldefrawi et al, 1977 (as cited
inATSDR, 2012)
Hall and Kamienski, 1981;
Akzo Nobel, 2001
^s S
Akzo Nobel, 2001
Cuthbert, 1989a;WHO, 1998
Bullock and Heil, 1981; Akzo
Nobel, 2001
Henderson and Jainer, 1981
DATA QUALITY

Limited study details reported in a
secondary source.
Test substance identified as Fyrol
FR-2; purity: not specified.
Test substance identified as Fyrol
FR-2; purity: not specified.
Reported in secondary source;
test substance identified as
TolgardTDCPMKl; study
predates the preferred study
guidelines.
Test substance identified as Fyrol
FR-2; purity not specified; The
available studies predate the
preferred study guidelines, and
did not report purity, but together
indicated no mortality at the
guideline limit dose of 2,000
mg/kg. The report specifying a
14-day observation period is
presented in more detail.
The available study on TDCPP
predates the preferred guidelines.
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Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT


Carcinogenicity

OncoLogic Results
Carcinogenicity (Rat and Mouse)
DATA
signs of moderate depression
Rat inhalation LC50 >5,220 mg/m3
(>5.22mg/L)
REFERENCE

Anderson, 1990; WHO, 1998
DATA QUALITY
The duration was shorter than
currently recommended and no
deaths were observed. Analysis of
aerosol particle size was not
mentioned so it is not known
whether the size was respirable.
Necropsies were not performed.
Purity not specified.
Limited study details reported in
secondary source; test substance
identified as aerosol of TDCPP
(Amgard TDCP); duration
unspecified.
HIGH: Based on sufficient evidence of Carcinogenicity in a two-year combined chronic toxicity and
Carcinogenicity assay in rats. This substance is also included as a substance known to cause cancer
on the Proposition 65 list of chemicals.




No data located.
No data located.
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Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT

Combined Chronic
Toxicity/Carcinogenicity
Other
Genotoxicity

Gene Mutation in vitro
J
DATA
Rat, oral, 2-year combined chronic
toxicity and carcinogenicity assay;
rats (60/sex/group) were administered
0, 5, 20, 80 mg/kg-day (in the diet)
for 2 years. Ten rats/sex/dose were
randomly chosen for termination at
12 months; the remainder at 24
months.
Results: Dose-related increased
incidences of renal cortical adenomas
in both sexes and testicular interstitial
tumors in males (> 20 mg/kg-day);
increased incidence of hepatocellular
adenomas, and carcinomas combined
in both sexes and adrenal cortical
adenomas in females (80 mg/kg-day)
TDCPP is included on the
Proposition 65 list of chemicals
known to cause cancer, July 5, 2013
REFERENCE
Freudenthal and Henrich, 2000;
ATSDR, 2012
^s S
California EPA, 2013
DATA QUALITY
The NRC (2000) concluded that
this study provides sufficient
evidence of carcinogenicity of
TDCPP in rats following chronic
oral exposure. Test substance
purity: 95%; The mode of action
for carcinogenicity could not be
determined.
TDCPP was originally listed on
October 28, 2011.
MODERATE: Based on a weight of evidence including positive results in in vitro gene mutation and
chromosomal aberration tests. Negative results were obtained in in vivo chromosomal aberration
and unscheduled DNA synthesis assays.
Positive in strain TA98 by liquid
preincubation assay (with metabolic
activation)
Positive in strain TA100 by plate
incorporation assay.
Negative: mammalian cell gene
mutation test in V79 Chinese hamster
lung cells (with or without metabolic
activation).
Doses: 0, 0.02 mM TDCPP
AbeandUrano, 1994
Gold et al, 1978; Soederlund et
al., 1985
Soederlund et al., 1985
Limited study details reported.
Limited study details reported.
Test substance purity: not
reported.
         7-535

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                                             JUNE 2014 DRAFT REPORT
                                Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                       Positive: dose-related positive results
                                       for TDCPP and its metabolite 1,3-
                                       dichloro-2-propanol in TA100 with
                                       S9 (phenobarbital-induced) in
                                       standard plate assays at
                                       concentrations up to 500 (ig/plate. In
                                       a liquid preincubation quantitative
                                       assay, results for TDCPP were
                                       essentially negative-only increasing
                                       mutation frequencies at cytotoxic
                                       concentrations (survival <3%).
                                       However, its metabolites increased
                                       mutant frequencies with less
                                       cytotoxicity: l,3-dichloro-2-
                                       propanone positive at <80% survival
                                       and l,3-dichloro-2-propanol positive
                                       at <30% survival.
                     Majeska and Matheson, 1983
                      Limited study details reported.
                                       Positive in Salmonella typhimurium
                                       strains TA97, TA100 (presence of S9
                                       from Aroclor-induced hamster liver)
                                       and in strain TA1535 (in the presence
                                       of S9 from Aroclor-induced rat or
                                       hamster liver); negative in S.
                                       typhimurium strains TA98
                                       andTA1537 with or without the
                                       presence of exogenous metabolic
                                       activation.
                                       Doses: 0, or 5 concentrations between
                                       10 and 10,000 (jg/plate
                     Mortelmans etal., 1986
                      Test substance purity reported as
                      94.4%; positive controls gave
                      expected increases; solvent
                      control and all other test
                      combinations were negative.
                                       Negative in S. typhimurium strains
                                       TA98, TA100, TA1535, TA1537,
                                       TA1538 (without metabolic
                                       activation) and in strains TA98,
                     Nakamura et al., 1979
                      Test substance purity: Assayed as
                       94% TDCPP, plus -6% bis(l-
                      chloromethyl-2-chloroethyl)(2,3-
                      dichloropropyl) phosphate.
                                                         7-536

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                                            JUNE 2014 DRAFT REPORT
                               Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
              DATA
        REFERENCE
       DATA QUALITY
   Gene Mutation in vivo
                                       TA1537, orTA1538 (with metabolic
                                       activation); weakly positive in TA100
                                       and TA1535 at the highest
                                       concentrations (with metabolic
                                       activation)
                                       Doses: 0,  10, 30, 100,. 300 (jg/plate
                                       Negative: mammalian cell gene
                                       mutation test in mouse lymphoma
                                       L5178Y cells (with or without
                                       metabolic activation).
                                       Doses: 0, and five concentrations up
                                       to ~32 nL/mL without S9, and six
                                       concentrations up to 70 nL/mL with
                                       S9.
                                  Brusick et al., 1979; Matheson
                                  andBrusick, 1981
                             Test substance purity: not
                             reported; test conditions chosen
                             based on preliminary assays so
                             that 50% growth reduction
                             occurred at highest concentration.
                                       Negative: TDCPP was not mutagenic
                                       in S. typhimurium strains TA100,
                                       TA1535, orTA1538 (without
                                       activation or when Aroclor-induction
                                       was used to prepare the S9 fraction).
                                  Privaletal., 1977
                             The highest exposure level was
                             10 (iL per plate.
Negative: sex-linked recessive lethal
test in Drosophila melanogaster (100
males/concentrations); TDCPP added
to feed of males for 24 hours,
subsequently mated with virgin
unexposed females; no metabolic
activation.
Doses: 2.5 and 25% in feed (1% gum
tragacanth in 3% sucrose)
Brusick and Jagannath, 1977;
Jagannath and Brusick, 1981;
WHO, 1998
Test substance: tragacanth in 3%
sucrose.
                                                        7-537

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                                           JUNE 2014 DRAFT REPORT
                               Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
             DATA
       REFERENCE
      DATA QUALITY
   Chromosomal Aberrations in vitro
Positive in chromosome aberration
assay in mouse lymphoma L5178Y
cells (with PCB- or phenobarbital-
induction metabolic activation
compared to noninduced S9
activation)
Brusick et al., 1979; Matheson
andBrusick, 1981
Test substance purity: not
reported.
                                      Positive in sister chromatid exchange
                                      assay in mouse lymphoma L5178Y
                                      cells; TDCPP increased the incidence
                                      of sister chromatid exchanges in
                                      mouse lymphocytes under all three
                                      test conditions.
                                 Brusick et al., 1979; Matheson
                                 andBrusick, 1981
                            Test substance purity: not
                            reported.
                                      Negative for chromosomal
                                      aberrations or polyploidy in CHO
                                      cells with or without metabolic
                                      activation
                                 EU, 2008
                             Sufficient study details from
                             unpublished study reported in a
                             secondary source.
                                                       7-538

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Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT



























Chromosomal Aberrations in vivo


























DATA
Negative in an in vivo bone marrow
chromosomal aberration assay in
CD1 mice (4-8 males/group);
Concentrations: 0, 0.05, 0.17, and 0.5
mL/kg; using the specific gravity of
1.52, the doses were 0, 76, 260, or
760 mg/kg. The highest dose was the
maximum tolerated dose. Negative
control was DMSO. Exposure
duration, frequency: By oral gavage
in once or daily on 5 consecutive
days. Mice were sacrificed at 6, 24,
and 48 hours after single dose or 6
hours after the last of 5 doses.
Between 233 and 400 cells were
scored. Triethylenemelamine was
used as the positive control.
No evidence of increased frequency
of chromosomal aberrations with
TDCPP. Positive control produced
expected large increase in
micronucleated polychromatic
erythrocytes.
TDCPP administered to mice (route
unspecified) at a dose of 2,000 mg/kg
did not induce micronuclei in bone
marrow erythrocytes
REFERENCE
Brusick et al., 1979; Matheson
andBrusick, 1981






^L
^V













Thomas and Collier, 1985;
WHO, 1998


DATA QUALITY
Test substance: Technical grade;
purity not reported





















Limited study details reported in a
secondary source.


         7-539

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Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT

































DNA Damage and Repair































Other
DATA
Negative in unscheduled DNA
synthesis in mammalian cells
(hepatocytes) in culture;
TDCPP was not genotoxic at 0.05
mM; at 0. 1 mM, a moderate response
was observed in hepatocytes from
untreated rats, but not phenobarbital-
treated rats. TBPP was used as the
positive control and yielded positive
results in induced and non-induced
hepatocytes.
Negative for unscheduled DNA
synthesis (UDS) in rat hepatocytes;
male Hsd:SD rats were administered
TDCPP by gavage at doses of 500,
1,000, and 2,000 mg/kg in 0.5%
methylcellulose; Rats were sacrificed
at 2-4 hours and at 14-16 hours
following dosing; vehicle controls
and positive controls
(dimethylnitrosamine) were used;
hepatocytes were cultured at the
selected sacrifice time points and
analyzed for UDS;
All treated groups at both time points
produced a negative response for
UDS and the vehicle and positive
control groups resulted in an
appropriate response.
Negative for unscheduled DNA
synthesis (UDS) assay in primary rat
hepatocyte cells.

REFERENCE
Soederlund et al., 1985








^\

EU, 2008

















EU, 2008



DATA QUALITY
Test substance purity: not
reported.









Sufficient study details from
unpublished study reported in a
secondary source.















Conducted according to OECD
guideline 486 and EC method
B.39
No data located.
         7-540

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JUNE 2014 DRAFT REPORT
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
Reproductive Effects

Reproduction/Developmental
Toxicity Screen
Combined Repeated Dose with
Reproduction/ Developmental
Toxicity Screen
Reproduction and Fertility Effects
J
DATA
REFERENCE
DATA QUALITY
HIGH: Based on a LOAEL of 5 mg/kg-day (NOAEL not established) for atrophy and decreased
secretory product of the seminal vesicle in an oral two-year combined chronic toxicity and
carcinogenicity assay in rats. Effects were also seen in the testes (eosinophilic material in lumen,
periarteritis nodosa) at 20 mg/kg-day and the epididymis (oligospermia and degenerated seminal
product) at 80 mg/kg-day.


Rat, oral, 2-year combined chronic
toxicity and carcinogenicity assay;
Rats (60/sex/group) were
administered 0, 5, 20, 80 mg/kg-day
(in the diet) for 2 years. Ten
rats/sex/dose were randomly chosen
for termination at 12 months; the
remainder at 24 months.
Reproductive effects in males
included effects on seminal vesicles
(atrophy, decreased secretory
product) at > 5 mg/kg-day, testes
(eosinophilic material in lumen,
periarteritis nodosa) at > 20 mg/kg-
day, and epididymis (oligospermia
and degenerated seminal product) at
80 mg/kg-day.
NOAEL: Not established
LOAEL: 5 mg/kg-day
In a 12-week oral study, rabbits were
gavaged with TDCPP and then mated
with untreated females.

r
Freudenthal and Henrich, 2000
Wilczynski et al., 1983;
ATSDR, 2012
No data located.
No data located.
The authors reported the lowest
dose of 5 mg/kg-day as a NOAEL
and the mid-dose of 20 mg/kg-
day as a LOAEL. However, as
evaluated in NRC (2000), the
lowest dose of 5 mg/kg-day was a
LOAEL for atrophy and
decreased secretory product of the
seminal vesicle; test substance
purity: 95%; These effects for
reproductive tissues are reported
from a 2-year combined chronic
toxicity and carcinogenicity
assay, and not from a study
designed to test reproductive
effects specifically; other
reproductive parameters were not
examined.
Data not sufficient to satisfy the
reproductive toxicity endpoint
since it was described only in an
         7-541

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JUNE 2014 DRAFT REPORT
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT


Other
Developmental Effects

Reproduction/ Developmental
Toxicity Screen
Combined Repeated Dose with
Reproduction/ Developmental
Toxicity Screen
DATA
Increased absolute kidney weight and
relative liver weight in high dose
animals; No effects on male
reproductive parameters was
reported; there were no
histopathological findings in testes, or
epididymides.
NOAEL: 20 mg/kg-day
LOAEL: 200 mg/kg-day (highest
dose tested)
(Estimated by analogy)

REFERENCE
^s S

DATA QUALITY
abstract and females were not
tested.
No data located.
MODERATE: Based on NOAELs of 100 and 200 mg/kg bw-day in two prenatal developmental
toxicity studies in rats. A LOAEL of 400 mg/kg-day was established for increased resorptions and
fetal mortality that occurred in conjunction with maternal toxicity and lethality. In addition,
abnormal development (short tail, reduced body weight) was evident in a study examining
developmental phenotypes in zebrafish embryos/larvae. This study adds weight of evidence for
developmental toxicity of TDCPP.
There were no data located for the developmental neurotoxicity endpoint.

^


No data located.
No data located.
         7-542

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Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT






























Prenatal Development





























DATA
Rat (Sprague-Dawley), oral (gavage),
0, 25, 100, or 400 mg/kg-day on GD
6-15.
Maternal: Clinical signs of toxicity
(urine stains, hunched appearance,
and alopecia) at 400 mg/kg-day;
decreased food consumption (100,
400 mg/kg/day); overall body
weights reduced in high-dose dams
Developmental: No effects on
implantation efficiency or mean
number of corpora lutea. Increased
number of resorptions and decreased
fetal viability (400 mg/kg-day);
decreased skeletal development,
related to growth retardation and
decreased fetal size (400 mg/kg/day);
incidences of malformations were not
determined to be treatment related.
Maternal toxicity:
NOAEL: 25 mg/kg-day
LOAEL: 100 mg/kg-day (based on
clinical signs and transient decreased
body weight gain)
Developmental toxicity:
NOAEL: 100 mg/kg-day
LOAEL: 400 mg/kg-day (based on
increased resorptions and fetal
mortality)
Rat (Wistar), oral (gavage), exposed
REFERENCE
Kappetal., 1981;ATSDR
2012






J^




















Tanakaetal., 1981
DATA QUALITY
Adverse developmental effects
occurred only at maternally lethal
doses. Test substance: Fyrol-2;
test substance purity not reported.
Conducted by methods consistent
with OECD Guideline 141























Adverse developmental effects
         7-543

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JUNE 2014 DRAFT REPORT
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT




















































DATA
to 0, 25, 50, 100, 200, or 400 mg/kg-
day on GD 7-19.
Maternal: mortality (400 mg/kg-day);
decreased food consumption (200,
400 mg/kg-day), reduced terminal
body weight on GD20 (400 mg/kg-
day); increased absolute and relative
kidney weight (200, 400 mg/kg-day)
Developmental: No effect on corpora
lutea, mean number of implants, fetal
body weight, fetal sex ratio, or
number of dead or live fetuses. No
effect on behavior and functional test.
Increased number of dead fetuses and
live fetuses (400 mg/kg-day, due to
the loss of one whole litter); No
malformations were reported in any
of the treated groups.
Maternal toxicity:
NOAEL: 100 mg/kg-day
LOAEL: 200 mg/kg-day (based on
increased kidney weight)
Developmental toxicity:





^r

NOAEL: 200 mg/kg-day
LOAEL: 400 mg/kg-day (based on
increased fetal death)
Zebrafish embryos/larvae exposed to
TDCPP (3 (JVI) from 0.75 h
postfertilization (hpf). Inhibition of
cell rearrangement (4 hpf), delay in
REFERENCE








J

















Fuetal.,2013



DATA QUALITY
occurred only at maternally lethal
doses; test substance purity not
reported.























Data are from a non-standard
study for assessing hazard for this
endpoint.

         7-544

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JUNE 2014 DRAFT REPORT
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT


Postnatal Development
Prenatal and Postnatal Development
Developmental Neurotoxicity
Other
Neurotoxicity

Neurotoxicity Screening Battery
(Adult)
Other
x^
J
DATA
epiboly (5.7 and 8.5 hpf), abnormal
development (short tail, reduced body
size) and death (14-45 hpf). Trunk
curvature was observed to be the
main phenotype (96 hpf) in larvae
exposed to 1 or 3 (JVI TDCPP.


Uncertain concern for developmental
neurotoxicity based on the potential
for Cholinesterase (ChE) inhibition in
dams that may result in alterations of
fetal neurodevelopment (Estimated)

REFERENCE



Professional judgment

DATA QUALITY

No data located.
No data located.
Estimated based on a structural
alert for organophosphates for the
neurotoxicity endpoint.
No data located.
LOW: Based on a weight of evidence. TDCPP did not produce neurotoxicity in acute, chronic or
developmental studies in rats or in acute and subchronic studies in hens. TDCPP induced oxidative
stress in undifferentiated PC12 cells, but did not impair cell growth or viability. However, there
may be some potential for neurotoxicity based on a structural alert for organophosphates.

Rat (Wistar), oral (gavage), exposed
to 0, 25, 50, 100, 200, or 400 mg/kg-
S1 on GD 7-19;
en dams from each of the control
200 mg/kg-day groups were
permitted to litter normally and
evaluated for implantation sites,
delivery index, number of live
offspring at birth and survival on
PND 4, at 4th week, and at 10th week.
Litters were culled to 10 offspring on
postnatal day 4 (PND 4) and

Tanakaetal., 1981
No data located.
Full descriptions of these tests
were not available in the English
summary and therefore could not
be compared to the guideline
protocol; this study does not fully
satisfy the developmental
neurotoxicity endpoint because it
omitted some parameters
specified under the guideline:
developmental landmarks for
sexual maturity, auditory startle
test, and neurohistopathological
         7-545

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                                            JUNE 2014 DRAFT REPORT
                                Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
              DATA
REFERENCE
DATA QUALITY
                                       subjected to behavioral tests (open
                                       field, water maze, rota rod, inclined
                                       screen, pain reflex and Preyer's
                                       reflex). Absolute organ weights of iM
                                       organs plus testis, uterus and ovary
                                       were measured in offspring.
                                       In postnatal observations, there were
                                       no effects on behavior and functional
                                       tests (< 200 mg/kg-day)

                                       NOAEL: 200 mg/kg-day (highest
                                       tested non-lethal dose)
                                       LOAEL: Not established
                                                               examinations.
                                       In a 2-year combined chronic toxicity
                                       and carcinogenicity assay, rats
                                       (60/sex/group) were fed 0, 5, 20, 80
                                       mg/kg-day. Ten rats/sex/dose were
                                       randomly chosen for termination at
                                       12 months; the remainder at 24
                                       months.
                                       There were no lesions of the brain or
                                       spinal cord in rats exposed to TDCPP
                                       at doses as high as 80 mg/kg-day
                                       reported.
                                  Freudenthal and Henrich, 2000
                      Test substance purity: 95%.; no
                      functional tests of neurotoxicity
                      were performed; this study was a
                      combined chronic
                      toxicity/carcinogenicity assay,
                      and was not designed to
                      specifically examine neurological
                      endpoints.
                                       NO
   AEL: 80 mg/kg-day (highest dose
tested)
LOAEL: Not established
                                       Oral, rat (10 rats/dose), 0, 2,000, or
                                       3,980 mg/kg in corn oil was
                                       administered by gavage to male
                                       Sprague-Dawley rats;
                                       There were no effects on plasma or
                                  Bullock et al., 1981
                      Test substance reported as Fyrol
                      FR-2; purity not specified.
                                                        7-546

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                                            JUNE 2014 DRAFT REPORT
                                Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                       erythrocyte cholinesterase levels
                                       measured at 4 or 14 hours after
                                       dosing.

                                       NOAEL: >3,980
                                       LOAEL: Not established
                                       Acute oral delayed neurotoxicity in
                                       White Leghorn Hens (4/dose); dosed
                                       (gavage) at 10,000 mg/kg once;
                                       Positive control: 500 mg/kg tri-ortho-
                                       tylol phosphate (TOCP), negative
                                       control: 15 mg/kg tetraethyl
                                       pyrophosphate (TEPP).
                                       Toxic signs were not reported
                                       specifically for TDCPP, but for all
                                       compounds tested at the maximum
                                       tolerated dose, signs included
                                       listlessness and ataxia. Inhibition of
                                       NTE activity was 7% for TDCPP and
                                       the negative control TEPP, but 85%
                                       for the positive control (TOCP).

                                       NOAEL: Not established
                                       LOAEL: 10,000 mg/kg
                    Morey et al., 1978
                      Test substance: Fyrol FR-2;
                      conflicting reports of test
                      substance purity (one part of the
                      report stated that the purity was
                      not reported, whereas another part
                      of the report indicated purity
                      >99%); the current guideline
                      specifies that testing is not
                      necessary at doses above 2,000
                      mg/kg; unpublished industrial
                      acute study performed prior to the
                      existence of the guidelines, do not
                      entirely conform to current
                      guidelines, and may lack detail
                      such as the purity of the TDCPP
                      sample; only one test substance
                      dose administered.
                                       Acute oral delayed neurotoxicity in
                                       Hohite Leghorn Hens (4/dose); dosed
                                       (gavage) at 420 mg/kg-day; Positive
                                       control: 90 or 120 mg/kg-day tri-
                                       ortho-tylol phosphate (TOCP);
                                       No overt signs of neurotoxicity with
                                       TDCPP treatment. Positive control
                                       caused inability to walk,
                                       hypertension, ataxia, and prostration.
                    Bullock and Kamienski, 1972;
                    Bullock and Kamienski, 1981b;
                    WHO, 1998
                      Test substance: Fyrol FR-2, purity
                      not reported; Navy MIL-H-
                      19457B (SHIPS) protocol;
                      Necropsy not performed;
                      unpublished industrial acute study
                      performed prior to the existence
                      of the guidelines, do not entirely
                      conform to current guidelines,
                      and may lack detail such as the
                                                        7-547

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Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
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J

DATA

NOAEL: 420 mg/kg-day (only dose
tested)
LOAEL: Not established
Subchronic oral delayed
neurotoxicity in Hohite Leghorn
Hens (10/dose); dosed (gavage) at 0,
4, 20, 100 mg/kg-day for 90 days;
TOCP was the positive control.
Hens treated with TDCPP at the high
dose exhibited mean reductions in
body weight during the latter part of
the study, but no overt signs of
neurotoxicity and no
histopathological effects in the
nervous tissues. Positive control hens
exhibited consistently lower body
weight gain, clinical signs of toxicity
(locomotor impairment and ataxia)
that became more severe with time.
Histopathology results were not
reported for the positive control.
NOAEL: Not established
LOAEL: Not established
Undifferentiated PC 12 cells exposed
to TDCPP for 24 hours; rapid mitotic
inhibition in undifferentiated cultures
and significantly reduced cell
numbers during neurodifferentiation.
TDCPP induced oxidative stress, but
did not impair cell growth or viability
There is potential for neurotoxicity
REFERENCE




Akzo Nobel, 2001



4<















Dishawetal., 2011






Professional judgment
DATA QUALITY
purity of the TDCPP sample; only
one test substance dose
administered.

Test substance purity not
reported. Robust summary from
Akzo-Nobel, 200 la; unpublished,
unidentified study dated 1979;
histopathology was not reported
for the positive control;
unpublished industrial acute study
performed prior to the existence
of the guidelines, do not entirely
conform to current guidelines,
and may lack detail such as the
purity of the TDCPP sample.








Adequate study details reported in
a primary source.





Estimated based on a structural
         7-548

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                                                          JUNE 2014 DRAFT REPORT
                                             Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
              PROPERTY/ENDPOINT
             DATA
REFERENCE
DATA QUALITY
                                                     based on a structural alert for
                                                     organophosphates. (Estimated)
                                                               alert for organophosphates and
                                                               professional judgment.
Repeated Dose Effects
HIGH: Based on a LOAEL of 5 mg/kg-day for atrophy and decreased secretory product of the
seminal vesicle in an oral 2-year combined chronic toxicity and carcinogenicity assay in rats
(NOAEL not established). Effects were also seen in the testes (eosinophilic material in lumen,
periarteritis nodosa) at 20 mg/kg-day and the epididymis (oligospermia and degenerated seminal
product) at 80 mg/kg-day.
                                                     Rat, oral, 2-year combined chronic
                                                     toxicity and carcinogenicity assay;
                                                     Rats (60/sex/group) were
                                                     administered 0, 5, 20, 80 mg/kg-day
                                                     (in the diet) for 2 years.
                                                     Increased mortality in high-dose
                                                     males; reduced body weights in high-
                                                     dose males and females; signs of
                                                     anemia (lower hemoglobin,
                                                     hematocrit, erythrocyte counts) in
                                                     high-dose rats. At the mid-dose,
                                                     increased absolute and relative
                                                     kidney weight males and females,
                                                     absolute liver weight and relative
                                                     thyroid weight in males, and relative
                                                     liver weight in females; increased
                                                     relative liver weight in males and
                                                     absolute and relative thyroid weights
                                                     in females at the high dose.
                                                     Increased incidences of nonneoplastic
                                                     lesions (not strictly dose-related in
                                                     that incidences were depressed in
                                                     high-dose groups): Kidney lesions
                                                     (convoluted tubule hyperplasia) in
                                                     males at > 20 mg/kg-day and in
                                                     females at 80 mg/kg-day. Other
                                  Freudenthal and Henrich, 2000;
                                  NRC, 2000
                     Freudenthal and Henrich (2000)
                     reported the lowest dose of 5
                     mg/kg-day as a NOAEL and the
                     mid-dose of 20 mg/kg-day as a
                     LOAEL. However, as evaluated
                     in NRC (2000), the lowest dose of
                     5 mg/kg-day was a LOAEL for
                     atrophy and decreased secretory
                     product of the seminal vesicle;
                     test substance purity: 95%.
                                                                      7-549

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                                            JUNE 2014 DRAFT REPORT
                                Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                       systemic lesions at 80 mg/kg/day
                                       involved the parathyroid
                                       (hyperplasia) in males and the liver
                                       (foci) and spleen (erythroid/myeloid
                                       hyperplasia) in females. Lesions in
                                       the vesicles (atrophy, decreased
                                       secretory product) at > 5 mg/kg-day,
                                       testes (eosinophilic material in lumen,
                                       periarteritis nodosa) at > 20 mg/kg-
                                       day, and epididymis (oligospermia
                                       and degenerated seminal product) at
                                       80 mg/kg-day.

                                       NOAEL: Not established
                                       LOAEL: 5 mg/kg-day (based on
                                       atrophy and decreased secretory
                                       product of the seminal vesicle;
                                       hyperplasia of convoluted tubule
                                       epithelium in males at 24 months)
                                       In a 90-day study, mice (Slc/ddY)
                                       were fed TDCPP at 0, 0.01, 0.04,
                                       0.13, 0.42, and 1.33 % in the diet
                                       (average daily dose: males-0, 13.2,
                                       47.3, 171.0, 576.0, 1,792.3 mg/kg-
                                       day; female - 0, 15.3, 62.5, 213.6,
                                       598.0, 1,973.1 mg/kg-day)
                                       Slight anemia in males at 0.42% after
                                       3 months; Anemia in females at 0.13
                                       % after  1 month and 0.42% at 3
                                       months; Elevated albumin/globulin
                                       rations in males in all groups at 3
                                       months; Increased alkaline
                                       phosphatase in females at 0.42% at 1
                    Kamataetal., 1989
                      Study reported limited relevant
                      information in English abstract
                      and data tables; histopathology
                      analysis appears limited to the
                      liver.
                                                        7-550

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                                            JUNE 2014 DRAFT REPORT
                                Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                       month, but did not differ from
                                       controls at the 3 month evaluation;
                                       dose-related increase in organ relative
                                       liver weight (0.13%) and relative
                                       kidney weight (0.42%), in males at 3
                                       months compared to controls;
                                       Increased relative liver weight
                                       (0.04%), absolute liver weight
                                       (0.42%), absolute and relative kidney
                                       weight (0.13%); slight focal necrosis
                                       of the liver was observe in 2/12^
                                       females at 0.42%.

                                       NOAEL: 0.01% (15.3 mg/kg-day)
                                       LOAEL: 0.04% (62.5 mg/kg-day )
                                       based on increased relative liver
                                       weight in females
                                       Morbidity survey conducted on 124
                                       male, full-time workers with
                                       occupational exposure at a TDCPP
                                       manufacturing plant to determine if
                                       there was an increased incidence of
                                       respiratory conditions among those
                                       exposed;
                                       The survey population had an
                                       occupational health program physical
                                       examination in 1981; survey group
                                       divided into groups according to age
                                       (20-29, 30-39, 40-49, >50); The
                                       control population consisted of non-
                                       exposed workers; The ratio of
                                       exposed to non-exposed workers was
                                       93:31 people; Full-shift time
                    Murphy, 1981;EU, 2008
                      Cohort study details reported in a
                      secondary source; the non-
                      exposed (control) populations was
                      about one third the size of the
                      exposed population; it is also
                      difficult to determine if non-
                      exposed workers may have been
                      previously exposed, or if exposed
                      workers may have been exposed
                      to other compounds outside of
                      their occupational environment;
                      actual  exposure doses were not
                      reported.
                                                        7-551

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                                             JUNE 2014 DRAFT REPORT
                                Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
              DATA
        REFERENCE
       DATA QUALITY
   Immune System Effects
                                       weighted averages (TWA) were
                                       determined for the breathing zone for
                                       December 1978 - May 1979. The
                                       exposure dose was calculated to be
                                       near the limit of detection at 8 ppb;
                                       the survey consisted of a 175-self-
                                       administered health questionnaire,
                                       physical examination, pulmonary
                                       function test, chest x-ray, and an
                                       electrocardiogram; clinical and
                                       biochemical analysis was also
                                       performed.

                                       After taking into account smoking
                                       status; exposed workers had a
                                       decreased incidence of respiratory
                                       conditions compared to non-exposed
                                       workers; in addition there were no
                                       abnormal clinical findings; There was
                                       an increase in benign neoplasms,
                                       dermatitis, and gynacomastia in
                                       exposed workers compared to non-
                                       exposed workers.
Mice were administered a
   'Cutaneous injection of 0, 0.25, 2.5,
or 25 mg/kg-day once daily for 4
days (total cumulative doses of 0, 1,
10, or 100 mg/kg)
Twenty percent of high-dose mice
exhibited lymphoid depletion of the
thymus. Statistically significant
decreases in lipopolysaccharide (B-
cell antigen) at 2.5 mg/kg-day and
Tanakaetal., 1981
Study predates the guideline for
immunotoxicity; There is some
uncertainty as the test material,
reported as Fyrol FR2, but miss-
identified by the authors as
tris(2,3-dichloropropyl)
phosphate; test substance purity
reported as >95%; The study
methods differed from the
guideline in the short exposure
                                                         7-552

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JUNE 2014 DRAFT REPORT
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT


Skin Sensitization

Skin Sensitization
Respiratory Sensitization
[Respiratory Sensitization
Eye Irritation

Eye Irritation
DATA
concanavalin A (T-cell antigen) at 25
mg/kg-day.
NOAEL: 0.25 mg/kg-day
LOAEL: 2.5 mg/kg-day
based on decreased concanavalin A,
T-cell antigen
REFERENCE
^s S
DATA QUALITY
period (4 rather than 28 days),
parenteral administration (rather
than oral or inhalation route),
measurement of serum
immunoglobulin in non-
immunized rather than
immunized mice, and the
omission of some tests
(enumeration of immunological
cell subpopulations, test for NK-
cell activity).
LOW: Not a skin sensitizer in guinea pigs.
Not a skin sensitizer in guinea pigs;
The Sensitization score for Fyrol FR-
2 was zero.
Akzo Nobel, 2001; EU, 2008
Study details reported in a robust
summary for an unpublished and
unidentified study dated 2001;
test substance identified as Fyrol
FR-2
No data were located

[No data located.
LOW: TDCPP produced slight conjunctival effects in rabbits that cleared within 24 to 48 hours.
Slightly irritating, rabbits; slight
conjunctival redness and slight
discharge were noted; effects cleared
by 24 hours.
Transient, mild conjunctival effects in
3/6 rabbits (reversible in 48 hours)
Not irritating, rabbits; average Draize
score of zero.
Cuthbert and Jackson, 1990;
WHO, 1998
Bullock and Kamienski, 198 la;
EU, 2008
Murphy, 1981; Akzo Nobel,
200 1;EU, 2008
Limited study details reported in a
secondary source; Test substance
identified as Tolgard TDCP
MK1; purity not specified.
Test substance identified as Fyrol
FR-2; purity not specified.
Test substance purity not
specified.
         7-553

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                                                          JUNE 2014 DRAFT REPORT
                                              Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
              PROPERTY/ENDPOINT
              DATA
        REFERENCE
       DATA QUALITY
Dermal Irritation
LOW: TDCPP produced mild skin irritation in rabbits that cleared within 72 hours.
                 Dermal Irritation
Mild skin irritant, rabbits (24-hour);
No edema on intact or abraded skin in
any rabbit; mild erythema was visible
at 24 hours, but cleared by 72 hours;
score of 0.63.
                                                     Irritating to skin, rabbits; well-
                                                     defined (score 2) erythema in 2 New
                                                     Zealand White rabbits and slight
                                                     erythema in a third rabbit 1 hour after
                                                     patch removal.
                                                     Not a skin irritant, rabbits (4-hour);
                                                     No erythema or edema on intact or
                                                     abraded skin in any rabbit.
Hicks etal., 1981; EU, 2008
Report cited EPA protocol. Back
hair was shaved, each rabbit
tested on intact and abraded skin,
occlusive dressing removed after
24 hours, observations at 24 and
72 hours; test substance identified
as Fyrol FR-2; purity unspecified.
                                  Cuthbert, 1989a;WHO, 1998;
                                  EU, 2008
                                  Bullock and Kamienski, 198 la;
                                  EU, 2008
                             Limited study details reported in a
                             secondary source; test substance
                             identified as Tolgard EDCPP
                             MK1; purity not specified;
                             duration of exposure not
                             specified.
                             Test substance identified as Fyrol
                             FR-2; purity not specified; Back
                             hair shaved, each rabbit tested on
                             intact and abraded skin, occlusive
                             dressing removed after 4 hours,
                             observations at 4, 24 and 48
                             hours.
                                                                      7-554

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                                                          JUNE 2014 DRAFT REPORT
                                             Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
              PROPERTY/ENDPOINT
             DATA
REFERENCE
DATA QUALITY
Endocrine Activity
TDCPP in house dust has been correlated with altered levels of hormones related to fertility and
thyroid function in men. TDCPP inhibited the luciferase expression induced by dihydrotestosterone
in a reporter-gene assay using cultured cells and induced delays in remethylation of the zygotic
genome (mechanism that may be associated with enhanced developmental toxicity) in zebrafish. In
addition, TDCPP  disrupted steroidogenic pathways and metabolism of estrogen in human cell lines
(H2925R and WVLN) and in zebrafish. A 2-year combined chronic toxicity and carcinogenicity
assay in rats resulted in changes of the parathyroid, testes, and epididymis; it is unclear if these
observed changes may be an indication of endocrine activity.
                                                    Hormone levels and semen quality
                                                    were assessed in men living in homes
                                                    with elevated TDCPP levels in house
                                                    dust. Each interquartile range  (IQR)
                                                    increase in TDCPP in dust was
                                                    associated with a 17% increase in
                                                    prolactin and a 3% decline in free
                                                    levels of the thyroid hormone
                                                    thyroxine.
                                                    In a luciferase reporter-gene assay
                                                    using cultured cells, TDCPP inhibited
                                                    the luciferase expression induced by
                                                    dihydrotestosterone. IC50 for
                                                    antiandrogenic activity = 4.7 x 10~5
                                                    IC50 for antiestrogenic activity = 8.9
                                                    TDCPP exposure during five stages
                                                    of embryogenesis in zebrafish
                                                    induced delays in remethylation of
                                                    the zygotic genome (mechanism that
                                                    may be associated with enhanced
                                                    developmental toxicity). Significant
                                                    increase in mortality and
                                                    developmental abnormalities at
                                                    exposure concentrations of 0.75-96
                                  Berts, 2010; Meeker and
                                  Stapleton, 2010
                                  Ohyama et al., 2006
                                  McGeeetal., 2012
                     Limited study details summarized
                     in a secondary source.
                     Primary source in Japanese with
                     English abstract
                     Sufficient study details reported.
                                                                     7-555

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JUNE 2014 DRAFT REPORT
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT































J

DATA
hours post-fertilization.
Human cell lines (H2925R and
WVLN cells) were tested for sex
hormone synthesis and steroidogenic
gene transcription (H295R) and
estrogen receptor binding activity
(MVLN); zebrafish (Danio rerio)
were tested for sex hormone levels
and gene transcriptions.
Increased 17 beta-estradiol (E2) and
testosterone (T) levels, transcription
of steroidogenic genes were
upregulated; two sulfotransferase
genes downregulated (H295R cells);
there was no estrogen receptor
agonist activity, while there was
antagonist inhibiting binding of E2 to
estrogen receptor (MVLN cells);
Increased plasma T and E2
concentrations in zebrafish exposed
to TDCPP for 14 days; decreased
testosterone and 11-ketotestosterone
and increased E2 in male zebrafish;
significant upregulation of CYP17
and CYP19 transcription (males and
females); vitellogenin (VTG)l gene
was down-regulated in female fish
and up-regulated in male fish.
Morbidity survey conducted on 124
male, full-time workers with
occupational exposure at a TDCPP
manufacturing plant to determine if
there was an increased incidence of
REFERENCE

Liu etal., 2012






4<



















Murphy, 1981;EU, 2008




DATA QUALITY

Sufficient study details reported
in a primary source.

























Cohort study details reported in a
secondary source; the non-
exposed (control) populations was
about one third the size of the
exposed population; it is also
         7-556

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                                            JUNE 2014 DRAFT REPORT
                               Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                       respiratory conditions among those
                                       exposed;
                                       After taking into account smoking
                                       status; exposed workers had a
                                       decreased incidence of respiratory
                                       conditions compared to non-exposed
                                       workers; in addition there were no
                                       abnormal clinical findings; There was
                                       an increase in gynacomastia in
                                       exposed workers compared to non-
                                       exposed workers.
                                                 difficult to determine if non-
                                                 exposed workers may have been
                                                 previously exposed, or if exposed
                                                 workers may have been exposed
                                                 to other compounds outside of
                                                 their occupational environment;
                                                 actual exposure doses were not
                                                 reported.
                                       Rat, oral, 2-year combined chronic
                                       toxicity and carcinogenicity assay;
                                       Rats (60/sex/group) were
                                       administered 0, 5, 20, 80 mg/kg-day
                                       (in the diet) for 2 years.
                                       Systemic lesions at 80 mg/kg/day
                                       involved the parathyroid
                                       (hyperplasia) in males and the liver
                                       (foci) and spleen (erythroid/myeloid
                                       hyperplasia) in females. Lesions in
                                       the vesicles (atrophy, decreased
                                       secretory product) at = 5 mg/kg-day,
                                       testes (eosinophilic material in lumen,
                                       periarteritis nodosa) at = 20 mg/kg-
                                       day, and epididymis (oligospermia
                                       and degenerated seminal product) at
                                       80 mg/kg-day. It is unclear if the
                                       observed changes may be an
                                       indication of endocrine activity.
                    Freudenthal and Henrich, 2000;
                    NRC, 2000
                     Freudenthal and Henrich (2000)
                     reported the lowest dose of 5
                     mg/kg-day as a NOAEL and the
                     mid-dose of 20 mg/kg-day as a
                     LOAEL. However, as evaluated
                     in NRC (2000), the lowest dose of
                     5 mg/kg-day was a LOAEL for
                     atrophy and decreased secretory
                     product of the seminal vesicle;
                     test substance purity: 95%.
                                                        7-557

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                                                          JUNE 2014 DRAFT REPORT
                                             Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
              PROPERTY/ENDPOINT
              DATA
       REFERENCE
       DATA QUALITY
Immunotoxicity
TDCPP produced lymphoid depletion of the thymus and decreases in LPS (B-cell antigen) and Con
A (T-cell antigen) in mice following subcutaneous injection for 4 days.
                 Immune System Effects
Mice were administered a
subcutaneous injection of 0, 0.25, 2.5,
or 25 mg/kg-day once daily for 4
days (total cumulative doses of 0, 1,
10, or 100 mg/kg)
Twenty percent of high-dose mice
exhibited lymphoid depletion of the
thymus. Statistically significant
decreases in lipopolysaccharide (B-
cell antigen) at 2.5 mg/kg-day and
concanavalin A (T-cell antigen) at 25
mg/kg-day.

NOAEL: 0.25 mg/kg-day
LOAEL: 2.5 mg/kg-day
based on decreased  concanavalin A,
T-cell antigen
Tanakaetal., 1981
Study predates the guideline for
immunotoxicity; There is some
uncertainty as to the test material
which was reported as Fyrol FR2
but mis-identified by the authors
as tris(2,3-dichloropropyl)
phosphate; test substance purity
reported as >95%; The study
methods differed from the
guideline in the short exposure
period (4 rather than 28 days),
parenteral administration (rather
than oral or inhalation route),
measurement of serum
immunoglobulin in non-
immunized rather than
immunized mice, and the
omission of some tests
(enumeration of immunological
cell subpopulations, test for NK-
cell activity).
                                                                      7-558

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                                                         JUNE 2014 DRAFT REPORT
                                             Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
              PROPERTY/ENDPOINT
             DATA
       REFERENCE
       DATA QUALITY
ECOSAR Class
                                                                ECOTOXICITY
Acute Aquatic Toxicity
HIGH: Based on a measured 96-hour LC50 of 1.1 mg/L in fish, a 48-hour LC50 of 3.8 mg/L in
daphnia and a 72-hour ErCi0 = 2.3 mg/L in green algae.
Fish LC50
Oncorhynchus mykiss (rainbow trout)
96-hour LC50 =1.1 mg/L
(semi-static test conditions)
96-hour NOEC = 0.56 mg/L
24-hour LC50 =1.8 mg/L
48-hour LC50= 1.5 mg/L
72-hour LC50 =1.3 mg/L
(Experimental)
                                                    Salmo gairdneri (Rainbow trout) 96-
                                                    hour LC50 =1.4 mg/L
                                                    Static conditions; exposed to 0, 0.63,
                                                    1.25,2.5,5, 10 mg/L
                                                    All mortalities occurred within the
                                                    first 24 hours. Mortality was dose
                                                    related. One fish died in the lowest
                                                    dose group (0.63 mg/L). All fish died
                                                    in the 5 and 10 mg/L groups.
                                                    (Experimental)
                                                    rvm
                                                        «;
                                                        i
Killifish (Oryzias latipes) 96-hour
     = 3.6mg/L
   tic test conditions)
Deformation of the spine was
observed in 7/10 killifish exposed to
3.5 mg/L TDCPP for 24 hours.
(Experimental)
                                                    Goldfish (Carassius auratus) 96-hour
                                                    LC50 = 5.1 mg/L (static test
                                                    conditions)
ECHA, 2012
                                 Akzo Nobel, 2001
                                                                                      Sasaki etal, 1981
                                 Sasaki etal, 1981
Test substance identified as
Amgard TDCP; study conducted
according to OECD guidelines;
the toxicity value is below the
reported water solubility of
TDCPP (18 mg/L).
                            A NOEC was not observed and is
                            therefore less than 0.63 mg/L.
                             The test concentrations used were
                             not reported. A control group was
                             not tested.
                             Goldfish are not a designated test
                             species, as per OPPTS 850.1075
                             (Fish Acute Toxicity Test,
                                                                     7-559

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                                            JUNE 2014 DRAFT REPORT
                               Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
       REFERENCE
       DATA QUALITY
                                       (Experimental)
                                       Goldfish (Carassius auratus);
                                       exposed to 1 and 5 mg/L (static test
                                       conditions)
                                       Fish were exposed to 1 or 5 mg/L
                                       TDCPP in water or acetone. None of
                                       the fish in the  1 mg/L treatment had
                                       died after 168  hours. All fish in the 5
                                       mg/L treatment died within 24 hours.
                                       The most conspicuous signs of
                                       toxicity were sluggishness and
                                       disoriented swimming prior to death.
                                       (Experimental)
                    Eldefrawi et al, 1977
                                       A laundered or unlaundered 38 cm x
                                       64 cm section of garment (0.24
                                       square meter area; 227 g/m3), which
                                       had been treated with Fyrol FR-2,
                                       was placed in tanks with six goldfish.
                                       Fish in the tank became progressively
                                       more sluggish and all died within 3
                                       hours. The measured concentration of
                                       Fyrol FR2 in the test water was 30
                                       mg/L. Fish exposed for 96 hours to
                                       the same section of fabric after it had
                                       been laundered did not die.
                                       (Experimental)
                    Ahrens et al., 1979
                                       Freshwater Fish 96-hour LC5C
                                       mg/L
                                       (Estimated)
                                       (Estimated)
                                       ECOSAR: Neutral organics
             = 12
ECOSAR v 1.11
                                                 Freshwater and Marine); used
                                                 were not reported. A control
                                                 group was not tested.
                             Goldfish are not a designated test
                             species, as per OPPTS 850.1075
                             (Fish Acute Toxicity Test,
                             Freshwater and Marine). The
                             study cannot be used to establish
                             an LC50 value.
                             Data for mortality in control fish
                             were not presented in the study;
                             goldfish are not a designated test
                             species, as per OPPTS 850.1075
                             (Fish Acute Toxicity Test,
                             Freshwater and Marine). This
                             study in inadequate for
                             determining a hazard designation.
ECOSAR also provided results
for the Esters, and Esters
(phosphate) classes; however,
professional judgment indicates
that this compound is not
                                                        7-560

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                                                         JUNE 2014 DRAFT REPORT
                                             Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
              PROPERTY/ENDPOINT
             DATA
       REFERENCE
       DATA QUALITY
                                                                                                                 currently well represented in
                                                                                                                 ECOSARvl.ll.
Daphnid LC50
Daphnia magna 48-hour LC50 = 3.8
mg/L (flow-through test conditions)
Negative control, solvent control
(dimethylformamide), 0.98, 1.6, 2.8,
3.8, 5.1 mg/L Daphnia in the negative
and solvent control groups appeared
normal, as did the organisms in the
0.98 and 1.6 mg/L groups. Mortality
in the 2.8, 3.8, and 5.1 mg/L groups
was 0, 70, and 80%, respectively.
Daphnids (15%) in the 2.8 mg/L
group were lethargic at study
termination.
(Experimental)
Akzo Nobel, 2001: EU, 2008

                                                    Daphnia magna 48-hour EC50 = 4.6
                                                    mg/L
                                                    (Experimental)
                                 EU, 2008
                                                    Daphnia 4 8-hour LC50 = 8 mg/L
                                                    (Estimated)
                                                    ECOSAR: Neutral organics
                                 ECOSARvl.ll

The amount of solvent used in the
control group and the TDCPP
treatments is estimated to be
approximately 300 mg/L. This
exceeds the recommended
maximum solvent concentration
of 100 mg/L. The estimate is
based on a reported
dimethylformamide volume of
0.1 ml, a test chamber volume of
300 ml and a specific gravity of
0.95.
                             Study did not include analysis of
                             exposure concentrations; values
                             are consistent with other
                             experimental value.
                            ECOSAR also provided results
                            for the Esters, and Esters
                            (phosphate) classes; however,
                            professional judgment indicates
                            that this compound is not
                            currently well represented in
                            ECOSARvl.ll.
Green Algae EC50
P. subcapitata 96-hour EC50 > 2.
mg/L (biomass and growth rate)
72-hour ErC10 = 2.3 mg/L
NOEO 1.2 mg/L
(Experimental)
EU, 2008
Study details reported in a
secondary source; conducted
according to OECD guideline 201
reported toxicity values are below
the reported water solubility for
TDCPP (18 mg/L).
                                                                     7-561

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                                                        JUNE 2014 DRAFT REPORT
                                            Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
              PROPERTY/ENDPOINT
             DATA
       REFERENCE
                                                                   DATA QUALITY
                                                   Selenastrum capricornutum 96-hour
                                                   EbC50 = 12 mg/L
                                                   96-hour ErC50 = 39 mg/L
                                                   96-hour NOAEC = 6 mg/L
                                                   static test conditions; 0, 2, 6, 18, 54,
                                                   or 162 mg/L
                                                   (Experimental)
                                 Akzo Nobel, 2001
                            A number of problems are evident
                            with this study, namely the pH
                            changed markedly during the
                            study, and the reported pH and
                            water temperature were outside of
                            the recommended values for this
                            algal species.
                                                   Green algae 96-hour EC50 =11 mg/L
                                                   (Estimated)
                                                   ECOSAR: Neutral organics
                                 ECOSARvl.ll
                            ECOSAR also provided results
                            for the Esters, and Esters
                            (phosphate) classes; however,
                            professional judgment indicates
                            that this compound is not
                            currently well represented in
                            ECOSARvl.ll.
Chronic Aquatic Toxicity
HIGH: Based on a measured 21-day NOEC of 0.5 mg/L (LOEC = 1.0 mg/L) in daphnid for reduced
reproduction; the NOEC and LOEC for reduced growth was 1.0 mg/L and 2.0 mg/L, respectively.
No experimental data were located for fish and green algae, but estimated data predicts HIGH
concern for fish and Moderate concern for algae.
Fish ChV
Freshwater fish ChV =1.4 mg/L
(Estimated)
ECOSAR: Neutral organics
ECOSARvl.ll
                                                             ECOSAR also provided results
                                                             for the Esters, and Esters
                                                             (phosphate) classes; however,
                                                             professional judgment indicates
                                                             that this compound is not
                                                             currently well represented in
                                                             ECOSARvl.ll.
Daphnid ChV
Daphnia magna 21-day LOEC =1.0
mg/L (reproduction)
21-day NOEC = 0.5 mg/L
(reproduction)
21-day NOEC = 1.0 mg/L (growth)
21-day LOEC = 2.0 mg/L (growth)
semi-static test conditions
(Experimental)
                                 EU, 2008
                            Study details reported in a
                            secondary source; test substance
                            identified as Fyrol FR-2; purity
                            >99%.
                                                                    7-562

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JUNE 2014 DRAFT REPORT
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT

Green Algae ChV
DATA
Daphnia magna ChV = 1.2 mg/L
(Estimated)
ECOSAR: Neutral organics
Green algae ChV = 4.0 mg/L
(Estimated)
ECOSAR: Neutral organics
REFERENCE
ECOSAR v 1.11
ECOSAR v 1.11
^ J
DATA QUALITY
ECOSAR also provided results
for the Esters, and Esters
(phosphate) classes; however,
professional judgment indicates
that this compound is not
currently well represented in
ECOSAR vl.ll.
ECOSAR also provided results
for the Esters, and Esters
(phosphate) classes; however,
professional judgment indicates
that this compound is not
currently well represented in
ECOSAR vl.ll.
ENVIRONMENTAL FATE
Transport

Henry's Law Constant (atm-m3/mole)
Sediment/Soil Adsorption/Desorption
- KOC
J
Level III fugacity models incorporating available physical and chemical property data indicate that
at steady state, TDCPP is expected to be found primarily in soil and to a lesser extent, sediment and
water. It is not expected to dissociate at environmentally-relevant pH values. TDCPP is expected to
have moderate mobility in soil, based on measured Koc values obtained from studies performed in
clay loam, loamy sand and clay samples. Leaching through soil to groundwater may occur, though
it is not expected to be an important transport mechanism. Estimated volatilization half-lives
indicate that it will be non-volatile from surface water. Based on the measured vapor pressure,
TDCPP is expected to exist in both the vapor and particulate phases in the atmosphere. Particulates
will be removed from air by wet or dry deposition.
<10"8 (Estimated)
J
1,780 according to OECD 106 using
GLP; 0.01 M calcium chloride was
equilibrated with each of three soils, a
clay loam, a loamy sand and a clay,
one sediment and one activated
sludge solid. Reported as a range of
1,540-2,010. (Measured)
Professional judgment; EPI
v4.11
Schaefer and Ponizovsky, 2006
(as cited in EU, 2008)
Cutoff value for nonvolatile
compounds.
Adequate, OECD guideline study.
         7-563

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                                                        JUNE 2014 DRAFT REPORT
                                            Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
              PROPERTY/ENDPOINT
                                               DATA
                                        REFERENCE
                                  DATA QUALITY
                Level III Fugacity Model
                                  Air = 0%
                                  Water = 4%
                                  Soil = 90%
                                  Sediment = 5% (Estimated)
                                EPIv4.11
                            Estimation model was calculated
                            using all applicable measured
                            input value.
Persistence
                                  HIGH: The persistence for TDCPP is based on experimental guideline biodegradation studies.
                                  There is evidence of TDCPP biodegradation resulting in a half-life greater than 60 days. A river die
                                  away test found 22% removal of TDCPP in 14 days and a non-guideline soil test reported 6%
                                  removal in 17 weeks with radiolabeled TDCPP. In ready biodegradability tests, OECD TG 301B,
                                  301C and 301D, 0 to <1% biodegradation of TDCPP occurred after 28 days. Additionally, no
                                  evidence of TDCPP removal was found in 28 days in an OECD 302C guideline study. TDCPP will
                                  undergo hydrolysis under alkaline conditions, with half-lives of 15 days measured at pH 9 and
                                  50°C. TDCPP is relatively stable to hydrolysis under neutral and acidic conditions, a half-life of >1
                                  year was found under pH 4 and pH 7 conditions. TDCPP is not expected to be susceptible to direct
                                  photolysis by sunlight, since it does not absorb light at wavelengths >290 nm.
Water
Aerobic Biodegradation
Passes Ready Test: No
Test method: OECD TG 30IB: CO2
Evolution Test

Modified Sturm Test 0% by CO2
evolution. DOC reduction not
calculated due to solubility issues.
0% by CO2 evolution. DOC red. Not
calculated due to solubility issues.
(Measured)
                                                   Passes Ready Test: No
                                                   Test method: OECD TG 30ID:
                                                   Closed Bottle Test

                                                   No inhibition of bacterial cultures in
                                                   10 days. (Measured)
                                                   Passes Ready Test: No
                                                   Test method: OECD TG 301C:
                                                   Modified MITI Test (I)
Hattori et al., 1981 (as cited in
Jenkins, 1990; Akzo Nobel,
2001;EU, 2008)
                                                                   Bisinger, 1990; Akzo Nobel,
                                                                   2001
                                                                   CERI, 1999 (as cited in EU,
                                                                   2008)
OECD guideline study, however
solubility issues were found.
                                                            Adequate, OECD guideline study
                                                            OECD guideline study, reported
                                                            in a secondary source.
                                                                   7-564

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                                           JUNE 2014 DRAFT REPORT
                               Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
             DATA
REFERENCE
DATA QUALITY
                                      Reported as average, 1% by BOD
                                      using activated sludge inoculum.
                                      Initial concentrations 100 mg/L (test
                                      substance), 30 mg/L (sludge). The
                                      sludge was from ten sites in Japan:
                                      four sewage plants and six surface
                                      waters. (Measured)
                                      Study results: 0%/28 days
                                      Test method: 302C: Inherent -
                                      Modified MITI Test (II)

                                      0% by O2 uptake (Measured)
                                 WHO, 1998
                     EURAR notes that this study can
                     only be seen as a short screening
                     test, from which no conclusions
                     regarding inherent
                     biodegradability of TDCPP can
                     be draw since no acclimation
                     period was used.
                                      Study results: 22%/14 days
                                      Test method: River Die-Away test

                                      Oh River:
                                      12.5%/7 days; 18.5%/14 days
                                      Neya River:
                                      0%/7days;5.4%/14days
                                      Osaka Bay:
                                      0%/7 days; 22%/14 days
                                 Hattori et al., 1981 (as cited in
                                 WHO, 1998; EU, 2008)
                     Adequate, guideline study.
u/o,

Init
                                      Initial concentrations: 20 mg/L in Oh
                                      River water and 1 mg/L in Neya
                                      River water. Concentration in
                                      seawater not reported.
                                      Analysis by Molybdenum Blue
                                      calorimetric assay for increase in
                                      phosphate ion. (Measured)
                                      Study results: 100%/12 hours
                                 Takahashi et al., 2012
                     Measured biodegradation rates
                                                       7-565

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JUNE 2014 DRAFT REPORT
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT

Soil

Volatilization Half-life for Model
River
Volatilization Half-life for Model
Lake
Aerobic Biodegradation
Anaerobic Biodegradation
Soil Biodegradation with Product
Identification f
Sediment/Water Biodegradation
DATA
Test method: Other
Using isolated bacterium strains,
Sphingobium sp. strain TCM1 and
1, 3 -DCP -degrading bacterium
Arthrobacter sp. Strain PY1,
complete detoxification of TDCPP
was achieved in 12 hours. The
degradation products were 1
phosphate, 6 HC1 and 3 glycerol.
(Measured)
>1 year (Estimated)
>1 year (Estimated)
Study results: 6%/17 weeks
Test method: Other
14C radiolabelled TDCPP was applied
to the soil surface and the soils (sand,
loam, clay loam and sandy loam)
were incubated at 20 ± 2°C. Each soil
type was analyzed at intervals of 0, 7,
14, 35, 63 and 122 days. (Measured)



REFERENCE
^s '
EPIv4.11
EPIv4.11
Schaefer and Ponizovsky, 2006
(as cited in EU, 2008)



DATA QUALITY
demonstrate removal by this
pathway using isolated strains.
Estimation model was calculated
using all applicable measured
input values.
Estimation model was calculated
using all applicable measured
input values.
Reported in a secondary source.
Study used 14C-labeled test
substance, analyzed by HPLC.
No data located; chlorinated alkyl
phosphates are outside the
domain of the available
estimation methods.
No data located.
No data located.
         7-566

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                                                         JUNE 2014 DRAFT REPORT
                                            Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
              PROPERTY/ENDPOINT
                                                DATA
                                        REFERENCE
                                   DATA QUALITY
Air
Atmospheric Half-life
1 day (Estimated)
EPIv4.11
                                                    Reaction of TDCPP with oxidative
                                                    species such as ozone or hydroxyl
                                                    radicals can proceed rapidly. Vacuum
                                                    UV light at 185 and 254 nm, the
                                                    study conditions were not
                                                    representative of typical
                                                    environmental conditions.
                                                    (Measured)
                                                                    Echigo et al., 1996 (as cited in
                                                                    EU, 2008)
                                                             Non guideline study reported in a
                                                             secondary source provides data
                                                             indicating a potential for removal
                                                             by photodegradation, although the
                                                             rate of removal and applicability
                                                             of this pathway under
                                                             environmental conditions is
                                                             unknown.
Reactivity
Photolysis
                 Hydrolysis
Not a significant fate process
(Estimated)
Professional judgment; Mill,
2000
The substance does not contain
functional groups that would be
expected to absorb light at
environmentally significant
wavelengths.
                                   50%/>1 year at pH 4 and 7; 14.7 days
                                   atpH9
                                   OECD 111; EPA Ser. 835 OPPTS
                                   No. 835.2110. GLP-compliant. Initial
                                   concentration, 10 mg/L. Study length,
                                   5 days at 50°C. Preliminary study.
                                   (Measured)
                                 Akzo Nobel, 2001 (as cited in
                                 EU, 2008)
                            GLP-compliant test run according
                            to accepted guidelines.
                                                    50%/28daysatpH9
                                                    OECD 111; EPA Ser. 835 OPPTS
                                                    No. 835.2110. GLP-compliant.
                                                    Definitive 30-day study at 40°C.
                                                    (Measured)
                                                                    Akzo Nobel, 2001
                                                             GLP-compliant test run according
                                                             to accepted guidelines.
                                                    50%/128daysatpH9
                                                    OECD 111; EPA Ser. 835 OPPTS
                                                    No. 835.2110. GLP-compliant.
                                                    Definitive 30-day study at 20°C.
                                                    (Measured)
                                                                    Akzo Nobel, 2001
                                                             GLP-compliant test run according
                                                             to accepted guidelines.
                                                                    7-567

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JUNE 2014 DRAFT REPORT
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
Environmental Half-life
Bioaccumulation

Fish BCF
Other BCF
DATA
>1 year (Estimated)
REFERENCE
PBT Profiler
DATA QUALITY
Half-life estimated for the
predominant compartment, as
determined by EPI methodology.
LOW: Based on multiple experimental BCF values below or near 100, the Low bioaccumulation
designation criteria. Toxicokinetic studies indicate that TDCPP and metabolites are rapidly formed
and eliminated. However, biomonitoring studies report detection of this compound in pine needles,
human adipose tissue, human seminal plasma samples, fish and herring gull eggs.
Cyprinus carpi o 0.3 -22 at two
concentrations over 6 weeks
(Measured)
<1 13 Oryzias latipes Reported as 1 13
at 24 hours, 1 10 at 55 hours and 77 at
96 hours; static study with killifish at
25 °C (Measured)
5 at 24 hours and 3 at 55 hours; static
study with goldfish at 25 °C
(Measured)
59 Oryzias latipes BCF values of 3 1
± 6 to 59 ± 16 reported. Samples
from fish taken at 3, 4, 6, 30 and 32
days. TDCPP concentrations of 40,
80, 300 and 400 ppb used in the flow-
through study with killifish at 25 °C
(Measured)

MITI Japan, 1993
r
Sasaki etal, 1981
Sasaki etal, 1981
Sasaki etal., 1981

Nonguideline study with results
consistent with other reported
values.
Consistent information for
killifish under both static and
flow-through conditions, over a
variety of observation times, and
with varying initial concentrations
of test substance.
Consistent information for
goldfish under both static and
flow-through conditions, over a
variety of observation times, and
with varying initial concentrations
of test substance.
BCF is independent of
concentration; continuous flow-
through results correlate to static
results
No data located.
         7-568

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JUNE 2014 DRAFT REPORT
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT

BAF
Metabolism in Fish
DATA
100 (Estimated)
Apparent metabolism is much faster
in killifish than in goldfish. -10% of
applied TDCPP remains in the water
in the presence of killifish after 96
hours (Measured)
Depuration rate/elimination half-life
of 1.65 hours in killifish when
exposed fish are moved to clean
water (Measured)
REFERENCE
EPIv4.11
Sasaki etal, 1981
Sasaki etal, 1982
DATA QUALITY
Estimation model was calculated
using all applicable measured
input values.
Non guideline study.
Non guideline study.
         7-569

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JUNE 2014 DRAFT REPORT
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA REFERENCE DATA QUALITY
ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring
Ecological Biomonitoring
Human Biomonitoring
TDCPP has been detected in water samples from surface water samples from 139 streams obtained in 30
states across the continental United States from 1999-2000. It has also been detected in groundwater
samples from 47 sites in 18 different states as part of a national reconnaissance program of water quality
in the United States. TDCPP was found in several streams in Johnson County, Kansas from 2002-2003,
public drinking water in the US and Puerto Rico, St. Vrain Creek, Colorado, the Netherlands Rhine delta,
Freshwater Streams in Hessen/Germany, Ruhr river in Germany, German Bight (an area heavily
influenced by the Elbe estuary plume) in the North Sea, ground water in UK, Arctic Ocean, Sea of Japan,
Northern Pacific Ocean, East Indian Archipelago, Philippine Sea, Indian Ocean, Southern Ocean, German
Bight, North Sea, Oslo, Norway, Birkenes, Southern Norway (remote), Ny Alesund, Norwegian Arctic
(remote), Northern Finland (remote), three volcanic lakes located in Central Italy, the Tiber River, Yodo
river basin, Yamato River in Japan; water in Galicia Spain. TDCPP has been detected in air and dust
samples from ambient air of Kitakyushu, Japan, indoor air environments in Tokyo, Japan, house dust in
Spain, indoor air or dust from Zurich, Sweden, New Zealand, Germany and the US. TDCPP has been
detected in precipitation samples from snow and rain in middle Germany and snow from northern
Sweden. TDCPP has been detected in sediment samples from Taihu Lake, China, the rivers Danube,
Neckar and Rhine, the Elbe river and Ruhr river (Bacaloni et al., 2007, 2008; EU, 2008; Regnery and
Puettmann, 2008; Kanazawa et al., 2010; Meeker and Stapleton, 2010; ATSDR 2012; Bollmann et al.,
2012; Rodil etal., 2012; Salamovaet al., 2014).
TDCPP has been detected in fish from the Yamato river, pine needles from nine sites in the Sierra Nevada
foothills and herring gull eggs from the Channel -Shelter Island colony in Lake Huron (Okumura, 1994;
Aston et al., 1996; EU, 2008; Chen et al., 201 1; Chen et al., 2012).
In Canada, TDCPP was detected in human adipose tissue and it has been identified in human seminal
plasma. This chemical was not included in the NHANES biomonitoring report (Hudec et al., 1981; LeBel
and Williams, 1986; EU, 2008; CDC, 2009; ATSDR, 2012).
         7-570

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                                                  JUNE 2014 DRAFT REPORT


ATSDR (2012) Toxicological profile for Phosphate Ester Flame Retardants. Atlanta, GA: Agency for Toxic Substances and Disease Registry.

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Contam Toxicol 21:409-412.

Akzo Nobel (2001) Robust summaries & test plans: Fyrol FR-2 (Tris[ l,3-dichloro-2-propyl] Phosphate). Akzo Nobel Functional Chemicals LLC.
Submitted under the HPV Challenge Program, http://www.epa.gov/hpv/pubs/summaries/phospho/cl2978.pdf

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                                                     *

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                                                              7-575

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                                                 JUNE 2014 DRAFT REPORT


Lynn RK, Wong K, Garvie-Gould C, etal. (1981) Disposition of the flame retardanttris(l, 3 -dichloro-2-propyl -phosphate in the rat. Drug Metab
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Matheson DW, Brusick DJ (1981) Mutagenicity evaluation of Fyrol FR-2 4619-1B in the mouse lymphoma multiple endpointtest (MET) final
report (1977). Toxicology reports on Fyrol FR-2 (volume I-II) with attachments and cover letter dated 020381. Prepared by Litton Bionetics for
Stauffer Chemical Company. Submitted to the U.S. Environmental Protection Agency under TSCA Section 8E, 438-503.

McGee SP, Cooper EM, Stapleton HM, et al. (2012) Early zebrafish embryogenesis is susceptible to developmental TDCPP exposure. Environ
Health Perspect 120:1585-1591.

Meeker JD, Stapleton HM (2010) House dust concentrations of organophosphate flame retardants in relation to hormone levels and semen quality
parameters. Environ Health Perspect 118(3):318-323.

Mill T (2000) Photoreactions in surface waters. In: Boethling R Mackay D, eds. Handbook of Property Estimation Methods for Chemicals,
Environmental Health Sciences. Boca Raton: Lewis Publishers, 355-381.

Morey H, Frudentahl RI,  Swigut T, et al. (1978) Summary of in vitro delayed neurotoxicity evaluation.  Report T-6303. Toxicology reports on
Fyrol FR-2. Vol I of II. Submitted to the U.S. Environmental Protection Agency under TSCA Section 8E, 27-38.

Mortelmans K, Haworth S, Lawlor T, et al. (1986) Salmonella mutagenicity tests: II. Results from the testing of 270 chemicals. Environ Mutagen
8(Suppl. 7): 1-119.

Murphy JP (1981) Toxicology reports on Fyrol FR-2 (volume I-II) with attachments and cover letter dated 020381. Stauffer Chemical Company.
Submitted to the U.S. Environmental Protection Agency under TSCA Section 8E.

NAS (2000) Toxicological risks of selected flame-retardant chemicals. Washington, DC: The National Academies Press, National Academy of
Sciences. http://www.nap.edu/catalog.php?record_id=9841.

NICNAS (2001) Triphosphates. National Industrial Chemicals Notification and Assessment Scheme, Commonwealth of Australia.
                                                             7-576

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                                                 JUNE 2014 DRAFT REPORT


Nakamura A, Tateno N, Kojima S, et al. (1979) Mutagenicity of halogenated alkanols and their phosphoric acid esters for Salmonella
typhimurium. Mutat Res 66:373-380.

Nomeir AA, Kato S, Matthews HB (1981) The metabolism and disposition of tris(l,3-dichloro-2-propyl) phosphate (Fyrol FR-2) in the rat.
Toxicol Appl Pharmacol 57:401-413.

NRC (2000) Tris(l,3-dichloropropyl-2) phosphate. Toxicological risks of selected flame retardant chemicals. Washington, DC: National Academy
Press, National Research Council, 358-386.

Ohyama K, Nagata S, Hosogoe N, et al. (2006) Hormonal effects of organic phosphate triesters study by the  reporter gene assay. Tokyo-to Kenko
Anzen Kenkyu Senta Kenkyu Nenpo 56:333-338.

Okumura T (1994) Levels of pesticides and chemicals in fish from the rivers (Yodo River, Yamato River, Okawa River) in Osaka Prefecture.
Journal of Environmental Chemistry:490-491.

PBT Profiler Persistent (P), Bioaccumulative (B), and Toxic (T) Chemical (PBT) Profiler, Version 1.301. Washington, DC: U.S. Environmental
Protection Agency, www.pbtprofiler.net.

Prival MJ, McCoy EC, Gutter B, et al. (1977) Tris(2,3-dibromopropyl) phosphate: mutagenicity of a widely used flame retardant. Science
195(4273):76-78.

Regnery J and Puettmann W (2008) Detection of organophosphates in still waters. LaborPraxis 32(9):30-32.

Rodil  R Quintana JB, Concha-Grana E, et al. (2012) Emerging pollutants in sewage, surface and drinking water in Galicia (NW Spain).
Chemosphere 86(10): 1040-1049.

Salamova A, Ma Y, Venier M, et al. (2014) Fiigh levels of organophosphate flame retardants in the Great Lakes atmosphere. Environ Sci Technol
Sasaki K, Suzuki T, Takeda M (1982) Bioconcentration and excretion of phosphoric acid triesters by killifish (Oryzeas latipes). Bull Environ
Contam Toxicol 28:752-759.

Sasaki K, Suzuki T, Uchiyama M (1984) Metabolism of phosphoric acid trimesters by rat liver homogenate. Bull Environ Contam Toxicol 33:281-
288.
                                                             7-577

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                                                  JUNE 2014 DRAFT REPORT


Sasaki K, Takeda M, Uchiyama M (1981) Toxicity, absorption, and elimination of phosphoric acid triesters by killifish and goldfish. Bull Environ
Contam Toxicol 27:775-782.

Schaefer EC and Ponizovsky AA (2006) Tris[2-chloro-l-chloromethyl)ethyl]-phosphate (TDCP): Adsorption/desorption characteristics in
representative soils, sediment, and sludge solids in accordance with OECD Guideline for Testing of Chemicals, 106: Adsorption/desorption using
a batch equilibrium method. Wildlife International, Ltd. project no.: 584E-101. Draft report 2nd.

Soederlund EJ, Dybing E, Holme JA, et al. (1985) Comparative genotoxicity and nephrotoxicity studies of the two halogenated flame retardants
tris(l,3-dichloro-2-propyl) phosphate andtris(2,3-dibromopropyl)phosphate. Acta Pharmacol Toxicol 56:20-29.

Takahashi S, Obana Y, Okada S, et al. (2012) Complete detoxification of tris(l,3-dichloro-2-propyl) phosphate by mixed two bacteria,
Sphingobium sp. strain TCM1 and Arthrobacter sp. strain PY1. Volume 113, Issue 1, January 2012, Pages 79-83. J Biosci Bioeng 113(l):79-83.

Tanaka S, Nakaura S, Kawashima K, et al. (1981) Effect of oral administration of tris(l,3dichloroisopropyl)phosphate to pregnant rats on prenatal
and postnatal developments. Eisei Shikenjo Hokoku 99:50-55.

Thomas MB and Collier TA (1985) Tolgard T.D.C.P. LV: OECD 474 Micronucleus study in the mouse. Experiment No. 164/8507. SafePharm
Laboratories.

Tremain SP (2002) TDCP: determination of vapour pressure. Report 1613/003, SafePharm Laboratories, PO Box 45, Derby, UK.

Van den Eede N, Maho W, Neels H, et al. (2013) Metabolism of phosphate flame retardants and plasticisers using human liver fractions. Sixth
International Symposium on Flame Retardants, San Francisco, CA, April 7-10, 2013

WHO (1998) International Programme on Chemical Safety (IPCS), Environmental Health Criteria 209, Flame retardants:
tris(chloropropyl)phosphate and tris(2-chloroethyl)phosphate. Geneva: International Programme on Chemical Safety, World Health Organisation.
http://whqlibdoc.who.int/ehc/WHO  EHC 209.pdf.

Wilczynski SI, Killinger JM, Zwicker GM, et al. (1983) Fyrol FR-2 fertility study in male rabbits. Toxicologist 3:22.
                                                              7-578

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                                    JUNE 2014 DRAFT REPORT
Tris (2-chloro-l-methylethyl) phosphate (TCPP)
Screening Level Toxicology Hazard Summary
This table only contains information regarding the inherent hazards of flame retardant chemicals. Evaluation of risk considers both the hazard and exposure associated with the
substance including combustion and degradation by-products. The caveats listed in the legend and footnote sections must be taken into account when interpreting the hazard
information in the table.
VL = Very Low hazard L = Low hazard = Moderate hazard = High hazard VH = Very High hazard - Endpoints in colored text (VL, L, , H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].








Chemical








CASRN
Human Health Effects



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Tris (2-chloro-l-methylethyl)
phosphate (TCPP)
13674-84-5
L
M
L
H
H
M

L

L
L

H

L

                                              7-579

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                                                         JUNE 2014 DRAFT REPORT
                                       Cl
o—
                                                                                                              CASRN: 13674-84-5
                                                                                                              MW: 327.57
                                                                                                              MF: C9H18C13O4P
Physical Forms: Liquid
Neat:
                                                                                                              Use: Flame retardant
SMILES: O=P(OC(CC1)C)(OC(CC1)C)OC(CC1)C
Synonyms: 2-Propanol, 1-chloro-, 2,2\2"-phosphate; TCPP; TCIPP; Tris(l-chloro-2-propyl)phosphate; Tris(2-chloroisopropyl)phosphate; 2-propanol, 1-
chlorophosphate (3:1); 1-chloro-2-propyl phosphate (1:3); tris(l-chloromethylethyl) phosphate; phosphoric acid, tris(2-chloro-l-methyl ethyl) ester
Chemical Considerations: CASRN 13674-84-5 is a discrete organic chemical with a MW below 1,000. EPI v4.11 was used to estimate physical/chemical and
environmental fate values in the absence of experimental data. Measured values from experimental studies were incorporated into the estimations. TCPP is produced
by the reaction of phosphorus oxychloride and propylene oxide. The most abundant isomer in commercial products is the branched isomer, 2-Propanol, 1-chloro-,
phosphate (3:1) (CASRN 13674-84-5) however other isomers are expected to be present and will be discussed in this report as appropriate when determining hazard
designations. Chemical, fate, and toxicity data for the isomers represented by other CASRN were collected in the preparation of this AA and are listed below:

• 1-Propanol, 2-chloro-, 1,1\1"-phosphate (3:1) (CASRN 6145-73-9);
• Phosphoric acid, bis(2-chloro-l-methylethyl) 2-chloropropyl ester (CASRN 76025-08-6)  and
  Phosphoric acid, 2-chloro-1-methylethyl bis(2-chloropropyl) ester (CASRN 76649-15-5)  (NAS, 2000).
                                                                     7-580

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JUNE 2014 DRAFT REPORT
Polymeric: No
Oligomeric: Not applicable
Metabolites, Degradates and Transformation Products: O,O-[bis(l-chloro-2-propyl)]-O-(2-Propionic acid) phosphate; bis(l-chloro-2-propyl) phosphate; bis(l-
chloro-2-propyl) l-hydroxy-2-propyl phosphate; bis(l-chloro-2-propyl) 1-carboxy -2-propyl phosphate; l-chloro-2-propyl,l-hydroxy-2-propyl phosphate (OECD-
SIDS, 2000; Van den Bade et al., 2013)
Analog: Isomers anticipated to be present in the commercial
product were considered in this evaluation, as indicated in the
chemical considerations section
Endpoint(s) using analog values: Not applicable
Analog Structure: Not applicable
Structural Alerts: Organophosphates; Neurotoxicity (EPA, 2012).
Risk Phrases: This substance is not classified in the Annex I of Directive 67/548/EEC (ESIS, 2012).
Hazard and Risk Assessments: Priority Existing Chemical Assessment report for Triphosphates by the National Industrial Chemicals Notification and Assessment
Scheme (NICNAS) in 2001, Environmental Health Criteria for Flame Retardants by the World Health Organization in 1998, SIDS Initial Assessment Profile, EU Risk
Assessment Report in 2008 and ATSDR Toxicological Profile for Phosphate Ester Flame Retardants in 2012 (WHO, 1998; OECD-SIDS, 2000; NICNAS, 2001; EU,
2008; ATSDR 2012). ^M ^^^
         7-581

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JUNE 2014 DRAFT REPORT
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
DATA
REFERENCE | DATA QUALITY
PHYSICAL/CHEMICAL PROPERTIES
Melting Point (°C)
Boiling Point (°C)
Vapor Pressure (mm Hg)
-51
value expressed as pour point;
Isoteniscopic ASTM D2897 Method
(Measured)
-42
value expressed as pour point .
(Measured)
-65
(Measured)
72
(Measured)
>288
GLP study (Measured)
235
reported as 235-248°C. (Measured)
220 Decomposes
(Measured)
244 at 700 mmHg Decomposes
(Measured)
J
359
(Measured)
lx!0-5at25°C
reported as 0.0014 Pa; GLP study
(Measured)
<2 at 25°C
OECD-SIDS, 2000; ECHA, 2013
EC, 2000
NICNAS, 2001
van der Veen and de Boer, 2012
ECHA, 2013
WHO, 1998; NAS, 2000
NICNAS, 2001
OECD-SIDS, 2000
van der Veen and de Boer, 2012
ECHA, 2013
OECD-SIDS, 2000
Guideline study reported in a
secondary source.
Reported in a secondary source
with limited study details.
Reported in a peer reviewed
secondary source for the isomeric
component CASRN 6145-73-9.
Cited in a peer reviewed source,
this value is higher than the other
studies which reported pour
points.
Reported in a secondary source.
Reported in a peer reviewed
source.
Reported in a peer reviewed
secondary source for the isomeric
component CASRN 6145-73-9.
Test substance 75 +/- 10% pure
with major impurities. Reported
in a secondary source.
Cited in a peer reviewed source.
Reported in a secondary source.
Adequate guideline study.
         7-582

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JUNE 2014 DRAFT REPORT
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT

Water Solubility (mg/L)
Log Kow
Flammability (Flash Point)
DATA
reported as 40 mm Hg at 1 10°C;
according to Isoteniscopic, ASTM
D2879 Method (Measured)
0.75at25°C
(Measured) ^
<0.098
Reported as <13 Pa; temperature not
specified (Measured)
2.9xlO'5
(Estimated) ^
1,080 (Measured)
according to GLP flask method study
1,200 (Measured)
1,600 (Measured)
0.11% at 25°C (Measured)
2.68
HPLC method (Measured)
2.59
(Measured) ^^^^
3.33
Reported at 20°C according to EC
Guideline 92/69 Annex V, Method A8;
non-GLP (Measured)
Flash point: 185°C according to
Pensky-Martens Closed Cup ASTM
D93 (Measured)
Flash point: 218°C (Measured)
REFERENCE

van der Veen and de Boer, 2012
NICNAS, 2001
EPIv4.11
ECHA, 2013
NICNAS, 2001
van der Veen and de Boer, 2012
OECD-SIDS, 2000; ECHA, 2013
ECHA, 2013
van der Veen and de Boer, 2012
OECD-SIDS, 2000
OECD-SIDS, 2000
van der Veen and de Boer, 2012
DATA QUALITY

Reported in a peer reviewed
source.
Reported in a peer reviewed
secondary source for the isomeric
component CASRN 6145-73-9.
According to the Modified Grain
Method.
Reported in a secondary source.
Reported in a peer reviewed
secondary source for isomeric
component CASRN 6145-73-9.
Reported in a peer reviewed
source.
Reported in secondary sources
with limited details.
Reported in a secondary source.
Reported in a peer reviewed
source.
Guideline study reported in a
secondary source; reproducibility
concerns noted in results.
Guideline study reported in s a
secondary source.
Guideline study reported in a
         7-583

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JUNE 2014 DRAFT REPORT
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT

Explosivity
Pyrolysis
pH
pKa
DATA

Flash point: 220°C Cleveland open
cup (Measured)


Not applicable (Estimated)
Not applicable (Estimated)
REFERENCE

NICNAS, 2001


Professional judgment
Professional judgment
DATA QUALITY
secondary source.
Reported in a peer reviewed
secondary source for isomeric
component CASRN 6145-73-9.
^o data located.
^o data located.
Does not contain functional
groups that are expected to ionize
under environmental conditions.
Does not contain functional
groups that are expected to ionize
under environmental conditions.
         7-584

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                                                         JUNE 2014 DRAFT REPORT
                                            Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
            PROPERTY/ENDPOINT
              DATA
         REFERENCE
      DATA QUALITY
                                                         HUMAN HEALTH EFFECTS
Toxicokinetics
TCPP is readily absorbed. Absorption through human skin membranes in vitro was calculated to be 2.3-
32.8% of the applied dose. Twelve hours post- oral exposure, TCPP was detected in the brain, heart,
muscle, and testes, more so in adipose tissue, spleen, and lungs, and in the highest amounts in the liver
and kidney. TCPP is quickly and extensively metabolized with main metabolites being O,O-[bis(l-chloro-
2-propyl)]-O-(2-propionic acid) phosphate, bis(l-chloro-2-propyl) monophosphoric acid and l-chloro-2-
propanol. TCPP was metabolized to a hydroxylated metabolite by chlorine substitution in liver S9
faction and liver slices followed by glucuronic acid conjugation. In incubation experiments, Phase I
metabolites included the oxidative dechlorination products of TCPP and the hydrolysis product bis(l-
chloro-2-propyl) phosphate (BCPP), bis(l-chloro-2-propyl) l-hydroxy-2-propyl phosphate, bis(l-chloro-
2-propyl) 1-carboxy -2-propyl phosphate and l-chloro-2-propyl,l-hydroxy- 2-propyl phosphate; there
were no phase II metabolites detected. BCPP  was the most abundant metabolite. Once the tissues, the
parent compound and metabolites are rapidly excreted. Excretion occurred primarily via the urine, but
also in the feces and bile.
Dermal Absorption in vitro
Concentrations of TCPP tested over an
8 hour exposure period were 2.049,
99.96, or 997.33 (jg/cm2. The mean
penetration of TCPP into the receptor
fluid after 24 hours was 0.39, 9.64 and
17.75 (jg/cm2, for the low, mid and
high dose,  respectively. At 0.002
mg/cm2, the total absorption ranged
from 17 % to 32.8%, with a mean total
absorption of 22.7 %. At the mid dose
of 0.1 mg/cm2, the total absorption
ranged from 9.8% to 18.2%, with the
mean total absorption of 13.6%. At 1
mg/cm2, the total absorption ranged
from 2.3% to 5.2%, with a mean total
absorption of 3.7%.
TNO, 2006 (as cited in EU, 2008)
                                               The actual concentrations of TCPP
                                               tested in an artificial sweat solution
                                               over an 8 hour exposure period were
                                  TNO, 2005 (as cited in EU, 2008)
Adequate; guideline and GLP-
compliant study. Data are from a
secondary source.
                                Guideline and GLP-compliant
                                study. Study details reported in a
                                secondary source.
                                                                     7-585

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                                                          JUNE 2014 DRAFT REPORT
                                             Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
            PROPERTY/ENDPOINT
                                            DATA
                                            REFERENCE
                                       DATA QUALITY
                                                76 (jg/mL and 506 (ig/L. At 24 hours
                                                after application, the total mean
                                                absorption of TCPP into the receptor
                                                fluid, the receptor compartment wash
                                                and the skin (excluding tape strips)
                                                was 33.3% and 38.1% for the low and
                                                high doses respectively. The mean
                                                recovery of TCPP in human skin was
                                                93.1% and 92.2% for the low and high
                                                doses respectively. The permeability
                                                constant (Kp) for TCPP in artificial
                                                sweat under infinite conditions (24
                                                hour exposure) was 7.65 x 10~3 cm/h.
Absorption,
Distribution,
Metabolism &
Excretion
Oral, Dermal or Inhaled
Male Wistar rats administered a single
50 (jmol/kg (~14 mg/kg) gavage dose
of14C-labeledTCPP
Maximum concentration in tissues: 5.7
hours. Low tissue/blood ratios were
recorded in the brain, heart, muscle,
and testes. Moderate ratios were
obtained in adipose tissue, the spleen,
and lung; high ratios were recorded in
the liver and kidneys. The highest
amounts of radioactivity in the liver
and kidney were detected during the
first 12 hours after dosing. Seven days
after dosing, the highest amount of
radioactivity was found in the liver.
The longest elimination half-lives from
any tissue corresponded to adipose
tissue (103 hours for TCPP).
Minegishi et al., 1988
Adequate
                                                14C-labeled Fyrol PCF given to
                                                Sprague-Dawley rats at 20 or 200
                                                                 Stauffer Chem Co, 1984 (as cited in
                                                                 OECD-SIDS, 2000; EU, 2008)
                                                                   Data provided in a secondary
                                                                   source based on scientific review
                                                                      7-586

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                                               JUNE 2014 DRAFT REPORT
                                 Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                     mg/kg via a single oral or i.v.
                                     administration. Urine was the major
                                     route of elimination. Test substance is
                                     rapidly metabolized with main
                                     metabolites being O,O-[bis(l-chloro-2-
                                     propyl)]-O-(2-propionic acid)
                                     phosphate, bis( 1 -chloro-2-propyl)
                                     monophosphoric acid and l-chloro-2-
                                     propanol. The total body burden at the
                                     end of 8 days was less than 1%
                                     suggesting insignificant
                                     bioaccumulation.
                                                      of peer literature.
                                     Male Wistar rats administered a single
                                     50 (jmol/kg (~14 mg/kg) gavage dose
                                     of 14C-labeled TCPP -60% of TCPP
                                     was excreted in the urine; recovery
                                     within the 7 days approached 100%.
                                     Experiments in rats with cannulated
                                     bile ducts showed that peak biliary
                                     excretion occurred approximately 2
                                     hours after dosing with TCPP. 45% of
                                     administered TCPP was excreted in the
                                     bile in 48 hours. Since the biliary/fecal
                                     excretion ratios for TCEP exceeded 1,
                                     it appeared that enterohepatic
                                     circulation occurred.
                     Minegishi et al., 1988
                       Adequate
                                     Male Wistar rats were administered 50
                                     (jmol/kg TCPP.
                                     97.8% of the radioactive dose was
                                     recovered; of the recovered dose, 67
                                     and 22% were recovered in the urine
                                     and feces (respectively), 7.7% in
                                     expired air, and <1% in the carcass.
                     Minegishi et al., 1988
                       Adequate
                                                           7-587

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                                              JUNE 2014 DRAFT REPORT
                                 Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
              DATA
         REFERENCE
       DATA QUALITY
      Other
                                    Little radioactivity remained in the
                                    tissues 168 hours after dosing.
14C-labeled TCPP incubated with rat
liver fractions for 4 or 24 hours. TCPP
was metabolized to a hydroxylated
metabolite by chlorine substitution in
liver S9 fraction and liver slices,
followed by glucuronic acid
conjugation in liver slices. 11% and
39% of unmetabolized TCPP were
detected in S9 fraction and liver slices,
respectively.
BASF, 2007 (as cited in EU, 2008)
Study details reported in a
secondary source. Documentation
insufficient for assessment of data
quality.
                                    Incubation experiments using 1.0
                                    mg/mL HLM or S9 proteins, 50
                                    TBOEP or TCEP, or TCPP, or 20
                                    TPHP or TDCPP and NADPH
                                    regenerating solution in 1 mM total
                                    volume were conducted for 1 hour.
                                    There was a 33% and 28% clearance
                                    of the compound in the HLM and S9
                                    incubations, respectively.
                                    Phase I metabolites included the
                                    oxidative dechlorination products of
                                    TCPP and the hydrolysis product
                                    bis(l-chloro-2-propyl) phosphate
                                    (BCPP, Ml), bis(l-chloro-2-propyl) 1-
                                    hydroxy-2-propyl phosphate (M2),
                                    bis(l-chloro-2-propyl)  1-carboxy -2-
                                    propyl phosphate (M3) and l-chloro-2-
                                    propyl,l-hydroxy- 2-propyl phosphate
                                    (M4); there were no phase II
                                    metabolites detected. BCPP was the
                                    most abundant metabolite.
                                   Van den Bade et al., 2013
                                Study details reported in an
                                abstract
                                                          7-588

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JUNE 2014 DRAFT REPORT
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
Acute Mammalian Toxicity
Acute Lethality
Oral
Dermal
DATA
REFERENCE
DATA QUALITY
LOW: Based on LD50 and LC50 values for the oral, dermal, and inhalation routes of exposure.
Rat LD50 (range) = 1,073 - 3,600
mg/kg
Rat LD50 = 1,546 - 1,824 mg/kg
(males); 1,017- 1,101 mg/kg
(females)
Rat LD50 = 2,800 mg/kg (females);
4,200 mg/kg (males)
Rats exposed at 200, 500, or 2,000
mg/kg. All rats (females) died at 2,000
mg/kg; no mortalities at other dose
levels.
LD50 > 500 mg/kg (males) and >632
mg/kg (females) V.^r
RatLD50 = 931- 1,550 mg/kg
Rat LD50 = 2,000 mg/kg (males) and
1,260 mg/kg (females)
Rat 96-h LD50 = 1,500 mg/kg
(females) ^^^
Rabbit LD50 >2,000 mg/kg
Rat LD50 >2,000 mg/kg
SafePharm Labs Ltd, 1979a, 1979b;
Stauffer Chem Co, 1972 (as cited in
EC, 2000; EU, 2008)
Mobil, 1980a, 198 la (as cited in
EC, 2000; OECD-SIDS, 2000; EU,
2008)
Huntingdon, 1997a, 1997b (as cited
in EC, 2000; OECD-SIDS, 2000;
EU, 2008)
Stropp, 1996 (as cited in EU, 2008;
ATSDR, 2012)
SafePharm Labs Ltd, 1994, 1996a,
1996b, 1997a, 1997b (as cited in
EU, 2008)
Litton Bionetics, 1977 (as cited in
ATSDR, 2012)
Kawasaki et al., 1982 (as cited in
ATSDR, 2012)
Stauffer Chem Co, 1970, 1979;
Mobil, 1980b, 1981b (as cited in
EC, 2000; EU, 2008)
Inveresk Res Int, 1989b (as cited in
Adequate by weight of evidence;
data obtained from multiple
secondary sources.
Adequate by weight of evidence;
data from secondary sources.
Adequate; performed according to
current standards and GLP-
compliant.
Study details reported in a
secondary source.
Adequate; conducted according to
OECD guidelines.
Study details from an anonymous
source reported in a secondary
source.
Study details reported in a
secondary source.
Study details reported in a
secondary source. Test substance
identified as TCPP in some
studies; Antiblaze 80 or Fyrol
PCF in others. Purity of the test
substance reported in some
studies.
Study details from several studies
         7-589

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Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT


Inhalation
Carcinogenicity

OncoLogic Results
Carcinogenicity (Rat and
Mouse)
Combined Chronic
Toxicity/Carcinogenicity
Other
DATA

Rat 4-h LC50 (whole-body): >5 mg/L
(males); ~5 mg/L (females)
Rat 4-h LC50 (nose-only) >7 mg/L
Rat 1-h LC50 (whole-body) >17.8
mg/L
REFERENCE
OECD-SIDS, 2000; EU, 2008)
Env Affairs, 1981a (as cited in EC,
2000; OECD-SIDS, 2000; EU,
2008)
Inveresk Res Int, 1990a (as cited in
EC, 2000; EU, 2008)
Env Affairs, 1981b (as cited in EC,
2000; EU, 2008)
DATA QUALITY
reported in secondary source. At
least one study was performed
according to OECD guidelines
and GLP.
Study based on EPA guidelines;
sufficient study details reported;
analyses of test concentrations
and cumulative mass of the
particles were performed.
OECD guideline study performed
according to GLP. Test
concentrations and particle size
distribution analyses were
performed; sufficient study details
reported. Purity (total of four
isomers) >97.9%.
Study based on EPA guidelines;
sufficient study details reported.
MODERATE: There were no experimental data located for this endpoint; carcinogenic effects cannot be
ruled out.








No data located.
^o data located.
No data located.
No data located.
         7-590

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Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
Genotoxicity

Gene Mutation in vitro
DATA
REFERENCE
DATA QUALITY
LOW: Based on weight of evidence from multiple studies. TCPP did not cause gene mutations in
bacteria in vitro or chromosome aberrations in rat bone marrow in vivo.
In multiple studies: Negative for
mutation in Salmonella typhimurium
strains TA97a, TA98, TA100, TA102,
TA104, TA1535, TA1537, and/or
TA1538 in the presence or absence of
metabolic activation at up to 1 mM.
Negative; gene mutation in E. coll
strains W3 1 1 0/po 1 A+ and
p3478/polA- at doses up to 20 (J/plate
in the presence or absence of
metabolic activation.
Negative; gene mutation in
Saccharomyces cerevisiae strain D4 in
the presence or absence of activation.
Positive in the presence of metabolic
activation; gene mutation in L5 178Y
mouse lymphoma cells. Negative in
the absence of metabolic activation.
Positive; transformation of BALB/3T3
cells
Negative; forward mutation in mouse
lymphoma L5 178Y cells at TK locus
in the presence or absence of
Zeiger et al., 1992; Abe and Urano,
1994; Follmann and Wober, 2006
(as cited in EU, 2008; ATSDR,
2012)
Tenneco Chem Inc, 1977 (as cited
in EU, 2008)
Stauffer Chem Co, 1976, 1978d (as
cited in EU, 2008)
Covance Labs, 2005; Env Affairs,
198 Ic (as cited in EU, 2008)
Stauffer Chem Co, 1978e (as cited
in EU, 2008)
Stauffer Chem Co, 1978c (as cited
in EU, 2008)
Study details reported in a
secondary source; similar to
guideline studies. Exact purity of
test substances was not reported,
but a reagent grade chemical was
used.
Adequate; data from a secondary
source.
Adequate; data reported in a
secondary source.
Adequate; data reported in a
secondary source. Results
considered equivocal in one assay
because a dose-response
relationship could not be
ascertained. Results were positive
with activation in a confirmatory
mouse lymphoma assay.
Data reported in a secondary
source. Positive at all doses (39-
312nl/ml50-400(jg/ml);
however, no dose-response
relationship was observed.
Acceptable, well-documented
publication report which meets
basic scientific principles. Data
         7-591

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Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT


Gene Mutation in vivo
Chromosomal Aberrations in
vitro
Chromosomal Aberrations in
vivo
DNA Damage and Repair
DATA
metabolic activation.
Negative; transformation of
BALB/3T3 cells at up to 40 nL/mL
(51.6jig/mL).


Negative for induction of micronuclei
in Sprague-Dawley rats administered
TCPP in the feed at up to 20,000 ppm
for 90 days.
Negative for chromosomal aberrations
in bone marrow of Sprague-Dawley
rats orally exposed.
Positive in males and negative in
female for induction of micronuclei in
B6C3F1 mice administered TCPP in
feed at 1, 1250, 2500, 5,000, 10,000,
or 20,000 ppm for 90 days.
Negative for DNA damage (comet
assay) in the presence or absence of
activation in Chinese hamster V79
cells. The test substance caused
cytotoxicity (neutral red uptake assay)
in the presence, but not absence of
activation.
Negative; UDS in rat liver cells
TCPP did not induce DNA damage in
REFERENCE

Stauffer Chem Co, 1980b (as cited
in EU, 2008)


NTP, 2013
Stauffer Chem Co, 1978b (as cited
in EU, 2008)
NTP, 2013
Follmann and Wober, 2006
Williams et al., 1989; Bayer, 1991b
(as cited in EU, 2008)
Covance Labs, 2006 (as cited in
DATA QUALITY
reported in a secondary source.
Adequate; similar to guideline
study. Data reported in a
secondary source. Although tests
were positive for one study, no
dose-response was observed.
No data located.
^o data located.
Adequate; limited study details
available from NTP website.
Study conducted according to
OECD guidelines; study details
reported in secondary source.
Adequate; limited study details
available from NTP website.
Purity of test substance was not
reported, but a reagent grade
chemical was used.
Adequate; data reported in a
secondary source. Guideline and
GLP -compliant study.
Study conducted similar to
         7-592

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Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT


Other
Reproductive Effects

Reproduction/Developmental
Toxicity Screen
Combined Repeated Dose with
Reproduction/ Developmental
Toxicity Screen
DATA
the liver or rats treated up to 1,500
mg/kg.
TCPP did not induce DNA strand
breaks in V79 cells in the presence or
absence of activation (alkaline comet
assay) at concentrations up to 1 mM.
Equivocal results UDS in human
diploid WI-38 cells. The test material
was weakly active at 0.01 (il/mL in
activated and nonactivated systems
without an associated dose response at
higher concentrations.

REFERENCE
EU, 2008; ECHA, 2013)
Follmann and Wober, 2006
^^^
Stauffer Chem Co, 1978a (as cited
in EU, 2008)

DATA QUALITY
guidelines and GLP-compliant;
study details reported in
secondary source.
Purity of test substance was not
reported, but a reagent grade
chemical was used.
Data were from a secondary
source. Test results were deemed
equivocal because no clear dose-
response relationship could be
ascertained, and performed using
a non-standard cell line. Results
in other cell types were negative.
No data located.
HIGH: Based on an unestablished NOAEL and a LOAEL of 99 mg/kg-day for decreased uterine weights
in FO female rats fed TCPP in a 2-generation reproduction study. Two other studies reported no
significant effects on reproductive parameters in rats exposed to TCPP in the diet at doses greater than
893 mg/kg-day.

^+


^o data located.
^o data located.
         7-593

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                                              JUNE 2014 DRAFT REPORT
                                 Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
              DATA
         REFERENCE
       DATA QUALITY
      Reproduction and Fertility
      Effects
Two-generation reproduction study in
Wistar rats (28/sex/group)
Doses: 0, 85, 293 and 925 mg
TCPP/kg-day for males and 0, 99, 330
and 988 mg TCPP/kg-day for females
(administered in the diet)
Decreased body weight and food
consumption was observed in mid and
high dose parental animals and the
effects on uterus weights seen in all
dosed FO animals.
There were no treatment related effects
in pre-coital time, mating index,
female fecundity  index, male and
female fertility index, duration of
gestation and post-implantation loss
There was no effect on sperm
parameters at necropsy
In females, the length of the longest
oestrus cycle and the mean number of
cycles per animal were statistically
significantly increased in high dose
animals of both generations. A
decrease in uterus weight was
observed in all dosed females in FO
and in high dose females in F1.
              J
NOAEL: Not established
LOAEL: 99 mg/kg-day based on
effects on uterus weights (lowest dose
tested).
TNO, 2007 (as cited in EU, 2008)
Adequate; guideline (OECD 416)
and GLP-compliant study. Data
obtained from a secondary source
only; primary source not
specified.
                                                          7-594

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                                                        JUNE 2014 DRAFT REPORT
                                           Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
           PROPERTY/ENDPOINT
              DATA
         REFERENCE
      DATA QUALITY
                 Other
Dietary study in rats; exposure: GD 0 -
20; doses: up to 893 mg/kg-day
No significant effect on the numbers of
implantations or resorptions.

NOAEL: 893 mg/kg-day (highest dose
tested)
LOAEL: Not established
Kawasaki et al., 1982 (as cited in
ATSDR, 2012)
Limited study details reported in a
secondary source. Unknown
purity of test substance. The 893
mg/kg-d dose level was the
highest dose tested. The true
NOAEL may be higher.
                                               In a 90 day study, 20 male and 20
                                               female Sprague Dawley rats were fed
                                               diets containing 0, 800, 2,500, 7,500
                                               and 20,000 ppm of TCPP, there were
                                               no effects observed in the testes or
                                               ovaries of treated animals when
                                               examined at necropsy

                                               NOAEL: 20,000 ppm (Highest
                                               concentration tested)
                                               LOAEL: Not established
                                  Freudenthal and Henrich, 1999
                                Inadequate for complete
                                assessment of reproductive
                                toxicity; data are for the Fyrol
                                PCF mixture (about tris (2-
                                chloroisopropyl) phosphate (about
                                70%) and 2-chloropropanol
                                phosphate (about 23%).
Developmental Effects
HIGH: Based on an unestablished NOAEL and a LOAEL of 99 mg/kg-day for an increased number of
runts in rats exposed to TCPP in the diet in a 2-generation reproduction study. Another study reported
no significant developmental effects in offspring of rats gestationally exposed to TCPP in the diet at
doses up to 893 mg/kg-day.
There were no data located for the developmental neurotoxicity endpoint; there is uncertain concern for
developmental neurotoxicity based on the potential for Cholinesterase (ChE) inhibition in dams that
may result in alterations of fetal neurodevelopment.
                 Reproduction/ Developmental
                 Toxicity Screen
                 Combined Repeated Dose with
                 Reproduction/ Developmental
                 Toxicity Screen
                                                                 No data located.
                                                                 No data located.
                                                                    7-595

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Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
































Prenatal Development
















Postnatal Development
Prenatal and Postnatal
Development
Developmental Neurotoxicity




Other






DATA
Dietary study in Wistar rats
Exposure: GD 0 - 20; doses: 0.01, 0.1,
and 1% in the diet (up to 893 mg/kg-
day)
No significant effects on fetal weight
or incidences of external
malformations. Cervical ribs, missing
ribs, and delayed ossification of
sternebrae were more frequent in
treated groups but not significantly
different from controls. Neonatal
growth and survival during the 4
weeks after weaning was comparable
among groups.
NOAEL: 893 mg/kg-day (highest dose
tested)
LOAEL: Not established



Uncertain concern for developmental
neurotoxicity based on the potential for
Cholinesterase (ChE) inhibition in
dams that may result in alterations of
fetal neurodevelopment (Estimated)
Two-generation reproduction study in
Wistar rats (28/sex/group)
Doses: 0, 85, 293 and 925 mg
TCPP/kg-day for males and 0, 99, 330
and 988 mg TCPP/kg-day for females
(administered in the diet)
Decreased mean number of pups
REFERENCE
Kawasaki et al., 1982 (as cited in
EU, 2008; ATSDR, 2012)



^^^



^^*










Professional judgment




TNO, 2007 (as cited in EU, 2008)






DATA QUALITY
Data obtained from a secondary
source; limited study details were
available in the secondary source.
Unknown purity of test substance.
The 893 mg/kg-d dose level was
the highest dose tested. The true
NOAEL may be higher.










No data located.
^o data located.

Estimated based on a structural
alert for organophosphates for the
neurotoxicity endpoint.


Data reported in a secondary
source. Adequate; guideline
(OECD 416) and GLP-compliant
study. Data obtained from a
secondary source.


         7-596

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                                              JUNE 2014 DRAFT REPORT
                                 Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                    delivered was observed in the mid
                                    dose group of the Fl generation and in
                                    the high dose groups of both
                                    generations. Pup mortality (PND1-4)
                                    was statistically significantly increased
                                    in the low and high dose FO groups
                                    and in the high doseFl group. This
                                    effect was only observed when the pup
                                    was used as the statistical unit. The
                                    effect observed in the Fl generation
                                    was mainly due to the loss of one litter
                                    (10 pups) of a single dam on PND4.
                                    There was no statistically significant
                                    difference in the mean number of pups
                                    on PND4.
                                    In the FO generation, the mean number
                                    of runts was statistically significantly
                                    increased in all dose groups on PND1
                                    and persisted to PND21 in the mid and
                                    high dose groups. In Fl generation, the
                                    number of runts was increased in the
                                    high dose group on PND 14 and in all
                                    dose groups on PND21.
                                    In both generations, the number of
                                    runts in the high dose groups increased
                                    during the course of the lactation
                                    period.
                                    There was no effect on pup weight at
                                    PND1 in either generation. There was
                                    no effect on pup weight on PND1 in
                                    both generations. Mean pup weights of
                                    the high dose group were significantly
                                    decreased in FO generation from
                                    PND 14 onwards and in the Fl
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                                              JUNE 2014 DRAFT REPORT
                                 Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                    generation from PND 7 onwards.
                                    Mean pup weights were decreased in
                                    mid dose groups on PND21
                                    No difference in anogenital distance of
                                    the male or female F2 pups was
                                    observed between the treated and
                                    control animals. Vaginal opening was
                                    delayed (not significantly) in the high
                                    dose group. Preputial separation was
                                    statistically significantly delayed in the
                                    high dose group. The body weight of
                                    the high dose male and females of the
                                    F2 generation was significantly
                                    decreased from PND28 until PND42
                                    (91% and 89% of control at PND42 for
                                    females and males of this group,
                                    respectively). The effects observed in
                                    this dose group on vaginal opening and
                                    preputial separation is most likely
                                    secondary to toxicity.
                                    At necropsy of the pups there were no
                                    treatment related macroscopic
                                    findings.

                                    NOAEL: Not established
                                    LOAEL: 99 mg/kg-day based on
                                    treatment related effect on the number
                                    of runts in FO generation (lowest dose
                                    tested).
                                                          7-598

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                                             Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
            PROPERTY/ENDPOINT
              DATA
         REFERENCE
       DATA QUALITY
Neurotoxicity
MODERATE: Based on the weight of evidence from a structural alert for organophosphates and an in
vitro study. In an in vitro study using undifferentiated and differentiating PC12 cells, TCPP promoted
differentiation of the cholinergic phenotype of PC12 cells. There were no effects on cholinesterase
activity in a dietary study in rats fed TDCPP and no evidence of delayed neurotoxicity in one study of
hens orally treated with TCPP.
                  Neurotoxicity Screening
                  Battery (Adult)
                  Other
Potential for neurotoxicity based on
structural alert for organophosphates
(Estimated)
                                                In vitro neurotoxicity study using
                                                undifferentiated and differentiating
                                                PC 12 cells. Changes in DNA
                                                synthesis, oxidative stress,
                                                differentiation into dopaminergic or
                                                cholinergic neurophenotypes, cell
                                                number, cell growth and neurite
                                                growth were assessed.
                                                TCPP promoted differentiation of the
                                                cholinergic phenotype only. There
                                                were no other adverse neurological
                                                effects.
                                                 14-day dietary study in CD-I rats
                                                treated with 0, 4200, 6600, 10,600, and
                                                 16,600 ppm (approximately 0, 417,
                                                648, 1,015, 1,636 mg/kg-day for males
                                                and 382, 575, 904, 1,517 mg/kg/day
                                                for females).
                                                There were no effects on
                                                cholinesterase activity.

                                                NOAEL: 16,600 ppm (1,636 mg/kg-
                                                day); highest dose tested
Professional judgment
                                   Dishawetal., 2011
                                   Stauffer Chem Co, 1980a
                                                                       data located.
Estimated based on a structural
alert and professional judgment.
                                 Study details reported in a
                                 primary source
                                 Test substance was identified as
                                 Fyrol PCF, a mixture containing
                                 TCPP (-70%) and 2-
                                 chloropropanol phosphate
                                   22%); limited study details
                                 reported in a robust summary.
                                                                      7-599

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                                                         JUNE 2014 DRAFT REPORT
                                            Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
           PROPERTY/ENDPOINT
              DATA
REFERENCE
      DATA QUALITY
                                               LOAEL: Not established
                                               Delayed oral neurotoxicity in White
                                               leghorn hens (18/treatment group and
                                               10 controls); doses: 13,200 mg/kg (10
                                               mL/kg) by gavage; exposure period:
                                               Two treatments, three weeks apart
                                               Treated hens showed loss of body
                                               weight and transient reductions in food
                                               consumption immediately following
                                               treatment. There was no evidence of
                                               delayed motor impairment; no
                                               histological changes to nervous tissues
                                               were found.
                                               NOAEL: Not established
                                               LOAEL: 13,200 mg/kg
                                  Sprague et al., 1981; OECD-SIDS,
                                  2000
                       Study details reported in a
                       primary source; not a guideline
                       study.
Repeated Dose Effects
MODERATE: Based on reported morphological changes in the kidney and thyroid reported in rats fed
the Fyrol PCF mixture (tris (2-chloroisopropyl) phosphate [~70%] and 2-chloropropanol phosphate [~
23%]) in the diet for 90 days at doses of 481 mg/kg-day and 570 mg/kg-day in males and females,
respectively. Decreased body weight gain and food consumption was reported in rats fed Fyrol PCF for
14 days. Also, rats exposed to TCPP in the diet for 28 days reported increased mortality in females at a
dose of 1,000 mg/kg-day; the NOAEL for this study was identified as 100 mg/kg-day which falls within
the Moderate hazard criteria range. Criteria values are tripled for chemicals evaluated in 28-day studies.
There is uncertainty about where effects may occur given that the identified NOAEL (100 mg/kg-day)
and LOAEL (1,000 mg/kg-day) bridges the Moderate (30 - 300 mg/kg-day) and Low (> 300 mg/kg-day)
hazard designation range; effects occurring within the Moderate range cannot be ruled out.
                                               90-day dietary study in CD Sprague-
                                               Dawley rats (20/sex/group)
                                               administered 0, 800, 2,500, 7,500, or
                                               20,000 ppm Fyrol PCF (average doses
                                               of 0, 52, 160, 481, and 1,349 mg/kg-
                                               day for males and 0, 62, 171, 570, and
                                  Freudenthal and Henrich,
                                  OECD-SIDS, 2000
             1999;
Data are for the Fyrol PCF
mixture (about tris (2-
chloroisopropyl) phosphate (about
70%) and 2-chloropropanol
phosphate (about 23%).
                                                                    7-600

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                                 Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                     1,352 mg/kg-day for females estimated
                                     by the study authors)
                                     At the high-dose, body weights were
                                     significantly decreased relative to
                                     controls. Significantly increased
                                     absolute and relative liver weights
                                     were observed in all treated males and
                                     in females in the two highest dose
                                     groups. Mild periportal hepatocellular
                                     swelling was noted in some animals at
                                     20,000 ppm; no changes in liver
                                     histopathology were seen at other
                                     doses. Males showed significantly
                                     increased relative kidney weights at >
                                     7,500 ppm; microscopic kidney
                                     changes (very mild cortical tubular
                                     degenerative effects) were observed in
                                     males at 7,500 ppm and at 20,000 ppm
                                     males and females. Increased
                                     incidence of very mild thyroid
                                     follicular  changes was noted  in the two
                                     highest dose groups. Histopathological
                                     changes occurred in the absence of
                                     significant effects on hematology or
                                     clinical chemistry endpoints (including
                                     those associated with liver and kidney
                                     function).

                                     NOAEL:  2,500 ppm (160 and 171
                                     mg/kg-day for males and females,
                                     respectively)
                                     LOAEL: 7,500 ppm (481 and 570
                                     mg/kg-day for males and females,
                                     respectively) based on minimal
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                                              JUNE 2014 DRAFT REPORT
                                 Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                    morphological changes (kidney,
                                    thyroid)
                                     14-day dietary study in CD-I rats
                                    treated with 0, 4,200, 6,600, 10,600,
                                    and 16,600 ppm (approximately 0,
                                    417, 648, 1,015, 1,63 6 mg/kg/day for
                                    males and 382, 575, 904, 1,517
                                    mg/kg/day for females)
                                    A significant reduction in body weight
                                    gain and decreased food consumption
                                    was observed in male rats at 10,600
                                    ppm in week 1. There were no effects
                                    on hematology, clinical chemistry, or
                                    cholinesterase  activity. Increased liver
                                    weights occurred in the absence of
                                    histopathological changes.

                                    NOAEL: 6,600 ppm (648 mg/kg-day)
                                    LOAEL: 10,600 ppm (1,015 mg/kg-
                                    day) based on decreased body weight
                                    gain and food consumption in males.
                     Stauffer Chem Co, 1980a (as cited
                     in EC, 2000; EU, 2008)
                       Test substance was identified as
                       Fyrol PCF, a mixture containing
                       TCPP (-70%) and 2-
                       chloropropanol phosphate
                       (-22%); limited study details
                       reported in a robust summary.
                                    28-day gavage study in Wistar rats
                                    (6/sex/group) dosed daily with 0, 10,
                                    100, or 1,000 mg/kg-day test substance
                                    (97.85% pure).
                                    Increased mortality in high-dose
                                    females. No effect on body weight or
                                    food consumption. Increased water
                                    intake in high-dose groups. No effect
                                    on hematology, clinical chemistry or
                                    urinalysis. Necropsy did not show
                                    gross alterations. Histopathology
                                    showed adaptive effects in the liver
                     Bayer, 1991c (as cited in EC, 2000;
                     EU, 2008)
                       Only qualitative data reported in a
                       secondary source. Study appears
                       to have examined a
                       comprehensive number of
                       endpoints; criteria values are
                       tripled for chemicals evaluated in
                       28-day studies; there is
                       uncertainty about where effects
                       may occur given that the
                       identified NOAEL (100 mg/kg-
                       day) and LOAEL (1,000 mg/kg-
                       day) bridges the Moderate (30 -
                                                          7-602

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Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT


Skin Sensitization

Skin Sensitization
Respiratory Sensitization
[Respiratory Sensitization
Eye Irritation

Eye Irritation
DATA
from high-dose rats.
NOAEL: 100 mg/kg-day;
LOAEL: 1,000 mg/kg-day (increased
mortality in females).
7-day repeated-dose gavage study in
rats exposed to 1,000 mg/kg-day (other
doses, if any, were not reported).
No effects on body weight gain or
relative organ weights (brain, heart,
lungs, liver, spleen, kidneys, or
adrenals) at doses up to 1,000 mg/kg-
day
NOAEL: 1,000 mg/kg-day
LOAEL: Not established
REFERENCE

Kawasaki et al., 1982 (as cited in
ATSDR, 2012)
l^^s '
DATA QUALITY
300 mg/kg-day) and Low (>300
mg/kg-day) hazard designation
range; effects occurring within the
Moderate range cannot be ruled
out.
Limited study details reported in a
secondary source.
LOW: TCPP is not a skin sensitizer.
Human; not sensitizing
Mouse (local lymph node assay); not
sensitizing
Guinea pig; not sensitizing
BASF, 1979 (as cited in EC, 2000)
SafePharm Labs Ltd, 2005 (as cited
in EU, 2008)
SafePharm Labs Ltd, 1979e (as
cited in EC, 2000; EU, 2008)
Limited data available from a
secondary source.
Adequate; guideline and GLP-
compliant. Study details reported
in a secondary source.
Limited data available from a
secondary source. Not performed
according to GLP.
No data located.

|No data located.
LOW: TCPP was not irritating to slightly irritating in rabbits.
Rabbit; not irritating
Stauffer Chem Co, 1972, 1979;
SafePharm Labs Ltd, 1979c; Bayer,
199 la (as cited in EC, 2000; EU,
2008)
Adequate by weight of evidence.
Data from secondary sources.
         7-603

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Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT


Dermal Irritation

Dermal Irritation
DATA
Rabbit; slightly irritating. Transient;
effects typically resolved 24 to 72
hours post-administration.
Extensive experimental data indicate
that TCPP is non-irritant to the rabbit
eye.
REFERENCE
Mobil, 1981d, 1980d; Inveresk Res
Int, 1990b (as cited in EC, 2000;
OECD-SIDS, 2000; EU, 2008)
EU, 2008
DATA QUALITY
Study details reported in a
secondary source.
Data are from a secondary source;
primary data sources not
specified.
LOW: Based on weight of evidence from multiple studies. TCPP is not irritating to skin in humans and
rabbits.
Human; not irritating
Rabbit; not irritating
Rabbit; slightly irritating. Transient;
effects typically resolved within 72
hours.
\
Extensive experimental data indicate
that TCPP in non-irritant to rabbit skin.
BASF, 1979 (as cited in EC, 2000)
Mobil, 198 Ic, 1980c; Stauffer
Chem Co, 1972 (as cited in EC,
2000; EU, 2008)
Stauffer Chem Co, 1979;
SafePharm Labs Ltd, 1979d;
Inveresk Res Int, 1989a (as cited in
EC, 2000; OECD-SIDS, 2000; EU,
2008)
EU, 2008
Study details reported in a
secondary source.
Study details reported in a
secondary source.
Study details reported in a
secondary source.
Study details reported in a
secondary source; primary data
sources not specified.
         7-604

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                                                         JUNE 2014 DRAFT REPORT
                                            Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
           PROPERTY/ENDPOINT
              DATA
REFERENCE
DATA QUALITY
Endocrine Activity
TCPP increased 17B estradiol and testosterone production in H295R cells, up-regulated steroidogenic
genes and down-regulated sulfotransferases. TCPP also inhibited dihydrotestosterone and 17B estradiol
induced expression indicating antiandrogenic or antiestrogenic activity, while TCPP was found to not
induce estrogenic or anti-estrogenic effects in a yeast reporter gene assay and a human endometrial
cancer cell assay.
                                               Two-generation reproduction study in
                                               Wistar rats (28/sex/group)
                                               Doses: 0, 85, 293 and 925 mg
                                               TCPP/kg-day for males and 0, 99, 330
                                               and 988 mg TCPP/kg-day for females
                                               (administered in the diet)
                                               Decreased body weight and food
                                               consumption was observed in mid and
                                               high dose parental animals and the
                                               effects on uterus weights seen in all
                                               dosed FO animals.
                                               In females, the length of the longest
                                               oestrus cycle and the mean number of
                                               cycles per animal were statistically
                                               significantly increased in high dose
                                               animals of both generations. A
                                               decrease in uterus weight was
                                               observed in all dosed females in FO
                                               and in high dose females in Fl.
                                  TOO, 2007 (as cited in EU, 2008)
                                               TCPP significantly increased 17B-
                                               estradiol (at 100 mg/L) and
                                               testosterone production (at>l mg/L) in
                                               H295R cells. The transcription of other
                                               steroidogenic genes (CYP11A1,
                                               CYP112B, HSD3B2) were up-
                                               regulated and sulfotransferases
                                               (SULT1E1, SULT2A1) were down-
                                  Liu etal., 2012
                       Adequate; guideline (OECD 416)
                       and GLP-compliant study. Data
                       obtained from a secondary source
                       only; primary source not
                       specified; the observed changes
                       may be an indication of endocrine
                       activity.
                       Test substance purity was not
                       reported.
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                                               JUNE 2014 DRAFT REPORT
                                 Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                     regulated in response to treatment with
                                     TCPP.
                                     TCPP inhibited expression induced by
                                     dihydrotestosterone (IC50 = 1.8 x 10"
                                     M) and 17B-estradiol (IC50 = 2.3 x 10"
                                     4M); indicating that TCPP may have
                                     antiandrogenic and/or antiestrogenic
                                     activities.
                     Ohyama et al., 2006
                        Study details from the primary
                        report are available; however,
                        only the study summary and
                        figure legends are reported in
                        English.
                                     TCPP did not induce estrogenic or
                                     anti-estrogenic effects at up to 10
                                     as based on results of the recombinant
                                     yeast reporter gene assay and Ishikawa
                                     (human endometrial cancer) cell assay.
                     Follmann and Wober, 2006
                       Adequate.
                                     7-day repeated-dose gavage study in
                                     rats exposed to 1,000 mg/kg-day (other ATSDR,
                                     doses, if any, were not reported). No
                                     effects on adrenals weights at doses up
                                     to 1,000 mg/kg-day
                     Kawasaki et al., 1982 (as cited in
                             2012)
                       Limited study details reported in a
                       secondary source.
                                     90-day dietary study in CD Sprague-
                                     Dawley rats (20/sex/group)
                                     administered 0, 800, 2,500, 7,500, or
                                     20,000 ppm Fyrol PCF (average doses
                                     of 0, 52, 160, 481, and 1,349 mg/kg-
                                     day for males and 0, 62, 171, 570, and
                                     1,352 mg/kg-day for females estimated
                                     by the study authors)
                                     Increased incidence of very mild
                                     thyroid follicular changes was noted in
                                     the two highest dose groups.
                                     Histopathological changes occurred in
                                     the absence of significant effects on
                                     hematology or clinical chemistry
                                     endpoints (including those associated
                     Freudenthal and Henrich, 1999 (as
                     cited in OECD-SIDS, 2000)
                       Data are for the Fyrol PCF
                       mixture (about tris (2-
                       chloroisopropyl) phosphate (about
                       70%) and 2-chloropropanol
                       phosphate (about 23%); the
                       observed changes may be an
                       indication of endocrine activity.
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                                              JUNE 2014 DRAFT REPORT
                                 Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                    with liver and kidney function).
                                    Two-generation reproduction study in
                                    Wistar rats (28/sex/group) Doses: 0,
                                    85, 293 and 925 mg TCPP/kg-day for
                                    males and 0, 99, 330 and 988 mg
                                    TCPP/kg-day for females
                                    (administered in the diet)
                                    No difference in anogenital distance of
                                    the male or female F2 pups was
                                    observed between the treated and
                                    control animals. Vaginal opening was
                                    delayed (not significantly) in the high
                                    dose group. Preputial separation was
                                    statistically significantly delayed in the
                                    high dose group. The body weight of
                                    the high dose male and females of the
                                    F2 generation was significantly
                                    decreased from PND28 until PND42
                                    (91% and 89% of control at PND42 for
                                    females and males of this group,
                                    respectively). The effects observed in
                                    this dose group on vaginal opening and
                                    preputial separation is most likely
                                    secondary to toxicity. At necropsy of
                                    the pups there were no treatment
                                    related macroscopic findings.

                                    NOAEL: Not established
                                    LOAEL: 99 mg/kg-day based on
                                    treatment related effect on the number
                                    of runts in FO generation (lowest dose
                                    tested).
                     TNO, 2007 (as cited in EU, 2008)
                       Data reported in a secondary
                       source. Adequate; guideline
                       (OECD 416) and GLP-compliant
                       study. Data obtained from a
                       secondary source.
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JUNE 2014 DRAFT REPORT
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
Immunotoxicity
Immune System Effects
DATA
REFERENCE
DATA QUALITY
No data located.

^^^ |No data located.
ECOTOXICITY
ECOSAR Class
Acute Aquatic Toxicity
Fish LC50

MODERATE: Based on experimental LC50 and EC50 values for fish, daphnia, and algae.
Poecilia reticulata 96 hour LC50 = 30
mg/L
(static test conditions)
(Experimental)
Pimephales promelas 96 hour LC50 =
5 1 mg/L
(static test conditions)
(Experimental)
Killifish (Oryzias latipes) 48-hour
LC5o = 54 mg/L
(Experimental)
Brachydanio rerio 96 hour LC50 = 56.2
mg/L
LC0 = 31.6mg/L;
Griebenow, 1998 (as cited in EC,
2000; EU, 2008)
^
Meeks, 1985c (as cited in EC, 2000;
OECD-SIDS, 2000; EU, 2008)
7
MITI, 1992 (as cited in EC, 2000;
EU, 2008)
Kanne, 1991 (as cited in EC, 2000;
EU, 2008)
The test substance was identified
as technical grade TCPP; specific
purity was not reported.
Guideline-like study (OECD
203); however analytical
monitoring was reportedly not
performed.
LC50 based on linear regression
from 168 hours exposure and
actual test concentrations.
Differences in nominal and actual
test concentrations were attributed
to limited water solubility of the
test substance. Analytical
monitoring was performed and
study was conducted according to
guideline (OECD 203) and GLP.
Not standard duration for acute
toxicity to fish; no additional
details were available. Reported
method: Japanese Industrial
Standard (JIS K0102-1986-71)
Testing Methods for Industrial
Waste Water.
Analytical monitoring was
performed; study was conducted
according to GLP. The test
         7-608

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                                              JUNE 2014 DRAFT REPORT
                                 Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                    LC10o= 100mg/L
                                    (static test conditions)
                                    (Experimental)
                                                    substance was 97.9% pure
                                                    including all isomers.
                                    Lepomis macrochirus 96 hour LC50:
                                    84 mg/L;
                                    NOEC = 9.8 mg/L
                                    (static test conditions)
                                    (Experimental)
                    Meeks, 1985b (as cited in EC, 2000:
                    OECD-SIDS, 2000; EU, 2008)
                                    Wild-type Zebrafish embryos (20 per
                                    replicate) exposed to TCPP under
                                    static conditions at 0.05 to 50 (JVI until
                                    96 hours post-fertilization (24 hours
                                    post-hatch).
                                    No effects on mortality, gross
                                    developmental malformations, delayed
                                    hatching, or obvious signs of impaired
                                    locomotion
                                    NOEC = 50 \M
                                    (Experimental)
                    McGeeetal., 2012
                                    Freshwater Fish 96-hour LC50 = 43
                                    mg/L
                                    (Estimated)
                                    ECOSAR: Neutral organics
                    ECOSARvl.ll
                       LC50 based on linear regression
                       from 120 hours exposure and
                       actual test concentrations.
                       Differences in nominal and actual
                       test concentrations were attributed
                       to limited water solubility of the
                       test substance. Analytical
                       monitoring was performed and
                       study was conducted according
                       guideline (OECD 203) and GLP.
                       Adequate details were provided;
                       purity of the test substance was
                       only 96%.
                       ECOSAR also provided results
                       for the Esters, and Esters
                       (phosphate) classes; however,
                       professional judgment indicates
                       that this compound is not
                       currently well represented in
                       ECOSARvl.ll.
                                                         7-609

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JUNE 2014 DRAFT REPORT
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
Daphnid LC50
Green Algae EC50
DATA
Daphnia magna EC50 =131 (65-335)
mg/L
48-hour NOEC = 33.5 mg/L
(Experimental)
Daphnia magna 48-hour EC50 = 63
mg/L
(Experimental)
Daphnia 48-hour LC50 = 27 mg/L
(Estimated)
ECOSAR: Neutral organics
^^\ X
Selenastrum capricornutum 96 hour
EC50 (biomass) = 47 (95% CI: 41-50)
mg/L
EC50 (growth rate) = 73 (95% CI: 57-
97) mg/L
NOEC = 6 mg/L
LOEC=18mg/L
(Experimental)
Scenedesmus subspicatus 72 hour EC50
(biomass) = 45 mg/L
(Experimental)
Pseudokirchneriella subcapitata 72-
REFERENCE
Meeks, 1985a (as cited in EC, 2000;
OECD-SIDS, 2000; EU, 2008)
^^^
Griebenow, 1998 (as cited in EC,
2000; EU, 2008)
ECOSAR v 1.11
7
Kroon and van Ginkel, 1992 (as
cited in EC, 2000; OECD-SIDS,
2000; EU, 2008)
Griebenow, 1998 (as cited in EC,
2000; EU, 2008)
Dejardins, 2004 (as cited in EC,
DATA QUALITY
Study was conducted according to
guideline (OECD 202) and GLP;
analytical monitoring was
performed. The 48 hour EC50 is
based on actual test
concentrations. Differences in
nominal and actual concentrations
were attributed to limited water
solubility of the test substance.
Not a guideline study; study not
conducted according to GLP.
ECOSAR also provided results
for the Esters, and Esters
(phosphate) classes; however,
professional judgment indicates
that this compound is not
currently well represented in
ECOSAR vl. 11.
Guideline (OECD 201) and GLP-
compliant. Value appears to be
based on nominal test
concentrations.
Study details reported in a
secondary source; not a guideline
study and not conducted
according to GLP. No additional
data were available.
Guideline study (OECD 201) and
         7-610

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                                                        JUNE 2014 DRAFT REPORT
                                           Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
           PROPERTY/ENDPOINT
              DATA
         REFERENCE
      DATA QUALITY
                                              hour EC50 (growth rate) = 82 mg/L;
                                              NOEC = 13 mg/L
                                              (Experimental)
                                  2000; EU, 2008)
                               GLP-compliant. Study details
                               reported in a secondary source;
                               primary source not specified
                               (identified as a review article).
                                               Green algae 96-hour EC50 = 28 mg/L
                                               (Estimated)
                                               ECOSAR: Neutral organics
                                  ECOSARvl.ll
                               ECOSAR also provided results
                               for the Esters, and Esters
                               (phosphate) classes; however,
                               professional judgment indicates
                               that this compound is not
                               currently well represented in
                               ECOSARvl.ll.
Chronic Aquatic Toxicity
HIGH: Based on estimated ChV values in fish (estimated for the phosphate esters ECOSAR class). An
experimental NOEC for Daphnia magna indicate a Low hazard designation for mortality and
reproduction, while estimated ChV values fall within a Low to Moderate hazard range. Estimated ChV
values for algae indicate a Moderate hazard designation. While experimental data for Daphnia suggest a
Low hazard, there are no experimental chronic aquatic toxicity data available for fish and algae;
therefore, an estimated High hazard designation is assigned to this endpoint.
Fish ChV
Freshwater fish ChV = 4.6 mg/L
(Estimated)
ECOSAR: Neutral organics
ECOSARvl.ll
ECOSAR also provided results
for the Esters, and Esters
(phosphate) classes; however,
professional judgment indicates
that this compound is not
currently well represented in
ECOSARvl.ll.
Daphnid ChV
Daphnia magna (4 replicates of 10
daphnia per concentration) were
exposed to 10, 18, 32, 56 and  100
mg/L of the test material for a period
of 21 days. All animals at 56 mg/L
died within 12 days.
21-day NOEC (mortality and
reproduction) = 32 mg/L
(Experimental)
Sewell et al., 1995 (as cited in
OECD-SIDS, 2000; EU, 2008)
Adequate; guideline (OECD 211)
and GLP study. Data are from a
secondary source; primary source
was not specified (from a review
article).
                                                                    7-611

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JUNE 2014 DRAFT REPORT
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT

Green Algae ChV
DATA
Daphnia magna ChV= 3.2 mg/L
(Estimated)
ECOSAR: Neutral organics
Green algae ChV = 8.7 mg/L
(Estimated)
ECOSAR: Neutral organics
REFERENCE
ECOSAR v 1.11
ECOSAR v 1.11
^^
DATA QUALITY
ECOSAR also provided results
for the Esters, and Esters
(phosphate) classes; however,
professional judgment indicates
that this compound is not
currently well represented in
ECOSAR vl. 11.
ECOSAR also provided results
for the Esters, and Esters
(phosphate) classes; however,
professional judgment indicates
that this compound is not
currently well represented in
ECOSAR vl. 11.
ENVIRONMENTAL FATE
Transport

Henry's Law Constant (atm-
m3/mole)
Sediment/Soil
Adsorption/Desorption - Koc
Level III Fugacity Model
Level III fugacity models incorporating available physical and chemical property data indicate that at
steady state, TCPP is expected to be found primarily in soil and to a lesser extent, water. TCPP is
expected to have moderate mobility in the soil, based on its measured Koc. TCPP will not volatilize from
moist soil and water surfaces based on its Henry's Law constant. Volatilization from dry surfaces is not
expected based on its vapor pressure. TCPP will exist almost entirely in the vapor phase in the
atmosphere.
6xlO"8 (Measured)
162 (Measured)
Air = 0.1%
Water = 12.4%
Soil = 86.1%
Sediment = 1.4% (Estimated)
van der Veen and de Boer, 2012
van der Veen and de Boer, 2012
EPIv4.11
Reported in a peer reviewed
source.
Reported in a peer reviewed
source.

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                                                       JUNE 2014 DRAFT REPORT
                                           Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
           PROPERTY/ENDPOINT
                                          DATA
                                          REFERENCE
                                                               DATA QUALITY
Persistence
                             HIGH: Based on measured persistence data. TCPP had 14% biodegradation after 28 days according to
                             OECD 301E, although in the modified MITI test, OECD 301C, 0% biodegradation was found after 28
                             days using an activated sludge inoculum. TCPP achieved 21% degradation after 28 days in an inherent
                             modified MITI test, OECD 302C. These data suggest a half-life greater than 60 days. TCPP is not
                             expected to be susceptible to direct photolysis by sunlight. The atmospheric half-life of vapor-phase
                             TCPP is estimated to be 2.9 hours, however it is not expected to partition greatly to the atmosphere.
Water
Aerobic Biodegradation
Passes Ready Test: No
Test method: OECD TG 301E:
Modified OECD Screening Test

Reported as 14% after 28 days. 97.9%
pure (Measured)
                                              Passes Ready Test: No
                                              Test method: OECD TG 301C:
                                              Modified MITI Test (I)

                                              Reported as 0% after 28 days.
                                              (Measured)
                                              Study results: 21%/28d
                                              Test method: 302C: Inherent
                                              Modified MITI Test (II)

                                              (Measured)
                                                              WHO, 1998
                 Volatilization Half-life for
                 Model River
                             >1
   year(
(Estimated)
                 Volatilization Half-life for
                 Model Lake
                             >1 year (Estimated)
                          OECD-SIDS, 2000
                                                              OECD-SIDS, 2000
EPIv4.11
                                 EPIv4.11
                               OECD Guideline study.
                                                                OECD Guideline study.
                                                                Reported in a peer reviewed
                                                                source.
Soil
Aerobic Biodegradation
Study results: 0%/80d
Test method: Field Test
No decrease in concentration after 80
days using a landfill leachate inoculum
under aerobic conditions. (Measured)
                          ATSDR2012
                               Reported in peer reviewed
                               secondary source.
                                                                   7-613

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JUNE 2014 DRAFT REPORT
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT

Air
Reactivity
Anaerobic Biodegradation
Soil Biodegradation with
Product Identification
Sediment/Water
Biodegradation
Atmospheric Half-life
Photolysis
Hydrolysis
Environmental Half-life
DATA



0.239 days
Based on a 12 hour day (Estimated)
Not a significant fate process.
(Estimated)
Hydrolyzes slowly under alkaline or
acidic conditions. (Measured)
50%/llyatpH7
Additional half-life estimates:
11 years atpH 5;
1 1 years at pH 6;
1 1 years at pH 8;
10yearsatpH9;
5 years at pH 10 (Estimated)
120 days (Estimated)
REFERENCE

^k ^

EPIv4.11
Professional judgment
WHO, 1998
EPIv4.11
PBT Profiler
DATA QUALITY
No data located; chlorinated alkyl
phosphates are outside the domain
of the available estimation
methods.
No data located.
No data located.

The substance does not contain
functional groups that would be
expected to absorb light at
environmentally significant
wavelengths.
Reported in peer reviewed
secondary source.

Half-life estimated for the
predominant compartment (soil),
as determined by EPI
methodology.
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JUNE 2014 DRAFT REPORT
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
Bioaccumulation

Fish BCF
Other BCF
BAF
Metabolism in Fish
DATA
REFERENCE
DATA QUALITY
LOW: Multiple experimental BCF values are below 100, the Low bioaccumulation designation criteria.
Toxicokinetic studies indicate that TCPP and metabolites are rapidly formed and eliminated, consistent
with the estimated BAF. Biomonitoring studies report detection of this compound in human milk
samples and herring gull eggs, demonstrating that these materials are likely bioavailable and could be
observed in a biological matrix. However, the rate of metabolism and elimination may be successfully
competing with that of uptake, which is also consistent with the experimental BCF results. The
biomonitoring studies are not inconsistent with a Low designation
4.6 Reported as < 1.9-4.6 in carp
(Measured)
2.8 Reported as -0.8-2.8 in carp
(Measured)
8.51 (Measured)
Root concentration factors: <1 for
barley, carrots
Leaf concentration factors: 26 for
barley; 3.9 for meadow fescue and 42
for carrot napoli
Seed concentration factors: <0.01 for
barley and rape (Measured)
12.8 (Estimated)

EC, 2000
EC, 2000
van der Veen and de Boer, 2012
Eggen et al., 2012, 2013; Trapp and
Eggen,2013
7
EPIv4.11

Consistent with other reported
measured values.
Consistent with other reported
measured values.
Reported in a peer reviewed
source.
Sfonguideline study indicating
that plant uptake and translocation
is possible for this compound.

No data located.
         7-615

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JUNE 2014 DRAFT REPORT
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
DATA REFERENCE DATA QUALITY
ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring
Ecological Biomonitoring
Human Biomonitoring
TCPP has been detected in drinking water, groundwater, surface water (coastal and marine); rain and snow
samples; sediment, household dust, indoor air, ambient air and airborne particles over the oceans near the polar
region (Staaf and Ostman, 2005; Regnery and Puttmann, 2009; Saito et al., 2009; Takigami et al., 2009;
Regnery et al., 201 1; Bollmann et al., 2012; Cao et al., 2012; Moller et al., 2012; Rodil et al., 2012; Salamova
etal., 2014).
TCPP was also detected in herring gull eggs collected at Lake Huron (Chen et al., 2012).
TCPP has been detected in human pooled milk collected from Swedish women after delivery of their first
babies in 1997-2006 at 22-82 ng/g lipid. TCPP was not included in the NHANES biomonitoring report (CDC,
2009; HSDB, 2013).
         7-616

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                                                  JUNE 2014 DRAFT REPORT


Abe A and Urano K (1994) Influence of chemicals commonly found in a water environment on the Salmonella mutagenicity test. Science of the
Total Environment 153:169-175.

ATSDR (2012) Toxicological profile for phosphate ester flame retardants. Atlanta, GA: Agency for Toxic Substances and Disease Registry.

BASF (1979) BASF AG, Abteilung Toxikologie, unveroefferentlichte Untersuchung.

BASF Aktiengesellschaft (2007) 14C-TCPP, TCEP and TDCP study on the in vitro metabolism in rats, (Unpublished report).

Bayer (199la) Study for skin and eye irritation/corrosion in rabbits. (Unpublished report).

Bayer (1991b) Tris-chlorisopropyl phosphate: Mutagenicity test on unscheduled DNA synthesis in rat liver primary cell cultures in vitro
(Unpublished report).

Bayer (1991c) [28-d study].

Bollmann UE, Moller A, Xie Z, et al. (2012) Occurrence and fate of organophosphorus flame retardants and plasticizers in coastal and marine
surface waters. Water Research 46(2):531-538.

CDC (2009) Fourth national report on human exposure to environmental chemicals. Atlanta, GA: Centers for Disease Control and Prevention.
http://www.cdc.gov/exposurereport/pdf/FourthReport.pdf.

Cao S, Zeng X, Song H, et al. (2012) Levels and distributions of organophosphate flame retardants and plasticizers in sediment from Taihu Lake,
China. Environ Toxicol Chem 31(7): 1478-1484.

Chen D, Letcher RJ, Chu S (2012) Determination of non-halogenated, chlorinated and brominated organophosphate flame retardants in herring
gull eggs based on liquid chromatography-tandem quadrupole mass spectrometry. Journal of Chromatography A 1220:169-174.
                                                     J
Covance Labs (2005) Tris (2-chloro-l-methylethyl) phosphate: Mutation at the Thymidine Kinase (tk) Locus of Mouse Lymphoma L5178Y Cells
(MLA) using the MitrotitreO Fluctuation Technique (Unpublished report). Covance Laboratories  Ltd.

Covance Labs (2006) Detection of DNA damage in the liver of treated rats using the Comet assay (Unpublished report). Covance Laboratories
Ltd.
                                                             7-617

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                                                  JUNE 2014 DRAFT REPORT


Dejardins D (2004) TCPP: A 72-hour toxicity test with the freshwater alga Pseudokirchneriella subcapitata. Project No: 583A-101. Wildlife
International Limited.

Dishaw LV, Powers CM, Ryde IT, et al. (2011) Is the PentaBDE replacement, tris (l,3-dichloro-2-propyl) phosphate (TDCPP), a developmental
neurotoxicant? Studies in PC12 cells. Toxicol Appl Pharmacol 256(3):281-289.

EC (2000) IUCLID dataset-tris(2-chloro-l-methylethyl) phosphate.

ECHA (2013) Tris(2-chloro-l-methylethyl) phosphate. Registered substances. European Chemicals Agency.
http://apps.echa.europa.eu/registered/data/dossiers/DISS-9ea6alc2-62db-49d4-e044-00144f67d031/AGGR-a6514290-db57-4d2e-91ce-
6c884332f676  DISS-9ea6alc2-62db-49d4-e044-00144f67d031.html#AGGR-a6514290-db57-4d2e-91ce-6c884332f676.

ECOSAR (Ecological Structure Activity Relationship), Version 1.11. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/oppt/newchems/tools/21ecosar.htm.

EPA (2012) Using noncancer screening within the SF initiative. Washington, DC: U.S. Environmental Protection Agency.
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and Toxicology Department.
                                                              7-618

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                                                   JUNE 2014 DRAFT REPORT


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                                                      J
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                                                               7-619

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                                                  JUNE 2014 DRAFT REPORT


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                                                              7-620

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                                                  JUNE 2014 DRAFT REPORT


Mobil (1981b) The acute dermal toxicity of Tris (2-chloropropyl) phosphate "Antiblaze 80" in albino rabbits (Unpublished report). Mobil
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Mobil (1980b) Dermal toxicity of Tris (2-chloropropyl) phosphate, lot PP-2B, in albino rabbits after a single exposure (Unpublished report). Mobil
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Mobil (1980c) Skin irritation of Tris (2-chloropropyl) phosphate, lot PP-2B, in albino rabbits after a single exposure (revised) (Unpublished
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Mobil (1981c) Primary skin irritation of Tris(2-chloropropyl) phosphate "Antiblaze 80" after a single application to albino rabbits (Unpublished
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Mobil (198Id) Primary eye irritation of Tris(2-chloropropyl) phosphate "Antiblaze 80" in albino rabbits (Unpublished report). Mobil
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Mobil (1980d) Eye irritation of Tris (2-chloropropyl) phosphate, lot PP-2B, in albino rabbits after a single exposure (revised) (Unpublished
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                                                              7-621

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                                                  JUNE 2014 DRAFT REPORT


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SafePharm Labs Ltd (1979c) Determination of the degree of ocular irritation caused by Tris Mono Chloropropyl Phosphate (Unpublished report).

SafePharm Labs Ltd (1979d) Determination of the degree of primary cutaneous irritation caused by Tris Mono Chloropropyl Phosphate
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SafePharm Labs Ltd (1979e) Determination of the contact sensitisation potential of Tris Mono Chloropropyl Phosphate (Unpublished report).

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SafePharm Labs Ltd (1997a) Amgard TMCP: Acute oral toxicity test in the rat (Unpublished report).

SafePharm Labs Ltd (1997b) TCPP Acute oral toxicity test in the rat (Unpublished report).
                                                              7-622

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                                                 JUNE 2014 DRAFT REPORT


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                                                    7
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                                                             7-623

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                                                  JUNE 2014 DRAFT REPORT


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                                                                            ^F ^S            *
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                                                              7-624

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Mutagen 21:2-141.
                                                              7-625

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                                    JUNE 2014 DRAFT REPORT
Tris (2-chloroethyl) phosphate (TCEP)
Screening Level Toxicology Hazard Summary
This table only contains information regarding the inherent hazards of flame retardant chemicals. Evaluation of risk considers both the hazard and exposure associated with the
substance including combustion and degradation by-products. The caveats listed in the legend and footnote sections must be taken into account when interpreting the hazard
information in the table.
VL = Very Low hazard L = Low hazard = Moderate hazard = High hazard VH = Very High hazard - Endpoints in colored text (VL, L, , H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].
Chemical
CASRN
Human Health Effects
Acute Toxicity
Carcinogenicity
Genotoxicity
Reproductive
Developmental
Neurological
Repeated Dose
Skin Sensitization
Respiratory
Sensitization
0
'•i
-^-i
"C
*_
HH
OJ
^s
w
_o
-*^
sS
+*
hH
"3
0)
p
Aquatic
Toxicity
0)
-*^
u
<
Chronic
Environmental
Fate
Persistence
Bioaccumulation

Tris (2-chloroethyl) phosphate
(TCEP)
115-96-8

H


H


L

L
L
H
H

L

                                             7-626

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JUNE 2014 DRAFT REPORT
Cl
Vo
CI^^X ,-R, / — Cl
-- o ^0_/
CASRN: 115-96-8
MW: 285.49
MF: C6H12C13O4P
Physical Forms: Liquid
Neat: Liquid
Use: Flame retardant
SMILES: O=P(OCCC1)(OCCC1)OCCC1
Synonyms: Ethanol, 2-chloro-, phosphate (3: 1); 2-chloroethanol phosphate; Phosphoric acid, tris(2-chloroethyl)ester; Tri(2-chloroethyl) phosphate Tri(2-chloroethyl)
phosphoric acid ethyl ester; Tri-beta-chloroethyl phosphate; Trichloroethyl phosphate; Tri(2-chloroethyl) orthophosphate; Tri(2-chloroethyl)ester phosphoric acid;
Tris-beta-chloroethyl phosphate; Tris(2-chloroethyl) phosphate; Tris(chloroethyl) phosphate; Tris(monochloroethyl) phosphate; TCEP
Trade names: 3CF; Celanese Celluflex CEF; Celluflex CEF; CLP; Disflamoll TCA; AI3-15023; Amgard TCEP; Antiblaze TCEP; Celanese Celluflex CEF;
Disflamoll TCA; Fyrol CEF; Fyrol CF; Genomoll P; Hostaflam UPS 10; Levagard EP; Niax 3CF; Max Flame retardant 3CF; Nuogard TCEP; Tolgard TCEP;
Triclofos
Chemical Considerations: This phosphate ester is a discrete organic chemical with a MW below 1,000. EPI v4. 1 1 was used to estimate some environmental fate
values due to an absence of experimental data. Measured values from experimental studies were incorporated into the EPI estimations. This compound may be
manufactured by epoxide opening with either ethylene oxide or ethylene chlorohydrin in the presence of phosphorus oxy chloride. 1,2 dichloroethane is an impurity in
some commercial products (IARC, 1990; CELLTECH, 2009; ATSDR, 2012).
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Polymeric: No
Oligomeric: Not applicable
Metabolites, Degradates and Transformation Products: Thermal degradation: Carbon monoxide, hydrogen chloride, 2-chloroethane and dichloroethane, carbon
dioxide, benzene, toluene, chloromethane, chloroethane, 1,2-dichloroethane, chloropropenes, 1,2,3-trichloropropane, 2-chloroethanol, acetaldehyde,
chloroacetaldehyde, chloroacetone, bis(2-chloroethyl) ether, bis(2-chloroethoxy)methane; methyl formate, methyl acetate, 2-chloroethyl acetate, phosphate and vinyl
chloride.

Metabolites: 2-chloroethanol and bis(2-chloroethyl)hydrogen phosphate and other unidentified metabolites by human and rat liver microsomes, liver, blood and
plasma samples. Other metabolites reported include bis(2-chloroethyl) carboxymethyl phosphate, bis(2-chloroethyl) hydrogen phosphate and bis(2-chloroethyl 2-
hydroxyethyl) phosphate glucuronide. Chloride ion and 2-chloroethanol degradation products from bacteria (Chapman et al., 1991; IPCS, 1998; NICNAS, 2001;
Takahashi et al., 2008; EU, 2009; Van den Bade et al., 2013).
Analog: None
Endpoint(s) using analog values: Not applicable
Analog Structure: Not applicable
Structural Alerts: Organophosphates, neurotoxicity; aliphatic substituted alkyl halides, genetic toxicity; chlorinated hydrocarbons, liver toxicity; chlorinated
hydrocarbons, reproductive toxicity. This chemical appears on the List of Chemicals Known to the State to Cause Cancer for the State of California: California
Proposition 65 cancer, List of Chemicals of High Concern to Children for Washington State, List of Substances of Very High Concern for Authorisation published in
accordance with Article 59(10) of the REACH Regulation (ECHA, 2009; State of Washington, 2011; EPA, 2012; California EPA, 2013).
Risk Phrases: R60: May impair fertility; R22: Harmful if swallowed; R40: Limited evidence of a carcinogenic effect; R51/53: Toxic to aquatic organisms, may cause
long-term adverse effects in the aquatic environment (ESIS, 2012).
Hazard and Risk Assessments: Priority Existing Chemical Assessment report for Triphosphates by NICNAS in 2001; EU Risk Assessment Report in 2009; IARC
Summaries & Evaluations report in 1990; part of the Toxicological profile for Phosphate Ester Flame Retardants by ATSDR (IARC, 1990; NICNAS, 2001; EU, 2009;
ATSDR, 2012).
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Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
PHYSICAL/CHEMICAL PROPERTIES
Melting Point (°C)
Boiling Point (°C)
-58
Measured by method DIN 5 1583,
ASTM D 97-66 (Measured)
-55
(Measured)
-60
Reported as about -60°C (Measured)
<-70
pour point (Measured)
202 at lOmmHg
Measured by ASTM D 1 160 method at a
reduced pressure (Measured)
320 Decomposes
99.5% purity (Measured) - J' ^
145 at 0 mmHg
Value reported as 145°C at 0.66 hPa
(Measured)
330
(Measured)
Decomposes
Rapid decomposition occurs above
220°C. Thermal decomposition products
are carbon monoxide, hydrogen
chloride, 2-chloroethane and
dichloroethane. (Measured)
OECD-SIDS, 2006
IARC, 1990; EC, 2000; ATSDR
2012
EC, 2000
NICNAS, 2001; OECD-SIDS,
2006; EU, 2009
EC, 2000
EU, 2009
EC, 2000; NICNAS, 2001
IARC, 1990; Lide, 2008; ATSDR,
2012
IPCS, 1998
Similar values are consistently
reported in secondary sources.
Similar values are consistently
reported in secondary sources.
Similar values are consistently
reported in secondary sources.
Value reported in a secondary
source. Assumed to be measured.
Adequate value measured by a
standard test method.
Limited details available from
secondary source.
Similar values are consistently
reported in secondary sources.
Value reported in a secondary
source.
Supporting information reported in
a secondary source with limited
details.
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                                                  Tris (2-chloroethyl) phosphate CASRN 115-96-8
           PROPERTY/ENDPOINT
               DATA
         REFERENCE
       DATA QUALITY
Vapor Pressure (mm Hg)
1.6x10° at 25°C

Values at higher temperatures measured
by dynamic method; measured values
reported as: 0.43 hPa at 136.9°C; 0.99
hPa at 143.5°C; 2.03 hPa at 158.6°C;
S.OOhPaat 174.1°C; 15.03 hPa at
196.2°C. (Extrapolated)
EU, 2009
The Clausius-Clapeyron equation
was used to calculate the VP at
20°C (reported as such in source).
Extrapolation to 25 °C yields the
value of 1.6xlO"5 mmHg.
                                              0.062 at 25°C

                                              Measured with a conventional
                                              isoteniscope using a nitrogen
                                              atmosphere (Measured)
                                    ATSDR, 2012
                               Value calculated from reported
                               equation coefficients determined by
                               experimental measurements and
                               equation fitting. The calculated
                               value is inconsistent with other
                               available vapor pressure data. It is
                               possible that the units of the
                               calculation apply to meters Hg
                               rather than mm Hg which would
                               change the value to 0.000062 mm
                               Hg at 25°C.
                                              8.55xlO-bat20°C

                                              Reported as 0.00114 Pa at 20°C
                                              (Extrapolated)
                                    OECD-SIDS, 2006; EU, 2009
                               Value was extrapolated from a
                               measured value of 43 Pa at 137°C.
                                              <0.075 at 20°C

                                              Reported as <0.1 hPa at 20°C. ASTM
                                              D232 method (Extrapolated)
                                    EC, 2000
                               Value was approximated from data
                               at higher temperatures
Water Solubility (mg/L)
7,000 (Measured)
Muir, 1984 (as cited in ATSDR,
2012)
Value reported in a secondary
source.
                                              7,943 (Measured)
                                    EC, 2000
                               Value reported in a secondary
                               source with limited study details.
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Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT

Log Kow
DATA
temperature not reported
7,820 (Measured)
Reported as 7820 mg/L at 20°C, pH 4.7
-6.1 according to Directive
84/449/EEC, A.6, Water Solubility
method, 1984 using GLP r
5,000 (Measured)
Reported as ca. 5 g/L at 20°C, 5.5 -7 pH
at 10 vol% and 20°C by Society of
Automotive Engineers (SAE) method
1.78
Reported as 1.78 at 20°C; Directive
84/449/EEC., A.8, Partition coefficient,
1984 Method, GLP (Measured)
1.47
OECD Guide-line 107, Partition
Coefficient (n-octanol/water), Flask-
shaking Method, 1981 (Measured)
1.7
(Measured)
1.6
(Estimated)
1.44
(Measured)
REFERENCE

EC, 2000; EU, 2009
^^^
EC, 2000
^^^
EC, 2000; EU, 2009
EC, 2000
IPCS, 1998; NICNAS, 2001
EPIv4.11
MITI, 1992a (as cited in ATSDR
2012)
DATA QUALITY

Adequate guideline study.
Adequate study
Similar to the log Kow of 1.47
reported for a shake -flask method,
but this is a more recent
measurement and both were
measured by the same source
(Akzo Nobel Chemicals). Also
similar to the KOWWFN program
estimate of 1.63.
Adequate guideline study.
Reported in a secondary source
with limited study details.
Estimated by the EPI Suite
KOWWIN program (vl.68)
Reported as measured in their
laboratory, but measurement
methods, temperatures and pH
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Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT

Flammability (Flash Point)
Explosivity
Pyrolysis
pH
pKa
DATA

Flash point: 216°C (Measured)
Flash point: 252°C Open cup
(Measured)
Flash point: 225°C Closed cup; DIN
51758 method (Measured)
Flash Point: 200°C ASTM D93 method
using GLP; sample appears to catch fire
at approx. 200°C, but does not show a
distinct flash point as defined by the test
method (Measured)

Decomposition products: 1,2
dichloroethane and vinyl chloride
0.1 mol TCEP was decomposed in 20-
mL flask at 250-260°C at 3 mmHg, the
decomposition products were separated
by gas-liquid chromatography, and
analyzed with NMR and MS (Measured)
Not applicable (Estimated)
Not applicable (Estimated)
J
REFERENCE

ATSDR, 2012
EC, 2000
EC, 2000
EC, 2000; EU, 2009
^^% r

Okamoto et al., 1974
Professional judgment
Professional judgment
DATA QUALITY
values are not reported.
Limited study details reported in a
secondary source.
Non-GLP, standardized study.
Adequate standardized method.
Adequate standardized method
reported in a secondary source.
No data located.
Supporting information provided.
Does not contain functional groups
that are expected to ionize under
environmental conditions.
Does not contain functional groups
that are expected to ionize under
environmental conditions.
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Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
HUMAN HEALTH EFFECTS
Toxicokinetics
Dermal Absorption in vitro
Absorption,
Distribution,
Metabolism &
Excretion
Oral, Dermal or Inhaled
TCEP is well absorbed and distributed following oral administration in rats and mice. TCEP and
metabolites are rapidly eliminated principally in the urine. Urinary metabolites include bis(2-chloroethyl)
carboxymethylphosphate, bis(2-chloroethyl)hydrogen phosphate and bis(2-chloroethyl)-2-hydroxyethyl-
phosphate glucuronide. TCEP is metabolized by hepatic microsomal fraction in male rats and in humans,
but is not metabolized by plasma or whole blood. In an incubation experiment, bis(2-chloroethyl)
phosphate (BCEP) and hydroxyethyl 2-chloroethyl hydrogen phosphate were the only detected
metabolites. No phase II metabolites were detected.

TCEP is metabolized by hepatic
microsomal fraction in male rats but not
in females. Liver slices and blood
plasma indicated metabolism in both
sexes. Liver slices and microsomes in
humans metabolized TCEP, but plasma
and whole blood did not.
Wistar rats orally dosed with 50 (jmol/kg
14C-labeled TCEP. During the first 6
hours following administration, TCEP
was distributed and concentrated by
several tissues; primarily the liver and
kidney. Most of the material was
excreted within 24 hours and by 168
hours, <1% remained in tissues.
Excretion was 96% in urine, 6% in feces
and 2% in expired air. Urinary
metabolites included: bis(2-chloroethyl)
carboxymethyl phosphate, bis(2-
chloroethyl) hydrogen phosphate and
bis(2-chloroethyl) 2-hydroxyethyl
phosphate glucuronide
Male and female Fischer-344 rats
gavaged with 0, 175, 350 or 700 mg/kg

Chapman et al., 1991 (as cited in
WHO, 1998)
Minegishi et al., 1988 (as cited in
WHO, 1998)
Herr et al., 1991 (as cited in WHO,
1998)
No data located.
Limited study details reported in a
secondary source.
Sufficient study details reported.
Sufficient study details reported.
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Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT


DATA
14C-labeled TCEP; plasma
concentrations and metabolites peaked
by 30 minutes in rats given 175 mg/kw.
No concentration differences of TCEP in
hippocampus and other brain tissues.
Male B6C3F1 mice orally dosed with
175 mg 14C-labeled TCEP/kg; >70%
excretion in urine within 8 hours.
Urinary metabolites: bis(2-chloroethyl)
carboxymethyl phosphate, bis(2-
chloroethyl) hydrogen phosphate and
bis(2-chloroethyl) 2-hydroxyethyl
phosphate glucuronide
TCEP is readily absorbed from the
gastrointestinal tract and excreted within
72 hours following oral administration
Absorption study in rats dosed with 14C
TCEP at 100-140 mg/kg via oral gavage
or in the diet. 80% of the administered
dose (gavage and diet) was excreted in
urine within 5 days
REFERENCE

Burka et al., 1991 (as cited in
WHO, 1998)
lr
EC, 2000
EC, 2000
DATA QUALITY

Sufficient study details reported.
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source.
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Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT

Other
Acute Mammalian Toxicity
Acute Lethality
Oral
DATA
Incubation experiments using 1.0
mg/mL HLM or S9 proteins, 50 (iM
TBOEP or TCEP, or TCPP, or 20 jiM
TPHP or TDCPP and NADPH
regenerating solution in 1 mM total
volume were conducted for 1 hour.
There was a 7% and 13% clearance of
the compound in the HLM and S9
incubations, respectively.
Bis(2-chloroethyl) phosphate (BCEP)
and hydroxyethyl 2-chloroethyl
hydrogen phosphate were the only
detected metabolites. No phase II
metabolites were detected. BCEP was
the major metabolite detected.
REFERENCE
Van den Bade et al., 2013
^^^
lr
DATA QUALITY

HIGH: Based on an oral LD50 of 46.4 mg/kg in rats. TCEP exhibits low toxicity via the inhalation and
dermal routes of exposure in rats and rabbits, respectively.
Rat oral LD50 = 46.4 - 1,000 mg/kg
Rat oral LD50 = 430 - 794 mg/kg
Rat oral LD50 =1150 mg/kg
^
Rat oral LD50 =1,230-1,410 mg/kg
Mouse oral LD50 = 1,500 mg/kg
Rat oral LD50 = 3,600 mg/kg (3.6 g/kg)
ATSDR, 2012
EC, 2000
Kynoch and Denton, 1990 (as cited
in WHO, 1998; EC, 2000)
Smyth et al., 195 1; Ulsamer et al.,
1980 (as cited in WHO, 1998; EC,
2000; ATSDR, 2012)
EC, 2000
Gardner, 1987 (as cited in WHO,
1998)
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source; study conducted
in accordance to GLP and Directive
84/449/EEC, B.I.
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source.
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Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT

Dermal
Inhalation
Carcinogenicity

OncoLogic Results
Carcinogenicity (Rat and
Mouse)
DATA
Rabbit dermal LD50 = 2150 - > 5,000
mg/kg
Rat 4-hour inhalation LC50 > 5 mg/L
(5,000 mg/m3)
Rat 1-hour inhalation LC50 > 25.7 mg/L
(nominal)
REFERENCE
EC, 2000; OECD-SIDS, 2006;
ATSDR, 2012
EC, 2000;ATSDR2012
OECD-SIDS, 2006
DATA QUALITY
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source.
HIGH: TCEP was carcinogenic in rats and mice. Renal adenomas/carcinomas were present in rats and
mice following 103 weeks of oral exposure. In addition, renal adenomas/carcinomas and forestomach and
hemapoietic tumors were evident in mice following 18 months of dietary exposure. IARC has classified
TCEP as a Category 3 carcinogen: "Not classifiable as to its Carcinogenicity" based on inadequate evidence
in experimental animals and no available human studies". However, NTP concludes that the renal
adenomas observed in rats are clear evidence of carcinogenic activity. In addition, this chemical appears on
the List of Chemicals Known to the State to Cause Cancer for the State of California.

In a 103 -week oral study, rats were
gavaged with TCEP at 0, 44 or 88
mg/kg-day, 5 days/week. Reduced
survival at the high dose. Renal tubular
adenomas (occurring in -50% of high-
dose males, 10% of high-dose females
and 10% of low-dose males); marked
increase in the incidence of renal tubule
cell hyperplasia in high dose males and
females. Although adenomas are benign
tumors, NTP concludes that renal
adenomas represent an early stage in the
development of carcinoma and is clear
evidence of carcinogenic activity.
In a 103 -week oral study, mice were
gavaged with TCEP at 0, 175, or 350
mg/kg-day 5 days/week. No significant
differences in survival or body weight

NTP, 1991 (as cited in EC, 2000;
ATSDR, 2012)
NTP, 1991 (as cited in ATSDR,
2012)
No data located.
Adequate study details reported in
a primary source.
Adequate study details reported in
a primary source.
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                                               JUNE 2014 DRAFT REPORT
                                       Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   gain in comparison with controls. Renal
                                   tubular karyomegaly in 80% of high
                                   animals (a marker of nephropathy);
                                   Marginal increase in harderian gland
                                   neoplasms (primary adenomas, high
                                   dose females). NTP concludes that there
                                   is equivocal evidence of carcinogenic
                                   activity based on renal tubule  cell
                                   neoplasms in male mice and marginally
                                   increased harderian gland adenomas in
                                   female mice.
                                   In an 18-month dietary study, mice
                                   (Slc:ddY) were fed TCEP at 0, 0.012,
                                   0.06, 0.3, and 1.5% daily (~0, 11, 53,
                                   267, and  1333 mg/kg-day) Increased
                                   mortality and reduced weight gain in
                                   comparison with controls at the high
                                   dose. Significantly increased incidence
                                   of renal cell adenomas and carcinomas
                                   (high dose males); increased incidence
                                   of benign liver adenomas (males, 0.3%
                                   and 1.5%); increased incidence of
                                   forestomach and hematopoietic tumors
                                   (females).
                     Takada et al., 1989 (as cited in EC,
                     2000; ATSDR, 2012)
                       Limited study details reported in a
                       secondary source (primary source
                       is in Japanese with English
                       abstract); doses are estimated
                       assuming a mean body weight of
                       0.045 kg and daily food
                       consumption of 0.004 kg/day
                       (ATSDR 2012).
                                   Female (Sl/ddy) mice were treated
                                   dermally with ethanol solutions
                                   containing 5% or 50% TCEP for 79
                                   weeks. No significant increase in tumors
                     Takada et al., 1991 (as cited in
                     WHO, 1998)
                       Limited details reported in a
                       secondary source.
       Combined Chronic
       Toxicity/Carcinogenicity
                                                     No data located.
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Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT

Other
Genotoxicity

Gene Mutation in vitro
DATA
This chemical appears on the List of
Chemicals Known to the State to Cause
Cancer for the State of California:
California Proposition 65
IARC has classified TCEP as a Category
3 carcinogen: "not classifiable as to its
carcinogenicity" based on inadequate
evidence in experimental animals and no
available human studies.
REFERENCE
California EPA, 20 13
IARC, 1990 (as cited in NICNAS,
2001)
DATA QUALITY
Added to the California Proposition
65 list for cancer on April 1, 1992.
The NTP (1991) oral bioassay in
rats and mice was not available to
IARC when this agency classified
TCEP.
MODERATE: Based on weight of evidence from multiple studies. Results were positive in in vitro gene
mutation and chromosomal aberrations tests. TCEP was cytotoxic in a neutral read uptake assay in
Chinese hamster V79 cells, produced sister chromatid exchanges in Chinese hamster V79 cells and mouse
lymphoma cells, and was positive in a cellular transformation study in mouse BALB/3t3 cells. TCEP was
not mutagenic in bacteria or yeast, and did not produce chromosomal aberrations in any available in vivo
studies. In addition, TCEP was negative in an Unscheduled DNA synthesis study in human WI-38 cells.
There is potential for genetic toxicity based on a structural alert for aliphatic substituted alkyl halides.
Positive, cytotoxicity in a neutral red
uptake assay in Chinese hamster V79
cells. Negative in the absence of
metabolic activation
Negative, Salmonella typhimurium
strains TA98, TA100, TA1535 and
TA1537, TA1538 with and without
metabolic activation.
Negative, Saccharomyces cerevisiae
with and without metabolic activation
Negative, mammalian cell HGPRT gene
mutation assay in Chinese hamster V79
lung cells with and without metabolic
activation
Negative, mammalian cell gene
mutation assay in L5 178Y mouse
Follmann and Wober, 2006 (as
citedinATSDR2012)
EC, 2000
EC, 2000
EC, 2000
EC, 2000
Sufficient study details reported in
a primary source.
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source; Study was
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Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT


Gene Mutation in vivo
Chromosomal Aberrations in
vitro
DATA
lymphoma cells with and without
metabolic activation
Negative, Salmonella typhimurium
strains TA98, TA100, TA1535, TA1537
or TA1538 with and without metabolic A
activation
Negative, Salmonella typhimurium
strains TA98, TA100 with and without
metabolic activation
Negative, Salmonella typhimurium
strains TA97,TA98, TA100, TA104,
TA1535, TA1537, and TA1538 with and
without metabolic activation
Negative, Salmonella typhimurium
strains TA100, TA1535, TA1537 or
TA98 with and without metabolic
activation

Positive, sister chromatid exchange
assay in hamster V79 lung cells with and
without metabolic activation. TCEP
induced SCE's but no clear dose
response was noted.
Positive, sister chromatid exchange
assay in L5 178Y mouse lymphoma cells
with metabolic activation. No increase in
SCE's without metabolic activation.
Negative, chromosomal aberrations in
CHO cells with and without metabolic
activation.
Equivocal, sister chromatid exchange
assay in Chinese hamster (CHO) cells
REFERENCE

EC, 2000
Kubo et al., 2002
Follmann and Wober, 2006 (as
citedinATSDR,2012)
NTP, 1991

EC, 2000
EC, 2000
Galloway et al., 1987 (as cited in
NTP, 1991; EC, 2000)
Galloway et al., 1987 (as cited in
NTP, 1991; EC, 2000)
DATA QUALITY
conducted in accordance with GLP
and OECD Guideline 476.
Limited study details reported in a
secondary source; Study was
conducted in accordance with
OECD Guideline 471
Sufficient study details reported in
a primary source.
Sufficient study details reported in
a primary source.
Sufficient study details reported.
No data located.
Limited study details reported in a
secondary source.
Study was conducted in accordance
with GLP and OECD Guideline
479.
Study was conducted in accordance
with OECD Guideline 473.
Sufficient study details reported in
a primary source.
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Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT


Chromosomal Aberrations in
vivo
DNA Damage and Repair
Other
DATA
with metabolic activation
Negative, mammalian erythrocyte
micronucleus assay in mice orally
gavaged with 1,000 mg/kg TCEP; cell
collection for 24, 48 or 72 hours after
dosing.
Negative, chromosomal aberrations in
rats orally gavaged with TCEP at doses
of 0.062, 0.021, or 0.0062 ml/kg.
Negative, mammalian erythrocyte
micronucleus assay in mice administered
175, 350 or 700 mg/kg TCEP via
intraperitoneal injection; cell collection
for 24, 48 or 72 hours after dosing.
Equivocal, chromosomal aberrations,
micronucleus assay in male and female
Chinese hamsters administered 62.5,
125, or 250 mg/kg TCEP via
intraperitoneal injection; cell collection
24 hours later.
Negative, Drosophila melanogaster ,
somatic cell damage
Negative, DNA damage in a comet
analysis in Chinese hamster V79 cells
with and without metabolic activation
Negative, DNA -binding in vitro (cell
type not reported)
Positive, Cellular transformation in
mouse BALB/3T3 cells. No further
details provided.
Negative, unscheduled DNA synthesis
REFERENCE

EC, 2000
EC, 2000
^r
EC, 2000
Sala et al., 1982 (as cited in
ATSDR, 2012)
Vogel and Nivard, 1993 (as cited in
WHO, 1998)
Follmann and Wober, 2006 (as
cited in ATSDR 20 12)
EC, 2000
EC, 2000
EC, 2000
DATA QUALITY

Limited study details reported in a
secondary source; study conducted
according to OECD Guideline 474.
Limited study details reported in a
secondary source; study conducted
according to GLP and OECD
Guideline 475.
Limited study details reported in a
secondary source; study conducted
according to GLP and OECD
Guideline 474.
Sufficient study details reported in
a primary source.
Sufficient study details reported in
a primary source.
Sufficient study details reported in
a primary source.
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source.
Limited study details reported in a
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Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT


DATA
in human WI-38 cells with and without
metabolic activation.
Equivocal, Cellular transformation assay
in C3H10T1/2 mouse embryo cells
without metabolic activation. No data
reported with presence of metabolic
activation.
There is potential for genotoxicity based
on the structural alert for aliphatic
substituted alkyl halides.
(Estimated)
REFERENCE

EC, 2000
^^^
Professional judgment
DATA QUALITY
secondary source; study was
conducted in accordance with GLP
and OECD Guideline 482.
Limited study details reported in a
secondary source.
Estimated based on a structural
alert for aliphatic substituted alkyl
halides and professional judgment.
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Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
Reproductive Effects

























Reproduction/Developmental
Toxicity Screen















Combined Repeated Dose
with Reproduction/
Developmental Toxicity
Screen
DATA
REFERENCE
DATA QUALITY
MODERATE: Based on the weight of evidence from multiple studies. Although a whole body inhalation
study resulted in a NOAEL of 0.5 mg/m3 and a LOAEL of 1.5 mg/m3 (0.0012 mg/L) in male rats; this study
is generally classified as having low reliability. TCEP was observed to have Moderate concern for
reproductive toxicity when administered orally in rats and mice. In addition, there is potential for
reproductive toxicity based on a structural alert for chlorinated hydrocarbons.
Male rats (strain not specified) were
exposed to 0, 0.5 or 1.5 mg/m3 TCEP via
whole body inhalation continuously for
4 months.
Testicular toxicity (0.5 and 1.5 mg/m3),
decreased sperm counts, decreased
sperm motility and abnormal sperm
morphology; increased number of
spermatogonia with decreased numbers
of sperm in the later stages of
development was reported; When mated
with untreated females: decreased
fertility (1.5 mg/m3); increased pre-and
post-implantation loss; decreased litter
size
NOAEL: 0.5 mg/m3
LOAEL: 1.5 mg/m3


7

Shepelskaya and Dyshinevich,
1981 (as cited in WHO, 1998)

^<








*








Limited study details reported in a
secondary source. Original study in
Russian. Study received a
reliability score of 4 in the IUCLID
data set.












No data located.



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                                               JUNE 2014 DRAFT REPORT
                                       Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
               DATA
         REFERENCE
       DATA QUALITY
       Reproduction and Fertility
       Effects
In a continuous breeding study, Swiss
CD-I mice were orally gavaged with
175, 350 or 700 mg/kg-day TCEP;
significant impairment of reproductive
capacity and fertility at the mid- and
high-dose groups

NOAEL: 175 mg/kg-day
LOAEL: 350 mg/kg-day (based on
impaired reproductive capacity and
fertility)
Chapin et al., 1997 (as cited in
WHO, 1998; NICNAS, 2001;
OECD-SIDS, 2006; ATSDR,
2012)
Sufficient study details reported.
                                   In a 13-week study, F-344 rats were
                                   orally gavaged with TCEP at 0, 22, 88
                                   and 175 mg/kg-day. No adverse effect
                                   on cauda weights, absolute and relative
                                   epididymal weights, absolute and
                                   relative testes weights, sperm
                                   concentration, and number of abnormal
                                   sperm; reduced sperm motility; no
                                   increase in estrous cycle.

                                   NOAEL/LOAEL: Not determined
                                    Morrissey et al., 1988 (as cited in
                                    WHO, 1998)
                                WHO 1998; Morrissey et al., 1988
                                (primary source). NOAEL/LOAEL
                                cannot be determined because
                                primary source provided only
                                qualitative description of results.
                                   In a 13-week study, B6C3F1 mice were
                                   orally gavaged with TCEP at 0, 44, 175
                                   and 700 mg/kg-day. No adverse effect
                                   on cauda weights, relative epididymis
                                   weight, motility or sperm concentration;
                                   decreased absolute epididymis weight
                                   and absolute and relative testes weights;
                                   increase in the number of sperm with
                                   abnormal morphology. No increase in
                                   estrous cycle length
                                    Morrissey et al., 1988 (as cited in
                                    WHO, 1998)
                                WHO 1998: Morrissey et al., 1988
                                (primary source). NOAEL/LOAEL
                                cannot be determined because
                                primary source provided only
                                qualitative description of results.
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Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT


Other
Developmental Effects

Reproduction/
Developmental Toxicity
Screen
Combined Repeated Dose
with Reproduction/
Developmental Toxicity
Screen
DATA
NOAEL/LOAEL: Not determined
There is potential for reproductive
toxicity based on a structural alert for
chlorinated hydrocarbons.
(Estimated)

REFERENCE

Professional judgment

DATA QUALITY

Estimated based on a structural
alert for chlorinated hydrocarbons
and professional judgment.
No data located.
HIGH: Based on the weight of evidence from multiple studies. Although a LOAEL of 175 mg/kg-day was
identified based on decreased live male F2 pups in an 18-week continuous breeding study, no NOAEL was
established. Effects < 50 mg/kg-day cannot be ruled out. Furthermore, since TCEP decreased
cholinesterase activity, and decreased cholinesterase activity in dams can influence fetal
neurodevelopment, there is also a concern for potential developmental neurotoxicity.
In a continuous breeding study, mice
were orally gavaged with 175, 300 or
700 mg/kg-day TCEP.
NOAEL: Not established
LOAEL: 175 mg/kg-day (based on
decreased number of live male F2 pups
per litter)

Chapin et al., 1997 (as cited in
WHO, 1998; NICNAS, 2001;
OECD-SIDS, 2006; ATSDR,
2012)
7

Adequate study details reported.
No data located.
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PROPERTY/ENDPOINT
               DATA
         REFERENCE
       DATA QUALITY
       Prenatal Development
Pregnant rats were orally gavaged with
0, 50, 100 or 200 mg/kg-day TCEP on
GDs 7-15. Reduced food consumption at
the high dose; clinical signs of toxicity
in dams (high dose) included
piloerection and general weakness.
Seven out of 30 females died during the
study. No morphological or behavioral
effects were observed in offspring.
Development of offspring was normal
and there were no abnormalities in
functional behavior tests (open field,
water maze, rota rod, inclined plane test,
pain reflex or Preyer's reflex).

Maternal:
NOAEL: 100 mg/kg-day
LOAEL: 200 mg/kg-day (based on
clinical signs of toxicity in dams)

Developmental:
NOAEL: 200 mg/kg-day (highest dose
tested)
LOAEL: Not established
Kawashima et al., 1983 (as cited in
WHO, 1998; EC, 2000; ATSDR,
2012)
Limited study details reported in a
secondary source. Primary source
is in Japanese with an English
abstract.
                                   Pregnant mice were orally gavaged with
                                   940 mg/kg-day TCEP (only dose tested)
                                   on GDs 6-13. Decreased maternal body
                                   weight gain. No adverse effects on
                                   viable litters, live born pups per litter,
                                   percent survival, birth weight, or pup
                                   weight gain.

                                   Maternal:
                                    Hardin et al., 1987 (as cited in
                                    WHO, 1998; EC, 2000; ATSDR,
                                    2012)
                               Limited study details reported in a
                               secondary source.
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Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT


Postnatal Development
Prenatal and Postnatal
Development
Developmental Neurotoxicity
Other
DATA
NOAEL: not established;
LOAEL: 940 mg/kg-day (based on
decreased maternal body weight gain);
only dose tested
Developmental:
NOAEL: 940 mg/kg-day (only dose
tested);
LOAEL: Not established


There were no data located for the
developmental neurotoxicity endpoint.
Decreased cholinesterase activity in
pregnant lab animals has been shown to
have a negative impact on fetal brain
development. As a result, there is
uncertain potential for developmental
neurotoxicity for this substance

REFERENCE
^^^


Professional judgment

DATA QUALITY

No data located.
No data located.
No data located.
No data located.
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                                                 Tris (2-chloroethyl) phosphate CASRN 115-96-8
          PROPERTY/ENDPOINT
              DATA
         REFERENCE
             DATA QUALITY
Neurotoxicity
MODERATE: Based on the weight of evidence from a number of studies. TCEP produced degenerative
lesions in the cerebral cortex in female rats gavaged with 88 mg/kg-day (NOAEL = 44 mg/kg-day) in a 103-
week study. In addition, necrotic lesions in the hippocampus were observed in female rats following oral
administration of 175 mg/kg-day TCEP (NOAEL = 88 mg/kg-day) for 16 weeks. Ataxia and convulsive
movements were observed in mice administered TCEP at doses of > 350 mg/kg-day (NOAEL = 175 mg/kg-
day) for 16 days. Convulsions were observed in female rats within 60 minutes following single oral gavage
of 275 mg TCEP/kg-day. TCEP was attributed to death in dogs following ingestion of car seat cushions
found to contain large amounts of the chemical. TCEP produced no evidence of neurotoxicity in white
leghorn hens. TCEP promoted differentiation of the cholinergic phenotype only in an in vitro neurotoxicity
study using undifferentiated and differentiating PC12 cells. There is potential for neurotoxicity based on  a
structural alert for organophosphates.
                 Neurotoxicity Screening
                 Battery (Adult)
                  Other
In a 103-week oral study, rats were
gavaged with TCEP at 0, 44 or 88
mg/kg-day, 5 days/week.
Degenerative lesions in the cerebral
cortex (high dose, females).

NOAEL: 44 mg/kg-day;
LOAEL: 88 mg/kg-day (based on
cerebrum gliosis in female rat)
NTP, 1991; Matthews et al.,
(ascitedinATSDR,2012)
                                             In 16-18 week oral studies, rats were
                                             gavaged with TCEP at 0, 22, 44, 88, 175
                                             or 350 mg/kg-day, 5 days/week. In the
                                             14-day study, serum cholinesterase
                                             (ChE) was decreased by 82 and 80% in
                                             female rats at 175 and 350 mg/kg-day,
                                             respectively. Inhibition was minimal in
                                             male rats. In the 16-18 week study, ChE
                                             decreased by 25 and 41% in female rats
                                             at 175 and 350 mg/kg-day, respectively
                                             and there was no change in male rats.
                                                                  No data located.
1993
                                   Matthews et al., 1990; NTP, 1991
                                   (as cited in EC, 2000; ATSDR,
                                   2012;NICNAS, 2001)
Sufficient study details reported.
                               Sufficient study details reported in
                               a primary source.
                                                                    7-647

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                                              JUNE 2014 DRAFT REPORT
                                      Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  Necrotic lesions in the hippocampus and
                                  thalamus (females, 175 mg/kg-day; male
                                  and females, 350 mg/kg-day).

                                  NOAEL: 88 mg/kg-day
                                  LOAEL: 175 mg/kg-day (based on
                                  necrotic lesions in hippocampus and
                                  thalamus)
                                  In a 16-day oral study, mice were
                                  gavaged with 0, 175, 350 or 700 mg
                                  TCEP kg-day. Ataxia and convulsive
                                  movements were observed at > 350
                                  mg/kg-day during the first 3 days of
                                  dosing.

                                  NOAEL: 175 mg/kg-day
                                  LOAEL: 350 mg/kg-day (ataxia and
                                  conclusive movements)
                     NTP, 1991;ATSDR,2012
                      Sufficient study details reported.
                                  Female Fischer-344 rats were gavaged
                                  once with 275 mg TCEP/kg.
                                  Convulsions within 60-90 minutes;
                                  extensive loss of CAI hippocampal
                                  pyramidal cells 7 days post-dosing.
                                  Impaired acquisition of a reference
                                  memory task in a water maze when
                                  trained and tested 3 weeks following
                                  treatment.

                                  NOAEL: Not established
                                  LOAEL: 275 mg/kg (based on impaired
                                  acquisition of a memory task 3 weeks
                                  post exposure); only dose  tested
                     Tilson et al., 1990 (as cited in
                     WHO, 1998; ATSDR, 2012)
                      Limited study details reported in a
                      secondary source. True
                      NOAEL/LOAEL cannot be
                      determined because only one dose
                      level was tested; it is uncertain if
                      effects occurred at a lower dose.
                                  Two case reports in dogs:
                     Lehneretal., 2010
                      Adequate case studies reported in a
                                                         7-648

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                                                JUNE 2014 DRAFT REPORT
                                        Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                    In one case, two American pit bulls
                                    presented with acute signs of central
                                    nervous system excitation (including
                                    seizures) in an emergency clinic; one
                                    dog died within  15 minutes and
                                    necropsy revealed frothy brown  fluid in
                                    the stomach and edematous lungs. The
                                    other dog recovered fully following
                                    treatment. In a second case, a German
                                    Shepherd and a Rottweiler were  found
                                    dead after having been left in a car
                                    overnight. Necropsy revealed signs of
                                    possible kidney damage and congested,
                                    dark lungs. Toxicological analysis in all
                                    deceased dogs revealed TCEP (> 2 ppm)
                                    in stomach contents and was  attributed
                                    to ingestion of car seat cushions.
                                                      primary source; actual ingested
                                                      doses were not determined.
                                    White leghorn hens were orally
                                    administered TCEP at 420 mg/kg-day
                                    for 5 days and were observed for 30
                                    days following treatment. No neurotoxic
                                    reactions were evident.
                      Bullock and Kamienski, 1972 (as
                      cited in WHO, 1998; EC, 2000)
                       Limited study details reported in a
                       secondary source.
                                    Single intraperitoneal application of 1.0
                                    mg/kg TCEP to white Leghorn hens. No
                                    evidence of delayed neurotoxicity.
                      EC, 2000
                       Limited study details reported in a
                       secondary source.
                                    Single oral administration of 2.5 or 14.2
                                    g/kg (2500 or 14,200 mg/kg) TCEP to
                                    white Leghorn hens. No microscopic
                                    changes in brain, spinal cord or sciatic
                                    nerve were found after the treatment.
                                    Plasma cholinesterase activity was
                                    inhibited by 87% and brain neuropathy
                                    target esterase by 30% (14.2 g/kg). No
                      Sprague et al., 1981 (as cited in
                      WHO, 1998; EC, 2000)
                       Sufficient study details reported.
                                                            7-649

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JUNE 2014 DRAFT REPORT
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT


DATA
evidence of delayed neurotoxicity.
In vitro neurotoxicity study using
undifferentiated and differentiating
PC 12 cells. Changes in DNA synthesis,
oxidative stress, differentiation into
dopaminergic or cholinergic
neurophenotypes, cell number, cell
growth and neurite growth were
assessed.
TCEP promoted differentiation of the
cholinergic phenotype only. There were
no other adverse neurological effects.
There is potential for neurotoxicity
based on a structural alert for
organophosphates .
(Estimated) ^~ ^p
REFERENCE

Dishawetal., 2011
^^^
^r
Professional judgment
DATA QUALITY

Sufficient study details reported in
a primary source.
Estimated based on a structural
alert for organophosphates and
professional judgment.
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                                                         JUNE 2014 DRAFT REPORT
                                                  Tris (2-chloroethyl) phosphate CASRN 115-96-8
           PROPERTY/ENDPOINT
               DATA
REFERENCE
       DATA QUALITY
Repeated Dose Effects
MODERATE: Based on a LOAEL of 88 mg/kg-day in a 103-week oral study in rats. Effects included renal
tubule epithelial hyperplasia and cerebral gliosis. Additional effects in rats following oral exposure to
higher doses included slightly reduced serum cholinesterase activity and increased kidney and liver weights
(175 and 270 mg/kg-day). Effects in mice following oral exposure included renal tubular karyomegaly
and/or cytomegaly (350 and 700 mg/kg-day). No studies were available to assess effects of repeated
exposures to TCEP via the inhalation or dermal routes of exposure. In addition, there is potential for liver
toxicity based on a structural alert for chlorinated hydrocarbons.
                                             In a 103-week oral study, rats were
                                             gavaged with TCEP at 0, 44 or 88
                                             mg/kg-day, 5 days/week.
                                             Reduced survival at the high dose. Renal
                                             tubule epithelial hyperplasia (high dose,
                                             both sexes), degenerative lesions in the
                                             cerebral cortex (high dose, females).
                                             There were no adverse effects on
                                             lymphoreticular tissues.

                                             NOAEL: 44 mg/kg-day
                                             LOAEL: 88 mg/kg-day (based on renal
                                             tubule epithelial hyperplasia in male and
                                             female rats and cerebrum gliosis in
                                             female rat)
                                    NTP, 1991; Matthews et al.,
                                    (as cited in ATSDR 2012)
                                             In a 103-week oral study, mice were
                                             gavaged with TCEP at 0, 175, or 350
                                             mg/kg-day, 5 days/week.
                                             No significant differences in survival or
                                             body weight gain in comparison with
                                             controls. Renal tubular karyomegaly in
                                             80% of high animals (a marker of
                                             nephropathy); Marginal increase in
                                             harderian gland neoplasms (primary
                                             adenomas, high dose females). There
                                             were no adverse effects on
                1993
                                    NTP, 1991; EC, 2000; ATSDR
                                    2012
Sufficient study details reported.
                       Sufficient study details reported.
                                                                     7-651

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                                                JUNE 2014 DRAFT REPORT
                                        Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   lymphoreticular tissues.

                                   NOAEL: 175 mg/kg-day
                                   LOAEL: 350 mg/kg-day (renal tubular
                                   karyomegaly)
                                   In a 16-day oral study, rats were orally
                                   gavaged with 0, 44, 88, 175 or 350
                                   mg/kg-day TCEP in corn oil 5 A
                                   days/week for a total of 12 doses.
                                   No treatment-related deaths, differences
                                   in final mean body weight or
                                   histopathological lesions. Slightly
                                   reduced serum cholinesterase activity
                                   (females, 175 and 350 mg/kg-day);
                                   Increased absolute and relative kidney
                                   weights (males, 175 and 350 mg/kg-
                                   day); increased absolute and relative
                                   liver weights (females, 350 mg/kg-day)

                                   NOAEL: 88 mg/kg-day;
                                   LOAEL: 175 mg/kg-day (decreased
                                   serum  cholinesterase activity, increased
                                   absolute and relative kidney weights)
                      Matthews et al., 1990 (as cited in
                      NTP, 1991)
                       Sufficient study details reported.
                                   In a 16-day oral study, mice were orally
                                   gavaged with 0, 22, 44, 88, 175, 350 or
                                   700 mg/kg-day TCEP in corn oil 5
                                   days/week for a total of 12 doses.
                                   No treatment-related deaths, differences
                                   in final mean body weight or
                                   histopathological lesions.

                                   NOAEL: 700 mg/kg-day (highest dose
                                   tested)
                      Matthews et al., 1990 (as cited in
                      NTP, 1991)
                       Sufficient study details reported.
                                                            7-652

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                                               JUNE 2014 DRAFT REPORT
                                       Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   LOAEL: Not established
                                   In a 16-18 week oral study, rats were
                                   gavaged with TCEP at 0, 22, 44, 88, 175
                                   or 350 mg/kg-day, 5 days/week.
                                   Mortality occurred at the high dose (4/10
                                   males and 3/10 females); Significantly
                                   increased liver and kidney to body
                                   weight ratios (> 44 mg/kg-day in
                                   females; 350 mg/kg-day for males);
                                   Necrotic lesions in the hippocampus and
                                   thalamus (females, 175 mg/kg-day; both
                                   sexes, 350 mg/kg-day).

                                   NOAEL: 88 mg/kg-day
                                   LOAEL: 175 mg/kg-day (necrotic
                                   lesions in hippocampus and thalamus-
                                   females)
                     Matthews et al., 1990; NTP, 1991
                     (as cited in EC, 2000; NICNAS,
                     2001;ATSDR, 2012)
                       Sufficient study details reported.
                                   In a 16-week oral study, mice were
                                   gavaged with TCEP (in corn oil) at 0,
                                   44, 88, 175, 350 and 700 mg/kg-day, 5
                                   days/week.
                                   No treatment-related deaths, differences
                                   in final mean body weight or differences
                                   in cholinesterase activity. Kidney
                                   effects: tubule epithelial cells with
                                   enlarged nuclei (cytomegaly and
                                   karyomegaly) at the highest dose.

                                   NOAEL: 350 mg/kg-day
                                   LOAEL: 700 mg/kg-day (kidney effects)
                     Matthews et al., 1990; NTP, 1991
                     (as cited in EC, 2000; ATSDR
                     2012)
                       Sufficient study details reported.
                                   In a 28-day dietary study, rats were fed
                                   TCEP at 0, 400, 1,000, 3,000 or 8,000
                                   ppm daily (0, 37, 91, 270 and 730
                     EC, 2000; EU, 2009
                       Limited study details reported in a
                       secondary source; doses were
                       reported as ppm in the diet but
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                                               JUNE 2014 DRAFT REPORT
                                       Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   mg/kg-day)
                                   No mortalities. Significant reductions in
                                   body weight and food consumption
                                   (8,000 ppm); No treatment-related
                                   changes in clinical chemistry,
                                   hematology or urinalysis parameters; no
                                   adverse gross or microscopic effects.
                                   Significant increase in relative liver and
                                   kidney weights (3,000 and 8,000 ppm)

                                   NOAEL:  1,000 ppm (91 mg/kg-day)
                                   LOAEL: 3,000 ppm (270 mg/kg-day)
                                                     were converted to mg/kg-day using
                                                     EPA 1988 reference values for
                                                     body weight and food
                                                     consumption.
                                   In a 28-day dietary study, rats were fed
                                   TCEP at 0, 500, 850, 1,500 and 2,000
                                   ppm daily (-46, 78, 140, and 180
                                   mg/kg-day).
                                   Decreased food consumption (8,000
                                   ppm). No further clinical effects were
                                   observed and necropsy revealed no
                                   abnormalities.

                                   NOAEL: > 2,000 ppm (180 mg/kg-day;
                                   highest dose tested)
                                   LOAEL: Not established
                     EC, 2000; EU, 2009
                       Limited study details reported in a
                       secondary source; doses were
                       reported as ppm in the diet but
                       were converted to mg/kg-day using
                       EPA 1988 reference values for
                       body weight and food
                       consumption.
                                   In a 30-day dietary study, rats were fed
                                   TCEP up to a maximum dose of 400
                                   mg/kg-day (other doses not reported).
                                   No deaths; no adverse effects were
                                   observed.

                                   NOAEL: 400 mg/kg-day (highest dose
                                   tested)
                                   LOAEL: Not established
                     Ulsamer et al., 1980 (as cited in
                     EC, 2000)
                       Limited study details reported in a
                       secondary source; Study received
                       reliability score of 4 in the IUCLID
                       data set.
                                                           7-654

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Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT


Skin Sensitization

Skin Sensitization
Respiratory Sensitization
(Respiratory Sensitization
Eye Irritation

Eye Irritation
Dermal Irritation

Dermal Irritation
DATA
There is potential for liver toxicity based
on a structural alert for chlorinated
hydrocarbons.
(Estimated)
REFERENCE
Professional judgment
DATA QUALITY
Estimated based on a structural
alert for chlorinated hydrocarbons
and professional judgment.
LOW: TCEP is not a skin sensitizer in guinea pigs.
Not sensitizing to guinea pigs
EC, 2000; OECD-SIDS, 2006
Limited study details reported in a
secondary source.
No data located.


No data located.
LOW: TCEP produced mild conjunctival irritation in rabbits.
Mild conjunctival irritation, rabbits
Not irritating to rabbit eyes
<^\ \
Not irritating to rabbit eyes
OECD-SIDS, 2006
EC, 2000
EC, 2000
Limited study details reported in a
secondary source; Study conducted
in accordance with OECD
Guideline 404.
Limited study details reported in a
secondary source; Study conducted
in accordance with GLP and
Directive 84/449/EEC, B.5 or
OECD Guideline 405.
Limited study details reported in a
secondary source.
LOW: TCEP was slightly irritating to rabbit skin.
Mild skin irritation, rabbits
J
Slightly irritating to rabbit skin
Not irritating to rabbit skin
OECD-SIDS, 2006
EC, 2000
EC, 2000
Limited study details reported in a
secondary source; Study was
conducted in accordance with
OECD Guideline 404.
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source; Study was
conducted in accordance with GLP
         7-655

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Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT

Endocrine Activity

DATA

REFERENCE

DATA QUALITY
and Directive 84/449/EEC, B.4 or
OECD Guideline 404.
TCEP increased 17-estradiol (E2) and testosterone (T) concentrations following exposure for 48 hours in
human H295R cells and inhibited luciferase expression induced by dihydrotestosterone in a reporter gene
assay. TCEP was negative for estrogenic activity in a yeast two-hybrid assay and was not an estrogen
receptor antagonist in human MVLN cells following a 72-hour incubation period. There were no adverse
effects on endocrine glands of rats and mice administered TCEP via oral gavage for up to 103 weeks.
In 103-week oral studies, rats were
gavaged with TCEP at 0, 44 or 88
mg/kg-day and mice were gavaged with
TCEP at 0, 175, or 350 mg/kg-day, 5
days/week. There were no adverse
effects on endocrine glands in either
species reported.
No estrogenic or anti -estrogenic activity
of TCEP in human endometrial cancer
cells in a recombinant yeast reporter
gene assay
TCEP inhibited luciferase expression
induced by dihydrotestosterone in a
reporter gene assay
No estrogen receptor antagonism in
human MVLN cells following 72-hour
incubation up to 10 mg/L TCEP
Increased 17B-estradiol (E2) and
testosterone (T) concentrations
following exposure to >0.1 mg/TCEP
for 48 hours in human H295R cells.
Negative for estrogenic activity in a
yeast two-hybrid assay
NTP, 1991; Matthews et al., 1993
(as cited in ATSDR 2012)
Follmann and Wober, 2006
HSDB, 2013
Liu etal., 2012
Liu etal., 2012
Nishihara et al., 2000
Sufficient study details reported.
Sufficient study details reported in
primary source.
Limited details reported in
secondary source; study is in
Chinese with an English abstract.
Sufficient study details reported in
primary source.
Sufficient study details reported in
primary source.
Sufficient study details reported in
primary source.
         7-656

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Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
Immunotoxicity

ECOSAR Class
Immune System Effects
DATA
REFERENCE
DATA QUALITY
TCEP produced a dose-dependent growth inhibition in B cells but not T cells in a mouse lymphocyte
mitogenesis test. The IC50 was l.OxlO"5 mol/L.
Lymphocyte mitogenesis test, mouse
splenic lymphocyte cells; dose-
dependent growth inhibition in B cell
test but no inhibition in T cell test. IC50
(50% inhibition concentration): l.OxlO"5
mol/L
In 103 week oral studies, rats were
gavaged with TCEP at 0, 44 or 88
mg/kg-day and mice were gavaged with
TCEP at 0, 175, or 350 mg/kg-day 5
days/week.
There were no adverse effects on
lymphoreticular tissues in either species.
Sakazakietal., 2001
^^^
NTP, 1991; Matthews et al., 1993
(ascitedinATSDR,2012)
Sufficient study details reported in
a primary source.
Sufficient study details reported.
ECOTOXICITY

Acute Aquatic Toxicity
Fish LC50

HIGH: Based on experimental LC50 values of 6.3 and 4.9 mg/L and fish and daphnia, respectively and an
acute EC50 of 1.1 mg/L for algae.
Freshwater fish (Oryzias latipes) 96-
hour LC50 = 6.3 mg/L
(static test conditions)
(Experimental)
Freshwater fish (Carassius auratus) 96-
hour LC50 = 90 mg/L
(Experimental)
Freshwater fish {Oryzias latipes) 96-
hour LC50 = 210 mg/L
(static test conditions)
(Experimental)
Freshwater fish (Salmo gairdneri} 96-
EC, 2000
Sasaki et al., 1981 (as cited in
WHO, 1998; EU, 2009)
Sasaki et al., 1981 (as cited in
WHO, 1998; EC, 2000; EU, 2009)
WHO, 1998; EC, 2000; EU, 2009
Limited study details reported in a
secondary source; Study was
conducted in accordance with
OECD Guideline 203. No data on
analytical monitoring.
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source. No data on
analytical monitoring.
Limited study details reported in a
         7-657

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JUNE 2014 DRAFT REPORT
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT

DATA
hour LC50 = 249 mg/L NOEC = 50 mg/L
(static test conditions; test dilution was
clear and colorless with colorless
droplets of material on the surface)
(Experimental)
Freshwater fish (Oryzias latipes) LC50 =
251 mg/L
(Experimental)
Freshwater fish (Leuciscus idus) 48-hour
LC5o = ca. 200 mg/L
(static test conditions)
(Experimental)
Freshwater fish (Oryzias latipes} 48-
hour LC50 = 300 mg/L
(static test conditions)
(Experimental)
Freshwater fish (Carassius auratus)
168-hour/7 day LC0/EC0 = 5 mg/L;
(static test conditions)
(Experimental)
Freshwater fish (Cyprinus carpio) 6-day
LC0 (dietary exposure) = 35 - 156 mg/kg
food
(Experimental)
Freshwater fish (Cyprinus carpio) 6-day
LC0= 156 mg/kg food
(Experimental)
Freshwater fish 96-hour L C50 =370
mg/L
(Estimated)
ECOSAR: Neutral organics
REFERENCE

Yoshioka et al., 1986 (as cited in
WHO, 1998)
EC, 2000; EU, 2009
MITI, 1992b (as cited in EC, 2000;
WHO, 1998; EU, 2009)
EC, 2000; EU, 2009
EC, 2000
EU, 2009
ECOSAR v 1.11
DATA QUALITY
secondary source; Study was
conducted in accordance with GLP
and OECD Guideline 203. No
analytical monitoring was
conducted.
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source. No data on
analytical monitoring.
Limited study details reported in a
secondary source. No data on
analytical monitoring.
Limited study details reported in a
secondary source. No data on
analytical monitoring.
Limited study details reported in a
secondary source. No data on
analytical monitoring.
Limited study details provided in a
secondary source.
ECOSAR also provided results for
the Esters, and Esters (phosphate)
classes; however, professional
judgment indicates that this
compound is not currently well
         7-658

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Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT

Daphnid LC50
Green Algae EC50
DATA

Daphnia magna 24-hour EC50 = 4.9
mg/L
(Experimental)
Daphnia magna 24-hour EC50 = 235
mg/L
(Experimental)
Daphnia magna 24-hour EC50 = 340
mg/L; EC0 = 100 mg/L; EC100 = 1,000
mg/L
(Experimental) ^^B
Daphnia magna 24-hour EC50 = 45 1
mg/L
(Experimental)
Daphnia LC50 = 1,000 mg/L
(Experimental)
Daphnid 48-hour LC50 = 206 mg/L
(Estimated)
ECOSAR: Neutral organics
Green algae (Scenedesmus subspicatus )
72-hour EC50 =1.1 mg/L (biomass)
Green algae (Scenedesmus subspicatus)
72-hour EC50 = 3.6 mg/L (growth rate)
(Experimental)
Green algae (Scenedesmus subspicatus )
96-hour EC50 =1.2 mg/L (biomass)
REFERENCE

EC, 2000
EC, 2000; EU, 2009
EC, 2000; EU, 2009
EC, 2000; EU, 2009
Yoshioka et al., 1986 (as cited in
WHO, 1998)
ECOSAR v 1.11
EC, 2000; EU, 2009
EC, 2000; EU, 2009
DATA QUALITY
represented in ECOSAR vl . 1 1 .
Limited study details reported in a
secondary source; Study conducted
in accordance with OECD
Guideline 202. No data on
analytical monitoring.
Limited study details reported in a
secondary source. No data on
analytical monitoring.
Limited study details reported in a
secondary source; Study conducted
in accordance with Directive
84/449/EEC, C.2.
Limited study details reported in a
secondary source. Non-GLP; no
data on analytical monitoring.
Limited study details provided in a
secondary source; study duration
not reported.
ECOSAR also provided results for
the Esters, and Esters (phosphate)
classes; however, professional
judgment indicates that this
compound is not currently well
represented in ECOSAR vl . 1 1 .
Limited study details reported in a
secondary source. Non-GLP; no
data on analytical monitoring.
Limited study details reported in a
secondary source; no data on
         7-659

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Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT

DATA
(Experimental)
Green algae (Scenedesmus subspicatus )
48-hour EC50 = 2 mg/L (biomass)
Green algae (Scenedesmus subspicatus}
4 8 -hour EC50 = 5 mg/L (growth rate)
(Experimental)
Green algae (Scenedesmus subspicatus )
72-hour EC50 = 271-278 mg/L (growth
rate)
NOEC = 100 mg/L
(Experimental)
Green algae (Scenedesmus subspicatus )
72-hour EC50 = 3.6 mg/L (growth rate)
(Experimental)
Green algae (Scenedesmus subspicatus )
4 8 -hour EC50 = 5 mg/L (growth rate)
(Experimental)
Green algae (Pseudokirchneriella
subcapitata ) 96-hour EC50 =117 mg/L
(growth rate)
NOEC = 5 mg/L
(Experimental)
Green algae EC50 (Tetrahymena
pyriformis ) = 126 mg/L
(Experimental)
Green algae 96-hour EC50 =141 mg/L
(Estimated)
ECOSAR: Neutral organics
REFERENCE

EC, 2000; EU, 2009
EC, 2000; EU, 2009
^r
EC, 2000; EU, 2009
EC, 2000; EU, 2009
EC, 2000; EU, 2009
Yoshioka et al, 1986 (as cited in
WHO, 1998)
ECOSAR v 1.11
DATA QUALITY
analytical monitoring.
Limited study details reported in a
secondary source; no data on
analytical monitoring.
Limited study details reported in a
secondary source. Study conducted
in accordance with GLP and OECD
Guideline 201. Analytical
monitoring was performed.
Limited study details reported in a
secondary source; no data on
analytical monitoring.
Limited study details reported in a
secondary source; no data on
analytical monitoring.
Limited study details reported in a
secondary source. Study conducted
in accordance with GLP and OECD
Guideline 201. No analytical
monitoring.
Limited study details provided in a
secondary source; study duration
not reported.
ECOSAR also provided results for
the Esters, and Esters (phosphate)
classes; however, professional
judgment indicates that this
compound is not currently well
represented in ECOSAR vl . 1 1 .
         7-660

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                                                        JUNE 2014 DRAFT REPORT
                                                Tris (2-chloroethyl) phosphate CASRN 115-96-8
          PROPERTY/ENDPOINT
              DATA
         REFERENCE
       DATA QUALITY
Chronic Aquatic Toxicity
HIGH: Two experimental studies were located for daphnia, while there were no experimental chronic
aquatic toxicity data for fish or algae. The experimental 14 and 21-day NOECs of 1.9 and 13 mg/L in
Daphnia magna are within the Moderate - Low hazard designation range; however, chronic aquatic
toxicity in fish and algae cannot be ruled out due to the lack of experimental data in fish and algae.
ECOSAR estimates indicate a High- to - Very High hazard in fish. In addition, this substance has been
assigned the risk phrase R51/53: Toxic to aquatic organisms, may cause long-term adverse effects in the
aquatic environment (ESIS, 2012). There is potential concern based on estimates and the uncertainty due
to the lack of experimental data; therefore a High hazard designation was assigned.
Fish ChV
Fish ChV = 35 mg/L
(Estimated)
ECOSAR: Neutral organics
ECOSAR v 1.11
ECOSAR also provided results for
the Esters, and Esters (phosphate)
classes; however, professional
judgment indicates that this
compound is not currently well
represented in ECOSAR vl. 11.
Daphnid ChV
Daphnia magna 14-day NOEC =1.9
mg/L
(Experimental)
EC, 2000
                                            Daphnia magna 21-day NOEC =13
                                            mg/L (reproduction rate)
                                            (Experimental)
                                   EC, 2000
                                            Daphnia ChV = 19 mg/L
                                            (Estimated)
                                            ECOSAR: Neutral organics
                                   ECOSAR v 1.11
Limited study details reported in a
secondary source; Study conducted
in accordance with OECD
Guideline 202. No data on
analytical monitoring.
                               Limited study details reported in a
                               secondary source; no data on
                               analytical monitoring.
                               ECOSAR also provided results for
                               the Esters, and Esters (phosphate)
                               classes; however, professional
                               judgment indicates that this
                               compound is not currently well
                               represented in ECOSAR vl. 11.
                                                                   7-661

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JUNE 2014 DRAFT REPORT
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
Green Algae ChV
	 ,
Transport

Henry's Law Constant (atm-
m3/mole)
Sediment/Soil
Adsorption/Desorption - Koc
Level III Fugacity Model
DATA
Green algae ChV = 35 mg/L
(Estimated)
ECOSAR: Neutral organics
REFERENCE
ECOSAR v 1.11
DATA QUALITY
ECOSAR also provided results for
the Esters, and Esters (phosphate)
classes; however, professional
judgment indicates that this
compound is not currently well
represented in ECOSAR vl . 1 1 .
ENVIRONMENTAL FATE
Level III fugacity models incorporating available physical and chemical property data indicate that at
steady state, TCEP is expected to be found primarily in soil and to a lesser extent, water. TCEP is expected
to have high mobility in soil, based on estimated K0c values. Leaching through soil to groundwater may
occur, though it is not expected to be an important transport mechanism. Estimated volatilization half-lives
indicate that it will be non-volatile from surface water. Volatilization from dry surface is also not expected
based on its vapor pressure. In the atmosphere, TCEP is expected to exist in the vapor phase based on its
vapor pressure.
2.6xlO'8 (Estimated)
<10"8 (Estimated)
100 (Estimated)
390 (Estimated)
Air = 0.004%
Water =10.9%
Soil = 88.8%
Sediment = 0.26% (Estimated)
EPIv4.11
EPIv4.11
EPIv4.11
EPIv4.11
EPIv4.11
Estimated by the HENRYWIN
program Bond estimation method.
Estimated from the measured
Water Solubility and extrapolated
Vapor Pressure.
Estimated by the KOCWIN Log
Kow method using the measured
Log Kow value, 1.78.
Estimated by the KOCWIN MCI
method.
Values were obtained from the
measured log Kow, water solubility
and extrapolated vapor pressure.
         7-662

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                                                        JUNE 2014 DRAFT REPORT
                                                 Tris (2-chloroethyl) phosphate CASRN 115-96-8
          PROPERTY/ENDPOINT
                                         DATA
                                            REFERENCE
                                      DATA QUALITY
Persistence
                           MODERATE: Based on guideline experimental biodegradation data that taken together indicate that the
                           resultant half-life is expected to be greater than 16 days but less than 60 days and therefore is consistent
                           with the moderate hazard designation. After 48 days 70-90% degradation of TCEP occurred in activated
                           sludge inoculum using OECD 301B, 50-90% degradation with adapted activated sludge using OECD 302A
                           and 45% degradation after 4 weeks with OECD 301C. No degradation was found in an anaerobic
                           biodegradation study after 58 days using ISO DIS 11734. TCEP is expected to hydrolyze slowly; although
                           hydrolysis rates will be dependent on temperature and pH conditions according to experimental studies.
                           TCEP is not expected to be susceptible to direct photolysis by sunlight, since it does not absorb light at
                           wavelengths >290 nm. TCEP is not susceptible to significant degradation by ozone or hydroxyl radicals in
                           experimental studies of water samples. The atmospheric half-live of vapor-phase TCEP is estimated to be
                           less than  one day.
Water
Aerobic Biodegradation
Passes Ready Test: No
Test method: OECD TG 301C:
Modified MITI Test (I)

4% degradation (by BOD) after a 4-
week incubation period using an
activated sludge inoculum (30 mg/L,
predominantly domestic sludge, non-
adapted) and 100 mg/L test substance
(Measured)
                                            Passes Ready Test: No
                                            Test method: OECD TG 30IB: CO2
                                            Evolution Test

                                            Activated sludge inoculum, 20 mg/L
                                            concentration of test substance, 70-90%
                                            degradation after 48 days; Result:
                                            Inherently biodegradable (Measured)
                                             Study results: 100%
                                             Test method: Other

                                             Isolated bacterial cultures containing
MITI, 1992a; EC, 2000
Guideline study performed
according to Japanese MITI and
OECD guidelines.
                                                              EC, 2000
                                                                  Adequate, guideline study.
                                                              Takahashi et al., 2012
                                                                  Nonguideline pure culture study
                                                                  indicating the potential for
                                                                  complete bacterial biodegradation.
                                                                    7-663

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                                              JUNE 2014 DRAFT REPORT
                                       Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                  Sphingobium sp. strain TCM1 and
                                  Xanthobacter autotrophicus strain GJ10
                                  degraded TCEP and the metabolite 2-
                                  chloroethanol (Measured)
                                   Study results: 50-90%/24 hour
                                   Test method: 302A: Inherent - Modified
                                   SCAS Test

                                   Degradation reported as 50-90% after 24
                                   hours; domestic, adapted activated
                                   sludge inoculum; 13 mg/L concentration
                                   of test substance; the 50-90%
                                   degradation was found within 24 hours
                                   after test periods ranging from 4 to 13
                                   weeks. (Measured)
                     EC, 2000
                      Adequate, guideline study.
                                   Study results: 15%/21 days
                                   Test method: 302B: Inherent - Zahn-
                                   Wellens/EMPA Test

                                   Degradation reported as 15% after 21
                                   days; industrial non-adapted activated
                                   sludge inoculum (Measured)
                     EC, 2000
                      Adequate, guideline study.
                                   Study results: 13%/28 days
                                   Test method: Other

                                   Method: domestic activated sludge
                                   inoculum; 20 mg/L concentration of test
                                   substance (Measured)
                     EC, 2000
                      Nonguideline test conducted by a
                      manufacturer.
                                   Study results: <10%/27 days
                                   Test method: 302B: Inherent - Zahn-
                                   Wellens/EMPA Test

                                   Degradation reported as <10% after 27
                     EC, 2000
                      Adequate, guideline study.
                                                          7-664

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                                                          JUNE 2014 DRAFT REPORT
                                                  Tris (2-chloroethyl) phosphate CASRN 115-96-8
           PROPERTY/ENDPOINT
                                           DATA
                                             REFERENCE
                                       DATA QUALITY
                                              days; Industrial, non-adapted activated
                                              sludge inoculum (Measured)
                                              Study results: 4%/28 days
                                              Test method: Other

                                              Method: domestic activated sludge
                                              inoculum; 20 mg/L concentration of test
                                              substance (Measured)
                                                                 EC, 2000
                                                                    Nonguideline test conducted by a
                                                                    manufacturer.
                                              Isolated bacterial cultures containing
                                              Acidovorax sp. BSB421 and
                                              Sphingomonas agrestis completely
                                              degraded 20 (JVI TCEP within 6 hours
                                              when they are the sole phosphorus
                                              sources. (Measured)
                                                                 Takahashi et al., 2008, 2010
                  Volatilization Half-life for
                  Model River
                            >1 year (Estimated)
                                    EPIv4.11
                  Volatilization Half-life for
                  Model Lake
                            >1 year (Estimated)
                                    EPIv4.11
                                                                    Nonguideline pure culture study
                                                                    indicating the potential for
                                                                    complete bacterial biodegradation.
                                Estimation model was calculated
                                using all applicable measured input
                                values and the Henry's Law
                                Constant obtained from the
                                measured water solubility and
                                extrapolated vapor pressure.
                                Estimation model was calculated
                                using all applicable measured input
                                values and the Henry's Law
                                Constant obtained from the
                                measured water solubility and
                                extrapolated vapor pressure.
Soil
Aerobic Biodegradation
Study results: DT50 = 167
Test method: Other
DT90 »100 days based on 5 mg/kg soil
in a laboratory test for 100 days; kinetic
curve fitted to a 2nd order square root
function (Measured)
EU, 2009
Nonguideline study reported in a
secondary source.
                                                                      7-665

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JUNE 2014 DRAFT REPORT
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT

Air
Reactivity
Anaerobic Biodegradation
Soil Biodegradation with
Product Identification
Sediment/Water
Biodegradation
Atmospheric Half-life
Photolysis
Hydrolysis
DATA
Study results: 0%/58 days
Test method: Other
Method = ISO DIS 1 1734; 80 mg/L
concentration test substance related to
DOC (Dissolved Organic Carbon); Test
condition of 35°C +/- 2°C (Measured)


0.5 days (Estimated)
0% Not a significant fate process
(Estimated)
Direct photolysis was insignificant;
second-order rates of reaction
determined by ultraviolet and ozone
generated -OH in water. (Measured)
<10% removal of TCEP in tertiary-
treated effluent samples collected from
three waste water treatment facilities
when exposed to O3 (Measured)
0%/1 day Hydrolysis measured in
buffered water at 20°C; pH 2 to pH 12
with a chlorine concentration (100
mg/L) from calcium hypochlorate and
hydrochloric acid. 100% of the chemical
remained after one day at pH 2 to pH 8.
(Measured)
5%/l day Hydrolysis measured in
buffered water at 20°C and pH 2 to pH
REFERENCE
EC, 2000

^^^
EPIv4.11
Professional judgment; Mill, 2000
Watts and Linden, 2009
Wert et al., 2009
Ishikawa and Baba, 1988
Ishikawa and Baba, 1988
DATA QUALITY
Adequate guideline study.
No data located.
No data located.

This compound does not contain
functional groups that would be
expected to absorb light of
wavelengths >290 nm.
Nonguideline study.
Nonguideline study indicating
limited susceptibility to hydroxyl
radical degradation.
Adequate hydrolysis study
examining hydrolysis in a water
treatment facility.
Adequate hydrolysis study
examining hydrolysis in a water
         7-666

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JUNE 2014 DRAFT REPORT
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT


Environmental Half-life
DATA
12 with a chlorine concentration (100
mg/L) from calcium hypochlorate and
hydrochloric acid. 95% of the chemical
remained after one day at pH 10. 40%
remained after one day at pH 12.
(Measured)
50%/20 days at pH 5 to pH 9
50%/17 days at pH 10 (Estimated)
Slow hydrolysis in water; hydrolysis
increases with temperature and at the
extremes of the pH range. (Estimated)
120 days (Estimated)
^
REFERENCE

EPIv4.11
lr
IPCS, 1998
PBT Profiler
DATA QUALITY
treatment facility.
Estimate generated by the
HYDROWIN program. For
phosphate esters, HYDROWIN
estimates hydrolysis half-lives that
consider both base-catalyzed and
neutral hydrolysis rate constants at
25 °C. Based on measured
hydrolysis data that indicates little
hydrolysis at acidic or neutral pH
over a one -day period (Ishikawa
and Baba, 1988), the estimates at
pH 5 to pH 7 may be too fast.
Supporting information provided in
a secondary source.
Half-life estimated for the
predominant compartment (soil), as
determined by EPI and the PBT
Profiler methodology.
         7-667

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JUNE 2014 DRAFT REPORT
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
Bioaccumulation

Fish BCF
Other BCF
BAF
Metabolism in Fish
DATA
REFERENCE
DATA QUALITY
LOW: Based on multiple experimental BCF values in four different species that are below 100, the cutoff
for the Low bioaccumulation designation criteria. Biomonitoring studies have reported the detection of this
compound in aquatic species, mammalian species, herring gull eggs and pine needles; DfE criteria
specifically require these data to be considered in the hazard designation on a case by case basis. Available
toxicokinetic studies indicate that in some species, metabolites of TCEP are rapidly formed and eliminated.
This demonstrates that these materials are likely bioavailable and could be observed in a biological matrix.
However, the rate of metabolism and elimination may be successfully competing with that of uptake, which
is also consistent with the experimental BCF results. The biomonitoring studies are not inconsistent with a
Low designation.
0.8 Cyprinus carpio Mean water
concentration of 1 mg/L; 42 days
exposure (Measured)
2.2 Oryzias latipes Static test system;
96-hour exposure period; 4 mg/L
concentration test substance (Measured)
1.3 Oryzias latipes Flow-through test
system; 96-hour exposure period; 4
mg/L concentration test substance
(Measured)
0.9 Carassius auratus Static test with a
96-hour exposure period to 4 mg/L test
substance (Measured) ^^^^
5 . 1 Cyprinus carpio Whole body tissue
analysis, a mean water concentration of
100 (Jg/L; 42 days exposure in flow-
through system (Measured)

6.3 (Estimated)

EC, 2000
EC, 2000
EC, 2000
EC, 2000
MITI, 1992a

EPIv4.11

Nonguideline study conducted for a
manufacturer.
Nonguideline study conducted for a
manufacturer.
Nonguideline flow-through study
conducted for a manufacturer.
Nonguideline study conducted for a
manufacturer.
Japanese MITI guideline study.
No data located.
Estimated by the BCFBAF
program using the measured log
Kow (1.78) and the Arnot-Gobas
method (upper trophic).
No data located.
         7-668

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JUNE 2014 DRAFT REPORT
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA REFERENCE DATA QUALITY
ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring
Ecological Biomonitoring
Human Biomonitoring
Detected in house dust, indoor air, urban and suburban air, river and sea sediments, surface waters, drinking
water, wastewater effluents, ground waters, rainwater samples and food samples (IARC, 1990; Suzuki et al.,
1994; Andresen et al., 2007; Bacaloni et al., 2008; Takigami et al., 2008, 2009; EU, 2009; Dougherty et al., 2010;
Regnery and Puttmann, 2010a, 2010b; Ali et al., 2012a, 2012b; Alvarez et al., 2012; ATSDR 2012; Bergh et al.,
2012; Bollmann et al., 2012; Cao et al., 2012; Dodson et al., 2012; Matamoros and Salvado, 2012; Matamoros et
al., 2012; Moller et al., 2012; Rodil et al., 2012; Eggen et al., 2013; HSDB, 2013; Kim et al., 2013; Kolpin et al.,
2013; Salamova et al., 2014).
Detected in pine needle samples collected in the Sierra Nevada foothills in California; herring gull eggs; mussel,
fish and shellfish samples (Yasuhara and Morita, 1987; IARC, 1990; IPCS, 1998; EU, 2009; Chen et al., 2012 ).
This chemical was not included in the NHANES biomonitoring report (CDC, 2009).
         7-669

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                                                  JUNE 2014 DRAFT REPORT


ATSDR (2012) Toxicological profile for phosphate ester flame retardants. Atlanta, GA: Agency for Toxic Substances and Disease Registry.

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exposure assessment. Chemosphere 88(11): 1276-1282.

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Bacaloni A, Cucci F, Guarino C, et al. (2008) Occurrence of organophosphorus flame retardant and plasticizers in three volcanic lakes of central
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house dust. Anal Bioanal Chem  402(l):51-59.

Bollmann UE, Moller A, Xie Z,  et al. (2012) Occurrence and fate of organophosphorus flame retardants and plasticizers in coastal and marine
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Bullock CH, Kamienski FX (1972) Richmond, California:  Stauffer Chemical Company, Western Research Center.

Burka LT, Sanders JM, Herr DW, et al. (1991) Metabolism of tris(2-chloroethyl) phosphate in rats and mice. Drug Metab Dispos 19(2):443-447.

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http://www.cdc.gov/exposurereport/pdf/FourthReport.pdf

California EPA (2013) Chemicals known to the state to cause cancer or reproductive toxicity July 05, 2013. California Environmental Protection
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Sakazaki H, Ueno H, Umetani K, et al. (2001) Immunotoxicological evaluation of environmental chemicals utilizing mouse lymphocyte
mitogenesis test. J Health Sci 47(3):258-271.

Sala M, Gu ZG, Moens G (1982) In vivo and in vitro biological effects of the flame retardants tris(2,3-dibromopropyl) phosphate and tris(2-
chlorethyl) orthophosphate. Eur J Cancer Clin Oncol 18(12).

Salamova A, Ma Y, Venier M, et al. (2014) High levels of organophosphate flame retardants in the Great Lakes atmosphere. Environ Sci Technol
Sasaki K, Takeda M, Uchiyama M (1981) Toxicity absorption and elimination of phosphoric-acid tri esters by killifish oryzias-latipes and goldfish
carassius-auratus . Bull Environ Contam Toxicol 27(6):775-782.

Shepelskaya NR Dyshinevich NE (1981)  [An experimental study of the gonadotoxic effect of tris(chloroethyl) phosphate]. Gigiena i sanitariia
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Smyth HF, Carpenter CP, Weil CS, et al. (195 1) Range-finding toxicity data: List FV. Arch Ind Hyg Occup Med 4(2): 1 19-122.

Sprague GL, Sandvik LL, Brookins-Hendricks MJ, et al. (1981) Neurotoxicity of two organophosphorus ester flame retardants in hens. J Toxicol
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State of Washington (201 1) Rationale for reporting list of chemicals of high concern to children. Tris(2-chloroethyl) phosphate (TCEP).
                                                     J
Suzuki T, Yaguchi K, Ohnishi K, et al. (1994) Gas chromatographic detection of tris(2-chloroethyl) and tris(2-butoxyethyl)phosphate in
groundwater by large -sample -volume injection. J AOAC Int 77(6): 1647-1651.

Takada K, Yasuhara K, Nakaji Y, et al. (1989) Carcinogenicity study of tris(2-chloroethyl) phosphate in ddY mice. J Toxicol Pathol 2(2):213-222.

Takada K, Yoshimoto H, Yasuhara K, et al. (1991) [Combined chronic toxicity/carcinogenicity test of tris(2-chloroethyl)phosphate (TCEP)
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                                                              7-675

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                                                  JUNE 2014 DRAFT REPORT


Takahashi S, Kawashima K, Kawasaki M, et al. (2008) Enrichment and characterization of chlorinated organophosphate ester-degrading mixed
bacterial cultures. J Biosci Bioeng 106(l):27-32.

Takahashi S, Miura K, Abe K, et al. (2012) Complete detoxification of tris(2-chloroethyl) phosphate by two bacterial strains: Sphingobium sp.
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                                                              7-676

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                                                JUNE 2014 DRAFT REPORT


Yoshioka Y, Ose Y, Sato T (1986) Correlation of five test methods to assess chemical toxicity and relation to physical properties. Ecotoxicol
Environ Saf 12:15-21.
                                                            7-677

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                                                            JUNE 2014 DRAFT REPORT
              Tris (p-t-butylphenyl) phosphate (TBPP)
                                                   Screening Level Toxicology Hazard Summary

This table only contains information regarding the inherent hazards of flame retardant chemicals. Evaluation of risk considers both the hazard and exposure associated with the
substance including combustion and degradation by-products. The caveats listed in the legend and footnote sections must be taken into account when interpreting the hazard
information in the table.
VL = Very Low hazard L = Low hazard   = Moderate hazard H = High hazard VH = Very High hazard - Endpoints in colored text (VL, L,   , H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].







Chemical







CASRN
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78-33-1
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                                                                        7-678

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                                                           JUNE 2014 DRAFT REPORT
                                                                                                                  CASRN: 78-33-1
                                                                                                                  MW: 494.6
                                                                                                                  MF:
                                                                                                                  Physical Forms: Solid
                                                                                                                  Neat:
                                                                                                                  Use: Flame Retardant
SMILES:
O=P(Oc(ccc(cl)C(C)(C)C)cl)(Oc(ccc(c2)C(C)(C)C)c2)Oc(ccc(c3)C(C)(C)C)c3 (CASRN 78-33-1; tris (t-butylphenyl) phosphate);
C(C)(C)(C)clccc(OP(=O)(Oc2ccc(C(C)(C)C)cc2)Oc2ccccc2)ccl (CASRN 65652-41-7; di-t-butylphenyl phenyl phosphate);
C(C)(C)(C)clccc(OP(=O)(Oc2ccccc2)Oc2ccccc2)ccl (CASRN 56803-37-3; p-(t-butylphenyl) diphenyl phosphate)
Synonyms: Phenol, 4-(l,l-dimethylethyl)-, 1,T,1"-phosphate; Phenol, 4-(l,l-dimethylethyl)-, phosphate (3:1); Phosphate, tris(tert-butylphenyl); Tris(p-t-
butylphenyl) phosphate; Tris(p-tert-butylphenyl) phosphate; Tris(tert-butylphenyl) phosphate; l-(5,6-dimethyl-lh-benzimidazol-2-yl)ethanol; 4-(l,l-
dimethylethyl)phenol, phosphate (3:1); p-tert-Butylphenol, phosphate (3:1); Phenol, 4-(l,l-dimethylethyl)-, 1,T,1"-phosphate; Phenol, 4-(l,l-dimethylethyl)-,
phosphate (3:1); Phenol, p-tert-butyl-, phosphate (3:1); Phenol, p-tert-butyl-, phosphate (3:1) (8CI); Phenol,4-(l,l-dimethylethyl)-,phosphate(3:l); Phosphate, tris(tert-
butylphenyl); Tris(4-tert-butylphenyl) phosphate; Tris(p-t-butylphenyl) phosphate; Tris(p-tert-butylphenyl) phosphate
Chemical Considerations: The alternative, TBPP, may contain a mixture of t-butyl isomers and t-butyl substituted phenyl phosphate esters depending on the
manufacturing, purification and processing of the compound. Isomers expected to be present will be discussed in this report as appropriate when determining hazard
designations. A description of the sample tested, mixture components or isomer content is included in the report when available. However this information was not
consistently reported in the literature. Chemical, fate, and toxicity data for components of the mixture represented by other CASRN were collected in the preparation
of this AA and are listed below:
  Phenol, 4-(l,l-dimethylethyl)-, 1,1\1"-phosphate (CASRN 78-33-1)
  Triphenyl phosphate (CASRN 115-86-6)
  t-Butylphenyl diphenyl phosphate (CASRN 56803-37-3)
  P-(t-butylphenyl) diphenyl phosphate (CASRN 981-40-8)
  Diphenyl-2-(tert-butyl)phenylphosphate (CASRN 83242-23-3)
  Bis(p-tert-butylphenyl) phenyl phosphate (CASRN 115-87-7)
  Di-(t-butyl) phenyl phenyl phosphate (CASRN 65652-41-7)
  Butylated triphenyl phosphate (CASRN 220352-35-2)
  Phenol, (1,1-dimethylethyl)-, phosphate (3:1) (CASRN 28777-70-0)
  4-(l,l-Dimethylethyl)phenyl diphenyl ester phosphoric acid mixt. With triphenyl phosphate (CASRN 96300-96-8)
Estimated values using representative structures as indicated in the SMILES section of this assessment will be used to fill assessment data gaps. EPI v4.11 was used to
estimate physical/chemical and environmental fate values in the absence of experimental data (Weil, 2001).
                                                                       7-679

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JUNE 2014 DRAFT REPORT
Polymeric: No
Oligomeric: Not applicable
Metabolites, Degradates and Transformation Products: Phenol; tert-butylphenol; diphenyl phosphate; triphenyl phosphate (Heitkamp and Cerniglia, 1986;
Heitkamp et al., 1986)
Analog: TBPP isomers and t-butyl substituted phenyl phosphate
esters anticipated to be present in the commercial product were
considered in this evaluation, as indicated in the chemical
considerations section; Phosflex 7 IB for skin sensitization.
Endpoint(s) using analog values: Not applicable
Analog Structure: Not applicable
Structural Alerts: Organophosphates; Neurotoxicity (EPA, 2012).
Risk Phrases: Not classified by Annex VI Regulation (EC) No 1272/2008 (ESIS, 2012).
Hazard and Risk Assessments: Hazard and risk assessments were not identified specifically for tris (t-butylphenyl) phosphate (CASRN 78-33-1), although the
following hazard and risk assessments for related substances were found: Hydraulic Fluids Assessment by the Agency for Toxic Substances and Disease Registry; an
Environmental risk evaluation report for Tertbutylphenyl diphenyl phosphate (CASRN 56803-37-3); and an Initial risk-based prioritization of HPV chemicals for
Butylated triphenyl phosphate (ATSDR, 1997; EPA, 2008; Environment Agency, 2009).
         7-680

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JUNE 2014 DRAFT REPORT
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
PHYSICAL/CHEMICAL PROPERTIES
Melting Point (°C)
Boiling Point (°C)
Vapor Pressure (mm Hg)

>300
(Estimated)
393 Decomposes
Thermal decomposition temperature
(Measured) ^J
405 Decomposes
Thermal decomposition temperature
(Measured)
300°C,
according to HPV assessment
guidance.
Reported for CASRN 65652-41-7
and CASRN 115-87-7.
Reported for CASRN 56803-37-3
and CASRN 98 1-40-8.
Estimated using representative
structures indicated in the
SMILES section for tris (p-t-
butylphenyl) phosphate and di-t-
butylphenyl phenyl phosphate.
Reported for CASRN 78-33-1.
The vapor pressure was
extrapolated from high
temperature data using linear log
vapor pressure versus molecular
weight approximation.
Reported for CASRN 65652-41-7.
The vapor pressure was
extrapolated from high
temperature data using linear log
vapor pressure versus molecular
weight approximation.
Reported for CASRN 56803-37-3.
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                                                         JUNE 2014 DRAFT REPORT
                                              Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
            PROPERTY/ENDPOINT
              DATA
        REFERENCE
       DATA QUALITY
Water Solubility (mg/L)
9.6x10  fortris (p-t-butylphenyl)
phosphate;
9.3xlO~5 for di-t-butylphenyl phenyl
phosphate (Estimated)
EPIv4.11
Estimated using representative
structures indicated in the
SMILES section. Values are less
than the cutoff value, <0.001
mg/L, for nonsoluble compounds
according to HPV assessment
guidance.
                                               0.008 (Estimated)

                                               for t-butylphenyl diphenyl phosphate
                                    EPIv4.11
                               Estimated using the representative
                               structure for t-butylphenyl
                               diphenyl phosphate indicated in
                               the SMILES section.
                                               3.2 (Measured)
                                    Saeger et al., 1979; ChemID,
                                    2013c
                               A nonguideline study reported for
                               a commercial mixture of CASRN
                               56803-37-3. This value is higher
                               than would be expected for the
                               pure substance.
Log Kow
85
for di-t-butylphenyl phenyl phosphate;
6.6
for t-butylphenyl diphenyl phosphate
(Estimated)
EPIv4.11
Estimated using representative
structures indicated in the
SMILES section.
                                                10
                                                (Estimated)
                                    EPIv4.11;EPA, 1999
                               Estimated for tris (p-t-
                               butylphenyl) phosphate. The
                               estimated value is greater than the
                               cutoff value, >10, for non-soluble
                               compounds according to HPV
                               assessment guidance.
                                               5.12
                                               (Measured)
                                    EPA, 1999; ChemID, 2013c
                               Reported for CASRN 56803-37-3
                               in a nonguideline study for a
                               commercial mixture.
                                                                     7-682

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JUNE 2014 DRAFT REPORT
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
Flammability (Flash Point)
Explosivity
Pyrolysis
pH
pKa
DATA
Nonflammable (Estimated)
Not expected to form explosive
mixtures with air (Estimated)

Not applicable (Estimated)
Not applicable (Estimated)
REFERENCE
Professional judgment
Professional judgment

Professional judgment
Professional judgment
DATA QUALITY
No data located; based on its use
as a flame retardant.
No experimental data located;
based on its use as a flame
retardant.
No data located.
Does not contain functional
groups that are expected to ionize
under environmental conditions.
Does not contain functional
groups that are expected to ionize
under environmental conditions.
HUMAN HEALTH EFFECTS
Toxicokinetics
Dermal Absorption in vitro
Absorption,
Distribution,
Metabolism &
Excretion
Oral, Dermal or Inhaled
Other
Based on analogy to closely related compounds, TBPP is expected to have poor absorption through the
skin, lungs and GI tract. There is evidence of dermal uptake in mixtures; however, it is uncertain if
TBPP or other components of the mixture are promoting absorption.

CASRN 56803-37-5 is not readily
absorbed when applied dermally to
guinea pig skin.
MIL-H-19457C hydraulic fluid
(CASRN 28777-70-0) is rapidly
absorbed following dermal
administration
*
Absorption is nil through skin as neat
solid, poor through skin when in
solution, and poor through lungs and GI
tract; based on analogy to closely
related compounds

Fabian, 1982
Dodd and Smith, 1994
Professional judgment
No data located.
Data are for CASRN 56803-37-5.
Data are for MIL-H-19457C
hydraulic fluid (CASRN 28777-
70-0). Limited study details
reported in a secondary source.
Species not specified.
Data are for CASRN 56803-37-3,
65652-41-7 and 78-33-1.
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JUNE 2014 DRAFT REPORT
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
Acute Mammalian Toxicity
Acute Lethality
Oral
Dermal
DATA
REFERENCE
DATA QUALITY
LOW: Based on experimental data for individual isomers and mixture components of TBPP via the oral,
inhalation and dermal routes of exposure in rats and rabbits.
Rat oral LD50 > 4,640 mg/kg
Rat oral LD50 > 5,000 mg/kg
Rat oral LD50 > 5 mL/kg (5,400 mg/kg)
Rat oral LD50 > 10 g/kg (10,000 mg/kg)
Rat oral LD50 > 15,800 mg/kg
Rat oral LD50 > 15,800 mg/kg
Rat oral LD50 = 20 g/kg (20,000 mg/kg)
Rabbit dermal LD50 > 2,000 or > 4,640
mg/kg
Rat dermal LD50 > 2,000 mg/kg
Murphy, 1979
Submitted confidential study
^^
^K y
ChemID, 2013b
Hagerman, 1984
ChemID, 201 3a
Submitted confidential study
Latourette, 1981
Murphy, 1979
Submitted confidential study
Data are for CASRN 56803-37-3.
Data are for Phosflex 5 IB; 75-80
percent w/w tertbutylphenyl
diphenyl phosphate (CASRN
56803-37-3), 20-25 percent w/w
triphenyl phosphate (CASRN 115-
86-6); conducted in accordance
with OECD Guideline 401.
Study details reported in a
secondary source; data are for
CASRN 28777-70-0.
Data are for CASRN 78-33-1;
phosphen plasticiser P-7.
Study details reported in a
secondary source; data are for
CASRN 98 1-40-8.
Data are for CASRN 56803-37-3.
Data are for CASRN 56803-37-3.
Mixed tert-butylphenyl
phosphates with a MW of 335.
Data are for CASRN 56803-37-3.
Data are for Phosflex 5 IB; 75-80
percent w/w tertbutylphenyl
diphenyl phosphate (CASRN
56803-37-3), 20-25 percent w/w
triphenyl phosphate (CASRN 115-
86-6); study equivalent to a limit
test under OPPTS 870.1200
except that the group size was
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JUNE 2014 DRAFT REPORT
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT


Inhalation
Carcinogenicity

OncoLogic Results
Carcinogenicity (Rat and
Mouse)
Combined Chronic
Toxicity/Carcinogenicity
Other
DATA

Rabbit dermal LD50 > 7,900 mg/kg
Rabbit dermal LD50 > 7,900 mg/kg
Rabbit dermal LD50 > 10 g/kg (10,000
mg/kg)
Rat 4-hour inhalation LC50 > 3. 1 - 18.9
mg/L
Rat inhalation LC50 > 200 mg/L
REFERENCE

Submitted confidential study
ChemID, 2013a
Latourette, 1981
Murphy, 1979
Latourette, 1981
DATA QUALITY
3/sex rather than 5/sex.
Data are for CASRN 56803-37-3.
Study details reported in a
secondary source; data are for
CASRN 98 1-40-8.
Data are for CASRN 56803-37-3.
Mixed tert-butylphenyl
phosphates with a MW of 335.
Data are for Phosflex 5 IB; 75-80
percent w/w tertbutylphenyl
diphenyl phosphate (CASRN
56803-37-3), 20-25 percent w/w
triphenyl phosphate (CASRN 115-
86-6).
Data are for CASRN 56803-37-3.
Mixed tert-butylphenyl
phosphates with a MW of 335.
MODERATE: TBPP is estimated to have marginal risk for Carcinogenicity based on the OncoLogic
program analysis; In addition, there is uncertainty due to lack of data for this substance; carcinogenic
effects cannot be ruled out.
Marginal; likely to have equivocal
carcinogenic activity.



Professional judgment



Data are for CASRN 56803-37-3,
65652-41-7 and 78-33-1.
No data located.
No data located.
No data located.
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JUNE 2014 DRAFT REPORT
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
Genotoxicity

Gene Mutation in vitro
Gene Mutation in vivo
Chromosomal Aberrations in
vitro
DATA
REFERENCE
DATA QUALITY
LOW: Based on experimental data for individual isomers and mixture components of TBPP, which were
negative for in vitro gene mutations and chromosomal aberrations. No in vivo data were located.
Negative, Salmonella typhimurium
strains TA97, TA98, TA100, TA1535,
TA137 with and without metabolic
activation
Negative, Salmonella typhimurium
TA98, TA100, TA1535, TA1537, or
TA1538, and Saccharomyces cerevisiae
D4 with or without metabolic activation
Negative, forward gene mutations,
cultured mouse lymphoma
L5 178Y/TK+/- cells with or without
metabolic activation
\

Negative, sister chromatid exchanges in
cultured mouse lymphoma
L5 178Y/TK+/- cells with or without
metabolic activation
Negative, chromosomal aberrations in
cultured mouse lymphoma
L5 178Y/TK+/-cells with or without
metabolic activation
Zeigeretal., 1987
Submitted confidential study;
Environment Agency, 2009
^^^
Submitted confidential study;
Environment Agency, 2009

Submitted confidential study;
Murphy, 1979; Environment
Agency, 2009
Submitted confidential study;
Murphy, 1979; Environment
Agency, 2009
Data are for CASRN 56803-37-3.
Data are for Phosflex 5 IB; 75-80
percent w/w tertbutylphenyl
diphenyl phosphate (CASRN
56803-37-3), 20-25 percent w/w
triphenyl phosphate (CASRN 115-
86-6). Study details reported in a
secondary source.
Data are for Phosflex 5 IB; 75-80
percent w/w tertbutylphenyl
diphenyl phosphate (CASRN
56803-37-3), 20-25 percent w/w
triphenyl phosphate (CASRN 115-
86-6). Study details reported in a
secondary source.
No data located.
Data are for Phosflex 5 IB; 75-80
percent w/w tertbutylphenyl
diphenyl phosphate (CASRN
56803-37-3), 20-25 percent w/w
triphenyl phosphate (CASRN 115-
86-6).
Data are for Phosflex 5 IB; 75-80
percent w/w tertbutylphenyl
diphenyl phosphate (CASRN
56803-37-3), 20-25 percent w/w
triphenyl phosphate (CASRN 115-
         7-686

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JUNE 2014 DRAFT REPORT
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT


Chromosomal Aberrations in
vivo
DNA Damage and Repair
Other
Reproductive Effects

Reproduction/Developmental
Toxicity Screen
Combined Repeated Dose with
Reproduction/ Developmental
Toxicity Screen
DATA




REFERENCE




DATA QUALITY
86-6).
No data located.
No data located.
No data located.
MODERATE: Based on experimental data for individual isomers of TBPP and its mixture components.
No adverse reproductive effects were observed in rats fed diets containing CASRN 56803-37-3 at doses
up to 1600 ppm (107.5 mg/kg-day; LOAEL not established), while abnormal reproductive cycles and
liver effects were noted in rats administered BTP (CASRN 220352-35-2) at a dose of 1.7 g/kg (1700
mg/kg-day, only dose tested). A NOAEL of 170 mg/kg-day (without an established LOAEL) leaves
uncertainty as to what dose adverse effects could occur; it is possible that effects could occur between
107.5 mg/kg-day and 250 mg/kg-day which falls within the DfE Moderate criteria range. Using a
conservative approach, a Moderate hazard designation was assigned.




No data located.
No data located.
         7-687

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                                              JUNE 2014 DRAFT REPORT
                                  Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
               DATA
         REFERENCE
       DATA QUALITY
      Reproduction and Fertility
      Effects
In an oral study, groups of intact and
ovariectomized female rats were
administered BTP at doses of 0 or 1.7
g/kg (0 or 1700 mg/kg) via oral gavage
in sesame oil vehicle or as neat BTP for
20, 40 or 60 days.
Abnormal reproductive cycles in treated
females that were significantly
prolonged in diestrus. Abnormal
reproductive cycles and liver effects
suggest fecundity could be affected as a
result of altered liver metabolism.

NOAEL: Not established
LOAEL:  1.7 g/kg-day (1,700 mg/kg-
day; only dose tested)
Latendresse et al., 1995
Data are for CASRN 220352-35-
2; Only one dose tested; there is
uncertainty as to if adverse effects
may have occurred at a lower
dose.
                                    In a reproductive study, groups of
                                    breeding pairs of F344 rats were
                                    administered 0, 0.6, or 1.0 g (0, 600,
                                    1,000 mg) BTP/kg via oral gavage in
                                    sesame oil or 1.7 g (1,700 mg) neat
                                    BTP/kg for up to 135 days.
                                    Significantly decreased fertility index
                                    and number of live litters (1.0 and 1.7
                                    g/kg-day); decreased uterine weight (1.0
                                    g/kg-day). No adverse effects on
                                    testicular or epididymal weights.

                                    NOAEL: 600 mg/kg-day
                                    LOAEL: 1,000 mg/kg-day
                                    Latendresse et al., 1994b;
                                    Environment Agency, 2009
                               Data are for a butylated triphenyl
                               phosphate-based hydraulic fluid
                               (CASRN 115-86-6) reported to
                               contain predominantly p-t-
                               butylphenyl phenyl phosphates
                               (84 percent wt, CASRN 220352-
                               35-2), with lesser amounts of
                               triphenyl phosphate (13 percent
                               wt., CASRN 115-86-6). This
                               study is described as invalid,
                               based on unknown impurities
                               present in the test compound and
                               the possibility of incorrect dosing
                               of animals.
                                    Sprague-Dawley rats (12/sex/group)
                                    were administered Phosflex 6IB at
                                    doses of 0, 50, 250 or 1,000 mg/kg-day
                                    Environment Agency, 2009
                               Data are for Phosflex 6IB;
                               commercial mixture of
                               tertbutylphenyl diphenyl
                                                          7-688

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                                              JUNE 2014 DRAFT REPORT
                                  Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
               DATA
        REFERENCE
       DATA QUALITY
      Other
                                    via oral gavage for two weeks prior to
                                    mating, during the two-week mating
                                    period and throughout gestation and
                                    lactation (total of ~8 weeks). No
                                    changes in reproductive organ weights.
                                    Histological changes in the reproductive
                                    organs were considered to be not
                                    treatment-related, however they were
                                    not described in detail. No significant
                                    difference in litter size or number of live
                                    pups.

                                    NOAEL > 1,000 mg/kg-day (highest
                                    dose tested)
                                    LOAEL: Not established
                                                                   phosphate (CASRN 56803-37-3).
                                                                   Purity and composition of test
                                                                   substance is not provided and
                                                                   study details are insufficient to
                                                                   assess robustness of results.
In a 90-day study, Sprague-Dawley rats
(20/sex/group) were fed diets containing
0, 100, 400, or 1,600 ppm (average
intakes of 0, 6.6, 26.7 or 107.5 mg/kg-
day in males and 0, 7.7, 30.0 or 124.8
mg/kg-day in females) test substance.
No adverse effect on histopathology or
weights of reproductive organs in males
or females.

NOAEL: 1600 ppm (107.5 mg/kg-day
for males and  124.8 mg/kg-day for
females; highest dose tested)
LOAEL: Not established
Submitted confidential study
Data are for CASRN 56803-37-3;
there is uncertainty as to if
adverse effects may have occurred
within the Moderate hazard
criteria range (50-250 mg/kg-
day).
                                    Rats were administered ML-H-19457C
                                    (CASRN 28777-70-0) and tricresyl
                                    phosphate (TCP) daily via oral gavage
                                    for up to  10 weeks (doses not specified).
                                    Dodd and Smith, 1994
                               Data are for MIL-H-19457C
                               hydraulic fluid (CASRN 28777-
                               70-0). Limited study details
                               reported in a secondary source;
                                                          7-689

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                                                        JUNE 2014 DRAFT REPORT
                                             Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
           PROPERTY/ENDPOINT
              DATA
REFERENCE
DATA QUALITY
                                               The estrous cycle was extended for high
                                               dose females administered ML-ML-H-
                                               19457C and relative testes weight was
                                               increased. Effects were reversed at 5
                                               and 10 weeks post-treatment.
                                                                 doses not specified.
                                               Rats, hamsters and rabbits were exposed
                                               to MIL-H-19457C hydraulic fluid
                                               (CASRN 28777-70-0) via inhalation 6
                                               hours/day at a concentration of 250
                                               mg/m3 for 21  days or 0, 10 and 100
                                               mg/m3 for 90  days. Effects were only
                                               observed in rats and consisted lesions in
                                               the ovaries after 90 days of exposure
                                               (no further details provided).
                                   Dodd and Smith, 1994
                      Data are for MIL-H-19457C
                      hydraulic fluid (CASRN 28777-
                      70-0).
Developmental Effects
LOW: Based on experimental data for mixture components of TBPP. In two studies using Santicizer 154
(a mixture containing TBPP and CASRN 56803-37-3), no biologically significant treatment-related
effects were observed in rats gavaged with up to 3,000 mg/kg-day undiluted test substance, while a
decrease in viable fetuses and increase in mean post implantation loss was noted at a dose of 5,000
mg/kg-day (NOAEL= 1,000 mg/kg-day). In a study using Phosflex 51B (a mixture containing 75-80%
CASRN 56803-37-3), embryotoxicity was indicated by reduced fetal body weight at a dose of 1,000
mg/kg-day; however, this response was considered to be secondary to maternal toxicity.
There were no data located for the developmental neurotoxicity endpoint. Decreased cholinesterase
activity in pregnant lab animals has been shown to have a negative impact on fetal brain development.
As a result, there is uncertain potential for developmental neurotoxicity for this substance.
                                                                    7-690

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JUNE 2014 DRAFT REPORT
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT































Reproduction/ Developmental
Toxicity Screen





























DATA
Groups of 25 pregnant CD rats received
2.5 mL of water or undiluted test
substance at doses of 300, 1,000, or
3,000 mg/kg-day via oral gavage on GD
6-19.
No adverse effect on maternal survival,
behavior, body weight gain, the
incidence of gross necropsy findings, or
most reproductive/developmental
parameters. Slight increase in yellow
staining and matting in the anogenital
area with or without staining in the
abdominal and thoracic areas (1,000 and
3,000 mg/kg-day). Increase in dried red
matter in the nasal region on forepaws
(3,000 mg/kg-day). Slight, non dose-
related increase in the percentage of
litters with skeletal malformations at
3,000 mg/kg-day (effect was not
considered to be biologically
significant).
Maternal toxicity:
NOAEL: 300 mg/kg-day
LOAEL: 1,000 mg/kg-day
Developmental toxicity:
NOAEL: 3,000 mg/kg-day (highest
dose tested)
LOAEL: Not established
In a pilot study, pregnant CD rats
(5/group) received undiluted Santicizer
154 at doses of 250, 500, 1,000, 2,500,
REFERENCE
Submitted confidential study;
Bowman, 1981; Keller, 1984



^^



^^*


















Submitted confidential study;
Bowman, 1981

DATA QUALITY
Data are for Santicizer 154; a
mixture containing 43.2% t-butyl
phenyl diphenyl phosphate
(CASRN 56803-37-3), 40.2%
triphenyl phosphate (CASRN 115-
86-6), 14% di-t-butylphenyl
phenyl phosphate (CASRN 2528-
36-1) and 2% tri-t-butyl phenyl
phosphate (CASRN 78-33-1).



















Data are for Santicizer 154; a
mixture containing 43 .2% t-butyl
phenyl diphenyl phosphate
         7-691

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JUNE 2014 DRAFT REPORT
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT















































Combined Repeated Dose with
Reproduction/ Developmental
Toxicity Screen
DATA
or 5,000 mg/kg-day via oral gavage on
gestational days (GD) 6-19.
Anogenital staining was observed in all
test groups and red and/or brown matter
around the nose, mouth, and forelimbs
in all receiving 5,000 mg/kg-day. Dose-
related reductions in body weight gain
for GD 0-20 were observed at > 1,000
mg/kg-day but were only biologically
significant at the highest dose.
Decreases in viable fetuses and
increases in mean post implantation
losses (5,000 mg/kg-day)
Maternal toxicity:
NOAEL: 500 mg/kg-day
LOAEL: 1,000 mg/kg-day
Developmental toxicity:
NOAEL: 2,500 mg/kg-day
LOAEL: 5,000 mg/kg-day (reduced
body weight gain; decreased number of
viable fetuses; increased mean post
implantation losses)

J

REFERENCE





^^



^^*


A












DATA QUALITY
(CASRN 56803-37-3), 40.2%
triphenyl phosphate (CASRN 115-
86-6), 14% di-t-butylphenyl
phenyl phosphate (CASRN 2528-
36-1) and 2% tri-t-butyl phenyl
phosphate (CASRN 78-33-1).
















No data located.


         7-692

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JUNE 2014 DRAFT REPORT
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT






Prenatal Development




Postnatal Development
Prenatal and Postnatal
Development
DATA
Pregnant rats were administered BPDP
at doses of 0, 100, 400 and 1,000
mg/kg-day (dosing volume of 5 ml) as a
solution in corn on GDs 6-20.
Dose-related increase in maternal liver
weight. Reduced food consumption on
gravid days 6-9 at the high dose. No
adverse effects on litter size or fetal
weights. No evidence of structural
teratogenicity at any dose.
Embryotoxicity as indicated by reduced
fetal body weight at 1,000 mg/kg; this
response was considered secondary to
maternal toxicity.
Maternal toxicity:
NOAEL: 400 mg/kg-day
LOAEL: 1,000 mg/kg-day
Developmental toxicity:
NOAEL: 1,000 mg/kg-day (highest
dose tested)
LOAEL: Not established


J
REFERENCE
Keller, 1984
^^
f^ S
*





DATA QUALITY
Data are for Phosflex 5 IB; 75-80
percent w/w tertbutylphenyl
diphenyl phosphate (CASRN
56803-37-3), 20-25 per cent w/w
triphenyl phosphate (CASRN 115-
86-6).




No data located.
No data located.

         7-693

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                                                         JUNE 2014 DRAFT REPORT
                                             Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
           PROPERTY/ENDPOINT
              DATA
        REFERENCE
       DATA QUALITY
                 Developmental Neurotoxicity
There were no data located for the
developmental neurotoxicity endpoint.
Decreased cholinesterase activity in
pregnant lab animals has been shown to
have a negative impact on fetal brain
development. As a result, there is
uncertain potential for developmental
neurotoxicity for this substance.
Professional judgment
No data located.
                 Other
                                                                  No data located.
Neurotoxicity
MODERATE: Based on a 3-week dermal study in rats exposed to Santicizer 154 where cholinesterase
inhibition was the major effect at 100 mg/kg-day (NOAEL = 10 mg/kg-day). Experimental data for
individual isomers and mixture components of TBPP and analogy to closely related compounds yielded
negative results for neurotoxicity in hens and rats. There is a structural alert for the neurotoxicity
endpoint based on organophosphates; however, TBPP is not expected to form intermolecular
intermediates that may result in neurotoxic mechanisms of action.
                 Neurotoxicity Screening
                 Battery (Adult)
MIL-H-19457C hydraulic fluid
(CASRN 28777-70-0) was found to
have minimal toxicity in an acute
delayed neurotoxicity test.
                                               In two acute delayed neurotoxicity
                                               studies, hens were treated via oral
                                               gavage with 1,000 mg/kg test substance
                                               5-7 times per day for 5 days. No adverse
                                               effects on mortality or body weight
                                               gain. No signs of ataxia; egg production
                                               was 50-70% of controls.

                                               NOAEL:  1,000 mg/kg (only dose
                                               tested)
                                               LOAEL: Not established
Dodd and Smith, 1994
                                   Submitted confidential study
Data are for MIL-H-19457C
hydraulic fluid (CASRN 28777-
70-0). Limited study details
reported in a secondary source.
No data on test species, route of
exposure, or exposure
concentrations.
                               Data are for CASRN 56803-37-3;
                               only one dose tested.
                                                                     7-694

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                                              JUNE 2014 DRAFT REPORT
                                  Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
               DATA
         REFERENCE
       DATA QUALITY
      Other
                                    In an acute delayed neurotoxicity study,
                                    White Leghorn chickens were treated
                                    via oral gavage with  10,000 mg/kg test
                                    substance twice a day for 3 days. No
                                    signs of ataxiaor
                                    neurohistopathological lesions.

                                    NOAEL: 10,000 mg/kg (only dose
                                    tested)
                                    LOAEL: Not established
                                    Submitted confidential study
                               Data are for CASRN 56803-37-3;
                               only one dose tested.
In a 3-week dermal study, test substance
was applied to the intact and abraded
skin of New Zealand White rabbits
(10/sex/group) at doses levels of 10,
100, or 1,000 mg/kg-day, 5  days/week.
No deaths or treatment-related changes
in clinical signs, body weight,
hematology, clinical chemistry, organ
weights, gross or microscopic lesions.
Edema and fissuring (1,000 mg/kg-day);
atonia (> 100 mg/kg-day);
desquamation (> 10 mg/kg-day);
increased blood urea nitrogen (1,000
mg/kg-day); depression of plasma
cholinesterase (> 100 mg/kg-day);
depression of erythrocyte and brain
cholinesterase (> 10 mg/kg-day).

NOAEL: 10 mg/kg-day
LOAEL: 100 mg/kg-day (based on
cholinesterase inhibition)
Submitted confidential study;
Hollister, 1979; Keller, 1984
Data are for Santicizer 154; a
mixture containing 43.2% t-butyl
phenyl diphenyl phosphate
(CASRN 56803-37-3), 40.2%
triphenyl phosphate (CASRN 115-
86-6), 14% di-t-butylphenyl
phenyl phosphate (CASRN 2528-
36-1) and 2% tri-t-butyl phenyl
phosphate (CASRN 78-33-1).
                                    In a 90-day study, Sprague-Dawley rats
                                    (20/sex/group) were fed diets containing
                                    Submitted confidential study
                               Data are for CASRN 56803-37-3.
                                                          7-695

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                                              JUNE 2014 DRAFT REPORT
                                  Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                    0, 100, 400, or 1,600 ppm (average
                                    intakes of 0, 6.6, 26.7 or 107.5 mg/kg-
                                    day in males and 0, 7.7, 30.0 or 124.8
                                    mg/kg-day in females) test substance.
                                    No neurohistopathology and no
                                    inhibition of brain cholinesterase
                                    activity.

                                    NOAEL: 1,600 ppm (107.5 mg/kg-day
                                    males, 124.8 mg/kg-day female; highest
                                    dose tested)
                                    LOAEL: Not established
                                    No signs of neurotoxicity in rats
                                    following acute gavage administration
                                    of Durad 220B at dose levels as high as
                                    5,000 mg/kg
                     ATSDR 1997
                                    Not neurotoxic by analogy to a closely
                                    related compound which yielded
                                    negative results in all reliable oral
                                    assays for delayed acute neurotoxicity
                                    in hens and subchronic neurobehavioral
                                    assays in rats
                     Professional judgment
                      Data are for Durad 200B (CASRN
                      28777-70-0); a t-Butylphenyl
                      diphenyl phosphate mixture
                      containing t-Butylphenyl phenyl
                      phosphate (CASRN 220352-35-2)
                      and triphenyl phosphate (CASRN
                      115-86-6).
                      Data are for CASRN 78-33-1.
                                                         7-696

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JUNE 2014 DRAFT REPORT
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
Repeated Dose Effects


DATA
REFERENCE
DATA QUALITY
HIGH: Based on weight of evidence for individual isomers and commercial formulation components
containing TBPP and CASRN 56803-37-3). In a 90-day inhalation study, rats exposed to Santicizer 154
aerosol showed clinical signs of toxicity, increased liver-body weight-ratios and changes in urinalysis
parameters at a concentration of 100 mg/m3 (0.1 mg/L; NOAEL= 0.01 mg/L). In a 3-week dermal study
in rats exposed to Santicizer 154, cholinesterase inhibition was the major effect at 100 mg/kg-day
(NOAEL= 10 mg/kg-day). The adrenal gland appeared to be a target organ in some inhalation and oral
studies (effects included lesions and increased weight). Several oral toxicity studies using CASRN 56803-
37-3, Phosflex 51B (a mixture containing CASRN 56803-37-3) and MIL-H-19457C hydraulic fluid
(CASRN 28777-70-0) indicate low concern for toxicity via this route of exposure.
In a 90-day inhalation study, rats
(15/sex/group) were exposed to
Santicizer- 154 aerosol at concentrations
of 0, 10 and 100 mg/m3 (actual)
analytical concentrations: 0, 10.1 and
101.1 mg/m3). No deaths attributed to
treatment. Clinical signs of toxicity at
the high dose included ptosis, ruffled
and discolored fur, rhinitis, sneezing,
hemorrhagic conjunctivitis and
wheezing. No effect on body weight
gain or clinical chemistry. Elevated
SGOT and SAP values upon urinalysis
of one high dose animal. Increased
liver-body weight-ratio in high dose
males. No gross or microscopic tissue
changes.
NOAEL: 10 mg/m3 (0.01 mg/L)
LOAEL: 100 mg/m3 (0.1 mg/L)
In a 3 -week dermal study, test substance
was applied to the intact and abraded
skin of New Zealand White rabbits
(10/sex/group) at doses levels of 10,
Clayton, 1983; Keller, 1984
Submitted confidential study;
Hollister, 1979; Keller, 1984
Data are for Santicizer 154; a
mixture containing 43 .2% t-butyl
phenyl diphenyl phosphate
(CASRN 56803-37-3), 40.2%
triphenyl phosphate (CASRN 115-
86-6), 14% di-t-butylphenyl
phenyl phosphate (CASRN 2528-
36-1) and 2% tri-t-butyl phenyl
phosphate (CASRN 78-33-1).
Data are for Santicizer 154; a
mixture containing 43 .2% t-butyl
phenyl diphenyl phosphate
(CASRN 56803-37-3), 40.2%
         7-697

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                                              JUNE 2014 DRAFT REPORT
                                  Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                    100, or 1,000 mg/kg-day, 5 days/week.
                                    No deaths or treatment-related changes
                                    in clinical signs, body weight,
                                    hematology, clinical chemistry, organ
                                    weights, gross or microscopic lesions.
                                    Edema and fissuring (1,000 mg/kg-day);
                                    atonia (> 100 mg/kg-day);
                                    desquamation (> 10 mg/kg-day);
                                    increased blood urea nitrogen (1,000
                                    mg/kg-day); depression of plasma
                                    cholinesterase (> 100 mg/kg-day);
                                    depression of erythrocyte and brain
                                    cholinesterase (> 10 mg/kg-day).

                                    NOAEL: Not established
                                    LOAEL: 10 mg/kg-day (Lowest dose
                                    tested; desquamation,  decreased
                                    erythrocytes and brain cholinesterase)
                                                    triphenyl phosphate (CASRN 115-
                                                    86-6), 14% di-t-butylphenyl
                                                    phenyl phosphate (CASRN 2528-
                                                    36-1) and 2% tri-t-butyl phenyl
                                                    phosphate (CASRN 78-33-1).
                                    In a 90-day study, Sprague-Dawley rats
                                    (20/sex/group) were fed diets containing
                                    0, 100, 400, or 1,600 ppm (average
                                    intakes of 0, 6.6, 26.7 or 107.5 mg/kg-
                                    day in males and 0, 7.7, 30.0 or 124.8
                                    mg/kg-day in females) test substance.
                                    No significant effect on survival, food
                                    consumption, body weight gain,
                                    hematology or clinical chemistry
                                    parameters, cholinesterase  values, or the
                                    incidence of gross or microscopic
                                    lesions. Increased liver, kidney, and
                                    adrenal gland weight (1600 ppm).

                                    NOAEL: 400 ppm (26.7 mg/kg-day for
                     Submitted confidential study;
                     Keller, 1984; Environment
                     Agency, 2009
                      Data are for Phosflex 5 IB; 75-80
                      percent w/w tertbutylphenyl
                      diphenyl phosphate (CASRN
                      56803-37-3), 20-25 percent w/w
                      triphenyl phosphate (CASRN 115-
                      86-6).
                                                          7-698

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                                             JUNE 2014 DRAFT REPORT
                                  Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   males and 30 mg/kg-day for females)
                                   LOAEL: 1600 ppm (107.5 mg/kg-day
                                   for males and 124.8 mg/kg-day for
                                   females); (based on organ weight
                                   changes)
                                   In a 30-day study, Sprague-Dawley rats
                                   (10/sex/group) were fed diets containing
                                   0, 250, 500, 750, 1,000, or 2,000 mg/kg-
                                   day (nominal doses of 213, 442, 660,
                                   898, and 1,710 mg/kg-day for males and
                                   234, 454, 690,  898, and 1,867 mg/kg-
                                   day for females) test chemical.
                                   No deaths. Reduced food consumption
                                   (2,000 mg/kg-day) and body weight
                                   gain (>750 mg/kg-day); hepatic
                                   enlargement (all doses); discoloration of
                                   kidneys (>500 mg/kg-day)

                                   NOAEL: Not established
                                   LOAEL: 250 mg/kg-day (hepatic
                                   enlargement; lowest dose tested)
                     Submitted confidential study;
                     Keller, 1984
                      Data are for CASRN 56803-37-3;
                      study deficiencies include lack of
                      examinations for histopathology,
                      hematology, or clinical chemistry.
                                   In a 90-day dietary study, CD rats were
                                   fed 0 or 5 mg/kg-day test substance.
                                   There were no compound-related effects
                                   on any parameter tested.
                                                 J
                                   NOAEL: 5 mg/kg-day (only dose
                                   tested)
                                   LOAEL: Not established
                     Keller, 1984
                      Data are for CASRN 56803-37-3.
                                   In a 90-day dietary study, rats were fed
                                   BPDP at concentrations of 0, 100, 300
                                   or 1,000 ppm (11, 32, and 110 mg/kg-
                                   day).  There were no clinical signs of
                     Matheson, 1980
                      Data are for CASRN 56803-37-3.
                      Doses were reported as ppm in the
                      diet but were converted to mg/kg-
                      day using EPA 1988 reference
                                                         7-699

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                                              JUNE 2014 DRAFT REPORT
                                  Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                    toxicity. No effect on hematology,
                                    clinical chemistry, or urinalysis
                                    parameters. No gross pathologic or
                                    microscopic lesions attributed to the
                                    BPDP.

                                    NOAEL: 1,000 ppm (110 mg/kg-day;
                                    highest dose tested)
                                    LOAEL: Not established
                                                    values for body weight and food
                                                    consumption.
                                    In a 90-day dietary study, albino rats
                                    were fed diets containing 0, 200, 1,000
                                    or 5,000 ppm (0, 21, 110, and 530
                                    mg/kg-day) test substance.
                                    No deaths or effect on body weight
                                    gain, food intake, hematology, clinical
                                    chemistry or urinalysis parameters.
                                    Increased mean liver and kidney weight
                                    with no associated histopathologic
                                    findings.

                                    NOAEL: 5,000 ppm (530 mg/kg-day;
                                    highest dose tested)
                                    LOAEL: Not established
                     Keller, 1984
                                    Rats, hamsters and rabbits were exposed
                                    to MIL-H-19457C hydraulic fluid
                                    (CASRN 28777-70-0) via inhalation 6
                                    hours/day at a concentration of 250
                                    mg/m3 for 21 days or 0, 10 and 100
                                    mg/m3 for 90 days. Effects were only
                                    observed in rats and consisted of
                                    increased liver and kidney weight (100
                                    and 250 mg/m3) and lesions in the
                                    adrenal glands and ovaries (90 day
                     Dodd and Smith, 1994
                      Data are for CASRN 56803-37-3.
                      Doses were reported as ppm in the
                      diet but were converted to mg/kg-
                      day using EPA 1988 reference
                      values for body weight and food
                      consumption.
                      Data are for MIL-H-19457C
                      hydraulic fluid (CASRN 28777-
                      70-0).
                                                         7-700

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JUNE 2014 DRAFT REPORT
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT


Skin Sensitization

Skin Sensitization
Respiratory Sensitization
(Respiratory Sensitization
DATA
exposure).
Rats were administered ML-H-19457C
(CASRN 28777-70-0) and tricresyl
phosphate (TCP) daily via oral gavage
for up to 10 weeks (doses not specified).
No mortality occurred and there was no
effect on body weight gain in either sex.
Target organs were the adrenal gland
and the liver. The estrous cycle was
extended for high dose females
administered ML-ML-H-19457C and
relative testes weights were increased.
Effects were reversed at 5 and 10 weeks
post-treatment.
Potential for systemic effects by
analogy to triphenyl phosphate (1 15-86-
6), including 28-d repeated-dose study
(inadequate), rats, diet, liver effects at
0.5%.
NOAEL: 0.1%
REFERENCE

Dodd and Smith, 1994
^^
^K 7
Professional judgment
DATA QUALITY

Data are for MIL-H-19457C
hydraulic fluid (CASRN 28777-
70-0); doses not specified.
Estimated by analogy to Triphenyl
Phosphate (115-86-6); Study was
determined to be inadequate and
does not satisfy standard
guidelines.
MODERATE: TBPP is expected to have low concern for Sensitization by analogy to closely related
compounds.
Moderate concern for Sensitization by
analogy to isobutylphenyl phosphate
(68937-40-6)
(Estimated based on analogy)
Professional judgment
Estimated based on analogy to
Isobutylphenyl phosphate (68937-
40-6).
No data located.


No data located.
         7-701

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JUNE 2014 DRAFT REPORT
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
Eye Irritation

Eye Irritation
Dermal Irritation

Dermal Irritation
DATA
REFERENCE
DATA QUALITY
LOW: Based on experimental data for mixture components of TBPP. Phosflex 51B (a commercial
mixture containing 75-80% CASRN 56803-37-3), produced slight irritation in rabbit eyes which cleared
within 72 hours. Additional studies with CASRN 56803-37-3 were negative for irritation.
Slightly irritating, rabbits. Mild redness
of the conjunctiva 24- and 4 8 -hours
after treatment; no irritation at 72- or
96-hours or 7 days after treatment.
Not irritating, rabbits
Not irritating, rabbits. Mild conjunctival
inflammation 1 hour after exposure, but
no evidence of irritation by 24 hours.
Environment Agency, 2009
^^
Submitted confidential study;
Bowman, 1981
Submitted confidential study;
Murphy, 1979
Data are for Phosflex 5 IB; 75-80
percent w/w tertbutylphenyl
diphenyl phosphate (CASRN
56803-37-3), 20-25 percent w/w
triphenyl phosphate (CASRN 115-
86-6); study details reported in a
secondary source.
Data are for CASRN 56803-37-3.
Data are for CASRN 56803-37-3;
conducted in accordance with
OECD Guideline 405
MODERATE: Based on weight of evidence from experimental data for mixture components of TBPP.
Phosflex 51B (a commercial mixture containing 75-80% CASRN 56803-37-3), produced mild irritation
in rabbits, which cleared within 72 hours. Additional studies using CASRN 56803-37-5 resulted in very
slight or well-defined erythema in rabbits that persisted for 8-10 days and slight destruction of guinea
pig skin, but only when the test substance was dissolved in Stoddard's solution. A study using mixture
component 78-33-1 was not irritating to rabbits.
Mildly irritating, rabbits. Mild to
moderate erythema 24 hours after
treatment; mild erythema at 48 hours;
no irritation at 72 hours
Very slight or well-defined erythema
(with or without very slight edema)
persisting though day 8 and day 10 in
rabbits
Not irritating, rabbits. Phosphen
Environment Agency, 2009
Submitted confidential study;
Latendresse, 1994
Hagerman, 1984
Data are for Phosflex 5 IB; 75-80
percent w/w tertbutylphenyl
diphenyl phosphate (CASRN
56803-37-3), 20-25 percent w/w
triphenyl phosphate (CASRN 115-
86-6)
Data are for CASRN 56803-37-3;
conducted in accordance with
OECD Guideline 404
Data are for CASRN 78-33-1;
         7-702

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JUNE 2014 DRAFT REPORT
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT


DATA
plasticiser P-7 applied as a 10% solution
in butyl carbitol acetate to the shaven
ear and belly. Very slight irritation on
the belly, but only after repeated and
prolonged exposure. ^
Not irritating, rabbits
Not irritating, rabbits
CASRN 56803-37-5 produced slight
destruction of tissue in guinea pig skin
when dissolved in Stoddard's solution.
No irritation occurred when the test
substance was dissolved in ethyl alcohol
or tertiary butyl alcohol.
REFERENCE

Submitted confidential study;
Bowman, 1981
ATSDR, 1997
^^^
Fabian, 1982
DATA QUALITY
phosphen plasticiser P-7
Data are for CASRN 56803-37-3
Data are for Durad 200B (CASRN
28777-70-0); a t-Butylphenyl
diphenyl phosphate mixture
containing t-Butylphenyl phenyl
phosphate (CASRN 220352-35-2)
and triphenyl phosphate (CASRN
115-86-6)
Data are for CASRN 56803-37-5
         7-703

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                                                          JUNE 2014 DRAFT REPORT
                                              Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
            PROPERTY/ENDPOINT
               DATA
REFERENCE
DATA QUALITY
Endocrine Activity
No data were available for TBPP. Rats exposed to hydraulic BTP (mixture of p-t-butylphenyl phenyl
phosphates (84%), triphenyl phosphate, and m-t-phenyl phosphate), had significantly prolonged
diestrus, hypertrophy and cholesteryl lipidosis of adrenocortical and ovarian interstitial cells and
minimal degeneration in the adrenal cortex and ovary. Lesions on the adrenal glands and ovaries were
observed in rats, hamsters and rabbits and relative testes weight was increased in rats following
inhalation exposure to MIL-H-19457C hydraulic fluid (CASRN 28777-70-0). Adrenal weights were
increased in rats after dietary exposure to Phosflex 51B.
                                                In an oral study, male and female rats
                                                were administered hydraulic BTP at
                                                doses of 0 or 1.7 g/kg-day (0 or 1,700
                                                mg/kg-day) via gavage in sesame oil or
                                                2.8 g/kg (2,800 mg/kg) neat hydraulic
                                                BTP for 20, 40 and 60 days.
                                                Hypertrophy and cholesteryl lipidosis of
                                                adrenocortical and ovarian interstitial
                                                cells; minimal degeneration in the
                                                adrenal cortex and ovary. No decreased
                                                testicular weight or degeneration of
                                                seminiferous tubules.
                                                In an oral study, groups of intact and
                                                ovariectomized female rats were
                                                administered BTP at doses of 0 or 1.7
                                                g/kg-day (0 or 1,700 mg/kg-day) via
                                                oral gavage in sesame oil vehicle or as
                                                neat BTP for 20, 40 or 60 days.
                                                Cholesteryl lipidosis in AC and OI
                                                cells; elevated estradiol levels (14.5
                                                times greater than controls). No effect
                                                on serum concentrations of
                                                androstenedione and corticosterone.
                                                Abnormal reproductive cycles in treated
                                                females that were significantly
                                                prolonged in diestrus. Increased liver
                                    Latendresse et al., 1994a
                                    Latendresse et al., 1993;
                                    Latendresse, 1994
                       Data are for CASRN 220352-35-
                       2; mixture of p-t-butylphenyl
                       phenyl phosphates (84%),
                       triphenyl phosphate, and m-t-
                       phenyl phosphate.
                       Data are for CASRN 220352-35-
                       2; mixture of p-t-butylphenyl
                       phenyl phosphates (84%),
                       triphenyl phosphate, and m-t-
                       phenyl phosphate.
                                                                      7-704

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                                              JUNE 2014 DRAFT REPORT
                                  Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                    weights (134% that of controls) and P-
                                    450 enzymes (3 times greater than
                                    controls).
                                    Rats were administered ML-H-19457C
                                    (CASRN 28777-70-0) and TCP daily
                                    via oral gavage for up to 10 weeks
                                    (doses not specified). No mortality
                                    occurred and there was no effect on
                                    body weight gain in either sex. Target
                                    organs were the adrenal gland and the
                                    liver. The estrous cycle was extended
                                    for high dose females administered ML-
                                    ML-H-19457C and relative testes
                                    weights were increased. Effects were
                                    reversed at 5 and 10 weeks post-
                                    treatment.
                     Dodd and Smith, 1994
                      Data are for MIL-H-19457C
                      hydraulic fluid (CASRN 28777-
                      70-0); doses not specified.
                                    Rats, hamsters and rabbits were exposed
                                    to MIL-H-19457C hydraulic fluid
                                    (CASRN 28777-70-0) via inhalation 6
                                    hours/day at a concentration of 250
                                    mg/m3 for 21 days or 0, 10 and 100
                                    mg/m3 for 90 days. Effects were only
                                    observed in rats; lesions in the adrenal
                                    glands and ovaries (90 day exposure).
                     Dodd and Smith, 1994
                      Data are for MIL-H-19457C
                      hydraulic fluid (CASRN 28777-
                      70-0).
                                    In a 90-day study, Sprague-Dawley rats
                                    (20/sex/group) were fed diets containing
                                    0, 100, 400, or 1,600 ppm (average
                                    intakes of 0, 6.6, 26.7 or 107.5 mg/kg-
                                    day in males and 0, 7.7, 30.0 or 124.8
                                    mg/kg-day in females) test substance.
                                    Adrenal weight was increased at 1,600
                                    ppm.
                     Submitted confidential study;
                     Keller, 1984; Environment
                     Agency, 2009
                      Data are for Phosflex 5 IB; 75-80
                      percent w/w tertbutylphenyl
                      diphenyl phosphate (CASRN
                      56803-37-3), 20-25 percent w/w
                      triphenyl phosphate (CASRN 115-
                      86-6).
                                                         7-705

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JUNE 2014 DRAFT REPORT
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT

Immunotoxicity
Immune System Effects
DATA
NOAEL: 400 ppm (26.7 mg/kg-day for
males and 30 mg/kg-day for females)
LOAEL: 1600 ppm (107.5 mg/kg-day
for males and 124.8 mg/kg-day for
females); (based on organ weight
changes)
REFERENCE

DATA QUALITY

No data located.


No data located.
ECOTOXICITY
ECOSAR Class
Acute Aquatic Toxicity
Fish LC50

VERY HIGH: Based on experimental data for mixture components of TBPP for fish and daphnia.
Experimental data for algae indicates HIGH hazard concern. The reported water solubility values from
studies on commercial mixtures may not adequately represent all components of the mixture. The TBPP
isomers and t-butyl substituted phenyl phosphate esters anticipated to be present in the commercial
product are expected to have a range of water solubility values. Therefore NES may be predicted for
some components but not others.
Freshwater fish (Ictalurus punctatus)
96-hour LC50 = 0. 8 mg/L
static test conditions
(Experimental)
^
J
Freshwater fish (Oncorhynchus mykiss)
96-hour LC50 =1.1 mg/L
(Experimental)
Environment Agency, 2009
Submitted confidential study
Data are for a commercial
tertbutylphenyl diphenyl
phosphate product consisting of
15-20 percent triphenyl
phosphate (CASRN 115-86-6)
with the remainder consisting
mainly of a mixture of isomers of
tertbutylphenyl diphenyl
phosphate (CASRN 56803-37-3) ,
along with isomers of di-
tertbutylphenyl diphenyl
phosphate (CASRN 65652-41-7).
Data are for t-Butylphenyl
diphenyl phosphate (CASRN
56803-37-3). The available acute
toxicity data for fish, aquatic
         7-706

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                                              JUNE 2014 DRAFT REPORT
                                  Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                                                                                     invertebrates, and algae were
                                                                                                     judged inadequate to meet the
                                                                                                     endpoints; summary did not
                                                                                                     provide sufficient information
                                                                                                     regarding study conditions,
                                                                                                     including test substance purity or
                                                                                                     water solubility, to allow for an
                                                                                                     independent evaluation of the
                                                                                                     studies.
                                    Freshwater fish (Oncorhynchus mykiss)
                                    96-hour LC50 = 2.0 mg/L
                                    static test conditions
                                    (Experimental)
                     Environment Agency, 2009
                      Data are for a commercial
                      tertbutylphenyl diphenyl
                      phosphate product consisting of
                      15-20 percent triphenyl
                      phosphate (CASRN 115-86-6)
                      with the remainder consisting
                      mainly of a mixture of isomers of
                      tertbutylphenyl diphenyl
                      phosphate (CASRN 56803-37-3),
                      along with isomers of di-
                      tertbutylphenyl diphenyl
                      phosphate (CASRN 65652-41-7).
                                    Freshwater fish (Salmo gairdneri) 96-
                                    hour LC50 = 2.0 mg/L
                                    96-hour NOEC = 0.56 mg/L
                                    24-hour LC50 = 26 mg/L
                                    48-hour LC50= 13 mg/L
                                    (Experimental)
                     Bucafusco, 1976b
                      Data are for Santicizer 154; a
                      mixture containing 43.2% t-butyl
                      phenyl diphenyl phosphate
                      (CASRN 56803-37-3), 40.2%
                      triphenyl phosphate (CASRN 115-
                      86-6), 14% di-t-butylphenyl
                      phenyl phosphate (CASRN 2528-
                      36-1) and 2% tri-t-butyl phenyl
                      phosphate (CASRN 78-33-1).
                                    Freshwater fish (Pimephales promelas)
                                    96-hour LC50 = 2.3 mg/L
                                    static test conditions
                     Environment Agency, 2009
                      Data are for a commercial
                      tertbutylphenyl diphenyl
                      phosphate product consisting of
                                                         7-707

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                                             JUNE 2014 DRAFT REPORT
                                 Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   (Experimental)
                                                   15-20 percent triphenyl
                                                   phosphate (CASRN 115-86-6)
                                                   with the remainder consisting
                                                   mainly of a mixture of isomers of
                                                   tertbutylphenyl diphenyl
                                                   phosphate (CASRN 56803-37-3),
                                                   along with isomers of di-
                                                   tertbutylphenyl diphenyl
                                                   phosphate (CASRN 65652-41-7).
                                   Freshwater fish (Oncorhynchus mykiss)
                                   96-hour LC50 = 2.4 - 5.4 mg/L
                                   static test conditions
                                   (Experimental)
                     Environment Agency, 2009
                      Data are for t-Butylphenyl
                      diphenyl phosphate (CASRN
                      56803-37-3).
                                   Freshwater fish (Lepomis macrochirus)
                                   96-hour LC50 = 3.1 mg/L
                                   static test conditions
                                   (Experimental)
                     Environment Agency, 2009
                      Data are for a commercial
                      tertbutylphenyl diphenyl
                      phosphate product consisting of
                      15-20 percent triphenyl
                      phosphate (CASRN 115-86-6)
                      with the remainder consisting
                      mainly of a mixture of isomers of
                      tertbutylphenyl diphenyl
                      phosphate (CASRN 56803-37-3),
                      along with isomers of di-
                      tertbutylphenyl diphenyl
                      phosphate (CASRN 65652-41-7).
                                   Freshwater fish (Pimephales promelas)
                                   96-hour LC50= 3.4 mg/L
                                   96-hour NOEC <  1.0 mg/L
                                   24-hour LC50 > 10 < 32 mg/L
                                   48-hour LC50 = 4.0 mg/L
                                   (Experimental)
                     Monsanto, 1976
                      Data are for Santicizer 154; a
                      mixture containing 43.2% t-butyl
                      phenyl diphenyl phosphate
                      (CASRN 56803-37-3), 40.2%
                      triphenyl phosphate (CASRN 115-
                      86-6), 14% di-t-butylphenyl
                      phenyl phosphate (CASRN 2528-
                      36-1) and 2% tri-t-butyl phenyl
                                                        7-708

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                                             JUNE 2014 DRAFT REPORT
                                 Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                                                                                    phosphate (CASRN 78-33-1).
                                   Freshwater fish (Pimephales promelas)
                                   96-hour LC50 > 268 - >647 (jg/L (0.268
                                   -0.647 mg/L)
                                   Measured exposure concentrations were
                                   not high enough to cause 50% mortality.
                                   The highest concentrations in clean and
                                   sediment pond tests were 286 and 647
                                   (jg/L (0.286 - 0.647 mg/L), respectively.
                                   (Experimental)
                     Adams etal., 1983
                                   Freshwater fish (Cyprinodon
                                   variegatus) 96-hour LC50 >1 mg/L
                                   NOEC = 1 mg/L
                                   static-renewal test conditions
                                   (Experimental)
                     Akzo Nobel, 2001
                                   Freshwater fish (Lepomis macrochirus)
                                   96-hour LC50 > 10 < 12 mg/L
                                   24-hour LC50 = 35 mg/L
                                   48-hour LC50 = 14 mg/L
                                   (Experimental)
                     Bucafusco, 1976a
                                   Freshwater fish 96-hour LC50 = 0.00001
                                   mg/L
                                   (Estimated)
                                   ECOSAR: Neutral organics
                     ECOSARvl.ll
                      Data are for Santicizer 154; a
                      mixture containing 43.2% t-butyl
                      phenyl diphenyl phosphate
                      (CASRN 56803-37-3), 40.2%
                      triphenyl phosphate (CASRN 115-
                      86-6), 14% di-t-butylphenyl
                      phenyl phosphate (CASRN 2528-
                      36-1) and 2% tri-t-butyl phenyl
                      phosphate (CASRN 78-33-1).
                      Data are for CASRN 220352-35-2
                      (75-80% w/w; impurity: 20-25%
                      w/w triphenyl phosphate (CASRN
                      115-86-6)). Study was conducted
                      according to OECD Guideline
                      203; details reported in a
                      secondary source.
                      Data are for Santicizer 154; a
                      mixture containing 43.2% t-butyl
                      phenyl diphenyl phosphate
                      (CASRN 56803-37-3), 40.2%
                      triphenyl phosphate (CASRN 115-
                      86-6), 14% di-t-butylphenyl
                      phenyl phosphate (CASRN 2528-
                      36-1) and 2% tri-t-butyl phenyl
                      phosphate (CASRN 78-33-1);
                      values are well above reported
                      water solubility values; NES may
                      be predicted.
                      Data are for Tris(p-t-butylphenyl)
                      phosphate (CASRN 78-33-1).
                      NES: The log Kow of 10 mg/L for
                      this chemical exceeds the SAR
                                                        7-709

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                                              JUNE 2014 DRAFT REPORT
                                  Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                                                                                       limitation for the log Kow of 5.0;
                                                                                                       NES are predicted for these
                                                                                                       endpoints. ECOSARalso
                                                                                                       provided results for the Esters,
                                                                                                       and Esters (phosphate) classes;
                                                                                                       however, professional judgment
                                                                                                       indicates that this compound is not
                                                                                                       currently well represented in
                                                                                                       ECOSARvl.ll.
                                    Freshwater fish (Lepomis macrochirus)
                                    96-hour LC50= l.Omg/L
                                    (Experimental)
                     Submitted confidential study
                       Data are for t-Butylphenyl
                       diphenyl phosphate (CASRN
                       56803-37-3). The available acute
                       toxicity data for fish, aquatic
                       invertebrates, and algae were
                       judged inadequate to meet the
                       endpoints; summary did not
                       provide sufficient information
                       regarding study conditions,
                       including test substance purity or
                       water solubility, to allow for an
                       independent evaluation of the
                       studies.
                                    Freshwater fish (Oncorhynchus mykiss)
                                    96-hourLC50 = 5.4mg/L
                                    static test conditions
                                    (Experimental)
                     Environment Agency, 2009
                       Data are for t-Butylphenyl
                       diphenyl phosphate (CASRN
                       56803-37-3; Fyrquel GT). The test
                       report indicates that the test
                       substance formed an oily film on
                       the surface of the water for all
                       concentrations tested and the
                       result is considered to be invalid
                       as undissolved test material
                       appeared to be present.
                                    Freshwater fish (Oncorhynchus mykiss) Environment Agency, 2009
                                                     Data are for t-Butylphenyl
                                                          7-710

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                                             JUNE 2014 DRAFT REPORT
                                  Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   96-hour LC50= 13.7mg/L
                                   flow-through test conditions
                                   (Experimental)
                                                   diphenyl phosphate (CASRN
                                                   56803-37-3). The reported LC50 is
                                                   well above the water solubility of
                                                   the test substance; effect level is
                                                   well above the estimated water
                                                   solubility therefore NES can be
                                                   predicted.
                                   Freshwater fish 96-hour LC50 = 0.50
                                   mg/L
                                   (Estimated)
                                   ECOSAR: Neutral organics
                     ECOSARvl.ll
                                   Freshwater fish 96-hour LC50 = 0.0005
                                   mg/L
                                   (Estimated)
                                   ECOSAR: Neutral organics
                     ECOSARvl.ll
                      Data are for t-Butylphenyl
                      diphenyl phosphate (CASRN
                      56803-37-3). NES: The log Kow of
                      5.12 mg/L for this chemical
                      exceeds the SAR limitation for the
                      log Kow of 5.0; NES are predicted
                      for these endpoints. ECOSAR also
                      provided results for the Esters,
                      and Esters (phosphate) classes;
                      however, professional judgment
                      indicates that this compound is not
                      currently well represented in
                      ECOSARvl.ll.
                      Data are for Bis(t-butylphenyl)
                      phenyl phosphate (CASRN
                      65652-41-7). NES: The log Kow of
                      8.5 mg/L for this chemical
                      exceeds the SAR limitation for the
                      log Kow of 5.0; NES are predicted
                      for these endpoints. ECOSAR also
                      provided results for the Esters,
                      and Esters (phosphate) classes;
                      however, professional judgment
                      indicates that this compound is not
                      currently well represented in
                      ECOSARvl.ll.
                                                         7-711

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                                                         JUNE 2014 DRAFT REPORT
                                             Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
           PROPERTY/ENDPOINT
              DATA
        REFERENCE
       DATA QUALITY
Daphnid LC50
Daphnia magna 48-hour EC50 = 0.25
mg/L
(Experimental)
Environment Agency, 2009
Data are for TB220-H;
tertbutylphenyl phosphate
(CASRN 78-33-1) with 18 percent
triphenyl phosphate (115-86-6);
effect level higher than the
estimated water solubility
therefore NES can be predicted.
                                               Daphnia magna 48-hour EC50 = 289 -
                                               321 (jg/L (0.289 - 0.321 mg/L, mean
                                               measured values)
                                               field tests from sediment or clean ponds,
                                               static conditions.
                                               (Experimental)
                                   Adams etal., 1983
                              Data are for Santicizer 154; a
                              mixture containing 43.2% t-butyl
                              phenyl diphenyl phosphate
                              (CASRN 56803-37-3), 40.2%
                              triphenyl phosphate (CASRN 115-
                              86-6), 14% di-t-butylphenyl
                              phenyl phosphate (CASRN 2528-
                              36-1) and 2% tri-t-butyl phenyl
                              phosphate (CASRN 78-33-1).
                                               Daphnia magna 48-hour LC50 = 0.30
                                               mg/L
                                               (Experimental)
                                   Submitted confidential study
                              Data are for CASRN 56803-37-3;
                              tertbutylphenyl diphenyl
                              phosphate (purity not given);
                              effect level higher than the
                              estimated water solubility
                              therefore NES can be predicted.
                                               Daphnia magna 48-hour EC50 = 0.30
                                               mg/L
                                               (Experimental)
                                                            7
                                   Environment Agency, 2009
                              Data are for Santicizer 154; a
                              mixture of tertbutylphenyl
                              diphenyl phosphate (CASRN
                              56803-37-3), di-tertbutylphenyl
                              phenyl phosphate (65652-41-7)
                              and triphenyl phosphate (115-86-
                              6).
                                               Daphnia magna 48-hour EC50 =1.1
                                               mg/L
                                               (Experimental)
                                   Environment Agency, 2009
                              Data are for TB220-L;
                              tertbutylphenyl diphenyl
                              phosphate (CASRN 56803-37-3)
                              with less than 1 percent triphenyl
                                                                    7-712

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                                             JUNE 2014 DRAFT REPORT
                                 Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                                                                                    phosphate (115-86-6); effect level
                                                                                                    higher than the estimated water
                                                                                                    solubility therefore NES can be
                                                                                                    predicted.
                                   Daphnia magna 48-hour EC50 = 2.9
                                   mg/L
                                   (Experimental)
                     Environment Agency, 2009
                                   Daphnia magna 48-hour EC50 = 5.0
                                   mg/L
                                   (Experimental)
                     Sanders et al., 1981
                                   Mysid shrimp (Mysidopsis bahid) 96-
                                   hour EC50 = 0.39 mg/L
                                   NOEC = 0.22 mg/L
                                   (Experimental)
                     Akzo Nobel, 2001
                                   Daphnia magna 48-hour LC50 = 0.38
                                   mg/L
                                   (Estimated)
                                   ECOSAR: Neutral organics
                     ECOSARvl.ll
                      Data are for Fyrquel GT;
                      commercial tertbutylphenyl
                      diphenyl phosphate product
                      (purity not given).
                      Data are for Santicizer 154; a
                      mixture containing 43.2% t-butyl
                      phenyl diphenyl phosphate
                      (CASRN 56803-37-3), 40.2%
                      triphenyl phosphate (CASRN 115-
                      86-6), 14% di-t-butylphenyl
                      phenyl phosphate (CASRN 2528-
                      36-1) and 2% tri-t-butyl phenyl
                      phosphate (CASRN 78-33-1);
                      effect level marginally higher than
                      the estimated water solubility of
                      the commercial mixture, therefore
                      NES may be predicted.
                      Data are for CASRN 220352-35-2
                      (75-80% w/w; impurity: 20-25%
                      w/w triphenyl phosphate (CASRN
                      115-86-6)). Study conducted
                      according to OECD Guide-line
                      202, part 1; details reported in a
                      secondary source.
                      Data are for t-Butylphenyl
                      diphenyl phosphate (CASRN
                      56803-37-3). NES: The log Kow of
                      5.12 mg/L for this chemical
                      exceeds the SAR limitation for the
                                                        7-713

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                                             JUNE 2014 DRAFT REPORT
                                  Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   Daphnia magna 48-hour LC50 = 0.0005
                                   mg/L
                                   (Estimated)
                                   ECOSAR: Neutral organics
                     ECOSARvl.ll
                                   Daphnia magna 48-hour LC50 =
                                   0.00001 mg/L
                                   (Estimated)
                                   ECOSAR: Neutral organics
                     ECOSARvl.ll
                                                                                                     log Kow of 5.0; NES are predicted
                                                                                                     for these endpoints. ECOSAR also
                                                                                                     provided results for the Esters,
                                                                                                     and Esters (phosphate) classes;
                                                                                                     however, professional judgment
                                                                                                     indicates that this compound is not
                                                                                                     currently well represented in
                                                                                                     ECOSARvl.ll.
                      Data are for Bis(t-butylphenyl)
                      phenyl phosphate (CASRN
                      65652-41-7). NES: The log Kow of
                      8.5 mg/L for this chemical
                      exceeds the SAR limitation for the
                      log Kow of 5.0; NES are predicted
                      for these endpoints. ECOSAR also
                      provided results for the Esters,
                      and Esters (phosphate) classes;
                      however, professional judgment
                      indicates that this compound is not
                      currently well represented in
                      ECOSARvl.ll.
                      Data are for Tris(p-t-butylphenyl)
                      phosphate (CASRN 78-33-1).
                      NES: The log Kow of 10 mg/L for
                      this chemical exceeds the SAR
                      limitation for the log Kow of 5.0;
                      NES are predicted for these
                      endpoints. ECOSAR also
                      provided results for the Esters,
                      and Esters (phosphate) classes;
                      however, professional judgment
                      indicates that this compound is not
                      currently well represented in
                                                         7-714

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                                                        JUNE 2014 DRAFT REPORT
                                            Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
           PROPERTY/ENDPOINT
              DATA
        REFERENCE
       DATA QUALITY
                                                                                                               ECOSARvl.ll.
Green Algae EC50
Green algae (Selenastrum
capricornutum) 96-hour EC50 (total
biomass) = 2.6 mg/L
96-hour EC50 (chlorophyll A) = 3.0
mg/L
(Experimental)
Environment Agency, 2009
Data are for CASRN 220352-35-2
(75-80% w/w; impurity: 20-25%
w/w triphenyl phosphate (CASRN
115-86-6)). Study details reported
in a secondary source.
                                              Green algae (Selenastrum
                                              capricornutum ) 96-hour EC50 = 3.0
                                              mg/L
                                              24-hour EC50> 10 mg/L
                                              48-hour EC50 = 5.9 mg/L
                                              72-hour EC50 = 3.4 mg/L
                                              (Experimental)
                                   Hollister, 1979
                              Data are for Santicizer 154; a
                              mixture containing 43.2% t-butyl
                              phenyl diphenyl phosphate
                              (CASRN 56803-37-3), 40.2%
                              triphenyl phosphate (CASRN 115-
                              86-6), 14% di-t-butylphenyl
                              phenyl phosphate (CASRN 2528-
                              36-1) and 2% tri-t-butyl phenyl
                              phosphate (CASRN 78-33-1).
                                              Green algae (Selenastrum
                                              capricornutum) 14-day NOEC = 1 mg/L
                                              (Experimental)
                                   Environment Agency, 2009
                              Data are for Fyrquel GT, a
                              commercial tertbutylphenyl
                              diphenyl phosphate product
                              (composition not given).
                                              Green algae 96-hour LC50 = 20 mg/L
                                              (Estimated)
                                              ECOSAR: Neutral organics
                                   ECOSARvl.ll
                              Data are for t-Butylphenyl
                              diphenyl phosphate (CASRN
                              56803-37-3); The log Kow of 8.5
                              mg/L for this chemical exceeds
                              the SAR limitation for the log Kow
                              of 5.0; NES are predicted for these
                              endpoints. ECOSAR also
                              provided results for the Esters,
                              and Esters (phosphate) classes;
                              however, professional judgment
                              indicates that this compound is not
                              currently well represented in
                              ECOSARvl.ll.
                                                                    7-715

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                                             JUNE 2014 DRAFT REPORT
                                 Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   Green algae 96-hour LC50 = 0.005 mg/L
                                   (Estimated)
                                   ECOSAR: Neutral organics
                     ECOSARvl.ll
                                   Green algae 96-hour LC50= 0.00025
                                   mg/L
                                   (Estimated)
                                   ECOSAR: Neutral organics
                     ECOSARvl.ll
                      Data are for Bis(t-butylphenyl)
                      phenyl phosphate (CASRN
                      65652-41-7). NES: The log Kow of
                      8.5 mg/L for this chemical
                      exceeds the SAR limitation for the
                      log Kow of 5.0; NES are predicted
                      for these endpoints. ECOSAR also
                      provided results for the Esters,
                      and Esters (phosphate) classes;
                      however, professional judgment
                      indicates that this compound is not
                      currently well represented in
                      ECOSARvl.ll.
                      Data are for Tris(p-t-butylphenyl)
                      phosphate (CASRN 78-33-1).
                      NES: The log Kow of 10 mg/L for
                      this chemical exceeds the SAR
                      limitation for the log Kow of 5.0;
                      NES are predicted for these
                      endpoints. ECOSAR also
                      provided results for the Esters,
                      and Esters (phosphate) classes;
                      however, professional judgment
                      indicates that this compound is not
                      currently well represented in
                      ECOSARvl.ll.
                                                         7-716

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                                                        JUNE 2014 DRAFT REPORT
                                            Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
           PROPERTY/ENDPOINT
              DATA
        REFERENCE
      DATA QUALITY
Chronic Aquatic Toxicity
VERY HIGH: Based on experimental NOEC values for mixture components of TBPP for fish and
daphnia. No experimental chronic data were available for green algae. The reported water solubility
values from studies on commercial mixtures may not adequately represent all components of the
mixture. The TBPP isomers and t-butyl substituted phenyl phosphate esters components anticipated to
be present in the commercial product are expected to have a range of water solubility values. Therefore
NES may be predicted for some components but not others.
Fish ChV
Freshwater fish (Pimephales promelas)
30-day NOEC (mortality) = 0.093 mg/L
30-day NOEC (growth) = 0.194 mg/L
(Experimental)
                                              Freshwater fish ChV = 0.068 mg/L
                                              (Estimated)
                                              ECOSAR: Neutral organics
                                              Freshwater fish ChV = 0.0001 mg/L
                                              (Estimated)
                                              ECOSAR: Neutral organics
Environment Agency, 2009
                                   ECOSAR vl. 11
                                   ECOSAR vl. 11
Data are for a commercial
tertbutylphenyl diphenyl
phosphate product consisting of
15-20 percent triphenyl
phosphate (CASRN 115-86-6)
with the remainder consisting
mainly of a mixture of isomers of
tertbutylphenyl diphenyl
phosphate (CASRN 56803-37-3),
along with isomers of di-
tertbutylphenyl diphenyl
phosphate (CASRN 65652-41-7).
                              Data are for t-Butylphenyl
                              diphenyl phosphate (CASRN
                              56803-37-3); effect level higher
                              than the estimated water solubility
                              therefore NES can be predicted.
                              ECOSAR also provided results for
                              the Esters, and Esters (phosphate)
                              classes; however, professional
                              judgment indicates that this
                              compound is not currently well
                              represented in ECOSAR v 1.11.
                              Data are for Bis(t-butylphenyl)
                              phenyl phosphate (CASRN
                              65652-41-7). NES: The log Kow of
                              8.5 mg/L for this chemical
                                                                   7-717

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                                                        JUNE 2014 DRAFT REPORT
                                             Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
           PROPERTY/ENDPOINT
              DATA
        REFERENCE
       DATA QUALITY
                                              Freshwater fish ChV = 0.000003 mg/L
                                              (Estimated)
                                              ECOSAR: Neutral organics
                                   ECOSARvl.ll
                                                                                                                exceeds the SAR limitation for the
                                                                                                                log Kow of 8.0; NES are predicted
                                                                                                                for these endpoints. ECOSAR also
                                                                                                                provided results for the Esters,
                                                                                                                and Esters (phosphate) classes;
                                                                                                                however, professional judgment
                                                                                                                indicates that this compound is not
                                                                                                                currently well represented in
                                                                                                                ECOSARvl.ll.
                              Data are for Tris(p-t-butylphenyl)
                              phosphate (CASRN 78-33-1).
                              NES: The log Kow of 10 mg/L for
                              this chemical exceeds the SAR
                              limitation for the log Kow of 5.0;
                              NES are predicted for these
                              endpoints. ECOSAR also
                              provided results for the Esters,
                              and Esters (phosphate) classes;
                              however, professional judgment
                              indicates that this compound is not
                              currently well represented in
                              ECOSARvl.ll.
Daphnid ChV
Daphnia magna 21-day LOEC
(mortality) < 100 (jg/L (0.1 mg/L)
NOEC (mortality and reproduction) =
40 (jg/L (0.04 mg/L)
(Experimental)
Akzo Nobel, 2001
Data are for CASRN 220352-35-2
(75-80% w/w; impurity: 20-25%
w/w triphenyl phosphate (CASRN
115-86-6)). Study details reported
in a secondary source.
                                              Daphnia magna 21-day NOEC
                                              (survival and reproduction) = 0.01 mg/L
                                              (Experimental)
                                   Environment Agency, 2009
                              Data are for Santicizer 154; a
                              commercial tertbutylphenyl
                              diphenyl phosphate product
                              (purity not given).
                                              Daphnia magna 21-day NOEC = 0.03
                                              mg/L
                                   Environment Agency, 2009
                              Data are for TB220-L;
                              tertbutylphenyl diphenyl
                                                                    7-718

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                                             JUNE 2014 DRAFT REPORT
                                 Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   (Experimental)
                                                   phosphate (CASRN 56803-37-3)
                                                   with less than 1 percent triphenyl
                                                   phosphate (115-86-6); effect level
                                                   higher than the estimated water
                                                   solubility therefore NES can be
                                                   predicted.
                                   Daphnia magna 21-day NOEC = 0.03
                                   mg/L
                                   (Experimental)
                     Environment Agency, 2009
                      Data are for TB220-H;
                      tertbutylphenyl phosphate
                      (CASRN 78-33-1) with 18 percent
                      triphenyl phosphate (115-86-6).
                                   Daphnia magna 21-day NOEC
                                   (survival and reproduction) = 0.032
                                   mg/L
                                   (Experimental)
                     Environment Agency, 2009
                      Data are for Fyrquel GT; a
                      commercial tertbutylphenyl
                      diphenyl phosphate product
                      (purity not given).
                                   Daphnia magna 21-day NOEC = 0.04
                                   mg/L
                                   (Experimental)
                     Environment Agency, 2009
                      Data are for Santicizer 154; a
                      mixture of tertbutylphenyl
                      diphenyl phosphate (CASRN
                      56803-37-3), di-tertbutylphenyl
                      phenyl phosphate (65652-41-7)
                      and triphenyl phosphate (115-86-
                      6).
                                   Daphnia magna 21-day NOEC >204 - <
                                   461 (jg/L (0.204 - 0.461 mg/L, mean
                                   measured values)
                                   21-day MATC > 23.6 - < 52.4 (jg/L
                                   (0.0236 - 0.0524 mg/L) field tests from
                                   sediment or clean ponds, static
                                   conditions
                                   (Experimental)
                     Adams etal., 1983
                      Data are for Santicizer 154; a
                      mixture containing 43.2% t-butyl
                      phenyl diphenyl phosphate
                      (CASRN 56803-37-3), 40.2%
                      triphenyl phosphate (CASRN 115-
                      86-6), 14% di-t-butylphenyl
                      phenyl phosphate (CASRN 2528-
                      36-1) and 2% tri-t-butyl phenyl
                      phosphate (CASRN 78-33-1).
                                   Daphnia magna ChV = 0.082 mg/L
                                   (Estimated)
                                   ECOSAR: Neutral organics
                     ECOSARvl.ll
                      Data are for t-Butylphenyl
                      diphenyl phosphate (CASRN
                      56803-37-3); effect level higher
                                                        7-719

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                                             JUNE 2014 DRAFT REPORT
                                  Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                   Daphnia magna ChV = 0.000012 mg/L
                                   (Estimated)
                                   ECOSAR: Neutral organics
                     ECOSARvl.ll
                                   Daphnia magna 4 8-hour ChV =
                                   0.00027 mg/L
                                   (Estimated)
                                   ECOSAR: Neutral organics
                     ECOSARvl.ll
                                                                                                     than the estimated water solubility
                                                                                                     therefore NES can be predicted.
                                                                                                     ECOSAR also provided results for
                                                                                                     the Esters, and Esters (phosphate)
                                                                                                     classes; however, professional
                                                                                                     judgment indicates that this
                                                                                                     compound is not currently well
                                                                                                     represented in ECOSAR v 1.11.
                      Data are for Tris(p-t-butylphenyl)
                      phosphate (CASRN 78-33-1).
                      NES: The log Kow of 10 mg/L for
                      this chemical exceeds the SAR
                      limitation for the log Kow of 5.0;
                      NES are predicted for these
                      endpoints. ECOSAR also
                      provided results for the Esters,
                      and Esters (phosphate) classes;
                      however, professional judgment
                      indicates that this compound is not
                      currently well represented in
                      ECOSARvl.ll.
                      Data are for Bis(t-butylphenyl)
                      phenyl phosphate (CASRN
                      65652-41-7). NES: The log Kow of
                      8.5 mg/L for this chemical
                      exceeds the SAR limitation for the
                      log Kow of 8.0; NES are predicted
                      for these endpoints. ECOSAR also
                      provided results for the Esters,
                      and Esters (phosphate) classes;
                      however, professional judgment
                      indicates that this compound is not
                      currently well represented in
                                                         7-720

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                                                        JUNE 2014 DRAFT REPORT
                                             Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
           PROPERTY/ENDPOINT
              DATA
        REFERENCE
       DATA QUALITY
                                                                                                                ECOSARvl.ll.
Green Algae ChV
Green algae ChV = 0.46 mg/L
(Estimated)
ECOSAR: Neutral organics
ECOSARvl.ll
                                              Green algae ChV = 0.005 mg/L
                                              (Estimated)
                                              ECOSAR: Neutral organics
                                   ECOSARvl.ll
                                              Green algae ChV = 0.00037 mg/L
                                              (Estimated)
                                              ECOSAR: Neutral organics
                                   ECOSARvl.ll
Data are for t-Butylphenyl
diphenyl phosphate (CASRN
56803-37-3); effect level higher
than the estimated water solubility
therefore NES can be predicted.
ECOSAR also provided results for
the Esters, and Esters (phosphate)
classes; however, professional
judgment indicates that this
compound is not currently well
represented in ECOSAR v 1.11.
                              Data are for Bis(t-butylphenyl)
                              phenyl phosphate (CASRN
                              65652-41-7). NES: The log Kow of
                              8.5 mg/L for this chemical
                              exceeds the SAR limitation for the
                              log Kow of 5.0; NES are predicted
                              for these endpoints. ECOSAR also
                              provided results for the Esters,
                              and Esters (phosphate) classes;
                              however, professional judgment
                              indicates that this compound is not
                              currently well represented in
                              ECOSARvl.ll.
                              Data are for Tris(p-t-butylphenyl)
                              phosphate (CASRN 78-33-1).
                              NES: The log Kow of 10 mg/L for
                              this chemical exceeds the SAR
                              limitation for the log Kow of 5.0;
                              NES are predicted for these
                              endpoints. ECOSAR also
                              provided results for the Esters,
                                                                    7-721

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JUNE 2014 DRAFT REPORT
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT

DATA

REFERENCE

DATA QUALITY
and Esters (phosphate) classes;
however, professional judgment
indicates that this compound is not
currently well represented in
ECOSARvl.ll.
ENVIRONMENTAL FATE
Transport

Henry's Law Constant (atm-
m3/mole)
Sediment/Soil
Adsorption/Desorption - Koc
Level III Fugacity Model
Level III fugacity models incorporating available physical and chemical property data indicate that at
steady state, TBPP is expected to be found primarily in soil and to a lesser extent, water. TBPP is
expected to have negligible mobility in soil based on the estimated Koc value. There is low to moderate
potential for volatilization from water or moist soil surfaces based upon the estimated Henry's Law
constant; however adsorption to soil is expected to attenuate this process. TBPP is not expected to
volatilize from dry soil surfaces based upon the extrapolated and measured vapor pressures. In the
atmosphere, TBPP is expected to exist primarily in the particulate phase. Particulate phase TBPP will be
removed from air by wet or dry deposition.
6.9xlO~7 fortris (p-t-butylphenyl)
phosphate;
2.7xlO~7 for di-t-butylphenyl phenyl
phosphate;
IxlO"7 for t-butylphenyl diphenyl
phosphate (Estimated)
8.8xlO'7 (Measured)
3,400 for t-butylphenyl diphenyl
phosphate using the MCI method
(Estimated)
*
>30,000 (Estimated)
Air = 0.1%
EPIv4.11
ChemID, 2013c
EPIv4.11
EPIv4.11;EPA, 2005
EPIv4.11
Estimated using representative
structures indicated in the
SMILES section for components
of the mixture using the
HENRYWIN (v3.20) Program.
Reported for CASRN 56803-37-3
in secondary source.
Estimated using the representative
structure for t-butylphenyl
diphenyl phosphate indicated in
the SMILES section.
Cutoff value fornonmobile
compounds. Estimated for both
tris (p-t-butylphenyl) phosphate
and for di-t-butylphenyl phenyl
phosphate.
Estimated for tris (p-t-
         7-722

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                                                        JUNE 2014 DRAFT REPORT
                                            Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
           PROPERTY/ENDPOINT
                                           DATA
                                           REFERENCE
                                     DATA QUALITY
                                              Water = 5%
                                              Soil = 93.2%
                                              Sediment = 1.67% (Estimated)
                                                                                              butylphenyl) phosphate.
Persistence
                             MODERATE: Based on primary and ultimate biodegradation in nonguideline experimental studies
                             using CASRN 56803-37-3 in river and pond water and sediment samples. These results indicate a half-
                             life for ultimate degradation of <60 days but >16 days in the environment and are consistent with
                             inherent degradation. 100% primary degradation of CASRN 56803-37-3 was reported after
                             approximately 11 days in a river die-away study and 93% primary degradation after 9 weeks in a SCAS
                             test using activated sludge inoculum under aerobic conditions. CASRN 56803-37-3 was found to have
                             half-lives based on disappearance of the parent compound of 4.2 and 8.4 days in pond and river
                             sediment, respectively, and showed mineralization of 1.7-37.2% after 8 weeks in water-sediment
                             microcosms. Hydrolysis in alkaline waters may be an important fate process based on experimental half-
                             lives for TBPP but slower under neutral conditions. In a nonguideline  photolysis study, no
                             transformation products were identified from a commercial mixture of TBPP in filtered Mississippi
                             River water after exposure to sunlight for 14 days.
Water
Aerobic Biodegradation
Study results: 93%/9 weeks
Test method: Biological Treatment
Simulation

SCAS test. 93% primary degradation
after 9 weeks in domestic activated
sludge at a test substance addition rate
of 3 mg/L every 24 hours. (Measured)
                                              Study results: 100%/~lldays
                                              Test method: Die-Away

                                              Complete primary degradation occurred
                                              after about 11 days in a river water die-
                                              away study. (Measured)
                                              Study results: 50%/7 days
                                              Test method: Die-Away

                                              Reported as the disappearance of the
Saegeretal., 1979
                                                                Saegeretal., 1979
                                                                Saugar, 1983
Nonguideline study reported for
CASRN 56803-37-3.
                                                                 Nonguideline study reported for
                                                                 CASRN 56803-37-3.
                                                                 Guideline test performed on a
                                                                 commercial product consisting of
                                                                 TPP (CASRN 115-86-6), di(t-
                                                                 butylphenyl)phenyl phosphate
                                                                    7-723

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JUNE 2014 DRAFT REPORT
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT

Soil

Volatilization Half-life for
Model River
Volatilization Half-life for
Model Lake
Aerobic Biodegradation
Anaerobic Biodegradation
Soil Biodegradation with
Product Identification
Sediment/Water
Biodegradation
DATA
parent compound.
TPP: 50%/<0.5 days
DTBPPP: 50%/1 day
TBPDPP: 50%/7 days
Mississippi River water over 27 days
(Measured)
79 days (Estimated)
54 days (Estimated)
190 days (Estimated)
>1 year (Estimated)
>1 year (Estimated)
>1 year (Estimated)

Not probable (Anaerobic-methanogenic
biodegradation probability model)

Mineralization of the test substance (2
mg) ranged from 1.7 to 37.2% after 8
weeks in microcosms containing
REFERENCE

EPIv4.11
EPIv4.11
EPIv4.11
EPIv4.11
EPIv4.11
EPIv4.11

EPIv4.11

Heitkamp and Cerniglia, 1986;
Heitkamp et al., 1986
DATA QUALITY
(DTBPPP) and t-
butylphenyldiphenyl phosphate
(TBPDPP).
Estimated for tris (p-t-
butylphenyl) phosphate.
Estimated using the representative
structure for p-(t-butylphenyl)
diphenyl phosphate.
Estimated using the representative
structure for di-t-butylphenyl
phenyl phosphate.
Estimated for tris (p-t-
butylphenyl) phosphate.
Estimated using the representative
structure for p-(t-butylphenyl)
diphenyl phosphate.
Estimated using the representative
structure for di-t-butylphenyl
phenyl phosphate.
No data located.
Estimated for tris (p-t-
butylphenyl) phosphate.
No data located.
Nonguideline study reported for
CASRN 56803-37-3.
         7-724

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                                                          JUNE 2014 DRAFT REPORT
                                              Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
            PROPERTY/ENDPOINT
                                             DATA
                                             REFERENCE
                                      DATA QUALITY
                                                sediment and water from lacustrine,
                                                riverine, and estuarine ecosystems. The
                                                rate of degradation was related to the
                                                nutrient level and contaminant
                                                (Measured)
                                                50%/4.2 days at 25°C in pond sediment.
                                                Half-life = 8.4 days at 25°C in river
                                                sediment based on disappearance of the
                                                parent compound from the sediment
                                                phase. 14C-labelled test substance was
                                                subject to static river and pond
                                                sediment-water incubations in
                                                respirometer flasks at temperatures and
                                                redox conditions typical  of aquatic
                                                environments. (Measured)
                                                                  Muiretal., 1989
                                                                   Nonguideline study reported for
                                                                   CASRN 56803-37-3.
Air
Atmospheric Half-life
0.7 days for t-butylphenyl diphenyl
phosphate;
0.74 tri-t-butylphenyl phosphate
0.81 for di-t-butylphenyl phenyl
phosphate; (Estimated)
EPIv4.11
Estimated using representative
structures indicated in the
SMILES section.
  = 3.9xl06
Thin film oxidation test analyzed by Gel
Permeation chromatography (GPC)
Hydrocarbon portion of the phosphate
oxidizes in the first step; oxidized
material undergoes condensation
(Measured)
                                                                                    Cho and Klaus, 1981
                                                                                                 Nonguideline study providing
                                                                                                 supporting information.
Reactivity
Photolysis
0%/14 days
No transformation products were
identified in filtered Mississippi River
water after exposure to sunlight for 14
days in a sealed quartz tube; analysis
with GC (Measured)
Sauger, 1983
Nonguideline study on a
commercial mixture.
                                                                      7-725

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JUNE 2014 DRAFT REPORT
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT

Hydrolysis
Environmental Half-life
Bioaccumulation

Fish BCF
DATA
pH5:50%/>100days
pH7:50%/31days
pH 9: 50%/19 days (Measured)
pH5:50%/>100days
pH 7: 50%/57 days
pH 9 : 5 0%/ 1 0 days (Measured) ^
pH7:50%/3.5years
pH5:50%/341years
pH 6: 50%/35 years
pH 8: 50%/127 days
pH 9: 50%/13 days
pH 10: 50%/1.3 days (Estimated)
0.44 day in pond water
39 days in bottom sediment
Field study; 360 days following the
addition of 50 (jg/L of the test substance
to artificial ponds of 5 cubic meter
volume (Measured)
360 days (Estimated)
REFERENCE
Michael, 1978
Michael, 1978
EPIv4.11
^^ S
Muiretal., 1985
PBT Profiler
DATA QUALITY
Reported for tri t-butylphenyl
phenyl phosphate.
Reported for CASRN 56803-37-3.
Estimated for tris (p-t-
butylphenyl) phosphate.
Reported for CASRN 56803-37-3.
Half-life estimated for tris (p-t-
butylphenyl) phosphate in the
predominant compartment, soil, as
determined by EPI methodology.
HIGH: The bioaccumulation designation is based on the measured BCF values for t-butylphenyl
diphenyl phosphate (CASRN 56803-37-3); BCF results >1,000 are from two different species. The
estimated BAF values for the di and tri-t-butylphenyl phosphate also indicate high potential for
bioaccumulation. The low estimated BCF values were determined from the estimated log Kow values,
which are >6.6.
1,096 whole fish, short-term static
exposure of 50 and 5 (jg/L in Rainbow
trout (Measured)
1,010 Whole fish, short-term static
Muiretal., 1983
Muiretal., 1983
Nonguideline study reported for
>98%pure CASRN 56803-37-3.
Nonguideline study reported for
         7-726

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JUNE 2014 DRAFT REPORT
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT


Other BCF
BAF
Metabolism in Fish
DATA
exposure of 50 and 5 (jg/L in Fathead
minnow (Measured)
42 (Estimated)
170 (Estimated)
360 (Estimated)

100,000 (Estimated)
460,000 (Estimated)
540 (Estimated)

REFERENCE

EPIv4.11
EPIv4.11
^^
EPIv4.11
^^^

EPIv4.11
EPIv.411
EPIv4.11

DATA QUALITY
>98%pure CASRN 56803-37-3.
Estimated for tris (p-t-
butylphenyl) phosphate.
Estimated using the representative
structure for p-(t-butylphenyl)
diphenyl phosphate.
Estimated using the representative
structure for di-t-butylphenyl
phenyl phosphate.
No data located.
Estimated for tris (p-t-
butylphenyl) phosphate. Given the
limited water solubility, this BAF
value may be overestimated.
Estimated using the representative
structure for di-t-butylphenyl
phenyl phosphate.
Estimated using the representative
structure for p-(t-butylphenyl)
diphenyl phosphate.
No data located.
ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring
Ecological Biomonitoring
Human Biomonitoring
t-Butylphenyl diphenyl phosphate (CASRN 56803-37-3) has been found in river sediments in industrial areas
(Muiretal, 1989).
No data located.
t-Butylphenyl diphenyl phosphate (CASRN 56803-37-3) was detected in human adipose samples. TBPP was
not included in the NHANES biomonitoring report (LeBel and Williams, 1983; CDC, 2009).
         7-727

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                                                  JUNE 2014 DRAFT REPORT


ATSDR (1997) Toxicological profile for hydraulic fluids. Agency for Toxic Substances and Disease Registry, U.S. Public Health Service, 339.

Adams WJ, Kimerle RA, Heidolph BB, et al. (1983) Field comparison of laboratory-derived acute and chronic toxicity data. In: Bishop, Cardwell,
Heidolph, eds. Aquatic Toxicology and Hazard Assessment, Sixth Symposium. ASTM Special Technical Publication 802, 367-385.

Akzo Nobel (2001) IUCLID data set Butylated triphenyl phosphate. Akzo Nobel Functional Chemicals.

Bowman KJ (1981) 2-Ethylhexyl diphenyl phosphate (Santicizer 141), isodecyl 2-ethylhexyl diphenyl phosphate (Santicizer 141), isodecyl
diphenyl phosphate (Santicizer 148) & t-butylphenyl dipheny phosphate (Santicizer 154) health & safety studies w-letter. Prepared by E G & G
Bionomics for Monsanto Chemical Company Submitted to the U.S. Environmental Protection Agency under TSCA Section 4.

Bucafusco RJ (1976a) Acute toxicity of Santicizer 154 to bluegill (Lepomis macrochirus). Prepared by E G & G Bionomics for Monsanto
Company Submitted to the U.S. Environmental Protection Agency under TSCA Section 8D.

Bucafusco RJ (1976b) Acute toxicity of Santicizer 154 to rainbow trout (Salmo gairdneri). Prepared by E G & G Bionomics for Monsanto
Company Submitted to the U.S. Environmental Protection Agency under TSCA Section 8D.

CDC (2009) Fourth national report on human exposure to environmental chemicals. Atlanta, GA: Centers for Disease Control and Prevention.
http://www.cdc.gov/exposurereport/pdf/FourthReport.pdf

Carre DJ, Bertrand PA (1999) Modeling and measurement of aryl phosphate ester vapor pressures at 50°C. Tribol Trans 42(4):777-782.

ChemID (2013a) Phosphoric acid, (p-tert-butylphenyl) diphenyl ester RN: 981-40-8. ChemID plus. National Library of Medicine.
http://chem.sis.nlm.nih.gov/chemidplus/.

ChemID (2013b) Phosphoric acid, tris(tert-butylphenyl)  ester RN: 28777-70-0. ChemID plus. National Library of Medicine.
http://chem.sis.nlm.nih.gov/chemidplus/.

ChemID (2013c) t-Butylphenyl diphenyl phosphate RN: 56803-37-3. ChemID plus. National Library of Medicine.
http://chem.sis.nlm.nih.gov/chemidplus/.

Cho L, Klaus EE (1981) Oxidative degradation of phosphate esters. ASLE Transactions 24(1): 119-124.

Clayton JW (1983) 90-Day subacute aerosol inhalation study with Santicizer 154 in albino rats (BTL-76-29). Prepared by Industrial Bio Test Labs
Inc for Monsanto Company Submitted to the U.S. Environmental Protection Agency under TSCA Section 8D.



                                                             7-728

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                                                  JUNE 2014 DRAFT REPORT


Dobry A, Keller R (1957) Vapor pressures of some phosphate and phosphonate esters. J Phys Chem 61(10): 1448-1449.

Dodd DE, Smith PM (1994) Toxic hazards research unit annual report 1993. Mantech Environmental Technology Inc. http://www.dtic.mil/cgi-
bin/GetTRDoc?Location=U2&doc=GetTRDoc.pdf&AD=ADA303823.

ECOSAR (Ecological Structure Activity Relationship), Version 1.11. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/oppt/newchems/tools/21ecosar.htm.

EPA (1999) Determining the adequacy of existing data. Washington, DC: U.S. Environmental Protection Agency.
http: //www .epa. gov/hpv/pubs/general/datadeqfn .pdf.

EPA (2005) Pollution prevention (P2) framework. Washington, DC: U.S. Environmental Protection Agency, Office of Pollution Prevention and
Toxics, http://www.epa.gov/opptintr/newchems/pubs/sustainable/p2frame-june05a2.pdf.

EPA (2008) Initial risk-based prioritization of high production volume chemicals: Butylated triphenyl phosphate. U.S. Environmental Protection
Agency.

EPA (2012) Using noncancer screening within the SF initiative. Washington, DC: U.S. Environmental Protection Agency.
http: //www .epa. gov/oppt/sf/pubs/noncan-screen .htm.

EPI Estimation Programs Interface (EPI)  Suite, Version 4.11. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm.

ESIS (2012) European chemical Substances Information System.  European Commission, http://esis.jrc.ec.europa.eu/.

Environment Agency (2009) Environmental risk evaluation report: Tertbutylphenyl diphenyl phosphate (CAS no. 56803-37-3).

Fabian FW (1982) Report of toxicity experiments. Dow Chemical Company Submitted to the U.S. Environmental Protection Agency under TSCA
Section 8D.

Hagerman RL (1984) Oral toxicity of p-tert butyl phenyl phosphate (preliminary report) with cover letter. Dow Chemical Company Submitted to
the U.S. Environmental Protection Agency under TSCA Section 8D.

Heitkamp MA, Cerniglia CE (1986) Microbial degradation of t-butylphenyl diphenyl phosphate: a comparative microcosm study among five
diverse ecosystems. Environ Toxicol Water Qual 1(1): 103-122.



                                                             7-729

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                                                 JUNE 2014 DRAFT REPORT


Heitkamp MA, Freeman JP, Cerniglia CE (1986) Biodegradation of tert butylphenyldiphenyl phosphate. Appl Environ Microbiol 51(2):316-322.

Hollister T (1979) Toxicity of S-154 (BN-79-1384328-2a) to the freshwater alga Selenastrum capricornutum. Prepared by E G & G Bionomics for
Monsanto Company Submitted to the U.S. Environmental Protection Agency under TSCA Section 8D.

Keller AS (1984) Letter & attachments from Monsanto Chemical Company to the USEPA regarding the response of the industry ad hoc Aryl
Phosphate Esters Committee to the USEPA's anar on aryl phosphate. Monsanto Chemical Company. Submitted to the U.S. Environmental
Protection Agency under TSCA Section 4.

Latendresse JR (1994) Support: toxic effects of butylated triphenyl phosphate-based hydraulic fluid & tricresyl phosphate in female F344 rats with
cover letter dated 060994. Prepared by Naval Medical Research Institute for Eastman Kodak Company. Submitted to the U.S. Environmental
Protection Agency under TSCA Section 8E.

Latendresse JR Azhar S, Brooks CL, et al. (1993) Pathogenesis of cholesteryl lipidosis of adrenocortical and ovarian interstitial cells in F344 rats
caused by tricresyl phosphate and butylated triphenyl phosphate. Toxicol Appl Pharmacol 122(2):281-289.

Latendresse JR Brooks CL, Capen CC (1994a) Pathologic effects of butylated triphenyl phosphate-based hydraulic fluid and tricresyl phosphate
on the adrenal gland, ovary, and testis in the Fischer-344 rat. Toxicol Pathol 22(4):341-352.

Latendresse JR Brooks CL, Capen CC (1995) Toxic effects of butylated triphenyl phosphate-based hydraulic fluid and tricresyl phosphate in
female F344 rats. Vet Pathol 32(4):394-402.

Latendresse JR Brooks CL, Flemming CD, et al. (1994b) Reproductive toxicity of butylated triphenyl phosphate and tricresyl phosphate fluids in
F344 rats. Fundam Appl Toxicol 22(3):392-399.

Latourette HK (1981) Aryl phosphate epidemiology study with cover letter & memo. FMC Corporation Submitted to the U.S. Environmental
Protection Agency under TSCA Section 8D.

LeBel GL, Williams DT (1983) Determination of organic phosphate triesters in human adipose tissue. J Assoc Off Anal Chem 66(3):691-699.

Matheson DW (1980) Twenty health effect studies from Monsanto. Prepared by Litton Bionetics for Monsanto  Company Submitted to the U.S.
Environmental Protection Agency under TSCA Section 4.

Michael PR (1978) Phosphate ester hydrolysis. Monsanto Company Submitted to the U.S. Environmental Protection Agency under TSCA Section
8D.
                                                             7-730

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                                                 JUNE 2014 DRAFT REPORT


Monsanto (1976) Acute toxicity of Santicizer 154 to fathead minnow (Pimephales promelas). Prepared by E G & G Bionomics for Monsanto
Company Submitted to the U.S. Environmental Protection Agency under TSCA Section 8D.

Muir CG, Yarechewski AL, Grift NP (1989) Biodegradation of four triaryl/alkyl phosphate esters in sediment under various temperature and redox
conditions. Toxicol Environ Chem 18(4):269-286.

Muir DC, Lint D, Grift NP (1985) Fate of three phosphate ester flame retardants in small ponds. Toxicol Environ Chem 4(5):663-676.

Muir DCG, Yarechewski AL, Grift NP (1983) Environmental dynamics of phosphate esters 3. Comparison of the bio concentration of 4 tri aryl
phosphates by fish. Chemosphere 12(2): 155-166.

Murphy JP (1979) Test protocols & data summaries for t-butyl phenyl diphenyl phosphate, tricresyl phosphate, trixylenyl phosphate, mixed triaryl
phosphate & isopropyl phenyl diphenyl w/ cover. Staufer Chemical Company. Submitted to the U.S. Environmental Protection Agency under
TSCA.

PBT Profiler Persistent (P), Bioaccumulative (B), and Toxic (T) Chemical (PBT) Profiler, Version  1.301. Washington, DC: U.S. Environmental
Protection Agency, www.pbtprofiler.net.

Saeger VW, Hicks O, Kaley RG, et al. (1979) Environmental fate of selected phosphate esters. Environ Sci Technol 13(7):840-844.

Sanders HO, Hunn JB, Robinson-Wilson E (1981) Six potential PCB substitutes: acute and chronic toxicity to algae and invertebrates. Prepared by
Columbia National Fisheries Laboratory for FMC Corporation. Submitted to the U.S. Environmental Protection Agency under TSCA Section 8D.

Sauger VW (1983) Sunlight photolysis screening of Santicizer 154. Monsanto Company. Submitted to the U.S. Environmental Protection Agency
under TSCA Section 8D.

Sauger VW (1983) Santicizer 154 river die-away biodegradation rate study.  Monsanto Company. Submitted to the U.S. Environmental Protection
Agency  under TSCA Section 8D.
  &   j

Weil ED (2001) Flame retardants, phosphorus. Kirk-Othmer's Encyclopedia of Chemical Technology. Wiley-Interscience, 484-510.

Zeiger E, Anderson B, Haworth S, et al. (1987) Salmonella mutagenicity tests III. Results from the  testing of 255 chemicals. Environ Mutagen
9(Suppl9):l-110.
                                                             7-731

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                                JUNE 2014 DRAFT REPORT
V6
Screening Level Toxicology Hazard Summary
This table only contains information regarding the inherent hazards of flame retardant chemicals. Evaluation of risk considers both the hazard and exposure associated with the
substance including combustion and degradation by-products. The caveats listed in the legend and footnote sections must be taken into account when interpreting the hazard
information in the table.
VL = Very Low hazard L = Low hazard = Moderate hazard = High hazard VH = Very High hazard - Endpoints in colored text (VL, L, , H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].
Chemical
CASRN
Human Health Effects
jO
u
Carcinogenicity
Genotoxicity
Reproductive
Developmental
Neurological
Repeated Dose
Skin Sensitization
Respiratory
Sensitization
Eye Irritation
0
1
*C
HH
13
0)
Q
Aquatic
Toxicity
u
Chronic
Environmental
Fate
Persistence
Bioaccumulation

Phosphoric acid, P,P'-[2,2-
bis(chloromethyl)-l,3-propanediyl]
P,P,P',P'-tetrakis(2-chloroethyl) ester
(V6)

38051-10-4


L


M


L





H


L





L





L


L





H





L


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JUNE 2014 DRAFT REPORT
Cl

D^P"0
CASRN: 3805 1-10-4
MW: 582.99
MF: C13H24C1608P2
Physical Forms: Liquid
Neat:
Use: Fire retardant; polyurethane
foam additive
SMILES: O=P(OCCC1)(OCCC1)OCC(CC1)(CC1)COP(=O)(OCCC1)OCCC1
Synonyms: V6; Amgard V6; BCMP-BCEP; 2,2-bis(chloromethyl)trimethylene bis(bis(2-chloroethyl) phosphate); tetrekis(2-chlorethyl)dichloroisopentyldiphosphate
Chemical Considerations: This is a discrete organic chemical with a MW below 1,000. EPI v4. 1 1 was used to estimate physical/chemical and environmental fate
values due to an absence of experimental data. Commercially available forms of this chemical have a purity of >85-90% (w/w). Impurities anticipated to be present in
the commercial product are: 1,2 dichloroethane (CASRN 107-06-2) and 4.5-7.5% TCEP or tris(chloroethyl) phosphate (CASRN 1 15-96-8) (EU, 2008a; CELLTECH,
2009).
Polymeric: No
Oligomeric: Not applicable
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                                                         JUNE 2014 DRAFT REPORT
Metabolites, Degradates and Transformation Products: Metabolites: ethylchloride; 2-chloroethanol; parent compound missing a chloroethyl moiety; parent
compound with chlorine replaced by an OH group; and parent compound with one chlorine oxidized to a carboxyl group (ECHA, 2012)
Analog: 2-Propanol, 1,3-dichloro-, phosphate (CASRN 13674-87-8)
Endpoint(s) using analog values: Carcinogenicity
Analog Structure:
Structural Alerts: Organophosphates, neurotoxicity. The commercial product may contain an impurity, CASRN 115-96-8, that appears on the List of Chemicals
Known to the State to Cause Cancer for the State of California: California Proposition 65 cancer (EPA, 2012; California EPA, 2013).
Risk Phrases: Not classified; although the commercial product is classified based on the amount of TCEP impurity present (ECHA, 2012; ESIS, 2012).
Hazard and Risk Assessments: A risk assessment was reported by the European Chemicals Industry; a SIDS initial assessment profile was completed under the
OECD HPV chemicals program; an environmental risk assessment was completed by the EU in 2008 (EC, 2000; EU, 2008a; OECD, 2009).
                                                                    7-734

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JUNE 2014 DRAFT REPORT
V6 CASRN 38051-10-4
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
PHYSICAL/CHEMICAL PROPERTIES
Melting Point (°C)
Boiling Point (°C)
Vapor Pressure (mm Hg)
<-50.5
reported as a freezing point; Good
laboratory practice (GLP) guideline
study OECD 102, EEC Directive 92/69;
test substance partially frozen but
temperature did not remain constant
(Measured)
90
(Measured)
252.29 Decomposes
According to EU Method A.2, during
experiment exotherm occurred resulting
in a final pressure of 78 1 .5 psi
(Measured)
>200 Decomposes
Decomposition products include
phosphorus oxides, carbon monoxide
and chlorides (Measured)
620
(Unknown)
7
2.06xlO-8at25°C
(Estimated)
<0.1atlOO°C
(Measured)
1.7at25°C
OECD, 2009; ECHA, 2012
van der Veen and de Boer, 2012
OECD, 2009; ECHA, 2012
EC, 2000; ECHA, 2012
van der Veen and de Boer, 2012
EPIv4.11
EC, 2000
ECHA, 2012
Guideline study reported for the
commercial product Antiblaze V6.
Inadequate, reported in a
secondary source, insufficient
details available to access the
quality of this value.
Guideline study reported in a
secondary source.
Reported in a secondary source.
Reported in a secondary source;
citing another secondary source
(ChemSpider, 201 1) that could not
be verified.

Reported in a secondary source;
test not applicable due to product
decomposition.
Reported for a commercial
         7-735

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JUNE 2014 DRAFT REPORT
V6 CASRN 38051-10-4
PROPERTY/ENDPOINT

Water Solubility (mg/L)
Log Kow
DATA
reported as 22.29 hPa at 25°C; according
to GLP guideline study EU Method A. 4
(Measured)
2.1 (Measured)
at 25 °C
232 (Measured)
at 20°C, pH 7.65; GLP guideline study
OECD 105 and EU Method A.6
0.31 (Estimated)
Insoluble in water, at pH 7 (Measured)
\
2.83
+/-0.05at20°C,pH8.5
GLP guideline study OECD 107 and EU
Method A. 8; average of 6 assays ranging
from 2.74-2.87 (Measured)
3.3
(Estimated)
REFERENCE

van der Veen and de Boer, 2012
OECD, 2009; ECHA, 2012
EPIv4.11
EC, 2000
ECHA, 2012
EPIv4.11
DATA QUALITY
product Amgard V6. Value
inconsistent with result expected
for this chemical; high vapor
pressure attributed to volatile
impurities in the commercial
product.
Reported in a secondary source.
Reported in a secondary source
for the commercial product
Antiblaze V6.

Qualitative value reported in a
secondary source with limited
details.
Reported in a secondary source
for the commercial product
Antiblaze V6.

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JUNE 2014 DRAFT REPORT
V6 CASRN 38051-10-4
PROPERTY/ENDPOINT
Flammability (Flash Point)
Explosivity
Pyrolysis
pH
pKa
DATA
Flash point: 191°C Closed cup; GLP
study in compliance with EU Method
A. 9 of Commission Directive 92/69/EEC
and OECD/GD(92)32
literature value of >230°C using
Cleveland Open Cup, atmospheric
pressure 100.39 kPa, corrected flash
point 191.215°C (Measured)
Auto flammability: >400°C at 100 kPa
GLP study in compliance with EU
Method A. 15 of Commission Directive
92/96/EEC and OECD (92)32;
performed at 15-20°C, atmospheric
pressure 100. 30 to 100.99 kPa
(Measured)
Not expected to form explosive mixtures
with air (Estimated)

Not applicable (Estimated)
Not applicable (Estimated)
REFERENCE
EC, 2000; ECHA, 2012
^
EC, 2000; ECHA, 2012
Professional judgment

Professional judgment
Professional judgment
DATA QUALITY
Reporting in a Secondary source
for the commercial product
Amgard V6.
Reported in a secondary source.
No experimental data located;
aased on its use as a flame
retardant.
No data located.
Does not contain functional
groups that are expected to ionize
under environmental conditions.
Does not contain functional
groups that are expected to ionize
under environmental conditions.
         7-737

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JUNE 2014 DRAFT REPORT
V6 CASRN 38051-10-4
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
HUMAN HEALTH EFFECTS
Toxicokinetics
Dermal Absorption in vitro
Absorption,
Distribution,
Metabolism &
Excretion
Oral, Dermal or Inhaled
Other
Absorption of Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-
chloroethyl) ester (V6) from the gastrointestinal tract is nearly 100% following oral exposure in rats. V6
and metabolites are distributed throughout the body. Excretion occurred via the biliary route (60%), in
urine (20%) and as exhaled 14CO2. Absorption of V6 via the dermal route in human skin membranes was
low (0.51% and 6% for undiluted V6 or in an ethanol vehicle, respectively). No inhalation studies were
located.
In vitro dermal absorption study in
human skin membranes; the delivery of
undiluted V6 and V6 in ethanol (0.2
mg/cm3) was 0.51% and 6%,
respectively.
Oral administration of 14C labeled 2,2-
Bis(chloromethyl)trimethylene bis(bis(2-
chloroethyl)phosphate (V6) in the rat.
Bioavailability was > 100% at the low
dose (15 mg/kg) and ~ 50% at the high
dose (600 mg/kg). Complete absorption
from the gastrointestinal tract at 15
mg/kg. Elimination half-life was 99 -
113 hours; excretion via the biliary route
(60%) and urine (20%) with the
remainder exhaled as 14CO2. V6 and
metabolites were distributed throughout
the body (no target organs); four major
metabolites were identified in feces.

EU, 2008b; OECD, 2009
^^^
EU, 2008b; OECD, 2009

Study details reported in a
secondary source. Study was
conducted in accordance with
OECD Guideline 428 and to GLP.
Study details reported in a
secondary source. Study was
conducted in accordance with
OECD Guideline 417 and to GLP.
No data located.
         7-738

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JUNE 2014 DRAFT REPORT
V6 CASRN 38051-10-4
PROPERTY/ENDPOINT
Acute Mammalian Toxicity
Acute Lethality
Oral
Dermal
Inhalation
Carcinogenicity

OncoLogic Results
Carcinogenicity (Rat and
Mouse)
DATA
REFERENCE
DATA QUALITY
LOW: Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl)
ester (V6) is not acutely toxic via the oral or inhalation routes of exposure in rats or via the dermal route
of exposure in rabbits.
Rat oral LD50 = between 2,000 - 5,000
mg/kg
Mortality (all within 48 hours of dosing)
was 1/10 at the low dose and 8/10 at the
high dose
Rat oral LD50 >2,000 mg/kg
Rabbit dermal LD50 >2,000 mg/kg
Rat inhalation (snout only) 4 -hour LC50
>1.65 mg/L (highest attainable aerosol
concentration)
EU, 2008b (as cited in OECD,
2009)
Submitted confidential study
Submitted confidential study (as
cited in EU, 2008b; OECD, 2009)
Submitted confidential study (as
cited in EU, 2008b; OECD, 2009)
Study details reported in a
secondary source. Study
conformed to OPPTS or OECD
guidelines except that survivors
were not necropsied.
Test substance purity and
composition not specified;
conducted according to OECD
401.
Study details reported in a
secondary source. Study was
conducted to OECD Guideline
402.
Study details reported in a
secondary source and in a
confidential study submitted to
EPA. Study was conducted in
accordance with OECD Guideline
403.
MODERATE: Based on the weight of evidence. There were no Carcinogenicity studies located for
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester
(V6), however; there was no evidence of mutagenicity from genotoxicity studies. The OncoLogic
program estimated a Low-Moderate concern for Carcinogenicity and there was an increase in benign
tumors of the adrenal cortex and liver in a 2-year study with an analog chemical 2-Propanol, 1,3-
dichloro-, phosphate (CASRN 13674-87-8). Due to concerns based on structure and analogs, a moderate
hazard designation is warranted.
Low-moderate concern

OncoLogic, 2008


^o data located.
         7-739

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JUNE 2014 DRAFT REPORT
V6 CASRN 38051-10-4
PROPERTY/ENDPOINT

Combined Chronic
Toxicity/Carcinogenicity
Other
Genotoxicity

Gene Mutation in vitro
Gene Mutation in vivo
DATA
In a 2-year combined oral chronic
toxicity and carcinogenicity assay,
Sprague-Dawley rats (60/sex/group)
were fed diets that provided doses of
containing 0, 5, 20, and 80 mg/kg-day of
the analog 2-Propanol, 1,3-dichloro-,
phosphate. Increased benign tumors of
the adrenal cortex in high-dose females,
and hepatocellular adenomas in high-
dose males and females, interstitial cell
tumors in the testes of high -dose males,
and renal cortical adenomas in mid- and
high -dose males and females. at 20 and
80 mg/kg-day.
(Estimated by analogy)

REFERENCE
Freudenthal and Henrich, 2000
^
r

DATA QUALITY
Estimated based on analogy to 2-
Propanol, 1,3-dichloro-, phosphate
(CASRN 13674-87-8). TheNRC
(2000) concluded that this study
provides sufficient evidence of
carcinogenicity of TDCPP in rats
following chronic oral exposure.
Test substance purity: 95%; The
mode of action for carcinogenicity
could not be determined.
No data located.
LOW: Based on no evidence of mutagenicity in either in vitro or in vivo genotoxicity studies.
Negative, gene mutations in mouse
lymphoma cells with and without
metabolic activation.
Negative, Salmonella typhimurium
strains TA98 and TA100 with or without
metabolic activation
J
Negative, Salmonella typhimurium
strains TA 1535, TA1537, TA98 and
TA100 with or without metabolic
activation

King, 1993 (as cited in OECD,
2009)
EC, 2000; OECD, 2009
Submitted confidential study

Study was conducted in
accordance with OECD Guideline
476; however, no information was
provided regarding positive
controls.
Study details reported in a
secondary source. Study was
conducted in accordance with
OECD Guideline 471 and GLP.
Study details reported in a
confidential study submitted to
EPA; test substance purity: 92.3%
""Jo data located.
         7-740

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JUNE 2014 DRAFT REPORT
V6 CASRN 38051-10-4
PROPERTY/ENDPOINT

Chromosomal Aberrations in
vitro
Chromosomal Aberrations in
vivo
DNA Damage and Repair
Other
Reproductive Effects

Reproduction/Developmental
Toxicity Screen
Combined Repeated Dose with
Reproduction/ Developmental
Toxicity Screen ^^^
DATA
Negative, chromosomal aberrations in
cultured human lymphocytes with and
without metabolic activation; Positive
controls yielded expected responses.
Negative, micronucleus formation in
bone marrow of mice exposed by to two
oral treatments (oral gavage) at a 24-
hour interval to 500, 1,000, or 2,000
mg/kg-day (males); 437.5, 875, 1,750
mg/kg-day. Positive controls yielded
expected responses.


REFERENCE
EC, 2000; OECD, 2009
Submitted confidential study (as
cited in OECD, 2009)
r*


DATA QUALITY
Study details reported in a
secondary source. Study was
conducted in accordance with
OECD Guideline 473and GLP.
Study details reported in a
secondary source and in a
submitted confidential study.
Study was conducted in
accordance with OECD Guideline
474.
^o data located.
No data located.
MODERATE: Based on weight of evidence from multiple studies. Phosphoric acid, P,P'-[2,2-
bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester (V6) did not produce
reproductive toxicity in an oral 2-generation reproductive study or in a 4-week gavage study in rats at
doses up to 600 mg/kg-day (LOAELs were not established). Data using the analog 2-Propanol, 1,3-
dichloro-, phosphate reported a LOAEL of 5 mg/kg-day (NOAEL not established) for atrophy and
decreased secretory product of the seminal vesicle in an oral two-year combined chronic toxicity and
carcinogenicity assay in rats. A 12-week fertility study in rabbits using the analog 2-Propanol, 1,3-
dichloro-, phosphate reported a NOAEL of 200 mg/kg-day; there is uncertainty if reproductive effect
could occur at a dose up to 250 mg/kg-day (the cutoff for the Moderate hazard designation criteria
range).




No data located.
No data located.
         7-741

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                                               JUNE 2014 DRAFT REPORT
                                                   V6 CASRN 38051-10-4
PROPERTY/ENDPOINT
               DATA
        REFERENCE
       DATA QUALITY
      Reproduction and Fertility
      Effects
In an oral 2-generation reproductive
toxicity study, rats (28/sex) were fed
diets containing the test chemical 2,2-
Bis(chloromethyl)trimethylene bis(bis(2-
chloroethyl)phosphate (0, 29, 86 or 262
mg/kg-day for males and 0, 33, 97 or
302 mg/kg-day for females). No effects
on the male and female reproductive
systems up to the highest doses tested.

NOAEL (fertility): 262 and 302 mg/kg-
day for males and females, respectively
(highest dose tested)
LOAEL: Not established
EU, 2008a; OECD, 2009
Study details reported in a
secondary source. Study was
conducted in accordance with
OECD Guideline 416; however,
corpora lutea were not counted at
scheduled sacrifice, which
represented a deviation from the
guideline.
                                     In a 12-week oral fertility study, rabbits
                                     (10 males/dose) were gavaged with 0, 2,
                                     20, or 200 mg/kg-day of the analog 2-
                                     Propanol, 1,3-dichloro-, phosphate.
                                     Males were treated for  12 weeks, then
                                     mated with untreated females. There
                                     were no alterations in mating behavior,
                                     fertility, or sperm quantity or quality.
                                     Neither gross necropsy nor microscopic
                                     examinations showed significant
                                     alterations in the reproductive tract.

                                     NOAEL: 20 mg/kg-day
                                     LOAEL: 200 mg/kg-day (highest dose
                                     tested)
                                     (Estimated by analogy)
                                     Wilczynski et al., 1983; ATSDR,
                                     2012
                               Study details were available in the
                               secondary source. Estimated by
                               analogy to 2-Propanol, 1,3-
                               dichloro-, phosphate (CASRN
                               13674-87-8). Data not sufficient
                               to satisfy the reproductive toxicity
                               endpoint since it was described
                               only in an abstract and there was a
                               lack of information in female
                               animals. This limits the usefulness
                               of the study for risk assessment.
                                                           7-742

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                                              JUNE 2014 DRAFT REPORT
                                                  V6 CASRN 38051-10-4
PROPERTY/ENDPOINT
               DATA
        REFERENCE
       DATA QUALITY
      Other
A confidential, 4-week repeated-dose
oral gavage study in rats was submitted.
No histopathology was found in the
reproductive organs in either sex at a
NOAEL of 600 mg/kg-day of the test
chemical; however, the study duration
was relatively short and reproductive
function was not tested.

NOAEL: 600 mg/kg-day (highest dose
tested)
LOAEL: Not established
Submitted confidential study
Study was conducted in
accordance with OECD Guideline
407
                                    Rat, oral, 2-year combined chronic
                                    toxicity and carcinogenicity assay; Rats
                                    (60/sex/group) were administered 0, 5,
                                    20, 80 mg/kg-day (in the diet) of the
                                    analog 2-Propanol, 1,3-dichloro-,
                                    phosphate for 2 years. Ten rats/sex/dose
                                    were randomly chosen for termination at
                                    12 months; the remainder at 24 months.
                                    Reproductive effects in males included
                                    effects on seminal vesicles (atrophy,
                                    decreased secretory product) at = 5
                                    mg/kg-day, testes (eosinophilic material
                                    in lumen, periarteritis nodosa) at = 20
                                    mg/kg-day, and epididymis
                                    (oligospermia and degenerated seminal
                                    product) at 80 mg/kg-day.

                                    NOAEL: Not established
                                    LOAEL:  5 mg/kg-day
                                     Freudenthal and Henrich, 2000
                              Estimated by analogy to 2-
                              Propanol, 1,3-dichloro-, phosphate
                              (CASRN 13674-87-8); Fertility
                              was not assessed in the study. The
                              authors reported the lowest dose
                              of 5 mg/kg-day as a NOAEL and
                              the mid-dose of 20 mg/kg-day as a
                              LOAEL.  However, as evaluated in
                              NRC (2000), the lowest dose of 5
                              mg/kg-day was a LOAEL for
                              atrophy and decreased secretory
                              product of the seminal vesicle; test
                              substance purity: 95%; These
                              effects for reproductive tissues are
                              reported from a 2-year combined
                              chronic toxicity and
                              carcinogenicity assay, and not
                              from a study designed to test
                              reproductive effects specifically;
                              other reproductive parameters
                              were not  examined.
                                                          7-743

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JUNE 2014 DRAFT REPORT
V6 CASRN 38051-10-4
PROPERTY/ENDPOINT
Developmental Effects

Reproduction/ Developmental
Toxicity Screen
DATA
REFERENCE
DATA QUALITY
HIGH: Based on a NOAEL of 29 mg/kg-day (LOAEL of 86 mg/kg-day) for increased number of runts
and decreased pup weight in an oral 2-generation study in rats. No developmental NOAEL/LOAEL
could be established in a prenatal toxicity study in rats due to low survival of dams.
There were no data located for the developmental neurotoxicity endpoint. Uncertain concern for the
developmental neurotoxicity based on the potential for Cholinesterase (ChE) inhibition in dams that
may result in alterations of fetal neurodevelopment.

|No data located.
         7-744

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                                              JUNE 2014 DRAFT REPORT
                                                  V6 CASRN 38051-10-4
PROPERTY/ENDPOINT
               DATA
        REFERENCE
       DATA QUALITY
      Combined Repeated Dose with
      Reproduction/ Developmental
      Toxicity Screen
In an oral 2-generation reproductive
toxicity study, rats were fed diets
containing 2,2-
Bis(chloromethyl)trimethylene bis(bis(2-
chloroethyl)phosphate (the overall intake
of V6 was (0, 29, 86 or 262 mg/kg-day
for males and 0, 33, 97 or 302 mg/kg-
day for females).
Increased number of runts on post-natal
day one and decrease in pup weights in
mid- and high-dose groups of both
generations. Decreased absolute spleen
weight in high dose FO pups and in all
treated Fl pups; decreased relative
spleen weight (high dose Fl pups),
decreased absolute brain weight but
increase in relative liver weights (all
treated Fl pups), decreased absolute
thymus weights (low and high dose  Fl
pups).

Maternal toxicity:
NOAEL: 33 mg/kg-day
LOAEL: 97 mg/kg-day

Developmental toxicity:
NOAEL: 29 and 33 mg/kg-day for males
and females, respectively
LOAEL: 86 and 97 mg/kg-day for males
and females, respectively (based on
increased number of runts and decreased
pup weight)
EU, 2008b; OECD, 2009
Study details reported in a
secondary source. Study was
conducted in accordance with
OECD Guideline 416; however,
corpora lutea were not counted at
scheduled sacrifice, which
represented a deviation from the
guideline.
                                                          7-745

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JUNE 2014 DRAFT REPORT
V6 CASRN 38051-10-4
PROPERTY/ENDPOINT































Prenatal Development






























DATA
Pregnant rats (5/group) were orally
gavaged with 0, 100, 200, 400, 800, and
1,600 mg/kg-day Phosgard 2XC20
(CASRN 3805 1-10-4) on GD 6-19.
Uterine examinations were conducted on
GD20.
Maternal toxicity occurred at the three
highest doses. One rat at 800 mg/kg and
all rats at 1,600 mg/kg died between GD
7 and 9, the cause of death was not
determined. Clinical signs of toxicity in
dams included dry red matter around the
nose and forepaws (400 and 800 mg/kg-
day) and staining of the anogenital area
(800 mg/kg-day). Reduced maternal
body weight (800 mg/kg-day). No
biologically significant differences in the
mean numbers of viable fetuses, post
implantation loss, early or late
resorption, total implantations or corpora
lutea. A slight increase in mean post
implantation losses at 800 mg/kg-day
was similar to historical controls.
Maternal toxicity:
NOAEL: 400 mg/kg-day
LOAEL: 800 mg/kg-day (based on
clinical signs and increased mortality)
Fetal toxicity:
NOAEL: 800 mg/kg-day
LOAEL: 1,600 mg/kg-day
Pregnant Sprague-Dawley rats (20/dose)
REFERENCE
Condray, 1990




^



^^




















Kappetal., 1981
DATA QUALITY
Limited study details of a pilot rat
teratology study provided in
secondary source (no quantitative
data were shown). Adequate
primary source. The small group
size (four surviving dams)
prevents the identification of fetal
NOAEL/LOAEL values. In
addition, the only fetal effect
(marginal increase in
postimplantation loss) occurred at
a maternally toxic dose.


















Estimated by analogy to 2-
         7-746

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JUNE 2014 DRAFT REPORT
V6 CASRN 38051-10-4
PROPERTY/ENDPOINT









Postnatal Development
Prenatal and Postnatal
Development ^ "^^
Developmental Neurotoxicity
Other
DATA
were gavaged with 0, 25, 100, and 400
mg/kg-day of analog 2-Propanol, 1,3-
dichloro-, phosphate on GD 6-15. Dams
were sacrificed on Gd 19. No effect on
implantation efficiency or mean number
of corpora lutea. Increased the number of
resorptions and reduced fetal viability at
the high dose.
Maternal toxicity:
NOAEL: 25 mg/kg-day
LOAEL: 100 mg/kg-day (clinical signs
and transient reduction in body weight
gain)
Fetal toxicity:
NOAEL: 100 mg/kg-day
LOAEL: 400 mg/kg-day (increased
resorption and fetal mortality)
(Estimated by analogy)



Uncertain concern for developmental
neurotoxicity based on the potential for
Cholinesterase (ChE) inhibition in dams
that may result in alterations of fetal
neurodevelopment (Estimated)

REFERENCE

^
r




Professional judgment

DATA QUALITY
Propanol, 1,3-dichloro-, phosphate
(CASRN 13674-87-8)



No data located.
No data located.

Estimated based on a structural
alert for organophosphates for the
neurotoxicity endpoint.
No data located.
         7-747

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                                                          JUNE 2014 DRAFT REPORT
                                                              V6 CASRN 38051-10-4
            PROPERTY/ENDPOINT
               DATA
        REFERENCE
       DATA QUALITY
Neurotoxicity
LOW: Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl)
ester (V6) was not neurotoxic to rats in a 4-week gavage study at doses up to 600 mg/kg-day (LOAEL not
established). The only effect in several acute studies in rats was depressed serum cholinesterase activity
following oral gavage of 250-1,500 mg/kg-day. In addition, no changes indicative of neurotoxicity were
observed in an acute and a 90-day delayed neurotoxicity study in hens gavaged with analog chemical 2-
Propanol, 1,3-dichloro-, phosphate (CASRN 13674-87-8).
                  Neurotoxicity Screening
                  Battery (Adult)
                  Other
In a 4-week repeated-dose oral gavage
study in rats included a neurotoxicity
screening battery. No behavioral effects
or neurohistopathology were found at the
highest dose tested.

NOAEL: 600 mg/kg-day (the highest
dose tested)
LOAEL: Not established
In several acute rat studies,
cholinesterase activity was depressed
following oral gavage of 250 - 1,500
mg/kg test substance. In rabbits dermally
administered 2,000 mg/kg test substance,
no significant suppression of
cholinesterase activity was measured in
serum, whole blood or the brain within
24 hours.
                                                NOAEL: Not established
                                                LOAEL: 250 mg/kg (by oral gavage)
                                                based on cholinesterase activity
                                                In an acute oral and a 90-day delayed
                                                neurotoxicity study in hens gavaged with
                                                2-Propanol, 1,3-dichloro-, phosphate,
                                                there was no inhibition of brain
                                                neurotoxic esterase (NTE) activity at a
Submitted confidential study; EU,
2008b
Submitted confidential study; EU,
2008b
                                     Morey et al., 1978
Study details reported in a
secondary source. Study
conducted to OECD guideline 424
(neurotoxicological investigation).
Limited study details reported.
                               Estimated by analogy to 2-
                               Propanol, 1,3-dichloro-, phosphate
                               (CASRN 13674-87-8).
                                                                      7-748

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                                                        JUNE 2014 DRAFT REPORT
                                                            V6 CASRN 38051-10-4
           PROPERTY/ENDPOINT
              DATA
REFERENCE
DATA QUALITY
                                              dose of 10,000 mg/kg-day and no
                                              behavioral effects or histopathological
                                              changes indicative of neurotoxicity at
                                              doses up to 100 mg/kg-day.

                                              NOAEL: Not established
                                              LOAEL: 10,000 mg/kg-day
                                              (Estimated by analogy)
Repeated Dose Effects
MODERATE: Based on a NOAEL of 29 mg/kg-day (LOAEL= 86 mg/kg-day) for liver and thyroid
weight changes and associated histopathology in an oral 2-generation study in rats. Liver effects were
also observed in rats at a dose of 150 mg/kg-day following oral administration for 28 days (NOAEL = 15
mg/kg-day). No neurological effects were reported in a 4-week repeated-dose oral study in rats at a dose
of 600 mg/kg-day (highest dose tested). In a 2-year combined oral chronic toxicity and carcinogenicity
study in rats using analog chemical, 2-Propanol, 1,3-dichloro-, phosphate (CASRN 13674-87-8), a
LOAEL of 5 mg/kg-day (lowest dose tested) was established for anomalies of the liver, kidneys, testes,
renal cortex, and adrenal cortex.
                                                                   7-749

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                                               JUNE 2014 DRAFT REPORT
                                                   V6 CASRN 38051-10-4
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                     In an oral 2-generation reproductive
                                     toxicity study, rats (28/sex) were fed
                                     diets containing 2,2-
                                     Bis(chloromethyl)trimethylene bis(bis(2-
                                     chloroethyl)phosphate over 2 successive
                                     generations (approximately 0, 29, 86 or
                                     262 mg/kg-day for males and 0, 33, 97
                                     or 302 mg/kg-day for females).
                                     Increased absolute and relative thyroid
                                     weight, accompanied by follicular
                                     hypertrophy and a reduction in colloid in
                                     males (FO generation, mid- and high
                                     dose); increased absolute and relative
                                     liver weight (both generations)
                                     accompanied by hepatocyte hypertrophy
                                     (FO generation).

                                     NOAEL (parental): 29  and 33 mg/kg-
                                     day for males and females, respectively
                                     LOAEL (parental):  86 and 97 mg/kg-day
                                     for males and females,  respectively
                                     (based on liver and thyroid weight
                                     changes and histopathology in mid- and
                                     high-dose groups)
                      EU, 2008a; OECD, 2009
                       Study details reported in a
                       secondary source. Study was
                       conducted in accordance with
                       OECD Guideline 416.
                                     In a 2 8-day oral study, V6 was
                                     administered to rats via gavage at doses
                                     of 0, 15, 150, or 600 mg/kg-day.
                                     Increased relative and absolute liver
                                     weight, hepatocellular hypertrophy and
                                     centrilobular hypertrophy (150 and 600
                                     mg/kg-day);  significantly increased
                                     cholesterol levels, increases in absolute
                                     and relative thyroid weight, increased
                      Submitted confidential study (as
                      cited in EU, 2008b; OECD, 2009)
                       Study details reported in a
                       secondary source with more
                       details provided in a submitted
                       confidential study. Study was
                       conducted in accordance with
                       OECD Guideline 407 and 424
                       (neurotoxicological investigation).
                                                           7-750

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                                              JUNE 2014 DRAFT REPORT
                                                  V6 CASRN 38051-10-4
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                    prothrombin time (600 mg/kg-day);

                                    NOAEL: 15 mg/kg-day
                                    LOAEL: 150 mg/kg-day (based on liver
                                    effects)
                                    A 4-week repeated-dose oral gavage
                                    study in rats included a neurotoxicity
                                    screening battery. No behavioral effects
                                    or neurohistopathology were found at the
                                    highest dose tested.

                                    NOAEL: 600 mg/kg-day (the highest
                                    dose tested)
                                    LOAEL: Not established
                      Submitted confidential study; EU.
                      2008b
                      Study details reported in a
                      secondary source. Study
                      conducted to OECD guideline 424
                      (neurotoxicological investigation)
                                    In a 2-year combined oral chronic
                                    toxicity and carcinogenicity assay,
                                    Sprague-Dawley rats (60/sex/group)
                                    were fed diets containing 0, 5, 20, and 80
                                    mg/kg-day of analog 2-Propanol, 1,3-
                                    dichloro-, phosphate. Increased
                                    mortality, decreased body weight,
                                    anomalies of the liver, kidneys, testes,
                                    renal cortex, and adrenal cortex.

                                    NOAEL: Not established
                                    LOAEL: 5 mg/kg-day (based on atrophy
                                    and decreased secretory product of the
                                    seminal vesicle; hyperplasia of
                                    convoluted tubule epithelium in males at
                                    24 months)
                                    (Estimated by analogy)
                      Freudenthal and Henrich, 2000
                      Estimated by analogy to 2-
                      Propanol, 1,3-dichloro-, phosphate
                      (CASRN 13674-87-8)
                                                          7-751

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JUNE 2014 DRAFT REPORT
V6 CASRN 38051-10-4
PROPERTY/ENDPOINT
Skin Sensitization

Skin Sensitization
Respiratory Sensitization
(Respiratory Sensitization
DATA
REFERENCE
DATA QUALITY
LOW: Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl)
ester (V6) did not produce dermal Sensitization in guinea pigs or in human volunteers. A single
submitted confidential study reported mild skin Sensitization in 17% of tested guinea pigs; however,
these data could not be validated.
In a maximization test in guinea pigs (20
test animals and 10 controls) treated
intradermally with diluted V6, induced
topically with neat material, and
challenged with both neat and diluted
test material, V6 lacked significant skin
Sensitization potential.
Not sensitizing to humans following 6
days of treatment and a 48-hour
challenge application
Mild skin Sensitization, guinea pigs
(17% of animals showing positive
results, no further details provided) in a
Magnusson and Kligman Maximization
study; intradermal induction: 5% w/v in
6% acetone v/v in arachis oil B.P.;
topical induction: undiluted as supplied;
topical challenge: undiluted as supplied
and 75% v/v in acetone., no further
details provided)
EU, 2008b; OECD, 2009
r
Submitted confidential study
Submitted confidential study
Study details reported in a
secondary source. Study was
conducted in accordance with
OECD Guideline 406.
Limited study details reported.
Study details from reported in a
confidential study; purity of
supplied test substance not
specified.
No data were located.

|No data located.
         7-752

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JUNE 2014 DRAFT REPORT
V6 CASRN 38051-10-4
PROPERTY/ENDPOINT
Eye Irritation

Eye Irritation
Dermal Irritation

Dermal Irritation
DATA
REFERENCE
DATA QUALITY
LOW: Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl)
ester (V6) produced slight conjunctival irritation in rabbits which resolved within 24 or 48 hours.
Not irritating, rabbits (n=3). Monitoring
of ocular damage/irritation was done for
up to 72 hours after instillation of 0. 1
mL of V6. No corneal or iridial
response; slight conjunctival redness in
one rabbit 24 hours post-instillation
which was reversible within 48 hours.
Not irritating, rabbits (n=3). Monitoring
of ocular damage/irritation was done for
up to 72 hours after instillation of 0. 1
mL of V6. No corneal or iridial
response. Minimal conjunctival irritation
was noted in all treated eyes 1 hour post-
instillation. All treated eyes appeared
normal 24 hours post-treatment.
classified as non-irritating
EC, 2000
Submitted confidential study (as
cited in EU, 2008b)
Study details reported in a
secondary source. Study was
conducted in accordance with
OECD Guideline 405 and GLP.
Study details reported in a
submitted confidential study;
conducted according to OECD
405; test substance purity not
specified.
LOW: Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl)
ester (V6) produced slight irritation (erythema, but no edema) in rabbits which resolved within 48 or 72
hours.
Slightly irritating to the intact skin of
rabbits (n=3) after semi -occluded
application of 0.5 mL V6 for 4 hours.
Slight irritation (erythema but no edema)
in rabbits following a 4-hour semi-
occluded exposure to 0.5 g of V6. All
treated skin sites had returned to normal
by 24 hours post-treatment
4-hour semi-occluded application to 0.5
g of V6;
EU, 2008b
Submitted confidential study (as
cited in EU, 2008b)
Submitted confidential study (as
cited in EU, 2008b)
Study details reported in a
secondary source. Study was
conducted in accordance with
OECD Guideline 404 and GLP.
Study details reported in a
secondary source and a submitted
confidential study. Study was
conducted in accordance with
OECD Guideline 404 and GLP.
Study details reported in a
submitted confidential study and a
         7-753

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                                              JUNE 2014 DRAFT REPORT
                                                  V6 CASRN 38051-10-4
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                    Not irritating, rabbits. Barely perceptible
                                    irritation (erythema) was detected in 2/3
                                    females at 26 hours, but in none at 72
                                    hours
                                    classified as mild irritant
                                    Produced a primary irritation index of
                                    1.2 and was classified as a mild irritant
                                    to rabbit skin according to the Draize
                                    classification scheme. No corrosive
                                    effects were noted.
                                                    secondary source; conducted
                                                    according to OECD 404; The test
                                                    material did not produce positive
                                                    criteria in any rabbit according to
                                                    the EEC labeling regulations and
                                                    was classified as Non-irritant to
                                                    rabbit skin. No symbol and risk
                                                    phrase are required; test substance
                                                    purity and formulation was not
                                                    reported.
                                                          7-754

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                                                          JUNE 2014 DRAFT REPORT
                                                              V6 CASRN 38051-10-4
            PROPERTY/ENDPOINT
               DATA
REFERENCE
DATA QUALITY
Endocrine Activity
There were thyroid weight changes and associated histopathology in an oral 2-generation study in rats
and there was an increase in benign tumors of the adrenal cortex and liver in a 2-year study with an
analog chemical 2-Propanol, 1,3-dichloro-, phosphate (CASRN 13674-87-8).
                                                In an oral 2-generation reproductive
                                                toxicity study, rats (28/sex) were fed
                                                diets containing 2,2-
                                                Bis(chloromethyl)trimethylene bis(bis(2-
                                                chloroethyl)phosphate over 2 successive
                                                generations (approximately 0, 29, 86 or
                                                262 mg/kg-day for males and 0, 33, 97
                                                or 302 mg/kg-day for females).
                                                Increased absolute and relative thyroid
                                                weight,  accompanied by follicular
                                                hypertrophy and a reduction in colloid in
                                                males (FO generation, mid- and high
                                                dose); increased absolute and relative
                                                liver weight (both generations)
                                                accompanied by hepatocyte hypertrophy
                                                (FO generation). NOAEL (parental): 29
                                                and 33 mg/kg-day for males and
                                                females, respectively LOAEL (parental):
                                                86 and 97 mg/kg-day for males and
                                                females, respectively (based on liver and
                                                thyroid weight changes and
                                                histopathology in mid- and high-dose
                                                groups).
                                                In a 2 8-day oral study, V6 was
                                                administered to rats via gavage at doses
                                                of 0, 15, 150, or 600 mg/kg-day.
                                                Increased relative and absolute liver
                                                weight, hepatocellular hypertrophy and
                                                centrilobular hypertrophy (150 and 600
                                                mg/kg-day); significantly increased
                                     EU, 2008b
                                     Submitted confidential study (as
                                     cited in EU, 2008b; OECD, 2009)
                      Study details reported in a
                      secondary source. Study was
                      conducted in accordance with
                      OECD Guideline 416.
                      Study details reported in a
                      secondary source with more
                      details provided in a submitted
                      confidential study. Study was
                      conducted in accordance with
                      OECD Guideline 407 and 424
                      (neurotoxicological investigation).
                                                                      7-755

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                                               JUNE 2014 DRAFT REPORT
                                                   V6 CASRN 38051-10-4
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                     cholesterol levels, increases in absolute
                                     and relative thyroid weight, increased
                                     prothrombin time (600 mg/kg-day);
                                     NOAEL: 15 mg/kg-day LOAEL: 150
                                     mg/kg-day (based on liver effects)
                                     In a 2-year combined oral chronic
                                     toxicity and carcinogenicity assay,
                                     Sprague-Dawley rats (60/sex/group)
                                     were fed diets containing 0, 5, 20, and 80
                                     mg/kg-day 2-Propanol, 1,3-dichloro-,
                                     phosphate. Increased mortality,
                                     decreased body weight, anomalies of the
                                     liver, kidneys, testes, renal cortex, and
                                     adrenal cortex. NOAEL: Not established
                                     LOAEL: 5 mg/kg-day (based on atrophy
                                     and decreased secretory product of the
                                     seminal vesicle; hyperplasia of
                                     convoluted tubule epithelium in males at
                                     24 months) (Estimated by analogy)
                      Freudenthal and Henrich, 2000
                      Estimated by analogy to 2-
                      Propanol, 1,3-dichloro-, phosphate
                      (CASRN 13674-87-8).
                                     In an oral 2-generation reproductive
                                     toxicity study, rats (28/sex) were fed
                                     diets containing 2,2-
                                     Bis(chloromethyl)trimethylene bis(bis(2-
                                     chloroethyl)phosphate over 2 successive
                                     generations (approximately 0, 29, 86 or
                                     262 mg/kg-day for males and 0, 33, 97
                                     or 302 mg/kg-day for females).
                                     Increased absolute and relative thyroid
                                     weight, accompanied by follicular
                                     hypertrophy and a reduction in colloid in
                                     males (FO generation, mid- and high
                                     dose); increased absolute and relative
                                     liver weight (both generations)
                      EU, 2008a; OECD, 2009
                       Study details reported in a
                       secondary source. Study was
                       conducted in accordance with
                       OECD Guideline 416.
                                                           7-756

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                                              JUNE 2014 DRAFT REPORT
                                                  V6 CASRN 38051-10-4
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
                                    accompanied by hepatocyte hypertrophy
                                    (FO generation).

                                    NOAEL (parental): 29 and 33 mg/kg-
                                    day for males and females, respectively
                                    LOAEL (parental): 86 and 97 mg/kg-day
                                    for males and females, respectively
                                    (based on liver and thyroid weight
                                    changes and histopathology in mid- and
                                    high-dose groups)
                                    In a 2-year combined oral chronic
                                    toxicity and carcinogenicity assay,
                                    Sprague-Dawley rats (60/sex/group)
                                    were fed diets that provided doses of
                                    containing 0, 5, 20, and 80 mg/kg-day 2-
                                    Propanol, 1,3-dichloro-, phosphate.
                                    Increased benign tumors of the adrenal
                                    cortex in high-dose females, and
                                    hepatocellular adenomas in high-dose
                                    males and females, interstitial cell
                                    tumors in the testes of high-dose males,
                                    and renal cortical adenomas in mid- and
                                    high-dose males and females at 20 and
                                    80 mg/kg-day. (Estimated by analogy)
                     Freudenthal and Henrich, 2000
                      Estimated by analogy to 2-
                      Propanol, 1,3-dichloro-, phosphate
                      (CASRN 13674-87-8).
                                                          7-757

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JUNE 2014 DRAFT REPORT
V6 CASRN 38051-10-4
PROPERTY/ENDPOINT
Immunotoxicity

Immune System Effects
DATA
REFERENCE
DATA QUALITY
Decreased absolute and relative spleen weights and decreased absolute thymus weights were observed in
pups in an oral 2-generation reproductive toxicity study in rats.
In an oral 2-generation reproductive
toxicity study, rats were fed diets
containing 2,2-
Bis(chloromethyl)trimethylene bis(bis(2-
chloroethyl)phosphate (the overall intake
of V6 was (0, 29, 86 or 262 mg/kg-day
for males and 0, 33, 97 or 302 mg/kg-
day for females). Decreased absolute
spleen weight in high dose FO pups and
in all treated Fl pups; decreased relative
spleen weight in high dose Fl pups.
Decreased absolute thymus weights in
low and high dose Fl pups.
EU, 2008b; OECD, 2009
r

ECOTOXICITY
ECOSAR Class
Acute Aquatic Toxicity
Fish LC50

MODERATE: Based on experimental fish acute LC50 of 52 and a daphnid EC50 of 42 mg/L. Phosphoric
acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester (V6) is not
acutely toxic to algae according to experimental studies.
Freshwater fish (Oncorhynchus mykiss)
96-hour LC50 = 52 mg/L
96-hour NOEC=3 8 mg/L; measured
concentrations were generally within
20% of initial concentrations (semi-static
test conditions)
(Experimental)
Freshwater fish (Oncorhynchus mykiss)
96-hour LC50> 10 mg/L
NOEC > 10 mg/L
The study was conducted under
semistatic conditions
Submitted confidential study (as
cited in EU, 2008b; OECD, 2009)
EC, 2000
Limited study details reported in a
secondary source with more study
details reported in a submitted
confidential study; study was
conducted in accordance with
OECD Guideline 203 and GLP.
Limited study details reported in a
secondary source. Study was
conducted in accordance with
OECD Guideline 203 and GLP.
Analytical monitoring was not
         7-758

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                                                        JUNE 2014 DRAFT REPORT
                                                            V6 CASRN 38051-10-4
           PROPERTY/ENDPOINT
               DATA
        REFERENCE
       DATA QUALITY
                                               (Experimental)
                                                                 performed.
                                               Freshwater fish 96-hour LC50 = 86 mg/L
                                               (Estimated)
                                               ECOSAR: Neutral organics
                                    ECOSARvl.ll
                             ECOSAR also provided results for
                             the Esters, and Esters (phosphate)
                             classes; however, professional
                             judgment indicates that this
                             compound is not currently well
                             represented in ECOSAR v 1.11.
Daphnid LC50
Daphnia magna 4 8-hour EC50 > 10 mg/L
NOEC > 10 mg/L
(Experimental)
EC, 2000; EU, 2008b
Limited study details reported in a
secondary source. Study was
conducted in accordance with
OECD Guideline 202 and GLP.
Analytical monitoring was not
performed.
                                              Daphnia magna 4 8-hour EC50 = 42 mg/L
                                              48-hour NOEC=21 mg/L; the test was
                                              conducted under static conditions.
                                              Measured concentrations were stable
                                              within 20% of initial concentrations.
                                              (Experimental)
                                    Submitted confidential study (as
                                    cited in EU, 2008b; OECD, 2009)
                              Study details reported in a
                              secondary source with more
                              details provided in a submitted
                              confidential study. Study was
                              conducted in accordance with
                              OECD Guideline 202 and GLP.
                                              Daphnia magna 48-hour LC50 = 53 mg/L
                                              (Estimated)
                                              ECOSAR: Neutral organics
                                    ECOSARvl.ll
                             ECOSAR also provided results for
                             the Esters, and Esters (phosphate)
                             classes; however, professional
                             judgment indicates that this
                             compound is not currently well
                             represented in ECOSAR v 1.11.
Green Algae EC50
Green algae (Scenedesmus subspicatus)
76-hour EC50> 10 mg/L
NOEC > 10 mg/L
(Experimental)
EC, 2000
Limited study details reported in a
secondary source. Study was
conducted in accordance with
OECD Guideline 201 and GLP.
Analytical monitoring was not
performed.
                                               Green algae (Pseudokirchneriella
                                    Submitted confidential study (as
                              Study details reported in a
                                                                    7-759

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                                                         JUNE 2014 DRAFT REPORT
                                                             V6 CASRN 38051-10-4
           PROPERTY/ENDPOINT
               DATA
        REFERENCE
       DATA QUALITY
                                               subcapitata) 72-hour EC50(growth) = 21
                                               mg/L
                                               72-hour ErC50 (biomass) = 35 mg/L
                                               (static test conditions). Measured
                                               concentrations were stable within 20%
                                               of initial concentrations.
                                               (Experimental)
                                    cited in EU, 2008b; OECD, 2009)
                              secondary source with more study
                              details provided in a submitted
                              confidential study; Study was
                              conducted in accordance with
                              OECD Guideline 209 and GLP.
                                               Green algae 96-hour EC50= 54 mg/L
                                               (Estimated)
                                               ECOSAR: Neutral organics
                                    ECOSARvl.ll
                              ECOSAR also provided results for
                              the Esters, and Esters (phosphate)
                              classes; however, professional
                              judgment indicates that this
                              compound is not currently well
                              represented in ECOSAR v 1.11.
Chronic Aquatic Toxicity
HIGH: Estimated based the estimated chronic aquatic toxicity value for fish of 0.022 mg/L (ECOSAR
class: esters, phosphate). Experimental data indicate that 2,2-Bis(chloromethyl)trimethylene bis(bis(2-
chloroethyl)phosphate (V6) does not produce chronic toxicity to daphnia and algae; in the absence of
experimental data for fish, an estimated High hazard designation was assigned.
Fish ChV
Freshwater Fish ChV = 9.2 mg/L
(Estimated)
ECOSARvl.ll
ECOSAR also provided results for
the Esters, and Esters (phosphate)
classes; however, professional
judgment indicates that this
compound is not currently well
represented in ECOSAR v 1.11.
Daphnid ChV
Daphnia magna 23-day NOEC > 3.68
mg/L
Test duration extended to 23 days in
order to achieve validity criteria for
control reproduction. Some measured
concentrations were not within nominal
values, therefore, results analyzed and
expressed relative to geometric mean
concentrations over 23 days.
(Experimental)
Submitted confidential study; EU,
2008b; OECD, 2009
The limited study details reported
in a secondary source with more
study details provided in a
submitted confidential study
indicate that the test system may
have been compromised, and that
the study results may not be valid.
                                                                     7-760

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JUNE 2014 DRAFT REPORT
V6 CASRN 38051-10-4
PROPERTY/ENDPOINT

Green Algae ChV
DATA
Daphnia magna ChV > 6.4 mg/L
(Estimated)
ECOSAR: Neutral organics
Green algae (Pseudokirchneriella
subcapitata) 72-hour NOEC =10 mg/L
Limit test
(Experimental)
Green algae ChV =17 mg/L
(Estimated)
ECOSAR: Neutral organics
REFERENCE
ECOSAR v 1.11
Submitted confidential study (as
cited in EU, 2008b; OECD, 2009)
^^^
ECOSAR v 1.11
DATA QUALITY
ECOSAR also provided results for
the Esters, and Esters (phosphate)
classes; however, professional
judgment indicates that this
compound is not currently well
represented in ECOSAR v 1 . 1 1 .
Limited study details reported in a
secondary source with more study
details available in a submitted
confidential study; concentrations
were not measured; test not
subjected to GLP.
ECOSAR also provided results for
the Esters, and Esters (phosphate)
classes; however, professional
judgment indicates that this
compound is not currently well
represented in ECOSAR v 1 . 1 1 .
ENVIRONMENTAL FATE
Transport
Henry's Law Constant (atm-
m3/mole)
Level III fugacity models incorporating available physical and chemical property data indicate that at
steady state, phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-
chloroethyl) ester, is expected to be found primarily in soil and sediment. The general partitioning of this
chemical is toward solid phases and out of water, with limited degradation in soil and sediment
predicted. It is not expected to dissociate at environmentally-relevant pH values. Based on measured and
estimated K0c values, it is expected to have negligible mobility in soil. Leaching through soil to
groundwater is not expected to be an important transport mechanism. Estimated volatilization half-lives
indicate that it will be non-volatile from surface water. Based on its estimated vapor pressure it is
expected to exist in the vapor and particulate phase in the atmosphere. Vapor-phase phosphoric acid,
P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester is degraded in the
atmosphere by reaction with photochemically-produced hydroxyl radicals. Particulates will be removed
from air by wet or dry deposition.
<10'8 (Estimated)
EPI v4. 1 1 ; Professional judgment
Cutoff value for nonvolatile
compounds.
         7-761

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JUNE 2014 DRAFT REPORT
V6 CASRN 38051-10-4
PROPERTY/ENDPOINT

Sediment/Soil
Adsorption/Desorption - Koc
Level III Fugacity Model
Persistence
Water
Aerobic Biodegradation
DATA
1 1,000 reported as Log Koc = 4.04; test
method C.19 of 2001/59/EC (Measured)
>3 0,000 MCI method (Estimated)
Air = 0%
Water = 0.7%
Soil = 54%
Sediment = 45% (Experimental)
REFERENCE
EU, 2008b
EPIv4.11;EPA, 2005
EPIv4.11
^^^
DATA QUALITY
Secondary source reporting
screening study for main
component of commercial product
V6, purity of test substance not
stated.
Cutoff value fornonmobile
compounds.

HIGH: The persistence hazard designation for Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-
propanediyl] P,P,P',PMetrakis(2-chloroethyl) ester (V6) is based on guideline biodegradation studies.
There is evidence for biodegradation to occur, at rates resulting in a high hazard designation. 37%
removal was found in 28 days with an OECD 302C guideline study. Under aerobic conditions in ready
biodegradability test OECD 301B, 5% biodegradation occurred after 28 days. This compound is
relatively stable to hydrolysis, with experimental half-lives of >1 year at pH 4, pH 7, and pH 9. This
compound is not expected to be susceptible to direct photolysis by sunlight, since it does not absorb light
at wavelengths >290 nm. It is expected to be degraded in the atmosphere by reaction with
photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 0.14
days.
Passes Ready Test: No
Test method: OECD TG 30 IB: CO2
Evolution Test
Achieved 5% degradation after 28 days
in domestic activated sludge.
Preliminary test OECD 209 confirmed
the test substance did not inhibit growth
of the microorganisms in the inoculum at
the test concentrations employed in the
ready test. (Measured)
Study results: 37%/28 days
EC, 2000; OECD, 2009; ECHA,
2012
EU, 2008b; ECHA, 2012
Guideline study reported in
secondary source for the
commercial product Amgard V6.
Non-GLP guideline study reported
         7-762

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JUNE 2014 DRAFT REPORT
V6 CASRN 38051-10-4
PROPERTY/ENDPOINT

Soil
Air
Reactivity

Volatilization Half-life for
Model River
Volatilization Half-life for
Model Lake
Aerobic Biodegradation
Anaerobic Biodegradation
Soil Biodegradation with
Product Identification
Sediment/Water
Biodegradation
Atmospheric Half-life
Photolysis
Hydrolysis
DATA
Test method: 302C: Inherent - Modified
MITI Test (II)
Achieved 37% of its theoretical oxygen
demand after 28 days using an activated
sludge inoculum; this chemical was not
considered inherently biodegradable.
(Measured)



k _ ^7


0.14 days based on 12-hour day
(Estimated)
Not a significant fate process
(Estimated)
50%/1 year at 25°C, pH 4, 7, and 9;
according to a GLP guideline study EU
Method C.7 92/69/EEC OECD 1 1 1
REFERENCE
^
^^^





EPIv4.11
Professional judgment; Mill,
2000
EU, 2008b;ECHA, 2012
DATA QUALITY
in a secondary source for the
commercial product Amgard V6.
^o data located.
^o data located.
No data located.
Mo data located; chlorinated alkyl
phosphates are outside the domain
of the available estimation
methods.
No data located.
^o data located.

The substance does not contain
functional groups that would be
expected to absorb light at
environmentally significant
wavelengths.
Guideline study reported in a
secondary source for the
commercial product Antiblaze V6.
         7-763

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JUNE 2014 DRAFT REPORT
V6 CASRN 38051-10-4
PROPERTY/ENDPOINT


Environmental Half-life
Bioaccumulation

Fish BCF
Other BCF
BAF
Metabolism in Fish
DATA
In a preliminary test hydrolysis was
below 10% after 5 days at pH 4,7 and 9,
50°C (Measured)
50%/ 99 days pH 10 (Estimated)
50%/ 1 1 1 days pH 9 (Estimated)
50%/ 1 13 days pH 8 (Estimated)
50%/1 13 pH 7 (Estimated)
50%/1 13 days pH 6 (Estimated)
50%/1 13 days pH 5 (Estimated)
>1 year Soil (Estimated)
REFERENCE

EPIv4.11
EPIv4.11
EPIv4.11
EPIv4.11
EPIv4.11
EPIv4.11
PBT Profiler
DATA QUALITY







Half-life estimated for the
predominant compartment, as
determined by EPI and the PBT
Profiler methodology.
LOW: Based on estimated BCF and BAF values.
1 1 Regression-based method (Estimated)

3 1 Arnot-Gobas method (Estimated)

EPIv4.11

EPIv4.11


^o data located.

No data located.
ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring ^^^^^^^
Ecological Biomonitoring
Human Biomonitoring
No data located.
No data located.
No data located.
         7-764

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                                                  JUNE 2014 DRAFT REPORT


ATSDR (2012) Toxicological profile for phosphate ester flame retardants. Atlanta, GA: Agency for Toxic Substances and Disease Registry.

California EPA (2013) Chemicals known to the state to cause cancer or reproductive toxicity July 05, 2013. California Environmental Protection
Agency, http://oehha.ca.gov/prop65/prop65 list/files/P65single072613.pdf

CELLTECH (2009) Material safety data sheet FR-100 flame retardant additive. Cellular Technology International Inc.

Condray JR (1990) US EPA status report: Phosgard 2XC20 with cover letter. Submitted to the U.S. Environmental Protection Agency under
TSCA Section 8E.

EC (2000) 2,2-bis (chloromethyl) trimethylene bis (bis(2-chloromethyl) phosphate). IUCLID data set. European Commission, European
Chemicals Bureau.

ECHA (2013) 2,2-Bis(chloromethyl)trimethylene bis(bis(2-chloroethyl)phosphate). Registered substances. European Chemicals Agency.
http://apps.echa.europa.eu/registered/data/dossiers/DISS-85adOOd6-491d-4f56-e044-00144fd73934/DISS-85adOOd6-491d-4f56-e044-
00144fd73934 DISS-85adOOd6-491d-4f56-e044-00144fd73934.html.

ECOSAR (Ecological Structure Activity Relationship), Version 1.11. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/oppt/newchems/tools/21ecosar.htm.

EPA (2005) Pollution prevention (P2) framework. Washington, DC: U.S. Environmental Protection Agency, Office of Pollution Prevention and
Toxics, http://www.epa.gov/opptintr/newchems/pubs/sustainable/p2frame-june05a2.pdf

EPA (2012) Using noncancer screening within the SF initiative. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/oppt/sf/pubs/noncan-screen.htm.

EPI Estimation Programs Interface (EPI) Suite, Version 4.11. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm.

ESIS (2012) European chemical Substances Information System. European Commission, http://esis.jrc.ec.europa.eu/.

EU (2008a) 2,2-Bis(chloromethyl) trimethylene, bis[bis(2-chloroethyl) phosphate], (V6), CAS No: 38051-10-4, EINECS No: 253-760-2.
Summary risk assessment report. European Union. European Communities. European Chemicals Agency.
http://echa.europa.eu/documents/10162/c38476f5-ebfc-43b2-8800-83fD4e623c74.
                                                              7-765

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                                                  JUNE 2014 DRAFT REPORT


EU (2008b) European Union risk assessment report: 2,2-Bis(Chloromethyl) trimethylene, bis[bis(2-chloroethyl) phosphate]. Risk assessment.
Final approved version. Luxembourg: European Union. European Communities. European Chemicals Agency.
http://www.echa.europa.eu/documents/10162/13630/trd rar Ireland tdcpen.pdf

Freudenthal RI, Henrich RT (2000) Chronic toxicity and carcinogenic potential of tris(l,3dichloro-2-propyl) phosphate in Sprague-Dawley rat. Int
JToxicol 19:119-125.

Kapp RW, Mossburg PA, Trutter JA, et al. (1981) Teratology study in rats. FR-2 (Fyrol). Final Report (1978). Toxicology reports on Fyrol FR-2
(volume I-II) with attachments and cover letter dated 020381. Prepared by Hazleton Laboratories America, Inc. for Stauffer Chemical Company.
Submitted to the U.S. Environmental Protection Agency under TSCA Section 8E, 57-103.

King FiH (1993) Evaluation of the mutagenic potential of Antiblaze 100 with 0.5% in the mouse lymphoma mutagenesis assay with cover letter
dated 081293 (sanitized). Submitted to the U.S. Environmental Protection Agency under TSCA.

Mill T (2000) Photoreactions in surface waters. In: Boethling R Mackay D, eds. Handbook of Property Estimation Methods for Chemicals,
Environmental Health Sciences. Boca Raton: Lewis Publishers, 355-381.

Morey H, Frudentahl RI, Swigut T, et al. (1978) Summary of in vitro delayed neurotoxicity evaluation. Report T-6303. Toxicology reports on
Fyrol FR-2. Vol I of II. Submitted to the U.S. Environmental Protection Agency under TSCA Section 8E, 27-38.

OECD (2009) SIDS initial assessment profile 2,2-Bis(chloromethyl) trimethylene bis (Bis(2-chloroethyl)phosphate) (V6).

OncoLogic (2008) U.S. EPA and LogiChem, Inc. 2005, Version 7.0. 2008.

PBT Profiler Persistent (P), Bioaccumulative (B), and Toxic (T) Chemical (PBT) Profiler, Version 1.301. Washington, DC: U.S. Environmental
Protection Agency, www.pbtprofiler.net.

Wilczynski SI, Killinger JM, Zwicker GM, et al. (1983) Fyrol FR-2 fertility study in male rabbits. Toxicologist 3:22.

van der Veen I, de Boer J (2012) Phosphorus flame retardants: Properties, production, environmental occurrence, toxicity and analysis.
Chemosphere 88(10): 1119-115.
                                                              7-766

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