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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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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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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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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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)
CASRN
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ester (TBB) ¥
Di(2-ethylhexyl) tetrabromophthalate (TBPH) A¥
Isopropylated triphenyl phosphate (IPTPP) A
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Chlorinated Phosphorus Alternatives
Tris (2-chloroethyl) phosphate (TCEP)
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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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Non-Halogenated Flame Retardant Alternatives
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)).
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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
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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.
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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.
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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.
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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
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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
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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• 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.
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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).
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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.
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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.
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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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JUNE 2014 DRAFT REPORT
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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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
http://www.epa.gov/dfe/alternatives assessment criteria for hazard eval.pdf.
U.S. EPA. (201 Ic). "Endocrine Disrupter Screening Program. Weight of the Evidence:
Evaluating Results of EDSP Tier 1 Screening to Identify the Need for Tier 2 Testing."
Retrieved November 18, 2013, from
http://www.regulations. gov/#! documentDetail:D=EPA-HQ-OPPT-2010-0877-0021.
U.S. EPA. (201 Id). "Estimation Program Interface (EPI) Suite." Retrieved April 18, 2012, from
http://www.epa. gov/oppt/exposure/pub s/epi suite, htm.
U.S. EPA. (201 le). "Interpretive Assistance Document for Assessment of Discrete Organic
Chemicals. Sustainable Futures Summary Assessment." Retrieved November 18, 2013,
from http://www.epa.gov/oppt/sf/pubs/iad_discretes_092011 .pdf.
U.S. EPA. (201 If). "On-line AOPWIN™ User's Guide." Retrieved November 18, 2013, from
http://www.epa. gov/oppt/exposure/pub s/epi suite, htm.
U.S. EPA. (201 Ig). "On-line BCFBAF™ User's Guide." Retrieved November 18, 2013, from
http://www.epa.gov/oppt/exposure/pubs/episuite.htm.
U.S. EPA. (201 Ih). "On-line KOWWIN™ User's Guide." from
http://www.epa. gov/oppt/exposure/pub s/epi suite, htm.
U.S. EPA. (201 li). "On-line WSKOWWIN™ User's Guide." from
http://www.epa. gov/oppt/exposure/pub s/epi suite, htm.
U.S. EPA. (2012a). "Analog Identification Methodology (AIM)." Retrieved April 17, 2012,
from http ://www. epa. gov/oppt/sf/tool s/aim. htm.
U.S. EPA. (2012b). "Endocrine Disrupter Screening Program (EDSP)." Retrieved April 17,
2012, from http://www.epa.gov/scipoly/oscpendo/index.htm.
U.S. EPA. (2012c). "Models & Methods." Retrieved April 17, 2012, from
http ://www. epa. gov/oppt/sf/tool s/methods .htm.
U.S. EPA. (2013a). "2012 Chemical Data Reporting Information. Chemical Data Access Tool.
Updated April 4, 2013." from http://java.epa.gov/oppt_chemical_search/.
U.S. EPA. (2013b). "Toxic Substances Control Act (TSCA) Work Plan Chemicals." from
http://www.epa.gov/oppt/existingchemicals/pubs/workplans.html.
UK Parliament. (1988). "The Furniture and Furnishings Fire Safety Regulations 1988 No. 1324."
from http://www.legislation.gov.uk/uksi/1988/1324/made.
van der Veen, I. and J. de Boer (2012). "Phosphorus flame retardants: properties, production,
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.
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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.
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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.
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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.
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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.
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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.
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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).
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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
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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.
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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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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"].
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CASRN
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Di(2-ethylhexyl) tetrabromophthalate | 26040-51-7
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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.
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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).
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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.
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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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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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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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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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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 >
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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.
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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
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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
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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.
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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
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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.
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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.
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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.
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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
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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.
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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
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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.
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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
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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.
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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-
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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.
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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.
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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.
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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
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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
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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
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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.
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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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VL
L
L
L
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)
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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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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.
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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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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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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).
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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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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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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;
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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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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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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
Human Health Effects
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Emerald Innovation™ NH-1*
Confidential C
Confidential D
Confidential E
Confidential
Confidential
Confidential
Confidential
L
L
M
M
M
M
L
L
L
L
M
M
L
L
L
VL
L
L
L
L
1YT
L
L
VL
JV1
VL
VH
VH
VH
VH
VH
VH
M
L
L
M
H
L
H
7-120
-------
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.
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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.
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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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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.
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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.
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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)
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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.
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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.
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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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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.
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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
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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.
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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.
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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.
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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.
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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
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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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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.
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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.
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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.
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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.
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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.
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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
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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
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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.
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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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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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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
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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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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.
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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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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
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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.
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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.
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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).
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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.
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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.
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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.
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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.
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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
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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
Chemical
CASRN
Human Health Effects
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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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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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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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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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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
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68937-41-7
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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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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).
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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
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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
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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.
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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.
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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.
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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
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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
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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.
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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
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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
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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.
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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.
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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.
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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).
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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
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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.
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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.
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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
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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.
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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.
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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
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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.
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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.
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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].
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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
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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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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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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
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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
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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
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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
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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.
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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.
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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.
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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
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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,
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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.
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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.
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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
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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).
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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.
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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.
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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.
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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.
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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.
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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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108-78-1
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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).
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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.
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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.
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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.
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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.
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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
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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
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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
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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.
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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.
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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.
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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.
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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.
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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
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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.
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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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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.
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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.
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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.
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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.
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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.
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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
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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
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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
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