U.S. EPA Design for the Environment
Flame Retardants Used in Flexible
Polyurethane Foam: An Alternatives
Assessment Update
United States
Environmental Protection
Agency
August 2015
EPA 744-R-15-002
U.S. EPA
-------
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 Addressed 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 5-18
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) 7-59
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate 7-102
Emerald Innovation™ NH-1 7-123
Expandable graphite 7-207
Fyrol™HF-5 7-229
Isopropylated triphenyl phosphate (TPTPP) 7-269
Melamine 7-333
Oligomeric ethyl ethylene phosphate 7-377
Oligomeric phosphonate polyol 7-394
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl]P,P,P',P'-tetrakis(2-chloroethyl)
ester 7-410
Tricresyl phosphate (TCP) 7-447
Triphenyl phosphate (TPP) 7-509
Tris (l,3-dichloro-2-propyl) phosphate (TDCPP) 7-543
Tris (2-chloro-l-methylethyl) phosphate (TCPP) 7-601
Tris (2-chloroethyl) phosphate (TCEP) 7-648
Tris (p-t-butylphenyl) phosphate (TBPP) 7-700
11
-------
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
EbCso Concentration at which 50% reduction of biomass is observed
EC50 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
in
-------
KQW
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
Octanol/water partition coefficient
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
IV
-------
TBPH Di(2-ethylhexyl) tetrabromophthalate
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
-------
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 20th 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, EPA's Design for the Environment Program (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
1 Available at: http://www2.epa.gov/saferchoice/environmental-profiles-chemical-flame-retardant-alternatives-low-
density-polyurethane.
1-1
-------
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
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 3 below). The impact
of these changes in terms of flame retardant selection and use 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.
As mentioned above, this report by EPA's DfE Program updates and supplements the previous
alternatives assessment report developed by the FFRP (U.S. EPA 2005a). DfE identified 16
flame retardant chemicals, one non-proprietary mixture, and 2 proprietary mixtures to be
evaluated in the update report. Additional information on polyurethane foam is available in the
2005 FFRP report (U.S. EPA 2005a).
The scope of this report was 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,
1-2
-------
rather than material-to-material comparison, a life cycle assessment (LCA) might be a better tool
for evaluating and comparing alternative materials (see Section 1.3).
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 2 may help
businesses avoid the cost of repeated substitution. Section 7 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 7. 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
1-3
-------
in guiding product-specific decision-making. In addition, information in this report can be used
to identify the Very Persistent Very Bioaccumulative chemicals, PBT chemicals, and those with
an "equivalent level of concern" targeted under European 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://www2.epa.gov/saferchoice/design-environment-alternatives-assessments.)
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.
1-4
-------
Under conditions where fire or incineration occurs, a halogenated substance may contribute to
halogenated dibenzodioxin and dibenzofuran formation, increase the generation of PAHs, and
impact fire parameters such as smoke and carbon monoxide (Sidhu, Morgan et al. 2013).
However, combustion reactions are complex and variable, and make inclusion of combustion
byproducts in hazard assessment challenging. Both halogenated and non-halogenated flame
retardants may yield other toxic by-products that would need to be compared, not only
halogenated dioxins and furans. For these reasons, the pyrolysis transformation products are not
assessed in this report.
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
1-5
-------
• 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.
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.
1-6
-------
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
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.
1-7
-------
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 4). These alternative technologies are not
assessed for hazard in this report. The DfE Hazard Evaluation Criteria (described in Section
5.1.2) 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.
2-1
-------
Table 2-1. Screening Level Toxicity Hazard Summary
This table contains hazard information for each chemical; evaluation of risk considers both hazard and exposure. Variations in end-of-life processes or degradation and
combustion by-products are discussed in the report but not addressed directly in the hazard profiles. The caveats listed below must be taken into account when interpreting the
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.
* Each hazard designation for a mixture is based upon the component with the highest hazard, whether it is an experimental or estimated value. For Firemaster® mixtures there is
no corresponding profile in Section 7.
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 7)
CASRN
Human Health Effects
Acute Toxicity
Carcinogenicity
Genotoxicity
Reproductive
Developmental
Neurological
Repeated Dose
Skin
Sensitization
Respiratory
Sensitization
Eye Irritation
Dermal Irritation
Aquatic
Toxicity
0)
-*^
1
Chronic
Environmental
Fate
Persistence
Bioaccumulation
Halogenated Flame Retardant Alternatives
Firemaster® 550 Components
Firemaster® 550*
Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl
ester (TBB) ¥
Di(2-ethylhexyl) tetrabromophthalate (TBPH)A¥
Isopropylated triphenyl phosphate (IPTPP) A
Triphenyl phosphate (TPP) A
Mixture
183658-27-7
26040-51-7
68937-41-7
115-86-6
L
L
L
L
L
M
M
M
M
M
JV1
L
L
L
M
M
L
H
M
M
H
L
H
M
M
H
L
M
M
M
L
L
L
L
M
L
L
L
L
L
L
L
VL
VH
L
L
VH
VH
VH
L
L
VH
VH
H
H
H
JVl
L
H
H
H
H
M
Firemaster® 600
Firemaster® 600*
Mixture;
Proprietary
L
M
M
M
M
H
M
L
M
VH
VH
H
Chlorinated Phosphorus Alternatives
Tris (2-chloroethyl) phosphate (TCEP)
Tris (2-chloro-l-methylethyl) phosphate (TCPP)
Tris (l,3-dichloro-2-propyl) phosphate (TDCPP)
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-
propanediyl]P,P,P',P'-tetrakis(2-chloroethyl)
ester
115-96-8
H
H
H
L
L
L
H
H
13674-84-5;
6145-73-9
L
M
L
H
H
M
1YT
L
L
L
1YT
M
13674-87-8
L
H
H
L
H
L
L
L
H
38051-10-4
L
M
L
H
L
L
L
L
H
M
H
H
H
L
L
L
L
2-2
-------
Table 2-2. Screening Level Toxicity Hazard Summary
This table contains hazard information for each chemical; evaluation of risk considers both hazard and exposure. Variations in end-of-life processes or degradation and combustion
by-products are discussed in the report but not addressed directly in the hazard profiles. The caveats listed below must be taken into account when interpreting the 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, 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.
* Expandable graphite commercial formulations are prepared using chemical washes that may be present in the final product as residues. The associated hazards vary depending on
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 7)
CASRN
Human Health Effects
>,
0
H
3
-*^
_u
0)
0
sS
U
•g
s
o
oj
O
0)
u
o
o.
M
^
0)
o
"3
P
13
o
'Si
_o
o
S
Z
0)
0
p
•a
"S3
0)
0)
a
_o
.a
'35
0)
C/5
a
C/5
r*> S
o '•§
SS _N
S. '35
5« fl
OJ g
0
1
•c
a
_o
sS
'C
HH
13
0)
p
Aquatic
Toxicity
3
'a
S
u
Environmental
Fate
0)
u
a
£
a.
0
«
"3
u
sS
o
P5
Non-Halogenated Flame Retardant Alternatives
Inorganic/Other Alternatives
Ammonium polyphosphate (APP)¥
68333-79-9
lL|Z,|z,|Z,|z,|Z,|Z,d|L|
VL
VH
Expandable graphite
12777-87-6
M*
L* \ L \ L \ M* \ L* \ * \ * \ * \
M*
H
.O.
Melamine
108-78-1
\H\M\L\ |L|
VL
H
2-3
-------
Table 2-2. Screening Level Toxicity Hazard Summary (Continued)
This table contains hazard information for each chemical; evaluation of risk considers both hazard and exposure. Variations in end-of-life processes or degradation and combustion by-
products are discussed in the report but not addressed directly in the hazard profiles. The caveats listed below must be taken into account when interpreting the 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, 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 with MW <1,000.
*Each hazard designation for a mixture is based upon the component with the highest hazard, whether it is an experimental or estimated value.
00 Based on experimental test data for a residual impurity reported to be present in this substance at levels up to 5% by weight.
Chemical
(for full chemical name and relevant
trade names see the individual profiles
in Section 7)
CASRN
Human Health Effects
Acute Toxicity
Carcinogenicity
Genotoxicity
Reproductive
Developmental
Neurological
Repeated Dose
Skin
Sensitization
Respiratory
Sensitization
.0
-*^
sS
+*
hH
-,
W
Dermal
Irritation
Aquatic
Toxicity
|
1
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) t
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
1VT
1330-78-5
L
L
H
H
M
L
L
VH
H
68937-41-7
L
M
L
H
H
H
H
L
L
L
VH
VH
H
78-33-1
L
M
L
L
H
M
L
VH
VH
2781-11-5
L
M
L
L
M
M
M
L
VL
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
M
VH
M
L
L
L
New-to-Market Proprietary Mixtures
Emerald Innovation™ NH-1*
Confidential C
Confidential D
Confidential E
Fyrol™HF-5*
Confidential A
Confidential B
Proprietary
Confidential
Confidential
Confidential
Proprietary
Confidential
Confidential
L
L
L
L
L
M
M
M
M
M$
L
M8
L
L
L
L
M
M
L
M
M
L
L
L
L
L
L
VL
L
L
L
JV1
L
s
s
M
§
L
H
d
LA
L
L
L
L
L
VL
L
VL
L
L
VL
VH
H
VH
VH
VH
L
VH
VH
H
VH
VH00
VH
L
VH00
M
L
L
M
VH
VH
H
H
rf
L
H%
:This assessment also includes information for other methylated triphenyl phosphate isomers (phosphoric acid, bis(methylphenyl) phenyl ester (CASRN 26446-73-1) and phosphoric acid,
methylphenyl diphenyl ester (CASRN 26444-49-5)).
2-4
-------
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. Similar to several of the alternatives
evaluated, the components TBB and TBPH lack full data characterization necessary to
adequately describe hazard and risk.
Firemaster® 600 is currently marketed for use in flexible polyurethane foams and other
applications as a mixture of phosphorus and bromine based flame retardants (Great Lakes
Solutions, 2010; Chemtura, 2014). Although the identity and composition of some of the
ingredients in Firemaster® 600 are proprietary and cannot be disclosed in this report, the
summary hazard designation profile is provided, based upon the mixture component with the
highest hazard. The hazard designations for Firemaster® 600 are similar to Firemaster® 550.
The chlorinated phosphorus alternatives are tris (2-chloroethyl) phosphate (TCEP), tris (2-
chloro-1-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.' Pseudo persistence is a term for chemicals that are observed to
be continually present in the environment because they are released at a rate greater than or equal
to their rate of removal.
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, it is predicted to be Low hazard
based on its structure and very high MW. 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 to Moderate 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.
2-5
-------
The profile for melamine identifies key hazards in human health endpoints including acute
toxicity, carcinogenicity, genotoxicity, reproductive and repeated dose toxicity. Bioaccumulation
potential is low, aquatic toxicity is Low, 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 to Moderate persistence) phosphate esters
triphenyl phosphate (TPP), tricresyl phosphate (TCP), isopropylated triphenyl phosphate
(IPTPP) and tris (p-t-butylphenyl) phosphate (TBPP) have High to Very 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
Moderate to Low aquatic toxicity and bioaccumulation designations.
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 heavy reliance on analog or modeled data (especially for the two
oligomers)--yielding conservative Moderate designations for several human health endpoints,
they may be the most preferable out of all the chemicals assessed in this report. Of these three
chemicals, the most preferable may be the oligomeric phosphonate polyol, which has Low to
Moderate aquatic toxicity, Moderate persistence, and Low bioaccumulation potential. Human
health and aquatic toxicity designations are Low or Moderate for this chemical. Also, 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 to make the end-use product meet 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 highest
hazards for aquatic toxicity, and 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
2-6
-------
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.
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.'
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.
2-7
-------
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 drive their use. For more details
about FPUF, and 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
Available at: http://www2.epa.gov/saferchoice/environmental-profiles-chemical-flame-retardant-alternatives-low-
density-polyurethane.
3-1
-------
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.
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.
Under conditions where fire or incineration occurs, a halogenated substance may contribute to
halogenated dibenzodioxin and dibenzofuran formation, increase the generation of PAHs, and
impact fire parameters such as smoke and carbon monoxide (Sidhu, Morgan et al. 2013).
However, combustion reactions are complex and variable, and make inclusion of combustion
byproducts in hazard assessment challenging. Both halogenated and non-halogenated flame
retardants may yield other toxic by-products that would need to be compared, not only
halogenated dioxins and furans. For these reasons, the pyrolysis transformation products are not
assessed in this report.
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
United States 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
3-2
-------
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.
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
3-3
-------
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
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
-------
Table 3-1. Flame Retardants 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
C15H18Br402
C24H34Br404
Br
^Cii Br
Br Br
Br~4 // Br
o=(Vo /—/~
— ^ 0 0 ^ — (
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
C6H12Cl3O4P
C9H18Cl304P
Ck
Cl
O-P=O
/ 1
Representative structure
3-5
-------
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)-
l,3-propanediyl]P,P,P',P'-tetrakis(2-chloroethyl)
ester
Common Names and
Acronyms15
TDCPP; Tris-(l,3-dichloro-2-
propyl)phosphate; TDCIPP
V6; BCMP-BCEP
Molecular
Formula (MF)
C9H15C16O4P
C13H24C1608P2
Structure
C'Xc,
o^cl
O-P=O Cl
ci \— ciy
Cl
\ S Ql
°' y J-o
^**J \
I O^^^CI
Cl
Inorganic/Other Alternatives
68333-79-9
12777-87-6
Polyphosphoric acids, ammonium salts
Sulfuric acid, compd. with graphite (1:?)
APP; Ammonium
polyphosphate
Expandable graphite
[NH4P03]n
[C]n[S03H]x
0 0
HO-^P-0-]— p'-OH
i HI
0- OH
NH4+
Representative structure
o
HO-S T^^L^L O
OH
Representative structure
3-6
-------
CASRN
108-78-1
Preferred Chemical Abstract Index Name
l,3,5-Triazine-2,4,6-triamine
Common Names and
Acronyms'5
Melamine
Molecular
Formula (MF)
C3H6N6
Structure
H2N
\-N
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
Methylated triphenyl
phosphates;
Bis(methylphenyl) phenyl
phosphate; MPHP
C18H1504P
CigHnC^P
C2oHi9O4P
*Q o
O-P-O
1 \
Q o
O-P-O
rV^\
k^ \=^
Representative structure
Q o
O-P-O
r"V° f^>
yj \=^
Representative structure
3-7
-------
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
C21H21O4P
Phenol, isopropylated, phosphate (3:1)
Commercial product may include mono-, di-, tri-
and higher substitutions with appropriate
CASRNs.
Representative structure
68937-41-7
IPPP; ITP; IPTPP;
Isopropylated triphenyl
phosphate; Isopropylated
phenol phosphate; TIPPP
Formula for tri-
propyl
substitution
Representative structure
78-33-1
Phenol, 4-(l,l-dimethylethyl)-, 1,1',1 "-phosphate
Includes mono-, di-, tri-, and higher substitutions
with appropriate CASRNs.
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
C9H22N05P
o
OH
3-8
-------
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,
-------
Table 3-2. Flame Retardants That Were Not 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.
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
Tribromoneopentyl alcohol;
TBNPA
C15H2oBr4O9;
C15H16Br407
C9H18Br2ClO4P
C5H9Br3O
0 Br
HO ^\ J-L JL Br
^1 ^ lr if'
o^^x^s/^v
1^ | °r
HO^^Q^^0 Br
Representative Structure
rBr
J
0^
1
1 /°~£~°
\ ^
Br^ I
kci
Representative Structure
Br
nr C\\ 1
Br un
\
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)C.
Appears to
have been an
unsuccessful
product.
3-10
-------
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)-
1 ,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
o 1 1
0 Br
C, / CS , C,
^-( 0 / L 0 )-V
o-p-o 1^ o-p-o
ci^y° C' °^ci
' '
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-, 1,1',1 "-phosphate
TDBPP; Tris-(2,3-
dibromopropyl)phosphate
C9H15Br604P
o
Br. O~P=O
\ / i
Br p x\/Br
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
A1(OH)3
HOy)H
OH
Inefficient,
requiring
very high
loadings.
Probably not
used in
FPUFd.
3-11
-------
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
Structure
•V
HO'M9~OH
Reason for
Exclusion15
Inefficient,
requiring
very high
loadings.
Possible use
in some
niche
applications.
Inefficient,
requiring
very high
loadings.
Probably not
used in
flexible
polyurethane
foamd.
Research
product; not
yet
commercially
available.
Vendor
described use
in
thermoplastic
polyurethane;
no other use
data
available.
3-12
-------
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
Triethyl phosphate; Levaguard
TEP-Z
C3H9O3P
C5H1303P
C6H1504P
o
^RX s
—d °
o^
O-P=O
/ 1
^^^
\l
o^ I
^^ ,p\ /
O — '
Used in rigid
polyurethane
foams.
PINFA
website lists
as
appropriate
forFPUF;
however, no
evidence of
such use is
available.
Thought to
be used in
rigid but not
flexible
polyurethane
foam;
however, not
reported on
listed on
CDRC.
Used in rigid
but not
flexible
polyurethane
foam. Could
be an
impurity
from other
flame
retardants.
3-13
-------
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.
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:7/www2.epa. gov/saferchoice/partnership-evaluate-
flame-retardant-altematives-decabde.
3-14
-------
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). New York State has banned
TDCPP from use in children's products, including baby products, toys, car seats, nursing
pillows, crib mattresses, strollers and other items intended for use by children under three
years of age, effective December 1, 2015 (New York State Governor's Office 2014).
Maryland has also prohibited importing, selling, or offering for sale any child care
product containing more than one-tenth of 1% (by mass) of TDCPP intended for use by
children under the age of three including baby products, toys, car seats, nursing pillows,
crib mattresses, and strollers (State of Maryland 2014). The ban became effective on
October 1, 2014, and does not contain a provision for phasing out existing stock.
• 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 was 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). New York
State banned the sale or offer for sale of children's products containing TCEP, effective
December, 1, 2013 (State of New York 2011). Maryland also passed a law prohibiting
the import, sale, or offer for sale of child care products containing more than one-tenth of
1% (by mass) of TCEP intended for use by children under the age of three, including
baby products, toys, car seats, nursing pillows, crib mattresses, and strollers (State of
Maryland 2014). The ban became effective on October 1, 2014, and does not contain a
provision for phasing out existing stock.
3 A chemical known to the State of California to cause cancer or reproductive toxicity; businesses are required to
provide a warning (e.g., label consumer products, distribute notices to residents) when exposure to a Proposition 65
chemical may occur.
3-15
-------
• 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, because 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).
• 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
3-16
-------
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.
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.) For example,
Firemaster® 600 is a mixture of phosphorus and bromine-based flame retardants marketed for
use in flexible polyurethane foams and other applications. Although the identity and composition
of some of the ingredients in Firemaster® 600 are proprietary and cannot be described in this
report, the summary hazard designations based upon the mixture component with the highest
hazard are provided.
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 (NRDC 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.
3-17
-------
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. In contrast to the 1975 standard, the
new TB117-2013 does not require open flame testing for filling materials used in upholstered
furniture. TB117-2013 tests for smolder resistance by applying a lit cigarette to a miniature
assembly of the cover fabrics, barrier materials, and filling materials that represents the finished
piece of furniture (Cal/DCA 2013b). 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) El353 standard (Cal/DCA 2013b). Manufacturers
were able to use the new testing requirements as of January 1, 2014, and required to be fully
compliant by January 1, 2015 (California Governor's Office 2013).
Although TB117-2013 does not regulate or mandate the use of flame retardant chemicals,
BEARHFTI anticipates that the new standard will significantly reduce or eliminate
manufacturers' use of flame retardant chemicals in upholstered furniture, because these products
may meet the new standards without the use of flame retardant chemicals (Cal/DCA 2013a).
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). Although not assessed for possible hazards in this report, Section 4 provides information
on flame retardant technologies that may provide increased fire safety, with and without the use
of flame retardant chemicals.
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
3-18
-------
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).
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 (NRDC 2013).
Other Standards and Laws
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. Also, as noted in Section 3.4, New York
4 This standard would apply to cushioned, upholstered seating products available for residential, home office, and/or
dormitory use.
3-19
-------
State has also passed a law (A4741/S3703-B) banning TDCPP from consumer products intended
for use by children under three years of age, such as baby products, toys, car seats, nursing
pillows, crib mattresses, and strollers, effective December 1, 2015 (New York State Governor's
Office 2014). New York State banned the sale of children's products containing TCEP in 2011,
effective December 1, 2013 (State of New York 2011).
As also noted in Section 3.4, Maryland passed a law prohibiting the importing, selling, or
offering for sale any child care product containing more than one-tenth of 1% (by mass) of
TDCPP and TCEP. Under the law, child care products are those intended for use by children
under the age of three, including baby products, toys, car seats, nursing pillows, crib mattresses,
and strollers (State of Maryland 2014). The ban became effective on October 1, 2014, and does
not contain a provision for phasing out existing stock.
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. In 2014, NFPA was 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" (Phosphoric acid,
P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester) has a higher
molecular weight (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, may lessen the need
for flame retardant additives in foam; however, for some fabrics, TB117-2013 will still require
flame retardant coatings or other modifications. The Consumer Product Safety Commission and
New York State have indicated that they may issue a performance-based standard that is more
difficult to meet than TB117 (e.g., an open flame test); if they do, it may need to be met either
with flame retardant inter-liners or with higher loads of flame retardants in foam, a choice made
by individual manufacturers and likely to be driven in many cases by costs.
3-20
-------
4 Alternative Flame Retardant Solutions not Addressed 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. Additionally, with the advent of changes to flammability standards,
manufacturers may also consider whether the standards can be met without incorporating flame
retardants to FPUF. In fact, several major furniture manufacturers have announced plans to
produce furniture that does not contain flame retardants (Chicago Tribune 2015).
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://www2.epa.gov/saferchoice/design-environment-alternatives-
assessments) - 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
4-1
-------
circuit boards), and there is great interest in the manufacturing industry in finding reactive flame
retardants for FPUF.
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).
4-2
-------
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 this DfE alternatives assessment
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
1.3.
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 7.
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 that DfE characterizes but to which it does
not assign criteria; 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. EPA 201 Ib). 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.
5-1
-------
Endpoint
Category
Endpoint
Definition
Carcinogenicity
Mutagenicity/Genotoxicity
Reproductive Toxicity
Developmental Toxicity
Neurotoxicity
Capability of a substance to increase the incidence of
malignant neoplasms, reduce their latency, or increase
their severity or multiplicity.
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.
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.
5-2
-------
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
alternatives 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.
5-3
-------
The hazard profile for each chemical contains endpoint specific summary statements (see Section
7). 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 DfE 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://www2.epa.gov/saferchoice/alternatives-assessment-criteria-hazard-evaluation.
Table 5-2: Criteria Used to Assign Hazard Designations
Endpoint
Very High
High
Moderate
Very Low
Human Health Effects
Acute mammalian toxicity
Oral median lethal dose
(LD5o) (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)
Limited or
marginal
evidence of
Carcinogenicity
(and inadequate
evidence in
humans)
Negative studies
or robust
mechanism-
based Structure
A ctivity
Relationship
(SAR)
(as described
above)
5-4
-------
Mutagenicity/Genotoxicity
Germ cell mutagenicity
Mutagenicity and
genotoxicity in somatic
cells
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
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.
-
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
-
-
5-5
-------
Inhalation - vapor, gas
(mg/L/day)
Inhalation - dust/mist/fume
(mg/L/day)
-
-
O.2
O.02
0.2-1.0
0.02-0.2
>1.0
>0.2
-
-
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 hah0 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
5-6
-------
Environmental persistence
Persistence in water, soil,
or sediment
Persistence in air (half -life
days)
Half-life
>180 days or
recalcitrant
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.
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)
Log BCF/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
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 alternatives 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.
5-7
-------
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 immunological 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.)
1A 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;
5-8
-------
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
5-9
-------
designation. This process is described, as appropriate, under the corresponding endpoints
appearing in Section 5.3.
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 7. 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
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
5-10
-------
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 alternatives 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.
For this 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.
5-11
-------
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.
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).
5-12
-------
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
gas/particulate mixture. Substances with a vapor pressure less than 1 x 10"8 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.
A maximum vapor pressure of 1 x 10"8 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 was considered to be insoluble, noting that these
guidelines might not match what is used elsewhere within the scientific literature for other
disciplines. Chemicals with higher water solubility are 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.
5-13
-------
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 chemical's 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.
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
5-14
-------
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
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.
5-15
-------
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 pKB, 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
model river and a model lake. A maximum value of 1 x 10"8 atm-m3/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.
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
5-16
-------
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
aMW>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
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
5-17
-------
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. 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).
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.
5-18
-------
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
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).
5-19
-------
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 the 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
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
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).
5-20
-------
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 environmental 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
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
5-21
-------
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
ECOSAR™ estimate were used, then an additional factor often 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. 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
Kow values from 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
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 were 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).
5-22
-------
For phosphate esters and phosphonate esters in this report, alternative predictive methodologies
such as data derived acute-to-chronic ratios (ACRs) and read across to analogous substances
were reported to address data gaps, using a weight of evidence approach instead of ECOSAR
predictions. Many of the chemicals and chemical mixture components in this assessment are
phosphate or phosphonate esters, including Diethyl bis(2-hydroxyethyl)aminomethyl-
phosphonate, Emerald Innovation™NH-l, Fyrol™ HF-5, Isopropylated triphenyl phosphate,
Oligomeric ethyl ethylene phosphate, Oligomeric phosphonate polyol, Phosphoric acid, P,P'-
[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester, Tricresyl
phosphate, Triphenyl phosphate, Tris (l,3-dichloro-2-propyl) phosphate, Tris (2-chloro-l-
methylethyl) phosphate, Tris (2-chloroethyl) phosphate, and Tris (p-t-butylphenyl) phosphate.
ECOSAR vl.l 1 provides estimates for these compounds based on the esters, esters (phosphate),
and neutral organic classes. These compounds are not well represented by ECOSAR vl. 11 esters
(phosphate) QSAR, which is based on underlying Log Kow methodology that does not
adequately distinguish weak-to-strong esterase inhibition, resulting in low correlation of the class
members. Additionally, certain modes of action have been previously associated with phosphate
ester chemicals (i.e., potential for esterase inhibition and alkylation); therefore, the ECOSAR
vl.ll esters and neutral organics QSARs are also not well representative of these chemicals. The
ECOSAR vl.l 1 esters estimated values are reported in the assessment for comparative purposes.
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
5-23
-------
<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
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 uses 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.
5-24
-------
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.
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 5-2). These half-life criteria were also used to assign a hazard designation for non-
guideline ultimate biodegradation studies reported in the scientific literature.
5-25
-------
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
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 EPISuite™ 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 provide
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 is 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) are also 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
5-26
-------
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
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 are assigned a High persistence designation in DfE alternatives
assessments, as these inorganic moieties are recalcitrant. In this instance, an 'R' footnote is
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 includes 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 are 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 7. 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).
5-27
-------
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.
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).
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
5-28
-------
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.
5-29
-------
6 References
ACE Organic (2013). "ACE Acidity and Basicity Calculator." Retrieved December 13, 2013,
from http://aceorganic.pearsoncmg.com/epoch-plugin/public/pKa.jsp.
Anastas, P. T. and J. C. Warner (1998). Green Chemistry: Theory and Practice. New York,
Oxford University Press.
Apaydin, K., A. Laachachi, et al. (2013). "Polyallylamine-montmorillonite as super flame
retardant coating assemblies by layer-by layer deposition on polyamide." Polymer
Degradation and Stability 98: 627-634.
Betts, K. S. (2008). "New Thinking on Flame Retardants." Environ. Health Perspect. 116(5):
A210-A213.
Bhagat, V. J. (2001). "Behaviour of expandable graphite as a flame retardant in flexible
polyurethane foam." Proceedings of the Technical Program of the Polyurethane Foam
Association, Arlington, VA, May 10, 2001,
from http://www.metachem.in/Presenation.pdf
Boethling, R. S. and J. V. Nabholz (1997). Environmental Assessment of Polymers under the
U.S. Toxic Substances Control Act. Ecological Assessment of Polymers Strategies for
Product Stewardship and Regulatory Programs. J. D. Hamilton and R. Sutcliffe. New
York, Van Nostrand Reinhold: 187-234.
Boston Fire Department (1995). "Regulation of Upholstered Furniture: BFD IX-10,"
from http://www.cityofboston.gov/fire/pdfs/BFD%20IX-
10%20Upholstered%20Furniture%20Regulation.pdf
Cal/DCA (2000). "Technical Bulletin 117: Requirements, Test Procedures, and Apparatus for
Testing the Flame Retardance of Resilient Filling Materials Used in Upholstered
Furniture. March 2000," from http://www.bhfti.ca.gov/industry/117.pdf.
Cal/DCA (2010). "Industry Advisory: Juvenile Furniture Exemption -Notice of Approval of
Regulatory Action," from http://www.bhfti.ca.gov/industry/iuvenile exemp.pdf.
Cal/DCA (2013a). "Initial Statement of Reasons. Subject Matter of Proposed Regulations: New
Flammability Standards for Upholstered Furniture and Articles Exempt from
Flammability Standards. Hearing Date: March 26, 2013,"
from http://www.bhfti.ca.gov/about/laws/isr.pdf.
Cal/DCA (2013b). "Technical Bulletin 117-2013: Requirements, Test Procedures, and Apparatus
for Testing the Smolder Resistance of Materials Used in Upholstered Furniture. June
2013," from http://www.bearhfti.ca.gov/about us/tb 1172013.pdf
California Governor's Office (2013). "Governor Brown Announces New Standards to Reduce
Toxic Chemicals in Furniture," from http://gov.ca.gov/home.php.
6-1
-------
Carignan, C. C., W. Heiger-Bernays, et al. (2013). "Flame Retardant Exposure among Collegiate
United States Gymnasts." Environ. Sci. Technol. 47(23): 13848-13856.
Carignan, C. C., M. D. McClean, et al. (2013). "Predictors of tris(l,3-dichloro-2-propyl)
phosphate metabolite in the urine of office workers." Environ. Int. 55: 56-61.
Chicago Tribune (2015). "Watchdog update: Nation's biggest furniture retailer drops flame
retardants." March 6, 2015.
CPSC (2008). "16 CFRPart 1634. Standard for the Flammability of Residential Upholstered
Furniture; Proposed Rule." Federal Register 73(43): 11702-11752.
CPSC (2013a). "16 CFRPart 1634. Upholstered Furniture Fire Safety Technology; Meeting and
Request for Comments." Federal Register 78(54): 17140-17142.
CPSC (2013b). "Upholstered Furniture Fire Safety Technology Meeting Agenda,"
from http://www.cpsc.gov/en/Newsroom/Public-Calendar/Agendas/Upholstered-
Furniture-Fire-Safety-Technology -Meeting-Agenda/.
Dodson, R. E., L. J. Perovich, 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.
Durso, F. (2013). "Hot Seat: A new look at the problem of furniture flammability and home fire
losses. NFPA Journal: September/October issue,"
from http://www.nfpa.org/newsandpublications/nfpa-journal/2013/september-october-
2013/features/old-problem-fresh-look.
ICL Industrial Products (2012). "ICL Industrial Products to expand polymeric flame retardant
production." Retrieved January 28, 2014, from http://www.chemicals-
technology.com/news/newsicl-industrial-products-us-polymeric-retardant.
International Agency for Research on Cancer (2006). "Preamble to the IARC Monographs."
Retrieved April 17, 2012,
from http://monographs.iarc.fr/ENG/Preamble/currentb6evalrationale0706.php.
ISOPA (2005). "Eco-profiles of the European Plastics Industry: Polyurethane Rigid Foam,"
from http://www.isopa.org/isopa/uploads/Documents/documents/rigid%20foam%20LCI.
rjdf.
Kim, Y. S., R. Harris, et al. (2012). "Innovative Approach to Rapid Growth of Highly Clay-
Filled Coatings on Porous Polyurethane Foam." ACS Macro Letters 1: 820-524.
Laufer, G., C. Kirkland, et al. (2012a). "Clay-ChitosanNanobrick Walls: Completely
Renewable Gas Barrier and Flame-Retardant Nanocoatings." ACS Appl Mater Interfaces
4(3): 1643-1649.
6-2
-------
Laufer, G., C. Kirkland, etal. (2012b). "Intumescent Mulitlayer Nanocoating, Made with
Renewable Poly electrolytes, for Flame-Retardant Cotton." Biomacromolecules 13(9):
2843-2848.
Li, Y.-C., J. Schulz, et al. (2009). "Polyelectrolyte/Nanosilicate Thin-Film Assemblies:
Influence of pH on Growth, Mechnical Behavior, and Flammability." ACS Appl Mater
Interfaces 1(10): 2338-2347.
Mayo-Bean, K., K. V. Nabholz, et al. (2011). Methodology Document for the Ecological
Structure-Activity Relationship Model (ECOSAR) Class Program. U.S. Environmental
Protection Agency, Office of Pollution Prevention and Toxics. Washington, DC.
Meylan, W. M. and P. H. Howard (1995). "Atom/fragment contribution method for estimating
octanol-water partition coefficients." J Pharm Sci 84(1): 83-92.
Meylan, W. M., P. H. Howard, et al. (1996). "Improved method for estimating water solubility
from octanol/water partition coefficient." Environ Toxicol Chem 15(2): 100-106.
Nabholz, J. V., R. G. Clements, et al. (1993). Validation of Structure Activity Relationships
Used by the USEPA's Office of Pollution Prevention and Toxics for the Environmental
Hazard Assessment of Industrial Chemcials. Environmental Toxicology and Risk
Assessment. J. W. Gorsuch, F. J. Dwyer, C. G. Ingersoll and T. W. La Point.
Philadelphia, American Society for Testing and Materials. 2: 571-590.
Nayani, M., S. Gunashekar, et al. (2013). "Synthesis and Characterization of Polyurethane-
Nanoclay Composites." International Journal of Polymer Science.
Nazare, S., R. D. Davis, et al. (2012). "Assessment of factors affecting fire performance of
mattresses: a review." Fire Science Reviews 1(2).
New York State Governor's Office (2014). "Governor Cuomo Signs Legislation to Protect
Young Children From Harmful Chemical Found in Consumer Products." Retrieved
October 9, 2014, from http://www.governor.ny.gov/press/09182014-harmful-chemical-
protection.
NFPA (2013). "New Projects and Documents."
NRDC (2013). "Memo to CPSC regarding Upholstered Furniture Fire Safety Technology. July 1,
2013," from http://www.regulations.gov/#!documentDetail:D=CPSC-2008-0005-0049.
NY State Assembly (2013). "Bill No. A06557,"
from http://assembly.state.ny.us/leg/?default_fld=&bn=A06557&term=2013&Summary=
Y&Actions=Y&Votes=Y&Memo=Y&Text=Y.
OEHHA (2011). "Chemicals Known to the State to Cause Cancer or Reproductive Toxicity.
October 28, 2011,"
from http://oehha.ca.gov/prop65/prop65 list/files/P65singlel02811.pdf.
6-3
-------
Patisaul, H. B., S. C. Roberts, et al. (2012). "Accumulation and Endocrine Disrupting Effects of
the Flame Retardant Mixture Firemaster® 550 in Rats: An Exploratory
Assessment." Journal of Biochemical and Molecular Toxicology 27(2): 124-136.
PFA (1992). "Information on Flexible Polyurethane Foam: California Technical Bulletin 133
(TB 133) and Furniture Fire Safety." In Touch 2(2).
PINFA (2012). "Product selector: Expandable graphite,"
from http://www.pinfa.org/component/chronocontact/7chronoformname=product_selecto
r detail s&product selector=98.
Sidhu, S., A. Morgan, et al. (2013). Use of Cone Calorimeter to Identify Selected
Polyhalogenated Dibenzo-P-Dioxins/Furans and Polyaromatic Hydrocarbon Emissions
from the Combustion of Circuit Board Laminates. Final Report. Prepared for the U.S.
Environmental Protection Agency.
Stapleton, H. M. (July 2013). Personal Communication.
Stapleton, H. M., J. G. Allen, et al. (2008). "Alternate and New Brominated Flame Retardants
Detected in U.S. House Dust." Environ Sci Technol 42: 6910-6916.
Stapleton, H. M., S. Eagle, et al. (2012). "Serum PBDEs in a North Carolina Toddler Cohort:
Associations with Handwipes, House Dust, and Socioeconomic Variables." Environ.
Health Perspect. 120(7): 1049-1054.
Stapleton, H. M., S. Klosterhaus, et al. (2011). "Identification of Flame Retardants in
Polyurethane Foam Collected from Baby Products." Environ. Sci. Technol. 45(12): 5323-
5331.
Stapleton, H. M., S. Sharma, et al. (2012). "Novel and High Volume Use Flame Retardants in
U.S. Couches Reflective of the 2005 PentaBDE Phase Out." Environ. Sci. Technol.
46(24): 13432-13439.
State of Maryland (2014). "Chapter 391. An Act Concerning Public Health - Child Care Products
Containing Flame-Retardant Chemicals - TDCPP - Prohibition,"
from http://mgaleg.maryland.gov/2014RS/chapters noln/Ch 391 hb0229T.pdf.
State of New York (2011). "An act to amend the environmental conservation law, in relation to
prohibiting the sale of child care products containing TCEP." Retrieved October 9, 2014,
from http://assemblv.state.ny.us/leg/7default fld=&bn=S04085&term=201 l&Summary=
Y&Actions=Y&Text=Y&Votes=Y.
U.S. EPA (1994). "Joint Project on the Evaluation of (Quantitative) Structure Activity
Relationships." Retrieved November 18, 2013,
from http://www.epa.gov/oppt/newchems/pubs/ene4147.pdf.
6-4
-------
U.S. EPA (1997). "Special Report on Environmental Endocrine Disruption: An Effects
Assessment and Analysis." Retrieved November 18, 2013,
from http ://www.epa.gov/raf/publications/pdfs/ENDOCRINE.PDF.
U.S. EPA (1999). "High Production Volume (HPV) Challenge: Determining the Adequacy of
Existing Data." Retrieved November 18, 2013,
from http://www.epa.gov/hpv/pubs/general/datadfm.htm.
U.S. EPA (2005a). "Furniture Flame Retardancy Partnership: Environmental Profiles of
Chemical Flame-Retardant Alternatives for Low-Density Polyurethane Foam (EPA 742-
R-05-002A)." Retrieved November 18, 2013,
from http://www2.epa.gov/saferchoice/environmental-profiles-chemical-flame-retardant-
alternatives-low-density-polyurethane.
U.S. EPA (2005b). "Pollution Prevention (P2) Framework." Retrieved November 18, 2013,
from http ://www.epa.gov/opptintr/newchems/pubs/sustainable/p2frame-juneOSa2.pdf.
U.S. EPA (2009). "Polybrominated Diphenyl Ethers (PBDEs) Action Plan,"
from http://www.epa.gov/oppt/existingchemicals/pubs/actionplans/pbdes_ap_2009_1230
final.pdf.
U.S. EPA (2010a). "Chemical Categories Report." Retrieved April 17, 2012,
from http ://www.epa.gov/opptintr/newchems/pubs/chemcat.htm.
U.S. EPA (201 Ob). TSCA New Chemicals Program (NCP) Chemical Categories. Office of
Pollution Prevention and Toxics. Washington, DC.
U.S. EPA (201 la). "Assay Development." Retrieved April 17, 2012,
from http://www.epa.gov/oscpmont/oscpendo/pubs/assayvalidation/index.htm.
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://www2.epa.gov/saferchoice/alternatives-assessment-criteria-hazard-
evaluation.
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/pubs/episuite.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
6-5
-------
U.S. EPA (201 If). "On-line AOPWIN™ User's Guide." Retrieved November 18, 2013,
from http://www.epa.gov/oppt/exposure/pubs/episuite.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/pubs/episuite.htm.
U.S. EPA (201 li). "On-line WSKOWWIN™ User's Guide,"
from http://www.epa.gov/oppt/exposure/pubs/episuite.htm.
U.S. EPA (2012a). "Analog Identification Methodology (AIM)." Retrieved April 17, 2012,
from http ://www.epa.gov/oppt/sf/tools/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/tools/methods.htm.
U.S. EPA (2013a). "2012 Chemical Data Reporting Information. Chemical Data Access Tool.
Updated April 4, 2013," from http://iava.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.
2012/04/28.
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
-------
7 Hazard Evaluations
Ammonium polyphosphate (APP)
Screening Level Toxicology Hazard Summary
This table contains hazard information for each chemical; evaluation of risk considers both hazard and exposure. Variations in end-of-life processes or degradation and combustion
by-products are discussed in the report but not addressed directly in the hazard profiles. The caveats listed below must be taken into account when interpreting the 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, M, H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].
d This hazard designation would be assigned MODERATE for a potential for lung overloading if >5% of the particles are in the respirable range as a result of dust forming
operations.
Chemical
CASRN
Human Health Effects
.-a"
o
H
"3
u
^
'0
3
O
'8
sS
U
+i
.y
o
"o
4)
O
4)
O
•a
S
a.
0)
C£
sS
•^
S
S
s.
_o
"3
0)
a
,
O
•a
o
B
s
4)
z
o
P
•a
4)
"S
4)
s.
4)
a
_o
N
S
C/5
a
>y
vi
K, B
s*.!
o -^
•§:1
P-l *5«
O aj
M cc
•c
hH
0>
w
0
1
•c
hH
13
4)
P
Aquatic
Toxicity**
"S
u
1
^3
u
Environmental
Fate
4)
U
's
0.
a
O
1
s
3
u
sS
PH
Ammonium polyphosphate
(APP)
68333-79-9
L
Z,
Z,
Z,
Z,
Z,
Ld
L
VL
L
Z,
Z,
VH
L
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.
7-1
-------
o
HO-K-0
0
NH4+
0
UP— OH
nOH
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
-------
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)
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 andNabholz, 1997
IUCLID, 2000; OECD-SIDS,
2007
Clariant, 2011
Wanjie International Co, 2007
IUCLID, 2000
Consistent with values reported in
other secondary sources.
Consistent with values reported in
other secondary sources.
Reported for the low MW
ammonium polyphosphate.
Reported in chemical datasheet,
consistent with the high melting
point expected for this chemical.
Cutoff value for large high MW
polymers.
Ammonium polyphosphate will have
negligible vapor pressure as an
inorganic salt. Any measurable
vapor pressure is due to
decomposition and the release of
ammonia gas.
Reported in chemical datasheet.
Inadequate. This value likely
represents a dispersion and is not an
indication of the material's true
water solubility.
This value is not consistent with the
other secondary sources; the value is
most likely for the low MW
ammonium polyphosphate.
7-3
-------
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.
Mo 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.
^o 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
shysical/chemical properties and
limited bioavailability.
7-4
-------
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
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
-------
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 andNabholz, 1997
No data located.
No data located.
No data located.
Based on cutoff value for large high
VTW 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, andE. coli WP2uvrA;
with and without metabolic activation
Professional judgment;
Boethling andNabholz, 1997
IUCLID, 2000; NAS, 2000
Based on cutoff value for large high
VTW polymers.
Reported in a secondary source,
study details and test conditions
were not provided.
No data located.
No data located.
7-6
-------
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
Prenatal Development
Postnatal Development
Prenatal and Postnatal
Development
DATA
REFERENCE
DATA QUALITY
No data located.
^o 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 andNabholz, 1997
^o data located.
^o data located.
No data located.
Based on cutoff value for large high
VIW 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.
^o data located.
^o data located.
No data located.
^o data located.
^o data located.
7-7
-------
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 andNabholz, 1997
DATA QUALITY
No data located.
Based on cutoff value for large high
VIW 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 andNabholz, 1997
No data located.
Based on cutoff value for large high
VIW 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)
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 andNabholz, 1997
Professional judgment;
Boethling andNabholz, 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
-------
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
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
-------
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 andNabholz, 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 andNabholz, 1997
Based on cutoff value for large high
MW polymers.
7-10
-------
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 - 1326 mg/L
(Experimental)
Freshwater fish (Oncorhynchus
tshawytschd) 96-hour LC50 = 685-1195
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.
J OO
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
polyphosphate with attapulgite clay,
7-11
-------
Ammonium polyphosphate CASRN 68333-79-9
PROPERTY/ENDPOINT
Daphnid LC50
DATA
Freshwater fish (Oncorhynchus mykiss)
LC50 = 872 -> 10,000 mg/L
(Experimental)
Freshwater fish (Oncorhynchus mykiss)
96-hour LC50 = 1,006 - 10,000 mg/L
(Experimental)
Freshwater fish (Pimephales promelas)
96-hour LC50 = 5 19-1080 mg/L
(Experimental)
Hyalella azteca 96-hour LC50 = 73 mg/L
(Experimental)
Daphnia magna 48-hour EC50 = 90.89
mg/L
(Experimental)
Daphnia magna 48-hour EC50 = 848 -
1,036 mg/L
(Experimental)
Daphnia magna 24-hour EC50 = 1,007
mg/L
Range = 780 - 1,300 mg/L
(Experimental)
NES
(Estimated)
REFERENCE
Gaikowski et al., 1996
EPA, 2013
EPA, 2013
McDonald et al., 1997
EPA, 2013
EPA, 2013
EPA, 2013
Professional judgment
DATA QUALITY
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.
The large MW, limited
bioavailability and low water
solubility suggest there will be NES.
7-12
-------
Ammonium polyphosphate CASRN 68333-79-9
PROPERTY/ENDPOINT
Green Algae EC50
Chronic Aquatic Toxicity
Fish ChV
Daphnid ChV
Green Algae ChV
DATA
NES
(Estimated)
REFERENCE
Professional judgment
DATA QUALITY
The large MW, limited
bioavailability and low water
solubility suggest there will be NES.
J OO
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.
J OO
The large MW, limited
bioavailability and low water
solubility suggest there will be NES.
J OO
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
Level III Fugacity Model
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)
>3 0,000 (Estimated)
Professional judgment;
Boethling andNabholz, 1997
Professional judgment;
Boethling andNabholz, 1997
Cutoff value for large high MW
polymers.
High MW polymers are expected to
adsorb strongly to soil and sediment.
This substance is not amenable to
the model.
7-13
-------
Ammonium polyphosphate CASRN 68333-79-9
PROPERTY/ENDPOINT
Persistence
Water
Soil
Aerobic Biodegradation
Volatilization Half-life for
Model River
Volatilization Half-life for
Model Lake
Aerobic Biodegradation
DATA
REFERENCE
DATA QUALITY
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 andNabholz, 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
-------
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)
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
3y microbial populations; therefore,
aiodegradation is not expected.
Not applicable; this nonguideline
study is for the liquid form of
ammonium polyphosphate.
No data located.
^o data located.
This substance is expected to exist
entirely in particulate form in air and
is not anticipated to undergo gas-
shase 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
-------
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)
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
3y aquatic organisms; therefore,
aioconcentration is not expected.
^o data located.
7-16
-------
Ammonium polyphosphate CASRN 68333-79-9
PROPERTY/ENDPOINT
BAF
Metabolism in Fish
DATA
REFERENCE
DATA QUALITY
No data located.
^o 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).
7-17
-------
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 Tshawytscha). 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/images/stories/factsheet/6APPFactSheetAB-l OO.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://onlinelibrary.wiley.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
-------
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/UI/SIDS Details.aspx?id=7AA7AAF3-3CDE-4F63-8A36-DAA7E786855F.
PINFA (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://onlinelibrary.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/ammoniumjolyphosphate.htm. February 16, 2011.
7-19
-------
Benzole acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester (TBB)
Screening Level Toxicology Hazard Summary
This table contains hazard information for each chemical; evaluation of risk considers both hazard and exposure. Variations in end-of-life processes or degradation and combustion
by-products are discussed in the report but not addressed directly in the hazard profiles. The caveats listed below must be taken into account when interpreting the 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
**%
-*^
'3
4
_u
'3
o
'S
sS
U
•a
CS
-*J
sS
u
'Si
o
sS
II
s.
.0
-*J
sS
.H
S
• et
SS N
a'35
5« fl
4) 8
.o
-*j
sS
^
a
o
•c
Aquatic
Toxicity**
4
S
A
u
Environmental
Fate
1
OJ
PH
_0
-*J
«
"3
s
sS
O
s
Benzoic acid, 2,3,4,5-tetrabromo-, 2-
ethvlhexvl ester (TBB)
183658-27-7
M
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
-------
Br
Br"V>
fir'' Y Y° ^"^
Br O
SMILES: O=C(clc(Br)c(Br)c(Br)c(Br)cl)OCC(CCCC)CC
CASRN: 183658-27-7
MW: 549.9
MF: C15H18Br4O2
Physical Forms: Liquid
Neat: Liquid
Use: Flame retardant
Synonyms: Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester; TBB; EH-TBB. Related trade names: this chemical is one of the components of the commercial
products BZ-54, CN-2065 and Firemaster 550 (FM550).
Chemical Considerations: This is a discrete organic chemical with a MW below 1,000. EPI v4.1 1 was used to estimate physical/chemical and environmental fate
values where adequate experimental data were lacking.
Polymeric: No
Oligomeric: Not applicable
Metabolites, Degradates and Transformation Products: 2,3,4,5-tetrabromobenzoic acid (TBBA CASRN 27581-13-1) (and the corresponding 2-ethylhexanol 104-
76-7) by metabolism and hydrolysis (Estimated); 2,3,4,5-tetrabromomethylbenzoate by metabolism di- and tri-brominated analogs by anaerobic biodegradation
(Estimated) and photodegradation (Davis and Stapleton, 2009; Bearr et al, 2012; Roberts et al., 2012; Patisaul et al., 2013).
Analog: Confidential analogs Analog Structure: Not applicable
Endpoint(s) using analog values: Reproductive, developmental,
repeated dose effects, carcinogenicity, eye irritation and dermal
irritation
Structural Alerts: Polyhalogenated aromatic hydrocarbons, immunotoxicity (EPA, 2012).
Risk Phrases: Not classified by Annex VI Regulation (EC) No 1272/2008 (ESIS, 2012).
Hazard and Risk Assessments: None identified.
7-21
-------
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
Flammability (Flash Point)
Explosivity
Pyrolysis
pH
pKa
>300
(Estimated)
<10-8at25°C
(Estimated)
0.000011 (Estimated)
8.8
(Estimated)
Flash Point: 2 15°C
Performed according to EEC Methods,
Directive 92/69/EEC (OJNo. L383A,
29. 12.92), Part A, Method A9, flash
point (Measured)
Not expected to form explosive mixtures
with air (Estimated)
Not applicable (Estimated)
Not applicable (Estimated)
EPIv4.11;EPA, 1999
EPIv4.11;EPA, 1999
EPIv4.11;EPA, 1999
EPIv4.11
Chemtura, 2013
Professional judgment
Professional judgment
Professional judgment
No data located.
Cutoff value for high boiling point
compounds according to HPV
assessment guidance.
Cutoff value for nonvolatile
compounds according to HPV
assessment guidance.
Estimated value is less than the cutoff
value, <0.001 mg/L, for non-soluble
compounds according to HPV
assessment guidance.
Adequate guideline study.
No experimental data located; based
on its use as a flame retardant.
No data located.
Does not contain functional groups
that are expected to ionize under
environmental conditions.
Does not contain functional groups
that are expected to ionize under
environmental conditions.
7-22
-------
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
-------
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 (iM and 0.644 ± 0.144 nmol min-1
mg protein-1, respectively in human
microsomes. No phase II metabolites of
TBBA were detected. The metabolism
of TBB in humans has not been
evaluated.
Roberts etal., 2012
Adequate study details reported.
Metabolism was measured in the fat
head minnow, common carp, mouse, and
snapping turtle by measuring the loss of
the parent compound (TBB and TBPH)
in hepatic subcellular fractions
Metabolic loss of TBB was observed for
all species with the exception of
snapping turtles; metabolism rates of
TBB were similar between the
subcellular fractions in the fathead
minnow and carp. There were
differences in the rated of metabolism
between the subcellular fraction in mice
with greater metabolism in microsomal
fractions than in cytosolic or S9
fractions. Observed metabolites,
including 2,3,4,5-
tetrabromomethylbenzoate (TBMB),
Bearr etal., 2012
Test substance identified as
Firemaster BZ-54 (TBB and TBPH
in approximate 3:1 ratio).
7-24
-------
Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
appeared to be derived from TBB. It was
concluded by the authors that some
species can metabolize TBB and TBPH
to form varying metabolites.
Estimated to have poor absorption by all
routes of exposure.
Professional judgment
Based on a closely related
confidential analog and professional
judgment.
Acute Mammalian Toxicity
LOW: Based on a rat oral LD50 >2,000 mg/kg. Acute toxicity values are estimated to be a Low hazard
for components of a commercial mixture containing TBB and TBPH (Firemaster 550).
Acute Lethality
Oral
Dermal
Rat oral LD50 >2,000 mg/kg
Rat oral LD50 > 5,000 mg/kg
(Estimated based on analogy)
Rat oral LD50 > 5,000 mg/kg
(Estimated)
Rabbit dermal LD50 > 2,000 mg/kg
(Estimated based on analogy)
Submitted confidential study
Chemtura, 2006
Chemtura, 2006
Chemtura, 2006
Confidential study submitted to EPA;
test substance purity: 99.7%;
conducted according to 92/69/EEC
guideline consistent with OECD
guideline 401.
No study details reported in an
MSDS; estimated based on analogy
to a similar compound to a
component of Firemaster 550
(commercial mixture containing TBB
and TBPH); it is not certain if this
component contains TBB.
No study details reported in an
MSDS; estimated based on one
component of Firemaster 550
(commercial mixture containing TBB
and TBPH); it is not certain if this
component contains TBB.
No study details reported in an
MSDS; estimated based on analogy
to a similar compound to a
component of Firemaster 550
(commercial mixture containing TBB
7-25
-------
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
-------
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)
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
-------
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
-------
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)
REFERENCE
Chemtura, 2006
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
-------
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 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,
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
-------
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 (F 1 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
Professional judgment
DATA QUALITY
Estimated based on a closely related
confidential analog and professional
judgment.
No data located.
7-31
-------
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
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
-------
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
-------
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:0.1mg/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
-------
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)
Chemtura, 2008
Chemtura, 2006
Chemtura, 2006
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.
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
-------
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
-------
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
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
-------
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
-------
Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Respiratory Sensitization
No data located.
Respiratory Sensitization
No data located.
Eye Irritation
MODERATE: Estimated to be irritating to mildly irritating based on experimental data reporting
irritation from a commercial mixture containing TBB, mild eye irritation in rabbits from a closely
related confidential analog and professional judgment.
Irritating; effects reversible by day 4
(Estimated)
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)
Submitted confidential study
Professional judgment
Chemtura, 2013
Chemtura, 2006
Chemtura, 2006
Estimated based on a closely related
confidential analog and professional
judgment.
Confidential study submitted to EPA.
Limited study details reported for a
commercial mixture containing TBB.
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
-------
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
Chemtura, 2013
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 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
-------
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
-------
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)
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
-------
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), NES 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), NES 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), NES are predicted
for this endpoint.
Fish 96-hour LC50
(Estimated)
= 0.008 mg/L
ECOSARvl.ll
NES: The estimated log Kow of 8.8
for this chemical exceeds the SAR
7-43
-------
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 < 0.001 mg/L
(Estimated)
ECOSAR: Neutral organics
ECOSARvl.ll
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
-------
Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT
Green Algae EC50
DATA
Daphnia magna 4 8 -hour LC50 =2.44
mg/L
(Estimated by analogy)
Daphnia 48-hour LC50 = 0.008 mg/L
(Estimated)
ECOSAR: Esters
Daphnia 48-hour LC50 < 0.001 mg/L
(Estimated)
ECOSAR: Neutral organics
Green algae 96 hour LC50 = No effects
at saturation (NES).
(Experimental)
Green algae 96-hour EC50 = 0.001 mg/L
(Estimated)
REFERENCE
Chemtura, 2006
ECOSARvl.ll
ECOSARvl.ll
Submitted confidential study
ECOSARvl.ll
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
-------
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 6.4; NES are
predicted for these endpoints.
Selenastrum capricornutum 96-hour
EC5o>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 < 0.001 mg/L
(Estimated)
ECOSAR: Neutral organics
ECOSARvl.ll
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.
Chronic Aquatic Toxicity
LOW: Based on estimated chronic toxicity values for fish, daphnid, and algae that indicate no effects at
saturation (NES).
Fish ChV
Fish ChV< 0.001 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
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.
7-46
-------
Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Green algae 96-hour EC50 < 0.001 mg/L
(Estimated)
ECOSAR: Neutral organics
ECOSARvl.ll
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 ChV
Daphnia carinata 15-day
NOEC: 15.6|^g/l(repro)
NOEC: 62.5 ng/1 (mortality)
LC50: 79.3 ng/1
Submitted confidential study
Daphnia ChV < 0.001 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Limited study details reported in a
submitted confidential Chronic
Toxicity/Reproductive toxicity test.
NES are predicted for this endpoint
based on a log Kow of 8.8 and the
reported effect level was above the
estimated water solubility (0.000011
mg/L).
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
-------
Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Daphnia ChV < 0.001 mg/L
(Estimated)
ECOSAR: Neutral organics
ECOSARvl.ll
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.
Green Algae ChV
Green algae ChV = 0.003
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Green algae ChV = 0.004
(Estimated)
ECOSAR: Neutral organics
ECOSARvl.ll
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.
7-48
-------
Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
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, 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
-------
Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT
Persistence
Water
Aerobic Biodegradation
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. There was 93% removal of a commercial mixture containing TBB in
an activated sludge simulation test due to sorption to sludge. 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 30 ID: Closed
Bottle Test
6% biodegradation after 28 days
(Measured)
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)
>93% removal
Submitted confidential study
Submitted confidential study
EPIv4.11
Submitted confidential study
Submitted confidential study
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.
Guideline study, submitted for a
7-50
-------
Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
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
Sediment/Water
Biodegradation
Atmospheric Half-life
Photolysis
Hydrolysis
DATA
Test method: 303A: Activated Sludge
Units - Simulation Test
(Measured)
8 days (Estimated)
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)
REFERENCE
EPIv4.11
EPIv4.11
Holligeretal., 2004; EPI
v4.11
EPIv4.11
Davis and Stapleton, 2009
EPIv4.11
DATA QUALITY
commercial mixture containing TBB.
The substances did not biodegrade
but showed removal (>93%) due to
sorption to sludge.
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.
Hydrolysis rates are expected to be
pH-dependent and may be limited the
by low water solubility of this
7-51
-------
Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT
Environmental Half-life
Bioaccumulation
Fish BCF
DATA
50%/>1 year at pH 4, 7, and 9
(Measured)
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
Submitted confidential study
de Jourdan et al., 2013
PBT Profiler
DATA QUALITY
compound.
Limited study details available. 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, 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.
BCFK edible tissue: 2.26
BCFK non-edible tissue: 2.70
BCFK whole fish: 2.47
According to OECD 3 05 C in Trout
(Measured)
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)
Submitted confidential study
Submitted confidential study
EPIv4.11
Guideline study, submitted for a
commercial mixture containing TBB.
Adequate guideline study.
Estimations run with using the
SMILES:
O=C(clc(Br)c(Br)c(Br)c(Br)cl)O.
7-52
-------
Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT
Other BCF
BAF
Metabolism in Fish
DATA
2 100 (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
(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
EPIv4.11
Bearretal., 2010
Patisauletal., 2013
EPIv4.11
DATA QUALITY
No data located.
BAFs were not calculated. Non
guideline study indicates that
absorption of this compound can
occur in fish through dietary
exposure.
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.
7-53
-------
Benzoic acid, 2,3,4,5-tetrabromo-, 2-ethylhexyl ester CASRN 183658-27-7
PROPERTY/ENDPOINT
DATA
REFERENCE DATA QUALITY
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 day care (Stapleton et al.,
2008, 2009; Ali etal., 2011, 2012, 2013; Covaci etal., 2012; Dodson etal., 2012; EFSA, 2012; Kopp etal.,
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; Briinnich'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 NFIANES biomonitoring report (CDC, 2013).
7-54
-------
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.
7-55
-------
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.
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): 973 5-9744.
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
(Corbicula flumined) and gastropod (Elimiaproximo). Environ Sci Technol 46(11):5798-5805.
7-56
-------
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.
7-57
-------
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.
7-58
-------
Di(2-ethylhexyl) tetrabromophthalate (TBPH)
Screening Level Toxicology Hazard Summary
This table contains hazard information for each chemical; evaluation of risk considers both hazard and exposure. Variations in end-of-life processes or degradation and combustion
by-products are discussed in the report but not addressed directly in the hazard profiles. The caveats listed below must be taken into account when interpreting the information in the
table.
VL = Very Low hazard L = Low hazard = Moderate hazard = High hazard VH = Very High hazard - Endpoints in colored text (VL, L, , H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"
Chemical
CASRN
•
Human Health Effects
g
y
H
o
H
4J
-£
U
<
^
•^
'0
'3
M
O
£
ft
u
>>
-^
_u
'H
o
-*^
o
g
O
0)
_tj
"S
•a
1
sS
g
S
a.
0
3
5
Q
"3
•a
_o
2™
S
z
2^
o
Q
•a
S
0)
g"
C£
B
O
13
.H
-*^
%
0)
C/5
1
C/5
^§
o +s
II
P-l %
S g
M $
B
_o
sS
-*^
•_
0)
^s
H
B
0
1
•_
hH
13
0)
Q
Aquatic
Toxicity**
u
_u
'a
S
A
u
Environmental
Fate
0)
u
g
-^^
%
£
0)
a.
a
0
"3
s
u
u
sS
o
S
Di(2-ethylhexyl) tetrabromophthalate
26040-51-7
L
M
M
M
M
L
L
L
L
z,
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.
7-59
-------
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 (TBMEHP) by in vitro metabolism (and the corresponding 2-
ethylhexanol 104-76-7) or hydrolysis (Estimated); di- and tri-brominated analogs of TBPH by anaerobic biodegradation (Estimated) and photodegradation (Davis and
Stapleton, 2009; Bearr et al., 2012; Roberts et al., 2012; Patisaul et al, 2013).
Analog: Confidential analogs
Endpoint(s) using analog values: Carcinogenicity, reproductive,
developmental effects and repeated dose effects
Analog Structure: Not applicable
Structural Alerts: Polyhalogenated aromatic hydrocarbons, immunotoxicity (EPA, 2012).
Risk Phrases: Not classified by Annex VI Regulation (EC) No 1272/2008 (ESIS, 2012).
Hazard and Risk Assessments: Di(2-ethylhexyl) tetrabromophthalate is part of the HPV Data Summary and Test Plan (ACC, 2004).
7-60
-------
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
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 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 nonsoluble
compounds according to HPV
assessment guidance.
Estimated value is greater than the
cutoff value, >10, according to
methodology based on HPV
assessment guidance.
Test substance identified as Uniplex
FRP-45 (TBPH >99.5% purity).
No experimental data located; based on
its use as a flame retardant.
No data located.
Does not contain functional groups that
are expected to ionize under
environmental conditions.
Does not contain functional groups that
are expected to ionize under
environmental conditions.
7-61
-------
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.
Pregnant 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.
7-62
-------
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 et al., 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).
7-63
-------
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
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
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
7-64
-------
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
7-65
-------
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
ACC, 2004
Chemtura, 2006
Chemtura, 2006
ACC, 2004
DATA QUALITY
source. Test material was RC9927; FR-
45B; CASRN 26040-51-7 (Purity >
95%).
No study details reported in an MSDS;
estimated based on one component of
Firemaster 550 (commercial mixture
containing TBB and TBPH); it is not
certain if this component contains
TBPH.
No data located.
Study details reported in a secondary
source. Test material was RC9927; FR-
45B; CASRN 26040-51-7 (Purity >
95%).
Limited study details reported in an
MSDS; estimated based on analogy to
a similar compound to a component of
Firemaster 550 (commercial mixture
containing TBB and TBPH); it is not
certain if this component contains
TBPH; study conducted according to
OECD 422.
No study details reported in an MSDS;
estimated based on one component of
Firemaster 550 (commercial mixture
containing TBB and TBPH); it is not
certain if this component contains
TBPH.
Study details reported in a secondary
source. Test material was RC9927; FR-
45B; CASRN 26040-51-7 (Purity >
7-66
-------
Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
95%).
DNA Damage and Repair
No data located.
Other
No data located.
Reproductive Effects
MODERATE: No reproductive effects were reported in a 2-generation oral (gavage) reproductive
toxicity study in rats at doses up to 165 mg/kg-day (highest dose tested) of Firemaster BZ 54
(commercial mixture of TBB and TBPH) with a larger constituent of TBB. The NOAEL of 165
mg/kg-day falls within the Moderate hazard criteria range; it is possible that effects driven by either
component may occur within the Moderate hazard range if tested at a higher dose. Exposure to
TBPH did not cause adverse changes in testes or ovary weights in a 28-day repeat dose study in rats;
however, while reproductive organs and tissues were examined, other reproductive parameters were
not reported to have been examined. Data from a reproductive/developmental toxicity screen in rats
exposed to a similar compound to a component of Firemaster 550 (commercial mixture containing
TBB and TBPH) indicated histopathological effects in female reproductive organs at doses > 25
mg/kg-day (lowest dose tested; a NOAEL was not identified). It is uncertain if the commercial
mixture contained TBPH.
Reproduction/Developmental
Toxicity Screen
Reproductive/developmental
toxicity screen in rats orally
administered 0, 25, 100, 400 mg/kg-
day of a similar compound to an
unspecified component of a
commercial mixture.
Reduced number of successful
pregnancies and viable offspring at
doses of 100 and 400 mg/kg-day;
histopathological effects reported in
thymus and male reproductive
organs (testes and epididymides) at
400 mg/kg-day; histopathological
effects in female reproductive
organs and adrenals at doses of > 25
mg/kg-day.
NOAEL: Not established
Chemtura, 2006
Limited study details reported in an
MSDS; estimated based on analogy to
a similar compound to a component of
Firemaster 550 (commercial mixture
containing TBB and TBPH); it is not
certain if this component contains
TBPH; study conducted according to
OECD 422.
7-67
-------
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
ACC, 2004
DATA QUALITY
Estimated based on a closely related
confidential analog and professional
judgment.
Test substance: Firemaster BZ 54
(commercial mixture of TBB and
TBPH) with a larger constituent of
TBB; it is not clear which component
or components of the mixture are
driving the reported developmental
effects.
Study details reported in a secondary
source. Test material was RC9927; FR-
45B; CASRN 26040-51-7 (Purity >
95%). It is reported that a full
complement of male and female
7-68
-------
Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
Other
Developmental Effects
[Reproduction/ Developmental
DATA
complement of male and female
reproductive organs and tissues
examined by gross necropsy and
histopathology; No changes in testes
and ovary weights.
NOAEL: 2,000 ppm (2,1 10 mg/kg-
day - highest dose tested)
LOAEL: Not established
Potential for reproductive effects
following long-term exposure to
BZ-54 HP
(Estimated)
REFERENCE
Chemtura, 2008
DATA QUALITY
reproductive tissues and organs were
evaluated, however, the list of tissues
and organs is unspecified. While
reproductive organs and tissues were
examined, other reproductive
parameters were not reported to be
examined.
No study details reported in an MSDS;
Estimated based on BZ-54 HP
(commercial mixture containing TBB
and TBPH); it is not clear which
component is driving repeated dose
effects.
MODERATE: Developmental effects were reported in a 2-generation reproductive toxicity study in
rats and a prenatal study in rats exposed to CN-2065 (a commercial mixture of TBB and TBPH with
the predominant constituent being TBB). Developmental effects were reported at doses of 165 mg/kg-
day and 100 mg/kg-day in the 2-generation and prenatal studies, respectively. Both studies had a
NOAEL of 50 mg/kg-day which falls within the Moderate hazard criteria range. It is not clear which
component or components of the commercial mixture caused the reported developmental effects.
Development/neurodevelopmental effects were reported in a study in pregnant Wistar rats
administered a FM550 mixture (sum total of TBB and TBPH approximately 50%) during gestation
though lactation (GD8 - PND21); developmental effects included early female puberty, weight gain,
altered exploratory behavior, and increased male left ventricle thickness (LOAEL = 1 mg/kg-day,
NOAEL = 0.1 mg/kg-day). It is uncertain which component or components of the FM 550 mixture is
driving the reported developmental effects. While the FM 550 mixture data indicates a High hazard
potential, it may be the other components driving the reported toxicity. Gestational exposure to the
TBPH monoester metabolite TBMEHP at a dose of 200 mg/kg-day resulted in an increased number
of altered seminiferous cords (MNGs) per cord area in male fetuses from exposed rat dams.
Experimental data indicated no effects on embryonic survival or development in exposed zebrafish
embryos.
Estimated to have moderate [Professional judgment
Estimated based on a closely related
7-69
-------
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 F1 parental
generation began treatment on PND
22 and continued treatment similar
to the FO generation.
Parental toxicity: lower body
weights and body weight gains
during premating period in parental
and Fl females at highest dose;
Lower body weights in the
premating period in Fl males; body
weight gains were not affected in
males.
Developmental toxicity: at highest
dose, lower body weights at birth
and throughout lactation were
reported in both generations of
offspring (Fl and F2); this resulted
in lower premating body weights of
the first female generation.
Decreased spleen weights at
lactation day 21 in Fl male pups
MPI Research, 2008a
Study details reported in an
unpublished report; test substance:
Firemaster BZ 54 (CN-2065)
commercial mixture of TBB and TBPH
with the predominant constituent being
TBB; it is not clear which component
or components of the mixture are
driving the reported developmental
effects.
7-70
-------
Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
and F2 male and female pups.
Parental toxicity:
NOAEL: 50 mg/kg-day
LOAEL: 165 mg/kg-day
Developmental toxicity:
NOAEL: 50 mg/kg-day
LOAEL: 165 mg/kg-day
7-71
-------
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.
Maternal toxicity:
NOAEL: 50 mg/kg-day
LOAEL: 100 mg/kg-day
Developmental toxicity:
NOAEL: 50 mg/kg-day
LOAEL: 100 mg/kg-day based on
decreased fetal weight
(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.
7-72
-------
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 et al., 2012
Estimated based on the assumption of
total conversion of TBPH to
TBMEHP; the test substance is
identified as the TBPH metabolite
TBMEHP; The doses reported are
based on TBMEHP; though TBPH is
expected to metabolize to TBMEHP, it
is uncertain if these effects would
occur or at what dose effects might
occur following TBPH exposure.
7-73
-------
Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
Postnatal Development
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
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
7-74
-------
Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
(GD8-PND21);
Maternal toxicity: Increased serum
thyroxine (T4) levels in the high
dose dams compared to controls was
reported. There was no significant
change in triiodothyronine (T3)
levels in dam serum. Decreased
hepatic carboxylesterease activity
was also reported in dams in the
high dose group.
Developmental toxicity: female
offspring in the high dose group
displayed a significantly earlier
vaginal opening when compared to
controls. A statistically significant
increase in weight was reported in
both males and females in the high
dose group at PND 120. This effect
persisted through PND 180 to PND
220 with high dose males and
females having significantly higher
weights than same sex controls. A
dose-dependent decrease in the
number of rats to enter with open
arms, (indicating anxiety), was
reported in both male and female
offspring. Increased blood glucose
levels were reported in male
offspring in the high-dose group
compared to controls. There was no
statistically significant difference in
heart weight of male or female
offspring. Left ventricular (LV) free
wall thickness was significantly
TBPH approximately 50%) and other
compounds including IPTPP (CASRN
68937-41-7) and TPP (CASRN 115-
86-6); it is not clear which component
or components of the mixture are
driving the reported developmental
effects.
7-75
-------
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:0.1mg/kg-day
LOAEL: 1 mg/kg-day
Developmental toxicity:
NOAEL: 0.1 mg/kg-day
LOAEL: 1 mg/kg-day (based on
early vaginal opening in females,
increased weight in males and
females, decreased open arm
behavior, increased blood glucose
levels in males and increased LV
thickness in males)
(Estimated)
Zebrafish embryos were exposed
under static conditions to purified
TBPH at concentrations up to 10
uM from 5.25 -96 hours post
fertilization (hpf).
There were no effects on embryonic
survival or development.
McGeeetal., 2013
Zebrafish is a nonstandard species;
current DfE criteria for this endpoint
are based on gestational and/or
postnatal exposure to mammalian
species. Thus, this study cannot be
used to assign a hazard designation for
the developmental endpoint.
Neurotoxicity
MODERATE: Estimated based on analogy to a similar compound to a component of Firemaster 550
(commercial mixture containing TBB and TBPH). There is potential for neurological effects after
breathing or swallowing large amounts or after long-term exposure to this analog. There were no
neurotoxic effects reported in a 28-day oral toxicity study in rats treated with the analog.
Neurotoxicity Screening Battery
(Adult)
28-day sub-chronic oral toxicity
study in rats treated with 0, 160,
400, 1,000 mg/kg-day;
Chemtura, 2006
Limited study details reported in an
MSDS; neurotoxicity was evaluated in
this study; estimated based on one
7-76
-------
Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
Other
DATA
No neurotoxicity effects were
reported.
NOAEL: 1,000 mg/kg-day (highest
dose tested)
LOAEL: Not established
(Estimated)
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)
REFERENCE
Chemtura, 2008
Chemtura, 2006
DATA QUALITY
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 BZ-54 HP
(commercial mixture containing TBB
and TBPH); it is not clear which
component is driving repeated dose
effects.
No study details reported in an MSDS;
estimated based on analogy to a similar
compound to a component of
Firemaster 550 (commercial mixture
containing TBB and TBPH); it is not
certain if this component contains
TBPH.
7-77
-------
Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Repeated Dose Effects
MODERATE: There was a slight decrease in body weight along with decreased calcium and
phosphorus levels in female rats with a LOAEL= 20,000 ppm (2,110 mg/kg-day). While this effect is
known to occur at values that fall within the hazard criteria range for a LOW hazard designation,
the NOAEL is identified as 2,000 ppm (211 mg/kg-day). The hazard criteria values are based on 90-
day studies; therefore, the hazard criteria values are tripled for chemicals evaluated in 28-day
studies. The LOAEL of 2,110 mg/kg-day remains in the Low hazard category, while the NOAEL of
211 mg/kg-day falls within the Moderate hazard designation (30 - 300 mg/kg-day). There is
uncertainty as to where effects may occur. A Moderate hazard was designated as a conservative
approach. TBPH is also estimated to have a Moderate potential for liver effects cerebral
hemorrhages based on a closely related confidential analog and professional judgment and is
estimated to have kidney, liver, adrenal, thymus, developmental, reproductive, and neurological
effects following long-term exposure to commercial mixtures that included TBPH. There was an
increased incidence of sparse hair in abdominal region, reduced body weight, and reduced food
consumption in dams during gestation in a prenatal study in rats exposed to CN-2065 (commercial
mixture of TBB and TBPH with the predominant constituent being TBB) on GD 6-19 at doses > 100
mg/kg-day (NOAEL = 50 mg/kg-day). Reduced body weight and body weight gain during the
premating period in parental FO and Fl female rats treated with 165 mg/kg-day CN-2065 (NOAEL =
50 mg/kg-day) was also reported in a 2-generation oral reproductive toxicity in rats.
Rat, 28-day dietary toxicity study; 0,
200, 2,000, and 20,000 ppm in diet
(~0, 21.1, 211, 2,110 mg/kg-day);
There was no mortality, clinical
signs of toxicity, or adverse effects
on examined organs or tissues;
There was a slight decrease in body
weight along with decreased
calcium and phosphorus levels in
females in the 20,000 ppm (2,110
mg/kg-day) group.
NOAEL: 2,000 ppm (211 mg/kg-
day)
LOAEL: 20,000 ppm (2,110 mg/kg-
ACC, 2004
Study details reported in a secondary
source. Test material was RC9927; FR-
45B; CASRN 26040-51-7 (Purity >
95%). Doses were reported as ppm in
the diet but were converted to
mg/kg/day using EPA 1988 reference
values for body weight and food
consumption. The hazard criteria for
repeat dose toxicity is based on 90 day
studies; the hazard criteria values are
tripled for chemicals evaluated in 28-
day studies. The LOAEL of 2,110
mg/kg-day remains in the Low hazard
category, while the NOAEL of 211
mg/kg-day falls within the Moderate
7-78
-------
Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
day) based on slightly decreased
body weight and decreased calcium
and phosphorus levels (females)
hazard designation (30-300 mg/kg-
day). There is uncertainty as to where
effects may occur.
Estimated to have moderate
potential for liver effects and
concern for cerebral hemorrhages.
(Estimated by analogy)
Professional judgment
Estimated based on a closely related
confidential analog and professional
judgment.
Potential for neurological effects
after breathing or swallowing large
quantities or repeated exposure over
a prolonged period of time is
possible for a similar compound to
an unspecified component of the
commercial mixture
(Estimated based on analogy)
Chemtura, 2006
No study details reported in an MSDS;
estimated based on analogy to a similar
compound to a component of
Firemaster 550 (commercial mixture
containing TBB and TBPH); it is not
certain if this component contains
TBPH.
Potential for kidney and liver effects
following long-term exposure to
BZ-54 HP
(Estimated)
Chemtura, 2008
No study details reported in an MSDS;
Estimated based on BZ-54 HP
(commercial mixture containing TBB
and TBPH); it is not clear which
component is driving repeated dose
effects.
2-generation oral (gavage)
reproductive toxicity study in rats
administered 15, 50, or 165 mg/kg-
day; FO generation was treated 10
weeks prior to pairing through the
mating period. Males were treated
until termination; females were
treated through gestation and
lactation, and until termination on
PND 21; pup selected (30/sex/dose)
to continue as Fl parental
generation began treatment on PND
MPI Research, 2008a
Study details reported in an
unpublished report; test substance:
Firemaster BZ 54 (CN-2065)
commercial mixture of TBB and TBPH
with the predominant constituent being
TBB; it is not clear which component
or components of the mixture are
driving the reported developmental
effects.
7-79
-------
Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
22 and continued treatment similar
to the FO generation.
Parental toxicity: lower body
weights and body weight gains
during premating period in parental
and Fl females at highest dose;
Lower body weights in the
premating period in Fl males; body
weight gains were not affected in
males.
Parental toxicity:
NOAEL: 50 mg/kg-day
LOAEL: 165 mg/kg-day (reduced
body weight and body weight gain)
(Estimated)
In a prenatal study in rats exposed to
0, 50, 100, 300 mg/kg-d on GD 6-
19; dams experienced increased
incidence of animals with sparse
hair in abdominal region, lower
gestation body weights and body
weight gain, and lower gestation
food consumption at doses > 100
mg/kg-day.
NOAEL: 50 mg/kg-day
LOAEL (maternal): 100 mg/kg-day
(Estimated)
MPI Research, 2008b
Study details reported in an
unpublished report Test substance:
Firemaster BZ54 (CN-2065);
commercial mixture of TBB and TBPH
with the predominant constituent being
TBB; it is not clear which component
or components of the mixture are
driving the reported developmental
effects.
28-day sub-chronic oral toxicity
study in rats treated with 0, 160,
400, 1,000 mg/kg-day;
Kidney effects were reported.
Chemtura, 2006
Limited study details reported in an
MSDS; neurotoxicity was evaluated in
this study; estimated based on one
component of Firemaster 550
7-80
-------
Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
NOAEL: 160 mg/kg-day
LOAEL: 1,000 mg/kg-day based on
kidney effects
(Estimated)
(commercial mixture containing TBB
and TBPH); it is not certain if this
component contains TBPH.
Skin Sensitization
LOW: TBPH is not a skin sensitizer in guinea pigs. There were positive results for skin sensitization
following exposure to components of commercial mixtures containing TBPH. It is not certain which
component or components caused the reported effects.
Skin Sensitization
Negative for skin sensitization in
guinea pigs
The commercial mixture Firemaster
BZ 54 is a skin sensitizer.
(Estimated)
An unspecified component of the
commercial mixture was reported to
be a sensitizer in a M&K
sensitization assay.
(Estimated)
An unspecified component of the
commercial mixture was not
sensitizing in a Buehler test.
(Estimated)
ACC, 2004
Chemtura, 2013
Chemtura, 2006
Chemtura, 2006
Study details reported in a secondary
source. Test material was RC9927; FR-
45B; CASRN 26040-51-7 (Purity >
95%).
Limited study details reported in an
MSDS; Test substance: Firemaster BZ
54 (commercial mixture of TBB and
TBPH) with a larger constituent of
TBB; it is not clear which component
or components of the mixture are
driving the reported effects.
No study details reported in an MSDS;
estimated based on one component of
Firemaster 550 (commercial mixture
containing TBB and TBPH); it is not
certain if this component contains
TBPH.
No study details reported in an MSDS;
estimated based on one component of
Firemaster 550 (commercial mixture
containing TBB and TBPH); it is not
certain if this component contains
TBPH.
7-81
-------
Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
Respiratory Sensitization
[Respiratory Sensitization
Eye Irritation
Eye Irritation
Dermal Irritation
Dermal Irritation
DATA
REFERENCE
DATA QUALITY
No data located.
[No data located.
LOW: TBPH is a slight eye irritant in rabbits. Experimental studies reported mild irritation to
components of a commercial mixture.
Slight eye irritant in rabbits
The commercial mixture Firemaster
BZ 54 is a slight eye irritant.
(Estimated)
An unspecified component of the
commercial mixture was reported to
be a slight eye irritant in rabbits.
(Estimated)
No eye irritation was reported in
rabbits for a similar compound to an
unspecified component of the
commercial mixture.
(Estimated based on analogy)
ACC, 2004
Chemtura, 2013
Chemtura, 2006
Chemtura, 2006
Study details reported in a secondary
source. Test material was RC9927; FR-
45B; CASRN 26040-51-7 (Purity >
95%).
Limited study details reported in an
MSDS; Test substance: Firemaster BZ
54 (commercial mixture of TBB and
TBPH) with a larger constituent of
TBB; it is not clear which component
or components of the mixture are
driving the reported effects.
No study details reported in an MSDS;
estimated based on one component of
Firemaster 550 (commercial mixture
containing TBB and TBPH); it is not
certain if this component contains
TBPH.
No study details reported in an MSDS;
estimated based on analogy to a similar
compound to a component of
Firemaster 550 (commercial mixture
containing TBB and TBPH); it is not
certain if this component contains
TBPH.
LOW: TBPH is a slight skin irritant in rabbits. Experimental data reported mild irritation from
components of a commercial mixture.
Slight skin irritant in rabbits
ACC, 2004
Study details reported in a secondary
source. Test material was RC9927; FR-
7-82
-------
Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
45B; CASRN 26040-51-7 (Purity >
95%).
No skin irritation was reported in
rabbits for a similar compound to an
unspecified component of the
commercial mixture.
(Estimated based on analogy)
Chemtura, 2006
No study details reported in an MSDS;
estimated based on analogy to a similar
compound to a component of
Firemaster 550 (commercial mixture
containing TBB and TBPH); it is not
certain if this component contains
TBPH.
An unspecified component of the
commercial mixture was reported to
be a slight skin irritant in rabbits.
(Estimated)
Chemtura, 2006
No study details reported in an MSDS;
estimated based on one component of
Firemaster 550 (commercial mixture
containing TBB and TBPH); it is not
certain if this component contains
TBPH.
The commercial mixture Firemaster
BZ 54 is a mild skin irritant.
(Estimated)
Chemtura, 2013
Limited study details reported in an
MSDS; Test substance: Firemaster BZ
54 (commercial mixture of TBB and
TBPH) with a larger constituent of
TBB; it is not clear which component
or components of the mixture are
driving the reported effects.
Endocrine Activity
One study indicated that TBPH does not cause changes in estrogenic and androgenic activity in yeast
reporter-gene assays. Increased serum thyroxine (T4) levels were reported in the serum of dams
following oral administration to FM500 (mixture of 50% sum total of TBB and TBPH); other
components of the mixture are TPP and IPTPP. It is unclear which component or components of the
mixture are driving the endocrine activity effects.
Potential for adrenal effects
following long-term exposure to
BZ-54 HP
(Estimated)
Chemtura, 2008
No study details reported in an MSDS;
Estimated based on BZ-54 HP
(commercial mixture containing TBB
and TBPH); it is not clear which
component is driving repeated dose
effects.
7-83
-------
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 etal., 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 etal., 2013
Reproductive/developmental
toxicity screen in rats orally
administered 0, 25, 100, 400 mg/kg-
day of a similar compound to an
unspecified component of a
commercial mixture. Reduced
number of successful pregnancies
and viable offspring at doses of 100
and 400 mg/kg-day;
histopathological effects reported in
Chemtura, 2006
Estimated based on data for FM550
mixture; non guideline study; the test
substance identified as FM550 is a
mixture made up of TBB, TBPH
(sum total of TBB and TBPH is
approximately 50%), TPP and
IPTPP; it is not clear which
component or components of the
mixture are driving the reported
endocrine activity effects.
Limited study details reported in an
MSDS; estimated based on analogy to
a similar compound to a component of
Firemaster 550 (commercial mixture
containing TBB and TBPH); it is not
certain if this component contains
TBPH; study conducted according to
OECD 422.
7-84
-------
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
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
Professional judgment
No study details reported in an MSDS;
Estimated based on BZ-54 HP
(commercial mixture containing TBB
and TBPH); it is not clear which
component is driving repeated dose
effects.
Estimated based on a structural alert
for polyhalogenated aromatic
hydrocarbons and professional
judgment.
ECOTOXICITY
ECOSAR Class
Acute Aquatic Toxicity
Fish LC50
Esters
LOW: Based on an estimated Log Kow of 12 and the fact that the experimental effect levels in fish,
daphnia, and algae were above the estimated water solubility (1.98 E-9 mg/L), NES are predicted for
this endpoint.
Fish 96-hour LD50 = No effects at
saturation (NES)
(Experimental)
Submitted confidential study
Study details reported in a submitted
confidential study.
7-85
-------
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 LC50 < 0.001 mg/L
(Estimated)
ECOSARvl.ll
No study details reported in an MSDS;
estimated based on one component of
Firemaster 550 and for Firemaster BZ-
54 (commercial mixtures containing
TBB and TBPH); Based on log Kow of
12 and the reported effect level was
above the estimated water solubility
(1.983 x 10'9 mg/L), NES are predicted
for this endpoint.
No study details reported in an MSDS;
estimated based on analogy to a similar
compound to a component of
Firemaster 550 (commercial mixture
containing TBB and TBPH); it is not
certain if this component contains
TBPH. Based on log Kow of 12 and the
reported effect level was above the
estimated water solubility (1.983 x 10"9
mg/L), NES are predicted for this
endpoint.
No study details reported in an MSDS;
estimated based on analogy to a similar
compound to a component of
Firemaster 550 (commercial mixture
containing TBB and TBPH); it is not
certain if this component contains
TBPH. Based on log Kow of 12 and the
reported effect level was above the
estimated water solubility (1.983 x 10"9
mg/L), NES are predicted for this
endpoint.
NES: The estimated log Kow of 12 for
this chemical exceeds the SAR
7-86
-------
Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
ECOSAR: Esters
Fish 96-hour LC50 < 0.001 mg/L
(Estimated)
ECOSAR: Neutral organics
ECOSAR v 1.11
limitation for log Kow of 5.0; NES are
predicted for these endpoints.
NES: The estimated log Kow of 12 for
this chemical exceeds the SAR
limitation for log Kow of 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 4 8-hour LC50
2.44 mg/L
(Estimated by analogy)
Chemtura, 2006
Study details reported in a secondary
source. Test material was RC9927; FR-
45B; CASRN 26040-51-7 (Purity >
95%). Based on an estimated log Kow
of 12 and the fact that the experimental
effect levels in Daphnia were above the
estimated water solubility (1.983 x 10"9
mg/L), NES are predicted for this
endpoint.
No study details reported in an MSDS;
estimated based on analogy to a similar
compound to a component of
Firemaster 550 (commercial mixture
containing TBB and TBPH); it is not
certain if this component contains
TBPH. Based on log Kow of 12 and the
reported effect level was above the
estimated water solubility (1.983 x 10"9
mg/L), NES are predicted for this
7-87
-------
Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
endpoint.
Daphnia magna 4 8-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 TBPH);
Based on log Kow of 12 and the
reported effect level was above the
estimated water solubility.
Daphnia 48-hour LC50 < 0.001
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 < 0.001
mg/L
(Estimated)
ECOSAR: Neutral organics
ECOSARvl.ll
NES: The estimated log Kow of 12 for
this chemical exceeds the SAR
limitation for log Kow of 5.0; NES are
predicted for these endpoints.
Narcosis classes (neutral organics) are
7-88
-------
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
Study details reported in an
unpublished study submitted to EPA.
Green algae 96-hour < O.OOlmg/L
(Estimated)
ECOSAR: Esters
ECOSAR v 1.11
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.
Green algae 96-hour EC50 < 0.001
mg/L
(Estimated)
ECOSAR: Neutral organics
ECOSAR v 1.11
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
provided by ECOSAR classes that
have a more specific mode of action
relative to narcosis.
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
12 and the reported effect level was
above the estimated water solubility
(0.000011 mg/L), NES are predicted
7-89
-------
Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
for this endpoint.
Chronic Aquatic Toxicity
LOW: Based on estimated chronic toxicity values for fish, daphnid, and algae that suggest no effects
at saturation (NES). An experimental effect level for an analog in algae was above the estimated
water solubility (1.98 E-9 mg/L) also suggesting NES.
Fish ChV
Fish ChV< 0.001 mg/L
(Estimated)
ECOSAR: Esters
Fish ChV < 0.001 mg/L
(Estimated)
ECOSAR: Neutral organics
ECOSAR v 1.11
ECOSAR v 1.11
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.
Daphnid ChV
Daphnia ChV < 0.001 mg/L
(Estimated)
ECOSAR: Esters
ECOSAR v 1.11
Daphnid ChV < 0.001 mg/L
(Estimated)
ECOSAR: Neutral organics
ECOSAR v 1.11
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
7-90
-------
Di(2-ethylhexyl) tetrabromophthalate CASRN 26040-51-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
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 72-hour NOAEC = 0.31
mg/L
96-hour NOAEC = 1.3 mg/L
(Estimated by analogy)
Chemtura, 2006
Green algae ChV < 0.001 mg/L
(Estimated)
ECOSAR: Esters
ECOSAR v 1.11
Green algae ChV < 0.001 mg/L
(Estimated)
ECOSAR: Neutral organics
ECOSAR v 1.11
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 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.
7-91
-------
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)
>3 0,000 (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.
7-92
-------
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 301B: CO2
Evolution Test
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
7-93
-------
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
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.
7-94
-------
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 TBPH was
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
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-
7-95
-------
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).
7-96
-------
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 High 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; Molleretal., 2011, 2012; Covaci etal., 2012; Dodson etal., 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 (Corbicula fluminea); 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
7-97
-------
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.
7-98
-------
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-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/.
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.
7-99
-------
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
(Corbicula flumined) and gastropod (Elimiaproximo). Environ Sci Technol 46(11):5798-5805.
Lam JC, Lau RK, Murphy MB, et al. (2009) Temporal trends of hexabromocyclododecanes (HBCDs) and polybrominated diphenyl ethers
(PBDEs) and detection of two novel flame retardants in marine mammals from Hong Kong, South China. Environ Sci Technol 43(18):6944-6949.
Ma Y, Venier M, Kites RA (2012) 2-Ethylhexyl tetrabromobenzoate and bis(2-ethylhexyl) tetrabromophthalate flame retardants in the Great
Lakes atmosphere. Environ Sci Technol 46(1):204-208.
McGee SP, Konstantinov A, Stapleton HM, et al. (2013) Aryl phosphate esters within a major pentaBDE replacement product induce
cardiotoxicity in developing zebrafish embryos: Potential role of the aryl hydrocarbon receptor. Toxicol Sci 133(1): 144-156.
Moller A, Xie Z, Cai M, et al. (2012) Polybrominated diphenyl ethers vs alternate brominated flame retardants and dechloranes from East Asia to
the Arctic. Environ Sci Technol 45(16):6793-6799.
Moller A, Xie Z, Sturm R, et al. (2011) Polybrominated diphenyl ethers (PBDEs) and alternative brominated flame retardants in air and seawater
of the European Arctic. Environ Pollut 159(6): 1577-1583.
MPI Research (2008a) CN-2065: An oral two-generation reproduction and fertility study in rats. MPI Research Inc.
7-100
-------
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):459-466.
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.
7-101
-------
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate
Screening Level Toxicology Hazard Summary
This table contains hazard information for each chemical; evaluation of risk considers both hazard and exposure. Variations in end-of-life processes or degradation and combustion
by-products are discussed in the report but not addressed directly in the hazard profiles. The caveats listed below must be taken into account when interpreting the information in
the table.
VL = Very Low hazard L = Low hazard = Moderate hazard = High hazard VH = Very High hazard - Endpoints in colored text (VL, L, , H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].
Chemical
CASRN
Human Health Effects
Acute Toxicity
Carcinogenicity
Genotoxicity
Reproductive
Developmental
Neurological
Repeated Dose
Skin Sensitization
Respiratory
Sensitization
Eye Irritation
Dermal Irritation
Aquatic
Toxicity
u
Chronic
Environmental
Fate
0)
u
0)
a.
Bioaccumulation
Diethyl bis(2-
hydroxyethyl)aminomethylphosphonate
2781-11-5
L
M
L
L
M
M
M
L
VL
L
L
7-102
-------
O-P=O
SMILES: O=P(OCC)(OCC)CN(CCO)CCO
CASRN:2781-ll-5
MW: 255.25
MF: C9H22NO5P
Physical Forms: Liquid
Neat: Liquid
Use: Flame retardant
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-Diethyl N,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 v4.1 1 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 (1 1 1-42-2) 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
^0 " \
Phosphonic acid, 4-morpholinyl-, dimethyl ester Phosphonic acid, P-methyl-, c
(CASRN 597-25-1) (CASRN 756-79-
\ I
0 P O
„ \
lim ethyl ester Phosphonic acid, dimethyl ester
5) (CASRN 868-85-9)
7-103
-------
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).
7-104
-------
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)
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
EPIv4.11;EPA, 1999
Supresta, 2006; Professional judgment
EPIv4.11
Supresta, 2006; Professional judgment
Supresta, 2006
Nonguideline study, sufficient details
were not available to assess the quality of
this study.
Adequate, value obtained from peer-
reviewed primary source. The study
showed that vaporization and
decomposition occur simultaneously, and
that 88% degradation had taken place by
700°C.
Cutoff value for high boiling compounds
according to HPV assessment guidance;
decomposition likely occurs before the
boiling point is reached.
Adequate, decomposition occurs upon
boiling as described in additional sources,
above. The data are for the commercial
mixture, reported as 85% purity. It is
possible that this measured boiling point
reflects vaporization of these impurities as
well as vaporization of the test substance.
Inadequate, the data is for the commercial
mixture, which is reported to have only
70-90% purity. The results are likely due
to volatile impurities in the substance.
Adequate, guideline study. The data are
for the commercial mixture, reported as
70-90% purity.
7-105
-------
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)
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, 20 13
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%
3urity.
Nonguideline study, sufficient details
were not available to assess the quality of
this study.
No experimental data located; based on its
use as a flame retardant.
No experimental data located; based on its
use as a flame retardant.
^o data located.
Nonguideline 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
No data located.
^o data located.
No data located.
7-106
-------
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
)W
Test conditions: 10 rats per sex;
gavage (in corn oil) at 5,000 mg/kg
jw; 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-
lour 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
tidney 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.
Hiere is evidence of Carcinogenicity
n males following exposure
increased incidence of squamous
OECD SIDS, 2004
^o data located.
Estimated based on analogy to phosphonic
acid, dimethyl ester (CASRN 868-85-9);
data reported in a secondary source.
7-107
-------
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate CASRN 2781-11-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
:ell carcinoma in lung and
ilveolar/bronchial cell adenoma or
:arcinoma)
Equivocal evidence was reported for
emale rats.
Estimated by analogy)
Vlice (B6C3F1) were orally
idministered 0, 100, 200 mg/kg-day
:>f the analog BMP.
Hiere was no evidence of
:arcinogenicity in male or female
nice.
Estimated by analogy)
OECD SIDS, 2004
ARC classification: The analog DMPIARC, 1999
'is not classifiable as to its
:arcinogenicity to humans (group 3)".
Estimated by analogy)
estimated based on analogy to phosphonic
icid, dimethyl ester (CASRN 868-85-9);
iata reported in a secondary source.
stimated based on analogy to phosphonic
icid, dimethyl ester (CASRN 868-85-9);
ARC classification; estimated based on
malogy to phosphonic acid, dimethyl ester
CASRN 868-85-9); data reported in a
secondary source.
Combined Chronic
Toxicity/Carcinogenicity
n a 2-year toxicology and
:arcinogenicity study, F344/N rats
re orally administered the analog
DMMPA at a dose of 0, 150, 300, 600
-ng/kg-day for 103 weeks.
Hiere was some evidence of
:arcinogenicity for male and female
•ats (increased incidence of
nononuclear cell leukemia).
Estimated by analogy)
NTP, 1986
estimated based on analogy to Phosphonic
icid, 4-morpholinyl-, dimethyl ester
CASRN 597-25-1).
7-108
-------
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate CASRN 2781-11-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
In a 2-year toxicology and
carcinogen!city study, B6C3F1
mice were orally administered the
analog DMMPA at a dose of 0,
150, 300, 600 mg/kg-day for 103
weeks.
There was no evidence of
carcinogenicity for male or female
rats.
(Estimated by analogy)
NTP, 1986
Estimated based on analogy to
Jhosphonic acid, 4-morpholinyl-,
dimethyl ester (CASRN 597-25-1).
7-109
-------
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate CASRN 2781-11-5
PROPERTY/ENDPOINT
Other
Genotoxicity
Gene Mutation in vitro
DATA
In a 2-year toxicology and
carcinogenicity study, F344/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 hyperplasia, tubular cell
adenocarcinomas, hyperplasia of
the transitional cell epithelium,
and transitional cell papillomas of
the kidney). There was also
increased incidence of
mononuclear cell leukemia in male
rats at the highest dose.
No evidence of carcinogenic
activity for female rats was
reported.
(Estimated by analogy)
REFERENCE
NTP, 1987
DATA QUALITY
Estimated based on analogy to
)hosphonic acid, P-methyl-, dimethyl
ester (CASRN 756-79-6).
•4o data located.
MODERATE: Based on weight of evidence from multiple studies. Diethyl bis(2-
hydroxyethyl)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 (L5178Y)
with and without metabolic activation
Supresta, 2006; EPA, 2009
Adequate studies summarized in reliable
secondary sources.
7-110
-------
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate CASRN 2781-11-5
PROPERTY/ENDPOINT
Gene Mutation in vivo
Chromosomal Aberrations in
vitro
Chromosomal Aberrations in
vivo
DNA Damage and Repair
Other
DATA
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
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; EPA, 2009
Supresta, 2006; EPA, 2009
Supresta, 2006
DATA QUALITY
Adequate study summarized in reliable
secondary sources.
Adequate study summarized in reliable
secondary sources.
No data located.
Adequate study summarized in reliable
secondary sources.
^o data located.
No data located.
Adequate study summarized in reliable
secondary sources.
7-111
-------
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate CASRN 2781-11-5
PROPERTY/ENDPOINT
Reproductive Effects
Reproduction/Developmental
Toxicity Screen
Combined Repeated Dose with
Reproduction/ Developmental
Toxicity Screen
Reproduction and Fertility
Effects
Other
DATA
REFERENCE
DATA QUALITY
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;
Mo LOAELs were established in the
study.
No data located.
No data located.
^o data located.
7-112
-------
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate CASRN 2781-11-5
PROPERTY/ENDPOINT
Developmental Effects
Reproduction/ Developmental
Toxicity Screen
Combined Repeated Dose with
Reproduction/ Developmental
Toxicity Screen
Prenatal Development
Postnatal Development
Prenatal and Postnatal
Development
DATA
REFERENCE
DATA QUALITY
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
Adequate; guideline study (OECD 421)
summarized in reliable secondary sources;
true NOAELs may be > 750 mg/kg-day;
Mo LOAELs were established in this
study.
No data located.
No data located.
^o data located.
^o data located.
7-113
-------
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate CASRN 2781-11-5
PROPERTY/ENDPOINT
Developmental Neurotoxicity
Other
Neurotoxicity
Neurotoxicity Screening
Battery (Adult)
Other
Repeated Dose Effects
DATA
REFERENCE
DATA QUALITY
No data located.
^o data located.
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.
7-114
-------
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate CASRN 2781-11-5
PROPERTY/ENDPOINT
Skin Sensitization
Skin Sensitization
Respiratory Sensitization
(Respiratory Sensitization
Eye Irritation
Eye Irritation
Dermal Irritation
Dermal Irritation
Endocrine Activity
Immunotoxicity
Immune System Effects
DATA
REFERENCE
DATA QUALITY
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.
LOW: Diethyl bis(2-hydroxyethyl)aminomethylphosphonate produced m
within 72-hours post-instillation.
Rabbit (9 of mixed sex); mild
conjunctival 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.
Supresta, 2006; EPA, 2009
ild irritation in rabbits which cleared
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
fSfo data located.
No data were located
|No data located.
7-115
-------
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate CASRN 2781-11-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
ECOTOXICITY
ECOSAR Class
Acute Aquatic Toxicity
Fish LC50
Daphnid LC50
MODERATE: Based on an experimental acute aquatic toxicity value of > 86 mg/L in daphnia. Estimated values
for fish, daphnia and green algae indicated a Low hazard.
Oncorhynchus mykiss (rainbow trout;
aka Salmo gairdnerf) 96-hr LC50 >
10,000 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 > 100
mg/L
(Estimated)
ECOSAR: Aliphatic amines
Freshwater fish 96-hour LC50 > 100
mg/L
(Estimated)
ECOSAR: Esters
Daphnia magna (water flea) 4 8 -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)
Daphnia magna 48-hour LC50 > 100
Supresta, 2006; EPA, 2009
ECOSARvl.ll
ECOSARvl.ll
Supresta, 2006; EPA, 2009
ECOSARvl.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.
Estimate for the Esters class was provided
for comparative purposes.
See Section 5.5.1.
Guideline study (OECD 202; EPA
OPPTS 850.1010) according to reliable
secondary sources.
7-116
-------
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate CASRN 2781-11-5
PROPERTY/ENDPOINT
Green Algae EC so
DATA
mg/L
(Estimated)
ECOSAR: Aliphatic amines
Daphnia magna 48-hour LC50 > 100
mg/L
(Estimated)
ECOSAR: Esters
Green algae (Pseudokirchneriella
subcapitata) 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 > 100
mg/L
(Estimated)
ECOSAR: Aliphatic amines
Green algae 96-hour EC50 > 100
mg/L
(Estimated)
ECOSAR: Esters
REFERENCE
ECOSARvl.ll
Supresta, 2006; EPA, 2009
ECOSARvl.ll
ECOSARvl.ll
DATA QUALITY
Estimate for the Esters class was provided
for comparative purposes.
See Section 5.5.1.
Study details reported in a secondary
source.
Estimate for the Esters class was provided
for comparative purposes.
See Section 5.5.1.
7-117
-------
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate CASRN 2781-11-5
PROPERTY/ENDPOINT
Chronic Aquatic Toxicity
Fish ChV
Daphnid ChV
Green Algae ChV
DATA
REFERENCE
DATA QUALITY
LOW: Based a NOEC of 86 mg/L in green algae and estimated values for fish, daphnia and algae.
Freshwater fish ChV > 417 mg/L
(Estimated)
Freshwater fish ChV > 10 mg/L
(Estimated)
ECOSAR: Aliphatic amines
Freshwater fish ChV > 10 mg/L
(Estimated)
ECOSAR: Esters
Daphnia magna ChV > 10 mg/L
(Estimated)
ECOSAR: Aliphatic amines
Daphnia magna ChV > 10 mg/L
(Estimated)
ECOSAR: Esters
Green algae (Pseudokirchneriella
subcapitata) 96-hour NOEC = 86
mg/L
(Experimental)
Green algae ChV > 10 mg/L
(Estimated)
ECOSAR: Aliphatic amines
Green algae ChV > 10 mg/L
Professional judgment
ECOSARvl.ll
ECOSARvl.ll
ECOSARvl.ll
ECOSARvl.ll
Supresta, 2006
ECOSARvl.ll
ECOSARvl.ll
An ACR of 24 was derived for the
phosphate ester class based on
experimental data for Tris (p-t-
butylphenyl) phosphate (TBPP). The
acute-to-chronic ratio was applied to
available experimental acute fish data for
Diethyl bis(2-
hydroxyethyl)aminomethylphosphonate
(ChV > 10,000 mg/L /24 = 417 mg/L)
Estimate for the Esters class was provided
for comparative purposes.
See Section 5.5.1.
Estimate for the Esters class was provided
for comparative purposes.
See Section 5.5.1.
Study details reported in a secondary
source.
Estimate for the Esters class was provided
7-118
-------
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate CASRN 2781-11-5
PROPERTY/ENDPOINT
DATA
(Estimated)
ECOSAR: Esters
REFERENCE
DATA QUALITY
for comparative purposes.
See Section 5.5.1.
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)
EPI v4. 11; Professional judgment
EPIv4.11
EPIv4.11
Cutoff value for non-volatile compounds.
7-119
-------
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate CASRN 2781-11-5
PROPERTY/ENDPOINT
Persistence
Water
Soil
Aerobic Biodegradation
Volatilization Half-life for
Model River
Volatilization Half-life for
Model Lake
Aerobic Biodegradation
Anaerobic Biodegradation
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)
Supresta, 2006
EPIv4.11
EPIv4.11
Adequate, guideline study.
^o data located.
7-120
-------
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate CASRN 2781-11-5
PROPERTY/ENDPOINT
Air
Reactivity
Soil Biodegradation with
Product Identification
Sediment/Water
Biodegradation
Atmospheric Half-life
Photolysis
Hydrolysis
Environmental Half-life
Bioaccumulation
Fish BCF
Other BCF
BAF
Metabolism in Fish
DATA
0.075 days (Estimated)
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
EPIv4.11
Professional judgment; Mill, 2000
Supresta, 2006
DATA QUALITY
No data located.
^o data located.
The substance does not contain functional
groups that would be expected to absorb
light at wavelengths >290 nm.
Adequate, valid guideline study. The
3urity 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)
EPIv4.11
EPIv4.11
^o data located.
^o data located.
ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring
Ecological Biomonitoring
Human Biomonitoring
No data located.
No data located.
No data located.
7-121
-------
ACE (2013) ACE Acidity and Basicity Calculator, http://aceorganic.pearsoncmg.com/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/21 ecosar.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.
7-122
-------
Emerald Innovation™ NH-1
Screening Level Toxicology Hazard Summary
This table contains hazard information for each chemical; evaluation of risk considers both hazard and exposure. Variations in end-of-life processes or degradation and combustion
by-products are discussed in the report but not addressed directly in the hazard profiles. The caveats listed below must be taken into account when interpreting the 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"
•
* Each hazard designation for a mixture is based upon the component with the highest hazard, whether it is an experimental or estimated value.
Chemical
CASRN
Human Health Effects
Acute Toxicity
Carcinogenicity
Genotoxicity
Reproductive
Developmental
Neurological
Repeated Dose
Skin Sensitization
Respiratory
Sensitization
.0
-*^
sS
^
•_
hH
0)
^j
W
Dermal Irritation
Aquatic
Toxicity
0)
1
Chronic
Environmental
Fate
Persistence
Bioaccumulation
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
M
1 '
L
L
VL
VL
VH
VH
VH
VH
VH
VH
M
L
L
M
H
L
H
7-123
-------
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.
7-124
-------
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 49-5 0°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 at 25 °C
Reported as 2.8xlO"7 hPa at 25 °C
(Measured)
Confidential C: 0.01 at20°C
Confidential study (as cited in
ATSDR, 2012)
Lide, 2008
EC, 2000
Confidential study
ATSDR, 2012
Confidential study
EPIv4.11;EPA, 1999
O'Neil et al., 2006
EC, 2000
ATSDR, 2012
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
7-125
-------
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: l.SxlO6
(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 at20°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
ATSDR, 2012
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.
7-126
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
Flammability (Flash Point)
Explosivity
Pyrolysis
pH
pKa
DATA
Confidential E: 1 1 (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
environmental conditions.
7-127
-------
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
Confidential study
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.
7-128
-------
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
between 1997 and 2007. Median
concentration across all subjects was
8.5 ng/g (min-max values: 3.2-11
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.
7-129
-------
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)
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
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
7-130
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
Inhalation
Carcinogenicity
DATA
> 1 0,000 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
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.
7-131
-------
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
DATA QUALITY
No data located.
^o data located.
^o 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.
7-132
-------
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
Confidential C: Negative,
Salmonella typhimurium strains
TA98, TA100, TA1535, TA1537,
TA1538 with and without metabolic
activation. Positive controls
responded as expected.
ECHA, 2013
Confidential C: Negative,
Salmonella typhimurium strains
TA1535, TA1537, TA98 and TA100
with and without metabolic activation.
ECHA, 2013
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
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
primary source.
Sufficient details in summaries of
three similar studies reported in a
secondary source. No data on test
substance purity.
Adequate study reported in a
secondary source. Study protocol in
line with Guideline for gene point
mutation assay in bacterial cells.
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.
Sufficient study details reported in a
secondary source. Acceptable
scientific method. No data on test
substance purity.
Confidential D: Negative, Ames
assay in Salmonella typhimurium
strains TA98, TA100, TA1537,
TA1538 with and without metabolic
ATSDR, 2009; ECHA, 2013
Reported in a secondary source.
7-133
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
Gene Mutation in vivo
DATA
activation
Confidential D: Negative, forward
mutation assay in mouse lymphoma
L5178Y cells
Confidential E: Negative, cell
transformation assay in BALB/3T3
cells without metabolic activation.
Test concentrations: 0.00125,
0.00250, 0.005, 0.01 and 0.02 nl/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 (il/plate
REFERENCE
OECD-SIDS, 2002; ECHA, 2013
ECHA, 2013
ECHA, 2013
ECHA, 2013
ECHA, 2013
DATA QUALITY
Reported in a secondary source.
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
No data located.
7-134
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Chromosomal Aberrations in
vitro
onfidential D: Negative in
chromosome aberration test in Chinese
lamster V79 cells; with and without
netabolic activation.
ECHA, 2013
onfidential E: Negative, sister
chromatid exchanges (SCEs) and
chromosome aberrations in mouse
ymphoma L5178Y cells with and
without metabolic activation.
Test concentrations: - S9 mix:
3.000625, 0.00125, 0.00250, 0.00500
and 0.01000 jil/ml; +S9 mix: 0.00125,
3.00250, 0.00500, 0.01000 and
3.02000 nl/ml
ECHA, 2013
Reported in a secondary source.
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
secondary source. No data on purity
of test substance.
Reported in a secondary source.
Other
Confidential D: Negative, mitotic
;ene conversion assay in
Saccharomyces cerevisiae with and
without activation
OECD-SIDS, 2002
Reported in a secondary source.
7-135
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Reproductive Effects
MODERATE: No adverse effects were observed on fetal viability, post-implantation loss, total implantations
or the incidence of fetal malformations at doses up to 1,500 mg/kg-day (LOAEL not established) following
gestational oral exposure to Confidential C in rats. Although no reproductive effects were observed in this
study, there is a lack of data on reproductive parameters as measured in fertility or multigenerational
studies and no data were available for other routes of exposure. It is uncertain if effects would occur in more
definitive studies or via other routes; a Moderate hazard has been designated based on this uncertainty.
Reproductive toxicity is LOW for Confidential D and E.
Reproduction/Developmental
Toxicity Screen
Confidential C: Confidential C was
administered by gavage in corn oil to
three groups of 25 mated Charles
River CD female rats at dose levels of
0 (corn oil), 250, 500 or 1,500 mg/kg-
day on days 6 to 15 of gestation. The
treatment had no effect at any dose
level on fetal resorption, fetal
viability, post-implantation loss, total
implantations or the incidence of fetal
malformations.
NOAEL: 1,500 mg/kg-day (highest
dose tested)
LOAEL: Not established
Confidential study
Sufficient details reported in a
secondary source.
7-136
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Combined Repeated Dose with
Reproduction/ Developmental
Toxicity Screen
onfidential D:
Reproductive/developmental dietary
>tudy; Confidential D was
idministered in the diet for 91 days at
concentrations of 0, 0.25, 0.50, 0.75,
3rl.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
>roup. All remained on the same diet
is in the subchronic study until day 20
:>f gestation when dams were
>acrificed. No signs of parental
oxicity, no reproductive effects
number pregnant, corpora lutea,
mplantations, implantation efficiency,
•esorptions).
VOAEL: 690 mg/kg-day (highest dose
ested)
-GAEL: Not established
OECD-SIDS, 2002; ATSDR, 2009 Reported in a secondary source
Reproduction and Fertility
Effects
onfidential 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-
lay)
VOAEL: 1,000 mg/kg-day (highest
lose 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
,vith 50, 250, 1,000 mg/kg-day
ECHA, 2013
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
7-137
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Confidential E. Exposure was 2 weeks
srior to mating, during mating period
up to 2 weeks, males and females)
ind during gestation, lactation and
intil post-partum day 4 (females).
Vo mortality or overt signs of parental
oxicity. No effect was seen on body
weight and food consumption. Gross
lecropsy and organ weight data and
listopathology of the reproductive
Drgans revealed no adverse findings.
VIean 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
ng/kg-day groups (not statistically
significant). Subsequently, a
statistically significant increase in the
ibsolute number of stillbirths in the
250 and 1,000 mg/kg-day groups was
loted. However, overall a similar
lumber of pup deaths were observed
icross all groups. Overall, pup
survival from day 0 to 4 was lower in
he 250 mg/kg-day group (due to 10
ieaths in one litter), higher in the 50
ng/kg-day group and approximately
he same as control in the 1,000
rig/kg-day group.
VOAEL: 1,000 mg/kg-day (highest
iose tested)
7-138
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
,OAEL: Not established
Other
onfidential D: Men living in
lomes with higher amounts of
Confidential D in house dust had
•educed sperm count and altered
lormone levels related to fertility
ind thyroid function. Each
nterquartile range (IQR)
Confidential D increase in house
lust samples was associated with a
9% decrease in sperm
concentrations and a 10% increase
n prolactin levels.
Confidential study
Hie actual exposure to Confidential
D is unknown; it is not known if
Confidential D or other substances
bund in the household dust caused
or contributed to the reported
oxicity.
7-139
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Developmental Effects
LOW: Based on a rat oral reproductive/developmental NOAEL = 690 mg/kg-day for fetal effects (highest
dose tested) following exposure to Confidential D. Developmental toxicity is also LOW for Confidential E
(based on a NOAEL and LOAEL of 400 and 1,000 mg/kg-day, respectively) and VERY LOW for
onfidential C (based on a NOAEL of 2,000 mg/kg-day).
There were no data located for the developmental neurotoxicity endpoint. Decreased cholinesterase activity
n pregnant lab animals has been shown to have a negative impact on fetal brain development. As a result,
;here is uncertain potential for developmental neurotoxicity for this substance.
Reproduction/ Developmental
Toxicity Screen
onfidential D:
Reproductive/developmental dietary
>tudy; Confidential D was
idministered in the diet for 91 days at
concentrations of 0, 0.25, 0.50, 0.75,
3rl.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
>roup. All remained on the same diet
is in the subchronic study until day 20
:>f gestation when dams were sacrifice.
Vo effects on fetal endpoints
viability, early or late deaths, fetal
weight, length or distribution) or
>keletal anomalies.
Developmental effects:
VOAEL: 690 mg/kg-day (highest dose
ested)
-GAEL: Not established
OECD-SIDS, 2002; ATSDR, 2009;
ECHA, 2012
LOAEL was not identified; there
were no effects at the highest dose
ested.
Combined Repeated Dose with
Reproduction/ Developmental
Toxicity Screen
No data located.
7-140
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
Prenatal Development
DATA
Confidential C: In a range-finding
developmental toxicity study,
Confidential C was administered by
gavage in corn oil to groups of 5
mated Charles River CD female rats
at dose levels of 0, 25, 250, 500
1,000, and 2,000 mg/kg-day on days 6
to 15 of gestation. At doses up to
1,000 mg/kg-day, all rats survived.
Two animals died or were sacrificed
in the high dose group. Maternal
toxicity (reduced righting reflex,
hypoactivity, lethargy, ataxia and
stained anogenital haircoat) was
observed in the animals receiving 500
mg/kg-day or greater. Maternal
weight gain was normal in animals
receiving 1,000 mg/kg-day or less.
The treatment had no effect at any
dose level on fetal resorption, fetal
viability, postimplantation loss and
total implantations.
Maternal Toxicity:
NOAEL: 250 mg/kg-day
LOAEL: 500 mg/kg-day
Developmental toxicity:
NOAEL: 2,000 mg/kg-day (highest
dose tested)
LOAEL: Not established
Confidential C: In a developmental
toxicity study, Confidential C was
REFERENCE
ECHA, 2013
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
7-141
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
administered by gavage in corn oil to
three groups of 25 mated Charles
River CD female rats at dose levels of
250, 500 and 1,500 mg/kg-day on
days 6 to 15 of gestation. Sacrifices
were conducted on Gd 20. Maternal
weight gain was depressed only in the
high-dose group. The treatment had
no effect at any dose level on fetal
resorption, fetal viability,
postimplantation loss, total
implantations or incidence of fetal
malformations.
Maternal Toxicity:
NOAEL: 500 mg/kg-day
LOAEL: 1,500 mg/kg-day
Developmental toxicity:
NOAEL: 1,500 mg/kg-day (highest
dose tested)
LOAEL: Not established
substance purity in secondary sources.
Confidential D: Pregnant Wistar rats
were administered 0, 0.1 or 1 mg/kg-
day of the confidential analog in the
diet during gestation and through
lactation (GD8 - PND 21); Maternal
toxicity: Increased serum thyroxine
(T4) levels in the high dose dams
compared to controls was reported.
There was no significant change in
triiodothyronine (T3) levels in dam
serum. Decreased hepatic
Confidential study
Estimated based on data for
confidential mixture; non guideline
study.
7-142
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
carboxylesterease activity was also
reported in dams in the high dose
group. Developmental toxicity:
female offspring in the high dose
group displayed a significantly earlier
vaginal opening when compared to
controls. A statistically significant
increase in weight was reported in
both males and females in the high
dose group at PND 120. This effect
persisted through PND 180 to PND
220 with high dose males and females
having significantly higher weights
than same sex controls. A dose-
dependent decrease in the number of
rats to enter with open arms,
(indicating anxiety), was reported in
both male and female offspring.
Increased blood glucose levels were
reported in male offspring in the high-
dose group compared to controls.
There was no statistically significant
difference in heart weight of male or
female offspring. Left ventricular
(LV) free wall thickness was
significantly increased in male
offspring in the high dose group; there
were no changes in LV thickness in
females at any dose.
Maternal Toxicity:
NOAEL:0.1mg/kg-day
LOAEL: 1 mg/kg-day
7-143
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Developmental toxicity:
NOAEL: O.lmg/kg-day
LOAEL: 1 mg/kg-day (based on early
vaginal opening in females, increased
weight in males and females,
decreased open arm behavior,
increased blood glucose levels in
males and increased LV thickness in
males)
Confidential E: Sprague-Dawley rats
(7 females/group) were administered
Confidential E via oral gavage at
doses on 100, 400, 1,000 mg/kg-day
on GD 6-20.
Reduced food consumption on GD 6-
9 (1,000 mg/kg-day). Increased body
weight gain (400 and 1,000 mg/kg-
day). Increased absolute and relative
liver weight in all treatment groups
(not considered by study authors to be
treatment-related). Embryo- or feto-
toxicity as indicated by a reduction in
fetal body weight (1,000 mg/kg-day).
Craniofacial malformations in 3
fetuses (1,000 mg/kg-day). Increased
maternal body weight gain was
reported on GDO-6 for the 100 and
400 mg/kg-day dose groups and on
GDI6-21 for the 400 mg/kg-day dose
group; absolute and relative liver
weights were increased in all
treatment groups.
ECHA, 2013
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
7-144
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Maternal toxicity:
NOAEL: Not established
LOAEL: 100 mg/kg-day (lowest dose
tested)
Developmental toxicity:
NOAEL: 400 mg/kg-day
LOAEL: 1,000 mg/kg-day
Confidential E: Charles River rats
(25 females) were administered
Confidential E via oral gavage at
doses of 0, 300, 1,000, 3,000 mg/kg-
day once daily on GD 6-19.
Clinical signs of toxicity in all groups,
including controls. Decrease in mean
number of early resorptions and mean
postimplantation loss (mid dose),
which was attributed by study authors
to a random occurrence. Slight
increase in number of litters with
malformations (high dose), but was
not considered biologically significant
by study authors (single incidences).
NOAEL (maternal and
developmental): 3,000 mg/kg-day
(highest dose tested)
LOAEL: Not established
ECHA, 2013
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
Confidential E: Charles River rats (5
females/group) were administered
Confidential E at doses of 250, 500,
ECHA, 2013
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
7-145
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
Postnatal Development
Prenatal and Postnatal
Development
Developmental Neurotoxicity
DATA
1,000, 2,500, 5,000 mg/kg-day once
daily on GD 6- 19.
No mortality or behavioral effects
were observed. Anogenital staining
and/or matting in all treatment groups.
Red and/or brown matter around the
nose, mouth and forelimbs (5,000
mg/kg-day). Slight reduction in body
weight gain (1,000 and 2,500 mg/kg-
day); severe reduction in mean
maternal body weight gain (5,000
mg/kg-day). Increase in
postimplantation loss, decrease in
viable fetuses (5,000 mg/kg-day).
Maternal toxicity:
NOAEL: 2,500 mg/kg-day
LOAEL: 5,000 mg/kg-day
Developmental toxicity:
NOAEL: 5,000 mg/kg-day
LOAEL: Not established
Confidential C: There were no data
located for the developmental
neurotoxicity endpoint. As a result,
there is uncertain potential for
developmental neurotoxicity for this
substance.
REFERENCE
Professional judgment
DATA QUALITY
No data located.
^o data located.
No data located.
7-146
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Confidential D: There were no data
located for the developmental
neurotoxicity endpoint. Decreased
cholinesterase activity in pregnant lab
animals has been shown to have a
negative impact on fetal brain
development. As a result, there is
uncertain potential for developmental
neurotoxicity for this substance.
Professional judgment
No data located.
Confidential E: Uncertain concern
for developmental neurotoxicity based
on the potential for Cholinesterase
(ChE) inhibition in dams that may
result in alterations of fetal
neurodevelopment.
(Estimated)
Professional judgment
Estimated based on a structural alert
for organophosphates for the
neurotoxicity endpoint.
Other
No data located.
Neurotoxicity
MODERATE: Neurotoxic effects following exposure to Confidential C included morphological changes to
the sciatic nerve, reduction in caudal nerve response and increases in absolute and relative refractory
periods at a dose of 255 mg/kg-day in rats (lowest dose tested). These studies indicated that there is some
potential for neurotoxicity at higher doses. In addition, there is potential for neurotoxic effects based on a
structural alert. A NOAEL and LOAEL of ~ 10 and ~ 100 mg/kg-day, respectively were established in
rabbits following dermal exposure to Confidential E. Adverse effects included decreased brain
cholinesterase. The potential for neurotoxic effects following exposure to Confidential D is LOW.
Neurotoxicity Screening
Battery (Adult)
Confidential C: Sprague-Dawley rats
(12/sex/dose), received Confidential C
daily via oral gavage at doses of 0.25
or 0.50 g/kg-day for 18 weeks. (255
or 510 mg/kg-day). Adverse
neurological signs were evident in
almost all exposed rats in the second
half of the study. Nerve conduction
ECHA, 2013; Confidential study
Sufficient study details study reported
in a secondary source. Study limited
by not establishing a NOAEL.
7-147
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
measurements were made with all rats
at the end of the 6th, 12th, and 18th
week.
No differences in body weights
throughout the study. Breathing
difficulty and ataxia were observed.
Tremors at high dose. Significantly
reduced conduction velocity in the
caudal nerve in both treatment groups.
Increased absolute (18 weeks) and
relative refractory periods (12 and 18
weeks). Morphological changes
(axonal degeneration and
demyelination) in both treated groups,
with a greater incidence in the high
dose animals. Both myelinated and
unmyelinated nerves were adversely
affected. The gradual development of
neurotoxicity after several weeks of
treatment confirms the progressive
nature of this form of toxicity, and
suggests that repeated exposure is
necessary to elicit a neurotoxic
response.
NOAEL: Not established
LOAEL: 255 mg/kg-day
7-148
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Confidential D: 4-month dietary
study, 10 rats/dose, 0.25, 0.5, 0.75 or
1% test concentration (161, 345, 517
or 711 mg/kg-day, respectively), no
neurobehavioral effects (open field,
accelerating rotarod, forelimb grip
strength and negative geotaxis
examinations).
NOAEL: 711 mg/kg-day (highest
dose tested)
LOAEL: Not established
ATSDR, 2009
Reported in a secondary source.
Confidential C: Single oral
administration of Confidential C to
rats (1,000 - 3,200 mg/kg for females,
1,000 - 9,000 mg/kg for males)
(20/sex/group). Three weeks after
administration, measurements of
nerve conduction velocity (NCV),
relative refractory period (RRP) and
absolute refractory period (ARP) were
conducted in the caudal nerve.
Dose related reductions in caudal
NCV in both sexes and a significant
increase in refractory period (both
RRP and ARP) recorded in the two
highest dosed male groups. No
morphological changes in the sciatic
nerves of low dose rats. At higher
doses some changes were recorded,
including sciatic nerve section
degenerative changes in some
myelinated and unmyelinated fibers.
ECHA, 2013; Confidential study
Sufficient study details reported in
secondary sources.
7-149
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
NOAEL: 1,500 mg/kg
LOAEL: 3,200 mg/kg for males and
1750 mg/kg for females
Confidential C: Sprague-Dawley rats
(20/sex/group) administered
Confidential C in the diet at
concentrations of 0, 300, 3,000 and
10,000 ppm (approximately 20.4, 204,
or 612 mg/kg-day) for 18-weeks
followed by an 8-week recovery
period.
No effect on bodyweight; no gross
signs of neurotoxicity; no significant
alterations in NCV, ARP, or RRP
except for significant reductions in
NCV in high-dose females; no
microscopic morphological changes
in central and peripheral nervous
tissues.
NOAEL: 204 mg/kg-day
LOAEL: 612 mg/kg-day
ECHA, 2013
Sufficient study details reported in a
secondary source.
Confidential E: White leghorn hens
were administered Confidential E via
oral gavage at an oral dose of 11,700
mg/kg-day for 6 weeks. Significant
inhibition of plasma cholinesterase
was found, but no significant
inhibition of brain neurotoxic
esterase.
NOAEL: > 11,700 mg/kg-day
ECHA, 2013
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
7-150
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
LOAEL: Not established
Confidential E: White leghorn
chickens were administered
Confidential E via oral gavage at an
oral dose of 0, 240, 300, 360 and 420
mg/kg-day for 5 consecutive days and
were observed for 30 days. No
behavioral signs of delayed
neurotoxicity were observed. Gross
pathological examination revealed no
lesions attributable to ingestion of the
test substance.
NOAEL: >420 mg/kg-day
LOAEL: Not established
Confidential study
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 primary source. Test
material is defined as confidential
product.
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
Other
Confidential C: There is potential for
neurotoxic effects based on a
structural alert for organophosphates.
(Estimated)
Professional judgment
Estimated based on a structural alert
and professional judgment.
Confidential C: In a 14-day gavage
study in rats (20/sex/group), at doses
of 0.8 and 1.12 ml/kg-day (814 and
1142 mg/kg-day) for females and at
0.8 and 2.24 ml/kg-day (814 and 2285
mg/kg-day) for males, no clinical
signs of neurotoxicity were reported.
ECHA, 2013; Confidential study
Sufficient study details in secondary
source.
7-151
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Significant reduction in caudal nerve
conduction velocity was observed in
high dose females and dose-related
increases of refractory (relative and
absolute) periods were also observed
in all animals immediately after
cessation of exposure. After 15 days
recovery increases in ARP and RRP
remained only in high dose females.
NOAEL: 814 mg/kg-day
LOAEL: 1,142 mg/kg-day (based on
electrophysiological changes still
present after the recovery period)
Confidential C: Twenty hens were
tested with two doses of 5,000 mg/kg
Confidential C administered in a
gelatin capsule or dermally 21-days
apart and were killed 21 days after the
second dose.
Esterase inhibition studies (NTE,
brain AChE and plasma BuChE) were
conducted following a single oral
dose of Confidential C to groups of 5
hens. Positive and negative controls
were also evaluated for comparison.
All 20 hens dosed with 2 x 5,000
mg/kg Confidential C survived. No
treatment-related findings of
neurotoxicity were observed in
Confidential C-treated hens dosed
orally or dermally. NTE activity in the
brain following Confidential C
ECHA, 2013; Confidential study
Sufficient study details reported in
secondary sources.
7-152
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
exposure was within normal limits;
brain AChE was inhibited by 45%
with no evidence of associated
clinical signs or cholinergic toxicity
and plasma BuChE activity was also
inhibited.
Exposure to Confidential C does not
induce delayed neurotoxicity in hens
and no neurologic deficits nor
histopathological changes
characteristic of OPIDN were
observed.
NOAEL: >5,000 mg/kg
LOAEL: Not established
Confidential D: There is potential for
neurotoxic effects based on a
structural alert for organophosphates
(Estimated)
Professional judgment
Estimated based on a structural alert
for organophosphates and
professional judgment.
Confidential D: Two female
hens/dose in delayed neurotoxicity
test, gavage, 2,000, 3,000, 5,000,
8,000, or 12,500 mg/kg, no signs of
toxicity in-life or at necropsy
NOAEL >12,500 mg/kg; highest dose
tested
LOAEL: Not established
OECD-SIDS, 2002
Reported in a secondary source. No
data on test substance purity.
Confidential D: Several acute oral
studies in hens, administered doses up
to 12,500 mg/kg, generally found no
signs of paralysis, histopathological
changes in examined nerve tissues, or
OECD-SIDS, 2002
Reported in a secondary source. No
data on test substance purity.
7-153
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
behavior immediately after or during
observation periods of up to 36 days.
However, blood cholinesterase was
decreased by up to 87% in studies
where it was measured.
NOAEL: >12,500 mg/kg; highest
dose tested
LOAEL: Not established
Confidential E: Rabbits
(10/sex/dose) were dermally exposed
to Confidential E at doses of 0, 10,
100, and 1,000 mg/kg 6 hours/ days, 5
days/week for 23 days.
No treatment-related deaths. Edema,
atonia, desquamation and fissuring.
Increased mean terminal blood urea
nitrogen values (high dose). Dose
response depression of RBC and brain
cholinesterase (mid and high dose).
No effect on body weights,
hematology and clinical chemistry
data, organ weights and organ/body
weight ratios. No treatment-related
gross or microscopic changes.
ECHA, 2013
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
NOAEL:
LOAEL:
: 10 mg/kg-day;
100 mg/kg-day
Confidential E: There is potential for
neurotoxic effects based on a
structural alert for organophosphates
(Estimated)
Professional judgment
Estimated based on a structural alert
and professional judgment.
7-154
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Repeated Dose Effects
HIGH: Based on weight of evidence including reduced body weight in male rats administered Confidential D
in the diet for 28-days. The NOAEL of 23.5 mg/kg-day and the LOAEL of 161.4 mg/kg-day span across the
High and Moderate hazard designation ranges (DfE criteria are for 90-day repeated dose studies; criteria
values are tripled for chemicals evaluated in 28-day studies making the High hazard range < 30 mg/kg-day
and the Moderate hazard range between 30 and 300 mg/kg-day). Repeated dose toxicity is of MODERATE
concern for Confidential E (based on a NOAEL and LOAEL of ~ 10 and ~ 100 mg/kg-day, respectively in a
dermal study in rabbits) and of LOW concern for Confidential C (based on a NOAEL and LOAEL value of
100 mg/kg-day and > 200 mg/kg-day, respectively, in rats following oral exposure).
Confidential C: Sprague Dawley rats
(10/sex/dose) were administered
Confidential C via oral gavage at
doses of 0, 1, 10 and 100 mg/kg once
per day for 14 days. Confidential C
did not have any effect on body
weight gain or organ weights in either
sex or at any dose level. There were
no treatment-related hematological
abnormalities or gross/microscopic
changes detected in major tissues and
organs following dosing with
Confidential C.
NOAEL: > 100 mg/kg-day (highest
dose tested)
LOAEL: Not established
Confidential C: In a 4-week study,
Sprague-Dawley rats were fed diets
containing 0, 500, 2,000, 7,500 or
15,000 mg Confidential C/kg
(approximately 25, 100, 375, or 750
mg/kg-bw/day). No signs of toxicity
were in males; slight decrease in body
weight and food consumption in
ECHA, 2013; Confidential study
Confidential study
Sufficient study details reported in
secondary sources. Study limited by
inability to establish a LOAEL.
Limited study details in secondary
sources.
7-155
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
females (7,500 or 15,000 mg/kg). No
compound-related changes were
observed at necropsy.
Toxicity in males:
NOAEL: >750 mg/kg-day (highest
dose tested)
LOAEL: Not established
Toxicity in females:
NOAEL: 100 mg/kg-day
LOAEL: 375 mg/kg-day
Confidential C: Sprague Dawley rats
(12/sex/dose) were administered
Confidential C via oral gavage at
doses of 0.25 and 0.5 mL/kg (255 and
510 mg/kg-day, based on a density of
1.018 g/cm3), 5 days/week for 18
weeks.
Reduced activity in all rats, clinical
signs of toxicity (difficulties in
breathing, piloerection, lacrimation,
increased urination) at high dose. No
hematological changes. Dose-related
decrease in red cell AChE and
reduction in GPT (high dose only).
Significant increase in both liver and
kidney weights (high dose females), a
significant increase in liver weight in
low dose females and similar increase
for high dose males when expressed
as percent body weight. Cardiac
lesions (males in both treated groups).
ECHA, 2013; Confidential study
Sufficient study details in secondary
sources. Limitations include inability
to determine a NOAEL.
7-156
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
NOAEL: Not established
LOAEL: 0.25 mL/kg (255 mg/kg-
day) based on increased liver weight
in females and decrease in red blood
cell AChE plus cardiac lesions in
males
Confidential C: Confidential C was
administered to four groups of
Sprague-Dawley rats (20/sex/group)
at target dietary concentrations of 0,
300, 3,000 and 10,000 ppm for 18-
weeks. Dietary analyses verified the
following average inclusion rates of
Confidential C in the diets: 280 ppm
(low); 3,000 ppm (intermediate);
9,900 ppm (high dose).
No ophthalmic lesions attributable to
Confidential C. All treatment group
rats gained weight. Reduced food
consumption during the first week in
high and intermediate dose groups.
Throughout the remaining period all
treatment groups consumed amounts
of diet similar to the controls.
Hematological and clinical chemistry
parameters were equivalent in dosed
and control rats with the following
exceptions: increased platelet counts
(10,000 ppm both sexes) and
increased serum gamma glutamyl
transpeptidase and a depressed plasma
cholinesterase in the 3,000 and 10,000
ECHA, 2013; Confidential study
Sufficient study details reported in
secondary sources. Conducted in
accordance with OECD Guideline
408.
7-157
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
ppm groups. Increased liver weight
(absolute and relative) at the high
dose (10,000 ppm). Microscopic
examination revealed mild periportal
hepatocellular hypertrophy and
periportal vacuolization in males only
at 3,000 and 10,000 ppm.
NOAEL: 300 ppm Confidential C in
the diet (equivalent to approximately
20.4 mg/kg-day), for both sexes
LOAEL: 3,000 ppm (approximately
204 mg/kg-bw/day) for periportal
vacuolization and hypertrophy in
males
Confidential C: New Zealand white
rabbits (6/sex/dose) were dermally
exposed to Confidential C at doses of
0, 10, 100 or 1,000 mg/kg-day, 5
days/week for 21 days.
There were no deaths and no adverse
clinical signs of toxicity were
observed in treated rabbits. No
adverse systemic toxicity was
observed following dosing at 1,000
mg/kg-day. Local irritation (minimal
to moderate erythema, edema, atonia
and desquamation) occurred in a
dose-related manner and severity and
increased with time. Microscopic
observations of treated skin from high
dose animals included squamous cell
hyperplasia, hyperkeratosis, hair
ECHA, 2013; Confidential study
Sufficient study details reported in
secondary sources. Conducted in
accordance with OECD Guideline
410.
7-158
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
follicles distended with keratin and
surface accumulation of keratin and
erosions/ulcers. No such observations
were seen in control males and only
infrequently in control females.
A no effect level (NOEL) for skin
irritation was not established in this
study, but irritation at the low dose
was minimal.
NOAEL: 1,000 mg/kg-day (for
systemic toxicity; highest dose tested)
LOAEL: Not established
Confidential C: Wistarrats
(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
%). Absolute and relative liver
weights in both sexes were
significantly increased in the top dose
group (3.0%) after both 5 and 14-
weeks of treatment. Histopathological
ECHA, 2013; Confidential study
English abstract only provides
qualitative data; therefore, magnitude
of the effects described cannot be
ascertained. NOAEL and LOAEL
derived by the authors are unreliable.
7-159
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
examination showed that only male
rats in the top dose group (3.0%)
exhibited moderate periportal
hepatocyte swelling after 14-weeks.
NOEL: 0.03 % diet (male rat: 20
mg/kg-day; female rat: 22 mg/kg-day)
LOAEL: 0.3% (-210 mg/kg-day for
males and 250 mg/kg-day for
females)
Confidential D: 28-day repeated dose
dietary study, rats were fed test
substance at concentrations of 0, 250,
1,000 and 4,000 ppm. Effects on body
weights were observed.
NOAEL (male): 250 ppm (23.5
mg/kg-day)
LOAEL (male): 1,000 ppm (161.4
mg/kg-day)
ECHA, 2012
Reported in secondary source. DfE
criteria are for 90-day repeated dose
studies. Criteria values are tripled for
chemicals evaluated in 28-day studies.
Confidential D: 35-day repeated-
dose oral (dietary) study, 5 male
rats/group, test compound
concentrations of 0, 0.5, and 5.0%
(~0, 350, and 3,500 mg/kg-day,
respectively), with a 0.1% (-70
mg/kg-day) dose replacing the high
dose group after 3 days. Slight
reduction in body weight gain and
increase in liver weight in 350 mg/kg-
day dose group.
NOAEL: 70 mg/kg-day
OECD-SIDS, 2002
Reported in a secondary source.
Limited study details provided.
7-160
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
LOAEL: 350 mg/kg-day
Confidential D: 4-month repeated-
dose dietary study, Sprague-Dawley
rats (10 rats/dose) were fed 0.25, 0.5,
0.75 or l%test concentration (161,
345, 517 or 711 mg/kg-day,
respectively). Reduced body weight
gain (11%) at 345 mg/kg-day.
NOAEL: 161 mg/kg-day
LOAEL: 345 mg/kg-day
OECD-SIDS, 2002; ATSDR, 2009
Reported in a secondary source.
Confidential D: 21-day repeated-
dose dermal study, rabbits
(10/sex/group) were exposed to test
compound concentrations of 0, 100,
and 1,000 mg/kg-day. No mortality,
clinical symptoms, or changes in body
weight, hematology, clinical
chemistry, necropsy, organ weights
and histopathology reported; only
decreased acetyl cholinesterase levels
in plasma, erythrocytes and brain
were reported and not considered to
be of toxicological relevance as there
was no clinical or histological
correlation.
NOAEL: 1,000 mg/kg-day; highest
dose tested
LOAEL: Not established
OECD-SIDS, 2002
Reported in a secondary source.
Treatment period only 21 days.
Confidential D: In a 3-month study,
rats were orally gavaged with test
substances at 0, 380 and 1,900 mg/kg-
ATSDR, 2009
Limited study details reported in a
secondary source. Primary source is
an abstract with few experimental
7-161
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
day. No toxic effects were observed.
NOEL: 1,900 mg/kg-day; highest
dose tested
LOEL: Not established
details.
Confidential E: Rabbits
(10/sex/dose) were dermally exposed
to Confidential E at doses of 0, 10,
100, and 1,000 mg/kg 6 hours/ days, 5
days/week for 23 days.
No treatment-related deaths. Edema,
atonia, desquamation and fissuring.
Increased mean terminal blood urea
nitrogen values (high dose). Dose
response depression of RBC and brain
cholinesterase (mid and high dose).
No effect on body weights,
hematology and clinical chemistry
data, organ weights and organ/body
weight ratios. No treatment-related
gross or microscopic changes.
ECHA, 2013
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
NOAEL:
LOAEL: ;
: 10 mg/kg-day;
100 mg/kg-day
Confidential E: Rabbits
(10/sex/dose) were dermally exposed
to Confidential E at doses of 100 and
1,000 mg/kg 6 hours/ days, 5
days/week for 3 weeks.
No deaths. No clinical signs of
toxicity. The test material was mildly
ECHA, 2013
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
7-162
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
to moderately irritating to the skin. A
dose-correlated body weight effect
was noted. Significant inhibition of
plasma, erythrocyte and brain
cholinesterase activity. No significant
gross or microscopic pathologic
alterations except for the local skin
lesions.
LOAEL:s lOOmg/kg-day
NOAEL: 1,000 mg/kg-day
Confidential E: Male and female rats
(15/sex/group) were fed Confidential
E in the diet at doses of 100, 300,
1,000 ppm (7.5, 21.4, 71.6 mg/kg-
day, males; 9.0, 26.5, 86.2 mg/kg-day,
females) for 90 days.
No adverse effects related to test
article treatment in any of the dosage
groups.
NOAEL: 1,000 ppm (71.6 mg/kg-day
for males, 86.2 mg/kg-day for
females; highest dose tested)
LOAEL: Not established
ECHA, 2013
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
Confidential E: Confidential E was
administered to Sprague-Dawley rats
(20/sex/dose) at concentrations of 0,
100, 400 and 1,600 ppm by diet for 90
days.
Confidential E: No treatment related
mortality and clinical signs.
ECHA, 2013
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
7-163
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Statistically significant differences in
hematology and clinical chemistry
values and in red blood cell, plasma
and brain cholinesterase activities
between control and treated animals
were minimal, inconsistent and
considered not to be of biological
significance. A biologically
significant increase in liver and
adrenal weights (only females) was
noted in the high-dose groups, but this
was not regarded as a toxic and
therefore not an adverse effect.
NOAEL: 1,600 ppm (107.5 mg/kg-
day for males and 124.8 mg/kg-day
for females; highest dose tested)
LOAEL: Not established
Confidential E: Sprague-Dawley rats
(10/sex/dose) were fed Confidential E
in the diet at doses of 0, 250, 500,
750, 1,000 and 2,000 mg/kg-day for 1
month.
No deaths or lexicologically
significant clinical signs. Hepatic
enlargement and mahogany red livers
at all doses (significant at >500
mg/kg-day). Rounding of hepatic
edges and diffuse green-tan
discoloration of kidneys (>500 mg/kg-
day).
ECHA, 2013
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
7-164
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
NOAEL: 250 mg/kg-day
LOAEL: >500 mg/kg-day
Confidential E: Charles River rats
(15/sex/dose) were exposed via
whole-body inhalation to Confidential
E aerosol at concentrations of 0, 10.1
or 101.1 mg/m3 (0, 0.0101, or 0.1011
mg/L), or 6 hours/day, 5 days/week
for a total of 62 exposures over 90
days.
No deaths attributed to test material.
Ruffed, discolored fur and ptosis
(both doses); rhinitis, sneezing,
wheezing and hemorrhagic
conjunctivitis (high dose). No
difference in body weights,
hematology parameters, clinical
chemistry values and urinalysis
parameters. Gross necropsy showed
no adverse effects. Increased liver
weight in high-dose males. No
treatment related histopathological
effects.
NOAEL: 101.1 mg/m3 (0.1011 mg/L)
LOAEL: Not established
ECHA, 2013
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
7-165
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Skin Sensitization
MODERATE: Confidential C and E produced positive responses in a local lymph node assays in mice but
did not produce sensitization in a modified Buehler test in guinea pigs or in repeated patch tests in human
volunteers. Confidential D was not a skin sensitizer in guinea pigs.
Skin Sensitization
Confidential C: Sensitizing, mouse
local lymph node assay (LLNA).
The test item solutions were applied
on the dorsal surface of ears of
experimental animals (25 (iL/ear) for
three consecutive days. A significant
lymphoproliferative response was
noted.
Confidential C: Not sensitizing,
guinea pigs, modified Buehler test
There were no signs of irritation at
any of the test sites during induction
or at challenge. No data provided
regarding positive controls.
Confidential C: Not sensitizing,
repeated human insult patch test in
209 volunteers.
3-week induction period, 4
applications of 0.2 mL per week for
24 hours to occluded skin. During the
fourth week, 4 similar applications
were made to previously untreated
sites. There was no dermal reaction to
challenge applications.
Confidential D: Several human case
studies have reported allergic
dermatitis; 15 of 23,192 (0.065%)
human volunteers patch tested from
1950 to 1962 had positive reactions to
cellulose acetate film containing 7-
ECHA, 2013
ECHA, 2013
Confidential study
OECD-SIDS, 2002
Sufficient study details reported in a
secondary source. Conducted
according to OECD Guideline 429.
The lack of positive controls
diminishes reliability of the results.
Sufficient information reported in a
secondary source.
Reported in a secondary source.
Limited study details provided; patch
testes conducted with mixtures;
unclear which component of mixture
caused low incidence of sensitization.
7-166
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
Respiratory Sensitization
Respiratory Sensitization
DATA
10% Confidential D and 3-4%
phthalic esters
Confidential D: A confidential skin
Sensitization study with negative
results in guinea pigs
Confidential D: None of the patients
tested in two separate studies of 343
and 174 patients, respectively, had
Sensitization reactions to triphenyl
phosphate
Confidential D: Not sensitizing,
guinea pig maximization test
Confidential E: Sensitizing, Mouse
local lymph node assay (LLNA).
Confidential E: Not sensitizing,
patch test, human volunteers
REFERENCE
Submitted confidential study
OECD-SIDS, 2002
OECD-SIDS, 2002
ECHA, 2013
ECHA, 2013
DATA QUALITY
Reported in a confidential study.
Reported in a secondary source.
Limited study details provided.
Study reported in a secondary source;
conducted according to OECD Guide-
line 406.
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
No data were located.
|No data located.
7-167
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Eye Irritation
MODERATE: Confidential C produced slight irritation in rabbits
animals. Confidential D is mildly irritating to the eyes with effects
did not produce eye irritation in rabbits.
which persisted up to 72 hours in some
clearing within 72 hours. Confidential E
Eye Irritation
Confidential C: Slightly irritating,
rabbits.
Undiluted 0.1 mL was applied; the
eye was washed 24 hours later. One
hour up to 72 hours, the treated
conjunctiva showed beefy-red blood
vessels and slight to moderate
swelling. From 24 to 48 hours, the iris
of one animal was reddened. Diffuse
translucent areas of the cornea were
observed one hour after
administration in two animals,
persisting to72 hours in one animal.
Clear colorless discharge was
observed in all animals, persisting to
48 hours in one animal. All signs of
irritation had resolved at 7 days.
Confidential C: Slightly irritating,
rabbits (3/sex).
Undiluted 0.1 mL was applied. All
dosed rabbits displayed excessive
blinking and rubbing on instillation.
No corneal opacity or iritis.
Conjunctival redness, chemosis and
discharge in all rabbits at 1-h post-
exposure and redness persisted in 1/6
rabbits through 48-h. Slight to
obvious swelling with partial eversion
of the eyelids and slight discharge was
observed in all rabbits at 1-h post-
ECHA, 2013
ECHA, 2013
Sufficient study details reported in a
secondary source. Conducted in
accordance with OECD Guideline
405.
Sufficient study details reported in a
secondary source.
7-168
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
instillation. All ocular lesions had
resolved at 72-h.
Confidential C: Slightly irritating,
rabbits (3 /sex).
Confidential C: No corneal opacity.
Iritis (grade 1) in one female rabbit.
Conjunct val irritation (grade 1 or 2)
in all test animals at Ihour post-
instillation, in 4 rabbits at 24 hours,
persisting to 72 hours in one rabbit.
Confidential C: Slightly irritating,
rabbits.
Undiluted 0.1 mL was applied. 3/6
rabbits exhibited moderate
conjunctival erythema and iritis which
resolved within 48-h.
Confidential C: In four studies
Confidential C was non-irritating to
the eyes of albino rabbits.
Confidential D: Not irritating, rabbits
Confidential D: Mild irritation in
rabbit eyes, clearing within 72 hours
Confidential E: Not irritating, rabbits
Confidential E: Not irritating,
rabbits;
No irritation in the washed and
unwashed eyes after 24, 48, 72 hours
and 4 days.
REFERENCE
ECHA, 2013
ECHA, 2013
Confidential study
OECD-SIDS, 2002
OECD-SIDS, 2002
Confidential study
ECHA, 2013
DATA QUALITY
Sufficient study details reported in a
secondary source.
Limited study details reported in a
secondary source.
No details provided in a secondary
source.
Study reported in a secondary source;
conducted according to OECD Guide-
line 405.
Study reported in a secondary source
Adequate primary source. Test
material is defined as confidential
product.
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
7-169
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Confidential E: Not irritating,
rabbits;
No irritation in the washed and
unwashed eyes after 1 hour or up to 4
days.
ECHA, 2013
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
Confidential E: Not irritating,
rabbits;
No irritation in the washed and
unwashed eyes after 24, 48, 72 hours
and 4 and 7 days.
ECHA, 2013
Adequate study reported in a
secondary source. Two studies, test
material is a confidential product.
Dermal Irritation
MODERATE: Based on weight of evidence. Confidential C produced moderate irritation in rabbits which
persisted up to 72 hours in some animals. Confidential E initially produced moderate to severe irritation in
rabbits with mild to moderate irritation and erythema persisting 72 hours post-administration. Confidential
D is not a skin irritant in rabbits.
Dermal Irritation
Confidential C: Moderately
irritating, three rabbits.
Undiluted 0.5 mL applied for 4 hours;
semi occlusive. Well-defined to
severe erythema up to 72 hours in 2
rabbits. Same rabbits showed very
slight to slight edema, with roughness
and scaling of the skin up to 7 days.
All effects were reversible within 14
days.
Confidential C: Moderately
irritating, six rabbits.
Undiluted 0.5 mL was applied.
Erythema was more severe in abraded
than intact sites at both 24- and 72-
hours. Effects were not fully
reversible within 72-hours.
Confidential C: Slightly irritating,
six rabbits
ECHA, 2013
ECHA, 2013
ECHA, 2013
Sufficient details reported in a
secondary source. Conducted in
accordance with OECD Guideline
404.
Sufficient study details reported in a
secondary source.
Sufficient study details reported in a
secondary source.
7-170
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Undiluted 0.5 mL was applied to
intact skin of rabbits under occlusion
for 4-hour induced a slight transient
irritation response.
Confidential C: Slightly irritating,
six rabbits.
Undiluted 0.5 mL applied for 2 hours;
occlusive. At 24-hour post exposure
rabbits had slight erythema at the
intact site with incidence and severity
of irritation increasing at 72-hour to
well-defined erythema. At the abraded
sites, the incidence and severity of
irritation remained the same over both
time periods. No edema or corrosive
effect was observed in any treated
rabbit at any site. Effects were no
fully reversible within 72 hours.
ECHA, 2013
Sufficient study details reported in a
secondary source.
Confidential C: Irritating, rabbits
(6/sex/group), 21-day dermal study.
Rabbits received 10, 100, or 1,000
mg/kg on unabraded skin followed by
occlusion for 6 hours. Slight to
moderate erythema. Microscopic
observations showed squamous cell
hyperplasia, hyperkeratosis, hair
follicles distended with keratin and
surface accumulation of keratin and
cellular debris, erosions ulcers,
acute/subacute inflammation and
congestion and hemorrhages in
various combinations. Dose-related
effects with increasing severity over
Confidential study
Sufficient study details reported in a
secondary source.
7-171
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
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
ATSDR, 2009
ECHA, 2013
ECHA, 2013
Confidential study
ECHA, 2013
DATA QUALITY
Sufficient study details reported in a
secondary source.
Study reported in secondary source;
conducted according to OECD Guide-
line 404
Reported in a secondary source.
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
Adequate primary source. Test
material is defined as confidential
product.
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
7-172
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
Endocrine Activity
DATA
following a 24 hour exposure.
Confidential E: Not irritating,
rabbits;
Mild erythema was noted at the 24
hour observation period in 2/6
animals. All scores were 0 by 72
hours.
REFERENCE
ECHA, 2013
DATA QUALITY
Adequate study reported in a
secondary source. Test material is
defined as confidential product.
Confidential C is listed in one study in the top 20 EOCs (endocrine disrupting chemicals) in U.S. stream
waters. It inhibited the luciferase expression induced by dihydrotestosterone and 1713-estradiol and increased
both 17 beta-estradiol (E2) and testosterone (T) concentrations in H295R cells. Confidential C was negative
for estrogenic activity in a yeast two-hybrid assay and did not act as an estrogen receptor agonist or
adversely affect sex hormones of zebrafish.
Confidential D was found to be inactive in estrogen-receptor binding assays; however, it was shown to be a
moderate androgen-receptor (AR) binder in a competitive binding assay. Confidential D was shown to
inhibit human AR in the absence of agonist and to inhibit testosterone-induced AR activity. In addition,
Confidential D significantly impaired reproduction in zebrafish and was correlated with decreased sperm
count and altered hormone levels in men. Increased serum thyroxine (T4) levels were reported in the serum
of dams following oral administration to a confidential product containing Confidential D; other components
of the mixture were not identified. It is unclear which component or components of the mixture are driving
the endocrine activity effects.
No data were available for Confidential E. By analogy, rats exposed to a mixture containing Confidential E
had significantly prolonged diestrus, hypertrophy and cholesteryl lipidosis of adrenocortical and ovarian
interstitial cells and minimal degeneration in the adrenal cortex and ovary. No effect on the testes was noted.
Confidential C: Ranked as atop 20
EOC (endocrine disrupting chemical)
in U.S. stream water
Confidential C: Confidential C
inhibited the luciferase expression
induced by dihydrotestosterone (10~9
M). The IC50 value was 4.7 x 10~5 -
6.0 x 10'4 M. Confidential C also
Confidential study
Confidential study
Adequate primary source; Japanese
with English abstract.
7-173
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
inhibited the luciferase expression
induced by 17B-estradiol (3 x 10"10
M). The IC50 value was 3.3 x 10~5 -
2.3xlO-4M.
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
Confidential study
Confidential study
DATA QUALITY
Adequate primary source.
Adequate primary source.
Adequate primary source.
7-174
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
study in zebrafish. Significant
decrease in fecundity, significant
increases of plasma 17B-estradiol
(E2) concentrations, vitellogenin
(VTG) levels, and E2/testosterone (T)
and E2/ll-ketotestosterone (11-KT)
ratios. Sex-dependent changes in
transcriptional profiles of several
genes of the hypothalamus-pituitary-
gonad (HPG) axis.
Confidential D: Study conducted to
determine effects of triaryl phosphates
on mouse and human nuclear
receptors. Mouse constitutively active
receptor (CAR) was activated by 1.3-
fold following exposure to
Confidential D. Testosterone-induced
AR-dependent activity was lowered
by 30-40%.
Confidential study
Adequate primary source.
Confidential D: Exposure to
Confidential D in zebrafish resulted in
severe pericardial edema and blocked
looping of the atrium and ventricle.
Confidential D-induced cardiotoxicity
in zebrafish embryos is mediated
through an AHR independent
pathway.
Confidential study
Adequate primary source.
Confidential D: In a luciferase
reporter-gene assay using cultured
cells, Confidential D inhibited the
luciferase expression induced by
dihydrotestosterone (10~9 M).
Confidential study
Primary source in Japanese with
English abstract.
7-175
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
IC50 for antiandrogenic activity =
0.000047 - 0.0006 M
Confidential D: Endocrine disrupting
potential was investigated using
human cells lines (H295R, MVLN)
and zebrafish plasma. Confidential D
was cytotoxic to H295R cells
(showing <80% cell viability at > 10
mg/L) and significantly increased E2
and T production. Transcription of
CYP19A1 was significantly up-
regulated and transcription of
SULT1E1 gene was down-regulated.
No binding affinity to E2 receptor in
MVLN cells, but binding of E2 to ER
was reduced in a dose-dependent
manner. Plasma E2 was significantly
increased in fish plasma and T and
11-KT were decreased (1 mg/L).
Changes in transcription of
steroidogenic genes and vitellogenin
gene were observed.
Confidential study
Adequate, primary source.
Confidential D: Men living in homes
with higher amounts of Confidential
D in house dust had reduced sperm
count and altered hormone levels
related to fertility and thyroid
function. Each interquartile range
(IQR) Confidential D increase in
house dust samples was associated
with a 19% decrease in sperm
concentrations and a 10% increase in
prolactin levels.
Confidential study
The actual exposure to Confidential D
is unknown; it is not known if
Confidential D or other substances
found in the household dust caused or
contributed to the reported toxicity.
7-176
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Confidential D: Pregnant Wistar rats
were administered 0, 0.1 or 1 mg/kg-
day of the analog confidential product
in the diet during gestation and
through lactation (GD8 - PND 21);
Increased serum thyroxine (T4) levels
(increase of 65%) in the high dose
dams compared to controls was
reported. There was no significant
change in triiodothyronine (T3) levels
in dam serum. There was no reported
statistically significant change in T4
or T3 levels in pup serum on PND 21
when compared to controls.
Confidential study
Estimated based on experimental data
for a confidential product.
Confidential D: Inhibited AR activity
in COS-1 cells transfected with
human AR both in the absence of
agonist, as well as inhibited
testosterone-induced AR activity by
30 40%. (Measured)
ATSDR, 2009
Reported in a secondary source.
Confidential D: Moderate binding in
a competitive androgen-receptor (AR)
binding assay using recombinant rat
protein expressed in Escherichia coli.
ATSDR, 2009
Reported in a secondary source.
Confidential D: Inactive in a binding
assay with the rat uteri estrogen
receptor from ovariectomized
Sprague-Dawley rats
ATSDR, 2009
Reported in a secondary source
Confidential E: In an oral study,
male and female rats were
administered Confidential E at doses
of 0 or 1.7 g/kg-day (0 or 1700
mg/kg-day) via gavage in sesame oil
Confidential study
Estimated based on analogy. Data are
for a confidential mixture.
7-177
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
or 2.8 g/kg (2,800 mg/kg) neat
Confidential E for 20, 40 and 60 days.
Hypertrophy and cholesteryl lipidosis
of adrenocortical and ovarian
interstitial cells; minimal degeneration
in the adrenal cortex and ovary. No
decreased testicular weight or
degeneration of seminiferous tubules.
(Estimated by analogy)
Confidential E: In an oral study,
groups of intact and ovariectomized
female rats were administered
Confidential E at doses of 0 or 1.7
g/kg-day (0 or 1,700 mg/kg-day) via
oral gavage in sesame oil vehicle or as
neat Confidential E for 20, 40 or 60
days. Cholesteryl lipidosis in AC and
OI cells; elevated estradiol levels
(14.5 times greater than controls). No
effect on serum concentrations of
androstenedione and corticosterone.
Abnormal reproductive cycles in
treated females that were significantly
prolonged in diestrus. Increased liver
weights (134% that of controls) and
P-450 enzymes (3 times greater than
controls)
(Estimated by analogy)
Confidential study
Estimated based on analogy. Data are
for a confidential mixture.
7-178
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Immunotoxicity
Confidential C produced weak inhibition of mouse lymphocyte mitogenesis for T-cells; no inhibition was
observed in B-cells. Oral exposure of rats to Confidential D for 4 months and dermal exposure of rabbits for
3 weeks produced no effects on immune function parameters.
Immune System Effects
Confidential C: Immunotoxicity
evaluation using the mouse splenic
lymphocyte mitogenesis test. No
inhibition for lymphocyte mitogenesis
in B-cells; weak inhibition for
lymphocyte mitogenesis for T cells.
Confidential D: 120-day dietary
study, rats, 0, 0.25, 0.5, 0.75, and 1%
of Confidential D(~0, 161, 345, 517
and 711 mg/kg-day); initial,
secondary, and tertiary immunizations
with sheep red blood cells performed
at 60, 81, and 102 days, respectively.
No significant effects were reported
on the weight and histopathology of
the spleen, thymus and lymph nodes,
and no significant changes to the
humoral response were reported.
Confidential D: Rabbits, up to 1,000
mg/kg-day, applied 5 days/week for 3
weeks to intact or abraded skin had no
gross or microscopic effects on the
spleen, thymus, or lymph nodes.
Confidential study
ATSDR, 2009
ATSDR, 2009
Reported in a secondary source.
Reported in a secondary source.
7-179
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
ECOTOXICITY
ECOSAR Class
Acute Aquatic Toxicity
Fish LC50
VERY HIGH: Based on experimental fish 96-hour LC50 values < 1.0 mg/L for Confidential D and E and a
48-hour EC so of 0.34 mg/L in daphnia for Confidential E. Acute aquatic toxicity is of HIGH concern for
Confidential C based on an experimental 48-hour LC50 of 6.8 mg/L in fish.
Confidential C: Freshwater fish
(Oryzias latipes) 4 8 -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)
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)
ECHA, 2013; Confidential study
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
7-180
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
Confidential C: Freshwater fish
(Oncorhynchus mykiss) 96-hour LC50
= 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 = 5.06mg/L
(Estimated)
ECOSAR: Esters
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)
Confidential D: Freshwater fish
(Lepomis macrochirus) 96-hour LC50
= 290 mg/L
(Experimental)
Confidential D: Fish 96-hour LC50 =
1.34mg/L
(Estimated)
ECOSAR: Esters
Confidential E: Freshwater fish
(Ictalurus punctatus)
96-hour LC50 = 0.8 mg/L (static);
REFERENCE
ECHA, 2013; Confidential study
ECOSAR v 1.11
OECD-SIDS, 2002
OECD-SIDS, 2002
OECD-SIDS, 2002
ECOSAR v 1.11
ECHA, 2013
DATA QUALITY
Adequate study reported in a
secondary source. No monitoring of
physico-chemical conditions.
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
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).
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
Adequate study reported in a
secondary source. Test material is a
confidential product.
7-181
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
Nominal concentrations: 0.06, 0.12,
0.25, 0.5 and l.Omg/L
(Experimental)
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,
10 14 182432425675 10
14, 18, 24, 32 and 49 mg/L
(Experimental)
Confidential E: Freshwater fish
(Oncorhynchus mykiss)
96-hour LC50 = 2 mg/L (static)
(Experimental)
Confidential E: Freshwater fish
(Pimephales promelas)
96-hour LC50 = 2.3 mg/L (static)
(Experimental)
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 01832
5. 6 and 10.0 mg/L
(Experimental)
Confidential E: Saltwater fish
(Cyprinodon variegatus)
REFERENCE
ECHA, 2013
ECHA, 2013
ECHA, 2013
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
7-182
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
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)
ECHA, 2013
Confidential E: Freshwater fish
(Pimephales promelas)
96-hour LC50 = 3.4 mg/L (static)
(Experimental)
ECHA, 2013
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)
ECHA, 2013
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)
ECHA, 2013
Confidential E: Saltwater fish
(Cyprinodon variegatus)
96-hour LC50 > 0.27 mg/L (semi-
ECHA, 2013
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
secondary source. Test material is a
confidential product.
7-183
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
static);
96-hour NOEC = 0.27 mg/L;
nominal concentrations: 0.13, 0.22,
0.36, 0.6 and 1.0 mg/L
(Experimental)
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 =< 0.001 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Adequate study reported in a
secondary source. Test material is a
confidential product.
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
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.
Daphnid LC50
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)
ECHA, 2013
Confidential C: Daphnia magna 48-
Confidential study
Adequate study reported in a
secondary source. Conducted in
accordance with OECD Guideline
202.
Adequate study reported in a
7-184
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
hour EC50 = 75 mg/L;
24-hour LC50 = 84 mg/L;
NOEC = 32 mg/L
(Experimental)
Confidential C: Daphnia magna 48-
hour LC50 = 8.73mg/L
(Estimated)
ECOSAR: Esters
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 = 2.11mg/L
(Estimated)
ECOSAR: Esters
Confidential E: Daphnia magna 48-
hour EC50 = 0.34 mg/L (static)
(Experimental)
Confidential E: Daphnia magna 48-
hour EC50 = 2.9 mg/L (static)
Test concentrations not specified
(Experimental)
Confidential E: Daphnia magna 48-
hour EC 50 = 5 mg/L (static)
Test concentrations not specified
REFERENCE
ECOSAR v 1.11
Confidential study
OECD-SIDS, 2002
Confidential study
ECOSAR v 1.11
ECHA, 2013
ECHA, 2013
ECHA, 2013
DATA QUALITY
secondary source.
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
Sufficient study details reported.
Study reported in a secondary source;
conducted according to US EPA
660/3-75-009.
Sufficient study details reported.
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
Adequate study reported in a
secondary source. Test material is a
confidential product.
Adequate study reported in a
secondary source. Test material is a
confidential product.
Adequate study reported in a
secondary source. Test material is a
confidential product.
7-185
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
Green Algae EC50
DATA
(Experimental)
Confidential E: Daphnia magna 48-
hour LC50 < 0.001 mg/L
(Estimated)
ECOSAR: Esters
Confidential C: Green algae
(Pseudokirchneriella subcapitata) 72-
hour EC 50 = 61 mg/L (growth rate);
Static conditions; nominal
concentrations: 0, 0.32, 1.0, 3.2, 10,
32, 100 mg/L
(Experimental)
Confidential C: Green algae 96-hour
EC50 = 2.82mg/L
(Estimated)
ECOSAR: Esters
Confidential D: Green algae
(Selenastrum capricornutum ) 96-
hour EC 50 = 2.0 mg/L
(Experimental)
Confidential D: Green algae 96-hour
EC50 = 2.0 mg/L
(Experimental)
Confidential D: Green algae 96-hour
EC50 = 0.60mg/L
(Estimated)
REFERENCE
ECOSAR v 1.11
ECHA, 2013
ECOSAR v 1.11
OECD-SIDS, 2002
Confidential study
ECOSAR v 1.11
DATA QUALITY
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
NES: The log Kow of 1 1 for this
chemical exceeds the SAR limitation
for the log Kow of 5.0; NES are
predicted for these endpoints.
Adequate study reported in a
secondary source. Conducted in
accordance with OECD Guideline
201.
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
Reported in a secondary source.
Sufficient study details reported.
Estimate for the Esters class was
provided for comparative purposes.
7-186
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
ECOSAR: Esters
See Section 5.5.1.
Confidential E: Green algae
(Pseudokirchneriella subcapitata) 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< 0.001 mg/L
(Estimated)
ECOSAR: Esters
ECOSAR v 1.11
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
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.
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. Chronic aquatic toxicity is of HIGH concern for
Confidential D and E based on experimental values for algae. A High concern is also indicated for
Confidential C based on estimated ChV values for fish using the ECOSAR Esters class.
Fish ChV
Confidential C: Freshwater fish ChV
= 0.26 mg/L
(Estimated)
ECOSAR: Esters
Confidential D: Freshwater fish
(Oncorhynchus mykiss} 30-day LOEC
= 0.037 mg/L
(Experimental)
ECOSAR v 1.11
ECHA, 2013
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
Reported in a secondary source.
7-187
-------
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 = 0.06
mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
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
Adequate study reported in a
secondary source. Test material is a
confidential product.
7-188
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Confidential E: Freshwater fish
(Pimephales promelas) 30-dayNOEC
(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: 0.06, 0.14,
0.25,0.41, 1.34 mg/L
(Experimental)
ECHA, 2013
Confidential E: Freshwater fish
(Pimephalespromelas) 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
< 0.001 mg/L
(Estimated)
ECOSAR: Esters
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.
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
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.
Daphnid ChV
Confidential C: Daphnia magna
ChV = 3.61 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
7-189
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Confidential D: Daphnid ChV = 0.69
mg/L
(Estimated)
ECOSAR: Esters
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
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
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
Adequate study reported in a
secondary source. Test material is a
confidential product.
Adequate study reported in a
secondary source. Test material is a
confidential product.
Adequate study reported in a
secondary source. Test material is a
confidential product.
7-190
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
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
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
Confidential E: Daphnia magna
ChV< 0.001 mg/L
(Estimated)
ECOSAR: Esters
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.
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
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.
7-191
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Green Algae ChV
Confidential C: Green algae
(Pseudokirchneriella subcapitata)
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
Confidential C: Green algae ChV
1.27 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
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 ChV =
0.35 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Confidential E: Green algae
(Pseudokirchneriella subcapitata) 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
Adequate study reported in a
secondary source. Conducted in
accordance with OECD Guideline
201.
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
Study reported in secondary source;
conducted according to OECD
guideline 201.
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
Adequate study reported in a
secondary source. Test material is a
confidential product.
7-192
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
Confidential E: Green algae ChV <
0.001 mg/L
(Estimated)
ECOSAR: Esters
REFERENCE
ECOSAR v 1.11
DATA QUALITY
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
NES: The log Kow of 1 1 for this
chemical exceeds the SAR limitation
for the log Kow of 8.0; NES are
predicted for these endpoints.
ENVIRONMENTAL FATE
Transport
Henry's Law Constant (atm-
m3/mole)
Sediment/Soil
Adsorption/Desorption - Koc
Level III fugacity models incorporating available physical and chemical property data indicate that at steady
state, 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)
EPIv4.11
Confidential study
EPIv4.11
EPIv4.11
Confidential study
Confidential study
Confidential study
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.
7-193
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
Level III Fugacity Model
DATA
Confidential E: >30,000 (Estimated)
Confidential C: Air = 0.1%
Water = 22. 4%
Soil = 76.8%
Sediment = 0.7% (Estimated)
Confidential D: Air = 0.7%
Water =14.5%
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;EPA, 2005
EPIv4.11
EPIv4.11
EPIv4.11
DATA QUALITY
Estimated value is greater than the
cutoff value, >30,000, for non-mobile
compounds.
Reported in a Level III Fugacity
model. Experimental data is
consistent with partitioning to
sediment.
7-194
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
Persistence
Water
Aerobic Biodegradation
DATA
REFERENCE
DATA QUALITY
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 301B: CO2
Evolution Test
87% degradation after 28 days
(Measured)
Confidential C: Passes Ready Test:
No
Test method: OECD TG 301C:
Modified MITI Test (I)
0% degradation after 4 weeks using
an activated sludge inoculum.
(Measured)
Confidential C: Study results:
Confidential study
Confidential study
Confidential study
Valid guideline study.
Valid guideline study.
Valid guideline study.
7-195
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
88%/28d
Test method: 302A: Inherent -
Modified SCAS Test
Primary degradation (Measured)
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
acclimatization period of several days
and a molybdenum blue colorimetric
method. (Measured)
Confidential study
Confidential C: Study results:
Test method: Other
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.
Reported in peer reviewed secondary
source. Limited study details were
provided.
7-196
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
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 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
sludge at a test substance addition rate
of 3 mg/L every 24 hours. (Estimated
by analogy)
Confidential study
Nonguideline study for confidential
analog.
Confidential E: Study results:
100%/lldays
Test method: Die-Away
Confidential study
Nonguideline study for confidential
analog.
7-197
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
Soil
Volatilization Half-life for
Model River
Volatilization Half-life for
Model Lake
Aerobic Biodegradation
DATA
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)
Confidential D: Study results:
77%/28 days
Pest method: Other
Reported as ultimately biodegradable.
Monsanto Shake Flask Procedure
precursor to Closed bottle test).
Measured)
REFERENCE
EPIv4.11
EPIv4.11
EPIv4.11
EPIv4.11
EPIv4.11
EPIv4.11
EC, 2000; OECD-SIDS, 2002
OECD-SIDS, 2002
DATA QUALITY
Reported in the volatilization from
water model.
Reported in the volatilization from
water model.
Reported in a guideline study.
Reported in a secondary source.
7-198
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
Anaerobic Biodegradation
Soil Biodegradation with
Product Identification
Sediment/Water
Biodegradation
DATA
Confidential D: Study results:
82%/28 days
Pest method: CO2 Evolution
Modified Sturm test. Reported as
ultimately biodegradable. Measured in
domestic, adapted activated sludge
Measured)
Confidential D:
Study results: 93%/49 days
Pest method: 302A: Inherent -
Modified SCAS Test
Reported as inherently biodegradable.
Measured)
Confidential C & E: Not probable
(Anaerobic-methanogenic
Biodegradation probability model)
Confidential 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)
Confidential D: 86.9%/40 days
Primary degradation in river sediment.
43. 3% after 3 days
86.9% after 40 days (Measured)
Confidential E: Mineralization of the
REFERENCE
OECD-SIDS, 2002
OECD-SIDS, 2002
EPIv4.11
OECD-SIDS, 2002
OECD-SIDS, 2002
Confidential study
DATA QUALITY
Reported in a secondary source.
Reported in a guideline study.
Reported in a secondary source.
^o data located.
Reported in a secondary source.
Nonguideline study for confidential
7-199
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
Air
Reactivity
Atmospheric Half-life
Photolysis
DATA
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
ecosystems. 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
Drocess. (Estimated)
Confidential D: A 0.1 mg/L solution
jwith acetone) was exposed to a
mercury lamp to examine the effect of
LTV light on the degradation of
Confidential D.
High pressure lamp (100W): 100%/20
REFERENCE
Confidential study
EPIv4.11
EPIv4.11
EPIv4.11
Mill, 2000; Professional judgment
EC, 2000
DATA QUALITY
analog.
Nonguideline study for confidential
analog.
This compound does not contain
functional groups that would be
expected to absorb light of
wavelengths >290 nm.
Reported in a secondary source under
laboratory conditions.
7-200
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
Hydrolysis
DATA
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
(Measured)
Confidential D: 100%/10 minutes at
pH 13 (Measured)
Confidential E: Half-lives:
460 years atpH5;
46 years at pH 6;
4.6 years at pH 7;
REFERENCE
Confidential study; ATSDR, 2012
EPIv4.11
EC, 2000; OECD-SIDS, 2002
OECD-SIDS, 2002
EC, 2000; OECD-SIDS, 2002
EC, 2000
EC, 2000
ECHA, 2013
EPIv4.11
DATA QUALITY
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.
Reported in secondary source.
Documentation of study details was
not sufficient to assess its reliability.
7-201
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
Environmental Half-life
Bioaccumulation
Fish BCF
DATA
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 2 1 days (anaerobic)
(Measured)
Confidential E: 120 days (Estimated)
REFERENCE
PBT Profiler
PBT Profiler
OECD-SIDS, 2002
PBT Profiler
DATA QUALITY
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.
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
HSDB, 2003
HSDB, 2003
Confidential study
EC, 2000
Guideline study reported in a peer
reviewed secondary source.
Guideline study reported in a peer
reviewed secondary source.
Adequate.
Reported in a secondary source.
7-202
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
Other BCF
BAF
Metabolism in Fish
DATA
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)
Confidential C: 54 (Estimated)
Confidential D: 73 (Estimated)
Confidential E: 18,000 (Estimated)
REFERENCE
OECD-SIDS, 2002
EC, 2000
EC, 2000
OECD-SIDS, 2002
OECD-SIDS, 2002
EPIv4.11
EPIv4.11
EPIv4.11
EPIv4.11
DATA QUALITY
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.
No data located.
Estimated using the representative
structure.
No data located.
7-203
-------
Emerald Innovation™ NH-1
PROPERTY/ENDPOINT
DATA REFERENCE DATA QUALITY
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).
7-204
-------
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.
7-205
-------
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.
7-206
-------
Expandable graphite
Screening Level Toxicology Hazard Summary
This table contains hazard information for each chemical; evaluation of risk considers both hazard and exposure. Variations in end-of-life processes or degradation and combustion
by-products are discussed in the report but not addressed directly in the hazard profiles. The caveats listed below must be taken into account when interpreting the information in the
table.
VL = Very Low hazard L = Low hazard = Moderate hazard H = High hazard VH = Very High hazard - Endpoints in colored text (VL, L, M, H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].
* Expandable graphite commercial formulations are prepared using chemical washes which may be present in the final product as residues. The associated hazards vary depending on
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
,
]y
o
H
3
&
•g
M
0
a
£
sS
U
^
.y
o
-^
o
1
OJ
O
o
8.
—
a
S
8.
O
"3
P
•a
M
0
O
s
z
0)
0
p
•a
sS
0)
1
B
•^
|
OJ
C/5
a
C/5
r*> S
o -g
SS N
II
_0
1
&•
0)
B
•_p
sS
•H
hH
••
2
0)
p
Aquatic
Toxicity**
QJ
3
u
B
s
u
Environmental
Fate
0)
u
a
S?
%
0)
PH
B
0
«
"3
s
u
sS
o
s
Expandable graphite
| 12777-87-6 | *
M M
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.
7-207
-------
° r-sr
Ho-s-^r-Wr-^
II r^W-^r^
Sr°
OH
Representative
5 o
5OI-OH
6
structure
CASRN: 12777-87-6
MW: > 1,000 (Estimated)
MF: [C]n[S03H]x
Physical Forms: Solid
Neat:
Use: Flame retardant
SMILES: Not applicable
Synonyms: Sulfuric acid, compd. with graphite; Sulfuric acid, compd. With graphite (1:?); Expandable graphite; exfoliated graphite; sulfuric acid, compound with
graphite; graphite hydrogen sulfate (CASRN 12689-13-3); graphite bisulfate (CASRN 12689-13-3); graphite intercalation compounds
Chemical Considerations: Expandable graphite is manufactured by a process where the carbon sheets of graphite are modified by oxidative chemical treatment. The
oxidation of graphite causes an increase in the distance between graphite crystal lattice planes and an increase in the specific volume of the graphite particles by a
factor of 200 to 400. There are different hazards that result from the specific wash chemicals used and, as a result, the hazards may change by manufacturer.
Commercial expandable graphite products may contain 0.1-3.0% free silica or quartz (CASRN 14808-60-7) as residuals from graphite. Synthetic and natural graphite
may be mixtures that contain deliberate additives such as cristobalite, clay, coal, and petroleum products. Also, natural graphite is usually found associated with
impurities such as mica, iron oxide, granite and free silica in 2-25%. Expandable graphite is typically 85-98% carbon (CASRN 7782-42-5); the other components of
the commercial products are the expansion agents (i.e., sulfuric acid CASRN 7664-93-9) and other formulation specific confidential additives. Nanoscale components
are not expected to be present and were not included in this assessment. Expandable graphite particle sizes reported in product documentation are typically >200(im x
30 (im, 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
7-208
-------
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
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.
7-209
-------
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
IPCS, 2013
No data located.
Very Limited data reported in a
secondary source for Graphite
(CASRN 7782-42-5), though there
is no indication what the data is
based on; this information was not
reported in any other source.
No data located.
7-210
-------
Expandable graphite CASRN 12777-87-6
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Acute Mammalian Toxicity
LOW: Expandable graphite is not acutely toxic via the oral or dermal routes in rats. No adequate
experimental data were located for the inhalation route; however, graphite dust may be irritating to the
respiratory tract.
Expandable graphite commercial formulations are prepared with chemical washes. There are variable
hazards from the specific wash chemicals used and, as a result the hazards may change by manufacturer.
A High hazard concern for acute toxicity is estimated for formulations containing one confidential wash
and also for washes containing chromic acid (CASRN 7738-94-5).
Acute Lethality
Oral
Dermal
Inhalation
Rat oral LD50 > 2,000 mg/kg bw
All animals survived until the end of the
study without showing any signs of
toxicity.
Rat dermal LD50
> 2,000 mg/kg bw
semi-occlusive conditions
Graphite dust is irritating to the
respiratory tract
Inhalation LC50 = not determined;
All attempts to generate an atmosphere
using the test substance as received were
unsuccessful.
ECHA, 2013b
ECHA, 2013b
REACH, 2006
ECHA, 2013b
Data are for Expandable Natural
Graphite (sulfuric acid, compound
with graphite), Purity > 93 %. Study
was conducted according to OECD
Guideline 423 and GLP.
Data are for Expandable Natural
Graphite (sulfuric acid, compound
with graphite), Purity > 93 %. Study
was conducted according to OECD
Guideline 402 and GLP.
Data are for Graphite (CASRN
7782-42-5); limited data reported in
a secondary source.
Data are for Expandable Natural
Graphite (sulfuric acid, compound
with graphite), Purity > 93 %. Study
was conducted according to OECD
Guideline 403 and GLP. The overall
results of the pre-test trials indicate
that the physical properties of the
test substance prevented the
achievement of the required testing
concentration.
7-211
-------
Expandable graphite CASRN 12777-87-6
PROPERTY/ENDPOINT
Carcinogenicity
OncoLogic Results
Carcinogenicity (Rat and
Mouse)
Combined Chronic
Toxicity/Carcinogenicity
Other
DATA
REFERENCE
DATA QUALITY
MODERATE: No experimental data were located for expandable graphite. Graphite (CASRN 7782-42-5)
is classified as a Group 1 carcinogen by IARC and a suspected carcinogen by NTP. These classifications
are based on quartz as an impurity, and do not apply to graphite that is completely free of quartz.
However, there is no evidence of graphite on the market in pure form. In order to remain conservative, a
MODERATE hazard is designated by analogy to graphite.
Expandable graphite commercial formulations are prepared with chemical washes. There are variable
hazards from the specific wash chemicals used and, as a result the hazards may change by manufacturer.
A High hazard concern for Carcinogenicity is estimated for formulations containing chromic acid (CASRN
7738-94-5).
Graphite is classified as a Group 1
carcinogen and suspected carcinogen by
IARC and NTP, respectively. The
classifications are a result of quartz as an
impurity, and do not apply to graphite that
is completely free of quartz. However,
there is no evidence of graphite on the
market in pure form.
GrafTech, 2013
No data located.
No data located.
No data located.
Data are for Graphite (CASRN
7782-42-5).
7-212
-------
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 (im)
Data are for Expandable Natural
Graphite (sulfuric acid, compound
with graphite), Purity > 93 %. Study
was conducted in accordance with
OECD Guidelines and GLP
No data located.
No data located.
No data located.
7-213
-------
Expandable graphite CASRN 12777-87-6
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Reproductive Effects
LOW: No experimental data were located for expandable graphite. There were no adverse reproductive
effects in rats at doses up to 1,159 mg/kg-day in an oral combined repeated dose
reproduction/developmental toxicity screening study using graphite (CASRN 7782-42-5).
Expandable graphite commercial formulations are prepared with chemical washes. There are variable
hazards from the specific wash chemicals used and, as a result the hazards may change by manufacturer.
A High hazard concern for reproductive toxicity is estimated for formulations containing chromic acid
(CASRN 7738-94-5).
Reproduction/Developmental
Toxicity Screen
Combined Repeated Dose
with Reproduction/
Developmental Toxicity
Screen
In a combined repeated dose toxicity
study with reproduction/developmental
toxicity screening, male and female
Wistar rats (10/sex/group) were fed
expanded graphite powder in the diet at
concentrations of 0, 91, 261, 813 mg/kg-
day (for males), 0, 120, 343, 1,067 mg/kg-
day (for females in premating period), 0,
106, 309, 930 mg/kg-day (for females
during gestation) and 0, 111, 370, 1,159
mg/kg-day (for females during lactation).
Mating was insufficient in all treatment
groups and control; it was reported that
the reason for insufficient mating was
unclear. No adverse effects on precoital
time or fertility, number of implantation
sites or number of live born pups. No
effect on litter size, pup survival, or pup
body weight. Sporadically observed
clinical findings in pups and controls
(reduced size of testes and epidydimides)
were not considered to be related to the
test substance.
No data located.
ECHA, 2013b
Data are for Expanded graphite
powder (CASRN 7782-42-5). Study
was conducted in accordance with
OECD Guideline 422 and GLP.
7-214
-------
Expandable graphite CASRN 12777-87-6
PROPERTY/ENDPOINT
Reproduction and Fertility
Effects
Other
Developmental Effects
Reproduction/
Developmental Toxicity
Screen
DATA
NOAEL (parental, reproductive and
developmental): 12,000 mg/kg diet (target
high limit, corresponding to 813 mg/kg-
day for males and 1,067, 930 and 1,159
mg/kg-day for females during premating,
gestation and lactation, respectively);
highest doses tested
LOAEL: Not established
REFERENCE
DATA QUALITY
No data located.
No data located.
LOW: No experimental data were located for expandable graphite. There were no adverse developmental
effects in rats at doses up to 1,159 mg/kg-day in an oral combined repeated dose
reproduction/developmental toxicity screening study using graphite (CASRN 7782-42-5). Sporadically
observed clinical findings in pups and controls (reduced size of testes and epidydimides) were not
considered to be related to the test substance.
No data located.
7-215
-------
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.
7-216
-------
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, 111, 370, 1159
mg/kg-day (for females during lactation).
No effects on locomotor activity or any of
the investigated endpoints of the
Functional Observational Battery.
NOAEL: 12,000 mg/kg-day diet (target
high limit, corresponding to 813 mg/kg-
day for males and 1067, 930 and 1 159
mg/kg-day for females during premating,
gestation and lactation, respectively);
highest doses tested
LOAEL: Not established
ECHA, 2013b
Data are for Expanded graphite
powder (CASRN 7782-42-5). Study
was conducted in accordance with
OECD Guideline 422 and GLP.
No data located.
7-217
-------
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).
7-218
-------
Expandable graphite CASRN 12777-87-6
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
In a combined repeated dose toxicity
study with reproduction/developmental
toxicity screening, male and female
Wistar rats (10/sex/group) were fed
expanded graphite powder in the diet at
concentrations of 0, 91, 261, 813 mg/kg
body weight/day (for males), 0, 120, 343,
1,067 mg/kg-day (for females in
premating period), 0, 106, 309, 930
mg/kg-day (for females during gestation)
and 0, 111, 370, 1,159 mg/kg-day (for
females during lactation).
No adverse effects on body weight gain or
food consumption; no effect on
hematology or clinical chemistry NOAEL
(parental, reproductive and
developmental): 12,000 mg/kg-day diet
(target high limit, corresponding to 813
mg/kg-day for males and 1067, 930 and
1,159 mg/kg-day for females during
premating, gestation and lactation,
respectively); highest doses tested
LOAEL: Not established
ECHA, 2013b
Data are for Expanded graphite
powder (CASRN 7782-42-5). Study
was conducted in accordance with
OECD Guideline 422 and GLP.
Male Wistar rats were exposed via
inhalation (head/nose) to target
concentrations of 0.5, 2.5, or 10 mg/m3
graphene or graphite nanoplatelets 6
hours/day for 5 days. No adverse clinical
signs or alterations in body weight.
Increases in lavage markers indicative for
inflammatory processes following
exposure to 10 mg/m
graphene. The calculated volumetric load
Ma-Hock etal., 2013
Study details reported in a primary
source; study conducted in
accordance with OECD Guideline
412 and GLP
7-219
-------
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.
7-220
-------
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
7-221
-------
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
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, 2013b
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-
7-222
-------
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, 2013b
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.
7-223
-------
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
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)
>30,000 (Estimated)
Professional judgment
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 for nonmobile
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
7-224
-------
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
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.
7-225
-------
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.
7-226
-------
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://onlinelibrarv.wilev.com/doi/10.1002/14356007.n05_n03/full#n05_n03-secl-0012.
MSDS (2012) Expandable flake graphite. Material Safety Data Sheet.
7-227
-------
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.
7-228
-------
Fyrol™ HF-5
Screening Level Toxicology Hazard Summary
This table contains hazard information for each chemical; evaluation of risk considers both hazard and exposure. Variations in end-of-life processes or degradation and combustion
by-products are discussed in the report but not addressed directly in the hazard profiles. The caveats listed below must be taken into account when interpreting the information in the
table.
VL = Very Low hazard L = Low hazard = Moderate hazard H = High hazard VH = Very High hazard - Endpoints in colored text (VL, L, M, H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].
* Each hazard designation for a mixture is based upon the component with the highest hazard, whether it is an experimental or estimated value.
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 with MW < 1,000.
00 Based on experimental test data for a residual impurity reported to be present in this substance at levels up to 5% by weight.
Chemical
CASRN
Human Health Effects
|y
o
H
u
^
|y
'a
Carcinoge
^>
Genotoxic
0)
Reproduc
sS
S
Developm
CJ
Neurologi
0)
0
a
Repeated
a
O
.a
0)
C/5
1
C/5
bg
Respirato
Sensitizati
a
•H
HH
0)
0
I
•H
Dermal Ir
Aquatic
Toxicity
u
Chronic
Environmental
Fate
4»
Persistenc
a
1
"3
Bioaccum
Fyrol™ HF-5*
Confidential A
Confidential B
Proprietary
Confidential
Confidential
L
L
L
M§
L
M§
M
M
L
L
L
L
L
M§
M
§
Md
Ld
M
L
L
L
L
L
L
VL
VH
L
VH
VH
L
VH™
VH
VH
H1
L
rf
7-229
-------
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 publicly 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.
7-230
-------
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: >3 00
(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
EPI v4.1 1; Professional
judgment; EPA, 1999
Confidential study
Confidential study
Confidential study
Confidential study
Confidential study
EPIv4.11
Professional judgment;
Boethling andNabholz, 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.
7-231
-------
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, 3 75 mg/L for n=l
93 3 mg/L for n=2
23 3 mg/L for n=3
1 mg/L for n=6 (Estimated)
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.
7-232
-------
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)
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.
No data located.
Does not contain functional groups that are
expected to ionize.
Does not contain functional groups that are
expected to ionize.
7-233
-------
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
exposure. 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
Confidential B: Studies were
onducted 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
or approximately 7 days and
metabolites were isolated and
Characterized; the brain, mesenteric
at, kidneys, liver, lungs, tests/ovaries
ind spleen were collected from rats at
ime of necropsy
onfidential B was absorbed and was
;xtensively metabolized; Metabolism
>vas consistent between species,
5exes, and individual animals;
xcretion occurred primarily in the
eces and then urine
Confidential study
Non-guideline study.
7-234
-------
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
xcreted 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
xposure, indicating that some of the
administered oral dose was not
absorbed through the gastrointestinal
route.
Confidential study
Non-guideline study.
7-235
-------
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-
Confidential B (purity: 99%) for 6
lours
20% of Confidential B was absorbed
n the systemic circulation in rats
Mowing the six-hour exposure and <
10% was absorbed in monkeys. 7
days 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
dose 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
?eces in males and 52% in females
allowing 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
be measured accurately for the inhalation
itudy.
7-236
-------
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.
7-237
-------
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
Submitted confidential study
EPA, 2010
Submitted confidential study
EPA, 2010
EPA, 2010
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
)ecause 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.
7-238
-------
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.
No 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 and E. coli.
Professional judgment
Submitted confidential study
Estimated for the low MW component due
to ethyl substituted phosphate.
Data reported in a submitted confidential
study.
7-239
-------
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 (ig/plate.
No cytotoxicity was evident.
Confidential B: Negative in
Escherichia coll (strains not
indicated) with and without
metabolic activation at
concentrations up to 5,000 (ig/plate.
No 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
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.
No data located.
No data located.
7-240
-------
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
data located.
Reproduction and Fertility
Effects
onfidential B: Two generation
lietary reproduction study in rats.
sprague-Dawley rats (30/sex/dose)
>vere fed 0, 50, 500, or 1,000 mg/kg-
lay Confidential B in the diet for 10
^eeks.
clinical signs of toxicity. No
;ffects on litter survival. No adverse
effects on any reproductive or fertility
jarameter measured. No treatment-
•elated lesions in any reproductive
Drgan.
VOAEL (parental systemic and
•eproductive toxicity) ~ 1,000 mg/kg-
lay
GAEL: not established
EPA, 2010; Confidential study
Study details reported in a secondary
ource. Data are for the commercial
polymeric mixture.
7-241
-------
Fyrol™ HF-5
PROPERTY/ENDPOINT
Other
Developmental Effects
Reproduction/ Developmental
Toxicity Screen
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 judgment
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
low 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.
7-242
-------
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-
day 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 Fj 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-
day
EPA, 2010; Confidential study
Guideline study. Data are for the
commercial polymeric mixture.
7-243
-------
Fyrol™ HF-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
onfidential B: Developmental oral
javage study in rabbits. Pregnant
Vew Zealand white rabbits
27/group) were dosed with 0, 50,
100 or 1,000 mg/kg-day Confidential
by oral gavage on GD 6-28.
clinical signs of toxicity. No
idverse effects on maternal food
consumption, body weight gain or
Drgan weights. No adverse effects on
"etal body weights, viability, or any
levelopmental endpoint measured.
VOAEL (maternal and developmental
oxicity): 1,000 mg/kg-day
GAEL: not established as highest
concentration tested did not produce
idverse effects
EPA, 2010
aideline study reported in a secondary
source. Data are for the commercial
3olymeric mixture.
7-244
-------
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
•4o deaths or clinical signs of toxicity.
•4o 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
Expert judgment
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: 1,000 mg/kg
Estimated by analogy)
Professional judgment;
Submitted confidential study
Estimated based on analogy to a
confidential analog.
7-245
-------
Fyrol™ HF-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
onfidential B: 28-day inhalation
,tudy 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
>uggestive of neurotoxic effect and
hE was not affected after study
ermination
VOAEL: 0.1 mg/L
-GAEL: 0.5 mg/L (plasma ChE
nhibition)
Confidential study; EPA, 2010
onfidential B: 28-day oral (gavage)
,tudy in mice; 0, 500, 1,500, 5,000
ng/kg
Dose-related decrease in plasma ChE
compared to controls, which was no
onger apparent after the 60 day
•ecovery period.
Vo NOAEL/LOAEL determined
Confidential study
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.
Other
'onfidential A: There is potential
neurotoxic effects based on a
structural alert for organophosphates.
(Estimated)
Professional judgment
Estimated based on a structural alert and
professional judgment.
Confidential A: Uncertain concern
br neurotoxicity (Estimated)
Professional judgment
Estimated for the low MW component due
to ethyl substituted phosphate.
7-246
-------
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.
7-247
-------
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.
7-248
-------
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.
7-249
-------
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 judgment
Expert judgment
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.
7-250
-------
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
sndocrine disruptor on the EU
Priority List of Suspected Endocrine
Disrupters.
European Commission, 2012
onfidential B: Two generation
lietary reproduction study in rats.
sprague-Dawley rats (30/sex/dose)
>vere fed 0, 50, 500, or 1,000 mg/kg-
lay Confidential B in the diet for 10
^eeks.
Vaginal opening and preputial
>eparation were delayed at 500 and
,000 mg/kg-day. This effect was
considered by study authors to be
>econdary to reduction of body
weight in Fj generation during week
(treated animals had decreased body
weights compared to controls during
>veek 1, reportedly due to an initial
iversion to taste of diet).
VOAEL: 50 mg/kg bw-day (for
aginal opening and preputial
>eparation)
-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.
7-251
-------
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.
7-252
-------
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.
7-253
-------
Fyrol™ HF-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
ECOTOXICITY
ECOSAR Class
Acute Aquatic Toxicity
Fish LC50
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.
Confidential A: Danio rerio
(Zebrafish) 96-hour LC50 > 1,000
mg/L according to OECD 203
(Experimental)
Confidential A: Freshwater fish 96-
hour LC50> 100 mg/L
(Estimated)
ECOSAR: Esters
Confidential B: Brachydanio rerio
96-hour LC50 = 12.3 mg/L
(Experimental)
Clariant,2011
ECOSAR v 1.11
EPA, 2010
Data reported in a confidential study
submitted to EPA; the toxicity value is well
above the water solubility for this
substance; therefore NES is predicted.
Estimates based on representative
oligomers where n=l-6.
Estimates for the Esters class were
provided for comparative purposes.
See Section 5.5.1.
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.
7-254
-------
Fyrol™ HF-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Confidential B: Fish 96-hour LC50
NES
(Estimated)
ECOSAR: Esters
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.
Estimate for the Esters class was provided
for comparative purposes.
See Section 5.5.1.
Daphnid LC50
Confidential A: Daphnia magna 48-
hour LC50> lOOmg/L
(Estimated)
ECOSAR: Esters
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: Esters
ECOSARvl.ll
Estimates based on representative
oligomers where n=l-6.
Estimates for the Esters class were
provided for comparative purposes.
See Section 5.5.1.
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.
Estimate for the Esters class was provided
for comparative purposes.
See Section 5.5.1.
7-255
-------
Fyrol™ HF-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Green Algae EC50
Confidential A: Green algae 96-hour
EC50> lOOmg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Confidential B: Pseudokirchneriella
subcapitata 72-hour EC50 = 48.6
mg/L
(Experimental)
EPA, 2010
Confidential B: Green algae 96-hour
EC50 = NES
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Estimates based on representative
oligomers where n=l-6.
Estimates for the Esters class were
provided for comparative purposes.
See Section 5.5.1.
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.
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
Estimate for the Esters class was provided
for comparative purposes.
See Section 5.5.1.
7-256
-------
Fyrol™ HF-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Chronic Aquatic Toxicity
VERY HIGH: Based on an experimental 21-day NOEC = 0.021 mg/L in Daphnia magna following
exposure to Confidential B that may contain a residual impurity (up to 5%) with a Very High
chronic aquatic toxicity. There were no effects observed at the highest dose tested (0.021 mg/L);
however, this value is within the "Very High" hazard criteria range. It is not certain if effects may
occur within this range (up to 0.1 mg/L). For Confidential A, an estimated chronic aquatic toxicity
value was derived using an acute-to-chronic ratio (ACR) for the phosphate ester class and was
applied to the available experimental acute data for this chemical and indicated a Low hazard.
Fish ChV
Confidential A: Freshwater fish
ChV > 41.7 mg/L
(Estimated)
Confidential A: Freshwater fish
ChV > 10 mg/L
(Estimated)
ECOSAR: Esters
Confidential B: ChV = NES
(Estimated)
ECOSAR: Esters
Professional judgment
ECOSAR v 1.11
ECOSAR v 1.11
An ACR of 24 was derived for the
phosphate ester class based on
experimental data for Tris (p-t-
butylphenyl) phosphate (TBPP).
The acute-to-chronic ratio was applied to
available experimental acute fish data for
this chemical (ChV = >1000 mg/L /24 =
41.7 mg/L)
Estimates based on representative
oligomers where n=l -6.
Estimates for the Esters class were
provided for comparative purposes.
See Section 5.5.1.
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.
Estimate for the Esters class was provided
for comparative purposes.
See Section 5.5.1.
7-257
-------
Fyrol™ HF-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Daphnid ChV
Confidential A: Daphnia magna
ChV>10mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Estimates based on representative
oligomers where n=l -6.
Estimates for the Esters class were
provided for comparative purposes.
See Section 5.5.1.
Confidential B: Daphnia magna
Mean measured concentrations of
0.99, 3.1,5.0, 9.3, and 21 (ig/Lwere
administered in flow-through test
conditions.
21-day NOEC = 0.021 mg/L
(Highest concentration tested)
21-day EC50> 0.021 mg/L
(immobility and reproduction)
(Experimental)
Submitted confidential study
Reported in a submitted confidential study.
The test substance is identified as the n=l
oligomer. There were no effects observed
at the highest dose tested (0.021 mg/L);
however, this value is within the "Very
High" hazard criteria range. It is not certain
if effects may occur within this range (up
to 0.1 mg/L). This substance also contains
a residual impurity (up to 5%) that is
known to be toxic to aquatic organisms.
Confidential B: Daphnia magna
21-day NOEC = 0.021 mg/L
21-day EC50 = 0.037 mg/L Semi-
static
(Experimental)
Submitted confidential study
Reported in a submitted confidential study;
Study conducted according to GLP and
OECD guideline 211 The test substance is
identified as the n=l oligomer. This
substance also contains a residual impurity
(up to 5%) that is known to be toxic to
aquatic organisms.
7-258
-------
Fyrol™ HF-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Confidential B: 21-day ChV = NES
(Estimated)
ECOSAR: Esters
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.
Estimate for the Esters class was provided
for comparative purposes.
See Section 5.5.1.
Green Algae ChV
Confidential A: Green algae ChV >
10 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Confidential B: Pseudokirchneriella
subcapitata 72-hourNOEC =10
mg/L (WAF) 72-hour LOEC = 100
mg/L (WAF)
(Experimental)
Confidential study
Confidential B: ChV = NES
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Estimates based on representative
oligomers where n=l-6.
Estimates for the Esters class were
provided for comparative purposes.
See Section 5.5.1.
Study details reported in a secondary
source. Study conducted according to GLP
and OECD guideline 201.
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.
Estimate for the Esters class was provided
for comparative purposes.
See Section 5.5.1.
7-259
-------
Fyrol™ HF-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
ENVIRONMENTAL FATE
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: <10
(Estimated)
forn>l
EPIv4.11
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.
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;
>3 0,000 for n>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.
7-260
-------
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
Estimate based on representative oligomer
where n=l.
Confidential B:
Air= 1%
Water = 1%
Soil = 40%
Sediment = 59% (Estimated for n
1)
EPIv4.11
Estimates were performed on
representative components of the polymer.
7-261
-------
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 30ID:
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
EPIv4.11
From a MSDS for a confidential
commercial product containing 95-100%
pure material.
Estimate based on representative oligomers
where n=l-2.
7-262
-------
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.
No data located.
Estimate based on representative oligomers
where n=l.
Estimated for the n>l components.
No data located.
No data located.
7-263
-------
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
Non-quantitative value from a MSDS for a
confidential commercial product
containing 95-100% pure material.
Confidential A:
50%/3.3 years at pH 5-8
50%/3yearsatpH9
forn=l (Estimated)
EPIv4.11
Estimate based on representative oligomer.
7-264
-------
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
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
Supporting information about this related
class of compounds.
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.
7-265
-------
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
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.
HIGH: Based on the estimated BCF value for the lower MW components (MW<1,000); it is above the High
hazard designation criteria indicating a high potential for bioaccumulation. The oligomers with a MW
>1,000 are expected to have limited water solubility, poor bioavailability and are not expected to be
bioaccumulative.
Confidential A: 3.2 (Estimated)
Confidential A: <100 oligomers
(Estimated)
Confidential B: 1,300 for n=l
5 9 for n=2 (Estimated)
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.
7-266
-------
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).
7-267
-------
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.
7-268
-------
Isopropylated triphenyl phosphate (IPTPP)
Screening Level Toxicology Hazard Summary
This table contains hazard information for each chemical; evaluation of risk considers both hazard and exposure. Variations in end-of-life processes or degradation and combustion
by-products are discussed in the report but not addressed directly in the hazard profiles. The caveats listed below must be taken into account when interpreting the information in the
table.
VL = Very Low hazard L = Low hazard = Moderate hazard = High hazard VH = Very High hazard - Endpoints in colored text (VL, L, , H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].
Chemical
CASRN
Human Health Effects
s
o
H
"3
u
^
'0
S
o
£
C^
u
^
|
o
0
O
O
>
|
•a
o
a.
1>
sS
•^
s
S
a.
0
3
>•
Q
_
I
2™
S
w
0
1
•c
HH
13
§
0)
Q
Aquatic
Toxicity
"S
u
^
'a
2
A
u
Environmental
Fate
0)
u
s
•g
4>
0.
a
O
13
s
s
S
Isopropylated triphenyl phosphate
(IPTPP)
68937-41-7
L
M
L
H
H
H
L
L
L
VH
VH
H
7-269
-------
Representative. Structure
CASRN: 68937-41-7
MW: 452
MF:
Physical Forms: Liquid
Neat:
Use: Flame retardant
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).
7-270
-------
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
Analog Structure: Not applicable
Structural Alerts: Organophosphates; Neurotoxicity (EPA, 2012).
Risk Phrases: R48/22 - harmful: danger of serious damage to health by prolonged exposure if swallowed; R62 - possible risk of impaired fertility; R63 - possible risk
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 isopropylated
triphenyl phosphate are generally classified based on the triphenyl phosphate content of the product (Environment Agency, 2009; ECHA, 2013b).
Hazard and Risk Assessments: An Environmental Risk Evaluation report for isopropylated triphenyl phosphate was published in August 2009. This substance is
part of EPA's HPV Challenge and is a registered substance with the European Chemicals Agency (Great Lakes Chemical Corporation, 2001; Environment Agency,
2009; ECHA, 2013a, 2013b).
7-271
-------
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 310M; reported in a
secondary source.
Data for a commercial product,
Reofos 65; reported in a secondary
source.
Data are for pure isomers at
reduced pressures; reported in a
secondary source. The
diisopropylated phenyl phosphate
and higher alkylated isomers are
expected to boil at higher
temperatures.
Reported in a secondary source for
7-272
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
Vapor Pressure (mm Hg)
DATA
Reported as 220-230°C at 1 mm Hg for
commercial isopropylphenyl diphenyl
phosphate (Measured)
>220 at 4 mmHg
Reported as 220-270° at 5.32 hPa
(Measured)
2.8xlO-7at30°C
(Measured)
5.8xlO-6at70°C
Reported for triphenyl phosphates with a
relatively high degree of alkylation
(such as tris(isopropylphenyl)
phosphate) (Measured)
2.3xlO'5 at 70°C
Reported for triphenyl phosphates with a
relatively low degree of alkylation (such
as isopropylphenyl diphenyl phosphate)
(Measured)
<0.026 at 150°C
Reported as 0.0346 hPa at 150°C
(Measured)
3.4at20°C
OECD Guideline 104; additional study
4.4 mm Hg at 25°C (Measured)
4xlO-8at25°C
(Estimated)
REFERENCE
1985
IUCLID, 2001
Environment Agency, 2009
Environment Agency, 2009
Environment Agency, 2009
IUCLID, 2001
ECHA, 2013b
EPIv4.11
DATA QUALITY
a commercial isopropylphenyl
diphenyl phosphate product, at
reduced pressure.
Data are for commercial products
Reofos and Durad; reported in a
secondary source.
Reported in a secondary source for
a commercial isopropylphenyl
diphenyl phosphate.
Reported in a secondary source.
Reported in a secondary source.
Reported in a secondary source for
commercial products, Reofos and
Durad.
Reported in a secondary source for
commercial product, Reofos 65 .
Based on a representative structure
for a component of the mixture,
with one isopropyl substituent
7-273
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
Water Solubility (mg/L)
DATA
<2xl(r8at250C
(Estimated)
0.026 (Estimated)
0.00083 (diisopropylated triphenyl
phosphate isomer);
2.6xlO"5 (triisopropylated triphenyl
phosphate isomer) (Estimated)
<2.2 (Measured)
Shake flask method
<2 (Measured)
Reported as 0.7 to 2 mg/L in water
considered insoluble in water
0.33 (Measured)
OECD 105; analyzed using GC/MS
REFERENCE
EPIv4.11
EPIv4.11
EPIv4.11;EPA, 1999
Saeger et al., 1979 (as cited in
Environment Agency, 2009)
IUCLID, 2001
ECHA, 2013b
DATA QUALITY
group.
Based on representative structures
for components of the mixture,
with two or more isopropyl
substituent groups.
Based on a representative structure
for a component of the mixture,
with one isopropyl substituent
group.
Estimated value is less than the
cutoff value, <0.001 mg/L, for non-
soluble compounds according to
HPV assessment guidance. Based
on representative structures for
components of the mixture, with
two or more isopropyl substituent
groups.
Reported in a secondary source for
Kronitex 1000, consisting of
isopropylphenyl diphenyl
phosphate along with triphenyl
phosphate and
bis(isopropylphenyl) phenyl
phosphate.
Reported in a secondary source for
commercial products Reofos and
Durad.
Reported in a secondary source for
a commercial product Reofos 65 .
7-274
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
0.367mg/L (Measured)
OECD 105; performed at 20°C
ECHA, 2013b
Data for commercial products,
REOFOS 35 using a guideline
study. Reported in a secondary
source.
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.
4.92 to 5.17
(Measured)
ECHA, 2013b
Data for commercial products,
Kronitex 50, Kronitex 100 and
Kronitex 200. Reported in a
7-275
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
Flammability (Flash Point)
Explosivity
Pyrolysis
pH
DATA
<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
High performance thin layer
chromatography (HPTLC) method for a
commercial product (Measured)
Flashpoints: >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,
565°C and 551°C at 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)
REFERENCE
Renberg et al., 1980 (as cited in
Environment Agency, 2009)
IUCLID, 2001 (as cited in
Environment Agency, 2009)
IUCLID, 2001 (as cited in
Environment Agency, 2009)
Professional judgment
Professional judgment
DATA QUALITY
secondary source.
Inadequate, reported in a secondary
source for a commercial product,
ECronitex 1000. The components of
this mixture are expected to have a
range of Kow values.
Reported in a secondary source for
commercial products.
Reported in a secondary source for
commercial products.
Mo experimental data located;
aased on its use as a flame
retardant.
^o data located.
Does not contain functional groups
that are expected to ionize under
environmental conditions.
7-276
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
pKa
DATA
Not applicable (Estimated)
REFERENCE
Professional judgment
DATA QUALITY
Does not contain functional groups
that are expected to ionize under
environmental conditions.
7-277
-------
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 (ig/cm2/h for
Reolube HYD 46 and Reofos 50,
respectively. Absorption rates for IPTPP
component 2-IDPP were 0.54 and 3.32
(ig/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 viagavage. Cyclic
metabolites of isopropylated phenyl
phosphates were detected in the bile
collected from the rabbits for up to 24
hours post-administration.
Yangetal., 1990
Reliable primary source. Study was
conducted using Isopropylated
phenyl phosphates, including R3
(tri-(o-iso-propylphenyl
phosphate)) and Reolube Hyd 46
Pregnant rats were administered 0, 0.1
or 1 mg/kg-day of FM550 in the diet
Patisauletal., 2013
Non guideline study indicates that
absorption of this compound can
7-278
-------
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
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.
No 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)
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 110 (100%
phenol, isopropylated phosphate
(3:1)); limit test using 3 rats/sex.
The LDLo value was converted to
mg/kg using a density of 1. 108
g/cm3.
Limited study details reported in a
secondary source. Study was
conducted using Durad 300 or
Reofos 50.
Limited study details reported in a
secondary source. Study was
7-279
-------
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 >1 0,000 mg/kg
Rat Inhalation 1-hour LC50 >200 mg/L
REFERENCE
IUCLID, 2000
ChemID, 2013
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
OncoLogic, 2008
^o data located.
No data located.
7-280
-------
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
HYD 46 (composition not
specified).
Limited study details reported in a
secondary source. This study is
7-281
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
Gene Mutation in vivo
Chromosomal Aberrations in
vitro
Chromosomal Aberrations in
vivo
DATA
metabolic activation
Negative, dominant lethal mutations in
mature germ cells of male Drosophila
melanogaster
Negative, sister chromatid exchanges
(SCEs) in male and female Chinese
hamsters (single oral gavage)
Negative, micronuclei induction in
NMRI female mice (single oral gavage)
Negative, chromosomal aberrations in
bone marrow from male and female
Chinese hamsters administered Reofos
50 or Reolube HYD 46 by gavage at
5000 mg/kg.
Positive, significantly increased
incidence of anomalies of nuclei in bone
REFERENCE
IUCLID, 2000
IUCLID, 2000
IUCLID, 2000
IUCLID, 2000
IUCLID, 2000
DATA QUALITY
classified as "not assignable" in the
IUCLID document.
Limited study details reported in a
secondary source. Studies were
conducted using commercial
mixture Reofos 50 (30% TPP, 70%
IPTPP). GLP-compliant.
^o data located.
Limited study details reported in a
secondary source. Studies were
conducted using commercial
mixtures Reofos 50 (30% TPP,
70% IPTPP) and Reolube HYD 46
(composition not specified). Non-
GLP.
Limited study details reported in a
secondary source. Study was
conducted using commercial
mixture Reolube HYD 46
(composition not specified). Non-
GLP, non-guideline.
Limited study details reported in a
secondary source. Studies were
conducted using commercial
mixtures Reofos 50 (30% TPP,
70% IPTPP and Reolube HYD 46
(composition not specified). GLP-
compliant, according to OECD
guideline 475 .
Limited study details reported in a
secondary source. Studies were
7-282
-------
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
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.
^o data located.
HIGH: Based on a LOAEL of 25 mg/kg-day in a combined subchronic reproductive/developmental toxicity
screening test in rats. Effects included changes in ovarian and epididymal weights (25 and 100 mg/kg-day,
respectively) and reduced fertility (100 and 400 mg/kg-day); the final study results were not available and
the formulation of the test substance was not specified. In addition, this substance has been assigned the risk
phrase R62 - possible risk of impaired fertility. In a dermal study with Reolube HYD (components not
specified) in rats, reduced absolute and relative testicular weights and slight testicular tubular atrophy were
observed at 1,000 mg/kg-day.
|No data located.
7-283
-------
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
DATA QUALITY
Results from 2 combined repeated
dose reproduction/developmental
toxicity screening tests of
isopropylated triphenyl phosphate
^formulation confidential).
^o data located.
7-284
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Other
In a dermal study in rats, test substance
was applied to shaved skin at 0, 40, 200
or 1,000 mg/kg for 6 hours/day, 5
days/week for 4 weeks. Reduced
absolute and relative testicular weights
(1,000 mg/kg-day); slight testicular
tubular atrophy (control and high-dose
males). No associated microscopic
findings).
NOAEL: 200 mg/kg-day
LOAEL: 1,000 mg/kg-day
IUCLID, 2000
Limited study details reported in a
secondary source. Study conducted
using commercial mixture Reolube
HYD (components not specified).
Developmental Effects
HIGH: Estimated based on analogy to Kronitex TCP (1330-78-5). Reduced fetal body weight was reported
at 20 mg/kg-day (NOAEL not established; lowest dose tested) in a developmental study in rats orally
exposed to the analog. In addition, increased skeletal variations were reported at 750 mg/kg-day for the
analog. A LOAEL of 400 mg/kg-day (NOAEL = 100 mg/kg-day) was reported following exposure to
Isopropylated triphenyl phosphate in a combined subchronic reproductive/developmental toxicity screening
test in rats. Effects included reduced pre- and post-natal survival; the final study results were not available
and the formulation of the test substance was not specified. Development effects were reported in a study in
pregnant Wistar rats administered a FM550 mixture (sum total of TBB and TBPH approximately 50%
with additional components identified as IPTPP and TPP) during gestation though lactation (GD8 -
PND21); developmental effects included early female puberty, weight gain, altered exploratory behavior,
and increased male left ventricle thickness (LOAEL = 1 mg/kg-day, NOAEL = 0.1 mg/kg-day). It is
uncertain which component or components of the FM 550 mixture is driving the reported developmental
effects. This substance has been assigned the risk phrase R63 - possible risk of harm to the unborn child.
There were no experimental data for the neurodevelopmental toxicity endpoint located; There is uncertain
concern for developmental neurotoxicity based on the potential for Cholinesterase (ChE) inhibition in dams
that may result in alterations of fetal neurodevelopment.
Reproduction/
Developmental Toxicity
Screen
data located.
7-285
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Combined Repeated Dose
with Reproduction/
Developmental Toxicity
Screen
In a combined repeat
dose/reproductive/developmental
toxicity screening study, male and
female rats were orally gavaged with 0,
25, 100 or 400 mg/kg-day test substance
(isopropylated triphenyl phosphate;
specific formulation confidential) for 14
days premating, during mating for a total
of at least 28 days of treatment for
males, and during gestation and up to 4
days postpartum for a total of up to 53
days of treatment for females.
Results: Limited to summary statements
that indicated decreased fertility at mid-
and high-dose levels, decreased litter
size and pup survival at least at high
dose, and treatment-related changes in
selected organ weights at all dose levels.
NOAEL (maternal): Not established
LOAEL (maternal): 25 mg/kg-day
(treatment-related organ weight
changes)
NOAEL (developmental): 100 mg/kg-
day
LOAEL (developmental): 400 mg/kg-
day (decreased litter size and pup
survival)
Submitted confidential study; Great
Lakes Chemical Corporation, 2004b
Results from 2 combined repeated
dose reproduction/developmental
toxicity screening tests of
isopropylated triphenyl phosphate
(formulation confidential).
7-286
-------
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
Patisauletal., 2013
DATA QUALITY
Estimated based on analogy; study
was conducted using Kronitex TCP
^tris (methylphenyl) phosphate;
CASRN 1330-78-5).
No data located.
Estimated based on data for
FM550 mixture; non guideline
study; the test substance identified
as FM550 is a mixture made up of
TBB, TBPH (sum total of TBB
and TBPH is approximately
7-287
-------
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: O.lmg/kg-day
50%), TPP and IPTPP; it is not
clear which component or
components of the mixture are
driving the reported developmental
effects.
7-288
-------
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.
^o data located.
7-289
-------
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
(TOCP) displayed lacrimation, tremors,
staining and had lowered body
temperatures. Significant inhibition of
brain cholinesterase and neuropathy
target esterase activity (35 and 50% less
than controls, respectively) in treated
animals. Serum cholinesterase activity in
treated animals was 87% less than that
of controls, compared to 94% less in
positive control (TOCP-treated) animals.
Rats were exposed (head only) for 20
minutes to an unspecified concentration
of smoke and decomposition gases from
foam containing equal proportions of the
test substance; There were no convulsive
seizures or characteristic of exposure to
toxic bicyclic phosphites or phosphates
observed.
In a dermal study in rats, test substance
IUCLID, 2000
Submitted confidential study
IUCLID, 2000
Limited study details reported in a
secondary source. Study conducted
using commercial mixture Reofos
65 (20% TPP, 80% IPTPP).
Study was not conducted according
to standard guidelines; study
evaluated neurotoxicity of test
substance. Test substance
identified as combustion products
of an isopropylated triaryl
phosphates/ triphenyl phosphate
mixture in the presence of cyclic
phosphonate compounds; exposure
concentration not specified.
Limited study details reported in a
7-290
-------
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
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
secondary source. Study conducted
using commercial mixture Reolube
HYD (components not specified)
Limited study details reported in a
secondary source. Study conducted
using commercial mixture
Kronitex 50 (components not
specified). Limited number of
endpoints assessed.
Estimated based on structural alert
for organophosphates.
Sufficient evidence that
commercial isopropylated phenyl
phosphate formulations cause
delayed neuropathy in hens.
IUCLID (2000) summarized
results from a number of
unpublished studies.
7-291
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
inhalation exposure route and reported
ataxia and degenerative neurological
effects following single 8-hour exposure
to aerosols of Reofos 50 at 2.4 mg/L (no
effects at 0.62 mg/L).
Potential for neurological effects; this
substance has the potential to undergo a
similar mechanism of action as ortho-
cresyl phosphate with the formation of
an intermolecular intermediate that
effects the nervous system.
(Estimated by analogy)
Professional judgment
Estimated based on analogy to
ortho-cresyl phosphate and
professional judgment.
7-292
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Repeated Dose Effects
HIGH: Based on a combined repeated dose with reproductive/developmental toxicity screen test in rats; a
LOAEL of 25 mg/kg-day (lowest dose tested) was determined for changes in organ weights (NOAEL was
not established); final study results were not available and the test substance formulation was not specified.
A LOAEL of 460 mg/kg-day in rats following 28 days of dietary exposure to commercial mixture Kronitex-
100 (composition not specified). Dermal NOAELs were 100 and 200 mg/kg-day in rats following 4 weeks of
exposure to commercial mixtures Kronitex 50 and Reolube HYD, respectively. In addition, there may be
some potential for repeated dose effects based on analogy to TPP, a component of the commercial mixture.
In a combined repeated dose
reproductive/developmental toxicity
screening study, male and female rats
were orally gavaged with 0, 25, 100 or
400 mg/kg-day test substance
(isopropylated triphenyl phosphate;
specific formulation confidential) for 14
days premating, during mating for a total
of at least 28 days of treatment of males,
and during gestation and up to 4 days
postpartum for a total of up to 53 days of
treatment of females.
Treatment-related changes in selected
organ weights at all dose levels
NOAEL: Not established
LOAEL: 25 mg/kg-day (based on
changes in organ weights)
Sprague-Dawley rats (10/sex) were
exposed to Kronitex 100 in the diet at
concentrations of 0, 0.1, 0.5, or 1.0%
(~0, 91, 460, or 910 mg/kg-day) for 28
days; Mortalities included 12 rats (1
control, 4 low-dose, 4 mid-dose, and 3
high-dose) that were determined not to
be treatment related; there were no
Submitted confidential study; Great
Lakes Chemical Corporation, 2004a,
2004b
Limited study results reported in
study summary statements;
screening tests of isopropylated
triphenyl phosphate (formulation
confidential).
Submitted confidential study;
IUCLID, 2000, 2001
Limited study details provided in a
secondary source. Study was
conducted using commercial
mixture Kronitex K-100 (purity,
composition not specified). Doses
were reported as % in the diet but
were converted by SRC, Inc. to
mg/kg bw-day using EPA 1988
7-293
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
effects on urinalysis results or incidence
of gross lesions at necropsy. Reduced
feed consumption was observed in the
mid-dose group in both sexes and
reduced body weight gain was noted in
high-dose females. Abnormalities (not
specified) were observed in clinical
chemistry measurements in mid- and
high-dose groups and in hematology
parameters at the high dose. Relative
liver weights were elevated in all treated
groups. There were no indications of
treatment-related histopathologic lesions
in livers or kidneys of high-dose groups.
NOAEL: 0.1% (-91 mg/kg-day)
LOAEL: 0.5% (-460 mg/kg-day) based
on unspecified abnormalities in clinical
chemistry
reference values for body weight
and food consumption.
In a dermal study in rats (5/sex/group),
Kronitex 50 was applied to shaved skin
at 0, 100, 500 or 2,000 mg/kg 6
hours/day, 5 days/week for 4 weeks.
Decreased plasma cholinesterase (ChE)
activity (females at 500 and 2,000
mg/kg-day); decreased erythrocyte ChE
activity (males, 2,000 mg/kg-day);
increased adrenal weights and slight
fatty change of the adrenal cortex (males
at 500 and 2,000 mg/kg-day
NOAEL: 100 mg/kg-day
LOAEL: 500 mg/kg-day
IUCLID, 2000
Limited study details reported in a
secondary source. Study conducted
using commercial mixture
Kronitex 50 (components not
specified). Limited number of
endpoints assessed.
7-294
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
Skin Sensitization
Skin 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)
7-295
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
Respiratory Sensitization
[Respiratory Sensitization
Eye Irritation
Eye Irritation
DATA
Inconclusive; shown to be ambiguous
for Sensitization potential in the Local
Lymph Node Assay in mice.
Stimulation Indices (SI) of 7.4, 12.9 and
10.4 were calculated for applied
concentrations of 25%, 50% and 100%
IPTPP, respectively.
No dose-response relationship was
observed within the study.
REFERENCE
ECHA, 2013b
DATA QUALITY
Limited study details reported in a
secondary source. Test substance:
Reofos 65 (Phenol, isopropylated,
phosphate); conducted according
to OECD guideline 429.
The SI threshold value of at least 3,
would normally be classified as a
sensitizer' however, a dose-
response relationship was not
observed, which is required of the
LLNA test design.
No data located
|No data located.
LOW: Based on no irritation to slight ocular irritation that cleared within 10 days postinstillation.
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 conjunctival erythema in rabbits;
cleared within 48 hours; characterized as
"practically non-irritating" based on a
maximum irritation score of 1 .3/1 10 at
24 hours; no conjunctival discharge or
effects on the cornea or iris were
IUCLID, 2000, 2001
Submitted confidential study
Weight of evidence indicates that
commercial isopropylated phenyl
phosphate is not a primary eye
irritant
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
7-296
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
Dermal Irritation
Dermal Irritation
DATA
reported.
non-irritating in rabbits; there were no
signs of eye irritation observed at
1,24,48, or 72 hours
REFERENCE
Submitted confidential study
DATA QUALITY
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].
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.
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
IUCLID, 2000; IUCLID, 2001
Submitted confidential study
Submitted confidential study
Weight of evidence indicates that
commercial isopropylated phenyl
phosphate is not a primary dermal
irritant.
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
7-297
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
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.
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].
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
IUCLID, 2000
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.
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.
7-298
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
Immunotoxicity
Immune System Effects
DATA
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
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
Patisauletal., 2013
DATA QUALITY
Estimated based on experimental
data for the FM550 mixture; non
guideline study; the test substance
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
7-299
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
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.
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)
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)
Cleveland et al, 1986
Nevins and Johnson 1978 (as cited
in Environment Agency, 2009)
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.
Adequate study reported in a
secondary source. Study was
conducted using commercial
product Houghto-Safe 1120
(isopropylphenyl diphenyl
phosphate as the principal
7-300
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
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)
Nevins and Johnson 1978 (as cited
in 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
The test was performed under flow-
through test conditions using acetone as
solvent; test substance concentrations
were nominal.
(Experimental)
Nevins and Johnson 1978 (as cited
in 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 = 0.9 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 = 1.15mg/L
NOEC: 0.4 mg/L
IUCLID, 2000
Limited study details reported in a
secondary source. Study was
conducted using commercial
7-301
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
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)
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)
Nevins and Johnson 1978 (as cited
in 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
LC50 = 4.5 mg/L
(Experimental)
Nevins and Johnson 1978 (as cited
in Environment Agency, 2009)
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).
Fish (Lepomis macrochirus) 96-hour
LC50 = 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
7-302
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
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)
Nevins and Johnson 1978 (as cited
in 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
substance concentrations were nominal
and at least 8 concentrations were tested.
(Experimental)
Nevins and Johnson 1978 (as cited
in 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 (Lepomis macrochirus) 96-hour
LC50 = 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
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.
7-303
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
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
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 (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
substance concentrations were nominal
(Experimental)
IUCLID, 2000, 2001
Limited study details reported in a
secondary source. Study was
conducted using commercial
product Reofos 50 (30% TPP, 70%
IPTPP).
Fish {Pimephales promelas) 96-hour
LC50 = 17 mg/L
20-day LC50 = 8.5 mg/L
The test was performed under static test
conditions using acetone as solvent; test
substance concentrations were nominal
(Experimental)
Nevins and Johnson 1978 (as cited
in 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)
Nevins and Johnson 1978 (as cited
in 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 value is well
above the water solubility of the
test substance.
7-304
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
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 = 50.1 mg/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
LC50 = 1.6 mg/L
NOEC <1 mg/L
The test was performed under static test
conditions using acetone as solvent; test
substance concentrations were nominal.
(Experimental)
IUCLID, 2000, 2001
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
IUCLID, 2001
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
secondary source. Two studies
conducted using commercial
product Reofos 50 (30% TPP, 70%
IPTPP) and Kronitex 50.
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
7-305
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
conditions with nominal test
concentrations
(Experimental)
Fish (Brachydanio rerid) 96-hour LC50
>l,OOOmg/L
The study was conducted using nominal
test conditions; test chamber conditions
(static, flow-through, etc.) not specified
(Experimental)
IUCLID, 2000
Fish 96-hour LC50 = 0.005 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Fish 96-hour LC50 = 0.03 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
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
considered valid.
Estimations for triisopropyl phenyl
phosphate;
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
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.
Estimations for diisopropyl phenyl
phosphate;
Estimate for the Esters class was
7-306
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
provided for comparative purposes.
See Section 5.5.1.
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.
Fish 96-hour LC50 = 0.18 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Estimations for monoisopropyl
phenyl phosphate;
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
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.
Daphnid LC50
Daphnia magna 48-hour LC50 = 0.25
mg/L
The test was performed under static test
conditions
(Experimental)
Ziegenfuss et al., 1986 (as cited in
Environment Agency, 2009)
Adequate study reported in a
secondary source. Study was
conducted using isopropyl phenyl
diphenyl phosphate (purity not
given).
Daphnia magna 48-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
Limited study details reported in a
secondary source. Study was
conducted using Kronitex-100
(components not specified).
7-307
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Daphnia magna 48-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
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
Daphnia magna 48-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
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).
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).
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.
7-308
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
The results of the study are
questionable.
Daphnia magna 48-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)
Knight and Allan, 2002 (as cited in
Environment Agency, 2009)
Daphnid 48-hour LC50= 0.004 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
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
uncertainties in the results that
included possible presence of some
test substance in the control water
and adherence of test substance to
daphnia. The test substance was
not acutely toxic to daphnid at
concentrations up to the solubility
limit (0.77 mg/L).
Estimations for triisopropyl phenyl
phosphate;
Estimate for the Esters class was
provided for comparative purposes.
7-309
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Daphnid 48-hour LC50 = 0.03 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Daphnid 48-hour LC50 = 0.25 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
See Section 5.5.1.
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.
Estimations for diisopropyl phenyl
phosphate;
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
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.
Estimations for monoisopropyl
phenyl phosphate;
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
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.
7-310
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
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 < 0.001 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Green algae 96-hour EC50 = 0.006 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.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;
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
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.
Estimations for diisopropyl phenyl
phosphate;
Estimate for the Esters class was
provided for comparative purposes.
7-311
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
Green algae 96-hour EC50 = 0.05 mg/L
(Estimated)
ECOSAR: Esters
REFERENCE
ECOSAR v 1.11
DATA QUALITY
See Section 5.5.1.
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.
Estimations for monoisopropyl
phenyl phosphate;
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
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.
7-312
-------
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 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. Experimental data for fish and algae indicate a High hazard
designation.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 (Pimephalespromelas) 30-, 60- and
90-day NOEC (growth) = 0.5 mg/L
(nominal)
30-day LOEC (growth) = 1.0 mg/L
NOEC (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)
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
7-313
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
60 and 90 day NOEC (growth) = 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 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 = 0.006 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Fish ChV < 0.001 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
(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 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.
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
Estimations for triisopropyl phenyl
phosphate;
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
The log Kow of 9.1 for this
chemical exceeds the SAR
limitation for log Kow of 8.0; NES
7-314
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Fish ChV< 0.00Img/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
are predicted for these endpoints.
Estimations for diisopropyl phenyl
phosphate.
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
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
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 < 0.001 mg/L
ECOSARvl.ll
Study was conducted using the
commercial mixture Kronitex 200
(major components: triphenyl
phosphate and 2-isopropylphenyl
diphenyl phosphate).
Study was conducted using the
commercial mixture Phosflex 3 IP
(major components: triphenyl
phosphate and 2-isopropylphenyl
diphenyl phosphate).
Estimations for triisopropyl phenyl
7-315
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
(Estimated)
ECOSAR: Esters
Daphnid ChV = 0.004 mg/L
(Estimated)
ECOSAR: Esters
ECOSAR v 1.11
Daphnid ChV = 0.05mg/L
(Estimated)
ECOSAR: Esters
ECOSAR v 1.11
phosphate;
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
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.
Estimations for diisopropyl phenyl
phosphate;
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
Estimations for monoisopropyl
phenyl phosphate.
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
Green Algae ChV
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
Adequate primary source. Study
was conducted using commercial
mixture Phosflex 3 IP (major
components triphenyl phosphate
and 2-isopropylphenyl diphenyl
phosphate).
7-316
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
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 ChV = 0.002 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Green algae ChV = 0.009 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Green algae ChV = 0.05 mg/L
ECOSARvl.ll
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;
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
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.
Estimations for diisopropyl phenyl
phosphate.
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
The estimated effect exceeds the
water solubility by lOx. NES are
predicted for these endpoints.
Estimations for monoisopropyl
7-317
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
(Estimated)
ECOSAR: Esters
REFERENCE
DATA QUALITY
phenyl phosphate.
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
The effect level exceeds the water
solubility of 0.027 mg/L, but not
by lOx as required to be considered
NES by ECOSAR.
ENVIRONMENTAL FATE
Transport
Henry's Law Constant (atm-
m3/mole)
Level III fugacity models incorporating available physical and chemical property data indicate that at
steady state, isopropylated triphenyl phosphate is expected to be found primarily in soil and to a lesser
extent, sediment and water. Isopropylated triphenyl phosphate is expected to have low mobility in soil,
based on estimated Koc values of the components. Leaching through soil to groundwater may occur, though
it is not expected to be an important transport mechanism. Estimated volatilization half-lives indicate that
the components of this mixture will be non-volatile from surface water. Volatilization from dry surface is
also not expected based on its vapor pressure. In the atmosphere, isopropylated triphenyl phosphate is
expected to exist in both the vapor phase and particulate phase, based on its vapor pressure. Vapor phase
isopropylated triphenyl phosphate will be degraded in the atmosphere by reaction with photochemically-
produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 0.7 days. Particulates may
be removed from air by wet or dry deposition.
7.7xlO~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 1 15-86-6) a
possible mixture component (Estimated
EPIv4.11
Mayer et al, 1981; Huckins et al.,
1991
Based on representative structures
for components of the mixture
using the HENRYWIN (v3.20)
Program.
Reported for triphenyl phosphate
(CASRN 115-86-6).
7-318
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
Sediment/Soil
Adsorption/Desorption - Koc
Level III Fugacity Model
DATA
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;EPA, 2005
Anderson et al., 1993
EPIv4.11
DATA QUALITY
Estimated using the representative
structures indicated in the SMILES
section. Cutoff value for
nonmobile compounds.
Reported for triphenyl phosphate
(CASRN 1 15-86-6) a component
of the mixture.
Based on a representative structure
for a component of the mixture, tri-
IPTPP.
7-319
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Persistence
MODERATE: The environmental half-life of the isopropylated triphenyl phosphate is expected to be >16
days based on experiments using commercial mixtures of this alternative. Commercial isopropylated
triphenyl phosphate mixtures passed some ready biodegradable tests, but not all (17.9% degradation in 28
days using a closed bottle test, OECD 301D). Substantial degradation seen over extended time periods
indicates that the substance can be considered to be inherently biodegradable. Ultimate degradation is
expected based on studies with mixed microbial populations from sludge acclimated to the test substance in
a semi-continuous activated sludge system (SCAS), a modified Sturm method experiment and a die-away
test. Some degradation under anaerobic conditions of the triaryl phosphate isomers mixture is also expected
based on an anaerobic sediment study. The isopropylated triphenyl phosphate mixture components will
undergo hydrolysis under alkaline conditions, with estimated hydrolysis half-lives of <13 days at pH 9. The
mixture is expected to be relatively stable to hydrolysis under neutral and acidic conditions, with estimated
half-lives of >2 years at pH 7. Isopropylated triphenyl phosphate mixture components are not expected to
be susceptible to direct photolysis by sunlight, since they do not absorb light at wavelengths >290 nm. The
atmospheric half-live of vapor-phase isopropylated triphenyl phosphate mixture components is estimated to
be <12 hours.
Water
Aerobic Biodegradation
Passes Ready Test: No
Test method: OECD TG 30ID: Closed
Bottle Test
17.9 % after 28 days in activated sludge
from a domestic waste water treatment
plant (Measured)
Passes Ready Test: No
Test method: OECD TG 30IB: CO2
Evolution Test
21% and 13% biodegradation after 28
days using activated sludge from a
sewage treatment plant (with 10.6 mg/L
and 21.5 mg/L, respectively) (Measured)
Passes Ready Test: No
Test method: OECD TG 30IB: CO2
Evolution Test
ECHA, 2013b
Reported in a secondary source for
a commercial product Reofos 65.
IUCLID, 2001 (as cited in
Environment Agency, 2009)
IUCLID, 2001 (as cited in
Environment Agency, 2009)
Reported in a secondary source for
a commercial product, Reofos 120.
Reported in a secondary source for
a commercial product Reolube
HYD46.
7-320
-------
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: DOC
Die-Away Test
94% degradation after 26 days; the test
protocol was not followed (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
46% ThOD after 28 days (Measured)
Environment Agency, 2009
This study is not sufficient to fully
characterize the aerobic
biodegradation under
environmental conditions.
Passes Ready Test: Yes
Test method: OECD TG 301 A: DOC
Die-Away Test
86% degradation was seen after 31 days
IUCLID, 2001 (as cited in
Environment Agency, 2009)
Reported in a secondary source for
a commercial product Reolube
HYD 46. Results should be
considered with caution as the Die-
Away test is not currently
7-321
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
using an activated sludge inoculum and
a test concentration of 32.6 mg/L.
(Measured)
recommended for substances of
low water solubility (below 100
mg/L).
Study results: 80%/28 days
Test method: Die-Away
Using settled Mississippi River water; 1
mg/L commercial product Kronitex
1000 (Measured)
Saeger et al., 1979 (as cited in
Environment Agency, 2009)
Reported in a secondary source
using a commercial product,
Kronitex 1000.
Study results: Inherently
Test method: Other
Inherently biodegradable based on study
based on the modified Sturm method
using acclimated bacteria; CO2 evolved
from the test substance (expressed as a
percentage of the maximum theoretical
amount): 9% after seven days, 49% after
28 days and 62% after 48 days
(Measured)
Saeger et al., 1979 (as cited in
Environment Agency, 2009)
Reported in a secondary source
using a commercial product,
Kronitex 1000.
Study results: 49%
Test method: Other
An equilibrium removal rate of 49 ± 8%
at 3 mg/L and 35 ± 11% at 13 mg/L
using a semi-continuous activated
sludge (SCAS) unit (Measured)
Saeger et al., 1979 (as cited in
Environment Agency, 2009)
Reported in a secondary source
using a commercial product,
Kronitex 1000.
Volatilization Half-life for
Model River
177 days (Estimated)
EPIv4.11
Based on a representative structure
for a component of the mixture,
with three isopropyl substituent
groups.
>1 year (Estimated)
EPIv4.11
Based on a representative structure
for a component of the mixture,
7-322
-------
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 7.1%-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
Muir et al., 1989
EPIv4.11
Heitkamp et al., 1984 (as cited in
Environment Agency, 2009)
Heitkamp et al., 1984 (as cited in
Environment Agency, 2009)
DATA QUALITY
with one isopropyl substituent
group.
Based on a representative structure
for a component of the mixture,
with three isopropyl substituent
groups.
Based on a representative structure
for a component of the mixture,
with one isopropyl substituent
group.
Sfonguideline study for a
component, TPP (CASRN 115-86-
6) of the mixture.
No data located.
Reported in a secondary source for
a component of the mixture,
isopropylphenyl diphenyl
phosphate.
Reported in a secondary source.
7-323
-------
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%/18.5daysatpH7,25°C
50%/43daysatpH7, 15°C;
50%/16.5 days at pH 9, 15°C;
50%/6.1daysatpH9,25°C;
stable at pH 4
In accordance with the OECD 111 using
GC/MS analysis (Measured)
Samples of Kronitex 100 and Kronitex
50 were refluxed under basic conditions
for several hours
The solutions were acidified and
REFERENCE
EPIv4.11
EPIv4.11
Professional judgment; Mill, 2000
EPIv4.11
EPIv4.11
ECHA, 2013b
Nobileetal, 1980
DATA QUALITY
Based on a representative structure,
monoisopropylated triphenyl
phosphate isomer.
Based on a representative structure,
triisopropylated triphenyl
phosphate isomer.
The components of this mixture do
not contain functional groups that
would be expected to absorb light
of wavelengths >290 nm.
Based on a representative structure,
with three isopropyl substituent
groups.
Based on a representative structure,
with one isopropyl substituent
groups.
Guideline study reported in a
secondary source based on a
commercial product, Reofos 65 .
Nonguideline study reported for
commercial products.
7-324
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
extracted; hydrolysis products (phenol,
2-isopropyl phenol, 4-isopropyl phenol,
3-isopropylphenol and diisopropyl
phenols) were identified by infrared
spectrometry (IR), gas liquid
chromatograph-mass spectrometry
(GLC-MS) and nuclear magnetic
resonance (NMR) (Measured)
Environmental Half-life
120 days in Soil (Estimated)
EPIv4.11;PBT Profiler
Half-life estimated for the
predominant compartment, as
determined by EPI and the PBT
Profiler methodology; using a
representative structure for a
component of the mixture, with
three isopropyl substituent groups.
Bioaccumulation
HIGH: The bioaccumulation designation is based on the estimated BAF values for the isopropylated
triphenyl phosphate compounds; these values are >1,000. Measured BCF of <9,250, are available for a
commercial mixture containing isopropylated triphenyl phosphate. However, there is lower confidence in
the experimental BCF values because they are not consistent with the limited water solubility of this
chemical, and because the studies were performed on a mixture of unquantified components. Toxicokinetic
and fish metabolism studies determined that in some species, isopropylated phenyl phosphate is likely to be
bioavailable and undergo metabolism and elimination. Additional, lower BCF values were reported from
studies with the isomer isopropylphenyl diphenyl phosphate that would result in a Moderate designation.
The BAF was used preferentially as the removal rate of isopropylated triphenyl phosphates in some species
of fish may not compete with the rate of uptake.
Fish BCF
<9,250 Pimephalespromelas flow-
through system; fish were exposed to
five concentrations of the test substance,
samples taken at 30, 60 and 90 days of
exposure and analyzed for both
isopropylphenyl diphenyl phosphates
and triphenyl phosphate (Measured)
495 Pimephales promelas flow-through
Cleveland et al, 1986 (as cited in
Environment Agency, 2009)
Environment Agency, 2009
Reported in a secondary source for
commercial products, Kronitex 200
andPhosflexSlP.
Adequate, nonguideline study
7-325
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Other BCF
BAF
system; using 14C-labelled
isopropylphenyl diphenyl phosphate, at
a concentration of 2.5 (ig/1 for 28 days
(Measured)
440-550; in fathead minnows using
deuterium and 14C labeled 2-
isopropyldiphenyl phosphate
(Measured)
Huckins and Petty, 1983
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 (TBB A) 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
using labeled components of the
mixture.
Adequate, nonguideline study
using labeled components of the
mixture.
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,
,vith three isopropyl substituent
groups.
No data located.
BAFs were not calculated. Non
guideline study indicates that
absorption of TBB can occur in
rats through oral exposure; the test
substance identified as FM550 is a
mixture made up of TBB, TBPH
(CASRN 26040-51-7), IPTPP
(CASRN 68937-41-7) and TPP
(CASRN 115-86-6).
7-326
-------
Isopropylated triphenyl phosphate CASRN 68937-41-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Metabolism in Fish
320,000 (Estimated)
EPIv4.11
Based on a representative structure
for a component of the mixture,
with three isopropyl substituent
groups.
69,000 (Estimated)
EPIv4.11
Based on a representative structure
for a component of the mixture,
with two isopropyl substituent
groups.
700 (Estimated)
EPIv4.11
Based on a representative structure
for a component of the mixture,
with one isopropyl substituent
group.
1,300-1,900 for Trixylenyl phosphate;
400 for Tricresyl phosphate
Based on whole fish wet-weight,
equilibrium in the fish was not reached
for these compounds (Estimated by
analogy)
Bengtsson et al., 1986
Non-guideline study using
commercial mixtures.
Fathead minnows were exposed to 14C-
2-isopropylphenyl diphenyl phosphate
for 28 days followed by a 14 day
elimination phase
Labeled diphenyl phosphate was
identified as a major metabolite in whole
body fish samples; additional 14C-
residues were associated with lipid and
protein materials (Measured)
Huckins and Petty, 1983 (as cited in
Environment Agency, 2009)
Adequate, nonguideline study.
The major route of metabolism of
isopropylphenyl diphenyl phosphate in
rainbow trout (Oncorhynchus mykiss) is
O-dearylation to yield diphenyl
phosphate; the diphenyl phosphate is
then eliminated either as the compound
Muir, 1984 (as cited in Environment
Agency, 2009); Boethling and
Cooper, 1985
Adequate, nonguideline study.
7-327
-------
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).
7-328
-------
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 tri-alkyl/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-
inventorv.echa.europa.eu/SummarvOfClassAndLabelling.aspx?SubstanceID=18683&HarmOnly=no?fc=true&lang=en.
ECF£A (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 DISS-9c7ba203-61eO-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.
Environment Agency (2009) Environmental risk evaluation report: Isopropylated triphenyl phosphate (CAS nos. 28108-99-8, 26967-76-0 &
68937-41-7). UK.
EPA (1999) Determining the adequacy of existing data. Washington, DC: U.S. Environmental Protection
Agency, http://www.epa.gov/hpv/pubs/general/datadeqfn.pdf
7-329
-------
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
Sci Technol 18(6):434-439.
Huckins JN, Petty JD (1983) Dynamics of isopropylphenyldiphenyl phosphate in fathead minnows (Pimephales promelas). Chemosphere
12(6):799-808.
Huckins JN, Fairchild JF, Boyle TP (1991) Role of exposure mode in the bioavailability of triphenyl phosphate to aquatic organisms. Arch
Environ Contam Toxicol 21:481-485.
IUCLID (2000) Phenol, isopropylated, phosphate. IUCLID data set.
IUCLID (2001) Isopropylated triphenyl phosphate. IUCLID data set. Great Lakes Chemical Corp.
7-330
-------
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 Encyclopedia of Chemical Technology. Wiley-Interscience, 484-510.
7-331
-------
Wightman RH, Malaiyandi M (1983) Physical properties of some synthetic trialkyl/aryl phosphates commonly found in environmental samples.
Environ Sci Technol 17(5):256-261.
Yang SM, Thieme RA, Von Meyerinck L, et al. (1990) Identification of cyclic metabolites of isopropylated phenyl phosphates in rabbit bile.
Biomed Environ Mass Spectrom 19(9): 5 73-5 76.
7-332
-------
Melamine
Screening Level Toxicology Hazard Summary
This table contains hazard information for each chemical; evaluation of risk considers both hazard and exposure. Variations in end-of-life processes or degradation and combustion
by-products are discussed in the report but not addressed directly in the hazard profiles. The caveats listed below must be taken into account when interpreting the information in the
table.
VL = Very Low hazard L = Low hazard = Moderate hazard H = High hazard VH = Very High hazard - Endpoints in colored text (VL, L, M, H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].
Chemical
CASRN
Human Health Effects
>>
+*
jy
'M
o
H
O
"3
u
^
^
"y
g
M
O
"y
La
SS
u
.-a"
o
"o
e
OJ
O
OJ
>
1
•a
o
Z
a.
0)
13
g
S
a.
_o
"3
o
0
I
2™
S
0)
Z
x
o
0
•a
"S
0)
S.
0)
X
a
_o
-*^
sS
.S
-^-1
*5«
gj
a>
vi
S3
^£
vi
t?.§
o +s
•^ 55
II
&• "S
5« fl
a> g
M cc
e
_o
-*^
sS
-*^
•c
HH
a>
w
0
'•i
+^
HH
13
fl
2
0)
a
Aquatic
Toxicity
-£^
s
u
^
'3
^3
u
Environmental
Fate
0)
u
a
S
•PN
s2
4>
0.
a
o
'S
C5
"3
g
3
S
Melamine
1 108-78-1 |M| I I H I M I Z, I |L| I L I VL I L I L I \
7-333
-------
H2N
N
H2N
CASRN: 108-78-1
MW: 126.13
MF: C3H6N6
Physical Forms: Solid
Neat: Solid
Use: Flame retardant
SMILES: nlc(N)nc(N)ncl(N)
Synonyms: l,3,5-triazine-2,4,6-triamine; Cyanuramide; Cyanurotriamide; Cymel, Isomelamine; Melamine; 2,4,6-triamino-S-triazine; S-Triazinetriamine; 1,3,5-
triazine-2,4,6(lH,3H,5H)-triimine
Chemical Considerations: This is a discrete organic chemical with a MW below 1,000. EPI v4.11 was used to estimate physical/chemical and environmental fate
values in the absence of experimental data. Measured values from experimental studies were incorporated into the estimations.
Polymeric: No
Oligomeric: Not applicable
Metabolites, Degradates and Transformation Products: Hydrolysis products: ammeline, ammelide and cyanuric acid; Metabolites: cyanuric acid; Pyrolysis:
ammonia, melem, melone (OECD-SIDS, 1998; Crews et al, 2006; Liu et al., 2010; Zheng et al., 2013).
Analog: None
Endpoint(s) using analog values: Not applicable
Analog Structure: Not applicable
Structural Alerts: Substituted triazines, aquatic toxicity; toxicity to the respiratory system, basic amines; systemic effects, amine groups; potential nephrotoxins,
amines; genetic toxicity, aromatic amines; developmental toxicity, aromatic amines (EPA, 2010, 2012).
Risk Phrases: None identified (ESIS, 2012).
Hazard and Risk Assessments: Melamine was assessed under the Screening information data set (SIDS) for HPV chemicals (OECD-SIDS, 1998).
7-334
-------
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)
354
Decomposes at >280°C forming
ammonia (Measured)
>280 Decomposes
Sublimes; Heat of sublimation: -121
kJ/mol at 25 °C (Measured)
3.59xlO-10 at 20°C (Extrapolated)
3.52xlO-10at20°C
Reported as 4.7xlO"8 Pa at 20°C;
Dynamic method with N2 or NH3
(Extrapolated)
3,480 (Measured)
using OECD 105
OECD-SIDS, 1998; ECHA, 2013
ECHA, 2013
PhysProp, 2012
OECD-SIDS, 1998
OECD-SIDS, 1998; ECHA, 2013
PhysProp, 2012
OECD-SIDS, 1998; ECHA, 2013
ECHA, 2013
This substance sublimes
according to results reported in
secondary source.
Guideline study reported in
secondary source.
Reported in a secondary source.
Reported in a secondary source.
This substance sublimes
according to results reported in
secondary source. Also indicated
in the melting point entry above.
Consistent with other reported
extrapolated values.
Nonguideline study reported in
secondary source.
Guideline study reported in a
secondary source.
7-335
-------
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
ECHA, 2013
PhysProp, 2012
OECD-SIDS, 1998
ECHA, 2013
OECD-SIDS, 1998
OECD-SIDS, 1998
DATA QUALITY
Reported in a secondary source.
Reported in a secondary source.
Guideline study reported in a
secondary source.
Guideline study reported in a
secondary source.
Reported in secondary source.
Reported in a secondary source.
Reported in a secondary source;
study details not provided.
Guideline study reported in a
secondary source.
Reported in a secondary source.
7-336
-------
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: 1 00 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
ECHA, 2013
OECD-SIDS, 1998
ECHA, 2013
Baynes et al., 2008
Crews et al., 2006
OECD-SIDS, 1998
DATA QUALITY
Supporting information provided.
Reported in a secondary source.
Approximate value reported in a
secondary source. No study
details provided.
Guideline study reported in a
secondary source.
Reported from a nonguideline
study.
Study details were not available.
Supporting information provided
in a secondary source.
7-337
-------
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
DATA
Neutral at pH values of 6 to 13;
Cation formation at the triazine ring
nitrogen at pH values of 1 to 4
(Measured)
5 (Measured)
REFERENCE
Weber, 1970; HSDB, 2008
DATA QUALITY
Reported in a secondary source.
7-338
-------
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 (-6-1 mg in <2 ml water) on
GD 17. Melamine was also
administered to neonates at postnatal
day 14 ((-0.3-0. 6mg in <0.2 mL in
Liu etal., 2010
Chuetal., 2010
No data located.
Adequate, primary source
Adequate primary source
7-339
-------
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Other
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.
ECHA, 2013
Study details reported in a
secondary source.
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.
Mastetal., 1983
Adequate, non-guideline study.
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.
Baynes et al, 2008
Adequate primary source
Placentas from mothers following
caesarean section or normal delivery
were perfused with 0 mM or 1 mM
melamine, or 10 mM melamine with
Partanen et al., 2012
Adequate, primary study
7-340
-------
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 LD5o = 3,160 mg/kg (male), 3,850
mg/kg (female)
Rat LD50 = 3,161 mg/kg (male), 3,828
mg/kg (female)
Rat LD50 >6,400 mg/kg
Mouse LD50 = 3,296 mg/kg (male),
7,0 14 mg/kg (female)
Mouse LD50 = 4,550 mg/kg
LD50 ~ 4,800 mg/kg
Rabbit LD50 >1,000 mg/kg
RatLC50 = 3.248mg/L
Trochimowicz et al., 2001
NTP, 1983; Melnick et al., 1984
BASF, 1969
NTP, 1983; Melnick et al., 1984
American Cyanamid Company,
1955; May, 1979; Trochimowicz et
al., 2001
Hoechst, 1963
Unknown, 1990; ECHA, 2013
Ubaidullajev, 1993
Sufficient study details were not
reported.
Sufficient study details reported.
Sufficient study details were not
available.
Sufficient study details reported.
Sufficient study details were not
available. Reported in secondary
sources.
Sufficient study details were not
available.
Sufficient study details were not
available. Study was not
conducted according to any
specific guideline; insufficient
description of the method.
The study details, if present, were
not translated into English.
7-341
-------
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Rat inhalation 4-hour LC50 >5.19
mg/L (nose only)
ECHA, 2013
Adequate study reported in a
secondary source. Study was
conducted according to OECD
Guideline 403 and GLP.
Potential for toxicity to the respiratory
system based on a structural alert for
basic amines.
Professional judgment
Estimated based on a structural
alert for basic amines and
professional judgment.
Carcinogenicity
MODERATE: The carcinogenicity hazard potential for melamine is based on evidence that oral
exposure to melamine causes cancer in experimental animals. However, there is no evidence for
carcinogenicity to humans. In addition, OncoLogic estimated a marginal concern that is consistent with
DfE Moderate hazard criteria. Tumor formation in animals appeared to be due to mechanical irritation
by bladder calculi/stones. IARC classifies melamine as Group 3: not classifiable as to its carcinogenicity to
humans.
OncoLogic Results
Marginal
Carcinogenicity (Rat and
Mouse)
Group 3: melamine is not classifiable
as to its carcinogenicity to humans;
there is inadequate evidence in humans
for the carcinogenicity of melamine,
and there is sufficient evidence in
experimental animals for the
carcinogenicity of melamine under
conditions in which it produces
bladder calculi.
Significant formation of transitional
cell carcinomas in the urinary bladder
of dosed male rats and significant
chronic inflammation in the kidney of
dosed female rats were observed
following exposure in the feed for up
to 103 weeks. Carcinoma formation
was significantly correlated with the
incidence of bladder stones. A
transitional-cell papilloma was
OncoLogic, 2005
IARC, 1999
NTP, 1983; Huff, 1984; Melnick et
al, 1984
IARC classification statement.
Sufficient study details reported.
7-342
-------
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
observed in the urinary bladder of a
single high dose male rat, and
compound related lesions were
observed in the urinary tract of dosed
animals. Based on the mechanical
nature of tumor formation, FDA and
EPA considered melamine
noncarcinogenic.
Increased incidence of acute and
chronic inflammation and epithelial
hyperplasia of the urinary bladder was
observed in male mice following oral
(feed) exposure for up to 103 weeks.
Bladder stones and compound related
lesions were observed in the urinary
tract of test animals. There was no
evidence of bladder tumor
development. Melamine was not
considered carcinogenic.
NTP, 1983; Melnick et al., 1984
Sufficient study details reported.
Melamine-induced proliferative
lesions of the rat urinary tract were
directly due to the irritant stimulation
of calculi, and not to molecular
interactions between melamine or its
metabolites with the bladder
epithelium.
Okumura et al., 1999
Sufficient study details reported.
Water intake, used as an index of
urinary output, was increased by NaCl
treatment. Calculus formation resulting
from melamine administration was
suppressed dose-dependently by the
simultaneous NaCl treatment. The
main constituents of calculi were
Ogasawara et al., 1995
Sufficient study details reported.
7-343
-------
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
melamine and uric acid (total contents
61.1-81.2%). The results indicate that
melamine-induced proliferative lesions
of the urinary tract of rats were
directly due to the irritation induced-
stimulation of calculi, and not
molecular interactions between
melamine itself or its metabolites with
the bladder epithelium.
Melamine: As an initiator, melamine
caused no significant increase in
papillomas per mouse when compared
to controls.
Perrella and Boutwell, 1983
Sufficient study details reported;
non-guideline study.
Diffuse papillary hyperplasia of the
bladder epithelium and bladder calculi
were observed in all melamine treated
rats. Elevated spermidine/spermine
Nl-acetyltransferase (SAT) activity
following melamine treatment was
considered to be an indicator of cell
proliferation.
Matsui-Yuasi et al., 1992
Sufficient study details reported;
non-guideline study.
Decreased antitumor activity was
correlated with increasing
demethylation; melamine was
considered inactive as an antitumor
drug.
Rutty and Connors, 1977
Sufficient study details were not
available.
In an in vitro cytotoxicity study in
cultured ADJ/PC6 plasmacytoma
ascites tumor cells the ID50 (median
ineffective dose) was 470 (ig/mL after
72 hours of treatment.
Rutty and Abel, 1980
Sufficient study details were not
available.
7-344
-------
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
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 lymphomatest:
Negative with and without liver
activation
Haworth et al., 1983; NCI/NTP,
2007
Seiler, 1973
Lusbyetal., 1979
Mastetal., 1982b
McGregor et al., 1988
Sufficient study details reported
Sufficient study details were not
available.
Sufficient study details were not
available.
Sufficient study details were not
available.
Sufficient study details reported.
7-345
-------
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
Gene Mutation in vivo
Chromosomal Aberrations in
vitro
Chromosomal Aberrations in
vivo
DATA
CHO/HGPRT forward mutation assay:
Negative with and without liver
activation
In vitro chromosomal aberrations test:
Negative in CHO with and without
liver activation
In vitro sister chromatid exchange
assay: Negative in CHO with and
without liver activation
In vitro sister chromatid exchange
assay: Negative in CHO with and
without liver activation
In vivo mouse micronucleus test: The
initial test gave a positive trend (P =
0.003) for chromosomal damage;
however, both peripheral blood smears
and the repeat bone marrow test were
negative. The overall conclusion was
that melamine does not induce
chromosomal damage.
In vivo mouse micronucleus test:
Negative without activation
In vivo chromosome aberrations test in
mice: Positive
In vivo sister chromatid exchange
assay in mice: Positive
REFERENCE
Mastetal., 1982b
Galloway et al., 1987; NCI/NTP,
2007
Mastetal., 1982b
Galloway et al., 1987; NCI/NTP,
2007
NTP, 1983; Shelby etal., 1993
Mastetal., 1982b
NCI/NTP, 2007
NCI/NTP, 2007
DATA QUALITY
Sufficient study details were not
available.
No data located.
Sufficient study details reported.
Sufficient study details were not
available.
Sufficient study details reported.
Sufficient study details reported.
Sufficient study details were not
available.
Sufficient study details reported.
Sufficient study details reported.
7-346
-------
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% (DI5o) at >300 jiM
Potential for genotoxicity based on a
structural alert for aromatic amines
Sex-linked recessive lethal mutations
were not induced in Drosophila
melanogaster .
Drosophila Muller-5 test: Negative for
mutagenicity
Drosophila melanogaster Sex-linked
recessive lethal: No mutagenic effects
were observed.
In vitro flow cytometric DNA repair
assay: Negative for genotoxic effects
Microscreen assay: Positive for genetic
toxicity in E. coli WP2s
Growth and genotoxic effects to
bacteria (Salmonella typhimurium) and
yeast (Saccharomyces cerevisiae):
Non-mutagenic in S. typhimurium with
REFERENCE
Mirsalis et al, 1983
Heil and Reifferscheid, 1992
Heil and Reifferscheid, 1992
Professional judgment
IARC, 1986; OECD-SIDS, 1998
Rohrborn, 1959
Luers and Rohrborn, 1963
Seldenetal., 1994
Rossman et al., 1991
Sugitaetal., 1991
DATA QUALITY
In vivo and in vitro unscheduled
DNA synthesis (UDS) test: None
of the tested chemicals, including
melamine, were genotoxic
hepatocarcinogens in the in vivo
assay, and melamine was negative
for UDS in the in vitro assay
Non-guideline study.
Sufficient study details were not
available.
Estimated based on a structural
alert for aromatic amines and
professional judgment.
Secondary source; sufficient
study details were not available.
Sufficient study details were not
available.
Sufficient study details were not
available.
Non-guideline study.
Non-guideline study.
Sufficient study details were not
available.
7-347
-------
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
No data located.
No data located.
Adequate, primary study
7-348
-------
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
OECD-SIDS, 1999
DATA QUALITY
Study details, including
administered dose information,
were not provided.
7-349
-------
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
No data located.
No data located.
Limited study details reported in a
secondary source; test material as
cited in study report: Melamine
(mixture of Melamine from
Agrolinz and BASF at a ratio of
1:1); analytical purity: about
100%.
No data located.
7-350
-------
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.
No 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 judgment
No data located.
Estimated based on expert
judgment.
7-351
-------
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Repeated Dose Effects
MODERATE: Based on repeated oral exposure to melamine in rats. Bladder stones were reported at a
dose of 72 mg/kg-day in a 90-day dietary study in rats. In addition, decreased body weight gain and feed
consumption was reported. NOAELs of 167.5 and 140 mg/kg bw-day were reported in 7 day and 14 day
oral studies in rats, respectively. A NOAEL of 0.0005 mg/L was reported in a 4-month inhalation study
in rats based on no general toxic or gonadotoxic symptoms. Nephrotoxicity was noted in a 3-month oral
study in monkeys at 200 mg/kg-day (NOAEL = 60 mg/kg-day). The formation of calculi, hyperactive
regeneration of renal tubular epithelium, tubular cell debris, crystal deposition, bladder ulcers and
bladder stones, epithelial cell atypia, hyperplasia of the urinary bladder, clinical signs, changes in clinical
chemistry, and decreased body weight gain were reported in laboratory animals following repeated oral
doses > 100 mg/kg-day. In addition, there is estimated potential for systemic effects based on a structural
alert for amine groups and an estimated potential for nephrotoxicity based on a structural alert for
amines.
Rat 90-day dietary toxicity study: One
male rat receiving 18,000 ppm and two
males receiving 6,000 ppm died. Mean
body weight gain and feed
consumption were reduced. Stones and
diffuse epithelial hyperplasia in the
urinary bladders were observed in
male rats of all treatment groups. Focal
epithelial hyperplasia was observed in
only 1 male. A second and third 13-
week repeated dose toxicity study was
conducted in rats at a dose range of
750 to 18,000 ppm; bladder stones
were observed at all dose levels. At
18,000 ppm, stones occurred in diets
with and without the addition of
ammonium chloride to drinking water.
NOAEL: Not established
LOAEL: 750 ppm (72 mg/kg-day;
bladder stones ); lowest dose tested
NTP, 1983; Melnick et al., 1984
Sufficient study details reported.
7-352
-------
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
In a 7-day oral study, male and female
F344 rats were fed melamine and
cyanuric acid (co-exposure) in the diet
at concentrations of 0, 7, 23, 69, 229,
or 694 ppm (0, 0.9, 2.8, 8.6, 17.6, or
29.8 mg/kg-day). Rats were also fed
Melamine or cyanuric acid alone at a
concentration of 1388 ppm (167.5
mg/kg-day).
Histopathological alterations
consistent with nephrotoxicity at 229
and 694 ppm (co-exposure); renal
injury as evidenced by alterations in
the expression of KIM-1, TIMP1,
clusterin, osteopontin, and NGAL
genes in kidney tissue. There were no
statistically significant gene expression
changes in rats fed melamine or
cyanuric acid only. Crystals were
present in the renal tubules in 5/12 rats
fed melamine only.
NOAEL: 1388 ppm (167.5 mg/kg-day;
only dose tested)
LOAEL: Not established
Camacho et al, 2011; Jacob et al.
2011
Study details reported in a
primary source. Toxicity was a
result of co-exposure of melamine
and cyanuric acid. No toxicity
was evident in rats fed melamine
in the absence of cyanuric acid;
only one melamine-only dose
tested.
Rat 28-day dietary toxicity study:
Incidence and size of bladder stones
were directly related to the amount of
substance administered. The larger
stones were found to be unchanged
melamine in a matrix of protein, uric
acid and phosphate.
American Cyanamid Company,
1984
Sufficient study details were not
available.
7-353
-------
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Lowest effect dose (LED): 1,500 ppm
(-125 mg/kg-day) in males.
In a 3-month oral study, monkeys were
administered melamine via nasal-
gastric gavage at doses of 0, 60, 200 or
700 mg/kg-day. Effects at 700 mg/kg-
day included turbid and whitish urine,
urine crystals, red blood cell changes,
increased serum alanine
aminotransferase and kidney and/or
liver weights, nephrotoxicity,
pericarditis and increased
hematopoiesis. Nephrotoxicity was
also evident at 200 mg/kg-day.
NOAEL: 60 mg/kg-day
LOAEL: 200 mg/kg-day
(nephrotoxicity)
Early etal., 2013
Study details reported in a
primary source.
Rat 28-day dietary toxicity study:
Clinical signs included a dose-related
increase in pilo-erection, lethargy,
bloody urine spots in the cage and on
the pelage of animals, and
chromodacryorrhea. The incidence of
urinary bladder calculi and urinary
bladder hyperplasia in treated animals
was dose dependent, with a significant
relationship between the calculi and
hyperplasia. Calculi composition
indicated the presence of an organic
matrix containing melamine,
phosphorus, sulfur, potassium, and
chloride. Crystals of dimelamine
RTI, 1983
Sufficient study details reported
7-354
-------
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
monophosphate were identified in the
urine.
NOAEL: 2,000 ppm (240 mg/kg-day),
excluding the observed increase in
water consumption and the incidence
of crystalluria.
LOAEL: 4,000 ppm (475 mg/kg-day)
based on the formation of calculi.
In a 14-day oral study, rats were
administered melamine at doses of 0,
140, 700, and 1,400 mg/kg-day
(lowered to 1,000 mg/kg-day
subsequently due to mortality). A 5-
day study was also conducted with
genomic biomarkers on kidney tissues.
Doses were 0, 350 and 1,050 mg/kg-
day.
Effects (14-day study) at 700 mg/kg-
day included clinical signs of toxicity
(red urine), decreased body weight,
changes in clinical chemistry
parameters (increased serum urea
nitrogen and creatinine), and kidney
effects (renal tubular cell debris,
crystal deposition, and hyperactive
regeneration of renal tubular
epithelium)
Systemic effects from the 5-day study
were similar to the 14-day study.
Significant up-regulation of Kim-1,
Clu, Sppl, A2m, Lcn2, Tcfrsfl2a,
Gpnmb, and CD44 and significant
Early etal., 2013
Study details reported in a
primary source.
7-355
-------
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
down-regulation of Tff3.
NOAEL: 140 mg/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.
7-356
-------
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
DATA
exposure for up to 103 weeks to 2,250
or 4,500 ppm. There was also
increased incidence of bladder stones
in male mice.
NOAEL: Not established
LOAEL: 2,250 ppm in the diet (lowest
concentration tested; hyperplasia of the
urinary bladder, bladder stones in
males)
Rat 24- to 30-month dietary toxicity
study: A dose related trend for dilated
glands in glandular gastric mucosa and
inflammation in non glandular gastric
mucosa was observed. Urinary bladder
calculi formation was not observed.
Rat 30-month dietary toxicity study:
Neither accumulation of calculi nor
any treatment-related urinary bladder
lesions were found.
Rabbit and dog 2 8 -day dietary toxicity
study: no significant rise in the body
temperature of rabbits was noted.
Gross histological examination of the
heart, lung, liver, spleen, thyroid,
pancreas, intestines, kidneys and
bladder did not show pathological
changes. A zone of fat was found in
the inner part of the renal cortex in two
dogs, but also in the kidneys of 3
control dogs.
Dog 1-year dietary toxicity study:
crystalluria started 60 to 90 days into
REFERENCE
Wolkowski, 1983
Mastetal., 1982a
Lipshitz and Stokey, 1945
American Cyanamid Company,
1955
DATA QUALITY
Sufficient study details were not
available.
Sufficient study details were not
available.
Sufficient study details were not
available.
Sufficient study details were not
available.
7-357
-------
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
treatment, and persisted during the
study period. No other effects
attributable to melamine were
observed.
Melamine may cause kidney stone
formation when ingested chronically in
dogs. In addition, pediatric patients
may be at increased risk for stone
formation when melamine is combined
with cyanuric acid in formula.
Skinner etal., 2010
Study details reported in a
primary source.
In a 42-day study, Broiler hens
(20/group) were fed diets containing
melamine only, melamine in
combination with cyanuric acid (CYA)
or CYA only. Group 1: control; group
II: 10 mg/kg MEL and 3.3 mg/kg
CYA; group III: 30 mg/kg MEL and
10 mg/kg CYA; group IV: 100 mg/kg
MEL and 33.3 mg/kg CYA; group V:
100 mg/kg MEL only; group VI: 33.3
mg/kg CYA only.
No clinical signs of toxicity. Melamine
alone had no effect on growth, but co-
administration and CYA alone had
adverse effects. Average daily weight
gain of group II was reduced and food
consumption was decreased in group
III. No pathological changes in the
livers of hens in group II. Swelling of
some hepatic cells and granular
degeneration in hens co-administered
melamine and CYA (severity
increased with dose). Lesions in the
Ding etal., 2012
Study details reported in a
primary source. It appears that
effects from melamine-only
exposures are minimal and that
toxicity is a result of co-
administration with cyanuric acid.
7-358
-------
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
Professional judgment
Professional judgment
DATA QUALITY
Insufficient description of the
study. It is not clear if a vapor,
dust or aerosol was applied. The
study is not considered to be
reliable.
Estimated based on a structural
alert for amine groups and
professional judgment.
Estimated based on a structural
alert for amine groups and
professional judgment.
LOW: Melamine is not a skin sensitizer to guinea pigs.
Non-sensitizing to guinea pigs
Non-sensitizing to guinea pigs
ECHA, 2013
Fasset and Roudabush, 1963;
Trochimowicz et al., 2001
Adequate study reported in a
secondary source. Study was
conducted in accordance with
OECD Guideline 406 and GLP.
Sufficient study details were not
available.
No data located.
No data located.
7-359
-------
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
Eye Irritation
Eye Irritation
Dermal Irritation
Dermal Irritation
Endocrine Activity
DATA
REFERENCE
DATA QUALITY
LOW: Melamine was mildly irritating to rabbit eyes.
Non-irritating to rabbit eyes
Non-irritating to rabbit eyes following
0.5 mL of 10% melamine
Mild irritant to rabbit eyes following
exposure to 30 mg of dry powder
Slightly irritating to rabbit eyes
BASF, 1969
American Cyanamid Company,
1955; Trochimowicz et al, 2001
American Cyanamid Company,
1955; Trochimowicz et al., 2001
Marhold, 1972
Sufficient study details were not
available.
Sufficient study details were not
available.
Sufficient study details were not
available.
Sufficient study details were not
available.
VERY LOW: Melamine was not irritating to rabbit skin.
Not irritating to rabbit skin
Not irritating to rabbit skin
Not irritating to rabbit skin
Not irritating to rabbit skin
Rijcken, 1995
BASF, 1969
American Cyanamid Company,
1955; Trochimowicz et al., 2001
Fasset and Roudabush, 1963;
Trochimowicz et al., 2001
OECD 404 guideline study.
Sufficient study details were not
available.
Sufficient study details were not
available.
Sufficient study details were not
available.
There was limited data located for the endocrine endpoint. Melamine showed no estrogenic activity (no
change in B-galactosidase activity) in an in vitro yeast two-hybrid assay in Saccharomyces cerevisiae Y
190.
Showed no estrogenic activity (no
change in B-galactosidase activity) in
an in vitro yeast two-hybrid assay in
Saccharomyces cerevisiae Y 190.
ECHA, 2011
Reported in a secondary source.
Non-guideline study.
7-360
-------
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
Immunotoxicity
Immune System Effects
DATA
REFERENCE
DATA QUALITY
There was limited data located for the immunotoxicity endpoint. Melamine did not inhibit the
mitogenesis of B- and T- lymphocytes in an in vitro mouse lymphocyte mitogenesis test. It is unclear how
well a mitogenesis test assesses immunotoxicity of chemicals. The available data are not sufficient to
determine the hazard potential for this endpoint.
Did not inhibit the mitogenesis of B-
and T- lymphocytes in an in vitro
mouse lymphocyte mitogenesis test.
ECHA, 2011
Reported in a secondary source.
Unclear how well mitogenesis test
assesses immunotoxicity of
chemicals.
ECOTOXICITY
ECOSAR Class
Acute Aquatic Toxicity
Fish LC50
Melamines
LOW: Based on experimental acute aquatic values > 100 mg/L in fish, daphnia, and algae. Estimated
toxicity values indicate No Effects at Saturation (NES).
Oryzias latipes 48-hour LC50 = 1,000
mg/L
(Experimental)
Freshwater fish (Leuciscus idus
melanotus) 48-hour LC50 >500 mg/L
(Experimental)
Poecilia reticulata 96-hour LC50
>3,000 mg/L
(Experimental)
Freshwater fish (Oncorhynchus
mykiss) 96-hour LC50 >3,000 mg/L
NOEC = 3,000 mg/L
semi-static; 0, 750, 1,500 and 3,000
ppm (nominal)
(Experimental)
Poecilia reticulata 4,400 mg/L dose
lethal to < 10%
(Experimental)
OECD-SIDS, 1999
OECD-SIDS, 1999; ECHA, 2013
OECD-SIDS, 1999; ECHA, 2013
ECHA, 2013
OECD-SIDS, 1999; ECHA, 2013
Study details reported in a
secondary source.
Study details reported in a
secondary source.
Study details reported in a
secondary source.
Adequate study reported in a
secondary source. Study was
conducted in accordance to a
method similar to present
guidelines; non-GLP.
Study details reported in a
secondary source.
7-361
-------
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
Daphnid LC50
DATA
Freshwater fish 96-hour LC50:
> 100 mg/L (ECOSAR class: Anilines,
amino-meta);
> 100 mg/L (ECOSAR class:
Melamines);
> 100 mg/L (ECOSAR class: Neutral
organics)
(Estimated)
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)
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)
Daphnia magna 48-hour LC50:
17 mg/L
REFERENCE
ECOSAR v 1.11
ECHA, 2013
ECHA, 2013
ECOSAR v 1.11
DATA QUALITY
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.
Adequate study reported in a
secondary source. Study was
conducted according to EPA
Office of Pesticide Programs
(OPP) 72-2, EU Method C.2 and
GLP.
Adequate study reported in a
secondary source. Study was
conducted according to EPA OPP
72-2, EU Method C.2 and GLP.
The estimated effect level for the
ECOSAR Neutral organics class
7-362
-------
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 EC s
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);
> 100 mg/L (ECOSAR class:
ECOSAR v 1.11
NES are predicted for these
endpoints.
Narcosis classes (neutral
organics) are provided for
7-363
-------
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Melamines);
> 100 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
LOW: Based on experimental data in fish, daphnia, and algae indicating a Low chronic aquatic toxicity
hazard.
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:
> 10 mg/L (ECOSAR class: Anilines,
amino-meta);
> 10 mg/L (ECOSAR class:
Melamines);
> 10 mg/L (ECOSAR class: Neutral
organics)
(Estimated)
OECD-SIDS, 1999
OECD-SIDS, 1999
ECOSAR v 1.11
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.
Narcosis classes (neutral
organics) are provided for
comparative purposes; DfE
7-364
-------
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
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);
> 10 mg/L (ECOSAR class:
Melamines);
> 10 mg/L (ECOSAR class: Neutral
organics)
(Estimated)
ECOSAR v 1.11
Study details reported in a
secondary source, study details
and test conditions were not
provided.
The toxicity value for the
ECOSAR Melamines class was
estimated through application of
acute-to-chronic ratios per
methods outlined in the ECOSAR
Methodology Document.
Narcosis classes (neutral
organics) are provided for
comparative purposes; DfE
assessment methodology will use
the lowest estimated toxicity
value provided by ECOSAR
classes that have a more specific
mode of action relative to
narcosis.
7-365
-------
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Green Algae ChV
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 ChV:
1.3 mg/L (ECOSAR class: Anilines,
amino-meta);
> 10 mg/L (ECOSAR class:
Melamines);
> 10 mg/L (ECOSAR class: Neutral
organics)
(Estimated)
ECOSAR v 1.11
The toxicity values for the
ECOSAR Anilines, amino-meta
and Melamines classes were
estimated through application of
acute-to-chronic ratios per
methods outlined in the ECOSAR
Methodology Document.
Narcosis classes (neutral
organics) are provided for
comparative purposes; DfE
assessment methodology will use
the lowest estimated toxicity
value provided by ECOSAR
classes that have a more specific
mode of action relative to
narcosis.
7-366
-------
Melamine CASRN 108-78-1
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
Persistence
Water
Aerobic Biodegradation
Level III fugacity models incorporating available physical and chemical property data indicate that at
steady state, melamine is expected to be found primarily in soil and to a lesser extent, water. Melamine is
expected to have high mobility in the soil, based on its calculated K0c- Melamine will not volatilize from
moist soil and water surfaces based on its Henry's Law constant. Volatilization from dry surfaces is not
expected based on its vapor pressure. In the atmosphere, melamine is expected to exist almost entirely in
the particulate phase. Particulates may be removed from air by wet or dry deposition.
<10"8 at 20°C (Estimated)
32 (Estimated)
Air = 0.01%
Water = 25%
Soil = 74.9%
Sediment = 0.1% (Estimated)
EPIv4.11
EPIv4.11
EPIv4.11
Estimated from experimental
water solubility and vapor
pressure.
HIGH: Experimental data indicate melamine undergoes slow degradation under stringent guideline
conditions, although melamine is readily degraded in acclimated treatment systems. Pure culture studies
have shown biodegradation of melamine by enzymatic hydrolytic deamination in less than 10 days.
However, an original MITI test detected less than 30% degradation after 14 days and two separate
guideline OECD 302B studies observed no degradation after 28 days and 16% degradation after 20 days.
The environmental persistence half-life of melamine is therefore expected to be between 60 and 180 days
based on the guideline biodegradation studies, consistent with a High hazard designation. Melamine was
found to hydrolyze in strong alkaline and acidic solutions but hydrolysis is not expected under neutral
conditions. Melamine is not expected to be susceptible to direct photolysis by sunlight. The atmospheric
half-life of vapor-phase melamine is estimated to be 16 days.
Passes Ready Test: No
Test method: Original MITI test
<30% after 14 days (Measured)
Study results: 16%/20 days
Test method: 302B: Inherent - Zahn-
OECD-SIDS, 1998
OECD-SIDS, 1998
Guideline study reported in a
secondary source.
Guideline study reported in a
secondary source.
7-367
-------
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
Volatilization Half-life for
Model River
Volatilization Half-life for
Model Lake
DATA
Wellens/EMPA Test
Elimination of 10% after 14 days; not
inherently degradable (Measured)
Study results: 0%/28 days
Test method: 302B: Inherent - Zahn-
Wellens/EMPA Test
(Measured)
Study results: 14± 10% 11 00 days
Test method: Activated sludge
treatment systems
Local municipal WWTP; 100 day
adaptation; average melamine removal
14±10% with the Modified Ludzack-
Ettinger process and 20±15% with the
continuous stirred tank reactor
(Measured)
Study results: 100%/<10 days
Test method: Other: Pure culture study
Bacterium, Nocardioides sp. strain
ATD6 rapidly degraded melamine and
accumulated cyanuric acid and
ammonium, via the intermediates
ammeline and ammelide. (Measured)
>1 year (Estimated)
>1 year (Estimated)
REFERENCE
OECD-SIDS, 1998
Xuetal.,2013
Takagietal., 2012
EPIv4.11
EPIv4.11
DATA QUALITY
Guideline study reported in a
secondary source.
Melamine degradation was found
to occur in species specific
biodegradation studies.
7-368
-------
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
Soil
Air
Reactivity
Aerobic Biodegradation
Anaerobic Biodegradation
Soil Biodegradation with
Product Identification
Sediment/Water
Biodegradation
Atmospheric Half-life
Photolysis
Hydrolysis
DATA
Study results: 100%/4 days
Test method: Other: Pure culture study
Bacterium, A. citrulli strain B- 12227
rapidly degraded melamine and
accumulated cyanuric acid, ammeline
and ammelide, via the intermediates
ammeline and ammelide. (Measured)
A set of soil bacteria has been
identified whose members rapidly
metabolize melamine as their source of
nitrogen to support growth; these
bacteria contain an enzyme which
hydrolytically deaminate melamine
(Measured)
Not probable (Anaerobic-
methanogenic biodegradation
probability model)
16 days (Estimated)
Melamine hydrolysis proceeds
stepwise, with loss of one to three
amino groups; hydrolysis occurs by
reaction with mineral acid or inorganic
alkali; Hydrolysis products include
ammeline (CASRN 645-92-1),
ammelide (CASRN 645-93-2) and
cyanuric acid (CASRN 108-80-5)
(Measured)
REFERENCE
Shiomi and Ako, 2012
Cook and Hutter, 1981, 1984
EPIv4.11
EPIv4.11
OECD-SIDS, 1998
DATA QUALITY
Melamine degradation was found
to occur in species specific
biodegradation studies.
Melamine degradation was found
to occur in species specific
biodegradation studies.
No data located.
No data located.
No data located.
Reported in a secondary source.
7-369
-------
Melamine CASRN 108-78-1
PROPERTY/ENDPOINT
Environmental Half-life
Bioaccumulation
Fish BCF
Other BCF
BAF
Metabolism in Fish
DATA
Melamine is hydrolyzed in strong
alkaline and acidic solutions.
The rate constants at 100°C:
k(s'1) = 3.8E-6[OH-]
k(s-l)=1.25E10-4[H+].
Hydrolysis products are ammeline,
ammelide and cyanuric acid.
(Measured)
2-3 years in soil (Measured)
75 days (Estimated)
REFERENCE
OECD-SIDS, 1998
OECD-SIDS, 1998
PBT Profiler
DATA QUALITY
Reported in a secondary source.
Study was conducted in the
extreme pH ranges at high
temperatures. This study is not
relevant for environmental
conditions.
Reported in a secondary source.
Half-life estimated for the
predominant compartment (soil),
as determined by EPI
methodology.
LOW: Measured BCF and estimated BAF values are below 100, the Low bioaccumulation designation
criteria.
<3.8 Cyprinus carpi o for 0.2 mg/L
<0. 3 8 for 2 mg/L; according to OECD
305C (Measured)
0.9 (Estimated)
OECD-SIDS, 1998
EPIv4.11
Guideline study reported in a
secondary source.
No data located.
No data located.
ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring
Ecological Biomonitoring
Human Biomonitoring
Melamine has been detected in river water and sediments in Japan (ECHA, 2013).
Melamine has been reported in fish in Japan (ECHA, 2013).
Melamine was not included in the NHANES biomonitoring report (CDC, 2009).
7-370
-------
American Cyanamid Company (1955) Melamine: Acute and chronic toxicity Report 55-21 Unpublished study.
American Cyanamid Company (1958) AERO melamine, in-house publication (As cited in TSCA Section 8(e) Substantial risk notice U.S. EPA,
8EHQ-0192-1995 (1992).
American Cyanamid Company (1984) Summary of company study.
BASF (1969) BASF AG, Department of Toxicology (XIX5), unpublished data (As cited in Melamine OECD SIDS document and melamine
IUCLID document).
Baynes RE, Smith G, Mason SE, et al. (2008) Pharmacokinetics of melamine in pigs following intravenous administration. Food Chem Toxicol
46:1196-1200.
CDC (2009) Fourth national report on human exposure to environmental chemicals. Atlanta, GA: Centers for Disease Control and
Prevention, http://www.cdc.gov/exposurereport/pdf/FourthReport.pdf.
Camacho L, Kelly KP, Beland FA, et al. (2011) Gene expression of biomarkers of nephrotoxicity in F344 rats co-exposed to melamine and
cyanuric acid for seven days. Toxicol Lett 206(2): 166-171.
Chu CY, Chu KO, Chan JY, et al. (2010) Distribution of melamine in rat foetuses and neonates. Toxicol Lett 199(3):398-402.
Cook AM, Hutter R (1981) s-Triazines as nitrogen sources for bacteria. J Agric Food Chem 29:1135-1143.
Cook AM, Hutter R (1984) Deethylsimazine: Bacterial dechlorination, deamination, and complete degradation. J Agric Food Chem 32:581-585.
Crews, GM, Ripperger W, et al. (2006) Melamine and guanamines. Ullmann's Encyclopedia of Industrial Chemistry, Vol 22. New York: John
Wiley & Sons, Inc.
Ding XM, Zhang KY, Wang L, et al. (2012) Toxicity of melamine and cyanuric acid in broilers and residues in tissues. Hum Exp Toxicol
31(2):174-184.
Early RJ, Yu H, Mu XP, et al. (2013) Repeat oral dose toxicity studies of melamine in rats and monkeys. Arch Toxicol 87(3):517-527.
7-371
-------
ECHA (2011) Melamine cyanurate. Registered substances. European Chemicals
Agency. http://apps.echa.europa.eu/registered/data/dossiers/DISS-9eb230bf-9edO-1955-e044-00144f67d031/AGGR-a3a77856-6622-456f-8995-
5483f815f4a4 DISS-9eb230bf-9edO-1955-e044-00144f67d031.html.
ECHA (2013) Melamine. Registered substances. European Chemicals Agency. http://apps.echa.europa.eu/registered/data/dossiers/DISS-
9c8039ea-8496-674c-e044-00144f67d249/AGGR-2f9a90f3-6e35-4292-937a-99dOf4cf998a DISS-9c8039ea-8496-674c-e044-
00144f67d249 .html#AGGR-2f9a90f3 -6e3 5 -4292-93 7a-99dOf4cf998a.
ECOSAR (Ecological Structure Activity Relationship), Version 1.11. Washington, DC: U.S. Environmental Protection
Agency, http://www.epa.gov/oppt/newchems/tools/21ecosar.htm.
EPA (2010) TSCA new chemicals program (NCP) chemical categories. Washington, DC: U.S. Environmental Protection
Agency, http://www.epa.gov/oppt/newchems/pubs/npcchemicalcategories.pdf.
EPA (2012) Using noncancer screening within the SF initiative. Washington, DC: U.S. Environmental Protection
Agency, http://www.epa.gov/oppt/sf/pubs/noncan-screen.htm.
EPI Estimation Programs Interface (EPI) Suite, Version 4.11. Washington, DC: U.S. Environmental Protection
Agency, http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm.
ESIS (2012) European chemical Substances Information System. European Commission, http://esis.jrc.ec.europa.eu/.
Fasset DW, Roudabush RL (1963) Unpublished data (Unpublished data referenced by melamine OECD SIDS document and Trochimowicz,
2001).
Galloway SM, Armstrong MJ, Reuben C, et al. (1987) Chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells:
evaluations of 108 chemicals. Environ Mol Mutagen 10(Suppl 10): 1-175.
HSDB (2008) Melamine. Hazardous Substances Data Bank. National Library of Medicine. http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen7HSDB.
Haworth S, Lawlor T, Mortelmans K, et al. (1983) Salmonella mutagenicity test results for 250 chemicals. Environ Mutagen 1:3-142.
Heil J, Reifferscheid G (1992) Detection of mammalian carcinogens with an immunological DNA synthesis-inhibition test. Carcinogenesis
13(12):2389-2394.
7-372
-------
Hellwig J, Gembrandt C, Hildebrandt B (1996) Prenatal toxicity in Wistar rats after oral administration (diet) Project Number 32R0242/94007.
Hoechst AG (1963) (Cited in melamine IUCLID document). Unveroffentl Unters Bericht 5(7)
Huff JE (1984) Carcinogenesis results on seven amines, two phenols, and one diisocyanate used in plastics and synthetic elastomers. Industrial
hazardous plastics and synthetic elastomers.
IARC (1986) Melamine. IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans vol 39. International Agency for
Research on Cancer World Health Organization, 333-346.
IARC (1999) Melamine. IARC monographs on the evaluation of carcinogenic risks to humans vol 73. International Agency for Research on
Cancer World Health Organization, 329-338.
Jacob CC, Reimschuessel R, Von Tungeln LS, et al. (2011) Dose-response assessment of nephrotoxicity from a 7-day combined exposure to
melamine and cyanuric acid in F344 rats. Toxicol Sci 119(2):391-397.
Lipshitz WL, Stokey E (1945) The mode of action of three diuretics: Melamine, adenine and formoguanamine. J Pharmacol Exp Ther 83:235-249.
Liu G, Li S, Jia J, et al. (2010) Pharmacokinetic study of melamine in rhesus monkey after a single oral administration of atolerable daily intake
dose. Regul Toxicol Pharmacol 56(2): 193-196.
Luers H, Rohrborn G (1963) The mutagenic activity of ethylenimine derivatives with different numbers of reactive groups. Genetic Today 1:64-
65.
Lusby AF, Simmons Z, McGuire PM (1979) Variation in mutagenicity of s-Triazine compounds tested on four salmonella strains. Environ
Mutagen 1:287-290.
Marhold JV (1972) [Sbornik vysledku toxixologickeho vysetreni latek a pripravku (Czechoslovakian).: 153.
Mast RW, Boyson BG, Giesler PJ (1982a) Evaluation of the chronic toxicity of melamine in a 30-month Fischer 344 rat feeding study.
Toxicologist.
Mast RW, Jeffcoat AR, Sadler BM, et al. (1983) Metabolism, disposition and excretion of [14C]melamine in male Fischer 344 rats. Food Chem
Toxicol 21(6):807-810.
7-373
-------
Mast RW, Naismith RW, Friedman MA (1982b) Mouse micronucleus assay of melamine. Environ Mutagen 4:340-341.
Matsui-Yuasa I, Otani S, Yano Y, et al. (1992) Spermidine/spermine Nl-acetyltransferase, a new biochemical marker for epithelial proliferation in
rat bladder. Jpn J Cancer Res 83:1037-1040.
May DR (1979) Cyanamids. In: Kirk-Othmer Encyclopedia of Chemical Technology, Vol 7 New York: John Wiley & Sons, 291-306.
McGregor DB, Brown A, Cattanach P, et al. (1988) Responses of the L5178Y tk+/tk- mouse lymphoma cell forward mutation assay: III. 72 coded
chemicals. Environ Mol Mutagen 12:85-154.
Melnick RL, Boorman GA, Haseman JK, et al. (1984) Urolithiasis and bladder carcinogenicity of melamine in rodents. Toxicol Appl Pharmacol
72(2):292-303.
Mirsalis J, Tyson K, Beck J, et al. (1983) Induction of unscheduled DNA synthesis (UDS) in hepatocytes following in vitro and in vivo treatment.
Environ Mutagen 5(482):344.
NCI/NTP (2007) Carcinogenesis Technical Report Series: Melamine. National Cancer Institute/National Toxicology
Program, http://ntpapps.mehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=l 08-78-1.
NTP (1983) Carcinogenesis Bioassay of Melamine (CAS No. 108-78-1) in F344/N Rats and B6C3F1 Mice (Feed Study). National Toxicology
Program Technical Report Series 245:1-171.
OECD-SIDS (1998) Screening information data set - SIDS - for high production volume chemicals - Volume 7, Parts 1, 2 and 3- Melamine.
United Nations Environment Programme, Case postale 356(1) Organisation for Economic Co-operation and Development, 3.
OECD-SIDS (1999) Full SIDS dossier on the HPV phase 2 chemical melamine. http://www.chem.unep.ch/irptc/sids/OECDSIDS/108781 .pdf.
Ogasawara H, Imaida K, Ishiwata H, et al. (1995) Urinary bladder Carcinogenesis induced by melamine in F344 male rats: correlation between
carcinogenicity and urolith formation. Carcinogenesis 16(11):2773-2777.
Okumura M, Hasegawa R, Shirai T, et al. (1999) Relationship between calculus formation and Carcinogenesis in the urinary bladder of rats
administered the non-genotoxic agents, thymine or melamine. Carcinogenesis 13(6): 1043-1045.
OncoLogic (2005) Version 6.0. U.S. EPA and LogiChem, Inc.
7-374
-------
PBT Profiler Persistent (P), Bioaccumulative (B), and Toxic (T) Chemical (PBT) Profiler, Version 1.301. Washington, DC: U.S. Environmental
Protection Agency, www.pbtprofiler.net.
Partanen H, Vahakangas K, Woo CS, et al. (2012) Transplacental transfer of melamine. Placenta 33(l):60-66.
Perrella FW, Boutwell RK (1983) Triethylenemelamine: An initiator of two-stage carcinogenesis in mouse skin which lacks the potential of a
complete carcinogen. Cancer Lett 21(1):37-41.
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.
RTI (1983) Evaluation of urolithiasis induction by melamine in male weanling Fischer 344 rats. Parts I and II. In-live observations, necropsy, and
histopathology of urinary bladders and analysis of plasma, urine and calculi. Research Triangle Park, NC: Research Triangle Institute.
Rijcken WRP (1995) Primary skin irritation/corrosion study with melamine in the rabbit Confidential NOTOX project 146205 for DSM melamine.
Rohrborn G (1959) Mutation tests with melamine and trimethylolmelamine. Dros Infor Serv 33:156.
Rossman TG, Molina M, Meyer L, et al. (1991) Performance of 133 compounds in the lambda prophage induction endpoint of the microscreen
assay and a comparison with S. typhimurium mutagenicity and rodent carcinogenicity assays. Mutat Res 260:349-367.
Rutty CJ, Abel G (1980) In vitro cytotoxicity of the methylmelamines. Chem Biol Interact 29(2):235-246.
Rutty CJ, Connors TA (1977) In vitro studies with hexamethylmelamine. Biochem Pharmacol 26(24):2385-2391.
Seiler JP (1973) A survey on the mutagenicity of various pesticides. Experientia 29:622-623.
Selden JR, Dolbeare F, Clair JH, et al. (1994) Validation of a flow cytometric in vitro DNA repair (UDS) assay in rat hepatocytes. Mutat Res
315(2):147-167.
Shelby MD, Erexson GL, Hook GJ, et al. (1993) Evaluation of a three-exposure mouse bone marrow micronucleus protocol: Results with 49
chemicals. Environ Mol Mutagen 21:160-179.
Shiomi N, Ako M (2012) Biodegradation of melamine and cyanuric acid by a newly-isolated microbacterium strain. Adv Microbiol 2:303-309.
7-375
-------
Skinner CG, Thomas JD, Osterloh JD (2010) Melamine toxicity. J Med Toxicol 6(l):50-55.
Sugita T, Ishiwata H, Maekawa A (1991) Intestinal absorption and urinary excretion of melamine in male Wistar rats. J Food Hyg Soc Jpn
32(5):439-443.
Takagi K, Fujii K, Yamazaki K, et al. (2012) Biodegradation of melamine and its hydroxyl derivatives by a bacterial consortium containing a
novel Nocardioides species. Appl Microbiol Biotechnol 94:1647-1656.
Trochimowicz HJ, Kennedy GL, Krivanek ND (2001) Alkylpyridines and miscellaneous organic nitrogen compounds. Patty's Toxicology.
Ubaidullajev RU (1993) (In Russian). Gigiena i Sanitariya 58:14-16.
Unknown (1990) Acute toxicity data. J Am Coll Toxicol 1:100.
Weber JB (1970) Mechanisms of absorption of s-triazines by clay colloids and factors affecting plant availability. Res Rev32:93-130.
Wolkowski R (1983) Evaluation of urolithiasis induction by melamine (CAS NO 108-78-1) in male weanling Fischer 344 rats. American
Cyanamid Company. Submitted to the US EPA under TSCA Section 8E.
Xu S, Zhang Y, Sims A, et al. (2013) Fate and toxicity of melamine in activated sludge treatment systems after a long-term sludge adaptation.
Water Res 47(7):2307-2314.
Yin RH, Wang XZ, Bai WL, et al. (2013) The reproductive toxicity of melamine in the absence and presence of cyanuric acid in male mice. Res
VetSci94(3):618-627.
Zheng X, Zhao A, Xie G, et al. (2013) Melamine-induced renal toxicity is mediated by the gut microbiota. Sci Transl Med 5(172): 122.
7-376
-------
Oligomeric ethyl ethylene phosphate
Screening Level Toxicology Hazard Summary
This table contains hazard information for each chemical; evaluation of risk considers both hazard and exposure. Variations in end-of-life processes or degradation and combustion
by-products are discussed in the report but not addressed directly in the hazard profiles. The caveats listed below must be taken into account when interpreting the information in the
table.
VL = Very Low hazard L = Low hazard = Moderate hazard H = High hazard VH = Very High hazard - Endpoints in colored text (VL, L, M, H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].
d This hazard designation would be assigned MODERATE for a potential for lung overloading if >5% of the particles are in the respirable range as a result of dust forming
operations.
Chemical
CASRN
Human Health Effects
£
0)
s
o
'0
S
0
_B
'o
S
ft
u
^
.S
'S
"o
a
3
0)
>•
s
S
2^
S
•a
-*^
a
0)
S
o
"3
P
u
M
0
S
s
S
z
0)
0
P
•a
0)
s.
a
o
1
-*^
OJ
C/5
C/5
^ a
M* O
S 13
rt N
a? fl
S^
a
O
-*^
HH
OJ
*%
a
13
'C
HH
2
0)
P
Aquatic
Toxicity
0)
s
u
u
a
U
Environmental
Fate
0)
0)
2
0)
a.
a
13
s
S
s
u
A
CO
Oligomeric ethyl ethylene phosphate | 184538-58-7 |L|z,|M|z,|M|M|z,d|z,| | |L|z,|l,| VH \ L
7-377
-------
Representative structure
CASRN: 184538-58-7
MW: Product MWN range from 300
to 4,000
MF: (C6H15O4P C2H4O O5P2)n
Physical Forms: Liquid
Neat:
Use: Flame retardant
SMILES: C(COP(=O)(OCC)OCC)OP(=O)(OCC)OCC (Representative structure used for n=l estimations)
The polymeric components with MW > 1,000 oligomers (n>6) are not amenable to SMILES notation.
Synonyms: Phosphoric acid, triethyl ester, polymer with oxirane and phosphorus oxide (P2O5); Oxirane, polymer with phosphorus oxide (P2O5) and triethyl
phosphate; Phosphorus oxide (P2O5), polymer with oxirane and triethyl phosphate; Alkylphosphate oligomer; Oligomeric ethyl ethylene phosphate
Trade names: Fyrol PNX; Fyrol PNX-LE; Modified oligomeric ethyl ethylene phosphate; Exolit 550;
Chemical Considerations: This alternative is a polymer consisting of oligomers with MWs above and below 1,000 daltons according to publicly available patents
and commercial product literature. A typical phosphorus content of 19% was reported from these sources. Residual monomers, unreacted starting material (triethyl
phosphate) and low MW oligomers are expected to be present at a level requiring their assessment. The n>6, oligomers have a MW > 1,000 and are assessed using the
available polymer assessment literature. The n<5 oligomers are those with a MW <1,000 and are assessed with EPI v4.11 and ECOSAR vl. 11 estimates due to an
absence of publically available experimental physical/chemical, environmental fate and aquatic toxicity values (Hardy and Jaffe, 1983; Boethling and Nabholz, 1997;
Akzo Nobel and Wuestenenk, 2005).
Polymeric: Yes
Oligomeric: The oligomers are produced by reacting phosphorus pentoxide with triethyl phosphate to form a polyphosphate ester that is in turn reacted with ethylene
oxide. The repeating phosphate ester units, represented between the brackets where n = 2 to 20 units, although n=500 has been reported in one patent. Both linear and
cross-linked polymers may be formed during polymerization. The polymers may be terminated with either an ethyl or hydroxyl ethyl group (Hardy and Jaffe, 1983;
Akzo Nobel and Wuestenenk, 2005; Professional judgment).
Metabolites, Degradates and Transformation Products: None identified; although biodegradation or hydrolysis pathways may yield diethyl phosphate, ethyl
phosphate, ethanol, phosphate and ethylene glycol (Professional judgment)
Analog: None
Endpoint(s) using analog values: Not applicable
Analog Structure: Not applicable
Structural Alerts: Organophosphates, neurotoxicity (EPA, 2012).
Risk Phrases: Not classified by Annex VI Regulation (EC) No 1272/2008 (ESIS, 2012).
Hazard and Risk Assessments: None identified.
7-378
-------
Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
PHYSICAL/CHEMICAL PROPERTIES
Melting Point (°C)
Boiling Point (°C)
Vapor Pressure (mm Hg)
Water Solubility (mg/L)
Log Kow
>300
forn>l (Estimated)
3.6xl(r6at250C
for n=l
2.1xlO-8forn=2-5
(Estimated)
6 oligomers
(Estimated)
3 3 75 mg/L for n=l
93 3 mg/L for n=2
23 3 mg/L for n=3
1 mg/L for n=6 (Estimated)
Soluble (Measured)
Miscible (Measured)
-0.58
(Measured)
0.42 for n=l
-0.03 for n=2
-0.48 for n=3
-1.33 for n=6
(Estimated)
<-l
EPI v4. 11; Professional
judgment; EPA, 1999
EPIv4.11
Professional judgment; Boethling
andNabholz, 1997
EPIv4.11
ICL, 2010
Submitted confidential study
Submitted confidential study
EPIv4.11
ICL, 2010
^o data located.
Estimate based on representative oligomers where
n=l-5 with MW < 1,000. Also estimated for
oligomers where n>6 with MWs > 1,000. Cutoff
value according to HPV assessment guidance and
cutoff value used for large, high MW solids.
Estimates based on representative oligomers where
n=l-5.
Cutoff value for large, high MW polymers.
Estimates based on representative oligomers where
n=l-6.
Non-quantitative value from a MSDS for the
commercial product Fyrol PNX LE containing 95-
100% pure material.
Non-quantitative value with limited details
reported.
Limited study details provided in a confidential
source.
Estimates based on representative oligomers where
n=l-6.
From a MSDS for the commercial product Fyrol
7-379
-------
Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
PROPERTY/ENDPOINT
Flammability (Flash Point)
Explosivity
Pyrolysis
pH
pKa
DATA
(Measured)
Not flammable (Measured)
Not explosive (Measured)
Not applicable (Estimated)
Not applicable (Estimated)
REFERENCE
ICL, 2010
ICL, 2010
Professional judgment
Professional judgment
DATA QUALITY
PNX LE containing 95-100% pure material.
From a MSDS for the commercial product Fyrol
PNX LE containing 95-100% pure material.
From a MSDS for the commercial product Fyrol
PNX LE containing 95-100% pure material.
No data located.
Does not contain functional groups that are
expected to ionize under environmental conditions.
Does not contain functional groups that are
expected to ionize under environmental conditions.
HUMAN HEALTH EFFECTS
Toxicokinetics
Dermal Absorption in vitro
Absorption,
Distribution,
Metabolism
& Excretion
Oral, Dermal or Inhaled
Other
For low MW components (n < 6), absorption is estimated to be low for all routes based on confidential analogs.
For high MW components, no absorption is expected through the skin and gastrointestinal tract. Poor absorption
is estimated in the lungs because the polymer is dispersible due to its physical chemical properties.
For low MW components (n <
6), absorption is expected to be
low for all routes based on
confidential analogs. For high
MW components, no absorption
is expected through the skin and
gastrointestinal tract. Poor
absorption is expected in the
lungs because the polymer is
dispersible due to its physical
chemical properties.
(Estimated)
Professional judgment
^o data located.
No data located.
Estimated based on analogy to a confidential
analog, physical chemical properties, and
professional judgment.
7-380
-------
Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
PROPERTY/ENDPOINT
Acute Mammalian Toxicity
Acute
Lethality
Oral
Dermal
Inhalation
Carcinogenicity
OncoLogic Results
Carcinogenicity (Rat and
Mouse)
Combined Chronic
Toxicity/Carcinogenicity
Other
DATA
REFERENCE
DATA QUALITY
LOW: Based on oral and dermal LD50 values > 2,000 mg/kg for the polymeric mixture that included LMW
components. No data were located for the inhalation route of exposure.
The higher MW components of this polymer (MW >1,000) are expected to have limited bioavailability and have
low potential for acute toxicity.
Rat oral LD50 = 5,000 mg/kg
Rabbit dermal LD50 > 2,000
mg/kg
Submitted confidential study
Submitted confidential study
Data reported in a confidential study submitted to
EPA for the polymeric mixture that included LMW
components.
Data reported in a confidential study submitted to
EPA for the polymeric mixture that included LMW
components.
^o data located.
LOW: Estimated based on predictions for the polymer containing lower MW components. The risk for
Carcinogenicity is estimated to be low considering that the residual monomers do not contain substituted terminal
double bonds, and reactive-functional-group-bearing side chains. The higher MW components of this polymer
(MW >1,000) are expected to have limited bioavailability and have low potential for Carcinogenicity. No
experimental data were located.
Based on estimates considering
that the residual monomers do
not contain substituted terminal
double bonds; the low MW
species do not contain reactive-
functional-group-bearing side
chains; the polymer is cross-
linked, is not linear, and has a
MW of less than 100,000.
OncoLogic, 2008
Estimated for the polymer containing lower MW
components.
No data located.
^o data located.
^o data located.
7-381
-------
Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
PROPERTY/ENDPOINT
Genotoxicity
Gene Mutation in vitro
Gene Mutation in vivo
Chromosomal Aberrations in
vitro
Chromosomal Aberrations in
vivo
DNA Damage and Repair
Other
Reproductive Effects
Reproduction/Developmental
Toxicity Screen
Combined Repeated Dose
with Reproduction/
Developmental Toxicity
Screen
Reproduction and Fertility
Effects
DATA
REFERENCE
DATA QUALITY
MODERATE: There is uncertain concern for mutagenicity based on the structure, ethyl substituted phosphate.
This substance did not cause gene mutations in bacteria; however, there is uncertainty due to the lack of
experimental data for this endpoint. Complete data requirements for this endpoint are both gene mutation and
chromosomal aberration assays. For instances of incomplete or inadequate mutagenicity/genotoxicity data, a
Low hazard designation cannot be given. The higher MW components of this polymer (MW >1,000) are expected
to have limited bioavailability and have low potential for genotoxicity.
Uncertain concern for
mutagenicity
(Estimated)
Negative for gene mutation in an
Ames test in S.typhimurium and
E. coli.
Professional judgment
Submitted confidential study
Estimated for the low MW component due to ethyl
substituted phosphate.
Data reported in a submitted confidential study.
""Jo data located.
""Jo data located.
""Jo data located.
No data located.
""Jo data located.
LOW: Estimated to have a low potential for reproductive effects based on expert judgment and a lack of
structural alert for this endpoint. No experimental data were located. The higher MW components of this
polymer (MW >1,000) are expected to have limited bioavailability and have low potential for reproductive
toxicity.
""Jo data located.
No data located.
""Jo data located.
7-382
-------
Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
PROPERTY/ENDPOINT
Other
Developmental Effects
Reproduction/ Developmental
Toxicity Screen
Combined Repeated Dose
with Reproduction/
Developmental Toxicity
Screen
Prenatal Development
Postnatal Development
Prenatal and Postnatal
Development
Developmental Neurotoxicity
Other
DATA
There is low potential for
reproductive effects
(Estimated)
REFERENCE
Expert judgment
DATA QUALITY
Estimated based on expert judgment and the lack of
structural alerts.
MODERATE: There were no experimental data for the developmental toxicity endpoint. There were no
structural alerts identified for this endpoint. The higher MW components of this polymer (MW >1,000) are
expected to have limited bioavailability and have low potential for developmental toxicity.
There were also no experimental data located for the developmental neurotoxicity endpoint. There is uncertain
potential for developmental neurotoxicity for this substance based on a structural alert for organophosphates for
the neurotoxicity endpoint; decreased cholinesterase activity in pregnant lab animals has been shown to have a
negative impact on fetal brain development. As a result, an estimated Moderate designation is assigned.
Uncertain concern for
developmental neurotoxicity
based on the potential for
Cholinesterase (ChE) inhibition
in dams that may result in
alterations of fetal
neurodevelopment.
(Estimated)
There is low potential for
developmental effects
(Estimated)
Professional judgment
Expert judgment
^o data located.
^o data located.
No data located.
^o data located.
^o data located.
estimated based on a structural alert for
organophosphates for the neurotoxicity endpoint.
Estimated based on expert judgment and the lack of
structural alerts.
7-383
-------
Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Neurotoxicity
MODERATE: Estimated to have uncertain potential for neurotoxic effects based on a structural alert and
professional judgment. No data were located. In the absence of experimental data, a Moderate hazard
designation is assigned. The higher MW components of this polymer (MW >1,000) are expected to have limited
bioavailability and have low potential for acute toxicity.
Neurotoxicity Screening
Battery (Adult)
data located.
Other
There is potential for neurotoxic
effects based on a structural alert
for organophosphates.
(Estimated)
Professional judgment
Estimated based on a structural alert and
srofessional judgment.
Uncertain concern for
neurotoxicity (Estimated)
Professional judgment
Estimated for the low MW component due to ethyl
substituted phosphate.
Repeated Dose Effects
LOW: Estimated to have low potential for repeated dose effects for the low MW components of this substance
based on expert judgment. This substance may contain polymer components with a MW >1,000. In this case, it is
expected to have limited bioavailability; however, there is the possibility of lung overloading. No experimental
data were located.
Estimated to have low potential
for repeated dose effects for the
low MW components of this
substance.
This substance may contain
polymer components with a MW
> 1,000. In this case, it is
expected to have limited
bioavailability; however, there is
the possibility of lung
overloading.
(Estimated)
Professional judgment
Estimated based on professional judgment.
7-384
-------
Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
PROPERTY/ENDPOINT
Skin Sensitization
Skin Sensitization
Respiratory Sensitization
(Respiratory Sensitization
Eye Irritation
Eye Irritation
Dermal Irritation
Dermal Irritation
Endocrine Activity
Immunotoxicity
Immune System Effects
DATA
REFERENCE
DATA QUALITY
LOW: Estimated to have low potential for skin Sensitization based on expert judgment. There were no
experimental data located.
There is low potential for skin
Sensitization
(Estimated)
Expert judgment
Estimated based on expert judgment.
No data located.
|No data located.
MODERATE: This substance was moderately to slightly irritating to rabbit eyes.
Moderate to slight eye irritation
in rabbits; conjunctival irritation
with redness and discharge;
cleared within 96 hours.
Submitted confidential study
Data reported in a confidential study submitted to
EPA.
LOW: This substance is slightly irritating to rabbit skin with irritation clearing within 3 days.
Slightly irritating to rabbit skin
Mild and transient dermal
irritation in rabbits; cleared
within 3 days.
Submitted confidential study
Submitted confidential study
Data reported in a confidential study submitted to
EPA
Data reported in a confidential study submitted to
EPA.
The potential for endocrine activity for the low MW components of this substance is uncertain.
The higher MW components of this polymer (MW >1,000) are expected to have limited bioavailability and have
low potential for endocrine activity.
fSfo data located.
Estimated to have a low potential for immunotoxic effects based on expert judgment. The higher MW
components of this polymer (MW >1,000) are expected to have limited bioavailability and have low potential for
immunotoxicity.
There is low potential for
immunotoxic effects
(Estimated)
Expert judgment
Estimated based on expert judgment.
7-385
-------
Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
ECOTOXICITY
ECOSAR Class
Acute Aquatic Toxicity
LOW: Based on estimated acute aquatic toxicity values for representative oligomers. Experimental data in fish
also indicate a Low hazard; experimental data was not located for daphnia or algae.
Fish LC50
Danio rerio (Zebrafish) 96-hour
LC5o>l,OOOmg/L
according to OECD 203
(Experimental)
Freshwater fish 96-hour LC50 =
> lOOmg/L
(Estimated)
ECOSAR: Esters
Clariant, 2011
ECOSARvl.ll
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.
Estimate based on representative oligomer n=l-6.
Estimates for the Esters class are provided for
comparative purposes.
See Section 5.5.1.
Daphnid LC50
Daphnia magna 48-hour LC50 >
100 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Estimate based on representative oligomers n=l-6.
Estimates from the Esters class are provided for
comparative purposes.
See Section 5.5.1.
Green Algae EC s
Green algae 96-hour EC50 > 100
mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Estimate based on representative oligomers n=l-6.
Estimates from the Esters class are provided for
comparative purposes.
See Section 5.5.1.
7-386
-------
Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Chronic Aquatic Toxicity
LOW: An estimated chronic aquatic toxicity value derived using an acute-to-chronic ratio (ACR) for the
phosphate ester class and was applied to the available experimental acute data for this chemical and indicated a
Low hazard. ECOSAR estimates for the Esters class also indicated Low hazard. There were no experimental
data available for daphnia or algae.
Fish ChV
Daphnid ChV
Freshwater fish ChV > 41.7
mg/L
(Estimated)
Freshwater fish ChV > 10 mg/L
(Estimated)
ECOSAR: Esters
Daphnia magna ChV = > 10
mg/L
(Estimated)
ECOSAR: Esters
Professional judgment
ECOSARvl.ll
ECOSARvl.ll
An ACR of 24 was derived for the phosphate ester
class based on experimental data for Tris (p-t-
butylphenyl) phosphate (TBPP).
The acute-to-chronic ratio was applied to available
experimental acute fish data for oligomeric ethyl
ethylene phosphate (ChV = >1000 mg/L /24 = 41.7
mg/L)
Estimate based on representative oligomer n=l-6.
Estimates for the Esters class are provided for
comparative purposes.
See Section 5.5.1.
Estimate based on representative oligomer n=l-6.
Estimates for the Esters class are provided for
comparative purposes.
See Section 5.5.1.
Green Algae ChV
Green algae ChV > 10 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Estimate based on representative oligomer n=l-6.
Estimates for the Esters class are provided for
comparative purposes.
See Section 5.5.1.
7-387
-------
Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
ENVIRONMENTAL FATE
Transport
The environmental fate for the lower MW oligomers where n is 1-5, with MW<1,000 are based on the estimated
moderate water solubility and low vapor pressure indicating that the lower MW oligomers are anticipated to
partition predominantly to soil. The higher MW oligomers where n>6, with MW>1,000 are expected to have
negligible water solubility and negligible vapor pressure indicating that the higher MW oligomers are anticipated
to partition predominantly to soil and sediment. The estimated Henry's Law Constant of <10~8 atm-m3/mole
indicates that the lower MW and higher MW oligomers are not expected to volatilize from water to the
atmosphere. The estimated K0c of >11,000 indicates that the lower MW and higher MW oligomers are not
anticipated to migrate through soil to groundwater and also have the potential to adsorb to sediment.
Henry's Law Constant (atm-
m3/mole)
<1(T forn>l (Estimated)
EPIv4.11; Professional
judgment; Boethling and
Nabholz, 1997
Estimates based on representative oligomers where
n=l-5; cutoff values for nonvolatile compounds.
Estimated by the HENRYWIN Group SAR Method
with no measured chemical property inputs.
Estimates based on representative oligomers where
n>6; cutoff value used for large, high MW
polymers. High MW polymers are expected to have
low vapor pressure and are not expected to undergo
volatilization.
Sediment/Soil
Adsorption/Desorption - Koc
ll,000forn=l
>30,000forn>2
(Estimated)
EPI v4.11; Professional judgment
Using MCI Method KOCWIN v2.00, estimate
based on representative oligomers where n=l-5.
Also estimated for oligomers where n>6 with MWs
>1,000 based on professional judgment.
Level III Fugacity Model
Air = 0%
Water = 0.55%
Soil = 52%
Sediment = 47% (Estimated)
EPIv4.11
Estimate based on representative oligomer where
n=6.
Air = 0%
Water =15%
Soil = 80%
Sediment = 4.8% (Estimated)
EPIv4.11
Estimate based on representative oligomer where
n=l.
7-388
-------
Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
PROPERTY/ENDPOINT
Persistence
Water
Soil
Aerobic Biodegradation
Volatilization Half-life for
Model River
Volatilization Half-life for
Model Lake
Aerobic Biodegradation
Anaerobic Biodegradation
DATA
REFERENCE
DATA QUALITY
VERY HIGH: The persistence designation for this polymer is based on its higher MW components (MW >1,000).
The lower MW oligomers (MW <1,000; n < 5) of this polymer are expected to have lower persistence because of
their higher water solubility and increased bioavailability to microorganisms. The higher MW components are
expected to have higher persistence because of their low water solubility and poor bioavailability, indicating that
neither biodegradation nor hydrolysis are expected to be important environmental fate processes. This is
supported by experimental studies with the commercial product. In a ready test using the OECD guideline 301D,
0% biodegradation occurred after 28 days and 2% biodegradation was achieved after 140 days. In a
nonguideline study with limited details, slow hydrolysis was reported for the commercial product at normal
temperatures in acidic and alkaline aqueous solutions. Additionally, this polymer does not contain functional
groups that would be expected to absorb light at environmentally significant wavelengths. Experimental values
for commercial products and evaluation of the higher MW components of this polymer suggest an environmental
half-life of >180 days.
Passes Ready Test: No
Test method: OECD TG 30 ID:
Closed Bottle Test
This commercial product
biodegraded 0% at day 28 and
2% at day 140 (Measured)
Hours-days (Primary Survey
Model)
Weeks (Ultimate Survey Model)
(Estimated)
>1 year for n>l (Estimated)
>1 year for n>l (Estimated)
Probable (Anaerobic-
methanogenic biodegradation
probability model)
ICL, 2010
EPIv4.11
EPIv4.11
EPIv4.11
EPIv4.11
From a MSDS for the commercial product Fyrol
PNX LE containing 95-100% pure material.
Estimate based on representative oligomers where
n=l-2.
Estimate based on representative oligomers where
n=l-6.
Estimate based on representative oligomers where
n=l-6.
^o data located.
Estimate based on representative oligomers where
n=l.
7-389
-------
Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
PROPERTY/ENDPOINT
Air
Reactivity
Soil Biodegradation with
Product Identification
Sediment/Water
Biodegradation
Atmospheric Half-life
Photolysis
Hydrolysis
Environmental Half-life
DATA
0.086 days for n=l
0.05 6 days for n=2
0.042 days for n=3
0.025 days for n=6
(Estimated)
Not a significant fate process
(Estimated)
Hydrolyzes slowly at normal
temperatures in acidic or
alkaline aqueous solutions
(Measured)
50%/340daysatpH5-8
50%/320daysatpH9
for n=6 (Estimated)
50%/3.3yearsatpH5-8
50%/3yearsatpH9
forn=l (Estimated)
> 180 days (Estimated)
30 (Estimated)
REFERENCE
EPIv4.11
Professional judgment; Mill, 2000
ICL, 2010
EPIv4.11
EPIv4.11
Professional judgment
EPIv4.11;PBT Profiler
DATA QUALITY
No data located.
^o data located.
Estimate based on representative oligomers where
n=l-6.
The substance does not contain functional groups
that would be expected to absorb light at
wavelengths >290 nm.
Non-quantitative value from a MSDS for the
commercial product Fyrol PNX LE containing 95-
100% pure material.
Estimate based on representative oligomer where
n=6.
Estimate based on representative oligomer where
n=l.
The n>6 oligomers with a MW >1,000 are not
anticipated to be assimilated by microorganisms.
Therefore, biodegradation is not expected to be an
important removal process. The higher MW
oligomers are also not expected to be removed by
other degradation processes under environmental
conditions because of limited water solubility and
limited partitioning to air.
Half-life estimated for the predominant
compartment (Soil) for the oligomer where n=l, as
7-390
-------
Oligomeric ethyl ethylene phosphate CASRN 184538-58-7
PROPERTY/ENDPOINT
Bioaccumulation
Fish BCF
Other BCF
BAF
Metabolism in Fish
DATA
REFERENCE
DATA QUALITY
determined by EPI and the PBT Profiler
methodology.
LOW: Both the higher MW and lower MW oligomers are estimated to have Low potential for bioaccumulation.
The representative oligomers with lower MW, where n=l-5, have estimated BCF values of 3.2 and estimated BAF
values below 1. The high MW oligomers, where n>6 (MW >1,000) are expected to have limited water solubility,
poor bioavailability and are not expected to be bioaccumulative.
3.2 for n= 1-5 (Estimated)
<100 for the n>6 oligomers
(Estimated)
0.94 for n=l
0.90 for n=2-5
(Estimated)
n>6 oligomers (Estimated)
EPIv4.11
Professional judgment
EPIv4.11
Professional judgment
Estimate based on representative oligomers where
n=l-5.
The substance has a MW >1,000 and is not
anticipated to be taken up by aquatic organisms;
therefore, bioconcentration is not expected.
No data located.
Estimate based on representative oligomers where
n=l-5.
Mo data located for MW > 1,000 oligomers where
n>6.
No data located.
ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring
Ecological Biomonitoring
Human Biomonitoring
No data located.
No data located.
This chemical was not included in the NHANES biomonitoring report (CDC, 2013).
7-391
-------
Akzo Nobel NV, Wuestenenk JA (2005) Flame-retardant soot-containing polyurethane foams.
Boethling RS, Nabholz JV (1997) Environmental assessment of polymers under the U.S. Toxic Substances Control Act. Washington, DC: U.S.
Environmental Protection Agency.
CDC (2013) Fourth national report on human exposure to environmental chemicals, updated tables, March 2013. Centers for Disease Control and
Prevention. http://www.cdc.gov/exposurereport/pdf/FourthReport UpdatedTables Mar2013.pdf Accessed May 10, 2013.
Clariant (2011) Safety data sheet in accordance with regulation (EU) No. 453/2010 Exolit OP 550 (LV).
ECOSAR (Ecological Structure Activity Relationship), Version 1.11. Washington, DC: U.S. Environmental Protection
Agency, http://www.epa.gov/oppt/newchems/tools/21ecosar.htm.
EPA (1999) Determining the adequacy of existing data. Washington, DC: U.S. Environmental Protection
Agency, http://www.epa.gov/hpv/pubs/general/datadeqfn.pdf.
EPA (2012) Using noncancer screening within the SF initiative. Washington, DC: U.S. Environmental Protection
Agency, http://www.epa.gov/oppt/sf/pubs/noncan-screen.htm.
EPI Estimation Programs Interface (EPI) Suite, Version 4.11. Washington, DC: U.S. Environmental Protection
Agency, http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm.
ESIS (2012) European chemical Substances Information System. European Commission, http://esis.jrc.ec.europa.eu/.
Gard DR (2005) Phosphoric acids and phosphates. Kirk-Othmer encyclopedia of chemical technology. Wiley-
Interscience. http://onlinelibrary.wiley.com/book/10.1002/0471238961.
Hardy TA, Jaffe F (1983) Method of preparing oligomeric phosphate esters US 4382042. http://www.google.com/patents/US4382042.
ICL (2010) Material Safety Data Sheet for phosphoric acid, triethyl ester, polymer with oxirane and phosphorus oxide. ICL Industrial Products.
Mill T (2000) Photoreactions in surface waters. In: Boethling R, Mackay D, eds. Handbook of Property Estimation Methods for Chemicals,
Environmental Health Sciences. Boca Raton: Lewis Publishers, 355-381.
OncoLogic (2008) U.S. EPA and LogiChem, Inc., Version 7.0. 2008.
7-392
-------
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.
7-393
-------
Oligomeric phosphonate polyol
Screening Level Toxicology Hazard Summary
This table contains hazard information for each chemical; evaluation of risk considers both hazard and exposure. Variations in end-of-life processes or degradation and combustion
by-products are discussed in the report but not addressed directly in the hazard profiles. The caveats listed below must be taken into account when interpreting the information in the
table.
VL = Very Low hazard L = Low hazard = Moderate hazard H = High hazard VH = Very High hazard - Endpoints in colored text (VL, L, M, H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].
Chemical
CASRN
Human Health Effects
o
H
I
o
'S
ft
U
>>
-*^
[0
o
-*j
o
u
•a
S
I
S
S
a.
_o
OJ
o
S
o
P
a
o
.H
1)
VI
I
a
o
•c
HH
OJ
O
ft
S
1)
P
Aquatic
Toxicity
I
I
U
Environmental
Fate
g
e
o
1
"3
S
1
o
S
Oligomeric phosphonate polyol
363626-50-0
M
M
L \ M
M
L \ L
\ L
VL
M
M
7-394
-------
CASRN: 363626-50-0
MW:<1,000;MWN311
MF: CH5O3P (C2H4O)n (C2H4O)n
Physical Forms: Liquid
Neat: Liquid
Use: Reactive flame retardant
SMILES: C(O)COP(C)(=O)OCCO (Representative structure where n=l; MW = 184)
Synonyms: Poly(oxy-l,2-ethanediyl), a,a'-(methylphosphinylidene)bis[co-hydroxy-; Bis(polyoxyethylene) methylphosphonate; Polyethylene glycol
methylphosphonate
Trade Names: Exolit OP 560
Chemical Considerations: : This alternative is a phosphonate polyol with an average MW of 311 daltons and a typical phosphorus content of 10-13% according to
publicly available product literature Representative monomers and oligomers were assessed with EPI v4.11 and ECOSAR 1.11 estimates due to an absence of publicly
available experimental physical/chemical, environmental fate and aquatic toxicity values.
This alternative is a reactive flame retardant designed for use in the production of polyurethane foams. It is incorporated into a polymer backbone (i.e. polyurethane)
by chemically bonding with raw materials during the polymerization process. Although not all reactive flame retardants have reactive functional groups, all reactive
flame retardants are irreversibly incorporated into a polymer during manufacture to improve flame retardancy. Once a reactive flame retardant is incorporated into a
polymer, it is unlikely to be released. Additive flame retardants, in contrast, are not reacted or chemically bonded with the manufactured product and have potential to
be released under certain conditions (Clariant, 2012; Clariant, 2013).
Polymeric: Yes
Oligomeric: This alternative is a polymer consisting of methylphosphonate substituted with polyethylene glycol.
Metabolites, Degradates and Transformation Products: None identified.
Analog: None
Endpoint(s) using analog values: Not applicable
Analog Structure: Not applicable
Structural Alerts: Organophosphates - neurotoxicity (EPA, 2012).
Risk Phrases: Not classified by Annex VI Regulation (EC) No 1272/2008 (ESIS, 2012).
Hazard and Risk Assessments: None identified.
7-395
-------
Oligomeric phosphonate polyol CASRN 363626-50-0
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
PHYSICAL/CHEMICAL PROPERTIES
Melting Point (°C)
Boiling Point (°C)
Vapor Pressure (mm Hg)
Water Solubility (mg/L)
Log Kow
Flammability (Flash Point)
<-30 (Measured)
>150 at 0.76 mm Hg decomposes;
using differential thermal analysis
(DTA) (Measured)
>300
for n= 1-7 (Estimated)
n=l: 6.9X10'6
n=2: 3.6xlO'8
<10-8at25°Cforn>3-7
(Estimated)
Slow hydrolysis in the presence of
water (Measured)
IxlO6 for n=l-7 (Estimated)
<-2
for n= 1-7
(Estimated)
Flash point: 196°C
According to Cleveland DIN 51376;
open cup (Estimated)
Not flammable (Estimated)
Clariant, 2012
Clariant, 2012
EPIv4.11;EPA, 1999
EPIv4.11;EPA, 1999
Clariant, 20 12; Clariant,
2013
EPIv4.11
EPIv4.11
Clariant, 2012
Professional judgment
Cutoff value reported in a Safety Data Sheet with
no study details.
Cutoff value reported in a Safety Data Sheet with
no study details.
Estimate based on representative structures where
n=l-7. Cutoff value for high boiling point
compounds according to HPV assessment
guidance; decomposition likely occurs before the
boiling point is reached.
Estimates based on representative structures
where n=l-7. Cutoff value for nonvolatile
compounds for n=3-7 oligomers according to
HPV assessment guidance.
No study details and no indication of measured
hydrolysis rates were reported in the Safety Data
Sheet; rates are expected to be pH dependent.
Estimates based on representative structures
where n=l-7. Slow hydrolysis expected in the
presence of water based on Safety Data Sheet.
Estimated values based on representative
structures where n=l-7, indicate high estimated
water solubility.
Reported in a product datasheet.
No experimental data located; based on its use as
a flame retardant.
7-396
-------
Oligomeric phosphonate polyol CASRN 363626-50-0
PROPERTY/ENDPOINT
Explosivity
Pyrolysis
pH
pKa
Particle Size
DATA
Not expected to form explosive
mixtures with air (Estimated)
4.5 at 10 g/L (Estimated)
REFERENCE
Professional judgment
Clariant, 2012; Clariant,
2013
DATA QUALITY
Mo experimental data located; based on its use as
a flame retardant.
^o data located.
Reported in a Safety Data Sheet.
^o data located.
No data located.
HUMAN HEALTH EFFECTS
Toxicokinetics
Dermal Absorption in vitro
Absorption,
Distribution,
Metabolism &
Excretion
Oral, Dermal or Inhaled
Other
There were no experimental data located for any route of exposure. There is potential for absorption from the
lungs and poor absorption is expected from the skin and gastrointestinal tract. This substance may undergo
metabolic oxidation to form a carboxylic acid.
There is potential for absorption via
inhalation. Absorption is expected to
be poor from the skin and
gastrointestinal tract.
The most relevant route of exposure
is inhalation due to potential worker
exposure and because greater
bioavailability is expected via the
inhalation route of exposure
compared to the oral route.
This substance may undergo
metabolic oxidation to form a
carboxylic acid
Professional judgment
No data located.
Based on these physical chemical properties and
professional judgment.
7-397
-------
Oligomeric phosphonate polyol CASRN 363626-50-0
PROPERTY/ENDPOINT
Acute Mammalian Toxicity
Acute Lethality
Oral
Dermal
Inhalation
Carcinogenicity
OncoLogic Results
Carcinogenicity (Rat and
Mouse)
Combined Chronic
Toxicity/Carcinogenicity
Other
Genotoxicity
Gene Mutation in vitro
Gene Mutation in vivo
Chromosomal Aberrations in
vitro
Chromosomal Aberrations in
vivo
DNA Damage and Repair
Other
DATA
REFERENCE
DATA QUALITY
LOW: Based on an oral LD50 value >2,000 mg/kg. No data were located for the dermal and inhalation routes
of exposure.
Rat oral LD50 >2,000 mg/kg
Clariant, 2012; Submitted
confidential study
Limited study details reported in a Safety Data
Sheet and in a submitted confidential study.
No data located.
No data located.
MODERATE: There is uncertainty due to lack of experimental data for this substance; carcinogenic effects
cannot be ruled out.
Structure could not be evaluated by OncoLogic.
""Jo data located.
""Jo data located.
No data located.
MODERATE: There is uncertainty due to the lack of experimental data for this endpoint. This substance was
not a mutagen in bacteria in one study. DfE criteria for this endpoint require both gene mutation and
chromosomal aberration assays. For instances of incomplete or inadequate mutagenicity/genotoxicity data, a
Low hazard designation cannot be assigned.
Negative for gene mutation in an
Ames test.
Clariant, 2012; Submitted
confidential study
Limited study details reported in a Safety Data
Sheet and in a submitted confidential study.
""Jo data located.
""Jo data located.
""Jo data located.
No data located.
No data located.
7-398
-------
Oligomeric phosphonate polyol CASRN 363626-50-0
PROPERTY/ENDPOINT
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
Prenatal Development
Postnatal Development
DATA
REFERENCE
DATA QUALITY
LOW: Estimated based on expert judgment and lack of structural alerts for reproductive toxicity identified
for this substance. No experimental data were located.
There is low potential for
reproductive effects
(Estimated)
Expert judgment
^o data located.
No data located.
No data located.
Estimated based on expert judgment and the lack
of structural alerts.
MODERATE: There were no experimental data for the developmental toxicity endpoint. There were no
structural alerts identified for this endpoint.
There were also no experimental data located for the developmental neurotoxicity endpoint. There is
uncertain potential for developmental neurotoxicity for this substance based on a structural alert for
organophosphates for the neurotoxicity endpoint; decreased cholinesterase activity in pregnant lab animals
has been shown to have a negative impact on fetal brain development. As a result, an estimated Moderate
designation is assigned.
^o data located.
No data located.
No data located.
No data located.
7-399
-------
Oligomeric phosphonate polyol CASRN 363626-50-0
PROPERTY/ENDPOINT
Prenatal and Postnatal
Development
Developmental Neurotoxicity
Other
Neurotoxicity
Neurotoxicity Screening
Battery (Adult)
Other
DATA
Uncertain concern for
developmental neurotoxicity based
on the potential for Cholinesterase
(ChE) inhibition in dams that may
result in alterations of fetal
neurodevelopment.
(Estimated)
There is low potential for
developmental effects (Estimated)
REFERENCE
Professional judgment
Expert judgment
DATA QUALITY
^o data located.
Estimated based on a structural alert for
organophosphates for the neurotoxicity endpoint.
Estimated based on expert judgment and the lack
of structural alerts.
MODERATE: Estimated to have uncertain potential for neurotoxic effects based on a structural alert for
organophosphates and professional judgment. Neurotoxicity is generally decreased for phosphonates
compared to phosphate esters and for structures without good leaving groups. However, there were no
experimental data located, particularly for the most relevant route of exposure (inhalation). Due to the lack of
data, the concern for the structural alert could not be ruled out; therefore, a conservative designation of
Moderate is assigned.
There is potential for neurotoxic
effects based on a structural alert for
organophosphates
(Estimated)
Professional judgment
No data located.
Estimated based on a structural alert for
organophosphates and professional judgment.
Neurotoxicity is generally decreased for
shosphonates when compared to phosphate esters
and for structures that lack "good" leaving
groups; alcohols are not considered "good"
leaving groups.
7-400
-------
Oligomeric phosphonate polyol CASRN 363626-50-0
PROPERTY/ENDPOINT
Repeated Dose Effects
Skin Sensitization
Skin Sensitization
Respiratory Sensitization
[Respiratory Sensitization
Eye Irritation
Eye Irritation
Dermal Irritation
Dermal Irritation
Endocrine Activity
Immunotoxicity
Immune System Effects
DATA
REFERENCE
DATA QUALITY
LOW: Estimated based on expert judgment and lack of structural alerts for repeated dose toxicity identified
for this substance. No experimental data were located.
Estimated to have low potential for
repeated dose effects
(Estimated)
Expert judgment
Estimated based on expert judgment and absence
of structural alerts.
LOW: Estimated based on expert judgment and lack of structural alerts for skin Sensitization identified for
this substance. No experimental data were located.
There is low potential for skin
Sensitization
(Estimated)
Expert judgment
Estimated based on expert judgment and the
absence of structural alerts.
No data located.
|No data located.
LOW: No eye irritation to slight eye irritation was reported.
Slight eye irritation
Not an eye irritant in rabbits.
Professional judgment;
Submitted confidential study
Clariant, 2012
Data reported in a confidential study submitted to
EPA.
Limited study details reported in a Safety Data
Sheet; conducted according to OECD 405 .
VERY LOW: This substance is not a skin irritant.
Not a skin irritant; 4-hour exposure
to rabbits.
Clariant, 2012; Submitted
confidential study
Limited study details reported in a Safety Data
Sheet and a submitted confidential study;
conducted according to OECD 404.
No experimental data were located.
|No data located.
There were no immunotoxicity structural alerts identified for substance. There were no experimental data
located.
There is low potential for
immunotoxic effects
(Estimated)
Expert judgment
Estimated based on expert judgment and the
absence of structural alerts.
7-401
-------
Oligomeric phosphonate polyol CASRN 363626-50-0
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
ECOTOXICITY
ECOSAR Class
Acute Aquatic Toxicity
LOW: Based on estimated acute aquatic toxicity values (Esters class) for representative oligomers (n=l
through n=7). Estimated values were all >100 mg/L. Experimental data in fish also indicated a Low hazard;
experimental data were not located for daphnia or algae.
Fish LC50
Brachydanio rerio (Zebrafish) 96-
hour LC50> 100 mg/L
(Experimental)
Freshwater fish 96-hour LC50 =
n=l-7: > 100 mg/L
(Estimated)
ECOSAR: Esters
Clariant, 2012; Submitted
confidential study
ECOSAR v 1.11
Limited study details reported in a Safety Data
Sheet and in a submitted confidential study;
conducted according to OECD 203.
Estimates based on representative oligomers
where n=l through n = 7.
Estimate for the Esters class was provided for
comparative purposes.
See Section 5.5.1.
Daphnid LC50
Daphnia magna 48-hour LC50
n=l-7: > 100 mg/L
(Estimated)
ECOSAR: Esters
ECOSAR v 1.11
Estimates based on representative oligomers
where n=l through n=7.
Estimate for the Esters class was provided for
comparative purposes.
See Section 5.5.1.
Green Algae EC50
Green algae 96-hour EC50 =
n=l-7: > 100 mg/L
(Estimated)
ECOSAR: Esters
ECOSAR v 1.11
Estimates based on representative oligomers
where n=l through n=7.
Estimate for the Esters class was provided for
comparative purposes.
See Section 5.5.1.
7-402
-------
Oligomeric phosphonate polyol CASRN 363626-50-0
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Chronic Aquatic Toxicity
MODERATE: The estimated chronic aquatic toxicity value derived using an acute-to-chronic ratio (ACR) for
the phosphate esters class and was applied to experimental acute data for this chemical and indicated a
Moderate hazard. Estimated values (Esters class) for all oligomers were >10 mg/L. There is potential concern
based on estimates and the uncertainty due to the lack of experimental data; therefore a Moderate hazard
designation was assigned.
Fish ChV
Freshwater fish ChV > 4.17 mg/L
(Estimated)
Freshwater fish ChV =
n=l-7: > 10 mg/L
(Estimated)
ECOSAR: Esters
Professional judgment
An ACR of 24 was derived for the phosphate
ester class based on experimental data for Tris (p-
t-butylphenyl) phosphate (TBPP).
The acute-to-chronic ratio was applied to
available experimental acute fish data for
oligomeric phosphonate polyol (ChV >100 mg/L
/24 = 4.17mg/L)
ECOSAR v 1.11
Estimates based on representative oligomers
where n=l through n=7.
Estimate for the Esters class was provided for
comparative purposes.
See Section 5.5.1.
compound is not currently well represented in
ECOSAR vl.ll.
7-403
-------
Oligomeric phosphonate polyol CASRN 363626-50-0
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Daphnid ChV
Daphnia magna ChV =
n=l-7: > 10 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Estimates based on representative oligomers
where n=l through n=7.
Estimate for the Esters class was provided for
comparative purposes.
See Section 5.5.1.
judgment indicates that this compound is not
currently well represented in ECOSAR vl. 11
Green Algae ChV
Green algae ChV =
n=l-7:> 10 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Estimates based on representative oligomers
where n=l through n=7.
Estimate for the Esters class was provided for
comparative purposes.
See Section 5.5.1.
ENVIRONMENTAL FATE
Transport
Level III fugacity models incorporating available physical and chemical property data indicate that at steady
state, the polymer is anticipated to be found predominantly in soil, and to a lesser extent, water. The estimated
Henry's Law Constant of <10"8 atm-m3/mole based on an estimated high water solubility and low vapor
pressure indicates that the polymer is not expected to volatilize from water to the atmosphere. The estimated
Koc values in the range of 10-260 indicate that components of the polymer are anticipated to migrate through
soil to groundwater.
7-404
-------
Oligomeric phosphonate polyol CASRN 363626-50-0
PROPERTY/ENDPOINT
Henry's Law Constant (atm-
m3/mole)
Sediment/Soil
Adsorption/Desorption - Koc
Level III Fugacity Model
DATA
<10"8 forn=l-7 (Estimated)
n=l-6: 10
n=7: 260 (Estimated)
Air = 0%
Water = 12%
Soil = 88%
Sediment = 0% (Estimated)
n=7
Air = 0%
Water = 31%
Soil = 69%
Sediment = 0% (Estimated)
n=l
REFERENCE
EPI v4.1 1; Professional
judgment
EPIv4.11
EPIv4.11
EPIv4.11
DATA QUALITY
Estimates based on representative structures
where n=l-7. Cutoff values for non -volatile
compounds. Estimated by the HENRYWIN Bond
SAR Method with no measured chemical
property inputs.
Using MCI Method KOCWIN v 2.00, estimates
based on representative structures where n=l-7.
Estimate based on a representative structure
where n=7.
Estimate based on a representative structure
where n=l.
7-405
-------
Oligomeric phosphonate polyol CASRN 363626-50-0
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Persistence
MODERATE: Biodegradation is expected to be an important mechanism of removal. Phosphonates occur
naturally in the environment where many strains of bacteria have been isolated that metabolize phosphonates.
Although no experimental biodegradation studies were located, estimates using representative components of
the polymer indicate that the lower MW components (where n<2) are expected to have ultimate persistence
with a half-life >16-<60 days, equivalent to a Moderate hazard designation using a conservative approach. The
larger representative oligomers, outside the domain of the biodegradation estimation methods, are anticipated
to behave similarly based on the chemical properties. Hydrolysis was reported in a Safety Data Sheet for this
polymer. The available study details did not provide key information of the rate of hydrolysis and important
test conditions, such as pH. This polymeric mixture does not contain functional groups that would be expected
to absorb light at environmentally significant wavelengths; therefore degradation by direct photolysis is not
expected.
Water
Aerobic Biodegradation
n=l: Days (Primary Survey Model)
Weeks (Ultimate Survey Model)
(Estimated)
n=7: Weeks (Primary Survey
Model)
Months (Ultimate Survey Model)
(Estimated)
In nature, phosphonates are found in
cell membranes of plants and
animals. Bacterial metabolism of
phosphonates with the C-P lyase
enzyme plays a major role in
biodegradation of phosphonates and
the phosphorus cycle in the
environment. The C-P lyase
enzyme, converts alkylphosphonates
to the corresponding alkane and
inorganic phosphate and is found in
many strains of bacteria with broad
specificity. Phosphonates are
considered to be inherently
EPIv4.11
EPIv4.11
The higher MW oligomer where n=7 is outside
the domain of the available estimation methods.
Ghisalba et al., 1987;
Nowack, 2003
Estimate based on a representative structure
where n=l.
Supporting information about the bacterial
biodegradation of this class of compounds.
7-406
-------
Oligomeric phosphonate polyol CASRN 363626-50-0
PROPERTY/ENDPOINT
Soil
Air
Reactivity
Volatilization Half-life for
Model River
Volatilization Half-life for
Model Lake
Aerobic Biodegradation
Anaerobic Biodegradation
Soil Biodegradation with
Product Identification
Sediment/Water
Biodegradation
Atmospheric Half-life
Photolysis
Hydrolysis
Environmental Half-life
DATA
biodegradable. (Estimated)
>1 year for n=l-7 (Estimated)
>1 year for n=l-7 (Estimated)
Probable (Anaerobic-methanogenic
biodegradation probability model)
n=l:0.19
n=2:0.13
n=3:0.10
n=7: 0.05
(Estimated)
Not a significant fate process
(Estimated)
Slow hydrolysis in the presence of
water (Measured)
n=l-7: >1 year at pH 5 to 9
(Estimated)
30 (Estimated)
REFERENCE
EPIv4.11
EPIv4.11
EPIv4.11
EPIv4.11
Professional judgment; Mill,
2000
Clariant, 2012; Clariant,
2013
EPIv4.11
PBT Profiler vl.301;EPI
v4.11
DATA QUALITY
Estimates based on representative structures
where n=l-7.
Estimates based on representative structures
where n=l-7.
No data located.
Estimate based on representative structure where
n=l-2. Estimates indicate anaerobic
aiodegradation is not probable for representative
structures where n=3-7.
No data located.
No data located.
Estimates based on representative structures
where n=l-7. The substance is expected to have
limited volatility; therefore, this is not expected to
3e an important removal pathway.
The substance does not contain functional groups
that would be expected to absorb light at
wavelengths >290 nm.
Mo study details and no indication of hydrolysis
rate were reported in the Safety Data Sheet; rates
are expected to be pH dependent.
Estimates based on representative structures
where for n= 1-7.
Half-life estimated for the predominant
compartment (Soil) for a representative structure
where n>l-2, as determined by EPI and the PBT
7-407
-------
Oligomeric phosphonate polyol CASRN 363626-50-0
PROPERTY/ENDPOINT
Bioaccumulation
Environmental
Fish BCF
Other BCF
BAF
Metabolism in Fish
DATA
>75 days (Estimated)
REFERENCE
PBT Profiler vl.301;EPI
v4.11
DATA QUALITY
Profiler methodology.
The higher MW oligomers where n=3-7, are
outside the domain of the available estimation
methods; the half-life estimated for the
predominant compartment is anticipated to be
shorter than the estimated output.
LOW: Estimated based on BCF values of 3.2 and BAF values of <1 for the representative structures of the
polymeric mixture.
n=l-7: 3. 2 (Estimated)
n=l-7: 0.9 (Estimated)
EPIv4.11
EPIv4.11
Estimates based on representative structures
where n=l-7.
^o data located.
Estimates based on representative structures
where n=l-7.
^o data located.
ENVIRONMENTAL MONITORING AND BIOMONITORING
Monitoring
Ecological Biomonitoring
Human Biomonitoring
No data located.
No data located.
This chemical was not included in the NHANES biomonitoring report. (CDC, 2013).
7-408
-------
CDC (2013) Fourth national report on human exposure to environmental chemicals, updated tables, March 2013.
http://www.cdc.gov/exposurereport/pdf/FourthReport_UpdatedTables_Mar2013.pdf.
Clariant (2012) Safety data sheet in accordance with Regulation (EU) No.453/2010: EXOLIT OP 560. Clariant.
Clariant (2013) Product data sheet - Flame retardants: Exolit OP 560: Phosphorus polyols. Clariant.
http://www.clariant.com/bu/additives/PDS_Additives.nsf/www/DS-OSTS-7SHC6G?open.
ECOSAR Ecological Structure Activity Relationship (ECOSAR). Estimation Programs Interface (EPI) Suite for Windows, Version 1.11.
Washington, DC: EPIWIN/EPISUITE. U.S. Environmental Protection Agency, http://www.epa.gov/oppt/newchems/tools/21ecosar.htm.
EPA (1999) Determining the adequacy of existing data. High Production Volume (HPV) Challenge. Washington, DC: U.S. Environmental
Protection Agency, http://www.epa.gov/hpv/pubs/general/datadeqfn.pdf
EPA (2012) Using noncancer screening within the SF initiative. Washington, DC: U.S. Environmental Protection Agency.
http://www.epa.gov/oppt/sf/pubs/noncan-screen.htm.
EPI Estimation Programs Interface (EPI) Suite, Version 4.11. Washington, DC: EPIWIN/EPISUITE. U.S. Environmental Protection Agency.
http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm.
ESIS (2012) European chemical Substances Information System. European Commission, http://esis.jrc.ec.europa.eu/.
Ghisalba O, Kueenzi M, Ramostombo GM, et al. (1987) Microbial degradation and utilization of selected organophosphorus compounds
Strategies and applications. 41:206-214.
Mill T (2000) Photoreactions in surface waters. In: Boethling R, Mackay D, eds. Handbook of Property Estimation Methods for Chemicals,
Environmental Health Sciences. Boca Raton: Lewis Publishers.:355-381.
PBT Profiler Persistent (P), Bioaccumulative (B), and Toxic (T) Chemical (PBT) Profiler, Version 1.301. Washington, DC: U.S. Environmental
Protection Agency, www.pbtprofiler.net.
7-409
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester
Screening Level Toxicology Hazard Summary
This table contains hazard information for each chemical; evaluation of risk considers both hazard and exposure. Variations in end-of-life processes or degradation and combustion
by-products are discussed in the report but not addressed directly in the hazard profiles. The caveats listed below must be taken into account when interpreting the information in the
table.
VL = Very Low hazard L = Low hazard = Moderate hazard H = High hazard VH = Very High hazard - Endpoints in colored text (VL, L, M, H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].
Chemical
CASRN
Human Health Effects
.•a
o
H
4J
X
U
^
'0
'3
o
c3
U
£>
.y
o
o
S
O
o
•a
o
a.
at
sS
§
S
0
3
a
u
"3
0)
Z
o
a
•a
•g
0)
M
a
_o
"S
.a
0)
C/5
•j|
C/5
^g
o -^
2-a
&• "7
s ?.
M cc
a
sS
•c
0)
W
0
1
HH
13
0)
Q
Aquatic
Toxicity
4J
U
^
_u
'3
u
Environmental
Fate
0)
u
2
4J
0.
a
O
1
"3
s
0
CO
Phosphoric acid, P,P'-[2,2-
bis(chloromethyl)-l,3-propanediyl]
P,P,P',P'-tetrakis(2-chloroethyl) ester
38051-10-4
L
M
L
H
L
L
L
L
M
L
7-410
-------
^-J
CASRN: 3805 1-10-4
MW: 582.99
MF: C13H24C1608P2
Physical Forms: Liquid
Neat:
Use: Fire retardant; polyurethane
foam additive
SMILES: O=P(OCCC1)(OCCC1)OCC(CC1)(CC1)COP(=O)(OCCC1)OCCC1
Synonyms: V6; Amgard V6; BCMP-BCEP; 2,2-bis(chloromethyl)trimethylene bis(bis(2-chloroethyl) phosphate); tetrekis(2-chlorethyl)dichloroisopentyldiphosphate
Chemical Considerations: This is a discrete organic chemical with a MW below 1,000. EPI v4.1 1 was used to estimate physical/chemical and environmental fate
values due to an absence of experimental data. Commercially available forms of this chemical have a purity of >85-90% (w/w). Impurities anticipated to be present in
the commercial product are: 1,2 dichloroethane (CASRN 107-06-2) and 4.5-7.5% TCEP or tris(chloroethyl) phosphate (CASRN 115-96-8) (EU, 2008a; CELLTECH,
2009).
Polymeric: No
Oligomeric: Not applicable
7-411
-------
Metabolites, Degradates and Transformation Products: Metabolites: ethylchloride; 2-chloroethanol; parent compound missing a chloroethyl moiety; parent
compound with chlorine replaced by an OH group; and parent compound with one chlorine oxidized to a carboxyl group (ECHA, 2012)
Analog: 2-Propanol, 1,3-dichloro-, phosphate (CASRN 13674-87-8)
Endpoint(s) using analog values: Carcinogenicity
Analog Structure:
Structural Alerts: Organophosphates, neurotoxicity. The commercial product may contain an impurity, CASRN 115-96-8, that appears on the List of Chemicals
Known to the State to Cause Cancer for the State of California: California Proposition 65 cancer (EPA, 2012; California EPA, 2013).
Risk Phrases: Not classified; although the commercial product is classified based on the amount of TCEP impurity present (ECHA, 2012; ESIS, 2012).
Hazard and Risk Assessments: A risk assessment was reported by the European Chemicals Industry; a SIDS initial assessment profile was completed under the
OECD HPV chemicals program; an environmental risk assessment was completed by the EU in 2008 (EC, 2000; EU, 2008a; OECD, 2009).
7-412
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
PHYSICAL/CHEMICAL PROPERTIES
Melting Point (°C)
Boiling Point (°C)
Vapor Pressure (mm Hg)
<-50.5
reported as a freezing point; Good
laboratory practice (GLP) guideline
study OECD 102, EEC Directive 92/69;
test substance partially frozen but
temperature did not remain constant
(Measured)
90
(Measured)
252.29 Decomposes
According to EU Method A. 2, during
experiment exotherm occurred resulting
in a final pressure of 78 1 .5 psi
(Measured)
>200 Decomposes
Decomposition products include
phosphorus oxides, carbon monoxide
and chlorides (Measured)
620
(Unknown)
2.06xlO-8at25°C
(Estimated)
<0.1atlOO°C
(Measured)
1.7at25°C
OECD, 2009; ECHA, 2012
van der Veen and de Boer, 2012
OECD, 2009; ECHA, 2012
EC, 2000; ECHA, 2012
van der Veen and de Boer, 2012
EPIv4.11
EC, 2000
ECHA, 20 12
Guideline study reported for the
commercial product Antiblaze V6.
Inadequate, reported in a
secondary source, insufficient
details available to access the
quality of this value.
Guideline study reported in a
secondary source.
Reported in a secondary source.
Reported in a secondary source;
citing another secondary source
(ChemSpider, 201 1) that could not
be verified.
Reported in a secondary source;
test not applicable due to product
decomposition.
Reported for a commercial
7-413
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
Water Solubility (mg/L)
Log Kow
DATA
reported as 22.29 hPa at 25°C; according
to GLP guideline study EU Method A. 4
(Measured)
2.1 (Measured)
at 25 °C
232 (Measured)
at 20°C, pH 7.65; GLP guideline study
OECD 105 and EU Method A.6
0.31 (Estimated)
Insoluble in water, at pH 7 (Measured)
2.83
+/-0.05at20°C,pH8.5
GLP guideline study OECD 107 and EU
Method A. 8; average of 6 assays ranging
from 2.74-2.87 (Measured)
3.3
(Estimated)
REFERENCE
van der Veen and de Boer, 2012
OECD, 2009; ECHA, 2012
EPIv4.11
EC, 2000
ECHA, 20 12
EPIv4.11
DATA QUALITY
product Amgard V6. Value
inconsistent with result expected
for this chemical; high vapor
pressure attributed to volatile
impurities in the commercial
product.
Reported in a secondary source.
Reported in a secondary source
for the commercial product
Antiblaze V6.
Qualitative value reported in a
secondary source with limited
details.
Reported in a secondary source
for the commercial product
Antiblaze V6.
7-414
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
Flammability (Flash Point)
Explosivity
Pyrolysis
pH
pKa
DATA
Flash point: 191°C Closed cup; GLP
study in compliance with EU Method
A.9 of Commission Directive 92/69/EEC
and OECD/GD(92)32
literature value of >230°C using
Cleveland Open Cup, atmospheric
pressure 100.39 kPa, corrected flash
point 191.215°C (Measured)
Auto flammability: >400°C at 100 kPa
GLP study in compliance with EU
Method A. 15 of Commission Directive
92/96/EEC and OECD (92)32;
performed at 15-20°C, atmospheric
pressure 100.30 to 100.99 kPa
(Measured)
Not expected to form explosive mixtures
with air (Estimated)
Not applicable (Estimated)
Not applicable (Estimated)
REFERENCE
EC, 2000; ECHA, 2012
EC, 2000; ECHA, 2012
Professional judgment
Professional judgment
Professional judgment
DATA QUALITY
Reporting in a Secondary source
for the commercial product
Amgard V6.
Reported in a secondary source.
No experimental data located;
based on its use as a flame
retardant.
No data located.
Does not contain functional
groups that are expected to ionize
under environmental conditions.
Does not contain functional
groups that are expected to ionize
under environmental conditions.
7-415
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
HUMAN HEALTH EFFECTS
Toxicokinetics
Dermal Absorption in vitro
Absorption,
Distribution,
Metabolism &
Excretion
Oral, Dermal or Inhaled
Other
Absorption of Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-
chloroethyl) ester (V6) from the gastrointestinal tract is nearly 100% following oral exposure in rats. V6
and metabolites are distributed throughout the body. Excretion occurred via the biliary route (60%), in
urine (20%) and as exhaled 14CO2. Absorption of V6 via the dermal route in human skin membranes
was low (0.51% and 6% for undiluted V6 or in an ethanol vehicle, respectively). No inhalation studies
were located.
In vitro dermal absorption study in
human skin membranes; the delivery of
undiluted V6 and V6 in ethanol (0.2
mg/cm3) was 0.51% and 6%,
respectively.
Oral administration of 14C labeled
Phosphoric acid, P,P'-[2,2-
bis(chloromethyl)-l,3-propanediyl]
P,P,P',P'-tetrakis(2-chloroethyl) ester
(V6) in the rat. Bioavailability was >
100% at the low dose (15 mg/kg) and ~
50% at the high dose (600 mg/kg).
Complete absorption from the
gastrointestinal tract at 15 mg/kg.
Elimination half-life was 99 - 1 13 hours;
excretion via the biliary route (60%) and
urine (20%) with the remainder exhaled
as 14CO2. V6 and metabolites were
distributed throughout the body (no
target organs); four major metabolites
were identified in feces.
EU, 2008b; OECD, 2009
EU, 2008b; OECD, 2009
Study details reported in a
secondary source. Study was
conducted in accordance with
OECD Guideline 428 and to GLP.
Study details reported in a
secondary source. Study was
conducted in accordance with
OECD Guideline 417 and to GLP.
No data located.
7-416
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
Acute Mammalian Toxicity
Acute Lethality
Oral
Dermal
Inhalation
Carcinogenicity
OncoLogic Results
Carcinogenicity (Rat and
Mouse)
DATA
REFERENCE
DATA QUALITY
LOW: Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl)
ester (V6) is not acutely toxic via the oral or inhalation routes of exposure in rats or via the dermal route
of exposure in rabbits.
Rat oral LD50 = between 2,000 - 5,000
mg/kg
Mortality (all within 48 hours of dosing)
was 1/10 at the low dose and 8/10 at the
high dose
Rat oral LD50 >2,000 mg/kg
Rabbit dermal LD50 >2,000 mg/kg
Rat inhalation (snout only) 4-hour LC50
>1.65 mg/L (highest attainable aerosol
concentration)
EU, 2008b (as cited in OECD,
2009)
Submitted confidential study
Submitted confidential study (as
cited in EU, 2008b; OECD, 2009)
Submitted confidential study (as
cited in EU, 2008b; OECD, 2009)
Study details reported in a
secondary source. Study
conformed to OPPTS or OECD
guidelines except that survivors
were not necropsied.
Test substance purity and
composition not specified;
conducted according to OECD
401.
Study details reported in a
secondary source. Study was
conducted to OECD Guideline
402.
Study details reported in a
secondary source and in a
confidential study submitted to
EPA. Study was conducted in
accordance with OECD Guideline
403.
MODERATE: Based on the weight of evidence. There were no Carcinogenicity studies located for
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester
(V6), however; there was no evidence of mutagenicity from genotoxicity studies. The OncoLogic
program estimated a Low-Moderate concern for Carcinogenicity and there was an increase in benign
tumors of the adrenal cortex and liver in a 2-year study with an analog chemical 2-Propanol, 1,3-
dichloro-, phosphate (CASRN 13674-87-8). Due to concerns based on structure and analogs, a moderate
hazard designation is warranted.
Low-moderate concern
OncoLogic, 2008
No data located.
7-417
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
Combined Chronic
Toxicity/Carcinogenicity
Other
Genotoxicity
Gene Mutation in vitro
Gene Mutation in vivo
DATA
In a 2-year combined oral chronic
toxicity and carcinogenicity assay,
Sprague-Dawley rats (60/sex/group)
were fed diets that provided doses of
containing 0, 5, 20, and 80 mg/kg-day of
the analog 2-Propanol, 1,3-dichloro-,
phosphate. Increased benign tumors of
the adrenal cortex in high-dose females,
and hepatocellular adenomas in high-
dose males and females, interstitial cell
tumors in the testes of high-dose males,
and renal cortical adenomas in mid- and
high-dose males and females. at 20 and
80 mg/kg-day.
(Estimated by analogy)
REFERENCE
Freudenthal and Henrich, 2000
DATA QUALITY
Estimated based on analogy to 2-
Propanol, 1,3-dichloro-, phosphate
(CASRN 13674-87-8). TheNRC
(2000) concluded that this study
provides sufficient evidence of
carcinogenicity of TDCPP in rats
following chronic oral exposure.
Test substance purity: 95%; The
mode of action for carcinogenicity
could not be determined.
No data located.
LOW: Based on no evidence of mutagenicity in either in vitro or in vivo genotoxicity studies.
Negative, gene mutations in mouse
lymphoma cells with and without
metabolic activation.
Negative, Salmonella typhimurium
strains TA98 and TA100 with or without
metabolic activation
Negative, Salmonella typhimurium
strains TA 1535, TA1537, TA98 and
TA100 with or without metabolic
activation
King, 1993 (as cited in OECD,
2009)
EC, 2000; OECD, 2009
Submitted confidential study
Study was conducted in
accordance with OECD Guideline
476; however, no information was
provided regarding positive
controls.
Study details reported in a
secondary source. Study was
conducted in accordance with
OECD Guideline 471 and GLP.
Study details reported in a
confidential study submitted to
EPA; test substance purity: 92.3%
No data located.
7-418
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
Chromosomal Aberrations in
vitro
Chromosomal Aberrations in
vivo
DNA Damage and Repair
Other
Reproductive Effects
Reproduction/Developmental
Toxicity Screen
Combined Repeated Dose with
Reproduction/ Developmental
Toxicity Screen
DATA
Negative, chromosomal aberrations in
cultured human lymphocytes with and
without metabolic activation; Positive
controls yielded expected responses.
Negative, micronucleus formation in
bone marrow of mice exposed by to two
oral treatments (oral gavage) at a 24-
hour interval to 500, 1,000, or 2,000
mg/kg-day (males); 437.5, 875, 1,750
mg/kg-day. Positive controls yielded
expected responses.
REFERENCE
EC, 2000; OECD, 2009
Submitted confidential study (as
cited in OECD, 2009)
DATA QUALITY
Study details reported in a
secondary source. Study was
conducted in accordance with
OECD Guideline 473and GLP.
Study details reported in a
secondary source and in a
submitted confidential study.
Study was conducted in
accordance with OECD Guideline
474.
No data located.
No data located.
MODERATE: Based on weight of evidence from multiple studies. Phosphoric acid, P,P'-[2,2-
bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester (V6) did not produce
reproductive toxicity in an oral 2-generation reproductive study or in a 4-week gavage study in rats at
doses up to 600 mg/kg-day (LOAELs were not established). Data using the analog 2-Propanol, 1,3-
dichloro-, phosphate reported a LOAEL of 5 mg/kg-day (NOAEL not established) for atrophy and
decreased secretory product of the seminal vesicle in an oral two-year combined chronic toxicity and
carcinogenicity assay in rats. A 12-week fertility study in rabbits using the analog 2-Propanol, 1,3-
dichloro-, phosphate reported a NOAEL of 200 mg/kg-day; there is uncertainty if reproductive effect
could occur at a dose up to 250 mg/kg-day (the cutoff for the Moderate hazard designation criteria
range).
No data located.
No data located.
7-419
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Reproduction and Fertility
Effects
In an oral 2-generation reproductive
toxicity study, rats (28/sex) were fed
diets containing the test chemical
Phosphoric acid, P,P'-[2,2-
bis(chloromethyl)-l,3-propanediyl]
P,P,P',P'-tetrakis(2-chloroethyl) ester (0,
29, 86 or 262 mg/kg-day for males and
0, 33, 97 or 302 mg/kg-day for females).
No effects on the male and female
reproductive systems up to the highest
doses tested.
NOAEL (fertility): 262 and 302 mg/kg-
day for males and females, respectively
(highest dose tested)
LOAEL: Not established
EU, 2008a; OECD, 2009
Study details reported in a
secondary source. Study was
conducted in accordance with
OECD Guideline 416; however,
corpora lutea were not counted at
scheduled sacrifice, which
represented a deviation from the
guideline.
In a 12-week oral fertility study, rabbits
(10 males/dose) were gavaged with 0, 2,
20, or 200 mg/kg-day of the analog 2-
Propanol, 1,3-dichloro-, phosphate.
Males were treated for 12 weeks, then
mated with untreated females. There
were no alterations in mating behavior,
fertility, or sperm quantity or quality.
Neither gross necropsy nor microscopic
examinations showed significant
alterations in the reproductive tract.
NOAEL: 20 mg/kg-day
LOAEL: 200 mg/kg-day (highest dose
tested)
(Estimated by analogy)
Wilczynski et al., 1983; ATSDR,
2012
Study details were available in the
secondary source. Estimated by
analogy to 2-Propanol, 1,3-
dichloro-, phosphate (CASRN
13674-87-8). Data not sufficient
to satisfy the reproductive toxicity
endpoint since it was described
only in an abstract and there was a
lack of information in female
animals. This limits the usefulness
of the study for risk assessment.
7-420
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Other
A confidential, 4-week repeated-dose
oral gavage study in rats was submitted.
No histopathology was found in the
reproductive organs in either sex at a
NOAEL of 600 mg/kg-day of the test
chemical; however, the study duration
was relatively short and reproductive
function was not tested.
NOAEL: 600 mg/kg-day (highest dose
tested)
LOAEL: Not established
Submitted confidential study
Study was conducted in
accordance with OECD Guideline
407
Rat, oral, 2-year combined chronic
toxicity and carcinogenicity assay; Rats
(60/sex/group) were administered 0, 5,
20, 80 mg/kg-day (in the diet) of the
analog 2-Propanol, 1,3-dichloro-,
phosphate for 2 years. Ten rats/sex/dose
were randomly chosen for termination at
12 months; the remainder at 24 months.
Reproductive effects in males included
effects on seminal vesicles (atrophy,
decreased secretory product) at = 5
mg/kg-day, testes (eosinophilic material
in lumen, periarteritis nodosa) at = 20
mg/kg-day, and epididymis
(oligospermia and degenerated seminal
product) at 80 mg/kg-day.
NOAEL: Not established
LOAEL: 5 mg/kg-day
Freudenthal and Henrich, 2000
Estimated by analogy to 2-
Propanol, 1,3-dichloro-, phosphate
(CASRN 13674-87-8); Fertility
was not assessed in the study. The
authors reported the lowest dose
of 5 mg/kg-day as a NOAEL and
the mid-dose of 20 mg/kg-day as a
LOAEL. However, as evaluated in
NRC (2000), the lowest dose of 5
mg/kg-day was a LOAEL for
atrophy and decreased secretory
product of the seminal vesicle; test
substance purity: 95%; These
effects for reproductive tissues are
reported from a 2-year combined
chronic toxicity and
carcinogenicity assay, and not
from a study designed to test
reproductive effects specifically;
other reproductive parameters
were not examined.
7-421
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
Developmental Effects
Reproduction/ Developmental
Toxicity Screen
DATA
REFERENCE
DATA QUALITY
HIGH: Based on a NOAEL of 29 mg/kg-day (LOAEL of 86 mg/kg-day) for increased number of runts
and decreased pup weight in an oral 2-generation study in rats. No developmental NOAEL/LOAEL
could be established in a prenatal toxicity study in rats due to low survival of dams.
There were no data located for the developmental neurotoxicity endpoint. Uncertain concern for the
developmental neurotoxicity based on the potential for Cholinesterase (ChE) inhibition in dams that
may result in alterations of fetal neurodevelopment.
No data located.
7-422
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Combined Repeated Dose with
Reproduction/ Developmental
Toxicity Screen
In an oral 2-generation reproductive
toxicity study, rats were fed diets
containing Phosphoric acid, P,P'-[2,2-
bis(chloromethyl)-l,3-propanediyl]
P,P,P',P'-tetrakis(2-chloroethyl) ester
(the overall intake of V6 was (0, 29, 86
or 262 mg/kg-day for males and 0, 33,
97 or 302 mg/kg-day for females).
Increased number of runts on post-natal
day one and decrease in pup weights in
mid- and high-dose groups of both
generations. Decreased absolute spleen
weight in high dose FO pups and in all
treated Fl pups; decreased relative
spleen weight (high dose Fl pups),
decreased absolute brain weight but
increase in relative liver weights (all
treated Fl pups), decreased absolute
thymus weights (low and high dose Fl
pups).
Maternal toxicity:
NOAEL: 33 mg/kg-day
LOAEL: 97 mg/kg-day
Developmental toxicity:
NOAEL: 29 and 33 mg/kg-day for males
and females, respectively
LOAEL: 86 and 97 mg/kg-day for males
and females, respectively (based on
increased number of runts and decreased
pup weight)
EU, 2008b; OECD, 2009
Study details reported in a
secondary source. Study was
conducted in accordance with
OECD Guideline 416; however,
corpora lutea were not counted at
scheduled sacrifice, which
represented a deviation from the
guideline.
7-423
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
Prenatal Development
DATA
Pregnant rats (5/group) were orally
gavaged with 0, 100, 200, 400, 800, and
1,600 mg/kg-day Phosgard 2XC20
(CASRN 38051-10-4) on GD 6-19.
Uterine examinations were conducted on
GD20.
Maternal toxicity occurred at the three
highest doses. One rat at 800 mg/kg and
all rats at 1,600 mg/kg died between GD
7 and 9, the cause of death was not
determined. Clinical signs of toxicity in
dams included dry red matter around the
nose and forepaws (400 and 800 mg/kg-
day) and staining of the anogenital area
(800 mg/kg-day). Reduced maternal
body weight (800 mg/kg-day). No
biologically significant differences in the
mean numbers of viable fetuses, post
implantation loss, early or late
resorption, total implantations or corpora
lutea. A slight increase in mean post
implantation losses at 800 mg/kg-day
was similar to historical controls.
Maternal toxicity:
NOAEL: 400 mg/kg-day
LOAEL: 800 mg/kg-day (based on
clinical signs and increased mortality)
Fetal toxicity:
NOAEL: 800 mg/kg-day
LOAEL: 1,600 mg/kg-day
Pregnant Sprague-Dawley rats (20/dose)
REFERENCE
Condray, 1990
Kappetal., 1981
DATA QUALITY
Limited study details of a pilot rat
teratology study provided in
secondary source (no quantitative
data were shown). Adequate
primary source. The small group
size (four surviving dams)
prevents the identification of fetal
NOAEL/LOAEL values. In
addition, the only fetal effect
(marginal increase in
postimplantation loss) occurred at
a maternally toxic dose.
Estimated by analogy to 2-
7-424
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
Postnatal Development
Prenatal and Postnatal
Development
Developmental Neurotoxicity
Other
DATA
were gavaged with 0, 25, 100, and 400
mg/kg-day of analog 2-Propanol, 1,3-
dichloro-, phosphate on GD 6-15. Dams
were sacrificed on Gd 19. No effect on
implantation efficiency or mean number
of corpora lutea. Increased the number of
resorptions and reduced fetal viability at
the high dose.
Maternal toxicity:
NOAEL: 25 mg/kg-day
LOAEL: 100 mg/kg-day (clinical signs
and transient reduction in body weight
gain)
Fetal toxicity:
NOAEL: 100 mg/kg-day
LOAEL: 400 mg/kg-day (increased
resorption and fetal mortality)
(Estimated by analogy)
Uncertain concern for developmental
neurotoxicity based on the potential for
Cholinesterase (ChE) inhibition in dams
that may result in alterations of fetal
neurodevelopment (Estimated)
REFERENCE
Professional judgment
DATA QUALITY
Propanol, 1, 3 -dichloro-, phosphate
(CASRN 13674-87-8)
No data located.
No data located.
Estimated based on a structural
alert for organophosphates for the
neurotoxicity endpoint.
No data located.
7-425
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Neurotoxicity
LOW: Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl)
ester (V6) was not neurotoxic to rats in a 4-week gavage study at doses up to 600 mg/kg-day (LOAEL not
established). The only effect in several acute studies in rats was depressed serum cholinesterase activity
following oral gavage of 250-1,500 mg/kg-day. In addition, no changes indicative of neurotoxicity were
observed in an acute and a 90-day delayed neurotoxicity study in hens gavaged with analog chemical 2-
Propanol, 1,3-dichloro-, phosphate (CASRN 13674-87-8).
Neurotoxicity Screening
Battery (Adult)
Other
In a 4-week repeated-dose oral gavage
study in rats included a neurotoxicity
screening battery. No behavioral effects
or neurohistopathology were found at the
highest dose tested.
NOAEL: 600 mg/kg-day (the highest
dose tested)
LOAEL: Not established
In several acute rat studies,
cholinesterase activity was depressed
following oral gavage of 250 - 1,500
mg/kg test substance. In rabbits dermally
administered 2,000 mg/kg test substance,
no significant suppression of
cholinesterase activity was measured in
serum, whole blood or the brain within
24 hours.
NOAEL: Not established
LOAEL: 250 mg/kg (by oral gavage)
based on cholinesterase activity
In an acute oral and a 90-day delayed
neurotoxicity study in hens gavaged with
2-Propanol, 1,3-dichloro-, phosphate,
there was no inhibition of brain
neurotoxic esterase (NTE) activity at a
Submitted confidential study; EU,
2008b
Study details reported in a
secondary source. Study
conducted to OECD guideline 424
(neurotoxicological investigation).
Submitted confidential study; EU,
2008b
Morey et al, 1978
Limited study details reported.
Estimated by analogy to 2-
Propanol, 1,3-dichloro-, phosphate
(CASRN 13674-87-8).
7-426
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
dose of 10,000 mg/kg-day and no
behavioral effects or histopathological
changes indicative of neurotoxicity at
doses up to 100 mg/kg-day.
NOAEL: Not established
LOAEL: 10,000 mg/kg-day
(Estimated by analogy)
Repeated Dose Effects
MODERATE: Based on a NOAEL of 29 mg/kg-day (LOAEL= 86 mg/kg-day) for liver and thyroid
weight changes and associated histopathology in an oral 2-generation study in rats. Liver effects were
also observed in rats at a dose of 150 mg/kg-day following oral administration for 28 days (NOAEL = 15
mg/kg-day). No neurological effects were reported in a 4-week repeated-dose oral study in rats at a dose
of 600 mg/kg-day (highest dose tested). In a 2-year combined oral chronic toxicity and carcinogenicity
study in rats using analog chemical, 2-Propanol, 1,3-dichloro-, phosphate (CASRN 13674-87-8), a
LOAEL of 5 mg/kg-day (lowest dose tested) was established for anomalies of the liver, kidneys, testes,
renal cortex, and adrenal cortex.
7-427
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
In an oral 2-generation reproductive
toxicity study, rats (28/sex) were fed
diets containing Phosphoric acid, P,P'-
[2,2-bis(chloromethyl)-1,3 -propanediyl]
P,P,P',P'-tetrakis(2-chloroethyl) ester
over 2 successive generations
(approximately 0, 29, 86 or 262 mg/kg-
day for males and 0, 33, 97 or 302
mg/kg-day for females).
Increased absolute and relative thyroid
weight, accompanied by follicular
hypertrophy and a reduction in colloid in
males (FO generation, mid- and high
dose); increased absolute and relative
liver weight (both generations)
accompanied by hepatocyte hypertrophy
(FO generation).
NOAEL (parental): 29 and 33 mg/kg-
day for males and females, respectively
LOAEL (parental): 86 and 97 mg/kg-day
for males and females, respectively
(based on liver and thyroid weight
changes and histopathology in mid- and
high-dose groups)
EU, 2008a; OECD, 2009
Study details reported in a
secondary source. Study was
conducted in accordance with
OECD Guideline 416.
In a 2 8-day oral study, V6 was
administered to rats via gavage at doses
ofO, 15, 150, or 600 mg/kg-day.
Increased relative and absolute liver
weight, hepatocellular hypertrophy and
centrilobular hypertrophy (150 and 600
mg/kg-day); significantly increased
cholesterol levels, increases in absolute
Submitted confidential study (as
cited in EU, 2008b; OECD, 2009)
Study details reported in a
secondary source with more
details provided in a submitted
confidential study. Study was
conducted in accordance with
OECD Guideline 407 and 424
(neurotoxicological investigation).
7-428
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
and relative thyroid weight, increased
prothrombin time (600 mg/kg-day);
NOAEL: 15 mg/kg-day
LOAEL: 150 mg/kg-day (based on liver
effects)
A 4-week repeated-dose oral gavage
study in rats included a neurotoxicity
screening battery. No behavioral effects
or neurohistopathology were found at the
highest dose tested.
NOAEL: 600 mg/kg-day (the highest
dose tested)
LOAEL: Not established
Submitted confidential study; EU,
2008b
Study details reported in a
secondary source. Study
conducted to OECD guideline 424
(neurotoxicological investigation)
In a 2-year combined oral chronic
toxicity and carcinogenicity assay,
Sprague-Dawley rats (60/sex/group)
were fed diets containing 0, 5, 20, and 80
mg/kg-day of analog 2-Propanol, 1,3-
dichloro-, phosphate. Increased
mortality, decreased body weight,
anomalies of the liver, kidneys, testes,
renal cortex, and adrenal cortex.
NOAEL: Not established
LOAEL: 5 mg/kg-day (based on atrophy
and decreased secretory product of the
seminal vesicle; hyperplasia of
convoluted tubule epithelium in males at
24 months)
(Estimated by analogy)
Freudenthal and Henrich, 2000
Estimated by analogy to 2-
Propanol, 1,3-dichloro-, phosphate
(CASRN 13674-87-8)
7-429
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
Skin Sensitization
Skin Sensitization
Respiratory Sensitization
(Respiratory Sensitization
DATA
REFERENCE
DATA QUALITY
LOW: Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl)
ester (V6) did not produce dermal Sensitization in guinea pigs or in human volunteers. A single
submitted confidential study reported mild skin Sensitization in 17% of tested guinea pigs; however,
these data could not be validated.
In a maximization test in guinea pigs (20
test animals and 10 controls) treated
intradermally with diluted V6, induced
topically with neat material, and
challenged with both neat and diluted
test material, V6 lacked significant skin
Sensitization potential.
Not sensitizing to humans following 6
days of treatment and a 48-hour
challenge application
Mild skin Sensitization, guinea pigs
(17% of animals showing positive
results, no further details provided) in a
Magnusson and Kligman Maximization
study; intradermal induction: 5% w/v in
6% acetone v/v in arachis oil B.P.;
topical induction: undiluted as supplied;
topical challenge: undiluted as supplied
and 75% v/v in acetone., no further
details provided)
EU, 2008b; OECD, 2009
Submitted confidential study
Submitted confidential study
Study details reported in a
secondary source. Study was
conducted in accordance with
OECD Guideline 406.
Limited study details reported.
Study details from reported in a
confidential study; purity of
supplied test substance not
specified.
No data were located.
No data located.
7-430
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
Eye Irritation
Eye Irritation
Dermal Irritation
Dermal Irritation
DATA
REFERENCE
DATA QUALITY
LOW: Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl)
ester (V6) produced slight conjunctival irritation in rabbits which resolved within 24 or 48 hours.
Not irritating, rabbits (n=3). Monitoring
of ocular damage/irritation was done for
up to 72 hours after instillation of 0. 1
mL of V6. No corneal or iridial
response; slight conjunctival redness in
one rabbit 24 hours post-instillation
which was reversible within 48 hours.
Not irritating, rabbits (n=3). Monitoring
of ocular damage/irritation was done for
up to 72 hours after instillation of 0. 1
mL of V6. No corneal or iridial
response. Minimal conjunctival irritation
was noted in all treated eyes 1 hour post-
instillation. All treated eyes appeared
normal 24 hours post-treatment.
classified as non-irritating
EC, 2000
Submitted confidential study (as
cited in EU, 2008b)
Study details reported in a
secondary source. Study was
conducted in accordance with
OECD Guideline 405 and GLP.
Study details reported in a
submitted confidential study;
conducted according to OECD
405; test substance purity not
specified.
LOW: Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl)
ester (V6) produced slight irritation (erythema, but no edema) in rabbits which resolved within 48 or 72
hours.
Slightly irritating to the intact skin of
rabbits (n=3) after semi -occluded
application of 0.5 mL V6 for 4 hours.
Slight irritation (erythema but no edema)
in rabbits following a 4-hour semi-
occluded exposure to 0.5 g of V6. All
treated skin sites had returned to normal
by 24 hours post-treatment
4-hour semi -occluded application to 0.5
g of V6;
EU, 2008b
Submitted confidential study (as
cited in EU, 2008b)
Submitted confidential study (as
cited in EU, 2008b)
Study details reported in a
secondary source. Study was
conducted in accordance with
OECD Guideline 404 and GLP.
Study details reported in a
secondary source and a submitted
confidential study. Study was
conducted in accordance with
OECD Guideline 404 and GLP.
Study details reported in a
submitted confidential study and a
7-431
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Not irritating, rabbits. Barely perceptible
irritation (erythema) was detected in 2/3
females at 26 hours, but in none at 72
hours
classified as mild irritant
Produced a primary irritation index of
1.2 and was classified as a mild irritant
to rabbit skin according to the Draize
classification scheme. No corrosive
effects were noted.
secondary source; conducted
according to OECD 404; The test
material did not produce positive
criteria in any rabbit according to
the EEC labeling regulations and
was classified as Non-irritant to
rabbit skin. No symbol and risk
phrase are required; test substance
purity and formulation was not
reported.
7-432
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Endocrine Activity
There were thyroid weight changes and associated histopathology in an oral 2-generation study in rats
and there was an increase in benign tumors of the adrenal cortex and liver in a 2-year study with an
analog chemical 2-Propanol, 1,3-dichloro-, phosphate (CASRN 13674-87-8).
In an oral 2-generation reproductive
toxicity study, rats (28/sex) were fed
diets containing Phosphoric acid, P,P'-
[2,2-bis(chloromethyl)-1,3 -propanediyl]
P,P,P',P'-tetrakis(2-chloroethyl) ester
over 2 successive generations
(approximately 0, 29, 86 or 262 mg/kg-
day for males and 0, 33, 97 or 302
mg/kg-day for females). Increased
absolute and relative thyroid weight,
accompanied by follicular hypertrophy
and a reduction in colloid in males (FO
generation, mid- and high dose);
increased absolute and relative liver
weight (both generations) accompanied
by hepatocyte hypertrophy (FO
generation). NOAEL (parental): 29 and
33 mg/kg-day for males and females,
respectively LOAEL (parental): 86 and
97 mg/kg-day for males and females,
respectively (based on liver and thyroid
weight changes and histopathology in
mid- and high-dose groups).
In a 2 8-day oral study, V6 was
administered to rats via gavage at doses
ofO, 15, 150, or 600 mg/kg-day.
Increased relative and absolute liver
weight, hepatocellular hypertrophy and
centrilobular hypertrophy (150 and 600
mg/kg-day); significantly increased
EU, 2008b
Study details reported in a
secondary source. Study was
conducted in accordance with
OECD Guideline 416.
Submitted confidential study (as
cited in EU, 2008b; OECD, 2009)
Study details reported in a
secondary source with more
details provided in a submitted
confidential study. Study was
conducted in accordance with
OECD Guideline 407 and 424
(neurotoxicological investigation).
7-433
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
cholesterol levels, increases in absolute
and relative thyroid weight, increased
prothrombin time (600 mg/kg-day);
NOAEL: 15 mg/kg-day LOAEL: 150
mg/kg-day (based on liver effects)
In a 2-year combined oral chronic
toxicity and carcinogenicity assay,
Sprague-Dawley rats (60/sex/group)
were fed diets containing 0, 5, 20, and 80
mg/kg-day 2-Propanol, 1,3-dichloro-,
phosphate. Increased mortality,
decreased body weight, anomalies of the
liver, kidneys, testes, renal cortex, and
adrenal cortex. NOAEL: Not established
LOAEL: 5 mg/kg-day (based on atrophy
and decreased secretory product of the
seminal vesicle; hyperplasia of
convoluted tubule epithelium in males at
24 months) (Estimated by analogy)
Freudenthal and Henrich, 2000
Estimated by analogy to 2-
Propanol, 1,3-dichloro-, phosphate
(CASRN 13674-87-8).
In an oral 2-generation reproductive
toxicity study, rats (28/sex) were fed
diets containing Phosphoric acid, P,P'-
[2,2-bis(chloromethyl)-1,3 -propanediyl]
P,P,P',P'-tetrakis(2-chloroethyl) ester
over 2 successive generations
(approximately 0, 29, 86 or 262 mg/kg-
day for males and 0, 33, 97 or 302
mg/kg-day for females).
Increased absolute and relative thyroid
weight, accompanied by follicular
hypertrophy and a reduction in colloid in
males (FO generation, mid- and high
dose); increased absolute and relative
EU, 2008a; OECD, 2009
Study details reported in a
secondary source. Study was
conducted in accordance with
OECD Guideline 416.
7-434
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
liver weight (both generations)
accompanied by hepatocyte hypertrophy
(FO generation).
NOAEL (parental): 29 and 33 mg/kg-
day for males and females, respectively
LOAEL (parental): 86 and 97 mg/kg-day
for males and females, respectively
(based on liver and thyroid weight
changes and histopathology in mid- and
high-dose groups)
In a 2-year combined oral chronic
toxicity and carcinogenicity assay,
Sprague-Dawley rats (60/sex/group)
were fed diets that provided doses of
containing 0, 5, 20, and 80 mg/kg-day 2-
Propanol, 1,3-dichloro-, phosphate.
Increased benign tumors of the adrenal
cortex in high-dose females, and
hepatocellular adenomas in high-dose
males and females, interstitial cell
tumors in the testes of high-dose males,
and renal cortical adenomas in mid- and
high-dose males and females at 20 and
80 mg/kg-day. (Estimated by analogy)
Freudenthal and Henrich, 2000
Estimated by analogy to 2-
Propanol, 1,3-dichloro-, phosphate
(CASRN 13674-87-8).
7-435
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
Immunotoxicity
Immune System Effects
DATA
REFERENCE
DATA QUALITY
Decreased absolute and relative spleen weights and decreased absolute thymus weights were observed in
pups in an oral 2-generation reproductive toxicity study in rats.
In an oral 2-generation reproductive
toxicity study, rats were fed diets
containing Phosphoric acid, P,P'-[2,2-
bis(chloromethyl)-l,3-propanediyl]
P,P,P',P'-tetrakis(2-chloroethyl) ester
(the overall intake of V6 was (0, 29, 86
or 262 mg/kg-day for males and 0, 33,
97 or 302 mg/kg-day for females).
Decreased absolute spleen weight in
high dose FO pups and in all treated Fl
pups; decreased relative spleen weight in
high dose Fl pups. Decreased absolute
thymus weights in low and high dose F 1
pups.
EU, 2008b; OECD, 2009
ECOTOXICITY
ECOSAR Class
Acute Aquatic Toxicity
Fish LC50
MODERATE: Based on experimental fish acute LC50 of 52 mg/L and a daphnid EC50 of 42 mg/L.
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester (V6)
is not acutely toxic to algae according to experimental studies.
Freshwater fish (Oncorhynchus mykiss)
96-hour LC50 = 52 mg/L
96-hour NOEC=3 8 mg/L; measured
concentrations were generally within
20% of initial concentrations (semi-static
test conditions)
(Experimental)
Freshwater fish (Oncorhynchus mykiss)
96-hour LC50> 10 mg/L
NOEO 10 mg/L
The study was conducted under
Submitted confidential study (as
cited in EU, 2008b; OECD, 2009)
EC, 2000
Limited study details reported in a
secondary source with more study
details reported in a submitted
confidential study; study was
conducted in accordance with
OECD Guideline 203 and GLP.
Limited study details reported in a
secondary source. Study was
conducted in accordance with
OECD Guideline 203 and GLP.
7-436
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
semistatic conditions
(Experimental)
Analytical monitoring was not
performed.
Freshwater fish 96-hour LC50 = 13.46
mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
The toxicity value exceeds the
water solubility by 10 times; NES
is predicted.
Daphnid LC50
Daphnia magna 48-hour EC50 > 10
mg/L
NOEO 10 mg/L
(Experimental)
EC, 2000; EU, 2008b
Limited study details reported in a
secondary source. Study was
conducted in accordance with
OECD Guideline 202 and GLP.
Analytical monitoring was not
performed.
Daphnia magna 48-hour EC50 = 42
mg/L
48-hour NOEC=21 mg/L; the test was
conducted under static conditions.
Measured concentrations were stable
within 20% of initial concentrations.
(Experimental)
Submitted confidential study (as
cited in EU, 2008b; OECD, 2009)
Study details reported in a
secondary source with more
details provided in a submitted
confidential study. Study was
conducted in accordance with
OECD Guideline 202 and GLP.
Daphnia magna 48-hour LC50 = 24.33
mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
7-437
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
The toxicity value exceeds the
water solubility by 10 times; NES
is predicted.
Green Algae EC50
Green algae (Scenedesmus subspicatus)
76-hour EC50> lOmg/L
NOEO lOmg/L
(Experimental)
EC, 2000
Limited study details reported in a
secondary source. Study was
conducted in accordance with
OECD Guideline 201 and GLP.
Analytical monitoring was not
performed.
Green algae (Pseudokirchneriella
subcapitatd) 72-hour EC50(growth) = 21
mg/L
72-hour ErC50 (biomass) = 35 mg/L
(static test conditions). Measured
concentrations were stable within 20%
of initial concentrations.
(Experimental)
Submitted confidential study (as
cited in EU, 2008b; OECD, 2009)
Green algae 96-hour EC50= 8.42 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Study details reported in a
secondary source with more study
details provided in a submitted
confidential study; Study was
conducted in accordance with
OECD Guideline 209 and GLP.
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
The toxicity value exceeds the
water solubility by 10 times; NES
is predicted.
7-438
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Chronic Aquatic Toxicity
MODERATE: Based on estimated chronic aquatic toxicity values. An estimated chronic aquatic toxicity
value derived using an acute-to-chronic ratio (ACR) for the phosphate esters class was applied to the
available experimental acute data for this chemical and indicated a Moderate hazard. An ECOSAR
estimate for fish of 1.6 mg/L (ECOSAR class: esters) also indicated a Moderate hazard. Experimental
data indicated that phosphoric acid, P, P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',PMetrakis(2-
chloroethyl) ester (V6) does not produce chronic toxicity to daphnia and algae; in the absence of
experimental data for fish, an estimated Moderate hazard designation was assigned.
Fish ChV
Freshwater fish ChV > 2.2 mg/L
(Estimated)
Freshwater Fish ChV = 0.77mg/L
(Estimated)
ECOSAR: Esters
Professional judgment
ECOSARvl.ll
An ACR of 24 was derived for the
phosphate ester class based on
experimental data for Tris (p-t-
butylphenyl) phosphate (TBPP).
The acute-to-chronic ratio was
applied to available experimental
acute fish data for phosphoric
acid, P,P'-[2,2-bis(chloromethyl)-
1,3-propanediyl] P,P,P',P'-
tetrakis(2-chloroethyl)ester (ChV
>52 mg/L 724 = 2.2 mg/L)
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
The toxicity value exceeds the
water solubility by 10 times; NES
is predicted.
7-439
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Daphnid ChV
Daphnia magna 23-day NOEC > 3.68
mg/L
Test duration extended to 23 days in
order to achieve validity criteria for
control reproduction. Some measured
concentrations were not within nominal
values, therefore, results analyzed and
expressed relative to geometric mean
concentrations over 23 days.
(Experimental)
Submitted confidential study; EU,
2008b: OECD, 2009
The limited study details reported
in a secondary source with more
study details provided in a
submitted confidential study
indicate that the test system may
have been compromised, and that
the study results may not be valid.
Daphnia magna ChV > 10 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
The toxicity value exceeds the
water solubility by 10 times; NES
is predicted.
Green Algae ChV
Green algae (Pseudokirchneriella
subcapitata) 72-hour NOEC =10 mg/L
Limit test
(Experimental)
Submitted confidential study (as
cited in EU, 2008b; OECD, 2009)
Limited study details reported in a
secondary source with more study
details available in a submitted
confidential study; concentrations
were not measured; test not
subjected to GLP.
Green algae (Scenedesmus subspicatus)
76-hour EC50> 10 mg/L
NOEO 10 mg/L
(Experimental)
EC, 2000
Limited study details reported in a
secondary source. Study was
conducted in accordance with
OECD Guideline 201 and GLP.
Analytical monitoring was not
performed.
Green algae ChV = 3.30 mg/L
(Estimated)
ECOSARvl.ll
Estimate for the Esters class was
provided for comparative
7-440
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
DATA
ECOSAR: Esters
REFERENCE
DATA QUALITY
purposes.
See Section 5.5.1.
The toxicity value exceeds the
water solubility by 10 times; NES
is predicted.
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, phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',PMetrakis(2-
chloroethyl) ester, is expected to be found primarily in soil and sediment. The general partitioning of this
chemical is toward solid phases and out of water, with limited degradation in soil and sediment
predicted. It is not expected to dissociate at environmentally-relevant pH values. Based on measured and
estimated K0c values, it is expected to have negligible mobility in soil. Leaching through soil to
groundwater is not expected to be an important transport mechanism. Estimated volatilization half-lives
indicate that it will be non-volatile from surface water. Based on its estimated vapor pressure it is
expected to exist in the vapor and particulate phase in the atmosphere. Vapor-phase phosphoric acid,
P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',PMetrakis(2-chloroethyl) ester is degraded in the
atmosphere by reaction with photochemically-produced hydroxyl radicals. Particulates will be removed
from air by wet or dry deposition.
<10'8 (Estimated)
1 1,000 reported as Log Koc = 4.04; test
method C.19 of 2001/59/EC (Measured)
>30,000 MCI method (Estimated)
Air = 0%
Water = 0.7%
Soil = 54%
EPI v4. 11; Professional judgment
EU, 2008b
EPI v4. 11; EPA, 2005
EPIv4.11
Cutoff value for nonvolatile
compounds.
Secondary source reporting
screening study for main
component of commercial product
V6, purity of test substance not
stated.
Cutoff value for nonmobile
compounds.
7-441
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Sediment = 45% (Experimental)
Persistence
HIGH: The persistence hazard designation for Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-
propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester (V6) is based on guideline biodegradation studies.
There is evidence for biodegradation to occur, at rates resulting in a high hazard designation. 37%
removal was found in 28 days with an OECD 302C guideline study. Under aerobic conditions in ready
biodegradability test OECD 301B, 5% biodegradation occurred after 28 days. This compound is
relatively stable to hydrolysis, with experimental half-lives of >1 year at pH 4, pH 7, and pH 9. This
compound is not expected to be susceptible to direct photolysis by sunlight, since it does not absorb light
at wavelengths >290 nm. It is expected to be degraded in the atmosphere by reaction with
photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 0.14
days.
Water
Aerobic Biodegradation
Passes Ready Test: No
Test method: OECD TG 301B: CO2
Evolution Test
Achieved 5% degradation after 28 days
in domestic activated sludge.
Preliminary test OECD 209 confirmed
the test substance did not inhibit growth
of the microorganisms in the inoculum at
the test concentrations employed in the
ready test. (Measured)
Study results: 37%/28 days
Test method: 302C: Inherent - Modified
MITI Test (II)
Achieved 37% of its theoretical oxygen
demand after 28 days using an activated
sludge inoculum; this chemical was not
considered inherently biodegradable.
(Measured)
Volatilization Half-life for
Model River
EC, 2000; OECD, 2009; ECHA,
2012
Guideline study reported in
secondary source for the
commercial product Amgard V6.
EU,2008b; ECHA, 2012
Non-GLP guideline study reported
in a secondary source for the
commercial product Amgard V6.
No data located.
7-442
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
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
0.14 days based on 12-hour day
(Estimated)
Not a significant fate process
(Estimated)
50%/1 year at 25°C, pH 4, 7, and 9;
according to a GLP guideline study EU
Method C.7 92/69/EEC OECD 1 1 1
In a preliminary test hydrolysis was
below 10% after 5 days at pH 4,7 and 9,
50°C (Measured)
50%/ 99 days pH 10 (Estimated)
50%/ 1 1 1 days pH 9 (Estimated)
50%/ 1 13 days pH 8 (Estimated)
50%/ 1 13 pH 7 (Estimated)
50%/1 13 days pH 6 (Estimated)
50%/1 13 days pH 5 (Estimated)
REFERENCE
EPIv4.11
Professional judgment; Mill,
2000
EU, 2008b;ECHA, 2012
EPIv4.11
EPIv4.11
EPIv4.11
EPIv4.11
EPIv4.11
EPIv4.11
DATA QUALITY
No data located.
No data located.
No data located; chlorinated alkyl
phosphates are outside the domain
of the available estimation
methods.
No data located.
No data located.
The substance does not contain
functional groups that would be
expected to absorb light at
environmentally significant
wavelengths.
Guideline study reported in a
secondary source for the
commercial product Antiblaze V6.
7-443
-------
Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-l,3-propanediyl] P,P,P',P'-tetrakis(2-chloroethyl) ester CASRN 38051-10-4
PROPERTY/ENDPOINT
Environmental Half-life
Bioaccumulation
Fish BCF
Other BCF
BAF
Metabolism in Fish
DATA
>1 year Soil (Estimated)
REFERENCE
PBT Profiler
DATA QUALITY
Half-life estimated for the
predominant compartment, as
determined by EPI and the PBT
Profiler methodology.
LOW: Based on estimated BCF and BAF values.
1 1 Regression-based method (Estimated)
3 1 Arnot-Gobas method (Estimated)
EPIv4.11
EPIv4.11
No data located.
No data located.
ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring
Ecological Biomonitoring
Human Biomonitoring
No data located.
No data located.
No data located.
7-444
-------
ATSDR (2012) Toxicological profile for phosphate ester flame retardants. Atlanta, GA: Agency for Toxic Substances and Disease Registry.
California EPA (2013) Chemicals known to the state to cause cancer or reproductive toxicity July 05, 2013. California Environmental Protection
Agency, http://oehha.ca.gov/prop65/prop65 list/files/P65single072613.pdf
CELLTECH (2009) Material safety data sheet FR-100 flame retardant additive. Cellular Technology International Inc.
Condray JR (1990) US EPA status report: Phosgard 2XC20 with cover letter. Submitted to the U.S. Environmental Protection Agency under
TSCA Section 8E.
EC (2000) 2,2-bis (chloromethyl) trimethylene bis (bis(2-chloromethyl) phosphate). IUCLID data set. European Commission, European
Chemicals Bureau.
ECHA (2013) 2,2-Bis(chloromethyl)trimethylene bis(bis(2-chloroethyl)phosphate). Registered substances. European Chemicals
Agency. http://apps.echa.europa.eu/registered/data/dossiers/DISS-85adOOd6-491d-4f56-e044-00144fd73934/DISS-85adOOd6-491d-4f56-e044-
00144fd73934 DISS-85adOOd6-491d-4f56-e044-00144fd73934.html.
ECOSAR (Ecological Structure Activity Relationship), Version 1.11. Washington, DC: U.S. Environmental Protection
Agency, http://www.epa.gov/oppt/newchems/tools/21ecosar.htm.
EPA (2005) Pollution prevention (P2) framework. Washington, DC: U.S. Environmental Protection Agency, Office of Pollution Prevention and
Toxics, http://www.epa.gov/opptintr/newchems/pubs/sustainable/p2frame-june05a2.pdf
EPA (2012) Using noncancer screening within the SF initiative. Washington, DC: U.S. Environmental Protection
Agency, http://www.epa.gov/oppt/sf/pubs/noncan-screen.htm.
EPI Estimation Programs Interface (EPI) Suite, Version 4.11. Washington, DC: U.S. Environmental Protection
Agency, http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm.
ESIS (2012) European chemical Substances Information System. European Commission, http://esis.jrc.ec.europa.eu/.
EU (2008a) 2,2-Bis(chloromethyl) trimethylene, bis[bis(2-chloroethyl) phosphate], (V6), CAS No: 38051-10-4, EINECS No: 253-760-2.
Summary risk assessment report. European Union. European Communities. European Chemicals
Agency, http://echa.europa.eu/documents/10162/c38476f5-ebfc-43b2-8800-83f04e623c74.
7-445
-------
EU (2008b) European Union risk assessment report: 2,2-Bis(Chloromethyl) trimethylene, bis[bis(2-chloroethyl) phosphate]. Risk assessment.
Final approved version. Luxembourg: European Union. European Communities. European Chemicals
Agency, http://www.echa.europa.eu/documents/10162/13630/trd rar Ireland tdcpen.pdf
Freudenthal RI, Henrich RT (2000) Chronic toxicity and carcinogenic potential of tris(l,3dichloro-2-propyl) phosphate in Sprague-Dawley rat. Int
JToxicol 19:119-125.
Kapp RW, Mossburg PA, Trutter JA, et al. (1981) Teratology study in rats. FR-2 (Fyrol). Final Report (1978). Toxicology reports on Fyrol FR-2
(volume I-II) with attachments and cover letter dated 020381. Prepared by Hazleton Laboratories America, Inc. for Stauffer Chemical Company.
Submitted to the U.S. Environmental Protection Agency under TSCA Section 8E, 57-103.
King FIH (1993) Evaluation of the mutagenic potential of Antiblaze 100 with 0.5% in the mouse lymphoma mutagenesis assay with cover letter
dated 081293 (sanitized). Submitted to the U.S. Environmental Protection Agency under TSCA.
Mill T (2000) Photoreactions in surface waters. In: Boethling R, Mackay D, eds. Handbook of Property Estimation Methods for Chemicals,
Environmental Health Sciences. Boca Raton: Lewis Publishers, 355-381.
Morey H, Frudentahl RI, Swigut T, et al. (1978) Summary of in vitro delayed neurotoxicity evaluation. Report T-6303. Toxicology reports on
Fyrol FR-2. Vol I of II. Submitted to the U.S. Environmental Protection Agency under TSCA Section 8E, 27-38.
OECD (2009) SIDS initial assessment profile 2,2-Bis(chloromethyl) trimethylene bis (Bis(2-chloroethyl)phosphate) (V6).
OncoLogic (2008) U.S. EPA and LogiChem, Inc. 2005, Version 7.0. 2008.
PBT Profiler Persistent (P), Bioaccumulative (B), and Toxic (T) Chemical (PBT) Profiler, Version 1.301. Washington, DC: U.S. Environmental
Protection Agency, www.pbtprofiler.net.
Wilczynski SI, Killinger JM, Zwicker GM, et al. (1983) Fyrol FR-2 fertility study in male rabbits. Toxicologist 3:22.
van der Veen I, de Boer J (2012) Phosphorus flame retardants: Properties, production, environmental occurrence, toxicity and analysis.
Chemosphere 88(10): 1119-115.
7-446
-------
Tricresyl phosphate (TCP)
Screening Level Toxicology Hazard Summary
This table contains hazard information for each chemical; evaluation of risk considers both hazard and exposure. Variations in end-of-life processes or degradation and combustion
by-products are discussed in the report but not addressed directly in the hazard profiles. The caveats listed below must be taken into account when interpreting the information in the
table.
VL = Very Low hazard L = Low hazard = Moderate hazard H = High hazard VH = Very High hazard - Endpoints in colored text (VL, L, M, H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].
Chemical
CASRN
Human Health Effects
+*
jy
o
H
4"^
d
^
'0
'g
O
^
c3
U
^
.y
o
o
g
O
|
u
•a
o
o.
o
sS
g
S
0
3
a
"3
u
"3
s
z
o
a
•a
•g
0)
g-
M
B
_o
.a
0)
C/5
1
C/5
>•> S
•_ _o
1 1
2 .a
S^'i
» j/j
a
_o
sS
•c
^s
0
1
hH
*c3
s
0)
Q
Aquatic
Toxicity
4"^
d
^
'a
U
Environmental
Fate
0)
u
s
• ^
4>
0.
B
O
"3
s
3
0
CO
Tricresyl phosphate (TCP)
This assessment also includes information for other methylated triphenyl phosphate isomers (phosphoric acid, bis(methylphenyl) phenyl ester (CASRN 26446-73-1) and
phosphoric acid, methylphenyl diphenyl ester (CASRN 26444-49-5)).
7-447
-------
Representative Structure
CASRN: 1330-78-5; 26446-73-1;
26444-49-5
MW: 368.37
MF:C2,H21O4P
Physical Forms: Liquid
Neat:
Use: Flame retardant
SMILES: O=P(Oclccc(C)ccl)(Oc2ccc(C)cc2)Oc3ccc(C)cc3 (Representative structure for tricresyl phosphate)
O=P(Oclccc(C)ccl)(Oc2ccc(C)cc2)Oc3ccccc3 (Representative structure for dicresyl phenyl phosphate)
O=P(Oclcccccl)(Oc2ccccc2)Oc3ccccc3C (Representative structure for monocresyl diphenyl phosphate)
Synonyms: TCP; Phosphoric acid, tris(methylphenyl) ester; Tritolyl phosphate; Phosphoric acid, tritolyl ester; Tri(methylphenyl) phosphate
Chemical Considerations: The alternative, tricresyl phosphate, may contain a mixture of methylated triphenyl phosphate isomers with an unspecified amount of
methyl substitution. The composition will be dependent on the manufacturing, purification and processing of the compound. Mono-o-cresyl and di-o-cresyl isomers
have well documented toxicity concerns. Efforts are made to minimize the amount of ortho-isomer present in commercial products, to amounts typically less than
0.4% (Weiner and Jortner, 1999). Therefore, preparations will consist mainly of meta- and para-substituted isomers (HSDB, 2013d). The isomers and components
expected to be present will be discussed in this report as appropriate when determining hazard designations. Test substance composition was not consistently reported
in the literature however a description of the test sample and isomer content is included in the data entries when available. Chemical, fate, and toxicity data for
components of the mixture represented by other CASRN were collected in the preparation of this AA and are listed below:
Phosphoric acid, tris(methylphenyl) ester (CASRN 1330-78-5)
tri-o-cresyl phosphate (CASRN 78-30-8)
tri-m-cresyl phosphate (CASRN 563-04-2)
tri-p-cresyl phosphate (CASRN 78-32-0)
phosphoric acid, bis(methylphenyl) phenyl ester (CASRN 26446-73-1)
p-cresyl diphenyl phosphate (CASRN 78-31-9)
2-methylphenyl diphenyl phosphate (CASRN 5254-12-6)
phenyl di(p-tolyl) phosphate (CASRN 34909-69-8)
phosphoric acid, 3-methylphenyl diphenyl ester (CASRN 69500-28-3)
(2,4-dimethylphenyl) diphenyl phosphate (CASRN 86864-87-1)
(2,3-dimethylphenyl) diphenyl phosphate (CASRN 25155-24-2)
diphenyl xylyl phosphate (CASRN 29660-68-2)
7-448
-------
• phosphoric acid, methylphenyl diphenyl ester (CASRN 26444-49-5)
Estimated values using representative structures as indicated in the SMILES section of this assessment, will be used to fill assessment data gaps. EPI v4.11 was used
to estimate physical/chemical and environmental fate values due to an absence of experimental data (Weiner and Jortner, 1999; EPA, 2010; van der Veen and de Boer,
2012; HSDB, 2013d).
• (2,5-dimethylphenyl) diphenyl phosphate (CASRN 73179-40-5)
• diphenyl 2,4,6-trimethylphenyl ester (CASRN 73179-43-8)
Polymeric: No
Oligomeric: Not applicable
Metabolites, Degradates and Transformation Products: Degradates include orthophosphate and phenolic moieties; phenol; p-cresyl p-carboxyphenyl phosphate; p-
hydroxybenzoic acid; di-p-cresyl phosphate; oxidized triesters di-p-cresyl p-carboxyphenyl phosphate and p-cresyl di-p-carboxyphenyl phosphate; p-hydroxybenzoic
acid; dicresylphosphate and cresol.
Metabolites: p-cresyl p-carboxyphenyl phosphate; p-hydroxybenzoic acid; di-p-cresyl phosphate; p-cresyl p-carboxyphenyl phosphate and the oxidized triesters; 2-(2-
cresyl)-4h-l-3-2-benzodioxaphosphorin-2-one (CASRN 1222-87-3) (Kurebayashi et al., 1985; WHO, 1990; NTP, 1994; Great Lakes Chemical Corporation, 2001;
van der Veen and de Boer, 2012; Schindler et al., 2013).
Analog: Tricresyl phosphate isomers and methyl substituted
phenyl phosphate esters anticipated to be present in the
commercial product were considered in this evaluation, as
described in the chemical considerations section.
Endpoint(s) using analog values: Not applicable
Analog Structure: Not applicable
Structural Alerts: Organophosphates; Neurotoxicity (EPA, 2012).
Risk Phrases: Not classified by Annex VI Regulation (EC) No 1272/2008 (ESIS, 2012).
Hazard and Risk Assessments: This alternative was included in a risk assessment prepared for phosphate ester flame retardants by the Agency for Toxic Substances
and Disease Registry. A screening level hazard characterization was prepared for tricresyl phosphate by EPA. HPV Data Summary, Test Plan, SIDS Initial
Assessment Profile and SIAM were completed for Diphenyl Cresyl Phosphate (OECD, 1998; Great Lakes Chemical Corporation, 2001; OECD-SIDS, 2002; EPA,
2010; ATSDR, 2012).
7-449
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
PHYSICAL/CHEMICAL PROPERTIES
Melting Point (°C)
Boiling Point (°C)
-33
(Measured)
-35
Crystallizing point (Measured)
-38
(Measured)
<-10
(Measured)
25.5
(Measured)
11
(Measured)
77
(Measured)
420
(Measured)
439
(Measured)
410
(Measured)
390
(Measured)
265
(Measured)
265 at lOmmHg
(Measured)
PhysProp, 2012
HSDB, 2013d
van der Veen and de Boer, 2012
OECD-SIDS, 2002
HSDB, 201 3b
PhysProp, 2012
van der Veen and de Boer, 2012
HSDB, 2013d
van der Veen and de Boer, 2012
PhysProp, 2012
HSDB, 201 3a
PhysProp, 2012
Aldrich, 1994
Reported in a secondary source.
Reported in a secondary source with
limited study details.
Reported in a secondary source for
cresyl diphenyl phosphate (CASRN
26444-49-5); purity not stated.
Reported for cresyl diphenyl
phosphate (CASRN 26444-49-5).
Reported for tri-m-cresyl phosphate
(CASRN 563-04-2).
Reported for tri-o-cresyl phosphate
(CASRN 78-30-8).
Limited study details and test method
not stated; inconsistent with other
values reported.
Reported in a secondary source, with
limited study details.
Reported in a secondary source; test
method not stated.
Reported for tri-o-cresyl phosphate
(CASRN 78-30-8).
Reported for cresyl diphenyl
phosphate (CASRN 26444-49-5).
Reported in a secondary source.
Similar values reported in other
sources at a reduced pressure.
Reported for a 90% mixture of
isomers at a reduced pressure.
7-450
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
Vapor Pressure (mm Hg)
Water Solubility (mg/L)
DATA
260 at 15 mmHg
(Measured)
241
Reported as a range 241-255°C at 0.533
hPa (Measured)
245
(Measured)
235
(Measured)
6xlO-7at25°C
(Extrapolated)
4.7xlO-6at25°C
(Measured)
1.46xlO-5at25°C
(Extrapolated)
<9xlO-7at25°C
Reported as <1.2xlO-4 Pa; OECD TG 104
Dynamic method (Measured)
0.003 at 150°C
Reported as 0.0044 hPa at 150°C
(Measured)
0.36 (Measured)
at 25 °C
0.24 (Measured)
REFERENCE
HSDB, 2013b
Great Lakes Chemical
Corporation, 200 1
OECD-SIDS, 2002
van der Veen and de Boer, 2012
PhysProp, 2012
PhysProp, 2012; van der Veen
and de Boer, 2012
PhysProp, 2012
OECD-SIDS, 2002
Great Lakes Chemical
Corporation, 200 1
Saeger et al., 1979 (as cited in
EPA, 2010; PhysProp, 2012;
HSDB, 2013d); van der Veen
and de Boer, 2012
PhysProp, 2012; van der Veen
and de Boer, 2012
DATA QUALITY
Reported for tri-m-cresyl phosphate
(CASRN 563-04-2) at a reduced
pressure.
Reported for tricresyl phosphate
(CASRN 1330-78-5) at a reduced
pressure.
Reported for cresyl diphenyl
phosphate (CASRN 26444-49-5).
Reported in a secondary source for
cresyl diphenyl phosphate (CASRN
26444-49-5) purity not stated.
Reported in a secondary source with
limited study details.
Reported in a secondary source for
cresyl diphenyl phosphate (CASRN
26444-49-5); purity not stated.
Reported for tri-o-cresyl phosphate
(CASRN 78-30-8).
Guideline study reported in a
secondary source for cresyl diphenyl
phosphate (CASRN 26444-49-5);
purity of test substance not indicated.
Reported in a secondary source at an
elevated temperature.
Nonguideline study reported for a
mixture of isomers; purity not stated.
Reported in a secondary source for
cresyl diphenyl phosphate (CASRN
7-451
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
Log Kow
DATA
0.15 (Measured)
0.1 (Measured)
at 25°C
2.4 (Measured)
Test method OECD TG 105; at 25°C
2.6 (Measured)
Reported as 0.0026 g/L at 25°C
5.11
(Measured)
5.9
(Measured)
4.51
(Measured)
3.7
Test method OECD TG 1 17; at 25°C
(Measured)
5.3
monocresyl diphenyl phosphate;
5.8
for dicresyl phenyl phosphate;
REFERENCE
PhysProp, 2012
HSDB, 2013d
OECD-SIDS, 2002
OECD-SIDS, 2002; HSDB,
2013a
Saeger et al., 1979 (as cited in
PhysProp, 2012; HSDB, 2013d);
van der Veen and de Boer, 2012
HSDB, 2013d; Great Lakes
Chemical Corporation, 200 1
Saeger et al., 1979 (as cited in
PhysProp, 2012; HSDB, 2013a);
van der Veen and de Boer, 2012
OECD-SIDS, 2002
EPIv4.11
DATA QUALITY
26444-49-5); purity not stated.
Reported for bis(methylphenyl)
phenyl phosphate (CASRN 26446-
73-1).
Reported in a secondary source;
purity and test method not stated.
Guideline study reported in a
secondary source for cresyl diphenyl
phosphate (CASRN 26444-49-5).
Purity of test substance not indicated.
Reported for cresyl diphenyl
phosphate (CASRN 26444-49-5); test
method and purity of substance not
indicated.
Nonguideline study on a mixture of
isomers, purity not stated.
Reported in a secondary source;
purity and test method not stated.
Reported in a secondary source for
cresyl diphenyl phosphate (CASRN
26444-49-5) for the commercial
product mixture Santicizer 140.
Guideline study reported in a
secondary source for cresyl diphenyl
phosphate (CASRN 26444-49-5);
purity of test substance not indicated.
Estimated using representative
structures indicated in the SMILES
section for methylated phenyl
phosphate with one, two and three
7-452
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
Flammability (Flash Point)
Explosivity
Pyrolysis
pH
pKa
DATA
6.3
for tricresyl phosphate (Estimated)
Flash point: 212°C (Measured)
Flash point: 232°C (Measured)
Auto flammability: 607°C (Measured)
Flash point: 225 °C closed cup (Measured)
Flash point: 242°C open cup (Measured)
Flash point: 240°C open cup (Measured)
Not expected to form explosive mixtures
with air (Estimated)
Not applicable (Estimated)
Not applicable (Estimated)
REFERENCE
van der Veen and de Boer, 2012
van der Veen and de Boer, 2012
Great Lakes Chemical
Corporation, 2001
Great Lakes Chemical
Corporation, 200 1
OECD-SIDS, 2002
OECD-SIDS, 2002
Professional judgment
Professional judgment
Professional judgment
DATA QUALITY
methyl substituent groups
respectively.
Reported in a secondary source for
cresyl diphenyl phosphate (CASRN
26444-49-5) with limited details.
Reported in a secondary source with
limited details.
Reported for tricresyl phosphate.
Reported for tricresyl phosphate.
Reported for cresyl diphenyl
phosphate (CASRN 26444-49-5).
Reported for cresyl diphenyl
phosphate (CASRN 26444-49-5).
No experimental data located; based
on its use as a flame retardant.
No data located.
Does not contain functional groups
that are expected to ionize under
environmental conditions.
Does not contain functional groups
that are expected to ionize under
environmental conditions.
7-453
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
HUMAN HEALTH EFFECTS
Toxicokinetics
Available information indicates that all three isomers of tricresyl phosphate are well absorbed following oral
and dermal exposure. TCP is widely distributed in tissues with highest concentrations in adipose tissue,
liver, kidneys, intestine, and stomach. Tri-p-cresyl metabolites were identified in blood, urine, feces, and
tissues of the rats up to 72 hours following oral administration. Oxidation that occurred in the liver and
hydrolysis in the intestine resulted in urinary metabolites that included hydroxybenzoic acid, di-p-cresyl
phosphate, and p-cresyl p-carboxyphenyl phosphate. Major metabolites found in the bile were dip-cresyl
phosphate, p-cresyl p-carboxyphenyl phosphate, and the oxidized triesters di-p-cresyl p-carboxyphenyl
phosphate and p-cresyl di-p-carboxyphenyl phosphate. The main fecal compound was the parent compound
(tri-p-cresyl phosphate). Elimination occurs through urine, feces and expiration. No information was located
regarding absorption, distribution, or excretion of inhaled tricresyl phosphate.
Dermal Absorption in vitro
No data located.
Absorption,
Distribution,
Metabolism &
Excretion
Oral, Dermal or Inhaled
Available information indicates that all
three isomers of tricresyl phosphate were
well absorbed following oral
administration to rats. Dermal application
of radiolabeled (14C)-tri-o-cresyl
phosphate to cats resulted in 28% and 20%
of the applied radioactivity being
recovered in urine and feces, respectively,
during 10 days post application; it was
stated that based on similarity of structure
and physical properties, other isomeric
tricresyl phosphate esters would likely
also be absorbed through the skin.
Following gavage administration of
radiolabeled (14C)-tri-p-cresyl phosphate
to rats, radioactivity was widely
distributed in the tissues at 24 hours with
highest concentrations in adipose tissue,
liver, kidneys, intestine, and stomach. At
72 hours, total internal radioactivity was
only 25% that observed at 24 hours.
Kurebayashi et al., 1985; NTP,
1994
Study details reported in reliable data
sources; Toxicokinetic data for
tricresyl phosphate (CASRN 1330-
78-5) mainly include results for the
tri-ortho isomer (CASRN 78-30-8)
and tri-para isomer (CASRN 78-32-
0), although limited information is
also available for the tri-meta isomer
(CASRN 563-04-2).
7-454
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
Other
DATA
Parent compound and p-cresyl p-
carboxyphenyl phosphate (a metabolite)
were present in liver at 24 hours post
dosing. Parent compound was also
detected in adipose tissue at 24 and 72
hours post dosing and at trace amounts in
the kidney at 72 hours post dosing. Tri-p-
cresyl metabolites were identified in
blood, urine, feces, and tissues of the rats
up to 72 hours following oral
administration; oxidation occurred in the
liver and hydrolysis in the intestine,
resulting in urinary metabolites that
included p-hydroxybenzoic acid, di-p-
cresyl phosphate, and p-cresyl p-
carboxyphenyl phosphate. Major
metabolites found in the bile were di-p-
cresyl phosphate, p-cresyl p-
carboxyphenyl phosphate, and the
oxidized triesters di-p-cresyl p-
carboxyphenyl phosphate and p-cresyl di-
p-carboxyphenyl phosphate. The main
fecal compound was the parent compound
(tri -p-cresyl phosphate). For 3 days post
dosing, expiratory excretion of 14CO2
amounted to 18% of the total radioactivity.
No information was located regarding
absorption, distribution, or excretion of
inhaled tricresyl phosphate.
REFERENCE
DATA QUALITY
No data located.
7-455
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
Acute Mammalian Toxicity
Acute Lethality
Oral
DATA
REFERENCE
DATA QUALITY
MODERATE: Based on an oral LD50 of 1,160 mg/kg in rats exposed to tri-o-cresyl phosphate (CASRN 78-
30-8). Acute toxicity values for the dermal and inhalation routes of exposure indicate a LOW hazard
concern.
Rat oral LD50 = 1,160 mg/kg bw
Rabbit oral LD50 >3,000 mg/kg bw
Rabbit oral LD50 >3,000 mg/kg bw
Mouse oral LD50 = 3,900 mg/kg bw
Rat oral LD50 >4,640 mg/kg/bw
Rat oral LD50 = 5,190 mg/kg bw
Rat oral LD50 = 6,400 mg/kg bw
Rat oral LD50 = 8,400 mg/kg bw
WHO, 1990
WHO, 1990
WHO, 1990
WHO, 1990
WHO, 1990
WHO, 1990
OECD-SIDS, 2002
Johannsen et al., 1977
Limited study details reported in a
secondary source; test substance: Tri-
o-cresyl phosphate (CASRN 78-30-
8).
Limited study details reported in a
secondary source; test substance: Tri-
p-cresyl phosphate (CASRN 78-32-
0).
Limited study details reported in a
secondary source; test substance: Tri-
m-cresyl phosphate (CASRN 563-04-
2).
Limited study details reported in a
secondary source; test substance:
Tricresyl phosphate (mixed isomers);
CASRN 1330-78-5.
Limited study details reported in a
secondary source; Test substance:
Tricresyl phosphate (mixed isomers);
CASRN 1330-78-5).
Limited study details reported in a
secondary source; Test substance:
tricresyl phosphate (mixed isomers);
CASRN 1330-78-5.
Limited study details reported in a
secondary source; test substance:
Diphenyl cresyl phosphate (CASRN
26444-49-5).
Limited study details reported in a
7-456
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Dermal
Inhalation
Single gavage dose (in corn oil) followed
by 14-day observation
primary source; test substance: Tri-o-
cresyl phosphate (CASRN 78-30-8).
Rat oral LD50 = 10,400 mg/kg bw
Johannsen et al., 1977
Limited study details reported in a
primary source; test substance: Cresyl
diphenyl phosphate (CASRN 26444-
49-5).
Rat oral LD50 range 15,750-31,320 mg/kg
bw
Single gavage dose; 14-day observation
Great Lakes Chemical
Corporation, 2001; EPA, 2010;
ATSDR,2012
Results summarized in reliable
secondary sources; Test substance:
Phosphoric acid,
tris(methylphenyl)ester (CASRN
1330-78-5).
Rabbit dermal LD50 = 3,700 mg/kg bw
24-hour occluded dermal application
followed by rinsing and 14-day
observation
Johannsen et al., 1977
Limited study details reported in a
primary source; test substance: Tri-o-
cresyl phosphate (CASRN 78-30-8).
Dermal LD50 >5,000 and <20,000 mg/kg
Single dermal application followed by 14-
day observation period
Great Lakes Chemical
Corporation, 2001; EPA, 2010;
ATSDR,2012
Limited study details reported in a
secondary sources; Test substance:
Phosphoric acid,
tris(methylphenyl)ester (CASRN
1330-78-5).
Rabbit dermal LD50 >5,000 mg/kg bw
Single 24-hour occluded application
followed by rinsing and 14-day
observation
Johannsen et al., 1977
Limited study details reported in a
primary source; test substance: Cresyl
diphenyl phosphate (CASRN 26444-
49-5).
Rabbit dermal LD50 >7,900 mg/kg bw
Single gavage dose (in corn oil) followed
by 14-day observation period
Johannsen et al., 1977
Limited study details reported in a
primary source; test substance:
Tricresyl phosphate (mixed isomers);
CASRN 1330-78-5.
Rat 4-hour LC50 >5.2 mg/L
Ten rats/sex exposed to tricresyl
phosphate aerosol at 5.2 mg/L for 4 hours,
observed for 14 days post exposure
Great Lakes Chemical
Corporation, 2001; EPA, 2010
Study considered valid without
restriction by secondary source; test
substance: Tricresyl phosphate
(CASRN 1330-78-5).
7-457
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
Carcinogenicity
OncoLogic Results
Carcinogenicity (Rat and
Mouse)
Combined Chronic
Toxicity/Carcinogenicity
DATA
No deaths
Rats, mice, guinea pigs; no deaths
Test conditions: 6-hour exposure to 3,530
mg/m3 vapors followed by 14-day
observation period
LC50>3.5mg/L
REFERENCE
ATSDR,2012
DATA QUALITY
Limited study details reported in a
reliable secondary source; Test
substance: Phosphoric acid,
tris(methylphenyl)ester (CASRN
1330-78-5).
LOW: Based on no evidence of Carcinogenicity in rats or mice following dietary exposure to a commercial
mixture of tricresyl phosphate for 2-years.
2-Year dietary study in Fischer 344/N rats
(95/sex/concentration)
Test substance concentrations: 0, 75, 150,
300 ppm (approximately 0, 3, 6, and 13
mg/kg bw-day for males and 0, 4, 7, and
15 mg/kg bw-day for females)
Chronic toxicity: NOAEL =13 mg/kg bw-
day (males); 4 mg/kg bw-day for females
LOAEL = 26 mg/kg bw-day (males) and 7
mg/kg bw-day (females) for cytoplasmic
vacuolization of adrenal cortex
No evidence of carcinogenic activity
2-Year dietary study in B6C3F1 mice
(95/sex/concentration)
Test substance concentrations: 0, 60, 125,
250 ppm (approximately 0, 7, 13, and 27
mg/kg bw-day for males and 0, 8, 18, and
37 mg/kg bw-day for females)
chronic toxicity NOAEL =18 mg/kg bw-
day for females, not established for males
NTP, 1994
NTP, 1994
No data located.
No data located.
Study details reported in a reliable
primary source; test substance:
Tricresyl phosphate (CASRN 1330-
78-5) as a commercial product
comprised of 18% dicresyl phosphate
esters (unconfirmed isomeric
composition) and 79% tricresyl
phosphate esters (21% confirmed as
tri-m-cresyl phosphate, 4% as tri-p-
cresyl phosphate, and no detectable
tri-o-cresyl phosphate [<0.1%]).
Study details reported in a reliable
primary source; test substance:
Tricresyl phosphate (CASRN 1330-
78-5) as a commercial product
comprised of 18% dicresyl phosphate
esters (unconfirmed isomeric
composition) and 79% tricresyl
phosphate esters (21% confirmed as
7-458
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
Other
Genotoxicity
Gene Mutation in vitro
Gene Mutation in vivo
DATA
LOAEL: 7 mg/kg bw-day (males) and 37
mg/kg bw-day (females) for ceroid
pigmentation of adrenal cortex
No evidence of carcinogenic activity
REFERENCE
DATA QUALITY
tri-m-cresyl phosphate, 4% as tri-p-
cresyl phosphate, and no detectable
tri-o-cresyl phosphate [<0.1%]).
No data located.
LOW: Based on negative results for gene mutations in bacteria after treatment with mixed isomers of cresyl
diphenyl phosphate or a commercial formulation of tricresyl phosphate and negative results for
chromosomal aberrations in CHO cells in vitro after treatment with tricresyl phosphate as a commercial
formulation. Negative results were also reported in a micronucleus test in Crj:BDFl mice treated with
commercial diphenyl cresyl phosphate by gavage.
Salmonella typhimurium strains TA98,
TA100, TA1535, TA1537 treated with or
without metabolic activation
Test substance concentrations: 100-10,000
micrograms/plate
Negative- test substance not mutagenic
with or without metabolic activation
Salmonella typhimurium strains TA98,
TA100, TA1535, TA1537 treated with or
without metabolic activation
Test substance concentrations: 100-10,000
micrograms/plate
Negative; test substance not mutagenic
with or without metabolic activation
Zeigeretal., 1987
NTP, 1994
Study details reported in a reliable
primary source; test substance: Cresyl
diphenyl phosphate (CASRN 26444-
49-5; mixed isomers).
Study details reported in a reliable
primary source; test substance:
Tricresyl phosphate (CASRN 1330-
78-5) as a commercial product
comprised of 18% dicresyl phosphate
esters (unconfirmed isomeric
composition) and 79% tricresyl
phosphate esters (21% confirmed as
tri-m-cresyl phosphate, 4% as tri-p-
cresyl phosphate, and no detectable
tri-o-cresyl phosphate [<0.1%]).
No data located.
7-459
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Chromosomal Aberrations in
vitro
CHO cells treated with or without
metabolic activation
Test substance concentrations: 50-5,000
micrograms/mL
Negative; test substance did not cause
chromosomal aberrations
NTP, 1994
CHO cells treated with or without
metabolic activation
Test substance concentrations: 0.05-16
micrograms/mL
Negative; test substance did not cause
sister chromatid exchanges
NTP, 1994
Chromosomal Aberrations in
vivo
DNA Damage and Repair
Other
Micronucleus test in Crj:BDFl mice
(5/sex) treated by single gavage
Test substance concentrations: 0, 312.5,
625, 1250 mg/kg bw (in olive oil)
Negative- test substance did not cause
micronucleated polychromatic
erythrocytes in bone marrow
OECD-SIDS, 2002
Study details reported in a reliable
primary source; test substance:
Tricresyl phosphate (CASRN 1330-
78-5) as a commercial product
comprised of 18% dicresyl phosphate
esters (unconfirmed isomeric
composition) and 79% tricresyl
phosphate esters (21% confirmed as
tri-m-cresyl phosphate, 4% as tri-p-
cresyl phosphate, and no detectable
tri-o-cresyl phosphate [<0.1%]).
Study details reported in a reliable
primary source; test substance:
Tricresyl phosphate (CASRN 1330-
78-5) as a commercial product
comprised of 18% dicresyl phosphate
esters (unconfirmed isomeric
composition) and 79% tricresyl
phosphate esters (21% confirmed as
tri-m-cresyl phosphate, 4% as tri-p-
cresyl phosphate, and no detectable
tri-o-cresyl phosphate [<0.1%]).
No data located.
No data located.
Study details reported in a secondary
source; conducted according to
OECD Test Guideline 474; test
substance: Commercial diphenyl
cresyl phosphate (CASRN 26444-49-
5; purity 41.9%).
7-460
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Reproductive Effects
HIGH: Based on a LOAEL of 7 mg/kg-day for ovarian interstitial cell hyperplasia (NOAEL = 4 mg/kg-day)
in female rats following a 2-year dietary exposure to tricresyl phosphate as a commercial mixture. A 13-
week oral (gavage) exposure to the same tricresyl phosphate mixture resulted in ovarian interstitial cell
vacuolization in both rats and mice at a dose of 50 mg/kg-day. Thirteen weeks of dietary exposure to the
tricresyl phosphate commercial mixture caused an increased incidence of interstitial cell hypertrophy in rats
at 55 mg/kg-day, and ovarian interstitial cell vacuolization in mice at 530 mg/kg-day.
Decreased sperm motility was reported in Fl mice that consumed a commercial tricresyl phosphate mixture
from the diet at an estimated dose of 62.5 mg/kg-day and whose parents had been exposed at the same
estimated dose during mating, gestation, and lactation in a continuous breeding dietary study; cross-over
matings at an estimated dose of 250 mg/kg-day revealed decreased numbers of live pups per litter from
matings of treated females to control males and treated males to control females. In a 1-generation study of
rats, abnormal sperm morphology was also noted following gavage dosing of commercial tricresyl phosphate
at 100 mg/kg-day).
Decreased fertility was reported in rats following gavage administration of a commercial diphenyl cresyl
phosphate mixture at 300 mg/kg-day (NOAEL = 60 mg/kg-day) during premating, mating, gestation, and
parturition. Decreased testicular and epididymal weights and increased ovarian weights were observed in
rats administered a hydraulic fluid (tricresyl phosphate being the major component) at 400 mg/kg-day from
7 days prior to breeding and throughout 63 days of continuous breeding and 28 days post breeding.
Reproduction/Developmental
Toxicity Screen
Combined Repeated Dose with
Reproduction/ Developmental
Toxicity Screen
Reproduction and Fertility
Effects
Continuous breeding protocol using
dietary exposure of CD-I mice (40
breeding pairs in control group, 20
breeding pairs in treatment group)
Test substance concentrations: 0, 0.05,
0.1, and 0.2% tricresyl phosphate by
weight (continuous breeding phase doses
estimated to have been 0, 62.5, 124, and
250 mg/kg-day, respectively); control and
0.2% dose level used for cross-over
No data located.
No data located.
Chapinetal., 1988
Well-designed study that followed a
continuous breeding protocol; test
substance: Tricresyl phosphate
(CASRN 1330-78-5); composed of
74.9% tricresyl phosphate (consisting
of mixed isomers and 20.6% pure m-
cresyl, 3.9% pure para-cresyl, and
<0.1% pure o-cresyl isomers), with
the remainder composed of dicresyl
phenyl and di- and tricresylxylyl
7-461
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
mating phase
Test substance treatment period:
Continuous breeding phase included 98
days (7 days prior to breeding); cross-over
mating phase included 7 days prior to
breeding; an additional 7 days of
cohabitation treatment (males and
females) and throughout gestation
(females); last Fl litter of mice continued
on treatment of their parents until sexual
maturity (postpartum day 74), throughout
a 1-week cohabitation period with mice of
the same dose group, and necropsied 3
weeks later for assessment of litters and
treatment-related gross and
histopathological effects
Continuous breeding phase results:
Significantly decreased fertility at 124 and
250 mg/kg-day; decreased sperm motility
in Fl males at 62.5 mg/kg-day
Cross-over mating phase results:
Significantly decreased numbers of live
pups per litter in treated male X control
female and treated female X control male
groups; significantly decreased proportion
of pups born alive in control male X
treated female group
NOAEL: Not established
LOAEL: 62.5 mg/kg-day (based on
decreased sperm motility in F 1 males)
One-generation oral (gavage) reproductive
toxicity study in Long-Evans rats (12
REFERENCE
Carlton et al., 1987
DATA QUALITY
phosphates;
Tricresyl phosphate doses were
estimated for the FO parental mice;
the LOAEL of 62.5 mg/kg bw-day
for decreased sperm motility in Fl
males assumes that the dose to the
growing and mating Fl males was the
same as that of their parents. EPAHC,
2010 reported a LOAEL of 62.5
mg/kg bw-day for significantly
decreased number of litters/pair in the
continuous breeding phase; however,
the study report noted significantly
"increased" number of litters/pair
(5.06 versus 4.87 in controls). The
LOAEL for the continuous breeding
phase should be the mid-dose level
(124 mg/kg bw-day) based on
significantly increased numbers of
dead pups in the 4th and 5th litters
and decreased live pup body weight;
a NOAEL of 62.5 mg/kg bw-day was
identified for the continuous breeding
phase of the study.
Study details reported in a primary
source; test substance: Tricresyl
7-462
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
males/dose, 24 females/dose)
Test substance doses (in corn oil): 0, 100,
200 mg/kg/day for males; 0, 200, 400
mg/kg-day for females
Dosing period: 56 days prior to mating
and during 10 days of mating for males;
14 days prior to mating and through 10
days of mating, gestation, and lactation for
females
Significantly increased percent abnormal
sperm in 100 and 200 mg/kg-day males;
decreased sperm concentration, motility
and progressive movement and minimal-
to-mild significantly increased
histopathologic lesions in testes and
epididymides of 200 mg/kg-day males;
dose-related severely decreased litter size
in both groups of dosed females
NOAEL: Not established
LOAEL: 100 mg/kg bw-day based on
abnormal sperm morphology
phosphate (CASRN 1330-78-5);
composition: <9% tri-o-cresyl
phosphate and remainder a mixture of
tri-p-, and tri-m-cresyl phosphate and
other tri-cresyl isomers.
Repeated-dose gavage study of male and
female Crj:CD (SD) rats (10/group)
administered commercial diphenyl cresyl
phosphate (CASRN 26444-49-5; purity
41.9%) for approximately 45 consecutive
days (14 days premating, mating,
gestation, until postpartum day 3).
Dose levels: 0, 12, 60, 300 mg/kg bw-day
NOAEL: 60 mg/kg bw-day
LOAEL: 300 mg/kg bw-day for decreased
OECD, 1998; OECD-SIDS,
2002
Study details reported in a secondary
source; conducted according to
OECD guidelines for a Combined
Repeated Dose and
Reproductive/Developmental
Screening Toxicity Test; test
substance: commercial diphenyl
cresyl phosphate (CASRN 26444-49-
5; purity 41.9%).
7-463
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
fertility
Modified continuous breeding protocol
using gavage treatment in F344 rats (40
breeding pairs in control group, 20
breeding pairs in treatment group)
Test substance concentrations: 0, 400
mg/kg-day (served as positive control for
a butylated triphenyl phosphate-containing
hydraulic fluid)
Treatment period: 98 days including 7
days prior to breeding period, 63-day
breeding period, 28-day postbreeding
period; a second phase (cross-over mating)
included a 28-day treatment period
Severely decreased numbers of test
substance-treated breeding pairs delivering
litters (9/20, 0/20, and 0/20 pairs
delivering litters 1, 2, and 3, respectively,
compared to 40/40, 39/40, and 28/40
control pairs) Cross-over mating trials
resulted in 0% fertility among the test-
substance-treated males, but no apparent
effect on test substance-treated females
Test substance-treated rats exhibited
significantly decreased testicular and
epididymal weights and increased ovarian
weights
NOAEL: Not established
LOAEL: 400 mg/kg bw-day (only dose
tested) based on severely decreased
numbers of breeding pairs delivering
litters, decreased testicular and epididymal
Latendresse et al., 1994
Study details reported in a primary
source; only one dose tested; test
substance: A mixture of compounds
in a hydraulic fluid of which tricresyl
phosphate (CASRN 1330-78-5) was a
major component; the test substance
was composed of mostly p- and o-
tricresyl phosphate isomers (62% by
weight), cresyl-xylyl (18% by
weight), and cresyl-ethyl-phenyl
phosphates (18% by weight).
7-464
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Other
weights, increased ovarian weight
2-Year dietary study in Fischer 344/N rats
(95/sex/concentration)
Test substance concentrations: 0, 75, 150,
300 ppm (approximately 0, 3, 6, and 13
mg/kg bw-day for males and 0, 4, 7, and
15 mg/kg bw-day for females)
NOAEL: 4 mg/kg bw-day (females)
LOAEL: 7 mg/kg bw-day for ovarian
interstitial cell hyperplasia
NTP, 1994
13-Week gavage study in B6C3F1 mice
(10/sex/dose)
Test substance concentrations: 0, 50, 100,
200, 400, 800 mg/kg bw-day (in corn oil)
Dosing frequency: Ix/d, 5d/w
NOAEL: not established
LOAEL: 50 mg/kg bw-day for ovarian
interstitial cell vacuolization
NTP, 1994
13-Week gavage study in Fischer 344/N
rats (10/sex/dose)
Test substance concentrations: 0, 50, 100,
200, 400, 800 mg/kg bw-d (in corn oil)
Dosing frequency: Ix/d, 5d/w
NOAEL: not established
LOAEL: 50 mg/kg bw-day for ovarian
interstitial cell vacuolization
NTP, 1994
13-Week dietary study in Fischer 344/N
rats (10/sex/dose)
NTP, 1994
Reliable NTP study; test substance:
Tricresyl phosphate (CASRN 1330-
78-5) as a commercial product
comprised of 18% dicresyl phosphate
esters (unconfirmed isomeric
composition) and 79% tricresyl
phosphate esters (21% confirmed as
tri-m-cresyl phosphate, 4% as tri-p-
cresyl phosphate, and no detectable
tri-o-cresyl phosphate [<0.1%]).
Reliable NTP study; test substance:
Tricresyl phosphate (CASRN 1330-
78-5) as a commercial product
comprised of 18% dicresyl phosphate
esters (unconfirmed isomeric
composition) and 79% tricresyl
phosphate esters (21% confirmed as
tri-m-cresyl phosphate, 4% as tri-p-
cresyl phosphate, and no detectable
tri-o-cresyl phosphate [<0.1%]).
Reliable NTP study; test substance:
Tricresyl phosphate (CASRN 1330-
78-5) as a commercial product
comprised of 18% dicresyl phosphate
esters (unconfirmed isomeric
composition) and 79% tricresyl
phosphate esters (21% confirmed as
tri-m-cresyl phosphate, 4% as tri-p-
cresyl phosphate, and no detectable
tri-o-cresyl phosphate [<0.1%]).
Reliable NTP study; test substance:
Tricresyl phosphate (CASRN 1330-
7-465
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Test substance concentrations: 0, 900,
1700, 3300, 6600, 13,000 ppm
(approximately 0, 55, 120, 220, 430, and
750 mg/kg bw-day for males and 0, 65,
120, 230, 430, and 770 mg/kg bw-day for
females)
NOAEL: not established
LOAEL: 55 mg/kg bw-day for ovarian
interstitial cell hypertrophy
78-5) as a commercial product
comprised of 18% dicresyl phosphate
esters (unconfirmed isomeric
composition) and 79% tricresyl
phosphate esters (21% confirmed as
tri-m-cresyl phosphate, 4% as tri-p-
cresyl phosphate, and no detectable
tri-o-cresyl phosphate [<0.1%]).
13-Week dietary study in B6C3F1 mice
(10/sex/concentration)
Test substance concentrations: 0, 250,
500, 1,000, 2,100, 4,200 ppm
(approximately 0, 45, 110, 180, 380, and
900 mg/kg bw-day for males and 0, 65,
130, 230, 530, and 1,050 mg/kg bw-day
for females)
NOAEL: 230 mg/kg bw-day
LOAEL: 530 mg/kg bw-day for ovarian
interstitial cell vacuolization
NTP, 1994
Reliable NTP study; test substance:
Tricresyl phosphate (CASRN 1330-
78-5) as a commercial product
comprised of 18% dicresyl phosphate
esters (unconfirmed isomeric
composition) and 79% tricresyl
phosphate esters (21% confirmed as
tri-m-cresyl phosphate, 4% as tri-p-
cresyl phosphate, and no detectable
tri-o-cresyl phosphate [<0.1%]).
Developmental Effects
MODERATE: Based on increased numbers of dead Fl pups per litter were reported among CD-I mice
receiving commercial tricresyl phosphate from the diet at an estimated dose of 124 mg/kg-day (NOAEL =
62.5 mg/kg-day) in a continuous breeding protocol. Decreases in litter size and postnatal pup survival were
also reported in a one-generation reproductive toxicity study of rats gavaged at 200 mg/kg-day (lowest dose
tested) during premating and mating (males and females) and gestation and lactation (females).
There were no data located for the developmental neurotoxicity endpoint.
Reproduction/ Developmental
Toxicity Screen
Combined Repeated Dose with
Reproduction/ Developmental
Toxicity Screen
No data located.
No data located.
7-466
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Prenatal Development
Continuous breeding protocol using
dietary exposure of CD-I mice (40
breeding pairs in control group, 20
breeding pairs in treatment group)
Test substance concentrations: 0, 0.05,
0.1, and 0.2% tricresyl phosphate by
weight (continuous breeding phase doses
estimated to have been 0, 62.5, 124, and
250 mg/kg-day, respectively); control and
0.2% dose level used for cross-over
mating phase
Test substance treatment period:
Continuous breeding phase included 98
days (7 days prior to breeding); cross-over
mating phase included 7 days prior to
breeding; an additional 7 days of
cohabitation treatment (males and
females) and throughout gestation
(females); last Fl litter of mice continued
on treatment of their parents until sexual
maturity (postpartum day 74), throughout
a 1-week cohabitation period with mice of
the same dose group, and necropsied 3
weeks later for assessment of litters and
treatment-related gross and
histopathological effects
Continuous breeding phase results:
Significantly decreased fertility at 124 and
250 mg/kg bw-day
Cross-over mating phase results:
Significantly decreased numbers of live
pups per litter in treated male X control
female and treated female X control male
groups; significantly decreased proportion
Chapinetal., 1988
Well-designed study that followed a
continuous breeding protocol; test
substance: Tricresyl phosphate
(CASRN 1330-78-5); composed of
74.9% tricresyl phosphate (consisting
of mixed isomers and 20.6% pure m-
cresyl, 3.9% pure para-cresyl, and
<0.1% pure o-cresyl isomers), with
the remainder composed of dicresyl
phenyl and di- and tricresylxylyl
phosphates; Tricresyl phosphate
doses were estimated for the FO
parental mice; the LOAEL of 62.5
mg/kg bw-day for decreased sperm
motility in Fl males assumes that the
dose to the growing and mating Fl
males was the same as that of their
parents. EPAHC, 2010 reported a
LOAEL of 62.5 mg/kg bw-day for
significantly decreased number of
litters/pair in the continuous breeding
phase; however, the study report
noted significantly "increased"
number of litters/pair (5.06 versus
4.87 in controls). The LOAEL for the
continuous breeding phase should be
the mid-dose level (124 mg/kg bw-
day) based on significantly increased
numbers of dead pups in the 4th and
5th litters and decreased live pup
body weight; a NOAEL of 62.5
mg/kg bw-day was identified for the
continuous breeding phase of the
study.
7-467
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
of pups born alive in control male X
treated female group
NOAEL: 62.5 mg/kg bw-day
LOAEL: 124 mg/kg bw-day based on
increased number of dead Fl pups/litter
One-generation oral (gavage) reproductive
toxicity study in Long-Evans rats (12
males/dose, 24 females/dose)
Test substance doses (in corn oil): 0, 100,
200 mg/kg-day for males; 0, 200, 400
mg/kg-day for females
Dosing period: 56 days prior to mating
and during 10 days of mating for males;
14 days prior to mating and through 10
days of mating, gestation, and lactation for
females
Dose-related severely decreased litter size
and decreased postnatal pup viability in
both groups of dosed females
NOAEL: Not established
LOAEL: 200 mg/kg bw-day based on
decreased litter size and postnatal pup
viability (lowest dose tested)
Carlton et al., 1987
Study details reported in a primary
source; test substance: Tricresyl
phosphate (CASRN 1330-78-5);
composition: <9% tri-o-cresyl
phosphate and remainder a mixture of
tri-p-, and tri-m-cresyl phosphate and
other tri-cresyl isomers.
Modified continuous breeding protocol
using gavage treatment in F344 rats (40
breeding pairs in control group, 20
breeding pairs in treatment group)
Test substance concentrations: 0, 400
mg/kg-day (served as positive control for
a butylated triphenyl phosphate-containing
hydraulic fluid)
Latendresse et al., 1994
Study details reported in a primary
source; only one dose tested; Test
substance: A mixture of compounds
in a hydraulic fluid of which tricresyl
phosphate (CASRN 1330-78-5) was a
major component; the test substance
was composed of mostly p- and o-
tricresyl phosphate isomers (62% by
7-468
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
Postnatal Development
Prenatal and Postnatal
Development
Developmental Neurotoxicity
Other
DATA
Treatment period: 98 days including 7
days prior to breeding period, 63-day
breeding period, 28-day postbreeding
period; a second phase (cross-over mating)
included a 28-day treatment period
Severely decreased numbers of test
substance-treated breeding pairs delivering
litters (9/20, 0/20, and 0/20 pairs
delivering litters 1, 2, and 3, respectively,
compared to 40/40, 39/40, and 28/40
control pairs)
NOAEL: Not established
LOAEL: 400 mg/kg bw-day (only dose
tested) based on reduced number of live
pups/litter
Uncertain concern for developmental
neurotoxicity based on the potential for
Cholinesterase (ChE) inhibition in dams
that may result in alterations of fetal
neurodevelopment (Estimated)
REFERENCE
Professional judgment
DATA QUALITY
weight), cresyl-xylyl (18% by
weight), and cresyl-ethyl-phenyl
phosphates (18% by weight).
No data located.
No data located.
Estimated based on a structural alert
for organophosphates for the
neurotoxicity endpoint.
No data located.
7-469
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Neurotoxicity
MODERATE: Multifocal axonal degeneration was observed in spinal nerve preparations from female mice
administered commercial tricresyl phosphate by gavage once per day, 5 days/week for 13 weeks at 100
mg/kg-day; at a dose level of 200 mg/kg-day, male and female rats exhibited decreased grip strength and
degenerative effects in spinal cord and sciatic nerve preparations. NOAELs of 100 and 50 mg/kg-day were
identified for neurotoxicity of males and females, respectively. Similar effects were reported following a 13-
week dietary study with the same commercial product in mice and rats, albeit at dietary concentrations
resulting in higher estimated oral doses (>750 mg/kg-day for rats and >380 mg/kg-day for mice)
Tri-o-cresyl phosphate and other organophosphorus compounds cause a delayed neuropathy that has been
termed organophosphate-induced delayed neurotoxicity (OPIDN). Neurological symptoms are typically
delayed by 1-3 weeks after initial exposure and begin to be expressed as ataxia and progressive development
of paralysis of hind limbs; partial recovery may follow. Chickens and cats are particularly sensitive to
organophosphate-induced OPIDN.
Tri-o-cresyl phosphate occurs as a contaminant in commercial tricresyl phosphate mixtures, but usually in
concentrations of <1%.
Neurotoxicity Screening
Battery (Adult)
Other
13-Week gavage study in B6C3F1 mice
(10/sex/dose)
Test substance concentrations: 0, 50, 100,
200, 400, 800 mg/kg bw-day (in corn oil)
Dosing frequency: Ix/d, 5d/w
NOAEL (males): 100 mg/kg bw-day
LOAEL (males): 200 mg/kg bw-day for
decreased fore- and hind limb grip
strength and degeneration in spinal cord
and sciatic nerve
NOAEL (females): 50 mg/kg bw-day
LOAEL (females): 100 mg/kg bw-day for
multifocal axonal degeneration in spinal
cord
NTP, 1994
No data located.
Reliable study, although not designed
to comprehensively assess
neurological endpoints; test
substance: Tricresyl phosphate
(CASRN 1330-78-5) as a commercial
product comprised of 18% dicresyl
phosphate esters (unconfirmed
isomeric composition) and 79%
tricresyl phosphate esters (21%
confirmed as tri-m-cresyl phosphate,
4% as tri-p-cresyl phosphate, and no
detectable tri-o-cresyl phosphate
[<0.1%]). In addition to the identified
LOAEL of 100 mg/kg bw-day for
multifocal axonal degeneration in the
spinal cord of female mice,
significantly decreased grip strength
7-470
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
13-Week dietary study in Fischer 344/N
rats (10/sex/dose)
Test substance concentrations: 0, 900,
1700, 3300, 6600, 13,000 ppm
(approximately 0, 55, 120, 220, 430, and
750 mg/kg bw-day for males and 0, 65,
120, 230, 430, and 770 mg/kg bw-day for
females)
NOAEL (males): 430 mg/kg bw-day
LOAEL (males): 750 mg/kg bw-day for
reduced hind limb grip strength
NOAEL (females): 770 mg/kg bw-day
(highest dose tested)
LOAEL (females): Not established
NTP, 1994
13-Week dietary study in B6C3F1 mice
(10/sex/concentration)
Test substance concentrations: 0, 250,
500, 1,000, 2,100, 4,200 ppm
(approximately 0, 45, 110, 180, 380, and
900 mg/kg bw-day for males and 0, 65,
130, 230, 530, and 1,050 mg/kg bw-day
for females)
NOAEL (males): 180 mg/kg bw-day
(males)
NTP, 1994
was observed at doses > 200 mg/kg
bw-day as well. Degeneration in
spinal cord and sciatic nerve
preparations was noted in male and
female mice at doses > 200 mg/kg
bw-day.
Reliable study, although not designed
to comprehensively assess
neurological endpoints; test
substance: Tricresyl phosphate
(CASRN 1330-78-5) as a commercial
product comprised of 18% dicresyl
phosphate esters (unconfirmed
isomeric composition) and 79%
tricresyl phosphate esters (21%
confirmed as tri-m-cresyl phosphate,
4% as tri-p-cresyl phosphate, and no
detectable tri-o-cresyl phosphate
[<0.1%]). Histopathologic
evaluations of spinal cord and sciatic
nerve preparations revealed no signs
of degenerative effects at any dose.
Reliable study, although not designed
to comprehensively assess
neurological endpoints; test
substance: Tricresyl phosphate
(CASRN 1330-78-5) as a commercial
product comprised of 18% dicresyl
phosphate esters (unconfirmed
isomeric composition) and 79%
tricresyl phosphate esters (21%
confirmed as tri-m-cresyl phosphate,
4% as tri-p-cresyl phosphate, and no
7-471
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
LOAEL (males): 380 mg/kg bw-day for
reduced forelimb grip strength
NOAEL (females): 230 mg/kg bw-day
LOAEL (females): 530 mg/kg bw-day for
reduced fore- and hind limb grip strength
13-Week gavage study in Fischer 344/N
rats (10/sex/dose)
Test substance concentrations: 0, 50, 100,
200, 400, 800 mg/kg bw-day (in corn oil)
Dosing frequency: Ix/d, 5d/w
Neurological endpoints included fore- and
hind limb grip strength and
histopathological evaluations of spinal
cord and sciatic nerve
NOAEL: 800 mg/kg bw-day (highest dose
tested)
LOAEL: Not established
NTP, 1994
detectable tri-o-cresyl phosphate
[<0.1%]). Histopathologic evaluation
of spinal cord and sciatic nerve
preparations revealed degenerative
effects at 530 and 1,050 mg/kg bw-
day in females and 900 mg/kg bw-
day in males.
Reliable study, although not designed
to comprehensively assess
neurological endpoints; test
substance: Tricresyl phosphate
(CASRN 1330-78-5) as a commercial
product comprised of 18% dicresyl
phosphate esters (unconfirmed
isomeric composition) and 79%
tricresyl phosphate esters (21%
confirmed as tri-m-cresyl phosphate,
4% as tri-p-cresyl phosphate, and no
detectable tri-o-cresyl phosphate
[<0.1%]). There were no effects on
grip strength or histopathology of
spinal cord or sciatic nerve of treated
male rats. Reported decreased hind
limb grip strength in female rats at
400- and 800 mg/kg bw-day was of
small magnitude (12 and 14% less,
respectively, than controls).
Furthermore, the 800 mg/kg bw-day
group of female rats exhibited
significantly lower grip strength than
the controls (10% less) at
examination prior to the initiation of
glutaraldehyde treatment. The 400
7-472
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Tri-o-cresyl phosphate and other
organophosphorus compounds cause a
delayed neuropathy that has been termed
organophosphate-induced delayed
neurotoxicity (OPIDN). Neurological
symptoms are typically delayed by 1-3
weeks after initial exposure and begin to
be expressed as ataxia and progressive
development of paralysis of hind limbs;
partial recovery may follow. Chickens and
cats are particularly sensitive to
organophosphate-induced OPIDN.
Neuropathologically, degeneration of
spinal cord and peripheral nerve fibers is
observed.
OPIDN has been elicited in rats as well,
but at relatively high repeated oral doses
(>840 mg/kg bw-day).
Tri-o-cresyl phosphate occurs as a
contaminant in commercial tricresyl
phosphate mixtures, but usually in
concentrations of <1%.
Ingestion of preparations contaminated by
TOCP by humans may be followed
WHO, 1990
mg/kg bw-day group of female rats
also exhibited 10% less hind limb
grip strength than controls (not
statistically significant) prior to the
initiation of glutaraldehyde treatment.
Therefore, the 800 mg/kg bw-day
dose level should be considered a
NOAEL for neurological effects in
the female rats as well.
Summary of Tri-o-cresyl phosphate
neurological effects.
7-473
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
polyneuropathy. Delayed neurotoxic
symptoms include pain and paraesthesia in
the lower extremities. Muscle weakness
can quickly progress to paralysis of the
lower extremities and may or may not
involve the upper extremities. Axonal
degeneration has been reported following
histopathological examination. There is
variation between individuals both in
response to TCP and recovery from the
toxic effects of TOCP. Severe symptoms
have been reported following the ingestion
of 0.15 g of TCP, while other individuals
failed to show any toxic effect after
ingesting 1-2 g. Some patients show
complete recovery while others do not.
2-Year dietary study in B6C3F1 mice
(95/sex/concentration)
Test substance concentrations: 0, 60, 125,
250 ppm (approximately 0, 7, 13, and 27
mg/kg bw-day for males and 0, 8, 18, and
37 mg/kg bw-day for females)
Neurological endpoints assessed included
grip strength testing and histopathological
evaluation of spinal cord and sciatic
preparations
NOAEL (males): 27 mg/kg bw-day
(highest dose tested)
LOAEL (males): Not established
NOAEL (females): 37 mg/kg bw-day
(highest dose tested)
NTP, 1994
Reliable study, although not designed
to comprehensively assess
neurological endpoints; test
substance: Tricresyl phosphate
(CASRN 1330.78-5) as a commercial
product comprised of 18% dicresyl
phosphate esters (unconfirmed
isomeric composition) and 79%
tricresyl phosphate esters (21%
confirmed as tri-m-cresyl phosphate,
4% as tri-p-cresyl phosphate, and no
detectable tri-o-cresyl phosphate
[<0.1%]). Neurobehavioral
evaluations were performed on 15
mice/sex from each exposure group.
At 3-month interim evaluation,
significantly decreased hind limb grip
7-474
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
LOAEL (females): Not established
2-Year dietary study in Fischer 344/N rats
(95/sex/concentration)
Test substance concentrations: 0, 75, 150,
300 ppm (approximately 0, 3, 6, and 13
mg/kg bw-day for males and 0, 4, 7, and
15 mg/kg bw-day for females)
Neurological endpoints assessed included
grip strength testing and histopathological
NTP, 1994
strength was observed in female mice
of the highest treatment level (250
ppm; ca. 7% lower than controls);
there was no significant change in
grip strength at 9- and 15-month
interim evaluations. There was no
histopathological evidence of
treatment related effects on sciatic
nerve or spinal cord. Note: Grip
strength was not decreased in male or
female mice in 13-week gavage and
dietary studies at much higher dose
levels; the 13-week studies were
performed using the same strains of
mice, the same formulation of
glutaraldehyde, and the same
laboratory as the 2-year dietary study.
These results suggest that the finding
of decreased hind limb grip strength
at the 3-month interim evaluation in
the 2-year dietary study are spurious.
In that case, the 2-year dietary study
identified NOAELs of 27 and 37
mg/kg-day for neurological effects in
male and female mice, respectively.
Reliable study, although not designed
to comprehensively assess
neurological endpoints; test
substance: Tricresyl phosphate
(CASRN 1330-78-5) as a commercial
product comprised of 18% dicresyl
phosphate esters (unconfirmed
isomeric composition) and 79%
7-475
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
evaluation of spinal cord and sciatic
preparations
NOAEL (males): 13 mg/kg bw-day
(highest dose tested)
LOAEL (males): Not established
NOAEL (females): 15 mg/kg bw-day
(highest dose tested)
LOAEL (females): Not established
tricresyl phosphate esters (21%
confirmed as tri-m-cresyl phosphate,
4% as tri-p-cresyl phosphate, and no
detectable tri-o-cresyl phosphate
[<0.1%]). Neurobehavioral
evaluations were performed on 15
rats/sex from each exposure group. At
3-month interim evaluation,
significantly decreased hind limb grip
strength was reported for male rats at
the two highest treatment levels (300
and 600 ppm; ca. 11% lower than
controls) and female rats at the
highest treatment level (600 ppm; ca.
7% lower than controls); there was no
significant treatment-related effect on
grip strength at 9- and 15-month
interim evaluations. There was no
histopathological evidence of
treatment-related effects on spinal
cord or sciatic nerve. Note: Grip
strength was not decreased in male or
female rats in 13-week gavage and
dietary studies at much higher dose
levels; the 13-week studies were
performed using the same strains of
rats, the same formulation of
glutaraldehyde, and the same
laboratory as the 2-year dietary study.
These results suggest that the finding
of decreased hind limb grip strength
at the 3-month interim evaluation in
the 2-year dietary study are spurious.
In that case, the 2-year dietary study
7-476
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
identified NOAELs of 13 and 15
mg/kg-day for neurological effects in
male and female rats, respectively.
Potential for neurotoxic effects based on a
structural alert for organophosphates
(Estimated by analogy)
Professional judgment
Estimated based on a structural alert
for organophosphates and
professional judgment.
Repeated Dose Effects
HIGH: In addition to the neurotoxicity effects described above, increased incidence of liver lesions was
reported in a 2-year dietary study in mice fed commercial tricresyl phosphate at a dose of 13 mg/kg bw-day
(NOAEL = 7 mg/kg bw-day); cytoplasmic vacuolization of the adrenal cortex and ovarian interstitial cell
hypertrophy were noted at 26 mg/kg bw-day (NOAEL = 13 mg/kg bw-day). Similar effects were reported
following a 13-week dietary study with the same commercial product in mice and rats at 50 mg/kg bw-day
(lowest dose tested). Furthermore, TCP is immunotoxic in the range of high hazard (see immunotoxicity
section).
2-Year dietary study in B6C3F1 mice
(95/sex/concentration)
Test substance concentrations: 0, 60, 125,
250 ppm (approximately 0, 7, 13, and 27
mg/kg bw-day for males and 0, 8, 18, and
37 mg/kg bw-day for females)
NOAEL: 7 mg/kg bw-day (males); 37
mg/kg bw-day (females; highest dose
tested)
LOAEL: 13 mg/kg bw-day for males
based on increased incidences of liver
lesions (ceroid pigmentation, clear cell
foci, fatty change)
NTP, 1994
2-Year dietary study in Fischer 344/N rats
(95/sex/concentration)
Test substance concentrations: 0, 75, 150,
300 ppm (approximately 0, 3, 6, and 13
mg/kg bw-day for males and 0, 4, 7, and
15 mg/kg bw-day for females)
NTP, 1994
Study details reported in a primary
source; test substance: Tricresyl
phosphate (CASRN 1330.78-5) as a
commercial product comprised of
18% dicresyl phosphate esters
(unconfirmed isomeric composition)
and 79% tricresyl phosphate esters
(21% confirmed as tri-m-cresyl
phosphate, 4% as tri-p-cresyl
phosphate, and no detectable tri-o-
cresyl phosphate [<0.1%]).
Study details reported in a primary
source; test substance: Tricresyl
phosphate (CASRN 1330-78-5) as a
commercial product comprised of
18% dicresyl phosphate esters
(unconfirmed isomeric composition)
7-477
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
NOAEL: 13 mg/kg bw-day (males); 7
mg/kg bw-day (females)
LOAEL: 26 mg/kg bw-day (males) and 15
mg/kg bw-day (females) for cytoplasmic
vacuolization of adrenal cortex at 3-month
interim evaluation
13-Week gavage study in B6C3F1 mice
(10/sex/dose)
Test substance concentrations: 0, 50, 100,
200, 400, 800 mg/kg bw-day (in corn oil)
Dosing frequency: Ix/d, 5d/w
NOAEL: not established
LOAEL: 50 mg/kg bw-day for
cytoplasmic vacuolization of the adrenal
cortex (males and females), ovarian
interstitial cell hypertrophy
NTP, 1994
13-Week gavage study in Fischer 344/N
rats (10/sex/dose)
Test substance concentrations: 0, 50, 100,
200, 400, 800 mg/kg bw-day (in corn oil)
Dosing frequency: Ix/d, 5d/w
NOAEL: not established
LOAEL: 50 mg/kg bw-day for
cytoplasmic vacuolization of the adrenal
NTP, 1994
and 79% tricresyl phosphate esters
(21% confirmed as tri-m-cresyl
phosphate, 4% as tri-p-cresyl
phosphate, and no detectable tri-o-
cresyl phosphate [<0.1%]).
Study details reported in a primary
source; test substance: Tricresyl
phosphate (CASRN 1330-78-5) as a
commercial product comprised of
18% dicresyl phosphate esters
(unconfirmed isomeric composition)
and 79% tricresyl phosphate esters
(21% confirmed as tri-m-cresyl
phosphate, 4% as tri-p-cresyl
phosphate, and no detectable tri-o-
cresyl phosphate [<0.1%]); EPA HC
(2010) suggested that relatively wide
range of NOAEL values among less-
than-lifetime repeated-dose oral
studies may be related to variations in
isomeric composition of CASRN
1330-78-5.
Study details reported in a primary
source; test substance: Tricresyl
phosphate (CASRN 1330-78-5) as a
commercial product comprised of
18% dicresyl phosphate esters
(unconfirmed isomeric composition)
and 79% tricresyl phosphate esters
(21% confirmed as tri-m-cresyl
phosphate, 4% as tri-p-cresyl
7-478
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
cortex (males and females)
13-Week dietary study in Fischer 344/N
rats (10/sex/dose)
Test substance concentrations: 0, 900,
1700, 3300, 6600, 13,000 ppm
(approximately 0, 55, 120, 220, 430, and
750 mg/kg bw-day for males and 0, 65,
120, 230, 430, and 770 mg/kg bw-day for
females)
NOAEL: not established
LOAEL: 55 mg/kg bw-day (males) for
cytoplasmic vacuolization of the adrenal
cortex, 65 mg/kg bw-day (females) for
cytoplasmic vacuolization of the adrenal
cortex and ovarian interstitial cell
hypertrophy
NTP, 1994
Repeated-dose gavage study of male and
female Crj:CD (SD) rats (10/group)
administered commercial diphenyl cresyl
phosphate (CASRN 26444-49-5; purity
41.9%) for approximately 45 consecutive
days (14 days premating, mating,
gestation, until postpartum day 3).
Dose levels: 0, 12, 60, 300 mg/kg bw-day
OECD-SIDS, 2002
phosphate, and no detectable tri-o-
cresyl phosphate [<0.1%]); EPA HC
(2010) suggested that relatively wide
range of NOAEL values among less-
than-lifetime repeated-dose oral
studies may be related to variations in
isomeric composition of CASRN
1330-78-5.
Study details reported in a primary
source; test substance: Tricresyl
phosphate (CASRN 1330-78-5) as a
commercial product comprised of
18% dicresyl phosphate esters
(unconfirmed isomeric composition)
and 79% tricresyl phosphate esters
(21% confirmed as tri-m-cresyl
phosphate, 4% as tri-p-cresyl
phosphate, and no detectable tri-o-
cresyl phosphate [<0.1%]); EPA HC
(2010) suggested that relatively wide
range of NOAEL values among less-
than-lifetime repeated-dose oral
studies may be related to variations in
isomeric composition of CASRN
1330-78-5.
Secondary source indicated the study
followed OECD guidelines for a
Combined Repeated Dose and
Reproductive/Developmental
Screening Toxicity Test; test
substance: commercial diphenyl
cresyl phosphate (CASRN 26444-49-
5; purity 41.9%).
7-479
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
NOAEL: 12 mg/kg bw-day
LOAEL: 60 mg/kg bw-day for
enlargement and vacuolization of adrenal
cortex
13-Week dietary study in B6C3F1 mice
(10/sex/concentration)
Test substance concentrations: 0, 250,
500, 1,000, 2,100, 4,200 ppm
(approximately 0, 45, 110, 180, 380, and
900 mg/kg bw-day for males and 0, 65,
130, 230, 530, and 1,050 mg/kg bw-day
for females)
NOAEL: 45 mg/kg bw-day (males); not
established for females
LOAEL: 110 mg/kg bw-day (males) and
65 mg/kg bw-day (females) for
cytoplasmic vacuolization of the adrenal
cortex
NTP, 1994
Study details reported in a primary
source; test substance: Tricresyl
phosphate (CASRN 1330-78-5) as a
commercial product comprised of
18% dicresyl phosphate esters
(unconfirmed isomeric composition)
and 79% tricresyl phosphate esters
(21% confirmed as tri-m-cresyl
phosphate, 4% as tri-p-cresyl
phosphate, and no detectable tri-o-
cresyl phosphate [<0.1%]); EPA HC
(2010) suggested that relatively wide
range of NOAEL values among less-
than-lifetime repeated-dose oral
studies may be related to variations in
isomeric composition of CASRN
1330-78-5.
3-Month gavage study in Sprague-Dawley
rats (5/sex/dose)
Test substance concentrations: 30, 100,
300, 1,000 mg/kg bw-day
Dosing frequency: Ix/d, 6d/w
NOAEL: 300 mg/kg bw-day
LOAEL: 1,000 mg/kg bw-day for
decreased body weight in males and
hypertrophy of the adrenal cortex in both
sexes
WHO, 1990; Great Lakes
Chemical Corporation, 2001;
EPA, 2010
Small group numbers (5
rats/sex/dose); study considered valid
with restrictions by secondary source;
test substance: Tricresyl phosphate
(CASRN 1330-78-5) in 5% gum
arabic; test substance purity: 100%;
EPA HC (2010) suggested that
relatively wide range of NOAEL
values among less-than-lifetime
repeated-dose oral studies may be
related to variations in isomeric
7-480
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
Skin Sensitization
Skin Sensitization
Respiratory Sensitization
(Respiratory Sensitization
DATA
28-Day dietary study in Sprague-Dawley
rats (10/sex/dose)
Test substance concentrations: 0, 0.1, 0.5,
1.0% (males: 0, 236, 1,281, 1,551 mg/kg
bw-day; females: 0, 250, 1,229, 2,130
mg/kg bw-day)
NOAEL: 236 mg/kg bw-day (males); 250
mg/kg bw-day (females)
LOAEL: 1,281 mg/kg bw-day (males) for
mortality; 1,229 mg/kg bw-day (females)
for mortality
REFERENCE
FMC, 1976
DATA QUALITY
composition of CASRN 1330-78-5.
Guideline not specified, but appears
to follow OECD test guideline 407;
test substance: Tricresyl phosphate
(CASRN 1330-78-5); this study was
summarized in ATSDR, 2012; Great
Lakes Chemical Corporation, 2001;
and EPA HC, 2010. However, the
estimated low- and mid-dose levels
provided by these secondary sources
are much lower than the doses
calculated using reported body weight
and compound consumption data in
the primary report (i.e., estimated
doses reported in EPAHC (2010)
were 0, 50, 250, and 500 mg/kg -day
and estimated doses reported in
ATSDR (2012) were 0, 140, 938, and
2647 mg/kg-day for the males, and 0,
120, 745, and 2258 mg/kg-day for the
females)
MODERATE: There is uncertain potential for skin Sensitization based on a protein binding alert for this
compound and professional judgment.
There is uncertain potential for skin
Sensitization based on a protein binding
alert for this compound. (Estimated)
Professional judgment
Estimated based on a protein binding
alert (nucleophilic substitution on
phosphonates) and professional
judgment.
No data located.
[No data located.
7-481
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
Eye Irritation
Eye Irritation
Dermal Irritation
Dermal Irritation
DATA
REFERENCE
DATA QUALITY
LOW: Tricresyl phosphate caused conjuctival effects in 2/6 rabbits that cleared within 48 hours.
Eye irritation study in rabbits (n=9)
Treated eye of 3/9 rabbits rinsed 4 seconds
post application
Conjunctival effects at 24 hours in 2/6
rabbits with unrinsed eyes which cleared
by 48 hours; no effects in rinsed eyes;
results considered to indicate that test
substance was not an eye irritant
Great Lakes Chemical
Corporation, 2001; EPA, 2010
Study details reported in secondary
sources; considered valid; test
substance: undiluted phosphoric acid,
tris(methylphenyl)ester (CASRN
1330-78-5).
LOW: Tricresyl phosphate caused erythema in 1/6 rabbits that cleared within 72 hours.
Skin irritation study in rabbits (n=6)
Test substance applied to shaved and
intact and abraded sites on the back of
each rabbit under semi occlusive
conditions for 24 hours and observed for
up to 7 days post application
Erythema on abraded skin of 1/6 rabbits at
24 hours resolved by 72 hours; no edema
at any site; results indicated that test
substance did not cause skin irritation
Great Lakes Chemical
Corporation, 2001; EPA, 2010
Study details reported in secondary
sources; considered valid; test
substance: undiluted phosphoric acid,
tris(methylphenyl)ester (CASRN
1330-78-5).
7-482
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
Endocrine Activity
DATA
REFERENCE
DATA QUALITY
Dose-related increasing severity of cytoplasmic vacuolization of the adrenal glands were noted in rats and
mice exposed to receiving commercial tricresyl phosphate by repeated gavage dosing or continuously via the
diet for 13 weeks at doses in the range of 50-800 mg/kg bw-day. Cytoplasmic vacuolization of the adrenal
cortex in male rats at the highest dose level (13 mg/kg bw-day) and female rats at all dose levels (4, 7, and 15
mg/kg bw-day) was observed in a 2-year dietary study, but primarily in the 7 mg/kg bw-day group at the 9-
and 15-month interim sacrifice and terminal sacrifice. Ceroid pigmentation of the adrenal cortex occurred
in all groups of mice (test substance doses 7-37 mg/kg bw-day) throughout most of the 2-year study.
Thirteen-week oral (gavage) and feeding
studies and 2-year feeding studies in
F344/N rats and B6C3F1 mice. Results of
13 -week studies: Rats and mice exposed
to test substance by repeated gavage
dosing or continuously via the diet at test
substance doses in the range of 50-800
mg/kg bw-day to male and female rats and
mice exhibited dose-related increasing
severity of cytoplasmic vacuolization of
the adrenal glands. Results of 2-year
studies: Cytoplasmic vacuolization of the
adrenal cortex was noted in male rats at
the highest dose level (13 mg/kg bw-day)
and female rats at all dose levels (4, 7, and
15 mg/kg bw-day); primarily in the 7
mg/kg bw-day group of female rats at 9-
and 15 -month interim sacrifice and
terminal sacrifice. Ceroid pigmentation of
the adrenal cortex occurred in all groups
of mice (test substance doses 7-37 mg/kg
bw-day) throughout most of the 2-year
study, with markedly increased severity in
the high-dose females (37 mg/kg bw-day).
3 -Month gavage study in Sprague-Dawley
rats (5/sex/dose) Test substance
NTP, 1994
WHO, 1990; Great Lakes
Chemical Corporation, 200 1 ;
Study details reported in a reliable
primary source; test substance:
Tricresyl phosphate (CASRN 1330-
78-5) as a commercial product
comprised of 18% dicresyl phosphate
esters (unconfirmed isomeric
composition) and 79% tricresyl
phosphate esters (21% confirmed as
tri-m-cresyl phosphate, 4% as tri-p-
cresyl phosphate, and no detectable
tri-o-cresyl phosphate [<0.1%]).
Small group numbers (5
rats/sex/dose); study considered valid
7-483
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
concentrations: 30, 100, 300, 1,000 mg/kg
bw-day Dosing frequency: Ix/d, 6d/w
NOAEL: 300 mg/kg bw-day
LOAEL: 1,000 mg/kg bw-day for
decreased body weight in males and
hypertrophy of the adrenal cortex in both
sexes
EPA, 2010
with restrictions by secondary source;
test substance: Tricresyl phosphate
(CASRN 1330-78-5) in 5% gum
arabic; test substance purity: 100%;
EPA HC (2010) suggested that
relatively wide range of NOAEL
values among less-than-lifetime
repeated-dose oral studies may be
related to variations in isomeric
composition of CASRN 1330-78-5.
Immunotoxicity
Decreased immune response to tetanus antigen significantly reduced at low doses in rats fed technical-grade
tricresyl phosphate for 6 weeks. Significant changes in gross immune organ weights and histology were
reported at high doses. Significantly decreased thymus weight was noted in male and female mice and rats
administered commercial tricresyl phosphate by repeated gavage for 16 days at doses > 1450 mg/kg-day.
Other effects seen at 2900 mg/kg bw-day included necrosis of mandibular lymph nodes and spleen and
lymphoid depletion in spleen and/or thymus.
Immune System Effects
Rats fed diets containing 0, 20, 50, or 100
ppm tricresyl phosphate and immunized
with tetanus toxoid 25 days following
initiation of exposure
After 6 weeks of treatment, doses of 6
mg/kg bw-day and higher resulted in
reduced antibody titer to tetanus toxoid
and significantly reduced cell-mediated
immune response (at 12 mg/kg bw-day,
serum IgM and IgG were significantly
reduced).
No effects were reported at 2.4 mg/kg bw-
day
16-day gavage study in mice
Test substance concentrations: 0, 360,
730, 1450, or 2900 mg/kg bw-day (in corn
oil), 5800 mg/kg bw-day (neat); 5
ATSDR,2012
Study details reported in a secondary
source; test substance: Technical-
grade (90% purity) tricresyl
phosphate (CASRN 1330-78-5);
unspecified mixture of ortho, meta,
and para isomers.
NTP, 1994
Study details reported in a primary
source; test substance: Tricresyl
phosphate (CASRN 1330-78-5) as a
commercial product comprised of
7-484
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
days/week
Significantly decreased thymus weight in
males and females at doses of 1450 mg/kg
bw-day or more; necrosis of mandibular
lymph node and lymphoid depletion in the
spleen of males and females at 2900
mg/kg bw-day (but not at 5800 mg/kg bw-
day); lymphoid depletion in the thymus of
males at 2900 mg/kg bw-day or more; and
necrosis and lymphoid depletion in the
thymus of females at 2900 mg/kg bw-day
(but not at 5800 mg/kg bw-day)
16-day gavage study in F344/N rats
Test substance concentrations: 0, 360,
730, 1450, or 2900 mg/kg bw-day (in corn
oil), 5800 mg/kg bw-day (neat); 5
days/week
Significantly decreased thymus weight in
males and females at doses of 1450 mg/kg
bw-day or more; necrosis of mandibular
lymph node in males at 2,900 mg/kg bw-
day (but not at 5800 mg/kg bw-day);
necrosis of spleen in males at 2900 and
5800 mg/kg bw-day and females at 2900
mg/kg bw-day (but not at 5800 mg/kg bw-
day); necrosis and lymphoid depletion in
thymus of males and females at 2900
mg/kg bw-day (but not at 5800 mg/kg bw-
day).
NTP, 1994
18% dicresyl phosphate esters
(unconfirmed isomeric composition)
and 79% tricresyl phosphate esters
(21% confirmed as tri-m-cresyl
phosphate, 4% as tri-p-cresyl
phosphate, and no detectable tri-o-
cresyl phosphate [<0.1%]).
Study details reported in a primary
source; test substance: Tricresyl
phosphate (CASRN 1330-78-5) as a
commercial product comprised of
18% dicresyl phosphate esters
(unconfirmed isomeric composition)
and 79% tricresyl phosphate esters
(21% confirmed as tri-m-cresyl
phosphate, 4% as tri-p-cresyl
phosphate, and no detectable tri-o-
cresyl phosphate [<0.1%]).
7-485
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
ECOTOXICITY
ECOSAR Class
Acute Aquatic Toxicity
Fish LC50
VERY HIGH: Based on experimental acute aquatic toxicity values < 1.0 mg/L in fish, daphnia, and algae.
Estimated aquatic toxicity values are also consistent with a Very High hazard designation. Both
experimental and estimated toxicity values are at or near the water solubility limit of this compound.
Lepomis macrochirus (bluegill) 96-hour
LC5o = 0.26 mg/L at water hardness 44
mg/L; 0.061 mg/L at water hardness 314
mg/L
Flow-through test conditions
(Experimental)
Oncorhynchus mykiss (rainbow trout) 96-
hour LC50 range 0.26-0.4 mg/L
Flow-through test conditions
(Experimental)
Danio rerio (Zebra Danio) 96-hour LC50
range 0.4-5.9 mg/L
Renewal test conditions
Solvent: sulfinyl bis(methane)
(Experimental)
Oncorhynchus mykiss (rainbow trout;
Salmo gairdneri); 10/group 96-hour LC50
= 0.75 mg/L (95% CL 0.54-1.04 mg/L)
Static test conditions with solvent controls
(solvent not specified)
Test substance concentrations: 0.56, 1.00,
1.80, 3.20, 5.60 mg/L (nominal)
(Experimental)
Oryzias latipes (Japanese Medaka) 96-
hour LC50 = 1.3 mg/L
Test substance concentrations: 0.29-3.09
EPA, 2013
EPA, 2013
EPA, 2013
Great Lakes Chemical
Corporation, 2001; EPA, 2010
OECD, 1998; OECD-SIDS,
2002
Limited study details reported in a
secondary source; test substance:
Phosphoric acid,
tris(methylphenyl)ester (CASRN
1330-78-5).
Limited study details reported in a
secondary source; test substance:
Phosphoric acid,
tris(methylphenyl)ester (CASRN
1330-78-5).
Limited study details reported in a
secondary source; test substance:
Phosphoric acid,
tris(methylphenyl)ester (CASRN
1330-78-5).
Limited study details reported in a
secondary source which did not
specify a reliability code; test
substance: Phosphoric acid,
tris(methylphenyl)ester (CASRN
1330-78-5); purity 100%.
Limited details reported in a
secondary source that indicated the
study followed OECD Test Guideline
7-486
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
mg/L (nominal); solvent: methanol
Semi-static open-system test conditions
(Experimental)
Oryzias latipes (Japanese Medaka) 96-
hour LC50 >3.2 <10 mg/L
Renewal test conditions
(Experimental)
EPA, 2013
Lepomis macrochirus (bluegill) 96-hour
LC50 range 29-7,000 mg/L
Static test conditions
(Experimental)
EPA, 2013
Pimephalespromelas (fathead minnow);
10/group 96-hour LC50 >100 mg/L
Static test conditions
Test substance concentrations: 10, 18, 32,
56, and 100 mg/L (nominal)
(Experimental)
Great Lakes Chemical
Corporation, 2001
Brachydanio rerio (Zebrafish) 96-hour
LC0 = 8.1 mg/L (not specified whether
nominal or analytical)
96-hour LC90 = 11.5 mg/L (not specified
whether nominal or analytical)
Test conditions not specified
(Experimental)
OECD-SIDS, 2002
Fish 96-hour LC50: 0.58 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
203; test substance: Diphenyl cresyl
phosphate (CASRN 26444-49-5);
Purity: stated as "phenol, m-cresol, p-
cresol = 59%, 22%, 12%".
Limited study details reported in a
secondary source; test substance:
Phosphoric acid,
tris(methylphenyl)ester (CASRN
1330-78-5).
Limited study details reported in
secondary sources; test substance:
Phosphoric acid,
tris(methylphenyl)ester (CASRN
1330-78-5).
Limited study details reported in a
secondary source which considered
the study valid with restrictions; test
substance: Phosphoric acid,
tris(methylphenyl)ester (CASRN
1330-78-5); purity 100%'
Limited details reported in a
secondary source; test substance:
Diphenyl cresyl phosphate (CASRN
26444-49-5); purity not specified.
Estimations for monocresyl diphenyl
phosphate The estimated log Kow of
5.2 for this chemical exceeds the
SAR limitation for log Kow of 5.0;
NES are predicted for these
endpoints. Dicresyl phenyl phosphate
7-487
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
and higher alkylated isomers have
higher estimated log Kow values;
therefore NES are predicted for the
higher alkylated isomers also.
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
Daphnid LC50
Daphnia magna (water flea) 4 8-hour LC50
= 0.27 mg/L
Static test conditions Test substance
concentrations: 0.06, 0.1, 0.18, 0.32, 0.56
mg/L (nominal)
Solvent: Acetone NOEC: 0.1 mg/L
(nominal)
(Experimental)
Great Lakes Chemical
Corporation, 2001; EPA, 2010
Daphnia magna (water flea) 4 8-hour LC50
= 5.6 mg/L
Flow-through test conditions
(Experimental)
WHO, 1990
Daphnid 48-hour LC50:
0.85 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Great Lakes Chemical Corporation
considered the study valid with
restrictions; test substance:
Phosphoric acid,
tris(methylphenyl)ester (CASRN
1330-78-5).
Limited study details in secondary
source; test substance: Phosphoric
acid, tritolyl ester (CASRN 1330-78-
5).
Estimations for monocresyl diphenyl
phosphate The estimated log Kow of
5.2 for this chemical exceeds the
SAR limitation for log Kow of 5.0;
NES are predicted for these
endpoints. Dicresyl phenyl phosphate
and higher alkylated isomers have
higher estimated log Kow values;
therefore NES are predicted for the
higher alkylated isomers also.
Estimate for the Esters class was
7-488
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
provided for comparative purposes.
See Section 5.5.1.
Green Algae EC50
Scenedesmus pannonicus (green algae)
96-hour EC50 = 0.56 mg/L (growth rate)
(Experimental)
EPA, 2010
Limited study details summarized in
reliable secondary source, test
substance: Phosphoric acid,
tris(methylphenyl)ester (CASRN:
1330-78-5).
Pseudokirchneriella subcapitata (formerly
Selenastrum capricornutum ; green algae)
72-hour EC50 = 0.99 mg/L (nominal)
Test substance concentrations: 0.31-3.24
mg/L (nominal); solvent: methanol
(Experimental)
OECD, 1998; OECD-SIDS,
2002
Limited study details reported in
secondary source that indicated the
study followed OECD Test Guideline
201; Test substance: Diphenyl cresyl
phosphate (CASRN 26444-49-5);
purity: stated as "phenol, m-cresol, p-
cresol = 59%, 22%, 12%".
Green algae 96-hour EC50 range 1.3-3.8
mg/L (growth)
Static test conditions
(Experimental)
WHO, 1990; EPA, 2013
Limited study details reported in
secondary sources; test substance:
Phosphoric acid,
tris(methylphenyl)ester (CASRN
1330-78-5).
Green algae 96-hour EC50 = 0.04 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Estimation for tricresyl phenyl
phosphate.
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
Green algae 96-hour EC50 = 0.09 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Estimation for dicresyl phenyl
phosphate.
Estimate for the Esters class was
7-489
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
provided for comparative purposes.
See Section 5.5.1.
Green algae 96-hour EC50 = 0.16 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Estimation for monocresyl diphenyl
phosphate.
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
Chronic Aquatic Toxicity
HIGH: Based on estimated chronic aquatic toxicity values. An estimated chronic aquatic toxicity value
derived using an acute-to-chronic ratio (ACR) for the phosphate esters class and was applied to the available
experimental acute data for this chemical and indicated a High hazard. Estimated chronic aquatic toxicity
values < 0.1 mg/L in fish, daphnia, and algae (Esters class) also indicated a High hazard concern.
Experimental studies for Daphnia magna and algae indicated a High hazard designation with toxicity values
within the 0.1 - 1 mg/L range. No experimental chronic studies were located for fish.
Fish ChV
Freshwater fish ChV = 0.01 mg/L
(Estimated)
Professional judgment
An ACR of 24 was derived for the
phosphate ester class based on
experimental data for Tris (p-t-
butylphenyl) phosphate (TBPP).
The acute-to-chronic ratio was
applied to available experimental
acute fish data for Phosphoric acid,
tris(methylphenyl) ester (CASRN
1330-78-5) (ChV = 0.26 mg/L /24 =
0.01 mg/L)
7-490
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Fish ChV = 0.004 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Estimation for tricresyl phenyl
phosphate.
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
Fish ChV = 0.01 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Estimation for dicresyl phenyl
phosphate.
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
Fish ChV = 0.02 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Estimation for monocresyl diphenyl
phosphate.
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
Daphnid ChV
Daphnia magna (water flea) 21-day LC50
= 0.35 mg/L (mortality)
21-day EC50 = 0.31 mg/L (reproduction)
21-day NOEC = 0.12 mg/L (reproduction)
Test substance concentrations: 0.038-3.8
mg/L (nominal); solvent: dimethyl
sulfoxide (DMSO)
Semi-static open-system test conditions
(Experimental)
OECD, 1998; OECD-SIDS,
2002
Secondary source indicated the study
followed OECD Test Guideline 202;
test substance: Diphenyl cresyl
phosphate (CASRN 26444-49-5)
Purity: stated as "phenol, m-cresol, p-
cresol = 59%, 22%, 12%".
Daphnia magna (water flea) 21-day EC
range 0.1-1.0
EPA, 2010, 2013
Limited study details reported in
secondary sources; test substance:
7-491
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Renewal test conditions
(Experimental)
Daphnid ChV = 0.04 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Daphnid ChV = 0.09 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Daphnid ChV = 0.23 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Phosphoric acid,
tris(methylphenyl)ester (CASRN
1330-78-5).
Estimation for tricresyl phenyl
phosphate.
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
Estimation for dicresyl phenyl
phosphate.
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
Estimation for monocresyl diphenyl
phosphate.
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
Green Algae ChV
Pseudokirchneriella subcapitata (formerly
Selenastrum capricornutum; green algae)
72-hour NOEC = 0.55 mg/L (nominal)
Test substance concentrations: 0.31-3.24
mg/L (nominal); solvent: methanol
(Experimental)
OECD, 1998; OECD-SIDS,
2002
Limited study details reported in
secondary source that indicated the
study followed OECD Test Guideline
201; Test substance: Diphenyl cresyl
phosphate (CASRN 26444-49-5);
purity: stated as "phenol, m-cresol, p-
cresol = 59%, 22%, 12%".
7-492
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Green algae ChV = 0.04 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Green algae ChV = 0.08 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Green algae ChV = 0.16 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Estimation for tricresyl phenyl
phosphate.
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
Estimation for dicresyl phenyl
phosphate.
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
Estimation for monocresyl diphenyl
phosphate.
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
7-493
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
ENVIRONMENTAL FATE
Transport
Henry's Law Constant (atm-
m3/mole)
Sediment/Soil
Adsorption/Desorption - Koc
Level III fugacity models incorporating available physical and chemical property data indicate that at
steady state, tricresyl phosphate is expected to be found primarily in soil and to a lesser extent, sediment.
Tricresyl phosphate is expected to have negligible to moderate mobility in soil based on both measured and
estimated K0c values. Leaching of tricresyl phosphate through soil to groundwater is not expected to be an
important transport mechanism. There is slight potential for volatilization from moist soil surfaces based
upon the measured Henry's Law constant; however adsorption to soil is expected to attenuate this process.
In the atmosphere, tricresyl phosphate is expected to exist in the vapor and particulate phase. Vapor phase
tricresyl phosphate will be degraded in the atmosphere by reaction with photochemically-produced
hydroxyl radicals; the half-life for this reaction in air is estimated to be 0.8 days. Particulate phase tricresyl
phosphate will be removed from air by wet or dry deposition.
8xlO'7 (Measured)
8.3xlO'5 (Measured)
4xlO~8 for monocresyl diphenyl phosphate;
5x1 0~8 for dicresyl phenyl phosphate and
tricresyl phosphate
Bond method (Estimated)
Reported as the adsorption coefficient per
gram of clay minerals.
Kaolin: 0.236 (236 L/kg)
Alumina: 0.1 77(1 77 L/kg)
Montmorillonite: 4.614 (4614 L/kg)
(Measured)
Reported as the adsorption coefficient per
gram of clay minerals.
Kaolin: 0.196 (196 L/kg)
Alumina: 0.144 (144 L/kg)
PhysProp, 2012
EPA, 2010
EPIv4.11
Takimoto et al., 1998
Takimoto et al., 1998
Reported in s a secondary source with
limited details.
Reported for tri-m-cresyl phosphate
(CASRN 563-04-2); purity and test
method not stated.
Estimated using representative
structures indicated in the SMILES
section for methylated phenyl
phosphate with one, two and three
methyl substituent groups
respectively.
Nonguideline, well-documented
study for reagent grade tri-p-cresyl
phosphate (CASRN 78-32-0).
Nonguideline, well-documented
study for reagent grade tri-m-cresyl
phosphate (CASRN 563-04-2).
7-494
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
Level III Fugacity Model
DATA
Montmorillonite: 1.361 (1361 L/kg)
(Measured)
Reported as the adsorption coefficient per
gram of clay minerals.
Kaolin: 0.158 (158 L/kg)
Alumina: 0.1 18 (118 L/kg)
Montmorillonite: 1.550 (1550 L/kg)
(Measured)
18,000 for monocresyl diphenyl
phosphate;
28,000 for dicresyl phenyl phosphate
MCI method (Estimated)
>3 0,000 MCI method (Estimated)
Air =0.3%
Water =9.9%
Soil = 64%
Sediment = 26% (Estimated)
REFERENCE
Takimoto et al., 1998
EPIv4.11
EPIv4.11;EPA, 2005
EPIv4.11
DATA QUALITY
Nonguideline, well-documented
study for reagent grade tri-o-cresyl
phosphate (CASRN 78-30-8).
Estimated using a representative
structure
Estimated using a representative
structure fortricresyl phosphate.
Cutoff value fornonmobile
compounds.
Estimated using a representative
structure fortricresyl phosphate.
7-495
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Persistence
MODERATE: Based on nonguideline studies that have demonstrated primary and ultimate biodegradation
of tricresylphosphate and related components under aerobic conditions. There is evidence of biodegradation
resulting in a half-life less than 60 days but greater than 16 days. Both CASRN 563-04-2 and 26444-49-5 did
not pass ready biodegradability OECD 301C tests, however some degradation, <43.1%, was observed after
28 days. Other biodegradation tests, including OECD 302A, 302C, CO2 Evolution and a Die Away test
indicated some degradation by this pathway. Experimental data for the direct photolysis of CASRN 26444-
49-5 reported a half-life of 4.86 years; therefore, direct photolysis of tricresyl phosphate is not expected to be
an important fate process. Experimental half-lives of 27 to 87 minutes for tricresyl phosphate and 2
individual isomers, demonstrate removal by hydrolysis under alkaline conditions.
Water
Aerobic Biodegradation
Passes Ready Test: No
Test method: OECD TG 301C: Modified
MITI Test (I)
30.8 and 43.1% degradation in 28 days
(Measured)
Passes Ready Test: No
Test method: OECD TG 301C: Modified
MITI Test (I)
Reported as 0, 0, and 0% after 28 days
from BOD; 11, 5 and 5% after 28 days
from high performance liquid
chromatography (HPLC); using GLP
(Measured)
Passes Ready Test: No
Test method: OECD TG 301C: Modified
MITI Test (I)
Using OECD Test Guideline 301C (100
mg/L concentration of test substance),
diphenyl cresyl phosphate had a 0%
theoretical BOD after 28 days of
incubation. (Measured)
EPA, 2010
OECD-SIDS, 2002
HSDB, 2013a
Reported for tri-m-cresyl phosphate
(CASRN 563-04-2); purity not stated.
Guideline study in a secondary source
for cresyl diphenyl phosphate
(CASRN 26444-49-5).
Reported for diphenyl cresyl
phosphate (CASRN 26444-49-5)
purity not stated. This study used an
initial concentration of compound
that was more than 40 times greater
than the water solubility.
7-496
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Study results: 78.6%/7 days
Test method: CO2 Evolution
In a modified Sturm test ultimate
degradation was measured. At 26.4 mg/L
tricresyl phosphate achieved 78.6% of its
theoretical CO2 in 7 days and 82% in 8
days. (Measured)
WHO, 1990; HSDB, 2013d
Study results: 100%/28 days
Test method: 302C: Inherent - Modified
MITI Test (II)
(Measured)
EPA, 2010
Study results: 65.7%/28 days
Test method: 302C: Inherent - Modified
MITI Test (II)
Inherently biodegradable (Measured)
EPA, 2010
Study results: 82%/22 weeks
Test method: 302A: Inherent - Modified
SCAS Test
Primary degradation measured; influent
concentrations of 3 mg/L/day (Measured)
HSDB, 2013a
Study results: 100%/4 days
Test method: Die-Away
River water; complete degradation in 4
days (Measured)
HSDB, 2013a
Study results: 75-100%/29 days
Test method: Die-Away
In die-away tests in Japanese river water
HSDB, 2013d
Nonguideline study reported in
secondary sources; purity not
indicated.
Reported in a secondary source with
limited study details for tri-p-cresyl
phosphate (CASRN 78-32-0); purity
not stated.
Reported in a secondary source with
limited study details for tri-o-cresyl
phosphate (CASRN 78-30-8).
Reported in a secondary source for
diphenyl cresyl phosphate (CASRN
26444-49-5).
Reported for diphenyl cresyl
phosphate (CASRN 26444-49-5);
purity not stated.
Nonguideline study reported in
secondary sources; purity not
indicated.
7-497
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
and Japanese bay water tricresyl
phosphate achieved 100% primary
degradation after 4 days at 26°C; 75-100%
degradation was observed after 29 days at
7°C, a lag-phase of 1-3 days was
observed. (Measured)
Study results: 82%/28 days
Test method: Die-Away
In a river die-away test, at a test
concentration of 26 mg/L, CO2 evolution
was 79% after 7 days, 82% after 28 days
and 86% after 48 days. (Measured)
HSDB, 2013c
Reported for tri-o-cresyl phosphate
(CASRN 78-30-8) purity and study
details not stated.
Study results: >97%/4 weeks
Test method: Die-Away
In a semi-continuous activated sludge test
using influent concentrations of 3 and 13
mg/L/day tricresyl phosphate was shown
to undergo 97% and >99% primary
degradation, respectively, after 4 weeks.
(Measured)
Saeger et al., 1979 (as cited in
EPA, 2010; HSDB, 2013d)
Nonguideline study reported for a
commercial grade mixture of isomers;
purity not indicated.
Study results: 100%/4 days
Test method: Die-Away
In a river die-away test in water from the
Mississippi river St. Louis, MO. Complete
primary degradation of tricresyl phosphate
was achieved after 4 days following an
initial lag-phase of 2 days with 8%
degradation. Rapid degradation attributed
to microbial adaptation. (Measured)
EPA, 2010; HSDB, 2013d
Nonguideline study reported in a
secondary source for a commercial
grade mixture of isomers; purity not
indicated.
A die-away study using Lake Ontario
Howard and Deo, 1979 (as cited
Reported for individual isomers.
7-498
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
water from Oswego, NY found that the
individual isomers exhibited a two-day lag
period before degrading rapidly; the ortho-
and meta-isomers were completely
degraded within 4 days while about half of
the para-isomer was degraded in 5 days.
(Measured)
in EPA, 2010; HSDB, 2013a,
2013c)
Study results: 82.1%/28 days
Test method: Screening Test
Inherently biodegradable. After 7, 28, and
48 days 78.6, 82.1, and 86.3% theoretical
CO2 evolution was achieved in acclimated
bacterial inoculum, respectively. There
was a 14-day acclimation period noted.
(Measured)
Saeger et al., 1979 (as cited in
EPA, 2010)
Study results: 97%/4 weeks
Test method: Other
99% after 7 weeks; activated sludge
inoculum and a test substance addition
rate of 3 and 13 mg/L per 24 hours.
(Measured)
HSDB, 2013c
Study results: 53.2%/7 days
Test method: Other
At test concentrations of 23.1 mg/L, this
chemical achieved 53.2, 84.5 and 91.3%
of its theoretical CO2 evolution in
activated sludge after 7, 28, and 48 days,
respectively. (Measured)
HSDB, 2013a
Study results: 50%/7.5 hours
Test method: Other
Great Lakes Chemical
Corporation, 2001
Reported for a commercial grade
sample; mixture of isomers purity not
stated.
Reported for tri-o-cresyl phosphate
(CASRN 78-30-8); purity and test
method not stated.
Reported for diphenyl cresyl
phosphate (CASRN 26444-49-5)
purity and test method not stated.
Reported for tri-p-cresyl phosphate
(CASRN 78-32-0).
7-499
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
1 (ig/ml of 14C-tri-p-cresyl phosphate
achieved 70-80% degradation after 24
hours in sewage sludge at 21° C.
Degradation was determined by liquid
scintillation counting, gas
chromatography, and thin layer
chromatography. The remaining test
material was associated with the sludge
solids. The major metabolite was p-
hydroxybenzoic acid. (Measured)
Study results: 40-60%/48 hour
Test method: Other
Rapid biodegradation was observed in
activated sludge. 40-60% degradation of
tricresyl phosphate was achieved in a 48-
hour wastewater treatment simulation test.
(Measured)
HSDB, 2013d
Biodegradable in tests using activated
sludge seed. (Measured)
HSDB, 2013b
Performed in sediment-water incubation
systems; Pond sediment half-life: 3.2, 4.1,
and 16.3 days at 25, 10, and 2°C,
respectively;
River sediment half-life: 10.1 days at
25 °C. (Measured)
HSDB, 2013b
Study results: 50%/10 days
Test method: Field Test
Biodegradation in river water and bottom
sediment followed first-order kinetics. The
HSDB, 2013c
Nonguideline study reported in a
secondary source. Purity of test
substance and test details not stated.
Reported for tri-m-cresyl phosphate
(CASRN 563-04-2) purity and test
method not stated.
Reported for tri-m-cresyl phosphate
(CASRN 563-04-2) purity not stated.
Reported for tri-o-cresyl phosphate
(CASRN 78-30-8); purity not stated.
7-500
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
Soil
Air
Volatilization Half-life for
Model River
Volatilization Half-life for
Model Lake
Aerobic Biodegradation
Anaerobic Biodegradation
Soil Biodegradation with
Product Identification
Sediment/Water
Biodegradation
Atmospheric Half-life
DATA
first-order rate constant in river water
ranged from approximately 0.0022 per
hour at 14°C to 0.0030 per hour at 25°C;
this corresponds to a half-life of about 13
days at 14°C and 10 days at 25 °C
(Measured)
Study results: 0%/8 weeks
Test method: Screening Test
The meta isomer of tricresyl phosphate did
not degrade in 1: 10 dilutions of primary
anaerobic sludge after 8 weeks.
(Measured)
River water half-life:
approx. 13 days at 14°C;
2.9 days at 20°C
Bottom sediment half-life:
approx. 8 days at 14°C;
5.4 days at 25°C (Measured)
58 days (Estimated)
>1 year (Estimated)
Not probable (Anaerobic-methanogenic
biodegradation probability model)
0.91 days for monocresyl diphenyl
REFERENCE
HSDB, 2013d
HSDB, 2013b
EPIv4.11
EPIv4.11
EPIv4.11
EPIv4.11
DATA QUALITY
Nonguideline study reported in a
secondary source fortri-m-cresyl
phosphate (CASRN 563-04-2); purity
not stated.
Reported for tri-m-cresyl phosphate
(CASRN 563-04-2) purity not stated.
River water and bottom sediment
biodegradation followed first-order
kinetics.
Estimated using a representative
structure for tricresyl phosphate.
Estimated using a representative
structure for tricresyl phosphate.
No data located.
Tricresyl phosphate (CASRN 1330-
78-5); estimated from representative
structure: tri-ortho-cresyl-phosphate.
No data located.
No data located.
Estimated using representative
7-501
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
Reactivity
Photolysis
Hydrolysis
Environmental Half-life
DATA
phosphate;
0.84 for dicresyl phenyl phosphate:
0.78 for tricresyl phosphate
(Estimated)
50%/4.86 years
Test performed in water using direct
sunlight. Concentration: 5xlO"5M;
Spectrum: Epsilon = 8.17xl03 at 300 nm
Degradation rate: 2.26xlO"13 mol/l/s
Quantum yield = 0.01 (Measured)
50%/47daysatpH7;25°C
50%/5.10 days at pH 9 and 25 °C
(Measured)
50%/27 minutes in 0.03 M NaBO3 at pH
10.3 (Measured)
50%/70 minutes in 0.03 M NaBO3 at pH
10.3 (Measured)
50%/87 minutes in 0.03 M NaBO3 at pH
10.3 (Measured)
In alkaline medium hydrolysis to
dicresylphosphate and cresol occurs;
stable in neutral and acidic media.
(Measured)
75 (Estimated)
REFERENCE
OECD-SIDS, 2002
OECD-SIDS, 2002
David and Seiber, 1999
David and Seiber, 1999
David and Seiber, 1999
van der Veen and de Boer, 2012
PBT Profiler
DATA QUALITY
structures indicated in the SMILES
section for methylated phenyl
phosphate with one, two and three
methyl substituent groups
respectively.
Nonguideline study reported in a
secondary source for cresyl diphenyl
phosphate (CASRN 26444-49-5)
purity of test substance and test
method not stated.
Reported in a secondary source for
cresyl diphenyl phosphate (CASRN
26444-49-5).
Reported for tri-p-cresyl phosphate
(CASRN 78-32-0).
Reported for tricresyl phosphate
(CASRN 1330-78-5) mixed isomers.
Reported for tri-o-cresyl phosphate
(CASRN 78-30-8).
Supporting information reported in a
secondary source.
Estimation for tricresyl phenyl
phosphate, dicresyl phenyl phosphate
and monocresyl phenyl phosphate.
Half-life estimated for the
predominant compartment, as
determined by EPI and the PBT
Profiler methodology.
7-502
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
Bioaccumulation
Fish BCF
DATA
REFERENCE
DATA QUALITY
HIGH: Multiple experimental BCF and estimated BAF values are above 1,000, the high bioaccumulation
designation criteria.
165 in fathead minnows; flow-through test
with 32 day exposure period (Measured)
169 in Rainbow trout; flow-through test;
BCF of 10 for white muscle and 169 for
gut and adipose tissue (Measured)
700 in Zebra fish; flow-through test with
14 day exposure period (Measured)
928 in fathead minnow; 24-hour static test
measured a BCF range of 596-928 based
on total 14C; since the 14C measurements
include tricresyl phosphate metabolites,
the observed BCF values indicate a worse-
case estimate only. (Measured)
980 (Measured)
1,420 in rainbow trout; 24-hour static test
measured a BCF range of 784-1420 based
on total 14C; since the 14C measurements
include tricresyl phosphate metabolites,
the observed BCF values indicate a worse-
case estimate only. (Measured)
1,711 (Measured)
3,700 in Gambusia fish; reported as an
ecological magnification factor; static test
using a model ecosystem. Tri-p-cresyl
HSDB, 2013d
HSDB, 2013d
HSDB, 2013d
HSDB, 2013d
OECD-SIDS, 2002
HSDB, 2013d
van der Veen and de Boer, 2012
Boethling and Cooper, 1985 (as
cited in HSDB, 2013d)
Reported in a secondary source, test
method not stated.
Reported in a secondary source for a
commercial mixture (IMOL S-140)
75% tricresyl phosphate and 18%
trixylyl phosphate (CASRN 25 155-
23-1).
Reported in a secondary source, test
method not stated.
Reported in a secondary source with
meta- and para-isomers specified,
although percent composition of the
components and purity not stated.
Reported in a secondary source for
cresyl triphenyl phosphate (CASRN
26444-49-5); test method not stated.
Reported in a secondary source with
meta- and para-isomers specified,
although percent composition of the
components and purity not stated.
Reported in a secondary source for
cresyl diphenyl phosphate (CASRN
26444-49-5); purity not stated.
Reported in a secondary source.
7-503
-------
Tricresyl phosphate CASRN 1330-78-5
PROPERTY/ENDPOINT
Other BCF
BAF
Metabolism in Fish
DATA
phosphate was found to accumulate and
persist in all aquatic test systems studied.
(Measured)
1381 (Estimated)
1422 (Estimated)
2 14 (Estimated)
REFERENCE
EPIv4.11
EPIv4.11
EPIv4.11
DATA QUALITY
No data located.
Estimated using the Arnot-Gobas
method with a representative
structure for tricresyl phosphate.
Estimated using the Arnot-Gobas
method with a representative
structure for dicresyl phenyl
phosphate.
Estimated using the Arnot-Gobas
method with a representative
structure for monocresyl phenyl
phosphate.
No data located.
ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring
Ecological Biomonitoring
Human Biomonitoring
Tricresyl phosphate has been detected in areas of Japan, Canada, US, UK, Italy, Norway, Sweden, Germany, and
Austria in river water, drinking water, rain water and snow, sediments, sea sediment and soil samples. Cresyl
diphenyl phosphate was detected in coastal marine sediments in the UK. Tricresyl phosphate has been detected in
atmospheric samples, indoor air of theaters, offices, electronic stores, an electronics dismantling facility and
airplanes. It has also been detected in fly ash and stack emissions, and various effluents, in dust samples/wipe
samples from automobile interiors, aircraft and vegetation samples. In one study, tricresyl phosphate isomers, m-
TCP and o-TCP were detected in atmospheric samples, while the para isomer was scarcely detected (Takimoto et
al., 1999; OECD-SIDS, 2002; Bacaloni et al, 2008; Takigami et al., 2009; Ibbotson and Ibhadon, 2010; Solbu et
al., 2011; HSDB, 2013d; Salamovaetal., 2014).
Tricresyl phosphate has been detected in fish (HSDB, 2013d).
Human biomonitoring found small amounts of metabolites of tri-m- and tri-p cresyl phosphates in the urine of
aircraft crews. Metabolites of tri-o-cresyl phosphates were not detected above the LOD of the study (Schindler et
al., 2013).
7-504
-------
ATSDR (2012) Toxicological profile for phosphate ester flame retardants. U.S. Department of Health and Human Services, Agency for Toxic
Substances and Disease Registry.
Aldrich (1994) Catalog handbook of fine chemicals 1994-1995. Milwaukee, WI: Aldrich Chemical Company, Inc.
Bacaloni A, Cucci F, Guarino C, et al. (2008) Occurrence of organophosphorus flame retardant and plasticizers in three volcanic lakes of central
Italy. Environ Sci Technol 42(6): 1898-1903.
Boethling RS, Cooper JC (1985) Environmental fate and effects of triaryl and tralkyl/aryl phosphate esters. Residue Rev 94:49-99.
Carlton BD, Basaran AH, Mezza LE, et al. (1987) Examination of the reproductive effects of tricresyl phosphate administered to Long-Evans rats.
Toxicology 46(3):321-328.
Chapin RE, George JD, Lamb JC (1988) Reproductive toxicity of tricresyl phosphate in a continuous breeding protocol in Swiss (CD-I) mice.
Fundam Appl Toxicol 10(2):344-354.
David MD, Seiber JN (1999) Accelerated hydrolysis of industrial organophosphates in water and soil using sodium perborate. Environ Pollut
ECO SAR (Ecological Structure Activity Relationship), Version 1.11. Washington, DC: U.S. Environmental Protection
Agency, http://www.epa.gov/oppt/newchems/tools/21ecosar.htm.
EPA (2005) Pollution prevention (P2) framework. Washington, DC: U.S. Environmental Protection Agency, Office of Pollution Prevention and
Toxics, http://www.epa.gov/opptintr/newchems/pubs/sustainable/p2frame-june05a2.pdf
EPA (2010) Screening level hazard characterization phosphoric acid tris(methylphenyl) ester (Tricresyl phosphate, CASRN 1330-78-5).
EPA (2012) Using noncancer screening within the SF initiative. Washington, DC: U.S. Environmental Protection
Agency, http : //www . epa. gov/oppt/sf/pubs/noncan-screen .htm .
EPA (2013) ECOTOX database, http://cfpub.epa.gov/ecotox/quick query.htm.
EPI Estimation Programs Interface (EPI) Suite, Version 4.11. Washington, DC: U.S. Environmental Protection
Agency, http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm.
7-505
-------
ESIS (2012) European chemical Substances Information System. European Commission, http://esis.jrc.ec.europa.eu/.
FMC (1976) Acute and subacute toxicity tests Kronitex TCP: Tricresyl phosphate (Report No ICD/T-76-030).
Great Lakes Chemical Corporation (2001) IUCLID data set. Phosphoric acid, tris(methylphenyl) ester
HSDB (2013a) Diphenyl cresyl phosphate. Hazardous Substances Data Base. National Library of Medicine, http://toxnet.nlm.nih.gov/cgi-
bin/sis/htmlgen?HSDB.
HSDB (2013b) Tri-M-cresyl phosphate. Hazardous Substances Data Bank. National Library of Medicine, http://toxnet.nlm.nih.gov/cgi-
bin/sis/htmlgen?HSDB.
HSDB (2013c) Tri-o-cresyl phosphate. Hazardous Substances Data Bank. National Library of Medicine, http://toxnet.nlm.nih.gov/cgi-
bin/sis/htmlgen?HSDB.
HSDB (2013d) Tricresyl phosphate. Hazardous Substances Data Base. National Library of Medicine, http://toxnet.nlm.nih.gov/cgi-
bin/sis/htmlgen?HSDB.
Howard PH, Deo PG (1979) Degradation of aryl phosphates in aquatic environments. Bull Environ Contam Toxicol 22(3):337-344.
Ibbotson J, Ibhadon AO (2010) Origin and analysis of aliphatic and cyclic hydrocarbons in northeast United Kingdom coastal marine sediments.
Mar Pollut Bull 60(7): 1136-1141.
Johannsen FR, Wright PL, Gordon DE, et al. (1977) Evaluation of delayed neurotoxicity and dose-response relationships of phosphate esters in the
adult hen. Toxicol Appl Pharmacol 41:291-304.
Kurebayashi H, Tanaka A, Yahama T (1985) Metabolism and disposition of the flame retardant plasticizer, tri-p-cresyl phosphate, in the rat.
Toxicol Appl Pharmacol 77:395-404.
Latendresse JR, Brooks CL, Flemming CD, et al. (1994) Reproductive toxicity of butylated triphenyl phosphate and tricresyl phosphate fluids in
F344 rats. Fundam Appl Toxicol 22(3):392-399.
NTP (1994) NTP technical report on the toxicology and carcinogenesis studies of tricresyl phosphate in F344/N rats and B6C3F1 mice (Gavage
and feed studies).
7-506
-------
OECD (1998) SIDS initial assessment profile for diphenyl cresyl phosphate. SIAM 7, 25-27.
OECD-SIDS (2002) Diphenyl cresyl phosphate: CAS No: 26444-49-5. SIDS Initial Assessment Profile. Organization for Economic Cooperation
and Development, Screening Information Data Set (SIDS), United Nations Environment
Programme. http://www.chem.unep.ch/irptc/sids/OECDSIDS/26444495.pdf
PBT Profiler Persistent (P), Bioaccumulative (B), and Toxic (T) Chemical (PBT) Profiler, Version 1.301. Washington, DC: U.S. Environmental
Protection Agency, www.pbtprofiler.net.
PhysProp (2012) Physical properties database. Estimation Programs Interface Suite, Version 4.10. Washington, DC: U.S. Environmental
Protection Agency, http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm.
Saeger VW, Hicks O, Kaley RG, et al. (1979) Environmental fate of selected phosphate esters. Environ Sci Technol 13(7):840-844.
Salamova A, Ma Y, Venier M, et al. (2014) High levels of organophosphate flame retardants in the Great Lakes atmosphere. Environ Sci Technol
Schindler BK, Weiss T, Schutze A, et al. (2013) Occupational exposure of air crews to tricresyl phosphate isomers and organophosphate flame
retardants after fume events. Arch Toxicol 87(4):645-648.
Solbu K, Daae Hanne L, Olsen R, et al. (201 1) Organophosphates in aircraft cabin and cockpit air-method development and measurements of
contaminants. J Environ Monit 13(5): 1393-1403.
Takigami H, Suzuki G, Hirai Y, et al. (2009) Flame retardants in indoor dust and air of a hotel in Japan. Environ Int 35(4):688-693.
Takimoto K, Hirakawa T, Ito K, et al. (1999) Source and transport of tricresyl phosphate (TCP) isomers in Kurose river basin. Atmos Environ
33(19):3191-3200.
Takimoto K, Ito K, Mukai T, et al. (1998) Effect of linear-dodecylbenzenesulfonate and humic acid on the adsorption of tricresyl phosphate
isomers onto clay materials. Environ Sci Technol 32(24):3907-3912.
WHO (1990) Tricresyl phosphate. Environmental Health Criteria 110(1990)
Weiner ML, Jortner BS (1999) Organophosphate-induced delayed neurotoxicity of triarylphosphates. Neurotoxicology 20(4):653-674.
7-507
-------
Zeiger E, Anderson B, Haworth S, et al. (1987) Salmonella mutagenicity tests III. Results from the testing of 255 chemicals. Environ Mutagen
9(Suppl. 9): 1-110.
van der Veen I, de Boer J (2012) Phosphorus flame retardants: Properties, production, environmental occurrence, toxicity and analysis.
Chemosphere 88(10): 1119-1153.
7-508
-------
Triphenyl phosphate (TPP)
Screening Level Toxicology Hazard Summary
This table contains hazard information for each chemical; evaluation of risk considers both hazard and exposure. Variations in end-of-life processes or degradation and combustion
by-products are discussed in the report but not addressed directly in the hazard profiles. The caveats listed below must be taken into account when interpreting the information in the
table.
VL = Very Low hazard L = Low hazard = Moderate hazard H = High hazard VH = Very High hazard - Endpoints in colored text (VL, L, M, H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].
Chemical
CASRN
Human Health Effects
|
H
0
H
3
-^-i
•|
4J
0
_a
sS
U
£
^
H
O
S
o
ej
O
0)
•^
u
a
•o
o
8.
0)
^
0)
s
QM
O
"3
P
13
'Si
_o
o
1
Z
0)
0
P
•a
4>
sS
0)
0)
a
.0
'-£
.H
a
OJ
C/5
a
C/5
r*> S
o '•§
5^ N
.^" "^
5« fl
OJ g
a
v^
S
•c
•_
hH
^j
a
_o
"S3
•H
hH
••
2
0)
P
Aquatic
Toxicity
QJ
3
u
'a
S
u
Environmental
Fate
0)
u
a
"S
1
PH
_0
«
"3
s
u
u
sS
_o
s
Triphenyl phosphate (TPP)
I 115-86-6 |L|M|L|L|L|L|H|L| |L|vL|vH|vHr
:
7-509
-------
CASRN: 115-86-6
MW: 326.29
MF: C18H1504P
Physical Forms:
Neat: Solid
Use: Flame retardant
SMILES: O=P(Oc 1 ccccc 1 )(Oc 1 ccccc 1 )Oc 1 ccccc 1
Synonyms: Phosphoric acid, triphenyl ester; O,O,O-Triphenyl phosphate; TPP
Chemical Considerations: This is a discrete organic chemical with a MW below 1,000. EPI v4.11 was used to estimate physical/chemical and environmental fate
values due to an absence of experimental data. Measured values from experimental studies were incorporated into the estimations.
Polymeric: No
Oligomeric: Not applicable
Metabolites, Degradates and Transformation Products: Diphenyl phosphate (CASRN 838-85-7) and phenol (CASRN 108-95-2) (OECD-SIDS, 2002)
Analog: No analog
Endpoint(s) using analog values: Not applicable
Analog Structure: Not applicable
Structural Alerts: Organophosphates; Neurotoxicity (EPA, 2012).
Risk Phrases: R50/53: Very toxic to aquatic organisms. May cause long-term adverse effects in the aquatic environment (OECD-SIDS, 2002).
Hazard and Risk Assessments: DfE Alternatives Assessment for Furniture Flame Retardancy Partnership and Flame Retardant Alternatives for DecaBDE
Partnership; Toxicological Profile for Phosphate Ester Flame Retardants, September, 2012; OECD SIDS Initial Assessment Report, October 2002 (OECD-SIDS,
2002; EPA, 2005, 2012; ATSDR, 2009).
7-510
-------
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
PHYSICAL/CHEMICAL PROPERTIES
Melting Point (°C)
Boiling Point (°C)
Vapor Pressure (mm Hg)
Water Solubility (mg/L)
Log Kow
Flammability (Flash Point)
50.5
(Measured)
49
Reported as 49-5 0°C (Measured)
>300
(Estimated)
245
Reported at 1 1 mm Hg (Measured)
220
Reported at 5 mm Hg (Measured)
6.28xlO-6at25°C
(Extrapolated)
l.SxlO'6
(Measured)
1.9 (Measured)
Reported at 25 °C
0.75 (Measured)
OECD Guideline 105
0.025 (Measured)
4.59
(Measured)
4.76
(Measured)
220°C (Measured)
Lide, 2008
EC, 2000
EPIv4.11;EPA, 1999
O'Neil et al., 2006
EC, 2000
Dobry and Keller, 1957
EC, 2000
Saegeretal., 1979
EC, 2000
EC, 2000
Hanschetal., 1995
OECD-SIDS, 2002
Lewis, 2007
Reported in a primary source.
Reported in a secondary source;
consistent with value reported in
primary source.
Cutoff value for high boiling
point compounds according to
HPV assessment guidance.
Reported in a primary source.
Reported in a secondary source;
consistent with value reported in
primary source.
Reported in a secondary source.
Reported in a secondary source.
Reported in a secondary source.
Guideline study reported in a
secondary source.
Reported in a secondary source;
not consistent with other
measured values.
Reported in a primary source.
Reported in a secondary source;
consistent with value reported in
primary source.
No study details reported.
7-511
-------
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
Explosivity
Pyrolysis
pH
pKa
DATA
Not expected to form explosive
mixtures with air (Estimated)
Not applicable (Estimated)
Not applicable (Estimated)
REFERENCE
Professional judgment
Professional judgment
Professional judgment
DATA QUALITY
No experimental data located;
based on its use as a flame
retardant.
No data located.
Does not contain functional
groups that are expected to
ionize under environmental
conditions.
Does not contain functional
groups that are expected to
ionize under environmental
conditions.
7-512
-------
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
HUMAN HEALTH EFFECTS
Toxicokinetics
Dermal Absorption in vitro
Absorption,
Distribution,
Metabolism &
Excretion
Oral, Dermal or Inhaled
Triphenyl phosphate is hydrolyzed in the liver to produce diphenyl phosphate as the primary
metabolite. TPP can be detected in human breast milk. Experimental data for the FM550 (a
mixture made up of a sum total of TBB and TBPH of 50% with additional components identified as
IPTPP and TPP) indicate that absorption of at least one component (TBB) can occur in rats
following oral exposure from gestation through lactation. TBB was detected in tissues of exposed
dams and the pups following exposure to FM550.
Pregnant rats were administered 0, 0. 1
or 1 mg/kg-day of FM550 in the diet
across gestation and through lactation
(GD8-PND21)
FM550 components including TBPH
was detected in adipose, liver, and
muscle tissues in Dams at PND 2 1 with
the highest concentration in the adipose
tissue (768 ng/g w.w. in high dose,
29.6 ng/g w.w. in low dose, < 7.0 ng/g
w.w. in controls). The primary
metabolite of TBB (TBB A) was also
detected in liver tissue of dams on
PND 21.
TBB was detected in pooled PND21
pup adipose tissue. TBB was not
detected in pooled pup adipose tissue
by PND220.
Triphenyl phosphate is hydrolyzed in
rat liver homogenate to produce the
metabolite diphenyl phosphate
Patisauletal., 2013
OECD-SIDS, 2002; ECHA,
2012
No data located.
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.
Reported in a secondary source.
7-513
-------
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
Other
Acute Mammalian Toxicity
Acute Lethality
Oral
Dermal
Inhalation
Carcinogenicity
OncoLogic Results
Carcinogenicity (Rat and Mouse)
DATA
TPP concentrations in milk were
analyzed in a human cohort study
conducted between 1997 and 2007.
Median concentration across all
subjects was 8.5 ng/g (min-max values:
3.2-llng/g).
REFERENCE
ECHA,2012
DATA QUALITY
Limited study details reported in
a secondary source
LOW: Oral LD50 in rats and mice is >5,000 mg/kg and the dermal LD50 in rabbits is >7,900 mg/kg.
No adequate data were located to assess the toxicity of inhalation exposure.
Rat, mouse, oral LD50 >5,000 mg/kg
Rat oral LD50 >6,400 mg/kg
Rat oral LD50 >20,000 mg/kg
Rat oral LD50 = 10,800 mg/kg
Rat oral LD50 = 3,500 mg/kg
Rabbit dermal LD50 >7,900 mg/kg
Rabbit dermal LD50 > 10,000 mg/kg
Rat 1-hour LC50 >200 mg/L
OECD-SIDS, 2002
ATSDR, 2009
OECD-SIDS, 2002
OECD-SIDS, 2002
OECD-SIDS, 2002
ATSDR, 2009
OECD-SIDS, 2002
OECD-SIDS, 2002; ATSDR,
2009
Reported in a secondary source.
Reported in a secondary source.
Study reported in a secondary
source.
Study reported in a secondary
source; number of animals not
reported.
Study reported in a secondary
source. Dose range and number
of animals is not provided.
Reported in a secondary source.
Reported in a secondary source.
Reported in a secondary source.
Insufficient exposure time (1
hour), no data on method or
GLP.
MODERATE: OncoLogic modeling indicates a marginal to low potential for Carcinogenicity. No
long-term Carcinogenicity assays were found.
Marginal; likely to have equivocal
carcinogenic activity.
Mouse lung adenoma test: Male A/St
mice (20/group) received i.p. injections
of either 20 mg/kg (18/6 weeks); 40
OncoLogic, 2008
OECD-SIDS, 2002
Reported in a secondary source.
Nonstandard study, limited
histopathology and short-
7-514
-------
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
Combined Chronic
Toxicity/Carcinogenicity
Other
Genotoxicity
Gene Mutation in vitro
Gene Mutation in vivo
Chromosomal Aberrations in vitro
Chromosomal Aberrations in vivo
DNA Damage and Repair
Other
DATA
mg/kg (3/1 week); or 80 mg/kg. No
significant increase in incidence of
adenoma compared to negative
controls, and positive control
(urethane) produced 19.6
tumors/mouse with 100% survival.
REFERENCE
DATA QUALITY
duration.
No data located.
No data located.
LOW: Triphenyl phosphate was not mutagenic in bacteria or mammalian cells in vitro and did not
cause chromosomal aberrations in vitro. In addition, triphenyl phosphate did not result in DNA
damage in hamster fibroblast cells.
Negative, Ames assay in Salmonella
typhimurium strains TA98, TA100,
TA1537, TA1538 with and without
metabolic activation
Negative, forward mutation assay in
mouse lymphoma L5 178Y cells
Negative in chromosome aberration
test in Chinese hamster V79 cells; with
and without metabolic activation.
Negative, unscheduled DNA synthesis
in hamster fibroblast cells
Negative, mitotic gene conversion
assay in Saccharomyces cerevisiae
with and without activation
ATSDR, 2009; ECHA, 2013
OECD-SIDS, 2002; ECHA,
2013
ECHA, 20 13
OECD-SIDS, 2002
OECD-SIDS, 2002
Reported in a secondary source.
Reported in a secondary source.
No data located.
Reported in a secondary source.
No data located.
Reported in a secondary source.
Reported in a secondary source.
7-515
-------
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Reproductive Effects
LOW: Based on a rat oral reproductive/developmental NOAEL = 690 mg/kg-day for reproductive
effects (highest dose tested). In addition, no histopathological effects on reproductive organs were
reported following 3 weeks of dermal exposure in rabbits. Correlation of TPP in house dust and
decreased sperm counts in humans has been reported, however rat studies did not measure the
same endpoint, so there is an insufficient data for this effect.
Reproduction/Developmental
Toxicity Screen
Combined Repeated Dose with
Reproduction/ Developmental
Toxicity Screen
Reproductive/developmental dietary
study; TPP was administered in the
diet for 91 days at concentrations of 0,
0.25, 0.50, 0.75, or 1.0% (~0, 166, 341,
516 or 690 mg/kg-day, respectively).
At the completion of this study,
females were mated with males from
the same group. All remained on the
same diet as in the subchronic study
until day 20 of gestation when dams
were sacrificed. No signs of parental
toxicity, no reproductive effects
(number pregnant, corpora lutea,
implantations, implantation efficiency,
resorptions).
NOAEL: 690 mg/kg-day (highest dose
tested)
LOAEL: Not established
Reproduction and Fertility Effects
Rabbits, dermal (clipped, intact),
5x/week, 3 weeks, 50% solution in
ethanol; no effect on the reproductive
organs reported up to the highest dose
tested (1,000 mg/kg-day)
NOAEL: 1,000 mg/kg-day
No data located.
OECD-SIDS, 2002; ATSDR,
2009
OECD-SIDS, 2002
Reported in a secondary source.
Reported in a secondary source.
Organs examined by
histopathology; there were no
effects at the highest dose tested;
dermal repeated-dose study.
7-516
-------
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
Other
Developmental Effects
Reproduction/ Developmental
Toxicity Screen
DATA
Men living in homes with higher
amounts of TPP in house dust had
reduced sperm count and altered
hormone levels related to fertility and
thyroid function. Each interquartile
range (IQR) TPP increase in house
dust samples was associated with a
19% decrease in sperm concentrations
and a 10% increase in prolactin levels.
REFERENCE
Berts, 20 10; Meeker and
Stapleton, 2010
DATA QUALITY
The actual exposure to TPP is
unknown; it is not known if TPP
or other substances found in the
household dust caused or
contributed to the reported
toxicity.
LOW: Based on a rat oral reproductive/developmental NOAEL = 690 mg/kg-day for fetal effects
(highest dose tested). Developmental effects were reported in a study in pregnant Wistar rats
administered the analog mixture FM550 (sum total of TBB and TBPH approximately 50%) during
gestation though lactation (GD8 - PND21); developmental effects included early female puberty,
weight gain, altered exploratory behavior, and increased male left ventricle thickness (LOAEL = 1
mg/kg-day, NOAEL = 0.1 mg/kg-day). It is uncertain which component or components of the FM
550 mixture is driving the reported developmental effects. While the FM 550 mixture data indicates
a High hazard potential, it may be the other components driving the reported toxicity.
There were no data located for the developmental neurotoxicity endpoint. Decreased cholinesterase
activity in pregnant lab animals has been shown to have a negative impact on fetal brain
development. As a result, there is uncertain potential for developmental neurotoxicity for this
substance.
No data located.
7-517
-------
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
Combined Repeated Dose with
Reproduction/ Developmental
Toxicity Screen
Prenatal Development
Postnatal Development
Prenatal and Postnatal Development
DATA
Reproductive/developmental dietary
study; TPP was administered in the
diet for 9 1 days at concentrations of 0,
0.25, 0.50, 0.75, or 1.0% (~0, 166, 341,
516 or 690 mg/kg-day, respectively).
At the completion of this study,
females were mated with males from
the same group. All remained on the
same diet as in the subchronic study
until day 20 of gestation when dams
were sacrifice. No effects on fetal
endpoints (viability, early or late
deaths, fetal weight, length or
distribution) or skeletal anomalies.
Developmental effects:
NOAEL: 690 mg/kg-day (highest dose
tested)
LOAEL: Not established
Pregnant Wistar rats were administered
0, 0.1 or 1 mg/kg-day of the analog
FM550 in the diet during gestation and
through lactation (GD8 - PND 21);
Maternal toxicity: Increased serum
thyroxine (T4) levels in the high dose
dams compared to controls was
reported. There was no significant
change in triiodothyronine (T3) levels
in dam serum. Decreased hepatic
carboxylesterease activity was also
reported in dams in the high dose
REFERENCE
OECD-SIDS, 2002; ATSDR,
2009; ECHA, 2012
Patisauletal., 2013
DATA QUALITY
A LOAEL was not identified;
there were no effects at the
highest dose tested.
No data located.
No data located.
Estimated based on data for
FM550 mixture; non guideline
study; the test substance
identified as FM550 is a mixture
made up of TBB, TBPH (sum
total of TBB and TBPH is
approximately 50%), TPP and
IPTPP; it is not clear which
component or components of the
mixture are driving the reported
developmental effects.
7-518
-------
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
group.
Developmental toxicity: female
offspring in the high dose group
displayed a significantly earlier vaginal
opening when compared to controls. A
statistically significant increase in
weight was reported in both males and
females in the high dose group at PND
120. This effect persisted through PND
180 to PND 220 with high dose males
and females having significantly higher
weights than same sex controls. A
dose-dependent decrease in the number
of rats to enter with open arms,
(indicating anxiety), was reported in
both male and female offspring.
Increased blood glucose levels were
reported in male offspring in the high-
dose group compared to controls.
There was no statistically significant
difference in heart weight of male or
female offspring. Left ventricular (LV)
free wall thickness was significantly
increased in male offspring in the high
dose group; there were no changes in
LV thickness in females at any dose.
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
7-519
-------
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
Developmental Neurotoxicity
Other
Neurotoxicity
Neurotoxicity Screening Battery
(Adult)
Other
DATA
vaginal opening in females, increased
weight in males and females, decreased
open arm behavior, increased blood
glucose levels in males and increased
LV thickness in males)
There were no data located for the
developmental neurotoxicity endpoint.
Decreased cholinesterase activity in
pregnant lab animals has been shown
to have a negative impact on fetal brain
development. As a result, there is
uncertain potential for developmental
neurotoxicity for this substance
REFERENCE
Professional judgment
DATA QUALITY
No data located.
No data located.
LOW: Based on an adult rat neurotoxicity screening battery NOAEL = 711 mg/kg-day; all other
experimental results are consistent with this hazard designation.
4-month dietary study, 10 rats/dose,
0.25, 0.5, 0.75 or 1% test concentration
(161, 345, 517 or 711 mg/kg-day,
respectively), no neurobehavioral
effects (open field, accelerating
rotarod, forelimb grip strength and
negative geotaxis examinations)
NOAEL: 711 mg/kg-day (highest dose
tested)
LOAEL: Not established
There is potential for neurotoxic effects
based on a structural alert for
organophosphates
(Estimated)
Two female hens/dose in delayed
ATSDR, 2009
Professional judgment
OECD-SIDS, 2002
Reported in a secondary source.
Estimated based on a structural
alert for organophosphates and
professional judgment.
Reported in a secondary source.
7-520
-------
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
neurotoxicity test, gavage, 2,000,
3,000, 5,000, 8,000, or 12,500 mg/kg,
no signs of toxicity in-life or at
necropsy
NOAEL >12,500 mg/kg; highest dose
tested
LOAEL: Not established
No data on test substance purity.
Several acute oral studies in hens,
administered doses up to 12,500
mg/kg, generally found no signs of
paralysis, histopathological changes in
examined nerve tissues, or behavior
immediately after or during
observation periods of up to 36 days.
However, blood cholinesterase was
decreased by up to 87% in studies
where it was measured.
NOAEL >12,500 mg/kg; highest dose
tested
LOAEL: Not established
OECD-SIDS, 2002
Reported in a secondary source.
No data on test substance purity.
15-day repeated dose dermal study,
rabbits (10/sex/group) were exposed to
test compound concentrations of 0,
100, and 1,000 mg/kg-day. No
mortality, clinical symptoms, or
changes in body weight, hematology,
clinical chemistry, necropsy, organ
weights and histopathology reported;
only decreased acetyl cholinesterase
levels in plasma, erythrocytes and
brain were reported and not considered
OECD-SIDS, 2002
Reported in a secondary source.
Treatment period only 15 days;
quantitative data, effect levels,
and test substance purity were
not presented in the study report.
7-521
-------
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
Repeated Dose Effects
DATA
to be of toxicological relevance as
there was no clinical or histological
correlation.
REFERENCE
DATA QUALITY
HIGH: Based on weight of evidence including reduced body weight in male rats administered
triphenyl phosphate in the diet for 28-days. The NOAEL of 23.5 mg/kg-day and the LOAEL of
161.4 mg/kg-day span across the High and Moderate hazard designation ranges (DfE criteria are
for 90-day repeated dose studies; criteria values are tripled for chemicals evaluated in 28-day
studies making the High hazard range < 30 mg/kg-day and the Moderate hazard range between 30
and 300 mg/kg-day).
28-day repeated dose dietary study,
rats were fed test substance at
concentrations of 0, 250, 1,000 and
4,000 ppm. Effects on body weights
were observed.
NOAEL (male): 250 ppm (23.5 mg/kg-
day)
LOAEL (male): 1,000 ppm (161.4
mg/kg-day)
3 5 -day repeated-dose oral (dietary)
study, 5 male rats/group, test
compound concentrations of 0, 0.5, and
5.0% (~0, 350, and 3,500 mg/kg-day,
respectively), with a 0.1% (-70 mg/kg-
day) dose replacing the high dose
group after 3 days. Slight reduction in
body weight gain and increase in liver
weight in 350 mg/kg-day dose group.
NOAEL: 70 mg/kg-day
LOAEL: 350 mg/kg-day
4-month repeated-dose dietary study,
Sprague-Dawley rats (10 rats/dose)
ECHA,2012
OECD-SIDS, 2002
OECD-SIDS, 2002; ATSDR,
2009
Reported in secondary source.
DfE criteria are for 90-day
repeated dose studies. Criteria
values are tripled for chemicals
evaluated in 28-day studies.
Reported in a secondary source.
Limited study details provided.
Reported in a secondary source.
7-522
-------
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
Immune System Effects
DATA
were fed 0.25, 0.5, 0.75 or l%test
concentration (161, 345, 517 or 711
mg/kg-day, respectively). Reduced
body weight gain (1 1%) at 345 mg/kg-
day.
NOAEL: 161 mg/kg-day
LOAEL: 345 mg/kg-day
15 day repeated-dose dermal study,
rabbits (10/sex/group) were exposed to
test compound concentrations of 0,
100, and 1,000 mg/kg-day. No
mortality, clinical symptoms, or
changes in body weight, hematology,
clinical chemistry, necropsy, organ
weights and histopathology reported;
only decreased acetyl cholinesterase
levels in plasma, erythrocytes and
brain were reported and not considered
to be of toxicological relevance as
there was no clinical or histological
correlation.
In a 3 -month study, rats were orally
gavaged with test substances at 0, 380
and 1,900 mg/kg-day. No toxic effects
were observed.
NOEL: 1,900 mg/kg-day; highest dose
tested
LOEL: Not established
120-day dietary study, rats, 0, 0.25,
0.5, 0.75, and l%of triphenyl
phosphate (~0, 161, 345, 517 and 711
REFERENCE
OECD-SIDS, 2002
ATSDR, 2009
ATSDR, 2009
DATA QUALITY
Reported in a secondary source.
Treatment period only 15 days;
quantitative data, effect levels,
and test substance purity were
not presented in the study report.
Limited study details reported in
a secondary source. Primary
source is an abstract with few
experimental details.
Reported in a secondary source.
7-523
-------
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
Skin Sensitization
Skin Sensitization
DATA
mg/kg-day); initial, secondary, and
tertiary immunizations with sheep red
blood cells performed at 60, 81, and
102 days, respectively. No significant
effects were reported on the weight and
histopathology of the spleen, thymus
and lymph nodes, and no significant
changes to the humoral response were
reported.
NOAEL: 711 mg/kg-day (highest dose
tested)
Rabbits, up to 1,000 mg/kg-day,
applied 5 days/week for 3 weeks to
intact or abraded skin had no gross or
microscopic effects on the spleen,
thymus, or lymph nodes.
NOAEL: 1,000 mg/kg-day (highest
dose tested)
REFERENCE
ATSDR, 2009
DATA QUALITY
Reported in a secondary source.
LOW: Based on an experimental study in guinea pigs indicating that triphenyl phosphate is not a
skin sensitizer.
Several human case studies have
reported allergic dermatitis; 15 of
23,192 (0.065%) human volunteers
patch tested from 1950 to 1962 had
positive reactions to cellulose acetate
film containing 7- 10% triphenyl
phosphate and 3-4% phthalic esters
A confidential skin Sensitization study
with negative results in guinea pigs
None of the patients tested in two
separate studies of 343 and 174
OECD-SIDS, 2002
Submitted confidential study
OECD-SIDS, 2002
Reported in a secondary source.
Limited study details provided;
patch tests conducted with
mixtures; unclear which
component of mixture caused
low incidence of Sensitization.
Reported in a confidential study.
Reported in a secondary source.
Limited study details provided.
7-524
-------
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
Respiratory Sensitization
(Respiratory Sensitization
Eye Irritation
Eye Irritation
Dermal Irritation
Dermal Irritation
DATA
patients, respectively, had Sensitization
reactions to triphenyl phosphate
Not sensitizing, guinea pig
maximization test
REFERENCE
OECD-SIDS, 2002
DATA QUALITY
Study reported in a secondary
source; conducted according to
OECD Guide-line 406
No data located.
No data located.
LOW: Triphenyl phosphate is mildly irritating to the eyes with effects clearing within 72 hours.
Not irritating, rabbits
Mild irritation in rabbit eyes, clearing
within 72 hours
OECD-SIDS, 2002
OECD-SIDS, 2002
Study reported in a secondary
source; conducted according to
OECD Guide-line 405
Study reported in a secondary
source
VERY LOW: Triphenyl Phosphate is not a skin irritant in rabbits
Not irritating, rabbits; semi-occlusive
or occlusive conditions for 4, 24 or 72
hours
Non-irritant, rabbit
OECD-SIDS, 2002
ATSDR, 2009
Study reported in secondary
source; conducted according to
OECD Guide-line 404
Reported in a secondary source.
7-525
-------
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Endocrine Activity
Triphenyl phosphate was found to be inactive in estrogen-receptor binding assays; however, it was
shown to be a moderate androgen-receptor (AR) binder in a competitive binding assay. Triphenyl
phosphate was shown to inhibit human AR in the absence of agonist and to inhibit testosterone-
induced AR activity. In addition, Triphenyl phosphate significantly impaired reproduction in
zebrafish and was correlated with decreased sperm count and altered hormone levels in men.
Increased serum thyroxine (T4) levels were reported in the serum of dams following oral
administration to FM550 (mixture of 50% sum total of TBB and TBPH with additional components
identified as IPTPP and TPP). It is unclear which component or components of the mixture are
driving the endocrine activity effects.
21-day reproduction study in zebrafish.
Significant decrease in fecundity,
significant increases of plasma 17B-
estradiol (E2) concentrations,
vitellogenin (VTG) levels, and
E2/testosterone (T) and E2/11-
ketotestosterone (11-KT) ratios. Sex-
dependent changes in transcriptional
profiles of several genes of the
hypothalamus-pituitary-gonad (HPG)
axis.
Study conducted to determine effects
of triaryl phosphates on mouse and
human nuclear receptors. Mouse
constitutively active receptor (CAR)
was activated by 1.3-fold following
exposure to TPP. Testosterone-induced
AR-dependent activity was lowered by
30-40%.
Exposure to TPP in zebrafish resulted
in severe pericardial edema and
blocked looping of the atrium and
ventricle. TPP-induced cardiotoxicity
in zebrafish embryos is mediated
Liu etal., 2013
Adequate primary source
Honkakoski et al., 2004
Adequate primary source
McGee etal., 2013
Adequate primary source
7-526
-------
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
through an AHR independent pathway.
In a luciferase reporter-gene assay
using cultured cells, TPP inhibited the
luciferase expression induced by
dihydrotestosterone (10~9 M).
IC50 for antiandrogenic activity =
0.000047 - 0.0006 M
Ohyama et al., 2006
Primary source in Japanese with
English abstract
Endocrine disrupting potential was
investigated using human cells lines
(H295R, MVLN) and zebrafish
plasma. TPP was cytotoxic to H295R
cells (showing <80% cell viability at >
10 mg/L) and significantly increased
E2 and T production. Transcription of
CYP19A1 was significantly up-
regulated and transcription of
SULT1E1 gene was down-regulated.
No binding affinity to E2 receptor in
MVLN cells, but binding of E2 to ER
was reduced in a dose-dependent
manner. Plasma E2 was significantly
increased in fish plasma and T and 11-
KT were decreased (1 mg/L). Changes
in transcription of steroidogenic genes
and vitellogenin gene were observed.
Liu etal., 2012
Adequate, primary source
Men living in homes with higher
amounts of TPP in house dust had
reduced sperm count and altered
hormone levels related to fertility and
thyroid function. Each interquartile
range (IQR) TPP increase in house
dust samples was associated with a
Berts, 2010; Meeker and
Stapleton, 2010
The actual exposure to TPP is
unknown; it is not known if TPP
or other substances found in the
household dust caused or
contributed to the reported
toxicity.
7-527
-------
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
DATA
19% decrease in sperm concentrations
and a 10% increase in prolactin levels.
Pregnant Wistar rats were administered
0, 0.1 or 1 mg/kg-day of the analog
FM550 in the diet during gestation and
through lactation (GD8 - PND 21);
Increased serum thyroxine (T4) levels
(increase of 65%) in the high dose
dams compared to controls was
reported. There was no significant
change in triiodothyronine (T3) levels
in dam serum. There was no reported
statistically significant change in T4 or
T3 levels in pup serum on PND 2 1
when compared to controls.
Inhibited AR activity in COS-1 cells
transfected with human AR both in the
absence of agonist, as well as inhibited
testosterone-induced AR activity by 30
40%. (Measured)
Moderate binding in a competitive
androgen-receptor (AR) binding assay
using recombinant rat protein
expressed in Escherichia coli.
Inactive in a binding assay with the rat
uteri estrogen receptor from
ovariectomized Sprague-Dawley rats
REFERENCE
Patisauletal., 2013
ATSDR, 2009
ATSDR, 2009
ATSDR, 2009
DATA QUALITY
Estimated based on data for
FM550 mixture; non guideline
study; the test substance
identified as FM550 is a mixture
made up of TBB, TBPH (sum
total of TBB and TBPH is
approximately 50%), TPP and
IPTPP; it is not clear which
component or components of the
mixture are driving the reported
endocrine activity effects.
Reported in a secondary source.
Reported in a secondary source.
Reported in a secondary source
7-528
-------
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
Immunotoxicity
Immune System Effects
DATA
REFERENCE
DATA QUALITY
Oral exposure of rats to triphenyl phosphate for 4 months and dermal exposure of rabbits for 3
weeks produced no effects on immune function parameters.
120-day dietary study, rats, 0, 0.25,
0.5, 0.75, and 1% of triphenyl
phosphate (~0, 161, 345, 517 and 711
mg/kg-day); initial, secondary, and
tertiary immunizations with sheep red
blood cells performed at 60, 81, and
102 days, respectively. No significant
effects were reported on the weight and
histopathology of the spleen, thymus
and lymph nodes, and no significant
changes to the humoral response were
reported.
Rabbits, up to 1,000 mg/kg-day,
applied 5 days/week for 3 weeks to
intact or abraded skin had no gross or
microscopic effects on the spleen,
thymus, or lymph nodes.
ATSDR, 2009
ATSDR, 2009
Reported in a secondary source.
Reported in a secondary source.
ECOTOXICITY
ECOSAR Class
Acute Aquatic Toxicity
Fish LC50
VERY HIGH: Based on experimental fish 96-hour LC50 values of 0.4 and 0.85 mg/L.
Freshwater fish (Oncorhynchus mykiss)
96-hour LC50 = 0.4 mg/L
(Experimental)
Freshwater fish (Oncorhynchus mykiss)
96-hour LC50 = 0.85 mg/L
(Experimental)
Freshwater fish (Lepomis macrochirus)
96-hour LC50 = 290 mg/L
(Experimental)
OECD-SIDS, 2002
OECD-SIDS, 2002
OECD-SIDS, 2002
Reported in a secondary source
Reported in a secondary source.
Guideline study.
Limited study details reported in
a secondary source. The study
does not meet important criteria
for standard methods (e.g., test
7-529
-------
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
Daphnid LC50
Other Invertebrate LC50
DATA
Fish 96-hour LC50 = 1.34 mg/L
(Estimated)
ECOSAR: Esters
Daphnid 48-hour LC50 = 1.28 mg/L
(Experimental)
Daphnid 48-hour EC50 = 1.35 mg/L
Static
(Experimental)
Daphnid 4 8 -hour LC50 = 1.0 mg/L
(Experimental)
Daphnid 4 8 -hour LC50 = 2.1 1 mg/L
(Estimated)
ECOSAR: Esters
Mysidopsis bahia 96-hour LC50 >0.18 -
0.32 mg/L
(Experimental)
REFERENCE
ECOSARvl.ll
FMC, 1979
OECD-SIDS, 2002
Mayer etal., 1981
ECOSARvl.ll
OECD-SIDS, 2002
DATA QUALITY
substance concentration at
solubility threshold in water).
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
Sufficient study details reported.
Study reported in a secondary
source; conducted according to
US EPA 660/3-75-009.
Sufficient study details reported.
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
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.
7-530
-------
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Green Algae EC50
Green algae (Selenastrum
capricornutum ) 96-hour EC50 = 2.0
mg/L
(Experimental)
OECD-SIDS, 2002
Reported in a secondary source.
Green algae 96-hour EC50 = 2.0 mg/L
(Experimental)
Mayer etal., 1981
Sufficient study details reported.
Green algae (Scenedesmus
subspicatus) 72-hour LOEC = 0.5-5
mg/L
NOEC = 0.25 - 2.5 mg/L
(Experimental)
OECD-SIDS, 2002
Study reported in secondary
source; conducted according to
OECD guideline 201.
Green algae 96-hour EC50 = 0.6 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
Chronic Aquatic Toxicity
VERY HIGH: Based on an experimental fish 30-day LOEC = 0.037 mg/L. Experimental data for
algae indicate a High hazard concern. No chronic experimental data were available for daphnia.
Fish ChV
Freshwater fish (Oncorhynchus mykiss)
30-day LOEC = 0.037 mg/L
(Experimental)
Fish (Pimephales promelas) 30-day
LOEC = 0.23 mg/L
NOEC = 0.087 mg/L
There were no changes in hatchability
of eggs, mean total length, and average
we weight of fry. There was reduced
percentage survival of fry through 30
days post-exposure at 0.23 mg/L.
Severe scoliosis was reported in
several fry and erratic swimming was
reported in all fry at 0.23 mg/L.
ECHA,2013
OECD-SIDS, 2002
Reported in a secondary source.
Sufficient study details reported.
7-531
-------
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
Daphnid ChV
Green Algae ChV
DATA
(Experimental)
Fish ChV = 0.06 mg/L
(Estimated)
ECOSAR: Esters
Daphnid ChV = 0.69 mg/L
(Estimated)
ECOSAR: Esters
Green algae (Scenedesmus
subspicatus) 72-hour LOEC = 0.5-5
mg/L
NOEC = 0.25 - 2.5 mg/L
(Experimental)
Green algae ChV = 0.35 mg/L
(Estimated)
ECOSAR: Esters
REFERENCE
ECOSARvl.ll
ECOSARvl.ll
OECD-SIDS, 2002
ECOSARvl.ll
DATA QUALITY
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
Study reported in secondary
source; conducted according to
OECD guideline 201.
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
ENVIRONMENTAL FATE
Transport
(Henry's Law Constant (atm-m3/mole)
Level III fugacity models incorporating available physical and chemical property data indicate that
at steady state, TPP is expected to be found primarily in soil and to a lesser extent, water. Triphenyl
phosphate is expected to have moderate mobility in soil, based on measured Koc values in silty clay,
loamy sand and silt loam. Leaching through soil to groundwater may occur, though it is not
expected to be an important transport mechanism. Triphenyl phosphate may volatilize from moist
soil and water surfaces based on its Henry's Law constant. Volatilization from dry surface is not
expected based on its vapor pressure. In the atmosphere, triphenyl phosphate is expected to exist in
both the vapor phase and particulate phase. Particulates may be removed from air by wet or dry
deposition.
1.2xlQ-5 (Measured)
Huckins et al., 1991 (Reported in a primary source.
7-532
-------
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
Sediment/Soil Adsorption/Desorption
- KOC
Level III Fugacity Model
DATA
2,5 14 Reported for silty clay
(Measured)
2,736 Reported for silt loam
(Measured)
3,561 Reported for loamy sand.
(Measured)
Air = 0.7%
Water =14.5%
Soil = 75. 8%
Sediment = 9.02% (Estimated)
REFERENCE
Anderson et al., 1993
Anderson et al., 1993
Anderson et al., 1993
EPIv4.11
DATA QUALITY
Reported in a primary source.
Reported in a primary source.
Reported in a primary source.
Reported in a Level III Fugacity
model. Experimental data is
consistent with partitioning to
sediment.
7-533
-------
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Persistence
LOW: The persistence of triphenyl phosphate is based on experimental data. Under aerobic
conditions in a Japanese MITI ready biodegradability test (OECD Test Guidelines (TG) 301C),
90% biodegradation of triphenyl phosphate occurred after 28 days, and 93.8% triphenyl phosphate
removal as dissolved organic carbon (DOC) occurred over 20 days in an OECD 303A guideline
study. TPP does not meet the criteria for very low persistence because the percent removal in the
criteria does not occur within a 10-day window. In loamy sand, a half-life of 37 days was observed
under aerobic conditions. Triphenyl phosphate was determined to be inherently biodegradable in a
river die-away test, after degrading 100% over 3 days in river water. Triphenyl phosphate may
degrade under anaerobic conditions, with primary degradation of 31.1% after 3 days (89.7% after
40 days) in river sediment. However, removal under anaerobic conditions is not anticipated to be an
important fate process. Triphenyl phosphate will undergo hydrolysis under alkaline conditions,
with half-lives of 3 days at pH 9; it is relatively stable to hydrolysis under neutral and acidic
conditions, with half-lives of 28 days at pH 5 and 19 days at pH 7. Triphenyl phosphate is not
expected to be susceptible to direct photolysis by sunlight, since it does not absorb light at
wavelengths >290 nm. The atmospheric half-live of vapor-phase triphenyl phosphate is estimated to
be 12 hours.
Water
Aerobic Biodegradation
Passes Ready Test: Yes
Test method: OECD TG 301C:
Modified MITI Test (I)
83-94% biodegradation after 28 days at
100 mg/L of test substance.
(Measured)
Study results: 100%/3 days
Test method: Die-Away
Reported as inherently biodegradable
in a river water/river die-away test
(Measured)
Volatilization Half-life for Model
River
4 days (Estimated)
Volatilization Half-life for Model
Lake
47 days (Estimated)
OECD-SIDS, 2002
OECD-SIDS, 2002
EPIv4.11
EPIv4.11
Reported in a guideline study.
Reported in a secondary source.
Reported in the volatilization
from water model.
Reported in the volatilization
from water model.
7-534
-------
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
Soil
Aerobic Biodegradation
Anaerobic Biodegradation
Soil Biodegradation with Product
Identification
DATA
Study results: 93.8%/20 days
Test method: 303A: Activated Sludge
Units - Simulation Test
Removal as DOC, using initial
concentration of 5 mg/L with activated
sludge. Reported as inherently
biodegradable. (Measured)
Study results: 77%/28 days
Test method: Other
Reported as ultimately biodegradable.
Monsanto Shake Flask Procedure
(precursor to Closed bottle test).
(Measured)
Study results: 82%/28 days
Test method: CO2 Evolution
Modified Sturm test. Reported as
ultimately biodegradable. Measured in
domestic, adapted activated sludge
(Measured)
Study results: 93%/49 days
Test method: 302A: Inherent -
Modified SCAS Test
Reported as inherently biodegradable.
(Measured)
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)
REFERENCE
EC, 2000; OECD-SIDS, 2002
OECD-SIDS, 2002
OECD-SIDS, 2002
OECD-SIDS, 2002
OECD-SIDS, 2002
DATA QUALITY
Reported in a guideline study.
Reported in a secondary source.
Reported in a secondary source.
Reported in a guideline study.
Reported in a secondary source.
No data located.
7-535
-------
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
Air
Reactivity
Sediment/Water Biodegradation
Atmospheric Half-life
Photolysis
Hydrolysis
DATA
86.9%/40 days
Primary degradation in river sediment.
43. 3% after 3 days
86.9% after 40 days (Measured)
1 day (Estimated)
Not a significant fate process
(Estimated)
A 0.1 mg/L solution (with acetone)
was exposed to a mercury lamp to
examine the effect of UV light on the
degradation of TPP.
High pressure lamp (100W): 100%/20
mins
Low pressure lamp (15W): 100%/1
hour
(Measured)
50%/>28 days
Reported at 25 °C; pH 5 (Measured)
50%/19 days
Reported at 25 °C; pH 7 (Measured)
50%/3 days
Reported at 25 °C; pH 9 (Measured)
50%/7.5 days
Reported at pH 8.2 in river/lake water
(Measured)
50%/1.3days
Reported at pH 9.5 in river/lake water
(Measured)
100%/10 minutes at pH 13 (Measured)
REFERENCE
OECD-SIDS, 2002
EPIv4.11
Mill, 2000; Professional
judgment
EC, 2000
EC, 2000; OECD-SIDS, 2002
OECD-SIDS, 2002
EC, 2000; OECD-SIDS, 2002
EC, 2000
EC, 2000
ECHA,2013
DATA QUALITY
Reported in a secondary source.
Triphenyl phosphate does not
contain functional groups that
would be expected to absorb
light of wavelengths >290 nm.
Reported in a secondary source
under laboratory conditions.
Reported in a secondary source.
Reported in a secondary source.
Reported in a secondary source.
Reported in a secondary source.
Reported in a secondary source.
Reported in secondary source.
7-536
-------
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
Environmental Half-life
Bioaccumulation
Fish BCF
Other BCF
DATA
75 days (Estimated)
In loamy sand, observed half-lives of
37 days (aerobic) and 21 days
(anaerobic) (Measured)
REFERENCE
PBT Profiler
OECD-SIDS, 2002
DATA QUALITY
Documentation of study details
was not sufficient to assess its
reliability.
Half-life estimated for the
predominant compartment, as
determined by the PBT Profiler
methodology.
Reported in a secondary source.
MODERATE: There is moderate potential for bioaccumulation based on experimental BCF values.
132-364 (Rainbow trout) (Measured)
271
Rainbow trout (Measured)
364
Reported as 132-364 in rainbow trout
(Measured)
193
Reported as 84-193 in Medaka
(Measured)
160
Reported as 68-160 in Fathead minnow
(Measured)
144
Medaka (Measured)
110
Goldfish (Measured)
Mayer etal., 1981
EC, 2000
OECD-SIDS, 2002
EC, 2000
EC, 2000
OECD-SIDS, 2002
OECD-SIDS, 2002
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.
No data located.
7-537
-------
Triphenyl phosphate CASRN 115-86-6
PROPERTY/ENDPOINT
BAF
Metabolism in Fish
DATA
The pregnant rats were administered 0,
0.1 or 1 mg/kg-day of FM550 by oral
gavage across gestation and through
lactation (GD8-PND 21).
(Estimated by analogy)
73 (Estimated)
REFERENCE
Patisaul et al., 2013
EPIv4.11
DATA QUALITY
BAFs were not calculated. This
study did not analyze the
samples for the presence of TPP.
Non guideline study. The test
substance identified as FM550 is
a mixture made up of TBB,
TBPH (CASRN 26040-51-7),
IPTPP (CASRN 68937-41-7)
and TPP (CASRN 115-86-6).
No data located.
ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring
Ecological Biomonitoring
Human Biomonitoring
Triphenyl phosphate has been detected in drinking water in samples collected by the USGS. It has also
been detected in household dust in the United States (at concentrations of (<173-1,798,100 ng/g),
Pakistan, New Zealand, Belgium, Spain and Japan. Triphenyl phosphate has been detected in sediment
from Taihu Lake in China at concentrations ranging from 0.41-5.54 (ig/kg and in sediment in the U.S. It
has also been detected in river water, seawater, rainwater, snow, wastewater effluent, ambient air, and
indoor air (OECD-SIDS, 2002; Stiles et al, 2008; Stapleton et al., 2009; Berts, 2010; Ali et al., 2012; Cao
et al., 2012; van der Veen and de Boer, 2012; HSDB, 2013; Salamova et al., 2014).
Triphenyl phosphate has been detected in fish tissues. It has also been detected in the blubber of
bottlenose dolphins collected from the Gulf of Mexico (Kuehl and Haebler, 1995; Campone et al., 2010).
Triphenyl phosphate was detected in human milk, adipose tissue and human plasma. This chemical was
not included in the NHANES biomonitoring report (Shah et al., 2006; ECHA, 2012; CDC, 2013).
7-538
-------
ATSDR (2009) Toxicological profile for phosphate ester flame retardants. Atlanta, GA: Agency for Toxic Substances and Disease Registry.
Ali N, Van den Eede N, Dirtu AC, et al. (2012) Assessment of human exposure to indoor organic contaminants via dust ingestion in Pakistan.
Indoor Air 22(3):200-211.
Anderson C, Wischer D, Schmieder A, et al. (1993) Fate of triphenyl phosphate in soil. Chemosphere 27(5):869-879.
Berts KS (2010) Endocrine damper? Flame retardants linked to male hormone, sperm count changes. Environ Health Perspect 118(3):A 130.
CDC (2013) Fourth national report on human exposure to environmental chemicals, updated tables, March 2013. Centers for Disease Control and
Prevention. http://www.cdc.gov/exposurereport/pdf/FourthReport UpdatedTables Mar2013.pdf Accessed May 10, 2013.
Campone L, Piccinelli AL, Ostman C, et al. (2010) Determination of organophosphorus flame retardants in fish tissues by matrix solid-phase
dispersion and gas chromatography. Anal Bioanal Chem 397(2):799-806.
Cao S, Zeng X, Song H, et al. (2012) Levels and distributions of organophosphate flame retardants and plasticizers in sediment from Taihu Lake,
China. Environ Toxicol Chem 31(7): 1478-1484.
Dobry A, Keller R (1957) Vapor pressures of some phosphate and phosphonate esters. J Phys Chem 61(10): 1448-1449.
EC (2000) IUCLID dataset triphenyl phosphate. http://esis.jrc.ec.europa.eu/doc/IUCLID/data sheets/115866.pdf
ECF£A (2012) Triphenyl phosphate. Registered substances. European Chemicals
Agency. http://apps.echa.europa.eu/registered/data/dossiers/DISS-9c823fa6-50fe-Ob74-e044-00144f67d249/AGGR-25e8a69c-b7a3-48f4-8aa3-
df36bOa9735f DISS-9c823fa6-50fe-Ob74-e044-00144f67d249.html#section 1.1.
ECFiA (2013) Triphenyl phosphate. Registered substances. European Chemicals
Agency. http://apps.echa.europa.eu/registered/data/dossiers/DISS-9c823fa6-50fe-Ob74-e044-00144f67d249/DISS-9c823fa6-50fe-Ob74-e044-
00144f67d249 DISS-9c823fa6-50fe-Ob74-e044-00144f67d249.html.
ECOSAR (Ecological Structure Activity Relationship), Version 1.11. Washington, DC: U.S. Environmental Protection
Agency, http://www.epa.gov/oppt/newchems/tools/21 ecosar.htm.
7-539
-------
EPA (1999) Determining the adequacy of existing data. Washington, DC: U.S. Environmental Protection
Agency, http://www.epa.gov/hpv/pubs/general/datadeqfh.pdf.
EPA (2005) Furniture flame retardancy partnership. Design for the Environment (DfE). http://www2.epa.gov/saferchoice/2014-update-report-
flame-retardants-used-flexible-polvurethane-foam.
EPA (2012) An alternatives assessment for the flame retardant decabromodiphenyl ether (DecaBDE) Draft report.
EPA (2012) Using noncancer screening within the SF initiative. Washington, DC: U.S. Environmental Protection
Agency, http://www.epa.gov/oppt/sf/pubs/noncan-screen.htm.
EPI Estimation Programs Interface (EPI) Suite, Version 4.11. Washington, DC: U.S. Environmental Protection
Agency, http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm.
FMC (1979) Acute aquatic toxicity of triphenyl phosphate. FMC Industrial Chemical Division.
HSDB (2013) Triphenyl phosphate. Hazardous Substances Data Bank. National Library of Medicine, http://toxnet.nlm.nih.gov/cgi-
bin/sis/htmlgen?HSDB.
Hansch C, Leo A, Hoekman D (1995) Exploring QSAR - hydrophobic, electronic, and steric constants. Washington, DC: American Chemical
Society.
Honkakoski P, Palvimo Jorma J, et al. (2004) Effects of triaryl phosphates on mouse and human nuclear receptors. Biochem Pharmacol 67(1):97-
106.
Huckins JN, Fairchild JF, Boyle TP (1991) Role of exposure mode in the bioavailability of triphenyl phosphate to aquatic organisms. Arch
Environ Contam Toxicol 21:481-485.
Kuehl DW, Haebler R (1995) Organochlorine, organobromine, metal, and selenium residues in bottlenose dolphins (Tursiops truncatus) collected
during an unusual mortality event in the Gulf of Mexico, 1990. Arch Environ Contam Toxicol 28:494-499.
Lewis RJ (2007) Hawley's Condensed Chemical Dictionary. 14 ed. New York: Wiley-Interscience.
Lide DR (2008) Tris(2-chloroethyl) phosphate. CRC Handbook of chemistry and physics. 88th ed. Boca Raton, FL: CRC Press, Taylor and
Francis Group, 3-512.
7-540
-------
Liu X, Ji K, Choi K (2012) Endocrine disruption potentials of organophosphate flame retardants and related mechanisms in H295R and MVLN
cell lines and in zebrafish. Aquat Toxicol 114-115:173-181.
Liu X, Ji K, Jo A, et al. (2013) Effects of TDCPP or TPP on gene transcriptions and hormones of HPG axis, and their consequences on
reproduction in adult zebrafish (Danio rerio). Aquat Toxicol 134-135:104-111.
Mayer F, Adams WJ, Finley MT, et al. (1981) Phosphate ester hydraulic fluids: An aquatic environmental assessment of pydrauls 50E and 115E.
In: Branson DR, Dickson KL, eds. American Society for Testing and Materials STP 737:103-123.
McGee SP, Konstantinov A, Stapleton 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.
Meeker JD, Stapleton HM (2010) House dust concentrations of organophosphate flame retardants in relation to hormone levels and semen quality
parameters. Environ Health Perspect 118(3):318-323.
Mill T (2000) Photoreactions in surface waters. In: Boethling R, Mackay D, eds. Handbook of Property Estimation Methods for Chemicals,
Environmental Health Sciences. Boca Raton: Lewis Publishers, 355-381.
O'Neil MJ, et al., eds (2006) The Merck index: an encyclopedia of chemicals, drugs, and biologicals. 14th ed. Whitehouse Station, N.J: Merck.
OECD-SIDS (2002) Triphenyl phosphate. CAS No: 115-86-6. Screening Information DataSet (SIDS). Organisation for Economic Co-operation
and Development, http://www.inchem.org/documents/sids/sids/115866.pdf.
Ohyama K, Nagata S, Hosogoe N, et al. (2006) Hormonal effects of organic phosphate triesters study by the reporter gene assay. Tokyo-to Kenko
Anzen Kenkyu Senta Kenkyu Nenpo 56:333-338.
OncoLogic (2008) U.S. EPA and LogiChem, Inc. 2005, Version 7.0. 2008.
Patisaul HB, Roberts SC, Mabrey N, et al. (2013) Accumulation and endocrine disrupting effects of the flame retardant mixture Firemaster 550 in
rats: an exploratory assessment. J Biochem Mol Toxicol 27(2): 124-36.
PBT Profiler Persistent (P),Bioaccumulative (B), and Toxic (T) Chemical (PBT) Profiler, Version 1.301. Washington, DC: U.S. Environmental
Protection Agency, www.pbtprofiler.net.
7-541
-------
Saeger VW, Hicks O, Kaley RG, et al. (1979) Environmental fate of selected phosphate esters. Environ Sci Technol 13(7):840-844.
Salamova A, Ma Y, Venier M, et al. (2014) High levels of organophosphate flame retardants in the Great Lakes atmosphere. Environ Sci Technol
Shah M, Meija J, Cabovska B, et al. (2006) Determination of phosphoric acid triesters in human plasma using solid-phase microextraction and gas
chromatography coupled to inductively coupled plasma mass spectrometry. J Chromatogr A 1 103(2):329-336.
Stapleton HM, Klosterhaus S, Eagle S, et al. (2009) Detection of organophosphate flame retardants in furniture foam and U.S. house dust. Environ
Sci Technol 43 (19): 7490-7495.
Stiles R, Yang I, Lippincott RL, et al. (2008) Measurement of drinking water contaminants by solid phase microextraction initially quantified in
source water samples by the USGS. Environ Sci Technol 42(8):2976-2981.van der Veen I, de Boer J (2012) Phosphorus flame retardants:
Properties, production, environmental occurrence, toxicity and analysis. Chemosphere 88(10): 1 1 19-1 153.
7-542
-------
Tris (l,3-dichloro-2-propyl) phosphate (TDCPP)
Screening Level Toxicology Hazard Summary
This table contains hazard information for each chemical; evaluation of risk considers both hazard and exposure. Variations in end-of-life processes or degradation and combustion
by-products are discussed in the report but not addressed directly in the hazard profiles. The caveats listed below must be taken into account when interpreting the information in the
table.
VL = Very Low hazard L = Low hazard = Moderate hazard = High hazard VH = Very High hazard - Endpoints in colored text (VL, L, , H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"
Chemical
CASRN
•
Human Health Effects
s
'H
o
H
u
^
'0
g
M
O
ft
U
^
|
o
0
S
O
>
|
•a
&
sS
•^
§
S
0
3
Q
^
'So
"o
S
z
o
P
•a
+s
0)
&
M
C
_o
13
.H
0)
C/5
d
C/5
r»> S
2 '•§
||
S g
M cc
=
-*^
sS
•c
^s
0
1
•c
HH
13
0)
Q
Aquatic
Toxicity
u
^
'3
S
u
Environmental
Fate
0)
u
a
S
4>
0.
a
o
13
s
g
0
S
Tris (l,3-dichloro-2-propyl) phosphate
(TDCPP)
13674-87-8
L
H
H
L
H
L
L
L
H
H
H
L
7-543
-------
Cll
ci^x0
cl^Y°^-°Y^ci
li
Cl^ ° Si
CASRN: 13674-87-8
MW: 430.91
MF: C9H15C16O4P
Physical Forms: Liquid
Neat: Liquid
Use: Flame retardant
SMILES: C1CC(CC1)OP(=O)(OC(CC1)CC1)OC(CC1)CC1
Synonyms: 2-Propanol, 1,3-dichloro-, phosphate (3:1); Tris(l,3-dichloro-2-propyl) phosphate; Tris(l-chloromethyl-2-chloroethyl) phosphate; Tris[2-chloro-l-
(chloromethyl)ethyl] phosphate; tris (1,3-dichloroisopropyl) phosphate; l,3-Dichloro-2-propanol phosphate (3:1); Phosphoric acid, tris(l,3-dichloro-2-propyl)ester;
TDCP; TDCPP; Antiblaze 195; Antiblaze TDCP; Amgard TDCP; CRP; Fyrol FR-2; Tolgard TDCP; Tris
Chemical Considerations: This is a discrete organic chemical with a MW below 1,000. EPI v4.1 1 was used to estimate physical/chemical and environmental fate
values due to an absence of experimental data. Measured values from experimental studies were incorporated into the estimations. Commercial formulations of this
substance may contain minor amounts of structural isomers such as tris(2,3-dichloro-l-propyl) phosphate (CASRN 78-43-3) (WHO, 1998; NAS, 2000).
7-544
-------
Polymeric: No
Oligomeric: Not applicable
Metabolites, Degradates and Transformation Products: Metabolites: Bis(l,3-dichloroisopropyl) hydrogen phosphate; bis(l,3-dichloro-2-propyl) phosphate, 1,3-
dichloro-2-propanediol, l,3-dichloro-2-propanol; an unidentified glutathione conjugate; l,3-dichloro-2-propyl, l-chloro-2-propanol phosphate; unidentified diester
metabolites; dimethyl derivative of l,3-dichloro-2-propyl phosphate; bis(l,3-dichloro-2-propyl) l-chloro-2-propanol phosphate; l-chloro-2-propanol phosphate;
bis(l,3-dichloro-2-propyl),l-carboxy-3-cloro-2-propyl phosphate.
Thermal Degradation products: carbon monoxide, carbon dioxide, hydrochloric acid, chloromethane, chloroethane, vinyl chloride, 1,2-dichloroethane,
chloropropenes, dichloropropenes, 1,2,3-trichloropropane, 2-chloroethanol, l,3-dichloro-2-propanol, acetaldehyde, acrolein, chloroacetone (Lynn et al., 1981; Nomeir
et al., 1981; Sasaki et al., 1984; NICNAS, 2001; BASF, 2007; EU, 2008; Van den Bade et al., 2013).
Analog: No analogs
Endpoint(s) using analog values: Not applicable
Analog Structure: Not applicable
Structural Alerts: Organophosphates, neurotoxicity. This chemical appears on the List of Chemicals Known to the State to Cause Cancer for the State of California:
California Proposition 65 cancer (EPA, 2012; California EPA, 2013).
Risk Phrases: R40 - limited evidence of a carcinogenic effect. R51/53 - toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment
(ECHA, 2012).
Hazard and Risk Assessments: A risk assessment for this chemical was completed by the European Union (EU) in 2008. This chemical was part of the HPV Data
Summary and Test Plan (Akzo Nobel, 2001; EU, 2008).
7-545
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
PHYSICAL/CHEMICAL PROPERTIES
Melting Point (°C)
Boiling Point (°C)
-58
Using differential scanning
calorimetry with a method compliant
with OECD Guideline 102. Freezing
point reported as -40°C. (Measured)
<-20
GLP study in accordance with
Directive 92/69/EC (Measured)
26.66
(Measured)
27
This substance exists as a
supercooled liquid and can crystallize
at temperatures below 27°C.
(Measured)
326
GLP study in accordance with
Directive 92/69/EC. Decomposition
was observed. (Measured)
236 at 5 mmHg
Reported as 236-237 at 5 mm Hg
(Measured)
200 at 4 mmHg
Reported as 200 at 4 mmHg
Akzo Nobel, 2001; EU, 2008
Cuthbert and Mullee, 2002; EU,
2008
Akzo Nobel, 2003; EU, 2008
CERI, 1999
Cuthbert and Mullee, 2002 (as
cited in EU, 2008)
WHO, 1998; Budavari, 2001
Akzo Nobel, 2003 (as cited in
EU, 2008)
Adequate OECD guideline study
reported in a secondary source.
Adequate guideline study
reported in a secondary source.
Sufficient details were not
available to assess the quality of
this study.
Sufficient details were not
available to assess the quality of
this study.
Guideline study reported in a
secondary source.
This value was measured at
lowered pressure.
This value was measured at
lowered pressure.
7-546
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
Vapor Pressure (mm Hg)
Water Solubility (mg/L)
DATA
(Measured)
200 at 4 mmHg Decomposes
Reported as 200 at 4 mmHg
(Measured)
200 Decomposes
Reported as gradual decomposition
above 200°C (Measured)
4.2xlO-8at25°C
Reported as 5.6xlO"6 Pa; GLP study
in accordance with Directive
92/69/EC vapor pressure balance
method. (Measured)
0.01at30°C
Results reported ranged from 0.01
mmHg at 30°C to 0.09 mmHg 20°C.
(Measured)
0.01at30°C
(Measured)
18.1 (Measured)
Reported as 18.1 ± 1.1 mg/L at 20°C,
GLP study in accordance with
Directive 92/69/EC
42 (Measured)
OECD Guideline 105: Shake-flask
method
100 (Measured)
REFERENCE
WHO, 1998
HSDB, 2003
Tremain, 2002 (as cited in EU,
2008)
EU, 2008
WHO, 1998; Akzo Nobel, 2001
Cuthbert and Mullee, 2002 (as
cited in EU, 2008)
Akzo Nobel, 2001 (as cited in
EU, 2008)
Eldefrawi et al., 1977 (as cited
DATA QUALITY
Decomposition may occur before
the boiling point is reached. This
value was measured at lowered
pressure.
Decomposition may occur before
the boiling point is reached.
Adequate OECD guideline study
reported in a secondary source.
Values are higher than might be
expected for the main component.
This measured vapor pressure is
high relative to the boiling points
reported for this chemical.
Adequate guideline study
reported in a secondary source.
Adequate OECD guideline study
reported in a secondary source.
Adequate guideline study
7-547
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
Log Kow
Flammability (Flash Point)
DATA
7 (Measured)
Study performed at 24°C
110 (Measured)
3.69
Using the GLP study in accordance
with 92/69/EC, HPLC method.
Reported as 3.69 ± 0.36 at 20°C.
(Measured)
3.75
Using shake -flask method
(Measured)
3.65
(Measured)
3.8
(Measured)
Auto ignition temperature: 512.77°C
(Measured)
>107.22°C Study performed using
Seta closed cup method (Measured)
252°C Study performed using
Cleveland open cup method
(Measured)
REFERENCE
in WHO, 1998; Budavari, 2001;
EU, 2008)
Hollifield, 1979 (as cited in
Aston etal., 1996; EU, 2008)
CERI, 1999 (as cited in EU,
2008)
Submitted confidential study (as
cited in EU, 2008)
Sasaki et al, 1981 (as cited in
EU, 2008)
HSDB, 2003 (as cited in EU,
2008)
WHO, 1998 (as cited in EU,
2008)
Akzo Nobel, 2003 (as cited in
EU, 2008)
Akzo Nobel, 2003 (as cited in
EU, 2008)
WHO, 1998; NAS, 2000;
HSDB, 2003; EU, 2008
DATA QUALITY
reported in a secondary source.
Sufficient details were not
available to assess the quality of
this study.
Sufficient details were not
available to assess the quality of
this study.
Adequate guideline study
reported in a secondary source.
Consistent value reported in a
secondary source.
Sufficient details were not
available to assess the quality of
this study.
Sufficient details were not
available to assess the quality of
this study.
Sufficient details were not
available to assess the quality of
this study.
Adequate standardized method
reported in a secondary source.
Adequate standardized method
reported in a secondary source.
7-548
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
Explosivity
Pyrolysis
pH
pKa
DATA
Not expected to form explosive
mixtures with air. (Estimated)
When heated to decomposition, it
emits toxic fumes of Cl+ and Pox
(Measured)
Thermal oxidative degradation in air
at 370°C: Hydrogen halides,
halogenated C2 and C3 species,
acrolein (Measured)
0.1 mole TDCPP heated at 250-
260°C under reduced pressure, 3 mm
Hg, results in an overall yield of 60
wt%. Pyrolysis products identified:
trans-l,3-dichloropropene 26.7%; cis-
1,3-dichloropropene 36.0%; 1,2,3-
trichloropropane 34.4%; l-chloro-2-
propene 2.9% (Measured)
Not applicable (Estimated)
Not applicable (Estimated)
REFERENCE
Professional judgment
Lewis, 2000
HSDB, 2003
Choudhry and Hutzinger, 1982
Professional judgment
Professional judgment
DATA QUALITY
No experimental data located;
based on its use as a flame
retardant.
Limited study details provided.
Limited study details provided.
Semi-quantitative description of
the pyrolysis products. No
oxygenated or phosphorus-
containing compounds as
pyrolysis products. This study
does not provide a complete
profile of the pyrolysis.
Does not contain functional
groups that are expected to ionize
under environmental conditions.
Does not contain functional
groups that are expected to ionize
under environmental conditions.
7-549
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
HUMAN HEALTH EFFECTS
Toxicokinetics
TDCPP is readily absorbed (100% assumed) by the oral route of exposure. Absorption through
human skin membranes in vitro was calculated to be 6.0 -15.4% of the applied dose. TDCPP is
distributed primarily to the liver, kidney and lung following oral, dermal, and intravenous
exposure. Once in the tissues, the parent compound and metabolites are rapidly excreted. TDCPP is
quickly and extensively metabolized by oxidation to its metabolite, bis (l,3-dichloro-2-propyl)
phosphate (BDCP). Phase I metabolites included BDCPP, bis(l,3-dichloro-2-propyl) l-chloro-2-
propanol phosphate, l,3-dichloro-2-propyl, l-chloro-2-propanol phosphate, a product of two
oxidative dechlorination reactions, and bis(l,3-dichloro-2-propyl),l-carboxy-3-cloro-2-propyl
phosphate. A substitution of a chlorine atom by glutathione was the only phase II metabolite
detected in this study. Excretion occurred primarily via the urine (50%), but also through feces and
expired air. No accumulation in the body is expected due to rapid elimination of the compound.
Dermal Absorption in vitro
In vitro absorption of TDCPP in
acetone through skin of adult hairless
mice.
Dermal loading rate: 0.013 - 0.067 -
0.13 (ig/cm
Absorption rate (SD%): 57-45-39
(7.3-11-13)
% Absorption vs. dermal loading:
Inverse, as dose increases percent
absorbed decreases
Buist et al., 2009
Adequate study details reported in
a secondary source.
Absorption,
Distribution,
Metabolism &
Excretion
Oral, Dermal or Inhaled
Radiolabelled TDCPP was orally
administered to male Sprague-
Dawley rats at a single dose of 0.2, 2,
and 20 (imol/kg (~ 86 jig/kg, 860
(ig/kg, and 8.6 mg/kg);
There was > 90% absorption from the
GI tract within 24 hours; TDCPP was
then distributed in the body to the
kidney > liver > lung > blood >
muscle.
Nomeir et al., 1981 (as cited in
ECHA,2012)
Study details reported in a
secondary source; Test substance
identified as Fyrol FR-2; test
substance purity not reported;
TDCPP is readily absorbed by the
EU, 2008
Summary of toxicokinetic studies
7-550
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
oral route of exposure with 100%
absorption assumed based on animal
studies. Absorption through human
skin membrane in vitro was
calculated to be 15.4, 10.69, and
6.0% for doses of 0.003, 0.01, and
0.12 mg/m3, respectively. TDCPP is
distributed preferentially to the liver,
kidney and lung following oral,
dermal, and intravenous exposure.
Once in the tissues, the parent
compound and metabolites were
rapidly excreted resulting in low
concentration levels in the tissues.
TDCPP is quickly and extensively
metabolized by oxidation to its
metabolite bis (l,3-dichloro-2-propyl)
phosphate (BDCP). Excretion
occurred primarily through the urine
(50%), but also through feces and
expired air. No accumulation in the
body is expected because of rapid
elimination of the compound.
reviewed in secondary source.
7-551
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Other
Male Sprague-Dawley rats were
administered an unspecified dose
of 14C-TDCPP by intravenous jugular
vein catheters; TDCPP was quickly
distributed from plasma to tissues.
Administered TDCPP was detected in
all tissues after 5 and 30 minutes, but
was only detected in fat after 8 hours.
TDCPP could not be detected in any
tissues 24 hours after administration;
In the tissues, the highest
concentration of TDCPP was in the
kidney (6.75 nmoles/g), liver (2.75
nmoles/g), small intestine (1.98
nmoles/g), and blood (1.84
nmoles/g);
In rats, BDCP is reported to be the
major metabolite of TDCPP;
Following intravenous administration
of TDCPP, only 19% could be
recovered in the body within a half
hour; 82% of TDCPP remained in the
body, while <0.1% was detected in
the urine and feces after 30 minutes.
The primary route of elimination of
TDCPP is due to its metabolism to
BDCP which is mainly excreted in
the urine and feces.
Lynn et al., 1981 (as cited in
ECHA,2012)
Study details reported in a
secondary source; Test substance
purity not reported.
Incubation experiments using 1.0
mg/mL HLM or S9 proteins, 50
TBOEP or TCEP, or TCPP, or 20
TPHP or TDCPP and NADPH
regenerating solution in 1 mM total
Van den Bade et al., 2013
Study details reported in an
abstract.
7-552
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
Acute Mammalian Toxicity
Acute Lethality
Oral
DATA
volume were conducted for 1 hour.
There was a 46% and 68% clearance
of the compound in the HLM and S9
incubations, respectively.
Phase I metabolites included the
oxidative dechlorination products of
TDCPP and the hydrolysis product
BDCPP, (Ml), bis(l,3-dichloro-2-
propyl) l-chloro-2-propanol
phosphate (M2), l,3-dichloro-2-
propyl, l-chloro-2-propanol
phosphate (M3), a product of two
oxidative dechlorination reactions
(M4), and bis(l,3-dichloro-2-
propyl),l-carboxy-3-cloro-2-propyl
phosphate (M5).
A substitution of a chlorine atom by
glutathione (M6), was the only phase
II metabolite detected; this adduct
was the primary metabolite present.
REFERENCE
DATA QUALITY
LOW: TDCPP is not acutely toxic via the oral, dermal and inhalation routes of exposure.
Rat oral LD50 of >2,000 mg/kg;
clinical signs observed during the
first 5 days after dosing included
hypokinesia, piloerection, soiled
coats, ataxia, chromodacryorrhea,
rhinorrhea, and salivation.
Mouse oral LD50 = 2,250 mg/kg
(female): LD50 = 2,670 mg/kg (male);
Treated animals exhibited ataxic gait,
hyperactivity, convulsion and death.
No mortality was observed in
controls or in males at 2,2 10 mg/kg
Cuthbert, 1989b;WHO, 1998
Kamataetal, 1989
Test substance identified as
Tolgard TDCP MK1; Other
studies available only in
secondary sources reported
similar results.
No body weight or gross necropsy
examination.
7-553
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
Dermal
Inhalation
DATA
or females at 1,890 mg/kg.
Rat oral LD50 = 2,830 mg/kg
Rat oral LD50 = 3,160 mg/kg:
No effects at 1,000 mg/kg. Dose-
related depression at or above 2,160
mg/kg; survivors appeared normal by
day 5. No gross lesions in survivors;
fatalities had congestion of heart,
lung, and liver
Rabbit oral LD50 = 6,800 mg/kg;
Clinical signs shortly after dosing
included ataxia, weakness, and
diarrhea; survivors normal by day 9.
Necropsy revealed no abnormalities.
Rat dermal LD50 > 2,000;
No deaths and no clinical signs were
noted 24 hours after treatment.
Rabbit dermal LD50 >4,650 mg/kg;
24-hour method, occluded.
Mortality after 14 days = 0/4. No
overt signs of toxicity and no gross
necropsy findings.
Rat inhalation LC50 >9.8 mg/L;
No mortality after 14 days; initial
REFERENCE
Eldefrawi et al., 1977 (as cited
inATSDR,2012)
Hall and Kamienski, 1981;
Akzo Nobel, 2001
Akzo Nobel, 2001
Cuthbert, 1989a; WHO, 1998
Bullock and Heil, 1981; Akzo
Nobel, 2001
Henderson and Jainer, 1981
DATA QUALITY
Limited study details reported in a
secondary source.
Test substance identified as Fyrol
FR-2; purity: not specified.
Test substance identified as Fyrol
FR-2; purity: not specified.
Reported in secondary source;
test substance identified as
TolgardTDCPMKl; study
predates the preferred study
guidelines.
Test substance identified as Fyrol
FR-2; purity not specified; The
available studies predate the
preferred study guidelines, and
did not report purity, but together
indicated no mortality at the
guideline limit dose of 2,000
mg/kg. The report specifying a
14-day observation period is
presented in more detail.
The available study on TDCPP
predates the preferred guidelines.
7-554
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
Carcinogenicity
OncoLogic Results
Carcinogenicity (Rat and Mouse)
DATA
signs of moderate depression
Rat inhalation LC50 >5,220 mg/m3
(>5.22mg/L)
REFERENCE
Anderson, 1990; WHO, 1998
DATA QUALITY
The duration was shorter than
currently recommended and no
deaths were observed. Analysis of
aerosol particle size was not
mentioned so it is not known
whether the size was respirable.
Necropsies were not performed.
Purity not specified.
Limited study details reported in
secondary source; test substance
identified as aerosol of TDCPP
(Amgard TDCP); duration
unspecified.
HIGH: Based on sufficient evidence of Carcinogenicity in a two-year combined chronic toxicity and
Carcinogenicity assay in rats. This substance is also included as a substance known to cause cancer
on the Proposition 65 list of chemicals.
|No data located.
|No data located.
7-555
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
Combined Chronic
Toxicity/Carcinogenicity
Other
Genotoxicity
Gene Mutation in vitro
DATA
Rat, oral, 2-year combined chronic
toxicity and carcinogenicity assay;
rats (60/sex/group) were administered
0, 5, 20, 80 mg/kg-day (in the diet)
for 2 years. Ten rats/sex/dose were
randomly chosen for termination at
12 months; the remainder at 24
months.
Results: Dose-related increased
incidences of renal cortical adenomas
in both sexes and testicular interstitial
tumors in males (> 20 mg/kg-day);
increased incidence of hepatocellular
adenomas, and carcinomas combined
in both sexes and adrenal cortical
adenomas in females (80 mg/kg-day)
TDCPP is included on the
Proposition 65 list of chemicals
known to cause cancer, July 5, 2013
REFERENCE
Freudenthal and Henrich, 2000;
ATSDR, 2012
California EPA, 2013
DATA QUALITY
The NRC (2000) concluded that
this study provides sufficient
evidence of carcinogenicity of
TDCPP in rats following chronic
oral exposure. Test substance
purity: 95%; The mode of action
for carcinogenicity could not be
determined.
TDCPP was originally listed on
October 28, 2011.
MODERATE: Based on a weight of evidence including positive results in in vitro gene mutation and
chromosomal aberration tests. Negative results were obtained in in vivo chromosomal aberration
and unscheduled DNA synthesis assays.
Positive in strain TA98 by liquid
preincubation assay (with metabolic
activation)
Positive in strain TA100 by plate
incorporation assay.
Negative: mammalian cell gene
mutation test in V79 Chinese hamster
lung cells (with or without metabolic
activation).
Doses: 0, 0.02 mM TDCPP
Abe and Urano, 1994
Gold et al., 1978; Soederlund et
al., 1985
Soederlund et al., 1985
Limited study details reported.
Limited study details reported.
Test substance purity: not
reported.
7-556
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Positive: dose-related positive results
for TDCPP and its metabolite 1,3-
dichloro-2-propanol in TA100 with
S9 (phenobarbital-induced) in
standard plate assays at
concentrations up to 500 (ig/plate. In
a liquid preincubation quantitative
assay, results for TDCPP were
essentially negative-only increasing
mutation frequencies at cytotoxic
concentrations (survival <3%).
However, its metabolites increased
mutant frequencies with less
cytotoxicity: l,3-dichloro-2-
propanone positive at <80% survival
and l,3-dichloro-2-propanol positive
at <30% survival.
Majeska and Matheson, 1983
Limited study details reported.
Positive in Salmonella typhimurium
strains TA97, TA100 (presence of S9
from Aroclor-induced hamster liver)
and in strain TA1535 (in the presence
of S9 from Aroclor-induced rat or
hamster liver); negative in S.
typhimurium strains TA98
andTA1537 with or without the
presence of exogenous metabolic
activation.
Doses: 0, or 5 concentrations between
10 and 10,000 (ig/plate
Mortelmans et al., 1986
Test substance purity reported as
94.4%; positive controls gave
expected increases; solvent
control and all other test
combinations were negative.
Negative in S. typhimurium strains
TA98, TA100, TA1535, TA1537,
TA1538 (without metabolic
activation) and in strains TA98,
Nakamura et al., 1979
Test substance purity: Assayed as
94% TDCPP, plus -6% bis(l-
chloromethyl-2-chloroethyl)(2,3-
dichloropropyl) phosphate.
7-557
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Gene Mutation in vivo
TA1537, or TA1538 (with metabolic
activation); weakly positive in TA100
and TA1535 at the highest
concentrations (with metabolic
activation)
Doses: 0, 10, 30, 100,. 300 (ig/plate
Negative: mammalian cell gene
mutation test in mouse lymphoma
L5178Y cells (with or without
metabolic activation).
Doses: 0, and five concentrations up
to ~32 nL/mL without S9, and six
concentrations up to 70 nL/mL with
S9.
Brusick et al., 1979; Matheson
andBrusick, 1981
Test substance purity: not
reported; test conditions chosen
based on preliminary assays so
that 50% growth reduction
occurred at highest concentration.
Negative: TDCPP was not mutagenic
in S. typhimurium strains TA100,
TA1535, or TA1538 (without
activation or when Aroclor-induction
was used to prepare the S9 fraction).
Privaletal., 1977
The highest exposure level was
10 \\L per plate.
Negative: sex-linked recessive lethal
test in Drosophila melanogaster (100
males/concentrations); TDCPP added
to feed of males for 24 hours,
subsequently mated with virgin
unexposed females; no metabolic
activation.
Doses: 2.5 and 25% in feed (1% gum
tragacanth in 3% sucrose)
Brusick and Jagannath, 1977;
Jagannath and Brusick, 1981;
WHO, 1998
Test substance: tragacanth in 3%
sucrose.
7-558
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Chromosomal Aberrations in vitro
Positive in chromosome aberration
assay in mouse lymphoma L5178Y
cells (with PCB- or phenobarbital-
induction metabolic activation
compared to noninduced S9
activation)
Brusick et al., 1979; Matheson
andBrusick, 1981
Test substance purity: not
reported.
Positive in sister chromatid exchange
assay in mouse lymphoma L5178Y
cells; TDCPP increased the incidence
of sister chromatid exchanges in
mouse lymphocytes under all three
test conditions.
Brusick et al., 1979; Matheson
andBrusick, 1981
Test substance purity: not
reported.
Negative for chromosomal
aberrations or polyploidy in CHO
cells with or without metabolic
activation
EU, 2008
Sufficient study details from
unpublished study reported in a
secondary source.
7-559
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
Chromosomal Aberrations in vivo
DATA
Negative in an in vivo bone marrow
chromosomal aberration assay in
CD1 mice (4-8 males/group);
Concentrations: 0, 0.05, 0.17, and 0.5
mL/kg; using the specific gravity of
1.52, the doses were 0, 76, 260, or
760 mg/kg. The highest dose was the
maximum tolerated dose. Negative
control was DMSO. Exposure
duration, frequency: By oral gavage
in once or daily on 5 consecutive
days. Mice were sacrificed at 6, 24,
and 48 hours after single dose or 6
hours after the last of 5 doses.
Between 233 and 400 cells were
scored. Triethylenemelamine was
used as the positive control.
No evidence of increased frequency
of chromosomal aberrations with
TDCPP. Positive control produced
expected large increase in
micronucleated polychromatic
erythrocytes.
TDCPP administered to mice (route
unspecified) at a dose of 2,000 mg/kg
did not induce micronuclei in bone
marrow erythrocytes
REFERENCE
Brusick et al., 1979; Matheson
andBrusick, 1981
Thomas and Collier, 1985;
WHO, 1998
DATA QUALITY
Test substance: Technical grade;
purity not reported
Limited study details reported in a
secondary source.
7-560
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DNA Damage and Repair
Other
DATA
Negative in unscheduled DNA
synthesis in mammalian cells
(hepatocytes) in culture;
TDCPP was not genotoxic at 0.05
mM; at 0. 1 mM, a moderate response
was observed in hepatocytes from
untreated rats, but not phenobarbital-
treated rats. TBPP was used as the
positive control and yielded positive
results in induced and non-induced
hepatocytes.
Negative for unscheduled DNA
synthesis (UDS) in rat hepatocytes;
male Hsd:SD rats were administered
TDCPP by gavage at doses of 500,
1,000, and 2,000 mg/kg in 0.5%
methylcellulose; Rats were sacrificed
at 2-4 hours and at 14-16 hours
following dosing; vehicle controls
and positive controls
(dimethylnitrosamine) were used;
hepatocytes were cultured at the
selected sacrifice time points and
analyzed for UDS;
All treated groups at both time points
produced a negative response for
UDS and the vehicle and positive
control groups resulted in an
appropriate response.
Negative for unscheduled DNA
synthesis (UDS) assay in primary rat
hepatocyte cells.
REFERENCE
Soederlund et al., 1985
EU, 2008
EU, 2008
DATA QUALITY
Test substance purity: not
reported.
Sufficient study details from
unpublished study reported in a
secondary source.
Conducted according to OECD
guideline 486 and EC method
B.39
^o data located.
7-561
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
Reproductive Effects
Reproduction/Developmental
Toxicity Screen
Combined Repeated Dose with
Reproduction/ Developmental
Toxicity Screen
Reproduction and Fertility Effects
DATA
REFERENCE
DATA QUALITY
HIGH: Based on a LOAEL of 5 mg/kg-day (NOAEL not established) for atrophy and decreased
secretory product of the seminal vesicle in an oral two-year combined chronic toxicity and
carcinogenicity assay in rats. Effects were also seen in the testes (eosinophilic material in lumen,
periarteritis nodosa) at 20 mg/kg-day and the epididymis (oligospermia and degenerated seminal
product) at 80 mg/kg-day.
Rat, oral, 2-year combined chronic
toxicity and carcinogenicity assay;
Rats (60/sex/group) were
administered 0, 5, 20, 80 mg/kg-day
(in the diet) for 2 years. Ten
rats/sex/dose were randomly chosen
for termination at 12 months; the
remainder at 24 months.
Reproductive effects in males
included effects on seminal vesicles
(atrophy, decreased secretory
product) at > 5 mg/kg-day, testes
(eosinophilic material in lumen,
periarteritis nodosa) at > 20 mg/kg-
day, and epididymis (oligospermia
and degenerated seminal product) at
80 mg/kg-day.
NOAEL: Not established
LOAEL: 5 mg/kg-day
In a 12-week oral study, rabbits were
gavaged with TDCPP and then mated
with untreated females.
Freudenthal and Henrich, 2000
Wilczynski et al., 1983;
ATSDR, 2012
No data located.
^o data located.
The authors reported the lowest
dose of 5 mg/kg-day as a NOAEL
and the mid-dose of 20 mg/kg-
day as a LOAEL. However, as
evaluated in NRC (2000), the
lowest dose of 5 mg/kg-day was a
LOAEL for atrophy and
decreased secretory product of the
seminal vesicle; test substance
purity: 95%; These effects for
reproductive tissues are reported
from a 2-year combined chronic
toxicity and carcinogenicity
assay, and not from a study
designed to test reproductive
effects specifically; other
reproductive parameters were not
examined.
Data not sufficient to satisfy the
reproductive toxicity endpoint
since it was described only in an
7-562
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
Other
Developmental Effects
Reproduction/ Developmental
Toxicity Screen
Combined Repeated Dose with
Reproduction/ Developmental
Toxicity Screen
DATA
Increased absolute kidney weight and
relative liver weight in high dose
animals; No effects on male
reproductive parameters was
reported; there were no
histopathological findings in testes, or
epididymides.
NOAEL: 20 mg/kg-day
LOAEL: 200 mg/kg-day (highest
dose tested)
(Estimated by analogy)
REFERENCE
DATA QUALITY
abstract and females were not
tested.
No data located.
MODERATE: Based on NOAELs of 100 and 200 mg/kg bw-day in two prenatal developmental
toxicity studies in rats. A LOAEL of 400 mg/kg-day was established for increased resorptions and
fetal mortality that occurred in conjunction with maternal toxicity and lethality. In addition,
abnormal development (short tail, reduced body weight) was evident in a study examining
developmental phenotypes in zebrafish embryos/larvae. This study adds weight of evidence for
developmental toxicity of TDCPP.
There were no data located for the developmental neurotoxicity endpoint.
No data located.
No data located.
7-563
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
Prenatal Development
DATA
Rat (Sprague-Dawley), oral (gavage),
0, 25, 100, or 400 mg/kg-day on GD
6-15.
Maternal: Clinical signs of toxicity
(urine stains, hunched appearance,
and alopecia) at 400 mg/kg-day;
decreased food consumption (100,
400 mg/kg/day); overall body
weights reduced in high-dose dams
Developmental: No effects on
implantation efficiency or mean
number of corpora lutea. Increased
number of resorptions and decreased
fetal viability (400 mg/kg-day);
decreased skeletal development,
related to growth retardation and
decreased fetal size (400 mg/kg/day);
incidences of malformations were not
determined to be treatment related.
Maternal toxicity:
NOAEL: 25 mg/kg-day
LOAEL: 100 mg/kg-day (based on
clinical signs and transient decreased
body weight gain)
Developmental toxicity:
NOAEL: 100 mg/kg-day
LOAEL: 400 mg/kg-day (based on
increased resorptions and fetal
mortality)
Rat (Wistar), oral (gavage), exposed
REFERENCE
Kappetal., 1981;ATSDR,
2012
Tanakaetal., 1981
DATA QUALITY
Adverse developmental effects
occurred only at maternally lethal
doses. Test substance: Fyrol-2;
test substance purity not reported.
Conducted by methods consistent
with OECD Guideline 141
Adverse developmental effects
7-564
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
to 0, 25, 50, 100, 200, or 400 mg/kg-
dayonGD7-19.
Maternal: mortality (400 mg/kg-day);
decreased food consumption (200,
400 mg/kg-day), reduced terminal
body weight on GD20 (400 mg/kg-
day); increased absolute and relative
kidney weight (200, 400 mg/kg-day)
Developmental: No effect on corpora
lutea, mean number of implants, fetal
body weight, fetal sex ratio, or
number of dead or live fetuses. No
effect on behavior and functional test.
Increased number of dead fetuses and
live fetuses (400 mg/kg-day, due to
the loss of one whole litter); No
malformations were reported in any
of the treated groups.
Maternal toxicity:
NOAEL: 100 mg/kg-day
LOAEL: 200 mg/kg-day (based on
increased kidney weight)
Developmental toxicity:
NOAEL: 200 mg/kg-day
LOAEL: 400 mg/kg-day (based on
increased fetal death)
Zebrafish embryos/larvae exposed to
TDCPP (3 nM) from 0.75 h
postfertilization (hpf). Inhibition of
cell rearrangement (4 hpf), delay in
REFERENCE
Fuetal, 2013
DATA QUALITY
occurred only at maternally lethal
doses; test substance purity not
reported.
Data are from a non-standard
study for assessing hazard for this
endpoint.
7-565
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
Postnatal Development
Prenatal and Postnatal Development
Developmental Neurotoxicity
Other
Neurotoxicity
Neurotoxicity Screening Battery
(Adult)
Other
DATA
epiboly (5.7 and 8.5 hpf), abnormal
development (short tail, reduced body
size) and death (14-45 hpf). Trunk
curvature was observed to be the
main phenotype (96 hpf) in larvae
exposed to 1 or 3 (iM TDCPP.
Uncertain concern for developmental
neurotoxicity based on the potential
for Cholinesterase (ChE) inhibition in
dams that may result in alterations of
fetal neurodevelopment (Estimated)
REFERENCE
Professional judgment
DATA QUALITY
No data located.
^o data located.
Estimated based on a structural
alert for organophosphates for the
neurotoxicity endpoint.
^o data located.
LOW: Based on a weight of evidence. TDCPP did not produce neurotoxicity in acute, chronic or
developmental studies in rats or in acute and subchronic studies in hens. TDCPP induced oxidative
stress in undifferentiated PC12 cells, but did not impair cell growth or viability. However, there
may be some potential for neurotoxicity based on a structural alert for organophosphates.
Rat (Wistar), oral (gavage), exposed
to 0, 25, 50, 100, 200, or 400 mg/kg-
dayonGD7-19;
Seven dams from each of the control
and 200 mg/kg-day groups were
permitted to litter normally and
evaluated for implantation sites,
delivery index, number of live
offspring at birth and survival on
PND 4, at 4th week, and at 10th week.
Litters were culled to 10 offspring on
postnatal day 4 (PND 4) and
Tanakaetal., 1981
^o data located.
Full descriptions of these tests
were not available in the English
summary and therefore could not
3e compared to the guideline
protocol; this study does not fully
satisfy the developmental
neurotoxicity endpoint because it
omitted some parameters
specified under the guideline:
developmental landmarks for
sexual maturity, auditory startle
test, and neurohistopathological
7-566
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
subjected to behavioral tests (open
field, water maze, rota rod, inclined
screen, pain reflex and Preyer's
reflex). Absolute organ weights of 10
organs plus testis, uterus and ovary
were measured in offspring.
In postnatal observations, there were
no effects on behavior and functional
tests (< 200 mg/kg-day)
NOAEL: 200 mg/kg-day (highest
tested non-lethal dose)
LOAEL: Not established
examinations.
In a 2-year combined chronic toxicity
and carcinogenicity assay, rats
(60/sex/group) were fed 0, 5, 20, 80
mg/kg-day. Ten rats/sex/dose were
randomly chosen for termination at
12 months; the remainder at 24
months.
There were no lesions of the brain or
spinal cord in rats exposed to TDCPP
at doses as high as 80 mg/kg-day
reported.
NOAEL: 80 mg/kg-day (highest dose
tested)
LOAEL: Not established
Freudenthal and Henrich, 2000
Test substance purity: 95%.; no
functional tests of neurotoxicity
were performed; this study was a
combined chronic
toxicity/carcinogenicity assay,
and was not designed to
specifically examine neurological
endpoints.
Oral, rat (10 rats/dose), 0, 2,000, or
3,980 mg/kg in corn oil was
administered by gavage to male
Sprague-Dawley rats;
There were no effects on plasma or
Bullock et al, 1981
Test substance reported as Fyrol
FR-2; purity not specified.
7-567
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
erythrocyte cholinesterase levels
measured at 4 or 14 hours after
dosing.
NOAEL: >3,980
LOAEL: Not established
Acute oral delayed neurotoxicity in
White Leghorn Hens (4/dose); dosed
(gavage) at 10,000 mg/kg once;
Positive control: 500 mg/kg tri-ortho-
tylol phosphate (TOCP), negative
control: 15 mg/kg tetraethyl
pyrophosphate (TEPP).
Toxic signs were not reported
specifically for TDCPP, but for all
compounds tested at the maximum
tolerated dose, signs included
listlessness and ataxia. Inhibition of
NTE activity was 7% for TDCPP and
the negative control TEPP, but 85%
for the positive control (TOCP).
NOAEL: Not established
LOAEL: 10,000 mg/kg
Morey et al, 1978
Test substance: Fyrol FR-2;
conflicting reports of test
substance purity (one part of the
report stated that the purity was
not reported, whereas another part
of the report indicated purity
>99%); the current guideline
specifies that testing is not
necessary at doses above 2,000
mg/kg; unpublished industrial
acute study performed prior to the
existence of the guidelines, do not
entirely conform to current
guidelines, and may lack detail
such as the purity of the TDCPP
sample; only one test substance
dose administered.
Acute oral delayed neurotoxicity in
Hohite Leghorn Hens (4/dose); dosed
(gavage) at 420 mg/kg-day; Positive
control: 90 or 120 mg/kg-day tri-
ortho-tylol phosphate (TOCP);
No overt signs of neurotoxicity with
TDCPP treatment. Positive control
caused inability to walk,
hypertension, ataxia, and prostration.
Bullock and Kamienski, 1972;
Bullock and Kamienski, 198 Ib;
WHO, 1998
Test substance: Fyrol FR-2, purity
not reported; Navy MIL-H-
1945 7B (SHIPS) protocol;
Necropsy not performed;
unpublished industrial acute study
performed prior to the existence
of the guidelines, do not entirely
conform to current guidelines,
and may lack detail such as the
7-568
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
NOAEL: 420 mg/kg-day (only dose
tested)
LOAEL: Not established
Subchronic oral delayed
neurotoxicity in Hohite Leghorn
Hens (10/dose); dosed (gavage) at 0,
4, 20, 100 mg/kg-day for 90 days;
TOCP was the positive control.
Hens treated with TDCPP at the high
dose exhibited mean reductions in
body weight during the latter part of
the study, but no overt signs of
neurotoxicity and no
histopathological effects in the
nervous tissues. Positive control hens
exhibited consistently lower body
weight gain, clinical signs of toxicity
(locomotor impairment and ataxia)
that became more severe with time.
Histopathology results were not
reported for the positive control.
NOAEL: Not established
LOAEL: Not established
Undifferentiated PC 12 cells exposed
to TDCPP for 24 hours; rapid mitotic
inhibition in undifferentiated cultures
and significantly reduced cell
numbers during neurodifferentiation.
TDCPP induced oxidative stress, but
did not impair cell growth or viability
There is potential for neurotoxicity
REFERENCE
Akzo Nobel, 2001
Dishawetal., 2011
Professional judgment
DATA QUALITY
purity of the TDCPP sample; only
one test substance dose
administered.
Test substance purity not
reported. Robust summary from
Akzo-Nobel, 200 la; unpublished,
unidentified study dated 1979;
histopathology was not reported
for the positive control;
unpublished industrial acute study
performed prior to the existence
of the guidelines, do not entirely
conform to current guidelines,
and may lack detail such as the
purity of the TDCPP sample.
Adequate study details reported in
a primary source.
Estimated based on a structural
7-569
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
based on a structural alert for
organophosphates. (Estimated)
alert for organophosphates and
professional judgment.
Repeated Dose Effects
HIGH: Based on a LOAEL of 5 mg/kg-day for atrophy and decreased secretory product of the
seminal vesicle in an oral 2-year combined chronic toxicity and carcinogenicity assay in rats
(NOAEL not established). Effects were also seen in the testes (eosinophilic material in lumen,
periarteritis nodosa) at 20 mg/kg-day and the epididymis (oligospermia and degenerated seminal
product) at 80 mg/kg-day.
Rat, oral, 2-year combined chronic
toxicity and carcinogenicity assay;
Rats (60/sex/group) were
administered 0, 5, 20, 80 mg/kg-day
(in the diet) for 2 years.
Increased mortality in high-dose
males; reduced body weights in high-
dose males and females; signs of
anemia (lower hemoglobin,
hematocrit, erythrocyte counts) in
high-dose rats. At the mid-dose,
increased absolute and relative
kidney weight males and females,
absolute liver weight and relative
thyroid weight in males, and relative
liver weight in females; increased
relative liver weight in males and
absolute and relative thyroid weights
in females at the high dose.
Increased incidences of nonneoplastic
lesions (not strictly dose-related in
that incidences were depressed in
high-dose groups): Kidney lesions
(convoluted tubule hyperplasia) in
males at > 20 mg/kg-day and in
females at 80 mg/kg-day. Other
Freudenthal and Henrich, 2000;
NRC, 2000
Freudenthal and Henrich (2000)
reported the lowest dose of 5
mg/kg-day as a NOAEL and the
mid-dose of 20 mg/kg-day as a
LOAEL. However, as evaluated
in NRC (2000), the lowest dose of
5 mg/kg-day was a LOAEL for
atrophy and decreased secretory
product of the seminal vesicle;
test substance purity: 95%.
7-570
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
systemic lesions at 80 mg/kg/day
involved the parathyroid
(hyperplasia) in males and the liver
(foci) and spleen (erythroid/myeloid
hyperplasia) in females. Lesions in
the vesicles (atrophy, decreased
secretory product) at > 5 mg/kg-day,
testes (eosinophilic material in lumen,
periarteritis nodosa) at > 20 mg/kg-
day, and epididymis (oligospermia
and degenerated seminal product) at
80 mg/kg-day.
NOAEL: Not established
LOAEL: 5 mg/kg-day (based on
atrophy and decreased secretory
product of the seminal vesicle;
hyperplasia of convoluted tubule
epithelium in males at 24 months)
In a 90-day study, mice (Slc/ddY)
were fed TDCPP at 0, 0.01, 0.04,
0.13, 0.42, and 1.33 % in the diet
(average daily dose: males-0, 13.2,
47.3, 171.0, 576.0, 1,792.3 mg/kg-
day; female - 0, 15.3, 62.5, 213.6,
598.0, 1,973.1 mg/kg-day)
Slight anemia in males at 0.42% after
3 months; Anemia in females at 0.13
% after 1 month and 0.42% at 3
months; Elevated albumin/globulin
rations in males in all groups at 3
months; Increased alkaline
phosphatase in females at 0.42% at 1
Kamataetal, 1989
Study reported limited relevant
information in English abstract
and data tables; histopathology
analysis appears limited to the
liver.
7-571
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
month, but did not differ from
controls at the 3 month evaluation;
dose-related increase in organ relative
liver weight (0.13%) and relative
kidney weight (0.42%), in males at 3
months compared to controls;
Increased relative liver weight
(0.04%), absolute liver weight
(0.42%), absolute and relative kidney
weight (0.13%); slight focal necrosis
of the liver was observe in 2/12
females at 0.42%.
NOAEL: 0.01% (15.3 mg/kg-day)
LOAEL: 0.04% (62.5 mg/kg-day )
based on increased relative liver
weight in females
Morbidity survey conducted on 124
male, full-time workers with
occupational exposure at a TDCPP
manufacturing plant to determine if
there was an increased incidence of
respiratory conditions among those
exposed;
The survey population had an
occupational health program physical
examination in 1981; survey group
divided into groups according to age
(20-29, 30-39, 40-49, >50); The
control population consisted of non-
exposed workers; The ratio of
exposed to non-exposed workers was
93:31 people; Full-shift time
Murphy, 1981;EU,2008
Cohort study details reported in a
secondary source; the non-
exposed (control) populations was
about one third the size of the
exposed population; it is also
difficult to determine if non-
exposed workers may have been
previously exposed, or if exposed
workers may have been exposed
to other compounds outside of
their occupational environment;
actual exposure doses were not
reported.
7-572
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Immune System Effects
weighted averages (TWA) were
determined for the breathing zone for
December 1978 - May 1979. The
exposure dose was calculated to be
near the limit of detection at 8 ppb;
the survey consisted of a 175-self-
administered health questionnaire,
physical examination, pulmonary
function test, chest x-ray, and an
electrocardiogram; clinical and
biochemical analysis was also
performed.
After taking into account smoking
status; exposed workers had a
decreased incidence of respiratory
conditions compared to non-exposed
workers; in addition there were no
abnormal clinical findings; There was
an increase in benign neoplasms,
dermatitis, and gynacomastia in
exposed workers compared to non-
exposed workers.
Mice were administered a
subcutaneous injection of 0, 0.25, 2.5,
or 25 mg/kg-day once daily for 4
days (total cumulative doses of 0, 1,
10, or lOOmg/kg)
Twenty percent of high-dose mice
exhibited lymphoid depletion of the
thymus. Statistically significant
decreases in lipopolysaccharide (B-
cell antigen) at 2.5 mg/kg-day and
TanakaetaL 1981
Study predates the guideline for
immunotoxicity; There is some
uncertainty as the test material,
reported as Fyrol FR2, but miss-
identified by the authors as
tris(2,3-dichloropropyl)
phosphate; test substance purity
reported as >95%; The study
methods differed from the
guideline in the short exposure
7-573
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
Skin Sensitization
Skin Sensitization
Respiratory Sensitization
[Respiratory Sensitization
Eye Irritation
Eye Irritation
DATA
concanavalin A (T-cell antigen) at 25
mg/kg-day.
NOAEL: 0.25 mg/kg-day
LOAEL: 2.5 mg/kg-day
based on decreased concanavalin A,
T-cell antigen
REFERENCE
DATA QUALITY
period (4 rather than 28 days),
parenteral administration (rather
than oral or inhalation route),
measurement of serum
immunoglobulin in non-
immunized rather than
immunized mice, and the
omission of some tests
(enumeration of immunological
cell subpopulations, test for NK-
cell activity).
LOW: Not a skin sensitizer in guinea pigs.
Not a skin sensitizer in guinea pigs;
The Sensitization score for Fyrol FR-
2 was zero.
Akzo Nobel, 2001; EU, 2008
Study details reported in a robust
summary for an unpublished and
unidentified study dated 2001;
test substance identified as Fyrol
FR-2
No data were located
|No data located.
LOW: TDCPP produced slight conjunctival effects in rabbits that cleared within 24 to 48 hours.
Slightly irritating, rabbits; slight
conjunctival redness and slight
discharge were noted; effects cleared
by 24 hours.
Transient, mild conjunctival effects in
3/6 rabbits (reversible in 48 hours)
Not irritating, rabbits; average Draize
score of zero.
Cuthbert and Jackson, 1990;
WHO, 1998
Bullock and Kamienski, 198 la;
EU, 2008
Murphy, 1981; Akzo Nobel,
200 1;EU, 2008
Limited study details reported in a
secondary source; Test substance
identified as Tolgard TDCP
MK1; purity not specified.
Test substance identified as Fyrol
FR-2; purity not specified.
Test substance purity not
specified.
7-574
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Dermal Irritation
LOW: TDCPP produced mild skin irritation in rabbits that cleared within 72 hours.
Dermal Irritation
Mild skin irritant, rabbits (24-hour);
No edema on intact or abraded skin in
any rabbit; mild erythema was visible
at 24 hours, but cleared by 72 hours;
score of 0.63.
Irritating to skin, rabbits; well-
defined (score 2) erythema in 2 New
Zealand White rabbits and slight
erythema in a third rabbit 1 hour after
patch removal.
Not a skin irritant, rabbits (4-hour);
No erythema or edema on intact or
abraded skin in any rabbit.
Hicks etal., 1981; EU, 2008
Report cited EPA protocol. Back
hair was shaved, each rabbit
tested on intact and abraded skin,
occlusive dressing removed after
24 hours, observations at 24 and
72 hours; test substance identified
as Fyrol FR-2; purity unspecified.
Cuthbert, 1989a; WHO, 1998;
EU, 2008
Bullock and Kamienski, 198 la;
EU, 2008
Limited study details reported in a
secondary source; test substance
identified as Tolgard EDCPP
MK1; purity not specified;
duration of exposure not
specified.
Test substance identified as Fyrol
FR-2; purity not specified; Back
hair shaved, each rabbit tested on
intact and abraded skin, occlusive
dressing removed after 4 hours,
observations at 4, 24 and 48
hours.
7-575
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Endocrine Activity
TDCPP in house dust has been correlated with altered levels of hormones related to fertility and
thyroid function in men. TDCPP inhibited the luciferase expression induced by dihydrotestosterone
in a reporter-gene assay using cultured cells and induced delays in remethylation of the zygotic
genome (mechanism that may be associated with enhanced developmental toxicity) in zebrafish. In
addition, TDCPP disrupted steroidogenic pathways and metabolism of estrogen in human cell lines
(H2925R and WVLN) and in zebrafish. A 2-year combined chronic toxicity and carcinogenicity
assay in rats resulted in changes of the parathyroid, testes, and epididymis; it is unclear if these
observed changes may be an indication of endocrine activity.
Hormone levels and semen quality
were assessed in men living in homes
with elevated TDCPP levels in house
dust. Each interquartile range (IQR)
increase in TDCPP in dust was
associated with a 17% increase in
prolactin and a 3% decline in free
levels of the thyroid hormone
thvroxine.
In a luciferase reporter-gene assay
using cultured cells, TDCPP inhibited
the luciferase expression induced by
dihydrotestosterone. IC50 for
antiandrogenic activity = 4.7 x 10~5
IC50 for antiestrogenic activity = 8.9
x ID'5
TDCPP exposure during five stages
of embryogenesis in zebrafish
induced delays in remethylation of
the zygotic genome (mechanism that
may be associated with enhanced
developmental toxicity). Significant
increase in mortality and
developmental abnormalities at
exposure concentrations of 0.75-96
Berts, 2010; Meeker and
Stapleton, 2010
Ohyama et al., 2006
McGeeetal., 2012
Limited study details summarized
in a secondary source.
Primary source in Japanese with
English abstract
Sufficient study details reported.
7-576
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
hours post-fertilization.
Human cell lines (H2925R and
WVLN cells) were tested for sex
hormone synthesis and steroidogenic
gene transcription (H295R) and
estrogen receptor binding activity
(MVLN); zebrafish (Danio rerio)
were tested for sex hormone levels
and gene transcriptions.
Increased 17 beta-estradiol (E2) and
testosterone (T) levels, transcription
of steroidogenic genes were
upregulated; two sulfotransferase
genes downregulated (H295R cells);
there was no estrogen receptor
agonist activity, while there was
antagonist inhibiting binding of E2 to
estrogen receptor (MVLN cells);
Increased plasma T and E2
concentrations in zebrafish exposed
to TDCPP for 14 days; decreased
testosterone and 11-ketotestosterone
and increased E2 in male zebrafish;
significant upregulation of CYP17
and CYP19 transcription (males and
females); vitellogenin (VTG)l gene
was down-regulated in female fish
and up-regulated in male fish.
Morbidity survey conducted on 124
male, full-time workers with
occupational exposure at a TDCPP
manufacturing plant to determine if
there was an increased incidence of
REFERENCE
Liu etal., 2012
Murphy, 1981;EU,2008
DATA QUALITY
Sufficient study details reported
in a primary source.
Cohort study details reported in a
secondary source; the non-
exposed (control) populations was
about one third the size of the
exposed population; it is also
7-577
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
respiratory conditions among those
exposed;
After taking into account smoking
status; exposed workers had a
decreased incidence of respiratory
conditions compared to non-exposed
workers; in addition there were no
abnormal clinical findings; There was
an increase in gynacomastia in
exposed workers compared to non-
exposed workers.
difficult to determine if non-
exposed workers may have been
previously exposed, or if exposed
workers may have been exposed
to other compounds outside of
their occupational environment;
actual exposure doses were not
reported.
Rat, oral, 2-year combined chronic
toxicity and carcinogenicity assay;
Rats (60/sex/group) were
administered 0, 5, 20, 80 mg/kg-day
(in the diet) for 2 years.
Systemic lesions at 80 mg/kg/day
involved the parathyroid
(hyperplasia) in males and the liver
(foci) and spleen (erythroid/myeloid
hyperplasia) in females. Lesions in
the vesicles (atrophy, decreased
secretory product) at = 5 mg/kg-day,
testes (eosinophilic material in lumen,
periarteritis nodosa) at = 20 mg/kg-
day, and epididymis (oligospermia
and degenerated seminal product) at
80 mg/kg-day. It is unclear if the
observed changes may be an
indication of endocrine activity.
Freudenthal and Henrich, 2000;
NRC, 2000
Freudenthal and Henrich (2000)
reported the lowest dose of 5
mg/kg-day as a NOAEL and the
mid-dose of 20 mg/kg-day as a
LOAEL. However, as evaluated
in NRC (2000), the lowest dose of
5 mg/kg-day was a LOAEL for
atrophy and decreased secretory
product of the seminal vesicle;
test substance purity: 95%.
7-578
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Immunotoxicity
TDCPP produced lymphoid depletion of the thymus and decreases in LPS (B-cell antigen) and Con
A (T-cell antigen) in mice following subcutaneous injection for 4 days.
Immune System Effects
Mice were administered a
subcutaneous injection of 0, 0.25, 2.5,
or 25 mg/kg-day once daily for 4
days (total cumulative doses of 0, 1,
10, or lOOmg/kg)
Twenty percent of high-dose mice
exhibited lymphoid depletion of the
thymus. Statistically significant
decreases in lipopolysaccharide (B-
cell antigen) at 2.5 mg/kg-day and
concanavalin A (T-cell antigen) at 25
mg/kg-day.
NOAEL: 0.25 mg/kg-day
LOAEL: 2.5 mg/kg-day
based on decreased concanavalin A,
T-cell antigen
Tanakaetal., 1981
Study predates the guideline for
immunotoxicity; There is some
uncertainty as to the test material
which was reported as Fyrol FR2
but mis-identified by the authors
as tris(2,3-dichloropropyl)
phosphate; test substance purity
reported as >95%; The study
methods differed from the
guideline in the short exposure
period (4 rather than 28 days),
parenteral administration (rather
than oral or inhalation route),
measurement of serum
immunoglobulin in non-
immunized rather than
immunized mice, and the
omission of some tests
(enumeration of immunological
cell subpopulations, test for NK-
cell activity).
7-579
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
ECOSAR Class
ECOTOXICITY
Acute Aquatic Toxicity
HIGH: Based on a measured 96-hour LC50 of 1.1 mg/L in fish, a 48-hour LC50 of 3.8 mg/L in
daphnia, and a 72-hour ErCi0 = 2.3 mg/L in green algae.
Fish LC50
Oncorhynchus mykiss (rainbow trout)
96-hour LC50 = 1.1 mg/L
(semi-static test conditions)
96-hour NOEC = 0.56 mg/L
24-hour LC50 = 1.8 mg/L
48-hour LC50 = 1.5 mg/L
72-hour LC50 = 1.3 mg/L
(Experimental)
Salmo gairdneri (Rainbow trout) 96-
hour LC50 = 1.4 mg/L
Static conditions; exposed to 0, 0.63,
1.25,2.5,5, 10 mg/L
All mortalities occurred within the
first 24 hours. Mortality was dose
related. One fish died in the lowest
dose group (0.63 mg/L). All fish died
in the 5 and 10 mg/L groups.
(Experimental)
Killifish (Oryzias latipes) 96-hour
LC50 = 3.6 mg/L
(static test conditions)
Deformation of the spine was
observed in 7/10 killifish exposed to
3.5 mg/L TDCPP for 24 hours.
(Experimental)
Goldfish (Carassius auratus) 96-hour
LC50 = 5.1 mg/L (static test
conditions)
ECHA, 2012
Akzo Nobel, 2001
Sasaki etal, 1981
Sasaki etal, 1981
Test substance identified as
Amgard TDCP; study conducted
according to OECD guidelines;
the toxicity value is below the
reported water solubility of
TDCPP (18 mg/L).
A NOEC was not observed and is
therefore less than 0.63 mg/L.
The test concentrations used were
not reported. A control group was
not tested.
Goldfish are not a designated test
species, as per OPPTS 850.1075
(Fish Acute Toxicity Test,
7-580
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
(Experimental)
Goldfish (Carassius auratus);
exposed to 1 and 5 mg/L (static test
conditions)
Fish were exposed to 1 or 5 mg/L
TDCPP in water or acetone. None of
the fish in the 1 mg/L treatment had
died after 168 hours. All fish in the 5
mg/L treatment died within 24 hours.
The most conspicuous signs of
toxicity were sluggishness and
disoriented swimming prior to death.
(Experimental)
Eldefrawi et al., 1977
A laundered or unlaundered 38 cm x
64 cm section of garment (0.24
square meter area; 227 g/m3), which
had been treated with Fyrol FR-2,
was placed in tanks with six goldfish.
Fish in the tank became progressively
more sluggish and all died within 3
hours. The measured concentration of
Fyrol FR2 in the test water was 30
mg/L. Fish exposed for 96 hours to
the same section of fabric after it had
been laundered did not die.
(Experimental)
Ahrensetal., 1979
Freshwater Fish 96-hour LC50 = 6.26
mg/L
(Estimated)
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Freshwater and Marine); used
were not reported. A control
group was not tested.
Goldfish are not a designated test
species, as per OPPTS 850.1075
(Fish Acute Toxicity Test,
Freshwater and Marine). The
study cannot be used to establish
an LC50 value.
Data for mortality in control fish
were not presented in the study;
goldfish are not a designated test
species, as per OPPTS 850.1075
(Fish Acute Toxicity Test,
Freshwater and Marine). This
study in inadequate for
determining a hazard designation.
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
7-581
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Daphnid LC50
Daphnia magna 48-hour LC50 = 3.8
mg/L (flow-through test conditions)
Negative control, solvent control
(dimethylformamide), 0.98, 1.6, 2.8,
3.8, 5.1 mg/L Daphnia in the negative
and solvent control groups appeared
normal, as did the organisms in the
0.98 and 1.6 mg/L groups. Mortality
in the 2.8, 3.8, and 5.1 mg/L groups
was 0, 70, and 80%, respectively.
Daphnid (15%) in the 2.8 mg/L group
were lethargic at study termination.
(Experimental)
Akzo Nobel, 2001; EU, 2008
Daphnia magna 48-hour EC50 = 4.6
mg/L
(Experimental)
EU, 2008
Daphnia 48-hour LC50 = 10.91 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
The amount of solvent used in the
control group and the TDCPP
treatments is estimated to be
approximately 300 mg/L. This
exceeds the recommended
maximum solvent concentration
of 100 mg/L. The estimate is
based on a reported
dimethylformamide volume of
0.1 ml, a test chamber volume of
300 ml and a specific gravity of
0.95.
Study did not include analysis of
exposure concentrations; values
are consistent with other
experimental value.
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
Green Algae EC50
P. subcapitata 96-hour EC50 > 2.8
mg/L (biomass and growth rate)
72-hour ErC10 = 2.3 mg/L
NOEO 1.2 mg/L
(Experimental)
EU, 2008
Selenastrum capricornutum 96-hour
EbC50 = 12 mg/L
96-hour ErC50 = 39 mg/L
96-hour NOAEC = 6 mg/L
static test conditions; 0, 2, 6, 18, 54,
Akzo Nobel, 2001
Study details reported in a
secondary source; conducted
according to OECD guideline 201
reported toxicity values are below
the reported water solubility for
TDCPP (18 mg/L).
A number of problems are evident
with this study, namely the pH
changed markedly during the
study, and the reported pH and
water temperature were outside of
7-582
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
or 162 mg/L
(Experimental)
the recommended values for this
algal species.
Green algae 96-hour EC50 = 3.58
mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
Chronic Aquatic Toxicity
HIGH: Based on a measured 21-day NOEC of 0.5 mg/L (LOEC = 1.0 mg/L) in daphnid for reduced
reproduction; the NOEC and LOEC for reduced growth was 1.0 mg/L and 2.0 mg/L, respectively.
Experimental data for algae indicate a Moderate hazard concern. No experimental data were
located for fish. ECOSAR estimates and an estimated ChV using an Acute-to-Chronic Ratio (ACR)
derived for the phosphate ester class that was applied to experimental acute data for this chemical
predicts a HIGH concern for fish.
Fish ChV
Freshwater fish ChV = 0.05 mg/L
(Estimated)
Freshwater fish ChV = 0.33 mg/L
(Estimated)
ECOSAR: Esters
Professional judgment
ECOSARvl.ll
An ACR of 24 was derived for
the phosphate ester class based on
experimental data for Tris (p-t-
butylphenyl) phosphate (TBPP).
The acute-to-chronic ratio was
applied to available experimental
acute fish data for Tris (1,3-
dichloro-2-propyl)phosphate
(ChV = 1.1 mg/L/24= 0.05
mg/L)
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
7-583
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Daphnid ChV
Daphniamagna 21-day LOEC =1.0
mg/L (reproduction)
21-day NOEC = 0.5 mg/L
(reproduction)
21-day NOEC = 1.0 mg/L (growth)
21-day LOEC = 2.0 mg/L (growth)
semi-static test conditions
(Experimental)
EU, 2008
Daphnia magna ChV = 4.64 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Study details reported in a
secondary source; test substance
identified as Fyrol FR-2; purity
>99%.
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
Green Algae ChV
P. subcapitata 96-hour EC50 > 2.8
mg/L (biomass and growth rate)
72-hour ErC10 = 2.3 mg/L
NOEO 1.2 mg/L
(Experimental)
EU, 2008
Selenastrum capricornutum 96-hour
EbC50 = 12 mg/L
96-hour ErC50 = 39 mg/L
96-hour NOAEC = 6 mg/L
static test conditions; 0, 2, 6, 18, 54,
or 162 mg/L
(Experimental)
Akzo Nobel, 2001
Green algae ChV =1.57 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Study details reported in a
secondary source; conducted
according to OECD guideline 201
reported toxicity values are below
the reported water solubility for
TDCPP(18mg/L).
A number of problems are evident
with this study, namely the pH
changed markedly during the
study, and the reported pH and
water temperature were outside of
the recommended values for this
algal species.
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
7-584
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
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, TDCPP is expected to be found primarily in soil and to a lesser extent, sediment and
water. It is not expected to dissociate at environmentally-relevant pH values. TDCPP is expected to
have moderate mobility in soil, based on measured Koc values obtained from studies performed in
clay loam, loamy sand and clay samples. Leaching through soil to groundwater may occur, though
it is not expected to be an important transport mechanism. Estimated volatilization half-lives
indicate that it will be non-volatile from surface water. Based on the measured vapor pressure,
TDCPP is expected to exist in both the vapor and particulate phases in the atmosphere. Particulates
will be removed from air by wet or dry deposition.
<10"8 (Estimated)
1,780 according to OECD 106 using
GLP; 0.01 M calcium chloride was
equilibrated with each of three soils, a
clay loam, a loamy sand and a clay,
one sediment and one activated
sludge solid. Reported as a range of
1,540-2,010. (Measured)
Air = 0%
Water = 4%
Soil = 90%
Sediment = 5% (Estimated)
Professional judgment; EPI
v4.11
Schaefer and Ponizovsky, 2006
(as cited in EU, 2008)
EPIv4.11
Cutoff value for nonvolatile
compounds.
Adequate, OECD guideline study.
Estimation model was calculated
using all applicable measured
input value.
7-585
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Persistence
HIGH: The persistence for TDCPP is based on experimental guideline biodegradation studies.
There is evidence of TDCPP biodegradation resulting in a half-life greater than 60 days. A river die
away test found 22% removal of TDCPP in 14 days and a non-guideline soil test reported 6%
removal in 17 weeks with radiolabeled TDCPP. In ready biodegradability tests, OECD TG 301B,
301C and 301D, 0 to <1% biodegradation of TDCPP occurred after 28 days. Additionally, no
evidence of TDCPP removal was found in 28 days in an OECD 302C guideline study. TDCPP will
undergo hydrolysis under alkaline conditions, with half-lives of 15 days measured at pH 9 and
50°C. TDCPP is relatively stable to hydrolysis under neutral and acidic conditions, a half-life of >1
year was found under pH 4 and pH 7 conditions. TDCPP is not expected to be susceptible to direct
photolysis by sunlight, since it does not absorb light at wavelengths >290 nm.
Water
Aerobic Biodegradation
Passes Ready Test: No
Test method: OECD TG 301B: CO2
Evolution Test
Modified Sturm Test 0% by CO2
evolution. DOC reduction not
calculated due to solubility issues.
0% by CO2 evolution. DOC red. Not
calculated due to solubility issues.
(Measured)
Passes Ready Test: No
Test method: OECD TG 30ID:
Closed Bottle Test
No inhibition of bacterial cultures in
10 days. (Measured)
Passes Ready Test: No
Test method: OECD TG 301C:
Modified MITI Test (I)
Reported as average, 1% by BOD
using activated sludge inoculum.
Initial concentrations 100 mg/L (test
Hattori et al., 1981 (as cited in
Jenkins, 1990; Akzo Nobel,
2001;EU, 2008)
Bisinger, 1990; Akzo Nobel,
2001
CERI, 1999 (as cited in EU,
2008)
OECD guideline study, however
solubility issues were found.
Adequate, OECD guideline study
OECD guideline study, reported
in a secondary source.
7-586
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
substance), 30 mg/L (sludge). The
sludge was from ten sites in Japan:
four sewage plants and six surface
waters. (Measured)
Study results: 0%/28 days
Test method: 302C: Inherent-
Modified MITI Test (II)
0% by O2 uptake (Measured)
WHO, 1998
EURAR notes that this study can
only be seen as a short screening
test, from which no conclusions
regarding inherent
biodegradability of TDCPP can
be draw since no acclimation
period was used.
Study results: 22%/14 days
Test method: River Die-Away test
Oh River:
12.5%/7days; 18.5%/14days
Neya River:
0%/7days;5.4%/14days
Osaka Bay:
0%/7 days; 22%/14 days
Initial concentrations: 20 mg/L in Oh
River water and 1 mg/L in Neya
River water. Concentration in
seawater not reported.
Analysis by Molybdenum Blue
calorimetric assay for increase in
phosphate ion. (Measured)
Hattori et al., 1981 (as cited in
WHO, 1998; EU, 2008)
Adequate, guideline study.
Study results: 100%/12 hours
Test method: Other
Using isolated bacterium strains,
Sphingobium sp. strain TCM1 and
Takahashi et al., 2012
Measured biodegradation rates
demonstrate removal by this
pathway using isolated strains.
7-587
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
Soil
Air
Volatilization Half-life for Model
River
Volatilization Half-life for Model
Lake
Aerobic Biodegradation
Anaerobic Biodegradation
Soil Biodegradation with Product
Identification
Sediment/Water Biodegradation
Atmospheric Half-life
DATA
1,3-DCP-degrading bacterium
Arthrobacter sp. Strain PY1,
complete detoxification of TDCPP
was achieved in 12 hours. The
degradation products were 1
phosphate, 6 HC1 and 3 glycerol.
(Measured)
>1 year (Estimated)
>1 year (Estimated)
Study results: 6%/17 weeks
Test method: Other
14C radiolabelled TDCPP was applied
to the soil surface and the soils (sand,
loam, clay loam and sandy loam)
were incubated at 20 ± 2°C. Each soil
type was analyzed at intervals of 0, 7,
14, 35, 63 and 122 days. (Measured)
1 day (Estimated)
Reaction of TDCPP with oxidative
species such as ozone or hydroxyl
radicals can proceed rapidly. Vacuum
REFERENCE
EPIv4.11
EPIv4.11
Schaefer and Ponizovsky, 2006
(as cited in EU, 2008)
EPIv4.11
Echigo et al., 1996 (as cited in
EU, 2008)
DATA QUALITY
Estimation model was calculated
using all applicable measured
input values.
Estimation model was calculated
using all applicable measured
input values.
Reported in a secondary source.
Study used 14C-labeled test
substance, analyzed by HPLC.
Mo data located; chlorinated alkyl
phosphates are outside the
domain of the available
estimation methods.
No data located.
^o data located.
Sfon guideline study reported in a
secondary source provides data
indicating a potential for removal
7-588
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
Reactivity
Photolysis
Hydrolysis
Environmental Half-life
DATA
UV light at 185 and 254 nm, the
study conditions were not
representative of typical
environmental conditions.
(Measured)
Not a significant fate process
(Estimated)
50%/>1 year at pH 4 and 7; 14.7 days
atpH9
OECD 111; EPA Ser. 835 OPPTS
No. 835.2110. GLP-compliant. Initial
concentration, 10 mg/L. Study length,
5 days at 50°C. Preliminary study.
(Measured)
50%/28 days at pH 9
OECD 111; EPA Ser. 835 OPPTS
No. 835.2110. GLP-compliant.
Definitive 30-day study at 40°C.
(Measured)
50%/128daysatpH9
OECD 111; EPA Ser. 835 OPPTS
No. 835.2110. GLP-compliant.
Definitive 30-day study at 20°C.
(Measured)
>1 year (Estimated)
REFERENCE
Professional judgment; Mill,
2000
Akzo Nobel, 2001 (as cited in
EU, 2008)
Akzo Nobel, 2001
Akzo Nobel, 2001
PBT Profiler
DATA QUALITY
by photodegradation, although the
rate of removal and applicability
of this pathway under
environmental conditions is
unknown.
The substance does not contain
functional groups that would be
expected to absorb light at
environmentally significant
wavelengths.
GLP-compliant test run according
to accepted guidelines.
GLP-compliant test run according
to accepted guidelines.
GLP-compliant test run according
to accepted guidelines.
Half-life estimated for the
predominant compartment, as
determined by EPI methodology.
7-589
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
Bioaccumulation
Fish BCF
Other BCF
BAF
DATA
REFERENCE
DATA QUALITY
LOW: Based on multiple experimental BCF values below or near 100, the Low bioaccumulation
designation criteria. Toxicokinetic studies indicate that TDCPP and metabolites are rapidly formed
and eliminated. However, biomonitoring studies report detection of this compound in pine needles,
human adipose tissue, human seminal plasma samples, fish and herring gull eggs.
Cyprinus carpi o 0.3 -22 at two
concentrations over 6 weeks
(Measured)
<1 13 Oryzias latipes Reported as 1 13
at 24 hours, 1 10 at 55 hours and 77 at
96 hours; static study with killifish at
25 °C (Measured)
5 at 24 hours and 3 at 55 hours; static
study with goldfish at 25 °C
(Measured)
59 Oryzias latipes BCF values of 3 1
± 6 to 59 ± 16 reported. Samples
from fish taken at 3, 4, 6, 30 and 32
days. TDCPP concentrations of 40,
80, 300 and 400 ppb used in the flow-
through study with killifish at 25 °C
(Measured)
100 (Estimated)
MITI Japan, 1993
Sasaki etal, 1981
Sasaki etal, 1981
Sasaki etal., 1981
EPIv4.11
Sfonguideline study with results
consistent with other reported
values.
Consistent information for
iillifish under both static and
flow-through conditions, over a
variety of observation times, and
with varying initial concentrations
of test substance.
Consistent information for
goldfish under both static and
flow-through conditions, over a
variety of observation times, and
with varying initial concentrations
of test substance.
BCF is independent of
concentration; continuous flow-
through results correlate to static
results
^o data located.
Estimation model was calculated
using all applicable measured
input values.
7-590
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
Metabolism in Fish
DATA
Apparent metabolism is much faster
in killifish than in goldfish. -10% of
applied TDCPP remains in the water
in the presence of killifish after 96
hours (Measured)
Depuration rate/elimination half-life
of 1.65 hours in killifish when
exposed fish are moved to clean
water (Measured)
REFERENCE
Sasaki etal, 1981
Sasaki etal, 1982
DATA QUALITY
Non guideline study.
Non guideline study.
7-591
-------
Tris (l,3-dichloro-2-propyl) phosphate CASRN 13674-87-8
PROPERTY/ENDPOINT
DATA REFERENCE DATA QUALITY
ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring
Ecological Biomonitoring
Human Biomonitoring
TDCPP has been detected in water samples from surface water samples from 139 streams obtained in 30
states across the continental United States from 1999-2000. It has also been detected in groundwater
samples from 47 sites in 18 different states as part of a national reconnaissance program of water quality
in the United States. TDCPP was found in several streams in Johnson County, Kansas from 2002-2003,
public drinking water in the US and Puerto Rico, St. Vrain Creek, Colorado, the Netherlands Rhine delta,
Freshwater Streams in Hessen/Germany, Ruhr river in Germany, German Bight (an area heavily
influenced by the Elbe estuary plume) in the North Sea, ground water in UK, Arctic Ocean, Sea of Japan,
Northern Pacific Ocean, East Indian Archipelago, Philippine Sea, Indian Ocean, Southern Ocean, German
Bight, North Sea, Oslo, Norway, Birkenes, Southern Norway (remote), Ny Alesund, Norwegian Arctic
(remote), Northern Finland (remote), three volcanic lakes located in Central Italy, the Tiber River, Yodo
river basin, Yamato River in Japan; water in Galicia Spain. TDCPP has been detected in air and dust
samples from ambient air of Kitakyushu, Japan, indoor air environments in Tokyo, Japan, house dust in
Spain, indoor air or dust from Zurich, Sweden, New Zealand, Germany and the US. TDCPP has been
detected in precipitation samples from snow and rain in middle Germany and snow from northern
Sweden. TDCPP has been detected in sediment samples from Taihu Lake, China, the rivers Danube,
Neckar and Rhine, the Elbe river and Ruhr river (Bacaloni et al., 2007, 2008; EU, 2008; Regnery and
Puettmann, 2008; Kanazawa et al., 2010; Meeker and Stapleton, 2010; ATSDR, 2012; Bollmann et al.,
2012; Rodil et al., 2012; Salamova et al., 2014).
TDCPP has been detected in fish from the Yamato river, pine needles from nine sites in the Sierra Nevada
foothills and herring gull eggs from the Channel-Shelter Island colony in Lake Huron (Okumura, 1994;
Aston et al., 1996; EU, 2008; Chen et al., 201 1; Chen et al., 2012).
In Canada, TDCPP was detected in human adipose tissue and it has been identified in human seminal
plasma. This chemical was not included in the NHANES biomonitoring report (Hudec et al., 1981; LeBel
and Williams, 1986; EU, 2008; CDC, 2009; ATSDR, 2012).
7-592
-------
ATSDR (2012) Toxicological profile for Phosphate Ester Flame Retardants. Atlanta, GA: Agency for Toxic Substances and Disease Registry.
Abe A, Urano K (1994) Influence of chemicals commonly found in a water environment on the Salmonella mutagenicity test. Sci Total Environ
153:169-175.
Ahrens VD, Maylin GA, Henion JD, et al. (1979) Fabric release, fish toxicity, and water stability of the flame retardant Fyrol FR-2. Bull Environ
Contam Toxicol 21:409-412.
Akzo Nobel (2001) Robust summaries & test plans: Fyrol FR-2 (Tris[ l,3-dichloro-2-propyl] Phosphate). Akzo Nobel Functional Chemicals LLC.
Submitted under the HPV Challenge Program, http://www.epa.gov/hpv/pubs/summaries/phospho/cl2978.pdf
Akzo Nobel (2003) Akzo Nobel functional chemicals LLC. Fyrol FR-2 Material Safety Data Sheet, MSDS No. 16-084513.
Anderson BT (1990) Amgard TDCP: Acute inhalation toxicity study in rats. Inveresk Research International.
Aston LS, Noda J, Reece CA (1996) Organophosphate flame retardants in needles of Pinus ponderosa in the Sierra Nevada foothills. Bull Environ
Contam Toxicol 57:859-866.
BASF (2007) 14C-TCPP, TCEP and TDCP study on the in vitro metabolism in rats, (Unpublished report). BASF Aktiengesellschaft.
Bacaloni A, Cavaliere C, Foglia P, et al. (2007) Liquid chromatography/tandem mass spectrometry determination of organophosphorus flame
retardants and plasticizers in drinking and surface waters. Rapid Commun Mass Spectrom 21(7): 1123-1130.
Bacaloni A, Cucci F, Guarino C, et al. (2008) Occurrence of organophosphorus flame retardant and plasticizers in three volcanic lakes of central
Italy. Environ Sci Technol 42(6): 1898-1903.
Berts KS (2010) Endocrine damper? Flame retardants linked to male hormone, sperm count changes. Environ Health Perspect 118(3):A130.
Bisinger EC (1990) Letter from Akzo Chemicals Incorporated to USEPA submitting enclosed reports on 2-propanol-(l,3-dichloro) phosphate and
ethanol-(2-chloro) phosphate with attachments. Studies prepared by Life Science Research Limited for Akzo Chemicals International. Submitted
to the U.S. Environmental Protection Agency under TSCA Section 8D.
Bollmann UE, Moller A, Xie Z, et al. (2012) Occurrence and fate of organophosphorus flame retardants and plasticizers in coastal and marine
surface waters. Water Res 46(2):531-538.
7-593
-------
Brusick D, Matheson D, Jagannath DR, et al. (1979) A comparison of the genotoxic properties of tris(2,3-dibromopropyl)phosphate and tris(l,3-
dichloro-2-propyl)phosphate in a battery of short-term bioassays. J Environ Pathol Toxicol 3:207-226.
Brusick DJ, Jagannath DR (1977) Sex-linked recessive lethal assay in Drosophila evaluation of Fyrol FR-2: Final report. Stauffer Chemical
Company.
Budavari S, ed. (2001) Fyrol FR-2. The Merck index - An encyclopedia of chemicals, drugs, and biologicals. 13th ed. Whitehouse Station, NJ:
Merck and Co., Inc.
Buist HE, Schaafsma G, van de Sandt JJ (2009) Relative absorption and dermal loading of chemical substances: Consequences for risk
assessment. Regul Toxicol Pharmacol 54(3):221-228.
Bullock C, Heil JF (1981) Acute dermal toxicity in rabbits. Report T-4287 (1973). Toxicology reports on Fyrol FR-2 (volume I-II) with
attachments and cover letter dated 020381. Stauffer Chemical Company. Submitted to the U.S. Environmental Protection Agency under TSCA
Section 8E, 25.
Bullock CH, Kamienski FX (1981a) 4-Hour skin irritation, eye irritation. Report T-4055-4 (1972). Toxicology reports on Fyrol FR-2 (volume I-II)
with attachments and cover letter dated 020381. Stauffer Chemical Company. Submitted to the U.S. Environmental Protection Agency under
TSCA Section 8E.
Bullock CH, Kamienski FX (198 Ib) Demyelination study in hens. Report T-4055 (1972). Toxicology reports on Fyrol FR-2 (volume I-II) with
attachments and cover letter dated 020381. Stauffer Chemical Company. Submitted to the U.S. Environmental Protection Agency under TSCA
Section 8E, 5-15.
Bullock CH, Hall A, McGowan M, et al. (1981) Cholinesterase inhibition in male rats. Report T-4055-1 (1972). Toxicology reports on Fyrol FR-2
(volume I-II) with attachments and cover letter dated 020381. Stauffer Chemical Company. Submitted to the U.S. Environmental Protection
Agency under TSCA Section 8E, 16-19.
Bullock, CH, et al. (1972) Stauffer Chemical Company, Western Research Center Report T-4055. Stauffer Chemical Company.
CDC (2009) Fourth national report on human exposure to environmental chemicals. Atlanta, GA: Centers for Disease Control and
Prevention, http://www.cdc.gov/exposurereport/pdf/FourthReport.pdf.
CERI (1999) Chemicals Evaluation and Research Institute, Japan, www.cerij.or.jp/ceri en/index e4.shtml.
7-594
-------
California EPA (2013) Chemicals known to the state to cause cancer or reproductive toxicity July 05, 2013. California Environmental Protection
Agency, http://oehha.ca.gov/prop65/prop65 list/files/P65single072613.pdf
Chen D, Letcher RJ, Chu S (2012) Determination of non-halogenated, chlorinated and brominated organophosphate flame retardants in herring
gull eggs based on liquid chromatography-tandem quadrupole mass spectrometry. J Chromatogr A 1220:169-174.
Chen D, Letcher RJ, Gauthier LT, et al. (2011) Novel methoxylated polybrominated diphenoxybenzene congeners and possible sources in herring
gull eggs from Laurentian Great Lakes of North America. Environ Sci Technol 45(22):9523-9530.
Choudhry CG, Hutzinger O (1982) Photochemical formation and degradation of poly chlorinated dibenzofurans and dibenzo-p-dioxins. Residue
Rev 84:113-161.
Cuthbert J, Mullee DM (2002) TDCP: Determination of general physicochemical properties, Report 1613/008, SafePharm Laboratories, PO Box
45, Derby, UK.
Cuthbert JA (1989a) Tolgard TDCP MK1: Acute dermal irritation test in rabbits. Inveresk Research International.
Cuthbert JA (1989b) Tolgard TDCP MK1: Acute oral toxicity (LD50) test in rats. Inveresk Research International.
Cuthbert JA, Jackson D (1990) Tolgard TDCP MK1: Acute eye irritation test in rabbits. Inveresk Research International.
Dishaw LV, Powers CM, Ryde IT, et al. (2011) Is the PentaBDE replacement, tris (l,3-dichloro-2-propyl) phosphate (TDCPP), a developmental
neurotoxicant? Studies in PC12 cells. Toxicol Appl Pharmacol 256(3):281-289.
ECHA (2012) Tris[2-chloro-l-(chloromethyl)ethyl] phosphate. Registered substances. European Chemicals
Agency. http://apps.echa.europa.eu/registered/data/dossiers/DISS-9eb07130-lbOd-1644-e044-00144f67d031/DISS-9eb07130-lbOd-1644-e044-
00144f67d031 DISS-9eb07130-lbOd-1644-e044-00144f67d031.html.
Echigo S, YamadaH, Matsui S, et al. (1996) Comparison between O3/VUV, O3/H2O2, VUV and O3 processes for the decomposition of
organophosphoric acid trimesters. Water Sci Technol 34(9):81-88.
ECOSAR (Ecological Structure Activity Relationship), Version 1.11. Washington, DC: U.S. Environmental Protection
Agency, http://www.epa.gov/oppt/newchems/tools/21ecosar.htm.
7-595
-------
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.
EU (2008) European Union Risk Assessment Report: Tris[2-chloro-l-(chloromethyl)ethyl] phosphate (TDCP) CAS No: 13674-87-8. European
Union.
Eldefrawi AT, Mansour NA, Brattsten LB, et al. (1977) Further toxicological studies with commercial and candidate flame retardant chemicals.
Part II. Bull Environ Contam Toxicol 17:720-726.
Freudenthal RI, Henrich RT (2000) Chronic toxicity and carcinogenic potential of Tris(l,3dichloro-2-propyl) phosphate in Sprague-Dawley rat.
IntJ Toxicol 19:119-125.
Fu J, Han J, Zhou B, et al. (2013) Toxicogenomic responses of zebrafish embryos/larvae to tris(l,3-dichloro-3-propyl) phosphate (TDCPP) reveal
possible molecular mechanisms of developmental toxicity. Environ Sci Technol 47(18): 10574-10582.
Gold MD, Blum A, Ames BN (1978) Another flame retardant, tris-(l,3-dichloro-2-propyl)phosphate, and its expected metabolites are mutagens.
Science 200:785-787.
Hall A, Kamienski FX (1981) Acute oral toxicity in male rats. Report T-4100-2 (1973). Toxicology reports on Fyrol FR-2 (volume I-II) with
attachments and cover letter dated 020381. Stauffer Chemical Company. Submitted to the U.S. Environmental Protection Agency under TSCA
Section 8E, 24.
Hattori Y, Ishitani H, Kuge Y, et al. (1981) Environmental fate of organic phosphate esters. Suishitsu Odaku Kenkyu 4(3):137-141.
Henderson L, Jainer RL (1981) Acute inhalation toxicity. Report T-4782 (1973). Toxicology reports on Fyrol FR-2 (volume I-II) with attachments
and cover letter dated 020381. Stauffer Chemical Company. Submitted to the U.S. Environmental Protection Agency under TSCA Section 8E, 26.
Hicks JS, Holmes PA, Castles TR (1981) 24-hour skin irritation, eye irritation. Report T-6773 (1979). Toxicology reports on Fyrol FR-2 (volume
I-II) with attachments and cover letter dated 020381. Stauffer Chemical Company. Submitted to the U.S. Environmental Protection Agency under
TSCA Section 8E, 39-40.
7-596
-------
Hollifield HC (1979) Rapid nephelometric estimate of water solubility of highly insoluble organic chemicals of environmental interest. Bull
Environ Contam Toxicol 23:579-586.
HSDB (2003) Tris(l,3-dichloro-2-propyl) phosphate CASRN: 13674-87-8. Hazardous Substances Data Bank. National Library of
Medicine. http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen7HSDB.
Hudec T, Thean J, Kuehl D, et al. (1981) Tris(dichloropropyl) phosphate, amutagenic flame retardant: frequent occurrence in human seminal
plasma. Science 211:951-952.
Jagannath DR, Brusick DJ (1981) Sex-linked recessive lethal assay in Drosophila. Evaluation of Fyrol FR-2 final report (1976). Toxicology
reports on Fyrol FR-2 (volume I-II) with attachments and cover letter dated 020381. Prepared by Litton Bionetics for Stauffer Chemical Company.
Submitted to the U.S. Environmental Protection Agency under TSCA Section 8E, 178-299.
Jenkins W (1990) FYROL FR-2: Assessment of its ready biodegradability, Report no. 90/AKL029/0232, Life Science Research, Eye, Suffolk,
UK.
Kamata E, Naito K, Nakaji Y, et al. (1989) Acute and subacute toxicity studies of tris (l,3dichloro-2-propyl) phosphate on mice. Eisei Shikenjo
Hokoku 107:36-43.
Kanazawa A, Saito I, Araki A, et al. (2010) Association between indoor exposure to semi-volatile organic compounds and building-related
symptoms among the occupants of residential dwellings. Indoor Air 20(l):72-84.
Kapp RW, Mossburg PA, Trutter JA, et al. (1981) Teratology study in rats. FR-2 (Fyrol). Final Report (1978). Toxicology reports on Fyrol FR-2
(volume I-II) with attachments and cover letter dated 020381. Prepared by Hazleton Laboratories America, Inc. for Stauffer Chemical Company.
Submitted to the U.S. Environmental Protection Agency under TSCA Section 8E, 57-103.
LeBel GL, Williams DT (1986) Levels of triaryl/alkyl phosphates in human adipose tissue from eastern Ontario. Bull Environ Contam Toxicol
37:41-46.
Lewis R (2000) Sax's dangerous properties of industrial materials. 10th ed. New York, NY: John Wiley & Sons, Inc.
Liu X, Ji K, Choi K (2012) Endocrine disruption potentials of organophosphate flame retardants and related mechanisms in H295R and MVLN
cell lines and in zebrafish. Aquat Toxicol 114-115:173-181.
7-597
-------
Lynn RK, Wong K, Garvie-Gould C, et al. (1981) Disposition of the flame retardanttris(l,3-dichloro-2-propyl-phosphate in the rat. Drug Metab
Dispos9(5):434-441.
MITI Japan (1993) Unpublished Report.
Majeska JB and Matheson DW (1983) Quantitative estimate of mutagenicity of tris-(l,3-dichloro2-propyl) phosphate (TCPP) and its possible
metabolites in Salmonella. Environ Mutagen 5:478-479.
Matheson DW, Brusick DJ (1981) Mutagenicity evaluation of Fyrol FR-2 4619-1B in the mouse lymphoma multiple endpointtest (MET) final
report (1977). Toxicology reports on Fyrol FR-2 (volume I-II) with attachments and cover letter dated 020381. Prepared by Litton Bionetics for
Stauffer Chemical Company. Submitted to the U.S. Environmental Protection Agency under TSCA Section 8E, 438-503.
McGee SP, Cooper EM, Stapleton HM, et al. (2012) Early zebrafish embryogenesis is susceptible to developmental TDCPP exposure. Environ
Health Perspect 120:1585-1591.
Meeker JD, Stapleton HM (2010) House dust concentrations of organophosphate flame retardants in relation to hormone levels and semen quality
parameters. Environ Health Perspect 118(3):318-323.
Mill T (2000) Photoreactions in surface waters. In: Boethling R, Mackay D, eds. Handbook of Property Estimation Methods for Chemicals,
Environmental Health Sciences. Boca Raton: Lewis Publishers, 355-381.
Morey H, Frudentahl RI, Swigut T, et al. (1978) Summary of in vitro delayed neurotoxicity evaluation. Report T-6303. Toxicology reports on
Fyrol FR-2. Vol I of II. Submitted to the U.S. Environmental Protection Agency under TSCA Section 8E, 27-38.
Mortelmans K, Haworth S, Lawlor T, et al. (1986) Salmonella mutagenicity tests: II. Results from the testing of 270 chemicals. Environ Mutagen
8(Suppl. 7): 1-119.
Murphy JP (1981) Toxicology reports on Fyrol FR-2 (volume I-II) with attachments and cover letter dated 020381. Stauffer Chemical Company.
Submitted to the U.S. Environmental Protection Agency under TSCA Section 8E.
NAS (2000) Toxicological risks of selected flame-retardant chemicals. Washington, DC: The National Academies Press, National Academy of
Sciences, http://www.nap.edu/catalog.php7record id=9841.
NICNAS (2001) Triphosphates. National Industrial Chemicals Notification and Assessment Scheme, Commonwealth of Australia.
7-598
-------
Nakamura A, Tateno N, Kojima S, et al. (1979) Mutagenicity of halogenated alkanols and their phosphoric acid esters for Salmonella
typhimurium. Mutat Res 66:373-380.
Nomeir AA, Kato S, Matthews HB (1981) The metabolism and disposition of tris(l,3-dichloro-2-propyl) phosphate (Fyrol FR-2) in the rat.
Toxicol Appl Pharmacol 57:401-413.
NRC (2000) Tris(l,3-dichloropropyl-2) phosphate. Toxicological risks of selected flame retardant chemicals. Washington, DC: National Academy
Press, National Research Council, 358-386.
Ohyama K, Nagata S, Hosogoe N, et al. (2006) Hormonal effects of organic phosphate triesters study by the reporter gene assay. Tokyo-to Kenko
Anzen Kenkyu Senta Kenkyu Nenpo 56:333-338.
Okumura T (1994) Levels of pesticides and chemicals in fish from the rivers (Yodo River, Yamato River, Okawa River) in Osaka Prefecture.
Journal of Environmental Chemistry:490-491.
PBT Profiler Persistent (P), Bioaccumulative (B), and Toxic (T) Chemical (PBT) Profiler, Version 1.301. Washington, DC: U.S. Environmental
Protection Agency, www.pbtprofiler.net.
Prival MJ, McCoy EC, Gutter B, et al. (1977) Tris(2,3-dibromopropyl) phosphate: mutagenicity of a widely used flame retardant. Science
195(4273):76-78.
Regnery J and Puettmann W (2008) Detection of organophosphates in still waters. LaborPraxis 32(9):30-32.
Rodil R, Quintana JB, Concha-Grana E, et al. (2012) Emerging pollutants in sewage, surface and drinking water in Galicia (NW Spain).
Chemosphere 86(10): 1040-1049.
Salamova A, Ma Y, Venier M, et al. (2014) High levels of organophosphate flame retardants in the Great Lakes atmosphere. Environ Sci Technol
Sasaki K, Suzuki T, Takeda M (1982) Bioconcentration and excretion of phosphoric acid triesters by killifish (Oryzeas latipes). Bull Environ
Contain Toxicol 28:752-759.
Sasaki K, Suzuki T, Uchiyama M (1984) Metabolism of phosphoric acid trimesters by rat liver homogenate. Bull Environ Contain Toxicol 33:281-
288.
7-599
-------
Sasaki K, Takeda M, Uchiyama M (1981) Toxicity, absorption, and elimination of phosphoric acid triesters by killifish and goldfish. Bull Environ
Contain Toxicol 27:775-782.
Schaefer EC and Ponizovsky AA (2006) Tris[2-chloro-l-chloromethyl)ethyl]-phosphate (TDCP): Adsorption/desorption characteristics in
representative soils, sediment, and sludge solids in accordance with OECD Guideline for Testing of Chemicals, 106: Adsorption/desorption using
a batch equilibrium method. Wildlife International, Ltd. project no.: 584E-101. Draft report 2nd.
Soederlund EJ, Dybing E, Holme JA, et al. (1985) Comparative genotoxicity and nephrotoxicity studies of the two halogenated flame retardants
tris(l,3-dichloro-2-propyl) phosphate and tris(2,3-dibromopropyl)phosphate. Acta Pharmacol Toxicol 56:20-29.
Takahashi S, Obana Y, Okada S, et al. (2012) Complete detoxification of tris(l,3-dichloro-2-propyl) phosphate by mixed two bacteria,
Sphingobium sp. strain TCM1 and Arthrobacter sp. strain PY1. Volume 113, Issue 1, January 2012, Pages 79-83. J Biosci Bioeng 113(l):79-83.
Tanaka S, Nakaura S, Kawashima K, et al. (1981) Effect of oral administration of tris(l,3dichloroisopropyl)phosphate to pregnant rats on prenatal
and postnatal developments. Eisei Shikenjo Hokoku 99:50-55.
Thomas MB and Collier TA (1985) Tolgard T.D.C.P. LV: OECD 474 Micronucleus study in the mouse. Experiment No. 164/8507. SafePharm
Laboratories.
Tremain SP (2002) TDCP: determination of vapour pressure. Report 1613/003, SafePharm Laboratories, PO Box 45, Derby, UK.
Van den Eede N, Maho W, Neels H, et al. (2013) Metabolism of phosphate flame retardants and plasticisers using human liver fractions. Sixth
International Symposium on Flame Retardants, San Francisco, CA, April 7-10, 2013
WHO (1998) International Programme on Chemical Safety (IPCS), Environmental Health Criteria 209, Flame retardants:
tris(chloropropyl)phosphate and tris(2-chloroethyl)phosphate. Geneva: International Programme on Chemical Safety, World Health
Organisation. http://whqlibdoc.who.int/ehc/WHO_EHC_209.pdf
Wilczynski SI, Killinger JM, Zwicker GM, et al. (1983) Fyrol FR-2 fertility study in male rabbits. Toxicologist 3:22.
7-600
-------
Tris (2-chloro-l-methylethyl) phosphate (TCPP)
Screening Level Toxicology Hazard Summary
This table contains hazard information for each chemical; evaluation of risk considers both hazard and exposure. Variations in end-of-life processes or degradation and combustion
by-products are discussed in the report but not addressed directly in the hazard profiles. The caveats listed below must be taken into account when interpreting the information in the
table.
VL = Very Low hazard L = Low hazard = Moderate hazard = High hazard VH = Very High hazard - Endpoints in colored text (VL, L, , H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].
Chemical
CASRN
Human Health Effects
|y
o
H
u
<
'0
|
o
'8
u
|y
o
"o
g
O
0)
|
•a
1
*
sS
g
S
_0
"3
Q
I
o
s
3
z
o
Q
•a
0)
M
a
_o
"S
.a
0)
C/5
'!
C/5
2 '•§
11
5B g*
PS 1/3
a
"S
•c
hH
a>
w
0
1
hH
13
0)
Q
Aquatic
Toxicity
u
^
1
U
Environmental
Fate
0)
u
4>
0.
a
O
1
"3
1
0
PH
Tris (2-chloro-l-methylethyl)
phosphate (TCPP)
13674-84-5
L
M
L
H
H
M
L
L
L
M
L
7-601
-------
Cl
o—
CASRN: 13674-84-5
MW: 327.57
MF:
Physical Forms: Liquid
Neat:
Use: Flame retardant
SMILES: O=P(OC(CC1)C)(OC(CC1)C)OC(CC1)C
Synonyms: 2-Propanol, 1-chloro-, 2,2\2"-phosphate; TCPP; TCIPP; Tris(l-chloro-2-propyl)phosphate; Tris(2-chloroisopropyl)phosphate; 2-propanol, 1-
chlorophosphate (3:1); l-chloro-2-propyl phosphate (1:3); tris(l-chloromethylethyl) phosphate; phosphoric acid, tris(2-chloro-1 -methyl ethyl) ester
Chemical Considerations: CASRN 13674-84-5 is a discrete organic chemical with a MW below 1,000. EPI v4.11 was used to estimate physical/chemical and
environmental fate values in the absence of experimental data. Measured values from experimental studies were incorporated into the estimations. TCPP is produced
by the reaction of phosphorus oxy chloride and propylene oxide. The most abundant isomer in commercial products is the branched isomer, 2-Propanol, 1-chloro-,
phosphate (3:1) (CASRN 13674-84-5) however other isomers are expected to be present and will be discussed in this report as appropriate when determining hazard
designations. Chemical, fate, and toxicity data for the isomers represented by other CASRN were collected in the preparation of this AA and are listed below:
1-Propanol, 2-chloro-, 1,1\1"-phosphate (3:1) (CASRN 6145-73-9);
Phosphoric acid, bis(2-chloro-l-methylethyl) 2-chloropropyl ester (CASRN 76025-08-6) and
Phosphoric acid, 2-chloro-1-methylethyl bis(2-chloropropyl) ester (CASRN 76649-15-5) (NAS, 2000).
7-602
-------
Polymeric: No
Oligomeric: Not applicable
Metabolites, Degradates and Transformation Products: O,O-[bis(l-chloro-2-propyl)]-O-(2-Propionic acid) phosphate; bis(l-chloro-2-propyl) phosphate; bis(l-
chloro-2-propyl) 1 -hydroxy-2-propyl phosphate; bis(l-chloro-2-propyl) 1-carboxy -2-propyl phosphate; l-chloro-2-propyl,l-hydroxy-2-propyl phosphate (OECD-
SIDS, 2000; Van den Bade et al, 2013)
Analog: Isomers anticipated to be present in the commercial
product were considered in this evaluation, as indicated in the
chemical considerations section
Endpoint(s) using analog values: Not applicable
Analog Structure: Not applicable
Structural Alerts: Organophosphates; Neurotoxicity (EPA, 2012).
Risk Phrases: This substance is not classified in the Annex I of Directive 67/548/EEC (ESIS, 2012).
Hazard and Risk Assessments: Priority Existing Chemical Assessment report for Triphosphates by the National Industrial Chemicals Notification and Assessment
Scheme (NICNAS) in 2001, Environmental Health Criteria for Flame Retardants by the World Health Organization in 1998, SIDS Initial Assessment Profile, EU Risk
Assessment Report in 2008 and ATSDR Toxicological Profile for Phosphate Ester Flame Retardants in 2012 (WHO, 1998; OECD-SIDS, 2000; NICNAS, 2001; EU,
2008;ATSDR,2012).
7-603
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
DATA
REFERENCE | DATA QUALITY
PHYSICAL/CHEMICAL PROPERTIES
Melting Point (°C)
Boiling Point (°C)
Vapor Pressure (mm Hg)
-51
value expressed as pour point;
Isoteniscopic ASTM D2897 Method
(Measured)
-42
value expressed as pour point
(Measured)
-65
(Measured)
72
(Measured)
>288
GLP study (Measured)
235
reported as 235-248°C. (Measured)
220 Decomposes
(Measured)
244 at 700 mmHg Decomposes
(Measured)
359
(Measured)
lx!0-5at25°C
reported as 0.0014 Pa; GLP study
(Measured)
<2 at 25°C
OECD-SIDS, 2000; ECHA, 2013
EC, 2000
NICNAS, 2001
van der Veen and de Boer, 2012
ECHA, 2013
WHO, 1998; NAS, 2000
NICNAS, 2001
OECD-SIDS, 2000
van der Veen and de Boer, 2012
ECHA, 2013
OECD-SIDS, 2000
Guideline study reported in a
secondary source.
Reported in a secondary source
with limited study details.
Reported in a peer reviewed
secondary source for the isomeric
component CASRN 6145-73-9.
Cited in a peer reviewed source,
this value is higher than the other
studies which reported pour
points.
Reported in a secondary source.
Reported in a peer reviewed
source.
Reported in a peer reviewed
secondary source for the isomeric
component CASRN 6145-73-9.
Test substance 75 +/- 10% pure
with major impurities. Reported
in a secondary source.
Cited in a peer reviewed source.
Reported in a secondary source.
Adequate guideline study.
7-604
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
Water Solubility (mg/L)
Log Kow
Flammability (Flash Point)
DATA
reported as 40 mm Hg at 1 10°C;
according to Isoteniscopic, ASTM
D2879 Method (Measured)
0.75at25°C
(Measured)
<0.098
Reported as <13 Pa; temperature not
specified (Measured)
2.9xlO'5
(Estimated)
1,080 (Measured)
according to GLP flask method study
1,200 (Measured)
1,600 (Measured)
0.11% at 25°C (Measured)
2.68
HPLC method (Measured)
2.59
(Measured)
3.33
Reported at 20°C according to EC
Guideline 92/69 Annex V, Method A8;
non-GLP (Measured)
Flash point: 185°C according to
Pensky-Martens Closed Cup ASTM
D93 (Measured)
Flash point: 218°C (Measured)
REFERENCE
van der Veen and de Boer, 2012
NICNAS, 2001
EPIv4.11
ECHA, 2013
NICNAS, 2001
van der Veen and de Boer, 2012
OECD-SIDS, 2000; ECHA, 2013
ECHA, 2013
van der Veen and de Boer, 2012
OECD-SIDS, 2000
OECD-SIDS, 2000
van der Veen and de Boer, 2012
DATA QUALITY
Reported in a peer reviewed
source.
Reported in a peer reviewed
secondary source for the isomeric
component CASRN 6145-73-9.
According to the Modified Grain
Method.
Reported in a secondary source.
Reported in a peer reviewed
secondary source for isomeric
component CASRN 6145-73-9.
Reported in a peer reviewed
source.
Reported in secondary sources
with limited details.
Reported in a secondary source.
Reported in a peer reviewed
source.
Guideline study reported in a
secondary source; reproducibility
concerns noted in results.
Guideline study reported in s a
secondary source.
Guideline study reported in a
7-605
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
Explosivity
Pyrolysis
pH
pKa
DATA
Flash point: 220°C Cleveland open
cup (Measured)
Not applicable (Estimated)
Not applicable (Estimated)
REFERENCE
NICNAS, 2001
Professional judgment
Professional judgment
DATA QUALITY
secondary source.
Reported in a peer reviewed
secondary source for isomeric
component CASRN 6145-73-9.
No data located.
No data located.
Does not contain functional
groups that are expected to ionize
under environmental conditions.
Does not contain functional
groups that are expected to ionize
under environmental conditions.
7-606
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
HUMAN HEALTH EFFECTS
Toxicokinetics
TCPP is readily absorbed. Absorption through human skin membranes in vitro was calculated to be 2.3-
32.8% of the applied dose. Twelve hours post- oral exposure, TCPP was detected in the brain, heart,
muscle, and testes, more so in adipose tissue, spleen, and lungs, and in the highest amounts in the liver
and kidney. TCPP is quickly and extensively metabolized with main metabolites being O,O-[bis(l-chloro-
2-propyl)]-O-(2-propionic acid) phosphate, bis(l-chloro-2-propyl) monophosphoric acid and l-chloro-2-
propanol. TCPP was metabolized to a hydroxylated metabolite by chlorine substitution in liver S9
faction and liver slices followed by glucuronic acid conjugation. In incubation experiments, Phase I
metabolites included the oxidative dechlorination products of TCPP and the hydrolysis product bis(l-
chloro-2-propyl) phosphate (BCPP), bis(l-chloro-2-propyl) l-hydroxy-2-propyl phosphate, bis(l-chloro-
2-propyl) 1-carboxy -2-propyl phosphate and l-chloro-2-propyl,l-hydroxy- 2-propyl phosphate; there
were no phase II metabolites detected. BCPP was the most abundant metabolite. Once the tissues, the
parent compound and metabolites are rapidly excreted. Excretion occurred primarily via the urine, but
also in the feces and bile.
Dermal Absorption in vitro
Concentrations of TCPP tested over an
8 hour exposure period were 2.049,
99.96, or 997.33 (ig/cm2. The mean
penetration of TCPP into the receptor
fluid after 24 hours was 0.39, 9.64 and
17.75 (ig/cm2, for the low, mid and
high dose, respectively. At 0.002
mg/cm2, the total absorption ranged
from 17 % to 32.8%, with a mean total
absorption of 22.7 %. At the mid dose
of 0.1 mg/cm2, the total absorption
ranged from 9.8% to 18.2%, with the
mean total absorption of 13.6%. At 1
mg/cm2, the total absorption ranged
from 2.3% to 5.2%, with a mean total
absorption of 3.7%.
The actual concentrations of TCPP
tested in an artificial sweat solution
over an 8 hour exposure period were
TNO, 2006 (as cited in EU, 2008)
Adequate; guideline and GLP-
compliant study. Data are from a
secondary source.
TNO, 2005 (as cited in EU, 2008)
Guideline and GLP-compliant
study. Study details reported in a
secondary source.
7-607
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
76 (ig/mL and 506 (ig/L. At 24 hours
after application, the total mean
absorption of TCPP into the receptor
fluid, the receptor compartment wash
and the skin (excluding tape strips)
was 33.3% and 38.1% for the low and
high doses respectively. The mean
recovery of TCPP in human skin was
93.1% and 92.2% for the low and high
doses respectively. The permeability
constant (Kp) for TCPP in artificial
sweat under infinite conditions (24
hour exposure) was 7.65 x 10~3 cm/h.
Absorption,
Distribution,
Metabolism &
Excretion
Oral, Dermal or Inhaled
Male Wistar rats administered a single
50 (imol/kg (-14 mg/kg) gavage dose
of14C-labeledTCPP
Maximum concentration in tissues: 5.7
hours. Low tissue/blood ratios were
recorded in the brain, heart, muscle,
and testes. Moderate ratios were
obtained in adipose tissue, the spleen,
and lung; high ratios were recorded in
the liver and kidneys. The highest
amounts of radioactivity in the liver
and kidney were detected during the
first 12 hours after dosing. Seven days
after dosing, the highest amount of
radioactivity was found in the liver.
The longest elimination half-lives from
any tissue corresponded to adipose
tissue (103 hours for TCPP).
Minegishi et al., 1988
Adequate
14C-labeled Fyrol PCF given to
Sprague-Dawley rats at 20 or 200
Stauffer Chem Co, 1984 (as cited in
OECD-SIDS, 2000; EU, 2008)
Data provided in a secondary
source based on scientific review
7-608
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
mg/kg via a single oral or i.v.
administration. Urine was the major
route of elimination. Test substance is
rapidly metabolized with main
metabolites being O,O-[bis(l-chloro-2-
propyl)]-O-(2-propionic acid)
phosphate, bis(l-chloro-2-propyl)
monophosphoric acid and l-chloro-2-
propanol. The total body burden at the
end of 8 days was less than 1%
suggesting insignificant
bioaccumulation.
of peer literature.
Male Wistar rats administered a single
50 (imol/kg (~14 mg/kg) gavage dose
of 14C-labeled TCPP -60% of TCPP
was excreted in the urine; recovery
within the 7 days approached 100%.
Experiments in rats with cannulated
bile ducts showed that peak biliary
excretion occurred approximately 2
hours after dosing with TCPP. 45% of
administered TCPP was excreted in the
bile in 48 hours. Since the biliary/fecal
excretion ratios for TCEP exceeded 1,
it appeared that enterohepatic
circulation occurred.
Minegishi et al., 1988
Adequate
Male Wistar rats were administered 50
(imol/kg TCPP.
97.8% of the radioactive dose was
recovered; of the recovered dose, 67
and 22% were recovered in the urine
and feces (respectively), 7.7% in
expired air, and <1% in the carcass.
Minegishi et al., 1988
Adequate
7-609
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Other
Little radioactivity remained in the
tissues 168 hours after dosing.
14C-labeled TCPP incubated with rat
liver fractions for 4 or 24 hours. TCPP
was metabolized to a hydroxylated
metabolite by chlorine substitution in
liver S9 fraction and liver slices,
followed by glucuronic acid
conjugation in liver slices. 11% and
39% of unmetabolized TCPP were
detected in S9 fraction and liver slices,
respectively.
BASF, 2007 (as cited in EU, 2008)
Study details reported in a
secondary source. Documentation
insufficient for assessment of data
quality.
Incubation experiments using 1.0
mg/mL HLM or S9 proteins, 50
TBOEP or TCEP, or TCPP, or 20
TPHP or TDCPP and NADPH
regenerating solution in 1 mM total
volume were conducted for 1 hour.
There was a 33% and 28% clearance
of the compound in the HLM and S9
incubations, respectively.
Phase I metabolites included the
oxidative dechlorination products of
TCPP and the hydrolysis product
bis(l-chloro-2-propyl) phosphate
(BCPP, Ml), bis(l-chloro-2-propyl) 1-
hydroxy-2-propyl phosphate (M2),
bis(l-chloro-2-propyl) 1-carboxy -2-
propyl phosphate (M3) and l-chloro-2-
propyl,l-hydroxy- 2-propyl phosphate
(M4); there were no phase II
metabolites detected. BCPP was the
most abundant metabolite.
Van den Bade et al., 2013
Study details reported in an
abstract
7-610
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
Acute Mammalian Toxicity
Acute Lethality
Oral
Dermal
DATA
REFERENCE
DATA QUALITY
LOW: Based on LD50 and LC50 values for the oral, dermal, and inhalation routes of exposure.
Rat LD50 (range) = 1,073 - 3,600
mg/kg
Rat LD50 = 1,546 - 1,824 mg/kg
(males); 1,017- 1,101 mg/kg
(females)
Rat LD50 = 2,800 mg/kg (females);
4,200 mg/kg (males)
Rats exposed at 200, 500, or 2,000
mg/kg. All rats (females) died at 2,000
mg/kg; no mortalities at other dose
levels.
LD50 > 500 mg/kg (males) and >632
mg/kg (females)
RatLD50 = 931- 1,550 mg/kg
Rat LD50 = 2,000 mg/kg (males) and
1,260 mg/kg (females)
Rat 96-h LD50 = 1,500 mg/kg
(females)
Rabbit LD50 >2,000 mg/kg
Rat LD50 >2,000 mg/kg
SafePharm Labs Ltd, 1979a, 1979b;
Stauffer Chem Co, 1972 (as cited in
EC, 2000; EU, 2008)
Mobil, 1980a, 198 la (as cited in
EC, 2000; OECD-SIDS, 2000; EU,
2008)
Huntingdon, 1997a, 1997b (as cited
in EC, 2000; OECD-SIDS, 2000;
EU, 2008)
Stropp, 1996 (as cited in EU, 2008;
ATSDR, 2012)
SafePharm Labs Ltd, 1994, 1996a,
1996b, 1997a, 1997b (as cited in
EU, 2008)
Litton Bionetics, 1977 (as cited in
ATSDR, 2012)
Kawasaki et al., 1982 (as cited in
ATSDR, 2012)
Stauffer Chem Co, 1970, 1979;
Mobil, 1980b, 1981b (as cited in
EC, 2000; EU, 2008)
Inveresk Res Int, 1989b (as cited in
Adequate by weight of evidence;
data obtained from multiple
secondary sources.
Adequate by weight of evidence;
data from secondary sources.
Adequate; performed according to
current standards and GLP-
compliant.
Study details reported in a
secondary source.
Adequate; conducted according to
OECD guidelines.
Study details from an anonymous
source reported in a secondary
source.
Study details reported in a
secondary source.
Study details reported in a
secondary source. Test substance
identified as TCPP in some
studies; Antiblaze 80 or Fyrol
PCF in others. Purity of the test
substance reported in some
studies.
Study details from several studies
7-611
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
Inhalation
Carcinogenicity
OncoLogic Results
Carcinogenicity (Rat and
Mouse)
Combined Chronic
Toxicity/Carcinogenicity
Other
DATA
Rat 4-h LC50 (whole-body): >5 mg/L
(males); ~5 mg/L (females)
Rat 4-h LC50 (nose-only) >7 mg/L
Rat 1-h LC50 (whole-body) >17.8
mg/L
REFERENCE
OECD-SIDS, 2000; EU, 2008)
Env Affairs, 198 la (as cited in EC,
2000; OECD-SIDS, 2000; EU,
2008)
Inveresk Res Int, 1990a (as cited in
EC, 2000; EU, 2008)
Env Affairs, 1981b (as cited in EC,
2000; EU, 2008)
DATA QUALITY
reported in secondary source. At
least one study was performed
according to OECD guidelines
and GLP.
Study based on EPA guidelines;
sufficient study details reported;
analyses of test concentrations
and cumulative mass of the
particles were performed.
OECD guideline study performed
according to GLP. Test
concentrations and particle size
distribution analyses were
performed; sufficient study details
reported. Purity (total of four
isomers) >97.9%.
Study based on EPA guidelines;
sufficient study details reported.
MODERATE: There were no experimental data located for this endpoint; carcinogenic effects cannot be
ruled out.
No data located.
No data located.
No data located.
No data located.
7-612
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
Genotoxicity
Gene Mutation in vitro
DATA
REFERENCE
DATA QUALITY
LOW: Based on weight of evidence from multiple studies. TCPP did not cause gene mutations in
bacteria in vitro or chromosome aberrations in rat bone marrow in vivo.
In multiple studies: Negative for
mutation in Salmonella typhimurium
strains TA97a, TA98, TA100, TA102,
TA104, TA1535, TA1537, and/or
TA1538 in the presence or absence of
metabolic activation at up to 1 mM.
Negative; gene mutation in E. coll
strains W3 1 1 0/po 1 A+ and
p3478/polA- at doses up to 20 ^I/plate
in the presence or absence of
metabolic activation.
Negative; gene mutation in
Saccharomyces cerevisiae strain D4 in
the presence or absence of activation.
Positive in the presence of metabolic
activation; gene mutation in L5 178Y
mouse lymphoma cells. Negative in
the absence of metabolic activation.
Positive; transformation of BALB/3T3
cells
Negative; forward mutation in mouse
lymphoma L5 178Y cells at TK locus
in the presence or absence of
Zeiger et al., 1992; Abe and Urano,
1994; Follmann and Wober, 2006
(as cited in EU, 2008; ATSDR,
2012)
Tenneco Chem Inc, 1977 (as cited
in EU, 2008)
Stauffer Chem Co, 1976, 1978d (as
cited in EU, 2008)
Covance Labs, 2005; Env Affairs,
198 Ic (as cited in EU, 2008)
Stauffer Chem Co, 1978e (as cited
in EU, 2008)
Stauffer Chem Co, 1978c (as cited
in EU, 2008)
Study details reported in a
secondary source; similar to
guideline studies. Exact purity of
test substances was not reported,
but a reagent grade chemical was
used.
Adequate; data from a secondary
source.
Adequate; data reported in a
secondary source.
Adequate; data reported in a
secondary source. Results
considered equivocal in one assay
because a dose-response
relationship could not be
ascertained. Results were positive
with activation in a confirmatory
mouse lymphoma assay.
Data reported in a secondary
source. Positive at all doses (39-
312nl/ml50-400(ig/ml);
however, no dose-response
relationship was observed.
Acceptable, well-documented
publication report which meets
basic scientific principles. Data
7-613
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
Gene Mutation in vivo
Chromosomal Aberrations in
vitro
Chromosomal Aberrations in
vivo
DNA Damage and Repair
DATA
metabolic activation.
Negative; transformation of
BALB/3T3 cells at up to 40 nL/mL
(51.6jig/mL).
Negative for induction of micronuclei
in Sprague-Dawley rats administered
TCPP in the feed at up to 20,000 ppm
for 90 days.
Negative for chromosomal aberrations
in bone marrow of Sprague-Dawley
rats orally exposed.
Positive in males and negative in
female for induction of micronuclei in
B6C3F1 mice administered TCPP in
feed at 1, 1250, 2500, 5,000, 10,000,
or 20,000 ppm for 90 days.
Negative for DNA damage (comet
assay) in the presence or absence of
activation in Chinese hamster V79
cells. The test substance caused
cytotoxicity (neutral red uptake assay)
in the presence, but not absence of
activation.
Negative; UDS in rat liver cells
TCPP did not induce DNA damage in
REFERENCE
Stauffer Chem Co, 1980b (as cited
in EU, 2008)
NTP, 2013
Stauffer Chem Co, 1978b (as cited
in EU, 2008)
NTP, 2013
Follmann and Wober, 2006
Williams et al., 1989; Bayer, 1991b
(as cited in EU, 2008)
Covance Labs, 2006 (as cited in
DATA QUALITY
reported in a secondary source.
Adequate; similar to guideline
study. Data reported in a
secondary source. Although tests
were positive for one study, no
dose-response was observed.
No data located.
No data located.
Adequate; limited study details
available from NTP website.
Study conducted according to
OECD guidelines; study details
reported in secondary source.
Adequate; limited study details
available from NTP website.
Purity of test substance was not
reported, but a reagent grade
chemical was used.
Adequate; data reported in a
secondary source. Guideline and
GLP -compliant study.
Study conducted similar to
7-614
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
Other
Reproductive Effects
Reproduction/Developmental
Toxicity Screen
Combined Repeated Dose with
Reproduction/ Developmental
Toxicity Screen
Reproduction and Fertility
Effects
DATA
the liver or rats treated up to 1,500
mg/kg.
TCPP did not induce DNA strand
breaks in V79 cells in the presence or
absence of activation (alkaline comet
assay) at concentrations up to 1 mM.
Equivocal results UDS in human
diploid WI-38 cells. The test material
was weakly active at 0.01 (il/mL in
activated and nonactivated systems
without an associated dose response at
higher concentrations.
REFERENCE
EU, 2008; ECHA, 2013)
Follmann and Wober, 2006
Stauffer Chem Co, 1978a (as cited
in EU, 2008)
DATA QUALITY
guidelines and GLP-compliant;
study details reported in
secondary source.
Purity of test substance was not
reported, but a reagent grade
chemical was used.
Data were from a secondary
source. Test results were deemed
equivocal because no clear dose-
response relationship could be
ascertained, and performed using
a non-standard cell line. Results
in other cell types were negative.
No data located.
HIGH: Based on an unestablished NOAEL and a LOAEL of 99 mg/kg-day for decreased uterine weights
in FO female rats fed TCPP in a 2-generation reproduction study. Two other studies reported no
significant effects on reproductive parameters in rats exposed to TCPP in the diet at doses greater than
893 mg/kg-day.
Two-generation reproduction study in
Wistar rats (28/sex/group)
Doses: 0, 85, 293 and 925 mg
TCPP/kg-day for males and 0, 99, 330
and 988 mg TCPP/kg-day for females
(administered in the diet)
Decreased body weight and food
consumption was observed in mid and
TNO, 2007 (as cited in EU, 2008)
No data located.
No data located.
Adequate; guideline (OECD 416)
and GLP-compliant study. Data
obtained from a secondary source
only; primary source not
specified; uterine and seminal
vesicle weight changes were not
accompanied by histopathological
changes.
7-615
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
high dose parental animals and the
effects on uterus weights seen in all
dosed FO animals.
There were no treatment related effects
in pre-coital time, mating index,
female fecundity index, male and
female fertility index, duration of
gestation and post-implantation loss
There was no effect on sperm
parameters at necropsy
In females, the length of the longest
oestrus cycle and the mean number of
cycles per animal were statistically
significantly increased in high dose
animals of both generations. A
decrease in uterus weight was
observed in all dosed females in FO
and in high dose females in F1.
Decreased relative and absolute
seminal vesicle weights were reported
in the mid and high dose FO and Fl
males.
NOAEL: Not established
LOAEL: 99 mg/kg-day based on
effects on uterus weights (lowest dose
tested).
FO Males:
NOAEL: 85 mg/kg-day
LOAEL: 293 mg/kg-day based on
decreased seminal vesicle weight
7-616
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Other
Dietary study in rats; exposure: GD 0 -
20; doses: up to 893 mg/kg-day
No significant effect on the numbers of
implantations or resorptions.
NOAEL: 893 mg/kg-day (highest dose
tested)
LOAEL: Not established
Kawasaki et al., 1982 (as cited in
ATSDR, 2012)
Limited study details reported in a
secondary source. Unknown
purity of test substance. The 893
mg/kg-d dose level was the
highest dose tested. The true
NOAEL may be higher.
In a 90 day study, 20 male and 20
female Sprague Dawley rats were fed
diets containing 0, 800, 2,500, 7,500
and 20,000 ppm of TCPP, there were
no effects observed in the testes or
ovaries of treated animals when
examined at necropsy
NOAEL: 20,000 ppm (Highest
concentration tested)
LOAEL: Not established
Freudenthal and Henrich, 1999
Inadequate for complete
assessment of reproductive
toxicity; data are for the Fyrol
PCF mixture (about tris (2-
chloroisopropyl) phosphate (about
70%) and 2-chloropropanol
phosphate (about 23%).
Developmental Effects
HIGH: Based on an unestablished NOAEL and a LOAEL of 99 mg/kg-day for an increased number of
runts in rats exposed to TCPP in the diet in a 2-generation reproduction study. Another study reported
no significant developmental effects in offspring of rats gestationally exposed to TCPP in the diet at
doses up to 893 mg/kg-day.
There were no data located for the developmental neurotoxicity endpoint; there is uncertain concern for
developmental neurotoxicity based on the potential for Cholinesterase (ChE) inhibition in dams that
may result in alterations of fetal neurodevelopment.
Reproduction/ Developmental
Toxicity Screen
Combined Repeated Dose with
Reproduction/ Developmental
Toxicity Screen
No data located.
No data located.
7-617
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
Prenatal Development
Postnatal Development
Prenatal and Postnatal
Development
Developmental Neurotoxicity
Other
DATA
Dietary study in Wistar rats
Exposure: GD 0 - 20; doses: 0.01, 0.1,
and 1% in the diet (up to 893 mg/kg-
day)
No significant effects on fetal weight
or incidences of external
malformations. Cervical ribs, missing
ribs, and delayed ossification of
sternebrae were more frequent in
treated groups but not significantly
different from controls. Neonatal
growth and survival during the 4
weeks after weaning was comparable
among groups.
NOAEL: 893 mg/kg-day (highest dose
tested)
LOAEL: Not established
Uncertain concern for developmental
neurotoxicity based on the potential for
Cholinesterase (ChE) inhibition in
dams that may result in alterations of
fetal neurodevelopment (Estimated)
Two-generation reproduction study in
Wistar rats (28/sex/group)
Doses: 0, 85, 293 and 925 mg
TCPP/kg-day for males and 0, 99, 330
and 988 mg TCPP/kg-day for females
(administered in the diet)
Decreased mean number of pups
REFERENCE
Kawasaki et al., 1982 (as cited in
EU, 2008; ATSDR, 2012)
Professional judgment
TNO, 2007 (as cited in EU, 2008)
DATA QUALITY
Data obtained from a secondary
source; limited study details were
available in the secondary source.
Unknown purity of test substance.
The 893 mg/kg-d dose level was
the highest dose tested. The true
NOAEL may be higher.
No data located.
No data located.
Estimated based on a structural
alert for organophosphates for the
neurotoxicity endpoint.
Data reported in a secondary
source. Adequate; guideline
(OECD 416) and GLP-compliant
study. Data obtained from a
secondary source.
7-618
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
delivered was observed in the mid
dose group of the Fl generation and in
the high dose groups of both
generations. Pup mortality (PND1-4)
was statistically significantly increased
in the low and high dose FO groups
and in the high doseFl group. This
effect was only observed when the pup
was used as the statistical unit. The
effect observed in the Fl generation
was mainly due to the loss of one litter
(10 pups) of a single dam on PND4.
There was no statistically significant
difference in the mean number of pups
on PND4.
In the FO generation, the mean number
of runts was statistically significantly
increased in all dose groups on PND1
and persisted to PND21 in the mid and
high dose groups. In Fl generation, the
number of runts was increased in the
high dose group on PND14 and in all
dose groups on PND21.
In both generations, the number of
runts in the high dose groups increased
during the course of the lactation
period.
There was no effect on pup weight at
PND1 in either generation. There was
no effect on pup weight on PND1 in
both generations. Mean pup weights of
the high dose group were significantly
decreased in FO generation from
PND 14 onwards and in the Fl
7-619
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
generation from PND 7 onwards.
Mean pup weights were decreased in
mid dose groups on PND21
No difference in anogenital distance of
the male or female F2 pups was
observed between the treated and
control animals. Vaginal opening was
delayed (not significantly) in the high
dose group. Preputial separation was
statistically significantly delayed in the
high dose group. The body weight of
the high dose male and females of the
F2 generation was significantly
decreased from PND28 until PND42
(91% and 89% of control at PND42 for
females and males of this group,
respectively). The effects observed in
this dose group on vaginal opening and
preputial separation is most likely
secondary to toxicity.
At necropsy of the pups there were no
treatment related macroscopic
findings.
NOAEL: Not established
LOAEL: 99 mg/kg-day based on
treatment related effect on the number
of runts in FO generation (lowest dose
tested).
7-620
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Neurotoxicity
MODERATE: Based on the weight of evidence from a structural alert for organophosphates and an in
vitro study. In an in vitro study using undifferentiated and differentiating PC12 cells, TCPP promoted
differentiation of the cholinergic phenotype of PC12 cells. There were no effects on cholinesterase
activity in a dietary study in rats fed TDCPP and no evidence of delayed neurotoxicity in one study of
hens orally treated with TCPP.
Neurotoxicity Screening
Battery (Adult)
Other
Potential for neurotoxicity based on
structural alert for organophosphates
(Estimated)
In vitro neurotoxicity study using
undifferentiated and differentiating
PC 12 cells. Changes in DNA
synthesis, oxidative stress,
differentiation into dopaminergic or
cholinergic neurophenotypes, cell
number, cell growth and neurite
growth were assessed.
TCPP promoted differentiation of the
cholinergic phenotype only. There
were no other adverse neurological
effects.
14-day dietary study in CD-I rats
treated with 0, 4200, 6600, 10,600, and
16,600 ppm (approximately 0, 417,
648, 1,015, 1,636 mg/kg-day for males
and 382, 575, 904, 1,517 mg/kg/day
for females).
There were no effects on
cholinesterase activity.
NOAEL: 16,600 ppm (1,636 mg/kg-
day); highest dose tested
Professional judgment
Dishawetal, 2011
Stauffer Chem Co, 1980a
No data located.
Estimated based on a structural
alert and professional judgment.
Study details reported in a
primary source
Test substance was identified as
Fyrol PCF, a mixture containing
TCPP (-70%) and 2-
chloropropanol phosphate
(-22%); limited study details
reported in a robust summary.
7-621
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
LOAEL: Not established
Delayed oral neurotoxicity in White
leghorn hens (18/treatment group and
10 controls); doses: 13,200 mg/kg (10
mL/kg) by gavage; exposure period:
Two treatments, three weeks apart
Treated hens showed loss of body
weight and transient reductions in food
consumption immediately following
treatment. There was no evidence of
delayed motor impairment; no
histological changes to nervous tissues
were found.
NOAEL: 13,200 mg/kg; highest dose
tested
LOAEL: Not established
Sprague et al., 1981; OECD-SIDS,
2000
Study details reported in a
primary source; not a guideline
study.
Repeated Dose Effects
MODERATE: Based on reported morphological changes in the kidney and thyroid reported in rats fed
the Fyrol PCF mixture (tris (2-chloroisopropyl) phosphate [~70%] and 2-chloropropanol phosphate [~
23%]) in the diet for 90 days at doses of 481 mg/kg-day and 570 mg/kg-day in males and females,
respectively. Decreased body weight gain and food consumption was reported in rats fed Fyrol PCF for
14 days. Also, rats exposed to TCPP in the diet for 28 days reported increased mortality in females at a
dose of 1,000 mg/kg-day; the NOAEL for this study was identified as 100 mg/kg-day which falls within
the Moderate hazard criteria range. Criteria values are tripled for chemicals evaluated in 28-day studies.
There is uncertainty about where effects may occur given that the identified NOAEL (100 mg/kg-day)
and LOAEL (1,000 mg/kg-day) bridges the Moderate (30 - 300 mg/kg-day) and Low (> 300 mg/kg-day)
hazard designation range; effects occurring within the Moderate range cannot be ruled out.
90-day dietary study in CD Sprague-
Dawley rats (20/sex/group)
administered 0, 800, 2,500, 7,500, or
20,000 ppm Fyrol PCF (average doses
Freudenthal and Henrich,
OECD-SIDS, 2000
1999;
Data are for the Fyrol PCF
mixture (about tris (2-
chloroisopropyl) phosphate (about
70%) and 2-chloropropanol
7-622
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
of 0, 52, 160, 481, and 1,349 mg/kg-
day for males and 0, 62, 171, 570, and
1,352 mg/kg-day for females estimated
by the study authors)
At the high-dose, body weights were
significantly decreased relative to
controls. Significantly increased
absolute and relative liver weights
were observed in all treated males and
in females in the two highest dose
groups. Mild periportal hepatocellular
swelling was noted in some animals at
20,000 ppm; no changes in liver
histopathology were seen at other
doses. Males showed significantly
increased relative kidney weights at >
7,500 ppm; microscopic kidney
changes (very mild cortical tubular
degenerative effects) were observed in
males at 7,500 ppm and at 20,000 ppm
males and females. Increased
incidence of very mild thyroid
follicular changes was noted in the two
highest dose groups. Histopathological
changes occurred in the absence of
significant effects on hematology or
clinical chemistry endpoints (including
those associated with liver and kidney
function).
NOAEL: 2,500 ppm (160 and 171
mg/kg-day for males and females,
respectively)
LOAEL: 7,500 ppm (481 and 570
phosphate (about 23%).
7-623
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
mg/kg-day for males and females,
respectively) based on minimal
morphological changes (kidney,
thyroid)
14-day dietary study in CD-I rats
treated with 0, 4,200, 6,600, 10,600,
and 16,600 ppm (approximately 0,
417, 648, 1,015, 1,636 mg/kg/day for
males and 382, 575, 904, 1,517
mg/kg/day for females)
A significant reduction in body weight
gain and decreased food consumption
was observed in male rats at 10,600
ppm in week 1. There were no effects
on hematology, clinical chemistry, or
cholinesterase activity. Increased liver
weights occurred in the absence of
histopathological changes.
NOAEL: 6,600 ppm (648 mg/kg-day)
LOAEL: 10,600 ppm (1,015 mg/kg-
day) based on decreased body weight
gain and food consumption in males.
Stauffer Chem Co, 1980a (as cited
in EC, 2000; EU, 2008)
Test substance was identified as
Fyrol PCF, a mixture containing
TCPP (-70%) and 2-
chloropropanol phosphate
(-22%); limited study details
reported in a robust summary.
28-day gavage study in Wistar rats
(6/sex/group) dosed daily with 0, 10,
100, or 1,000 mg/kg-day test substance
(97.85% pure).
Increased mortality in high-dose
females. No effect on body weight or
food consumption. Increased water
intake in high-dose groups. No effect
on hematology, clinical chemistry or
urinalysis. Necropsy did not show
Bayer, 1991c (as cited in EC, 2000;
EU, 2008)
Only qualitative data reported in a
secondary source. Study appears
to have examined a
comprehensive number of
endpoints; criteria values are
tripled for chemicals evaluated in
28-day studies; there is
uncertainty about where effects
may occur given that the
identified NOAEL (100 mg/kg-
7-624
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
Skin Sensitization
Skin Sensitization
Respiratory Sensitization
|Respiratory Sensitization
DATA
gross alterations. Histopathology
showed adaptive effects in the liver
from high-dose rats.
NOAEL: 100 mg/kg-day;
LOAEL: 1,000 mg/kg-day (increased
mortality in females).
7-day repeated-dose gavage study in
rats exposed to 1,000 mg/kg-day (other
doses, if any, were not reported).
No effects on body weight gain or
relative organ weights (brain, heart,
lungs, liver, spleen, kidneys, or
adrenals) at doses up to 1,000 mg/kg-
day
NOAEL: 1,000 mg/kg-day
LOAEL: Not established
REFERENCE
Kawasaki et al., 1982 (as cited in
ATSDR, 2012)
DATA QUALITY
day) and LOAEL (1,000 mg/kg-
day) bridges the Moderate (30 -
300 mg/kg-day) and Low (>300
mg/kg-day) hazard designation
range; effects occurring within the
Moderate range cannot be ruled
out.
Limited study details reported in a
secondary source.
LOW: TCPP is not a skin sensitizer.
Human; not sensitizing
Mouse (local lymph node assay); not
sensitizing
Guinea pig; not sensitizing
BASF, 1979 (as cited in EC, 2000)
SafePharm Labs Ltd, 2005 (as cited
in EU, 2008)
SafePharm Labs Ltd, 1979e (as
cited in EC, 2000; EU, 2008)
Limited data available from a
secondary source.
Adequate; guideline and GLP-
compliant. Study details reported
in a secondary source.
Limited data available from a
secondary source. Not performed
according to GLP.
No data located.
No data located.
7-625
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
Eye Irritation
Eye Irritation
Dermal Irritation
Dermal Irritation
DATA
REFERENCE
DATA QUALITY
LOW: TCPP was not irritating to slightly irritating in rabbits.
Rabbit; not irritating
Rabbit; slightly irritating. Transient;
effects typically resolved 24 to 72
hours post-administration.
Extensive experimental data indicate
that TCPP is non-irritant to the rabbit
eye.
Stauffer Chem Co, 1972, 1979;
SafePharm Labs Ltd, 1979c; Bayer,
1991a (as cited in EC, 2000; EU,
2008)
Mobil, 1981d, 1980d; Inveresk Res
Int, 1990b (as cited in EC, 2000;
OECD-SIDS, 2000; EU, 2008)
EU, 2008
Adequate by weight of evidence.
Data from secondary sources.
Study details reported in a
secondary source.
Data are from a secondary source;
primary data sources not
specified.
LOW: Based on weight of evidence from multiple studies. TCPP is not irritating to skin in humans and
rabbits.
Human; not irritating
Rabbit; not irritating
Rabbit; slightly irritating. Transient;
effects typically resolved within 72
hours.
Extensive experimental data indicate
that TCPP in non-irritant to rabbit skin.
BASF, 1979 (as cited in EC, 2000)
Mobil, 198 Ic, 1980c; Stauffer
Chem Co, 1972 (as cited in EC,
2000; EU, 2008)
Stauffer Chem Co, 1979;
SafePharm Labs Ltd, 1979d;
Inveresk Res Int, 1989a (as cited in
EC, 2000; OECD-SIDS, 2000; EU,
2008)
EU, 2008
Study details reported in a
secondary source.
Study details reported in a
secondary source.
Study details reported in a
secondary source.
Study details reported in a
secondary source; primary data
sources not specified.
7-626
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Endocrine Activity
TCPP increased 17B estradiol and testosterone production in H295R cells, up-regulated steroidogenic
genes and down-regulated sulfotransferases. TCPP also inhibited dihydrotestosterone and 17B estradiol
induced expression indicating antiandrogenic or antiestrogenic activity, while TCPP was found to not
induce estrogenic or anti-estrogenic effects in a yeast reporter gene assay and a human endometrial
cancer cell assay.
Two-generation reproduction study in
Wistar rats (28/sex/group)
Doses: 0, 85, 293 and 925 mg
TCPP/kg-day for males and 0, 99, 330
and 988 mg TCPP/kg-day for females
(administered in the diet)
Decreased body weight and food
consumption was observed in mid and
high dose parental animals and the
effects on uterus weights seen in all
dosed FO animals.
In females, the length of the longest
oestrus cycle and the mean number of
cycles per animal were statistically
significantly increased in high dose
animals of both generations. A
decrease in uterus weight was
observed in all dosed females in FO
and in high dose females in F1.
TCPP significantly increased 17B-
estradiol (at 100 mg/L) and
testosterone production (at >1 mg/L) in
H295R cells. The transcription of other
steroidogenic genes (CYP11A1,
CYP112B, HSD3B2) were up-
regulated and sulfotransferases
(SULT1E1, SULT2A1) were down-
TNO, 2007 (as cited in EU, 2008)
Adequate; guideline (OECD 416)
and GLP-compliant study. Data
obtained from a secondary source
only; primary source not
specified; the observed changes
may be an indication of endocrine
activity.
Liu etal., 2012
Test substance purity was not
reported.
7-627
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
regulated in response to treatment with
TCPP.
TCPP inhibited expression induced by
dihydrotestosterone (IC50 = 1.8 x 10"
4M) and 17B-estradiol (IC50 = 2.3 x
10"4M); indicating that TCPP may
have antiandrogenic and/or
antiestrogenic activities.
Ohyamaetal., 2006
Study details from the primary
report are available; however,
only the study summary and
figure legends are reported in
English.
TCPP did not induce estrogenic or
anti-estrogenic effects at up to 10
as based on results of the recombinant
yeast reporter gene assay and Ishikawa
(human endometrial cancer) cell assay.
Follmann and Wober, 2006
Adequate.
7-day repeated-dose gavage study in
rats exposed to 1,000 mg/kg-day (other
doses, if any, were not reported). No
effects on adrenals weights at doses up
to 1,000 mg/kg-day
Kawasaki et al., 1982 (as cited in
ATSDR, 2012)
Limited study details reported in a
secondary source.
90-day dietary study in CD Sprague-
Dawley rats (20/sex/group)
administered 0, 800, 2,500, 7,500, or
20,000 ppm Fyrol PCF (average doses
of 0, 52, 160, 481, and 1,349 mg/kg-
day for males and 0, 62, 171, 570, and
1,352 mg/kg-day for females estimated
by the study authors)
Increased incidence of very mild
thyroid follicular changes was noted in
the two highest dose groups.
Histopathological changes occurred in
the absence of significant effects on
hematology or clinical chemistry
endpoints (including those associated
Freudenthal and Henrich, 1999 (as
cited in OECD-SIDS, 2000)
Data are for the Fyrol PCF
mixture (about tris (2-
chloroisopropyl) phosphate (about
70%) and 2-chloropropanol
phosphate (about 23%); the
observed changes may be an
indication of endocrine activity.
7-628
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
with liver and kidney function).
Two-generation reproduction study in
Wistar rats (28/sex/group) Doses: 0,
85, 293 and 925 mg TCPP/kg-day for
males and 0, 99, 330 and 988 mg
TCPP/kg-day for females
(administered in the diet)
No difference in anogenital distance of
the male or female F2 pups was
observed between the treated and
control animals. Vaginal opening was
delayed (not significantly) in the high
dose group. Preputial separation was
statistically significantly delayed in the
high dose group. The body weight of
the high dose male and females of the
F2 generation was significantly
decreased from PND28 until PND42
(91% and 89% of control at PND42 for
females and males of this group,
respectively). The effects observed in
this dose group on vaginal opening and
preputial separation is most likely
secondary to toxicity. At necropsy of
the pups there were no treatment
related macroscopic findings.
NOAEL: Not established
LOAEL: 99 mg/kg-day based on
treatment related effect on the number
of runts in FO generation (lowest dose
tested).
TNO, 2007 (as cited in EU, 2008)
Data reported in a secondary
source. Adequate; guideline
(OECD 416) and GLP-compliant
study. Data obtained from a
secondary source.
7-629
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
Immunotoxicity
Immune System Effects
DATA
REFERENCE
DATA QUALITY
No data located.
No data located.
ECOTOXICITY
ECOSAR Class
Acute Aquatic Toxicity
Fish LC50
MODERATE: Based on experimental LC50 and EC50 values for fish, daphnia, and algae.
Poecilia reticulata 96 hour LC50 = 30
mg/L
(static test conditions)
(Experimental)
Pimephales promelas 96 hour LC50 =
51 mg/L
(static test conditions)
(Experimental)
Killifish (Oryzias latipes) 48-hour
LC50 = 54 mg/L
(Experimental)
Brachydanio rerio 96 hour LC50 =
56.2 mg/L
LC0 = 31.6mg/L;
Griebenow, 1998 (as cited in EC,
2000; EU, 2008)
Meeks, 1985c (as cited in EC, 2000;
OECD-SIDS, 2000; EU, 2008)
MITI, 1992 (as cited in EC, 2000;
EU, 2008)
Kanne, 1991 (as cited in EC, 2000;
EU, 2008)
The test substance was identified
as technical grade TCPP; specific
purity was not reported.
Guideline-like study (OECD
203); however analytical
monitoring was reportedly not
performed.
LC50 based on linear regression
from 168 hours exposure and
actual test concentrations.
Differences in nominal and actual
test concentrations were attributed
to limited water solubility of the
test substance. Analytical
monitoring was performed and
study was conducted according to
guideline (OECD 203) and GLP.
Not standard duration for acute
toxicity to fish; no additional
details were available. Reported
method: Japanese Industrial
Standard (JIS K0102-1986-71)
Testing Methods for Industrial
Waste Water.
Analytical monitoring was
performed; study was conducted
according to GLP. The test
7-630
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
LC10o = 100mg/L
(static test conditions)
(Experimental)
substance was 97.9% pure
including all isomers.
Lepomis macrochirus 96 hour LC50
84 mg/L;
NOEC = 9.8 mg/L
(static test conditions)
(Experimental)
Meeks, 1985b (as cited in EC, 2000:
OECD-SIDS, 2000; EU, 2008)
Wild-type Zebrafish embryos (20 per
replicate) exposed to TCPP under
static conditions at 0.05 to 50 (iM until
96 hours post-fertilization (24 hours
post-hatch).
No effects on mortality, gross
developmental malformations, delayed
hatching, or obvious signs of impaired
locomotion
NOEC = 50 nM
(Experimental)
McGeeetal., 2012
Freshwater Fish 96-hour LC50 = 13.3
mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
LC50 based on linear regression
from 120 hours exposure and
actual test concentrations.
Differences in nominal and actual
test concentrations were attributed
to limited water solubility of the
test substance. Analytical
monitoring was performed and
study was conducted according
guideline (OECD 203) and GLP.
Adequate details were provided;
purity of the test substance was
only 96%.
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
7-631
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
Daphnid LC50
Green Algae EC50
DATA
Daphnia magna EC50 = 131 (65-335)
mg/L
48-hour NOEC = 33.5 mg/L
(Experimental)
Daphnia magna 48-hour EC50 = 63
mg/L
(Experimental)
Daphnia 48-hour LC50 = 25. Img/L
(Estimated)
ECOSAR: Esters
Selenastntm capricornutum 96 hour
EC50 (biomass) = 47 (95% CI: 41-50)
mg/L
EC50 (growth rate) = 73 (95% CI: 57-
97) mg/L
NOEC = 6 mg/L
LOEC=18mg/L
(Experimental)
Scenedesmus subspicatus 72 hour
EC50 (biomass) = 45 mg/L
(Experimental)
Pseudokirchneriella subcapitata 72-
hour EC50 (growth rate) = 82 mg/L;
REFERENCE
Meeks, 1985a (as cited in EC, 2000;
OECD-SIDS, 2000; EU, 2008)
Griebenow, 1998 (as cited in EC,
2000; EU, 2008)
ECOSAR v 1.11
Kroon and van Ginkel, 1992 (as
cited in EC, 2000; OECD-SIDS,
2000; EU, 2008)
Griebenow, 1998 (as cited in EC,
2000; EU, 2008)
Dejardins, 2004 (as cited in EC,
2000; EU, 2008)
DATA QUALITY
Study was conducted according to
guideline (OECD 202) and GLP;
analytical monitoring was
performed. The 48 hour EC50 is
based on actual test
concentrations. Differences in
nominal and actual concentrations
were attributed to limited water
solubility of the test substance.
Not a guideline study; study not
conducted according to GLP.
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
Guideline (OECD 201) and GLP-
compliant. Value appears to be
based on nominal test
concentrations.
Study details reported in a
secondary source; not a guideline
study and not conducted
according to GLP. No additional
data were available.
Guideline study (OECD 201) and
GLP -compliant. Study details
7-632
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
NOEC = 13 mg/L
(Experimental)
reported in a secondary source;
primary source not specified
(identified as a review article).
Green algae 96-hour EC50 = 9.3 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
Chronic Aquatic Toxicity
MODERATE: Based on experimental aquatic toxicity values for algae and estimated ChV values in fish,
daphnia, and algae. An estimated chronic aquatic toxicity value derived using an acute-to-chronic ratio
(ACR) for the phosphate esters class and was applied to the available experimental acute data for this
chemical and indicated a Moderate hazard. An experimental NOEC for Daphnia magna indicated a Low
hazard designation for mortality and reproduction, while estimated ChV values (Esters class) range
from Low to High hazard range. There were no experimental chronic aquatic toxicity data located for
fish. There is potential concern based on estimates and the uncertainty due to the lack of experimental
data; therefore a Moderate hazard designation was assigned.
Fish ChV
Freshwater fish ChV = 1.25 mg/L
(Estimated)
Freshwater fish ChV = 0.83 mg/L
(Estimated)
ECOSAR: Esters
Professional judgment
ECOSARvl.ll
An ACR of 24 was derived for the
phosphate ester class based on
experimental data for Tris (p-t-
butylphenyl) phosphate (TBPP).
The acute-to-chronic ratio was
applied to available experimental
acute fish data for Tris (2-chloro-
l-methylethyl) phosphate (ChV =
30 mg/L (96-hr fish LC50) /24=
1.25 mg/L)
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
7-633
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Daphnid ChV
Daphnia magna (4 replicates of 10
daphnia per concentration) were
exposed to 10, 18, 32, 56 and 100
mg/L of the test material for a period
of 21 days. All animals at 56 mg/L
died within 12 days.
21-day NOEC (mortality and
reproduction) = 32 mg/L
(Experimental)
Sewell et al., 1995 (as cited in
OECD-SIDS, 2000; EU, 2008)
Adequate; guideline (OECD 211)
and GLP study. Data are from a
secondary source; primary source
was not specified (from a review
article).
Daphnia magna ChV > 10 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
Selenastntm capricornutum 96 hour
NOEC = 6 mg/L
LOEC= 18 mg/L
(Experimental)
Green Algae ChV
Kroon and van Ginkel, 1992 (as
cited in EC, 2000; OECD-SIDS,
2000; EU, 2008)
Guideline (OECD 201) and GLP-
compliant. Value appears to be
based on nominal test
concentrations.
Pseudokirchneriella subcapitata 72-
hour NOEC = 13 mg/L
(Experimental)
Dejardins, 2004 (as cited in EC,
2000; EU, 2008)
Guideline study (OECD 201) and
GLP-compliant. Study details
reported in a secondary source;
primary source not specified
(identified as a review article).
Green algae ChV = 3.18 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
7-634
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
ENVIRONMENTAL FATE
Transport
Henry's Law Constant (atm-
m3/mole)
Sediment/Soil
Adsorption/Desorption - Koc
Level III Fugacity Model
Persistence
Water
Aerobic Biodegradation
Level III fugacity models incorporating available physical and chemical property data indicate that at
steady state, TCPP is expected to be found primarily in soil and to a lesser extent, water. TCPP is
expected to have moderate mobility in the soil, based on its measured Koc. TCPP will not volatilize from
moist soil and water surfaces based on its Henry's Law constant. Volatilization from dry surfaces is not
expected based on its vapor pressure. TCPP will exist almost entirely in the vapor phase in the
atmosphere.
6x1 0~8 (Measured)
162 (Measured)
Air = 0.1%
Water = 12.4%
Soil = 86.1%
Sediment = 1 .4% (Estimated)
van der Veen and de Boer, 2012
van der Veen and de Boer, 2012
EPIv4.11
Reported in a peer reviewed
source.
Reported in a peer reviewed
source.
HIGH: Based on measured persistence data. TCPP had 14% biodegradation after 28 days according to
OECD 301E, although in the modified MITI test, OECD 301C, 0% biodegradation was found after 28
days using an activated sludge inoculum. TCPP achieved 21% degradation after 28 days in an inherent
modified MITI test, OECD 302C. These data suggest a half-life greater than 60 days. TCPP is not
expected to be susceptible to direct photolysis by sunlight. The atmospheric half-life of vapor-phase
TCPP is estimated to be 2.9 hours, however it is not expected to partition greatly to the atmosphere.
Passes Ready Test: No
Test method: OECD TG 30 IE:
Modified OECD Screening Test
Reported as 14% after 28 days. 97.9%
pure (Measured)
Passes Ready Test: No
Test method: OECD TG 301C:
Modified MITI Test (I)
Reported as 0% after 28 days.
OECD-SIDS, 2000
OECD-SIDS, 2000
OECD Guideline study.
OECD Guideline study.
7-635
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
Soil
Air
Reactivity
Volatilization Half-life for
Model River
Volatilization Half-life for
Model Lake
Aerobic Biodegradation
Anaerobic Biodegradation
Soil Biodegradation with
Product Identification
Sediment/Water
Biodegradation
Atmospheric Half-life
Photolysis
Hydrolysis
DATA
(Measured)
Study results: 21%/28d
Test method: 302C: Inherent -
Modified MITI Test (II)
(Measured)
>1 year (Estimated)
>1 year (Estimated)
Study results: 0%/80d
Test method: Field Test
No decrease in concentration after 80
days using a landfill leachate inoculum
under aerobic conditions. (Measured)
0.239 days
Based on a 12 hour day (Estimated)
Not a significant fate process.
(Estimated)
Hydrolyzes slowly under alkaline or
REFERENCE
WHO, 1998
EPIv4.11
EPIv4.11
ATSDR, 2012
EPIv4.11
Professional judgment
WHO, 1998
DATA QUALITY
Reported in a peer reviewed
source.
Reported in peer reviewed
secondary source.
No data located; chlorinated alkyl
phosphates are outside the domain
of the available estimation
methods.
No data located.
No data located.
The substance does not contain
functional groups that would be
expected to absorb light at
environmentally significant
wavelengths.
Reported in peer reviewed
7-636
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
Environmental Half-life
Bioaccumulation
Fish BCF
Other BCF
DATA
acidic conditions. (Measured)
50%/llyatpH7
Additional half-life estimates:
11 years atpH 5;
1 1 years at pH 6;
11 years atpH 8;
10 years atpH 9;
5 years at pH 10 (Estimated)
120 days (Estimated)
REFERENCE
EPIv4.11
PBT Profiler
DATA QUALITY
secondary source.
Half-life estimated for the
predominant compartment (soil),
as determined by EPI
methodology.
LOW: Multiple experimental BCF values are below 100, the Low bioaccumulation designation criteria.
Toxicokinetic studies indicate that TCPP and metabolites are rapidly formed and eliminated, consistent
with the estimated BAF. Biomonitoring studies report detection of this compound in human milk
samples and herring gull eggs, demonstrating that these materials are likely bioavailable and could be
observed in a biological matrix. However, the rate of metabolism and elimination may be successfully
competing with that of uptake, which is also consistent with the experimental BCF results. The
biomonitoring studies are not inconsistent with a Low designation
4.6 Reported as < 1.9-4.6 in carp
(Measured)
2.8 Reported as -0.8-2.8 in carp
(Measured)
8.51 (Measured)
Root concentration factors: <1 for
barley, carrots
Leaf concentration factors: 26 for
barley; 3.9 for meadow fescue and 42
for carrot napoli
EC, 2000
EC, 2000
van der Veen and de Boer, 2012
Eggen et al., 2012, 2013; Trapp and
Eggen, 2013
Consistent with other reported
measured values.
Consistent with other reported
measured values.
Reported in a peer reviewed
source.
Nonguideline study indicating
that plant uptake and translocation
is possible for this compound.
7-637
-------
Tris (2-chloro-l-methylethyl) phosphate CASRN 13674-84-5
PROPERTY/ENDPOINT
BAF
Metabolism in Fish
DATA
Seed concentration factors: <0.01 for
barley and rape (Measured)
12.8 (Estimated)
REFERENCE
EPIv4.11
DATA QUALITY
No data located.
ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring
Ecological Biomonitoring
Human Biomonitoring
TCPP has been detected in drinking water, groundwater, surface water (coastal and marine); rain and snow
samples; sediment, household dust, indoor air, ambient air and airborne particles over the oceans near the polar
region (Staaf and Ostman, 2005; Regnery and Puttmann, 2009; Saito et al., 2009; Takigami et al., 2009;
Regnery et al., 201 1; Bollmann et al., 2012; Cao et al., 2012; Moller et al., 2012; Rodil et al., 2012; Salamova
etal., 2014).
TCPP was also detected in herring gull eggs collected at Lake Huron (Chen et al., 2012).
TCPP has been detected in human pooled milk collected from Swedish women after delivery of their first
babies in 1997-2006 at 22-82 ng/g lipid. TCPP was not included in the NHANES biomonitoring report (CDC,
2009; HSDB, 2013).
7-638
-------
Abe A and Urano K (1994) Influence of chemicals commonly found in a water environment on the Salmonella mutagenicity test. Science of the
Total Environment 153:169-175.
ATSDR (2012) Toxicological profile for phosphate ester flame retardants. Atlanta, GA: Agency for Toxic Substances and Disease Registry.
BASF (1979) BASF AG, Abteilung Toxikologie, unveroefferentlichte Untersuchung.
BASF Aktiengesellschaft (2007) 14C-TCPP, TCEP and TDCP study on the in vitro metabolism in rats, (Unpublished report).
Bayer (199la) Study for skin and eye irritation/corrosion in rabbits. (Unpublished report).
Bayer (1991b) Tris-chlorisopropyl phosphate: Mutagenicity test on unscheduled DNA synthesis in rat liver primary cell cultures in vitro
(Unpublished report).
Bayer (1991c) [28-d study].
Bollmann UE, Moller A, Xie Z, et al. (2012) Occurrence and fate of organophosphorus flame retardants and plasticizers in coastal and marine
surface waters. Water Research 46(2):531-538.
CDC (2009) Fourth national report on human exposure to environmental chemicals. Atlanta, GA: Centers for Disease Control and
Prevention, http://www.cdc.gov/exposurereport/pdf/FourthReport.pdf.
Cao S, Zeng X, Song H, et al. (2012) Levels and distributions of organophosphate flame retardants and plasticizers in sediment from Taihu Lake,
China. Environ Toxicol Chem 31(7): 1478-1484.
Chen D, Letcher RJ, Chu S (2012) Determination of non-halogenated, chlorinated and brominated organophosphate flame retardants in herring
gull eggs based on liquid chromatography-tandem quadrupole mass spectrometry. Journal of Chromatography A 1220:169-174.
Covance Labs (2005) Tris (2-chloro-l-methylethyl) phosphate: Mutation at the Thymidine Kinase (tk) Locus of Mouse LymphomaL5178Y Cells
(MLA) using the MitrotitreO Fluctuation Technique (Unpublished report). Covance Laboratories Ltd.
Covance Labs (2006) Detection of DNA damage in the liver of treated rats using the Comet assay (Unpublished report). Covance Laboratories
Ltd.
7-639
-------
Dejardins D (2004) TCPP: A 72-hour toxicity test with the freshwater alga Pseudokirchneriella subcapitata. Project No: 583A-101. Wildlife
International Limited.
Dishaw LV, Powers CM, Ryde IT, et al. (2011) Is the PentaBDE replacement, tris (l,3-dichloro-2-propyl) phosphate (TDCPP), a developmental
neurotoxicant? Studies in PC12 cells. Toxicol Appl Pharmacol 256(3):281-289.
EC (2000) IUCLID dataset-tris(2-chloro-l-methylethyl) phosphate.
ECHA (2013) Tris(2-chloro-l-methylethyl) phosphate. Registered substances. European Chemicals
Agency. http://apps.echa.europa.eu/registered/data/dossiers/DISS-9ea6alc2-62db-49d4-e044-00144f67d031/AGGR-a6514290-db57-4d2e-91ce-
6c884332f676 DISS-9ea6alc2-62db-49d4-e044-00144f67d031.html#AGGR-a6514290-db57-4d2e-91ce-6c884332f676.
ECOSAR (Ecological Structure Activity Relationship), Version 1.11. Washington, DC: U.S. Environmental Protection
Agency, http://www.epa.gov/oppt/newchems/tools/21 ecosar.htm.
EPA (2012) Using noncancer screening within the SF initiative. Washington, DC: U.S. Environmental Protection
Agency, http://www.epa.gov/oppt/sf/pubs/noncan-screen.htm.
EPI Estimation Programs Interface (EPI) Suite, Version 4.11. Washington, DC: U.S. Environmental Protection
Agency, http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm.
ESIS (2012) European chemical Substances Information System. European Commission, http://esis.jrc.ec.europa.eu/.
EU (2008) European Union risk assessment report for Tris(2-chloro-l-methylethyl) phosphate
(TCPP). http://esis.jrc.ec.europa.eu/doc/risk assessment/REPORT/tcppreport425.pdf
Eggen T, Heimstad ES, Stuanes AO, et al. (2012) Uptake and translocation of organophosphates and other emerging contaminants in food and
forage crops. Environmental Science and Pollution Research International epub.
Eggen T, Heimstad ES, Stuanes AO, et al. (2013) Uptake and translocation of organophosphates and other emerging contaminants in food and
forage crops. Environmental Science and Pollution Research International 20(7):4520-4531.
Env Affairs (198 la) Four hour acute inhalation toxicity study in Sprague-Dawley rats with 2425-80 (Unpublished report). Environmental Affairs
and Toxicology Department.
7-640
-------
Env Affairs (1981b) Acute inhalation toxicity study of tri(2-chloropropyl) phosphate (Unpublished report). Environmental Affairs and Toxicology
Department.
Env Affairs (1981c) Amurine lymphoma mutagenesis assay, heterozygous at the thymidine kinase locus for the determination of the potential
mutagenicity of Antiblaze 80 (Unpublished report). Environmental Affairs and Toxicology Department.
Follmann W and Wober J (2006) Investigation of cytotoxic, genotoxic, mutagenic, and estrogenic effects of the flame retardants tris-(2-
chloroethyl)-phosphate (TCEP) andtris-(2-chloropropyl)-phosphate (TCPP) in vitro. Toxicol Lett 161(2): 124-134.
Freudenthal RI, Henrich RT (1999) A subchronic toxicity study of Fyrol PCF in Sprague-Dawley rats. International Journal of Toxicology
18(3):173-176.
Griebenow (1998) Okotoxikologische Bewertung (Fischtest, Daphnientest, Algentest, Leuchtbakerientest). Report Number: 19/01/98. BASF
Schwarzheide GmbH, Schwarzheide.
HSDB (2013) Tri-(2-chloroisopropyl) phosphate. Hazardous Substances Data Bank. National Library of Medicine, http://toxnet.nlm.nih.gov/cgi-
bin/sis/htmlgen?HSDB.
Huntingdon (1997a) Amgard TMCP 2 Acute oral toxicity to the rat (Unpublished report). Huntingdon Life Sciences Ltd.
Huntingdon (1997b) Amgard TMCP 1 Acute oral toxicity to the rat (Unpublished report). Huntingdon Life Sciences Ltd.
Inveresk Res Int (1989a) Tolgard TMCP: Acute dermal irritation test in rabbits (Unpublished report). Inveresk Research International.
Inveresk Res Int (1989b) Tolgard TMCP: Acute dermal toxicity (LD50) test in rats (Unpublished report). Inveresk Research International.
Inveresk Res Int (1990a) Amgard TMCP: Acute inhalation toxicity study in rats (Unpublished report). Inveresk Research International.
Inveresk Res Int (1990b) Tolgard TMCP: Acute eye irritation test in rabbits (Unpublished report). Inveresk Research International.
Kanne (1991) Akute Fischtoxizitat von: Tris-chloroisopropylphosphat. Report Number: 202A/90 F. Bayer AG, Institut fur Umweltanalyse,
Leverkusen.
Kawasaki H and et al (1982) Studies on the toxicity of insecticides and food additives in pregnant rats - foetal toxicity of Tris-(chloropropyl)
phosphate. Oyo Yakuri 24(5):697-702.
7-641
-------
Kroon AGM, van Ginkel CG (1992) Toxicity of Fyrol PCF to the freshwater alga Selenastrum capricornutum. Arnhem, The Netherlands: Akzo
Research Laboratories.
Litton Bionetics (1977) Health and safety data for 4 chemicals with cover letter dated 021089 (sanitized). Litton Bionetics, Inc. Submitted to the
U.S. Environmental Protection Agency under TSCA Section 8D.
Liu X, Ji K, Choi K (2012) Endocrine disruption potentials of organophosphate flame retardants and related mechanisms in H295R and MVLN
cell lines and in zebrafish. Aquatic toxicology (Amsterdam, Netherlands) 114-115:173-181.
MITI (1992) Ministry of International Trade & Industry, eds. Biodegradation and Bioaccumulation Data on Existing Chemicals based on the
CSCL in Japan. Compiled under the supervision of Chemical Products Safety Division, Basic Industries Bureau MITI. Tokyo: Japan Chemical
Industry Ecology-Toxicology & Information Center.
McGee SP, Cooper EM, Stapleton HM, et al. (2012) Early zebrafish embryogenesis is susceptible to developmental TDCPP exposure. Environ
Health Perspect 120(11):1585-1591.
Meeks JR (1985a) Static 48-hour acute toxicity of Antiblaze 80 to Daphnia magna. Report of test number: 50591. Mobil Environmental Health
Science Laboratory.
Meeks JR (1985b) Static 96-hour acute toxicity of Antiblaze 80 to Bluegill Sunfish. Report of test number: 50592. Mobil Environmental Health
Science Laboratory.
Meeks JR (1985c) Static 96-hour acute toxicity of Antiblaze 80 to Fathead Minnows. Report of test number: 50593. Mobil Environmental Health
Science Laboratory.
Minegishi K, Kurebayashi H, Nambaru S, et al. (1988) Comparative studies on absorption, distribution, and excretion of halogenated alkyl
phosphate flame retardants in rats. Eisei Kagaku 34(2): 102-114.
Mobil (1980a) Oral LD50 of Tris (2-Chloropropyl) Phosphate in Sprague-Dawley rats after a single administration. (Unpublished report). Mobil
Environmental and Health Science Laboratory.
Mobil (198 la) The acute oral toxicity of Tris(2-chloropropyl) phosphate "Antiblaze 80" in albino rabbits (Unpublished report). Mobil
Environmental and Health Science Laboratory.
7-642
-------
Mobil (1981b) The acute dermal toxicity of Tris (2-chloropropyl) phosphate "Antiblaze 80" in albino rabbits (Unpublished report). Mobil
Environmental and Health Science Laboratory.
Mobil (1980b) Dermal toxicity of Tris (2-chloropropyl) phosphate, lot PP-2B, in albino rabbits after a single exposure (Unpublished report). Mobil
Environmental and Health Science Laboratory.
Mobil (1980c) Skin irritation of Tris (2-chloropropyl) phosphate, lot PP-2B, in albino rabbits after a single exposure (revised) (Unpublished
report). Mobil Environmental and Health Science Laboratory.
Mobil (1981c) Primary skin irritation of Tris(2-chloropropyl) phosphate "Antiblaze 80" after a single application to albino rabbits (Unpublished
report). Mobil Environmental and Health Science Laboratory.
Mobil (1981d) Primary eye irritation of Tris(2-chloropropyl) phosphate "Antiblaze 80" in albino rabbits (Unpublished report). Mobil
Environmental and Health Science Laboratory.
Mobil (1980d) Eye irritation of Tris (2-chloropropyl) phosphate, lot PP-2B, in albino rabbits after a single exposure (revised) (Unpublished
report). Mobil Environmental and Health Science Laboratory.
Moller A, Sturm R, Xie Z, et al. (2012) Organophosphorus flame retardants and plasticizers in airborne particles over the Northern Pacific and
Indian Ocean toward the polar regions: Evidence for global occurrence. Environ Sci Technol 46:3127-3134.
NAS (2000) In: National Academy of Sciences, eds. Toxicological risks of selected flame-retardant chemicals. Washington, DC: The National
Academies Press, http://www.nap.edu/catalog.php7record id=9841.
NICNAS (2001) Trisphosphates. NICNAS: Priority existing chemical assessment report 17(2001)
NTP (2013) National Toxicology Program Database search application CASRN13674-84-
5. http://tools.niehs.nih.gov/ntp tox/index.cfm?fuseaction=ntpsearch.showStudiesForChemical&casno=13674-84-5.
OECD-SIDS (2000) Tris(l-chloro-2-propyl)phosphate. CAS No: 13674-84-5. Screening Information Data Set.46 Organisation for Economic Co-
operation and Development, http://www.inchem.org/documents/sids/sids/ 13674845.pdf
Ohyama K, Nagata S, Hosogoe N, et al. (2006) Hormonal effects of organic phosphate triesters study by the reporter gene assay. Tokyo-to Kenko
Anzen Kenkyu Senta Kenkyu Nenpo 56:333-338.
7-643
-------
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.
Regnery J and Puttmann W (2009) Organophosphorus flame retardants and plasticizers in rain and snow from middle Germany. Clean: Soil, Air,
Water 37(4-5):334-342.
Regnery J, Puttmann W, Merz C, et al. (2011) Occurrence and distribution of Organophosphorus flame retardants and plasticizers in
anthropogenically affected groundwater. J Environ Monitl3(2):347-354.
Rodil R, Quintana JB, Concha-Grana E, et al. (2012) Emerging pollutants in sewage, surface and drinking water in Galicia (NW Spain).
Chemosphere 86(10): 1040-1049.
SafePharm Labs Ltd (1979a) Determination of the acute oral median lethal dose (LD50) of Tris mono chloropropyl phosphate (Unpublished
report). Safepharm Laboratories Ltd.
SafePharm Labs Ltd (1979b) Determination of the acute oral median lethal dose (LD50) of Tris mono chloropropyl phosphate (Unpublished
report).
SafePharm Labs Ltd (1979c) Determination of the degree of ocular irritation caused by Tris Mono Chloropropyl Phosphate (Unpublished report).
SafePharm Labs Ltd (1979d) Determination of the degree of primary cutaneous irritation caused by Tris Mono Chloropropyl Phosphate
(Unpublished report).
SafePharm Labs Ltd (1979e) Determination of the contact sensitisation potential of Tris Mono Chloropropyl Phosphate (Unpublished report).
SafePharm Labs Ltd (1994) Amgard TMCP: Acute oral toxicity test in the rat (Unpublished report).
SafePharm Labs Ltd (1996a) Amgard TMCP: Acute oral toxicity test in the rat (Unpublished).
SafePharm Labs Ltd (1996b) Amgard TMCP: Acute oral toxicity test in the rat (Unpublished).
SafePharm Labs Ltd (1997a) Amgard TMCP: Acute oral toxicity test in the rat (Unpublished report).
SafePharm Labs Ltd (1997b) TCPP Acute oral toxicity test in the rat (Unpublished report).
7-644
-------
SafePharm Labs Ltd (2005) TCPP: Local Lymph Node Assay in the Mouse (Unpublished report).
Saito I, Onuki A, Yaguchi K, et al. (2009) Summary of indoor air pollution by plasticizers, flame retardants, and pesticides followed by an
estimation of inhalation exposure in Tokyo. Tokyo-to Kenko Anzen Kenkyu Senta Kenkyu Nenpo 59:27-38.
Salamova A, Ma Y, Venier M, et al. (2014) High levels of organophosphate flame retardants in the Great Lakes atmosphere. Environ Sci Technol
Sewell IG, Foulger J, Bartlett AJ (1995) Daphnia magna reproduction test. Report of SPL Project Number: 071/386. SafePharm Laboratories Ltd.,
Derby.
Sprague GL, Sandvik LL, Brookins-Hendricks MJ, et al. (1981) Neurotoxicity of two organophosphorus ester flame retardants in hens. Journal of
Toxicology and Environmental Health 8(3):507-518.
Staaf T, Ostman C (2005) Organophosphate triesters in indoor environments. J Environ Monit 7(9):883-887.
Stauffer Chemical Co (1970) Acute toxicity of Fyrol PCF (Unpublished report). Stauffer Chemical Company.
Stauffer Chemical Co (1972) Acute toxicity of Fyrol PCF (Unpublished report). Stauffer Chemical Company.
Stauffer Chemical Co (1976) Mutagenicity evaluation of Fyrol PCF (Unpublished report). Stauffer Chemical Company.
Stauffer Chemical Co (1978a) Evaluation of Fyrol PCF in the unscheduled DNA synthesis in human WI-38 cells assay (Unpublished report).
Stauffer Chemical Company.
Stauffer Chemical Co (1978b) Mutagenicity evaluation of Fyrol PCF in the rat bone marrow cytogenetic analysis (Unpublished report). Stauffer
Chemical Company.
Stauffer Chemical Co (1978c) Mutagenicity evaluation of Fyrol PCF in the mouse lymphoma forward mutation assay (Unpublished report).
Stauffer Chemical Company.
Stauffer Chemical Co (1978d) Mutagenicity evaluation of Fyrol PCF in the Ames Salmonella/microsome plate tests (Unpublished report). Stauffer
Chemical Company.
7-645
-------
Stauffer Chemical Co (1978e) Mutagenicity evaluation of Fyrol PCF in the in vitro transformation of BALB/3T3 cells assay (Unpublished report).
Stauffer Chemical Company.
Stauffer Chemical Co (1979) Acute toxicity of Fyrol PCF (Unpublished report). Stauffer Chemical Company.
Stauffer Chemical Co (1980a) Fyrol PCF: A Two-week dietary acute toxicity range finding study in male and female Charles River Sprague-
Dawley derived rats (Unpublished report). Stauffer Chemical Company.
Stauffer Chemical Co (1980b) Morphological transformation of BALB/3T3 cells (Unpublished report). Stauffer Chemical Company.
Stauffer Chemical Co (1984) Fyrol PCF metabolism/pharmacokinetic study in rats (Unpublished report). Stauffer Chemical Company.
Stropp G (1996) Tris(2-chloroisopropyl)phosphat- acute oral toxicity study in male and female Wistar rats, with TSCA HLTH & SFTY study
CVR LTR dated 8/23/96. Bayer AG. Submitted to the U.S. Environmental Protection Agency under TSCA Section 8D.
TNO Quality of Life (2005) In vitro percutaneous absorption of [14C]tris(2-chloro-l-methylethyl)phosphate (TCPP) through human skin
membranes using flow-through diffusion cells (Unpublished report).
TNO Quality of Life (2006) In vitro percutaneous absorption of neat [14C]TCPP (Tris(2-chloro-l-methylethyl)phosphate) through human skin
membranes using flow-through diffusion cells (Unpublished report).
TNO Quality of Life (2007) Oral two-generation reproduction toxicity study (including a dose range finding study) with Tris(2-chloro-l-
methylethyl)-phosphate in rats (Unpublished report).
Takigami H, Suzuki G, Hirai Y, et al. (2009) Flame retardants in indoor dust and air of a hotel in Japan. Environ Int 35(4):688-693.
Tenneco Chemical Inc (1977) Activity of TCPP in a test for differential inhibition of repair deficient and repair competent strains of Escherichia
coli: Repair test (Unpublished report).
Trapp S, Eggen T (2013) Simulation of the plant uptake of organophosphates and other emerging pollutants for greenhouse experiments and field
conditions. Environmental Science and Pollution Research International 20(6):4018-4029.
Van den Eede N, Maho W, Neels H, et al. (2013) Metabolism of phosphate flame retardants and plasticisers using human liver fractions. Sixth
International Symposium on Flame Retardants, San Francisco, CA, April 7-10, 2013
7-646
-------
van der Veen I, de Boer J (2012) Phosphorus flame retardants: Properties, production, environmental occurrence, toxicity and analysis.
Chemosphere 88(10): 1119-1153.
WHO (1998) International Programme on Chemical Safety (IPCS), Environmental Health Criteria 209, Flame retardants:
tris(chloropropyl)phosphate and tris(2-chloroethyl)phosphate. Geneva: International Programme on Chemical Safety, World Health
Organisation. http://whqlibdoc.who.int/ehc/WHO_EHC_209.pdf
Williams GM, Mori H, McQueen CA (1989) Structure-activity relationships in the rat hepatocyte DNA-repair test for 300 chemicals. Mutat Res
221:263-286.
Zeiger E, Anderson B, Haworth S, et al. (1992) Salmonella mutagenicity tests: V. Results from the testing of 311 chemicals. Environ Mol
Mutagen 21:2-141.
7-647
-------
Tris (2-chloroethyl) phosphate (TCEP)
Screening Level Toxicology Hazard Summary
This table contains hazard information for each chemical; evaluation of risk considers both hazard and exposure. Variations in end-of-life processes or degradation and combustion
by-products are discussed in the report but not addressed directly in the hazard profiles. The caveats listed below must be taken into account when interpreting the information in the
table.
VL = Very Low hazard L = Low hazard = Moderate hazard H = High hazard VH = Very High hazard - Endpoints in colored text (VL, L, M, H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].
Chemical
CASRN
Human Health Effects
y
0
^H
QJ
|
•^
:!
o
t>
M
0
a
'5
sS
U
.
_u
0
V
O
0)
U
^^
4j
3
"a
§
a.
^
0)
P
53
'So
_o
0
•_
3
z
o
Q
4)
sS
4)
iJ
a
_o
.a
^
rt
S
C/5
_a
C/5
a
o '•§
SS N
•- S
^ s
a
-2
•c
hH
^s
S-
O
1
'C
hH
••
C^
4)
P
Aquatic
Toxicity
o
3
_u
'a
B
u
Environmental
Fate
o
a
"S
1
PH
_0
«
a
s
u
sS
o
M
Tris (2-chloroethyl) phosphate
(TCEP)
115-96-8
H
H
L
L
L
H
"
L
7-648
-------
Cl
o1!
Cl -^X^A" y^CI
- o ^0_/
CASRN: 115-96-8
MW: 285.49
MF: C6H12C13O4P
Physical Forms: Liquid
Neat: Liquid
Use: Flame retardant
SMILES: O=P(OCCC1)(OCCC1)OCCC1
Synonyms: Ethanol, 2-chloro-, phosphate (3:1); 2-chloroethanol phosphate; Phosphoric acid, tris(2-chloroethyl)ester; Tri(2-chloroethyl) phosphate Tri(2-chloroethyl)
phosphoric acid ethyl ester; Tri-beta-chloroethyl phosphate; Trichloroethyl phosphate; Tri(2-chloroethyl) orthophosphate; Tri(2-chloroethyl)ester phosphoric acid;
Tris-beta-chloroethyl phosphate; Tris(2-chloroethyl) phosphate; Tris(chloroethyl) phosphate; Tris(monochloroethyl) phosphate; TCEP
Trade names: 3CF; Celanese Celluflex CEF; Celluflex CEF; CLP; Disflamoll TCA; AI3-15023; Amgard TCEP; Antiblaze TCEP; Celanese Celluflex CEF;
Disflamoll TCA; Fyrol CEF; Fyrol CF; Genomoll P; Hostaflam UPS 10; Levagard EP; Niax 3CF; Niax Flame retardant 3CF; Nuogard TCEP; Tolgard TCEP;
Triclofos
Chemical Considerations: This phosphate ester is a discrete organic chemical with a MW below 1,000. EPI v4.1 1 was used to estimate some environmental fate
values due to an absence of experimental data. Measured values from experimental studies were incorporated into the EPI estimations. This compound may be
manufactured by epoxide opening with either ethylene oxide or ethylene chlorohydrin in the presence of phosphorus oxy chloride. 1,2 dichloroethane is an impurity in
some commercial products (IARC, 1990; CELLTECH, 2009; ATSDR, 2012).
7-649
-------
Polymeric: No
Oligomeric: Not applicable
Metabolites, Degradates and Transformation Products: Thermal degradation: Carbon monoxide, hydrogen chloride, 2-chloroethane and dichloroethane, carbon
dioxide, benzene, toluene, chloromethane, chloroethane, 1,2-dichloroethane, chloropropenes, 1,2,3-trichloropropane, 2-chloroethanol, acetaldehyde,
chloroacetaldehyde, chloroacetone, bis(2-chloroethyl) ether, bis(2-chloroethoxy)methane; methyl formate, methyl acetate, 2-chloroethyl acetate, phosphate and vinyl
chloride.
Metabolites: 2-chloroethanol and bis(2-chloroethyl)hydrogen phosphate and other unidentified metabolites by human and rat liver microsomes, liver, blood and
plasma samples. Other metabolites reported include bis(2-chloroethyl) carboxymethyl phosphate, bis(2-chloroethyl) hydrogen phosphate and bis(2-chloroethyl 2-
hydroxyethyl) phosphate glucuronide. Chloride ion and 2-chloroethanol degradation products from bacteria (Chapman et al., 1991; IPCS, 1998; NICNAS, 2001;
Takahashi et al., 2008; EU, 2009; Van den Bade et al., 2013).
Analog: None
Endpoint(s) using analog values: Not applicable
Analog Structure: Not applicable
Structural Alerts: Organophosphates, neurotoxicity; aliphatic substituted alkyl halides, genetic toxicity; chlorinated hydrocarbons, liver toxicity; chlorinated
hydrocarbons, reproductive toxicity. This chemical appears on the List of Chemicals Known to the State to Cause Cancer for the State of California: California
Proposition 65 cancer, List of Chemicals of High Concern to Children for Washington State, List of Substances of Very High Concern for Authorisation published in
accordance with Article 59(10) of the REACH Regulation (ECHA, 2009; State of Washington, 2011; EPA, 2012; California EPA, 2013).
Risk Phrases: R60: May impair fertility; R22: Harmful if swallowed; R40: Limited evidence of a carcinogenic effect; R51/53: Toxic to aquatic organisms, may cause
long-term adverse effects in the aquatic environment (ESIS, 2012).
Hazard and Risk Assessments: Priority Existing Chemical Assessment report for Triphosphates by NICNAS in 2001; EU Risk Assessment Report in 2009; IARC
Summaries & Evaluations report in 1990; part of the Toxicological profile for Phosphate Ester Flame Retardants by ATSDR (IARC, 1990; NICNAS, 2001; EU, 2009;
ATSDR,2012).
7-650
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
PHYSICAL/CHEMICAL PROPERTIES
Melting Point (°C)
Boiling Point (°C)
-58
Measured by method DIN 5 1583,
ASTM D 97-66 (Measured)
-55
(Measured)
-60
Reported as about -60°C (Measured)
<-70
pour point (Measured)
202 at 10 mmHg
Measured by ASTM Dl 160 method at a
reduced pressure (Measured)
320 Decomposes
99.5% purity (Measured)
145 at 0 mmHg
Value reported as 145°C at 0.66 hPa
(Measured)
330
(Measured)
Decomposes
Rapid decomposition occurs above
220°C. Thermal decomposition products
are carbon monoxide, hydrogen
chloride, 2-chloroethane and
dichloroethane. (Measured)
OECD-SIDS, 2006
IARC, 1990; EC, 2000; ATSDR,
2012
EC, 2000
NICNAS, 2001; OECD-SIDS,
2006; EU, 2009
EC, 2000
EU, 2009
EC, 2000; NICNAS, 2001
IARC, 1990; Lide, 2008; ATSDR,
2012
IPCS, 1998
Similar values are consistently
reported in secondary sources.
Similar values are consistently
reported in secondary sources.
Similar values are consistently
reported in secondary sources.
Value reported in a secondary
source. Assumed to be measured.
Adequate value measured by a
standard test method.
Limited details available from
secondary source.
Similar values are consistently
reported in secondary sources.
Value reported in a secondary
source.
Supporting information reported in
a secondary source with limited
details.
7-651
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Vapor Pressure (mm Hg)
1.6xl(Tat250C
Values at higher temperatures measured
by dynamic method; measured values
reported as: 0.43 hPaat 136.9°C; 0.99
hPa at 143.5°C; 2.03 hPa at 158.6°C;
5.00hPaatl74.1°C; 15.03 hPa at
196.2°C. (Extrapolated)
EU, 2009
The Clausius-Clapeyron equation
was used to calculate the VP at
20°C (reported as such in source).
Extrapolation to 25°C yields the
value of 1.6xlO"5 mmHg.
0.062 at 25°C
Measured with a conventional
isoteniscope using a nitrogen
atmosphere (Measured)
ATSDR,2012
Value calculated from reported
equation coefficients determined by
experimental measurements and
equation fitting. The calculated
value is inconsistent with other
available vapor pressure data. It is
possible that the units of the
calculation apply to meters Hg
rather than mm Hg which would
change the value to 0.000062 mm
Hg at 25 °C.
8.55xlO-6at20°C
Reported as 0.00114 Pa at 20°C
(Extrapolated)
OECD-SIDS, 2006: EU, 2009
Value was extrapolated from a
measured value of 43 Pa at 137°C.
<0.075at20°C
Reported as <0.1 hPa at 20°C. ASTM
D232 method (Extrapolated)
EC, 2000
Value was approximated from data
at higher temperatures
Water Solubility (mg/L)
7,000 (Measured)
Muir, 1984 (as cited in ATSDR,
2012)
Value reported in a secondary
source.
7,943 (Measured)
EC, 2000
Value reported in a secondary
source with limited study details.
7-652
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
Log Kow
DATA
temperature not reported
7,820 (Measured)
Reported as 7820 mg/L at 20°C, pH 4.7
-6.1 according to Directive
84/449/EEC, A.6, Water Solubility
method, 1984 using GLP
5,000 (Measured)
Reported as ca. 5 g/L at 20°C, 5.5 -7 pH
at 10 vol% and 20°C by Society of
Automotive Engineers (SAE) method
1.78
Reported as 1.78 at 20°C; Directive
84/449/EEC., A.8, Partition coefficient,
1984 Method, GLP (Measured)
1.47
OECD Guide-line 107, Partition
Coefficient (n-octanol/water), Flask-
shaking Method, 1981 (Measured)
1.7
(Measured)
1.6
(Estimated)
1.44
(Measured)
REFERENCE
EC, 2000; EU, 2009
EC, 2000
EC, 2000; EU, 2009
EC, 2000
IPCS, 1998; NICNAS, 2001
EPIv4.11
MITI, 1992a (as cited in ATSDR,
2012)
DATA QUALITY
Adequate guideline study.
Adequate study
Similar to the log Kow of 1 .47
reported for a shake-flask method,
but this is a more recent
measurement and both were
measured by the same source
(Akzo Nobel Chemicals). Also
similar to the KOWWIN program
estimate of 1.63.
Adequate guideline study.
Reported in a secondary source
with limited study details.
Estimated by the EPI Suite
KOWWIN program (vl.68)
Reported as measured in their
laboratory, but measurement
methods, temperatures and pH
7-653
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
Flammability (Flash Point)
Explosivity
Pyrolysis
pH
pKa
DATA
Flash point: 216°C (Measured)
Flash point: 252°C Open cup
(Measured)
Flash point: 225°C Closed cup; DIN
51758 method (Measured)
Flash Point: 200°C ASTM D93 method
using GLP; sample appears to catch fire
at approx. 200°C, but does not show a
distinct flash point as defined by the test
method (Measured)
Decomposition products: 1,2
dichloroethane and vinyl chloride
0.1 mol TCEP was decomposed in 20-
mL flask at 250-260°C at 3 mmHg, the
decomposition products were separated
by gas-liquid chromatography, and
analyzed with NMR and MS (Measured)
Not applicable (Estimated)
Not applicable (Estimated)
REFERENCE
ATSDR,2012
EC, 2000
EC, 2000
EC, 2000; EU, 2009
Okamoto et al., 1974
Professional judgment
Professional judgment
DATA QUALITY
values are not reported.
Limited study details reported in a
secondary source.
Non-GLP, standardized study.
Adequate standardized method.
Adequate standardized method
reported in a secondary source.
No data located.
Supporting information provided.
Does not contain functional groups
that are expected to ionize under
environmental conditions.
Does not contain functional groups
that are expected to ionize under
environmental conditions.
7-654
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
HUMAN HEALTH EFFECTS
Toxicokinetics
Dermal Absorption in vitro
Absorption,
Distribution,
Metabolism &
Excretion
Oral, Dermal or Inhaled
TCEP is well absorbed and distributed following oral administration in rats and mice. TCEP and
metabolites are rapidly eliminated principally in the urine. Urinary metabolites include bis(2-chloroethyl)
carboxymethylphosphate, bis(2-chloroethyl)hydrogen phosphate and bis(2-chloroethyl)-2-hydroxyethyl-
phosphate glucuronide. TCEP is metabolized by hepatic microsomal fraction in male rats and in humans,
but is not metabolized by plasma or whole blood. In an incubation experiment, bis(2-chloroethyl)
phosphate (BCEP) and hydroxyethyl 2-chloroethyl hydrogen phosphate were the only detected
metabolites. No phase II metabolites were detected.
TCEP is metabolized by hepatic
microsomal fraction in male rats but not
in females. Liver slices and blood
plasma indicated metabolism in both
sexes. Liver slices and microsomes in
humans metabolized TCEP, but plasma
and whole blood did not.
Wistar rats orally dosed with 50
(imol/kg 14C-labeled TCEP. During the
first 6 hours following administration,
TCEP was distributed and concentrated
by several tissues; primarily the liver
and kidney. Most of the material was
excreted within 24 hours and by 168
hours, <1% remained in tissues.
Excretion was 96% in urine, 6% in feces
and 2% in expired air. Urinary
metabolites included: bis(2-chloroethyl)
carboxymethyl phosphate, bis(2-
chloroethyl) hydrogen phosphate and
bis(2-chloroethyl) 2-hydroxyethyl
phosphate glucuronide
Male and female Fischer-344 rats
gavaged with 0, 175, 350 or 700
Chapman et al., 1991 (as cited in
WHO, 1998)
Minegishi et al., 1988 (as cited in
WHO, 1998)
Herr et al., 1991 (as cited in WHO,
1998)
No data located.
Limited study details reported in a
secondary source.
Sufficient study details reported.
Sufficient study details reported.
7-655
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
mg/kg 14C-labeled TCEP; plasma
concentrations and metabolites peaked
by 30 minutes in rats given 175 mg/kw.
No concentration differences of TCEP in
hippocampus and other brain tissues.
Male B6C3F1 mice orally dosed with
175 mg 14C-labeled TCEP/kg; >70%
excretion in urine within 8 hours.
Urinary metabolites: bis(2-chloroethyl)
carboxymethyl phosphate, bis(2-
chloroethyl) hydrogen phosphate and
bis(2-chloroethyl) 2-hydroxyethyl
phosphate glucuronide
TCEP is readily absorbed from the
gastrointestinal tract and excreted within
72 hours following oral administration
Absorption study in rats dosed with 14C
TCEP at 100-140 mg/kg via oral gavage
or in the diet. 80% of the administered
dose (gavage and diet) was excreted in
urine within 5 days
REFERENCE
Burka et al., 1991 (as cited in
WHO, 1998)
EC, 2000
EC, 2000
DATA QUALITY
Sufficient study details reported.
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source.
7-656
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
Other
Acute Mammalian Toxicity
Acute Lethality
Oral
DATA
Incubation experiments using 1.0
mg/mL HLM or S9 proteins, 50 (iM
TBOEP or TCEP, or TCPP, or 20 jiM
TPHP or TDCPP and NADPH
regenerating solution in 1 mM total
volume were conducted for 1 hour.
There was a 7% and 13% clearance of
the compound in the HLM and S9
incubations, respectively.
Bis(2-chloroethyl) phosphate (BCEP)
and hydroxyethyl 2-chloroethyl
hydrogen phosphate were the only
detected metabolites. No phase II
metabolites were detected. BCEP was
the major metabolite detected.
REFERENCE
Van den Bade et al, 2013
DATA QUALITY
HIGH: Based on an oral LD50 of 46.4 mg/kg in rats. TCEP exhibits low toxicity via the inhalation and
dermal routes of exposure in rats and rabbits, respectively.
Rat oral LD50 = 46.4 - 1,000 mg/kg
Rat oral LD50 = 430 - 794 mg/kg
Rat oral LD50 = 1 150 mg/kg
Rat oral LD50 = 1,230 - 1,410 mg/kg
Mouse oral LD50 = 1,500 mg/kg
Rat oral LD50 = 3,600 mg/kg (3.6 g/kg)
ATSDR,2012
EC, 2000
Kynoch and Denton, 1990 (as cited
in WHO, 1998; EC, 2000)
Smyth et al., 1951; Ulsamer et al.,
1980 (as cited in WHO, 1998; EC,
2000;ATSDR,2012)
EC, 2000
Gardner, 1987 (as cited in WHO,
1998)
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source; study conducted
in accordance to GLP and Directive
84/449/EEC, B.I.
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source.
7-657
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
Dermal
Inhalation
Carcinogenicity
OncoLogic Results
Carcinogenicity (Rat and
Mouse)
DATA
Rabbit dermal LD50 = 2150 - > 5,000
mg/kg
Rat 4-hour inhalation LC50 > 5 mg/L
(5,000 mg/m3)
Rat 1-hour inhalation LC50 > 25.7 mg/L
(nominal)
REFERENCE
EC, 2000; OECD-SIDS, 2006;
ATSDR, 20 12
EC, 2000; ATSDR, 2012
OECD-SIDS, 2006
DATA QUALITY
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source.
HIGH: TCEP was carcinogenic in rats and mice. Renal adenomas/carcinomas were present in rats and
mice following 103 weeks of oral exposure. In addition, renal adenomas/carcinomas and forestomach and
hemapoietic tumors were evident in mice following 18 months of dietary exposure. IARC has classified
TCEP as a Category 3 carcinogen: "Not classifiable as to its Carcinogenicity" based on inadequate evidence
in experimental animals and no available human studies". However, NTP concludes that the renal
adenomas observed in rats are clear evidence of carcinogenic activity. In addition, this chemical appears on
the List of Chemicals Known to the State to Cause Cancer for the State of California.
In a 103 -week oral study, rats were
gavaged with TCEP at 0, 44 or 88
mg/kg-day, 5 days/week. Reduced
survival at the high dose. Renal tubular
adenomas (occurring in -50% of high-
dose males, 10% of high-dose females
and 10% of low-dose males); marked
increase in the incidence of renal tubule
cell hyperplasia in high dose males and
females. Although adenomas are benign
tumors, NTP concludes that renal
adenomas represent an early stage in the
development of carcinoma and is clear
evidence of carcinogenic activity.
In a 103 -week oral study, mice were
gavaged with TCEP at 0, 175, or 350
mg/kg-day 5 days/week. No significant
differences in survival or body weight
NTP, 1991 (as cited in EC, 2000;
ATSDR, 20 12)
NTP, 1991 (as cited in ATSDR,
2012)
No data located.
Adequate study details reported in
a primary source.
Adequate study details reported in
a primary source.
7-658
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
gain in comparison with controls. Renal
tubular karyomegaly in 80% of high
animals (a marker of nephropathy);
Marginal increase in harderian gland
neoplasms (primary adenomas, high
dose females). NTP concludes that there
is equivocal evidence of carcinogenic
activity based on renal tubule cell
neoplasms in male mice and marginally
increased harderian gland adenomas in
female mice.
In an 18-month dietary study, mice
(Slc:ddY) were fed TCEP at 0, 0.012,
0.06, 0.3, and 1.5% daily (~0, 11, 53,
267, and 1333 mg/kg-day) Increased
mortality and reduced weight gain in
comparison with controls at the high
dose. Significantly increased incidence
of renal cell adenomas and carcinomas
(high dose males); increased incidence
of benign liver adenomas (males, 0.3%
and 1.5%); increased incidence of
forestomach and hematopoietic tumors
(females).
Takada et al., 1989 (as cited in EC,
2000;ATSDR,2012)
Limited study details reported in a
secondary source (primary source
is in Japanese with English
abstract); doses are estimated
assuming a mean body weight of
0.045 kg and daily food
consumption of 0.004 kg/day
(ATSDR2012).
Female (Sl/ddy) mice were treated
dermally with ethanol solutions
containing 5% or 50% TCEP for 79
weeks. No significant increase in tumors
Takada et al., 1991 (as cited in
WHO, 1998)
Limited details reported in a
secondary source.
Combined Chronic
Toxicity/Carcinogenicity
No data located.
7-659
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
Other
Genotoxicity
Gene Mutation in vitro
DATA
This chemical appears on the List of
Chemicals Known to the State to Cause
Cancer for the State of California:
California Proposition 65
IARC has classified TCEP as a Category
3 carcinogen: "not classifiable as to its
carcinogenicity" based on inadequate
evidence in experimental animals and no
available human studies.
REFERENCE
California EPA, 2013
IARC, 1990 (as cited in NICNAS,
2001)
DATA QUALITY
Added to the California Proposition
65 list for cancer on April 1, 1992.
The NTP (1991) oral bioassay in
rats and mice was not available to
IARC when this agency classified
TCEP.
MODERATE: Based on weight of evidence from multiple studies. Results were positive in in vitro gene
mutation and chromosomal aberrations tests. TCEP was cytotoxic in a neutral read uptake assay in
Chinese hamster V79 cells, produced sister chromatid exchanges in Chinese hamster V79 cells and mouse
lymphoma cells, and was positive in a cellular transformation study in mouse BALB/3t3 cells. TCEP was
not mutagenic in bacteria or yeast, and did not produce chromosomal aberrations in any available in vivo
studies. In addition, TCEP was negative in an Unscheduled DNA synthesis study in human WI-38 cells.
There is potential for genetic toxicity based on a structural alert for aliphatic substituted alkyl halides.
Positive, cytotoxicity in a neutral red
uptake assay in Chinese hamster V79
cells. Negative in the absence of
metabolic activation
Negative, Salmonella typhimurium
strains TA98, TA100, TA1535 and
TA1537, TA1538 with and without
metabolic activation.
Negative, Saccharomyces cerevisiae
with and without metabolic activation
Negative, mammalian cell HGPRT gene
mutation assay in Chinese hamster V79
lung cells with and without metabolic
activation
Negative, mammalian cell gene
mutation assay in L5 178Y mouse
Follmann and Wober, 2006 (as
cited in ATSDR, 2012)
EC, 2000
EC, 2000
EC, 2000
EC, 2000
Sufficient study details reported in
a primary source.
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source; Study was
7-660
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
Gene Mutation in vivo
Chromosomal Aberrations in
vitro
DATA
lymphoma cells with and without
metabolic activation
Negative, Salmonella typhimurium
strains TA98, TA100, TA1535, TA1537
or TA1538 with and without metabolic
activation
Negative, Salmonella typhimurium
strains TA98, TA100 with and without
metabolic activation
Negative, Salmonella typhimurium
strains TA97,TA98, TA100, TA104,
TA1535, TA1537, and TA1538 with and
without metabolic activation
Negative, Salmonella typhimurium
strains TA100, TA1535, TA1537 or
TA98 with and without metabolic
activation
Positive, sister chromatid exchange
assay in hamster V79 lung cells with and
without metabolic activation. TCEP
induced SCE's but no clear dose
response was noted.
Positive, sister chromatid exchange
assay in L5 178Y mouse lymphoma cells
with metabolic activation. No increase in
SCE's without metabolic activation.
Negative, chromosomal aberrations in
CHO cells with and without metabolic
activation.
Equivocal, sister chromatid exchange
assay in Chinese hamster (CHO) cells
REFERENCE
EC, 2000
Kubo et al, 2002
Follmann and Wober, 2006 (as
cited in ATSDR, 2012)
NTP, 1991
EC, 2000
EC, 2000
Galloway et al., 1987 (as cited in
NTP, 1991; EC, 2000)
Galloway et al., 1987 (as cited in
NTP, 1991; EC, 2000)
DATA QUALITY
conducted in accordance with GLP
and OECD Guideline 476.
Limited study details reported in a
secondary source; Study was
conducted in accordance with
OECD Guideline 471
Sufficient study details reported in
a primary source.
Sufficient study details reported in
a primary source.
Sufficient study details reported.
No data located.
Limited study details reported in a
secondary source.
Study was conducted in accordance
with GLP and OECD Guideline
479.
Study was conducted in accordance
with OECD Guideline 473.
Sufficient study details reported in
a primary source.
7-661
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
Chromosomal Aberrations in
vivo
DNA Damage and Repair
Other
DATA
with metabolic activation
Negative, mammalian erythrocyte
micronucleus assay in mice orally
gavaged with 1,000 mg/kg TCEP; cell
collection for 24, 48 or 72 hours after
dosing.
Negative, chromosomal aberrations in
rats orally gavaged with TCEP at doses
of 0.062, 0.021, or 0.0062 ml/kg.
Negative, mammalian erythrocyte
micronucleus assay in mice administered
175, 350 or 700 mg/kg TCEP via
intraperitoneal injection; cell collection
for 24, 48 or 72 hours after dosing.
Equivocal, chromosomal aberrations,
micronucleus assay in male and female
Chinese hamsters administered 62.5,
125, or 250 mg/kg TCEP via
intraperitoneal injection; cell collection
24 hours later.
Negative, Drosophila melanogaster,
somatic cell damage
Negative, DNA damage in a comet
analysis in Chinese hamster V79 cells
with and without metabolic activation
Negative, DNA-binding in vitro (cell
type not reported)
Positive, Cellular transformation in
mouse BALB/3T3 cells. No further
details provided.
Negative, unscheduled DNA synthesis
REFERENCE
EC, 2000
EC, 2000
EC, 2000
Sala et al., 1982 (as cited in
ATSDR,2012)
Vogel and Nivard, 1993 (as cited in
WHO, 1998)
Follmann and Wober, 2006 (as
cited in ATSDR, 2012)
EC, 2000
EC, 2000
EC, 2000
DATA QUALITY
Limited study details reported in a
secondary source; study conducted
according to OECD Guideline 474.
Limited study details reported in a
secondary source; study conducted
according to GLP and OECD
Guideline 475.
Limited study details reported in a
secondary source; study conducted
according to GLP and OECD
Guideline 474.
Sufficient study details reported in
a primary source.
Sufficient study details reported in
a primary source.
Sufficient study details reported in
a primary source.
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source.
Limited study details reported in a
7-662
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
in human WI-38 cells with and without
metabolic activation.
Equivocal, Cellular transformation assay
in C3H10T1/2 mouse embryo cells
without metabolic activation. No data
reported with presence of metabolic
activation.
There is potential for genotoxicity based
on the structural alert for aliphatic
substituted alkyl halides.
(Estimated)
REFERENCE
EC, 2000
Professional judgment
DATA QUALITY
secondary source; study was
conducted in accordance with GLP
and OECD Guideline 482.
Limited study details reported in a
secondary source.
Estimated based on a structural
alert for aliphatic substituted alkyl
halides and professional judgment.
7-663
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
Reproductive Effects
Reproduction/Developmental
Toxicity Screen
Combined Repeated Dose
with Reproduction/
Developmental Toxicity
Screen
DATA
REFERENCE
DATA QUALITY
MODERATE: Based on the weight of evidence from multiple studies. Although a whole body inhalation
study resulted in a NOAEL of 0.5 mg/m3 and a LOAEL of 1.5 mg/m3 (0.0012 mg/L) in male rats; this study
is generally classified as having low reliability. TCEP was observed to have Moderate concern for
reproductive toxicity when administered orally in rats and mice. In addition, there is potential for
reproductive toxicity based on a structural alert for chlorinated hydrocarbons.
Male rats (strain not specified) were
exposed to 0, 0.5 or 1.5 mg/m3 TCEP via
whole body inhalation continuously for
4 months.
Testicular toxicity (0.5 and 1.5 mg/m3),
decreased sperm counts, decreased
sperm motility and abnormal sperm
morphology; increased number of
spermatogonia with decreased numbers
of sperm in the later stages of
development was reported; When mated
with untreated females: decreased
fertility (1.5 mg/m3); increased pre-and
post-implantation loss; decreased litter
size
NOAEL: 0.5 mg/m3
LOAEL: 1.5 mg/m3
Shepelskaya and Dyshinevich,
1981 (as cited in WHO, 1998)
Limited study details reported in a
secondary source. Original study in
Russian. Study received a
reliability score of 4 in the IUCLID
data set.
No data located.
7-664
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Reproduction and Fertility
Effects
In a continuous breeding study, Swiss
CD-I mice were orally gavaged with
175, 350 or 700 mg/kg-day TCEP;
significant impairment of reproductive
capacity and fertility at the mid- and
high-dose groups
NOAEL: 175 mg/kg-day
LOAEL: 350 mg/kg-day (based on
impaired reproductive capacity and
fertility)
Chapin et al., 1997 (as cited in
WHO, 1998; NICNAS, 2001;
OECD-SIDS, 2006; ATSDR,
2012)
Sufficient study details reported.
In a 13-week study, F-344 rats were
orally gavaged with TCEP at 0, 22, 88
and 175 mg/kg-day. No adverse effect
on cauda weights, absolute and relative
epididymal weights, absolute and
relative testes weights, sperm
concentration, and number of abnormal
sperm; reduced sperm motility; no
increase in estrous cycle.
NOAEL/LOAEL: Not determined
Morrissey et al., 1988 (as cited in
WHO, 1998)
WHO 1998; Morrissey et al., 1988
(primary source). NOAEL/LOAEL
cannot be determined because
primary source provided only
qualitative description of results.
In a 13-week study, B6C3F1 mice were
orally gavaged with TCEP at 0, 44, 175
and 700 mg/kg-day. No adverse effect
on cauda weights, relative epididymis
weight, motility or sperm concentration;
decreased absolute epididymis weight
and absolute and relative testes weights;
increase in the number of sperm with
abnormal morphology. No increase in
estrous cycle length
Morrissey et al., 1988 (as cited in
WHO, 1998)
WHO 1998: Morrissey et al., 1988
(primary source). NOAEL/LOAEL
cannot be determined because
primary source provided only
qualitative description of results.
7-665
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
Other
Developmental Effects
Reproduction/
Developmental Toxicity
Screen
Combined Repeated Dose
with Reproduction/
Developmental Toxicity
Screen
DATA
NOAEL/LOAEL: Not determined
There is potential for reproductive
toxicity based on a structural alert for
chlorinated hydrocarbons.
(Estimated)
REFERENCE
Professional judgment
DATA QUALITY
Estimated based on a structural
alert for chlorinated hydrocarbons
and professional judgment.
No data located.
HIGH: Based on the weight of evidence from multiple studies. Although a LOAEL of 175 mg/kg-day was
identified based on decreased live male F2 pups in an 18-week continuous breeding study, no NOAEL was
established. Effects < 50 mg/kg-day cannot be ruled out. Furthermore, since TCEP decreased
cholinesterase activity, and decreased cholinesterase activity in dams can influence fetal
neurodevelopment, there is also a concern for potential developmental neurotoxicity.
In a continuous breeding study, mice
were orally gavaged with 175, 300 or
700 mg/kg-day TCEP.
NOAEL: Not established
LOAEL: 175 mg/kg-day (based on
decreased number of live male F2 pups
per litter)
Chapin et al., 1997 (as cited in
WHO, 1998; NICNAS, 2001;
OECD-SIDS, 2006; ATSDR,
2012)
Adequate study details reported.
No data located.
7-666
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Prenatal Development
Pregnant rats were orally gavaged with
0, 50, 100 or 200 mg/kg-day TCEP on
GDs 7-15. Reduced food consumption at
the high dose; clinical signs of toxicity
in dams (high dose) included
piloerection and general weakness.
Seven out of 30 females died during the
study. No morphological or behavioral
effects were observed in offspring.
Development of offspring was normal
and there were no abnormalities in
functional behavior tests (open field,
water maze, rota rod, inclined plane test,
pain reflex or Preyer's reflex).
Maternal:
NOAEL: 100 mg/kg-day
LOAEL: 200 mg/kg-day (based on
clinical signs of toxicity in dams)
Developmental:
NOAEL: 200 mg/kg-day (highest dose
tested)
LOAEL: Not established
Kawashima et al., 1983 (as cited in
WHO, 1998; EC, 2000; ATSDR,
2012)
Limited study details reported in a
secondary source. Primary source
is in Japanese with an English
abstract.
Pregnant mice were orally gavaged with
940 mg/kg-day TCEP (only dose tested)
on GDs 6-13. Decreased maternal body
weight gain. No adverse effects on
viable litters, live born pups per litter,
percent survival, birth weight, or pup
weight gain.
Maternal:
Hardin et al., 1987 (as cited in
WHO, 1998; EC, 2000; ATSDR,
2012)
Limited study details reported in a
secondary source.
7-667
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
Postnatal Development
Prenatal and Postnatal
Development
Developmental Neurotoxicity
Other
DATA
NOAEL: not established;
LOAEL: 940 mg/kg-day (based on
decreased maternal body weight gain);
only dose tested
Developmental:
NOAEL: 940 mg/kg-day (only dose
tested);
LOAEL: Not established
There were no data located for the
developmental neurotoxicity endpoint.
Decreased cholinesterase activity in
pregnant lab animals has been shown to
have a negative impact on fetal brain
development. As a result, there is
uncertain potential for developmental
neurotoxicity for this substance
REFERENCE
Professional judgment
DATA QUALITY
No data located.
No data located.
No data located.
No data located.
7-668
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Neurotoxicity
MODERATE: Based on the weight of evidence from a number of studies. TCEP produced degenerative
lesions in the cerebral cortex in female rats gavaged with 88 mg/kg-day (NOAEL = 44 mg/kg-day) in a 103-
week study. In addition, necrotic lesions in the hippocampus were observed in female rats following oral
administration of 175 mg/kg-day TCEP (NOAEL = 88 mg/kg-day) for 16 weeks. Ataxia and convulsive
movements were observed in mice administered TCEP at doses of > 350 mg/kg-day (NOAEL = 175 mg/kg-
day) for 16 days. Convulsions were observed in female rats within 60 minutes following single oral gavage
of 275 mg TCEP/kg-day. TCEP was attributed to death in dogs following ingestion of car seat cushions
found to contain large amounts of the chemical. TCEP produced no evidence of neurotoxicity in white
leghorn hens. TCEP promoted differentiation of the cholinergic phenotype only in an in vitro neurotoxicity
study using undifferentiated and differentiating PC12 cells. There is potential for neurotoxicity based on a
structural alert for organophosphates.
Neurotoxicity Screening
Battery (Adult)
Other
In a 103-week oral study, rats were
gavaged with TCEP at 0, 44 or 88
mg/kg-day, 5 days/week.
Degenerative lesions in the cerebral
cortex (high dose, females).
NOAEL: 44 mg/kg-day;
LOAEL: 88 mg/kg-day (based on
cerebrum gliosis in female rat)
NTP, 1991; Matthews et al.,
(as cited in ATSDR, 2012)
In 16-18 week oral studies, rats were
gavaged with TCEP at 0, 22, 44, 88, 175
or 350 mg/kg-day, 5 days/week. In the
14-day study, serum cholinesterase
(ChE) was decreased by 82 and 80% in
female rats at 175 and 350 mg/kg-day,
respectively. Inhibition was minimal in
male rats. In the 16-18 week study, ChE
decreased by 25 and 41% in female rats
at 175 and 350 mg/kg-day, respectively
and there was no change in male rats.
No data located.
1993
Matthews et al., 1990; NTP, 1991
(as cited in EC, 2000; ATSDR,
2012;NICNAS, 2001)
Sufficient study details reported.
Sufficient study details reported in
a primary source.
7-669
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Necrotic lesions in the hippocampus and
thalamus (females, 175 mg/kg-day; male
and females, 350 mg/kg-day).
NOAEL: 88 mg/kg-day
LOAEL: 175 mg/kg-day (based on
necrotic lesions in hippocampus and
thalamus)
In a 16-day oral study, mice were
gavaged with 0, 175, 350 or 700 mg
TCEP kg-day. Ataxia and convulsive
movements were observed at > 350
mg/kg-day during the first 3 days of
dosing.
NOAEL: 175 mg/kg-day
LOAEL: 350 mg/kg-day (ataxia and
conclusive movements)
NTP, 1991;ATSDR,2012
Sufficient study details reported.
Female Fischer-344 rats were gavaged
once with 275 mg TCEP/kg.
Convulsions within 60-90 minutes;
extensive loss of CAI hippocampal
pyramidal cells 7 days post-dosing.
Impaired acquisition of a reference
memory task in a water maze when
trained and tested 3 weeks following
treatment.
NOAEL: Not established
LOAEL: 275 mg/kg (based on impaired
acquisition of a memory task 3 weeks
post exposure); only dose tested
Tilson et al., 1990 (as cited in
WHO, 1998; ATSDR, 2012)
Limited study details reported in a
secondary source. True
NOAEL/LOAEL cannot be
determined because only one dose
level was tested; it is uncertain if
effects occurred at a lower dose.
Two case reports in dogs:
Lehneretal., 2010
Adequate case studies reported in a
7-670
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
In one case, two American pit bulls
presented with acute signs of central
nervous system excitation (including
seizures) in an emergency clinic; one
dog died within 15 minutes and
necropsy revealed frothy brown fluid in
the stomach and edematous lungs. The
other dog recovered fully following
treatment. In a second case, a German
Shepherd and a Rottweiler were found
dead after having been left in a car
overnight. Necropsy revealed signs of
possible kidney damage and congested,
dark lungs. Toxicological analysis in all
deceased dogs revealed TCEP (> 2 ppm)
in stomach contents and was attributed
to ingestion of car seat cushions.
primary source; actual ingested
doses were not determined.
White leghorn hens were orally
administered TCEP at 420 mg/kg-day
for 5 days and were observed for 30
days following treatment. No neurotoxic
reactions were evident.
Bullock and Kamienski, 1972 (as
cited in WHO, 1998; EC, 2000)
Limited study details reported in a
secondary source.
Single intraperitoneal application of 1.0
mg/kg TCEP to white Leghorn hens. No
evidence of delayed neurotoxicity.
EC, 2000
Limited study details reported in a
secondary source.
Single oral administration of 2.5 or 14.2
g/kg (2500 or 14,200 mg/kg) TCEP to
white Leghorn hens. No microscopic
changes in brain, spinal cord or sciatic
nerve were found after the treatment.
Plasma cholinesterase activity was
inhibited by 87% and brain neuropathy
target esterase by 30% (14.2 g/kg). No
Sprague et al., 1981 (as cited in
WHO, 1998; EC, 2000)
Sufficient study details reported.
7-671
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
evidence of delayed neurotoxicity.
In vitro neurotoxicity study using
undifferentiated and differentiating
PC 12 cells. Changes in DNA synthesis,
oxidative stress, differentiation into
dopaminergic or cholinergic
neurophenotypes, cell number, cell
growth and neurite growth were
assessed.
TCEP promoted differentiation of the
cholinergic phenotype only. There were
no other adverse neurological effects.
There is potential for neurotoxicity
based on a structural alert for
organophosphate s .
(Estimated)
REFERENCE
Dishawetal., 2011
Professional judgment
DATA QUALITY
Sufficient study details reported in
a primary source.
Estimated based on a structural
alert for organophosphates and
professional judgment.
7-672
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Repeated Dose Effects
MODERATE: Based on a LOAEL of 88 mg/kg-day in a 103-week oral study in rats. Effects included renal
tubule epithelial hyperplasia and cerebral gliosis. Additional effects in rats following oral exposure to
higher doses included slightly reduced serum cholinesterase activity and increased kidney and liver weights
(175 and 270 mg/kg-day). Effects in mice following oral exposure included renal tubular karyomegaly
and/or cytomegaly (350 and 700 mg/kg-day). No studies were available to assess effects of repeated
exposures to TCEP via the inhalation or dermal routes of exposure. In addition, there is potential for liver
toxicity based on a structural alert for chlorinated hydrocarbons.
In a 103-week oral study, rats were
gavaged with TCEP at 0, 44 or 88
mg/kg-day, 5 days/week.
Reduced survival at the high dose. Renal
tubule epithelial hyperplasia (high dose,
both sexes), degenerative lesions in the
cerebral cortex (high dose, females).
There were no adverse effects on
lymphoreticular tissues.
NOAEL: 44 mg/kg-day
LOAEL: 88 mg/kg-day (based on renal
tubule epithelial hyperplasia in male and
female rats and cerebrum gliosis in
female rat)
NTP, 1991; Matthews et al.,
(as cited in ATSDR, 2012)
In a 103-week oral study, mice were
gavaged with TCEP at 0, 175, or 350
mg/kg-day, 5 days/week.
No significant differences in survival or
body weight gain in comparison with
controls. Renal tubular karyomegaly in
80% of high animals (a marker of
nephropathy); Marginal increase in
harderian gland neoplasms (primary
adenomas, high dose females). There
were no adverse effects on
1993
NTP, 1991; EC, 2000; ATSDR,
2012
Sufficient study details reported.
Sufficient study details reported.
7-673
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
lymphoreticular tissues.
NOAEL: 175 mg/kg-day
LOAEL: 350 mg/kg-day (renal tubular
karyomegaly)
In a 16-day oral study, rats were orally
gavaged with 0, 44, 88, 175 or 350
mg/kg-day TCEP in corn oil 5
days/week for a total of 12 doses.
No treatment-related deaths, differences
in final mean body weight or
histopathological lesions. Slightly
reduced serum cholinesterase activity
(females, 175 and 350 mg/kg-day);
Increased absolute and relative kidney
weights (males, 175 and 350 mg/kg-
day); increased absolute and relative
liver weights (females, 350 mg/kg-day)
NOAEL: 88 mg/kg-day;
LOAEL: 175 mg/kg-day (decreased
serum cholinesterase activity, increased
absolute and relative kidney weights)
Matthews et al., 1990 (as cited in
NTP, 1991)
Sufficient study details reported.
In a 16-day oral study, mice were orally
gavaged with 0, 22, 44, 88, 175, 350 or
700 mg/kg-day TCEP in corn oil 5
days/week for a total of 12 doses.
No treatment-related deaths, differences
in final mean body weight or
histopathological lesions.
NOAEL: 700 mg/kg-day (highest dose
tested)
Matthews et al., 1990 (as cited in
NTP, 1991)
Sufficient study details reported.
7-674
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
LOAEL: Not established
In a 16-18 week oral study, rats were
gavaged with TCEP at 0, 22, 44, 88, 175
or 350 mg/kg-day, 5 days/week.
Mortality occurred at the high dose (4/10
males and 3/10 females); Significantly
increased liver and kidney to body
weight ratios (> 44 mg/kg-day in
females; 350 mg/kg-day for males);
Necrotic lesions in the hippocampus and
thalamus (females, 175 mg/kg-day; both
sexes, 350 mg/kg-day).
NOAEL: 88 mg/kg-day
LOAEL: 175 mg/kg-day (necrotic
lesions in hippocampus and thalamus-
females)
Matthews et al., 1990; NTP, 1991
(as cited in EC, 2000; NICNAS,
2001;ATSDR,2012)
Sufficient study details reported.
In a 16-week oral study, mice were
gavaged with TCEP (in corn oil) at 0,
44, 88, 175, 350 and 700 mg/kg-day, 5
days/week.
No treatment-related deaths, differences
in final mean body weight or differences
in cholinesterase activity. Kidney
effects: tubule epithelial cells with
enlarged nuclei (cytomegaly and
karyomegaly) at the highest dose.
NOAEL: 350 mg/kg-day
LOAEL: 700 mg/kg-day (kidney effects)
Matthews et al., 1990; NTP, 1991
(as cited in EC, 2000; ATSDR,
2012)
Sufficient study details reported.
In a 2 8-day dietary study, rats were fed
TCEP at 0, 400, 1,000, 3,000 or 8,000
ppm daily (0, 37, 91, 270 and 730
EC, 2000; EU, 2009
Limited study details reported in a
secondary source; doses were
reported as ppm in the diet but
7-675
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
mg/kg-day)
No mortalities. Significant reductions in
body weight and food consumption
(8,000 ppm); No treatment-related
changes in clinical chemistry,
hematology or urinalysis parameters; no
adverse gross or microscopic effects.
Significant increase in relative liver and
kidney weights (3,000 and 8,000 ppm)
NOAEL: 1,000 ppm (91 mg/kg-day)
LOAEL: 3,000 ppm (270 mg/kg-day)
In a 2 8-day dietary study, rats were fed
TCEP at 0, 500, 850, 1,500 and 2,000
ppm daily (-46, 78, 140, and 180
mg/kg-day).
Decreased food consumption (8,000
ppm). No further clinical effects were
observed and necropsy revealed no
abnormalities.
NOAEL: > 2,000 ppm (180 mg/kg-day;
highest dose tested)
LOAEL: Not established
EC, 2000; EU, 2009
were converted to mg/kg-day using
EPA 1988 reference values for
body weight and food
consumption.
Limited study details reported in a
secondary source; doses were
reported as ppm in the diet but
were converted to mg/kg-day using
EPA 1988 reference values for
body weight and food
consumption.
In a 30-day dietary study, rats were fed
TCEP up to a maximum dose of 400
mg/kg-day (other doses not reported).
No deaths; no adverse effects were
observed.
NOAEL: 400 mg/kg-day (highest dose
tested)
LOAEL: Not established
Ulsamer et al., 1980 (as cited in
EC, 2000)
Limited study details reported in a
secondary source; Study received
reliability score of 4 in the IUCLID
data set.
7-676
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
Skin Sensitization
Skin Sensitization
Respiratory Sensitization
(Respiratory Sensitization
Eye Irritation
Eye Irritation
Dermal Irritation
Dermal Irritation
DATA
There is potential for liver toxicity based
on a structural alert for chlorinated
hydrocarbons.
(Estimated)
REFERENCE
Professional judgment
DATA QUALITY
Estimated based on a structural
alert for chlorinated hydrocarbons
and professional judgment.
LOW: TCEP is not a skin sensitizer in guinea pigs.
Not sensitizing to guinea pigs
EC, 2000; OECD-SIDS, 2006
Limited study details reported in a
secondary source.
No data located.
No data located.
LOW: TCEP produced mild conjunctival irritation in rabbits.
Mild conjunctival irritation, rabbits
Not irritating to rabbit eyes
Not irritating to rabbit eyes
OECD-SIDS, 2006
EC, 2000
EC, 2000
Limited study details reported in a
secondary source; Study conducted
in accordance with OECD
Guideline 404.
Limited study details reported in a
secondary source; Study conducted
in accordance with GLP and
Directive 84/449/EEC, B.5 or
OECD Guideline 405.
Limited study details reported in a
secondary source.
LOW: TCEP was slightly irritating to rabbit skin.
Mild skin irritation, rabbits
Slightly irritating to rabbit skin
Not irritating to rabbit skin
OECD-SIDS, 2006
EC, 2000
EC, 2000
Limited study details reported in a
secondary source; Study was
conducted in accordance with
OECD Guideline 404.
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source; Study was
conducted in accordance with GLP
7-677
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
Endocrine Activity
DATA
REFERENCE
DATA QUALITY
and Directive 84/449/EEC, B.4 or
OECD Guideline 404.
TCEP increased 17-estradiol (E2) and testosterone (T) concentrations following exposure for 48 hours in
human H295R cells and inhibited luciferase expression induced by dihydrotestosterone in a reporter gene
assay. TCEP was negative for estrogenic activity in a yeast two-hybrid assay and was not an estrogen
receptor antagonist in human MVLN cells following a 72-hour incubation period. There were no adverse
effects on endocrine glands of rats and mice administered TCEP via oral gavage for up to 103 weeks.
In 103-week oral studies, rats were
gavaged with TCEP at 0, 44 or 88
mg/kg-day and mice were gavaged with
TCEP at 0, 175, or 350 mg/kg-day, 5
days/week. There were no adverse
effects on endocrine glands in either
species reported.
No estrogenic or anti-estrogenic activity
of TCEP in human endometrial cancer
cells in a recombinant yeast reporter
gene assay
TCEP inhibited luciferase expression
induced by dihydrotestosterone in a
reporter gene assay
No estrogen receptor antagonism in
human MVLN cells following 72-hour
incubation up to 10 mg/L TCEP
Increased 17B-estradiol (E2) and
testosterone (T) concentrations
following exposure to >0.1 mg/TCEP
for 48 hours in human H295R cells.
Negative for estrogenic activity in a
yeast two-hybrid assay
NTP, 1991; Matthews et al., 1993
(as cited in ATSDR, 2012)
Follmann and Wober, 2006
HSDB, 2013
Liu etal., 2012
Liu etal., 2012
Nishihara et al., 2000
Sufficient study details reported.
Sufficient study details reported in
primary source.
Limited details reported in
secondary source; study is in
Chinese with an English abstract.
Sufficient study details reported in
primary source.
Sufficient study details reported in
primary source.
Sufficient study details reported in
primary source.
7-678
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
Immunotoxicity
ECOSAR Class
Immune System Effects
DATA
REFERENCE
DATA QUALITY
TCEP produced a dose-dependent growth inhibition in B cells but not T cells in a mouse lymphocyte
mitogenesis test. The IC50 was l.OxlO"5 mol/L.
Lymphocyte mitogenesis test, mouse
splenic lymphocyte cells; dose-
dependent growth inhibition in B cell
test but no inhibition in T cell test. IC50
(50% inhibition concentration): l.OxlO"5
mol/L
In 103 week oral studies, rats were
gavaged with TCEP at 0, 44 or 88
mg/kg-day and mice were gavaged with
TCEP at 0, 175, or 350 mg/kg-day 5
days/week.
There were no adverse effects on
lymphoreticular tissues in either species.
Sakazakietal., 2001
NTP, 1991; Matthews et al., 1993
(as cited in ATSDR, 2012)
Sufficient study details reported in
a primary source.
Sufficient study details reported.
ECOTOXICITY
Acute Aquatic Toxicity
Fish LC50
HIGH: Based on experimental LC50 values of 6.3 and 4.9 mg/L for fish and daphnia, respectively and an
acute EC50 of 1.1 mg/L for algae.
Freshwater fish (Oryzias latipes) 96-
hour LC50 = 6.3 mg/L
(static test conditions)
(Experimental)
Freshwater fish (Carassius auratus) 96-
hour LC50 = 90 mg/L
(Experimental)
Freshwater fish (Oryzias latipes) 96-
hour LC50 = 210 mg/L
(static test conditions)
(Experimental)
Freshwater fish (Salmo gairdneri} 96-
EC, 2000
Sasaki et al., 1981 (as cited in
WHO, 1998; EU, 2009)
Sasaki et al., 1981 (as cited in
WHO, 1998; EC, 2000; EU, 2009)
WHO, 1998; EC, 2000; EU, 2009
Limited study details reported in a
secondary source; Study was
conducted in accordance with
OECD Guideline 203. No data on
analytical monitoring.
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source. No data on
analytical monitoring.
Limited study details reported in a
7-679
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
hour LC50 = 249 mg/L NOEC = 50
mg/L
(static test conditions; test dilution was
clear and colorless with colorless
droplets of material on the surface)
(Experimental)
Freshwater fish (Oryzias latipes) LC50 =
251 mg/L
(Experimental)
Freshwater fish (Leuciscus idus) 48-hour
LC50 = ca. 200 mg/L
(static test conditions)
(Experimental)
Freshwater fish {Oryzias latipes) 48-
hour LC50 = 300 mg/L
(static test conditions)
(Experimental)
Freshwater fish (Carassius auratus)
168-hour/7 day LC0/EC0 = 5 mg/L;
(static test conditions)
(Experimental)
Freshwater fish (Cyprinus carpio) 6-day
LC0 (dietary exposure) = 35 - 156 mg/kg
food
(Experimental)
Freshwater fish (Cyprinus carpio) 6-day
LC0 = 156 mg/kg food
(Experimental)
Freshwater fish 96-hour L C50 =51
mg/L
(Estimated)
ECOSAR: Esters
REFERENCE
Yoshioka et al., 1986 (as cited in
WHO, 1998)
EC, 2000; EU, 2009
MITI, 1992b (as cited in EC, 2000;
WHO, 1998; EU, 2009)
EC, 2000; EU, 2009
EC, 2000
EU, 2009
ECOSAR v 1.11
DATA QUALITY
secondary source; Study was
conducted in accordance with GLP
and OECD Guideline 203. No
analytical monitoring was
conducted.
Limited study details reported in a
secondary source.
Limited study details reported in a
secondary source. No data on
analytical monitoring.
Limited study details reported in a
secondary source. No data on
analytical monitoring.
Limited study details reported in a
secondary source. No data on
analytical monitoring.
Limited study details reported in a
secondary source. No data on
analytical monitoring.
Limited study details provided in a
secondary source.
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
7-680
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
Daphnid LC50
Green Algae EC50
DATA
Daphnia magna 24-hour EC50 = 4.9
mg/L
(Experimental)
Daphnia magna 24-hour EC50 = 235
mg/L
(Experimental)
Daphnia magna 24-hour EC50 = 340
mg/L; EC0 = 100 mg/L; EC100 = 1,000
mg/L
(Experimental)
Daphnia magna 24-hour EC50 = 45 1
mg/L
(Experimental)
Daphnia LC50 = 1,000 mg/L
(Experimental)
Daphnid 48-hour LC50 > 100 mg/L
(Estimated)
ECOSAR: Esters
Green algae (Scenedesmus subspicatus )
72-hour EC50 = 1.1 mg/L (biomass)
Green algae (Scenedesmus subspicatus)
72-hour EC50 = 3.6 mg/L (growth rate)
(Experimental)
Green algae (Scenedesmus subspicatus )
96-hour EC50 = 1.2 mg/L (biomass)
(Experimental)
Green algae (Scenedesmus subspicatus )
48-hour EC50 = 2 mg/L (biomass)
REFERENCE
EC, 2000
EC, 2000; EU, 2009
EC, 2000; EU, 2009
EC, 2000; EU, 2009
Yoshioka et al., 1986 (as cited in
WHO, 1998)
ECOSAR v 1.11
EC, 2000; EU, 2009
EC, 2000; EU, 2009
EC, 2000; EU, 2009
DATA QUALITY
Limited study details reported in a
secondary source; Study conducted
in accordance with OECD
Guideline 202. No data on
analytical monitoring.
Limited study details reported in a
secondary source. No data on
analytical monitoring.
Limited study details reported in a
secondary source; Study conducted
in accordance with Directive
84/449/EEC, C.2.
Limited study details reported in a
secondary source. Non-GLP; no
data on analytical monitoring.
Limited study details provided in a
secondary source; study duration
not reported.
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
Limited study details reported in a
secondary source. Non-GLP; no
data on analytical monitoring.
Limited study details reported in a
secondary source; no data on
analytical monitoring.
Limited study details reported in a
secondary source; no data on
7-681
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
Green algae (Scenedesmus subspicatus}
48-hour EC50 = 5 mg/L (growth rate)
(Experimental)
Green algae (Scenedesmus subspicatus )
72-hour EC50 = 271-278 mg/L (growth
rate)
NOEC= 100 mg/L
(Experimental)
Green algae (Scenedesmus subspicatus )
72-hour EC50 = 3.6 mg/L (growth rate)
(Experimental)
Green algae (Scenedesmus subspicatus )
48-hour EC50 = 5 mg/L (growth rate)
(Experimental)
Green algae (Pseudokirchneriella
subcapitata ) 96-hour EC50 = 117 mg/L
(growth rate)
NOEC = 5 mg/L
(Experimental)
Green algae 96-hour EC50 = 48 mg/L
(Estimated)
ECOSAR: Esters
REFERENCE
EC, 2000; EU, 2009
EC, 2000; EU, 2009
EC, 2000; EU, 2009
EC, 2000; EU, 2009
ECOSAR v 1.11
DATA QUALITY
analytical monitoring.
Limited study details reported in a
secondary source. Study conducted
in accordance with GLP and OECD
Guideline 201. Analytical
monitoring was performed.
Limited study details reported in a
secondary source; no data on
analytical monitoring.
Limited study details reported in a
secondary source; no data on
analytical monitoring.
Limited study details reported in a
secondary source. Study conducted
in accordance with GLP and OECD
Guideline 201. No analytical
monitoring.
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
7-682
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Chronic Aquatic Toxicity
HIGH: Two experimental studies were located for daphnia and two for algae, while there were no
experimental chronic aquatic toxicity data for fish. The experimental 14 and 21-day NOECs of 1.9 and 13
mg/L in Daphnia magna and NOECs of 5 and 100 mg/L in Pseudokirchneriella subcapitata are within the
Moderate - Low hazard designation range; however, chronic aquatic toxicity in fish cannot be ruled out
due to the lack of experimental data . An estimated chronic aquatic toxicity value derived using an acute-
to-chronic ratio (ACR) for the phosphate esters class and was applied to the available experimental acute
data for this chemical and indicated a High hazard. ECOSAR estimates (Esters class) indicate a Moderate
to Low hazard in fish, daphnia, and algae. In addition, this substance has been assigned the risk phrase
R51/53: Toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment
(ESIS, 2012). There is potential concern based on estimates and the uncertainty due to the lack of
experimental data; therefore a High hazard designation was assigned.
Fish ChV
Freshwater fish ChV = 0.26 mg/L
(Estimated)
Fish ChV = 4.04 mg/L
(Estimated)
ECOSAR: Esters
Professional judgment
ECOSAR v 1.11
An ACR of 24 was derived for the
phosphate ester class based on
experimental data for Tris (p-t-
butylphenyl) phosphate (TBPP).
The acute-to-chronic ratio was
applied to available experimental
acute fish data for Tris (2-
chloroethyl) phosphate (ChV = 6.3
mg/L/24= 0.26 mg/L)
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
Daphnid ChV
Daphnia magna 14-day NOEC =1.9
mg/L
(Experimental)
EC, 2000
Daphnia magna 21-day NOEC =13
mg/L (reproduction rate)
(Experimental)
EC, 2000
Limited study details reported in a
secondary source; Study conducted
in accordance with OECD
Guideline 202. No data on
analytical monitoring.
Limited study details reported in a
secondary source; no data on
analytical monitoring.
7-683
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
Green Algae ChV
Transport
Henry's Law Constant (atm-
m3/mole)
DATA
DaphniaChV> lOmg/L
(Estimated)
ECOSAR: Esters
Green algae (Scenedesmus subspicatus )
72-hour (growth rate)
NOEC= lOOmg/L
(Experimental)
Green algae (Pseudokirchneriella
subcapitata ) 96-hour (growth rate)
NOEC = 5 mg/L
(Experimental)
Green algae ChV > 10 mg/L
(Estimated)
ECOSAR: Esters
REFERENCE
ECOSAR v 1.11
EC, 2000; EU, 2009
EC, 2000; EU, 2009
ECOSAR v 1.11
DATA QUALITY
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
Limited study details reported in a
secondary source. Study conducted
in accordance with GLP and OECD
Guideline 20 1 . Analytical
monitoring was performed.
Limited study details reported in a
secondary source. Study conducted
in accordance with GLP and OECD
Guideline 201. No analytical
monitoring.
Estimate for the Esters class was
provided for comparative purposes.
See Section 5.5.1.
ENVIRONMENTAL FATE
Level III fugacity models incorporating available physical and chemical property data indicate that at
steady state, TCEP is expected to be found primarily in soil and to a lesser extent, water. TCEP is expected
to have high mobility in soil, based on estimated K0c values. Leaching through soil to groundwater may
occur, though it is not expected to be an important transport mechanism. Estimated volatilization half-lives
indicate that it will be non-volatile from surface water. Volatilization from dry surface is also not expected
based on its vapor pressure. In the atmosphere, TCEP is expected to exist in the vapor phase based on its
vapor pressure.
2.6xlO'8 (Estimated)
<10'8 (Estimated)
EPIv4.11
EPIv4.11
Estimated by the HENRYWIN
program Bond estimation method.
Estimated from the measured
Water Solubility and extrapolated
Vapor Pressure.
7-684
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Sediment/Soil
Adsorption/Desorption - K0
100 (Estimated)
EPIv4.11
Estimated by the KOCWIN Log
Kow method using the measured
Log Kow value, 1.78.
390 (Estimated)
EPIv4.11
Estimated by the KOCWIN MCI
method.
Level III Fugacity Model
Air = 0.004%
Water =10.9%
Soil = 88.8%
Sediment = 0.26% (Estimated)
EPIv4.11
Values were obtained from the
measured log Kow, water solubility
and extrapolated vapor pressure.
Persistence
MODERATE: Based on guideline experimental biodegradation data that taken together indicate that the
resultant half-life is expected to be greater than 16 days but less than 60 days and therefore is consistent
with the moderate hazard designation. After 48 days 70-90% degradation of TCEP occurred in activated
sludge inoculum using OECD 301B, 50-90% degradation with adapted activated sludge using OECD 302A
and 45% degradation after 4 weeks with OECD 301C. No degradation was found in an anaerobic
biodegradation study after 58 days using ISO DIS 11734. TCEP is expected to hydrolyze slowly; although
hydrolysis rates will be dependent on temperature and pH conditions according to experimental studies.
TCEP is not expected to be susceptible to direct photolysis by sunlight, since it does not absorb light at
wavelengths >290 nm. TCEP is not susceptible to significant degradation by ozone or hydroxyl radicals in
experimental studies of water samples. The atmospheric half-live of vapor-phase TCEP is estimated to be
less than one day.
Water
Aerobic Biodegradation
Passes Ready Test: No
Test method: OECD TG 301C:
Modified MITI Test (I)
4% degradation (by BOD) after a 4-
week incubation period using an
activated sludge inoculum (30 mg/L,
predominantly domestic sludge, non-
adapted) and 100 mg/L test substance
(Measured)
Passes Ready Test: No
Test method: OECD TG 301B: CO2
Evolution Test
MITI, 1992a; EC, 2000
EC, 2000
Guideline study performed
according to Japanese MITI and
OECD guidelines.
Adequate, guideline study.
7-685
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Activated sludge inoculum, 20 mg/L
concentration of test substance, 70-90%
degradation after 48 days; Result:
Inherently biodegradable (Measured)
Study results: 100%
Test method: Other
Isolated bacterial cultures containing
Sphingobium sp. strain TCM1 and
Xanthobacter autotrophicus strain GJ10
degraded TCEP and the metabolite 2-
chloroethanol (Measured)
Takahashi et al., 2012
Nonguideline pure culture study
indicating the potential for
complete bacterial biodegradation.
Study results: 50-90%/24 hour
Test method: 302A: Inherent - Modified
SCAS Test
Degradation reported as 50-90% after 24
hours; domestic, adapted activated
sludge inoculum; 13 mg/L concentration
of test substance; the 50-90%
degradation was found within 24 hours
after test periods ranging from 4 to 13
weeks. (Measured)
EC, 2000
Adequate, guideline study.
Study results: 15%/21 days
Test method: 302B: Inherent - Zahn-
Wellens/EMPA Test
Degradation reported as 15% after 21
days; industrial non-adapted activated
sludge inoculum (Measured)
EC, 2000
Adequate, guideline study.
Study results: 13%/28 days
Test method: Other
EC, 2000
Nonguideline test conducted by a
manufacturer.
7-686
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Method: domestic activated sludge
inoculum; 20 mg/L concentration of test
substance (Measured)
Study results: <10%/27 days
Test method: 302B: Inherent - Zahn-
Wellens/EMPA Test
Degradation reported as <10% after 27
days; Industrial, non-adapted activated
sludge inoculum (Measured)
EC, 2000
Adequate, guideline study.
Study results: 4%/28 days
Test method: Other
Method: domestic activated sludge
inoculum; 20 mg/L concentration of test
substance (Measured)
EC, 2000
Nonguideline test conducted by a
manufacturer.
Isolated bacterial cultures containing
Acidovorax sp. BSB421 and
Sphingomonas agrestis completely
degraded 20 (iM TCEP within 6 hours
when they are the sole phosphorus
sources. (Measured)
Takahashi et al., 2008, 2010
Nonguideline pure culture study
indicating the potential for
complete bacterial biodegradation.
Volatilization Half-life for
Model River
>1 year (Estimated)
EPIv4.11
Estimation model was calculated
using all applicable measured input
values and the Henry's Law
Constant obtained from the
measured water solubility and
extrapolated vapor pressure.
7-687
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
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
DATA
>1 year (Estimated)
Study results: DT50 = 167
Test method: Other
DT90 »100 days based on 5 mg/kg soil
in a laboratory test for 100 days; kinetic
curve fitted to a 2nd order square root
function (Measured)
Study results: 0%/58 days
Test method: Other
Method = ISO DIS 1 1734; 80 mg/L
concentration test substance related to
DOC (Dissolved Organic Carbon); Test
condition of 35°C +/- 2°C (Measured)
0.5 days (Estimated)
0% Not a significant fate process
(Estimated)
Direct photolysis was insignificant;
second-order rates of reaction
determined by ultraviolet and ozone
generated -OH in water. (Measured)
<10% removal of TCEP in tertiary-
REFERENCE
EPIv4.11
EU, 2009
EC, 2000
EPIv4.11
Professional judgment; Mill, 2000
Watts and Linden, 2009
Wert et al., 2009
DATA QUALITY
Estimation model was calculated
using all applicable measured input
values and the Henry' s Law
Constant obtained from the
measured water solubility and
extrapolated vapor pressure.
Nonguideline study reported in a
secondary source.
Adequate guideline study.
No data located.
No data located.
This compound does not contain
functional groups that would be
expected to absorb light of
wavelengths >290 nm.
Nonguideline study.
Nonguideline study indicating
7-688
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Hydrolysis
treated effluent samples collected from
three waste water treatment facilities
when exposed to O3 (Measured)
0%/1 day Hydrolysis measured in
buffered water at 20°C; pH 2 to pH 12
with a chlorine concentration (100
mg/L) from calcium hypochlorate and
hydrochloric acid. 100% of the chemical
remained after one day at pH 2 to pH 8.
(Measured)
Ishikawa and Baba, 1988
5%/l day Hydrolysis measured in
buffered water at 20°C and pH 2 to pH
12 with a chlorine concentration (100
mg/L) from calcium hypochlorate and
hydrochloric acid. 95% of the chemical
remained after one day at pH 10. 40%
remained after one day at pH 12.
(Measured)
Ishikawa and Baba, 1988
50%/20 days at pH 5 to pH 9
50%/17 days at pH 10 (Estimated)
EPIv4.11
Slow hydrolysis in water; hydrolysis
increases with temperature and at the
extremes of the pH range. (Estimated)
IPCS, 1998
limited susceptibility to hydroxyl
radical degradation.
Adequate hydrolysis study
examining hydrolysis in a water
treatment facility.
Adequate hydrolysis study
examining hydrolysis in a water
treatment facility.
Estimate generated by the
HYDROWIN program. For
phosphate esters, HYDROWIN
estimates hydrolysis half-lives that
consider both base-catalyzed and
neutral hydrolysis rate constants at
25 °C. Based on measured
hydrolysis data that indicates little
hydrolysis at acidic or neutral pH
over a one-day period (Ishikawa
and Baba, 1988), the estimates at
pH 5 to pH 7 may be too fast.
Supporting information provided in
a secondary source.
7-689
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
Environmental Half-life
Bioaccumulation
Fish BCF
Other BCF
DATA
120 days (Estimated)
REFERENCE
PBT Profiler
DATA QUALITY
Half-life estimated for the
predominant compartment (soil), as
determined by EPI and the PBT
Profiler methodology.
LOW: Based on multiple experimental BCF values in four different species that are below 100, the cutoff
for the Low bioaccumulation designation criteria. Biomonitoring studies have reported the detection of this
compound in aquatic species, mammalian species, herring gull eggs and pine needles; DfE criteria
specifically require these data to be considered in the hazard designation on a case by case basis. Available
toxicokinetic studies indicate that in some species, metabolites of TCEP are rapidly formed and eliminated.
This demonstrates that these materials are likely bioavailable and could be observed in a biological matrix.
However, the rate of metabolism and elimination may be successfully competing with that of uptake, which
is also consistent with the experimental BCF results. The biomonitoring studies are not inconsistent with a
Low designation.
0.8 Cyprinus carpi o Mean water
concentration of 1 mg/L; 42 days
exposure (Measured)
2.2 Oryzias latipes Static test system;
96-hour exposure period; 4 mg/L
concentration test substance (Measured)
1.3 Oryzias latipes Flow-through test
system; 96-hour exposure period; 4
mg/L concentration test substance
(Measured)
0.9 Carassius auratus Static test with a
96-hour exposure period to 4 mg/L test
substance (Measured)
5.1 Cyprinus carpio Whole body tissue
analysis, a mean water concentration of
100 (ig/L; 42 days exposure in flow-
through system (Measured)
EC, 2000
EC, 2000
EC, 2000
EC, 2000
MITI, 1992a
Nonguideline study conducted for a
manufacturer.
Nonguideline study conducted for a
manufacturer.
Nonguideline flow-through study
conducted for a manufacturer.
Nonguideline study conducted for a
manufacturer.
Japanese MITI guideline study.
No data located.
7-690
-------
Tris (2-chloroethyl) phosphate CASRN 115-96-8
PROPERTY/ENDPOINT
BAF
Metabolism in Fish
DATA
6.3 (Estimated)
REFERENCE
EPIv4.11
ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring
Ecological Biomonitoring
Human Biomonitoring
DATA QUALITY
Estimated by the BCFBAF
program using the measured log
Kow (1.78) and the Arnot-Gobas
method (upper trophic).
No data located.
Detected in house dust, indoor air, urban and suburban air, river and sea sediments, surface waters, drinking
water, wastewater effluents, ground waters, rainwater samples and food samples (IARC, 1990; Suzuki et al.,
1994; Andresen et al., 2007; Bacaloni et al., 2008; Takigami et al., 2008, 2009; EU, 2009; Dougherty et al., 2010;
Regnery and Puttmann, 2010a, 2010b; Ali et al., 2012a, 2012b; Alvarez et al., 2012; ATSDR, 2012; Bergh et al.,
2012; Bollmann et al., 2012; Cao et al., 2012; Dodson et al., 2012; Matamoros and Salvado, 2012; Matamoros et
al., 2012; Moller et al., 2012; Rodil et al., 2012; Eggen et al., 2013; HSDB, 2013; Kim et al., 2013; Kolpin et al.,
2013; Salamova et al., 2014).
Detected in pine needle samples collected in the Sierra Nevada foothills in California; herring gull eggs; mussel,
fish and shellfish samples (Yasuhara and Morita, 1987; IARC, 1990; IPCS, 1998; EU, 2009; Chen et al., 2012 ).
This chemical was not included in the NHANES biomonitoring report (CDC,
2009).
7-691
-------
ATSDR (2012) Toxicological profile for phosphate ester flame retardants. Atlanta, GA: Agency for Toxic Substances and Disease Registry.
Ali N, Dirtu AC, Eede NV, et al. (2012a) Occurrence of alternative flame retardants in indoor dust from New Zealand: Indoor sources and human
exposure assessment. Chemosphere 88(11): 1276-1282.
Ali N, Van den Eede N, Dirtu AC, et al. (2012b) Assessment of human exposure to indoor organic contaminants via dust ingestion in Pakistan.
Indoor Air 22(3):200-211.
Alvarez David A, Rosen Michael R, Perkins Stephanie D, et al. (2012) Bottom sediment as a source of organic contaminants in Lake Mead,
Nevada, USA. Chemosphere 88(5):605-611.
Andresen JA, Muir D, Ueno D, et al. (2007) Emerging pollutants in the North Sea in comparison to Lake Ontario, Canada, data. Environ Toxicol
Chem 26(6): 1081-1089.
Bacaloni A, Cucci F, Guarino C, et al. (2008) Occurrence of organophosphorus flame retardant and plasticizers in three volcanic lakes of central
Italy. Environ Sci Technol 42(6): 1898-1903.
Bergh C, Luongo G, Wise S, et al. (2012) Organophosphate and phthalate esters in standard reference material 2585 organic contaminants in
house dust. Anal Bioanal Chem 402(l):51-59.
Bollmann UE, Moller A, Xie Z, et al. (2012) Occurrence and fate of organophosphorus flame retardants and plasticizers in coastal and marine
surface waters. Water Res 46(2):531-538.
Bullock CH, Kamienski FX (1972) Richmond, California: Stauffer Chemical Company, Western Research Center.
Burka LT, Sanders JM, Herr DW, et al. (1991) Metabolism of tris(2-chloroethyl) phosphate in rats and mice. Drug Metab Dispos 19(2):443-447.
CDC (2009) Fourth national report on human exposure to environmental chemicals. Atlanta, GA: Centers for Disease Control and
Prevention, http://www.cdc.gov/exposurereport/pdf/FourthReport.pdf.
California EPA (2013) Chemicals known to the state to cause cancer or reproductive toxicity July 05, 2013. California Environmental Protection
Agency, http://oehha.ca.gov/prop65/prop65 list/files/P65single072613.pdf
Cao S, Zeng X, Song H, et al. (2012) Levels and distributions of organophosphate flame retardants and plasticizers in sediment from Taihu Lake,
China. Environ Toxicol Chem 31(7): 1478-1484.
7-692
-------
CELLTECH (2009) Material safety data sheet FR-100 flame retardant additive. Cellular Technology International Inc.
Chapin R, Gulati D, Barnes L (1997) Reproductive toxicology. Tris(2-chloroethyl)phosphate. Environ Health Perspect 105(Suppl l):365-366.
Chapman DE, Michener SR, Powis G (1991) Metabolism of the flame retardant plasticizer tris(2-chloroethyl)phosphate by human and rat liver
preparations. Fundam Appl Toxicol 17(2):215-224.
Chen D, Letcher RJ, Chu S (2012) Determination of non-halogenated, chlorinated and brominated organophosphate flame retardants in herring
gull eggs based on liquid chromatography-tandem quadrupole mass spectrometry. J Chromatogr A 1220:169-174.
Dishaw LV, Powers CM, Ryde IT, et al. (2011) Is the PentaBDE replacement, tris (l,3-dichloro-2-propyl) phosphate (TDCPP), a developmental
neurotoxicant? Studies in PC12 cells. Toxicol Appl Pharmacol 256(3):281-289.
Dodson Robin E, Perovich Laura J, 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.
Dougherty JA, Swarzenski PW, Dinicola RS, et al. (2010) Occurrence of herbicides and pharmaceutical and personal care products in surface
water and groundwater around Liberty Bay, Puget Sound, Washington. Journal of Environmental Quality 39(4): 1173-1180.
EC (2000) [Tris(2-chloroethyl) phosphate CAS No. 115-96-8]. IULCID dataset. European Commission, European Chemicals Bureau.
ECHA (2009) Substance name: Tris (2-chloroethyl) phosphate, EC number: 204-118-5, CAS number: 115-96-8. Member State Committee support
document for identification of tris(2-chloroethyl) phosphate as a substance of very high concern because of its CMR properties. European
Chemicals Agency. http://echa.europa.eu/documents/10162/dOf5cl71-5086-49c3-a6a3-3a31cb4e08eb.
ECOSAR (Ecological Structure Activity Relationship), Version 1.11. Washington, DC: U.S. Environmental Protection
Agency, http://www.epa.gov/oppt/newchems/tools/21 ecosar.htm.
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/.
7-693
-------
EU (2009) European Union risk assessment report tris (2-chloroethyl) phosphate, TCEP.
Eggen T, Heimstad ES, Stuanes AO, et al. (2013) Uptake and translocation of organophosphates and other emerging contaminants in food and
forage crops. Environ Sci Pollut Res Int 20(7):4520-4531.
Follmann W, Wober J (2006) Investigation of cytotoxic, genotoxic, mutagenic, and estrogenic effects of the flame retardants tris-(2-chloroethyl)-
phosphate (TCEP) andtris-(2-chloropropyl)-phosphate (TCPP) in vitro. Toxicol Lett 161(2): 124-134.
Galloway SM, Armstrong MJ, Reuben C, et al. (1987) Chromosome Aberrations And Sister Chromatid Exchanges in Chinese Hamster Ovary
Cells: Evaluations of 108 Chemicals. Environ Mol Mutagen 10(Suppl 10): 1-175.
Gardner JR (1987) Acute oral toxicity to rats of trichloropropyl phosphate. Huntingdon, England: Huntingdon Research Center.
HSDB (2013) Tris(2-chloroethyl) phosphate-. Hazardous Substances Data Bank. National Library of Medicine, http://toxnet.nlm.nih.gov/cgi-
bin/sis/htmlgen?HSDB.
Hardin BD, Schuler RL, Burg JR, et al. (1987) Evaluation of 60 chemicals in a preliminary developmental toxicity test. Teratogenesis,
Carcinogenesis, and Mutagenesis 7:29-48.
Herr DW, Sanders JM, Matthews HB (1991) Brain distribution and fate of tris(2-chloroethyl) phosphate in Fischer 344 rats. Drug metabolism and
disposition: the biological fate of chemicals 19(2):436-442.
IARC (1990) IARC Monographs on the evaluation of carcinogenic risks to humans - Some flame retardants and textile chemicals, and exposures
in the textile manufacturing industry. World Health Organization, Distribution and Sales 27
IPCS (1998) Flame retardant: Tris(2-chloro ethyl)phosphate. Environmental Health Criteria 209(1998):51-94.
Ishikawa S, Baba K (1988) Reaction of organic phosphate esters with chlorine in aqueous solution. Bull Environ Contam Toxicol 41:143-150.
Kawashima K, Tanaka S, Nakaura S, et al. (1983) Effect of oral administration of tris(2-chloroethyl)phosphate to pregnant rats on prenatal and
postnatal developments. Eisei Shikenjo Hokoku 101:55-61.
Kim J, Isobe T, Sudaryanto A, et al. (2013) Organophosphorus flame retardants in house dust from the Philippines: occurrence and assessment of
human exposure. Environ Sci Pollut Res Int 20(2):812-822.
7-694
-------
Kolpin Dana W, Blazer Vicki S, Gray James L, et al. (2013) Chemical contaminants in water and sediment near fish nesting sites in the Potomac
River basin: determining potential exposures to smallmouth bass (Micropterus dolomleu). Sci Total Environ 443:700-716.
Kubo T, Urano K, Utsumi H (2002) Mutagenicity characteristics of 255 environmental chemicals. J Health Sci 48(6):545-554.
Kynoch SR, Denton SM (1990) Acute oral toxicity to rats of tris (2-chloroethyl) phosphate. Huntingdon, England: Huntingdon Research Center.
Lehner AF, Samsing F, Rumbeiha WK (2010) Organophosphate ester flame retardant-induced acute intoxications in dogs. J Med Toxicol
6(4):448-458.
Lide DR (2008) Tris(2-chloroethyl) phosphate. CRC Handbook of chemistry and physics. 88th ed. Boca Raton, FL: CRC Press, Taylor and
Francis Group, 3-512.
Liu X, Ji K, Choi K (2012) Endocrine disruption potentials of organophosphate flame retardants and related mechanisms in H295R and MVLN
cell lines and in zebrafish. Aquat Toxicol 114-115:173-181.
Matamoros V, Salvado V (2012) Evaluation of the seasonal performance of a water reclamation pond-constructed wetland system for removing
emerging contaminants. Chemosphere 86(2): 111-117.
Matamoros V, Arias CA, Nguyen LX, et al. (2012) Occurrence and behavior of emerging contaminants in surface water and a restored wetland.
Chemosphere 88(9): 1083-1089.
Matthews HB, Dixon D, Tilson H (1990) Subchronic toxicity studies indicate that tris(2-chloroethyl) phosphate administration results in lesions in
the rat hippocampus. Toxicology and Industrial Health 6(1): 1-15.
Matthews HB, Eustis SL, Haseman J (1993) Toxicity and carcinogenicity of chronic exposure to tris(2-chloroethyl)phosphate. Fundam Appl
Toxicol 20(4):477-485.
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.
Minegishi K, Kurebayashi H, Nambaru S, et al. (1988) Comparative studies on absorption, distribution, and excretion of halogenated alkyl
phosphate flame retardants in rats. Eisei Kagaku 34(2): 102-114.
7-695
-------
MITI (1992a) 2,2-Bis (4'-hydroxy-3',5'-dibromophenyl) propane. In: Chemicals Inspection &Testing Institute, Japan, eds. Biodegradation and
bioaccumulation data of existing chemicals based on the CSCL Japan. Tokyo: Japan Chemical Industry Ecology- Toxicology & Information
Center. Ministry of International Trade & Industry, 4-14.
MITI (Ministry of International Trade and Industry) (1992b) Tris (2-chloroethyl) phosphate. In: Chemicals Inspection & Testing Institute Japan,
eds. Biodegradation and bioaccumulation data on existing chemicals based on the CSCL Japan. Tokyo: Japan Chemical Industry Ecology-
Toxicology & Information Center. Ministry of International Trade & Industry, 2-109.
Moller A, Sturm R, Xie Z, et al. (2012) Organophosphorus flame retardants and plasticizers in airborne particles over the Northern Pacific and
Indian Ocean toward the polar regions: Evidence for global occurrence. Environ Sci Technol 46:3127-3134.
Morrissey RE, Schwetz BA, Lamb JC, et al. (1988) Evaluation of rodent sperm, vaginal cytology, and reproductive organ weight data from
National Toxicology Program 13-week studies. Fundam Appl Toxicol ll(2):345-358.
Muir DCG (1984) Phosphate esters. Handbook of Environmental Chemistry Anthropogenic Substances. Berlin, Germany: Springer-Berlag, 41-66.
NICNAS (2001) Trisphosphates. NICNAS: Priority existing chemical assessment report 17.
NTP (1991) Toxicology and carcinogenesis studies of tris(2-chloroethyl) phosphate (CAS No. 115-96-8) in F344/N rats and B6C3F1 mice
(gavage studies). Research Triangle Park, NC: National Toxicology Program.
Nishihara T, Nishikawa J, Kanayama T, et al. (2000) Estrogenic activities of 517 chemicals by yeast two-hybrid assay. J Health Sci 46(4):282-298.
OECD-SIDS (2006) Tris(2-chloroethyl)phosphate (CAS No. 15-96-8). SIDS Initial Assessment Profile for SIAM 23. Organization for Economic
Cooperation and Development, Screening Information Data Set, United Nations Environment Programme.
Okamoto Y, KimuraN, Sakurai H (1974) Pyrolysis of tris(2,3-dibromopropyl) phosphate and its related compounds. Bull Chem Soc Jpn
47(5): 1299-1300.
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.
Regnery J, Puttmann W (2010a) Occurrence and fate of Organophosphorus flame retardants and plasticizers in urban and remote surface waters in
Germany. Water Res 44(14):4097-4104.
7-696
-------
Regnery J, Puttmann W (201 Ob) Seasonal fluctuations of organophosphate concentrations in precipitation and storm water runoff. Chemosphere
78(8):958-964.
Rodil R, Quintana JB, Concha-Grana E, et al. (2012) Emerging pollutants in sewage, surface and drinking water in Galicia (NW Spain).
Chemosphere 86(10): 1040-1049.
Sakazaki H, Ueno H, Umetani K, et al. (2001) Immunotoxicological evaluation of environmental chemicals utilizing mouse lymphocyte
mitogenesis test. J Health Sci 47(3):258-271.
Sala M, Gu ZG, Moens G (1982) In vivo and in vitro biological effects of the flame retardants tris(2,3-dibromopropyl) phosphate and tris(2-
chlorethyl) orthophosphate. Eur J Cancer Clin Oncol 18(12).
Salamova A, Ma Y, Venier M, et al. (2014) High levels of organophosphate flame retardants in the Great Lakes atmosphere. Environ Sci Technol
Sasaki K, Takeda M, Uchiyama M (1981) Toxicity absorption and elimination of phosphoric -acid tri esters by killifish oryzias-latipes and goldfish
carassius-auratus . Bull Environ Contam Toxicol 27(6):775-782.
Shepelskaya NR, Dyshinevich NE (1981) [An experimental study of the gonadotoxic effect of tris(chloroethyl) phosphate]. Gigiena i sanitariia
6:20-21.
Smyth HF, Carpenter CP, Weil CS, et al. (195 1) Range-finding toxicity data: List IV. Arch Ind Hyg Occup Med 4(2): 1 19-122.
Sprague GL, Sandvik LL, Brookins-Hendricks MJ, et al. (1981) Neurotoxicity of two organophosphorus ester flame retardants in hens. J Toxicol
Environ Health 8(3):507-518.
State of Washington (201 1) Rationale for reporting list of chemicals of high concern to children. Tris(2-chloroethyl) phosphate (TCEP).
Suzuki T, Yaguchi K, Ohnishi K, et al. (1994) Gas chromatographic detection of tris(2-chloroethyl) and tris(2-butoxyethyl)phosphate in
groundwater by large-sample-volume injection. J AOAC Int 77(6): 1647-165 1 .
Takada K, Yasuhara K, Nakaji Y, et al. (1989) Carcinogenicity study of tris(2-chloroethyl) phosphate in ddY mice. J Toxicol Pathol 2(2):213-222.
Takada K, Yoshimoto H, Yasuhara K, et al. (1991) [Combined chronic toxicity/carcinogenicity test of tris(2-chloroethyl)phosphate (TCEP)
applied to female mouse skin]. Eisei Shikenjo Hokoku (109): 18-24.
7-697
-------
Takahashi S, Kawashima K, Kawasaki M, et al. (2008) Enrichment and characterization of chlorinated organophosphate ester-degrading mixed
bacterial cultures. J Biosci Bioeng 106(l):27-32.
Takahashi S, Miura K, Abe K, et al. (2012) Complete detoxification of tris(2-chloroethyl) phosphate by two bacterial strains: Sphingobium sp.
strain TCM1 and Xanthobacter autotrophicus strain GJ10. Journal of Bioscience and Bioengineering 114(3):306-311.
Takahashi S, Satake I, Konuma I, et al. (2010) Isolation and identification of persistent chlorinated organophosphorus flame retardant-degrading
bacteria. Applied and Environmental Microbiology 76(15):5292-5296.
Takigami H, Suzuki G, Hirai Y, et al. (2008) Flame retardants in indoor air and dust of a hotel in Japan. Organohalogen Compounds 70:186-189.
Takigami H, Suzuki G, Hirai Y, et al. (2009) Flame retardants in indoor dust and air of a hotel in Japan. Environ Int 35(4):688-693.
Tilson F£A, Veronesi B, McLamb RL, et al. (1990) Acute exposure to tris(2-chloroethyl)phosphate produces hippocampal neuronal loss and
impairs learning in rats. Toxicol Appl Pharmacol 106(2):254-269.
Ulsamer AG, Osterberg REC, McLaughlin J Jr (1980) Flame-retardant chemicals in textiles. Clin Toxicol 17(1):101-131.
Van den Eede N, Maho W, Neels H, et al. (2013) Metabolism of phosphate flame retardants and plasticisers using human liver fractions. Sixth
International Symposium on Flame Retardants, San Francisco, CA, April 7-10, 2013
Vogel EW and Nivard MJ (1993) Performance of 181 chemicals in a Drosophila assay predominantly monitoring interchromosomal mitotic
recombination. Mutagenesis 8(1):57-81.
WHO (1998) International Programme on Chemical Safety (IPCS), Environmental Health Criteria 209, Flame retardants:
tris(chloropropyl)phosphate and tris(2-chloroethyl)phosphate. Geneva: International Programme on Chemical Safety, World Health
Organisation. http://whqlibdoc.who.int/ehcAVHO EHC 209.pdf.
Watts MJ and Linden KG (2009) Advanced oxidation kinetics of aqueous trialkyl phosphate flame retardants and plasticizers. Environ Sci
Technol 43 (8): 293 7-2942.
Wert EC, Rosario-Ortiz FL, Snyder SA (2009) Effect of ozone exposure on the oxidation of trace organic contaminants in wastewater. Water Res
43(4): 1005-1014.
Yasuhara A, Morita M (1987) Identification of volatile organic components in mussel. Chemosphere 16(10-12):2559-2566.
7-698
-------
Yoshioka Y, Ose Y, Sato T (1986) Correlation of five test methods to assess chemical toxicity and relation to physical properties. Ecotoxicol
Environ Saf 12:15-21.
7-699
-------
Tris (p-t-butylphenyl) phosphate (TBPP)
Screening Level Toxicology Hazard Summary
This table contains hazard information for each chemical; evaluation of risk considers both hazard and exposure. Variations in end-of-life processes or degradation and combustion
by-products are discussed in the report but not addressed directly in the hazard profiles. The caveats listed below must be taken into account when interpreting the information in the
table.
VL = Very Low hazard L = Low hazard = Moderate hazard = High hazard VH = Very High hazard - Endpoints in colored text (VL, L, , H, and VH) were
assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment
[(Quantitative) Structure Activity Relationships "(Q)SAR"].
Chemical
CASRN
Human Health Effects
g
jy
'M
o
H
+5
u
<
>i
'0
1
M
O
a
sS
U
>>
+*
jy
o
-*^
o
OJ
o
0)
>
1
•a
o
•-
a.
OJ
C£
sS
§
S
o.
0
3
>•
w
Q
"3
u
'M
_o
"3
•_
s
OJ
2^
o
Q
•a
S
0)
s.
0)
C£
a
o
sS
.H
-*^
*5«
0)
C/5
a
2
C/5
t?.§
o +s
2-H
& %
5« fl
a» S
M $
a
_o
-*^
sS
•c
0)
^
H
0
1
•_
HH
13
§
0)
Q
Aquatic
Toxicity
*5
u
^
_y
'3
S
A
u
Environmental
Fate
0)
u
a
8
-^^
%
2
a.
a
o
1
"3
«
CS
S
Tris (p-t-butylphenyl) phosphate
(TBPP)
78-33-1
L
M
L
L
H
M
L
VH
VH
7-700
-------
CASRN: 78-33-1
MW: 494.6
MF:
Physical Forms: Solid
Neat:
Use: Flame Retardant
SMILES:
O=P(Oc(ccc(cl)C(C)(C)C)cl)(Oc(ccc(c2)C(C)(C)C)c2)Oc(ccc(c3)C(C)(C)C)c3 (CASRN 78-33-1; tris (t-butylphenyl) phosphate);
C(C)(C)(C)clccc(OP(=O)(Oc2ccc(C(C)(C)C)cc2)Oc2ccccc2)ccl (CASRN 65652-41-7; di-t-butylphenyl phenyl phosphate);
C(C)(C)(C)clccc(OP(=O)(Oc2ccccc2)Oc2ccccc2)ccl (CASRN 56803-37-3; p-(t-butylphenyl) diphenyl phosphate)
Synonyms: Phenol, 4-(l,l-dimethylethyl)-, 1,T,1"-phosphate; Phenol, 4-(l,l-dimethylethyl)-, phosphate (3:1); Phosphate, tris(tert-butylphenyl); Tris(p-t-
butylphenyl) phosphate; Tris(p-tert-butylphenyl) phosphate; Tris(tert-butylphenyl) phosphate; l-(5,6-dimethyl-lh-benzimidazol-2-yl)ethanol; 4-(l,l-
dimethylethyl)phenol, phosphate (3:1); p-tert-Butylphenol, phosphate (3:1); Phenol, 4-(l,l-dimethylethyl)-, l,r,l"-phosphate; Phenol, 4-(l,l-dimethylethyl)-,
phosphate (3:1); Phenol, p-tert-butyl-, phosphate (3:1); Phenol, p-tert-butyl-, phosphate (3:1) (8CI); Phenol,4-(l,l-dimethylethyl)-,phosphate(3:l); Phosphate, tris(tert-
butylphenyl); Tris(4-tert-butylphenyl) phosphate; Tris(p-t-butylphenyl) phosphate; Tris(p-tert-butylphenyl) phosphate
Chemical Considerations: The alternative, TBPP, may contain a mixture of t-butyl isomers and t-butyl substituted phenyl phosphate esters depending on the
manufacturing, purification and processing of the compound. Isomers expected to be present will be discussed in this report as appropriate when determining hazard
designations. A description of the sample tested, mixture components or isomer content is included in the report when available. However this information was not
consistently reported in the literature. Chemical, fate, and toxicity data for components of the mixture represented by other CASRN were collected in the preparation
of this AA and are listed below:
Phenol, 4-(l,l-dimethylethyl)-, 1,T,1"-phosphate (CASRN 78-33-1)
Triphenyl phosphate (CASRN 115-86-6)
t-Butylphenyl diphenyl phosphate (CASRN 56803-37-3)
P-(t-butylphenyl) diphenyl phosphate (CASRN 981-40-8)
Diphenyl-2-(tert-butyl)phenylphosphate (CASRN 83242-23-3)
Bis(p-tert-butylphenyl) phenyl phosphate (CASRN 115-87-7)
Di-(t-butyl) phenyl phenyl phosphate (CASRN 65652-41-7)
Butylated triphenyl phosphate (CASRN 220352-35-2)
Phenol, (1,1-dimethylethyl)-, phosphate (3:1) (CASRN 28777-70-0)
4-(l,l-Dimethylethyl)phenyl diphenyl ester phosphoric acid mixt. With triphenyl phosphate (CASRN 96300-96-8)
Estimated values using representative structures as indicated in the SMILES section of this assessment will be used to fill assessment data gaps. EPI v4.11 was used to
estimate physical/chemical and environmental fate values in the absence of experimental data (Weil, 2001).
7-701
-------
Polymeric: No
Oligomeric: Not applicable
Metabolites, Degradates and Transformation Products: Phenol; tert-butylphenol; diphenyl phosphate; triphenyl phosphate (Heitkamp and Cerniglia, 1986;
Heitkamp et al, 1986)
Analog: TBPP isomers and t-butyl substituted phenyl phosphate
esters anticipated to be present in the commercial product were
considered in this evaluation, as indicated in the chemical
considerations section; Phosflex 7 IB for skin sensitization.
Endpoint(s) using analog values: Not applicable
Analog Structure: Not applicable
Structural Alerts: Organophosphates; Neurotoxicity (EPA, 2012).
Risk Phrases: Not classified by Annex VI Regulation (EC) No 1272/2008 (ESIS, 2012).
Hazard and Risk Assessments: Hazard and risk assessments were not identified specifically for tris (t-butylphenyl) phosphate (CASRN 78-33-1), although the
following hazard and risk assessments for related substances were found: Hydraulic Fluids Assessment by the Agency for Toxic Substances and Disease Registry; an
Environmental risk evaluation report for Tertbutylphenyl diphenyl phosphate (CASRN 56803-37-3); and an Initial risk-based prioritization of HPV chemicals for
Butylated triphenyl phosphate (ATSDR, 1997; EPA, 2008; Environment Agency, 2009).
7-702
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
PHYSICAL/CHEMICAL PROPERTIES
Melting Point (°C)
Boiling Point (°C)
Vapor Pressure (mm Hg)
>300
(Estimated)
393 Decomposes
Thermal decomposition temperature
(Measured)
405 Decomposes
Thermal decomposition temperature
(Measured)
300°C,
according to HPV assessment
guidance.
Reported for CASRN 65652-41-7
and CASRN 115-87-7.
Reported for CASRN 56803-37-3
and CASRN 98 1-40-8.
Estimated using representative
structures indicated in the
SMILES section for tris (p-t-
butylphenyl) phosphate and di-t-
butylphenyl phenyl phosphate.
Reported for CASRN 78-33-1.
The vapor pressure was
extrapolated from high
temperature data using linear log
vapor pressure versus molecular
weight approximation.
Reported for CASRN 65652-41-7.
The vapor pressure was
extrapolated from high
temperature data using linear log
vapor pressure versus molecular
weight approximation.
Reported for CASRN 56803-37-3.
7-703
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Water Solubility (mg/L)
9.6x10 fortris (p-t-butylphenyl)
phosphate;
9.3xlO'5 for di-t-butylphenyl phenyl
phosphate (Estimated)
EPIv4.11
Estimated using representative
structures indicated in the
SMILES section. Values are less
than the cutoff value, <0.001
mg/L, for nonsoluble compounds
according to HPV assessment
guidance.
0.008 (Estimated)
for t-butylphenyl diphenyl phosphate
EPIv4.11
Estimated using the representative
structure for t-butylphenyl
diphenyl phosphate indicated in
the SMILES section.
3.2 (Measured)
Saegeretal., 1979; ChemID,
2013c
A nonguideline study reported for
a commercial mixture of CASRN
56803-37-3. This value is higher
than would be expected for the
pure substance.
Log Kon
8.5
for di-t-butylphenyl phenyl phosphate;
6.6
for t-butylphenyl diphenyl phosphate
(Estimated)
EPIv4.11
Estimated using representative
structures indicated in the
SMILES section.
10
(Estimated)
EPIv4.11;EPA, 1999
Estimated for tris (p-t-
butylphenyl) phosphate. The
estimated value is greater than the
cutoff value, >10, for non-soluble
compounds according to HPV
assessment guidance.
5.12
(Measured)
EPA, 1999; ChemID, 2013c
Reported for CASRN 56803-37-3
in a nonguideline study for a
commercial mixture.
7-704
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
Flammability (Flash Point)
Explosivity
Pyrolysis
pH
pKa
DATA
Nonflammable (Estimated)
Not expected to form explosive
mixtures with air (Estimated)
Not applicable (Estimated)
Not applicable (Estimated)
REFERENCE
Professional judgment
Professional judgment
Professional judgment
Professional judgment
DATA QUALITY
No data located; based on its use
as a flame retardant.
No experimental data located;
based on its use as a flame
retardant.
No data located.
Does not contain functional
groups that are expected to ionize
under environmental conditions.
Does not contain functional
groups that are expected to ionize
under environmental conditions.
HUMAN HEALTH EFFECTS
Toxicokinetics
Dermal Absorption in vitro
Absorption,
Distribution,
Metabolism &
Excretion
Oral, Dermal or Inhaled
Other
Based on analogy to closely related compounds, TBPP is expected to have poor absorption through the
skin, lungs and GI tract. There is evidence of dermal uptake in mixtures; however, it is uncertain if
TBPP or other components of the mixture are promoting absorption.
CASRN 56803-37-5 is not readily
absorbed when applied dermally to
guinea pig skin.
MIL-H-19457C hydraulic fluid
(CASRN 28777-70-0) is rapidly
absorbed following dermal
administration
Absorption is nil through skin as neat
solid, poor through skin when in
solution, and poor through lungs and GI
tract; based on analogy to closely
related compounds
Fabian, 1982
Dodd and Smith, 1994
Professional judgment
No data located.
Data are for CASRN 56803-37-5.
Data are for MIL-H-19457C
hydraulic fluid (CASRN 28777-
70-0). Limited study details
reported in a secondary source.
Species not specified.
Data are for CASRN 56803-37-3,
65652-41-7 and 78-33-1.
7-705
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
Acute Mammalian Toxicity
Acute Lethality
Oral
Dermal
DATA
REFERENCE
DATA QUALITY
LOW: Based on experimental data for individual isomers and mixture components of TBPP via the oral,
inhalation and dermal routes of exposure in rats and rabbits.
Rat oral LD50 > 4,640 mg/kg
Rat oral LD50 > 5,000 mg/kg
Rat oral LD50 > 5 mL/kg (5,400 mg/kg)
Rat oral LD50 > 10 g/kg (10,000 mg/kg)
Rat oral LD50 > 15,800 mg/kg
Rat oral LD50 > 15,800 mg/kg
Rat oral LD50 = 20 g/kg (20,000 mg/kg)
Rabbit dermal LD50 > 2,000 or > 4,640
mg/kg
Rat dermal LD50 > 2,000 mg/kg
Murphy, 1979
Submitted confidential study
ChemID, 2013b
Hagerman, 1984
ChemID, 201 3a
Submitted confidential study
Latourette, 1981
Murphy, 1979
Submitted confidential study
Data are for CASRN 56803-37-3.
Data are for Phosflex 5 IB; 75-80
percent w/w tertbutylphenyl
diphenyl phosphate (CASRN
56803-37-3), 20-25 percent w/w
triphenyl phosphate (CASRN 115-
86-6); conducted in accordance
with OECD Guideline 401.
Study details reported in a
secondary source; data are for
CASRN 28777-70-0.
Data are for CASRN 78-33-1;
phosphen plasticiser P-7.
Study details reported in a
secondary source; data are for
CASRN 98 1-40-8.
Data are for CASRN 56803-37-3.
Data are for CASRN 56803-37-3.
Mixed tert-butylphenyl
phosphates with a MW of 335.
Data are for CASRN 56803-37-3.
Data are for Phosflex 5 IB; 75-80
percent w/w tertbutylphenyl
diphenyl phosphate (CASRN
56803-37-3), 20-25 percent w/w
triphenyl phosphate (CASRN 115-
86-6); study equivalent to a limit
test under OPPTS 870.1200
except that the group size was
7-706
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
Inhalation
Carcinogenicity
OncoLogic Results
Carcinogenicity (Rat and
Mouse)
Combined Chronic
Toxicity/Carcinogenicity
Other
DATA
Rabbit dermal LD50 > 7,900 mg/kg
Rabbit dermal LD50 > 7,900 mg/kg
Rabbit dermal LD50 > 10 g/kg (10,000
mg/kg)
Rat 4-hour inhalation LC50 > 3. 1 - 18.9
mg/L
Rat inhalation LC50 > 200 mg/L
REFERENCE
Submitted confidential study
ChemID, 2013a
Latourette, 1981
Murphy, 1979
Latourette, 1981
DATA QUALITY
3/sex rather than 5/sex.
Data are for CASRN 56803-37-3.
Study details reported in a
secondary source; data are for
CASRN 98 1-40-8.
Data are for CASRN 56803-37-3.
Mixed tert-butylphenyl
phosphates with a MW of 335.
Data are for Phosflex 5 IB; 75-80
percent w/w tertbutylphenyl
diphenyl phosphate (CASRN
56803-37-3), 20-25 percent w/w
triphenyl phosphate (CASRN 115-
86-6).
Data are for CASRN 56803-37-3.
Mixed tert-butylphenyl
phosphates with a MW of 335.
MODERATE: TBPP is estimated to have marginal risk for Carcinogenicity based on the OncoLogic
program analysis; In addition, there is uncertainty due to lack of data for this substance; carcinogenic
effects cannot be ruled out.
Marginal; likely to have equivocal
carcinogenic activity.
Professional judgment
Data are for CASRN 56803-37-3,
65652-41-7 and 78-33-1.
No data located.
No data located.
No data located.
7-707
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
Genotoxicity
Gene Mutation in vitro
Gene Mutation in vivo
Chromosomal Aberrations in
vitro
DATA
REFERENCE
DATA QUALITY
LOW: Based on experimental data for individual isomers and mixture components of TBPP, which were
negative for in vitro gene mutations and chromosomal aberrations. No in vivo data were located.
Negative, Salmonella typhimurium
strains TA97, TA98, TA100, TA1535,
TA137 with and without metabolic
activation
Negative, Salmonella typhimurium
TA98, TA100, TA1535, TA1537, or
TA1538, and Saccharomyces cerevisiae
D4 with or without metabolic activation
Negative, forward gene mutations,
cultured mouse lymphoma
L5 178Y/TK+/- cells with or without
metabolic activation
Negative, sister chromatid exchanges in
cultured mouse lymphoma
L5 178Y/TK+/- cells with or without
metabolic activation
Negative, chromosomal aberrations in
cultured mouse lymphoma
L5 178Y/TK+/-cells with or without
metabolic activation
Zeigeretal., 1987
Submitted confidential study;
Environment Agency, 2009
Submitted confidential study;
Environment Agency, 2009
Submitted confidential study;
Murphy, 1979; Environment
Agency, 2009
Submitted confidential study;
Murphy, 1979; Environment
Agency, 2009
Data are for CASRN 56803-37-3.
Data are for Phosflex 5 IB; 75-80
percent w/w tertbutylphenyl
diphenyl phosphate (CASRN
56803-37-3), 20-25 percent w/w
triphenyl phosphate (CASRN 115-
86-6). Study details reported in a
secondary source.
Data are for Phosflex 5 IB; 75-80
percent w/w tertbutylphenyl
diphenyl phosphate (CASRN
56803-37-3), 20-25 percent w/w
triphenyl phosphate (CASRN 115-
86-6). Study details reported in a
secondary source.
No data located.
Data are for Phosflex 5 IB; 75-80
percent w/w tertbutylphenyl
diphenyl phosphate (CASRN
56803-37-3), 20-25 percent w/w
triphenyl phosphate (CASRN 115-
86-6).
Data are for Phosflex 5 IB; 75-80
percent w/w tertbutylphenyl
diphenyl phosphate (CASRN
56803-37-3), 20-25 percent w/w
triphenyl phosphate (CASRN 115-
7-708
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
Chromosomal Aberrations in
vivo
DNA Damage and Repair
Other
Reproductive Effects
Reproduction/Developmental
Toxicity Screen
Combined Repeated Dose with
Reproduction/ Developmental
Toxicity Screen
DATA
REFERENCE
DATA QUALITY
86-6).
No data located.
No data located.
No data located.
MODERATE: Based on experimental data for individual isomers of TBPP and its mixture components.
No adverse reproductive effects were observed in rats fed diets containing CASRN 56803-37-3 at doses
up to 1600 ppm (107.5 mg/kg-day; LOAEL not established), while abnormal reproductive cycles and
liver effects were noted in rats administered BTP (CASRN 220352-35-2) at a dose of 1.7 g/kg (1700
mg/kg-day, only dose tested). A NOAEL of 170 mg/kg-day (without an established LOAEL) leaves
uncertainty as to what dose adverse effects could occur; it is possible that effects could occur between
107.5 mg/kg-day and 250 mg/kg-day which falls within the DfE Moderate criteria range. Using a
conservative approach, a Moderate hazard designation was assigned.
No data located.
No data located.
7-709
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Reproduction and Fertility
Effects
In an oral study, groups of intact and
ovariectomized female rats were
administered BTP at doses of 0 or 1.7
g/kg (0 or 1700 mg/kg) via oral gavage
in sesame oil vehicle or as neat BTP for
20, 40 or 60 days.
Abnormal reproductive cycles in treated
females that were significantly
prolonged in diestrus. Abnormal
reproductive cycles and liver effects
suggest fecundity could be affected as a
result of altered liver metabolism.
NOAEL: Not established
LOAEL: 1.7g/kg-day (1,700 mg/kg-
day; only dose tested)
Latendresse et al., 1995
Data are for CASRN 220352-35-
2; Only one dose tested; there is
uncertainty as to if adverse effects
may have occurred at a lower
dose.
In a reproductive study, groups of
breeding pairs of F344 rats were
administered 0, 0.6, or 1.0 g (0, 600,
1,000 mg) BTP/kg via oral gavage in
sesame oil or 1.7 g (1,700 mg) neat
BTP/kg for up to 135 days.
Significantly decreased fertility index
and number of live litters (1.0 and 1.7
g/kg-day); decreased uterine weight (1.0
g/kg-day). No adverse effects on
testicular or epididymal weights.
NOAEL: 600 mg/kg-day
LOAEL: 1,000 mg/kg-day
Latendresse et al., 1994b;
Environment Agency, 2009
Data are for a butylated triphenyl
phosphate-based hydraulic fluid
(CASRN 115-86-6) reported to
contain predominantly p-t-
butylphenyl phenyl phosphates
(84 percent wt, CASRN 220352-
35-2), with lesser amounts of
triphenyl phosphate (13 percent
wt., CASRN 115-86-6). This
study is described as invalid,
based on unknown impurities
present in the test compound and
the possibility of incorrect dosing
of animals.
Sprague-Dawley rats (12/sex/group)
were administered Phosflex 6IB at
doses of 0, 50, 250 or 1,000 mg/kg-day
Environment Agency, 2009
Data are for Phosflex 6IB; a
commercial mixture of
tertbutylphenyl diphenyl
7-710
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Other
via oral gavage for two weeks prior to
mating, during the two-week mating
period and throughout gestation and
lactation (total of ~8 weeks). No
changes in reproductive organ weights.
Histological changes in the reproductive
organs were considered to be not
treatment-related, however they were
not described in detail. No significant
difference in litter size or number of live
pups.
NOAEL > 1,000 mg/kg-day (highest
dose tested)
LOAEL: Not established
phosphate (CASRN 56803-37-3).
Purity and composition of test
substance is not provided and
study details are insufficient to
assess robustness of results.
In a 90-day study, Sprague-Dawley rats
(20/sex/group) were fed diets containing
0, 100, 400, or 1,600 ppm (average
intakes of 0, 6.6, 26.7 or 107.5 mg/kg-
day in males and 0, 7.7, 30.0 or 124.8
mg/kg-day in females) test substance.
No adverse effect on histopathology or
weights of reproductive organs in males
or females.
NOAEL: 1600 ppm (107.5 mg/kg-day
for males and 124.8 mg/kg-day for
females; highest dose tested)
LOAEL: Not established
Submitted confidential study
Data are for CASRN 56803-37-3;
there is uncertainty as to if
adverse effects may have occurred
within the Moderate hazard
criteria range (50-250 mg/kg-
day).
Rats were administered ML-H-19457C
(CASRN 28777-70-0) and tricresyl
phosphate (TCP) daily via oral gavage
for up to 10 weeks (doses not specified).
Dodd and Smith, 1994
Data are for MIL-H-19457C
hydraulic fluid (CASRN 28777-
70-0). Limited study details
reported in a secondary source;
7-711
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
The estrous cycle was extended for high
dose females administered ML-ML-H-
19457C and relative testes weight was
increased. Effects were reversed at 5
and 10 weeks post-treatment.
doses not specified.
Rats, hamsters and rabbits were exposed
to MIL-H-19457C hydraulic fluid
(CASRN 28777-70-0) via inhalation 6
hours/day at a concentration of 250
mg/m3 for 21 days or 0, 10 and 100
mg/m3 for 90 days. Effects were only
observed in rats and consisted lesions in
the ovaries after 90 days of exposure
(no further details provided).
Dodd and Smith, 1994
Data are for MIL-H-19457C
hydraulic fluid (CASRN 28777-
70-0).
Developmental Effects
LOW: Based on experimental data for mixture components of TBPP. In two studies using Santicizer 154
(a mixture containing TBPP and CASRN 56803-37-3), no biologically significant treatment-related
effects were observed in rats gavaged with up to 3,000 mg/kg-day undiluted test substance, while a
decrease in viable fetuses and increase in mean post implantation loss was noted at a dose of 5,000
mg/kg-day (NOAEL= 1,000 mg/kg-day). In a study using Phosflex 51B (a mixture containing 75-80%
CASRN 56803-37-3), embryotoxicity was indicated by reduced fetal body weight at a dose of 1,000
mg/kg-day; however, this response was considered to be secondary to maternal toxicity.
There were no data located for the developmental neurotoxicity endpoint. Decreased cholinesterase
activity in pregnant lab animals has been shown to have a negative impact on fetal brain development.
As a result, there is uncertain potential for developmental neurotoxicity for this substance.
7-712
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
Reproduction/ Developmental
Toxicity Screen
DATA
Groups of 25 pregnant CD rats received
2.5 mL of water or undiluted test
substance at doses of 300, 1,000, or
3,000 mg/kg-day via oral gavage on GD
6-19.
No adverse effect on maternal survival,
behavior, body weight gain, the
incidence of gross necropsy findings, or
most reproductive/developmental
parameters. Slight increase in yellow
staining and matting in the anogenital
area with or without staining in the
abdominal and thoracic areas (1,000 and
3,000 mg/kg-day). Increase in dried red
matter in the nasal region on forepaws
(3,000 mg/kg-day). Slight, non dose-
related increase in the percentage of
litters with skeletal malformations at
3,000 mg/kg-day (effect was not
considered to be biologically
significant).
Maternal toxicity:
NOAEL: 300 mg/kg-day
LOAEL: 1,000 mg/kg-day
Developmental toxicity:
NOAEL: 3,000 mg/kg-day (highest
dose tested)
LOAEL: Not established
In a pilot study, pregnant CD rats
(5/group) received undiluted Santicizer
154 at doses of 250, 500, 1,000, 2,500,
REFERENCE
Submitted confidential study;
Bowman, 1981; Keller, 1984
Submitted confidential study;
Bowman, 1981
DATA QUALITY
Data are for Santicizer 154; a
mixture containing 43 .2% t-butyl
phenyl diphenyl phosphate
(CASRN 56803-37-3), 40.2%
triphenyl phosphate (CASRN 115-
86-6), 14% di-t-butylphenyl
phenyl phosphate (CASRN 2528-
36-1) and 2% tri-t-butyl phenyl
phosphate (CASRN 78-33-1).
Data are for Santicizer 154; a
mixture containing 43 .2% t-butyl
phenyl diphenyl phosphate
7-713
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
Combined Repeated Dose with
Reproduction/ Developmental
Toxicity Screen
DATA
or 5,000 mg/kg-day via oral gavage on
gestational days (GD) 6-19.
Anogenital staining was observed in all
test groups and red and/or brown matter
around the nose, mouth, and forelimbs
in all receiving 5,000 mg/kg-day. Dose-
related reductions in body weight gain
for GD 0-20 were observed at > 1,000
mg/kg-day but were only biologically
significant at the highest dose.
Decreases in viable fetuses and
increases in mean post implantation
losses (5,000 mg/kg-day)
Maternal toxicity:
NOAEL: 500 mg/kg-day
LOAEL: 1,000 mg/kg-day
Developmental toxicity:
NOAEL: 2,500 mg/kg-day
LOAEL: 5,000 mg/kg-day (reduced
body weight gain; decreased number of
viable fetuses; increased mean post
implantation losses)
REFERENCE
DATA QUALITY
(CASRN 56803-37-3), 40.2%
triphenyl phosphate (CASRN 115-
86-6), 14% di-t-butylphenyl
phenyl phosphate (CASRN 2528-
36-1) and 2% tri-t-butyl phenyl
phosphate (CASRN 78-33-1).
No data located.
7-714
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
Prenatal Development
Postnatal Development
Prenatal and Postnatal
Development
DATA
Pregnant rats were administered BPDP
at doses of 0, 100, 400 and 1,000
mg/kg-day (dosing volume of 5 ml) as a
solution in corn on GDs 6-20.
Dose-related increase in maternal liver
weight. Reduced food consumption on
gravid days 6-9 at the high dose. No
adverse effects on litter size or fetal
weights. No evidence of structural
teratogenicity at any dose.
Embryotoxicity as indicated by reduced
fetal body weight at 1,000 mg/kg; this
response was considered secondary to
maternal toxicity.
Maternal toxicity:
NOAEL: 400 mg/kg-day
LOAEL: 1,000 mg/kg-day
Developmental toxicity:
NOAEL: 1,000 mg/kg-day (highest
dose tested)
LOAEL: Not established
REFERENCE
Keller, 1984
DATA QUALITY
Data are for Phosflex 5 IB; 75-80
percent w/w tertbutylphenyl
diphenyl phosphate (CASRN
56803-37-3), 20-25 per cent w/w
triphenyl phosphate (CASRN 115-
86-6).
No data located.
No data located.
7-715
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Developmental Neurotoxicity
There were no data located for the
developmental neurotoxicity endpoint.
Decreased cholinesterase activity in
pregnant lab animals has been shown to
have a negative impact on fetal brain
development. As a result, there is
uncertain potential for developmental
neurotoxicity for this substance.
Professional judgment
No data located.
Other
No data located.
Neurotoxicity
MODERATE: Based on a 3-week dermal study in rats exposed to Santicizer 154 where cholinesterase
inhibition was the major effect at 100 mg/kg-day (NOAEL = 10 mg/kg-day). Experimental data for
individual isomers and mixture components of TBPP and analogy to closely related compounds yielded
negative results for neurotoxicity in hens and rats. There is a structural alert for the neurotoxicity
endpoint based on organophosphates; however, TBPP is not expected to form intermolecular
intermediates that may result in neurotoxic mechanisms of action.
Neurotoxicity Screening
Battery (Adult)
MIL-H-19457C hydraulic fluid
(CASRN 28777-70-0) was found to
have minimal toxicity in an acute
delayed neurotoxicity test.
In two acute delayed neurotoxicity
studies, hens were treated via oral
gavage with 1,000 mg/kg test substance
5-7 times per day for 5 days. No adverse
effects on mortality or body weight
gain. No signs of ataxia; egg production
was 50-70% of controls.
NOAEL: 1,000 mg/kg (only dose
tested)
LOAEL: Not established
Dodd and Smith, 1994
Submitted confidential study
Data are for MIL-H-19457C
hydraulic fluid (CASRN 28777-
70-0). Limited study details
reported in a secondary source.
No data on test species, route of
exposure, or exposure
concentrations.
Data are for CASRN 56803-37-3;
only one dose tested.
7-716
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Other
In an acute delayed neurotoxicity study,
White Leghorn chickens were treated
via oral gavage with 10,000 mg/kg test
substance twice a day for 3 days. No
signs of ataxia or
neurohistopathological lesions.
NOAEL: 10,000 mg/kg (only dose
tested)
LOAEL: Not established
Submitted confidential study
Data are for CASRN 56803-37-3;
only one dose tested.
In a 3-week dermal study, test substance
was applied to the intact and abraded
skin of New Zealand White rabbits
(10/sex/group) at doses levels of 10,
100, or 1,000 mg/kg-day, 5 days/week.
No deaths or treatment-related changes
in clinical signs, body weight,
hematology, clinical chemistry, organ
weights, gross or microscopic lesions.
Edema and fissuring (1,000 mg/kg-day);
atonia (> 100 mg/kg-day);
desquamation (> 10 mg/kg-day);
increased blood urea nitrogen (1,000
mg/kg-day); depression of plasma
cholinesterase (> 100 mg/kg-day);
depression of erythrocyte and brain
cholinesterase (> 10 mg/kg-day).
NOAEL: 10 mg/kg-day
LOAEL: 100 mg/kg-day (based on
cholinesterase inhibition)
Submitted confidential study;
Hollister, 1979; Keller, 1984
Data are for Santicizer 154; a
mixture containing 43.2% t-butyl
phenyl diphenyl phosphate
(CASRN 56803-37-3), 40.2%
triphenyl phosphate (CASRN 115-
86-6), 14% di-t-butylphenyl
phenyl phosphate (CASRN 2528-
36-1) and 2% tri-t-butyl phenyl
phosphate (CASRN 78-33-1).
In a 90-day study, Sprague-Dawley rats
(20/sex/group) were fed diets containing
Submitted confidential study
Data are for CASRN 56803-37-3.
7-717
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
0, 100, 400, or 1,600 ppm (average
intakes of 0, 6.6, 26.7 or 107.5 mg/kg-
day in males and 0, 7.7, 30.0 or 124.8
mg/kg-day in females) test substance.
No neurohistopathology and no
inhibition of brain cholinesterase
activity.
NOAEL: 1,600 ppm (107.5 mg/kg-day
males, 124.8 mg/kg-day female; highest
dose tested)
LOAEL: Not established
No signs of neurotoxicity in rats
following acute gavage administration
of Durad 220B at dose levels as high as
5,000 mg/kg
ATSDR, 1997
Data are for Durad 200B (CASRN
28777-70-0); a t-Butylphenyl
diphenyl phosphate mixture
containing t-Butylphenyl phenyl
phosphate (CASRN 220352-35-2)
and triphenyl phosphate (CASRN
115-86-6).
Not neurotoxic by analogy to a closely
related compound which yielded
negative results in all reliable oral
assays for delayed acute neurotoxicity
in hens and subchronic neurobehavioral
assays in rats
Professional judgment
Data are for CASRN 78-33-1.
7-718
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
Repeated Dose Effects
DATA
REFERENCE
DATA QUALITY
HIGH: Based on weight of evidence for individual isomers and commercial formulation components
containing TBPP and CASRN 56803-37-3). In a 90-day inhalation study, rats exposed to Santicizer 154
aerosol showed clinical signs of toxicity, increased liver-body weight-ratios and changes in urinalysis
parameters at a concentration of 100 mg/m3 (0.1 mg/L; NOAEL= 0.01 mg/L). In a 3-week dermal study
in rats exposed to Santicizer 154, cholinesterase inhibition was the major effect at 100 mg/kg-day
(NOAEL= 10 mg/kg-day). The adrenal gland appeared to be a target organ in some inhalation and oral
studies (effects included lesions and increased weight). Several oral toxicity studies using CASRN 56803-
37-3, Phosflex 51B (a mixture containing CASRN 56803-37-3) and MIL-H-19457C hydraulic fluid
(CASRN 28777-70-0) indicate low concern for toxicity via this route of exposure.
In a 90-day inhalation study, rats
(15/sex/group) were exposed to
Santicizer- 154 aerosol at concentrations
of 0, 10 and 100 mg/m3 (actual)
analytical concentrations: 0, 10.1 and
101.1 mg/m3). No deaths attributed to
treatment. Clinical signs of toxicity at
the high dose included ptosis, ruffled
and discolored fur, rhinitis, sneezing,
hemorrhagic conjunctivitis and
wheezing. No effect on body weight
gain or clinical chemistry. Elevated
SGOT and SAP values upon urinalysis
of one high dose animal. Increased
liver-body weight-ratio in high dose
males. No gross or microscopic tissue
changes.
NOAEL: 10 mg/m3 (0.01 mg/L)
LOAEL: 100 mg/m3 (0.1 mg/L)
In a 3 -week dermal study, test substance
was applied to the intact and abraded
skin of New Zealand White rabbits
(10/sex/group) at doses levels of 10,
Clayton, 1983; Keller, 1984
Submitted confidential study;
Hollister, 1979; Keller, 1984
Data are for Santicizer 154; a
mixture containing 43 .2% t-butyl
phenyl diphenyl phosphate
(CASRN 56803-37-3), 40.2%
triphenyl phosphate (CASRN 115-
86-6), 14% di-t-butylphenyl
phenyl phosphate (CASRN 2528-
36-1) and 2% tri-t-butyl phenyl
phosphate (CASRN 78-33-1).
Data are for Santicizer 154; a
mixture containing 43 .2% t-butyl
phenyl diphenyl phosphate
(CASRN 56803-37-3), 40.2%
7-719
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
100, or 1,000 mg/kg-day, 5 days/week.
No deaths or treatment-related changes
in clinical signs, body weight,
hematology, clinical chemistry, organ
weights, gross or microscopic lesions.
Edema and fissuring (1,000 mg/kg-day);
atonia (> 100 mg/kg-day);
desquamation (> 10 mg/kg-day);
increased blood urea nitrogen (1,000
mg/kg-day); depression of plasma
cholinesterase (> 100 mg/kg-day);
depression of erythrocyte and brain
cholinesterase (> 10 mg/kg-day).
NOAEL: Not established
LOAEL: 10 mg/kg-day (Lowest dose
tested; desquamation, decreased
erythrocytes and brain cholinesterase)
triphenyl phosphate (CASRN 115-
86-6), 14% di-t-butylphenyl
phenyl phosphate (CASRN 2528-
36-1) and 2% tri-t-butyl phenyl
phosphate (CASRN 78-33-1).
In a 90-day study, Sprague-Dawley rats
(20/sex/group) were fed diets containing
0, 100, 400, or 1,600 ppm (average
intakes of 0, 6.6, 26.7 or 107.5 mg/kg-
day in males and 0, 7.7, 30.0 or 124.8
mg/kg-day in females) test substance.
No significant effect on survival, food
consumption, body weight gain,
hematology or clinical chemistry
parameters, cholinesterase values, or the
incidence of gross or microscopic
lesions. Increased liver, kidney, and
adrenal gland weight (1600 ppm).
NOAEL: 400 ppm (26.7 mg/kg-day for
Submitted confidential study;
Keller, 1984; Environment
Agency, 2009
Data are for Phosflex 5 IB; 75-80
percent w/w tertbutylphenyl
diphenyl phosphate (CASRN
56803-37-3), 20-25 percent w/w
triphenyl phosphate (CASRN 115-
86-6).
7-720
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
males and 30 mg/kg-day for females)
LOAEL: 1600 ppm (107.5 mg/kg-day
for males and 124.8 mg/kg-day for
females); (based on organ weight
changes)
In a 30-day study, Sprague-Dawley rats
(10/sex/group) were fed diets containing
0, 250, 500, 750, 1,000, or 2,000 mg/kg-
day (nominal doses of 213, 442, 660,
898, and 1,710 mg/kg-day for males and
234, 454, 690, 898, and 1,867 mg/kg-
day for females) test chemical.
No deaths. Reduced food consumption
(2,000 mg/kg-day) and body weight
gain (>750 mg/kg-day); hepatic
enlargement (all doses); discoloration of
kidneys (>500 mg/kg-day)
NOAEL: Not established
LOAEL: 250 mg/kg-day (hepatic
enlargement; lowest dose tested)
Submitted confidential study;
Keller, 1984
Data are for CASRN 56803-37-3;
study deficiencies include lack of
examinations for histopathology,
hematology, or clinical chemistry.
In a 90-day dietary study, CD rats were
fed 0 or 5 mg/kg-day test substance.
There were no compound-related effects
on any parameter tested.
NOAEL: 5 mg/kg-day (only dose
tested)
LOAEL: Not established
Keller, 1984
Data are for CASRN 56803-37-3.
In a 90-day dietary study, rats were fed
BPDP at concentrations of 0, 100, 300
or 1,000 ppm (11, 32, and 110 mg/kg-
day). There were no clinical signs of
Matheson, 1980
Data are for CASRN 56803-37-3.
Doses were reported as ppm in the
diet but were converted to mg/kg-
day using EPA 1988 reference
7-721
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
toxicity. No effect on hematology,
clinical chemistry, or urinalysis
parameters. No gross pathologic or
microscopic lesions attributed to the
BPDP.
NOAEL: 1,000 ppm (110 mg/kg-day;
highest dose tested)
LOAEL: Not established
In a 90-day dietary study, albino rats
were fed diets containing 0, 200, 1,000
or 5,000 ppm (0, 21, 110, and 530
mg/kg-day) test substance.
No deaths or effect on body weight
gain, food intake, hematology, clinical
chemistry or urinalysis parameters.
Increased mean liver and kidney weight
with no associated histopathologic
findings.
NOAEL: 5,000 ppm (530 mg/kg-day;
highest dose tested)
LOAEL: Not established
Keller, 1984
Rats, hamsters and rabbits were exposed
to MIL-H-19457C hydraulic fluid
(CASRN 28777-70-0) via inhalation 6
hours/day at a concentration of 250
mg/m3 for 21 days or 0, 10 and 100
mg/m3 for 90 days. Effects were only
observed in rats and consisted of
increased liver and kidney weight (100
and 250 mg/m3) and lesions in the
adrenal glands and ovaries (90 day
Dodd and Smith, 1994
values for body weight and food
consumption.
Data are for CASRN 56803-37-3.
Doses were reported as ppm in the
diet but were converted to mg/kg-
day using EPA 1988 reference
values for body weight and food
consumption.
Data are for MIL-H-19457C
hydraulic fluid (CASRN 28777-
70-0).
7-722
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
Skin Sensitization
Skin Sensitization
Respiratory Sensitization
(Respiratory Sensitization
DATA
exposure).
Rats were administered ML-H-19457C
(CASRN 28777-70-0) and tricresyl
phosphate (TCP) daily via oral gavage
for up to 10 weeks (doses not specified).
No mortality occurred and there was no
effect on body weight gain in either sex.
Target organs were the adrenal gland
and the liver. The estrous cycle was
extended for high dose females
administered ML-ML-H-19457C and
relative testes weights were increased.
Effects were reversed at 5 and 10 weeks
post-treatment.
Potential for systemic effects by
analogy to triphenyl phosphate (1 15-86-
6), including 28-d repeated-dose study
(inadequate), rats, diet, liver effects at
0.5%.
NOAEL:0.1%
REFERENCE
Dodd and Smith, 1994
Professional judgment
DATA QUALITY
Data are for MIL-H-19457C
hydraulic fluid (CASRN 28777-
70-0); doses not specified.
Estimated by analogy to Triphenyl
Phosphate (115-86-6); Study was
determined to be inadequate and
does not satisfy standard
guidelines.
MODERATE: TBPP is expected to have low concern for Sensitization by analogy to closely related
compounds.
Moderate concern for Sensitization by
analogy to isobutylphenyl phosphate
(68937-40-6)
(Estimated based on analogy)
Professional judgment
Estimated based on analogy to
Isobutylphenyl phosphate (68937-
40-6).
No data located.
No data located.
7-723
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
Eye Irritation
Eye Irritation
Dermal Irritation
Dermal Irritation
DATA
REFERENCE
DATA QUALITY
LOW: Based on experimental data for mixture components of TBPP. Phosflex 51B (a commercial
mixture containing 75-80% CASRN 56803-37-3), produced slight irritation in rabbit eyes which cleared
within 72 hours. Additional studies with CASRN 56803-37-3 were negative for irritation.
Slightly irritating, rabbits. Mild redness
of the conjunctiva 24- and 48-hours
after treatment; no irritation at 72- or
96-hours or 7 days after treatment.
Not irritating, rabbits
Not irritating, rabbits. Mild conjunctival
inflammation 1 hour after exposure, but
no evidence of irritation by 24 hours.
Environment Agency, 2009
Submitted confidential study;
Bowman, 1981
Submitted confidential study;
Murphy, 1979
Data are for Phosflex 5 IB; 75-80
percent w/w tertbutylphenyl
diphenyl phosphate (CASRN
56803-37-3), 20-25 percent w/w
triphenyl phosphate (CASRN 115-
86-6); study details reported in a
secondary source.
Data are for CASRN 56803-37-3.
Data are for CASRN 56803-37-3;
conducted in accordance with
OECD Guideline 405
MODERATE: Based on weight of evidence from experimental data for mixture components of TBPP.
Phosflex 51B (a commercial mixture containing 75-80% CASRN 56803-37-3), produced mild irritation
in rabbits, which cleared within 72 hours. Additional studies using CASRN 56803-37-5 resulted in very
slight or well-defined erythema in rabbits that persisted for 8-10 days and slight destruction of guinea
pig skin, but only when the test substance was dissolved in Stoddard's solution. A study using mixture
component 78-33-1 was not irritating to rabbits.
Mildly irritating, rabbits. Mild to
moderate erythema 24 hours after
treatment; mild erythema at 48 hours;
no irritation at 72 hours
Very slight or well-defined erythema
(with or without very slight edema)
persisting though day 8 and day 10 in
rabbits
Not irritating, rabbits. Phosphen
Environment Agency, 2009
Submitted confidential study;
Latendresse, 1994
Hagerman, 1984
Data are for Phosflex 5 IB; 75-80
percent w/w tertbutylphenyl
diphenyl phosphate (CASRN
56803-37-3), 20-25 percent w/w
triphenyl phosphate (CASRN 115-
86-6)
Data are for CASRN 56803-37-3;
conducted in accordance with
OECD Guideline 404
Data are for CASRN 78-33-1;
7-724
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
plasticiser P-7 applied as a 10% solution
in butyl carbitol acetate to the shaven
ear and belly. Very slight irritation on
the belly, but only after repeated and
prolonged exposure.
Not irritating, rabbits
Not irritating, rabbits
CASRN 56803-37-5 produced slight
destruction of tissue in guinea pig skin
when dissolved in Stoddard's solution.
No irritation occurred when the test
substance was dissolved in ethyl alcohol
or tertiary butyl alcohol.
REFERENCE
Submitted confidential study;
Bowman, 1981
ATSDR, 1997
Fabian, 1982
DATA QUALITY
phosphen plasticiser P-7
Data are for CASRN 56803-37-3
Data are for Durad 200B (CASRN
28777-70-0); a t-Butylphenyl
diphenyl phosphate mixture
containing t-Butylphenyl phenyl
phosphate (CASRN 220352-35-2)
and triphenyl phosphate (CASRN
115-86-6)
Data are for CASRN 56803-37-5
7-725
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Endocrine Activity
No data were available for TBPP. Rats exposed to hydraulic BTP (mixture of p-t-butylphenyl phenyl
phosphates (84%), triphenyl phosphate, and m-t-phenyl phosphate), had significantly prolonged
diestrus, hypertrophy and cholesteryl lipidosis of adrenocortical and ovarian interstitial cells and
minimal degeneration in the adrenal cortex and ovary. Lesions on the adrenal glands and ovaries were
observed in rats, hamsters and rabbits and relative testes weight was increased in rats following
inhalation exposure to MIL-H-19457C hydraulic fluid (CASRN 28777-70-0). Adrenal weights were
increased in rats after dietary exposure to Phosflex 51B.
In an oral study, male and female rats
were administered hydraulic BTP at
doses of 0 or 1.7 g/kg-day (0 or 1,700
mg/kg-day) via gavage in sesame oil or
2.8 g/kg (2,800 mg/kg) neat hydraulic
BTP for 20, 40 and 60 days.
Hypertrophy and cholesteryl lipidosis of
adrenocortical and ovarian interstitial
cells; minimal degeneration in the
adrenal cortex and ovary. No decreased
testicular weight or degeneration of
seminiferous tubules.
In an oral study, groups of intact and
ovariectomized female rats were
administered BTP at doses of 0 or 1.7
g/kg-day (0 or 1,700 mg/kg-day) via
oral gavage in sesame oil vehicle or as
neat BTP for 20, 40 or 60 days.
Cholesteryl lipidosis in AC and OI
cells; elevated estradiol levels (14.5
times greater than controls). No effect
on serum concentrations of
androstenedione and corticosterone.
Abnormal reproductive cycles in treated
females that were significantly
prolonged in diestrus. Increased liver
Latendresse et al., 1994a
Latendresse et al., 1993;
Latendresse, 1994
Data are for CASRN 220352-35-
2; mixture of p-t-butylphenyl
phenyl phosphates (84%),
triphenyl phosphate, and m-t-
phenyl phosphate.
Data are for CASRN 220352-35-
2; mixture of p-t-butylphenyl
phenyl phosphates (84%),
triphenyl phosphate, and m-t-
phenyl phosphate.
7-726
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
weights (134% that of controls) and P-
450 enzymes (3 times greater than
controls).
Rats were administered ML-H-19457C
(CASRN 28777-70-0) and TCP daily
via oral gavage for up to 10 weeks
(doses not specified). No mortality
occurred and there was no effect on
body weight gain in either sex. Target
organs were the adrenal gland and the
liver. The estrous cycle was extended
for high dose females administered ML-
ML-H-19457C and relative testes
weights were increased. Effects were
reversed at 5 and 10 weeks post-
treatment.
Dodd and Smith, 1994
Data are for MIL-H-19457C
hydraulic fluid (CASRN 28777-
70-0); doses not specified.
Rats, hamsters and rabbits were exposed
to MIL-H-19457C hydraulic fluid
(CASRN 28777-70-0) via inhalation 6
hours/day at a concentration of 250
mg/m3 for 21 days or 0, 10 and 100
mg/m3 for 90 days. Effects were only
observed in rats; lesions in the adrenal
glands and ovaries (90 day exposure).
Dodd and Smith, 1994
Data are for MIL-H-19457C
hydraulic fluid (CASRN 28777-
70-0).
In a 90-day study, Sprague-Dawley rats
(20/sex/group) were fed diets containing
0, 100, 400, or 1,600 ppm (average
intakes of 0, 6.6, 26.7 or 107.5 mg/kg-
day in males and 0, 7.7, 30.0 or 124.8
mg/kg-day in females) test substance.
Adrenal weight was increased at 1,600
ppm.
Submitted confidential study;
Keller, 1984; Environment
Agency, 2009
Data are for Phosflex 5 IB; 75-80
percent w/w tertbutylphenyl
diphenyl phosphate (CASRN
56803-37-3), 20-25 percent w/w
triphenyl phosphate (CASRN 115-
86-6).
7-727
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
Immunotoxicity
Immune System Effects
DATA
NOAEL: 400 ppm (26.7 mg/kg-day for
males and 30 mg/kg-day for females)
LOAEL: 1600 ppm (107.5 mg/kg-day
for males and 124.8 mg/kg-day for
females); (based on organ weight
changes)
REFERENCE
DATA QUALITY
No data located.
No data located.
ECOTOXICITY
ECOSAR Class
Acute Aquatic Toxicity
Fish LC50
VERY HIGH: Based on experimental data for mixture components of TBPP for fish and daphnia.
Experimental data for algae indicates HIGH hazard concern. The reported water solubility values from
studies on commercial mixtures may not adequately represent all components of the mixture. The TBPP
isomers and t-butyl substituted phenyl phosphate esters anticipated to be present in the commercial
product are expected to have a range of water solubility values. Therefore NES may be predicted for
some components but not others.
Freshwater fish (Ictalurus punctatus)
96-hour LC50 = 0. 8 mg/L
static test conditions
(Experimental)
Freshwater fish (Oncorhynchus mykiss)
96-hour LC50 = 1.1 mg/L
(Experimental)
Cleveland et al, 1986 (as cited in
Environment Agency, 2009)
Submitted confidential study
Data are for a commercial
tertbutylphenyl diphenyl
phosphate product consisting of
15-20 percent triphenyl
phosphate (CASRN 115-86-6)
with the remainder consisting
mainly of a mixture of isomers of
tertbutylphenyl diphenyl
phosphate (CASRN 56803-37-3) ,
along with isomers of di-
tertbutylphenyl diphenyl
phosphate (CASRN 65652-41-7).
Data are for t-Butylphenyl
diphenyl phosphate (CASRN
56803-37-3). The available acute
toxicity data for fish, aquatic
7-728
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
invertebrates, and algae were
judged inadequate to meet the
endpoints; summary did not
provide sufficient information
regarding study conditions,
including test substance purity or
water solubility, to allow for an
independent evaluation of the
studies.
Freshwater fish (Oncorhynchus mykiss)
96-hour LC50 = 2.0 mg/L
static test conditions
(Experimental)
Cleveland et al, 1986 (as cited in
Environment Agency, 2009)
Data are for a commercial
tertbutylphenyl diphenyl
phosphate product consisting of
15-20 percent triphenyl
phosphate (CASRN 115-86-6)
with the remainder consisting
mainly of a mixture of isomers of
tertbutylphenyl diphenyl
phosphate (CASRN 56803-37-3),
along with isomers of di-
tertbutylphenyl diphenyl
phosphate (CASRN 65652-41-7).
Freshwater fish (Salmo gairdneri) 96-
hour LC50 = 2.0 mg/L
96-hour NOEC = 0.56 mg/L
24-hour LC50 = 26 mg/L
48-hour LC50 = 13 mg/L
(Experimental)
Bucafusco, 1976b
Data are for Santicizer 154; a
mixture containing 43.2% t-butyl
phenyl diphenyl phosphate
(CASRN 56803-37-3), 40.2%
triphenyl phosphate (CASRN 115-
86-6), 14% di-t-butylphenyl
phenyl phosphate (CASRN 2528-
36-1) and 2% tri-t-butyl phenyl
phosphate (CASRN 78-33-1).
Freshwater fish (Pimephales promelas)
96-hour LC50 = 2.3 mg/L
static test conditions
Cleveland et al., 1986 (as cited in
Environment Agency, 2009)
Data are for a commercial
tertbutylphenyl diphenyl
phosphate product consisting of
7-729
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
(Experimental)
15-20 percent triphenyl
phosphate (CASRN 115-86-6)
with the remainder consisting
mainly of a mixture of isomers of
tertbutylphenyl diphenyl
phosphate (CASRN 56803-37-3),
along with isomers of di-
tertbutylphenyl diphenyl
phosphate (CASRN 65652-41-7).
Freshwater fish (Oncorhynchus mykiss)
96-hour LC50 = 2.4 - 5.4 mg/L
static test conditions
(Experimental)
Akzo Nobel, 2003 (as cited in
Environment Agency, 2009)
Data are for t-Butylphenyl
diphenyl phosphate (CASRN
56803-37-3).
Freshwater fish (Lepomis macrochirus)
96-hour LC50 = 3.1 mg/L
static test conditions
(Experimental)
Cleveland et al., 1986 (as cited in
Environment Agency, 2009)
Data are for a commercial
tertbutylphenyl diphenyl
phosphate product consisting of
15-20 percent triphenyl
phosphate (CASRN 115-86-6)
with the remainder consisting
mainly of a mixture of isomers of
tertbutylphenyl diphenyl
phosphate (CASRN 56803-37-3),
along with isomers of di-
tertbutylphenyl diphenyl
phosphate (CASRN 65652-41-7).
Freshwater fish (Pimephales promelas)
96-hour LC50= 3.4 mg/L
96-hour NOEC < 1.0 mg/L
24-hour LC50 > 10 < 32 mg/L
48-hour LC50 = 4.0 mg/L
(Experimental)
Monsanto, 1976
Data are for Santicizer 154; a
mixture containing 43.2% t-butyl
phenyl diphenyl phosphate
(CASRN 56803-37-3), 40.2%
triphenyl phosphate (CASRN 115-
86-6), 14% di-t-butylphenyl
phenyl phosphate (CASRN 2528-
36-1) and 2% tri-t-butyl phenyl
7-730
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Freshwater fish (Pimephales promelas)
96-hour LC50 > 0.268 - 0.647 mg/L
Measured exposure concentrations were
not high enough to cause 50% mortality.
The highest concentrations in clean and
sediment pond tests were 0.286 - 0.647
mg/L.
(Experimental)
Adams etal., 1983
Freshwater fish (Cyprinodon
variegatus) 96-hour LC50 >1 mg/L
NOEC = 1 mg/L
static-renewal test conditions
(Experimental)
Akzo Nobel, 2001
Freshwater fish (Lepomis macrochirus)
96-hour LC50 > 10 < 12 mg/L
24-hour LC50 = 35 mg/L
48-hour LC50 = 14 mg/L
(Experimental)
Bucafusco, 1976a
Freshwater fish 96-hour LC50 < 0.001
mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
phosphate (CASRN 78-33-1).
Data are for Santicizer 154; a
mixture containing 43.2% t-butyl
phenyl diphenyl phosphate
(CASRN 56803-37-3), 40.2%
triphenyl phosphate (CASRN 115-
86-6), 14% di-t-butylphenyl
phenyl phosphate (CASRN 2528-
36-1) and 2% tri-t-butyl phenyl
phosphate (CASRN 78-33-1).
Data are for CASRN 220352-35-2
(75-80% w/w; impurity: 20-25%
w/w triphenyl phosphate (CASRN
115-86-6)). Study was conducted
according to OECD Guideline
203; details reported in a
secondary source.
Data are for Santicizer 154; a
mixture containing 43.2% t-butyl
phenyl diphenyl phosphate
(CASRN 56803-37-3), 40.2%
triphenyl phosphate (CASRN 115-
86-6), 14% di-t-butylphenyl
phenyl phosphate (CASRN 2528-
36-1) and 2% tri-t-butyl phenyl
phosphate (CASRN 78-33-1);
values are well above reported
water solubility values; NES may
be predicted.
Data are for Tris(p-t-butylphenyl)
phosphate (CASRN 78-33-1).
NES: The log Kow of 10 for this
chemical exceeds the SAR
7-731
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
limitation for the log Kow of 5.0;
NES are predicted for these
endpoints.
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
Freshwater fish (Lepomis macrochirus)
96-hour LC50 = l.Omg/L
(Experimental)
Submitted confidential study
Data are for t-Butylphenyl
diphenyl phosphate (CASRN
56803-37-3). The available acute
toxicity data for fish, aquatic
invertebrates, and algae were
judged inadequate to meet the
endpoints; summary did not
provide sufficient information
regarding study conditions,
including test substance purity or
water solubility, to allow for an
independent evaluation of the
studies.
Freshwater fish (Oncorhynchus mykiss)
96-hourLC50 = 5.4mg/L
static test conditions
(Experimental)
Union Carbide, 1978 (as cited in
Environment Agency, 2009)
Data are for t-Butylphenyl
diphenyl phosphate (CASRN
56803-37-3; Fyrquel GT). The test
report indicates that the test
substance formed an oily film on
the surface of the water for all
concentrations tested and the
result is considered to be invalid
as undissolved test material
appeared to be present.
Freshwater fish (Oncorhynchus mykiss)
IUCLID, 2001 (as cited in
Data are for t-Butylphenyl
7-732
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
96-hour LC50 = 13.7mg/L
flow-through test conditions
(Experimental)
Environment Agency, 2009)
Freshwater fish 96-hour LC50 = 0.77
mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Freshwater fish 96-hour LC50 = 0.009
mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
diphenyl phosphate (CASRN
56803-37-3). The reported LC50 is
well above the water solubility of
the test substance; effect level is
well above the estimated water
solubility therefore NES can be
predicted.
Data are for t-Butylphenyl
diphenyl phosphate (CASRN
56803-37-3). NES: The log Kow
of 5.12 for this chemical exceeds
the SAR limitation for the log Kow
of 5.0; NES are predicted for these
endpoints.
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
Data are for Bis(t-butylphenyl)
phenyl phosphate (CASRN
65652-41-7). NES: The log Kow
of 8.5 for this chemical exceeds
the SAR limitation for the log Kow
of 5.0; NES are predicted for these
endpoints.
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
7-733
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Daphnid LC50
Daphnia magna 48-hour EC50 = 0.25
mg/L
(Experimental)
Adams and Heidolph, 1985 (as
cited in Environment Agency,
2009)
Data are for TB220-H;
tertbutylphenyl phosphate
(CASRN 78-33-1) with 18 percent
triphenyl phosphate (115-86-6);
effect level higher than the
estimated water solubility
therefore NES can be predicted.
Daphnia magna 48-hour EC50 = 0.289 -
0.321 mg/L, mean measured values
field tests from sediment or clean ponds,
static conditions.
(Experimental)
Adams etal, 1983
Data are for Santicizer 154; a
mixture containing 43.2% t-butyl
phenyl diphenyl phosphate
(CASRN 56803-37-3), 40.2%
triphenyl phosphate (CASRN 115-
86-6), 14% di-t-butylphenyl
phenyl phosphate (CASRN 2528-
36-1) and 2% tri-t-butyl phenyl
phosphate (CASRN 78-33-1).
Daphnia magna 48-hour LC50 = 0.30
mg/L
(Experimental)
Submitted confidential study
Data are for CASRN 56803-37-3;
tertbutylphenyl diphenyl
phosphate (purity not given);
effect level higher than the
estimated water solubility
therefore NES can be predicted.
Daphnia magna 48-hour EC50 = 0.30
mg/L
(Experimental)
Ziegenfuss et al., 1986 (as cited in
Environment Agency, 2009)
Data are for Santicizer 154; a
mixture of tertbutylphenyl
diphenyl phosphate (CASRN
56803-37-3), di-tertbutylphenyl
phenyl phosphate (65652-41-7)
and triphenyl phosphate (115-86-
6).
Daphnia magna 48-hour EC50 = 1.1
mg/L
(Experimental)
Adams and Heidolph, 1985 (as
cited in Environment Agency,
2009)
Data are for TB220-L;
tertbutylphenyl diphenyl
phosphate (CASRN 56803-37-3)
with less than 1 percent triphenyl
7-734
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
phosphate (115-86-6); effect level
higher than the estimated water
solubility therefore NES can be
predicted.
Daphnia magna 48-hour EC50 = 2.9
mg/L
(Experimental)
Sanders et al., 1985 (as cited in
Environment Agency, 2009)
Daphnia magna 48-hour EC50 = 5.0
mg/L
(Experimental)
Sanders et al., 1981
Daphnia magna 48-hour LC50 = 1.15
mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Data are for Fyrquel GT;
commercial tertbutylphenyl
diphenyl phosphate product
(purity not given).
Data are for Santicizer 154; a
mixture containing 43.2% t-butyl
phenyl diphenyl phosphate
(CASRN 56803-37-3), 40.2%
triphenyl phosphate (CASRN 115-
86-6), 14% di-t-butylphenyl
phenyl phosphate (CASRN 2528-
36-1) and 2% tri-t-butyl phenyl
phosphate (CASRN 78-33-1);
effect level marginally higher than
the estimated water solubility of
the commercial mixture, therefore
NES may be predicted.
Data are for t-Butylphenyl
diphenyl phosphate (CASRN
56803-37-3). NES: The log Kow
of 5.12 for this chemical exceeds
the SAR limitation for the log Kow
of 5.0; NES are predicted for these
endpoints.
Estimate for the Esters class was
provided for comparative
purposes.
7-735
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Daphnia magna 48-hour LC50 = 0.009
mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Daphnia magna 48-hour LC50 < 0.001
mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
See Section 5.5.1.
Data are for Bis(t-butylphenyl)
phenyl phosphate (CASRN
65652-41-7). NES: The log Kow
of 8.5 for this chemical exceeds
the SAR limitation for the log Kow
of 5.0; NES are predicted for these
endpoints.
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
Data are for Tris(p-t-butylphenyl)
phosphate (CASRN 78-33-1).
NES: The log Kow of 10 for this
chemical exceeds the SAR
limitation for the log Kow of 5.0;
NES are predicted for these
endpoints.
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
Other Invertebrate LC50
Mysid shrimp (Mysidopsis bahia) 96-
hour EC50 = 0.39 mg/L
NOEC = 0.22 mg/L
(Experimental)
Akzo Nobel, 2001
Data are for CASRN 220352-35-2
(75-80% w/w; impurity: 20-25%
w/w triphenyl phosphate (CASRN
115-86-6)). Study conducted
according to OECD Guide-line
202, part 1; details reported in a
7-736
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
secondary source.
Green Algae EC s
Green algae (Selenastrum
capricornutum) 96-hour EC50 (total
biomass) = 2.6 mg/L
96-hour EC50 (chlorophyll A) = 3.0
mg/L
(Experimental)
IUCLID, 2001 (as cited in
Environment Agency, 2009)
Data are for CASRN 220352-35-2
(75-80% w/w; impurity: 20-25%
w/w triphenyl phosphate (CASRN
115-86-6)). Study details reported
in a secondary source.
Green algae (Selenastrum
capricornutum) 96-hour EC50
mg/L
24-hour EC50> 10 mg/L
48-hour EC50 = 5.9 mg/L
72-hour EC50 = 3.4 mg/L
(Experimental)
Hollister, 1979
= 3.0
Data are for Santicizer 154; a
mixture containing 43.2% t-butyl
phenyl diphenyl phosphate
(CASRN 56803-37-3), 40.2%
triphenyl phosphate (CASRN 115-
86-6), 14% di-t-butylphenyl
phenyl phosphate (CASRN 2528-
36-1) and 2% tri-t-butyl phenyl
phosphate (CASRN 78-33-1).
Green algae (Selenastrum
capricornutum)
14-day NOEC = 1 mg/L
14-day LOEC = 10 mg/L
(Experimental)
Sanders et al., 1985 (as cited in
Environment Agency, 2009)
Data are for Fyrquel GT, a
commercial tertbutylphenyl
diphenyl phosphate product
(composition not given).
Green algae 96-hour LC50 = 0.30 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Data are for t-Butylphenyl
diphenyl phosphate (CASRN
56803-37-3); The log Kow of 5.1
for this chemical exceeds the SAR
limitation for the log Kow of 6.4;
Estimate for the Esters class was
provided for comparative
7-737
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Green algae 96-hour LC50 = 0.001 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Green algae 96-hour LC50 < 0.001 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
purposes.
See Section 5.5.1.
Data are for Bis(t-butylphenyl)
phenyl phosphate (CASRN
65652-41-7). NES: The log Kow
of 8.5 for this chemical exceeds
the SAR limitation for the log Kow
of 6.4; NES are predicted for these
endpoints.
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
Data are for Tris(p-t-butylphenyl)
phosphate (CASRN 78-33-1).
NES: The log Kow of 10 for this
chemical exceeds the SAR
limitation for the log Kow of 6.4;
NES are predicted for these
endpoints.
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
7-738
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Chronic Aquatic Toxicity
VERY HIGH: Based on experimental NOEC values for mixture components of TBPP for fish and
daphnia. The reported water solubility values from studies on commercial mixtures may not adequately
represent all components of the mixture. The TBPP isomers and t-butyl substituted phenyl phosphate
esters components anticipated to be present in the commercial product are expected to have a range of
water solubility values. Therefore NES may be predicted for some components but not others.
Fish ChV
Freshwater fish (Pimephales promelas)
30-day NOEC (mortality) = 0.093 mg/L
30-day NOEC (growth) = 0.194 mg/L
(Experimental)
Freshwater fish ChV = 0.03 mg/L
(Estimated)
ECOSAR: Esters
Freshwater fish ChV < 0.001 mg/L
(Estimated)
ECOSAR: Esters
Cleveland et al, 1986 (as cited in
Environment Agency, 2009)
ECOSAR v 1.11
ECOSAR v 1.11
Data are for a commercial
tertbutylphenyl diphenyl
phosphate product consisting of
15-20 percent triphenyl
phosphate (CASRN 115-86-6)
with the remainder consisting
mainly of a mixture of isomers of
tertbutylphenyl diphenyl
phosphate (CASRN 56803-37-3),
along with isomers of di-
tertbutylphenyl diphenyl
phosphate (CASRN 65652-41-7).
Data are for t-Butylphenyl
diphenyl phosphate (CASRN
56803-37-3) Estimate for the
Esters class was provided for
comparative purposes.
See Section 5.5.1.
Data are for Bis(t-butylphenyl)
phenyl phosphate (CASRN
65652-41-7). NES: The log Kow
of 8.5 for this chemical exceeds
the SAR limitation for the log Kow
of 8.0; NES are predicted for these
endpoints.
Estimate for the Esters class was
7-739
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Freshwater fish ChV < 0.001 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
provided for comparative
purposes.
See Section 5.5.1.
Data are for Tris(p-t-butylphenyl)
phosphate (CASRN 78-33-1).
NES: The log Kow of 10 for this
chemical exceeds the SAR
limitation for the log Kow of 8.0;
NES are predicted for these
endpoints.
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
Daphnid ChV
Daphnia magna 21-day LOEC
(mortality) < 0.1 mg/L
NOEC (mortality and reproduction) =
0.04 mg/L
(Experimental)
Akzo Nobel, 2001
Data are for CASRN 220352-35-2
(75-80% w/w; impurity: 20-25%
w/w triphenyl phosphate (CASRN
115-86-6)). Study details reported
in a secondary source.
Daphnia magna 21-day NOEC
(survival and reproduction) = 0.01 mg/L
(Experimental)
Sanders et al., 1985 (as cited in
Environment Agency, 2009)
Data are for Santicizer 154; a
commercial tertbutylphenyl
diphenyl phosphate product
(purity not given).
Daphnia magna 21-day NOEC = 0.03
mg/L
(Experimental)
Sanders et al., 1985 (as cited in
Environment Agency, 2009)
Data are for TB220-L;
tertbutylphenyl diphenyl
phosphate (CASRN 56803-37-3)
with less than 1 percent triphenyl
phosphate (115-86-6); effect level
higher than the estimated water
7-740
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
solubility therefore NES can be
predicted.
Daphnia magna 21-day NOEC = 0.03
mg/L
(Experimental)
Sanders et al., 1985 (as cited in
Environment Agency, 2009)
Data are for TB220-H;
tertbutylphenyl phosphate
(CASRN 78-33-1) with 18 percent
triphenyl phosphate (115-86-6).
Daphnia magna 21-day NOEC
(survival and reproduction) = 0.032
mg/L
(Experimental)
Sanders et al., 1985 (as cited in
Environment Agency, 2009)
Data are for Fyrquel GT; a
commercial tertbutylphenyl
diphenyl phosphate product
(purity not given).
Daphnia magna 21-day NOEC = 0.04
mg/L
(Experimental)
Adams and Heidolph et al., 1985
(as cited in Environment Agency,
2009)
Daphnia magna 21-day NOEC >0.204 -
0.461 mg/L, mean measured values
21-day MATC > 0.0236 - 0.0524 mg/L,
field tests from sediment or clean ponds,
static conditions
(Experimental)
Adams etal, 1983
Daphnia magna ChV = 0.32 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Data are for Santicizer 154; a
mixture of tertbutylphenyl
diphenyl phosphate (CASRN
56803-37-3), di-tertbutylphenyl
phenyl phosphate (65652-41-7)
and triphenyl phosphate (115-86-
6).
Data are for Santicizer 154; a
mixture containing 43.2% t-butyl
phenyl diphenyl phosphate
(CASRN 56803-37-3), 40.2%
triphenyl phosphate (CASRN 115-
86-6), 14% di-t-butylphenyl
phenyl phosphate (CASRN 2528-
36-1) and 2% tri-t-butyl phenyl
phosphate (CASRN 78-33-1).
Data are for t-Butylphenyl
diphenyl phosphate (CASRN
56803-37-3). Estimate for the
Esters class was provided for
comparative purposes.
7-741
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Daphnia magna ChV < 0.001 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Daphnia magna 48-hour ChV < 0.001
mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
See Section 5.5.1.
Data are for Tris(p-t-butylphenyl)
phosphate (CASRN 78-33-1).
NES: The log Kow of 10 for this
chemical exceeds the SAR
limitation for the log Kow of 8.0;
NES are predicted for these
endpoints.
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
Data are for Bis(t-butylphenyl)
phenyl phosphate (CASRN
65652-41-7). NES: The log Kow
of 8.5 for this chemical exceeds
the SAR limitation for the log Kow
of 8.0; NES are predicted for these
endpoints.
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
7-742
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Green Algae ChV
Green algae (Selenastrum
capricornutum)
14-day NOEC = 1 mg/L
14-day LOEC = 10 mg/L
(Experimental)
Sanders et al., 1985 (as cited in
Environment Agency, 2009)
Green algae ChV = 0.21 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Green algae ChV = 0.003 mg/L
(Estimated)
ECOSAR: Esters
ECOSARvl.ll
Green algae ChV < 0.001 mg/L
(Estimated)
ECOSAR: Ester
ECOSARvl.ll
Data are for Fyrquel GT, a
commercial tertbutylphenyl
diphenyl phosphate product
(composition not given).
Data are for t-Butylphenyl
diphenyl phosphate (CASRN
56803-37-3) Estimate for the
Esters class was provided for
comparative purposes.
See Section 5.5.1.
Data are for Bis(t-butylphenyl)
phenyl phosphate (CASRN
65652-41-7). NES: The log Kow
of 8.5 for this chemical exceeds
the SAR limitation for the log Kow
of 8.0; NES are predicted for these
endpoints.
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
Data are for Tris(p-t-butylphenyl)
phosphate (CASRN 78-33-1).
NES: The log Kow of 10 for this
chemical exceeds the SAR
limitation for the log Kow of 8.0;
7-743
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
NES are predicted for these
endpoints.
Estimate for the Esters class was
provided for comparative
purposes.
See Section 5.5.1.
ENVIRONMENTAL FATE
Transport
Henry's Law Constant (atm-
m3/mole)
Sediment/Soil
Adsorption/Desorption - Koc
Level III fugacity models incorporating available physical and chemical property data indicate that at
steady state, TBPP is expected to be found primarily in soil and to a lesser extent, water. TBPP is
expected to have negligible mobility in soil based on the estimated K0c value. There is low to moderate
potential for volatilization from water or moist soil surfaces based upon the estimated Henry's Law
constant; however adsorption to soil is expected to attenuate this process. TBPP is not expected to
volatilize from dry soil surfaces based upon the extrapolated and measured vapor pressures. In the
atmosphere, TBPP is expected to exist primarily in the particulate phase. Particulate phase TBPP will be
removed from air by wet or dry deposition.
6.9xlO'7 for tris (p-t-butylphenyl)
phosphate;
2.7xlO~7 for di-t-butylphenyl phenyl
phosphate;
IxlO"7 for t-butylphenyl diphenyl
phosphate (Estimated)
8.8xlO'7 (Measured)
3,400 for t-butylphenyl diphenyl
phosphate using the MCI method
(Estimated)
>30,000 (Estimated)
EPIv4.11
ChemID, 2013c
EPIv4.11
EPIv4.11;EPA, 2005
Estimated using representative
structures indicated in the
SMILES section for components
of the mixture using the
HENRYWIN (v3.20) Program.
Reported for CASRN 56803-37-3
in secondary source.
Estimated using the representative
structure for t-butylphenyl
diphenyl phosphate indicated in
the SMILES section.
Cutoff value fornonmobile
compounds. Estimated for both
tris (p-t-butylphenyl) phosphate
7-744
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
Level III Fugacity Model
Persistence
Water
Aerobic Biodegradation
DATA
Air = 0.1%
Water = 5%
Soil = 93 .2%
Sediment = 1.67% (Estimated)
REFERENCE
EPIv4.11
DATA QUALITY
and for di-t-butylphenyl phenyl
phosphate.
Estimated for tris (p-t-
butylphenyl) phosphate.
MODERATE: Based on primary and ultimate biodegradation in nonguideline experimental studies
using CASRN 56803-37-3 in river and pond water and sediment samples. These results indicate a half-
life for ultimate degradation of <60 days but >16 days in the environment and are consistent with
inherent degradation. 100% primary degradation of CASRN 56803-37-3 was reported after
approximately 11 days in a river die-away study and 93% primary degradation after 9 weeks in a SCAS
test using activated sludge inoculum under aerobic conditions. CASRN 56803-37-3 was found to have
half-lives based on disappearance of the parent compound of 4.2 and 8.4 days in pond and river
sediment, respectively, and showed mineralization of 1.7-37.2% after 8 weeks in water-sediment
microcosms. Hydrolysis in alkaline waters may be an important fate process based on experimental half-
lives for TBPP but slower under neutral conditions. In a nonguideline photolysis study, no
transformation products were identified from a commercial mixture of TBPP in filtered Mississippi
River water after exposure to sunlight for 14 days.
Study results: 93%/9 weeks
Test method: Biological Treatment
Simulation
SCAS test. 93% primary degradation
after 9 weeks in domestic activated
sludge at a test substance addition rate
of 3 mg/L every 24 hours. (Measured)
Study results: 100%/~11 days
Test method: Die-Away
Complete primary degradation occurred
after about 1 1 days in a river water die-
away study. (Measured)
Study results: 50%/7 days
Saegeretal., 1979
Saegeretal., 1979
Saugar, 1983
Nonguideline study reported for
CASRN 56803-37-3.
Nonguideline study reported for
CASRN 56803-37-3.
Guideline test performed on a
7-745
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
Soil
Volatilization Half-life for
Model River
Volatilization Half-life for
Model Lake
Aerobic Biodegradation
Anaerobic Biodegradation
Soil Biodegradation with
Product Identification
DATA
Test method: Die-Away
Reported as the disappearance of the
parent compound.
TPP: 50%/<0.5 days
DTBPPP: 50%/1 day
TBPDPP: 50%/7 days
Mississippi River water over 27 days
(Measured)
79 days (Estimated)
54 days (Estimated)
190 days (Estimated)
>1 year (Estimated)
>1 year (Estimated)
>1 year (Estimated)
Not probable (Anaerobic-methanogenic
biodegradation probability model)
REFERENCE
EPIv4.11
EPIv4.11
EPIv4.11
EPIv4.11
EPIv4.11
EPIv4.11
EPIv4.11
DATA QUALITY
commercial product consisting of
TPP (CASRN 115-86-6), di(t-
butylphenyl)phenyl phosphate
(DTBPPP) and t-
butylphenyldiphenyl phosphate
(TBPDPP).
Estimated for tris (p-t-
butylphenyl) phosphate.
Estimated using the representative
structure for p-(t-butylphenyl)
diphenyl phosphate.
Estimated using the representative
structure for di-t-butylphenyl
phenyl phosphate.
Estimated for tris (p-t-
butylphenyl) phosphate.
Estimated using the representative
structure for p-(t-butylphenyl)
diphenyl phosphate.
Estimated using the representative
structure for di-t-butylphenyl
phenyl phosphate.
No data located.
Estimated for tris (p-t-
butylphenyl) phosphate.
No data located.
7-746
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Sediment/Water
Biodegradation
Mineralization of the test substance (2
mg) ranged from 1.7 to 37.2% after 8
weeks in microcosms containing
sediment and water from lacustrine,
riverine, and estuarine ecosystems. The
rate of degradation was related to the
nutrient level and contaminant
(Measured)
Heitkamp and Cerniglia, 1986;
Heitkamp et al, 1986
50%/4.2 days at 25°C in pond sediment.
Half-life = 8.4 days at 25°C in river
sediment based on disappearance of the
parent compound from the sediment
phase. 14C-labelled test substance was
subject to static river and pond
sediment-water incubations in
respirometer flasks at temperatures and
redox conditions typical of aquatic
environments. (Measured)
Muir et al., 1989
Nonguideline study reported for
CASRN 56803-37-3.
Nonguideline study reported for
CASRN 56803-37-3.
Air
Atmospheric Half-life
0.7 days for t-butylphenyl diphenyl
phosphate;
0.74 tri-t-butylphenyl phosphate
0.81 for di-t-butylphenyl phenyl
phosphate; (Estimated)
EPIv4.11
= 3.9xl06
Thin film oxidation test analyzed by Gel
Permeation chromatography (GPC)
Hydrocarbon portion of the phosphate
oxidizes in the first step; oxidized
material undergoes condensation
(Measured)
Cho and Klaus, 1981
Estimated using representative
structures indicated in the
SMILES section.
Nonguideline study providing
supporting information.
Reactivity
Photolysis
0%/14 days
No transformation products were
identified in filtered Mississippi River
Sauger, 1983
Nonguideline study on a
commercial mixture.
7-747
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
Hydrolysis
Environmental Half-life
DATA
water after exposure to sunlight for 14
days in a sealed quartz tube; analysis
with GC (Measured)
pH5:50%/>100days
pH7:50%/31days
pH 9: 50%/19 days (Measured)
pH5:50%/>100days
pH 7: 50%/57 days
pH 9: 50%/10 days (Measured)
pH7:50%/3.5years
pH5:50%/341years
pH 6: 50%/35 years
pH 8: 50%/127 days
pH 9: 50%/13 days
pH 10: 50%/1.3 days (Estimated)
0.44 day in pond water
39 days in bottom sediment
Field study; 360 days following the
addition of 50 (ig/L of the test substance
to artificial ponds of 5 cubic meter
volume (Measured)
360 days (Estimated)
REFERENCE
Michael, 1978
Michael, 1978
EPIv4.11
Muir et al., 1985
PBT Profiler
DATA QUALITY
Reported for tri t-butylphenyl
phenyl phosphate.
Reported for CASRN 56803-37-3.
Estimated for tris (p-t-
butylphenyl) phosphate.
Reported for CASRN 56803-37-3.
Half-life estimated for tris (p-t-
butylphenyl) phosphate in the
predominant compartment, soil, as
determined by EPI methodology.
7-748
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
Bioaccumulation
Fish BCF
Other BCF
BAF
Metabolism in Fish
DATA
REFERENCE
DATA QUALITY
HIGH: The bioaccumulation designation is based on the measured BCF values for t-butylphenyl
diphenyl phosphate (CASRN 56803-37-3); BCF results >1,000 are from two different species. The
estimated BAF values for the di and tri-t-butylphenyl phosphate also indicate high potential for
bioaccumulation. The low estimated BCF values were determined from the estimated log Kow values,
which are >6.6.
1,096 whole fish, short-term static
exposure of 50 and 5 (ig/L in Rainbow
trout (Measured)
1,010 Whole fish, short-term static
exposure of 50 and 5 (ig/L in Fathead
minnow (Measured)
42 (Estimated)
170 (Estimated)
360 (Estimated)
100,000 (Estimated)
460,000 (Estimated)
540 (Estimated)
Muir et al., 1983
Muir et al., 1983
EPIv4.11
EPIv4.11
EPIv4.11
EPIv4.11
EPIv.411
EPIv4.11
Nonguideline study reported for
>98% pure CASRN 56803-37-3.
Nonguideline study reported for
>98% pure CASRN 56803-37-3.
Estimated for tris (p-t-
butylphenyl) phosphate.
Estimated using the representative
structure for p-(t-butylphenyl)
diphenyl phosphate.
Estimated using the representative
structure for di-t-butylphenyl
phenyl phosphate.
No data located.
Estimated for tris (p-t-
butylphenyl) phosphate. Given the
limited water solubility, this BAF
value may be overestimated.
Estimated using the representative
structure for di-t-butylphenyl
phenyl phosphate.
Estimated using the representative
structure for p-(t-butylphenyl)
diphenyl phosphate.
No data located.
7-749
-------
Tris (p-t-butylphenyl) phosphate (TBPP) CASRN 78-33-1
PROPERTY/ENDPOINT
DATA REFERENCE
ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring
Ecological Biomonitoring
Human Biomonitoring
DATA QUALITY
t-Butylphenyl diphenyl phosphate (CASRN 56803-37-3) has been found in river sediments in industrial areas
(Muir et al., 1989).
No data located.
t-Butylphenyl diphenyl phosphate (CASRN 56803-37-3) was detected in human adipose samples. TBPP was
not included in the NHANES biomonitoring report (LeBel and Williams, 1983; CDC, 2009).
7-750
-------
ATSDR (1997) Toxicological profile for hydraulic fluids. Agency for Toxic Substances and Disease Registry, U.S. Public Health Service, 339.
Adams WJ, Kimerle RA, Heidolph BB, et al. (1983) Field comparison of laboratory-derived acute and chronic toxicity data. In: Bishop, Cardwell,
Heidolph, eds. Aquatic Toxicology and Hazard Assessment, Sixth Symposium. ASTM Special Technical Publication 802, 367-385.
Adams WJ, Heidolph (1985) Short-cut chronic toxicity estimates using Daphnia magna. Aquatic Toxicology and Hazard Assessment: 7th
Symposium. ASTM STP 854, American Society for Testing and Materials, 87-103 (as cited in Environment Agency).
Akzo Nobel (2001) IUCLID data set Butylated triphenyl phosphate. Akzo Nobel Functional Chemicals.
Akzo Nobel (2003) Personal communication, as reported in comments from European Flame Retardants Association, 01/07/03 (as cited in
Environment Agency)
Bowman KJ (1981) 2-Ethylhexyl diphenyl phosphate (Santicizer 141), isodecyl 2-ethylhexyl diphenyl phosphate (Santicizer 141), isodecyl
diphenyl phosphate (Santicizer 148) & t-butylphenyl dipheny phosphate (Santicizer 154) health & safety studies w-letter. Prepared by E G & G
Bionomics for Monsanto Chemical Company Submitted to the U.S. Environmental Protection Agency under TSCA Section 4.
Bucafusco RJ (1976a) Acute toxicity of Santicizer 154 to bluegill (Lepomis macrochirus). Prepared by E G & G Bionomics for Monsanto
Company Submitted to the U.S. Environmental Protection Agency under TSCA Section 8D.
Bucafusco RJ (1976b) Acute toxicity of Santicizer 154 to rainbow trout (Salmo gairdneri). Prepared by E G & G Bionomics for Monsanto
Company Submitted to the U.S. Environmental Protection Agency under TSCA Section 8D.
CDC (2009) Fourth national report on human exposure to environmental chemicals. Atlanta, GA: Centers for Disease Control and
Prevention, http://www.cdc.gov/exposurereport/pdf/FourthReport.pdf.
Carre DJ, Bertrand PA (1999) Modeling and measurement of aryl phosphate ester vapor pressures at 50°C. Tribol Trans 42(4):777-782.
ChemID (2013a) Phosphoric acid, (p-tert-butylphenyl) diphenyl ester RN: 981-40-8. ChemID plus. National Library of
Medicine, http://chem.sis.nlm.nih.gov/chemidplus/.
ChemID (2013b) Phosphoric acid, tris(tert-butylphenyl) ester RN: 28777-70-0. ChemID plus. National Library of
Medicine, http://chem.sis.nlm.nih.gov/chemidplus/.
7-751
-------
ChemID (2013c) t-Butylphenyl diphenyl phosphate RN: 56803-37-3. ChemID plus. National Library of
Medicine, http://chem.sis.nlm.nih.gov/chemidplus/.
Cho L, Klaus EE (1981) Oxidative degradation of phosphate esters. ASLE Transactions 24(1): 119-124.
Clayton JW (1983) 90-Day subacute aerosol inhalation study with Santicizer 154 in albino rats (BTL-76-29). Prepared by Industrial Bio Test Labs
Inc for Monsanto Company Submitted to the U.S. Environmental Protection Agency under TSCA Section 8D.
Dobry A, Keller R (1957) Vapor pressures of some phosphate and phosphonate esters. J Phys Chem 61(10): 1448-1449.
Dodd DE, Smith PM (1994) Toxic hazards research unit annual report 1993. Mantech Environmental Technology Inc. http://www.dtic.mil/cgi-
bin/GetTRDoc?Location=U2&doc=GetTRDoc.pdf&AD=ADA303823.
ECOSAR (Ecological Structure Activity Relationship), Version 1.11. Washington, DC: U.S. Environmental Protection
Agency, http://www.epa.gov/oppt/newchems/tools/21 ecosar.htm.
EPA (1999) Determining the adequacy of existing data. Washington, DC: U.S. Environmental Protection
Agency, http://www.epa.gov/hpv/pubs/general/datadeqfn.pdf.
EPA (2005) Pollution prevention (P2) framework. Washington, DC: U.S. Environmental Protection Agency, Office of Pollution Prevention and
Toxics, http://www.epa.gov/opptintr/newchems/pubs/sustainable/p2frame-june05a2.pdf
EPA (2008) Initial risk-based prioritization of high production volume chemicals: Butylated triphenyl phosphate. U.S. Environmental Protection
Agency.
EPA (2012) Using noncancer screening within the SF initiative. Washington, DC: U.S. Environmental Protection
Agency, http://www.epa.gov/oppt/sf/pubs/noncan-screen.htm.
EPI Estimation Programs Interface (EPI) Suite, Version 4.11. Washington, DC: U.S. Environmental Protection
Agency, http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm.
ESIS (2012) European chemical Substances Information System. European Commission, http://esis.jrc.ec.europa.eu/.
Environment Agency (2009) Environmental risk evaluation report: Tertbutylphenyl diphenyl phosphate (CAS no. 56803-37-3).
7-752
-------
Fabian FW (1982) Report of toxicity experiments. Dow Chemical Company Submitted to the U.S. Environmental Protection Agency under TSCA
Section 8D.
Hagerman RL (1984) Oral toxicity of p-tert butyl phenyl phosphate (preliminary report) with cover letter. Dow Chemical Company Submitted to
the U.S. Environmental Protection Agency under TSCA Section 8D.
Heitkamp MA, Cerniglia CE (1986) Microbial degradation of t-butylphenyl diphenyl phosphate: a comparative microcosm study among five
diverse ecosystems. Environ Toxicol Water Qual 1(1): 103-122.
Heitkamp MA, Freeman JP, Cerniglia CE (1986) Biodegradation of tert butylphenyldiphenyl phosphate. Appl Environ Microbiol 51(2):316-322.
Hollister T (1979) Toxicity of S-154 (BN-79-1384328-2a) to the freshwater alga Selenastrum capricornutum. Prepared by E G & G Bionomics for
Monsanto Company Submitted to the U.S. Environmental Protection Agency under TSCA Section 8D.
IUCLID (2001) IUCLID Data set for butylated triphenyl phosphate. Akzo Nobel Functional Chemicals. Submitted to US EPA HPV Challenge.
Available from: http://www.epa.gOv/HPV/pubs/summaries/butpp/c 13164rs.pdf (as cited un Environment Agency 2009)
7-753
-------
Keller AS (1984) Letter & attachments from Monsanto Chemical Company to the USEPA regarding the response of the industry ad hoc Aryl
Phosphate Esters Committee to the USEPA's anar on aryl phosphate. Monsanto Chemical Company. Submitted to the U.S. Environmental
Protection Agency under TSCA Section 4.
Latendresse JR (1994) Support: toxic effects of butylated triphenyl phosphate-based hydraulic fluid & tricresyl phosphate in female F344 rats with
cover letter dated 060994. Prepared by Naval Medical Research Institute for Eastman Kodak Company. Submitted to the U.S. Environmental
Protection Agency under TSCA Section 8E.
Latendresse JR, Azhar S, Brooks CL, et al. (1993) Pathogenesis of cholesteryl lipidosis of adrenocortical and ovarian interstitial cells in F344 rats
caused by tricresyl phosphate and butylated triphenyl phosphate. Toxicol Appl Pharmacol 122(2):281-289.
Latendresse JR, Brooks CL, Capen CC (1994a) Pathologic effects of butylated triphenyl phosphate-based hydraulic fluid and tricresyl phosphate
on the adrenal gland, ovary, and testis in the Fischer-344 rat. Toxicol Pathol 22(4):341-352.
Latendresse JR, Brooks CL, Capen CC (1995) Toxic effects of butylated triphenyl phosphate-based hydraulic fluid and tricresyl phosphate in
female F344 rats. Vet Pathol 32(4):394-402.
Latendresse JR, Brooks CL, Flemming CD, et al. (1994b) Reproductive toxicity of butylated triphenyl phosphate and tricresyl phosphate fluids in
F344 rats. Fundam Appl Toxicol 22(3):392-399.
Latourette HK (1981) Aryl phosphate epidemiology study with cover letter & memo. FMC Corporation Submitted to the U.S. Environmental
Protection Agency under TSCA Section 8D.
LeBel GL, Williams DT (1983) Determination of organic phosphate triesters in human adipose tissue. J Assoc Off Anal Chem 66(3):691-699.
Matheson DW (1980) Twenty health effect studies from Monsanto. Prepared by Litton Bionetics for Monsanto Company Submitted to the U.S.
Environmental Protection Agency under TSCA Section 4.
Michael PR (1978) Phosphate ester hydrolysis. Monsanto Company Submitted to the U.S. Environmental Protection Agency under TSCA Section
8D.
Monsanto (1976) Acute toxicity of Santicizer 154 to fathead minnow (Pimephales promelas). Prepared by E G & G Bionomics for Monsanto
Company Submitted to the U.S. Environmental Protection Agency under TSCA Section 8D.
7-754
-------
Muir CG, Yarechewski AL, Grift NP (1989) Biodegradation of four triaryl/alkyl phosphate esters in sediment under various temperature and redox
conditions. Toxicol Environ Chem 18(4):269-286.
Muir DC, Lint D, Grift NP (1985) Fate of three phosphate ester flame retardants in small ponds. Toxicol Environ Chem 4(5):663-676.
Muir DCG, Yarechewski AL, Grift NP (1983) Environmental dynamics of phosphate esters 3. Comparison of the bio concentration of 4 tri aryl
phosphates by fish. Chemosphere 12(2): 155-166.
Murphy JP (1979) Test protocols & data summaries for t-butyl phenyl diphenyl phosphate, tricresyl phosphate, trixylenyl phosphate, mixed triaryl
phosphate & isopropyl phenyl diphenyl w/ cover. Staufer Chemical Company. Submitted to the U.S. Environmental Protection Agency under
TSCA.
PBT Profiler Persistent (P), Bioaccumulative (B), and Toxic (T) Chemical (PBT) Profiler, Version 1.301. Washington, DC: U.S. Environmental
Protection Agency, www.pbtprofiler.net.
Saeger VW, Hicks O, Kaley RG, et al. (1979) Environmental fate of selected phosphate esters. Environ Sci Technol 13(7):840-844.
Sanders HO, Hunn JB, Robinson-Wilson E (1981) Six potential PCB substitutes: acute and chronic toxicity to algae and invertebrates. Prepared by
Columbia National Fisheries Laboratory for FMC Corporation. Submitted to the U.S. Environmental Protection Agency under TSCA Section 8D.
Sanders HO, Hunn JB, Robinson-Wilson ER, et al. (1985) Toxicity of seven potential polychlorinated biphenyl substitutes to algae and aquatic
invertebrates. Environmental Toxicology and Chemistry, 4, 149-154 (As cited in Environment Agency, 2009).
Sauger VW (1983) Sunlight photolysis screening of Santicizer 154. Monsanto Company. Submitted to the U.S. Environmental Protection Agency
under TSCA Section 8D.
Sauger VW (1983) Santicizer 154 river die-away biodegradation rate study. Monsanto Company. Submitted to the U.S. Environmental Protection
Agency under TSCA Section 8D.
Union Carbide, 1978. Acute toxicity offyrquel GT to the rainbow trout Salmo gairdneri. Richardson. Union Carbide Environmental Services,
UCES Project 11506- 92-17 (as cited in Environment Agency, 2009).
7-755
-------
Weil ED (2001) Flame retardants, phosphorus. Kirk-Othmer Encyclopedia of Chemical Technology. Wiley-Interscience, 484-510.
Ziegenfuss PS, Renaudette WJ, Adams WJ (1986) Methodology for assessing the acute toxicity of chemicals sorbed to sediments: testing the
equilibrium partitioning theory. ASTM Special Technical Publication 921, Aquatic Toxicology and Environmental Fate, 9, 479-493 (as cited in
Environment Agency, 2009).
Zeiger E, Anderson B, Haworth S, et al. (1987) Salmonella mutagenicity tests III. Results from the testing of 255 chemicals. Environ Mutagen
9(Suppl9):l-110.
7-756
------- |