SEPA
United States
Environmental Protection Agency
EPA Document** 740-R1-5001
August 2015
Office of Chemical Safety and
Pollution Prevention
TSCA Work Plan Chemical
Problem Formulation and Initial Assessment
Chlorinated Phosphate Ester Cluster
Flame Retardants
O
RO P OR
OR
CASRN
115-96-8
13674-84-5
13674-87-8
NAME
Ethanol, 2-chloro-, phosphate (3:1);
(TCEP)
2-Propanol, 1-chloro-, 2,2',2"-phosphate;
(TCPP)
2-Propanol, 1,3-dichloro-, phosphate (3:1);
(TDCPP)
R =
-CH2-CH2-CI
-CH(CH3)-CH2-CI*
-CH-(CH2-CI )2
Major isomer
August 2015
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TABLE OF CONTENTS
TABLE OF CONTENTS 2
AUTHORS / CONTRIBUTORS / ACKNOWLEDGEMENTS 4
ABBREVIATIONS 5
EXECUTIVE SUMMARY 7
1 INTRODUCTION 10
1.1 SCOPE OF THE ASSESSMENT 11
1.2 REGULATORY AND ASSESSMENT HISTORY 13
2 PROBLEM FORMULATION 14
2.1 PHYSICAL CHEMISTRY 15
2.2 PRODUCTION VOLUME AND USE 17
2.3 FATE AND TRANSPORT 22
2.4 EXPOSURES 22
2.4.1 Releases to the Environment 23
2.4.2 Presence in the Environment 23
2.4.3 Occupational Exposures 23
2.4.4 General Population Exposures 24
2.4.5 Consumer Exposures 24
2.5 HAZARD ENDPOINTS 24
2.5.1 Ecological Hazard 25
2.5.2 Human Health Hazard 25
2.6 RESULTS OF PROBLEM FORMULATION 27
2.6.1 Conceptual Models 27
2.6.2 Analysis Plan 32
2.6.3 Sources and Pathways Excluded From Further Assessment 36
2.6.4 Uncertainties and Data Gaps 36
2.6.4.1 Release and Exposure Uncertainties 37
2.6.4.2 Hazard Data Uncertainties 38
2.7 CRITICAL DATA NEEDS 39
REFERENCES 41
APPENDICES 54
Appendix A Data Availability Tables 55
Appendix B Regulatory and Assessment History 60
B-l DOMESTIC 60
B-2 INTERNATIONAL 61
Appendix C Uses Supplemental Information 63
Appendix D Exposure Data Summaries 66
Appendix E Ecological Hazard Studies 69
Appendix F Human Health Hazard Study Summaries 70
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LIST OF TABLES
Table 1-1: CPE FR Cluster Members and Structures 12
Table 1-2: Select Physical Chemical Properties Used For Selecting Cluster Members 12
Table 2-1: Data Required for Risk Assessment 15
Table 2-2: CPE FR Substituents, "R" groups 16
Table 2-3: TCPP in commercial products 16
Table 2-4: Physical Chemical Properties 17
Table 2-5: 2012 CDR Reported Use and Production Volumes 19
Table 2-6: Assessment of Environmental Exposures 28
Table 2-7: Assessment of Toxicity in Aquatic Organisms 29
Table 2-8: Assessment of Exposure to Consumers 31
Table 2-9: Assessment of Exposure to General Population 32
Table 2-10: Relevant Endpoints for Human Receptors 32
Table 2-11: Analysis Plan for Releases to Water 33
Table 2-12: Analysis Plan for Assessing Risks to Aquatic Organisms 33
Table 2-13: Analysis Plan for General Population and Consumer Risks 35
Table 2-14: Analysis Plan for Risks from Aggregate Oral Exposures 36
LIST OF APPENDIX TABLES
Table_Apx A-l: Available Occupational Exposure and Release Data 55
Table_Apx A-2: Available General Population and Environmental Exposure Data 56
Table_Apx A-3: Available Mammalian and Aquatic Toxicity Data 58
Table_Apx B-l: Existing State Regulations 60
Table_Apx E-l: Ecological Toxicity Data 69
LIST OF FIGURES
Figure 2-1: CPE FR Structure 15
Figure 2-2: Conceptual Model for Ecological Receptors 28
Figure 2-3: Conceptual Model for Human Receptors 30
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AUTHORS / CONTRIBUTORS / ACKNOWLEDGEMENTS
This report was developed by the United States Environmental Protection Agency (US EPA), Office of
Chemical Safety and Pollution Prevention (OCSPP), Office of Pollution Prevention and
Toxics (OPPT). The Work Plan Chemical Problem Formulation for the chlorinated phosphate ester
cluster was prepared based on currently available data. Mention of trade names does not constitute
endorsement by EPA.
EPA Assessment Team
Lead:
Cal Baier-Anderson, OPPT/Risk Assessment Division (RAD)
Team Members:
Charles Bevington, OPPT/RAD
Chris Brinkerhoff, OPPT/RAD
Majd El-Zoobi, OPPT/RAD
Ernest Falke, OPPT/RAD
Gregory Fritz, OPPT/Chemistry, Economics & Sustainable Strategies Division (CESSD) (Retired)
Amuel Kennedy, OPPT/RAD
Timothy Lehman, OPPT/CESSD
Laurence Libelo, OPPT/RAD
Kendra Moran, OPPT/RAD
Nick Nairn-Birch, formerly, OPPT/Chemical Control Division (CCD)
Eva Wong, OPPT/RAD
Yintak Woo, OPPT/RAD
Management Lead:
Stan Barone, OPPT/RAD
Acknowledgements
We appreciate the assistance from members of OPPT's Environmental Assistance Division (John Shoaff,
Ana Corado and Pamela Buster) for providing information and updates to the regulatory history of CPE
FRs.
Also, portions of this document were prepared for EPA/OPPT by Abt Associates, the Eastern Research
Group (ERG), Inc., the Syracuse Research Corporation (SRC) and Versar.
Please visit the public docket (Docket: EPA-HQ-OPPT-2015-0068) to view supporting information.
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ABBREVIATIONS
°C Degrees Celsius
BAF Bioaccumulation factor
BCF Bioconcentration factor
BW Body weight
CASRN Chemical Abstracts Service Registry Number
CDC Center for Disease Control and Prevention
CoC Concentration of Concern
CPE Chlorinated phosphate ester(s)
EC European Commission
EFAST Exposure and Fate Assessment Screening Tool
EFH Exposures Factors Handbook
EPA Environmental Protection Agency
EU European Union
FR Flame retardant(s)
GD Gestation day
HHE Health hazard evaluation
HPV High production volume
hr Hour(s)
IRIS Integrated Risk Information System
IURR Inventory Update Reporting Rule
kg kilogram(s)
L Liter(s)
Lb(s) Pound(s)
LCso Lethal concentration 50 percent
LDso Lethal dose 50 percent
LOAEL Lowest-observed-adverse-effect level
m3 Cubic meter(s)
mg Milligram(s)
mg/g Milligram(s) per gram
mg/kg Milligram(s) per kilogram
mg/L Milligram(s) per liter
u.g/L Microgram(s) per liter
MOE Margin of exposure
ng/g Nanogram per gram
NIH National Institutes of Health
NOAEC No-observed-adverse-effect concentration
NOAEL No-observed-adverse-effect level
OCSPP Office of Chemical Safety and Pollution Prevention
OECD Organisation for Economic Cooperation and Development
OPPT Office of Pollution Prevention and Toxics
PBPK Physiologically based pharmacokinetic
pg picogram
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POTW Publicly Owned Treatment Works
PPE Personal protection equipment
PPRTV Provisional Peer-Reviewed Toxicity Values
PU Polyurethane
PUF Polyurethane Foam(s)
SIDS Screening Information Data Set
TCEP Tris(2-chloroethyl) phosphate
TCPP 2-Propanol, 1-chloro-, phosphate
TDCPP 2-Propanol, 1,3-dichloro-, phosphate
TRI Toxic Release Inventory
TSCA Toxic Substances Control Act
US United States
WHO World Health Organization
WWTP Wastewater Treatment Plant
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EXECUTIVE SUM MARY
As a part of EPA/OPPT's comprehensive approach to enhance the Agency's management of existing
chemicals, EPA/OPPT identified a work plan of chemicals for further assessment under the Toxic
Substances Control Act (TSCA)1 in March 2012. Chemical risk assessments will be conducted if, as a
result of scoping and problem formulation, there are exposures of concern, identified hazards and
sufficient data for quantitative analysis. If an assessment identifies unreasonable risks to humans or
the environment, EPA will pursue risk reduction. This document presents the problem formulation and
initial assessment of a cluster of chlorinated phosphate ester flame retardants (CPE FR), comprised of
tris(2-chloroethyl) phosphate (TCEP), 2-Propanol, 1-chloro-, phosphate (TCPP) and 2-Propanol, 1,3-
dichloro-, phosphate (TDCPP), as part of the TSCA Work Plan.
EPA/OPPT has identified a cluster of three CPE FR chemicals - TCEP, TCPP and TDCP - for risk
assessment. These three chemicals have similar physical and chemical properties and environmental
fate characteristics. All three chemicals are, or have been used as flame-retardants in polyurethane
foams. In addition, they have similar toxicological properties. Given the common use, widespread
exposure and potential health hazards, EPA/OPPT conducted a problem formulation based on the
evaluation of readily available data and information to determine the feasibility of conducting a
quantitative risk assessment.
The conclusions from this problem formulation and initial assessment are that EPA/OPPT will conduct
additional analyses as follows:
Assess potential risks to aquatic organisms from CPEs in the environment.
Assess potential risks to human health from incidental ingestion of CPEs in inhaled dust or via
hand-to-mouth transfer of settled dust released from consumer products.
Assess potential risks to children from incidental ingestion of CPEs from mouthing of consumer
products.
Assess potential risks to human health from consumption of CPEs in drinking water, or fish
(recreational and subsistence fishers).
Evaluate potential risks to human health from aggregate oral exposure to CPEs.
EPA/OPPT has determined that several uses are not expected to result in significant releases to the
environment and therefore will not be assessed:
Releases from manufacturing and processing resulting in exposures to adjacent communities.
The manufacture of printed circuit boards.
The formulation of paints and coatings.
The use of TDCPP in fabric, textiles and leather products.
EPA/OPPT has determined that a number of scenarios lack sufficient data to quantify risks and
therefore will not be assessed at this time:
Exposures of birds, terrestrial wildlife, or sediment-dwelling organisms (insufficient toxicity
data).
1 http://www.epa.gov/oppt/existingchemicals/pubs/workplans.html
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Releases to the environment from non-industrial (e.g., office worker) and consumer uses of
products containing CPEs (insufficient data to quantify releases).
Industrial workers via inhalation of vapor and dermal exposure (no route-specific toxicity data).
Consumer exposures via inhalation and dermal exposures (no route-specific toxicity data).
Exposures to CPE FRs in food (other than fish) will not be assessed, as this is the purview of other
federal agencies.
During scoping and problem formulation, EPA/OPPT identified available fate, exposure and hazard
data, and characterized potential exposures, receptors and effects. EPA/OPPT examined likely
exposure and hazard scenarios based on current production, use, and fate information to identify
scenarios amenable to risk analysis. The result of EPA/OPPT problem formulation was a conceptual
models and an analysis plan.
Likely sources and pathways considered for analysis include:
Releases of CPE FRs from chemical manufacturing and processing, resulting in exposures to
aquatic organisms via contact with contaminated water.
Releases of CPE FRs from consumer products, resulting in exposures via the incidental ingestion
of air-suspended particulates or resuspended dust and hand-to-mouth transfer of settled dust.
Mouthing of consumer and children's products containing CPE FRs by children, resulting in
incidental oral exposures.
Releases of CPE FRs from chemical manufacturing and processing, resulting in exposures via the
ingestion of contaminated drinking water and fish.
Releases to water from chemical manufacturing, polyurethane foam manufacturing and textile
processing are possible and could result in exposures to ecological receptors. EPA/OPPT anticipates
that available toxicological data will support the evaluation of acute and chronic exposures in fish,
daphnids (invertebrates) and algae.
The evaluation of human health risks will focus on general population and consumer oral exposures.
For children and adults, exposures in the home and in other common microenvironments (e.g.,
schools, daycares, public and commercial buildings, vehicles) may be considered. Consumer exposures
to CPE FRs are expected via multiple exposure pathways due to their migration from the polymer
matrix into the environment where they are used, either via emission from the products and
adsorption to particulates and settled dust or via matrix decomposition, aging or release. Because the
predominant consumer uses of CPE-containing polymers, such as insulation and furniture, are in indoor
environments, the potential for exposure via all exposure routes (i.e., inhalation of indoor air and dust,
dermal contact with products and incidental ingestion of dust) is high.
Mouthing of consumer and children's products containing CPE FRs could result in the migration from
the polymer matrix into a child's mouth, resulting in oral exposures. General population oral exposures
will be evaluated based on assessed industrial releases and the presence of CPE FRs in fish and drinking
water.
Human endpoints include cancer and non-cancer effects. Two CPEs (i.e., TCEP and TDCPP) are known
animal carcinogens. Other non-cancer laboratory animal studies have shown effects on the kidney,
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liver and the neurological system. Thyroid effects and developmental and reproductive toxicity were
more variable across studies.
Inhalation exposures and dermal contact are expected to be significant exposure routes for industrial
workers and consumers. However, as there are no toxicological data for inhalation or dermal exposure
routes, therefore EPA/OPPT will not assess inhalation or dermal exposure. Inhalation and dermal
toxicity studies have been identified as a critical data gap, necessary to evaluate these exposure
pathways.
In summary, as a result of this problem formulation, EPA/OPPT proposes to conduct an assessment to
evaluate potential risks to aquatic organisms and human health. This document describes the results of
problem formulation and the proposed approach for the risk assessment under the TSCA Existing
Chemicals Program using existing data and methods. EPA/OPPT plans to carefully review and evaluate
the results of previous exposure assessments and health benchmarks. EPA will develop margins of
exposure and cancer risk estimates to evaluate the potential risks from consumer and general
population exposure to CPE FRs.
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1 INTRODUCTION
As a part of EPA/OPPT's comprehensive approach to enhance the Agency's management of existing
chemicals, in March 2012 EPA/OPPT identified a work plan of chemicals for further assessment under
the Toxic Substances Control Act (TSCA)2. After gathering input from stakeholders, EPA/OPPT
developed criteria used for identifying chemicals for further assessment3. The criteria focused on
chemicals that meet one or more of the following factors: (1) potentially of concern to children's
health (for example, because of reproductive or developmental effects); (2) neurotoxic effects; (3)
persistent, bioaccumulative and toxic (PBT); (3) probable or known carcinogens; (4) used in children's
products; or (5) detected in biomonitoring programs. Using this methodology, EPA/OPPT identified a
TSCA Work Plan of chemicals as candidates for risk assessment in the next several years. In the
prioritization process, a cluster of chlorinated phosphate ester flame retardant chemicals, including
tris(2-chloroethyl) phosphate (TCEP2-propanol, 1-chloro-, phosphate (TCPP) and 2-propanol, 1,3-
dichloro-, phosphate (TDCPP), was identified for assessment based on human health and ecotoxicity
concerns, potential for human exposure, moderate releases to the environment and moderate
environmental persistence.
EPA/OPPT is performing risk assessments on chemicals in the work plan. If an assessment identifies
unacceptable risks to humans or the environment, EPA/OPPT will pursue risk reduction. The target
audience for this risk assessment is primarily EPA risk managers; however, it may also be of interest to
the broader risk assessment community as well as US stakeholders interested in TCEP, TCPP and
TDCPP. The information presented in the risk assessment may be of assistance to other federal, state
and local agencies as well as to members of the general public who are interested in the risks of TCEP,
TCPP and TDCPP.
The initial steps in EPA/OPPT's risk assessment development process, which is distinct from the initial
prioritization exercise, includes scoping and problem formulation. During these steps EPA/OPPT
reviews currently available data and information, including but not limited to, assessments conducted
by others (e.g., authorities in other countries), published or readily available reports and published
scientific literature.
This document includes the results of scoping and problem formulation for the chlorinated phosphate
ester cluster. In the initial prioritization and scoping stages, EPA/OPPT determined which chemicals
would be included in the cluster and which uses would be considered in the assessment. During
problem formulation, EPA/OPPT identified available exposure and hazard data, and characterized
potential exposures, receptors and effects. EPA/OPPT developed the conceptual models (Figure 2-2
and Figure 2-3) and analysis plan (section 2.6.2) as a result of problem formulation.
2 http://www.epa.gov/oppt/existingchemicals/pubs/workplans.html
3 http://www.epa.gov/oppt/existingchemicals/pubs/wpmethods.pdf
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1.1 Scope of the Assessment
Chlorinated phosphate ester (CPE) flame retardants (FR) are high production volume chemicals (up to
50M Ibs/yr, based on publicly available information) produced or imported into the United States (EPA,
2012). CPE FRs are widely used in applications for paints and coatings, textiles, insulation and
polyurethane foam. Restrictions on the use of polybrominated diphenyl ethers (PBDEs) (EPA, 2012)
have likely spurred the increased use of alternative flame retardants, such as CPE FRs, to meet
flammability standards for many consumer products, such as mattress pads, furniture or automobile
seating. The general US population may be exposed to these chemicals through multiple pathways
(Wei etal., 2015).
Animal toxicity studies indicate effects that may be suggestive of human health concerns. Two CPEs
(i.e., TCEP and TDCPP) are known animal carcinogens. TCPP is currently under study4. Other animal
studies have shown effects on the kidney, liver and the neurological system. Thyroid effects and
developmental and reproductive toxicity were more variable across studies. Given the common use,
widespread exposure and potential health hazards, EPA/OPPT conducted a problem formulation and
evaluation of readily available data and information to determine the feasibility of conducting a
quantitative risk assessment.
EPA/OPPT selected cluster members and uses for inclusion in this assessment based on available data,
including chemical structure, physical chemical properties, toxicological information from existing
assessments, production volume and reported uses. During the initial work plan chemical prioritization
process described above, EPA/OPPT identified TCEP as a work plan chemical, although commercial
uses of TCEP as a flame retardant were declining, since TCPP and TDCPP were structurally similar and
increasing as substitutes for TCEP. As a result, EPA/OPPT grouped the three chemicals for evaluation
(Table 1-1). The rationale for taking a "use cluster approach" is to evaluate chemicals that have a
common pattern of use and may have similar fate, exposure and toxicity. Additionally, the cluster
approach presents efficiencies in data evaluation and analysis.
4 http://ntp.niehs.nih.gov/testing/status/agents/ts-m20263.html
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Table 1-1: CPE FR Cluster Members and Structures
CASRN
NAME
STRUCTURE
115-96-8
Ethanol, 2-chloro-, phosphate (3:1);
Tris(2-chloroethyl) phosphate
(TCEP)
Ck /\
13674-84-5
2-Propanol, 1-chloro-, 2,2',2"-phosphate;
2-Propanol, 1-chloro-, phosphate
(TCPP)
Ck
(representative structure)
13674-87-8
2-Propanol, 1,3-dichloro-, phosphate (3:1);
2-Propanol, 1,3-dichloro-, phosphate
(TDCPP)
Ck
Cl
Ck
. ^^
o i o
Cl
EPA/OPPT considered additional CPE FR chemicals for inclusion in the cluster. This process began with
the universe of chlorine- and phosphorus- containing chemicals on the TSCA Inventory. Selection
criteria included chemical structure, physical chemical properties and data availability. Data availability
requirements included sufficient exposure and toxicity data to permit a quantitative assessment. In
addition to shared structural similarity, the three CPE FR cluster chemicals are most similar in terms of
physical chemical properties and fate, in particular vapor pressure, water solubility and octanol water
partition coefficient (Table 1-2). The three chemicals also have sufficient data for risk assessment
(Appendix A).
Table 1-2: Select Physical Chemical Properties Used For Selecting Cluster Members
Property
Physical State at Room
Temperature
Boiling Point3
°C
Vapor Pressure0
Pa
Water Solubility0 mg/L
Octanol Water Partition Coeff.
Log Kowc
TCEP
CASRN
115-96-8
Liquid
> 200° C [decb]
1.14 E-3
7820
1.78
TCPP
CASRN
13674-84-5
Liquid
> 200° C [dec]
1.4 E-3C
1080
2.68
TDCPP
CASRN
13674-87-8
Liquid
> 200° C [dec]
5.6 E-6
18
3.68
Notes:
"Stability of C-CI bond loss HCI begins 200° C
bdec = decomposition noted
CEU (2008b)
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1.2 Regulatory and Assessment History
EPA/OPPT reviewed the regulatory and assessment history of TCEP, TCPP, and TDCPP, to identify
exposures, hazards and risks that have been previously documented.
National
TCEP, TDCPP and TCPP are existing chemicals on the TSCA Inventory and therefore were not subject to
EPA's new chemicals review process and were grandfathered in with the passage of the Toxic
Substances Control Act of 1976. EPA has established Provisional Peer-Reviewed Toxicity Values
(PPRTVs) for TCEP5.
The ATSDR Toxicological Profile for Phosphate Ester Flame Retardants (2012) included TCEP, TDCPP
and TCPP and provided detailed analyses of available hazard data. An earlier evaluation by the CPSC
(2006) assessed the cancer risks associated with inhalation of TDCPP vapor released from furniture
foam and cover fabrics. Estimated cancer risks from lifetime exposure in the home was 300 per million
for adults and estimated cancer risk for children from inhalation exposure during the first two years of
life was 20 per million. The Hazard Index (a comparison of exposure and critical effect level) was 2 for
adults and 5 for children. CPSC estimated that 98-99% of exposure was via the inhalation route.
State
TCEP and TDCPP are both listed on California's proposition 65 list of chemicals known to the state of
California to cause cancer6. In addition, California Department of Toxic Substances Control (DTSC) has
proposed TDCPP and TCEP in Children's Foam Padded Sleeping Products for regulation under the Safer
Consumer Products Regulations.7
These CPEs are subject to regulations by a number of states. Other states that have proposed
legislation that could affect the use of TCEP, TDCPP and TCPP include Washington, Massachusetts and
North Carolina.
International
The European Union (EU) has conducted risk assessments for TCEP, TCPP and TDCPP (EU, 2008a,
2008b, 2009). Occupational, general population, consumer and ecological exposures were included in
these assessments and in some cases, unacceptable risks were identified. Specifically, risks to workers
from inhalation and dermal exposure to TCEP were identified, as were risks to children from mouthing
of objects made with TCEP (EU, 2009). For all scenarios, risk estimates were based on both
carcinogenic and repeat dose effects. For children's risk, the assessment assumed high migration rates
via mouthing of articles containing TCEP. The EU concluded that the use of TCEP in toys should be
avoided (EU, 2012). TCEP is listed in the EU Authorisation List based on reproductive toxicity (category
IB) with a sunset date of August 21, 2015. No concerns were identified for ecological receptors.
5 http://hhpprtv.ornl.gov/quickview/pprtv.php
6 http://oehha.ca.gov/prop65/prop65 list/Newlist.html
7 http://www.dtsc.ca.gov/SCP/index.cfm
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Based on a screening assessment of TCEP, Canada passed a Significant New Activity provision in
January 2013 (Health Canada, 2014). As of April 2014, products made, in whole or in part, of
polyurethane foam that contains TCEP and are intended for children under three years of age were
added to Schedule 2 of the Canada Consumer Product Safety Act (CCPSA), based on concerns for
carcinogenicity and impaired fertility. These products are prohibited from manufacture, import,
advertising or sale.
Although the EU risk assessment for TDCPP also identified potential risks to workers, it concluded that
current risk management measures should be effective (EU, 2008b). No risks were identified for
consumers, general population, or ecological receptors. These conclusions took into account the EU
determination that the cancer risks were below the threshold of concern.
The EU risk assessment for TCPP did not identify unacceptable risks for workers, consumers, general
population, or ecological receptors (EU, 2008a).
Appendix B contains additional information on the assessment and regulatory history of these
chemicals.
2 PROBLEM FORMULATION
Problem formulation aims to determine the major factors to be considered in an assessment, including
exposure pathways, receptors and health endpoints (EPA, 1998, 2014b). Accordingly, this problem
formulation summarized the exposure pathways, receptors and health endpoints EPA/OPPT
considered to determine whether to conduct further risk analysis and what exposure/hazard scenarios
to include in a potential risk assessment. To make this determination, EPA/OPPT conducted a
preliminary data review to identify available fate, exposure and hazard data and determine its likely
suitability for quantitative analysis and to identify exposure pathways, receptors and health endpoints
for quantitative analysis.
EPA/OPPT summarized the outcome of this evaluation in conceptual models for ecological and human
health that illustrate the exposure pathways, receptor populations and effects that will be considered
in the risk assessment. EPA/OPPT also prepared analysis plans to demonstrate the proposed approach
to answering the defined assessment questions for ecological and human health.
Data Needs
This section summarizes data identified and considered during problem formulation and used to
construct the conceptual models. The process by which use and exposure scenarios were selected for
inclusion in the conceptual model was informed by the identification of high volume uses that are
known or likely to be associated with exposures. The selection process was further aided by the
identification of data quality objectives to establish study boundaries and determine the type of data
needed to complete the assessment (EPA, 1994b, 1998). Following these established guidelines,
EPA/OPPT identified the approach that will be used to assess risks, the data inputs needed and
requirements for these inputs.
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To determine if CPE FRs present a risk to human health, non-cancer risks will be assessed using the
Margin of Exposure (MOE) approach. This approach requires the selection of a critical effect in a key
study to determine the Point of Departure (POD). Cancer risks will be determined based on low-dose
linear extrapolation, which requires the derivation of a cancer slope factor. To assess risks to ecological
receptors, the Concentration of Concern (CoC) will be established. Both approaches require the
comparison of estimated exposure with a critical effect level (e.g., the POD or the CoC). The types of
data required for conducting this type of quantitative risk assessment are defined in Table 2-1.
Table 2-1: Data Required for Risk Assessment
Exposure
Scenarios
Exposure
Hazard/Toxicity
Workers
Manufacture and
processing.
General
Population
Releases to the
environment
(affecting water
and edible).
Consumers
Consumer
product uses
resulting in
direct
exposures or
releases to
indoor
environments.
Ecological
Receptors
Releases to the
environment.
Measured or modeled concentrations in relevant media may be used. A
combination of these approaches may be considered depending on the
receptor and exposure scenario of interest.
Route-specific mammalian toxicity data [or
physiologically based pharmacokinetic (PBPK)
models to estimate internal doses]. Toxicological
effects that are sensitive, adverse and relevant to
the potentially exposed populations.
Acute and chronic
effects data.
2.1 Physical Chemistry
CPE FRs are formed via reaction derived from the addition of epoxide with O=P(CI)3. TCEP is formed
using ethylene oxide. TDCPP is formed using epichlorohydrin. TCPP is a chloropropyl phosphate,
formed using propylene oxide. The common chemical structure is shown in Figure 2-1. The main
substituents or "R" groups are shown in Table 2-2. TCPP has a chiral center and is comprised of four
isomers (EU, 2008a), as displayed in Table 2-3. All commercial mixtures contain varying amounts of the
isomers and available toxicity data are based on the commercial mixture (NRC, 2000).
RO
O
P OR
OR
Figure 2-1: CPE FR Structure
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Table 2-2: CPE FR Substituents, "R" groups
CASRN
115-96-8
13674-84-5
13674-87-8
Name
Ethanol, 2-chloro-, phosphate (3:1);
(TCEP)
2-Propanol, 1-chloro-, 2,2',2"-phosphate;
(TCPP)
2-Propanol, 1,3-dichloro-, phosphate (3:1);
(TDCPP)
R =
-CH2-CH2-CI
-CH(CH3)-CH2-CI*
-CH-(CH2-CI )2
Note: * Major isomer
TCPP has chiral centers and is typically comprised of a mixture of four isomers (EU, 2008a), as displayed
in Table 2-3. All commercial mixtures contain varying amounts of the isomers and available toxicity
data is based on the commercial mixture (NRC, 2000).
Table 2-3: TCPP in commercial products
CASRN
13674-84-5
76025-08-6
76649-15-5
6145-73-9
Chemical Name
2-Propanol, 1-chloro-, 2,2',2"-phosphate
Bis(2-chloro-l-methylethyl) 2-
chloropropyl) phosphate
2-Chloro-l-methylethyl bis(2-
chloropropyl) phosphate
1-Propanol, 2-chloro-, phosphate (3:1);
Chemical Structure
/ I
O
\x\
01 \ ii /L /ci
Vo-p-cr ^-^
/ 0
y
O-P-O
V
Cl
1
o 1
cy
w/w % TCPP in commercial
products
50 - 85%*
15 - 40%
«»,
<»
Note:
*Commercial manufacture produces TCPP as 70 - 85% CASRN = [13674-84-5].
The most abundant isomer in commercial products is the completely branched isomer, 2-Propanol, 1-
chloro-, 2,2',2"-phosphate (CASRN = 13674-84-5) and the least abundant form is the completely linear
isomer, 1-Propanol, 2-chloro-, phosphate (3:1) (CASRN = 6145-73-9) (NRC, 2000). Variations in
manufacturing methods result in commercial formulations that contain different proportions of the four
isomers. The different isomers may produce differential toxicity and EPA/OPPT will consider this
potential variability when evaluating data for use in the risk assessment.
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Select physical and chemical properties are displayed in Table 1-2 of section 1.1. A more complete
listing of physical and chemical properties is presented in Table 2-4 below.
Table 2-4: Physical Chemical Properties
Property
Molecular Weight (grams/mol)
Physical State at Room
Temperature
Odor
Density at 25° C
Melting Point
Boiling Point3
°C
Vapor Pressure0
Pa
Water Solubility0 mg/L
Octanol Water Partition Coeff.
Log Kowc
TCEP
CASRN
115-96-8
285.50
Liquid
Slight Odor
1.425 g/cm3
-55° C
> 200° C [decb]
1.14 E-3
7820
1.78
TCPP
CASRN
13674-84-5
327.57
Liquid
Mild Odor
1.29 g/cm3
-40° C
> 200° C [dec]
1.4 E-3C
1080
2.68
TDCPP
CASRN
13674-87-8
430.88
Liquid
Mild Odor
1.48 g/cm3
27° C
> 200° C [dec]
5.6 E-6
18
3.68
Notes:
"Stability of C-CI bond loss HCI begins 200° C
bdec = decomposition noted
CEU (2008b)
2.2
Production Volume and Use
EPA/OPPT searched the 2012 Chemical Data Reporting (CDR) database and market reports, to identify
the uses and associated production volumes of each chemical, summarized in Table 2-5. Some
information claimed as confidential business information cannot be included in this report.
Additionally, primary literature and the Washington State's Children's Safe Product Act Database8 were
searched for other potential uses. Additional information is provided in Appendix B.
TCEP's only CDR reported use is under the "paints and coatings" sector for both the industrial and
consumer/commercial categories. Although not reported to the CDR, TCEP has also been reported to
be used as a flame retardant in children's car seats (Washington State, 2014) and has been detected in
changing table pads, sleep positioners, portable mattresses, nursing pillows, baby carriers and infant
bath mats (Stapleton et al., 2011).
TCPP is reported to the CDR in a variety of industrial use categories such as "furniture and related
products" for the manufacture of flexible polyurethane foam and under "textiles, apparel and leather"
for fabric finishing processing. Other industrial uses are given in Table 2-5. TCPP is reported to be used
8 https://fortress.wa.gov/ecy/cspareporting/Default.aspx
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in a variety of commercial and consumer use categories as well. Potential end-uses within the reported
commercial and consumer products include household upholstered furniture and foam baby products,
printed circuit boards in automotive electronics, fire stop sealants and panels and laminates for
insulation and roofing applications. TCPP has been detected in household furniture including
footstools, ottomans and chairs (Stapleton et al., 2009). TCPP has also been detected in polyurethane
foam in certain baby products including car seats, changing table pads, sleep positioners, portable
mattresses, nursing pillows and rocking chairs (Stapleton et al., 2011).
TDCPP is listed in the CDR's industrial use category under the construction sector and in the
commercial and consumer use category under "building/construction materials." These sectors may
refer to TDCPP's use in the manufacture of rigid polyurethane foam, which is used in laminates, pipes
and ducts. Although not reported as a use in the CDR, TDCPP has been detected in furniture such as
sofas, chairs and futons and in baby products including rocking chairs, baby strollers, car seats,
changing pads, sleep positioners, portable mattresses, nursing pillows and infant bathmats (Stapleton
et al., 2009; Stapleton et al., 2011). TDCPP has also been reported to the Washington State Children's
Safe Product Act database (2014) for its use as a flame retardant in "arts/crafts variety pack" and also
as a contaminant in footwear for children9.
9 Arts/Crafts Variety Pack" includes any products that may be described/observed as two or more distinct Arts and Crafts
products sold together, which exist within the schema but belong to different classes; that is, two or more products
contained within the same pack, which cross classes within the Arts and Crafts Family (GS1, 2014).
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Table 2-5: 2012 CDR Reported Use and Production Volumes
Industrial Use
Reported to the
2012 CDR
Description of Industrial
Use (Based on the
Industrial Use Reported to
the 2012 CDR)
Commercial or
Consumer Use
Reported to the 2012
CDR
Potential End-Uses
Within CDR Category
2012 CDR Production Volume
Industrial
(Ibs)
Consumer/
Commercial
(Ibs)
Approximate %
of National PV
by Use
TCEP, (Ethanol, 2-chloro-, phosphate (3:1); Tris(2-chloroethyl) phosphate); 115-96-8
2012 CDR National Production Volume = CBI
Processing: Paints
and Coating
Formulation of Paints and
Coatings
Paints and coatings
(not known if intended
for consumer/
commercial or both)
Paints and Coatings
CBI
CBI
CBI
TCPP (2-Propanol, 1-chloro-, phosphate); 13674-84-5
2012 National Production Volume = 54,673,933
Processing:
Furniture and
Related Products
(337)
Processing:
Textiles, apparel
and leather (313-
316)
Processing:
Plastics Material
and Resins
(325211)
Construction
Manufacture of flexible PU
Foam for the manufacture
of upholstered furniture
Fabric finishing process
Material Fabrication
Process for the
Manufacture of Printed
Circuit Boards
Formulation of Adhesives
and Sealants (Not reported
as aflame retardant)
No Data Reported
Foam Seating and
Bedding Products
(commercial and
consumer use)
Electrical and
Electronic Products
(commercial and
consumer use)
Adhesives and
Sealants (Commercial)
Polyurethane foam
in household
furniture (e.g.,
footstools, ottomans
and chairs)
Polyurethane foam
in baby products
(e.g., car seats,
changing table pads,
sleep positioners,
portable mattresses,
nursing pillows and
rocking chairs)
Automotive
electronics/printed circuit
boards
- fire stop sealants
43,312,813
780, 604
17,325,125
12,993,844
12,993,844
780, 604
32
24
24
1.4
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Industrial Use
Reported to the
2012 CDR
Construction*
Processing: Paints
and Coatings
All Other Basic
Organic Chemical
Processing
Description of Industrial
Use (Based on the
Industrial Use Reported to
the 2012 CDR)
Manufacture of Rigid PU
Foam (boardstock/
laminate, pour-in-place, or
spray applied)
Formulation of Paints and
Coatings
Unknown
Commercial or
Consumer Use
Reported to the 2012
CDR
Construction Products
Building/ Construction
Materials Not Covered
Elsewhere
(commercial and
consumer use)
N/A
Potential End-Uses
Within CDR Category
Panels and laminates
for insulation
applications
Roofing laminate
N/A
2012 CDR Production Volume
Industrial
(Ibs)
1,896,664
CBI
CBI
Consumer/
Commercial
(Ibs)
CBI
CBI
CBI
Approximate %
of National PV
by Use
<20%
TDCPP, (2-Propanol, 1,3-dichloro-, phosphate); 13674-87-8
2012 CDR National Production Volume = 10-50 million pounds
Construction
Manufacture of Rigid PU
Foam (boardstock/
laminate, pour-in-place, or
spray applied)
Building/Construction
Materials, e.g.
Laminates, pipes, &
ducts. (Consumer &
commercial)
- Laminates
- Pipes
- Ducts
CBI
CBI
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Industrial Use
Reported to the
2012 CDR
Processing:
Furniture and
Related Products
Description of Industrial
Use (Based on the
Industrial Use Reported to
the 2012 CDR)
Manufacture of flexible PU
Foam for the manufacture
of upholstered furniture
Commercial or
Consumer Use
Reported to the 2012
CDR
Foam Seating and
Bedding Products
(Consumer &
commercial)
Fabric, Textile and
Leather Products Not
Covered Elsewhere
(Commercial)
Potential End-Uses
Within CDR Category
Furniture (e.g., sofas,
chairs, futons,
rocking chairs)
Automotive seating
(i.e., cushions and
headrests)
Baby products (e.g.,
strollers, car seats,
changing pads, sleep
positioners, portable
mattresses, nursing
pillows, infant
bathmats)
Automotive fabric
lining
Car roofing
Textile back coating
(specific textiles are
not known)
2012 CDR Production Volume
Industrial
(Ibs)
CBI
CBI
Consumer/
Commercial
(Ibs)
CBI
CBI
Approximate %
of National PV
by Use
CBI
CBI
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2.3 Fate and Transport
The EPA Design for the Environment Branch (DfE) recently published draft hazard profiles for TCEP,
TCPP and TDCPP (EPA, 2014a) and included in these hazard profiles are assessments of fate,
persistence and bioaccumulation. The summary below is based on information included in the DfE
Report.
Although Level III fugacity models incorporating available physical and chemical property data indicate
that at steady state TCEP and TCPP are expected to be found primarily in soil and to a lesser extent,
water, available data from environmental monitoring indicates that TCEP and TCPP are routinely found
in water. TCEP and TCPP are expected to have high mobility in soil, based on measured or estimated
Koc values. Leaching through soil to groundwater may occur. In the atmosphere, TCEP is expected to
exist in the vapor phase based on its vapor pressure (EPA, 2014a).
Level III fugacity models indicate that at steady state TDCPP will likely be found primarily in soil and to
a lesser extent, sediment and water. Leaching through soil to groundwater may occur. Monitoring data
suggests TDCPP is bound to particulates in the atmosphere (EPA, 2014a; Moeller et al., 2011).
TCEP persistence is anticipated to be moderate, whereas TCPP and TDCPP are generally highly
persistent. TCEP is expected to hydrolyze slowly; although hydrolysis rates will be dependent on
temperature and pH conditions according to experimental studies. 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. None of the chemicals are expected to be susceptible to direct photolysis by sunlight,
since they do 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-lives of vapor-phase TCEP and TCPP are estimated to be less than one day, although TCPP is not
expected to partition significantly to the atmosphere (EPA, 2014a).
Monitoring studies have reported the detection of TCEP in aquatic species, mammalian species,
herring gull eggs and pine needles. 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 (EPA, 2014a).
2.4 Exposures
This section provides an overview of available exposure data and the receptors identified for
quantitative risk assessment. Data availability tables are available in Appendix A. More detailed
exposure summaries, including additional references, are presented in Appendix D. This appendix also
includes literature references for the data that is related to releases of CPE FRs to the environment
from industrial sites and that EPA took into account in preparing this document.
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2.4.1 Releases to the Environment
EPA/OPPT reviewed readily available sources for information related to the release of flame-retardants
in general from industrial sources. EPA/OPPT also searched the scientific literature for data related to
releases to the environment from industrial sites, but did not find any chemical-specific data. US Toxic
Release Inventory (TRI) data are not available for these chemicals. Releases to water from industrial
operations are possible and may have localized impacts on ecological receptors. CPEs are present in
WWTPs, sludge and biosolids, although in most cases, the source or sources are not known. Additional
information is available in Appendix D.
2.4.2 Presence in the Environment
Several studies throughout the US and abroad have reported levels of the CPEs in the effluent and
influent of wastewater. Measurements in sludge have been made in the EU. However, no US data were
identified. Several studies throughout the US and abroad have reported levels of the CPEs in surface
water. CPEs have been detected in several studies of US drinking water. Collectively, these data
indicate high potential for exposures to ecological receptors, and in particular, aquatic organisms.
Additional information is available in Appendix D.
2.4.3 Occupational Exposures
EPA/OPPT considers inhalation of vapor and dermal exposure to be the most important CPE FR
exposure pathways for industrial workers based on (EU (2008a), (2008b)). Occupational inhalation
exposure monitoring data for industrial workers in the US are not available, but monitoring data for
inhalation exposure of European workers to TCPP or TDCPP vapors at industrial facilities are reported
(EU, 2008a, 2008b). Worker exposure to PU foam dust that contains TCPP or TDCPP due to cutting of
PU foam has been reported to be possible but was not assessed (EU, 2008a, 2008b). Use of
engineering controls (dust extractors) that limit the possibility of dust exposure were reported in
Europe (EU, 2008a, 2008b).
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2.4.4 General Population Exposures
General population exposures include exposures through food and drinking water. Several European
studies (from Spain, Sweden and Norway) and one Canadian study have identified CPE FRs in fish.
Several studies show that the levels of contaminants varied in relation to their proximity to sewage
treatment plants. EPA/OPPT is not aware of data indicating presence of CPE FRs in fish from the US.
However, as noted above, CPE FRs have been detected in US drinking water. Data summaries and
additional references are available in Appendix D. EPA/OPPT considers it possible that presence in fish
and drinking water may contribute to aggregate oral exposures.
2.4.5 Consumer Exposures
Consumer exposures to CPE FRs may include:
Inhalation of vapor,
Dermal exposure to vapor,
Direct skin contact with CPE FRs on the surface of objects or articles,
Incidental ingestion of air-suspended particulates or resuspended dust that is subsequently
trapped in mucous and moved from the respiratory system to the gastrointestinal tract
(referred to here as incidental ingestion of inhaled dust), and
Incidental ingestion of indoor settled dust via hand-to-mouth behaviors.
In addition, children may experience incidental ingestion via object-to-mouth behaviors.
A number of published studies have reported levels of CPEs in indoor air and dust. For children and
adults, exposures in the home and in other common microenvironments (e.g., schools, daycares, public
and commercial buildings, vehicles) may be considered. EPA/OPPT considers exposures to CPE FRs
indoor environments to be possible through inhalation of vapor, incidental ingestion of inhaled dust
and hand-to-mouth transfer of settled dust (Cao et al., 2014; EPA, 2011; Makinen et al., 2009; Staaf
and Ostman, 2005a; Yang et al., 2014). Additional details and summary data are available in Appendix
D.
Numerous studies have measured concentrations of CPE FRs in infant products such as high chairs,
bath mats, car seats, nursing pillows, carriers (Fang et al., 2013; Stapleton et al., 2011) sofas (Stapleton
et al., 2009; Stapleton et al., 2012) and camping tents (Keller et al., 2014). Because many of these
products are used in indoor environments, such as homes, consumer and children are likely to be
exposed on a continuing basis using these products. CPE FRs are present in air and dust within the
home. Exposures may be through inhalation of vapor or dust, dermal contact and incidental ingestion
of inhaled dust. Small children may have additional exposures through contact with baby products
containing CPEs and via mouthing behaviors. Data summaries are presented in Appendix D.
2.5 Hazard Endpoints
EPA's Integrated Risk Information System (IRIS) program has not developed a toxicological review for
any of the CPE FRs in this cluster. In the absence of an IRIS assessment, EPA/OPPT's preliminary hazard
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evaluation for CPE FRs was based on several existing assessments. In particular, the following studies
were deemed helpful, as they were peer reviewed, widely distributed and largely concordant:
Toxicological Profile for Phosphate Ester Flame Retardants (human health hazards only)
(ATSDR, 2012)
EU Risk Assessment Report: Tris (2-Chloroethyl) Phosphate, (TCEP) CAS No: 115-96-8 (EU, 2009)
EU Risk Assessment Report: Tris(2-Chloro-l-Methylethyl) Phosphate (TCPP) CAS No: 13674-84-5
(EU, 2008a)
EU Risk Assessment Report: Tris[2-Chloro-l-(Chloromethyl)Ethyl] Phosphate (TDCP) CAS No:
13674-87-8 (EU, 2008b)
2.5.1 Ecological Hazard
Data availability tables are presented in Appendix A. Available hazard information for ecological
receptors, summarized in Appendix E, is limited to aquatic organisms. There is a robust data set for
acute aquatic toxicity, including fish, invertebrate and algal toxicity data for all three chemicals. Chronic
aquatic toxicity data is available for daphnids, but not fish. There are no sediment toxicity data or
terrestrial toxicity data.
Sublethal effects were observed in acute tests with fish that included loss of coordination that
culminated in overturned fish, edema, darkened pigmentation and hyperventilation. These effects
suggest potential for long-term population level concerns in fish. In the absence of studies that
characterize fish life stages to address population level concerns, EPA/OPPT will consider alternative
approaches for evaluating chronic toxicity concerns in fish that may include use of acute-to-chronic
ratios derived from halogenated phosphate esters with pesticidal use and non-halogenated phosphate
esters with a comparison of sub-lethal effects observed in acute studies.
2.5.2 Human Health Hazard
Bioavailability and Metabolism
Animal studies show that TDCPP, TCEP and TCPP are rapidly and extensively absorbed following oral
dosing. Dermal absorption was significant for rats exposed to TDCPP and for in vitro studies of human
skin exposed to TCPP. Exposure to nebulized TCEP also found extensive absorption (Yoshida et al.,
1997), suggestive of the potential for absorption via inhalation although no toxicokinetic data are
available for quantifying inhalation absorption. Absorbed TDCPP, TCEP and TCPP distribute throughout
the body without preferential accumulation in specific tissues or organs. Transfer to human breast milk
is indicated by biomonitoring studies that have found TCEP, TCPP and TDCPP in human breast milk.
TDCPP, TCEP and TCPP are rapidly metabolized by extensive Phase I and Phase II metabolism. TDCPP is
likely metabolized by a combination of MFO, hydrolase and GST reactions producing glutathione
conjugates. TCEP and TCPP are likely metabolized by a similar pathway of hydroxylation possibly by
MFO and CYP 450 enzymes then conjugated with glucuronic acid. Some of the metabolism of TCEP may
occur extrahepatically, possibly via B-esterases. The metabolic products of TDCP, TCEP and TCPP are
rapidly excreted, primarily in the urine. The biliary/fecal excretion ratios for TCEP and TCPP indicate
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enterohepatic re-circulation occurs. PBPK models have not been developed for any of the phosphate
ester flame retardants.
Toxicological Effects
A review of existing assessments and other readily accessible information during scoping and problem
formulation reveals a number of well-characterized toxicological effects. The ATSDR Toxicological
Profile provides a detailed summary of available toxicological data for these chemicals (ATSDR, 2012).
Data availability tables are available in Appendix A. Key endpoints are summarized below, but
additional detail, including complete references, can also be found in Appendix F.
Animal studies show that TDCPP, TCEP and TCPP are rapidly and extensively absorbed following oral
dosing. Dermal absorption was significant for rats exposed to TDCPP and for in vitro studies of human
skin exposed to TCPP. Exposure to nebulized TCEP also found extensive absorption (Yoshida et al.,
1997), suggestive of the potential for absorption via inhalation although no toxicokinetic data are
available for quantifying inhalation absorption. Absorbed TDCPP, TCEP and TCPP distribute throughout
the body without preferential accumulation in specific tissues or organs. Transfer to human breast milk
is indicated by biomonitoring studies that have found TCEP, TCPP and TDCPP in human breast milk.
TDCPP, TCEP and TCPP are rapidly metabolized by extensive Phase I and Phase II metabolism. TDCPP is
likely metabolized by a combination of MFO, hydrolase and GST reactions producing glutathione
conjugates. TCEP and TCPP are likely metabolized by a similar pathway of hydroxylation possibly by
MFO and CYP 450 enzymes then conjugated with glucuronic acid. Some of the metabolism of TCEP may
occur extrahepatically, possibly via B-esterases. The metabolic products of TDCP, TCEP and TCPP are
rapidly excreted, primarily in the urine. The biliary/fecal excretion ratios for TCEP and TCPP indicate
enterohepatic re-circulation occurs. PBPK models have not been developed for any of the phosphate
ester flame-retardants.
Repeat dose studies indicate that the kidney is a key target organ. In subchronic toxicity tests, kidney
effects were noted with all three chemicals. In chronic studies with TCEP (NTP, 1991) and TDCPP
(Freudenthal and Henrich, 2000), precancerous and cancerous lesions were observed in the kidneys.
Mild liver toxicity (increased liver weights) was also observed in two studies, one on TCDPP (Stauffer
Chemical Company, 1981) and another with TCEP (NTP, 1991). Thyroidal effects were seen in TCPP and
TDCPP (Freudenthal and Henrich, 1999, 2000).
As noted previously, TCEP and TDCPP are considered animal carcinogens. For example, TCEP exposure
was associated with renal tubule adenomas and carcinomas (rats, mice) and follicular cell adenoma or
carcinoma of the thyroid (female, high dose rats). A two-year study of TDCPP in rats identified kidney
tumors (males, females, testicular tumors (males) and adrenocortical tumors (females) (Freudenthal
and Henrich, 1999).
The chemicals in this cluster are considered weak inhibitors of acetylcholinesterase. The toxicological
impact of such inhibition continues to be debated. Blood and plasma cholinesterase studies are often
conflicting. A number of studies testing TCEP identified neurological effects, such as seizures or
convulsions (NTP, 1991; Tilson et al., 1990). A 16-week study in rats found hippocampal lesions, with
females more impacted (NTP, 1991). Degenerative brain lesions were also found in female rats in a 2-
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year study (NTP, 1991). A similar 2-year study on TDCPP did not identify brain lesions or clinical signs
(Freudenthal and Henrich, 1999).
Two studies are available that assess CPEs effect on fertility; high doses of TCEP (>350 mg/kg/day)
reduced the number of litters in a continuous breeding study and sperm parameters were reduced. In
contrast, there were no effects on reproductive toxicity caused by TDCPP in rabbits (Anonymous,
1977), although in a two-year study with rodents, testicular lesions were noted (Freudenthal and
Henrich, 1999).
Two studies are available to assess the developmental toxicity of TCEP; high doses of TCEP (>350
mg/kg/day) reduced the number of live pups per litter in a continuous breeding study and the number
of male pups born to the treated Fl generation were reduced at concentrations > 175 mg/kg. No fetal
or developmental effects were observed in a study of rats administered TCEP on GD 7-15 (Kawashima
etal., 1983).
A study of rats administered TDCPP on GD 6-15 resulted in increased resorptions, reduced fetal
viability, decreased skeletal development and decreased mean fetal weight at 400 mg/kg/day and a
developmental NOAEL of 100 mg/kg was identified (Stauffer Chemical Company, 1981). In this same
study, maternal weight gain was also reduced.
EPA/OPPT considers the most significant hazards from exposure to CPEs to be cancer, kidney and liver
effects, neurotoxicity and developmental toxicity.
2.6 Results of Problem Formulation
2.6.1 Conceptual Models
Conceptual Model for Ecological Receptors
There is a potential for releases to water from chemical manufacturing, polyurethane foam
manufacture and textile processing, which could result in exposures to ecological receptors. Available
toxicological data will support the evaluation of acute and chronic exposures in fish, daphnids
(invertebrates) and algae.
The following conceptual model (Figure 2-2) illustrates the flow (arrows) of the CPE FRs from chemical
manufacture and processing, releases to the environment and potential exposure pathways for
ecological receptors. Down the drain releases to water from consumer uses are plausible, as described
in Schreder and La Guardia (2014), yet there are insufficient data to quantify these inputs.
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SOURCES
EXPOSURE PATHWAYS
ECOLOGICAL RECEPTORS
EFFECTS
Chemical Manufacture
Processing:
Foams
Textiles
Processing:
* Electronics
* Paints & Coatings
Non-industrial use of
products containing CPEs:
Homes,
Care Facilities,
Offices, etc.
LEGEND
Solid lines = Pathway can be quantified
Dashed lines = Pathway uncertain, or not quantifiable
Shaded boxes/ovals = Elements proposed for inclusion in this risk assessment;
exposure and toxicity can be quantified
Unshaded boxes/ovals = Elements excluded from this risk assessment
EPA DRAFT DELIBERATIVE -
Do Not Quote or Cite
Figure 2-2: Conceptual Model for Ecological Receptors
The key assessment question for ecological receptors is:
Do levels of CPEs in the environment pose risk to aquatic organisms?
Based on the identified presence of the CPEs in multiple environmental media, many ecological
receptors are potentially exposed. Fish and other wildlife are exposed to these chemicals via ambient
air, surface water, sediment, or soil. EPA/OPPTs has limited ability to quantify risks for sediment, soil,
sludge and ambient air because very little monitoring data and no hazard endpoints exist for these
media. The focus of the environmental risk assessment will therefore be on assessing risks to aquatic
organisms from CPE FRs in surface water.
Table 2-6: Assessment of Environmental Exposures
Use Scenario
And Applicable
Chemicals
Rationale
Limitations
Manufacture:
TCPP
TDCPP
(TCEP is not present at
the single import site
(CDR))
There is a potential for large releases to
water at ICL-IP America's Gallipolis Ferry,
WV site. 79% of the national TCPP
production volume is produced at this
location and this is the only site at which
TDCPP is manufactured.
Releases must be estimated, which
introduces uncertainty.
PL) Foam and Textile
finishing:
TCPP
TDCPP (PU foam only)
Releases to water of TCPP or TDCPP are
expected.
Releases must be estimated, which
introduces uncertainty.
TCEP, TCPP and TDCPP
in water
Limited US monitoring data available.
Representativeness must be evaluated.
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Risks from acute exposures will be evaluated for fish, invertebrates (daphnids) and algae (Table 2-7).
Data for acute aquatic toxicity are available for fish, daphnid and algae; there is only one chronic
daphnid study, limiting EPA/OPPT's ability to assess chronic aquatic toxicity. It is possible that sublethal
effects observed in fish in the acute study may be informative for a qualitative evaluation of chronic
toxicity based on the use of acute-to-chronic ratios from similar halogenated phosphate esters with
pesticide uses, and non-halogenated phosphate esters.
Table 2-7: Assessment of Toxicity in Aquatic Organisms
Scenario
And Applicable
Chemicals
Rationale
Limitations
Aquatic Organisms
TCEP
TCPP
TDCPP
Known or likely presence of CPEs in aquatic
environments. Available acute toxicity for fish,
daphnids and algae. Chronic toxicity data
available for daphnids only.
Absence of chronic data for fish is
a major limitation. It may be
possible to do a qualitative
assessment based on sublethal
effects in acute studies with a
quantitative screening level
assessment using predictive
methodologies.
Conceptual Model for Human Receptors
EPA/OPPT expects industrial worker exposures to be primarily via inhalation of vapor and dermal
contact; given the lack of toxicity data for inhalation and dermal routes of exposure, these exposure
pathways cannot be quantified in a risk assessment. Workers cutting PU foam at industrial sites may
inhale dust containing CPEs, but EPA/OPPT does not have the necessary data to evaluate this potential
exposure.
The potential sources of consumer exposure to CPE FRs include a number of consumer products in the
home. The CPE FRs in this cluster are chemicals added to polyurethane foam and other matrices and
are not chemically bonded to the polymers. Thus, CPE FRs in products are expected to migrate from
the matrix into the environment where they are used, either via emission from the products and
adsorption deposition to particulates or via matrix decomposition, aging or release. Because the
predominant consumer uses of CPE-containing polymers, such as insulation and furniture, are in indoor
environments, the potential for consumer exposure via inhalation of indoor air and dust, dermal
contact with products and incidental ingestion of dust is high. As described above, neither inhalation
nor dermal contact will be considered in this assessment due to absence of route-relevant toxicological
data.
The following conceptual model (Figure 2-3) illustrates the flow (arrows) of the CPE FRs from chemical
manufacture and processing, releases to the environment and potential exposure pathways for human
(consumer and general population) receptors.
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SOURCES
EXPOSURE PATHWAYS
HUMAN RECEPTORS
EFFECTS
LEGEND
Solid lines = Pathway can be quantified
Dashed lines - Pathway uncertain, or not quantifiable
Shaded boxes/ovals - Elements proposed for inclusion in risk assessment;
exposure and toxicity can be quantified
Unshaded boxes/ovals - Elements excluded from this risk assessment
EPA DRAFT DELIBERATIVE-
Do Not Quote or Cite
Figure 2-3: Conceptual Model for Human Receptors
There are four assessment questions associated with the conceptual model for human receptors:
Does incidental ingestion of CPEs in particulates or dust derived from consumer products pose
a risk to human health?
Does incidental ingestion of CPEs from mouthing of consumer products pose a risk to children?
Does consumption of CPEs in drinking water, or fish (recreational and subsistence fishers) result
in risks to human health?
Does aggregate oral exposure to CPEs pose a risk to human health?
Consumers
Ingestion of particulates and dust may occur through the incidental swallowing of inhaled particulates
and hand-to-mouth contact, and is likely to be greater for small children due to their activity patterns
and increased proximity to areas where dust may gather. Children may also be exposed via ingestion
during direct mouthing of toys made with FR-impregnated PU foam if the chemical migrates from the
foam and is sufficiently soluble (Table 2-8). For children and adults, exposures in the home and in other
common microenvironments (e.g., schools, daycares, public and commercial buildings, vehicles) are
likely.
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Table 2-8: Assessment of Exposure to Consumers
Exposure Scenario
And Applicable
Chemicals
Rationale
Limitations
Exposure of children in
the home via hand-to-
mouth transfer of dust,
incidental ingestion of
inhaled dust and
mouthing of products.
Exposure of adults in the
home via hand-to-mouth
transfer of dust and
incidental ingestion of
inhaled dust.
TCEP
TCPP
TDCPP
Exposures are expected to be highest
in children.
Sufficient data to quantify oral
exposure and toxicity.
Although there are data on occurrence of
CPE FRs in air-suspended particulates,
settled dust and on (children's) hands,
these data are not informative as to the
source; hence, these metrics will be
considered as integrative surrogate
exposures.
EPA is considering the possibility of
quantifying potential incidental ingestion of
inhaled dust.
Much less is known about consumer exposures to textiles or printed circuit boards containing CPE FRs.
It is expected that the FRs can migrate out of the textiles and printed circuit boards, but it is not
possible at this time to quantify migration rates that may result in exposures. Dust can be considered
an integrative metric that combines exposures from multiple sources.
General Population
Consumption of drinking water and fish are pathways by which humans may be exposed (Table 2-9).
EPA/OPPT can estimate exposure to CPE FRs via drinking water and fish ingestion based on releases
from industrial sources. These estimates can then be compared to measures of CPE FRs in water and
fish samples collected and analyzed in the US and abroad.
For those whose diet relies more heavily upon locally sourced fish consumption, such as recreational
and subsistence fishers and their children, exposures from this pathway may be an important
contribution to aggregate exposure. A recent Canadian study evaluated the presence of
organophosphate FRs, including several CPEs, in fish collected from the Great Lakes and other regions
(McGoldrick et al., 2014). Low concentrations (ng/g wet weight) were frequently detected in a Lake
Trout and Walleye. From a study in Sweden (Sundkvist et al., 2010), fish collected at points
downstream from wastewater treatment plants (WWTPs) had markedly higher concentrations of CPEs
when compared to fish collected upstream of the WWTP.
While there are not similar data available from the US for fish, the CPEs have been detected in urban
rivers receiving wastewater effluent during low flow conditions (Sengupta et al., 2014). Although it is
unknown if concentrations in fish in Sweden would be similar to the US, the samples taken from the
Canadian side of the Great Lakes may be broadly representative of that environment. Though exposure
factors may exist for fish consumption, there would be uncertainty in determining the concentration of
phosphate esters in edible fish.
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Table 2-9: Assessment of Exposure to General Population
Scenario
And Applicable
Chemicals
Rationale
Limitations
General population,
including high-end fish
consumption
(recreational and
subsistence fishers) by
children and adults:
TCEP
TCPP
TDCPP
Based on stakeholder interest, this
exposure pathway will be considered,
based on feasibility.
Modeling will be needed to generate
estimates of water ingestion and fish
consumption. Fish ingestion rates will need
to be modified to account for high-end
consumption. There are uncertainties that
could limit the reliability of these
estimates.
A number of hazard endpoints have been identified for consideration in the risk assessment, including
cancer, target organ effects, reproductive and developmental effects and neurotoxicity (Table 2-10).
More detailed data summaries are available in Appendix F. Each of these effects has been observed in
at least two of the three chemicals.
Table 2-10: Relevant Endpoints for Human Receptors
Receptor
Children
Adults
Pregnant
Women
Acute Exposure
(Transient)
Not applicable
Not applicable
Developmental toxicity (fetal
effects)
Subchronic Exposure
(Short-term)
Kidney, Liver, Male
Reproductive Effects,
Neurotoxicity
Kidney, Liver, Male
Reproductive Effects,
Neurotoxicity
Developmental toxicity (fetal
effects)
Chronic Exposure
(Lifetime)
Not applicable
Kidney Cancer
Kidney, Liver, Male
Reproductive Effects,
Neurotoxicity
Not applicable
2.6.2 Analysis Plan
The analysis plans summarize EPA/OPPT's proposed approach and methods, based on available data as
described above (see Data Needs description under section 2, Problem Formulation).
Analysis Plan for Ecological Receptors
Based on Problem Formulation, EPA/OPPT plans to use available data to evaluate:
Potential risks to aquatic organisms from acute and chronic exposures to CPE releases to, and
presence in the water.
To assess potential ecological risks, releases of TCPP and TDCPP from manufacturing and processing to
water must be quantified. EPA/OPPT can consider environmental exposures in two ways. In the risk
assessment, EPA/OPPT will assess releases of TCPP and TDCPP to wastewater from manufacturing and
processing; and subsequent release to surface water resulting in exposures to aquatic organisms.
Current industrial uses of TCEP are not expected to be significant (Table 2-11). Second, EPA/OPPT will
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evaluate TCEP, TCPP and TDCPP exposures based on measured concentrations in surface water (Table
2-6). Note that TCEP is no longer manufactured or imported into the US, hence releases from
manufacturing and processing will not be quantified. Due to past uses, as well as presence in articles,
TCEP continues to be measured in the environment and, risks can be evaluated based on measured
concentrations.
Table 2-11: Analysis Plan for Releases to Water
Use Scenario
Scope
Assessment Approach
Releases to
water from
chemical
manufacture
TCPP and TDCPP
Releases will be assessed based on CDR site-specific production volumes.
Releases due to cleaning of equipment in batch operation will be assessed
in accordance with OPPT's method for assessing releases of New
Chemicals from equipment cleaning. The literature will be searched for
data that is useful for estimating releases from the washing and
dehydration unit operations, including process water consumption rate or
emission factor data for analogous processes and releases will be assessed
based on the results of this literature search.
Releases to
water due to
processing for
the
manufacture
and use of PL)
foam
TCPP and TDCPP
Releases from the following processes will be assessed: blending with
polyols (applicable to TCPP only), the slabstock and molded foam
processes for the manufacture of flexible PL) foam (processing in the
molded foam process is applicable to TDCPP only), processing for the
manufacture of rigid PL) foam and use in the manufacture of upholstered
furniture. Releases will be estimated based on a number of sources,
including emission factors reported in (EL) (2008a), (2008b)), generic
scenarios or other New Chemicals Program methods (refer to Appendix D
for additional information.)
Releases to
water due to
processing for
the finishing of
textiles
TCPP
Release from the pad/dry/cure process for textile finishing will be assessed
in accordance with the assessment approach described in EPA (1994a) and
OECD (2004b).
Presence of CPE
FRs in water
TCEP, TCPP and
TDCPP
Appendix D includes summaries of available data on CPE FR concentrations
in water. Conduct a literature search to identify additional measured data
and evaluate for use in risk assessment.
The analysis of risks to aquatic organisms will include effects from both acute and chronic exposures
(Table 2-12).
Table 2-12: Analysis Plan for Assessing Risks to Aquatic Organisms
Exposure
Scenario
Scope
Assessment Approach
Industrial
releases and
presence in
surface water
TCEP, TCPP and
TDCPP
A literature search will be conducted to identify any additional, relevant
ecotoxicity data for fish, daphnids and algae. Concentrations of Concern
(CoCs) will be derived based on results of acute toxicity data. A qualitative
assessment will consider the potential effects of chronic exposure on
aquatic species.
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Analysis Plan for Human Receptors
Based on Problem Formulation, EPA/OPPT plans to use available data to evaluate:
Potential risks from incidental ingestion of CPEs in inhaled dust or via hand-to-mouth transfer
of CPEs in settled dust released from consumer products.
Potential risks from incidental ingestion of CPEs from mouthing of consumer products.
Potential risks from consumption of CPEs in drinking water, or fish (recreational and
subsistence fishers).
Potential risks from aggregate oral exposure to CPEs.
During problem formulation, EPA/OPPT identified a subset of toxicological endpoints (Table 2-10) as
relevant and sensitive, based on a review of existing hazard and risk assessments, as described in
section 2.5.2. For the risk assessment, EPA/OPPT will perform a literature search to determine if new
data exist and collect the studies identified during problem formulation, to refine the hazard
identification and complete the dose-response analysis. To select studies for inclusion, available data
will be reviewed to determine test species, test conditions, toxicity endpoints, statistical significance
and strengths/limitations of the study, then summarized and evaluated for data quality. Data quality
criteria will include use of appropriate analytical and test controls, identification of test substance and
test organism, stated exposure duration time and administration route, a clear description of the effect
endpoints and transparent reporting of effect concentrations. Guideline studies as well as studies using
other protocols will be included if they meet data quality criteria. Studies that meet the criteria for
inclusion will then be evaluated in the dose response assessment. The evaluation of TCPP will need to
incorporate the potential differential toxicity of isomers.
General Population and Consumers
Table 2-13 describes the analysis plan for investigating general population and consumer risks. The
evaluation of risks to the general population includes risks to adults and children from consumption of
CPEs in drinking water and risks to recreational and subsistence fishers from high-end consumption of
fish contaminated with CPEs. Consideration of ingestion by pregnant women will be included in this
analysis.
Consumer exposures to CPE FRs will be evaluated based on incidental ingestion of inhaled dust (as
described above), and incidental ingestion of indoor settled dust via hand-to-mouth behaviors. In
addition, exposures to children from incidental ingestion via object-to-mouth behaviors will also be
quantified.
Oral exposure by incidental ingestion of house dust via inhalation and hand-to-mouth transfer can be
quantified based on US values of monitored house dust. Several recent studies of house dust are
available which are expected to be representative of US households. The EPA Exposure Factors
Handbook can be utilized to determine typical quantities of dust ingested and time-activity patterns.
The evaluation of risks to general population and consumers will begin with an evaluation of published
assessments, including the risk assessment reports produced by the EU and CPSC and the ATSDR
toxicological review. The evaluation will determine if components of these published reports are
consistent with OPPT methodology, or if additional efforts are needed to supplement or supplant the
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existing assessments. If we identify the need to review primary data that is not available in the US,
EPA/OPPT will work to negotiate access to these studies. The analysis of primary data will be
conducted in accordance with OPPT data adequacy guidelines. The evaluation of cancer and non-
cancer risks will be conducted in accordance with EPA guidelines (Table 2-13) (EPA, 2005a, 2005b,
2013).
Table 2-13: Analysis Plan for General Population and Consumer Risks
Exposure
Scenario
Scope
Assessment Approach
High-end fish
consumption
TCEP, TCPP
andTDCPP
Appendix D includes summaries of available data on CPE FR concentrations in
fish. Conduct additional literature search to identify additional US data. Search
for and review literature on high-end fish consumption by recreational and
subsistence fishers. Use EFAST modeling with comparison to European fish
data and US data. Age specific activity patterns and exposure factors will be
considered. Fish ingestion rates will be higher for subsistence fishers. Risks will
be assessed based on MOE (non-cancer), or by low dose linear extrapolation
(cancer). EPA/OPPT will systematically review the existing human health data and
select the relevant benchmarks according to the relevant route of exposure. The
exposure estimates will be adjusted for expected duration and frequency in agreement
with the hazard assessment.
Drinking Water
consumption
TCEP, TCPP
andTDCPP
Appendix D includes summaries of available data on CPE FR concentrations in
drinking water. Conduct additional literature search to identify additional US
data. Use EFAST modeling with comparison to US water data. Age specific
activity patterns and exposure factors will be considered. Risks will be assessed
based on MOE (non-cancer), or by low dose linear extrapolation (cancer).
EPA/OPPT will systematically review the existing human health data and will select the
relevant benchmarks according to the relevant route of exposure. The exposure
estimates will be adjusted for expected duration and frequency in agreement with the
hazard assessment.
Exposure of
adults and
children via
incidental
ingestion air-
suspended
particulates
and hand-to-
mouth transfer
of settled dust
TCEP, TCPP
andTDCPP
Appendix D includes summaries of available data on CPE FR concentrations in
dust. Conduct additional literature search to identify any US data. Select for
inclusion dust monitoring data, based on a range of different indoor
environments. Consider both hand-to-mouth and ingestion of inhaled dust
particles. Exposure factors (e.g. time and activity patterns or ingestion values)
will be based on US EPA Exposure Factors Handbook where available. Risks will
be assessed based on MOE (non-cancer), or by low dose linear extrapolation
(cancer). EPA/OPPT will systematically review the existing human health data
and will select the relevant benchmarks according to the relevant route of
exposure. The exposure estimates will be adjusted for expected duration and
frequency in agreement with the hazard assessment.
Mouthing of
products by
children
TCEP, TCPP
andTDCPP
Migration rates will be based on assessment of available data, as well as
estimates used in other assessments. Consult with CPSC and conduct
additional literature search to identify if extraction data are available. Age
specific activity patterns and exposure factors will be considered. Younger
children are expected to have higher rates of dust ingestion and longer
duration of mouthing activity when compared to older children and adults.
Risks will be assessed based on MOE (non-cancer), or by low dose linear
extrapolation (cancer). EPA/OPPT will systematically review the existing human
health data and will select the relevant benchmarks according to the relevant
route of exposure. The exposure estimates will be adjusted for expected
duration and frequency in agreement with the hazard assessment.
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Aggregate Exposures and Risk
Aggregate oral exposures will be assessed considering hand-to-mouth dust ingestion, incidental
ingestion of inhaled dust, water ingestion, mouthing of objects (children) and high end fish
consumption (Table 2-14).
Table 2-14: Analysis Plan for Risks from Aggregate Oral Exposures
Exposure
Scenario
Scope
Assessment Approach
Aggregate oral
exposures
TCEP, TCPP and
TDCPP
Conduct additional literature search on averaging times and sensitive life
stages for various endpoints. Age-specific activity patterns and exposure
factors will be identified. Exposures over time will be aggregated for the
pathways described and averaged over periods relevant for younger
children, older children and adults. Risks will be assessed based on MOE
(non-cancer), or by low dose linear extrapolation (cancer).
2.6.3 Sources and Pathways Excluded From Further Assessment
The following sources, uses or exposure pathways are excluded from further assessment:
EPA/OPPT has determined that several uses are not expected to result in significant releases to
the environment:
o Releases from manufacturing and processing resulting in exposures to adjacent
communities.
o The manufacture of printed circuit boards.
o The formulation of paints and coatings.
o The use of TDCPP in fabric, textiles and leather products.
EPA/OPPT has determined that a number of scenarios lack sufficient data to quantify risks:
o Exposures of birds, terrestrial wildlife, or sediment-dwelling organisms (insufficient
toxicity data).
o Releases to the environment from non-industrial (e.g., office worker) and consumer
uses of products containing CPEs (insufficient data to quantify releases).
o Industrial workers via inhalation of vapor and dermal exposure (no route-specific
toxicity data).
o Consumer exposures via inhalation and dermal exposures (no route-specific toxicity
data).
Exposures to CPE FRs in food (other than fish) will not be assessed.
2.6.4 Uncertainties and Data Gaps
There are a number of important uncertainties and data gaps that must be considered when
characterizing risks associated with CPE FRs. Uncertainties and data gaps limit the scope of the
assessment and can contribute to both the over- and under-estimation of risk.
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2.6.4.1 Release and Exposure Uncertainties
Industrial Releases
The processing volumes and number of sites for the following particular processing steps are unknown
or uncertain: TCPP blending with polyol, processing of TDCPP in the molded foam process for the
manufacture of flexible PU, processing of TCPP and TDCPP for the manufacture of rigid PU foam.
Data Representativeness
Some exposure data are only available from other countries. There is uncertainty regarding its
relevance to US exposure scenarios. Some of the available measurements were made outside the US
and it is not clear how well the exposure scenarios derived from them are representative of similar
exposure scenarios within the US. Available US monitoring data may not be representative of
concentrations in the environment across all areas of the US. Uncertainties may exist in a quantitative
evaluation. Mathematical modeling approaches can be used to yield exposure estimates. EPA/OPPT
will consider the use of sensitivity analyses to determine key elements of uncertainty.
Fish Consumption
There are no reported US data of CPEs in fish that are representative of the US and it is unknown if
concentrations in fish in Canada and Sweden would be similar to concentrations offish in the US. Fish
ingestion exposures will need to be modeled based on releases to the environment from
manufacturing/processing/use. Though exposure factors may exist for fish consumption, there would
be uncertainty in determining the concentration of phosphate esters in edible fish. If specific receiving
waters are not identified, there will be uncertainty in the amount of dilution that may occur. EPA/OPPT
will document the uncertainty and limitations associated with the fish consumption analyses.
Exposure Route Extrapolation
There is no PBPK model readily available for route-to-route extrapolation. EPA/OPPT has identified this
as a critical data gap since the exclusion of dermal and inhalation exposure routes will result in the
underestimation of risks. EPA/OPPT will acknowledge this in the risk characterization.
Child Mouthing Exposures
Data limitations may result in the under- or over-estimation of exposure from mouthing of toys and
other consumer products. Oral exposure by direct mouthing of foam-based toys may yield tentative
values, as empirical values for migration of FRs out of foam into saliva are not available, nor is there
definitive data detailing concentrations of FRs in toys that children may mouth. Expert judgment and
assumptions may need to be employed, which will increase the uncertainty of the assessment of this
particular scenario. EPA/OPPT will specify all assumptions used in the estimation of exposure to
children via mouthing.
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Microenvironment Variability
The concentration of CPE FRs in indoor air or dust in different microenvironments are expected to vary;
concentrations in offices or workplaces may be greater than in homes. There are uncertainties using
existing methodologies to estimate exposure for these different microenvironments. In general,
incidental ingestion of dust by adults is expected to be low. EPA/OPPT will derive estimates of
exposure via incidental ingestion of dust based on data that represents a variety of different
microenvironments.
Source to Dose Models
Source-to-dose models are absent or limited for most of the identified exposure scenarios, therefore
the exposure cannot be linked to specific products or the use patterns of any one product. It is not
possible to develop source-to-dose exposure models with currently available information. EPA/OPPT
will consider the presence of CPE FRs in dust, fish, drinking water and food to be integrative measures
of exposure from a number of sources.
Model Uncertainties
Modeled releases to water from industrial facilities may result in the over- or under-estimation of
concentrations in the aquatic environment. Modeling will be needed to generate estimates of fish
ingestion. Modeling default values will need to be modified (e.g., fish consumption frequency) to
account for high-end consumption. In all cases, model assumptions will be clearly articulated.
EPA/OPPT will consider the use of sensitivity analyses to determine key elements of uncertainty.
2.6.4.2 Hazard Data Uncertainties
Aquatic Toxicity
Chronic aquatic toxicity data are needed to better quantify risks to aquatic organisms. In general,
availability of information for many of the aquatic toxicity studies are limited to secondary sources; to
establish study validity, often a full study report is needed. Sufficient experimental data are not
available to characterize chronic population level effects to fish and population level effects towards
birds. EPA/OPPT will acknowledge these limitations in the risk characterization.
Toxicity Associated With Inhalation and Dermal Exposure
There are no toxicity data via the inhalation exposure route that would permit a robust assessment of
inhalation exposure risks. This problem applies to inhalation exposure to dust and particulates. In
addition, there are no toxicity data via the dermal route that would permit a robust assessment of
dermal exposure risks. The absence of data to inform health effects that may be associated with
inhalation and dermal exposure significantly limits the scope of this assessment and may lead to the
underestimation of risk. Although it is possible to estimate exposures via route-to-route extrapolation,
these calculations would be highly speculative and potentially misleading. EPA/OPPT has identified this
as a critical data gap since the exclusion of dermal and inhalation exposure routes will result in the
underestimation of risks.
A chemical specific PBPK model would necessary to develop robust estimates of exposures via multiple
routes. EPA/OPPT has identified this as a critical data gap since the exclusion of dermal and inhalation
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exposure routes will result in the underestimation of risks. EPA/OPPT will acknowledge this in the risk
characterization.
Neurotoxicity and Developmental Neurotoxicity
There is uncertainty regarding the neurotoxic potency of CPE FRs with regard to cholinesterase
inhibition. The structural similarity of the chemicals in the CPE cluster make it possible to perform read-
across; however, the uncertainty that comes with read-across also must be considered in
characterizing the risks associated with the identified exposure scenarios. The majority of available
toxicological data are for TCEP and TDCPP. The National Toxicology Program is in the process of
collecting toxicological data on TCPP (see http://ntp.niehs.nih.gov/testing/status/agents/ts-
m20263.html). EPA Office of Research and Development is expected to publish the results of additional
studies, as well. These data will help clarify biological similarity and differences among the three
structurally similar chemicals.
There are limited data on developmental neurotoxicity. CPE FRs are considered to be weak inhibitors
of cholinesterase; there is uncertainty regarding the relationship between weak cholinesterase
inhibition and brain development and if this can result in adverse impacts. EPA/OPPT will acknowledge
these limitations in the risk characterization.
Inter-individual Variability
Co-morbidities, genetics, lifestyle and other chemical exposures that influence underlying toxic
processes could also modulate risk (NRC, 2009). Currently there are no data to inform an analysis of
these factors in the proposed risk assessment. EPA/OPPT will acknowledge these limitations in the risk
characterization.
EPA/OPPT has identified the absence of inhalation and dermal route-specific toxicity data as a critical
data need because EPA/OPPT expects that these may be important exposure pathways that cannot be
assessed due to data gaps. Inhalation and/or dermal exposures are possible in a number of
occupational and consumer settings. The absence of sufficient route-specific toxicity data effectively
prohibits the assessment of risks to workers in the occupational setting and to consumers in a
residential setting. This data gap may result in the underestimation of aggregate risks associated with
exposure to the CPE FR cluster chemicals.
The physical form of the chemical during its use is likely to influence the exposure pathway of interest.
Similar to many other semi-volatile organic chemicals, CPE FR cluster chemicals are likely to be present
in vapor phase air, total suspended particulates in air and in settled particles on the floor or other
indoor surfaces in dust. Sub-chronic and chronic toxicity rather than acute toxicity may be of interest
for multiple exposure routes. Air concentrations, dust concentrations, or surface loadings on articles,
for example, need to be averaged over some duration (months, years) relevant to toxicity. Examples of
exposure scenarios of potential interest, should adequate toxicity and exposure information become
available, include:
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Industrial workers who routinely spend the majority of their day in close contact with CPE FR
cluster chemicals or materials containing these chemicals;
Consumers and non-industrial workers in indoor environments who routinely contact or spray
apply products containing CPE FRs;
Pregnant women who meet any of the above scenarios;
Young children who may routinely spend time exercising in gymnasiums, as the children likely
have elevated breathing rates in these environments.
The magnitude of the exposures for these scenarios is highly dependent on individual activity patterns
and exposure factors, which are highly variable across the population.
The development of a PBPK model for oral, inhalation (vapor and dust) and dermal routes of exposure
would provide the ability to perform route-to-route extrapolation. Route-to-route extrapolation would
allow internal doses to be calculated from the oral route toxicity studies and compared with internal
doses calculated from exposure scenarios for any of the routes as well as aggregate exposures to
multiple routes. To construct a PBPK model, adequate toxicokinetic data would be needed for each
route of exposure and these data are lacking for inhalation and dermal exposures.
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Page 53 of 72
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APPENDICES
Page 54 of 72
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Appendix A Data Availability Tables
The following data availability tables provide a high-level overview of available data through December
2014. They do not reflect study or data quality; nor do they represent suitability for use in risk
assessment, which will be determined during the assessment process.
Table_Apx A-l: Available Occupational Exposure and Release Data
CASRN
NAME
Production Volume
Number of Manufacturing and
Processing Sites / Workers
Occupational Exposure Limits
Exposure Monitoring Data
Engineering Controls or PPE
Emission Factors
Manufacture
Processing or Use
Release Frequency
115-96-8
Ethanol, 2-
chloro-,
phosphate (3:1);
Tris(2-
chloroethyl)
phosphate
(TCEP)
N/A
13674-84-5
2-Propanol, 1-
chloro-,
phosphate
(TCPP)
13674-87-8
2-Propanol, 1,3-
dichloro-,
phosphate
(TDCPP)
Note:
= some data available, US or international
Page 55 of 72
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Table_Apx A-2: Available General Population and Environmental Exposure Data
CAS NUMBER
Chemical Name
Abbreviation
115-96-8
Tris(2-chloro-ethyl)
phosphate
Ethanol, 2-chloro-,
phosphate (3:1)
TCEP
13674-84-5
(6145-73-9)
Tris(2-chloro-l-
methylethyl)
phosphate
2-Propanol, 1-chloro,
2,2',2"-phosphate, (1-
Propanol, 2-chloro-,
l,l',l"-phosphate)
TCPP
13674-87-8
2-Propanol, 1,3-
dichloro-,
phosphate
2-Propanol, 1,3-dichloro-,
phosphate (3:1), (1-
Propanol, 2,3-dichloro-,
l,l',l"-phosphate)
TDCPP
BIOMONITORING (HUMAN)
Blood
Breast Milk
Adipose Tissue
Placenta
Urine*
A
A
A
HUMAN EXPOSURE
Dust ingestion
USGS NWIS Data
Water
Suspended sediment
Solids
Biota
AIR
Ambient Air
Indoor Air
SOIL
INDOOR DUST
SEDIMENT
Freshwater
Marine
SLUDGE
amended soil
biosolids
landfill
sewage
WATER
drinking water
groundwater
leachate
precipitation
surface water
Page 56 of 72
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CAS NUMBER
Chemical Name
wastewater
115-96-8
Tris(2-chloro-ethyl)
phosphate
Ethanol, 2-chloro-,
phosphate (3:1)
13674-84-5
(6145-73-9)
Tris(2-chloro-l-
methylethyl)
phosphate
2-Propanol, 1-chloro-,
2,2',2"-phosphate, (1-
Propanol, 2-chloro-,
l,l',l"-phosphate)
13674-87-8
2-Propanol, 1,3-
dichloro-,
phosphate
2-Propanol, 1,3-dichloro-,
phosphate (3:1), (1-
Propanol, 2,3-dichloro-,
l,l',l"-phosphate)
AIR + WATER
deposition
BIOTA
avian
fish
aquatic animals
terrestrial animals
vegetation
Notes:
A = presence of metabolite
= some data available, US or international
Page 57 of 72
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Table_Apx A-3: Available Mammalian and Aquatic Toxicity Data
CASRN
NAME
115-96-8
Ethanol, 2-
chloro-,
phosphate (3:1);
Tris(2-
chloroethyl)
phosphate
(TCEP)
13674-84-5
2-Propanol, 1-
chloro-,
phosphate
(TCPP)
13674-87-8
2-Propanol, 1,3-
dichloro-, phosphate
(TDCPP)
HUMAN HEALTH
Acute Oral
Toxicity
Acute Dermal
Toxicity
Acute Inhalation
Toxicity
Repeated-Dose
Toxicity
Reproductive
Toxicity
Developmental
Toxicity
Neurotoxicity
Cholinesterase
inhibition
Developmental
Neurotoxicity
Endocrine
Activity
Carcinogenicity
Genetic Toxicity
Mutations in
vitro
Chromosomal
Aberrations in
vitro
Chromosomal
Aberrations in
vivo
Skin Irritation
Eye Irritation
Sensitization
o
o
o
O
o
o
O
o
o
o
ECOLOGICAL RECEPTORS
Log Kow (P)
Fish 96-h LC50
Daphnid 48-h
LC50
Page 58 of 72
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CASRN
NAME
Green algae 96-h
EC50
Fish ChV
Daphnid ChV
Green algae ChV
115-96-8
Ethanol, 2-
chloro-,
phosphate (3:1);
Tris(2-
chloroethyl)
phosphate
(TCEP)
13674-84-5
2-Propanol, 1-
chloro-,
phosphate
(TCPP)
13674-87-8
2-Propanol, 1,3-
dichloro-, phosphate
(TDCPP)
Notes:
9 = data available, likely to be useful for quantitative analysis
= no data available
O = data available, but may not be useful for quantitative analysis
Page 59 of 72
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Appendix B Regulatory and Assessment History
B-l
Domestic
TCEP, TDCPP and TCPP are existing chemicals on the TSCA Inventory and therefore were not subject to
EPA's new chemicals review process and were grandfathered in with the passage of the Toxic
Substances Control Act of 1976.
No occupational exposure limits have been developed by the Occupational Safety and Health
Administration, the National Institute for Occupational Safety and Health, or the American Conference
of Government Industrial Hygienists. The EPA IRIS program has not determined reference doses and
the EPA Office of Water has not set limits or goals for drinking water.
These CPEs are subject to regulations by a number of states, summarized in Table_Apx B-l. Other
states that have proposed legislation that could affect the use of TCEP, TDCPP and TCPP include
Washington, Massachusetts and North Carolina.
Table_Apx B-l: Existing State Regulations
State
California
California
California
Connecticut
Maine
Maryland
Minnesota
New York
Vermont
Chemical(s)
TCEP and
TDCPP
TCEP, TCPP
and TDCPP
TDCPP
TCEP, TCPP
and TDCPP
TCEP
TCEP
TCEP and
TDCPP
TCEP
TCEP and
TDCPP
Regulation
Proposition 65
(http://oehha.ca.gov/prop65/prop65 list/newlist.html)
Identified as candidate chemicals under the Safer Consumer
Product Regulations (https://dtsc.ca.gov/SCP/ChemList.cfm)
Identified as a priority chemical product combination (foam
padded children's sleeping products) under the Safer Consumer
Products Regulations
(https://dtsc.ca.gov/SCP/PriorityProducts.cfm)
Regulates the use in children's products.
(http://www.cga.ct.gov/2013/FC/pdf/2013HB-06332-R000040-
FC.pdf)
Identified as a Chemical of High Concern
(http://www.maine.gov/dep/safechem/highconcern/)
Prohibits sale of certain children's products made with TCEP
(http://mgaleg.maryland.gov/webmga/frmLegislation.aspx?pid=
Iegisnpage&tab=subject3; see 2013, either HB0099 or CH0349)
Identified as a Chemicals of High Concern
(http://www.health.state.mn.us/divs/eh/hazardous/topics/toxfr
eekids/highconcern.html)
Prohibits sale of certain children's products made with TCEP
(http://assemblv.state.ny.us/leg/; see 2003-2004, S 7621)
Banned from use in children's products and residential
upholstered furniture
(http://www.atg.state.vt.us/issues/consumer-
protection/product-saftev/flame-retardants.php)
Hazard Basis
Cancer
Cancer,
reproductive
toxicity
Cancer
Cancer,
reproductive
toxicity
Prioritized by
Canada
Cancer
Cancer,
reproductive
toxicity
Cancer,
reproductive
toxicity,
neurotoxicity
Cancer
Page 60 of 72
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State
Washington
Chemical(s)
TCEP and
TDCPP
Regulation
Identified as a Chemicals of High Concern
(http://www.ecv.wa.gov/programs/swfa/cspa/chcc.html) and
the Children's Safe Products Act requires manufacturers to
report on chemicals of high concern in children's products
(http://www.ecv.wa.gov/programs/swfa/cspa/)
Hazard Basis
Cancer,
reproductive
toxicity
There are several domestic assessments for chlorinated phosphate ester flame retardants:
The ATSDR Toxicological Profile for Phosphate Ester Flame Retardants (2012) included TCEP,
TDCPP and TCPP and provided detailed analyses of available hazard data.
EPA derived Provisional Peer-Reviewed Toxicity Values (PPRTVs) for TCEP: an oral subchronic
RfD of 0.02 mg/kg-day (kidney effects); an oral chronic RfD of 0.007 mg/kg-day (kidney effects).
EPA also identified oral exposures of 5 x 10'3 - 5 x 10'5 mg/kg-day as associated with cancer
risks (renal tubular cell adenomas and carcinomas) ranging from 1 x 10~4 - 1 x 10~6. EPA
determined that there was not sufficient data to derive PPRTVs for two TCPP isomers.
The US Consumer Product Safety Commission (2006) assessed the cancer risks associated with
inhalation of TDCPP vapor released from furniture foam and cover fabrics. Estimated cancer
risks from lifetime exposure in the home was 300 per million for adults and estimated cancer
risk for children from inhalation exposure during the first two years of life was 20 per million.
The Hazard Index (Average Daily Dose^- Acceptable Daily Intake) was 2 for adults and 5 for
children. CPSC estimated that 98-99% of exposure was via the inhalation route.
The California Environmental Protection Agency, Department of Toxic Substances Control
(2014) released a draft document supporting the selection TDCPP in children's foam-padded
sleeping products as a candidate priority chemical-product combination requiring an analysis of
alternatives, per the California Safer Consumer Products Regulations
(https://dtsc.ca.gov/LawsRegsPolicies/Regs/SCPA.cfm).
The National Toxicology Program is in the process of evaluating TCPP in a 90 day toxicity study,
a 2-year cancer bioassay and a developmental toxicity study
(http://ntp.niehs.nih.gov/testing/status/agents/ts-m20263.html). At the time of writing, the
results these studies have not yet been made available.
B-2
International
There are numerous international activities relevant to the chemicals in this cluster. In 2009, Canada
conducted a screening assessment of TCEP and concluded that TCEP is harmful to human health. In
addition, Canada proposed a risk management approach for TCEP and recommended a prohibition
relating to the presence of TCEP in products and materials. To that end, a Significant New Activity
provision was concluded in January 2013. In April 2014, products made, in whole or in part, of
polyurethane foam that contains TCEP and intended for children under three years of age were added
to Schedule 2 of the Canada Consumer Product Safety Act (CCPSh), based on concerns for
carcinogenicity and impaired fertility. Products listed in Schedule 2 are prohibited from manufacture,
import, advertising or sale under section 5 of the CCPSA. Canada has also prepared a draft risk
assessment of TDCPP and TCPP, but as of this date has not released the document to the public.
The EU conducted a Risk Assessment of TCEP, TCPP and TDCPP (EU, 2008a, 2008b, 2009):
Page 61 of 72
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TCEP: The EU considered three occupational exposure scenarios: production, product
formulation and paints and coatings. Worker risks from inhalation and dermal exposure
associated with all scenarios were identified. Risks to children from mouthing of objects were
also identified. For all scenarios, risk estimates were based on both carcinogenic and repeat
dose effects and potential doses were estimated using probabilistic models. For children's risk,
the assessment assumed very high migration rates via mouthing of articles containing TCEP.
TCEP: Listed in the EU Authorisation List based on reproductive toxicity (category IB), with a
sunset date of August 21, 2015. No concerns were identified for ecological receptors.
TCPP: The risk assessment identified concerns for workers in chemical manufacturing due to
potential effects on fertility and developmental toxicity from dermal exposure. The EU noted
that there is need for further information and/or testing for female reproductive effects, but
that the LOAEL of 5 mg/kg from the chronic study will likely be protective for female
reproductive effects. There were no risk concerns identified for consumer exposure based on
the evaluation of exposure to TCPP in three kinds of foam products. The European Commission
Scientific Committee on Health and Environmental Risks (SCHER) noted in review of the TCPP
RAR that at least 40% of the CPE could volatilize from the PUF product.
TDCPP: The EU concluded that there is a need for further information and/or testing regarding
the effects on female fertility for all worker exposure scenarios, all consumer exposures and
both regional and local exposures. Occupational exposure scenarios were considered and
dermal and inhalation exposures were modeled using limited available input data. Consumer
exposure data considered releases from flexible polyurethane foam. The EU concluded cancer
risks were of low concern, but cancer risks were evaluated assuming a threshold mode of
action, an approach that is not used by EPA. The EU assumed that the LOAEL of 5 mg/kg from
the chronic study would likely be protective for female reproductive effects.
Based on a screening assessment of TCEP, Canada passed a Significant New Activity provision in
January 2013. As of April 2014, products made, in whole or in part, of polyurethane foam that
contains TCEP and intended for children under three years of age were added to Schedule 2 of
the Canada Consumer Product Safety Act (CCPSh), based on concerns for carcinogenicity and
impaired fertility, meaning that they are prohibited from manufacture, import, advertising or
sale
Canada provided EPA/OPPT/RAD with a draft copy (not released to public) risk assessment for
TDCPP and TCPP, based on intake from air, water, food, beverages and dust (general
population) and from dermal and oral exposure to consumer products (consumer) for review
and comment.
Australia conducted a preliminary assessment of TCEP, TCPP and TDCPP as part of the NICNAS
Priority Existing Chemical (PEC) assessment process in June 2001. Based on these assessments,
the need for occupational exposure data was identified. Australia also recommends additional
labeling and training for risk mitigation.
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Appendix C Uses Supplemental Information
TCEP
The Aceto Corporation was the only company that reported manufacturing TCEP during the 2012 CDR
reporting cycle. The company's reported industrial, commercial and consumer uses of TCEP during this
period are summarized in Table 2-5. Although use of TCEP in polyurethane foam was not reported in
2012, this use has occurred in the past. This has been confirmed with the detection of TCEP in baby
products including car seats, changing table pads, sleep positioners, portable mattresses, nursing
pillows, baby carriers and infant bath mats at loading levels ranging from 1.08-5.95 mg/g (Stapleton et
al., 2011). Additionally, TCEP has been reported to the Washington States Children's Safe Product Act
Database for its use in children's products. The database includes supporting evidence for its use in car
seats for its flame retardant properties. Non flame-retardant uses reported to the database include as
a manufacturing additive in textiles for children's clothing and as a contaminant in footwear, sleepwear
and bedding (Washington State 2014). TCEP is included in the EPA's Design for the Environment
Program's Furniture Flame Retardancy Report Update (see
http://www.epa.gov/dfe/pubs/proiects/flameret/about.htm for more information) which evaluates
the hazards associated with flame retardants used in upholstered items for consumer use.
Additional flame retardant uses which have been identified for TCEP that do not overlap with the CDR
reported use include: cast acrylic sheets, carpet backing, building insulation, electronics, rubber and
plastics, furniture, adhesives and wood-resin composites (e.g. particle board) (ECHA, 2010; Health
Canada, 2012; Joseph and Ebdon, 2010). Additionally, TCEP reportedly can be applied to polyester
resins in thermosets, bathtubs and shower stalls (Weil and Levchik, 2009).
TCPP
In addition to the industrial, commercial and use categories reported in 2012 CDR (see Table 2-5),
secondary sources identified specific products in which TCPP may be used. With respect to the
"building and construction not covered elsewhere" category, TCPP is known to be an additive flame
retardant in rigid polyurethane foam in panels and laminates for insulation applications (EU, 2008a).
Additionally, TCPP is typically added to pentane-blown foam (15 parts by weight), which is used in
applications such as roofing laminate (Weil and Levchik, 2009). ICL-IP's website confirms that Fyrol
PFC, their commercial TCPP product, is widely used for laminate roofing (ICL Industrial Products, No
Date-a).
Further, regarding the foam seating and bedding products category, TCPP has been used in
polyurethane elastomers and in flexible polyurethane foams when combined with melamine (Kirk-
Othmer, 1993; Weil and Levchik, 2009). TCPP has been detected in household furniture including
footstools, ottomans and chairs at loading levels ranging from 0.5 percent to 1.5 percent by foam
weight. TCPP has also been detected in the polyurethane foam from certain baby products including
car seats, changing table pads, sleep positioners, portable mattresses, nursing pillows and rocking
chairs in concentrations ranging from 1.11-14.4 mg/g. TCPP is included in the EPA's Design for the
Environment Program's Furniture Flame Retardancy Report Update (see
http://www.epa.gov/dfe/pubs/proiects/flameret/about.htm for more information) which evaluates
the hazards associated with flame retardants used in upholstered items for consumer use.
Page 63 of 72
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As for the uses in the electrical and electronic products category reported in the 2012 CDR, the only
company who reported this useforTCPP is ICL-IP. Their commercial product of TCPP is Fyrol PCF,
which is advertised on their website as used in the automotive, bedding and seating and construction
industries. Given that, electrical and electronic products would only fall under the automotive category
it is reasonable to assume that this is the category of use that TCPP is used in electronics. Further,
Fyrol PCF is advertised on ICL-IP's website as a flame retardant in phenolics in printed circuit boards
(ICL Industrial Products, No Date-a). Based on these two data sources EPA concluded that TCPP is likely
used in the circuit boards of automobiles.
Lastly, use of TCPP in the adhesives and sealants category was reported by Hilti, Inc., a construction
service company which provides both firestop sealants and other construction chemicals where TCPP
maybe used (Hilti, 2013).
TDCPP
The industrial, commercial and consumer uses of TCDPP reported in 2012 CDR are summarized in Table
2-5. Since reporting use of TDCPP in the building/construction materials not covered elsewhere
category in 2012 CDR, Albemarle - the only company to report this use - has since discontinued their
production of phosphorous-based flame-retardants. Additional searches on company websites,
government sources and academic publications on flame retardant uses did not specify where TDCPP
has been used in building and construction. However, ICL-IP's website states that its Fyrol FR-2, their
commercial TDCPP product, can be used phenolics and unsaturated polyester resins (ICL Industrial
Products, No Date-b) which can be used in the construction industry in applications such as laminates,
pipes and ducts (ICL Industrial Products, No Date-c, No Date-d; The Dow Chemical Company, No Date).
The other commercial/consumer uses reported to 2012 appear to be in the automotive and furniture
sectors. For example, ICL-IP's website promotes Fyrol FR-2, which can be used in flexible
polyurethane foam, as a chemical to assist in meeting automotive flammability tests. Additionally, the
European Union Risk Assessment for TDCPP (EU, 2008b) states that TDCPP may be used in molded
automotive seating foam (seat cushions, headrests) and slabstock foam in automotive fabric lining and
car roofing .
TDCPP has been detected in furniture such as sofas, chairs and futons at loading levels of 1-5 percent
by weight and in baby products including rocking chairs, baby strollers, car seats, changing pads, sleep
positioners, portable mattresses, nursing pillows and infant bathmats at concentrations ranging from
2.4 to 124 mg/g (Stapleton et al., 2009; Stapleton et al., 2011). TDCPP reportedly can also be used in
styrene-butadiene and acrylic lattices for textile back coatings and binding of nonwovens (Joseph and
Ebdon, 2010; Weil and Levchik, 2009). TDCPP has also been reported to the Washington State
Children's Safe Product Act database (2014) for its use as a flame retardant in "Arts/Crafts Variety
Pack" and also as a contaminant in footwear for children.10 Additionally, TDCPP is included in the EPA's
10 The product categories used by Washington State are defined by GS1 Global Product Classification Standards. They define
"Arts/Crafts Variety Pack" as "Includes any products that may be described/observed as two or more distinct Arts and
Crafts products sold together, which exist within the schema but belong to different classes, that is, two or more products
contained within the same pack, which cross classes within the Arts and Crafts Family... Includes products such as
Needlework Supplies sold with Beads. Excludes products such as Printmaking equipment sold with Airbrushing Supplies and
Artists Supplies sold with Stationery. "(GS1, 2014)
Page 64 of 72
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Design for the Environment Program's Furniture Flame Retardancy Report Update (see
http://www.epa.gov/dfe/pubs/proiects/flameret/about.htm for more information) which is evaluating
the hazards associated with flame retardants used in upholstered items for consumer use.
Page 65 of 72
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Appendix D Exposure Data Summaries
The following summaries reflect information identified through December 2014.
Products - Numerous studies have shown measured concentrations of these FRs in infant products
such as high chairs, bath mats, car seats, nursing pillows, carriers (Stapleton et al., 2011; Stapleton et
al., 2012), sofas (Stapleton et al., 2009; Stapleton et al., 2012) and camping tents (Keller et al., 2014).
Because many of these products are used in indoor environments, such as homes, the general
population and children are likely to be exposed on a continuing basis through the use of these
products. Small children may have additional exposures through contact with baby products containing
CPEs and via mouthing behaviors.
Dust-TDCPP has been detected in household, office, automobile and commercial airplane dust in the
US and abroad (AN, Dirtu, et al., 2012; AN, Van den Eede, et al., 2012; Allen et al., 2013; Bergh et al.,
2011; Brommer et al., 2012; Carignan et al., 2013; Dodson et al., 2012; Marklund et al., 2003; Meeker
and Stapleton, 2010; Stapleton et al., 2009; Takigami et al., 2009). All three CPE FRs were identified in
particulates in indoor air and settled dust collected from four different microenvironments (office,
hotel, kindergarten and student dormitory) (Cao et al., 2014). There are several US studies which have
quantified concentrations of CPEs in house dust (Dodson et al., 2012; Keller et al., 2014; Stapleton et
al., 2009; Stapleton et al., 2012), with a most recent study finding CPEs in 100% of house dust samples
and 47-96% of handwipe samples (Stapleton et al., 2014).
Indoor Air Monitoring of indoor air concentrations is limited to studies outside the US, primarily
from the EU (Bergh et al., 2011; Bjorklund et al., 2004; Green et al., 2008; Hartmann et al., 2004;
Ingerowski et al., 2001; Makinen et al., 2009; Marklund et al., 2005c; Sanchez et al., 2003; Staaf and
Ostman, 2005a, 2005b; Tollback et al., 2006) and Japan (Kanazawa et al., 2010; Ohura et al., 2006;
Otake et al., 2004; Otake et al., 2001; Saito et al., 2007). Several of these studies also included air
sampling in vehicles with many NDs (Hartmann et al., 2004; Sanchez et al., 2003; Staaf and Ostman,
2005a, 2005b), homes, commercial spaces, daycare/school (Bergh et al., 2011; Marklund et al., 2005c;
Tollback et al., 2006), offices and public spaces (Hartmann et al., 2004).
Industrial Releases to l/l/ofer-The TCPP manufacturing process is batch or continuous (OECD, 2000).
The TCPP and TDCPP manufacturing processes involve washing and then dehydration and result in
releases of these chemicals to water (EU, 2008a, 2008b). TCPP may be blended with polyols prior to
processing for the manufacture of flexible or rigid polyurethane foam (EU, 2008a). There are two
processes for the manufacture of flexible polyurethane foam: the slabstock and the molded foam
processes (EPA, 2004a, 2004b); TCPP or TDCPP are processed in the slabstock process (EU, 2008a,
2008b) and EPA believes TDCPP is also processed in the molded foam process based on the use of
TDCPP in automobile and airplane seats. Sources of release to water and the associated emission
factors or loss factors that pertain to the aforementioned processing steps and, additionally, the use of
TCPP and TDCPP in upholstered furniture, are reported in EU (2008b), EU (2008a), EPA (U.S.
Environmental Protection Agency) (2004), EPA (U.S. Environmental Protection Agency) (2004), and
OECD (2004a).
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AmbientXl/r-The concentrations of phosphate esters in air are several orders of magnitude higher
indoors than outdoors, indicating that the major sources of these indoor air pollutants are located in
the indoor environment (Bergh et al., 2011). One study of ambient air in the Great Lakes region has
shown concentrations in «1 ng/m3 range (Shoeib et al., 2014). Other studies from the EU, Asia and
Scandinavia have shown ambient air concentrations in the range of pg/m3 to ng/m3 range with the
highest level of 58 ng/m3reported for a location outside a residence in Japan (Ohura et al., 2006). One
study has identified TCEP, TCPP and TDCPP in the ambient air of the Antarctic Peninsula (Cheng et al.,
2013), but the authors attribute these concentrations to human activities from a research station
rather than global transport. Other studies such as one with measurements of ambient air in a remote
area of Finland conclude that the observed concentrations are the result of long-range global transport
(Marklundetal., 2005).
Wastewater- Several studies throughout the US (Gerrity et al., 2012; Glassmeyer et al., 2005; Jackson
and Sutton, 2008; Vidal-Dorsch et al., 2012) and abroad have reported levels of the CPEs in the
effluent and influent of wastewater: the highest reported effluent concentration was >6000 u.g/L (EU,
2008a). In a recently published study (Sengupta et al., 2014), water samples were collected during 2
low-flow events at locations above and below the discharge points of water reclamation plants in
Southern California. Concentrations of chlorinated phosphate flame-retardants were highest among
the chemicals of emerging concern tested, with mean total aggregate concentrations of TCEP, TCPP,
TDCPP of 3.4 u.g/L and 2.4 u.g/L for the 2 rivers.
Sludge- Measurements in sludge have been made in the EU (Bester, 2005; Green et al., 2008;
Marklund et al., 2005a; Olofsson et al., 2012; Olofsson et al., 2013), however there are no data for the
US.
Soil - Studies of soil with measured US values are not readily available. The only measured
concentrations of CPE in soil are from Germany at the ng/g level (Mihajlovic and Fries, 2012;
Mihajlovicetal., 2011).
Sediment - CPEs have been detected in sediment in China, Taiwan and Norway (Cao et al., 2012; Green
et al., 2008; Leonards, 2011), however no US studies in the open literature were found. There may be
some measurements performed by the USGS through their National Information Water System.
Surface Water- Several studies throughout the US (Alvarez et al., 2013; Hoppe-Jones et al., 2010;
Kolpin et al., 2002; Oros et al., 2003; Vanderford et al., 2003; Vidal-Dorsch et al., 2012) and abroad
(Andresen and Bester, 2006; Andresen et al., 2004; Andresen et al., 2007; Bacaloni et al., 2008; Bendz
et al., 2005; Bollmann et al., 2012; Clara et al., 2010; Cristale et al., 2013a; Cristale et al., 2013b; Fries
and Puttmann, 2003; Garcia-Lopez et al., 2010; Kim et al., 2007; Martinez-Carballo et al., 2007;
Matamoros et al., 2012; Quednow and Puttmann, 2009; Quednow and Puttmann, 2008; Regnery and
Puttmann, 2010; Rodil et al., 2012; Schwarzbauer and Heim, 2005; Stepien et al., 2013; Weigel et al.,
2005; Yoon et al., 2010) have reported levels of the CPEs in surface water: the highest reported water
concentration was 8.9 u.g/LTCPP (Alvarez et al., 2013). Additional data may be available from the USGS
NWIS.
Drinking Water- CPEs have been detected in several studies of US drinking water (Benotti et al., 2009;
Snyder et al., 2007; Stackelberg et al., 2007). One study of 19 water utilities across the US examining
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source water, finished water and tap water (Benotti et al., 2009) showed maximum concentrations of
up to 720 ng/L with CPEs detected in up to 50% of the samples.
Edible Fish - See description of biota, below.
Biota - Fish and other wildlife may be exposed to the cluster via surface water, sediment or soil.
Measurable levels of the CPEs in fish and other marine species from Canada, Spain, Sweden, Norway
have been detected (Evenset, 2009; Green et al., 2008; Jakimska et al., 2013; Leonards, 2011;
McGoldrick et al., 2014; Sundkvist et al., 2010). In a study from Sweden (Sundkvist et al., 2010), there
were marked differences in CPE concentrations and profiles in fish from sample locations near known
sources when compared to background locations. For example, TDCPP was detected (36-140 ng/g lipid
weight) in fish collected at points downstream of sewage treatment plants, whereas fish upstream of
the sewage treatment plant had a similar profile to other background samples. In the screening study
from the Norwegian Arctic (Evenset, 2009), TCEP, TCPP and TDDCP were detected in the fish samples
(< 0.6 - 26 ng/g ww), while only TCEP and TCPP were detected in the seabird samples (< 0.5 - 4.7 ng/g
ww). TCEP, TCPP and TDCPP in herring gull eggs from the Lake Huron area in the US have been
measured (Chen et al., 2012).
Chlorinated phosphate esters have been detected in the breast milk of women from Sweden
(Sundkvist et al., 2010) and Asia (Kim et al., 2014). Breast milk was collected from women in four
Swedish towns and obtained from the Swedish National Food Administration. The milk was pooled
with samples from up to 90 women. TCEP, TDCPP and TCPP were detected with TCPP having the
highest reported concentration (median 45 ng/g lipid wt) and TCEP (4.9 ng/g lipid wt) and TDCPP (4.3
ng/g lipid wt) detected at lower levels. TCPP was one of the most frequently occurring FRs in this study.
A study of organophosphorus flame-retardants in human breast milk from Japan, Philippines and
Vietnam found that TCEP was one of the most predominant compounds, detected in more than 60% of
samples from all three countries. Samples were collected from women living in urban settings including
near a municipal waste dumping site in the Philippines and near an e-recycling site in Vietnam. The
highest concentration of TCEP from these samples was found in breast milk from the Philippines
(median 42 ng/g lipid wt). TDCPP was not detected in the samples from Vietnam and the Philippines
and was detected in only 2% of the samples from Japan with the highest value 162 ng/g lipid wt
(median ND).
Metabolites of this cluster have been detected in human urine from men and women and children in
the US (Carignan et al., 2013; Cooper et al., 2011; Hoffman et al., 2014; Meeker et al., 2013; Stapleton
et al., 2014; Van den Eede et al., 2013); and Germany (Schindler et al., 2009).
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Appendix E Ecological Hazard Studies
The following summaries reflect information identified through December 2014.
Aquatic Toxicity- Experimental acute aquatic toxicity data are available to characterize fish and
aquatic invertebrates for all the CPE members; these data were largely obtained from secondary
sources and study reports will need to be located for further evaluation of acceptability. The acute 96-
hour LCsovalues ranges from 1.1 mg/L to 249 mg/L for fish and the acute 48-hour ECso values ranges
from 4.2 mg/L to 170 mg/L for aquatic invertebrates. Available algae toxicity data suggest 72-hour ECso
value ranges from 2.3 mg/L to 278 mg/L and chronic effects ranges from 4.3 mg/L to 25 mg/L for
aquatic plants. In addition, chronic duration studies are available to characterize aquatic invertebrate
population level effects.
Sediment Toxicity- No data were available to characterize the toxicity of sediment dwelling
organisms.
Terrestrial Toxicity- Limited data were available to characterize the toxicity of terrestrial organisms. A
single in ovo study suggests potential for sub-lethal effects in TDCPP and TCPP.
Table_Apx E-l: Ecological Toxicity Data
Endpoint
Aquatic Plants
Toxicity
72 to 96-h ECso (mg/L)
Growth rate
biomass
Aquatic Invertebrates
Acute
48-h ECso (mg/L)
Fish Acute
96-h LCso (mg/L)
Fish Chronic
Aquatic Plants
(NOEC/LOEC/GMAT)
Sediment/Soil
Avian Toxicity
Tris(2-chloroethyl)
phosphate (TCEP)
(CAS RN 115-96-8)
278 (m)
170 (m)
6.3- 249 (m)
ND
25 (m)
ND
ND
Tris(2-chloro-l-
methylethyl) phosphate
(TCPP )
(CAS RN 13674-84-5)
73 (m)
47 (m)
97 (m)
55.3 (m)
ND
10.4 (m)
ND
ND
Tris(l,3-dichloro-2-
propyl)phosphate
(TDCPP)
(CAS RN 13674-87-8)
2.3 (m)
4.2 (m)
1.1 (m)
ND
4.3 (m)
ND
ND
Notes:
ND = no data
(m) = measured data
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Appendix F Human Health Hazard Study Summaries
Based on a review of existing literature identified through December 2014, we propose the following
endpoints for inclusion in the quantitative evaluation of risk:
Acute Toxicity- Oral LD50s range from 430 - 3160 mg/kg BW. TCEP has the lowest reported LD50s,
ranging from 430-794 mg/kg BW, while TDCPP has the highest LD50 (3160 mg/kg BW). LD50s for TCPP
are more variable (ATSDR, 2012).
Repeated Dose Toxicity - In addition to kidney tumors, there is evidence of non-cancer kidney and liver
effects associated with repeated oral dosing, including renal tubular hyperplasia and altered liver
weights (Freudenthal and Henrich, 1999, 2000; Matthews et al., 1993). Thyroid follicular cell
hyperplasia was associated with TCPP (OECD SIDS) and TCEP (Matthews et al., 1993). In addition an
epidemiological study identified a correlation between decreased thyroid hormone levels in men with
TDCPP levels in dust (Meeker and Stapleton, 2010).
Male Reproductive Toxicity - One study in rats has noted effects on male reproductive organs.
Freudenthal and Henrich (2000) observed a higher incidence of atrophy in seminal vesicles, decreased
secretory product and testicular enlargement in a two-year bioassay. Two studies in rabbits yielded no
adverse effects, however the duration of these studies were shorter. The European Union determined
that the weight of evidence yielded no concern for male reproductive. Given the uncertainty
surrounding the impact of long-term exposures and male reproductive toxicity, it is not possible to
quantify risks at this time.
Developmental Toxicity - Two studies are available to assess the developmental toxicity of TCEP; high
doses of TCEP (>350 mg/kg/day) reduced the number of live pups per litter in a continuous breeding
study and the number of male pups born to the treated Fl generation were reduced at concentrations
> 175 mg/kg (Chapin et al., 1997). No fetal or developmental effects were observed in a study of rats
administered TCEP on GD 7-15 (Kawashima et al., 1983).
A study of rats administered TDCPP on GD 6-15 resulted in increased resorptions, reduced fetal
viability, decreased skeletal development and decreased mean fetal weight at 400 mg/kg/day and a
developmental NOAEL of 100 mg/kg was identified (Stauffer Chemical Company, 1981). In this same
study, maternal weight gain was also reduced.
Endocrine Activity-There is some evidence for modulation of endocrine activity. In a small human
population study, gynecomastia was noted in workers at a TDCPP manufacturing plant (Stauffer
Chemical Company, 1981). Several studies evaluated the association between TDCPP and thyroid
activity. Decreased whole body changes in T3 and T4 and genes related to thyroid hormone synthesis,
metabolism and gland development were noted in a zebrafish model (Wang et al., 2013). Decreased
plasma T4 was observed in chick embryos treated with TDCPP (Farhat et al., 2013). In a human
exposure study there was an association between TDCPP in house dust and decreased T4 levels in men
(Meeker and Stapleton, 2010). But in a recent study evaluating the relationship between TDCPP
exposure in rats and thyroid weight or serum T3/T4, no changes were observed (Moser et al., 2014).
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Chlorinated Alkyl Phosphate Flame Retardants
The conflicting data and lack of consistent adverse endpoints makes it difficult to evaluate
quantitatively.
Genetic Toxicity in vitro and in vivo - Mutagenicity data on chemicals in this cluster yield mixed results.
In general, Ames assays were negative, while several chromosomal aberration assays were positive
(ATSDR, 2012). Therefore, the putative mechanism of carcinogenicity is not clear.
Carcinogenicity - Animal studies have demonstrated that TCEP and TDCPP are carcinogenic in rodents.
Takada et al. (1989) showed that ddY mice given TCEP in the diet for 18 months had dose-related
increases in the incidences of renal cell adenomas/carcinomas and hepatocellular
adenomas/carcinomas in males and forestomach papillomas/squamous cell carcinomas and leukemia
in females. NTP cancer bioassays (gavage studies) indicated that TCEP treatment was associated with
increased kidney and thyroid tumors in rats and harderian gland tumors in mice (NTP, 1991). In a 2-
year oral study involving TDCPP exposure, rats of both sexes developed kidney and liver tumors and
males also had higher incidences of testicular tumors (Freudenthal and Henrich, 1999). NTP is
currently in the process of evaluating data from a cancer study on TCPP; we will track progress in this
study and incorporate data as soon as it is available (http://ntp.mehs.nih.gov//?obiectid=BD724190-
123F-7908-7BA185DA18C1EBB8). Based on a comparison of the calculated doses causing 50%
incidence of tumor (TDso), TDCPP (TDso= 46.4 mg/kg/day) appears to have a higher carcinogenic
potency than that of TCEP (TDso= 86.7 mg/kg/day) in the rat by the oral route
(http://toxnet.nlm.nih.gov/cpdb/ ). The chlorinated alcohol metabolite of TDCPP (i.e., l,3-dichloro-2-
propanol) has also been shown to be carcinogenic by the oral route (IARC, 2012; NTP, 2005). The
corresponding metabolite of TCEP (2-chloroethanol) was considered not carcinogenic in a dermal study
by (NTP, 1985).
Neurotoxicity - A number of studies present evidence that moderate to high exposure to TCEP can
decrease plasma cholinesterase activity in rodents and birds. In rats, brain lesions were noted following
short term high-dose exposure (Matthews et al., 1990). The same study found convulsions associated
with high doses in rats and mice. The study authors noted that female rats appear to be more sensitive
than male rats and rats appear to be more sensitive than mice. There is anecdotal evidence of acute
poisoning in dogs, who consumed seat cushions when left in cars overnight (Lehner et al., 2010). All
studies were based on oral exposure.
Additional endpoints are of interest, but will not be included in the quantitative assessment for
reasons described below.
Developmental Neurotoxicity - Decreased plasma cholinesterase levels observed in female rats is
considered representative of modulation of cholinesterase levels in the fetus of pregnant rats.
Decreased fetal cholinesterase levels pose a risk to fetal neurological development, in particular,
altering critical proliferation and differentiation events (e.g., see Rice and Barone 2000). Additional
evidence lending weight to this hypothesis comes from in vitro studies using PC12 cells as a model for
neurological development (Dishaw et al., 2011). When treated with TDCPP, TCEP, TCPP and
chlorpyrifos (as a model OP), the cells exhibited decreased DNA content - a marker of development-
induced cell proliferation, oxidative stress and altered neurodifferentiation. The concern for
modulation of neurological development based on mechanistic data does not seem to manifest in
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Chlorinated Alkyl Phosphate Flame Retardants
available animal studies. As described by ATSDR (2012) TCEP oral exposure in pregnant rats did not
induce abnormalities in functional behavioral tests (Kawashima et al., 1983). A more recent study by
Moser et al. (2014) also did not identify alternations in behavioral effects, based on an examination of
righting reflex and locomotor activities. Additional studies are underway and should be reported this
year.
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