United States EPA Document# 740-R1-5001 

Environmental Protection Agency August 2015 

Office of Chemical Safety and 

Pollution Prevention 

TSCA Work Plan Chemical 

Problem Formulation and Initial Assessment 

Chlorinated Phosphate Ester Cluster 

Flame Retardants 

CASRN NAME R = 

115-96-8 Ethanol, 2-chloro-, phosphate (3:1); 

(TCEP) -CH2-CH2-Cl 

13674-84-5 2-Propanol, 1-chloro-, 2,2',2''-phosphate; 

(TCPP) -CH(CH3)-CH2-Cl* 

13674-87-8 2-Propanol, 1,3-dichloro-, phosphate (3:1); 

(TDCPP) -CH-(CH2-Cl )2 

* Major isomer 

August 2015 

O

RO P OR

OR
Page 2 of 72 

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-1 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
Page 3 of 72 

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-1: 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-1: Existing State Regulations ................................................................................................................................. 60

Table_Apx E-1: 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

 
Page 4 of 72 

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. 
Page 5 of 72 

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) 

LC50 Lethal concentration 50 percent 

LD50 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 

μg/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 
Page 6 of 72 

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 
Page 7 of 72 

EXECUTIVE SUMMARY 

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
Page 8 of 72 

• 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, 
Page 9 of 72 

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. 
Page 10 of 72 

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
Page 11 of 72 

1.1 Scope of the Assessment 

Chlorinated phosphate ester (CPE) flame retardants (FR) are high production volume chemicals (up to 

50M lbs/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 et al., 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 
Page 12 of 72 

Table 1-1: CPE FR Cluster Members and Structures 

CAS RN NAME STRUCTURE 

115-96-8 Ethanol, 2-chloro-, phosphate (3:1); 

Tris(2-chloroethyl) phosphate 

(TCEP) 

13674-84-5 2-Propanol, 1-chloro-, 2,2',2''-phosphate; 

2-Propanol, 1-chloro-, phosphate 

(TCPP) 

(representative structure) 

13674-87-8 2-Propanol, 1,3-dichloro-, phosphate (3:1); 

2-Propanol, 1,3-dichloro-, phosphate 

(TDCPP) 

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 

TCEP 

CAS RN 

115-96-8 

TCPP 

CAS RN 

13674-84-5 

TDCPP 

CAS RN 

13674-87-8 

Physical State at Room 

Temperature 

Liquid Liquid Liquid 

Boiling Pointa

°C > 200° C [decb

] > 200° C [dec] > 200° C [dec] 

Vapor Pressurec

Pa 

1.14 E-3 1.4 E-3c 5.6 E-6 

Water Solubilityc mg/L 7820 1080 18 

Octanol Water Partition Coeff. 

Log Kow

c 

1.78 2.68 3.68 

Notes: 

 aStability of C-Cl bond loss HCl begins 200° C 

 bdec = decomposition noted 

cEU (2008b) 

Cl

O

P

O

Cl

O

O

Cl

Cl

O

P

O

Cl

O

O

Cl

Cl

O

P

O

Cl

O

O

Cl

Cl

Cl Cl
Page 13 of 72 

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 

1B) 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 
Page 14 of 72 

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. 
Page 15 of 72 

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 

Workers General 

Population 

Consumers Ecological 

Receptors 

Exposure 

Scenarios 

Manufacture and 

processing. 

Releases to the 

environment 

(affecting water 

and edible). 

Consumer 

product uses 

resulting in 

direct 

exposures or 

releases to 

indoor 

environments.

Releases to the 

environment. 

Exposure 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. 

Hazard/Toxicity 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(Cl)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). 

Figure 2-1: CPE FR Structure 

O

RO P OR

OR
Page 16 of 72 

Table 2-2: CPE FR Substituents, "R" groups 

CAS RN Name R = 

115-96-8 Ethanol, 2-chloro-, phosphate (3:1); 

(TCEP) -CH2-CH2-Cl 

13674-84-5 2-Propanol, 1-chloro-, 2,2',2''-phosphate; 

(TCPP) -CH(CH3)-CH2-Cl* 

13674-87-8 2-Propanol, 1,3-dichloro-, phosphate (3:1); 

(TDCPP) -CH-(CH2-Cl )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 

CAS RN Chemical Name Chemical Structure w/w % TCPP in commercial 

products 

13674-84-5 2-Propanol, 1-chloro-, 2,2',2''-phosphate 50 – 85%* 

76025-08-6 Bis(2-chloro-1-methylethyl) 2-

chloropropyl) phosphate 15 – 40% 

76649-15-5 2-Chloro-1-methylethyl bis(2-

chloropropyl) phosphate < 15% 

6145-73-9 1-Propanol, 2-chloro-, phosphate (3:1); < 1% 

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. 

O

Cl

O

Cl

P O

O

Cl
Page 17 of 72 

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 

TCEP 

CAS RN 

115-96-8 

TCPP 

CAS RN 

13674-84-5 

TDCPP 

CAS RN 

13674-87-8 

Molecular Weight (grams/mol) 285.50 327.57 430.88 

Physical State at Room 

Temperature Liquid Liquid Liquid

Odor Slight Odor Mild Odor Mild Odor 

Density at 25° C 1.425 g/cm3

 1.29 g/cm3 1.48 g/cm3

Melting Point -55° C -40° C 27° C 

Boiling Pointa

°C > 200° C [decb

] > 200° C [dec] > 200° C [dec] 

Vapor Pressurec

Pa 

1.14 E-3 1.4 E-3c 5.6 E-6 

Water Solubilityc mg/L 7820 1080 18 

Octanol Water Partition Coeff. 

Log Kow

c 

1.78 2.68 3.68 

Notes: 

 aStability of C-Cl bond loss HCl 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 
Page 18 of 72 

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). 
Page 19 of 72 

Table 2-5: 2012 CDR Reported Use and Production Volumes 

2012 CDR Producti

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 

Industrial 

(lbs) 

Consumer/ 

Commercial 

(lbs) 

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 

TCPP (2-Propanol, 1-chloro-, phosphate); 13674-84-52012 National Production Volume = 54,673,933 

Processing: 

Furniture and 

Related Products 

(337)

Manufacture of flexible PU Foam for the manufacture of upholstered furniture

No Data Reported

• 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) 

43,312,813 

17,325,125 

Processing: Textiles, apparel and leather (313-316)

Fabric finishing process

Foam Seating and Bedding Products (commercial and consumer use)

12,993,844 

Processing: Plastics Material and Resins (325211)

Material Fabrication Process for the Manufacture of Printed Circuit Boards

Electrical and Electronic Products (commercial and consumer use)

Automotive electronics/printed circuit boards 12,993,844 

Construction

Formulation of Adhesives and Sealants (Not reported as a flame retardant)

Adhesives and Sealants (Commercial)

- fire stop sealants 

780, 604 780, 604 
Page 20 of 72 

2012 CDR Producti

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 

Industrial 

(lbs) 

Consumer/ 

Commercial 

(lbs) 

Construction*

Manufacture of Rigid PU Foam (boardstock/ laminate, pour-in-place, or spray applied)

Construction Products

• Panels and laminates 

for insulation applications 

• Roofing laminate 

1,896,664 CBI 

Processing: Paints and Coatings 

Formulation of Paints and Coatings

Building/ Construction Materials Not Covered Elsewhere (commercial and consumer use)

CBI CBI 

All Other Basic Organic Chemical Processing

Unknown N/A N/A CBI CBI 

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 
Page 21 of 72 

2012 CDR Producti

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 

Industrial 

(lbs) 

Consumer/ 

Commercial 

(lbs) 

Processing: Furniture and Related Products 

Manufacture of flexible PU Foam for the manufacture of upholstered furniture 

Foam Seating and Bedding Products (Consumer & commercial) 

• 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) 

CBI CBI 

Fabric, Textile and Leather Products Not Covered Elsewhere (Commercial) 

• Automotive fabric 

lining 

• Car roofing 

• Textile back coating 

(specific textiles are not known) 

CBI CBI 
Page 22 of 72 

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. 
Page 23 of 72 

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). 
Page 24 of 72 

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 
Page 25 of 72 

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-1-Methylethyl) Phosphate (TCPP) CAS No: 13674-84-5 

(EU, 2008a) 

• EU Risk Assessment Report: Tris[2-Chloro-1-(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 
Page 26 of 72 

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-
Page 27 of 72 

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 F1 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 

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. 

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. 
Page 28 of 72 

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. 

PU 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. 
Page 29 of 72 

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. 
Page 30 of 72 

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. 
Page 31 of 72 

Table 2-8: Assessment of Exposure to Consumers 

Exposure Scenario 

And Applicable 

Chemicals 

Rationale Limitations 

Exposure of children in 

the home via hand-tomouth 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. 
Page 32 of 72 

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 Acute Exposure 

(Transient) 

Subchronic Exposure 

(Short-term) 

Chronic Exposure 

(Lifetime) 

Children Not applicable Kidney, Liver, Male 

Reproductive Effects, 

Neurotoxicity 

Not applicable

Adults Not applicable Kidney, Liver, Male 

Reproductive Effects, 

Neurotoxicity 

Kidney Cancer

Kidney, Liver, Male 

Reproductive Effects, 

Neurotoxicity 

Pregnant 

Women 

Developmental toxicity (fetal 

effects)

Developmental toxicity (fetal 

effects)

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
Page 33 of 72 

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 

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. 

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 PU 

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 PU foam (processing in the 

molded foam process is applicable to TDCPP only), processing for the 

manufacture of rigid PU foam and use in the manufacture of upholstered 

furniture. Releases will be estimated based on a number of sources, 

including emission factors reported in (EU (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. 
Page 34 of 72 

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 
Page 35 of 72 

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 noncancer 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 

and TDCPP

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 

and TDCPP

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 airsuspended 

particulates 

and hand-tomouth transfer 

of settled dust 

TCEP, TCPP 

and TDCPP 

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 

and TDCPP 

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. 
Page 36 of 72 

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. 
Page 37 of 72 

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 of fish 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. 
Page 38 of 72 

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 
Page 39 of 72 

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 readacross; 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/tsm20263.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. 

2.7 Critical Data Needs 

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: 
Page 40 of 72 

• 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. 
Page 41 of 72 

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Chloroethyl)Phosphate Produces Hippocampal Neuronal Loss and Impairs Learning in Rats. 

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Contaminants of Emerging Concern in Municipal Wastewater Effluents and Marine Receiving 

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Embryos/Larvae to TDCPP Alters Concentrations of Thyroid Hormones and Transcriptions of 

Genes Involved in the Hypothalamic–Pituitary–Thyroid Axis. Aquatic Toxicology, 126(0), 207-

213. 

Wei, G.-L., D.-Q. Li, M.-N. Zhuo, Y.-S. Liao, Z.-Y. Xie, T.-L. Guo, J.-J. Li, S.-Y. Zhang, and Z.-Q. Liang. 2015. 

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Chemicals, and Organobromine Compounds of Medium to High Polarity in the North Sea. 

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Exposure Assessments of Organophosphate Flame Retardants in Office Air Particulate Matter. 

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Page 54 of 72 

APPENDICES 
Page 55 of 72 

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-1: Available Occupational Exposure and Release Data 

CAS RN 115-96-8 13674-84-5 13674-87-8 

NAME 

Ethanol, 2-

chloro-, 

phosphate (3:1); 

Tris(2-

chloroethyl) 

phosphate 

(TCEP) 

2-Propanol, 1-

chloro-, 

phosphate 

(TCPP) 

2-Propanol, 1,3-

dichloro-, 

phosphate 

(TDCPP) 

Production Volume   

Number of Manufacturing and 

Processing Sites / Workers   

Occupational Exposure Limits 

Exposure Monitoring Data  

Engineering Controls or PPE 

Emission Factors 

Manufacture N/A 

Processing or Use  

Release Frequency 

Note: 

 = some data available, US or international
Page 56 of 72 

Table_Apx A-2: Available General Population and Environmental Exposure Data 

CAS NUMBER 115-96-8 13674-84-5 

(6145-73-9) 

13674-87-8 

Chemical Name

Tris(2-chloro-ethyl) 

phosphate 

Tris(2-chloro-1-

methylethyl) 

phosphate 

2-Propanol, 1,3-

dichloro-, 

phosphate 

Ethanol, 2-chloro-, 

phosphate (3:1) 

2-Propanol, 1-chloro-, 

2,2',2''-phosphate, (1-

Propanol, 2-chloro-, 

1,1',1''-phosphate) 

2-Propanol, 1,3-dichloro-, 

phosphate (3:1), (1-

Propanol, 2,3-dichloro-, 

1,1',1''-phosphate) 

Abbreviation TCEP TCPP TDCPP 

BIOMONITORING (HUMAN) 

Blood 

Breast Milk    

Adipose Tissue 

Placenta 

Urine*    

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 57 of 72 

CAS NUMBER 115-96-8 13674-84-5 

(6145-73-9) 

13674-87-8 

Chemical Name

Tris(2-chloro-ethyl) 

phosphate 

Tris(2-chloro-1-

methylethyl) 

phosphate 

2-Propanol, 1,3-

dichloro-, 

phosphate 

Ethanol, 2-chloro-, 

phosphate (3:1) 

2-Propanol, 1-chloro-, 

2,2',2''-phosphate, (1-

Propanol, 2-chloro-, 

1,1',1''-phosphate) 

2-Propanol, 1,3-dichloro-, 

phosphate (3:1), (1-

Propanol, 2,3-dichloro-, 

1,1',1''-phosphate) 

wastewater    

AIR + WATER 

deposition    

BIOTA 

avian    

fish    

aquatic animals    

terrestrial animals 

vegetation 

Notes: 

 = presence of metabolite 

 = some data available, US or international 
Page 58 of 72 

Table_Apx A-3: Available Mammalian and Aquatic Toxicity Data 

CASRN 115-96-8 13674-84-5 13674-87-8 

NAME 

Ethanol, 2-

chloro-, 

phosphate (3:1); 

Tris(2-

chloroethyl) 

phosphate 

(TCEP) 

2-Propanol, 1-

chloro-, 

phosphate 

(TCPP) 

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 ○  

ECOLOGICAL RECEPTORS

Log Kow (P)   

Fish 96-h LC50  

Daphnid 48-h 

LC50 

 
Page 59 of 72 

CASRN 115-96-8 13674-84-5 13674-87-8 

NAME 

Ethanol, 2-

chloro-, 

phosphate (3:1); 

Tris(2-

chloroethyl) 

phosphate 

(TCEP) 

2-Propanol, 1-

chloro-, 

phosphate 

(TCPP) 

2-Propanol, 1,3-

dichloro-, phosphate 

(TDCPP) 

Green algae 96-h 

EC50 

  

Fish ChV 

Daphnid ChV  

Green algae ChV  

Notes: 

 = data available, likely to be useful for quantitative analysis 

--- = no data available 

○ = data available, but may not be useful for quantitative analysis 
Page 60 of 72 

Appendix B Regulatory and Assessment History 

B-1 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-1. 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-1: Existing State Regulations 

State Chemical(s) Regulation Hazard Basis 

California TCEP and 

TDCPP 

Proposition 65 

(http://oehha.ca.gov/prop65/prop65_list/newlist.html) 

Cancer 

California TCEP, TCPP 

and TDCPP 

Identified as candidate chemicals under the Safer Consumer 

Product Regulations (https://dtsc.ca.gov/SCP/ChemList.cfm) 

Cancer, 

reproductive 

toxicity 

California TDCPP 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) 

Cancer 

Connecticut TCEP, TCPP 

and TDCPP 

Regulates the use in children’s products. 

(http://www.cga.ct.gov/2013/FC/pdf/2013HB-06332-R000040-

FC.pdf) 

Cancer, 

reproductive 

toxicity 

Maine TCEP Identified as a Chemical of High Concern

(http://www.maine.gov/dep/safechem/highconcern/) 

Prioritized by 

Canada 

Maryland TCEP Prohibits sale of certain children’s products made with TCEP 

(http://mgaleg.maryland.gov/webmga/frmLegislation.aspx?pid=

legisnpage&tab=subject3; see 2013, either HB0099 or CH0349) 

Cancer 

Minnesota TCEP and 

TDCPP 

Identified as a Chemicals of High Concern 

(http://www.health.state.mn.us/divs/eh/hazardous/topics/toxfr

eekids/highconcern.html) 

Cancer, 

reproductive 

toxicity 

New York TCEP Prohibits sale of certain children’s products made with TCEP 

(http://assembly.state.ny.us/leg/; see 2003-2004, S 7621) 

Cancer, 

reproductive 

toxicity, 

neurotoxicity 

Vermont TCEP and 

TDCPP 

Banned from use in children’s products and residential 

upholstered furniture 

(http://www.atg.state.vt.us/issues/consumerprotection/product-saftey/flame-retardants.php) 

Cancer 
Page 61 of 72 

State Chemical(s) Regulation Hazard Basis 

Washington TCEP and 

TDCPP 

Identified as a Chemicals of High Concern 

(http://www.ecy.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.ecy.wa.gov/programs/swfa/cspa/) 

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 (CCPSA), 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 62 of 72 

• 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 1B), 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 (CCPSA), 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. 
Page 63 of 72 

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/projects/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 FyrolTM 

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 (KirkOthmer, 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/projects/flameret/about.htm for more information) which evaluates 

the hazards associated with flame retardants used in upholstered items for consumer use. 
Page 64 of 72 

As for the uses in the electrical and electronic products category reported in the 2012 CDR, the only 

company who reported this use for TCPP is ICL-IP. Their commercial product of TCPP is FyrolTM 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,

FyrolTM 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 

may be 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 FyrolTM 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 FyrolTM 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 65 of 72 

Design for the Environment Program’s Furniture Flame Retardancy Report Update (see 

http://www.epa.gov/dfe/pubs/projects/flameret/about.htm for more information) which is evaluating 

the hazards associated with flame retardants used in upholstered items for consumer use. 
Page 66 of 72 

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 (Ali, Dirtu, et al., 2012; Ali, 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 Water – 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). 
Page 67 of 72 

Ambient Air – 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/m3

reported 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 

(Marklund et al., 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 μg/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 μg/L and 2.4 μg/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 (Mihajlović and Fries, 2012; 

Mihajlovic et al., 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 Püttmann, 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 μg/L TCPP (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 
Page 68 of 72 

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 LC50 values ranges from 1.1 mg/L to 249 mg/L for fish and the acute 48-hour EC50 values ranges 

from 4.2 mg/L to 170 mg/L for aquatic invertebrates. Available algae toxicity data suggest 72-hour EC50

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-1: Ecological Toxicity Data 

Endpoint Tris(2-chloroethyl) 

phosphate (TCEP) 

(CAS RN 115-96-8) 

Tris(2-chloro-1-

methylethyl) phosphate 

(TCPP ) 

(CAS RN 13674-84-5) 

Tris(1,3-dichloro-2-

propyl)phosphate 

(TDCPP) 

(CAS RN 13674-87-8)

Aquatic Plants 

Toxicity 

72 to 96-h EC50 (mg/L)

Growth rate

biomass

278 (m) 

73 (m) 

47 (m) 2.3 (m) 

Aquatic Invertebrates

Acute 

48-h EC50 (mg/L) 

170 (m) 97 (m) 4.2 (m) 

Fish Acute 

96-h LC50 (mg/L) 6.3 – 249 (m) 55.3 (m) 1.1 (m) 

Fish Chronic ND ND ND 

Aquatic Plants 

(NOEC/LOEC/GMAT) 25 (m) 10.4 (m) 4.3 (m) 

Sediment/Soil ND ND ND 

Avian Toxicity ND ND ND 

Notes: 

ND = no data 

(m) = measured data
Chlorinated Alkyl Phosphate Flame Retardants 

Page 70 of 72 

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 F1 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). 
Chlorinated Alkyl Phosphate Flame Retardants 

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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.niehs.nih.gov//?objectid=BD724190-

123F-7908-7BA185DA18C1EBB8). Based on a comparison of the calculated doses causing 50% 

incidence of tumor (TD50), TDCPP (TD50= 46.4 mg/kg/day) appears to have a higher carcinogenic 

potency than that of TCEP (TD50= 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., 1,3-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 developmentinduced cell proliferation, oxidative stress and altered neurodifferentiation. The concern for 

modulation of neurological development based on mechanistic data does not seem to manifest in 
Chlorinated Alkyl Phosphate Flame Retardants 

Page 72 of 72 

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.