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

P OR RO

ORPage 2 of 72 

## TABLE OF CONTENTS

TABLE OF CONTENTS .................................

................................................... ..................................... 2
AUTHORS / CONTRIBUTORS / ACKNOWLEDGEMENTS .........

................................................... ........... 4

ABBREVIATIONS .....................................

................................................... ........................................ 5

EXECUTIVE SUMMARY .................................

................................................... .................................. 7

1 INTRODUCTION ......................................

................................................... ............................... 10

1.1 S COPE OF THE A SSESSMENT

.................................................. ................................................... ....................................... 11
1.2 R EGULATORY AND A SSESSMENT H ISTORY

.................................................. ................................................... ...................... 13

2 PROBLEM FORMULATION ...............................

................................................... ...................... 14

2.1 P HYSICAL C HEMISTRY

.................................................. ................................................... ................................................ 15
2.2 P RODUCTION V OLUME AND U SE

.................................................. ................................................... ................................. 17
2.3 F ATE AND T RANSPORT

.................................................. ................................................... ............................................... 22
2.4 E XPOSURES

.................................................. ................................................... ................................................... .......... 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 H AZARD E NDPOINTS

.................................................. ................................................... ................................................. 2 4
**2.5.1 Ecological Hazard .................................** 

**................................................... ...................................................**  **.......... 25**
**2.5.2 Human Health Hazard ...............................** 

**................................................... ...................................................**  **..... 25**
2.6 R ESULTS OF P ROBLEM F ORMULATION

.................................................. ................................................... .......................... 27
**2.6.1 Conceptual Models .................................** 

**................................................... ...................................................**  **........ 27**
**2.6.2 Analysis Plan .....................................** 

**................................................... ...................................................**  **.............. 32**
**2.6.3 Sources and Pathways Excluded From Further Assessme**  **nt ................................................ ................................. 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 C RITICAL D ATA N EEDS

.................................................. ................................................... ............................................... 39

REFERENCES ........................................

................................................... ......................................... 41

APPENDICES ........................................

................................................... ......................................... 54
Appendix A Data Availability Tables ..........................

................................................... ................. 55
Appendix B Regulatory and Assessment History .................

................................................... ........ 60

B-1 D OMESTIC

.................................................. ................................................... ................................................... .......... 60

B-2 I NTERNATIONAL

.................................................. ................................................... ................................................... ... 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 ...............

................................................... ... 70Page 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 Volu mes ...............................................

................................................... . 19 Table 2-6: Assessment of Environmental Exposures ..

................................................... ................................................... ......... 28 Table 2-7: Assessment of Toxicity in Aquatic Organi sms ...............................................

................................................... ......... 29 Table 2-8: Assessment of Exposure to Consumers ....

................................................... ................................................... .......... 31 Table 2-9: Assessment of Exposure to General Popula tion ..............................................

................................................... ...... 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 Aq uatic Organisms ...................................

................................................... ... 33 Table 2-13: Analysis Plan for General Population an d 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 Env ironmental Exposure Data .......................... ......................................... 56 Table_Apx A-3: Available Mammalian and Aquatic Toxi city 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 Recepto rs ................................................

................................................... ......... 28 Figure 2-3: Conceptual Model for Human Receptors ..

................................................... ................................................... ........ 30Page 4 of 72 

## AUTHORS / CONTRIBUTORS / ACKNOWLEDGEMENTS

This report was developed by the United States Envi ronmental Protection Agency (US EPA), Office of Chemical Safety and Pollution Prevention (OCSPP), O ffice of Pollution Prevention and Toxics (OPPT). The Work Plan Chemical Problem Formu lation for the chlorinated phosphate ester cluster was prepared based on currently available d ata. 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 & Sustaina ble 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 informa tion and updates to the regulatory history of CPE

FRs.

Also, portions of this document were prepared for EPA/OPP T by Abt Associates, the Eastern Research Group (ERG), Inc., the Syracuse Research Corporatio n (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)

LC 50 Lethal concentration 50 percent

LD 50 Lethal dose 50 percent
LOAEL Lowest-observed-adverse-effect level

m 3 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 Preve ntion OECD Organisation for Economic Cooperation and Deve lopment
OPPT Office of Pollution Prevention and Toxics PBPK Physiologically based pharmacokinetic pg picogramPage 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 PlantPage 7 of 72 

## EXECUTIVE SUMMARY

As a part of EPA/OPPT’s comprehensive approach to e nhance the Agency’s management of existing chemicals, EPA/OPPT identified a work plan of chemi cals for further assessment under the Toxic Substances Control Act (TSCA) 1 in March 2012. Chemical risk assessments will be c onducted if, as a result of scoping and problem formulation, there ar e exposures of concern, identified hazards and sufficient data for quantitative analysis. If an as sessment identifies unreasonable risks to humans or the environment, EPA will pursue risk reduction. Th is document presents the problem formulation and initial assessment of a cluster of chlorinated phos phate 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 W ork Plan.

EPA/OPPT has identified a cluster of three CPE FR c hemicals - TCEP, TCPP and TDCP - for risk assessment. These three chemicals have similar phys ical and chemical properties and environmental fate characteristics. All three chemicals are, or h ave 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 con ducted a problem formulation based on the evaluation of readily available data and informatio n to determine the feasibility of conducting a quantitative risk assessment.

The conclusions from this problem formulation and i nitial assessment are that EPA/OPPT will conduct additional analyses as follows:

• Assess potential risks to aquatic organisms from CP Es in the environment.

• Assess potential risks to human health from inciden tal ingestion of CPEs in inhaled dust or via
hand-to-mouth transfer of settled dust released fro m consumer products.

• Assess potential risks to children from incidental ingestion of CPEs from mouthing of consumer products.

• Assess potential risks to human health from consump tion of CPEs in drinking water, or fish (recreational and subsistence fishers).

• Evaluate potential risks to human health from aggre gate oral exposure to CPEs.

EPA/OPPT has determined that several uses are not e xpected to result in significant releases to the
environment and therefore will not be assessed:

• Releases from manufacturing and processing resultin g 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 pr oducts.

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 sedime nt-dwelling organisms (insufficient toxicity data).

1 http://www.epa.gov/oppt/existingchemicals/pubs/work plans.htmlPage 8 of 72

• Releases to the environment from non-industrial (e. g., office worker) and consumer uses of products containing CPEs (insufficient data to quan tify releases).

• Industrial workers via inhalation of vapor and derm al exposure (no route-specific toxicity data).

• Consumer exposures via inhalation and dermal exposu res (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 id entified available fate, exposure and hazard data, and characterized potential exposures, recept ors and effects. EPA/OPPT examined likely exposure and hazard scenarios based on current prod uction, 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 wat er.

• Releases of CPE FRs from consumer products, resulti ng in exposures via the incidental ingestion of air-suspended particulates or resuspended dust a nd hand-to-mouth transfer of settled dust.

• Mouthing of consumer and children’s products contai ning 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, poly urethane foam manufacturing and textile processing are possible and could result in exposur es 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 pathw ays due to their migration from the polymer matrix into the environment where they are used, ei ther 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 polymer s, such as insulation and furniture, are in indoor environments, the potential for exposure via all ex posure routes (i.e., inhalation of indoor air and d ust, dermal contact with products and incidental ingesti on of dust) is high.

Mouthing of consumer and children’s products contai ning CPE FRs could result in the migration from the polymer matrix into a child’s mouth, resulting in oral exposures. General population oral exposure s will be evaluated based on assessed industrial rele ases and the presence of CPE FRs in fish and drinki ng
water.

Human endpoints include cancer and non-cancer effec ts. Two CPEs (i.e., TCEP and TDCPP) are known animal carcinogens. Other non-cancer laboratory ani mal 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 expecte d to be significant exposure routes for industrial workers and consumers. However, as there are no tox icological data for inhalation or dermal exposure routes, therefore EPA/OPPT will not assess inhalati on 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 h uman health. This document describes the results of problem formulation and the proposed approach for t he 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 he alth 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 e nhance 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 f or further assessment 3 . The criteria focused on chemicals that meet one or more of the following fa ctors: (1) potentially of concern to children’s health (for example, because of reproductive or dev elopmental effects); (2) neurotoxic effects; (3) persistent, bioaccumulative and toxic (PBT); (3) pr obable 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 ph osphate ester flame retardant chemicals, including tris(2-chloroethyl) phosphate (TCEP2-propanol, 1-ch loro-, phosphate (TCPP) and 2-propanol, 1,3- dichloro-, phosphate (TDCPP), was identified for as sessment based on human health and ecotoxicity concerns, potential for human exposure, moderate re leases to the environment and moderate environmental persistence.

EPA/OPPT is performing risk assessments on chemical s in the work plan. If an assessment identifies unacceptable risks to humans or the environment, EP A/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 assess ment may be of assistance to other federal, state and local agencies as well as to members of the gen eral public who are interested in the risks of TCEP

, TCPP and TDCPP.

The initial steps in EPA/OPPT’s risk assessment dev elopment process, which is distinct from the initia l prioritization exercise, includes scoping and probl em formulation. During these steps EPA/OPPT reviews currently available data and information, i ncluding but not limited to, assessments conducted by others (e.g., authorities in other countries), p ublished or readily available reports and published
scientific literature.

This document includes the results of scoping and p roblem formulation for the chlorinated phosphate ester cluster. In the initial prioritization and sc oping stages, EPA/OPPT determined which chemicals
would be included in the cluster and which uses wou ld be considered in the assessment. During problem formulation, EPA/OPPT identified available exposure and hazard data, and characterized potential exposures, receptors and effects. EPA/OPP T developed the conceptual models (Figure 2-2 and Figure 2-3) and analysis plan (section 2.6.2) a s a result of problem formulation.

2 http://www.epa.gov/oppt/existingchemicals/pubs/work plans.html

3 http://www.epa.gov/oppt/existingchemicals/pubs/wpme thods.pdfPage 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 polyb rominated diphenyl ethers (PBDEs) (EPA, 2012) have likely spurred the increased use of alternativ e 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 t o these chemicals through multiple pathways (Wei et al., 2015).

Animal toxicity studies indicate effects that may b e suggestive of human health concerns. Two CPEs (i.e., TCEP and TDCPP) are known animal carcinogens . TCPP is currently under study 4 . Other animal studies have shown effects on the kidney, liver and the neurological system. Thyroid effects and developmental and reproductive toxicity were more v ariable across studies. Given the common use, widespread exposure and potential health hazards, E PA/OPPT conducted a problem formulation and evaluation of readily available data and informatio n to determine the feasibility of conducting a quantitative risk assessment.

EPA/OPPT selected cluster members and uses for incl usion in this assessment based on available data, including chemical structure, physical chemical pro perties, toxicological information from existing assessments, production volume and reported uses. D uring the initial work plan chemical prioritization process described above, EPA/OPPT identified TCEP a s a work plan chemical, although commercial uses of TCEP as a flame retardant were declining, s ince TCPP and TDCPP were structurally similar and increasing as substitutes for TCEP. As a result, EP A/OPPT grouped the three chemicals for evaluation (Table 1-1). The rationale for taking a “use cluste r approach” is to evaluate chemicals that have a common pattern of use and may have similar fate, ex posure and toxicity. Additionally, the cluster approach presents efficiencies in data evaluation a nd analysis.

4 http://ntp.niehs.nih.gov/testing/status/agents/ts-m 20263.htmlPage 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- containin g chemicals on the TSCA Inventory. Selection criteria included chemical structure, physical chem ical properties and data availability. Data availab ility requirements included sufficient exposure and toxic ity 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 particula r vapor pressure, water solubility and octanol wate r partition coefficient (Table 1-2). The three chemic als 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 Point a
°C > 200° C [dec b ] > 200° C [dec] > 200° C [dec]

Vapor Pressure c

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

Water Solubility c mg/L 7820 1080 18

Octanol Water Partition Coeff.

Log K ow c 1.78 2.68 3.68

Notes:

a Stability of C-Cl bond loss HCl begins 200° C

b dec = decomposition noted

c EU (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 ClPage 13 of 72



### 1.2 Regulatory and Assessment History

EPA/OPPT reviewed the regulatory and assessment his tory of TCEP, TCPP, and TDCPP, to identify exposures, hazards and risks that have been previou sly 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 grandfa thered in with the passage of the Toxic
Substances Control Act of 1976. EPA has established Provisional Peer-Reviewed Toxicity Values (PPRTVs) for TCEP 5

.

The ATSDR Toxicological Profile for Phosphate Ester Flame Retardants (2012) included TCEP, TDCPP and TCPP and provided detailed analyses of availabl e hazard data. An earlier evaluation by the CPSC (2006) assessed the cancer risks associated with in halation 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 f rom inhalation exposure during the first two years of life was 20 per million. The Hazard Index (a compar ison of exposure and critical effect level) was 2 f or adults and 5 for children. CPSC estimated that 98-9 9% of exposure was via the inhalation route.

State

TCEP and TDCPP are both listed on California’s prop osition 65 list of chemicals known to the state of
California to cause cancer 6 . In addition, California Department of Toxic Subst ances Control (DTSC) has proposed TDCPP and TCEP in Children’s Foam Padded S leeping Products for regulation under the Safer Consumer Products Regulations. 7

These CPEs are subject to regulations by a number o f states. Other states that have proposed legislation that could affect the use of TCEP, TDCP P and TCPP include Washington, Massachusetts and
North Carolina.

International

The European Union (EU) has conducted risk assessme nts for TCEP, TCPP and TDCPP (EU, 2008a, 2008b, 2009). Occupational, general population, con sumer and ecological exposures were included in these assessments and in some cases, unacceptable r isks were identified. Specifically, risks to worker s from inhalation and dermal exposure to TCEP were id entified, as were risks to children from mouthing of objects made with TCEP (EU, 2009). For all scena rios, 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 co ncluded that the use of TCEP in toys should be avoided (EU, 2012). TCEP is listed in the EU Author isation List based on reproductive toxicity (catego ry 1B) with a sunset date of August 21, 2015. No conce rns 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.cfmPage 14 of 72

Based on a screening assessment of TCEP, Canada pas sed a Significant New Activity provision in January 2013 (Health Canada, 2014). As of April 201 4, products made, in whole or in part, of polyurethane foam that contains TCEP and are intend ed 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 produ cts are prohibited from manufacture, import, advertising or sale.

Although the EU risk assessment for TDCPP also iden tified potential risks to workers, it concluded tha t current risk management measures should be effectiv e (EU, 2008b). No risks were identified for consumers, general population, or ecological recept ors. 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 un acceptable risks for workers, consumers, general population, or ecological receptors (EU, 2008a).

Appendix B contains additional information on the a ssessment and regulatory history of these
chemicals.



## 2 PROBLEM FORMULATION

Problem formulation aims to determine the major fac tors to be considered in an assessment, including exposure pathways, receptors and health endpoints ( EPA, 1998, 2014b). Accordingly, this problem formulation summarized the exposure pathways, recep tors 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 identi fy exposure pathways, receptors and health endpoint s for quantitative analysis.

EPA/OPPT summarized the outcome of this evaluation in conceptual models for ecological and human health that illustrate the exposure pathways, recep tor populations and effects that will be considered in the risk assessment. EPA/OPPT also prepared anal ysis plans to demonstrate the proposed approach to answering the defined assessment questions for e cological and human health.

Data Needs

This section summarizes data identified and conside red during problem formulation and used to construct the conceptual models. The process by whi ch use and exposure scenarios were selected for inclusion in the conceptual model was informed by t he identification of high volume uses that are known or likely to be associated with exposures. Th e selection process was further aided by the identification of data quality objectives to establ ish 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 hea lth, non-cancer risks will be assessed using the Margin of Exposure (MOE) approach. This approach re quires the selection of a critical effect in a key study to determine the Point of Departure (POD). Ca ncer risks will be determined based on low-dose linear extrapolation, which requires the derivation of a cancer slope factor. To assess risks to ecolo gical receptors, the Concentration of Concern (CoC) will be established. Both approaches require the comparison of estimated exposure with a critical ef fect level (e.g., the POD or the CoC). The types of data required for conducting this type of quantitat ive 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 medi a may be used. A

combination of these approaches may be considered d epending 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 ad dition of epoxide with O=P(Cl)3. TCEP is formed using ethylene oxide. TDCPP is formed using epichlo rohydrin. TCPP is a chloropropyl phosphate, formed using propylene oxide. The common chemical s tructure 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 o f the isomers and available toxicity data are based on th e commercial mixture (NRC, 2000).

Figure 2-1: CPE FR Structure



### O

P OR RO

ORPage 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 displa yed in Table 2-3. All commercial mixtures contain varyi ng 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% C ASRN = [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) an d the least abundant form is the completely linear isomer, 1-Propanol, 2-chloro-, phosphate (3:1) (CAS RN = 6145-73-9) (NRC, 2000). Variations in manufacturing methods result in commercial formulat ions that contain different proportions of the four isomers. The different isomers may produce differen tial 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 ClPage 17 of 72

Select physical and chemical properties are display ed in Table 1-2 of section 1.1. A more complete listing of physical and chemical properties is pres ented 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/cm 3 1.29 g/cm 3 1.48 g/cm 3

Melting Point -55° C -40° C 27° C

Boiling Point a
°C > 200° C [dec b ] > 200° C [dec] > 200° C [dec]

Vapor Pressure c

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

Water Solubility c mg/L 7820 1080 18

Octanol Water Partition Coeff.

Log K ow c 1.78 2.68 3.68

Notes:

a Stability of C-Cl bond loss HCl begins 200° C

b dec = decomposition noted

c EU (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 inform ation cannot be included in this report. Additionally, primary literature and the Washington State’s Children’s Safe Product Act Database 8 were searched for other potential uses. Additional infor mation is provided in Appendix B.

TCEP’s only CDR reported use is under the “paints a nd coatings” sector for both the industrial and consumer/commercial categories. Although not report ed to the CDR, TCEP has also been reported to
be used as a flame retardant in children’s car seat s (Washington State, 2014) and has been detected in changing table pads, sleep positioners, portable ma ttresses, nursing pillows, baby carriers and infant bath mats (Stapleton et al., 2011).

TCPP is reported to the CDR in a variety of industr ial use categories such as “furniture and related products” for the manufacture of flexible polyureth ane foam and under “textiles, apparel and leather” for fabric finishing processing. Other industrial u ses are given in Table 2-5. TCPP is reported to be used

8 https://fortress.wa.gov/ecy/cspareporting/Default.a spxPage 18 of 72

in a variety of commercial and consumer use categor ies 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, f ire 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 (Sta pleton et al., 2011).

TDCPP is listed in the CDR’s industrial use categor y under the construction sector and in the commercial and consumer use category under “buildin g/construction materials.” These sectors may refer to TDCPP’s use in the manufacture of rigid po lyurethane foam, which is used in laminates, pipes and ducts. Although not reported as a use in the CD R, TDCPP has been detected in furniture such as sofas, chairs and futons and in baby products inclu ding rocking chairs, baby strollers, car seats, changing pads, sleep positioners, portable mattress es, nursing pillows and infant bathmats (Stapleton et al., 2009; Stapleton et al., 2011). TDCPP has al so been reported to the Washington State Children’s Safe Product Act database (2014) for its use as a f lame retardant in “arts/crafts variety pack” and al so as a contaminant in footwear for children 9

.

9 Arts/Crafts Variety Pack” includes any products tha t may be described/observed as two or more distinct Arts and Crafts products sold together, which exist within the sche ma 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 72Table 2-5: 2012 CDR Reported Use and Production Volumes2012 CDR Production VolumeIndustrial UseReported to the2012 CDRDescription of IndustrialUse (Based on theIndustrial Use Reported tothe 2012 CDR)Commercial orConsumer UseReported to the 2012CDRPotential End-UsesWithin CDR CategoryIndustrial(lbs)Consumer/Commercial(lbs)Approximate %of National PVby UseTCEP, (Ethanol, 2-chloro-, phosphate (3:1); Tris(2-chloroethyl) phosphate); 115-96-82012 CDR National Production Volume = CBIProcessing: Paintsand CoatingFormulation of Paints andCoatingsPaints and coatings(not known if intendedfor consumer/commercial or both)Paints and CoatingsCBICBICBITCPP (2-Propanol, 1-chloro-, phosphate); 13674-84-52012 National Production Volume = 54,673,933Processing:Furniture andRelated Products(337)Manufacture of flexible PUFoam for the manufactureof upholstered furnitureNo Data Reported•Polyurethane foamin householdfurniture (e.g.,footstools, ottomansand chairs)•Polyurethane foamin baby products(e.g., car seats,changing table pads,sleep positioners,portable mattresses,nursing pillows androcking chairs)43,312,81317,325,12532Processing:Textiles, appareland leather (313-316)Fabric finishing processFoam Seating andBedding Products(commercial andconsumer use)12,993,84424Processing:Plastics Materialand Resins(325211)Material FabricationProcess for theManufacture of PrintedCircuit BoardsElectrical andElectronic Products(commercial andconsumer use)Automotiveelectronics/printed circuitboards12,993,84424ConstructionFormulation of Adhesivesand Sealants(Not reportedas a flame retardant)Adhesives andSealants (Commercial)- fire stop sealants780, 604 780, 604 1.4Page 20 of 722012 CDR Production VolumeIndustrial UseReported to the2012 CDRDescription of IndustrialUse (Based on theIndustrial Use Reported tothe 2012 CDR)Commercial orConsumer UseReported to the 2012CDRPotential End-UsesWithin CDR CategoryIndustrial(lbs)Consumer/Commercial(lbs)Approximate %of National PVby UseConstruction*Manufacture of Rigid PUFoam (boardstock/laminate, pour-in-place, orspray applied)Construction Products•Panels and laminatesfor insulationapplications•Roofing laminate1,896,664 CBI<20%Processing: Paintsand CoatingsFormulation of Paints andCoatingsBuilding/ ConstructionMaterials Not CoveredElsewhere(commercial andconsumer use)CBI CBIAll Other BasicOrganic ChemicalProcessingUnknownN/AN/A CBI CBITDCPP, (2-Propanol, 1,3-dichloro-, phosphate); 13674-87-82012 CDR National Production Volume = 10-50 millionpoundsConstructionManufacture of Rigid PUFoam (boardstock/laminate, pour-in-place, orspray applied)Building/ConstructionMaterials, e.g.Laminates, pipes, &ducts. (Consumer &commercial)- Laminates- Pipes- DuctsCBI CBIPage 21 of 722012 CDR Production VolumeIndustrial UseReported to the2012 CDRDescription of IndustrialUse (Based on theIndustrial Use Reported tothe 2012 CDR)Commercial orConsumer UseReported to the 2012CDRPotential End-UsesWithin CDR CategoryIndustrial(lbs)Consumer/Commercial(lbs)Approximate %of National PVby UseProcessing:Furniture andRelated ProductsManufacture of flexible PUFoam for the manufactureof upholstered furnitureFoam Seating andBedding Products(Consumer &commercial)•Furniture (e.g., sofas,chairs, futons,rocking chairs)•Automotive seating(i.e., cushions andheadrests)•Baby products (e.g.,strollers, car seats,changing pads, sleeppositioners, portablemattresses, nursingpillows, infantbathmats)CBI CBI CBIFabric, Textile andLeather Products NotCovered Elsewhere(Commercial)•Automotive fabriclining•Car roofing•Textile back coating(specific textiles arenot known)CBI CBI CBIPage 22 of 72



### 2.3 Fate and Transport

The EPA Design for the Environment Branch (DfE) rec ently published draft hazard profiles for TCEP, TCPP and TDCPP (EPA, 2014a) and included in these h azard 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 av ailable physical and chemical property data indicat e 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 m obility in soil, based on measured or estimated

K OC values. Leaching through soil to groundwater may o ccur. In the atmosphere, TCEP is expected to exist in the vapor phase based on its vapor pressur e (EPA, 2014a).

Level III fugacity models indicate that at steady s tate TDCPP will likely be found primarily in soil a nd to a lesser extent, sediment and water. Leaching throu gh soil to groundwater may occur. Monitoring data suggests TDCPP is bound to particulates in the atmo sphere (EPA, 2014a; Moeller et al., 2011).

TCEP persistence is anticipated to be moderate, whe reas TCPP and TDCPP are generally highly persistent. TCEP is expected to hydrolyze slowly; a lthough hydrolysis rates will be dependent on temperature and pH conditions according to experime ntal studies. TDCPP will undergo hydrolysis under alkaline conditions, with half-lives of 15 da ys measured at pH 9 and 50°C. TDCPP is relatively stable to hydrolysis under neutral and acidic condi tions, 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 experi mental studies of water samples. The atmospheric half-lives of vapor-phase TCEP and TCPP are estimat ed to be less than one day, although TCPP is not expected to partition significantly to the atmosphe re (EPA, 2014a).

Monitoring studies have reported the detection of T CEP in aquatic species, mammalian species, herring gull eggs and pine needles. Available toxic okinetic studies indicate that in some species, metabolites of TCEP are rapidly formed and eliminat ed. This demonstrates that these materials are likely bioavailable and could be observed in a biol ogical 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 expo sure data and the receptors identified for quantitative risk assessment. Data availability tab les 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 accoun t in preparing this document.Page 23 of 72

2.4.1 Releases to the Environment

EPA/OPPT reviewed readily available sources for inf ormation related to the release of flame-retardants in general from industrial sources. EPA/OPPT also s earched the scientific literature for data related to releases to the environment from industrial sites, but did not find any chemical-specific data. US Tox ic Release Inventory (TRI) data are not available for these chemicals. Releases to water from industrial operations are possible and may have localized impa cts 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 r eported 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 a broad have reported levels of the CPEs in surface
water. CPEs have been detected in several studies o f 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 e xposure 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 no t assessed (EU, 2008a, 2008b). Use of engineering controls (dust extractors) that limit t he 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 thro ugh food and drinking water. Several European studies (from Spain, Sweden and Norway) and one Can adian study have identified CPE FRs in fish.
Several studies show that the levels of contaminant s varied in relation to their proximity to sewage treatment plants. EPA/OPPT is not aware of data ind icating 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 fis h 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 sy stem to the gastrointestinal tract (referred to here as incidental ingestion of inhale d dust), and

• Incidental ingestion of indoor settled dust via han d-to-mouth behaviors. In addition, children may experience incidental ing estion 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 m icroenvironments (e.g., schools, daycares, public and commercial buildings, vehicles) may be consider ed. EPA/OPPT considers exposures to CPE FRs indoor environments to be possible through inhalati on 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 CP E FRs in infant products such as high chairs, bath mats, car seats, nursing pillows, carriers (Fa ng et al., 2013; Stapleton et al., 2011) sofas (Sta pleton et al., 2009; Stapleton et al., 2012) and camping t ents (Keller et al., 2014). Because many of these products are used in indoor environments, such as h omes, 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 su mmaries are presented in Appendix D.



### 2.5 Hazard Endpoints

EPA’s Integrated Risk Information System (IRIS) pro gram 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 hazar dPage 25 of 72

evaluation for CPE FRs was based on several existin g assessments. In particular, the following studies were deemed helpful, as they were peer reviewed, wi dely distributed and largely concordant:

• Toxicological Profile for Phosphate Ester Flame Ret ardants (human health hazards only) (ATSDR, 2012)

• EU Risk Assessment Report: Tris (2-Chloroethyl) Pho sphate, (TCEP) CAS No: 115-96-8 (EU, 2009)

• EU Risk Assessment Report: Tris(2-Chloro-1-Methylet hyl) Phosphate (TCPP) CAS No: 13674-84-5 (EU, 2008a)

• EU Risk Assessment Report: Tris[2-Chloro-1-(Chlorom ethyl)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, invertebrat e and algal toxicity data for all three chemicals. Chronic aquatic toxicity data is available for daphnids, bu t 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 pigm entation and hyperventilation. These effects suggest potential for long-term population level co ncerns 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 wi th pesticidal use and non-halogenated phosphate esters with a comparison of sub-lethal effects obse rved in acute studies.

2.5.2 Human Health Hazard

Bioavailability and Metabolism

Animal studies show that TDCPP, TCEP and TCPP are r apidly 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 al so found extensive absorption (Yoshida et al., 1997), suggestive of the potential for absorption v ia inhalation although no toxicokinetic data are available for quantifying inhalation absorption. Ab sorbed TDCPP, TCEP and TCPP distribute throughout the body without preferential accumulation in speci fic tissues or organs. Transfer to human breast mil k is indicated by biomonitoring studies that have fou nd TCEP, TCPP and TDCPP in human breast milk. TDCPP, TCEP and TCPP are rapidly metabolized by ext ensive Phase I and Phase II metabolism. TDCPP is likely metabolized by a combination of MFO, hydrola se 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 glucur onic acid. Some of the metabolism of TCEP may occur extrahepatically, possibly via B-esterases. T he metabolic products of TDCP, TCEP and TCPP are rapidly excreted, primarily in the urine. The bilia ry/fecal excretion ratios for TCEP and TCPP indicat ePage 26 of 72

enterohepatic re-circulation occurs. PBPK models ha ve 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 to xicological 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, c an also be found in Appendix F.

Animal studies show that TDCPP, TCEP and TCPP are r apidly 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 al so found extensive absorption (Yoshida et al., 1997), suggestive of the potential for absorption v ia inhalation although no toxicokinetic data are available for quantifying inhalation absorption. Ab sorbed TDCPP, TCEP and TCPP distribute throughout the body without preferential accumulation in speci fic tissues or organs. Transfer to human breast mil k is indicated by biomonitoring studies that have fou nd TCEP, TCPP and TDCPP in human breast milk. TDCPP, TCEP and TCPP are rapidly metabolized by ext ensive Phase I and Phase II metabolism. TDCPP is likely metabolized by a combination of MFO, hydrola se 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 glucur onic acid. Some of the metabolism of TCEP may occur extrahepatically, possibly via B-esterases. T he metabolic products of TDCP, TCEP and TCPP are rapidly excreted, primarily in the urine. The bilia ry/fecal excretion ratios for TCEP and TCPP indicat e enterohepatic re-circulation occurs. PBPK models ha ve not been developed for any of the phosphate
ester flame-retardants.

Repeat dose studies indicate that the kidney is a k ey target organ. In subchronic toxicity tests, kidn ey effects were noted with all three chemicals. In chr onic 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 a lso 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 carci nomas (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) a nd adrenocortical tumors (females) (Freudenthal and Henrich, 1999).

The chemicals in this cluster are considered weak i nhibitors of acetylcholinesterase. The toxicologica l impact of such inhibition continues to be debated. Blood and plasma cholinesterase studies are often conflicting. A number of studies testing TCEP ident ified 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 bra in lesions were also found in female rats in a 2-Page 27 of 72

year study (NTP, 1991). A similar 2-year study on T DCPP did not identify brain lesions or clinical sig ns (Freudenthal and Henrich, 1999).

Two studies are available that assess CPEs effect o n fertility; high doses of TCEP (≥350 mg/kg/day)
reduced the number of litters in a continuous breed ing study and sperm parameters were reduced. In contrast, there were no effects on reproductive tox icity caused by TDCPP in rabbits (Anonymous, 1977), although in a two-year study with rodents, t esticular lesions were noted (Freudenthal and Henrich, 1999).

Two studies are available to assess the development al toxicity of TCEP; high doses of TCEP (≥350 mg/kg/day) reduced the number of live pups per litt er 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 o f rats administered TCEP on GD 7-15 (Kawashima et al., 1983).

A study of rats administered TDCPP on GD 6-15 resul ted in increased resorptions, reduced fetal viability, decreased skeletal development and decre ased mean fetal weight at 400 mg/kg/day and a developmental NOAEL of 100 mg/kg was identified (St auffer Chemical Company, 1981). In this same study, maternal weight gain was also reduced.

EPA/OPPT considers the most significant hazards fro m 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 che mical manufacturing, polyurethane foam manufacture and textile processing, which could res ult in exposures to ecological receptors. Available toxicological data will support the evaluation of a cute and chronic exposures in fish, daphnids (invertebrates) and algae.

The following conceptual model (Figure 2-2) illustr ates the flow (arrows) of the CPE FRs from chemical manufacture and processing, releases to the environ ment and potential exposure pathways for ecological receptors. Down the drain releases to wa ter from consumer uses are plausible, as described in Schreder and La Guardia (2014), yet there are in sufficient data to quantify these inputs.Page 28 of 72

Figure 2-2: Conceptual Model for Ecological Recepto rs

The key assessment question for ecological receptor s is:

• Do levels of CPEs in the environment pose risk to a quatic organisms?

Based on the identified presence of the CPEs in mul tiple environmental media, many ecological receptors are potentially exposed. Fish and other w ildlife are exposed to these chemicals via ambient air, surface water, sediment, or soil. EPA/OPPTs ha s limited ability to quantify risks for sediment, s oil, sludge and ambient air because very little monitori ng data and no hazard endpoints exist for these
media. The focus of the environmental risk assessme nt 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 fi sh, invertebrates (daphnids) and algae (Table 2-7). Data for acute aquatic toxicity are available for f ish, daphnid and algae; there is only one chronic daphnid study, limiting EPA/OPPT’s ability to asses s chronic aquatic toxicity. It is possible that sub lethal 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 ratio s from similar halogenated phosphate esters with pesticide uses, and non-halogenated phosphate ester s.

Table 2-7: Assessment of Toxicity in Aquatic Organi sms

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 inhala tion 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 F Rs include a number of consumer products in the
home. The CPE FRs in this cluster are chemicals add ed to polyurethane foam and other matrices and are not chemically bonded to the polymers. Thus, CP E 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 polymer s, such as insulation and furniture, are in indoor environments, the potential for consumer exposure v ia inhalation of indoor air and dust, dermal contact with products and incidental ingestion of d ust is high. As described above, neither inhalation
nor dermal contact will be considered in this asses sment due to absence of route-relevant toxicologica l
data.

The following conceptual model (Figure 2-3) illustr ates the flow (arrows) of the CPE FRs from chemical manufacture and processing, releases to the environ ment 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 o r 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 throug h the incidental swallowing of inhaled particulates and hand-to-mouth contact, and is likely to be grea ter for small children due to their activity patter ns and increased proximity to areas where dust may gat her. Children may also be exposed via ingestion during direct mouthing of toys made with FR-impregn ated PU foam if the chemical migrates from the foam and is sufficiently soluble (Table 2-8). For c hildren and adults, exposures in the home and in ot her 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 text iles 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 t hat 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 drink ing water and fish ingestion based on releases
from industrial sources. These estimates can then b e compared to measures of CPE FRs in water and fish samples collected and analyzed in the US and a broad.

For those whose diet relies more heavily upon local ly sourced fish consumption, such as recreational and subsistence fishers and their children, exposur es from this pathway may be an important contribution to aggregate exposure. A recent Canadi an study evaluated the presence of organophosphate FRs, including several CPEs, in fis h 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 (Sundkvis t 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 WWT P.

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 flo w conditions (Sengupta et al., 2014). Although it i s unknown if concentrations in fish in Sweden would b e similar to the US, the samples taken from the Canadian side of the Great Lakes may be broadly rep resentative 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 Popula tion

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 f or consideration in the risk assessment, including cancer, target organ effects, reproductive and deve lopmental effects and neurotoxicity (Table 2-10). More detailed data summaries are available in Appen dix 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 ap proach and methods, based on available data as described above (see Data Needs description under s ection 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 T CPP and TDCPP from manufacturing and processing to water must be quantified. EPA/OPPT can consider env ironmental exposures in two ways. In the risk assessment, EPA/OPPT will assess releases of TCPP a nd 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 willPage 33 of 72

evaluate TCEP, TCPP and TDCPP exposures based on me asured concentrations in surface water (Table 2-6). Note that TCEP is no longer manufactured or i mported 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 an d, 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 inc lude effects from both acute and chronic exposures (Table 2-12).

Table 2-12: Analysis Plan for Assessing Risks to Aq uatic 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 a ny additional, relevant

ecotoxicity data for fish, daphnids and algae. Conc entrations of Concern (CoCs) will be derived based on results of acute to xicity data. A qualitative assessment will consider the potential effects of c hronic 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-specifi c production volumes. Releases due to cleaning of equipment in batch oper ation will be assessed in accordance with OPPT’s method for assessing rele ases of New Chemicals from equipment cleaning. The literature w ill be searched for data that is useful for estimating releases from th e washing and dehydration unit operations, including process wate r consumption rate or emission factor data for analogous processes and re leases 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 processe s will be assessed: blending with polyols (applicable to TCPP only), the slabstock an d molded foam processes for the manufacture of flexible PU foam ( processing in the molded foam process is applicable to TDCPP only), p rocessing for the manufacture of rigid PU foam and use in the manufac ture of upholstered
furniture. Releases will be estimated based on a nu mber of sources, including emission factors reported in (EU (2008a), (2008b)), generic scenarios or other New Chemicals Program methods (r efer 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 tex tile finishing will be assessed in accordance with the assessment approach describe d 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 a dditional 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 i n inhaled dust or via hand-to-mouth transfer of CPEs in settled dust released from consumer prod ucts.

• Potential risks from incidental ingestion of CPEs f rom mouthing of consumer products.

• Potential risks from consumption of CPEs in drinkin g water, or fish (recreational and subsistence fishers).

• Potential risks from aggregate oral exposure to CPE s.

During problem formulation, EPA/OPPT identified a s ubset of toxicological endpoints (Table 2-10) as relevant and sensitive, based on a review of existi ng hazard and risk assessments, as described in section 2.5.2. For the risk assessment, EPA/OPPT wi ll perform a literature search to determine if new
data exist and collect the studies identified durin g problem formulation, to refine the hazard identification and complete the dose-response analy sis. To select studies for inclusion, available dat a will be reviewed to determine test species, test co nditions, toxicity endpoints, statistical significa nce and strengths/limitations of the study, then summar ized and evaluated for data quality. Data quality criteria will include use of appropriate analytical and test controls, identification of test substanc e and test organism, stated exposure duration time and ad ministration route, a clear description of the effe ct endpoints and transparent reporting of effect conce ntrations. Guideline studies as well as studies usi ng other protocols will be included if they meet data quality criteria. Studies that meet the criteria fo r inclusion will then be evaluated in the dose respon se 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 investig ating general population and consumer risks. The evaluation of risks to the general population inclu des risks to adults and children from consumption o f CPEs in drinking water and risks to recreational an d subsistence fishers from high-end consumption of fish contaminated with CPEs. Consideration of inges tion by pregnant women will be included in this analysis.

Consumer exposures to CPE FRs will be evaluated bas ed on incidental ingestion of inhaled dust (as described above), and incidental ingestion of indoo r settled dust via hand-to-mouth behaviors. In addition, exposures to children from incidental ing estion 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 du st. Several recent studies of house dust are available which are expected to be representative o f US households. The EPA Exposure Factors Handbook can be utilized to determine typical quant ities of dust ingested and time-activity patterns.

The evaluation of risks to general population and c onsumers 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 thePage 35 of 72

existing assessments. If we identify the need to re view primary data that is not available in the US, EPA/OPPT will work to negotiate access to these stu dies. The analysis of primary data will be conducted in accordance with OPPT data adequacy gui delines. The evaluation of cancer and noncancer risks will be conducted in accordance with E PA guidelines (Table 2-13) (EPA, 2005a, 2005b, 2013).

Table 2-13: Analysis Plan for General Population an d 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 ident ify additional US data. Search for and review literature on high-end fish consumpt ion by recreational and subsistence fishers. Use EFAST modeling with compar ison to European fish data and US data. Age specific activity patterns an d 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 do se linear extrapolation (cancer). EPA/OPPT will systematically review the existing human health data and select the relevant benchmarks according to the rel evant route of exposure. The exposure estimates will be adjusted for expected du ration 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 searc h to identify additional US data. Use EFAST modeling with comparison to US wate r data. Age specific activity patterns and exposure factors will be cons idered. Risks will be assessed based on MOE (non-cancer), or by low dose linear ex trapolation (cancer). EPA/OPPT will systematically review the existing human health data and will sel ect the relevant benchmarks according to the relevant route of exposure. The exposure estimates will be adjusted for expected duration an d frequency in agreement with the
hazard assessment. Exposure of
adults and
children via
incidentalingestion 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 ident ify any US data. Select for inclusion dust monitoring data, based on a range of different indoor environments. Consider both hand-to-mouth and inges tion of inhaled dust particles. Exposure factors (e.g. time and activity patterns or ingestion values) will be based on US EPA Exposure Factors Handbook w here available. Risks will be assessed based on MOE (non-cancer), or by low do se linear extrapolation (cancer). EPA/OPPT will systematically review the e xisting human health data and will select the relevant benchmarks according t o 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 avai lable data, as well as

estimates used in other assessments. Consult with C PSC and conduct additional literature search to identify if extract ion data are available. Age specific activity patterns and exposure factors wil l be considered. Younger children are expected to have higher rates of dust ingestion and longer duration of mouthing activity when compared to olde r children and adults. Risks will be assessed based on MOE (non-cancer), o r by low dose linear extrapolation (cancer). EPA/OPPT will systematicall y 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 consideri ng hand-to-mouth dust ingestion, incidental ingestion of inhaled dust, water ingestion, mouthin g 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 t imes and sensitive life

stages for various endpoints. Age-specific activity patterns and exposure factors will be identified. Exposures over time wil l be aggregated for the pathways described and averaged over periods releva nt 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 Assessme nt

The following sources, uses or exposure pathways ar e excluded from further assessment:

• EPA/OPPT has determined that several uses are not e xpected to result in significant releases to
the environment:

o Releases from manufacturing and processing resultin g 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 pr oducts.

• EPA/OPPT has determined that a number of scenarios lack sufficient data to quantify risks:

o Exposures of birds, terrestrial wildlife, or sedime nt-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 derm al exposure (no route-specific toxicity data).

o Consumer exposures via inhalation and dermal exposu res (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 d ata gaps that must be considered when characterizing risks associated with CPE FRs. Uncer tainties 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 co untries. There is uncertainty regarding its relevance to US exposure scenarios. Some of the ava ilable 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 moni toring data may not be representative of
concentrations in the environment across all areas of the US. Uncertainties may exist in a quantitativ e evaluation. Mathematical modeling approaches can be used to yield exposure estimates. EPA/OPPT will consider the use of sensitivity analyses to de termine 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 b e similar to concentrations of fish in the US. Fish ingestion exposures will need to be modeled based o n releases to the environment from manufacturing/processing/use. Though exposure facto rs may exist for fish consumption, there would be uncertainty in determining the concentration of phosphate esters in edible fish. If specific receiv ing waters are not identified, there will be uncertaint y in the amount of dilution that may occur. EPA/OPP T will document the uncertainty and limitations assoc iated with the fish consumption analyses.

Exposure Route Extrapolation There is no PBPK model readily available for route- to-route extrapolation. EPA/OPPT has identified thi s as a critical data gap since the exclusion of derma l 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-e stimation of exposure from mouthing of toys and other consumer products. Oral exposure by direct mo uthing of foam-based toys may yield tentative values, as empirical values for migration of FRs ou t of foam into saliva are not available, nor is the re definitive data detailing concentrations of FRs in toys that children may mouth. Expert judgment and assumptions may need to be employed, which will inc rease the uncertainty of the assessment of this particular scenario. EPA/OPPT will specify all assu mptions 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 grea ter than in homes. There are uncertainties using existing methodologies to estimate exposure for the se 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 mos t 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 measure s of exposure from a number of sources.

Model Uncertainties
Modeled releases to water from industrial facilitie s 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, mod el assumptions will be clearly articulated. EPA/OPPT will consider the use of sensitivity analy ses 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 toward s birds. EPA/OPPT will acknowledge these limitations in the risk characterization.

Toxicity Associated With Inhalation and Dermal Expo sure There are no toxicity data via the inhalation expos ure 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 infor m 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 extrapolatio n, these calculations would be highly speculative and potentially misleading. EPA/OPPT has identified thi s as a critical data gap since the exclusion of derma l and inhalation exposure routes will result in the
underestimation of risks.

A chemical specific PBPK model would necessary to d evelop robust estimates of exposures via multiple routes. EPA/OPPT has identified this as a critical data gap since the exclusion of dermal and inhalati onPage 39 of 72

exposure routes will result in the underestimation of risks. EPA/OPPT will acknowledge this in the ris k
characterization.

Neurotoxicity and Developmental Neurotoxicity There is uncertainty regarding the neurotoxic poten cy of CPE FRs with regard to cholinesterase inhibition. The structural similarity of the chemic als in the CPE cluster make it possible to perform readacross; however, the uncertainty that comes with re ad-across also must be considered in characterizing the risks associated with the identi fied exposure scenarios. The majority of available toxicological data are for TCEP and TDCPP. The Nati onal 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 expect ed to publish the results of additional studies, as well. These data will help clarify biol ogical similarity and differences among the three structurally similar chemicals.

There are limited data on developmental neurotoxici ty. CPE FRs are considered to be weak inhibitors of cholinesterase; there is uncertainty regarding t he relationship between weak cholinesterase inhibition and brain development and if this can re sult in adverse impacts. EPA/OPPT will acknowledge
these limitations in the risk characterization.

Inter-individual Variability Co-morbidities, genetics, lifestyle and other chemi cal exposures that influence underlying toxic processes could also modulate risk (NRC, 2009). Cur rently 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 a nd dermal route-specific toxicity data as a critica l data need because EPA/OPPT expects that these may b e 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 ro ute-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 th e underestimation of aggregate risks associated wit h exposure to the CPE FR cluster chemicals.

The physical form of the chemical during its use is likely to influence the exposure pathway of intere st. Similar to many other semi-volatile organic chemica ls, CPE FR cluster chemicals are likely to be prese nt 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 to xicity rather than acute toxicity may be of interes t for multiple exposure routes. Air concentrations, d ust 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 ad equate 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 che micals;

• Consumers and non-industrial workers in indoor envi ronments 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 exercis ing 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 acr oss the population.

The development of a PBPK model for oral, inhalatio n (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, adequat e toxicokinetic data would be needed for each route of exposure and these data are lacking for in halation and dermal exposures.Page 41 of 72 

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Wang, Q., K. Liang, J. Liu, L. Yang, Y. Guo, C. Liu , and B. Zhou. 2013. **Exposure of Zebrafish Embryos/Larvae to TDCPP Alters Concentrations of Th**  **yroid Hormones and Transcriptions of Genes Involved in the Hypothalamic–Pituitary–Thyroi**  **d 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. L iang. 2015. **Organophosphorus Flame Retardants and Plasticizers: Sources, Occurrence, Toxicity and Human**  **Exposure** . Environmental Pollution, 196(0), 29-46.Page 53 of 72

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## APPENDICESPage 55 of 72 

## Appendix A Data Availability Tables

The following data availability tables provide a hi gh-level overview of available data through Decembe r 2014. They do not reflect study or data quality; no r do they represent suitability for use in risk assessment, which will be determined during the ass essment 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 internationalPage 56 of 72

Table_Apx A-2: Available General Population and Env ironmental 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 internationalPage 58 of 72

Table_Apx A-3: Available Mammalian and Aquatic Toxi city 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 quantit ative analysis
--- = no data available

○ = data available, but may not be useful for quantit ative analysisPage 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 grandfa thered 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 Occupati onal Safety and Health, or the American Conference of Government Industrial Hygienists. The EPA IRIS p rogram 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 o f states, summarized in Table_Apx B-1. Other states that have proposed legislation that could af fect 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 C onsumer

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 Safe r 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-R000 040- 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.as px?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/top ics/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 resident ial

upholstered furniture ( http://www.atg.state.vt.us/issues/consumerprotection/product-saftey/flame-retardants.php ) CancerPage 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 manufactu rers to report on chemicals of high concern in children’s p roducts ( http://www.ecy.wa.gov/programs/swfa/cspa/ ) Cancer, reproductive toxicity

There are several domestic assessments for chlorina ted phosphate ester flame retardants:

• The ATSDR Toxicological Profile for Phosphate Ester Flame Retardants (2012) included TCEP, TDCPP and TCPP and provided detailed analyses of av ailable hazard data.

• EPA derived Provisional Peer-Reviewed Toxicity Valu es (PPRTVs) for TCEP: an oral subchronic RfD of 0.02 mg/kg-day (kidney effects); an oral chr onic 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 de rive PPRTVs for two TCPP isomers.

• The US Consumer Product Safety Commission (2006) as sessed the cancer risks associated with inhalation of TDCPP vapor released from furniture f oam and cover fabrics. Estimated cancer risks from lifetime exposure in the home was 300 pe r million for adults and estimated cancer risk for children from inhalation exposure during t he first two years of life was 20 per million. The Hazard Index (Average Daily Dose÷ Acceptable Da ily Intake) was 2 for adults and 5 for children. CPSC estimated that 98-99% of exposure wa s via the inhalation route.

• The California Environmental Protection Agency, Dep artment of Toxic Substances Control (2014) released a draft document supporting the sel ection 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 Pro ducts Regulations ( https://dtsc.ca.gov/LawsRegsPolicies/Regs/SCPA.cfm ).

• The National Toxicology Program is in the process o f evaluating TCPP in a 90 day toxicity study, a 2-year cancer bioassay and a developmental toxici ty study ( http://ntp.niehs.nih.gov/testing/status/agents/ts-m 20263.html ). At the time of writing, the results these studies have not yet been made availa ble.



### B-2 International

There are numerous international activities relevan t to the chemicals in this cluster. In 2009, Canada conducted a screening assessment of TCEP and conclu ded that TCEP is harmful to human health. In addition, Canada proposed a risk management approac h for TCEP and recommended a prohibition relating to the presence of TCEP in products and ma terials. To that end, a Significant New Activity provision was concluded in January 2013. In April 2 014, products made, in whole or in part, of polyurethane foam that contains TCEP and intended f or 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 li sted 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 h as not released the document to the public.

The EU conducted a Risk Assessment of TCEP, TCPP an d 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 f rom inhalation and dermal exposure
associated with all scenarios were identified. Risk s 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 usi ng probabilistic models. For children’s risk, the assessment assumed very high migration rates vi a 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 id entified for ecological receptors.

• TCPP: The risk assessment identified concerns for w orkers in chemical manufacturing due to potential effects on fertility and developmental to xicity from dermal exposure. The EU noted that there is need for further information and/or t esting for female reproductive effects, but that the LOAEL of 5 mg/kg from the chronic study wi ll likely be protective for female reproductive effects. There were no risk concerns i dentified for consumer exposure based on the evaluation of exposure to TCPP in three kinds o f foam products. The European Commission
Scientific Committee on Health and Environmental Ri sks (SCHER) noted in review of the TCPP
RAR that at least 40% of the CPE could volatilize f rom the PUF product.

• TDCPP: The EU concluded that there is a need for fu rther information and/or testing regarding the effects on female fertility for all worker expo sure scenarios, all consumer exposures and both regional and local exposures. Occupational exp osure scenarios were considered and dermal and inhalation exposures were modeled using limited available input data. Consumer exposure data considered releases from flexible pol yurethane foam. The EU concluded cancer risks were of low concern, but cancer risks were ev aluated 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 fe male reproductive effects.

• Based on a screening assessment of TCEP, Canada pas sed a Significant New Activity provision in January 2013. As of April 2014, products made, in w hole 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 prohibite d 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, fo od, beverages and dust (general population) and from dermal and oral exposure to co nsumer products (consumer) for review
and comment.

• Australia conducted a preliminary assessment of TCE P, 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 identif ied. 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 rep orted 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 b een 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 load ing levels ranging from 1.08-5.95 mg/g (Stapleton e t 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 da tabase 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, sleepwe ar and bedding (Washington State 2014). TCEP is includ ed 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 i n upholstered items for consumer use.

Additional flame retardant uses which have been ide ntified for TCEP that do not overlap with the CDR reported use include: cast acrylic sheets, carpet b acking, building insulation, electronics, rubber an d plastics, furniture, adhesives and wood-resin compo sites (e.g. particle board) (ECHA, 2010; Health Canada, 2012; Joseph and Ebdon, 2010). Additionall y, TCEP reportedly can be applied to polyester resins in thermosets, bathtubs and shower stalls (W eil and Levchik, 2009).

TCPP In addition to the industrial, commercial and use c ategories reported in 2012 CDR (see Table 2-5), secondary sources identified specific products in w hich TCPP may be used. With respect to the “building and construction not covered elsewhere” c ategory, 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-bl own foam (15 parts by weight), which is used in applications such as roofing laminate (Weil and Le vchik, 2009). ICL-IP’s website confirms that Fyrol TM PFC, their commercial TCPP product, is widely used for laminate roofing (ICL Industrial Products, No Date-a).

Further, regarding the foam seating and bedding pro ducts category, TCPP has been used in polyurethane elastomers and in flexible polyurethan e foams when combined with melamine (KirkOthmer, 1993; Weil and Levchik, 2009). TCPP has be en detected in household furniture including footstools, ottomans and chairs at loading levels r anging from 0.5 percent to 1.5 percent by foam weight. TCPP has also been detected in the polyuret hane 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 Re port Update (see http://www.epa.gov/dfe/pubs/projects/flameret/about .htm for more information) which evaluates
the hazards associated with flame retardants used i n upholstered items for consumer use.Page 64 of 72

As for the uses in the electrical and electronic pr oducts category reported in the 2012 CDR, the only company who reported this use for TCPP is ICL-IP. T heir commercial product of TCPP is Fyrol TM PCF,
which is advertised on their website as used in the automotive, bedding and seating and construction industries. Given that, electrical and electronic p roducts would only fall under the automotive catego ry it is reasonable to assume that this is the categor y of use that TCPP is used in electronics. Further, Fyrol TM PCF is advertised on ICL-IP’s website as a flame re tardant in phenolics in printed circuit boards (ICL Industrial Products, No Date-a). Based on thes e two data sources EPA concluded that TCPP is likel y used in the circuit boards of automobiles.

Lastly, use of TCPP in the adhesives and sealants c ategory was reported by Hilti, Inc., a construction service company which provides both firestop sealan ts and other construction chemicals where TCPP may be used (Hilti, 2013).

TDCPP The industrial, commercial and consumer uses of TCD PP reported in 2012 CDR are summarized in Table 2-5. Since reporting use of TDCPP in the building/c onstruction 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. A dditional searches on company websites, government sources and academic publications on fla me 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, the ir commercial TDCPP product, can be used phenolics and unsaturated polyester resins (ICL Industrial Products, No Date-b) which can be used in the const ruction 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 Fyr olTM FR-2, which can be used in flexible polyurethane foam, as a chemical to assist in meeti ng 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 ch airs, baby strollers, car seats, changing pads, sle ep positioners, portable mattresses, nursing pillows a nd 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 al so 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 chi ldren. 10 Additionally, TDCPP is included in the EPA’s

10 The product categories used by Washington State ar e defined by GS1 Global Product Classification Stan dards. They define “Arts/Crafts Variety Pack” as “Includes any products that may be described/observed as two or more dist inct Arts and Crafts products sold together, which exist within t he 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 produc ts such as Needlework Supplies sold with Beads. **Excludes products such as Printmaking equipment sol d with Airbrushing Supplies and**  **Artists Supplies sold with Stationery.”(GS1, 2014)**Page 65 of 72

Design for the Environment Program’s Furniture Flam e 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 i n upholstered items for consumer use.Page 66 of 72 

## Appendix D Exposure Data Summaries

The following summaries reflect information identif ied through December 2014.

Products – Numerous studies have shown measured concentratio ns of these FRs in infant products such as high chairs, bath mats, car seats, nursing pillows, carriers (Stapleton et al., 2011; Stapleto n et al., 2012), sofas (Stapleton et al., 2009; Stapleto n et al., 2012) and camping tents (Keller et al., 2 014). Because many of these products are used in indoor e nvironments, 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 exposu res through contact with baby products containing CPEs and via mouthing behaviors.

Dust – TDCPP has been detected in household, office, au tomobile and commercial airplane dust in the US and abroad (Ali, Dirtu, et al., 2012; Ali, Van d en 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; Takig ami et al., 2009). All three CPE FRs were identifie d in particulates in indoor air and settled dust collect ed 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 (Do dson et al., 2012; Keller et al., 2014; Stapleton e t al., 2009; Stapleton et al., 2012), with a most rec ent study finding CPEs in 100% of house dust sampl es and 47-96% of handwipe samples (Stapleton et al., 2 014).

Indoor Air

– – Monitoring of indoor air concentrations is lim ited 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; Mark lund et al., 2005c; Sanchez et al., 2003; Staaf and Ostman, 2005a, 2005b; Tollback et al., 2006) and Ja pan (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 ai r sampling in vehicles with many NDs (Hartmann et al. , 2004; Sanchez et al., 2003; Staaf and Ostman, 2005a, 2005b), homes, commercial spaces, daycare/sc hool (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 conti nuous (OECD, 2000). The TCPP and TDCPP manufacturing processes involve washing and then dehydration and result in releases of these chemicals to water (EU, 2008a, 20 08b). 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 polyureth ane foam: the slabstock and the molded foam processes (EPA, 2004a, 2004b); TCPP or TDCPP are pr ocessed 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 aforeme ntioned processing steps and, additionally, the use of TCPP and TDCPP in upholstered furniture, are report ed 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 ar e several orders of magnitude higher indoors than outdoors, indicating that the major so urces of these indoor air pollutants are located in the indoor environment (Bergh et al., 2011). One st udy of ambient air in the Great Lakes region has shown concentrations in <<1 ng/m 3 range (Shoeib et al., 2014). Other studies from th e EU, Asia and
Scandinavia have shown ambient air concentrations i n the range of pg/m 3 to ng/m 3 range with the highest level of 58 ng/m 3 reported for a location outside a residence in Japa n (Ohura et al., 2006). One study has identified TCEP, TCPP and TDCPP in the am bient air of the Antarctic Peninsula (Cheng et al., 2013), but the authors attribute these concentratio ns 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 concentr ations are the result of long-range global transpor t (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 a broad have reported levels of the CPEs in the effluent and influent of wastewater: the highest re ported 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 di scharge 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; Olof sson et al., 2013), however there are no data for t he

US.

Soil – Studies of soil with measured US values are not r eadily available. The only measured concentrations of CPE in soil are from Germany at t he ng/g level (Mihajlović and Fries, 2012; Mihajlovic et al., 2011).

Sediment – CPEs have been detected in sediment in China, Ta iwan and Norway (Cao et al., 2012; Green et al., 2008; Leonards, 2011), however no US studie s in the open literature were found. There may be some measurements performed by the USGS through the ir 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; Bend z et al., 2005; Bollmann et al., 2012; Clara et al., 2010; Cristale et al., 2013a; Cristale et al., 2013 b; 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 an d Heim, 2005; Stepien et al., 2013; Weigel et al., 2005; Yoon et al., 2010) have reported levels of th e CPEs in surface water: the highest reported water concentration was 8.9 μg/L TCPP (Alvarez et al., 20 13). 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 examinin gPage 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 t he samples.

Edible Fish – See description of biota, below.

Biota – Fish and other wildlife may be exposed to the cl uster via surface water, sediment or soil.
Measurable levels of the CPEs in fish and other mar ine species from Canada, Spain, Sweden, Norway have been detected (Evenset, 2009; Green et al., 20 08; Jakimska et al., 2013; Leonards, 2011; McGoldrick et al., 2014; Sundkvist et al., 2010). I n a study from Sweden (Sundkvist et al., 2010), the re were marked differences in CPE concentrations and p rofiles 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 s ewage 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, TC PP 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 Nationa l Food Administration. The milk was pooled with samples from up to 90 women. TCEP, TDCPP and T CPP were detected with TCPP having the highest reported concentration (median 45 ng/g lipi d wt) and TCEP (4.9 ng/g lipid wt) and TDCPP (4.3 ng/g lipid wt) detected at lower levels. TCPP was o ne of the most frequently occurring FRs in this stu dy.

A study of organophosphorus flame-retardants in hum an breast milk from Japan, Philippines and Vietnam found that TCEP was one of the most predomi nant compounds, detected in more than 60% of samples from all three countries. Samples were coll ected from women living in urban settings including near a municipal waste dumping site in the Philippi nes and near an e-recycling site in Vietnam. The highest concentration of TCEP from these samples wa s found in breast milk from the Philippines (median 42 ng/g lipid wt). TDCPP was not detected i n the samples from Vietnam and the Philippines and was detected in only 2% of the samples from Jap an with the highest value 162 ng/g lipid wt (median ND).

Metabolites of this cluster have been detected in h uman 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; Staplet on et al., 2014; Van den Eede et al., 2013); and Germa ny (Schindler et al., 2009).Page 69 of 72 

## Appendix E Ecological Hazard Studies

The following summaries reflect information identif ied through December 2014.

Aquatic Toxicity – Experimental acute aquatic toxicity data are avai lable to characterize fish and aquatic invertebrates for all the CPE members; thes e data were largely obtained from secondary sources and study reports will need to be located f or further evaluation of acceptability. The acute 9 6-
hour LC 50 values ranges from 1.1 mg/L to 249 mg/L for fish an d the acute 48-hour EC 50 values ranges from 4.2 mg/L to 170 mg/L for aquatic invertebrates . Available algae toxicity data suggest 72-hour EC 50 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 studi es are available to characterize aquatic invertebra te population level effects.

Sediment Toxicity

– No data were available to characterize the toxic ity of sediment dwelling organisms.

Terrestrial Toxicity – Limited data were available to characterize the t oxicity of terrestrial organisms. A single in ovo study suggests potential for sub-leth al 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 EC 50 (mg/L)

Growth rate
biomass 278 (m) 73 (m) 47 (m) 2.3 (m)

Aquatic Invertebrates

Acute
48-h EC 50 (mg/L) 170 (m) 97 (m) 4.2 (m)

Fish Acute
96-h LC 50 (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 dataChlorinated 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 evaluat ion 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, inclu ding renal tubular hyperplasia and altered liver weights (Freudenthal and Henrich, 1999, 2000; Matt hews et al., 1993). Thyroid follicular cell hyperplasia was associated with TCPP (OECD SIDS) an d TCEP (Matthews et al., 1993). In addition an epidemiological study identified a correlation betw een 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 repro ductive organs. Freudenthal and Henrich (2000) observed a higher in cidence of atrophy in seminal vesicles, decreased secretory product and testicular enlargement in a t wo-year bioassay. Two studies in rabbits yielded no adverse effects, however the duration of these stud ies 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 m ale reproductive toxicity, it is not possible to quantify risks at this time.

Developmental Toxicity

- Two studies are available to assess the developm ental toxicity of TCEP; high doses of TCEP (≥350 mg/kg/day) reduced the number o f live pups per litter in a continuous breeding study and the number of male pups born to the treat ed F1 generation were reduced at concentrations ≥ 175 mg/kg (Chapin et al., 1997). No fetal or deve lopmental effects were observed in a study of rats administered TCEP on GD 7-15 (Kawashima et al., 198 3).

A study of rats administered TDCPP on GD 6-15 resul ted in increased resorptions, reduced fetal viability, decreased skeletal development and decre ased mean fetal weight at 400 mg/kg/day and a developmental NOAEL of 100 mg/kg was identified (St auffer Chemical Company, 1981). In this same study, maternal weight gain was also reduced.

Endocrine Activity

- There is some evidence for modulation of endocri ne 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 ze brafish model (Wang et al., 2013). Decreased plasma T4 was observed in chick embryos treated wit h TDCPP (Farhat et al., 2013). In a human exposure study there was an association between TDC PP in house dust and decreased T4 levels in men (Meeker and Stapleton, 2010). But in a recent stud y 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

Page 71 of 72 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 y ield mixed results. In general, Ames assays were negative, while severa l chromosomal aberration assays were positive (ATSDR, 2012). Therefore, the putative mechanism of carcinogenicity is not clear.

Carcinogenicity

- Animal studies have demonstrated that TCEP and T DCPP are carcinogenic in rodents. Takada et al. (1989) showed that ddY mice given TCE P 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 papill omas/squamous cell carcinomas and leukemia in females. NTP cancer bioassays (gavage studies) i ndicated that TCEP treatment was associated with increased kidney and thyroid tumors in rats and har derian gland tumors in mice (NTP, 1991). In a 2- year oral study involving TDCPP exposure, rats of b oth sexes developed kidney and liver tumors and males also had higher incidences of testicular tumo rs (Freudenthal and Henrich, 1999). NTP is currently in the process of evaluating data from a cancer study on TCPP; we will track progress in thi s study and incorporate data as soon as it is availab le ( http://ntp.niehs.nih.gov//?objectid=BD724190-

123F-7908-7BA185DA18C1EBB8 ). Based on a comparison of the calculated doses ca using 50% incidence of tumor (TD 50 ), TDCPP (TD 50 = 46.4 mg/kg/day) appears to have a higher carcinog enic potency than that of TCEP (TD 50 = 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 moderat e to high exposure to TCEP can decrease plasma cholinesterase activity in rodents and birds. In rats, brain lesions were noted follow ing short term high-dose exposure (Matthews et al., 199 0). 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 i n female rats is considered representative of modulation of cholines terase levels in the fetus of pregnant rats. Decreased fetal cholinesterase levels pose a risk t o fetal neurological development, in particular, altering critical proliferation and differentiation events (e.g., see Rice and Barone 2000). Additiona l evidence lending weight to this hypothesis comes fr om in vitro studies using PC12 cells as a model for neurological development (Dishaw et al., 2011). Whe n treated with TDCPP, TCEP, TCPP and chlorpyrifos (as a model OP), the cells exhibited d ecreased DNA content – a marker of developmentinduced cell proliferation, oxidative stress and al tered neurodifferentiation. The concern for modulation of neurological development based on mec hanistic data does not seem to manifest inChlorinated Alkyl Phosphate Flame Retardants

Page 72 of 72 available animal studies. As described by ATSDR (20 12) 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 alternati ons in behavioral effects, based on an examination of righting reflex and locomotor activities. Additiona l studies are underway and should be reported this

year.