EPA Document# EPA-740-R-20-010

August 2020

United States Office of Chemical Safety and

Environmental Protection Agency Pollution Prevention

Final Scope of the Risk Evaluation for

Triphenyl Phosphate

(TPP)

TABLE OF CONTENTS

ACKNOWLEDGEMENTS ......................................................................................................................6

ABBREVIATIONS AND ACRONYMS ..................................................................................................7

EXECUTIVE SUMMARY .......................................................................................................................9

1 INTRODUCTION ............................................................................................................................12

2 SCOPE OF THE EVALUATION ...................................................................................................12

Activities Excluded from the Scope of the Risk Evaluation ................................................. 27

Production Volume ................................................................................................................ 28

Overview of Conditions of Use and Lifecycle Diagram ....................................................... 28

Physical and Chemical Properties ......................................................................................... 30

Environmental Fate and Transport ........................................................................................ 32

Releases to the Environment ................................................................................................. 32

Environmental Exposures ...................................................................................................... 32

Occupational Exposures ........................................................................................................ 33

Consumer Exposures ............................................................................................................. 34

Conceptual Model for Industrial and Commercial Activities and Uses ................................ 36

Conceptual Model for Consumer Activities and Uses .......................................................... 38

Conceptual Model for Environmental Releases and Wastes: Potential Exposures and

Hazards .................................................................................................................................. 40

Physical and Chemical Properties and Environmental Fate .................................................. 42

Exposure ................................................................................................................................ 43

2.7.2.1 Environmental Releases ................................................................................................. 43

2.7.2.2 Environmental Exposures ............................................................................................... 45

2.7.2.3 Occupational Exposures ................................................................................................. 46

Summary of Risk Approaches for Characterization .............................................................. 55

REFERENCES .........................................................................................................................................57

APPENDICES ..........................................................................................................................................62

ABBREVIATED METHODS FOR SEARCHING AND SCREENING ................... 62

A.1.1 Search Term Genesis and Chemical Verification ...................................................................62

A.1.2 Publicly Available Database Searches ....................................................................................63

A.1.2.1 Query Strings for the Publicly Available Database Searches on TPP .............................63

A.1.2.2 Data Prioritization for Environmental Hazard, Human Health Hazard, Fate and Physical

Chemistry ................................................................................................................67

A.2.1.4 PESO for Fate and Transport ..........................................................................................74

A.2.1.5 Generation of Hazard Heat Maps ....................................................................................76

A.3.1 Screening of Gray Literature ..................................................................................................77

A.3.2 Initial Screening of Sources using Decision Logic Tree ........................................................78

A.3.3 TSCA Submission Searching and Title Screening .................................................................79

A.3.4 Gray Literature Search Results for TPP .................................................................................80

PHYSICAL AND CHEMICAL PROPERTIES .......................................................... 83

ENVIRONMENTAL FATE AND TRANSPORT PROPERTIES ............................ 84

REGULATORY HISTORY .......................................................................................... 86

PROCESS, RELEASE AND OCCUPATIONAL EXPOSURE INFORMATION .. 91

E.1.2.3 Recycling .........................................................................................................................91

E.1.3 Uses .........................................................................................................................................92

E.1.3.1 Paints and Coatings .........................................................................................................92

E.1.3.2 Plastic and Rubber Products ............................................................................................92

E.1.3.3 Laboratory Chemicals .....................................................................................................92

E.1.3.4 Operational Fluids, Maintenance Fluids and Semisolids, Reactive Fluids, and Solids

Used in Aerospace Industry ....................................................................................92

E.1.3.5 Turbine Engine Oils Used in Aviation ............................................................................93

E.1.3.6 Turbine Engine Oils Used in Non-Aviation Industries ...................................................93

E.1.3.7 Foam Seating and Bedding Products ...............................................................................93

E.1.3.8 Furniture and Furnishings ................................................................................................93

ACTIVITIES AND USES ............................................................................................ 108

SUPPORTING INFORMATION – CONCEPTUAL MODEL FOR

ENVIRONMENTAL RELEASES AND WASTES ................................................... 112

LIST OF TABLES

Table 2-1. Results of Title Screening of Submissions to EPA under Various Sections of TSCA ........... 24

Table 2-2. Categories and Subcategories of Conditions of Use Included in the Scope of the Risk

Evaluation ......................................................................................................................... 25

Table 2-3. Physical and Chemical Properties of TPP ............................................................................... 30

Table 2-4. Categories and Sources of Environmental Release Data ........................................................ 43

Figure 2-4. Peer-reviewed Literature Inventory Heat Map - Fate and Transport Search Results for TPP17

Figure 2-5. Peer-reviewed Literature Inventory Tree - Engineering Search Results for TPP .................. 18

Figure 2-6. Peer-reviewed Literature Inventory Heat Map - Engineering Search Results for TPP ......... 19

Figure 2-7. Peer-reviewed and Gray Literature Inventory Tree - Exposure Search Results for TPP ....... 20

Figure 2-8. Peer-reviewed and Gray Literature Inventory Heat Map – Exposure Search Results for TPP

........................................................................................................................................... 21

Figure 2-9. Peer-reviewed Literature Inventory Tree - Human Health and Environmental Hazard Search

Results for TPP ................................................................................................................. 22

Figure 2-10. Peer-reviewed Literature Inventory Heat Map – Human Health and Environmental Hazards

Search Results for TPP ..................................................................................................... 23

Figure 2-14. TPP Conceptual Model for Consumer Activities and Uses: Consumer Exposures and

Hazards ............................................................................................................................. 39

Figure 2-15. TPP Conceptual Model for Environmental Releases and Wastes: Environmental and

General Population Exposure and Hazards ....................................................................... 41

ACKNOWLEDGEMENTS

ABBREVIATIONS AND ACRONYMS

PNOR Particulates Not Otherwise Regulated

POD Point Of Departure

PPE Personal Protective Equipment

RCRA Resource Conservation and Recovery Act

RESO Receptors, Exposure, Setting or Scenario, and Outcomes

SDWA Safe Drinking Water Act

SIDS Screening Information Data Sets

VP Vapor Pressure

WS Water solubility

EXECUTIVE SUMMARY

In December 2019, EPA designated Triphenyl Phosphate (TPP) (CASRN 115-86-6) as a high-priority

substance for risk evaluation following the prioritization process required by Section 6(b) of the Toxic

Substances Control Act (TSCA) and implementing regulations (40 CFR Part 702) (Docket ID: EPA-

HQ-OPPT-2019-0131). The first step of the risk evaluation process is the development of the draft scope

document. EPA published the Draft Scope of the Risk Evaluation for Triphenyl Phosphate (CASRN 115-

86-6) (EPA Document No. EPA-740-D-20-010) (U.S. EPA, 2020c) and provided a 45-day comment

period on the draft scope per 40 CFR 702.41(c)(7). EPA has considered comments received (Docket ID:

reasonably available information, conceptual model, analysis plan and science approaches, and plan for

peer review for this chemical substance.

General Information. TPP is a colorless solid that is primarily used as a flame retardant with a total

production volume in the United States between 1 million and 10 million pounds.

Reasonably Available Information. EPA leveraged the data and information sources already described

in the Proposed Designation of Triphenyl Phosphate (CASRN 115-86-6) as a High-Priority Substance

for Risk Evaluation (U.S. EPA, 2019d) to inform the development of this scope document. Furthermore,

EPA conducted a comprehensive search to identify and screen multiple evidence streams (i.e.,

chemistry, fate, release and engineering, exposure, hazard), and the search and screening results to date

are provided in Section 2.1. EPA used the systematic review process described in Appendix A to search

consider additional information identified following publication of this scope document, as appropriate,

in developing the risk evaluation, including the Chemical Data Reporting (CDR) information that the

Agency will receive by the end of November 2020.

Conditions of Use. EPA plans to evaluate manufacturing (including importing); processing; distribution

in commerce; industrial, commercial and consumer uses; and disposal of TPP in the risk evaluation. TPP

is manufactured (including imported) in the United States. The chemical is processed as a reactant;

incorporated into formulation, mixture, or reaction products; and incorporated into articles. Several

commercial uses were identified, such as paints and coatings and plastic and rubber products. Consumer

uses were reported in foam seating and bedding products. EPA identified these conditions of use from

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17

may be added to the interactive version as they become available.

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Figure 2-5. Peer-reviewed Literature Inventory Tree – Engineering Search Results for TPP

Click here to view the interactive literature inventory tree. Data in this figure represent references

obtained from the publicly available databases search (see Appendix A.1.2.) that were included during

full-text screening as of August 5, 2020. Additional data may be added to the interactive version as they

become available.

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references obtained from the publicly available databases search (see Appendix A.1.2) that were

included during full-text screening as of August 5, 2020. Additional data may be added to the interactive

version as they become available.

20

Figure 2-7. Peer-reviewed and Gray Literature Inventory Tree – Exposure Search Results for

TPP

Click here to view the interactive literature inventory tree. Data in this figure represent all references

21

Figure 2-8. Peer-reviewed and Gray Literature Inventory Heat Map – Exposure Search Results

for TPP

Click here to view the interactive version for additional study details. The column totals, row totals, and

grand totals indicate total numbers of unique references, as some references may be included in multiple

cells. The various shades of color visually represent the number of relevant references identified by

exposure media or data type. The darker the color, the more references are available for a given

exposure media or data type. Data in this figure represent all references obtained from the publicly

available databases search (see Appendix A.1.2), and gray literature references search (see Appendix

A.3) that were included during full-text screening as of July 31, 2020. Additional data may be added the

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Search Results for TPP

Click here to view the interactive literature inventory tree. Data in this figure represent references

obtained from the publicly available databases search (see Appendix A.1.2.) that were included during

full-text screening as of June 10, 2020. Additional data may be added to the interactive version as they

become available.

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Figure 2-10. Peer-reviewed Literature Inventory Heat Map – Human Health and Environmental

represented. If a study evaluated multiple health outcomes or included multiple populations or study

designs, it is shown here multiple times. Data in this figure represents references obtained from the

publicly available databases search (see Appendix A.1.2) that were included during full-text screening

as of June 10, 2020. Additional data may be added to the interactive version as they become available.

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Table 2-1 presents the results of screening the titles of data sources and reports submitted to EPA under

following:

• Summary of other reports

• Draft of a published report that would be identified via peer literature searches

• Submission on a different chemical

• Data not relevant to any discipline

• Letter with no attached report

• Status report

• Notification of study initiation

Table 2-1. Results of Title Screening of Submissions to EPA under Various Sections of TSCA

a

Individual submissions may be relevant to multiple disciplines.

b

Included submissions may contain supplemental data for other disciplines, which will be identified at full-text review.

2.2 Conditions of Use

As described in the Proposed Designation of Triphenyl Phosphate (CASRN 115-86-6) as a High-

publications. To identify formulated products containing TPP, EPA searched for safety data sheets

(SDS) using internet searches, EPA Chemical and Product Categories (CPCat) data, and other resources

in which SDSs could be found. SDSs were cross-checked with company websites to make sure that each

4

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product SDS was current. In addition, EPA incorporated communications with companies, industry

groups, environmental organizations, and public comments to supplement the use information.

EPA identified and described the categories and subcategories of conditions of use that EPA plans to

include in the scope of the risk evaluation (Section 2.2.1; Table 2-2). The conditions of use included in

the scope are those reflected in the life cycle diagrams and conceptual models.

Table 2-2 lists the conditions of use that are included in the scope of the risk evaluation.

Table 2-2. Categories and Subcategories of Conditions of Use Included in the Scope of the Risk

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Figure 2-12. Box and Whisker Plots of Reported Physical and Chemical Property Values

Releases to the environment from conditions of use are a component of potential exposure and may be

derived from reported data that are obtained through direct measurement, calculations based on

empirical data and/or assumptions and models.

TPP is not reported to the Toxics Release Inventory (TRI). There may be releases of TPP from industrial

sites to wastewater treatment plants (WWTP), surface water, air and landfill. Articles that contain TPP

may release TPP to the environment during use or through recycling and disposal. EPA plans to review

this data in conducting the exposure assessment component of the risk evaluation for TPP.

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are informed by releases into the environment, overall persistence, degradation, bioaccumulation and

partitioning across different media. Concentrations of chemical substances in biota provide evidence of

exposure. EPA plans to review available environmental exposure data in biota in the risk evaluation.

Monitoring data were identified in EPA’s search for reasonably available information on environmental

exposures in biota to inform development of the environmental exposure assessment for TPP.

EPA plans to review available environmental monitoring data for TPP. TPP was detected in wastewater

Section 2.2. In addition, EPA plans to evaluate exposure to occupational non-users (ONUs), i.e.,

workers who do not directly handle the chemical but perform work in an area where the chemical is

present. EPA also plans to consider the effect(s) that engineering controls (EC) and/or personal

EPA plans to evaluate potential exposures from the processing of TPP as it is incorporated into

formulations and products. TPP is used as an additive flame retardant. In general, EPA plans evaluate

Examples of worker activities associated with the conditions of use within the scope of the risk

evaluation for TPP that EPA may analyze include, but are not limited to:

• Unloading and transferring TPP to and from storage containers to process vessels during

manufacturing, processing and use;

• Handling and disposing of waste containing TPP;

• Cleaning and maintaining equipment;

• Sampling chemicals, formulations or products containing TPP for quality control;

• Repackaging chemicals, formulations or products containing TPP during manufacturing,

• Performing other work activities in or near areas where TPP is used.

EPA generally does not evaluate occupational exposures through the oral route. Workers and ONUs

may inadvertently ingest inhaled particles that deposit in the upper respiratory tract. In addition, workers

may transfer chemicals from their hands to their mouths. The frequency and significance of this

exposure route are dependent on several factors including the physical and chemical properties of the

substance during expected worker activities, workers’ awareness of the chemical hazards, the visibility

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of the chemicals on the hands while working, workplace training and practices, and personal hygiene

that is difficult to predict (Cherrie et al., 2006). EPA will consider the relevance of this exposure route

on a case-by-case basis, taking into consideration the aforementioned factors and any reasonably

available information, and may assess oral exposure for workers for certain COUs and worker activities

where warranted. For certain conditions of use of TPP, EPA plans to consider inhalation exposure to

dust/particulates for workers and ONUs. As inhalation exposure to dust/particulates may occur, EPA

plans to consider potential exposure for particulates that deposit in the upper respiratory tract from

(NIOSH, 2019) and an Immediately Dangerous to Life or Health (IDLH) value of 1,000 mg/m

(NIOSH, 2016).

According to CDR, TPP is used in consumer products used in indoor environments, including foam

seating and bedding products, plastic and rubber products, and (U.S. EPA, 2019a). The 2012 CDR also

reported the use of TPP in electrical and electronic products (U.S. EPA, 2019a). Several of these

products have the potential to be mouthed by children. In addition, consumer handling of the disposal on

TPP containing materials can lead to consumer and bystander exposures. The main exposure routes for

these uses where consumers interact with products and articles containing TPP are dermal, inhalation,

and dust ingestion, including children’s mouthing of articles (e.g., plastics, textiles, wood products)

containing TPP. Based on these potential sources and pathways of exposure, EPA plans to analyze oral,

dermal and inhalation routes of exposure to consumers, and the inhalation route for bystanders that may

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developmental, endocrine, gastrointestinal, hematological and immune, hepatic, mortality, musculo-

skeletal, neurological, nutritional and metabolic, ocular and sensory, reproductive, respiratory and skin

and connective tissue (Figure 2-10). A summary of references identified during the screening step of

systematic review is included in the interactive literature inventory trees (Figure 2-9). As EPA continues

EPA considered reasonably available information (e.g., federal and international government chemical

assessments) on TPP as well as public comments on the Proposed Designation of Triphenyl Phosphate

(CASRN 115-86-6) as a High-Priority Substance for Risk Evaluation (U.S. EPA, 2019d), and draft

scope for TPP (U.S. EPA, 2020c) to identify potential human health hazards. During prioritization, EPA

endocrine, gastrointestinal, hematological and immune, hepatic, mortality, musculoskeletal,

neurological, nutritional and metabolic, ocular and sensory, renal, reproductive and skin and connective

tissue (Figure 2-10). A summary of references identified during the screening step of systematic review

is included in the interactive literature inventory trees (Figure 2-9). As EPA continues to evaluate

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EPA identified the following PESS based on CDR information and studies reporting developmental and

reproductive effects: children, women of reproductive age (e.g., pregnant women), lactating females,

workers, including ONUs and users, and consumers, including users and bystanders (U.S. EPA, 2019b).

EPA plans to evaluate these PESS in the risk evaluation. Following further evaluation of the reasonably

available information, EPA may evaluate PESS in the general population as they relate to fence line

communities.

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human receptors from consumer activities and uses of TPP that EPA plans to include in the risk

40

from air emissions via inhalation as well as from water, liquid, and solid waste releases and orally via

48

production volume used, and exposure/release sources) corresponding to conditions of use as

additional information is reviewed during risk evaluation. EPA may perform supplemental

targeted searches of peer-reviewed or gray literature to better understand certain conditions of

use to further develop exposure scenarios.

7) Evaluate the weight of the scientific evidence of occupational exposure data, which may

include qualitative and quantitative sources of information.

1) Group each condition of use to consumer exposure assessment scenario(s).

Refine and finalize exposure scenarios for consumers by considering combinations of sources

(ongoing consumer uses), exposure pathways including routes, and exposed populations.

For TPP, the following are noteworthy considerations in constructing consumer exposure

scenarios:

- Conditions of use

- Duration, frequency and magnitude of exposure

- Weight fraction of chemical in products

EPA plans to review all reasonably available information in developing the consumer exposure

scenarios and evaluating the exposure pathways in indoor environments.

Exposure Model (CEM) and other similar models can be used to estimate indoor air exposures

from consumer products.

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Models that estimate emission and migration of semi-volatile organic compounds (SVOCs) into

the indoor environment models generally consider indoor fate and transport properties such as

mass transfer as informed by the gas-phase mass transfer coefficient, the solid-phase diffusion

coefficient and the material-air partition coefficient. These properties vary based on physical and

chemical properties and properties of the material. The OPPT’s Indoor Environmental

Concentrations in Buildings with Conditioned and Unconditioned Zones (IECCU) model and

other similar models can be used to estimate indoor air and dust exposures from indoor sources.

5) Review reasonably available consumer product-specific sources to determine how those

exposure estimates compare with each other and with indoor monitoring data reporting

TPP in specific media (e.g., indoor dust, indoor air).

The availability of TPP concentration for various conditions of use will be evaluated. This data

provides the source term for any subsequent indoor modeling. EPA plans to analyze source

attribution between overall indoor air and dust levels and various indoor sources.

6) Review reasonably available population- or subpopulation-specific exposure factors and

activity patterns to determine if potentially exposed or susceptible subpopulations need to

be further refined.

During risk evaluation, EPA plans to evaluate and integrate exposure evidence identified in the

literature inventory using the methods described in the Application of Systematic Review in

quantitative sources of information. EPA plans to integrate the data using systematic review

methods to assemble the relevant data, evaluate the data for quality and relevance, including

strengths and limitations, followed by synthesis and integration of the evidence.

2.7.2.5 General Population

EPA plans to analyze general population exposures as follows:

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edible aquatic and terrestrial organisms.

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4) Review reasonably available exposure modeled estimates. For example, existing models

developed for a previous TPP chemical assessment may be applicable to EPA’s assessment.

are reasonably available.

To the extent other organizations have already modeled TPP general population exposure

scenario that is relevant to the OPPT’s assessment, EPA plans to evaluate those modeled

estimates. In addition, if modeled estimates for other chemicals with similar physical and

6) Review reasonably available information about population- or subpopulation-specific

exposure factors and activity patterns to determine if potentially exposed or susceptible

subpopulations need to be further defined (e.g., early life and/or puberty as a potential

critical window of exposure).

For TPP, exposure scenarios that involve PESS will consider age-specific behaviors, activity

patterns, and exposure factors unique to those subpopulations. For example, children will have

different intake rates for dust, soil, and diet than adults.

7) Evaluate the weight of the scientific evidence of general population exposure estimates

based on different approaches.

During risk evaluation, EPA plans to evaluate and integrate the exposure evidence identified in

the literature inventory using the methods described in the Application of Systematic Review in

TSCA Risk Evaluation (U.S. EPA, 2018a).

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EPA plans to evaluate environmental hazard data using the evaluation strategies laid out in the

Mechanistic data may include analyses of alternative test data such as novel in vitro test methods

and high throughput screening. The association between acute and chronic exposure scenarios to

the agent and each health outcome will also be integrated. Study results will be extracted and

presented in evidence tables or another appropriate format by organ/system.

by the application of hazard and exposure benchmarks to characterize environmental risk (U.S.

EPA, 1998) (U.S. EPA, 1998; Barnthouse et al., 1982). Analysis of risk for characterization

includes a confidence statement in risk estimation which qualitative judgment describing the

certainty of the risk estimate considering the strength the evidence scores for hazard and

exposure and the limitations, and relevance.

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2.7.3.2 Human Health Hazards

EPA plans to analyze human health hazards as follows:

1) Review reasonably available human health hazard data, including data from alternative

test methods (e.g., computational toxicology and bioinformatics; high-throughput screening

methods; data on categories and read-across; in vitro studies; systems biology).

Mechanistic data may include analyses of alternative test data such as novel in vitro test methods

and high throughput screening. The association between acute and chronic exposure scenarios to

the agent and each health outcome will also be integrated. Study results will be extracted and

presented in evidence tables or another appropriate format by organ/system.

2) In evaluating reasonably available data, determine whether particular human receptor

population.

Reasonably available human health hazard data will be evaluated to ascertain whether some

human receptor groups may have greater susceptibility than the general population to TPP

hazard(s). Susceptibility of particular human receptor groups to TPP will be determined by

and information.

3) Conduct hazard identification (the qualitative process of identifying non-cancer and cancer

endpoints) and dose-response assessment (the quantitative relationship between hazard

and exposure) for identified human health hazard endpoints.

Human health hazards from acute and chronic exposures will be identified by evaluating the

human and animal data that meet the systematic review data quality criteria described in the

Application of Systematic Review in TSCA Risk Evaluations (U.S. EPA, 2018a). Hazards

identified by studies meeting data quality criteria will be grouped by routes of exposure relevant

to humans (e.g., oral, dermal, inhalation) and by the cancer and noncancer endpoints identified in

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Dose-response assessment will be performed in accordance with EPA guidance (U.S. EPA,

2012a, 2011a, 1994) developing points of departure (POD) for either margins of exposure

(MOEs), cancer slope factors (CSFs), oral slope factors (OSFs), and/or inhalation unit risks

(IURs). Dose-response analyses may be used if the data meet data quality criteria and if

additional information on the identified hazard endpoints are not reasonably available or would

not alter the analysis

4) Derive points of departure (PODs) where appropriate; conduct benchmark dose modeling

depending on the reasonably available data. Adjust the PODs as appropriate to conform

(e.g., adjust for duration of exposure) to the specific exposure scenarios evaluated.

Hazard data will be evaluated to determine the type of dose-response modeling that is applicable.

Where modeling is feasible, a set of dose-response models that are consistent with a variety of

potentially underlying biological processes will be applied to empirically model the dose-

response relationships in the range of the observed data consistent with EPA’s Benchmark Dose

Technical Guidance Document (U.S. EPA, 2012a). Where dose-response modeling is not

feasible, NOAELs or LOAELs will be identified. Non-quantitative data will also be evaluated

for contribution to weight of the scientific evidence or for evaluation of qualitative endpoints that

are not appropriate for dose-response assessment.

5) Evaluate the weight of the scientific evidence of human health hazard data.

During risk evaluation, EPA plans to evaluate and integrate the human health hazard evidence

identified in the literature inventory under acute and chronic exposure conditions using the

methods described in the Application of Systematic Review in TSCA Risk Evaluations (U.S. EPA,

2018a).

6) Consider the route(s) of exposure (e.g., oral, inhalation, dermal), reasonably available

route-to-route extrapolation approaches; biomonitoring data; and approaches to correlate

internal and external exposures to integrate exposure and hazard assessment.

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At this stage of review, EPA believes there will be sufficient reasonably available data to

conduct a dose-response analysis and/or benchmark dose modeling for the oral route of

exposure. EPA plans to also evaluate any potential human health hazards following dermal and

inhalation exposure to TPP, which could be important for worker, consumer and general

population risk analysis. Reasonably available data will be assessed to determine whether or not

a point of departure can be identified for the dermal and inhalation routes.

If there are acceptable inhalation data after completion of systematic review, EPA may also

consider extrapolating from the inhalation to the dermal route if first-pass metabolism through

the liver via the oral route is expected because in that case, use of data from the oral route is not

recommended (U.S. EPA, 1994). EPA may also consider inhalation-to-dermal route

extrapolation if an inhalation toxicity study with a sensitive hazard endpoint is used to evaluate

risks. Based on these considerations, EPA extrapolated from the inhalation to the dermal route

for several of the first ten risk evaluations under amended TSCA, including methylene chloride

(U.S. EPA, 2020d) and carbon tetrachloride (U.S. EPA, 2020b).

7) Conduct a human health risk estimation and characterization of TPP.

Analysis of risk for characterization includes a confidence statement in risk estimation. This

confidence statement is based on qualitative judgment describing the certainty of the risk

risk characterization integrates information from the preceding components of the risk evaluation and

synthesizes an overall conclusion about risk that is complete, informative and useful for decision

to bring all important considerations about risk, not only the likelihood of the risk but also the strengths

and limitations of the assessment, and a description of how others have assessed the risk into an

integrated picture.

The level of information contained in each risk characterization varies according to the type of

assessment for which the characterization is written. Regardless of the level of complexity or

information, the risk characterization for TSCA risk evaluations will be prepared in a manner that is

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transparent, clear, consistent, and reasonable (U.S. EPA, 2000b), and consistent with the requirements of

the Procedures for Chemical Risk Evaluation Under the Amended Toxic Substances Control Act (82 FR

33726, July 20, 2017). As discussed in 40 CFR 702.43, risk characterization has a number of

considerations. This is the step where EPA integrates the hazard and exposure assessments into risk

estimates for the identified populations (including any PESS) and ecological characteristics and weighs

the scientific evidence for the identified hazards and exposures. The risk characterization does not

consider costs or other nonrisk factors, and takes into account, “where relevant, the likely duration,

lower bound estimate of risk; (4) each significant uncertainty identified in the process of the assessment

of risk effects and the studies that would assist in resolving the uncertainty; and (5) peer reviewed

studies known to the Agency that support, are directly relevant to, or fail to support any estimate of risk

effects and the methodology used to reconcile inconsistencies in the scientific information.

2.8 Peer Review

evaluations, including using EPA’s Peer Review Handbook (U.S. EPA, 2015a) and other methods

consistent with Section 26 of TSCA (see 40 CFR 702.45). As explained in the Risk Evaluation Rule, the

purpose of peer review is for the independent review of the science underlying the risk assessment. Peer

review will therefore address aspects of the underlying science as outlined in the charge to the peer

review panel such as hazard assessment, assessment of dose-response, exposure assessment, and risk

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REFERENCES

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Online (HERO) database for literature screening.

Table_Apx A-2. Summary of Data Sources, Search Dates and Number of Peer-Reviewed

Literature Search Results for TPP

necessary to construct searches as noted for each of the sources. The search terms are listed below in full

for each source and noted if the general search terms or other search terms were used.

"Antioxidant TTP" OR "BRN 1888236" OR "Celluflex TPP" OR "DHPF 005" OR "Disflamoll TP" OR

"NSC 57868" OR "O,O,O-Triphenyl phosphate" OR "Phenyl phosphate" OR "Phoscon FR 903N" OR

"Phosflex TPP" OR "Phosphoric acid, triphenyl ester" OR "Phosphoric acid, triphenyl ester radical

ion(1+)" OR "Reofos TPP" OR "Sumilizer TPP" OR "Triphenol phosphate" OR "Triphenoxyphosphine

oxide" OR "Triphenyl phosphate" OR "Triphenylphosphat" OR "Triphenylphosphate" OR "UN 3077"

OR "UNII-YZE19Z66EA" OR "Wako TPP" OR "WSFR-TPP"

General Search Terms applied to the search strategy for Current Contents.

Date Searched: 05.02.19

Date Range of Search: 1970 to Present

N = 497

65

General Search Terms applied to the search strategy for ProQuest Agricultural and Scientific Database.

Date Searched: 05.02.19

Date Range of Search: 1900 to Present

N = 1092

ALL("Antioxidant TTP" OR "BRN 1888236" OR "Celluflex TPP" OR "DHPF 005" OR "Disflamoll

PROQUEST Dissertations and Theses: (search.proquest.com)

General Search Terms applied to the search strategy for ProQuest Dissertations and Theses.

Date Searched: 05.03.19

Date Range of Search: 1900 to Present

N = 6

ALL("Antioxidant TTP" OR "BRN 1888236" OR "Celluflex TPP" OR "DHPF 005" OR "Disflamoll

TP" OR "NSC 57868" OR "O,O,O-Triphenyl phosphate" OR "Phenyl phosphate" OR "Phoscon FR

903N" OR "Phosflex TPP" OR "Phosphoric acid, triphenyl ester" OR "Phosphoric acid, triphenyl ester

radical ion(1+)" OR "Reofos TPP" OR "Sumilizer TPP" OR "Triphenol phosphate" OR

"Triphenoxyphosphine oxide" OR "Triphenyl phosphate" OR "Triphenylphosphat" OR

"Triphenylphosphate" OR "UN 3077" OR "UNII-YZE19Z66EA" OR "Wako TPP" OR "WSFR-TPP")

Date Searched: 05.02.19

Date Range of Search: 1823 to Present

N = 258

Science Direct 01:

"Antioxidant TTP" OR "BRN 1888236" OR "Celluflex TPP" OR "DHPF 005" OR "Disflamoll TP" OR

"NSC 57868" OR "O,O,O-Triphenyl phosphate" OR "Phenyl phosphate" OR "Phoscon FR 903N"

N = 209

66

Science Direct 02:

"Phosflex TPP" OR "Phosphoric acid, triphenyl ester" OR "Phosphoric acid, triphenyl ester radical

ion(1+)" OR "Reofos TPP" OR "Sumilizer TPP" OR "Triphenol phosphate" OR "Triphenoxyphosphine

oxide" OR "Triphenyl phosphate" OR "Triphenylphosphat"

N = 0

Date Searched: 05.02.19

Date Range of Search: 15

N = 270

Agricola 01:

Antioxidant TTP

BRN 1888236

Celluflex TPP

DHPF 005

Disflamoll TP

NSC 57868

O,O,O-Triphenyl phosphate

Agricola 02:

Phosphoric acid, triphenyl ester

Phosphoric acid, triphenyl ester radical ion(1+)

Reofos TPP

Sumilizer TPP

Triphenol phosphate

Triphenoxyphosphine oxide

Triphenyl phosphate

Triphenylphosphat

Triphenylphosphate

67

N = 234

Agricola 03:

UNII-YZE19Z66EA

Wako TPP

WSFR-TPP

TOXNET 01:

115-86-6 OR 106971-30-6 OR 402955-02-6

68

(MeSH) fields content. The applied SWIFT Review filters focused on lines of evidence: human, animal

models for human health, ecological taxa (which includes ecotoxicological animal models, plants, and

other taxa), and in vitro studies. The details of the search strategies that underlie the filters are available

online. Studies not retrieved using these filters were not considered further. Studies that included one or

more of the search terms in the title, abstract, keyword, or MeSH fields were exported as a RIS file for

screening in Swift-ActiveScreener or DistillerSR

.

were assumed to be conference reports, editorials, or letters). During title/abstract or full-text level

screening in DistillerSR, studies that did not meet the PECO criteria, but which could provide

supporting information were categorized (or “tagged”) as supplemental information.

It is important to emphasize that being tagged as supplemental material does not mean the study would

necessarily be excluded from consideration in an assessment. The initial screening level distinctions

between a study meeting the PECO criteria and a supplemental study are often made for practical

reasons and the tagging structures (as seen in the literature inventory trees and heat maps in Section 2.1

of this document) are designed to ensure the supplemental studies are categorized for easy retrieval if

needed while conducting the assessment. The impact on the assessment conclusions of individual studies

DistillerSR is a web-based systematic review software used to screen studies available at

https://www.evidencepartners.com/products/distillersr-systematic-review-software.

69

maybe be tagged as supplemental material during either title and abstract or full-text screening. When

tagged as supplemental material during title and abstract screening, it may not be completely clear

whether the chemical of interest is reported in the study (i.e., abstracts may not describe all chemicals

investigated). In these cases, studies are still tagged with the expectation that if full-text retrieval is

pursued, then additional screening would be needed to clarify if the study is pertinent.

A.2.1 Inclusion/Exclusion Criteria

A PECO statement is typically used to focus the research question(s), search terms, and

inclusion/exclusion criteria in a systematic review. PECO criteria were developed a priori to screening

and modified to fit the various discipline areas supporting the TSCA risk evaluations. Variations include

the RESO (receptor, exposure, scenario/setting, and outcome) used for the occupational exposure and

environmental releases discipline, and PESO (pathways/processes, exposures, setting/scenario, and

containing potentially relevant supplemental material were tracked and categorized during the literature

screening process as outlined in Table_Apx A-4.

70

Susceptible

populations

Mixture studies

71

A.2.1.2 PECO for Consumer, Environmental, and General Population Exposures

Table_Apx A-5. Generic Inclusion Criteria for the Data Sources Reporting Exposure Data on

General Population, Consumers and Environmental Receptors

72

Table_Apx A-6. Pathways Identified as Supplemental for TPP

a

“Supplemental pathways” refer to pathways addressed by other EPA administered statutes.

Assessors seek information on various chemical-specific engineering and occupational exposure data

the RESO statement (Table_Apx A-7.) along with the information in Table_Apx A-8. when screening

the engineering and occupational exposure data and information.

Table_Apx A-7. Inclusion Criteria for Data Sources Reporting Engineering and Occupational

Exposure Data

Setting or

73

worker exposures and by exposure assessors for releases; also, the Engineering, Release and Occupational Exposure Data

TSCA=Toxic Substances Control Act

Table_Apx A-8. Engineering, Environmental Release and Occupational Data Necessary to

Develop the Environmental Release and Occupational Exposure Assessments