EPA SCIENTIFIC ADVISORY COMMITTEE ON CHEMICALS
CHARGE TO THE PANEL TRICHLOROETHYLENE

As amended by the Frank R. Lautenberg Chemical Safety for the 2 1 st Century Act on June 22,
2016, the Toxic Substances Control Act (TSCA), requires the U.S. Environmental Protection
Agency (EPA) to conduct risk evaluations on existing chemicals. In December of 20 6, EPA
published a list of the initial ten chemical substances that are the subject of the Agency?s chemical
risk evaluation process (81 FR 91927), as required by TSCA. Trichloroethylene (TCE) is one of
the ?rst ten chemical substances and the ninth of the ten to undergo a peer review by the Scienti?c
Advisory Committee on Chemicals (SACC). In response to this requirement, EPA has prepared
and published a draft risk evaluation for TCE. The EPA has solicited cements from the public on
the draft and will incorporate them as appropriate, along with comments ?om peer reviewers, into
the ?nal risk evaluation.

The focus of this meeting is to conduct the peer review of the Agency?s draft risk evaluation of
TCE and associated supplemental materials. At the end of the peer review process, EPA will use
the reviewers? comments/recommendations, as well as public comment, to ?nalize the risk
evaluation.

This draft risk evaluation contains the following components:
a Discussion of chemistry and physical-chemical properties
Characterization of uses/sources
Environmental fate and transport assessment
Environmental exposure assessment
Human health hazard assessment
Environmental hazard assessment
Risk characterization
Risk determination
Detailed description of the systematic review process developed by the Of?ce of Pollution
Prevention and Toxics to search, screen, and evaluate scienti?c literature for use in the risk

evaluation process.

CHARGE QUESTIONS:

Systematic Review (Section 1.5 of the Draft Risk Evaluation):.
The Toxic Substances Control Act (TSCA) requires that EPA use data and/or information in a
manner consistent with the ?best available science? and that EPA base decisions on the ?weight
of the scienti?c evidence?. The Final Rule, Procedures for Chemical Risk Evaluation
Qnder the Amended Toxic Substances Control Act (82 de?nes ?best available
science? as science that is reliable and unbiased. This involves the use of supporting studies
conducted in accordance with sound and objective science practices, including, when available,
peer reviewed science and supporting studies and data collected by accepted methods or best
available methods (if the reliability of the method and the nature of the decision justi?es use of
the data). The Final Rule also de?nes the ?weight of the scienti?c evidence? as a systematic
review method, applied in a manner suited to the nature of the evidence or decision, that uses a
pre-cstablished protocol to comprehensively, objectively, transparently, and consistently identify

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and evaluate each stream of evidence, including the limitations, and relevance of each
study and to integrate evidence as necessary and appropriate based upon limitations,
and relevance.

To meet these scienti?c standards, EPA applied systematic review approaches and methods to
support the TCE draft risk evaluation. Information on the approaches and/or methods is

described in the draft risk evaluation as well as the following documents:

0 Strategy for Conducting Literature Searches for Trichloroethylene: Supplemental File for
the TSCA Sc0pe Document, 

Trichloroethylene (CASRN 79-01-6) Bibliography: Supplemental File for the TSCA Scope
Document, 

Trichloroethylene Problem Formulation 6-073 7)

 

0 Application of Systematic Review in TSCA Risk Evaluations

EPA has solicited peer review and public feedback on systematic review approaches and methods
for prior evaluations. A general question on these approaches is not included in this charge;
however, EPA will accept comment on the systematic review approaches used for this evaluation if
provided.

1. Environmental Fate and Exposure:
EPA qualitatively analyzed the sediment, land application, and biosolids pathways based on 

physical/chemical and fate properties. Exposure estimates to the environment were developed for
the conditions of use for exposures to aquatic organisms.

1.1. Please comment on qualitative analysis of pathways based on physical/chemical and
fate properties. (Section 2.1)

1.2. Please comment on the data, approaches, and/or methods used to characterize exposure to
aquatic receptors. (Section 2.2)

1.3 Please comment on assumption that TCE concentrations in sediment pore water are
expected to be similar to the concentrations in the overlying water or lower in the deeper
part of sediment, in which anaerobic conditions prevail. Thus, the TCE detected in
sediments is likely from the pore. (Section 4.1.3)

2. Environmental Exposure and Releases:

EPA evaluated releases to water and aquatic exposures for conditions of use in industrial and
commercial settings. EPA used Toxics Release Inventory (TRI) and Discharge Monitoring Report
(DMR) data to provide a basis for estimating releases. EPA used these releases and associated
inputs within EFAST 2014 to estimate instream chemical concentrations and days of exceedance.

EPA also evaluated monitored values of TCE in surface water and where possible compared those
values to estimated release concentrations.

2.1. Please comment on the approaches, models, and data used in the water release assessment
including comparison to monitored data. (Section 2.2)

2.2. Please provide any speci?c suggestions or recommendations for alternative data or
estimation methods, including modeling approaches, that could be considered by EPA for
conducting or re?ning the water release assessment and relation to monitored data.
(Section 2.2)

3. Environmental Hazard:

EPA evaluated environmental hazards for aquatic species from acute and chronic exposure
scenarios.

3.1. Please comment on approach for characterizing environmental hazard for each
risk scenario acute aquatic, chronic aquatic). What other additional information, if
any, should be considered?

3.2. Please comment on the use and interpretation of Species Sensitivity Distributions
(S SDs) and hazardous concentrations (HCoss) for ecological risk characterization and
provide any speci?c suggestions or recommendations for how this information could
inform risk assessment for TCE or other solvents.

4. Occupational and Consumer onsure:

Occupational Exposure

EPA evaluated acute and chronic exposures to workers for conditions of use in industrial and
commercial settings. For exposure via the inhalation pathway, EPA quanti?ed occupational
exposures for both workers and occupational non-users based on a combination of monitoring data
and modeled exposure concentrations. For exposure via the dermal route, EPA modeled exposure
for workers, accounting for the effect of volatilization. EPA assumed dermal contact with liquids
would not occur for occupational non-users. EPA assumed that workers and occupational non-
users, exposed via the inhalation and dermal pathways, would be adolescents and adults of both
sexes (216 and older, including males and females of reproductive age, and pregnant women and
their developing embryo and fetus).

4.1. Please comment on the approaches and estimation methods, models, and data used in the
occupational exposure assessment. (Section 2.3.1.2)

4.2. Please provide any speci?c suggestions or recommendations for alternative data
(modeling or monitoring) or estimation methods that could be considered by the Agency
for conducting the occupational exposure assessment. If so, please provide speci?c
literature, reports, or data that would help us re?ne the exposure assessment. (Section

2.3.1.2)

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4.3. Please comment on assumptions used in the absence of speci?c exposure information 
dermal surface area assumptions: high-end values, which represents two full hands in
contact with a liquid: 890 cm2 (mean for females), 1070 cm2 (mean for males); central
tendency values, which is half of two ?ill hands (equivalent to one full hand) in contact
with a liquid and represents only the palm-side of both hands exposed to a liquid: 445 cm2
(females), 535 cm2 (males)). Please also consider these values in the context of different
lifestages and body weights. (Section 2.3.1.2)

4.4. Please comment on approach to characterizing the limitations and overall
con?dence for each occupational exposure scenarios presented in Section 2.3.1. Please
comment on the appropriateness of these con?dence ratings for each scenario. Please also
comment on EPAs approach to characterizing the uncertainties summarized in Section
2.3.1.3.

To estimate occupational non-user (ONU) inhalation exposure, EPA reviewed personal monitoring
data, area monitoring data and modeled far-?elddexposure concentrations. When EPA did not
identify personal or area data or parameters for modeling potential ONU inhalation exposures, EPA
assumed ONU inhalation exposures could be lower than worker inhalation exposures; however,
relative exposure of ONUs to workers could not be quanti?ed. When exposures to ONUs were not
quanti?ed, EPA considered the central tendency from worker personal breathing zones to estimate
ONU exposures.

4.5. Please comment on the adequacy, appropriateness, and transparency of approach
and the assumptions EPA used to characterize ONU exposure via this approach. (Section
2.3 . 1) 

4.6. Are there other approaches or methods for assessing ONU exposure for the speci?c
condition of use?

Consumer Exposure

Consumer exposure estimates were developed for the conditions of use for inhalation and dermal
exposures to consumers. EPA performed systematic review, collected data from available sources
and conducted modeling for estimating consumer inhalation and dermal exposures using the
Consumer Exposure Model (CEM) model.

Product speci?c consumer monitoring information was not identi?ed during the systematic review
process, therefore, model inputs related to consumer use patterns (duration of use, mass of product
used, room of use, and similar inputs) are based on survey data found in the literature as described
and referenced within the TCE draft risk evaluation. Weight fractions of chemical within products
are based on product speci?c safety data sheets (SDS). Default values utilized within the models
are based on literature reviewed as part of model development as well as Exposure Factors
Handbook.

4.7. Please comment on the appropriateness cf the approaches, models, exposure or use
information and overall characterization of consumer inhalation exposure for users and

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bystanders for each of the identi?ed conditions of use. What other additional information,
or approaches, if any, should be considered? (Section 2.3.2)

4.8. Please comment on the appropriateness of the approaches, models, exposure or use
information, and overall characterization of consumer dermal exposure for each of the
identi?ed conditions of use. What other additional information or modeling approaches, if
any, should be considered? (Section 2.3.2)

4.9. Dermal exposure was evaluated using the permeability sub-model Within CEM. Please
comment on the suitability and use of this modeling approach for this evaluation. Please
provide any suggestions or recommendations for alternative approaches, dermal methods,
models or other information which may guide EPA in developing and re?ning the dermal
exposure estimates. (Section 2.3.2.4.1)

4.10. Please comment on EPAs approach to characterizing the limitations and overall
con?dence for each consumer exposure scenarios presented in Section 2.3.2. Please
comment on the appropriateness of these con?dence ratings for each scenario. Please also

comment on approach for characterizing the uncertainties summarized in Section
2.3.2.7.

5. Human Health Hazard:

For hazard identi?cation and dose-response, EPA reviewed the evidence for TCE toxicity

and selected liver toxicity, kidney toxicity, reproductive toxicity, developmental toxicity,
neurotoxicity, immunotoxicity, and cancer, that taken as a whole, demonstrated the most robust,
sensitive and consistent adverse human health effects for risk characterization. EPA used
benchmark dose (BMD) modeling where practicable and, when BMD values were adequate, they

were used to generate the Point of Departure (POD) for characterizing chronic and acute exposure
scenarios.

5.1. Please comment on the appropriateness of the. approach, including the data quality
evaluation, and the underlying assumptions, and weaknesses.

5.2. Have the most scienti?cally supported health effects and PODs been identi?ed for 
Are there additional data regarding sensitive life stages or health effects for TCE that EPA
needs to consider? If data gaps exist in the TCE database, how could the uncertainty about
sensitive health effects and critical windows of exposure be better accounted for in the risk
characterization?

Non-Cancer
5.3. EPA performed a weight of evidence assessment for the endpoint of developmental

cardiac defects based on available epidemiological, in vivo animal, and mechanistic data.
EPA concluded that the available literature overall supported a causal relationship between
develoPmental exposure to TCE or its metabolites and cardiac defects (Section 3.2.4.1.6
and Appendix G.2). Additionally, EPA determined that the Charles River Laboratories
(2019) developmental toxicity study was insuf?cient as a replication of the Johnson et a1.
(2003) study (Appendix G. 1). The Charles River dissection methodology differed from

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5.4.

5.5.

Cancer
5.6.

5.7.

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Johnson et. a1. (2003), resulting in reduced sensitivity to the full range of cardiac defects
compared to Johnson et al. (2003) and other studies. Therefore, EPA concluded that the
Charles River study did not adequately recapitulate the methodology of the Johnson et a1.
(2003) study. Please comment on Weight of Evidence (WOE) analysis approach
and conclusions for this endpoint.

EPA did not input the data on response to pulmonary infection from Selgrade and Gilmour
(2010) into the TCE PBPK model due to uncertainty over the proper dose metric to be
used. Therefore, EPA relied on standard methods for cross-species scaling bloodzair
partition coef?cient for HEC, allometric scaling for HED) and accordingly reduced the
default 10X UFA uncertainty factor to 3 (see Section 3.2.5.3.2). Please comment on
whether this approach is appropriate and whether the UF is sufficient.

Please comment on the assumptions, and weaknesses of the non-cancer dose-
response approaches used to estimate the non-cancer and cancer risks to workers,
occupational non-users, and consumers. Please comment on whether EPA suf?ciently
justi?ed its selections of BMRs for BMD modeling results and uncertainty factor values in
deriving the PODS and benchmark margin of exposures (MOEs) (Sections 32.532 and
3.2.5.3.3). As part of this discussion, please comment on justi?cation for selecting a
1% BMR for the cardiac malformation endpoint based on the severity of the endpoint 
potential mortality).

EPA performed a meta-analysis on the published database for liver cancer, kidney cancer,
and non-Hodgkins (NHL), concluding that there was a statistically signi?cant
association between TCE exposure and all three cancers when accounting for various
sensitivity analyses. Please comment on methodology and conclusions.

For the cancer dose-response assessment, EPA derived an inhalation unit risk (IUR) and
oral cancer slope factor (OSF) based on epidemiological kidney cancer data from
Charbotel et a1, 2006, adjusted upward to also account for the relative contribution NHL
and liver cancer. Per EPA Guidelines for Carcinogen Risk Assessment, overall, the totality
of the available data/information and the WOE analysis for the cancer endpoint was
suf?cient to support a linear non-threshold model (Section 3.2.4.2.2). Please comment
whether the cancer hazard assessment has adequately described the methodology and
justi?cation for the cancer dose-response approach, including the use of a linear model and
the adjustments made for the other tumor sites (Section 3.2.5.3.4).

6. Risk Characterization:

EPA calculated environmental risk using exposure data modeling tools and monitored
datasets) and environmental toxicity information, accounting for variability within the
environment. EPA concludes that TCE poses a hazard to environmental aquatic receptors, with
invertebrates and ?sh being the most sensitive taxa identi?ed for aquatic exposures. Risk Quotients
(RQs) and the number of days a concentration of concern (C 0C) was exceeded were used to assess

environmental risks. The risk characterization section provides a discussion of the risk and
uncertainties around the risk calculations.

EPA calculated human health risks for acute and chronic exposures. For non-cancer effects EPA
used an MOE, which is the ratio of the hazard value to the exposure. EPA evaluated potential risks
for workers and ONUs, consumer users, and bystanders/non?users children, women of
childbearing age). For the most sensitive endpoint of congenital heart defects, a benchmark MOE
of 10 was used for both acute and chronic risks. An IUR and OSF that account for the combined
extra risk kidney cancer, liver cancer, and NHL was used to evaluate potential chronic risks to
cancer endpoints for the worker exposure scenarios. The risk characterization also provides a
discussion of the uncertainties surrounding the risk calculations.

After consideration of all identi?ed information, EPA concluded that TCE presents an
unreasonable risk of injury to workers, ONUs, consumers, and bystanders by inhalation and dermal
exposure based on the potential for adverse human health effects (See Section 4.2). EPA also
concludes that TCE does not present an unreasonable risk to environmental receptors exposed via
surface water (see Section 4.1). EPA makes this determination considering risk to potentially
exposed and susceptible subpopulations identi?ed as relevant, under the conditions of use without
considering costs or other non-risk factors.

6.1. Please comment on whether the information presented to the panel supports the
conclusions outlined in the draft risk characterization section concerning TCE. If not,
please suggest alternative approaches or information that could be used to further develop
a risk estimates within the context of the requirements stated in Final Rule,
Procedures for Chemical Risk Evaluation Under the Amended Toxic Substances Control
Act (82 FR 33726). (Section 5)

6.2. Please comment on the validity of speci?c con?dence summaries presented in Section 4.3.

6.3. Please comment on any other aspect of the environmental or human health risk
characterization that has not been mentioned above.

6.4. Please comment on the calculation of risk derived from different exposure data sources
modeling tools and monitored datasets) and how they account for variability in
environmental and human exposure. Please provide speci?c recommendations as needed
for improving the risk characterization and references to support any recommendations.

6.5. Please comment on whether the risk evaluation document has adequately described the
uncertainties and data limitations associated with the methodologies used to assess the
environmental and human health risks. Please comment on Whether this information is
presented in a clear and transparent manner.

The Frank R. Lautenberg Chemical Safety for the 21st Century Act (2016) (amended TSCA) states
that ?potentially exposed or susceptible subpopulations? (PESS) be considered in the risk
evaluation process. PESS is de?ned in the Lautenberg Act to include populations with greater

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exposure or greater response, including due to lifestyle, dietary, and biological susceptibility
factors, than the general population.

6.6. Has a thorough and transparent review of the available information been conducted that
has led to the identi?cation and characterization of all PESS (Sections 2.3.3, 3.2.5.2, and
Do you know of additional information about PESS that EPA needs to consider?
Additionally, has the uncertainty around PESS been adequately characterized?

The EPA characterization of human health risk from inhalation exposure to workers includes
estimates of risk for respirator use. These estimates are calculated by multiplying the high end and
central tendency MOE or extra cancer risk estimates without respirator use by the respirator
assigned protection factors (APFs) of 10 or 50 and the glove protection factors of 5, 10, or 20. EPA
also characterized exposure scenarios in which respirator use was unlikely. EPA did not assume
occupational non users (ONUS) or consumers used personal protective equipment (PPE) in the risk
estimation process.

6.7. Please comment on whether EPA has adequately, clearly, and appropriately presented the
reasoning, approach, assumptions, and uncertainties for characterizing risk to workers and
ONUS using PPE.

7. Overall Content and Organization:

Final Rule, Procedures for Chemical Risk Evaluation Under the Amended Toxic Substances
Control Act (82 FR 33726) stipulates the process by which EPA is to complete risk evaluations
under the Frank R. Lautenberg Chemical Safety for the 2lst Century Act.

As part of this draft risk evaluation for TCE, EPA evaluated potential environmental, occupational
and consmner exposures. The evaluation considered reasonably available information, including
manufacture, use, and release information, and physical-chemical characteristics. It is important
that the information presented in the risk evaluation and accompanying documents is clear and
concise and describes the process in a scienti?cally credible manner.

To increase the quality and credibility of scienti?c information disseminated by EPA, EPA uses the
peer review process speci?cally as a tool for determining ?tness of scienti?c information for the
intended purpose. The questions below are intended to guide the peer reviewers toward
determining if EPA collected, used and disseminated information that is for purpose? based on
utility (the data's utility for its intended users and for its intended purpose), integrity (the data's
security), and objectivity (whether the disseminated information is accurate, reliable, and unbiased
as a matter of presentation and substance). The peer reviewers? critical focus should pertain to
recommendations of the technical information?s usefulness for intended users and the public.

7.1. Please comment on the overall content, organization, and presentation of the NMP draft
risk evaluation. Please provide suggestions for improving the clarity of the information
presented.

7.2. Please comment on the objectivity of the underlying data used to support the risk
characterization and the sensitivity of the agency's conclusions to analytic assumptions made.