United States Office of Chemical Safety and
ฎ Environmental Protection Agency Pollution Prevention
Summary of External Peer Review and Public Comments and
Disposition for Trichloroethylene (TCE)
Response to Support Risk Evaluation of
Trichloroethylene (TCE)
November 2020
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Table of Contents
Environmental Fate and Exposure 8
Environmental Exposure and Releases 37
Environmental Hazard 72
Occupational and Consumer Exposure 85
Human Health Hazard 177
Risk Characterization 291
Overall Content and Organization 369
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This document summarizes the public and external peer review comments that the EPA's Office
of Pollution Prevention and Toxics (OPPT) received for the risk evaluation of trichloroethylene
(TCE). It also provides EPA's response to the comments received from the public and the peer
review panel.
EPA appreciates the valuable input provided by the public and peer review panel. The input
resulted in numerous revisions to the hazard summary.
Peer review charge questions1 are used to categorize the peer review and public comments into
specific issues related to the five main themes.
1. Environmental Fate and Exposure
2. Environmental Exposure and Releases
3. Environmental Hazard
4. Occupational and Consumer Exposure
5. Human Health Hazard
6. Risk Characterization
7. Overall Content and Organization
All peer review comments for the seven charge questions are presented first, organized by charge
question in the following section. These are followed by the public comments. For each theme,
general comments are presented first, and then additional comments follow.
1 These are the questions that EPA/OPPT submitted to the panel to guide the peer review process.
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List of Comments
#
Docket File
Submitter
31
EPA-HO-OPPT-2019-0500-0031
Anonymous
32
EPA-HO-OPPT-2019-0500-0032
Anonymous
33
EPA-HO-OPPT-2019-0500-0033
Tox Strategies
34
EPA-HO-OPPT-2019-0500-0034
Anonymous
35
EPA-HO-OPPT-2019-0500-003 5
Anonymous
36
EPA-HO-OPPT-2019-0500-0036
W. Germann
37
EPA-HO-OPPT-2019-0500-003 7
Jennifer McPartland, Senior Scientist, Environmental Defense Fund (EDF)
38
EPA-HO-OPPT-2019-0500-003 8
Anonymous
39
EPA-HO-OPPT-2019-0500-0039
Anonymous
44
EPA-HO-OPPT-2019-0500-0044
Richard A. Denison, Lead Senior Scientist, EDF
45
EPA-HO-OPPT-2019-0500-0045
Anonymous
47
EPA-HO-OPPT-2019-0500-0047
Michelle Roos, Environmental Protection Network (EPN)
48
EPA-HO-OPPT-2019-0500-0048
Exponent, Inc. on behalf of the American Chemistry Council and the Halogenated
Solvents Industry Alliance
49
EPA-HO-OPPT-2019-0500-0049
Liz Hitchcock, Director, Safer Chemicals Healthy Families (SCHF) et al.
50
EPA-HO-OPPT-2019-0500-0050
Suzanne Hartigan, Senior Director, Regulatory and Technical Affairs, American
Chemistry Council (ACC)
51
EPA-HO-OPPT-2019-0500-0051
Stephen P. Risotto, Senior Director, ACC
52
EPA-HO-OPPT-2019-0500-0052
ToxStrategies on behalf of the ACC
56
EPA-HO-OPPT-2019-0500-0056
Richard A. Denison, Lead Senior Scientist, EDF
57
EPA-HO-OPPT-2019-0500-0057
Richard A. Denison, Lead Senior Scientist, EDF
58
EPA-HO-OPPT-2019-0500-0058
Jennifer Sass, Senior Scientist, Natural Resources Defense Council (NRDC)
60
EPA-HO-OPPT-2019-0500-0060
Daniele Wikoff, Health Sciences Practice Director, ToxStrategies
61
EPA-HO-OPPT-2019-0500-0061
David Michaels, Department of Environmental and Occupational Health, Milken
Institute School of Public Health, The George Washington University
62
EPA-HO-OPPT-2019-0500-0062
I. Rusyn
63
EPA-HO-OPPT-2019-0500-0063
James Bus, Toxicologist, Exponent, Inc. for the Halogenated Solvents Industry
Alliance (HSIA)
64
EPA-HO-OPPT-2019-0500-0064
Jennifer Sass, Senior Scientist, NRDC
65
EPA-HO-OPPT-2019-0500-0065
Lindsay McCormick, EDF
Page 4 of 408
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l.isl of ( oinincnls
#
Docket l;ilc
Siihinillor
66
EP A-HG-GPPT-2019-0500-0066
Raymond Runyan, Professor of Cellular and Molecular Medicine, University of
Arizona
67
EP A-HG-OPPT-2019-0500-0067
Tony Tweedale, R.I.S.K. Consultancy
68
EP A-HG-GPPT-2019-0500-0068
ToxStrategies for the ACC
69
EP A-HO-OPPT-2019-0500-0069
Richard A. Denison, Lead Senior Scientist, EDF
70
EP A-HO-OPPT-20
19-0500-0070
Richard A. Denison, Lead Senior Scientist, EDF
71
EP A-HO-OPPT-20
19-05
Richard A. Denison, Lead Senior Scientist, EDF
72
EP A-HO-OPPT-20
19-0500-0072
J. M. DeSesso, and A. L. Williams
73
EP A-HO-OPPT-20
19-0500-0073
Jennifer McPartland, EDF
74
EP A-HO-OPPT-20
19-05
Jennifer McPartland, Richard Denison, and Lindsay McCorm, EDF
75
EP A-HO-OPPT-20
19-05
John M. DeSesso and Amy Lavin Williams, Exponent, Inc.
76
EP A-HO-OPPT-20
19-05
John M. DeSesso and Amy Lavin Williams, Exponent, Inc.
77
EP A-HO-OPPT-20
19-0500-0077
Nicholas Chartres, Research Scientist, Program on Reproductive Health and the
Environment, University of California, San Francisco
78
EPA-HO-OPPT-2019-0500-0078
Andre Ourso, Administrator, Center for Health Protection, Public Health Division,
Oregon Health Authority (OHA) and Ali Mirzakkhalili, Air Division Administrator,
State of Oregon Department of Environmental Quality (DEQ)
79
EPA-HO-OPPT-2019-0500-0079
Stephen P. Risotto, Senior Director, ACC
80
EPA-HO-OPPT-2019-0500-0080
Eric Berg, Deputy Chief, Research and Standards, California Division of Occupational
Safety and Health (Cal/OSHA)
81
EP A-HO-OPPT-20
19-0500-0081
Elemar Marine Services Company
82
EP A-HO-OPPT-20
19-0500-0082
Lucas Allen, American Academy of Pediatrics et al.
83
EP A-HO-OPPT-20
19-0500-0083
Anonymous
84
EPA-HO-OPPT-2019-0500-0084
Laura Reinhard, Vice President and General Manager, Honeywell International Inc.
85
EPA-HO-OPPT-2019-0500-0085
Mass Comment Campaign sponsored by If It Was Your Child (web)
86
EPA-HO-OPPT-2019-0500-0086
Mass Comment Campaign sponsored by If It Was Your Child (web)
87
EPA-HO-OPPT-2019-0500-0087
Kari Rhinehart & Stacie Davidson, Co-Founders, If It Was Your Child
88
EP A-HO-OPPT-20
19-0500-0088
Mass Comment Campaign sponsored by EDF (17,321 signatories)
89
EP A-HO-OPPT-20
19-0500-0089
Anonymous
Page 5 of 408
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l.isl of ( oinincnls
#
Docket l;ilc
Siihinillor
90
EPA-HO-OPPT-2019-0500-0090
Trevor M. Penning, Director, Center of Excellence in Environmental Toxicology
(CEET), University of Pennsylvania
91
EP A-HG-OPPT-2019-0500-0091
Anonymous
92
EPA-HO-OPPT-2019-0500-0092
Anonymous
93
EPA-HO-OPPT-2019-0500-0093
Victoria Bogdan Tejeda, Associate Attorney, Earthjustice and Maria Lopez-Nunez,
Deputy Director, Organizing and Advocacy, Ironbound Community Corporation (ICC)
94
EPA-HO-OPPT-20
vo
I
o
o
0
1
o
o
o
Christopher Bevan, Director, Scientific Programs, HSIA
95
EPA-HO-OPPT-20
vo
I
o
o
0
1
o
o
o
Stephen P. Risotto, Senior Director, ACC
96
EPA-HO-OPPT-20
19-0500-0096
Rebecca J. Rentz, Senior Environmental Counsel, Occidental Chemical Corporation
97
EPA-HO-OPPT-20
vo
I
O
o
0
1
o
o
o
**>4
Rebecca J. Bernstein, Senior Director, Product Safety & Regulatory Affairs, Health
Environment & Safety, Arkema Inc.
98
EPA-HO-OPPT-2019-0500-0098
Amy Chyao, Assistant Corporation Counsel and Amy McCamphill, Senior Counsel,
Environmental Division, New York City Law Department
99
EPA-HO-OPPT-2019-0500-0099
Liz Hitchcock, Director, SCHF et al.
100
EPA-HO-OPPT-2019-0500-0100
Jonathan Kalmuss-Katz, Staff Attorney, Earthjustice and Randy Rabinowitz, Executive
Director, Occupational Safety & Health Law Project
101
EPA-HO-OPPT-2019-0500-0101
Richard Krock, Senior Vice President, Regulatory and Technical Affairs, Vinyl
Institute (VI)
102
EPA-HO-OPPT-2019-0500-0102
Julia M. Rege, Vice President, Energy & Environment, Alliance for Automotive
Innovation
103
EPA-HO-OPPT-20
19-0500-0
103
Suzanne Hartigan, Senior Director, Regulatory and Technical Affairs, ACC
104
EPA-HO-OPPT-20
19-0500-0
104
Dianne C. Barton, Chair, National Tribal Toxics Council (NTTC)
105
EPA-HO-OPPT-20
19-0500-0
105
Lauren Zeise, Director, Office of Environmental Health Hazard Assessment (OEHHA),
California Environmental Protection Agency
106
EPA-HO-OPPT-2019-05(
Swati Rayasam et al., Science Associate, Program on Reproductive Health and the
Environment, Department of Obstetrics, Gynecology and Reproductive Sciences,
University of California, San Francisco (UCSF PRHE)
107
EPA-HO-OPPT-2019-0500-0107
Diane VanDe Hei, Chief Executive Officer, Association of Metropolitan Water
Agencies (AMWA)
108
EPA-HO-OPPT-2019-0500-0108
EDF
Page 6 of 408
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l.isl of ( oinincnls
#
Docket l;ilc
Siihinillor
109
EP A-HG-GPPT-2019-0500-0109
Christopher Bevan, Director, Scientific Programs, HSIA
SACC
N/A
Science Advisory Committee on Chemicals (SACC)
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1. Environmental Fate and Exposure
Environmental Fate and Exposure
Charge Question 1.1: Please comment on EPA's qualitative analysis of pathways based on physical/chemical and fate properties
(Section 2.1).
Charge Question 1.2: Please comment on the data, approaches, and/or methods used to characterize exposure to aquatic receptors
(Section 2.2).
Charge Question 1.3: Please comment on EPA's 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).
#
Summary of Comments for Specific Issues Related to Charge
Question 1
EPA/OPPT Response
Ecological populations assessed are incomplete
SACC
SACC COMMENTS:
Recommendation: Include additional discussion and justification for the
decision to not assess risk to sediment and terrestrial organisms.
The Committee questioned EPA's decision not to evaluate risk to
sediment and terrestrial organisms based on low sorption and rapid
volatilization even though TCE is one of the most widespread
groundwater and soil gas contaminants in the United States.
For sediment-dwelling organisms, during
problem formulation, EPA determined that an
insignificant portion of TCE is available to enter
the sediment compartment. Therefore, while the
sediment pathway was included, EPA did not
plan to further analyze exposure to sediment-
dwelling species, and in the draft risk evaluation,
sediment-dwelling organisms were only assessed
qualitatively. However, in response to SACC
comments a quantitative assessment of sediment-
dwelling organisms was added to the final TCE
risk evaluation in Section 4.1.3.
For terrestrial organisms, during problem
formulation exposure pathways to these
organisms through water and biosolids were
within scope, but not further analyzed, because
physical-chemical properties do not support these
pathways. The land-applied biosolids pathway is
within the scope of the risk evaluation, but during
Page 8 of 408
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problem formulation EPA determined risks
would not be quantitatively evaluated for land-
applied biosolids because based on fate
properties, TCE is not anticipated to partition to
biosolids during wastewater treatment. Any TCE
present in the water portion of biosolids
following wastewater treatment and land
application would be expected to rapidly
volatilize into air. And the air exposure pathway
from biosolids and surface water are
insignificant. Based on the Guidance for
Ecological Soil Screening Levels (EPA 2003a.
b) document, for terrestrial wildlife, relative
exposures associated with inhalation and dermal
exposure pathways are insignificant, even for
volatile substances, compared to direct ingestion
and ingestion of food (by approximately 1,000-
fold). In addition, TCE is not expected to
bioaccumulate in tissues, and concentrations will
not increase from prey to predator in either
aquatic or terrestrial food webs. EPA has added
language to the final risk evaluation document in
Section 4.1.4 explaining this rationale.
For terrestrial organisms, pathways that were out
of scope include ambient air from industrial
sources, disposal in landfills, incineration units,
and underground injection. Environmental
exposure pathways covered under the jurisdiction
of other EPA-administered statutes and
regulatory programs are not within the scope of
the risk evaluation. Emissions to ambient air from
commercial and industrial stationary sources, and
Page 9 of 408
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associated inhalation exposures of terrestrial
species, are covered under the jurisdiction of the
Clean Air Act (CAA). Pathways from disposal to
sediment, soil, water, and air are covered under
Resource Conservation and Recovery Act
(RCRA), the Comprehensive Environmental
Response, Compensation, and Liability Act
(CERCLA), CAA's Maximum Achievable
Control Technology (MACT), and the Safe
Drinking Water Act (SDWA). Clarifying
language about what pathways are addressed
under other statutes has been added to Section
1.4.2 of the Risk Evaluation.
SACC
SACC COMMENTS:
Recommendation: Better justify exclusion in the exposure assessment
of soil invertebrates and burrowing mammals in functionally confined
spaces. In Section 3.1.5, volatilization rates are assumed to not
contribute to exposure for terrestrial organisms. Several Committee
members expressed concern regarding exposures to soil invertebrates
and burrowing mammals in functionally confined spaces exposed to
TCE through vapor intrusion from contaminated underground sources.
This is considered in other Agency regulations (Comprehensive
Environmental Response, Compensation, and Liability Act [CERCLA])
for human health concerns. A more robust justification or assessment is
needed to dismiss exposures for these organisms. Another acceptable
response may include appropriate jurisdiction by other laws or
regulation.
The Committee noted that acute exposures to terrestrial organisms that
may spend significant time at the soil/air or water/air interface where
volatilization may produce inhalation exposures cannot be ruled out.
As explained in more detail in Section 1.4.2 of
the Final Risk Evaluation, EPA believes it is both
reasonable and prudent to tailor TSCA Risk
Evaluations when other EPA offices have
expertise and experience to address specific
environmental media, rather than attempt to
evaluate and regulate potential exposures and
risks from those media under TSCA. Section
1.4.2 has been updated to reflect the regulatory
authority and risks addressed by CERCLA.
For terrestrial organisms, during problem
formulation exposure pathways to these
organisms through water and biosolids were
within scope, but not further analyzed, because
physical-chemical properties do not support these
pathways. The air exposure pathway from
biosolids and surface water are insignificant.
Based on the Guidance for Ecological Soil
56, 108
PUBLIC COMMENTS:
Page 10 of 408
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EPA did not perform a quantitative assessment of exposures to
terrestrial organisms because "TCE is not expected to partition to soil
but is expected to volatilize to air, based on its physical-chemical
properties." This statement ignores TCE exposures to terrestrial
organisms through air, which is a primary pathway of exposure to TCE.
EPA does not present or analyze data confirming this analysis. EPA
dismisses exposure to terrestrial organisms from the ambient air
pathway based on the unsupported argument that such exposures are
adequately managed by the CAA.
TCE present in soil vapor will not degrade via atmospheric
reactions. EPA has disregarded impacts from such exposure to
terrestrial organisms whose habitat exists in the vadose zone.
Fossorial and semi-fossorial organisms (those that burrow) have an
"increased exposure potential from inhalation at site contaminated
with volatile chemicals in the subsurface." EPA has ignored these
sources of environmental exposure to such organisms.
Emission pathways to ambient air from commercial and industrial
stationary sources or associated inhalation exposure of terrestrial
species were considered to be outside of the scope of the risk
evaluation because stationary source releases of TCE to ambient air
are adequately assessed and any risks effectively managed when
under the jurisdiction of the CAA.
Screening Levels (EPA. 2003a, b) document for
terrestrial wildlife, including soil invertebrates
and burrowing mammals, relative exposures
associated with inhalation and dermal exposure
pathways are insignificant, even for volatile
substances, compared to direct ingestion and
ingestion of food (by approximately 1,000-fold).
TCE is not expected to bioaccumulate in tissues,
and concentrations will not increase from prey to
predator in either aquatic or terrestrial food webs.
In addition, concentrations will not increase from
prey to predator in either aquatic or terrestrial
food webs. EPA has added language to the final
risk evaluation document in Section 4.1.4
explaining this rationale.
56, 108
PUBLIC COMMENTS:
EPA is ignoring exposures to terrestrial organisms that may occur from
contaminated water and soil. EPA must comprehensively consider all
routes of exposure to terrestrial organisms in its risk evaluation. In
addition to the fact that nearly two million pounds of TCE are released
annually into the air, due to its volatility, disposal to water and land may
also create a route of exposure to organisms living at the water-
atmosphere or water-soil interface (e.g., amphibians, birds and
shorebirds, and burrowing organisms).
EPA has not provided rational and clear analysis based on the best
available science and information to support its conclusions.
For terrestrial organisms, during problem
formulation exposure pathways to these
organisms through water and biosolids were
within scope but not further analyzed, because
physical-chemical properties do not support these
pathways. The land-applied biosolids pathway is
within the scope of the risk evaluation, but during
problem formulation EPA determined risks
would not be quantitatively evaluated for land-
applied biosolids because based on fate
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properties, TCE is not anticipated to partition to
biosolids during wastewater treatment. Any TCE
present in the water portion of biosolids
following wastewater treatment and land
application would be expected to rapidly
volatilize into air. And the air exposure pathway
from biosolids and surface water are
insignificant. Based on the Guidance for
Ecological Soil Screening Levels (EPA 2003a.
b) document, for terrestrial wildlife, relative
exposures associated with inhalation and dermal
exposure pathways are insignificant, even for
volatile substances, compared to direct ingestion
and ingestion of food (by approximately 1,000-
fold). In addition, TCE is not expected to
bioaccumulate in tissues, and concentrations will
not increase from prey to predator in either
aquatic or terrestrial food webs. EPA has added
language to the final risk evaluation document in
Section 4.1.4 explaining this rationale.
For terrestrial organisms, pathways that were out
of scope include ambient air from industrial
sources, disposal in landfills, incineration units,
and underground injection. Environmental
exposure pathways covered under the jurisdiction
of other EPA-administered statutes and
regulatory programs are not within the scope of
the risk evaluation. Emissions to ambient air from
commercial and industrial stationary sources, and
associated inhalation exposures of terrestrial
species, are covered under the jurisdiction of the
Clean Air Act (CAA). Pathways from disposal to
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sediment, soil, water, and air are covered under
Resource Conservation and Recovery Act
(RCRA), the Comprehensive Environmental
Response, Compensation, and Liability Act
(CERCLA), CAA's Maximum Achievable
Control Technology (MACT), and the Safe
Drinking Water Act (SDWA). Clarifying
language about what pathways are addressed
under other statutes has been added to Section
1.4.2 of the Risk Evaluation.
56, 108
PUBLIC COMMENTS:
Impacts on sediment dwelling organisms need to be evaluated.
EPA stated in its problem formulation: "No data on the toxicity to
sediment organisms were found; however, TCE is not expected to
partition to sediment, based on physical chemical properties."
Absence of hazard data does not equate to absence of hazard. A
cursory review of the literature identified a study that found
sensitivity of nematodes (sediment-dwelling organisms) to TCE at
concentrations of 1 ug/ml (or 1000 ppb). At 30 mg/L, the
researchers reported a significant reduction in the nematode
maturity index, described as an index of diversity based on trophic
groupings in nematodes in riparian soil microcosms. TCE has been
measured in the sediment at concentrations of up to 26,000 (J,g/kg
(or 26,000 ppb).
The scope of the draft risk evaluation limited the COUs included to
those with applicable OESs. EPA then appears to have illogically
limited its evaluation of risks to environmental receptors to just
these COUs. As a result, it is likely that some environmental
receptors potentially impacted by TCE discharges have been
ignored because those discharges are not associated with a specific
COU chosen based on worker exposure potential. Ignoring TCE-
impacted sediment data illustrates this point.
EPA disregarded data associated with contaminated sites from its
For sediment-dwelling organisms, during
problem formulation, EPA determined that an
insignificant portion of TCE is available to enter
the sediment compartment. Therefore, while the
sediment pathway was included, EPA did not
plan to further analyze exposure to sediment-
dwelling species, and in the draft risk evaluation,
sediment-dwelling organisms were only assessed
qualitatively. However, in response to SACC
comments a quantitative assessment of sediment-
dwelling organisms was added to the final TCE
risk evaluation in Section 4.1.3.
EPA has evaluated the known, intended, and
reasonably foreseen COUs for TCE, unless a
COU was specifically excluded, and has not
limited COUs only to OESs. Rather, OESs are
used to group occupational COUs for purposes of
risk evaluation.
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water monitoring data ("Data Filtering and Cleansing," p. 89) and
excluded monitoring data potentially impacted by Superfund sites in
its watershed analysis ("Geospatial Analysis Approach," p. 89).
While EPA acknowledges that TCE has been measured in
sediments, it immediately dismisses these data, asserting that this
detection is likely for TCE present in pore water; on this basis, EPA
does not address risk to sediment-dwelling organisms.
Even if TCE were only associated with pore water, sediment-
dwelling organisms often live in or are in contact with the pore
water of sediment systems. Given that some of these organisms exist
in the interstitial spaces in sediment and sand, pore water can be a
key route of exposure to these organisms. Therefore, EPA cannot
ignore this exposure pathway for sediment-dwelling organisms.
108
PUBLIC COMMENTS:
EPA ignores certain hazards by completely failing to provide
quantitative analysis of environmental hazards to sediment-dwelling,
terrestrial, or avian organisms (limiting such analysis to aquatic
hazards).
EPA must analyze all of the environmental risks presented by TCE
through ambient water. EPA did not analyze the risks to terrestrial
or sediment-dwelling species from exposure through ambient water
for TCE, despite the fact that terrestrial and sediment-dwelling
species also can experience exposures through surface water, (p.
29). When EPA evaluates the risks presented by exposure through
ambient water, EPA must consider the risks presented to terrestrial
and sediment-dwelling ecological receptors as well as aquatic
species.
For sediment-dwelling organisms, during
problem formulation, EPA determined that an
insignificant portion of TCE is available to enter
the sediment compartment. Therefore, while the
sediment pathway was included, EPA did not
plan to further analyze exposure to sediment-
dwelling species, and in the draft risk evaluation,
sediment-dwelling organisms were only assessed
qualitatively. However, in response to SACC
comments a quantitative assessment of sediment-
dwelling organisms was added to the final TCE
risk evaluation in Section 4.1.3.
For terrestrial organisms, during problem
formulation exposure pathways to these
organisms through water and biosolids were
within scope, but not further analyzed, because
physical-chemical properties do not support these
pathways. The land-applied biosolids pathway is
Page 14 of 408
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within the scope of the risk evaluation, but during
problem formulation EPA determined risks
would not be quantitatively evaluated for land-
applied biosolids because based on fate
properties, TCE is not anticipated to partition to
biosolids during wastewater treatment. Any TCE
present in the water portion of biosolids
following wastewater treatment and land
application would be expected to rapidly
volatilize into air. And the air exposure pathway
from biosolids and surface water are
insignificant. Based on the Guidance for
Ecological Soil Screening Levels (EPA 2003a.
b) document, for terrestrial wildlife, relative
exposures associated with inhalation and dermal
exposure pathways are insignificant, even for
volatile substances, compared to direct ingestion
and ingestion of food (by approximately 1,000-
fold). In addition, TCE is not expected to
bioaccumulate in tissues, and concentrations will
not increase from prey to predator in either
aquatic or terrestrial food webs. EPA has added
language to the final risk evaluation document in
Section 4.1.4 explaining this rationale.
For terrestrial organisms, pathways that were out
of scope include ambient air from industrial
sources, disposal in landfills, incineration units,
and underground injection. Environmental
exposure pathways covered under the jurisdiction
of other EPA-administered statutes and
regulatory programs are not within the scope of
the risk evaluation. Emissions to ambient air from
Page 15 of 408
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commercial and industrial stationary sources, and
associated inhalation exposures of terrestrial
species, are covered under the jurisdiction of the
Clean Air Act (CAA). Pathways from disposal to
sediment, soil, water, and air are covered under
Resource Conservation and Recovery Act
(RCRA), the Comprehensive Environmental
Response, Compensation, and Liability Act
(CERCLA), CAA's Maximum Achievable
Control Technology (MACT), and the Safe
Drinking Water Act (SDWA). Clarifying
language about what pathways are addressed
under other statutes has been added to Section
1.4.2 of the Risk Evaluation.
Eco exposure concentration data/modeling/values are incomplete or invalid
SACC
SACC COMMENTS:
U.S. Environmental Protection Agency (EPA) expects limited exposure
to aquatic organisms due to a high volatilization rate. However,
trichloroethylene (TCE) only slowly biodegrades under aerobic
conditions and the predicted volatilization half-lives in river waters (1.2
hours) and lake waters (110 hours) are not negligible.
Risk analysis for aquatic organisms is based on
modeled surface water concentrations from E-
FAST (U.S. EPA 2014c) and monitored surface
water concentrations.
SACC
SACC COMMENTS:
Recommendation: Clarify why the Exposure and Fate Assessment
Screening Tool (E-FAST), considered inappropriate for volatile organic
compounds (VOCs), is relied on for evaluating environmental
exposures.
Committee members questioned why a comparison is performed
between E-FAST modeled and measured data when, according to EPA
documentation, the model is not appropriate for TCE, and stream flow
data are not current. The Committee was uncertain on which data
should be used to assess environmental exposures, since modeled data
seemed inappropriate for the task and monitoring data are limited. A
EPA has conducted additional fate analysis for
two sites with chronic COC (920 |ig/L)
exceedances (See Section 4.3.1 and 2.2.6.3).
EPISuite fugacity modeling using WVOLWIN
was conducted to inform the degree to which
volatilization may impact the modeled stream
concentrations estimated in E-FAST (U.S. EPA
2014c). Parameters (wind speed, current speed,
and water depth) reflective of two releasing sites
with the highest predicted surface water
concentrations (Praxair Technology Center in
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Committee member questioned whether it is even appropriate to make
the comparison between the two datasets.
One Committee member noted that the PDM portion of the E-FAST
2014 model was specifically written to handle surface runoff from
nonpoint sources. It is used in this draft risk evaluation for
determining the number of days exceeding the concentration of
concern (COC) in free-flowing water bodies from a point source.
The use of this model for evaluating a source with continuous point
source releases needs justification because inputs to the model
represent nonpoint source releases, not necessarily appropriate for
point source releases. The draft risk evaluation has explicitly
omitted non-point source releases. In using this model, it is unclear
what assumptions are being made related to the upstream and initial
downstream concentrations. Without further clarification, it is not
possible for the Committee to comment on the appropriateness of
this model in this evaluation.
A Committee member questioned whether the search for Superfund
sites used five river miles or a simple five-mile radius from the
water sampling point. If a Superfund site was within five miles,
would Superfund site information be queried to determine that TCE
exceeded a COC?
Page 17 of 408
Tonawanda, NY and NASA Michoud in New
Orleans, LA; see Table 4-1) were used to
estimate TCE volatilization half-lives, which
varied from one day to more than 10 years. The
effect of volatility on estimating instream
concentrations is expected to be highly variable
and site-specific depending on stream flow and
environmental conditions. For discharges to still,
shallow water bodies, E-FAST estimates are less
likely to overestimate surface water
concentrations, as TCE is predicted to have a
long half-life in such still water bodies. For
discharges to faster-flowing, deeper water bodies,
E-FAST estimates may inadequately reflect
instream volatile losses expected within the
timeframe of one day. Given this variation and
the predicted half-life of TCE in flowing water
bodies, E-FAST surface water concentrations
may best represent concentrations found at the
point of discharge.
EPA agrees that the lack of colocation between
monitored values of TCE and estimated surface
water concentrations from known releases for the
majority of results makes it difficult to draw
definitive conclusions. Nevertheless, the
evaluated monitoring data within the United
States from recent years showed that the majority
of samples had detectable levels of TCE below
identified COCs. EPA appreciates the suggestion
to do modeling across similar classes of
chemicals to evaluate model performance and
predictive ability and will consider those
-------
suggestions for future risk evaluations. However,
absent monitoring programs designed to measure
these concentrations proximal to discharging
facilities, the colocation of monitoring
information with known facility releases is
expected to be small thereby limiting model
verification with actual monitored values.
The scope of this EPA TSCA risk evaluation
does not include on-site releases to the
environment of trichloroethylene at Superfund
sites and subsequent exposure of the general
population or non-human species. However, the
geospatial analysis component of the aquatic
exposure assessment included a search for
Superfund sites within 1 to 5 miles of the surface
water monitoring stations. Superfund sites in
2016 were identified and mapped using
geographic coordinates of the "front door," as
reported in in Envirofacts; therefore, EPA did not
utilize the five river miles noted by the
commenter. Co-location of releasing facilities
and monitoring sampling locations was examined
for presence in the same watershed (HUC-8 and
HUC-12). Co-location does not necessarily
indicate there is an upstream/downstream
connection between release and sampling sites.
The monitoring stations co-located with facilities
in the same HUC in the 2016 dataset were also
examined for proximity to Superfund sites;
however, no Superfund sites were identified
within five miles of these sites.
56, 108
PUBLIC COMMENTS:
Page 18 of 408
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The EPA based its exposure estimates on unreliable surface water
concentrations and uncertain calculations. EPA ignored environmental
impacts to surface water from TCE discharges, and the existing surface
water data may not be representative of TCE concentrations. EPA
acknowledges the limitations of data in the U.S. Geological Survey
(USGS)-National Water Information System (NWIS) and STOrage and
RETrieval (STORET) databases.
When calculating surface water release estimates, EPA correctly
states that "release estimates serve as the key inputs into the
exposure mode and are therefore a key component of the overall
aquatic exposure scenario confidence." Based on available data, and
other considerations relating to the estimation of rates of discharges
from various facilities - including outdated stream flow data in E-
FAST, some of which are decades old - EPA was over-generous in
assigning a "moderate" confidence in wastewater discharge
estimates.
EPA applied a wastewater treatment removal rate of 81% to all indirect
releases, as well as to direct releases from wastewater treatment plants
(WWTPs). EPA did not establish that this assumed that removal
actually occurs, so EPA may be underestimating the total risk presented
by releases from these facilities.
EPA utilized national surface water monitoring
datasets from the WQP/WQX, as well as
published literature obtained and evaluated for
quality through a systematic review process.
Uncertainties underlying the modeling approach
are discussed in Section 2.2.6.3.
EPA has corrected the footnotes to state that the
81% removal rate was applied to indirect releases
only. The supplemental file [Aquatic Exposure
Modeling Outputs from E-FAST] demonstrates
than 0% removal is applied to numerous WWTP
or POTW facilities, if they were categorized as
direct releasers. The WWR% of 81% was
applied, when appropriate, to volumes
characterized as being transferred off-site for
treatment at a water treatment facility prior to
discharge to surface water. A WWR% of zero
was used for direct releases to surface water
because the release estimates are based on
estimated release (post-treatment).
Physica
-chemical properties are not valid or complete
56, 108
PUBLIC COMMENTS:
EPA reported that the organic carbon:water partition coefficient (log
Koc) for TCE ranged between 1.8 and 2.17, which generally suggests
that soil and sediment sorption of TCE is low. Other EPA sources cite a
moderately higher log Koc of 2.4, and note that in practice, "[mjeasured
partition coefficients, however, may be considerably higher than
calculated values, especially at lower aqueous concentrations." TCE
partitioning in the environment is affected by more than just organic
carbon, and there are numerous sorption studies for TCE. One such
study, conducted at the Savannah River Site, noted that measured soil
Although the log Koc indicates that TCE will
partition to sediment organic carbon, organic
matter typically comprises 25% or less of
sediment composition (e.g.,
httos://oubs.us8s.8ov/of/2006/1053/downloads/od
f/of- 1 of which approximately 40-
60%) is organic carbon (Schwarzenbach et al..
2003). Based on these values, the sediment-water
Kd (where Kd = K oc *f oc) is expected to be
Page 19 of 408
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distribution coefficient values for TCE were "60 to 100 times higher
than those estimated based on [sediment organic fraction] and KOC."
The predicted value that EPA relies on for TCE associated with soil
could well underestimate what is actually present.
equal to or less than 9.5, indicating that at
equilibrium, concentrations in sediment would be
expected to be less than 10 times higher than in
porewater. For a log K oc of 2.4 concentrations in
sediment would be expected to be less than 38
times higher than in porewater. In either case
TCE is expected to be in sediment and pore water
with concentrations similar to or less than the
overlying water due to partitioning to organic
matter in sediment and biodegradability in
anaerobic environments. Ecotoxicity from
ingestion of sediments was not quantitatively
evaluated.
Discussion of the partitioning of TCE between
sediment solids and pore water has been added to
Section 2.1.2 Summary of Fate and Transport.
In the case of spills or leaks of TCE, TCE may
sink in water and fill sediment pore space as a
dense non-aqueous phase liquid (DNAPL),
resulting in sediment concentrations many times
higher than would be predicted by partitioning to
sediment by TCE dissolved in water. However,
such spills and leaks from legacy disposal, as at
SRS, are not considered to be within the scope of
the risk evaluation.
SACC
SACC COMMENTS:
Recommendation: Explain why estimated Koc values are used in place
of measured values.
There are many experimentally derived estimates of TCE's sorption
coefficient that are available in the literature that show values ranging as
high as a log Koc of 4.2 (e.g., see Allen-King et al., 1997). Committee
EPA's literature search for environmental fate
properties did not identify any studies measuring
Koc thus systematic review was not performed
for the endpoint. There are two Koc-estimation
methods included in the EPI Suite KOCWIN
Page 20 of 408
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members questioned why a predicted value of log K0c is used when
there are experimentally derived values available.
module. The value produced by the molecular
connectivity index (MCI) method was presented
in the draft risk evaluation and is somewhat less
than the value estimated using the regression
from log Kow (log Koc = 2.1 by log Kow and 1.8
by MCI).
Table 2-1 has been edited to present both
estimated log Koc values.
SACC
SACC COMMENTS:
Recommendation: Include the range of physical-chemical properties
where multiple values are available.
It is not clear how the physical-chemical properties listed in Table 1-1
were selected over other values reported in the literature (many of
which are listed in the supplemental data) or why a range of values is
not provided. A range of physical-chemical properties should be
reported and used in the environmental fate modeling to determine how
sensitive the models are to the key chemical input properties.
Although the physical and chemical properties
selected for use in the TCE risk evaluation were
primarily drawn from the PhysProp database in
EPI Suite (U.S. EPA 2012b), those data were
selected from among the values collected from
the publicly-accessible Reaxys, ChemSpider,
STN/CAS, and PhysProp (integrated into EPI
Suite) databases and from data submitted to
EPA under the authority of various TSCA
sections. EPA used p-chem properties data from
studies with the highest Systematic Review data
quality evaluation scores for use in the Risk
Evaluation.
56, 108
PUBLIC COMMENTS:
The physical-chemical properties of TCE will lead to longer half-lives
in water than predicted by the Estimation Programs Interface Suite (EPI
Suite) volatilization module, which likely biases predictions of
concentrations in surface water to be artificially low. In its draft risk
evaluation, EPA reports the modeled volatilization half-life of TCE in a
model river will be 1.2 hours and the half-life in a model lake will be
110 hours. TCE is a dense non-aqueous phase liquid (DNAPL). In its
2014 TCE work plan risk assessment, EPA notes that TCE's "density
may cause it to sink in the water column, potentially increasing the
aquatic residence time of TCE." It further notes that the "|V|olatilization
A discussion of the uncertainty in the estimation
of TCE volatilization half-lives from water has
been added to section 2.1.3, Assumptions and
Key Sources of Uncertainty for Fate and
Transport in the final Risk Evaluation. Under the
conditions of use for TCE examined under this
final Risk Evaluation, it is not expected that TCE
would be found at concentrations greater than 1%
of its aqueous solubility, or 12,800 ug/L. Under
conditions in which TCE is present in surface
Page 21 of 408
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half-lives in an experimental field mesocosm consisting of seawater,
planktonic, and microbial communities ranged from 10.7 to 28 days,"
contrasting those values to measured "half-lives of evaporation from
laboratory water surfaces (distilled water) [that] have been reported to
be on the order of several minutes to hours, depending upon the
turbulence." This suggests that the volatilization half-life used by EPA
in this evaluation is too low. Even considering less-turbulent water
bodies (lakes), the half-life reported by EPA is one-half to one-fifth the
value of that found in natural conditions.
The density of TCE, coupled with its relatively low solubility,
indicates that sampling surface water using grab samples at the tops
of water columns will bias the analysis, resulting in artificially low
environmental concentrations. Such an approach to sampling may
not represent the actual concentrations of TCE found in surface
water.
water at concentrations of less than 1% of its
solubility, the physical and chemical properties of
TCE that lead to TCE's classification as a
DNAPL are not likely to increase the residence
time in surface water.
Mesocosm tests do not necessarily simulate the
turbulence in natural systems, and it would
therefore be expected that decreased rates of
volatilization would be observed under
mesocosm conditions where the effects of wind
velocity, water velocity, turbulence, and mixing
are not representative of environmental
conditions.
Fate assumptions/models are not valid or complete
SACC
SACC COMMENTS:
Recommendation: Modify the discussion on the lack of TCE in
biosolids based on the suitability of the analytical methods used in the
cited surveys.
The draft risk evaluation states that TCE is not anticipated to partition to
biosolids during wastewater treatment, reporting that TCE is not
detected in the Targeted National Sewage Sludge Survey (TNSSS) nor
is it reported in biosolids during EPA's Biennial Reviews for Biosolids,
a robust biennial literature review conducted by EPA's Office of Water
(U.S. EPA, 2019). The Committee noted that the methods used to
analyze the biosolids in these surveys are not suitable for TCE and that
the targeted analysis did not appear to specifically look for TCE.
During problem formulation EPA determined
risks would not be evaluated for land-applied
biosolids because based on fate properties, TCE
is not anticipated to partition to biosolids during
wastewater treatment. Any TCE present in the
water portion of biosolids following wastewater
treatment and land application would be expected
to rapidly volatilize into air.
In addition, TCE is not expected to
bioaccumulate in tissues, and concentrations will
not increase from prey to predator in either
aquatic or terrestrial food webs. Lastly, based on
the Guidance for Ecological Soil Screening
Levels ( 003a, b) document for terrestrial
wildlife, relative exposures associated with
47
PUBLIC COMMENTS:
Modeling based on physical and chemical properties and fate
parameters support the view that TCE is not expected to partition to
biosolids and sediment in sewage treatment plants. There is agreement
Page 22 of 408
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with EPA's draft risk evaluation to conduct no further analysis beyond
what was done in the problem formulation document for environmental
exposure pathways for land application of biosolids and sediment and
water or soil pathways for terrestrial organisms. Physical and chemical
properties confidently predict TCE will be mobile in soil and migrate to
water, or volatilize to air.
inhalation and dermal exposure pathways are
insignificant, even for volatile substances,
compared to direct ingestion and ingestion of
food (by approximately 1,000-fold). EPA has
added language to the final risk evaluation
document in Section 4.1.4 explaining this
rationale.
103
PUBLIC COMMENTS:
EPA should explain its approach to the assessment of the environmental
fate of TCE clarify the assumptions and limitations associated with
fugacity modeling. EPA's approach includes some measured data, as
well as estimates from EPI Suite. Fugacity models require detailed
understanding of the inputs in order to appropriately interpret the model
outputs. This is particularly challenging for the EPI Suite model due
to the setup of the interface.
Fugacity modeling should be conducted as a tiered process.
Multimedia models are available via the Chemical Properties
Research Group website, including Level I and Level II models, that
can provide access to the various inputs. EPA should provide more
detail regarding the inputs for fugacity modeling and explain
limitations associated with this information for the purposes of risk
assessment.
EPA should address the Science Advisory Committee on Chemicals
(S ACC) comments that the Level III fugacity model seemed to
indicate that TCE emissions to the air could ultimately result in
higher concentrations in the water. However, there are a number of
assumptions and limitations to the model. EPA should clarify these
assumptions and limitations in its final risk evaluation of TCE to
more fully explain why EPA's approach was appropriate.
Discussion of fugacity modeling has been added
to Section 2.1 Fate and Transport.
56, 108
PUBLIC COMMENTS:
Partition coefficients assume that chemical equilibrium has been
established. However, chemicals of concern can occur in high
concentrations in different environmental compartments prior to
During problem formulation EPA conducted a
screening level analysis to consider whether
pathways of exposure for sediment and terrestrial
Page 23 of 408
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reaching equilibrium. When considering an open, multi-media system, a
better approach for approximation might be the Level III Fugacity
model, which predicts that 9.9% of TCE will be distributed to soil,
36.8% to air, 53% to water, and the remainder (0.26%) to sediment, as
calculated using EPI Suite 4.11. A 10% percent distribution to soil
cannot be dismissed as de minimis.
organisms should be further analyzed and
determined that terrestrial organism exposures to
TCE was not of concern partially based on
estimates of soil concentrations from evaluated
COUs being several orders of magnitude below
concentrations observed to cause effects in
terrestrial organisms.
For sediment-dwelling organisms, during
problem formulation, EPA determined that an
insignificant portion of TCE is available to enter
the sediment compartment. Therefore, while the
sediment pathway was included, EPA did not
plan to further analyze exposure to sediment-
dwelling species, and in the draft risk evaluation,
sediment-dwelling organisms were only assessed
qualitatively. However, in response to SACC
comments a quantitative assessment of sediment-
dwelling organisms was added to the final TCE
risk evaluation in Section 4.1.3.
SACC
SACC COMMENTS:
Kinetics cannot be directly inferred from equilibrium properties. The
rate of volatilization depends on environmental conditions more than
equilibrium properties. Koc values are assumed to reflect equilibrium.
Sorption kinetics depend on the chemical and sorbent combination.
When considering exposure pathways, it is important to note that
movement between compartments goes both ways based on
equilibrium. For instance, movement from water to air is only true in
scenarios where air does not contain significant TCE concentrations.
Chemical kinetics are included in the Fugacity,
STPWIN, and Water Volatilization models which
use the two-film model to estimate the rate of
transfer between air and water. The two-film
model uses mass transfer coefficients with units
of meters per hour to account for the rate at
which chemicals move toward or away from the
air-water interface. The equilibrium coefficient
{i.e., Henry's Law Constant) is only used to
estimate the air or water concentration at the air-
water interface where equilibrium conditions
exist.
Page 24 of 408
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56, 108
PUBLIC COMMENTS:
The high volatility of TCE leads to air exposure through releases to soil
and water, not just through direct emissions to ambient air. When TCE
moves to the atmosphere, its half-life through degradation by reactants
in the atmosphere is nearly two weeks, which has led EPA to conclude
that "long range transport is possible." The logical conclusion is that
land-applied TCE and TCE-contaminated wastewater sent to treatment
facilities are likely an important source of air-exposures of TCE, which
EPA has not addressed.
This type of degradation will only occur in the atmosphere.
However, migration of TCE in soil does not always result in
volatilization to the atmosphere. EPA notes that, "in soil, TCE can
become associated with soil pore water, enter the gas phase..., or
exist as a nonaqueous phase liquid (NAPL). It is possible that
upward or downward movement of TCE can occur in each of these
three phases."
Page 25 of 408
For terrestrial organisms, during problem
formulation exposure pathways to these
organisms through water and biosolids were
within scope, but not further analyzed, because
physical-chemical properties do not support these
pathways. The land-applied biosolids pathway is
within the scope of the risk evaluation, but during
problem formulation EPA determined risks
would not be quantitatively evaluated for land-
applied biosolids because based on fate
properties, TCE is not anticipated to partition to
biosolids during wastewater treatment. Any TCE
present in the water portion of biosolids
following wastewater treatment and land
application would be expected to rapidly
volatilize into air. And the air exposure pathway
from biosolids and surface water are
insignificant. Based on the Guidance for
Ecological Soil Screening Levels (EPA 2003a.
b) document, for terrestrial wildlife, relative
exposures associated with inhalation and dermal
exposure pathways are insignificant, even for
volatile substances, compared to direct ingestion
and ingestion of food (by approximately 1,000-
fold). In addition, TCE is not expected to
bioaccumulate in tissues, and concentrations will
not increase from prey to predator in either
aquatic or terrestrial food webs. EPA has added
language to the final risk evaluation document in
Section 4.1.4 explaining this rationale.
Additionally, based on its vapor density (2.93
-------
relative to air) and atmospheric oxidation half-life
of 1 to 11 days (Table 2-1), TCE vapor may
accumulate under specific conditions, but
typically will disperse readily into the air. For
these reasons, the final risk evaluation does not
include further analysis of this pathway to
terrestrial species, and EPA was able to assess
risk based on qualitative analysis.
SACC
SACC COMMENTS:
According to one Committee member, EPA discounts the findings of
their own 2014 TCE Work Plan (p. 158, C-l-3). For example, the
environmental fate sections in that document state: "there are several
factors that can limit the aerobic biodegradation of TCE, including TCE
concentration, pH, and temperature. Toxicity of the degradation
products (e.g., dichloroethylene, vinyl chloride, chloromethane) to the
degrading microorganisms may also reduce the rates of biodegradation
of TCE in aerobic soils."
The rate of aerobic biodegradation is the key area
of uncertainty in the fate assessment for TCE. A
description of this has been added to the fate
section (2.1.3). Due to the differences among
study conditions, generating confidence intervals
for each property would be very complex.
However, the range and quality of available data
were considered in the fate assessment of TCE.
SACC
SACC COMMENTS:
The Committee continued to be concerned about the potential impact of
groundwater to surface water pathway to the evaluation. Members also
mentioned that landfill releases to surface water should be included
inasmuch as they derive from current uses of TCE. If the partitioning to
sediments and soil is considered minimal, then the risk to groundwater,
especially unregulated drinking water sources, must be objectively
determined. Furthermore, TCE-contaminated storm water must have
resulted from landfill and industrial use and should be assessed.
Landfill exposures were not included in the
environmental exposure conceptual model or
assessed because disposal of TCE via
underground injection, RCRA Subtitle C
hazardous waste landfills, RCRA Subtitle D
municipal solid waste (MSW) landfills, and on-
site releases to land from industrial non-
hazardous waste and construction/demolition
waste landfills are covered under the jurisdiction
of RCRA.
Because the drinking water exposure pathway for
TCE is covered in the SDWA regulatory
analytical process for public water systems, EPA
Page 26 of 408
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did not include this pathway in the risk evaluation
for TCE under TSCA.
SACC
SACC COMMENTS:
Recommendation: Include a diagram that displays pathway and rates
(e.g., biodegradation, exchange, discharge).
Members commented that the qualitative analysis is generally
adequate, but some members found this draft risk evaluation for
TCE less concise and more difficult to read than previous
evaluations.
An environmental fate diagram for TCE has been
inserted into section 2.1 Environmental Fate and
Transport.
SACC
SACC COMMENTS:
Recommendation: Include additional discussion on uncertainties for
exposure based on the potential for persistent exposure.
Based on the log Kow and predicted log K0c, EPA predicts limited
partitioning into biosolids. EPA states that this is confirmed with
TNSSS data (reference not provided in the draft risk evaluation),
which did not detect TCE. While a similar argument is made for
partitioning into sediments, there are no measured data to support
this qualitative estimate.
Additional text regarding uncertainties for the predictions is needed.
For example, EPA indicates that TCE would not bioaccumulate
based upon a log Kow of ~2. This value indicates that TCE would
partition into the organic phase 100 times more than in the aqueous
phase. If TCE is continuously discharged into aquatic systems,
"pseudo-persistent" exposure would occur because there is limited
aerobic biodegradation. While only 1% is predicted to be discharged
into surface water from EPI Suite, based on the production
volume and multiple detections observed in surface waters across
the United States, persistent exposure may be a possibility and
should be addressed as an uncertainty.
During problem formulation EPA determined
risks would not be evaluated for land-applied
biosolids because, based on fate properties, TCE
is not anticipated to partition to biosolids during
wastewater treatment. Any TCE present in the
water portion of biosolids following wastewater
treatment and land application would be expected
to rapidly volatilize into air. And the air exposure
pathway from biosolids and surface water are
insignificant. Based on the Guidance for
Ecological Soil Screening Levels (EPA 2003a,
b) document, for terrestrial wildlife, relative
exposures associated with inhalation and dermal
exposure pathways are insignificant, even for
volatile substances, compared to direct ingestion
and ingestion of food (by approximately 1,000-
fold). In addition, TCE is not expected to
bioaccumulate in tissues, and concentrations will
not increase from prey to predator in either
aquatic or terrestrial food webs. EPA has added
language to the final risk evaluation document in
Section 4.1.4 explaining this rationale.
Page 27 of 408
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For sediment-dwelling organisms, during
problem formulation, EPA determined that a
significant portion of TCE is available to enter
the sediment compartment. Therefore, while the
sediment pathway was included, EPA did not
plan to further analyze exposure to sediment-
dwelling species, and in the draft risk evaluation,
sediment-dwelling organisms were only assessed
qualitatively. However, in response to SACC
comments, a quantitative assessment of sediment-
dwelling organisms was added to the final TCE
risk evaluation in Section 4.1.3.
SACC
SACC COMMENTS:
Recommendation: Add confidence intervals to the estimate of
proportional removal and conduct a model sensitivity analysis to
determine if variability associated with the physical-chemical properties
would change EPA's fate assessment.
The draft risk evaluation states that the Sewage Treatment Plant
(STP) model in EPI Suite predicts 81% removal via volatilization
and 1% removal via sorption. It is further stated that TCE is not
reported in EPA's Biennial Review for Biosolids. The 81% removal
is used in subsequent modeling efforts without considering any
variability as is the 1% removal via sorption.
Due to the differences among study conditions,
generating confidence intervals for each property
would be very complex. However, the range and
quality of reasonably available data were
considered in the fate assessment of TCE.
For the TCE Risk Evaluation the STP model in
EPI Suite (U.S. EPA 2012b) was run usins the
assumption that TCE would not biodegrade
during aerobic treatment. Physical-chemical
properties input from table 1-1 were used. A
sensitivity analysis varying key physical-
chemical properties driving removal of TCE by
volatilization was also conducted. The results
indicated that a 25 percent increase in the value
of TCE vapor pressure, water solubility or Kow
input to the STP model made no more than a one
percent difference in removal of TCE by
volatilization or adsorption to activated sludge.
The 25 percent value was chosen to represent
hypothetical variability around the values of the
Page 28 of 408
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water solubility, vapor pressure and Kow input to
the STP model. Because the STP model output
changes very little when inputs vary around a
25% change in their values, a single removal
estimate was considered adequate for the purpose
of estimating removal in wastewater treatment.
SACC
SACC COMMENTS:
If release is to lake waters (110-hour half-life), is daily averaging an
appropriate measure of average water concentrations (there is an issue
of carry-over of the undegraded fraction from day one added to new
releases on day two)?
Some of the releasing facilities did discharge to
still water bodies such as lakes or bays, for which
surface water concentrations are estimated using
a dilution factor rather than a stream flow
distribution. However, the analysis did not
estimate or aggregate undegraded TCE day over
day. This has been added to the uncertainties
discussion in Section 2.2.6.3.
SACC
SACC COMMENTS:
There is no mention of the influence that TCE density has on
environmental fate. TCE density and partitioning to suspended
sediments means that TCE will deposit in bottom sediments, where it
may form a DNAPL. Density-dependent deposition to sediments is
acknowledged, but not considered in the draft risk evaluation.
EPA added discussion of uncertainty in
considering the influence of TCE density on
environmental fate in Section 2.1.3., Assumptions
and Key Sources of Uncertainty for Fate and
Transport.
SACC
SACC COMMENTS:
Wipe cleaning - uses towels, rags, paper - may end up in landfills.
What impact would there be, if any, from this slow release of TCE to
the environment?
Landfill exposures were not included in the
environmental exposure conceptual model or
assessed because disposal of TCE via
underground injection, RCRA Subtitle C
hazardous waste landfills, RCRA Subtitle D
municipal solid waste (MSW) landfills, and on-
site releases to land from industrial non-
hazardous waste and construction/demolition
waste landfills are covered under the jurisdiction
of RCRA.
Page 29 of 408
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Mass balance approach recommended
SACC
SACC COMMENTS:
Recommendation: Provide better mass balance analysis to determine
whether unaccounted TCE should be considered an environmental
release.
Most of the Committee discussed the desire for a "mass balance"
approach particularly for environmental exposure.
The problem formulation document (U.S. EPA, 2018) indicated that
recycling and disposal at 172 reporting facilities totaled 91,000,000
pounds. Yet the draft risk evaluation assesses only 52 pounds of
releases. It is scientifically indefensible to disregard 91,000,000
pounds of reported emissions from reporting facilities and base a
nationwide environmental risk assessment on 0.003% of the known
releases. Similarly, the Toxics Release Inventory (TRI) reported
91,000,000 pounds released is a fraction of the 172,000,000 pounds
used in commerce. Much of the remainder is unaccounted for.
Some Committee members noted the difficulty of assigning any
"unaccounted TCE" to a condition of use (COU). Other Committee
members emphasized that 83.6% of TCE manufactured/imported is
known to be consumed in the production of refrigerant 134a.
EPA's analvsis uses TRI (U.S. EPA 2017s) and
DMR (U.S. EPA 2016a) to estimate the highest
local per site water releases of TCE. EPA has
added a mass balance analysis as suggested to
Appendix R of the Risk Evaluation.
Based on use patterns for TCE, approximately
84% of manufactured and/or imported TCE is
consumed during manufacturing refrigerants.
108
PUBLIC COMMENTS:
EPA's risk evaluation lacks an adequate mass balance. EPA's draft
risk evaluations have failed to account for a chemical substance's
presence and flow at the different stages of its lifecycle. In the case
of TCE, over 170 million pounds of TCE are manufactured in or
imported into the United States annually, yet only about 2.2 million
pounds of TCE were identified as released to the air, water, and
land; the draft risk evaluation does not make clear where the rest of
it goes.
According to the Emergency Planning and Community Right-to-Know
act (EPCRA), mass balance is "an accumulation of the annual quantities
of chemicals transported to a facility, produced at a facility, consumed
at a facility, used at a facility, accumulated at a facility, released from a
Page 30 of 408
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facility, and transported from a facility as a waste or as a commercial
product or byproduct or component of a commercial product or
byproduct." While EPA relies on the Chemical Data Reporting (CDR)
and TRI to compile some estimates of these values, there are limitations
on both of those reporting schemes that result in an incomplete picture
of the chemical's lifecycle.
TCE concentrations in sediment pore water are/are not valid
47
PUBLIC COMMENTS:
EPA did not quantitatively assess exposure to sediment-dwelling
organisms because TCE is expected to remain in aqueous phases and
not adsorb to sediment due to its water solubility and low partitioning to
organic matter. Limited sediment monitoring data for TCE suggest that
TCE is present in sediments, but because of its relatively low partition
coefficient for organic matter and because it biodegrades slowly, 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 where anaerobic conditions prevail. Thus, TCE detected in
sediments is likely from the pore water. There is agreement with EPA's
assessment and decision not to further pursue characterizing risks due to
TCE exposure to sediment-dwelling organisms.
For sediment-dwelling organisms, during
problem formulation, EPA determined that an
insignificant portion of TCE is available to enter
the sediment compartment. Therefore, while the
sediment pathway was included, EPA did not
plan to further analyze exposure to sediment-
dwelling species, and in the draft risk evaluation,
sediment-dwelling organisms were only assessed
qualitatively. However, in response to SACC
comments a quantitative assessment of sediment-
dwelling organisms was added to the final TCE
risk evaluation in Section 4.1.3.
SACC
SACC COMMENTS:
The Committee noted that it appears likely that TCE pore-water
concentrations are similar to overlying water. The movement from
sediment is dependent upon the organic carbon content of the sediment.
With a predicted log K0c of ~2, the likelihood that TCE will be in
organic carbon is 100 times greater. The lack of detected TCE in
sewage sludge, which has high concentrations of organic carbon,
suggests that partitioning into pore water does occur even with this log
Koc.
Although the log Koc indicates that TCE will
partition to sediment organic carbon, organic
matter typically comprises 25% or less of
sediment composition (e.g.,
https://pubs.usss.sov/of/2006/1053/downloads/pd
f/of-2006-1053.Ddf) of which approximately 40-
60% is orsanic carbon (Schwarzenbach et al..
2003). Based on these values, the sediment-water
Kd (where Kd = KOC*fOC) is expected to be
equal to or less than 9.5, indicating that at
equilibrium, concentrations in sediment would be
expected to be less than ten times higher than in
Page 31 of 408
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porewater. However, the porewater interacts with
overlying surface water from which TCE may be
lost via volatilization. Thus, concentrations in
sediment and pore water are expected to be equal
to or less than concentrations in overlying water.
A narrative to this effect has been added to the
final risk evaluation (Section 2.1)
EPA should obtain/use measured data on TCE levels in sediments
56, 108
PUBLIC COMMENTS:
EPA has ignored STORET data available for evaluating sediment
impacts. As a DNAPL, TCE is likely to be present in the sediment, at
the bottom of a water column. In its problem formulation EPA noted
that the STORET database would be examined for recent data on TCE
levels in sediment. However, these data are absent from the draft risk
evaluation. A review and analysis of data reported in the National Water
Quality Monitoring Council database of Water Quality Data for TCE in
sediment (above detection) in the last 10 years resulted in 21
quantifiable analyses of TCE in sediment; the maximum detected
concentration was 26,000 (J,g/kg.
EPA overlooked these data, which are environmentally relevant and
describe measured impacts to environmental systems, simply
because of its assertion that TCE "is not expected to accumulate in
sediments."
STORET data showing detections in 6% of
samples was analvzed bv (Staples et al 1985),
and summarized by ATSDR, which stated that
the median concentration measured in sediment
was < 5 (J,g/kg (dry weight), equivalent to 5 ppb,
which is more than 2 orders of magnitude below
the chronic (920 ppb) and acute concentration of
concern (COC) (2,000 ppb) values estimated for
sediment invertebrates by read-across from COCs
reported for aquatic invertebrates.
Although the log Koc indicates that TCE will
partition to sediment organic carbon, organic
matter typically comprises 25% or less of
sediment composition
(e.g., httDs://Dubs.usss.sov/of/2006/1053/downlo
ads/pdf/of-2006-1053.pdf) of which
approximately 40-60% is organic
carbon (Schwarzenbach et al.. 2003). Based on
these values, and using a log Koc of 1.8 the
sediment-water Kd (where Kd =
Koc*/oc) is expected to be equal to or less than
9.5, indicating that at equilibrium, concentrations
Page 32 of 408
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in sediment would be expected to be less than ten
times higher than in porewater. However,
biodegradation can be expected to be rapid in
anaerobic sediments and the porewater also
interacts with overlying surface water from which
TCE may be lost via volatilization and/or aerobic
biodegradation. Thus, concentrations in sediment
and pore water are expected to be equal to or less
than concentrations in overlying water. A
narrative to this effect has been added to the final
risk evaluation (Section 2.1).
SACC
SACC COMMENTS:
Recommendation: Consider obtaining measurements of TCE in
sediments near release sites.
The draft risk evaluation does not consider the fact that a K0c of
between 60 and 126 demonstrates higher TCE concentrations in
sediment than in water for all situations where sediment organic
carbon (OC) is 0.8-1.6% of the water mass. Sediments most often
have OC content much higher than 1.6%. These values are relatively
simple to obtain from the USGS or from direct measurements in
sediments near discharging facilities.
The draft risk evaluation seems to assume that all systems are at
thermodynamic equilibrium and that kinetics do not exist. Water in
sediment (i.e., pore water) and overlying water can only be at
equilibrium with high turbulence and at significant distance
downriver from inflow. In sediments of rivers with low turbulence,
only the first few centimeters of sediment are in equilibrium with
overlying water. There is virtually no advection between stationary
sediment and water. So, once TCE-laden sediments are deposited,
the TCE is less likely to partition back into water than might be
predicted in ideal situations. Measurements of TCE in sediments
near commercial releases are needed.
A Committee member noted that the partition coefficient from
Although the log K0c indicates that TCE will
partition to sediment organic carbon, organic
matter typically comprises 25% or less of
sediment composition (e.g.,
https://pubs.usss.sov/of/2006/1053/downloads/pd
f/of-2006-1053.Ddf) of which approximately 40-
60% is orsanic carbon (Schwarzenbach et al.,
2003). Based on these values, the sediment-water
Kd (where Kd = K0c *f oc) is expected to be equal
to or less than 9.5, indicating that at equilibrium,
concentrations in sediment would be expected to
be less than 10 times higher than in porewater. A
narrative to this effect has been added to the final
risk evaluation, in a subsection of Section 2.1.
STORET data showing detections in 6% of
samples was analvzed bv (Staples et al.. 1985),
and summarized by ATSDR, which stated that
the median concentration measured in sediment
was < 5 (J,g/kg (dry weight), equivalent to 5 ppb,
which is more than 2 orders of magnitude below
Page 33 of 408
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measured data (U.S. EPA, 1977) shows field measured partition
coefficients of 0.076 and 0.32 when using geometric mean and
arithmetic mean concentrations in water and sediment media,
respectively. The draft risk evaluation should justify that 0.32 (32%)
represents low partitioning to sediments.
The review of available data raised questions regarding the extent to
which TCE may be present in sediments, yet no monitoring studies
have been conducted to refute the available data. This means that
the draft risk evaluation erroneously states that "review and
evaluation of reasonably available information on TCE confirmed"
problem formulation conclusions.
the chronic (920 ppb) and acute concentration of
concern (COC) (2,000 ppb) values estimated for
sediment invertebrates by read-across from COCs
reported for aquatic invertebrates.
Considerations of TCE either as a degradant/byproduct or degradants/byproducts of TCE
SACC,
56, 108
SACC COMMENTS:
Recommendation: Include available information on specific
degradation/hydrolysis substances in the draft risk evaluation.
Several sections of the draft risk evaluation state that anaerobic
biodegradation of TCE is rapid. The Committee noted that this is
not always the case, and in many situations, toxic biodegradation
intermediates are formed, including dichloroethylene and vinyl
chloride. Atmospheric photolysis via the hydroxyl radical (OH) also
can result in the formation of chloroform and other chlorinated
byproducts (Itoh et al., 1994).
PUBLIC COMMENTS:
EPA concluded that the rate of anaerobic biodegradation is "fast."
Under ideal conditions with correct microbial consortia that carry the
metabolic capability to reductively dehalogenate TCE to ethene, this
conclusion is valid; however, there are important caveats. EPA
acknowledges that there is inherent variability in the reported
biodegradation rates, yet still concludes that the "weight of evidence
shows the anaerobic biodegradation in anaerobic condition is fast."
Biologically mediated processes that transform compounds cannot
be assumed to lead to complete removal of a compound. Under
anaerobic conditions, TCE biologically degrades via sequential
EPA removed the characterization of anaerobic
biodegradation as "fast," instead noting that
anareobic biodegredation occurs.
In anaerobic environments, TCE biodegradation
products include potentially hazardous substances
including trichloroethylene, dichloroethene and
vinvl chloride (Vosel and McCartv, 1985).
Page 34 of 408
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removal of chloride ions first to cis-dichloroethene, and next to
vinyl chloride, which is itself a potent carcinogen. Vinyl chloride
degradation to ethane (under anaerobic conditions) is often the rate-
limiting step in this transformation, as it is mediated by a select
group of microorganisms. As the rate4imiting step, there are many
documented cases of stalled TCE-degradation, which has led to
elevated vinyl chloride concentrations in the environment -
arguably a condition as bad as or worse than TCE alone.
Where TCE is discharged into the environment, simply reporting
standard biodegradation rates can obscure important impacts due to
transformation processes.
EPA should consider legacy uses
98
PUBLIC COMMENTS:
EPA should consider the legacy risks and exposures posed by TCE. To
fulfill its statutory mandate, EPA must consider all forms of TCE's use
and disposal. Failure to do so results in an incomplete accounting of the
risks of injury TCE presents. Legacy exposure contributes to the rate of
background exposure to individuals, and may result when people live or
work in environments that contain legacy chemicals as well as when
legacy disposals cause individuals to come into contact with a chemical
substance through the air, water, or another exposure pathway.
Cumulative exposures, including legacy exposures, increase the health
risks faced by individuals and place a greater burden on subpopulations
that have heightened sensitivity to TCE or face especially high
exposures to it.
Legacy exposures to TCE are of particular concern in New York
City due to the presence of TCE in detectable quantities in soil
vapor and groundwater in many locations. The extent of exposure
may be substantial in certain New York City neighborhoods given
the vast historical use of this compound, its relative persistence in
anaerobic conditions, and the variable age and condition of New
York City buildings.
The use of TCE in the past are not "legacy" uses.
As described in EPA's Risk Evaluation Rule (82
FR 33726 (July 20, 2017)), a legacy use is an
ongoing use of a chemical substance in a
particular application where the chemical
substance is no longer being manufactured,
processed, or distributed in commerce for that
application. The example provided in the Rule is
insulation, which may be present in buildings
after a chemical substance component is no
longer being made for that use.
EPA has evaluated disposal as a condition of use
and determined that it presents an unreasonable
risk of injury to health. EPA has determined that
general population exposures due to drinking
water contamination, groundwater contamination,
and air emissions are under the jurisdiction of
other statutes administered by EPA and are
outside the scope of this risk evaluation. In
104
PUBLIC COMMENTS:
Page 35 of 408
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EPA is urged to consider the impacts of legacy use of TCE on tribal
populations. The Ninth Circuit Court of Appeals ruled that EPA can no
longer exclude "legacy" chemical uses from a risk evaluation, nor can it
exclude any COUs from consideration. It also affirmed that the Toxic
Substances Control Act (TSCA) "definition of 'conditions of use'
clearly includes uses and future disposals of chemicals." Legacy use of
products containing TCE was not considered in this draft risk
evaluation. In order to accurately address the risks that TCE may pose
to human health and the environment, environmental releases from
unlined landfills containing it have to be evaluated. Not considering
such environmental releases and the risks that they pose
disproportionately affects tribes' exposures, in this case due to the
unique disposal circumstances on tribal lands and in tribal communities.
Page 36 of 408
exercising its discretion under TSCA section
6(b)(4)(D) to identify the conditions of use that
EPA expects to consider in a risk evaluation,
EPA believes it is important for the Agency to
have the discretion to make reasonable,
technically sound scoping decisions.
EPA did not include legacy disposals, {i.e.,
disposals that have already occurred), because
they do not fall under the definition of conditions
of use under TSCA section 3(4).
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2. Environmental Exposure and Releases
Kn\ ironmenlal Kxposure and Releases
Charge Question 2.1: Please comment on the approaches, models, and data used in the water release assessment including
comparison of modeled data to monitored data (Section 2.2).
Charge Question 2.2.: Please provide any specific suggestions or recommendations for alternative data or estimation methods,
including modeling approaches, that could be considered by EPA for conducting or refining the water release assessment and
relation to monitored data (Section 2.2).
#
Summary ol*Comments lor Specific Issues Related to Charge
Question 2
KPA/OPPT Response
Concerns with release modeling or comparison of model results to monitoring data
SACC
SACC COMMENTS:
Recommendation: Compare model estimates with values from
municipal wastewater or National Pollutant Discharge Elimination
System (NPDES) discharge data from industrial wastewater treatment
facilities to determine model sensitivity.
Modeling estimates were obtained from E-FAST using data compiled
from TRI, DMR, and CDR. A probabilistic dilution module is then used
to estimate surface water concentrations in freshwater streams and still
water systems.
Several Committee members indicated that it is unclear how these
data are used in the model. For example, it is uncertain how NPDES
data from DMR are used. Based upon the draft risk evaluation, it
seems that the only data compiled from DMR are dilution data. It is
unclear why monitoring data for TCE in wastewater effluent was
not obtained from NPDES. It seems that only the 10th percentile
value of stream dilution is used from DMR and is considered a
conservative estimate.
The Committee found it unclear why the upper end conservative
(i.e., 90th percentile) of E-FAST values are not used or why effluent
values are not used. In fact, it appears that municipal wastewater
measurements are excluded from the water quality exchange
(WQX) measured data.
NPDES reporting data from DMR were not
used for dilution factors in modeling. NPDES
data were used for many releasing sites as the
bases for the annual loading/release volumes
that serve as the key inputs for the aquatic
exposure model. Surface water concentrations
are estimated using loading volumes (not
effluent concentrations) with receiving water
body stream flow.
E-FAST ( ) surface water
concentrations described as 10th percentile are
the more conservative values. These are based
on low-end (10th percentile) stream flow
distributions for sites modeled using industry-
specific stream flow distributions rather than
known or estimated stream flow for a specific
site. Therefore, use of the 10th percentile stream
flow for receiving water bodies results in more
conservative surface water concentration
estimates for use in risk characterization.
Surface water monitoring data from WQP were
Page 37 of 408
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Concerns were expressed on the use of a model that is specifically
designed for runoff scenarios, but spills and runoff are excluded
from the draft TCE risk evaluation.
There is a lack of clarity regarding references to concentrations. For
example, the range of measured surface water concentrations near
facilities reported as 0.4-477 parts per billion (ppb) is not the
observed concentration range. The observed range is -0.05-9090
|ig/L. As such, the text is misleading as written.
One Committee member thought that the approaches followed by
EPA to assess water releases seemed adequate. This member
thought that the draft risk evaluation did a good job in highlighting
the limitations and uncertainties of the assessment. For instance, the
TRI data are probably the best source for mass flows, but given its
inherent limitations (e.g., excluding companies with less than 10
full-time employees, minimum thresholds, potential
underreporting), the Committee suggested that this is likely to be an
underestimation of loading.
considered relevant for comparison with the
modeled surface water concentrations in water
bodies.
E-FAST (U.S. EPA 2014c) and its underlying
models and equations have been peer reviewed
and used to estimate surface water
concentrations resulting from industrial point
source releases for many years.
The highest reported measured concentration
level from Table 2-11 is 447|ig/L, while the
highest estimated/modeled concentration
exceeds 9,000 |ig/L (Tables 2-7 through 2-9,
Appendix C). EPA has edited the titles of
Tables 2-7 through 2-9 to clarify that these
concentrations are estimated and not measured.
EPA appreciates the feedback and this point
related to potential underestimations based on
TRI's minimum reporting thresholds is
discussed in Section 2.2.6.3.
SACC
SACC COMMENTS:
Recommendation: Compare E-FAST advantages and disadvantages
with other models.
In Section 2.2.3, the advantages of using EPA's E-FAST are listed.
Several Committee members thought that to be fair to readers, at least
one disadvantage to using this tool for everything should be listed. For
example, using a model that does not consider the fate of the chemical
is problematic. Members wondered if other models could be compared
to the E-FAST results.
E-FAST does not estimate stream concentrations based on the
potential for downstream transport and dilution. This implies that E-
Section 2.2.6.3 discusses the uncertainties
associated with using E-FAST in this
evaluation, including the disadvantages noted.
EPA states "E-FAST 2014 estimates surface
water concentrations at the point of release,
without post-release accounting for
environmental fate or degradation such as
volatilization, biodegradation, photolysis,
hydrolysis, or partitioning." In light of this
shortcoming, EPA has conducted additional
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FAST is acceptable for near-field environmental concentration
estimation but not acceptable for estimating downstream
concentrations, which are the bulk of environmental measurements.
E-FAST stream flow data are 15-30 years old. The draft risk
evaluation needs more recent data (last 10 years) to significantly
decrease uncertainty.
Page 39 of 408
fate analysis for two sites with chronic COC
(920 |ig/L) exceedances (See Section 4.3.1 and
2.2.6.3). EPISuite fugacity modeling using
W VOL WIN was conducted to inform the
degree to which volatilization may impact the
modeled stream concentrations estimated in E-
FAST (U.S. EPA 2014c). Parameters (wind
speed, current speed, and water depth)
reflective of two releasing sites with the highest
predicted surface water concentrations (Praxair
Technology Center in Tonawanda, NY and
NASA Michoud in New Orleans, LA; see Table
4-1) were used to estimate TCE volatilization
half-lives, which varied from one day to more
than 10 years. The effect of volatility on
estimating instream concentrations is expected
to be highly variable and site-specific
depending on stream flow and environmental
conditions. For discharges to still, shallow
water bodies, E-FAST estimates are less likely
to overestimate surface water concentrations, as
TCE is predicted to have a long half-life in such
still water bodies. For discharges to faster-
flowing, deeper water bodies, E-FAST
estimates may inadequately reflect instream
volatile losses expected within the timeframe of
one day. Given this variation and the predicted
half-life of TCE in flowing water bodies, E-
FAST surface water concentrations may best
represent concentrations found at the point of
discharge.
In Section 2.2.6.3, EPA addresses this point by
-------
stating "Additionally, E-FAST does not
estimate stream concentrations based on the
potential for downstream transport and dilution.
These considerations tend to lead to higher
predicted surface water concentrations.
Dilution is incorporated, but it is based on the
stream flow applied. Therefore, there is
uncertainty regarding the level of TCE that
would be predicted downstream of a releasing
facility or after accounting for potential
volatilization from the water surface, which is
dependent on the degree of mixing in a
receiving water body."
The assumptions and uncertainties of the stream
flow dataset within E-FAST, including the old
age of the data, are discussed in Section 2.2.6.3.
Uncertainty in release estimates
SACC
SACC COMMENTS:
One Committee member thought that Table 2-10, although not a full
uncertainty assessment, provides a good sense of the potential
uncertainty through presenting data ranges and standard deviations.
EPA appreciates the feedback.
SACC
SACC COMMENTS:
Recommendation: Discuss the potential uncertainties of other
wastewater treatment processes (e.g., aeration), particularly with
volatile chemicals.
The estimated percent removal from wastewater treatment is based
on a specific kind of industrial wastewater treatment facility
(IWTF). Variation in types of IWTFs (sludge [dewatering],
chemical, biological [aerobic, anaerobic, composting], physical
[screening, sedimentation, skimming]) that manufacture or process
TCE should be discussed. This is particularly important because
aeration is typically used in secondary treatment. At a minimum, a
Possible uncertainties in the WWTP removal
estimates include confidence in the physical-
chemical properties, the range of reported
aerobic biodegradation rates, and variation in
performance among wastewater treatment
plants. The physical-chemical properties
reported in Table 1-1 and used in the STPWIN
model are reported in high-quality data sources
and align with expected values for TCE, and
thus are of high-confidence. The uncertainty in
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range of estimated removal percentages (or a confidence interval
around the estimate of percent removal) should be provided.
biodegradation rates is discussed in Section
2.1.3, and TCE removal from wastewater by
biodegradation was assessed to range from
negligible to complete depending on the
conditions in a given WWTP. The TCE
removal performance may vary among WWTP,
but the STPWIN model is designed to estimate
removal from a model, conventional WWTP.
The removal estimated by STPWIN for abiotic
processes alone is 81%.
Geospal
ial/geographic analysis of releases concerns
SACC
SACC COMMENTS:
Several Committee members expressed concerns about the
geospatial analysis approach. If the geospatial analysis finds a
Superfund site within 1-5 miles of the facility, then the draft risk
evaluation indicated that those monitoring sites were excluded.
One Committee member was uncertain how Department of Defense
(DOD) facilities that use TCE are treated. Of additional concern
would be the possibility that the DOD facility also included a
Superfund site. This member also had concerns for situations where
the monitoring site is downstream (down slope) of the TCE use
facility but upstream (up slope) from the Superfund site.
In Section 2.2.6.2.3, EPA states that the
monitoring stations co-located with facilities in
the same HUC in the 2016 set were also
examined for proximity to Superfund sites;
however, no Superfund sites were identified
within five miles of these sites. While
monitoring data from WQP/WQX clearly
associated with superfund sites were not
included in the monitoring data summary in
Table 2-10, superfund sites were still
considered in the GIS analysis to identify
whether any of the observed concentrations
may be associated with superfund sites rather
than the scoped COUs.
Facilities modeled were based on the scoped
COUs and Occupational Exposure Scenarios
(OES). Release sites were not excluded from
the release and exposure assessment unless they
were deemed not to fall within the scope of this
evaluation.
Page 41 of 408
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SACC
SACC COMMENTS:
Geographic coordinates (p. 90): One Committee member thought that
location of release points is needed rather than the "address" of the
facility or the "front door" of the Superfund site. This member thought
that the geographic analysis sounded quite cursory even though it is a
screening analysis. This member also thought that incorporating land
slope, Superfund site boundaries, and facility discharge points would
not be that much extra work.
EPA appreciates the feedback on its GIS
analysis in this evaluation and will consider
how to make such analyses more robust.
SACC
SACC COMMENTS:
Geographic information systems (GIS) work has not been validated
through ground truthing.
Release data and data presentation concerns
SACC
SACC COMMENTS:
Recommendation: Add a few explanatory paragraphs immediately after
the concept of "cleansed data set."
Several Committee members pointed out that in the beginning of
Section 2.2.6.2.2, it was unclear what 'cleansed data sets' means.
The Committee recommended enhancing the clarity with a quick
reminder of the definition, given the length of the overall report.
EPA has updated language in Section 2.2.4.2
and 2.2.6.2.2 to clarify what was meant by
"cleansed" dataset. Section 2.2.4.2 now reads
"The "Site data only" and "Sample results
(physical/chemical metadata)" files were linked
using the common field "Monitoring Location
Identifier" and then filtered to eliminate records
not relevant to the scope of the environmental
evaluation. Specifically, filtering was applied to
select the media of interest (i.e., surface water),
eliminate records that were quality control
samples (i.e., field blanks) or identified as
having analytical quality concerns (i.e., quality
control issues, sample contamination, or
estimated values), and eliminate records
associated with contaminated sites (i.e.,
Superfund)" Section 2.2.6.2.2 now refers to the
"filtered" dataset rather than "cleansed."
SACC
SACC COMMENTS:
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One Committee member thought that the state of active facility releases
and release characteristics should be reported in Section 2.2.2.2.2 or that
Section 2.2.2.2.2 text should be moved or cross-referenced to pp. 92 and
93.
EPA will investigate either referencing or
moving this information for improved clarity in
future risk evaluations.
SACC
SACC COMMENTS:
Table 2-10: One Committee member indicated that with such a high
fraction of non-detect (ND) levels, the average is likely an overestimate
of central tendency while standard deviation is likely an underestimate
of variability. The member noted that in all years, the average of
detections is less than the average of all data, suggesting that there are a
lot of NDs from sites where the detection level is closer to 5 than to
0.022.
EPA added language addressing this point in
the uncertainties discussion in Section 2.2.6.3.
SACC
SACC COMMENTS:
A Committee member commented that the estimates of release days
(Section 2.2.2.2.2.3) are really assumptions, not estimates. There are no
data on exactly how these facilities operate.
'Footnote a' to Table 2-2 assumes 260 days of operation per year in
assessing annual releases from TRI and DMR data. But Appendix I
apparently assumes and justifies the use of 350 operating days per
year (see 'footnote c' to Table Apx 1-2). The number of operating
days that form the basis for the range of manufacturing estimated
daily releases reported in Table 2-2 is not reported and is not clear in
the associated text. Appendix I discusses the approach to estimating
water releases from manufacturing sites using effluent guidelines in
the situation where TRI and DMR data were not available or where
TRI and DMR data did not sufficiently represent releases of TCE to
water for a COU.
It would be useful to know what fraction of manufacturing sites had
water releases that were estimated by this approach and what
fraction used monitoring data directly. Similarly, it would be useful
to know what fraction of processing facilities under each COU were
represented by estimates and which by monitoring data. This has
direct relevance on the uncertainty that would be assigned to the
EPA assessed releases from TCE
manufacturing sites at 350 days per year based
on assuming seven days per week and 50 weeks
per year with two weeks per year for shutdown
activities which is consistent with the
information provided in Appendix I. Release
days per year for other OES are discussed in
Section 2.2.2.2.3. Footnote a refers to vapor
degreasing OES.
Information on release estimations versus
monitoring data for manufacturing sites (as well
as all other OES sites) are available in the
Supplemental Information File: Environmental
Releases and Occupational Exposure
Assessment.
Appendix I is meant to illustrate how releases
were calculated for TCE manufacturing sites
Page 43 of 408
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range of estimates reported in Table 2-2 (this table should refer to
Table 2-4 for clearer description of assumption on release days).
Difficulty justifying pounds per day values in Table 2-2 with
kg/site-day estimates presented in Appendix I.
'Footnote a' to Table 2-2 justifies using the Open Top Vapor
Degreasers (OTVD) range of water releases for multiple other
degreasing, cleaning, and metalworking applications because
"releases were estimated using TRI and DMR data." This sounds
less like a justification than an acknowledgement that there are only
reliable water release data for larger OTVD operations.
where monitoring data were not available. The
pounds per day values can be verified in the
Supplemental Information File: Environmental
Releases and Occupational Exposure
Assessment.
The days of water releases from all vapor
degreasing OES were based on the 2017 ESD
on the Use of Vapor Degreasing as shown in
Table 2-4.
SACC
SACC COMMENTS:
Recommendation: Incorporate an estimate for releases from all facilities
that are likely to use TCE but that do not report TRI data.
Several Committee members recommended that EPA should
incorporate an estimate for releases (via maximum likelihood,
censored regression, or equivalent; see Helsel, 1990 and Helsel,
2005) from approximately 68,400 facilities that are likely to use
TCE but that do not report TRI data. This approach uses the
distribution of known observations to predict the unknown
observations (non-detects). The draft risk evaluation lists 68,600
potential or likely users (Table 2-3). EPA states that reports are
available from 183 facilities and 8 WWTPs. Data from these
locations could be used to develop a population distribution that
could be used to estimate total releases from all facilities.
EPA's analysis uses TRI (U.S. EPA 2017a)
and DMR (U.S. EPA 2016a) to estimate the
highest local per site water releases of TCE.
EPA has added a mass balance analysis as
suggested to Appendix R of the Risk
Evaluation.
SACC
SACC COMMENTS:
Recommendation: To be conservative, high percentile estimates of
releases should be used anytime monitoring data are not available.
Several Committee members indicated that the exclusion of spills is
inappropriate as spills result from TCE uses in commerce. One
Committee member expressed concern that this decision is
unprotective (e.g., not appropriately conservative).
The impact of spills needs to be discussed. Several of the National
Spills and leaks generally are not included
within the scope of a TSCA risk evaluation
because in general they are not considered to be
circumstances under which a chemical
substance is intended, known or reasonably
foreseen to be manufactured, processed,
distributed, used, or disposed of. To the extent
there may be potential exposure from spills and
Page 44 of 408
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Institute for Occupational Safety and Health (NIOSH) Health leaks, EPA is also declining to evaluate
Hazard Evaluations (HHE) report that workers are concerned about environmental exposure pathways addressed by
the impact of spills and cleanup and that those are reported as other EPA-administered statutes and associated
associated with headaches, dizziness, and other symptoms. regulatory programs.
First, EPA does not identify TCE spills or leaks
as "conditions of use." EPA does not consider
TCE spills or leaks to constitute circumstances
under which TCE is manufactured, processed,
distributed, used, or disposed of, within
TSCA's definition of "conditions of use."
Congress specifically listed discrete, routine
chemical lifecycle stages within the statutory
definition of "conditions of use" and EPA does
not believe it is reasonable to interpret
"circumstances" under which TCE is
manufactured, processed, distributed, used, or
disposed of to include uncommon and
unconfined spills or leaks for purposes of the
statutory definition. Further, EPA does not
generally consider spills and leaks to constitute
"disposal" of a chemical for purposes of
identifying a COU in the conduct of a risk
evaluation.
In addition, even if spills or leaks of TCE could
be considered part of the listed lifecycle stages
of TCE, EPA has "determined" that spills and
leaks are not circumstances under which TCE
is intended, known or reasonably foreseen to be
manufactured, processed, distributed, used, or
disposed of, as provided by TSCA's definition
of "conditions of use," and EPA is therefore
Page 45 of 408
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exercising its discretionary authority under
TSCA section 3(4) to exclude TCE spills and
leaks from the scope of the TCE risk
evaluation. The exercise of that authority is
informed by EPA's experience in developing
scoping documents and risk evaluations, and on
various TSCA provisions indicating the intent
for EPA to have some discretion on how best to
address the demands associated with
implementation of the full TSCA risk
evaluation process. Specifically, since the
publication of the Risk Evaluation Rule, EPA
has gained experience by conducting ten risk
evaluations and designating forty chemical
substances as low- and high-priority
substances. These processes have required EPA
to determine whether the case-specific facts
and the reasonably available information justify
identifying a particular activity as a "condition
of use." With the experience EPA has gained, it
is better situated to discern circumstances that
are appropriately considered to be outside the
bounds of "circumstances... under which a
chemical substance is intended, known, or
reasonably foreseen to be manufactured,
processed, distributed in commerce, used, or
disposed of' and to thereby meaningfully limit
circumstances subject to evaluation. Because
of the expansive and potentially boundless
impacts that could result from including spills
and leaks as part of the risk evaluation (e.g.,
due to the unpredictable and irregular scenarios
that would need to be accounted for, including
Page 46 of 408
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variability in volume, frequency, and
geographic location of spills and leaks;
potential application across multiple exposure
routes and pathways affecting myriad
ecological and human receptors; and far-
reaching analyses that would be needed to
support assessments that account for
uncertainties but are based on best available
science), which could make the conduct of the
risk evaluation untenable within the applicable
deadlines, spills and leaks are determined not to
be circumstances under which TCE is intended,
known or reasonably foreseen to be
manufactured, processed, distributed, used, or
disposed of, as provided by TSCA's definition
of "conditions of use."
Exercising the discretion to not identify spills
and leaks of TCE as a COU is consistent with
the discretion Congress provided in a variety of
provisions to manage the challenges presented
in implementing TSCA risk evaluation. See
e.g., TSCA sections 3(4), 3(12), 6(b)(4)(D),
6(b)(4)(F). In particular, TSCA section
6(b)(4)(F)(iv) instructs EPA to factor into
TSCA risk evaluations "the likely duration,
intensity, frequency, and number of exposures
under the conditions of use...suggesting
that activities for which duration, intensity,
frequency, and number of exposures cannot be
accurately predicted or calculated based on
reasonably available information, including
spills and leaks, were not intended to be the
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Page 48 of 408
focus of TSCA risk evaluations. And, as noted
in the preamble to the Risk Evaluation Rule,
EPA believes that Congress intended there to
be some reasonable limitation on TSCA risk
evaluations, expressly indicated by the
direction in TSCA section 2(c) to "carry out
[TSCA] in a reasonable and prudent manner."
For these reasons, EPA is exercising this
discretion to not consider spills and leaks of
TCE to be COUs.
Second, even if TCE spills or leaks could be
identified as exposures from a COU in some
cases, these are generally not forms of exposure
that EPA expects to consider in risk evaluation.
TSCA section 6(b)(4)(D) requires EPA, in
developing the scope of a risk evaluation, to
identify the hazards, exposures, conditions of
use, and potentially exposed or susceptible
subpopulations the Agency "expects to
consider" in a risk evaluation. As EPA
explained in the "Procedures for Chemical Risk
Evaluation Under the Amended Toxic
Substances Control Act" ("Risk Evaluation
Rule"), EPA may, on a case-by-case basis tailor
the scope of the risk evaluation "in order to
focus its analytical efforts on those exposures
that are likely to present the greatest concern,
and consequently merit an unreasonable risk
determination." 82 FR 33726, 33729 (July 20,
2017).
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Page 49 of 408
In the problem formulation documents for
many of the first 10 chemicals undergoing risk
evaluation, EPA applied the same authority and
rationale to certain exposure pathways,
explaining that "EPA is planning to exercise its
discretion under TSCA 6(b)(4)(D) to focus its
analytical efforts on exposures that are likely to
present the greatest concern and consequently
merit a risk evaluation under TSCA...." This
approach is informed by the legislative history
of the amended TSCA, which supports the
Agency's exercise of discretion to focus the
risk evaluation on areas that raise the greatest
potential for risk. See June 7, 2016 Cong. Rec.,
S3519-S3520.
In addition to TSCA section 6(b)(4)(D), the
Agency also has discretionary authority under
the first sentence of TSCA section 9(b)(1) to
"coordinate actions taken under [TSCA] with
actions taken under other Federal laws
administered in whole or in part by the
Administrator." TSCA section 9(b)(1)
provides EPA authority to coordinate actions
with other EPA offices, including coordination
on tailoring the scope of TSCA risk evaluations
to focus on areas of greatest concern rather than
exposure pathways addressed by other EPA-
administered statutes and regulatory programs,
which does not involve a risk determination or
public interest finding under TSCA section
9(b)(2). EPA has already tailored the scope of
this risk evaluation using such discretionary
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Page 50 of 408
authorities with respect to exposure pathways
covered under the jurisdiction of other EPA-
administered statutes and associated regulatory
programs (see section 1.4.2).
Following coordination with EPA's Office of
Land and Emergency Management (OLEM),
EPA has found that exposures of TCE from
spills and leaks fall under the jurisdiction of
RCRA. See 40 CFR 261.33(d) (defining in
part a hazardous waste as "any residue or
contaminated soil, water or other debris
resulting from the cleanup of a spill into or on
any land or water of any commercial chemical
product or manufacturing chemical
intermediate having the generic name listed [40
CFR 261.33(e) or (f)], or any residue or
contaminated soil, water or other debris
resulting from the cleanup of a spill, into or on
any land or water, of any off-specification
chemical product and manufacturing chemical
intermediate which, if it met specifications,
would have the generic name listed in [40 CFR
261.33(e) or (f)]"); 40 CFR 261.33(f) (listing
TCE as hazardous waste no. U080). As a
result, EPA believes it is both reasonable and
prudent to tailor the TSCA risk evaluation for
TCE by declining to evaluate potential
exposures from spills and leaks, rather than
attempt to evaluate and regulate potential
exposures from spills and leaks under TSCA.
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Releases from municipal landfills are regulated
under RCRA. As explained in more detail in
Section 1.4.2, EPA believes that coordinated
action on exposure pathways and risks
addressed by other EPA-administered statutes
and regulatory programs is consistent with
statutory text and legislative history,
particularly as they pertain to TSCA's function
as a "gap-filling" statute, and also furthers EPA
aims to efficiently use Agency resources, avoid
duplicating efforts taken pursuant to other
Agency programs, and meet the statutory
deadline for completing risk evaluations.
EPA does not expect exposure to consumers
from disposal of consumer products. It is
anticipated that most products will be disposed
of in original containers, particularly those
products that are purchased as aerosol cans. As
described in section 1.4.2 EPA is not evaluating
on-site releases to land from RCRA Subtitle D
municipal solid waste (MSW) landfills or
exposures of the general population from such
releases in the TSCA evaluation because they
are adequately addressed by other EPA statutes.
Disposal of household waste to municipal
landfills is covered under the jurisdiction of
RCRA as discussed in section 1.4.2.
SACC
SACC COMMENTS:
Recommendation: EPA should consider the impact on discharge
estimates of multiple facilities discharging to a single publicly-owned
treatment work (POTW).
The STPWIN model assumes an influent
concentration of 10 |ig/L flow at 1,000,000 L/hr
(6.3 millions of gallons per day) (Clark et al.,
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In evaluating Appendix P, one Committee member concluded that
releases from degreasing operations were estimated based on "best
practices" for OTVDs. Under this approach, 80% of wastewater is
released to a water treatment facility. If this assumption is made, the
Committee member concluded that aggregates from all commercial
users within a water treatment district could discharge to a single
POTW.
Data presented in the draft risk evaluation did not allow
determination of the extent to which multiple facilities were
discharging to a single facility and if the magnitude of any such
discharges would be essential to estimate high centile releases from
POTWs receiving TCE from multiple commercial users.
1995). This equates to 0.24 kg/day of TCE
entering the model treatment plant. The
estimated daily water releases reported in Table
2-2 of the Risk Evaluation ranged from 2.53E-
07 to 24.1 kg/site-day. Therefore, the STPWIN
model covers most of the estimated daily water
releases except for those at the higher range
which exceed the mass loading considered in
STPWIN. The maximum amount of TCE that
could be removed by volatilization is 100,000
kg/day, which is based on the 8960 g/m3 air
flow in the STPWIN model aeration. From this
analysis the STPWIN model predicted TCE
removal of 80% by volatilization likely covers
the aggregate discharge from multiple facilities.
SACC
SACC COMMENTS:
Recommendation: The Committee restated the need for robust
monitoring data to be used in exposure assessments.
One Committee member concluded that the hydrologic unit code
approach can be valuable if and only if assessments can show that
measurements at downstream monitoring sites are predictive of
discharges from upstream facilities. Otherwise, the Committee
member expressed concern that the approach is likely to underreport
TCE concentrations downstream of manufacturing facilities.
For this evaluation, EPA utilized data from the
Water Quality Portal (WQP), which integrates
publicly available US water quality data from
multiple databases: 1) the United States
Geological Survey National Water Information
System (USGS NWIS); 2) EPA's STOrage and
RETrieval (STORET); and 3) the United States
Department of Agriculture Agricultural
Research Service (USDA ARS) Sustaining The
Earth's Watersheds - Agricultural Research
Database System (STEWARDS). EPA also
conducted a full systematic review to identify
surface water monitoring data from peer
reviewed literature and grey literature sources.
EPA appreciates the feedback on its GIS
analysis and co-location analysis using HUCs.
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However, since modeled releases are site-
specific and associated with scoped COUs,
resultant surface water concentration estimates
may or may not be near or associated with
sampling sites with measured data from
national or peer reviewed data sources.
SACC
SACC COMMENTS:
Tables 2-7 to 2-9: Several Committee members thought that the
aqueous concentrations should be consistently expressed as mg/L.
Concentrations in Tables 2-7 through 2-9 are
now consistently expressed in |ig/L units,
aligning with units in Tables 2-10, and 2-11.
108
PUBLIC COMMENTS:
EPA appears to have made no significant effort to identify data on the
TCE in soil or sediment, available for example in EPA's STORET
database, which it used to obtain surface water data on TCE, despite the
fact that EPA does mention in passing that "[ljimited sediment
monitoring data ... suggest that TCE is present in sediments." EPA did
conduct such searches and located substantial amounts of data for
another chemical undergoing risk evaluation (methylene chloride).
There is every reason to believe that analogous data for TCE would
have been located had EPA conducted the same kinds of searches it did
for methylene chloride.
As shown in the conceptual model in Figure 1-
6, soil and land-applied biosolid exposure
compartments are indicated as being associated
with pathways not further analyzed based on
work done during problem formulation. The
systematic review process for identifying,
screening, and evaluating data was tailored
based on these decisions.
However, in response to SACC comments,
EPA added a quantitative assessment of
sediment-dwelling organisms using E-FAST
(U.S. EPA 2014c) results and aquatic
invertebrate data to the TCE risk evaluation in
Section 4.1.3.
Eco exposure pathways included are incomplete or not relevant
103
PUBLIC COMMENTS:
EPA should clarify the purpose of evaluating acute environmental risks.
Typically, acute environmental risks would be characterized to
represent a large, sudden environmental exposure such as a spill. The
COUs evaluated represent continuous, regular releases, which are
characteristic of a chronic exposure.
Acute environmental risks are considered
because there is uncertainty around the
frequency of environmental releases. The
assumptions were made that each facility would
release their total volume of TCE to surface
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water over 20 days and over a maximum
number of days (e.g., 260 days, 350 days
depending on the exposure scenario). Because
EPA does not know the exact number of days
over which the environmental release occurs,
EPA found it essential to assess acute
environmental risk.
108
PUBLIC COMMENTS:
EPA dismissed potential exposure based on land-applied biosolids (p.
90), stating that: "TCE was not detected in EPA's TNSSS, nor was it
reported in biosolids during EPA's Biennial Reviews for Biosolids.
(U.S. EPA, 2019d). However, our review of the cited document as well
as the TNSSS Sampling and Analysis Technical Report did not indicate
that TCE was included in the sample analysis, which calls into question
use of the biennial review as support for EPA's conclusions. TCE has
been detected in biosolids at concentrations as high as 8,770 |ig/kg.
A recent Office of Inspector General (OIG) report indicates EPA
"lacks the data or risk assessment tools" to make determinations on
the risk levels for pollutants found in biosolids. According to the
OIG, "[t]he regulations for biosolids do not require the EPA to
obtain the data necessary to complete risk assessments."
EPA states that "[u]sing reasonably available information,
exposures will be estimated (usually quantitatively) for the
identified conditions of use." EPA cannot prepare an accurate
quantitative estimate for exposure if EPA has excluded exposure
pathways. "For environmental evaluations specifically, EPA plans
to include a discussion of the nature and magnitude of the effects,
the spatial and temporal patterns of the effects, [and] implications at
the species, population, and community level" (82 Fed. Reg. at
33,743). EPA cannot accurately discuss the magnitude of the effects
on the environment or the spatial and temporal patterns of those
effects if EPA ignores the vast majority of the environmental
exposures, as EPA proposes to do.
EPA based its decision not to further evaluate
TCE exposure via land-applied biosolids in the
Risk Evaluation on fate properties; in particular,
TCE is not anticipated to partition to biosolids
during wastewater treatment. Any TCE present
in the water portion of biosolids following
wastewater treatment and land application
would be expected to rapidly volatilize into air.
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EPA did not conduct a significant analysis of biosolids in the draft
risk evaluation; EPA instead dismissed this pathway on the basis of
physical-chemical and fate properties of TCE. EPA should obtain
some monitoring data to confirm these analyses, but in any event,
EPA cannot rationalize ignoring exposures from biosolids on the
basis that TCE will enter the water and air and then also choose to
ignore the exposure pathways through water and air. EPA's
justification for ignoring the biosolids pathways for TCE highlights
that EPA's decision to ignore other pathways is particularly
arbitrary and capricious.
EPA should consider background releases to the environment
49, 99
56, 108
PUBLIC COMMENTS:
The draft ignores the human health implications of TCE releases to the
environment. TCE air emissions and contaminated groundwater,
drinking water, and soil are pervasive across the United States.
By considering only water releases, EPA ignored the 48,245 pounds
of TCE released on-site for land disposal. Updated TRI data from
2018 show that "other" TCE releases to land totaled nearly 157,000
pounds. This release appears to be from a single facility that seems
to have been discharging TCE to land for a number of years. It is
unclear how this facility is permitted for such a discharge.
EPA has given TRI and DMR data a "medium" confidence rating
due to potential underreporting. Hence, the data cited above likely
understate the extent of discharges of TCE to the environment.
For EPA to dismiss environmental impacts to soil and sediment
based on predicted environmental partitioning does not represent
consideration of the best available science or reasonably available
information.
EPA acknowledges that it did not consider
background exposure from the environment
that workers, ONUs, consumers, or bystanders
using products containing TCE might be
exposed to in addition to exposures from the
evaluated conditions of use. There is
insufficient information reasonably available
related to the likelihood of this scenario or the
relative distribution of exposures from each
pathway. This may result in an underestimation
of risk, and EPA acknowledges that risk is
likely to be elevated for individuals who
experience TCE exposure in multiple contexts.
Additional discussion of this issue has been
added to Sections 2.3.2.6.1, 2.3.2.2.1, and 4.4.2.
Emissions to ambient air from commercial or
industrial stationary sources, or inhalation
exposures of terrestrial species are covered
under the jurisdiction of the Clean Air Act
(CAA).
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The assumptions and uncertainties associated
with using TRI and DMR data sources, such as
limitations on required reporters, are discussed
in Sections 2.2.6.3 and 4.3.
For sediment-dwelling organisms, during
problem formulation, EPA determined that an
insignificant portion of TCE is available to
enter the sediment compartment. Therefore,
while the sediment pathway was included, EPA
did not plan to further analyze exposure to
sediment-dwelling species, and in the draft risk
evaluation, sediment-dwelling organisms were
only assessed qualitatively. However, in
response to SACC comments a quantitative
assessment of sediment-dwelling organisms
was added to the final TCE risk evaluation in
Section 4.1.3.
For terrestrial organisms, during problem
formulation exposure pathways to these
organisms through water and biosolids were
within scope, but not further analyzed, because
physical-chemical properties do not support
these pathways. The land-applied biosolids
pathway is within the scope of the risk
evaluation, but during problem formulation
EPA determined risks would not be
quantitatively evaluated for land-applied
biosolids because based on fate properties, TCE
is not anticipated to partition to biosolids
during wastewater treatment. Any TCE present
in the water portion of biosolids following
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wastewater treatment and land application
would be expected to rapidly volatilize into air.
And the air exposure pathway from biosolids
and surface water are insignificant. Based on
the Guidance for Ecological Soil Screening
Levels (EPA. 2003a. b) document, for
terrestrial wildlife, relative exposures
associated with inhalation and dermal exposure
pathways are insignificant, even for volatile
substances, compared to direct ingestion and
ingestion of food (by approximately 1,000-
fold). In addition, TCE is not expected to
bioaccumulate in tissues, and concentrations
will not increase from prey to predator in either
aquatic or terrestrial food webs. EPA has added
language to the final risk evaluation document
in Section 4.1.4 explaining this rationale.
For terrestrial organisms, pathways that were
out of scope include ambient air from industrial
sources, disposal in landfills, incineration units,
and underground injection. Environmental
exposure pathways covered under the
jurisdiction of other EPA-administered statutes
and regulatory programs are not within the
scope of the risk evaluation. Emissions to
ambient air from commercial and industrial
stationary sources, and associated inhalation
exposures of terrestrial species, are covered
under the jurisdiction of the Clean Air Act
(CAA). Pathways from disposal to sediment,
soil, water, and air are covered under Resource
Conservation and Recovery Act (RCRA),
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CAA's Maximum Achievable Control
Technology (MACT), and the Safe Drinking
Water Act (SDWA). Clarifying language about
what pathways are addressed under other
statutes has been added to Section 1.4.2 of the
Risk Evaluation.
49, 99
PUBLIC COMMENTS:
TRI requirements apply to a narrow subset of facilities that release
chemicals to the environment and thus understate total emissions. For
example, the 2011 EPA National Emission Inventory (NEI) estimated
U.S. TCE emissions of 3,250 tons - or 7,150,000 pounds, compared
with the only ~2 million pounds indicated by TRI in 2017.
NEI is compiled every 3 years for the purpose
of supporting residual risk evaluations as
required by NESHAPs. NEI contains air
emission estimates, which can be estimated by
sites using a variety of methods, such as
emission factors, mass balance, and stack
monitoring. Purchase and disposal records are
not reported to NEI. However, EPA was unable
to use NEI data to reasonably estimate water
releases as it only includes air releases from
larger facilities and would not include releases
from many smaller shops that use TCE.
49, 99
PUBLIC COMMENTS:
TCE is frequently found at contaminated sites, resulting in
contamination of groundwater and release of TCE vapors into ambient
air and buildings. This is a significant concern at contaminated sites
within the purview of the EPA Superfund program. Given the ubiquity
of TCE in soil and groundwater, there are assuredly far more sites with
TCE contamination than are identified. At these sites, volatilization of
TCE from contaminated soils is relatively rapid and may lead to
elevated ambient air levels in nearby communities.
EPA evaluated and considered the impact of
existing laws and regulations (e.g., regulations
on landfill disposal, design, and operations) in
the problem formulation step to determine
what, if any future analysis might be necessary
as part of the risk evaluation. During problem
formulation EPA analyzed the TRI data and
examined the definitions of elements in the TRI
data to determine the level of confidence that a
release would result from certain types of
disposal to land (e.g., RCRA Subtitle C
hazardous landfill and Class I underground
Injection wells) and incineration. EPA also
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examined how TCE is treated at industrial
facilities. EPA did not include emissions to
ambient air from commercial and industrial
stationary sources, which are under the
jurisdiction of and addressed by Section 112 of
the Clean Air Act. EPA did not include
emissions to ambient air from municipal and
industrial waste incineration and energy
recovery units in the risk evaluation, as they are
regulated under section 129 of the Clean Air
Act. EPA did not include disposal to
underground injection, RCRA Subtitle C
hazardous waste landfills, RCRA Subtitle D
municipal solid waste (MSW) landfills, and on-
site releases to land from industrial non-
hazardous waste and construction/demolition
waste landfills in this Risk Evaluation. EPA did
not include Superfund on-site releases to the
environment, as they are under the jurisdiction
of CERCLA. These methods of disposal fall
under the jurisdiction of and are addressed by
other EPA-administered statutes and associated
regulatory programs.
56, 108
PUBLIC COMMENTS:
EPA cannot ignore environmental releases of a chemical because it
cannot attribute each release to a particular COU. EPA has indicated
that "only a few USGS-NWIS and STORET monitoring stations
aligned with the watersheds of the TCE-releasing facilities
identified under the scope of this assessment, and the co-located
monitoring stations had samples with concentrations below the
detection limit; therefore, no direct correlation can be made between
them."
This language suggests that EPA may believe it must be able to
EPA has considered all identified measured
surface water monitoring data regardless of
whether it can be traced back to a specific
COU. The GIS analysis was not conducted to
exclude any of the measured data, but to
identify potential associations between modeled
and measured data, where possible. However,
regardless of the outcome of the GIS analysis,
monitoring data were considered for exposure
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attribute every environmental release of a chemical to a particular
COU or facility in order to consider its risks in a risk evaluation.
Nothing in TSCA allows EPA to ignore data simply because they
have not been tied to a particular COU, let alone a particular facility.
EPA must conduct risk evaluations under TSCA that consider all
"reasonably available" information relating to a chemical substance,
including information that may not be tied to specific COUs.
EPA is ignoring exposures from other COUs, such as
"manufacturing]," "processing]," and potentially distribution in
commerce, by for example ignoring the emissions from the
manufacturing and processing facilities.
and risk characterization.
Regarding exposures from COUs such as
manufacturing, processing, and distribution in
commerce, EPA has evaluated those conditions
of use. EPA described background exposure in
the uncertainties section acknowledging that the
risk estimations in the Risk Evaluation may be
underestimations, because background
exposures and risk are not incorporated to the
risk estimations for each COU. Emissions to
ambient air from commercial or industrial
stationary sources, or inhalation exposures of
terrestrial species are covered under the
jurisdiction of the Clean Air Act (CAA).
104
PUBLIC COMMENTS:
EPA is strongly urged to consider environmental release from waste
management sites, including transfer sites, construction and demolition
sites, materials recovery facilities, and Subtitle D landfills. These should
be evaluated with consideration of unlined facilities with resulting
leachate subsurface flow, ponded water, direct surface water, and
snowmelt runoff; ambient emissions from uncovered disposal areas; and
untreated waste burning emissions.
Releases from landfills were not included in the
risk evaluation as landfills are under the
jurisdiction of RCRA (see section 1.4.2 of the
risk evaluation).
105
PUBLIC COMMENTS:
The conceptual models only included exposure
pathways that are within the scope of the risk
evaluation. The environmental exposure
pathways covered under the jurisdiction of
other EPA-administered statutes and regulatory
programs are not within the scope of the risk
evaluation. As explained in more detail in
Section 1.4.2 of the Final Risk Evaluation, EPA
"Conditions of use" must certainly include releases into air, water,
waste sites, and food, as these releases are inseparable from the use of a
chemical.
EPA provides no analysis whatsoever as to: the extent to which the
standards or criteria cover the full range of exposure to the chemical
through the pathway; the extent and magnitude of releases of the
chemical allowed under each of the regulatory standards or criteria;
or any other factors that would be necessary to analyze to determine
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the extent and nature of potential risk allowed under the standards.
By not considering these releases, EPA is effectively reducing this
substantial amount of TCE released into the environment to zero.
believes it is both reasonable and prudent to
tailor TSCA Risk Evaluations when other EPA
offices have expertise and experience to address
specific environmental media, rather than
attempt to evaluate and regulate potential
exposures and risks from those media under
TSCA. EPA believes that coordinated action on
exposure pathways and risks addressed by other
EPA-administered statutes and regulatory
programs is consistent with statutory text and
legislative history, particularly as they pertain
to TSCA's function as a "gap-filling" statute,
and also furthers EPA aims to efficiently use
Agency resources, avoid duplicating efforts
taken pursuant to other Agency programs, and
meet the statutory deadline for completing Risk
Evaluations. EPA has therefore tailored the
scope of the Risk Evaluation for TCE using
authorities in TSCA Sections 6(b) and 9(b)(1).
Confidence in release/discharge/spill data
SACC
SACC COMMENTS:
Recommendation: Clarify how confidence is assessed on overall release
estimates.
The Committee noted that everything is assessed as having
"medium" confidence in the summary of overall confidence in
release estimates. It was not clear to the Committee that there are
any rules as to what qualifies as "high" or "low." There seems to be
a lot of uncertain components that go into a "medium" confidence
assessment. Specifically, the Committee thought that the "medium"
confidence for Commercial Printing and Copying is unjustified
based as it is on one facility that is likely not representative of the
whole industry. This should be an example of a "low" confidence
occupational exposure scenario (OES) water release estimate.
Confidence in release estimates are thoroughly
explained in Section 2.2.2.3.1. The assumptions
and uncertainties associated with using TRI and
DMR data sources, such as limitations on
required reporters, are discussed in Section
4.3.1.
Table 2-11 provides the full reported range of
surface water concentrations from all but two of
the identified data sources. Therefore, the high-
end of measured ambient water TCE levels is
shown regardless of whether the source
Page 61 of 408
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A Committee member recommended that the Not Reported values
in draft risk evaluation Table 2-11 be replaced with values
calculated using the data in the source publications (an example
table is provided). These publications contain ambient air data that
show significant concentrations near manufacturing facilities.
Another example table shows extracted data from U.S. EPA (1977)
that were used to compute statistics. The same should be able to be
done for data from other sources, especially federal documents, or
publications from researchers at federal laboratories.
One Committee member commented that the draft risk evaluation
does not adequately explain why historical measured concentrations
of TCE are not considered representative of current releases (p. 95,
lines 671-675 and p. 99, lines 787-792).
Another Committee member noted that the reduction in TCE use
and process modifications over the last four decades make use of
historical concentrations in the risk evaluation problematic.
reported central tendency estimates, which are
sometimes shown in the Table as Not Reported.
For the two data sources that did not report a
full range of measured concentrations, the
reported central tendency values are shown.
EPA states that "These samples were collected
in 1976-1977 near facilities producing and/or
using methylchloroform, thus the
concentrations reflect historical levels of TCE
and are not considered to be representative of
current conditions." Methylchloroform
production is not included as a condition of use
in this evaluation.
SACC
SACC COMMENTS:
Modeling of TCE concentrations in river water is highly problematic
without downstream monitoring data to parameterize modeling efforts.
This would require both near and intermediate distances from facilities.
A Committee member noted that the draft risk evaluation does not
use physiologically based pharmacokinetic (PBPK) models for fetal
transfers and suggested that this may reflect a lack of data to
parameterize those models. The same criteria should be used here,
and if there are no data for model parameterization, conservative
assumptions should be used throughout the draft risk evaluation.
According to the Committee member, these conservative
assumptions include the 1977 data, use of high centile
concentrations, and inclusion of lower centile of degradation. None
of these conservative considerations have been included in the draft
risk evaluation.
Other Committee members commented that volume or use patterns
do not consider any handling procedures, process, or engineering
The assessment is based on the reasonably
available data regarding volume, use patterns,
handling procedures, process or engineering
changes.
Conservative assumptions are used in the
evaluation of aquatic exposures and are
described in Sections 2.2.3 and 2.2.6.3. For
example, a low-end estimate for days of release
{i.e., 20 days) is included for direct releasers.
Additionally, the model itself does not
incorporate downstream transport or post-
release degradation or loss mechanisms such as
volatilization.
Page 62 of 408
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changes that may have taken place over the intervening years,
particularly after regulatory limits were enacted.
This point is acknowledged in Section 2.2.6.3
as a primary uncertainty associated with the E-
FAST model (U.S. EPA 2014c). Lansuase has
been added following additional fugacity
modeling, which is discussed in Section 4.3.1:
"The effect of volatility on estimating instream
concentrations is expected to be highly variable
and site-specific depending on stream flow and
environmental conditions. For discharges to
still, shallow water bodies, E-FAST estimates
are less likely to overestimate surface water
concentrations, as TCE is predicted to have a
long half-life in such still water bodies. For
discharges to faster-flowing, deeper water
bodies, E-FAST estimates may inadequately
reflect instream volatile losses expected within
the timeframe of one day. Given this variation
and the predicted half-life of TCE in flowing
water bodies, E-FAST surface water
concentrations may best represent
concentrations found at the point of discharge.
Despite these uncertainties, E-FAST is
considered an appropriate screening model for
near-field environmental concentrations."
SACC
SACC COMMENTS:
Recommendation: More detailed GIS modeling is needed to raise
confidence to moderate.
The draft assessment concludes overall moderate confidence in
Aquatic Exposure Scenarios. Many on the Committee concluded
that despite a lot of work and best intentions, confidence in exposure
scenarios is low, primarily due to high propagation of uncertainties.
More detailed GIS modeling is needed to raise confidence to
moderate.
EPA will consider how to bolster such GIS
analyses in future evaluations; however, some
additional fugacity modeling was conducted
and is presented in the final risk evaluation to
address some of the primary uncertainties
associated with E-FAST modeling, i.e., the
inability to incorporate downstream transport
and fate processes such as volatilization. Please
Page 63 of 408
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see Sections 2.2.6.3 and 4.3.1 for a description
of the fugacity modeling using W VOL WIN
within EPISuite and findings.
SACC
SACC COMMENTS:
Using notes from Supplemental Document lOEnvironmental Data
Extraction, one Committee member noted that data from the Lake
Charles PPG Facility released TCE that produced mean surface
water concentrations of 282 |ig/L and median of 353 |ig/L (U.S.
EPA, 1977). Surface water concentrations at the Dow plant in
Freeport, TX, ranged from 0.9 to 126 |ig/L.
The table of environmental monitoring studies in Supplemental
Document 10 reports ranges and standard deviations. In reporting
the number of samples and detection frequencies in column 4 of the
table, a value of 1 indicates that all samples had detectable
concentrations. This is not completely clear, because it could also be
read as there being only one sample with a detectable concentration
in the sample.
EPA appreciates this feedback on the
supplemental file. The detection frequency
reported in parentheses reports the frequency or
rate and not the number of samples with
detections. For consistency with the other
published risk evaluations, this column header
is retained; however, EPA will consider
clarifying this column header in future
evaluations.
SACC
SACC COMMENTS:
The Committee noted that Section 2.2.6.2, lines 567-572 has no
mention of Appendix P, suggesting there is no way to determine the
adequacy of the underlying information upon which surface water
concentrations are based (Tables 2-7, 2-8, and 2-9). The Committee
concluded that Appendix P contains assumptions that are not
conservative and are improper for use in the absence of measured data
for releases from commercial operations.
Cross-references to Section 2.2.2.1 and
Appendix Q (formerly Appendix P) containing
details on facility release data have been added
to Section 2.2.2.6.
Release estimates are based on reasonably
available information obtained from the Toxics
Release Inventory, Discharge Monitoring
Report, National Emissions Inventory,
Chemical Data Reporting, Effluent Limitation
Guidelines, and Emission Scenario Documents.
Alternai
tive data/approaches for release estimates are recommended
SACC
SACC COMMENTS:
Recommendation: Use NPDES data to confirm E-Fast outputs for TCE.
NPDES measurements of TCE from permit-required sampling
NPDES data were used for many releasing sites
as the bases for the annual loading/release
Page 64 of 408
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results and notifications to state/EPA of compliance or
noncompliance should be obtained. These data would allow a much
more robust method of comparison of modeled E-FAST data versus
measured data to be performed. While measured data are obtained
from the WQX, these data are primarily surface water
measurements that are rarely obtained from discharge sites where
TRI or other input data are used in E-FAST.
The Committee expressed concern that available monitoring data
could not be used to corroborate the monitoring approach given the
downstream distance, which may represent an opportunity for EPA
to implement a program of monitoring that can provide more data
with greater confidence.
volumes that serve as the key inputs for the
aquatic exposure model. Surface water
concentrations are estimated using loading
volumes (not effluent concentrations) with
receiving water body stream flow.
Release estimates and modeled concentrations
in receiving water bodies are based on the
scoped conditions of use, while monitoring data
obtained from the WQP and/or peer-reviewed
or grey literature sources are not. Therefore,
there may or may not be a relevant proximity
between the modeled surface water
concentrations and the sampling sites with
measured data obtained through systematic
review.
SACC
SACC COMMENTS:
Recommendations: (1) Clarify the use of ranges in number of facilities
in Table 2-3. (2) Range estimates or a statement of uncertainty should
be provided on the number of facilities for each OES.
A Committee member questioned the use of ranges in number of
facilities in Table 2-3. For example, line 2 of the table reports 5 to
440 facilities that are in the scenario "Processing as a Reactant." Is
one to assume that this means that EPA acknowledges that they are
not sure of the number of facilities? Does this mean something like
"we know of 5, and there could be as many as 435 or more facilities
that do this?"
In Table 2-3 where the summary of estimates for the number of
facilities for each OES are provided, one Committee member
thought that the estimation of the number of facilities could be
enhanced by adding a sense of uncertainty ฑ X percent or X
facilities. This member thought that these data are evidently needed,
as one sees the number of facilities for "processing as reactant"
The range provided for the number of sites
from Processing as a Reactant is a function of
known sites for this OES from TRI (U.S. EPA
2017a) and DMR fU.S. EPA 2016a) data and
integrating it with sites reporting NAICS codes
for this type of use. EPA acknowledges the
uncertainties associated with these data in
Section 2.2.2.3 of the Risk Evaluation.
Page 65 of 408
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estimated at "5 to 440," which is quite a range, whereas the rest of
the estimations are left without any measure of uncertainty.
SACC
SACC COMMENTS:
One Committee member could not find the surface water concentration
maps mentioned in Section 2.2.5. This member was concerned that the
color coding is provided but was not certain that the maps were found in
Section 4 of the draft risk evaluation. If so, this member could not see
the immediate reference.
EPA has addressed this point by including the
referenced maps into Section 2.2.6.2.3.
SACC
SACC COMMENTS:
In Figure 2-4, one Committee member thought that the choice of a
tornado graph is not the best one to promote clarity and suggested that a
set of pie charts or a sectioned bar graph may better illustrate the point.
EPA has addressed this point by removing the
tornado plot and clearly describing the pictured
observations in text (see Section 2.2.6.2.1).
SACC
SACC COMMENTS:
Recommendation: Perform a sensitivity assessment for environmental
exposures.
Given the uncertainties and medium confidence ranking for the
environmental exposure and releases, a sensitivity assessment is needed
to better understand the impact of key assumptions and limitations in
the final conclusions.
The Committee noted the inclusion of a sensitivity assessment
performed on species (species sensitivity distribution [SSD] in
Section 3), which is a good step forward.
Some Committee members recommended including an evaluation of
how sensitive the environmental exposure estimations are to the
assumptions, or at least provide a semiqualitative assessment.
Section 2.2.6.3 discusses the key sources of
uncertainty in the aquatic exposure modeling.
The key inputs driving exposure estimations are
the release volume input (kg/site-day), the days
of release, and the stream flow of the receiving
waterbody. Section 2.2.2.3 and Table 2-5
outline sources of uncertainty and confidence in
two of those key inputs: release days and
release volumes.
SACC
SACC COMMENTS:
Several Committee members noted that the draft risk evaluation
indicates that when it is not possible to confidently assign a facility
to a specific COU based on TRI or DMR reporting information, it is
assigned to its "most likely" or "primary" COU. It is not clear why
the facilities were not asked for more information on how TCE is
used on site. This seems reasonable, for example, for the
manufacturing sites, where only three or maybe five are identified.
As noted in the document entitled EPA's
Responses to Public Comments Received on
the Scope Documents for the First Ten
Chemicals for Risk Evaluation under TSCA,
(EP A-HO-OPPT-2016-0723 -00671 EPA
conducted extensive and varied data gathering
activities for each of the first 10 chemicals,
Page 66 of 408
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One member suggested that this approach be used to reduce
uncertainty by obtaining information on the days of manufacture
versus assuming 350 days/year for all.
including:
Extensive and transparent searches of public
databases and sources of scientific literature,
government and industry sector or other
reports;
Searches of EPA TSCA 8(e), Chemical Data
Reporting, and other EPA information
holdings; and CBI submission holdings;
Searches for Safety Data Sheets (SDSs)
using the internet, EPA Chemical and
Product Categories (CPCat) data, the
National Institute for Health's (NIH)
Household Product Database, and other
resources in which SDS could be found;
Preparation of a market analysis using
proprietary databases and repositories;
Outreach meetings with chemical
manufacturers, processors, chemical users,
non-governmental organizations, trade
organizations, and other experts, including
other State and Federal Agencies (e.g., Dept
of Defense, NASA, OSHA, NIOSH, FDA
and CPSC); and
Publication of conditions of use documents,
scope documents, and problem formulation
documents to solicit information generally
from industry, nongovernmental
organizations, and the public.
SACC
SACC COMMENTS:
Recommendation: Link the National Hydrological Dataset to E-FAST.
Several Committee members noted that material flows are not the
same as in the E-FAST database. The Committee recommended that
a mass balance approach would be helpful to address some issues in
EPA has added a mass balance analysis as
suggested to Appendix R of the Risk
Evaluation to provide come context when
comparing TCE production and releases.
Page 67 of 408
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comparing TCE production and releases. Several Committee
members recommended that EPA link the National Hydrological
Dataset to E-FAST.
EPA will consider updating its stream flow
database or using the more recent sources for
stream flow distributions in future evaluations
to address this point.
SACC
SACC COMMENTS:
Recommendation: Provide separate Supplement for EPI Suite data or
change the title of the current supplement.
The supplemental PDF document, "5_TCE-Data Extraction for
Environmental Fate and Transport Studies Public" (U.S. EPA, 2020)
discusses results and assigns data quality for studies from which the
input parameters used in EPI Suite are obtained. It also presents
some EPI Suite model output. This is not clear from the document
title, yet this is key information for draft risk evaluation readers.
The supplemental file in question is data
extraction, which includes data obtained either
from identified studies or from modeling
results.
SACC
SACC COMMENTS:
Recommendation: The implications of the Fugacity Level 3 modeling
needs to be better explained.
EPI Suite consists of several models. Some are used to predict
physical-chemical properties, one is used to predict removal from
WWTPs and another is the Fugacity Level 3 model. In some cases, they
are linked, and in others, they are not. For example, physical-chemical
properties can be manually added or estimated within EPI Suite, then
used in the STP model or fugacity models.
One Committee member concluded that the fugacity model predicts
TCE movement from air to water, not water to air (p. 30; U.S. EPA,
2020b). The member noted that any consideration of TCE
degradation in wastewater will only lower the initial concentration
released to water and increase the predicted air-to-water flux.
Several Committee members thought that this was a serious flaw in
the draft risk evaluation's assessment of environmental fate data
(see Table 2-1 provided in the SACC report). The Committee
suggested that this pertains to all chlorinated solvent TSCA risk
assessments.
EPA ran the level III fugacity model in
EPISuite (U.S. EPA 2012b) usins emissions
from a mass balance developed to account for
the amount of TCE entering and leaving all
facilities in the United States. For the mass
balance EPA attempted to quantify the amount
of trichloroethylene associated with each of its
life cycle stages from introduction into
commerce in the U.S. (from both domestic
manufacture and import), processing, use,
release, and disposal. The results of the
modeling are presented in Appendix S.
Discussion of assumptions and uncertainties
associated with TCE level III fugacity
modeling and the SACC level III fugacity
modeling results is presented in 2.1.3
Assumptions and Key Sources of Uncertainty
for Fate and Transport.
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Several Committee members suggested that the ratios and mass
loadings assumed in the default Fugacity Level 3 (fugacity model)
within EPI Suite do not represent the draft risk evaluation's
estimates of environmental releases (problem formulation Table 2-
7). Default assumptions are 1000 kg/hour release of the chemical
being evaluated into the compartments of air, water, and soil. More
refinement of fugacity model within EPI Suite estimates can be
done by using data from problem formulation Table 2-7 (U.S. EPA,
2018).
The draft risk evaluation for TCE did not list estimates for total TCE
releases to water or any other media. Therefore, the problem
formulation contains the most comprehensive summary of the data
available to estimate TCE releases to the environment. Data from
problem formulation Table 2.7 (U.S. EPA, 2018) show annual TCE
releases to air, water, and soil of 1,881,000, 52, and 50,000 pounds,
respectively (the SACC only lists the higher mass numbers to the
nearest 1000 pounds). There are also 2016 DMR data that show that
1,564 pounds of TCE released from the top 10 TCE producers (problem
formulation 2.3.4, p. 34, last line).
SACC
SACC COMMENTS:
The SACC report provides a table including six scenarios to
demonstrate using environmentally realistic release ratios of TCE to air,
water, and soil that multimedia models such as EPI Suite show TCE
moving from air to water, not from water to air.
Scenario 1 (Default): The default case, which shows equilibrium
TCE concentrations in water that exceed releases to water by 63%.
Scenario 2 (Scaled Default): Retains the equal ratios of the default
case but scaled to the total releases to all compartments (problem
formulation Table 2-7). This scenario is provided to show that as
long as the ratios released into the three compartments are the same,
the relative distributions are predicted to be the same.
Scenario 3 (problem formulation): Shows the release rates to each
compartment as calculated from Problem Formulation Table 2-7
EPA ran the level III fugacity model in
EPISuite (U.S. EPA 2012b) usins emissions
from a mass balance developed to account for
the amount of TCE entering and leaving all
facilities in the United States. For the mass
balance EPA attempted to quantify the amount
of trichloroethylene associated with each of its
life cycle stages from introduction into
commerce in the U.S. (from both domestic
manufacture and import), processing, use,
release, and disposal. The results of the
modeling are presented in Appendix S.
Discussion of assumptions and uncertainties
Page 69 of 408
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(U.S. EPA, 2018). This scenario estimates aqueous TCE
concentrations that are 13,100% (131 times) above those estimated
from TRI data. This would represent 6,812 pounds released to water
by industrial uses.
Scenario 4 (problem formulation - High): Used to determine if
using the higher 2016 DMR aqueous release estimates of 1,560
pounds (problem formulation 2.3.4 p. 34, last line) would lower the
flux to water. Using this higher annual aqueous release (problem
formulation 2.3.4 p. 34, last line) rather than the 52 pounds release
(Table 2-7) produced an EPI Suite fugacity model output of 792%
TCE increase in water over the concentration released to water. That
represents 12,350 pounds of TCE released to water from industrial
uses. So, a 30X increase in release to water only increases modeled
surface water concentrations by 2X because the flux from other
compartments is the dominant contributor to aqueous
concentrations.
Scenarios 5 (Water Low + Air) and 6 (Water High + Air): Use the
TCE releases to air and water from Scenarios 3 and 4 but assume
that there is no release to surface soils and that there is no hydraulic
connectivity from soils to surface water (both of which are not
protective assumptions). Scenario 5 shows a 10,900% increase in
TCE over the 52 pounds in Table 2-7, and Scenario 6 shows a 732%
increase over the 1,560 pounds from 2016 DMR data, clearly
demonstrating partitioning from air to water.
One Committee member noted that overall, these EPI Suite fugacity
outputs show that TCE releases to other abiotic media must be
considered if aquatic receptors are to be protected. This fugacity
evaluation also clearly demonstrates why EPA cannot pretend that
discharges to non-aqueous media can be assessed separately. All biotic
and abiotic compartments are interconnected through phase boundaries,
and material transport across those boundaries does not behave as any
policy or regulatory nexus dictates.
associated with TCE level III fugacity
modeling and the SACC level III fugacity
modeling results is presented in 2.1.3
Assumptions and Key Sources of Uncertainty
for Fate and Transport.
SACC
SACC COMMENTS:
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Recommendation: Link monitoring data to upstream sources.
The Committee recommended that monitoring data must have some
downstream hydraulic connection to the source. The Committee
suggested that the simplest way to incorporate these data would be
to identify which ones are indeed downstream with transit time of
no more than 3 days and to situate another monitoring station
downstream from the source, approximately 1/3 of the way (transit
time) to the current monitoring station.
Release estimates and modeled concentrations
in receiving water bodies are based on the
scoped conditions of use, while monitoring data
obtained from the WQP and/or peer-reviewed
or grey literature sources are not. Therefore,
there may or may not be a relevant proximity
between the modeled surface water
concentrations and the sampling sites with
measured data obtained through systematic
review.
Ethylene dichloride (EDC)/vinyl chloride monomer (VCM) facility releases are already regulated and should be separate
COUs
101
PUBLIC COMMENTS:
EDC and VCM facilities have been regulated since 1994 under the
Clean Air Act (CAA) by EPA's Hazardous Organics National Emission
Standards for Hazardous Air Pollutants (NESHAP) rule, which
established maximum achievable control technology standards to
regulate the emissions of hazardous air pollutants (HAPs) from major
source facilities. TCE is regulated as a HAP under section 112 of the
CAA. Under this rule, emissions of HAPs at EDC/VCM facilities are
highly controlled by this rule, including leak detection and repair
requirements to prevent occupational exposure. As a result of this
extensive regulation, all HAPs produced from this source category
including TCE have been controlled and EPA must consider this a
separate COU.
EPA agrees air releases from these facilities are
regulated under NESHAPs, but TCE releases to
water from these facilities is in scope for the
risk evaluation as discussed in Section 1.4.2 of
the risk evaluation.
Impact of pandemic
81
PUBLIC COMMENTS:
How will the global outbreak of COVID-19 affect TSCA and the
percentage of TCE or any other toxic in drinking water?
Thank you for your question related to
Coronavirus (COVID-19). Please refer to
freciuent Questions to Coronavirus (COVID-19).
Page 71 of 408
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3. Environmental Hazard
Kn\ ironmcnlal lla/arri
Charge Question 3.1: Please comment on EPA's approach for characterizing em ironmenlal hazard for each risk scenario (e.g.,
acute aquatic, chronic aquatic). What other additional information, if any, should be considered (Section 3.1)
Charge Question 3.2: Please comment on the use and interpretation of Species Sensitivity Distributions (SSDs) and hazardous
concentrations (HCoss) for ecological risk characterization and provide any specific suggestions or recommendations for how this
information could inform EPA's risk assessment for TCE or other solvents (Section 3.1).
#
Summary of Comments for Specific Issues Related to Charge
Question 3
I PA/OPPI Response
Use/interpretation of SSDs and/or HCo? values for ecological risk characterization
SACC
SACC COMMENTS:
The Committee supports EPA's use of SSDs in the development of
values intended to be protective of all aquatic receptors. It was
encouraging that an SSD is used in conjunction with most sensitive
species data for COC determinations. The inclusion of most sensitive
species estimates of toxicity are warranted as often there is not enough
sublethal endpoint data (e.g., reproduction data) to support SSD
calculations. Thus, the Committee considered a combination of both
processes for development and further support of the COC as an
appropriate exercise.
With one potential exception, values that were derived for acute and
chronic exposures to aquatic organisms are reasonable, although
there was not agreement on the magnitude of assessment factors
(AFs) used; however, appropriate references are provided. It was
also encouraging that sublethal endpoints of growth and
reproduction were used to determine chronic values (ChV) for
aquatic invertebrates.
EPA appreciates the support of SSDs and
sublethal endpoints used in the Risk Evaluation
and considered the modification of the
assessment factors (AFs) used to derive COCs
from the HCoss (from the SSDs). In response to
the SACC comments, EPA modified the AF for
the algae SSD from 1 to 5 because ECsos were
used to derive the SSD rather than ECios or
ChVs. EPA also modified the AF for the acute
SSD from 1 to 5 to account for the small sample
size used in the SSD, which encompassed
multiple taxa.
SACC
SACC COMMENTS:
Recommendation: Describe how the HCos is computed and what it
represents.
It is unclear how to interpret an HCos comprised of both ECso and LCso
data. More description is needed on the methods used to derive those
EPA added the raw data used in each SSD and
how it was decided to exclude any toxicity values
from the SSD in Appendix E. EPA also added
more explanation of what the HCos represents in
Section 3.1.3 in the Risk Evaluation.
Page 72 of 408
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values and how they would be valuable in advance. Section El only
describes the tool used to compute the values, provides no additional
justifications, and cites Etterson (2019), which does not provide a
description of the methods used.
The SSD for algae used only ECso values
measuring growth, and the SSD for acute aquatic
organisms used LCsos for fish, amphibians, and
invertebrates, and for invertebrates ECsos
measuring immobilization were also used
because it is difficult to distinguish between death
and immobilization for aquatic invertebrates. The
above explanation was added to Section 3.1.3 of
the Risk Evaluation.
SACC
SACC COMMENTS:
One Committee member suggested that the mantra that only toxic
endpoints of mortality, growth, and reproduction are "populationally
relevant" is fundamentally flawed. Since there is no direct
knowledge regarding the criteria important in regulating the
populations of any of the aquatic communities from where there are
releases, it is improper to characterize any toxic endpoint
necessarily of having "direct population level effects." Many
populations are regulated by predator activity that makes narcosis or
lethargy very important. In many natural systems, r-selected
organisms {i.e., ones that produce many eggs/individuals) lose a
large proportion to events resulting in mortality or otherwise
removing individuals from the population in pristine ecosystems.
The member recommended selecting endpoints by thinking in terms
of any adverse effects that are potentially relevant to maintaining
population size; such endpoints would include those such as
lethargy (which is the result of narcosis and results in slow
movement making individuals more susceptible to predation) and
developmental affects that could ultimately result in mortality or
otherwise removing individuals from of the reproduction pool.
However, many of the described mechanistic effects could be
characterized as endpoints of uncertain biological significance or
those of an adaptive response, which would not fit this definition.
EPA used the best available science and
reasonably available information during the data
integration process, including effects on behavior
and reproduction. The committee correctly notes
that mechanistic data found in the studies for
TCE could not be directly connected to an apical
endpoint that would have an effect on population
size. Therefore, EPA did not use them
quantitatively to calculate Concentrations of
Concern (COCs). However, the mechanistic data
was described and used qualitatively.
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Two other Committee members mentioned that there are regulatory
requirements associated with mortality, growth, and reproduction
and recommended EPA consider those criteria when choosing
endpoints.
103
PUBLIC COMMENTS:
EPA should clarify the importance of ecological risks to algae
compared to all other aquatic species which were assessed and
aggregated (i.e., fish, amphibians, and aquatic invertebrates). It is
unclear as to why algae represent a special case that should be evaluated
independently.
Algae were assessed separately from other
aquatic species, because algae tests and endpoints
do not fit into the traditional definitions of acute
and chronic durations. Algae was assessed
separately and not incorporated into acute or
chronic COCs, because durations normally
considered acute for other species (e.g., 48, 72
hours) can encompass several generations of
algae.
47
PUBLIC COMMENTS:
For purposes of environmental risk assessment, EPA selected and used
a chemical concentration (HCos = 52,000 ppb) as a hazard level that was
extrapolated from the algal SSD by using a specified percentile of the
distribution. We believe that it is inappropriate for EPA to override the
more sensitive algal COC (3 ppb) by using the SSD projections in
assessing risks.
EPA acknowledges that the algal SSD only includes ECso values to
compare between high- and medium-quality studies of nine species,
and it does not capture some of the lowest reported toxicity values.
We believe it would be more environmentally protective to include
results from testing these more sensitive species. EPA specifically
excludes lowest-observed-effect concentrations (LOECs) and no-
observed-effect concentrations (NOECs), e.g., the ChV of 0.03
mg/L for algal growth and metabolism derived from Labra et al.
(2010). Given the great difference between the acute and chronic
values and the need to protect the most sensitive species, it is very
important to use only the algal COC of 3 ppb.
Does TSCA mandate protecting 95% of all species or 100% of all
EPA had more confidence in the probabilistic
approach used to derive the COC from the SSDs,
and the SACC generally agreed with EPA's
approach for algae. The SACC suggested using a
higher assessment factor, and EPA agreed. From
draft to final version of the TCE Risk Evaluation
EPA changed the assessment factor from 1 to 5 to
account for the uncertainties around using ECsos
rather than ChVs. If sufficient ChVs had been
available EPA would have used them instead of
EC50S. This change has been made in Section
3.1.5.
TSCA does not mandate 95% of all species be
protected; however, the 95% cutoff is a widely
accepted cutoff accepted by jurisdictions around
the world after extensive back and forth with
scientists and policv makers (U.S. EPA 1985).
Page 74 of 408
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species? Given the very wide range of separation (four orders of
magnitude) between the algal COC (3 ppb) and the SSD-generated
algal HCos (52,000 ppb) for TCE, it is important to address the
sensitivity of all algal species. Guiry (2012) conservatively
estimated that there are 72,500 algal species, discounting diatoms
whose numbers have been estimated to be over 200,000 species.
TSCA obligates protection of the most sensitive species, and a more
protective approach would be to use the 3 ppb COC, and to not use
the statistically derived HC05 of 52,000 ppb.
For comparative purposes, approaches for setting ChVs for aquatic
invertebrates and fish have traditionally made use of the maximum
acceptable toxicant concentration (MATC) concept to help set water
quality regulations for protecting aquatic life. MATCs are usually
reported as geometric means between a NOECs and LOECs. Given
the need to protect all algal species, and the very wide range
between the algal ECso and HCos for the same species, it is critically
important to firmly establish the COC at 3 ppb, and to not use the
statistically derived HCos of 52,000 ppb.
103
PUBLIC COMMENTS:
EPA does not state why it has chosen to take the SSD approach for the
ecotoxicity data within the context of tiered environmental risk
assessment. The TCE assessment appears to not conform to the general
data structures (minimum numbers of taxa, SSD quality assessment,
goodness-of-fit assessment, and other factors) to either Office of Water
(OW) or Office of Pesticide Programs (OPP) practices. EPA should
consider developing guidance specific to OPPT for use of SSD and also
should consider adding a flow chart to indicate when an SSD is
necessary for risk evaluation purposes under TSCA. Specific
recommendations on SSD include:
EPA should provide greater transparency regarding its tiered
environmental risk assessment process and the decision to evaluate
the algae ecotoxicity data separately using the SSD approach. EPA
should clarify its tiered environmental risk assessment process and
EPA had more confidence, given the weight of
the scientific evidence, in the probabilistic
approach used to derive the COC from the SSDs,
and the SACC generally agreed with EPA's
approach. The SACC suggested using a higher
assessment factor for the COCs derived from the
HCoss, and EPA agreed. From draft to final
version of the TCE Risk Evaluation EPA changed
the assessment factor from 1 to 5 to account for
the uncertainties around using ECsos rather than
ChVs. If sufficient ChVs had been reasonably
available, EPA would have used them instead of
ECsos. The AF change has been made in Section
3.1.5.
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the place the SSD occupies in tiered ecological hazard assessment,
including how an SSD is fit-for-purpose in this instance.
EPA should articulate and apply best practices in developing an
SSD. Several recent peer-reviewed articles are available that
describe these practices, including Belanger et al. (2017), Carr and
Belanger (2019), and Belanger and Carr (2019).
EPA should clarify whether its COC in practice will be derived from
the lowest single chronic inhibition value from among the algal
studies or the HC5 based on acute inhibition. As these are 3+ orders
of magnitude apart, the choice and assumptions applied are critical.
It does not appear that the public has access to EPA's SSD
calculator algorithms (Etterson et al., 2019). In order to allow for
recreation of the SSD estimates using other software available to the
public, it would be helpful to have an actual table of input values
that EPA used. This would give a firmer assessment of model
choice and the quality of the SSD output.
OPPT consulted with other offices within the
EPA including OW, OPP, and ORD as it used
SSDs under TSCA. OPPT is in the process of
developing an SOP for using SSDs in TSCA Risk
Evaluations. EPA added more explanation to the
TCE Risk Evaluation in Section 3.1.3 and 3.1.4.
EPA has since made the SSD algorithms publicly
available on HERO: (Etterson. 2020).
50
PUBLIC COMMENTS:
EPA evaluated the algal ecotoxicity data and acute ecotoxicity data
using the SSD approach. The SACC should evaluate and comment on
the appropriateness of using the SSD approach on ecotoxicity data and
the details of EPA's application of the approach.
The SACC was in support of using the SSD and
asked for more transparency in what data was
used in the SSD and more explanation about what
the results of the SSD mean. Both were added to
Section 3.1.3, 3.1.4, and Appendix E of the Risk
Evaluation.
56, 108
PUBLIC COMMENTS:
EPA's analysis may have underestimated the risk from these releases
especially for algae. EPA justifies its calculated COC as being
representative for algae species "as a whole." EPA determined that "as a
whole" in this case constitutes nine species of algae. Yet algae are an
incredibly diverse (and poorly defined) group of organisms that
represent 15 phyla and 54 classes; estimates of total species of algae are
between 72,000 and 1 million. To conclude that a COC of 52 mg/L is
protective of algae "as a whole," based on only nine species, with a
concentration that is over 17,000 times higher than the COC EPA
EPA had more confidence, given the weight of
the scientific evidence, in the probabilistic
approach used to derive the COC from the SSDs,
and the SACC generally agreed with EPA's
approach for algae. The SACC suggested using a
higher assessment factor, and EPA agreed. From
draft to final version of the TCE Risk Evaluation
EPA changed the assessment factor from 1 to 5 to
account for the uncertainties around using EC50s
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derived for the most sensitive species of algae identified for the draft
risk evaluation is indefensible. Instead, EPA should use the most
sensitive species as its indicator organism to develop appropriately
protective COCs.
Using the far more appropriate COC of 3 ppb, EPA identified risks
from exposure to TCE to the most sensitive algae specie at 521
facilities (p. 354); nevertheless, EPA dismissed these risk quotients
(RQs) as actually showing no risk for "algae species as a whole"
based on its questionably calculated COC (pp. 378-379).
rather than ChVs. If sufficient ChVs had been
reasonably available EPA would have used them
instead of ECsos. This change has been made in
Section 3.1.5.
47
PUBLIC COMMENTS:
EPA used algal data for nine species to produce an SSD, which was
then used to calculate an HCos of 52 mg/L (or 52,000 ppb). This
HCos estimates a concentration that EPA maintains is hazardous for
5% of species. EPA maintains that HCos can also be used, in
addition to the algal COC, to estimate the concentration of TCE that
is expected to protect 95% of algae species. We would ask EPA to
provide further explanation for the basis and methods for
extrapolating from COC-based adequate-quality results of testing
nine species to protecting 95% of all of the approximately 72,500
algal species, i.e., 0.95 x 72,500 algal species = 68,875 species.
Table 4-1 in the draft risk evaluation indicates at least 30 instances
where RQs >1 appear to have been met or exceeded, indicating
potential risks to the aquatic environment. EPA used algal SSD to
argue that these were not appreciable risks to most algal species and
that algal species as a whole were not a problem for aquatic
environmental risk. We disagree with this finding because the algal
SSD works to diminish protection for the more sensitive algal
species. These RQs clearly indicate a potential risk to aquatic algae.
The commenter highlighted several examples from Table 4-1 where
RQs >1 were exceeded under the TCE use categories of processing
reactant, in repackaging, open-top vapor degreasing, adhesives,
sealants, paints and coatings, other industrial uses, industrial
processing aid, other commercial uses, and process solvent
EPA had more confidence, based on the weight
of the scientific evidence, in the probabilistic
approach used to derive the COC from the SSDs
than the deterministic approach, and the SACC
generally agreed with EPA's approach for algae.
The SACC suggested using a higher assessment
factor for the COC derived from the HCos due to
the fact that less than 20 species were used to
create the SSD. EPA agreed to make the change.
From draft to final version of the TCE Risk
Evaluation EPA changed the assessment factor
from 1 to 5 to account for the uncertainties
around using EC50s rather than ChVs. If
sufficient ChVs had been reasonably available
EPA would have used them instead of ECsos.
This change has been made in Section 3.1.5.
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recycling and worker handling of wastes, thereby underscoring
EPA's inappropriate approach to assessing risks to algae.
47
PUBLIC COMMENTS:
There is agreement that the New Rochelle STP appears to present little
or no risk to aquatic algal species.
Thank you for your comment.
Alternal
tive use/interpretation of SSDs or HCos values is suggested
SACC
SACC COMMENTS:
Recommendations: (1) Use ECso or EC20 values in computing the SSD.
(2) If computing an SSD is not possible, use the EC20 of the most
sensitive species as the point of departure (POD).
The SSDs are a good visualization tool for determining the potential
relative impact to different species and may inform actions
depending on the dynamics of TCE in an aquatic environment.
However, for TCE, given data gaps for the development of the
curves, one Committee member asserted that no definitive
conclusions can be made for algae. In addition, one limitation of
SSDs is that outputs do not include the lowest toxicity values
reported (including LOECs and NOECs). Adding the values may
provide additional visualization of the data that may help in
supporting COC derivation.
The Committee recommended that SSDs be developed using EC50
(or optimally EC20) values exclusively to develop a sublethal value
that is expected to be protective for 95% of the species. If sufficient
data are not available for an SSD derivation, then the use of the
EC20 for the most sensitive species as a POD from which to apply an
AF to derive a COC is reasonable.
Aqueous concentrations should be consistently expressed as |ig/L or
mg/L in the main text, to avoid confusion. In fact, the information in
Appendix E shows the average of HCos is 9,900 |ig/L and a safety
factor of 5 places that value at 1,959 |ig/L. To further illustrate this,
Figure Apx E7 shows three closely agreeing fits for HCos and one
outlier. Thus, the acute COC should exclude the Gumbel fit and thus
For the chronic COC EPA did use the EC20 as the
most sensitive point of departure.
For the algae COC, EPA used ECsos measuring
growth to create the SSD, and for the acute COC
EPA used LCsos for consistency across taxa to
create the SSD. The SACC suggested using a
higher assessment factor for the COCs derived
from the HCoss from the acute SSD and the algae
SSD. EPA agreed to make the change. From draft
to final version of the TCE Risk Evaluation EPA
changed the assessment factor from 1 to 5 to
account for the uncertainties around using
LC50s/EC50s rather than ChVs and to account
for the number of species used in each SSD being
smaller than 20. This change has been made in
Section 3.1.5.
Page 78 of 408
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the HCos would be -6.3 mg/L or 6,300 |ig/L. A safety factor for not
having over 20 species (i.e., the SSD computation is extrapolating
beyond the range of the data) would then provide a concentration
that is lower than currently estimated by EPA.
COC derivation
SACC
SACC COMMENTS:
While a fish 32-day growth value is used for COC determination (7.88
mg/L), it is unclear why the lower 4 mg/L tadpole survival NOEC is
neglected. Since the values are on the same order of magnitude, it does
not appear to affect overall COC estimates.
To assess aquatic toxicity from chronic
exposures, data for three taxonomic groups were
described in the acceptable literature: fish,
amphibians, and aquatic invertebrates. However,
for amphibians, only a NOEC was established.
Therefore, the endpoints for fish and aquatic
invertebrates (ChVs, an EC20, and an EC50) were
more biologically relevant, because they
measured a toxic effect, whereas the NOEC did
not. Of the more relevant values, the most
sensitive was the EC20 measuring growth in fish
at 7.88 mg/L. The EC20 was from a high-quality
study, whereas the NOEC of 4 mg/L was from a
medium quality study. Considering both the
relevance and the quality, EPA had more
confidence in the EC20 for fish than in the NOEC
for tadpoles. Additional explanation was added to
the Risk Evaluation in Section 3.1.4 Weight of
the Scientific Evidence.
SACC
SACC COMMENTS:
It is typically inappropriate to treat median lethal and median sub-lethal
values equally (draft risk evaluation, p. 198). However, if the mode of
action (MOA) or endpoints are consistent with those that could
reasonably be assumed to result in mortality (e.g., narcosis, terata),
values would largely be equivalent, and hence appropriate, to treat
equally. The draft risk evaluation needs to specify the endpoints for the
ECso values used. If not, use the lowest biologically relevant endpoint
The SSD for algae used only ECso values
measuring growth, and the SSD for acute aquatic
organisms used LCsos for fish, amphibians, and
invertebrates, and for invertebrates ECsos
measuring immobilization were also used
because it is difficult to distinguish between death
and immobilization for aquatic invertebrates. The
Page 79 of 408
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value and apply an AF, then carry this value through the risk
assessment.
above explanation was added to Section 3.1.3 of
the Risk Evaluation.
SACC
SACC COMMENTS:
Recommendation: Justify the use of the geometric mean in calculating
lethal and nonlethal acute effects for invertebrates.
That the geometric mean is used to calculate a COC from both lethal
and non-lethal data for acute invertebrate effects also requires
further justification. What justifies the mean value when endpoints
are different? Are all studies otherwise equivalent (see previous
comment)? What data justify the geometric and not the arithmetic
mean? Precisely, why is the HCos not used as a POD for acute
exposures to aquatic invertebrates (9.9 mg/L)?
For invertebrates LCsos and ECsos measuring
immobilization were used, because it is difficult
to distinguish between death and immobilization
for aquatic invertebrates. A mention of this was
added to Section 3.1.3 of the Risk Evaluation.
EPA derived the geometric mean, because the
hazard values for all three species were similar,
and because EPA had more confidence in a COC
derived from a geometric mean for three species
than a COC derived from one value from one
species. EPA added a justification for using the
geometric mean in calculating an acute COC in
the 3.1.5 Section of the Risk Evaluation.
SACC
SACC COMMENTS:
Recommendation: Distinguish between study quality and study
relevance in weight-of-evidence (WOE) considerations.
There is a difference between data quality and data relevance (see p.
197, lines 287-315). Some very high quality toxicity data are not
relevant to derive toxicity values from (e.g., mechanistic, in vitro
data, population data, lack of dose response); however, they still
have utility in addressing questions regarding biological plausibility
and addressing issues associated with extrapolation of effects across
species and populations.
The Committee recommended that EPA make this distinction
between quality and relevance in judging total WOE in the
development of toxicity reference values. Here, data relevance
would directly refer to dose response information that could be used
to develop a POD or COC.
The difference between quality and relevance is
outlined in Section 3.1.4 Weight of the Scientific
Evidence. EPA did consider both quality and
relevance separately and added detail to Section
3.1.4 about studies used to derive the COCs to
more clearly explain the thought process that
went into deciding which toxicity values to use.
SACC
SACC COMMENTS:
Page 80 of 408
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Recommendation: Consider taxonomic representativeness of data and
MOA information in setting AFs.
Several Committee members found that the use of AFs of 10 and 5
to adjust the PODs for chronic and acute COCs appropriate and
consistent with the scientific literature that have evaluated
sensitivities of aquatic organisms using SSDs andNOECs; however,
it is stressed thatNOECs are often artifacts of study design and
recommended that EPA consider taxonomic representativeness of
the data and any available MOA or mechanistic data when deciding
on the magnitude of AFs (see Belanger and Carr, 2019).
One Committee member proposed that the lack of an aquatic
vertebrate reproduction endpoint may suggest an uncertainty factor
(UF) of 100 rather than 10 be used; however, if retained, the
sensitivity of algae seems to allow conservatism in other COC
calculations (Keinzler et al., 2017). The lack of reproductive data
should also be discussed as an uncertainty.
EPA is in the process of evaluating the body of
reasonably available literature in order to
determine whether to revise standards for
application of AFs and acute to chronic ratios for
the next 20 high-priority substances undergoing
risk evaluation. EPA considered the (Kienzler.
2017) studv in its assessment for the final Risk
Evaluation. Until the body of scientific evidence
for assessment factors is evaluated, EPA will
continue to use OPPT methodology as cited in
the risk evaluation ( v ซซ \ ^13. J) and
apply an AF of 5 for acute and 10 for chronic
aquatic invertebrate data. EPA considers these
AFs to be protective of aquatic invertebrates from
acute and chronic exposures to neutral organic
substances such as TCE, which produce toxicity
from simple narcosis.
SACC
SACC COMMENTS:
Recommendation: Summarize environmental hazard conclusions in a
table. An example table was provided.
EPA added the suggested summary table to
Section 3.1.7.
103
PUBLIC COMMENTS:
EPA should provide more detail in the ecological hazard assessment
section, specifically addressing the impact of the multiple
concentrations of concern that were calculated, the data quality of key
algal study, and the application of SSD.
EPA should consider providing a flow chart to describe the tiered
approach to ecological hazard assessment to better explain when the
application of advanced tools, such as SSD, is necessary
EPA added information in multiple subsections in
Section 3 and in Appendix E to explain the
toxicity data that went into the COCs, and the
decisions that were made to use the SSD over the
deterministic approach for calculating COCs.
103, 50
PUBLIC COMMENTS:
EPA should clarify the purpose of each of the COCs and indicate which,
if any, is most important for understanding whether an unreasonable
risk might occur.
EPA added information in multiple subsections in
Section 3 and in Appendix E to explain the
toxicity data that went into the COCs, and the
Page 81 of 408
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EPA derived an acute COC, a chronic COC (with algal ecotoxicity
data excluded), an algal COC (using only algal ecotoxicity data),
and an algal HCos using the SSD approach. The importance of each
of these is unclear and certainly the extreme divergence between the
algal COC and algal HCos (four orders of magnitude) is confusing.
The SACC should comment on EPA's approach and the
appropriateness and relevance of each of these thresholds.
decisions that were made to use the SSD over the
deterministic approach for calculating COCs.
Additionally, EPA added a summary table to
Section 3.1.7 with a description of each COC,
and what toxicity data and AF was used to
calculate it.
47
PUBLIC COMMENTS:
EPA calculated the COCs for aquatic species using geometric means
and statistical modeling of toxicity values for multiple species. Instead,
EPA should have used both acute and chronic toxicity values for the
most sensitive species within each major taxonomic group (e.g., algae,
aquatic invertebrates, and fish).
TSCA clearly requires EPA to protect all exposed aquatic, benthic,
and terrestrial species against adverse effects from exposure to
industrial chemicals. Modeling chemical toxicity is useful to
investigate groupings and trends in toxicity data and, where no data
exist, to generate toxicity data using structure-activity relationships.
Nevertheless, valid testing results are always preferable to results of
modeling, particularly where the models work to reduce apparent
toxicity, e.g., by using averaged results of individual studies in place
of results from studies of the most sensitive species, and,
consequently, minimizing levels of concern for adverse effects to
the natural environment.
EPA weighed the scientific evidence and during
data integration considered the reasonably
available data to calculate the COCs with the
highest quality and relevant data. EPA generally
prefers probabilistic approaches (e.g., SSDs) to
data integration than deterministic ones (e.g.,
using just the most sensitive value, or a geometric
mean of several values).
Consideration of Labra et al. (2010) study in COC derivation
SACC
SACC COMMENTS:
Recommendation: Discuss reasons for the 4-fold difference in acute
algal COC estimates based on the EC20 versus the SSD HC05 values.
The draft risk evaluation computes two COCs for acute algal effects,
one using the EC20 for the most sensitive species and one using the
SSD HC05 value. These values vary by more than four orders of
magnitude, yet no explanation is provided for why this might be
reasonable. When values differ by such a large extent, further
TCE had a robust dataset for algae in the
reasonably available literature. The data show
that there is a wide range in toxicity values for
algae exposed to TCE, likely because of species
to species variation but also because of lab to lab
variation. Additionally, the Labra value was
derived from NOEC and LOEC values rather
Page 82 of 408
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investigation is warranted. There could be study quality issues or
simply false positive outcomes that may help explain these results.
Was this study repeated?
The Committee recommended a more robust assessment of the
Labra et al. (2010) study to evaluate its potential as outlier data and
further justify the use of these data over the HCos designed to
protect 95% of the species. Further, it is not clear why the Labra et
al. (2010) quality metric is downgraded to medium while most
individual quality components are rated high.
than the ECsos that were used in the SSD.
Unfortunately, the same species from the Labra
study did not have an EC50 available in the
literature for comparison.
Labra et al. (2010) was not downgraded to a
medium. The first draft of the supplemental file
looked as though it was downgraded, but the
quality score it received should have categorized
it as a medium. This was corrected in the final
version of the supplemental file for
environmental hazard data quality evaluation.
103
PUBLIC COMMENTS:
The key algal study by Labra et al. (2010) should be viewed as an
outlier. Raphidocelis is nearly always equivalent in sensitivity to
Desmodesmus subspicatus. According to Brill et al. (2016), one would
expect these taxa to be within a factor of 2 of each other, yet for TCE,
they are about 50-fold different. The variance estimates of the algal cell
density data are incredibly small, while a coefficient of variation (CV)
of 5-15% is expected. The inoculum density to terminal cell density
should be at least 16-fold and for this species, more like 100-fold, where
in this case, it is about 8-fold and would not meet standard test validity
criteria. Moreover, the general acute:chronic ratio for algae is typically
in the realm of 3-5; in large data reviews, it is about 4.35.
EPA should more closely review the data from Labra et al. (2010)
and determine whether it is appropriate for inclusion within the
environmental hazard data set.
Labra et al. (2010) was evaluated for ciualitv and
given a medium quality score. However, during
data integration EPA was also able derive a COC
using a probabilistic method using an SSD, which
was preferred over the deterministic method
using Labra et al. (2010). EPA has more
confidence, based on the weight of the scientific
evidence, and prefers using probabilistic methods
over deterministic methods. Part of the reason
EPA has confidence in and prefers the
probabilistic method for calculating a COC is that
it takes multiple studies and species into
consideration instead of a single study and
species, which reduces the effect that an outlier
study may have on the COC.
47
PUBLIC COMMENTS:
The paper (Labra et al., 2010) used to set the 3 ppb algal COC was
evidently not used in developing the algal COC, and EPA explained that
omission by pointing out that Labra et al. (2010) had data quality
limitations, and that the SSD used only medium- or high-quality studies.
Labra et al. (2010) was evaluated for ciualitv and
given a medium quality score. However, during
data integration EPA was also able derive a COC
using a probabilistic method using an SSD, which
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A more environmentally-protective approach would have been to
include Labra et al. (2010) in developing the SSD because the effect
levels for growth and metabolism (ca. 30 ppb) reported in Labra et al.
(2010) were orders of magnitude below those used in the SSD.
While the algal testing results reported by Ando et al. (2003) were
of considerably lower quality than Labra et al. (2010), they found
effect levels (Volvalina steinii 10-day LOEC: 3 ppb) that were more
sensitive by a factor of 10 than those Labra et al. (2010) reported.
Acknowledging the weaknesses found in both the Labra et al.
(2010) and Ando et al. (2003) studies, they demonstrate the
existence of effects to different algal species occurring at
concentrations that are orders of magnitude lower than those used in
EPA's algal SSD. This argues for the importance of not diminishing
the merits of results from testing more sensitive species.
Also, data from Labra et al. (2010) resulted in a ChV (3 ppb) used in
EPA's TCE report. Had the Ando et al. (2003) study been more
rigorous, it would have resulted in a ChV of 0.3 ppb. The SSD
resulted in an HCio of 52,000 ppb based on toxicity testing designed
with relatively short durations (typically 96 or fewer hours)
compared to the 10-day duration reported by Ando et al. (2003).
While their results were not used quantitatively during data
integration, they are useful in pointing out the need for not
diminishing the 3 ppb COC based on Labra et al. (2010). This is
because the data demonstrate that algal effects at unusually low
TCE concentrations to different species are real and should be
incorporated in, not diminished by, SSD analyses in EPA's TCE
risk evaluation and would be more protective of the natural
environment.
Page 84 of 408
was preferred over the deterministic method
using Labra et al. (2010). EPA has more
confidence, based on the weight of the scientific
evidence, and prefers using probabilistic methods
over deterministic methods. Part of the reason
EPA has confidence in and prefers the
probabilistic method for calculating a COC is that
it takes multiple studies and species into
consideration instead of a single study and
species, which reduces the effect that an outlier
study may have on the COC.
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4. Occupational and Consumer Exposure
Omipalional :intl C onsumer l.xposurc
Charge Question 4.1: Please comment on the approaches and estimation methods, models, and data used in the occupational
exposure assessment (Section 2.3.1).
Charge Question 4.2: Please provide any specific 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 specific literature, reports, or data that would help us refine the exposure assessment (Section 2.3.1).
Charge Question 4.3: Please comment on assumptions used in the absence of specific exposure information (e.g., 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)] and [central tendency values, which is half of two full 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).
Charge Question 4.4: Please comment on EPA's approach to characterizing the strengths, limitations and overall confidence for
each occupational exposure scenarios presented in Section 2.3.1. Please comment on the appropriateness of these confidence ratings
for each scenario. Please also comment on EPAs approach to characterizing the uncertainties summarized in Section 2.3.1.3.
Charge Question 4.5: Please comment on the adequacy, appropriateness, and transparency of EPA's approach and the assumptions
EPA used to characterize ONU exposure via this approach (Section 2.3.1).
Charge Question 4.6: Are there other approaches or methods for assessing ONU exposure for the specific condition of use (Section
2.3.1)?
Charge Question 4.7: Please comment on the appropriateness of the approaches, models, exposure or use information and overall
characterization of consumer inhalation and dermal exposures for users and bystanders for each of the identified conditions of use.
What other additional information, or approaches, if any, should be considered (Section 2.3.2)?
Charge Question 4.8: Please recommend any additional data sources or studies that may be more reflective of current consumer use
patterns for specific conditions of use (Section 2.3.2).
Charge Question 4.9: Dermal exposure was evaluated using the permeability sub-model (P_DER2b) within CEM Version 2.1.
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
refining the dermal exposure estimates (Section 2.3.2.4.1).
Charge Question 4.10: Please comment on EPA's approach to characterizing the strengths, limitations and overall confidence for
each consumer exposure scenario presented in Section 2.3.2. Please comment on the appropriateness of the confidence ratings for
each scenario. Please also comment on EPA's approach for characterizing the uncertainties summarized in Section 2.3.2.7.
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Summary orCommcnls lor Specific Issues Related lo Charge
Question 4
KPA/OPPT Response
EPA's exclusion of exposure to the general population is invalid
49, 56,
65, 74,
86, 90,
99,
104,
108
PUBLIC COMMENTS:
EPA abdicated its responsibility under TSCA to identify and evaluate
risks to the general population by excluding release of TCE to indoor and
outdoor air, water, and land, or to consider exposure to background
levels. The most recent TRI data for TCE establishes that TCE is
released to air, water, and land in significant quantities.
Each of these pathways is alone responsible for cancer and non-
cancer risks to large segments of the population that exceed EPA
benchmarks.
There is a potential for underestimating consumer inhalation
exposures, particularly for populations living near a facility emitting
TCE or living in a home with other sources of TCE, such as TCE-
containing products in the home.
EPA asserted that exposures to the general population are
"adequately managed" without providing scientific rationale for the
assumption or analysis of the standards under the other statutes,
which may not be strictly health based. Unlike TSCA, other statutes
consider factors such as cost and feasibility when setting standards.
TSCA empowers EPA to look at the risk posed by the chemical
broadly without focusing on source-specific technology, costs of
regulation, or what standards are "achievable" for each source
category. EPA must evaluate a chemical's risk "without
consideration of costs or other non-risk factors." TSCA requires EPA
to consider the "COU" of a chemical, with no distinction drawn
between stationary sources and other sources, and focuses on the
risks posed by chemical substances and EPA actions that can
ameliorate those risks, without considering "standards of
performance."
First, the updated law specifies that, "the Administrator shall
consider and publish a statement based on reasonably available
During Problem Formulation, EPA
acknowledged that general population exposures
may occur through air, water, and land/soil
pathways. However, in the Risk Evaluation,
EPA did not include pathways under programs
of other environmental statutes, administered by
EPA. Because stationary source releases of TCE
to ambient air are covered under the CAA, EPA
did not evaluate emission pathways to ambient
air from commercial and industrial stationary
sources or associated inhalation exposure of the
general population. Because the drinking water
exposure pathway for TCE is covered in the
SDWA regulatory analytical process for public
water systems, EPA did not include this pathway
in the risk evaluation for TCE under TSCA. In
Problem Formulation, EPA also found general
population exposures to TCE via underground
injection, RCRA Subtitle C hazardous waste
landfills, RCRA Subtitle D municipal solid
waste (MSW) landfills, and on-site releases to
land from industrial non-hazardous waste and
construction/demolition waste landfills are under
the jurisdiction of and addressed by other EPA-
administered statutes and associated regulatory
programs. EPA did not include Superfund on-
site releases to the environment, as they are
under the jurisdiction of CERCLA. Lastly, EPA
did not include emissions to ambient air from
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information with respect to (i) the effects of the chemical substance
or mixture on health and the magnitude of the exposure of human
beings to the chemical substance or mixture..This requirement is
chemical-specific and is not conditioned on specific COU.
EPA can only rely on statutory authorities other than TSCA in
compliance with TSCA Section 9 (notably, the TSCA Section 9
process occurs after EPA has completed a comprehensive risk
evaluation finding unreasonable risk).
EPA should conduct sensitivity analyses to quantify the potential
extent of underestimation due to excluding these background
exposures.
Ignoring exposures subject to non-TSCA regulation will likely delay
protection to U.S. residents, as it is not likely that a TSCA evaluation
will immediately trigger a regulatory review by other EPA programs.
EPA must justify this decision or quantify the number of people
expected to experience substantial exposures to background
concentrations of TCE.
Congress expressly chose to separate risk evaluation and risk
management into different procedural steps (with risk evaluation
preceding risk management) to ensure that EPA provided a robust
risk evaluation uncolored by non-risk factors or other risk
management concerns.
The draft risk evaluation failed to provide missing analysis to support
the conclusion that there is no unreasonable risk from certain
exposures or combinations of exposures.
In order to decline an exposure pathway, EPA must first assess the
level of exposure from the pathway individually and then consider
how it combines with other sources of exposure.
municipal and industrial waste incineration and
energy recovery units in the risk evaluation, as
they are regulated under section 129 of the Clean
Air Act.
As explained in more detail in Section 1.4.2 of
the Final Risk Evaluation, EPA believes it is
both reasonable and prudent to tailor TSCA Risk
Evaluations when other EPA offices have
expertise and experience to address specific
environmental media, rather than attempt to
evaluate and regulate potential exposures and
risks from those media under TSCA. EPA
believes that coordinated action on exposure
pathways and risks addressed by other EPA-
administered statutes and regulatory programs is
consistent with statutory text and legislative
history, particularly as they pertain to TSCA's
function as a "gap-filling" statute, and also
furthers EPA aims to efficiently use Agency
resources, avoid duplicating efforts taken
pursuant to other Agency programs, and meet
the statutory deadline for completing Risk
Evaluations. EPA has therefore tailored the
scope of the Risk Evaluation for TCE using
authorities in TSCA Sections 6(b) and 9(b)(1).
56, 74,
90, 108
PUBLIC COMMENTS:
Exclusion of general population exposure violates intent of the
Lautenberg Act's and are contrary to the core mission of EPA to protect
public health. Major exposure pathways are ignored. EPA, Centers for
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Disease Control and Prevention (CDC)/Agency for Toxic Substances
and Disease Registry (ATSDR), and most states have documented TCE
concentrations in ambient air, with elevated levels around sources and in
highly populated areas. Exclusion of pathways of exposure from the risk
evaluation is the definition of arbitrary and capricious conduct and a
violation of TSCA.
TCE is pervasive in indoor air at concentrations documented to be
several times higher than outdoor levels due to consumer products,
vapor intrusion from subsurface contamination, and volatilization
from contaminated drinking water.
CDC/ATSR has reported that TCE is the most frequently detected
chemical contaminant in groundwater.
TCE has been found in a wide variety of foods. TCE has been
detected in breast milk in the general population. Formula fed infants
are also vulnerable because of the pervasive contamination of
drinking water and their high ingestion rate.
Little or no explanation was provided for the decision to not to
further analyze specific exposure pathways or receptors.
90
PUBLIC COMMENTS:
The general population and specifically low income and minority
populations that are entitled to enhanced protection under Executive
Order 12898 on Environmental Justice have been shown to be
overburdened by community sources of TCE. ATSDR in its 2019
updated toxicologic profile on TCE notes that the most important routes
of TCE exposure to the general public are through ambient air and the
ingestion of drinking water.
Environmental Justice have been shown to be overburdened by
community sources of TCE. It is the responsibility under TSCA to
combine and assess various sources to the general population and in
particular to vulnerable segments of the population.
EPA acknowledges low socioeconomic status as
a susceptibility factor for PESS groups in
Section 3.2.5.2. EPA uses the 99th percentile
output of the PBPK model in order to account
for the most toxicokinetically sensitive
proportion of the population. See Sections 2.3.3,
3.2.5.2, and 4.4.1 in the risk evaluation for
further discussions of PESS.
TSCA ง 6(b)(4)(A) requires that EPA conduct a
risk evaluation to "determine whether a
chemical substance presents an unreasonable
risk of injury to health or the environment,
without consideration of cost or other non-risk
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factors, including an unreasonable risk to a
potentially exposed or susceptible
subpopulation identified as relevant to the risk
evaluation by the Administrator, under the
conditions of use." TSCA ง 3(12) states that
"the term 'potentially exposed or susceptible
subpopulation' means a group of individuals
within the general population identified by the
Administrator who, due to either greater
susceptibility or greater exposure, may be at
greater risk than the general population of
adverse health effects from exposure to a
chemical substance or mixture, such as infants,
children, pregnant women, workers, or the
elderly." EPA believes that the statutory
directive to consider potentially exposed or
susceptible subpopulations (PESS) and the
statutory definition of PESS inherently include
environmental justice populations. Thus, EPA's
consideration of PESS in this risk evaluation
addresses the requirements of the Executive
Order.
EPA seeks to achieve the fair treatment and
meaningful involvement of any group, including
minority and/or low-income populations, in the
development, implementation, and enforcement
of environmental laws, regulations, and policies.
To this end, the Agency has already sought
input from specific populations and public
health experts in implementing TSCA and will
continue to do so. EPA will also consider
environmental justice populations in accordance
Page 89 of 408
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with the Executive Order as it develops risk
management actions based on final TSCA
section 6(b) risk evaluations.
56, 108
PUBLIC COMMENTS:
EPA has ignored "take home exposures" whereby the family of a
worker, including children, may be exposed via contact with the
worker's contaminated clothing or skin.
The frequency and magnitude of take-home
exposure is dependent on several factors,
including personal hygiene and visibility of the
chemical on skin or clothing. EPA does not have
methods to reliably predict take-home exposure
consistent with the mandate under TSCA section
26(h) to use the best available science.
SACC
SACC COMMENTS:
Recommendation: Use other TCE exposure sources (e.g., drinking water
from wells, and other contributors to indoor concentrations) in addition
to those from TCE-containing products to characterize consumer risks.
One Committee member suggested that the draft risk evaluation could
better characterize consumer risks by using an upper percentile of the
residential exposures reported in the general population studies cited in
the draft risk evaluation.
EPA did not consider background exposure that
workers and consumers using products
containing TCE might be exposed to in addition
to exposures from conditions of use in the scope
of the risk evaluation. This may result in an
underestimation of risk, and additional
discussion of this underestimation is found in
Sections 2.3.2.6.1 and 4.4.2.
49, 99
PUBLIC COMMENTS:
There is considerable evidence of TCE's ubiquitous presence in air, soil,
and drinking water at levels that likely harm human health and contribute
to ozone depletion and climate change. These exposure pathways cannot
be ignored.
EPA justification for excluding exposure pathways is not valid (general comments); EPA must assess total exposure
104, 49
PUBLIC COMMENTS:
In order to have a complete picture of how TCE endangers human health
and the environment, all exposure pathways need to be considered and
EPA should revise the draft risk evaluation of TCE to account for all
sources of exposure including all reasonably foreseen COU.
The conceptual models only included exposure
pathways that are within the scope of the risk
evaluation. The environmental exposure
pathways covered under the jurisdiction of other
EPA-administered statutes and regulatory
programs are not within the scope of the risk
evaluation. As explained in more detail in
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Section 1.4.2 of the Final Risk Evaluation, EPA
believes it is both reasonable and prudent to
tailor TSCA Risk Evaluations when other EPA
offices have expertise and experience to address
specific environmental media, rather than
attempt to evaluate and regulate potential
exposures and risks from those media under
TSCA. EPA believes that coordinated action on
exposure pathways and risks addressed by other
EPA-administered statutes and regulatory
programs is consistent with statutory text and
legislative history, particularly as they pertain to
TSCA's function as a "gap-filling" statute, and
also furthers EPA aims to efficiently use Agency
resources, avoid duplicating efforts taken
pursuant to other Agency programs, and meet
the statutory deadline for completing Risk
Evaluations. EPA has therefore tailored the
scope of the Risk Evaluation for TCE using
authorities in TSCA Sections 6(b) and 9(b)(1).
108,
49, 99,
104, 88
PUBLIC COMMENTS:
The exclusion of background exposures that workers and consumers
experience through air, water, and other pathways undermines EPA's
analysis of circumstances that EPA does analyze in the draft risk
evaluation because it is the total level of exposure to a chemical that
determines risk, and this includes exposures that are not generally
attributable to any one use or source.
Congress wanted EPA to examine the combined impact of all sources
and pathways of exposure and provided no exemption for
environmental releases that might be subject to other environmental
laws.
Other laws are not adequately addressing the contribution of air, soil,
and drinking water to total risk. If these pathways are ignored, the
EPA did not consider background exposure that
workers and consumers using products
containing TCE might be exposed to in addition
to exposures from conditions of use in the scope
of the risk evaluation. This may result in an
underestimation of risk, and additional
discussion of this underestimation is found in
Sections 2.3.2.6.1 and 4.4.2.
EPA did not consider background exposure for
workers, ONUs, consumers, and bystanders
using products containing TCE who might be
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result will likely be an incomplete understanding of TCE's risks and
inadequate protection of health and the environment and for
subpopulations with higher background TCE exposure levels.
EPA's decision to ignore exposures one-by-one rather than look at
combined exposure is inherently inaccurate and will invariably lead
to an underestimation of exposure and risk.
EPA should revise the draft TCE risk evaluation so it accounts for all
sources of exposure and risk and provides a complete understanding of
how TCE endangers public health.
exposed to in addition to exposures from other
conditions of use in the scope of the risk
evaluation. This may result in an
underestimation of risk, and additional
discussion of this underestimation is found in
Sections 2.3.2.6.1 and 4.4.2.
108
PUBLIC COMMENTS:
For numerous sources of exposure, EPA treats the overall exposure from
a particular pathway as "zero" or non-existent despite the fact that the
available evidence that exposure occurs at levels well above zero.
Humans and the environment are experiencing levels of exposure that
EPA is willfully ignoring.
The draft risk evaluation does not establish that the regulation of
these chemical substances under other statutes will eliminate
exposures, and in fact establishes that exposures continue to occur in
the real-world despite these statutes.
TSCA does not authorize EPA to ignore exposures because of other
statutory authorities; EPA has to analyze all exposures.
EPA may only rely on actions under another statute if those actions
will reduce an identified risk "to the extent necessary so that [it] no
longer presents [an unreasonable risk of injury to health or the
environment]." EPA cannot assume that other statutes, with different
standards, meet TSCA requirements.
EPA makes no showing that its actions under other statutes reduce
the risk "to the extent necessary so that [it] no longer presents [an
unreasonable risk of injury to health or the environment]," and EPA
does not present any actual analysis of "all relevant aspects of the
risk" arising from the ignored exposures. EPA has undisputedly
failed to comply with TSCA.
During Problem Formulation, EPA
acknowledged that general population exposures
may occur through inhalation, oral, and dermal.
However, in the Risk Evaluation EPA did not
include pathways under programs of other
environmental statutes, administered by EPA.
Because stationary source releases of TCE to
ambient air are covered under the CAA, EPA
did not evaluate emission pathways to ambient
air from commercial and industrial stationary
sources or associated inhalation exposure of the
general population. Because the drinking water
exposure pathway for TCE is covered in the
SDWA regulatory analytical process for public
water systems, EPA did not include this pathway
in the risk evaluation for TCE under TSCA. In
Problem Formulation, EPA also found general
population exposures to TCE via underground
injection, RCRA Subtitle C hazardous waste
landfills, RCRA Subtitle D municipal solid
waste (MSW) landfills, and on-site releases to
land from industrial non-hazardous waste and
construction/demolition waste landfills are under
Page 92 of 408
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the jurisdiction of and addressed by other EPA-
administered statutes and associated regulatory
programs. EPA did not include Superfund on-
site releases to the environment, as they are
under the jurisdiction of CERCLA. Lastly, EPA
did not include emissions to ambient air from
municipal and industrial waste incineration and
energy recovery units in the risk evaluation, as
they are regulated under section 129 of the Clean
Air Act.
As explained in more detail in Section 1.4.2 of
the Final Risk Evaluation, EPA believes it is
both reasonable and prudent to tailor TSCA Risk
Evaluations when other EPA offices have
expertise and experience to address specific
environmental media, rather than attempt to
evaluate and regulate potential exposures and
risks from those media under TSCA. EPA
believes that coordinated action on exposure
pathways and risks addressed by other EPA-
administered statutes and regulatory programs is
consistent with statutory text and legislative
history, particularly as they pertain to TSCA's
function as a "gap-filling" statute, and also
furthers EPA aims to efficiently use Agency
resources, avoid duplicating efforts taken
pursuant to other Agency programs, and meet
the statutory deadline for completing Risk
Evaluations. EPA has therefore tailored the
scope of the Risk Evaluation for TCE using
authorities in TSCA Sections 6(b) and 9(b)(1).
108
PUBLIC COMMENTS:
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TSCA requires that, in conducting a risk evaluation, EPA evaluate "the
likely duration, intensity, frequency, and number of exposures,"
including exposures resulting from those allowable emissions,
discharges, or releases. EPA needs to provide this analysis.
The conceptual models only included exposure
pathways that are within the scope of the risk
evaluation. The environmental exposure
pathways covered under the jurisdiction of other
EPA-administered statutes and regulatory
programs are not within the scope of the risk
evaluation. Clarifying language about what
pathways are addressed under other statutes has
been added to Section 1.4.2 of the Risk
Evaluation.
49, 99
PUBLIC COMMENTS:
Previously, the SACC indicated that "[gjeneral human population and
biota exposure must be assessed for inhalation, ingestion, and dermal
routes [and that] [different sub-populations may have different extents
of exposure, but each route must be assessed."
If risks have been assessed by other program offices of EPA, then
EPA should present them as part of the underlying data to support
this TSCA draft risk evaluation - if not, EPA must gather the data for
an assessment or include an assessment based on the assumption of
near-worst-case exposures.
EPA should aggregate across COU and exposure pathways (inhalation and dermal routes; occupational and consumer)
SACC,
47, 49,
56, 65,
74, 75,
99,
100,
104,
108
SACC COMMENTS:
Non-consideration of aggregate exposures (e.g., workers who are also
consumer users; workers that may be exposed in more than one scenario)
will be a standing problem unless EPA places their estimates in the
context of risks from sources and pathways not included in the TSCA
draft risk evaluation.
Recommendation: Improve the discussion on aggregate exposure and
justification for it not being performed. The issue of aggregate exposure
combining inhalation and dermal routes is inadequately discussed and
ignored.
Recommendation: Consider aggregating dermal and inhalation exposures
for consumer users when simultaneous exposures by both routes are
expected.
There were different opinions expressed by Committee members about
aggregation of dermal and inhalation exposures. Some Committee
members noted that exposures by both routes should be aggregated in all
scenarios. One member noted that aggregating dermal and inhalation
exposure in all cases is not warranted because if there is dermal
TSCA section 6(b)(4)(F)(ii) directs EPA to
"describe whether aggregate or sentinel
exposures to a chemical substance under the
conditions of use were considered, and the basis
for that consideration" in risk evaluations. EPA
defines aggregate exposures as the combined
exposures to an individual from a single
chemical substance across multiple routes (i.e.,
dermal, inhalation, or oral) and across multiple
pathways (i.e., exposure from different sources).
40 CFR 702.33. EPA defines sentinel exposures
as the exposure from a single chemical
substance that represents the plausible upper
bound of exposure relative to all other exposures
within a broad category of similar or related
exposures. 40 CFR 702.33. EPA considered the
reasonably available information and used the
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exposure, there is almost certainly inhalation exposure, but the converse
is not necessarily always true.
PUBLIC COMMENTS:
EPA failed to assess "the combined exposures to an individual from a
single chemical substance across multiple routes and across multiple
pathways" as required by TSCA. It failed to consider combined
exposures of workers from multiple COUs, including aggregate exposure
among individuals exposed both in an occupational and consumer
context, at work and at home, indicating that there is insufficient
information reasonably available as to the likelihood of this scenario or
the relative distribution of exposures from each pathway.
EPA should use its information authorities to gain more information
about these scenarios.
EPA could combine its exposure estimates for workplace COUs with
those it has developed for consumer COUs (with adjustments). These
aggregated exposure estimates would be representative of a large
subset of workers who use (or are bystanders to the use of) TCE-
containing consumer products. By defining a subgroup with high-end
exposure and risk, this would enable EPA to meet its obligation
under TSCA to determine unreasonable risks to "potentially exposed
or susceptible subpopulations" or PESS.
EPA failed to consider workers' combined exposure from multiple routes
as required by TSCA EPA recognizes that workers could readily
experience exposures by both inhalation and dermal routes, including
over the same time period, and states that it is essential to evaluate
exposures from both of these routes in combination, including
simultaneously, to assess total body burden and the associated effects.
EPA, however, dismisses employing an additivity approach to assess
overall exposure with insufficient justification, and then fails to
acknowledge that this will result in an underestimation of exposure.
EPA's concern about overestimating exposure is not credible.
Page 95 of 408
best available science to determine whether to
consider aggregate or sentinel exposures for a
particular chemical.
EPA has determined that using the high-end risk
estimate for inhalation and dermal risks
separately as the basis for the unreasonable risk
determination is a best available science
approach. There is low confidence, based on the
weight of the scientific evidence, in the result of
aggregating the dermal and inhalation risks for
this chemical if EPA uses an additive approach,
due to the uncertainty in the data. EPA does not
have reasonably available data that could be
reliably modeled for aggregating dermal
exposure with other routes without a dermal
compartment in the PBPK model, which would
be a more accurate approach than simple
additivity. Using an additive approach to
aggregate risk in this case could result in an
overestimate of risk. Given all the limitations
that exist with the data, EPA's approach is the
best available science. EPA has added language
to Sections 2.3.2.6.1 and 4.4.2 describing these
assumptions and uncertainties.
EPA did not consider background exposure that
workers, ONUs, consumers, and bystanders
using products containing TCE who might be
exposed to in addition to exposures from the
conditions of use in the scope of the risk
evaluation. Risk is likely to be elevated for
individuals who experience TCE exposure in
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EPA has failed to consider previous SACC recommendations to
combine the inhalation and dermal exposures.
Risk determinations for all occupational and consumer COUs should be
based upon aggregation of all exposures.
Aggregation of exposures within a COU, coupled with exposures known
to exist outside a COU, should always be implemented as a benchmark
of a credible and responsible exposure assessment.
EPA's contrary approach of evaluating each COU in isolation is an
unlawful attempt to minimize the assessment of the total risk posed
by TCE and avoid regulation. EPA must examine the combined
combination of all COUs to total risk and exposure and cannot
determine unreasonable risk for each COU in isolation
Risks to workers and consumers should be a function of the aggregate
contribution of each activity and pathway to total exposure. However,
the draft risk evaluation looks at each exposure pathway in isolation
from others, thus underestimating total risk.
The World Health Organization has warned that workers "living in the
vicinity of plants emitting TCE to the air" are likely to face "higher than
usual exposure levels." By looking at individual uses in isolation and
ignoring the additional contributions of off-the-job exposures, EPA
grossly understates TCE's total risks to workers.
multiple contexts. This may result in an
underestimation of risk, and additional
discussion of this underestimation is found in
Sections 2.3.2.6.1 and 4.4.2.
Per 40 CFR 702.47 ".. EPA will determine
whether the chemical substance presents an
unreasonable risk of injury to health or the
environment under each condition of use within
the scope of the risk evaluation...." This
approach in the implementing regulations for
TSCA risk evaluations, is consistent with
statutory text in TSCA section 6(b)(4)(A), which
instructs EPA to conduct risk evaluations to
determine whether a chemical substance
presents an unreasonable risk "under the
condition of use."
49, 56,
99, 108
PUBLIC COMMENTS:
EPA has ignored all non-occupational baseline exposures worker
experience, due to its exclusion of all exposures via environmental
releases to air, water, and land.
EPA at least needs to take these into account as baseline exposures
for workers even if it does not intend to assess risks from
environmental releases. EPA cannot ignore real-world exposures
when assessing individual risks to TCE.
For example, workers in vapor degreasing may live in industrialized
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areas with high ambient air levels or Superfund sites and consume
TCE-contaminated drinking water. In the aggregate, TCE exposure
by these workers would be significantly greater than exposure in the
workplace alone and health risks (which are already alarmingly high
for worker activities) would be correspondingly higher.
Because TCE exposure levels are higher for these subpopulations
than for the general population, they face elevated risks of TCE-
related health effects that the draft risk evaluation ignores.
56, 65,
74,
100,
108
EPA does not dispute that failing to aggregate inhalation and dermal
exposures may lead to an underestimate of exposure. EPA invokes
uncertainty as its excuse for that underestimation. To the extent that there
are uncertainties in an aggregating analysis, these do not support
assuming exposure is less than the sum of the exposures. Uncertainty
does not justify ignoring the fact that these exposures are actually
experienced in combination.
56, 108
PUBLIC COMMENTS:
EPA did not establish that it prepared adequate aggregate or sentinel
exposure assessments in its risk evaluation and failed to explain how its
decision to rely on other exposure assessments can be reconciled with
TSCA.
EPA has not explicitly stated whether, in identifying sentinel
exposures for workers, use of personal protective equipment (PPE)
was assumed, although it is clear that PPE use was assumed.
EPA should consider exposures without any PPE unless it can
establish it is always and effectively used for a particular COU.
EPA's approach for developing exposure
assessments for workers is to use the reasonably
available information and expert judgement.
When appropriate, in the risk evaluation, EPA
will use exposure scenarios both with and
without engineering controls and/or PPE that
may be applicable to particular worker tasks on a
case-specific basis for a given chemical. While
EPA has evaluated worker risk with and without
PPE, as a matter of policy, EPA does not believe
it should assume that workers are unprotected by
PPE where such PPE might be necessary to meet
federal regulations, unless it has evidence that
workers are unprotected. For the purposes of
determining whether or not a condition of use
presents unreasonable risks, EPA incorporates
assumptions regarding PPE use based on
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information and judgment underlying the
exposure scenarios. These assumptions are
described in the unreasonable risk determination
for each condition of use, in section 5.2.
Additionally, in consideration of the
uncertainties and variabilities in PPE usage,
EPA uses the high-end exposure value when
making its unreasonable risk determination in
order to address those uncertainties. EPA has
also outlined its PPE assumptions in section 5.1.
Further, in the final risk evaluation for TCE,
EPA has determined that most conditions of use
pose an unreasonable risk to workers even with
the assumed PPE.
EPA should include exposure from vapor intrusion in the risk evaluation
49, 90,
93, 99
PUBLIC COMMENTS:
According to EPA, "TCE levels measured indoors have been directly
linked to vapor intrusion," and "[vjapor intrusion is a likely significant
source in situations where residences are located near soils or
groundwater with high contamination levels."
ATSDR describes vapor intrusion as a "notable exposure route" and
cites several studies that attributed elevated TCE indoor air levels to
vapor intrusion from TCE-contaminated cleanup sites or
groundwater.
TCE vapor intrusion resulting from disposal and from contaminated
groundwater or soil near Ironbound facilities, which qualify as
"spills, leaks, and other uncontrolled discharges" has been reported.
Studies have also reported indoor air levels of TCE in residences,
schools, and stores. EPA ignores this readily available data.
EPA's document detailing the rationale for incorporating subsurface
vapor intrusion into the Superfund Hazard Ranking System details a
statistically significant burden of sites involving vapor intrusion on
low income populations (p. 30, EPA-HQ-SFUND-2010-1086-0076).
During the TCE Problem Formulation, EPA
acknowledged the historic groundwater
contamination and resulting vapor intrusion
concerns. EPA also acknowledged that general
population exposures may occur through
inhalation, oral, and dermal. However, in the
Risk Evaluation, EPA did not include pathways
under programs of other environmental statutes,
administered by EPA, for which long-standing
regulatory and analytical processes already exist.
EPA has determined that general population
exposures due to drinking water contamination,
groundwater contamination, and air emissions
are under the jurisdiction of other statutes and
are outside the scope of this risk evaluation. In
addition, EPA determined that spills and leaks
are not TSCA conditions of use as these
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EPA must evaluate exposures from ongoing TCE vapor intrusion in
its final risk evaluation.
EPA has, or can reasonably generate or obtain, the information
necessary to evaluate TCE vapor intrusion, meaning that the
information is "reasonably available" under TSCA.
unintentional activities are covered by other
statues, described further in Section 1.4.2.
In exercising its discretion under TSCA section
6(b)(4)(D) to identify the conditions of use that
EPA expects to consider in a risk evaluation,
EPA believes it is important for the Agency to
have the discretion to make reasonable,
technically sound scoping decisions. EPA did
not include legacy disposals, (i.e., disposals that
have already occurred), because they do not fall
under the definition of conditions of use under
TSCA section 3(4).
93
PUBLIC COMMENTS:
While EPA recommends the consideration of vapor intrusion at certain
federal Superfund and Resource Conservation and Recovery Act
(RCRA) corrective action sites, many sites with TCE contamination
from disposal are not, and will never be, remediated under Superfund or
RCRA. For those sites that are, remediation is slow and depends on the
identification of a financially viable responsible party, which often does
not exist.
Thus, the possibility that some vapor intrusion incidents may be
addressed under other laws does not alter EPA's duty to consider
vapor intrusion in the TCE risk evaluation and to issue risk
management rules that regulate TCE "to the extent necessary so
that [this] chemical substance ... no longer presents
[unreasonable] risk" to the residents of Manufacturers Place or
other residential areas exposed to TCE from vapor intrusion.
EPA's exclusion of exposures through air is invalid
108
PUBLIC COMMENTS:
With >12 million pounds of TCE emitted to the air in 2014, it is absurd
to treat the overall exposure through this pathway as if it were "zero."
EPA did not include the emission pathways to
ambient air because releases of TCE from
stationary source to ambient air are under the
jurisdiction of and addressed by Section 112 of
the Clean Air Act (CAA). Clarifying language
about what pathways are addressed under other
statutes has been added to Section 1.4.2 of the
Risk Evaluation.
49, 99,
56,
108, 74
PUBLIC COMMENTS:
Large segments of the U.S. population are likely exposed to TCE levels
in air that present unreasonable risks of cancer and non-cancer effects.
EPA did not consider background exposure that
workers and consumers using products
Page 99 of 408
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Based on Integrated Risk Information System (IRIS)-determined
cancer risk levels (70-year lifetime exposure) for different TCE
ambient air concentrations, levels in ambient air for all locations
except forests would present lifetime cancer risks above 1 in 1
million. Risks for higher levels within the range measured would
exceed 1 in 100,000.
Mean ambient air levels in most locations (which range between 0.89
and 1.6 (j,g/m3) would be close to the IRIS non-cancer reference
concentration (RfC) of 0.0004 ppm (0.4 ppb or 2 (j,g/m3), which IRIS
describes as having "robust support [from] . . . estimates for multiple
effects from multiple studies." For individuals exposed to ambient
TCE levels near the higher end of the reported range, the RfC would
be exceeded.
TCE is listed as a HAP and EPA relies on the CAA to dismiss the
need to assess exposures to TCE from air emissions; however, the
CAA is for individual source categories, meaning that the exposures
to TCE from all sources in combination are never considered.
Therefore, EPA's approach to risk evaluations under TSCA ensures
that EPA never evaluates, and the public never finds out, the risk
from all air emissions of TCE or any other chemical substance. The
control of pollutants through CAA regulation differ in scope from
EPA's authority to regulate or prohibit the production or use of these
substances under TSCA.
By EPA's own account, its CAA regulation of TCE did not eliminate
all risk from facilities engaged in halogenated solvent cleaning, or
consider how exposure to TCE from the regulated facilities might
combine with exposures from other facilities and sources to increase
overall risk.
It cannot therefore be assumed that the CAA will eliminate risk to
exposed populations.
containing TCE might be exposed to in addition
to exposures from conditions of use in the scope
of the risk evaluation. This may result in an
underestimation of risk, and additional
discussion of this underestimation has been
added to Sections 2.3.2.6.1 and 4.4.2.
The purpose of risk evaluation under TSCA is
"to determine whether a chemical substance
presents an unreasonable risk of injury to health
or the environment, without consideration of
costs or other nonrisk factors, including an
unreasonable risk to a potentially exposed or
susceptible subpopulation identified as relevant
to the risk evaluation by the Administrator,
under the conditions of use." TSCA section
6(b)(4)(A). EPA described background exposure
in the uncertainties section acknowledging that
the risk estimations in the Risk Evaluation may
be underestimations, because background
exposures and risk are not incorporated into the
risk estimations for each OES. Emissions to
ambient air from commercial or industrial
stationary sources, or inhalation exposures of
terrestrial species are managed under the
jurisdiction of the Clean Air Act (CAA).
90, 108
PUBLIC COMMENTS:
EPA's exclusion of exposure levels through the ambient air pathway,
particularly near sites where people may experience greater exposure due
EPA has determined that general population
exposures due to drinking water contamination,
Page 100 of 408
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to their proximity to COUs or contamination sites, will seriously
underestimate the levels of exposure across the country. EPA should use
its information authorities to obtain information about exposure levels
experienced by the subpopulations living near COUs.
Adding to the TRI air exposure is the exposure from Superfund sites,
over 50% of which include TCE as a contaminant of concern under
CERLA's provisions. Elevated levels of TCE in indoor air near
Superfund sites has been documented in California, and North
Carolina (ROD Middlefield-Ellis-Whisman, OIG Report No. 16-P-
0296).
groundwater contamination, and air emissions
are under the jurisdiction of other statutes and
are outside the scope of this risk evaluation.
In exercising its discretion under TSCA section
6(b)(4)(D) to identify the conditions of use that
EPA expects to consider in a risk evaluation,
EPA believes it is important for the Agency to
have the discretion to make reasonable,
technically sound scoping decisions. EPA did
not include legacy disposals, {i.e., disposals that
have already occurred), because they do not fall
under the definition of conditions of use under
TSCA section 3(4).
49, 99,
93
PUBLIC COMMENTS:
According to IRIS, "TCE can be released to indoor air from use of
consumer products that contain it {i.e., adhesives and tapes), vapor
intrusion (migration of volatile chemicals from the subsurface into
overlying buildings) and volatilization from the water supply."
Consistently measured indoor levels have been shown to be higher
than outdoor levels.
Several studies, including Wallace (1987), Andelman (1985), Shah
and Singh (1988), Hers et al. (2001), Sapkota et al. (2005), Sexton et
al. (2005), and Zhu et al. (2005), report levels that exceed a 1 in 1
million cancer risk and, at the higher end of the reported range,
would exceed the IRIS RfC.
ATSDR reports that the contribution to TCE indoor levels of
volatilization of contaminated drinking water is well-documented:
Andelman, (1985); McKone and Knezovich (1991).
EPA has repeatedly acknowledged the risks associated with TCE
vapor intrusion and has published guidance governing the calculation
of vapor intrusion risks. There is no basis for EPA to exclude vapor
Unlike other EPA programs, TSCA requires
chemical risk be assessed and determined for
each "condition of use" and not by media {e.g.,
indoor air). EPA did an extensive assessment of
TCE in 7 consumer product categories covering
25 COU and concluded their use presented
unreasonable inhalation risk {i.e., from the air
pathway) in all indoor uses. See Section 2.3.3
for details about the consumer risk assessments.
Regarding volatilization from the water supply,
EPA acknowledged the historic groundwater
contamination and resulting vapor intrusion
concerns in the TCE Problem Formulation. EPA
also acknowledged that general population
exposures may occur through inhalation, oral,
and dermal routes. However, in the Risk
Page 101 of 408
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intrusion and other disposal-related TCE emissions from the draft
risk evaluation.
The draft risk evaluation does not look more broadly at indoor TCE air
concentrations to which consumers are exposed, and overlooks the
combined contributions to exposure of product use and other indoor
exposure pathways like volatilization of TCE from contaminated water
and intrusion of TCE vapors from contaminated soil and groundwater.
This underestimates TCE risks in the indoor environment.
Evaluation, EPA did not include pathways under
programs of other environmental statutes,
administered by EPA, for which long-standing
regulatory and analytical processes already exist.
EPA exclusion of exposures through drinking and ambient water is invalid
SACC
SACC COMMENTS:
Exposure from drinking water is not adequately covered in the risk
assessment.
As part of the problem formulation for TCE,
EPA identified exposure pathways under other
environmental statutes administered by EPA,
e.g., the Clean Air Act (CAA), the Safe Drinking
Water Act (SDWA), the Clean Water Act
(CWA) and the Resource Conservation and
Recovery Act (RCRA). As explained in more
detail in Section 1.4.2 of the Final Risk
Evaluation, EPA believes it is both reasonable
and prudent to tailor TSCA Risk Evaluations
when other EPA offices have expertise and
experience to address specific environmental
media, rather than attempt to evaluate and
regulate potential exposures and risks from those
media under TSCA. EPA believes that
coordinated action on exposure pathways and
risks addressed by other EPA-administered
statutes and regulatory programs is consistent
with statutory text and legislative history,
particularly as they pertain to TSCA's function
as a "gap-filling" statute, and also furthers EPA
aims to efficiently use Agency resources, avoid
74, 90,
99, 108
PUBLIC COMMENTS:
EPA ignored all exposures through drinking water despite available
evidence that exposures do occur through this pathway.
The existence of a Maximum Contaminant Level (MCL) does not
result in zero exposures to TCE through drinking water; EPA should
analyze the real-world exposures.
EPA has not shown that the MCL of 5.0 [j,g/L eliminates any
unreasonable risk or assessed all relevant aspects of the risk. The
current MCL is outdated and not health protective. The IRIS non-
cancer reference dose (RfD) is 0.5 (^g/L.
The Safe Water Drinking Act (SWDA) MCL is based on non-risk
factors including what is feasible (e.g., with regard to treatment and
monitoring) and cost. EPA cannot consider these during the risk
evaluation process.
The MCL is higher than the maximum contaminant level goal
(MCLG) for TCE, which is zero, indicating that in order to avoid
adverse effects on human health from drinking water TCE should not
be in drinking water at any level, EPA must address the risks posed
by ongoing exposure to TCE at levels in drinking water below the
MCL.
Page 102 of 408
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The SWDA does not regulate all sources of water including private
drinking wells; this source needs to be evaluated.
Analyzing exposure through drinking water is important to obtain an
accurate estimate of the exposure of infants and children.
Exceedances of the MCL have been recorded in 149 PWSs. Cancer and
non-cancer risks to this subpopulation exceed EPA benchmarks for
unreasonable risk, even without considering the volatilization of
household water during showering and other daily activities and
resulting in TCE inhalation exposure.
duplicating efforts taken pursuant to other
Agency programs, and meet the statutory
deadline for completing Risk Evaluations. EPA
has therefore tailored the scope of the Risk
Evaluation for TCE using authorities in TSCA
Sections 6(b) and 9(b)(1).
The conceptual models only included exposure
pathways that are within the scope of the risk
evaluation. The environmental exposure
pathways covered under the jurisdiction of other
EPA-administered statutes and regulatory
programs are not within the scope of the risk
evaluation.
Because the drinking water exposure pathway
for TCE is currently addressed in the SDWA
regulatory analytical process for public water
systems, EPA did not include this pathway in the
risk evaluation for TCE under TSCA. In
Problem Formulation, EPA also found general
population exposures to TCE via underground
injection, RCRA Subtitle C hazardous waste
landfills, RCRA Subtitle D municipal solid
waste (MSW) landfills, and on-site releases to
land from industrial non-hazardous waste and
construction/demolition waste landfills are under
the jurisdiction of and addressed by other EPA-
administered statutes and associated regulatory
programs. EPA did not include Superfund on-
site releases to the environment, as they are
under the jurisdiction of CERCLA. Lastly, EPA
SACC
SACC COMMENTS:
Exclusion of groundwater on the basis of regulation under clean water or
safe drinking water statutes is erroneous, because private wells are not
regulated under the Clean Water Act (CWA) or SDWA.
108
PUBLIC COMMENTS:
EPA ignores exposures through ambient water citing regulation through
the CWA.
Not all states have updated their criteria to reflect the current CWA
criteria and are using less stringent standards. Therefore, EPA cannot
rely on the CWA recommendations to assume that risks are
adequately managed.
EPA has not demonstrated that the established criteria reflect the
current best available science.
EPA has not acknowledged the ongoing uncertainty surrounding the
definition of "waters of the United States" regulated under the CWA
including the regulatory reach of the CWA as well as compliance and
enforcement activities. EPA cannot assume that all ambient water is
adequately managed under the CWA when EPA itself expresses
ongoing uncertainty over the jurisdictional reach of the CWA.
In the draft risk evaluation, EPA describes monitoring data and
published literature showing that TCE is present in surface water. EPA's
own modeling shows that TCE is present in surface water at significant
Page 103 of 408
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concentrations. EPA cannot assume that TCE has nonexistent exposure
through ambient water.
EPA should examine and summarize that exposure information when
evaluating the risks presented by TCE; if that information is
insufficient, EPA should use its authorities to require the
development of additional needed information.
EPA must analyze the ambient water pathway in the risk evaluations.
did not include emissions to ambient air from
municipal and industrial waste incineration and
energy recovery units in the risk evaluation, as
they are regulated under section 129 of the Clean
Air Act.
Clarifying language about what pathways are
addressed under other statutes has been added to
Section 1.4.2 of the Risk Evaluation.
107
PUBLIC COMMENTS:
EPA's failure to include drinking water exposure results in an
underestimation of exposure and ultimately, risk. It is easier, more
effective, and more equitable to control pollutants at the source, where
they are highly concentrated, than it is to remove them at the consumer's
expense after they have entered a water body or supply source. EPA has
the authority under TSCA to control the introduction into the
environment of contaminants such as TCE that degrade water quality and
increase the cost of water treatment.
EPA exclusion of exposures through disposal is invalid
108
PUBLIC COMMENTS:
EPA limited analysis of exposure from "Process Solvent Recycling and
Worker Handling of Wastes," to workers and occupational non-users
(ONUs). General population exposure to all ambient air, land disposal,
and waste incineration pathways were excluded as well as exposures
from all disposal-related pathways and associated activities (e.g.,
collection, processing, storage, and transport) due to regulation of
disposal under the RCRA, CAA, SDWA, and various state programs.
EPA has not established or shown that disposal regulations
"adequately assess and effectively manage exposures."
EPA recognized that not all disposal occurs in RCRA Subtitle C
landfills, and that other disposal sites do not meet the requirements of
Subtitle C. Some state programs don't include requirements for liners
to limit release of landfill leachate.
EPA acknowledged that enforcement and regulation under RCRA is
inconsistent, so it cannot simply assume that RCRA implementation
EPA evaluated and considered the impact of
existing laws and regulations (e.g., regulations
on landfill disposal, design, and operations) in
the problem formulation step to determine what,
if any future analysis might be necessary as part
of the risk evaluation. During problem
formulation EPA analyzed the TRI data and
examined the definitions of elements in the TRI
data to determine the level of confidence that a
release would result from certain types of
disposal to land (e.g., RCRA Subtitle C
hazardous landfill and Class I underground
Injection wells) and incineration. EPA also
examined how TCE is treated at industrial
facilities. EPA did not include emissions to
Page 104 of 408
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provides a basis for ignoring exposures.
Congress specifically directed EPA to analyze the risks of chemicals
presented "under the conditions of use," and Congress consciously
decided to specify that "disposal" is a COU under TSCA.
"Conditions of use" expressly includes "the circumstances under
which a chemical substance is intended, known, or reasonably
foreseen to be to be manufactured, processed, distributed in
commerce, used, or disposed of."
Page 105 of 408
ambient air from commercial and industrial
stationary sources, which are under the
jurisdiction of and addressed by Section 112 of
the Clean Air Act. EPA did not include
emissions to ambient air from municipal and
industrial waste incineration and energy
recovery units in the risk evaluation, as they are
regulated under section 129 of the Clean Air
Act. EPA did not include disposal to
underground injection, RCRA Subtitle C
hazardous waste landfills, RCRA Subtitle D
municipal solid waste (MSW) landfills, and on-
site releases to land from industrial non-
hazardous waste and construction/demolition
waste landfills in this Risk Evaluation. EPA did
not include Superfund on-site releases to the
environment, as they are under the jurisdiction
of CERCLA. These methods of disposal fall
under the jurisdiction of and are addressed by
other EPA-administered statutes and associated
regulatory programs.
As explained in more detail in Section 1.4.2 of
the Final Risk Evaluation, EPA believes it is
both reasonable and prudent to tailor TSCA Risk
Evaluations when other EPA offices have
expertise and experience to address specific
environmental media, rather than attempt to
evaluate and regulate potential exposures and
risks from those media under TSCA. EPA
believes that coordinated action on exposure
pathways and risks addressed by other EPA-
administered statutes and regulatory programs is
-------
consistent with statutory text and legislative
history, particularly as they pertain to TSCA's
function as a "gap-filling" statute, and also
furthers EPA aims to efficiently use Agency
resources, avoid duplicating efforts taken
pursuant to other Agency programs, and meet
the statutory deadline for completing Risk
Evaluations. EPA has therefore tailored the
scope of the Risk Evaluation for TCE using
authorities in TSCA Sections 6(b) and 9(b)(1).
108
PUBLIC COMMENTS:
There are almost 1,300 instances of required rules for which various state
hazardous waste programs have not been authorized. When states have
out-of-date hazardous waste programs, citizens in different states are
unevenly protected from hazardous waste-related risks.
EPA cannot rely on assumptions of consistent implementation and
enforcement of RCRA to ensure adequate management.
For EPA to treat these exposure levels as "zero" when they exist does
not comport with the best available science.
EPA should use their authority to obtain additional information about
the exposures arising from disposal for TCE.
See below response regarding the Land Disposal
Program Flexibility Act of 1996, codified at
RCRA section 3010a(c)(5) and (6).
EPA must consider exposures in tribal communities
104
PUBLIC COMMENTS:
Environmental statutes do not guarantee protection from exposures,
particularly in the case of tribes, which may be disproportionately
impacted. Disposal circumstances on tribal lands are different from those
of urban areas with municipal landfills. In the case of many tribal and
rural communities, the disposal site may be in close proximity to
residents, be unlined, open access, or include open burning as a
management practice. These present multiple exposure pathways and
routes for intake and uptake.
EPA states that "Studies clearly associated with releases from
Superfund sites, improper disposal methods, landfills were
The commenter appears to be describing aspects
of the Land Disposal Program Flexibility Act of
1996, codified at RCRA section 3010a(c)(5) and
(6). The law directed EPA to provide additional
flexibility to approved states for landfills that
receive 20 tons or less of municipal solid waste
per day. The additional flexibility applies to
alternative frequencies of daily cover,
frequencies of methane monitoring, infiltration
layers for final cover, and means for
Page 106 of 408
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considered not to meet the PECO statement and [were] excluded
from data evaluation and extraction." Leachate samples were
excluded because they were considered an "off-topic" media.
TCE is considered hazardous waste under RCRA but many tribal
communities do not have access to Subtitle C landfills. There is not a
single Subtitle C landfill in the State of Alaska. Tribes experience
exposures even where responsibility rests on other environmental
statutes.
EPA should revise this risk evaluation to include TCE releases from
landfills, including those that are characteristic of tribal communities.
Disposal is a main route for TCE to enter the environment; it is
unacceptable to exclude disposal, and the resulting exposures, from
consideration.
demonstrating financial assurance. Section
3010a(c)(6). Further, under section 3010a(c)(5),
if the Alaska governor certifies that application
of the requirements for groundwater monitoring,
siting, or corrective action to a solid waste
landfill unit of a Native village, or a unit located
in or near a small, remote Alaska village, would
be infeasible, would not be cost-effective, or
would be otherwise inappropriate because of the
remote location of the unit, Alaska may exempt
the unit from some or all of those requirements.
It is not at all clear to EPA that Congress
intended for TSCA to override the flexibilities
specifically provided for small municipal solid
waste landfills and the additional flexibilities
specifically provided to Alaska in the Land
Disposal Program Flexibility Act of 1996. EPA
believes that the 1996 Act represents
Congressional recognition that the RCRA
Subtitle D program is not always feasible, or
practicable, for the small landfills covered by the
Act, and the additional flexibility provided by
the Act is therefore necessary and appropriate.
104
PUBLIC COMMENTS:
EPA must consider aggregate and cumulative exposures for tribal
communities. A single person may be a landfill worker, an occupational
bystander, and a near-facility general population, as well as a consumer.
They will likely derive their food and water, including untreated water,
near-source. Such scenarios are the norm for landfill workers in the over
200 Alaska tribal communities.
EPA did not consider aggregate or background
exposure that workers, ONUs, consumers, or
bystanders using products containing TCE might
be exposed to in addition to exposures from the
conditions of use in the scope of the risk
evaluation because there is insufficient
information reasonably available as to the
likelihood of this scenario or the relative
distribution of exposures from each pathway.
Page 107 of 408
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This may result in an underestimation of risk,
and EPA acknowledges that risk is likely to be
elevated for individuals who experience TCE
exposure in multiple contexts. Additional
discussion of this issue has been added to
Sections 2.3.2.6.1, 2.3.2.2.1, and 4.4.2.
104
PUBLIC COMMENTS:
Native Americans are more highly exposed to contaminants with
environmental fate and transport than other populations because their
lifeways revolve around environmental activities for dietary sustenance,
socio-cultural activities, ceremonial and spiritual purposes, recreation,
and general well-being. Tribal lifeways can lead to chronic exposures to
toxins in the environment, due to longer duration and higher frequency
of exposures, and a higher cumulative dose from multiple exposure
pathways. Native Americans experience significant health disparities
from the general population and the practice of leaving them out of any
protections will only contribute to further health disparities.
EPA recognizes that Native Americans have
unique lifeways and has considered established
differences in patterns in relevant exposure
pathways (e.g., increased fish consumption).
However, general population exposure pathways
were not included in the scope of the risk
evaluation as discussed in Section 1.4.2 and a
review of reasonably available information did
not produce data for establishing a differential
experience for the evaluated exposure pathways,
namely occupational and consumer activities.
An additional statement about the uncertainty
associated with subpopulations patterns of use
has been added to Section 2.3.2.6.2.
104
PUBLIC COMMENTS:
EPA is urged to consider data submitted by the Tribe that produced it.
Where data are not available, modeling should be employed so that all
significant Tribal exposures are captured. Evaluation of chemicals
should then include tribal peoples' multiple unique exposures.
EPA must consider exposures due to accidental releases
56, 108
PUBLIC COMMENTS:
EPA does not consider risks of exposure due to potential accidental
releases. This risk is "reasonably foreseen" and EPA has authority to
mandate steps to reduce those risks. EPA needs to give more
consideration to the potential for accidental releases.
Accidental releases, spills and leaks generally
are not included within the scope of a TSCA risk
evaluation because in general they are not
considered to be circumstances under which a
chemical substance is intended, known or
reasonably foreseen to be manufactured,
processed, distributed, used, or disposed of. To
the extent there may be potential exposure from
accidents, EPA is also declining to evaluate
56, 90,
100,
108
PUBLIC COMMENTS:
EPA excluded exposures from spills and leaks.
There are many documented spills of TCE both within the workplace
and to the environment. These exposures should be considered
"reasonably foreseen" under TSCA.
Page 108 of 408
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EPA should evaluate exposures and risks posed by reasonably foreseen
spills and other occupational releases of TCE.
Page 109 of 408
environmental exposure pathways addressed by
another EPA-administered statutes and
associated regulatory programs.
First, EPA does not identify TCE accidental
releases, spills and leaks as "conditions of use."
EPA does not consider TCE accidental releases,
spills and leaks to constitute circumstances
under which TCE is manufactured, processed,
distributed, used, or disposed of, within TSCA's
definition of "conditions of use." Congress
specifically listed discrete, routine chemical
lifecycle stages within the statutory definition of
"conditions of use" and EPA does not believe it
is reasonable to interpret "circumstances" under
which TCE is manufactured, processed,
distributed, used, or disposed of to include
uncommon and unconfined accidents, spills or
leaks for purposes of the statutory definition.
Further, EPA does not generally consider
accidental releases, spills and leaks to constitute
"disposal" of a chemical for purposes of
identifying a COU in the conduct of a risk
evaluation.
In addition, even if accidents, spills or leaks of
TCE could be considered part of the listed
lifecycle stages of TCE, EPA has "determined"
that accidents, spills and leaks are not
circumstances under which TCE is intended,
known or reasonably foreseen to be
manufactured, processed, distributed, used, or
disposed of, as provided by TSCA's definition
-------
of "conditions of use," and EPA is therefore
exercising its discretionary authority under
TSCA section 3(4) to exclude TCE accidental
releases, spills and leaks from the scope of the
TCE risk evaluation. The exercise of that
authority is informed by EPA's experience in
developing scoping documents and risk
evaluations, and on various TSCA provisions
indicating the intent for EPA to have some
discretion on how best to address the demands
associated with implementation of the full
TSCA risk evaluation process. Specifically,
since the publication of the Risk Evaluation
Rule, EPA has gained experience by conducting
ten risk evaluations and designating forty
chemical substances as low- and high-priority
substances. These processes have required EPA
to determine whether the case-specific facts and
the reasonably available information justify
identifying a particular activity as a "condition
of use." With the experience EPA has gained, it
is better situated to discern circumstances that
are appropriately considered to be outside the
bounds of "circumstances... under which a
chemical substance is intended, known, or
reasonably foreseen to be manufactured,
processed, distributed in commerce, used, or
disposed of' and to thereby meaningfully limit
circumstances subject to evaluation. Because of
the expansive and potentially boundless impacts
that could result from including accidents, spills
and leaks as part of the risk evaluation (e.g., due
to the unpredictable and irregular scenarios that
Page 110 of 408
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would need to be accounted for, including
variability in volume, frequency, and geographic
location of accidents, spills and leaks; potential
application across multiple exposure routes and
pathways affecting myriad ecological and
human receptors; and far-reaching analyses that
would be needed to support assessments that
account for uncertainties but are based on best
available science), which could make the
conduct of the risk evaluation untenable within
the applicable deadlines, accidents, spills and
leaks are determined not to be circumstances
under which TCE is intended, known or
reasonably foreseen to be manufactured,
processed, distributed, used, or disposed of, as
provided by TSCA's definition of "conditions of
use."
Exercising the discretion to not identify
accidents, spills and leaks of TCE as a COU is
consistent with the discretion Congress provided
in a variety of provisions to manage the
challenges presented in implementing TSCA
risk evaluation. See e.g., TSCA sections 3(4),
3(12), 6(b)(4)(D), 6(b)(4)(F). In particular,
TSCA section 6(b)(4)(F)(iv) instructs EPA to
factor into TSCA risk evaluations "the likely
duration, intensity, frequency, and number of
exposures under the conditions of use....,"
suggesting that activities for which duration,
intensity, frequency, and number of exposures
cannot be accurately predicted or calculated
based on reasonably available information,
Page 111 of 408
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including accidents, were not intended to be the
focus of TSCA risk evaluations. And, as noted
in the preamble to the Risk Evaluation Rule,
EPA believes that Congress intended there to be
some reasonable limitation on TSCA risk
evaluations, expressly indicated by the direction
in TSCA section 2(c) to "carry out [TSCA] in a
reasonable and prudent manner."
For these reasons, EPA is exercising this
discretion to not consider accidents, spills and
leaks of TCE to be COUs.
Second, even if TCE accidents, spills and leaks
could be identified as exposures from a COU in
some cases, these are generally not forms of
exposure that EPA expects to consider in risk
evaluation. TSCA Section 6(b)(4)(D) requires
EPA, in developing the scope of a risk
evaluation, to identify the hazards, exposures,
conditions of use, and potentially exposed or
susceptible subpopulations the Agency "expects
to consider" in a risk evaluation. This language
suggests that EPA is not required to consider all
conditions of use, hazards, or exposure
pathways in risk evaluations. EPA has chosen to
tailor the scope of the risk evaluation to exclude
spills and leaks in order to focus analytical
efforts on those exposures that present the
greatest potential for risk.
In the problem formulation documents for many
of the first 10 chemicals undergoing risk
Page 112 of 408
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Page 113 of 408
evaluation, EPA applied the same authority and
rationale to certain exposure pathways,
explaining that "EPA is planning to exercise its
discretion under TSCA 6(b)(4)(D) to focus its
analytical efforts on exposures that are likely to
present the greatest concern and consequently
merit a risk evaluation under TSCA...." This
approach is informed by the legislative history
of the amended TSCA, which supports the
Agency's exercise of discretion to focus the risk
evaluation on areas that raise the greatest
potential for risk. See June 7, 2016 Cong. Rec.,
S3519-S3520.
In addition to TSCA section 6(b)(4)(D), the
Agency also has discretionary authority under
the first sentence of TSCA section 9(b)(1) to
"coordinate actions taken under [TSCA] with
actions taken under other Federal laws
administered in whole or in part by the
Administrator." TSCA section 9(b)(1) provides
EPA authority to coordinate actions with other
EPA offices, including coordination on tailoring
the scope of TSCA risk evaluations to focus on
areas of greatest concern rather than exposure
pathways addressed by other EPA-administered
statutes and regulatory programs, which does
not involve a risk determination or public
interest finding under TSCA section 9(b)(2).
EPA has already tailored the scope of this risk
evaluation using such discretionary authorities
with respect to exposure pathways covered
under the jurisdiction of other EPA-administered
-------
statutes and associated regulatory programs (see
section 1.4.2).
Following coordination with EPA's Office of
Land and Emergency Management (OLEM),
EPA has found that exposures of TCE from
accidents, spills and leaks fall under the
jurisdiction of RCRA. See 40 CFR 261.33(d)
(defining in part a hazardous waste as "any
residue or contaminated soil, water or other
debris resulting from the cleanup of a spill into
or on any land or water of any commercial
chemical product or manufacturing chemical
intermediate having the generic name listed [40
CFR 261.33(e) or (f)], or any residue or
contaminated soil, water or other debris
resulting from the cleanup of a spill, into or on
any land or water, of any off-specification
chemical product and manufacturing chemical
intermediate which, if it met specifications,
would have the generic name listed in [40 CFR
261.33(e) or (f)]"); 40 CFR 261.33(f) (listing
TCE as hazardous waste no. U080). As a result,
EPA believes it is both reasonable and prudent
to tailor the TSCA risk evaluation for TCE by
declining to evaluate potential exposures from
accidents, spills and leaks, rather than attempt to
evaluate and regulate potential exposures from
accidents under TSCA.
Releases from municipal landfills are regulated
under RCRA. As explained in more detail in
Section 1.4.2, EPA believes that coordinated
Page 114 of 408
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action on exposure pathways and risks
addressed by other EPA-administered statutes
and regulatory programs is consistent with
statutory text and legislative history, particularly
as they pertain to TSCA's function as a "gap-
filling" statute, and also furthers EPA aims to
efficiently use Agency resources, avoid
duplicating efforts taken pursuant to other
Agency programs, and meet the statutory
deadline for completing risk evaluations.
EPA does not expect exposure to consumers
from disposal of consumer products. It is
anticipated that most products will be disposed
of in original containers, particularly those
products that are purchased as aerosol cans. As
described in section 1.4.2 EPA is not evaluating
on-site releases to land from RCRA Subtitle D
municipal solid waste (MSW) landfills or
exposures of the general population from such
releases in the TSCA evaluation because they
are adequately addressed by other EPA statutes.
Disposal of household waste to municipal
landfills is covered under the jurisdiction of
RCRA as discussed in section 1.4.2.
Additionally, the following has been added to
Section 2.4.2.2 discussing possible consumer
Exposure Routes: "EPA does not expect
exposure to consumers from disposal of
consumer products. It is anticipated that most
products will be disposed of in original
Page 115 of 408
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containers, particularly those products that are
purchased as aerosol cans."
EPA cannot rely on other authorities due to numerous problems with compliance, implementation, and enforcement
108
PUBLIC COMMENTS:
State enforcement of these environmental statutes is inconsistent and
often deficient. Even where enforcement has been consistently deficient,
EPA has generally not de-authorized states. Implementation and
enforcement of these statutes remains deficient in a number of states,
resulting in continued excessive exposure to these chemicals through air,
water, and land. These exposures must be assessed under TSCA.
Specific examples of deficiencies under each of the statutes that EPA
cites as justification for excluding multiple exposure pathways follow.
SWDA:
EPA often receives unreliable data from states. EPA relies on state
data to determine whether there is compliance with the SDWA.
Without reliable data, EPA has no way to verify that the
requirements of the SDWA are being met by the states.
Due to understaffing, SWDA violations doubled in Pennsylvania
from 4,298 to 7,922.
CWA:
Over half of assessed U.S. river and stream miles violate state water
quality standards. EPA's own analysis, provided below, indicates
that waters remained impaired throughout the United States, despite
the CWA standards.
EPA published the Annual Noncompliance Report (2015) indicates
enforcement actions were taken on only 8.9% of violations.
CAA:
The OIG found performance varied significantly across the country;
particular issues in FL, NC, and OH were highlighted.
RCRA:
There are serious state enforcement problems with RCRA in addition
to issues with accurate identification and documentation of
EPA did not consider background exposure that
workers, ONUs, consumers, and bystanders
using products containing TCE might be
exposed to in addition to exposures from
conditions of use in the scope of the risk
evaluation. This may result in an
underestimation of risk, and additional
discussion of this underestimation has been
added to the document in the uncertainties
section.
See section 1.4.2 of the risk evaluation regarding
EPA's approach to exposure pathways and risks
addressed by other EPA-administered statutes.
EPA evaluated and considered the impact of
existing laws and regulations (e.g., regulations
on landfill disposal, design, and operations) in
the problem formulation step to determine what,
if any future analysis might be necessary as part
of the risk evaluation. During problem
formulation EPA analyzed the TRI data and
examined the definitions of elements in the TRI
data to determine the level of confidence that a
release would result from certain types of
disposal to land (e.g., RCRA Subtitle C
hazardous landfill and Class I underground
Injection wells) and incineration. EPA also
Page 116 of 408
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violations.
Reduced EPA enforcement provides even less assurance that exposures
through the excluded pathways are being effectively managed. Under the
current Administration, enforcement of these environmental statutes has
been significantly curbed. EPA cannot legally ignore exposures that
occur under other EPA-administered statutes and treating exposures that
are known to occur in the world as nonexistent is arbitrary and
capricious.
Page 117 of 408
examined how TCE is treated at industrial
facilities. EPA did not include emissions to
ambient air from commercial and industrial
stationary sources, which are under the
jurisdiction of and addressed by Section 112 of
the Clean Air Act. EPA did not include
emissions to ambient air from municipal and
industrial waste incineration and energy
recovery units in the risk evaluation, as they are
regulated under section 129 of the Clean Air
Act. EPA did not include disposal to
underground injection, RCRA Subtitle C
hazardous waste landfills, RCRA Subtitle D
municipal solid waste (MSW) landfills, and on-
site releases to land from industrial non-
hazardous waste and construction/demolition
waste landfills in this Risk Evaluation. EPA did
not include Superfund on-site releases to the
environment, as they are under the jurisdiction
of CERCLA. These methods of disposal fall
under the jurisdiction of and are addressed by
other EPA-administered statutes and associated
regulatory programs.
As explained in more detail in Section 1.4.2 of
the Final Risk Evaluation, EPA believes it is
both reasonable and prudent to tailor TSCA Risk
Evaluations when other EPA offices have
expertise and experience to address specific
environmental media, rather than attempt to
evaluate and regulate potential exposures and
risks from those media under TSCA. EPA
believes that coordinated action on exposure
-------
pathways and risks addressed by other EPA-
administered statutes and regulatory programs is
consistent with statutory text and legislative
history, particularly as they pertain to TSCA's
function as a "gap-filling" statute, and also
furthers EPA aims to efficiently use Agency
resources, avoid duplicating efforts taken
pursuant to other Agency programs, and meet
the statutory deadline for completing Risk
Evaluations. EPA has therefore tailored the
scope of the Risk Evaluation for TCE using
authorities in TSCA Sections 6(b) and 9(b)(1).
108
PUBLIC COMMENTS:
In its proposed 2020 budget, the current Administration sought a
31% reduction in funding for EPA. This reduction would affect
EPA's enforcement budget and the resources available to ensure
enforcement of the statutes. EPA cannot rely on its actions under
other authorities when EPA has itself taken steps to ensure that those
authorities are not adequately addressing the risks presented.
Under the current Administration, enforcement of environmental
statutes has been significantly curbed. Management at EPA has
directed EPA investigators to seek authorization before asking
companies to conduct testing or sampling under the CAA, RCRA, or
CWA. The memo also states that investigators need authorization if
they do not have information specific to a company that it may have
violated the law, or if state authorities objected to the tests. EPA
budget cuts are also expected to affect EPA's enforcement budget.
EPA has taken steps in to improve state programs, but
implementation/enforcement of these statutes remains deficient
resulting in continued excessive exposure to chemicals through air,
water, and land. EPA cannot rely on other statutes and must assess
exposures on their real-world existence.
Thank you for your comment. Per 15 U.S.C
ง 2605, EPA is required to prioritize, evaluate
and manage unreasonable risks of chemical
substances and mixtures.
Page 118 of 408
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EPA should coordinate with other statutes
108
PUBLIC COMMENTS:
TSCA provides that EPA "shall coordinate actions taken under [TSCA]
with actions taken under other Federal laws administered in whole or in
part by the Administrator." This does not contemplate EPA excluding
exposures from the analyses prepared under TSCA.
The conceptual models only included exposure
pathways that are within the scope of the risk
evaluation. The environmental exposure
pathways covered under the jurisdiction of other
EPA-administered statutes and regulatory
programs are not within the scope of the risk
evaluation. As explained in more detail in
Section 1.4.2 of the Final Risk Evaluation, EPA
believes it is both reasonable and prudent to
tailor TSCA Risk Evaluations when other EPA
offices have expertise and experience to address
specific environmental media, rather than
attempt to evaluate and regulate potential
exposures and risks from those media under
TSCA. EPA believes that coordinated action on
exposure pathways and risks addressed by other
EPA-administered statutes and regulatory
programs is consistent with statutory text and
legislative history, particularly as they pertain to
TSCA's function as a "gap-filling" statute, and
also furthers EPA aims to efficiently use Agency
resources, avoid duplicating efforts taken
pursuant to other Agency programs, and meet
the statutory deadline for completing Risk
Evaluations. EPA has therefore tailored the
scope of the Risk Evaluation for TCE using
authorities in TSCA Sections 6(b) and 9(b)(1).
103
PUBLIC COMMENTS:
EPA should be more transparent about its inter- and intra-agency
consultation and coordination to inform the risk evaluation.
EPA should provide more information in its scoping documents and
In the 2017 Procedures for Chemical Risk
Evaluation Under the Amended Toxic
Substances Control Act (82 FR 33726, July 20,
Page 119 of 408
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draft risk evaluations about how it determines whether existing
regulations under other statutes are adequate to address potential
risks associated with a chemical under certain COU.
It is recommended that EPA OPPT convene a broader discussion with
EPA's other program offices about how OPPT can:
Better understand the regulatory requirements and processes of the
various environmental statutes under EPA's purview;
Reach agreement with other program offices on the criteria to use to
determine when and under what circumstances TSCA evaluations
should address air, water, and other waste pathways under the COU
of a high-priority chemical; and
Establish better approaches for coordinating with each program
office to improve environmental protection under each statutory
authority more efficiently and without duplication.
2017), EPA committed to, by codifying,
interagency collaboration to give the public
confidence that EPA will work with other
agencies to gain appropriate information on
chemical substances. This is an ongoing
deliberative process and EPA is not obligated to
provide descriptions of predecisional and
deliberative discussions or consultations with
other federal agencies. In the interest of
continuing to have open and candid discussions
with our interagency partners, EPA is not
intending to include the content of those
discussions in the risk evaluation.
103
PUBLIC COMMENTS:
TSCA contemplates consultation between EPA and the Occupational
Safety and Health Administration (OSHA) and authorizes OSHA to
decide whether it agrees with EPA's risk determination concerning
worker health. EPA has failed to include any discussion of its
coordination/consultation with OSHA on its approaches, considerations,
and conclusions in the risk evaluation. EPA should include such a
discussion in the final TCE risk evaluation.
EPA consults regularly with its federal partners
and will consult with state agencies if they are
known to have relevant occupational exposure
data. Additionally, EPA conferred with OSHA
and NIOSH during interagency review and their
contributions during review are reflected in both
the Draft and Final Risk Evaluation.
EPA regularly engages with OSHA along with
its other federal partners. However, it should be
noted that under section 6 of TSCA, EPA is not
mandated to consult with OSHA. Under section
9(a) of TSCA, the Administrator may determine
it is appropriate, after making an unreasonable
risk finding, to refer an action to OSHA, but the
Agency is not mandated to do so. Regarding
monitoring data from state agencies and
industry, EPA has considered the reasonably
61
PUBLIC COMMENTS:
EPA should provide the SACC with all of the materials and
communications sent from OSHA and NIOSH to EPA for TCE and other
chemicals.
Page 120 of 408
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available data, including from states, and has
provided several opportunities for all entities to
submit workplace monitoring data or other
information for consideration in the risk
evaluation.
COUs assessed are not valid/complete; use of qualitative approach for some C<
3Us
SACC
SACC COMMENTS:
EPA should attempt to get information on use of products directly (from
distributors, retailers, etc.) as an alternative means to obtain market
penetration information. For some uses (e.g., dry cleaning, metal
working fluids, and others), the number of vendors is not overwhelming.
Contacting these vendors for information would more fully inform the
risk evaluation.
As noted in the document entitled EPA's
Responses to Public Comments Received on the
Scope Documents for the First Ten Chemicals
for Risk Evaluation under TSCA, EPA-HQ-
OPPT-2016-0723-0067, EPA conducted
extensive and varied data gathering activities for
each of the first 10 chemicals, including:
Extensive and transparent searches of
public databases and sources of scientific
literature, government and industry sector
or other reports;
Searches of EPA TSCA 8(e), Chemical
Data Reporting, and other EPA information
holdings; and CBI submission holdings;
Searches for Safety Data Sheets (SDSs)
using the internet, EPA Chemical and
Product Categories (CPCat) data, the
National Institute for Health's (NIH)
Household Product Database, and other
resources in which SDS could be found;
Preparation of a market analysis using
proprietary databases and repositories;
Outreach meetings with chemical
manufacturers, processors, chemical users,
Page 121 of 408
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non-governmental organizations, trade
organizations, and other experts, including
other State and Federal Agencies (e.g., Dept
of Defense, NASA, OSHA, NIOSH, FDA
and CPSC); and
Publication of conditions of use documents,
scope documents, and problem formulation
documents to solicit information generally
from industry, nongovernmental
organizations, and the public.
These sources provided sufficient information to
conduct the risk evaluation and to make
determinations on whether conditions of use
pose an unreasonable risk. Information on
market penetration would not change those
findings and, while there are limited vendors
collecting information from them is not
necessarily straight forward. EPA cannot
mandate that vendors provide market penetration
information and this type of information is often
considered to be sensitive and claimed as
confidential business information. Also, when
collecting similar information by more than nine
entities, EPA is obligated (under the Paperwork
Reduction Act) to develop an Information
Collection Request which the schedule for the
development of the Risk Evaluation did not
allow.
98
PUBLIC COMMENTS:
TSCA does not authorize EPA to identify particular COUs and make
individualized determinations as to whether each COU, rather than each
Per 40 CFR 702.47 ".. EPA will determine
whether the chemical substance presents an
unreasonable risk of injury to health or the
Page 122 of 408
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chemical, presents an unreasonable risk. This underestimates risks posed
by a chemical by artificially segmenting the analysis.
environment under each condition of use within
the scope of the risk evaluation...." This
approach in the implementing regulations for
TSCA risk evaluations, is consistent with
statutory text in TSCA section 6(b)(4)(A), which
instructs EPA to conduct risk evaluations to
determine whether a chemical substance
presents an unreasonable risk "under the
condition of use."
108
PUBLIC COMMENTS:
EPA assertion that it has authority to ignore COUs under other agencies'
jurisdiction is incorrect.
EPA's Risk Evaluation Rule does not grant EPA discretion to exclude
COUs. The relevant provisions "unambiguously do not grant EPA the
discretion" to pick-and-choose COUs for inclusion and therefore, the
assertion of discretion to exclude COUs in the preamble meaningless.
EPA must also consider all hazards and all exposures under the
COU. None of these duties are qualified or provide an authority for
EPA to exclude hazards or sources of exposures from analysis.
EPA's arguments for excluding certain COUs cannot be extended to
exclude consideration of exposures and hazards.
As explained in more detail in section 1.4.2 of
the risk evaluation, EPA believes it is both
reasonable and prudent to tailor TSCA risk
evaluations when other EPA offices have
expertise and experience to address specific
environmental media, rather than attempt to
evaluate and regulate potential exposures and
risks from those media under TSCA. EPA
believes that coordinated action on exposure
pathways and risks addressed by other EPA-
administered statutes and regulatory programs is
consistent with statutory text and legislative
history, particularly as they pertain to TSCA's
function as a "gap-filling" statute, and also
furthers EPA aims to efficiently use Agency
resources, avoid duplicating efforts taken
pursuant to other Agency programs, and meet
the statutory deadline for completing risk
evaluations. EPA has therefore tailored the
scope of the risk evaluation for TCE using
authorities in TSCA sections 6(b) and 9(b)(1).
94, 101
PUBLIC COMMENTS:
Page 123 of 408
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There is a central flaw in EPA's exposure assessments for TCE use as
feedstock or reactant or release as byproduct in intermediate operations.
There are essential differences between TCE unintentionally produced as
a byproduct in EDC manufacturing and the intentional production of
TCE. EPA's draft risk evaluation for TCE fails to distinguish these
different manufacturing scenarios as separate COUs. Contrary to EPA's
assumption, these are not comparable to the manufacture of TCE itself.
When TCE is used as a feedstock or process agent, as in the manufacture
of HFC-134a, it is "used and entirely consumed (except for trace
quantities)." Exposure data submitted by fluorocarbon producers should
confirm this.
During the majority of time TCE is present only in closed vessels or
process equipment with no dermal contact.
Small magnitude exposures during short-term tasks can occur in unit
operations and maintenance activities. This is usually a mixture of
residuals from the process and not neat TCE. The duration of active
liquid contact is also typically short (e.g., minutes) and diminishes
once the equipment has been drained.
Based on typical industrial hygiene practices, the use of gloves
achieves much greater protection than the default assumptions that
were used in the draft risk evaluation for manufacturing and use as
process reactants.
Gross or continuous exposures would not be consistent with required
chemical handling programs in such facilities.
Some EDC companies have commercial ethylene chlorination units and
manufacture TCE as a finished product. These facilities can transfer
heavy end liquids from the EDC purification to that process as a
feedstock, but that process should be assessed in this risk evaluation as
part of the primary production of TCE, not as part of EDC. Unintended
yields of TCE in manufacturing EDC are recovered in light and heavy
ends and primarily used as feedstocks to make HC1 or other chlorinated
organics, or destroyed on site and should be considered a low exposure,
site-limited impurity.
Page 124 of 408
EPA will address on a case-by-case basis
circumstances where the chemical substance
subject to risk evaluation is unintentionally
present as an impurity, or as a byproduct,
resulting from a process for another chemical
substance undergoing risk evaluation. In this
instance, EPA included additional language in
the final scope document for 1,2-dichloroethane
(107-06-2) to indicate that the byproduct TCE
(79-01-6) formed during the manufacture of 1,2-
dichloroethane will be addressed in the 1,2-
dichloroethane risk evaluation. EPA believes
that the regulatory tools under TSCA section
6(a) are better suited to address any
unreasonable risks that might arise from these
activities through regulation of the activities that
generate 1,2-dichloroethane than they are to
addressing them through direct regulation of
TCE.
Inhalation monitoring data from manufacturing
facilities were used as surrogate for other
conditions of use. This data was chosen as TCE
concentrations for these conditions of use would
be similar to manufacturing, and TCE exposures
during unloading would be comparable in
magnitude to TCE loading following
manufacture.
Following publication of the draft risk
evaluation, one industry stakeholder that uses
TCE as a feedstock in the manufacture of
refrigerants provided occupational exposure
-------
PUBLIC COMMENTS:
EPA's risk evaluation must recognize that operations and data from
facilities intentionally manufacturing TCE are foundationally different
than operation and occupational exposures during EDC manufacturing
where TCE is unintentionally produced.
During EDC production, a combination of engineering and
administrative controls are used to protect workers from exposure to
TCE. Aside from fugitive emissions, the only other time possible
exposure may occur is during maintenance. For this material, all first
line breaks are completed using breathing air and line break suits.
EPA's dermal exposure modeling of one exposure event per day to
TCE in liquid form at 99-100% concentration is a massive
overestimate of dermal exposure to TCE during EDC manufacturing.
Similarly, the potential for inhalation exposure is significantly
reduced by the much lower concentration of TCE in all process
streams.
EPA must correct its draft risk evaluation and assess the production
of TCE as a byproduct in EDC production as a separate COU,
considering the low levels of TCE in these facilities. Because EPA
did not apply available data for byproduct production operations, the
calculations and unreasonable risk conclusion for the production of
TCE during EDC manufacture are erroneous and unsupported.
Page 125 of 408
information which was added to the
manufacturing data. As a result, occupational
exposure estimates for three OES have been
revised in the final risk evaluation.
As noted in the document entitled EPA's
Responses to Public Comments Received on the
Scope Documents for the First Ten Chemicals
for Risk Evaluation under TSCA (EPA-HQ-
QPPT-2016-0723-0067). EPA conducted
extensive and varied data gathering activities for
each of the first 10 chemicals, including:
Extensive and transparent searches of
public databases and sources of scientific
literature, government and industry sector
or other reports;
Searches of EPA TSCA 8(e), Chemical
Data Reporting, and other EPA information
holdings; and CBI submission holdings;
Searches for Safety Data Sheets (SDSs)
using the internet, EPA Chemical and
Product Categories (CPCat) data, the
National Institute for Health's (NIH)
Household Product Database, and other
resources in which SDS could be found;
Preparation of a market analysis using
proprietary databases and repositories;
Outreach meetings with chemical
manufacturers, processors, chemical users,
non-governmental organizations, trade
organizations, and other experts, including
-------
other State and Federal Agencies (e.g., Dept
of Defense, NASA, OSHA, NIOSH, FDA
and CPSC); and
Publication of conditions of use documents,
scope documents, and problem formulation
documents to solicit information generally
from industry, nongovernmental
organizations, and the public.
Inhalation monitoring data from facilities
manufacturing TCE were used as surrogate for
other conditions of use such as refrigerants
manufacturing.
Following publication of the draft risk
evaluation, one industry stakeholder that uses
TCE as a feedstock in the manufacture of
refrigerants provided occupational exposure
information which was added to the
manufacturing data. As a result, occupational
exposure estimates for three OES have been
revised in the final risk evaluation.
56, 108
PUBLIC COMMENTS:
In the draft risk evaluation, EPA states that "distribution in commerce"
"presents an unreasonable risk of injury to health (workers and ONUs),"
but does not describe the analysis supporting this finding.
EPA did not prepare even a qualitative evaluation of distribution in
commerce of TCE. EPA should clarify how it analyzed distribution
and provide the basis for its finding of unreasonable risk.
EPA states that a "quantitative evaluation of the distribution of TCE was
not included in the risk evaluation because exposures and releases from
distribution were considered within each condition of use"
For the purposes of the risk evaluation,
distribution in commerce is the transportation
associated with moving TCE in commerce.
Unloading and loading activities are associated
with other conditions of use. EPA assumes
transportation of TCE is in compliance with
existing regulations for the transportation of
hazardous materials, and emissions are therefore
minimal (with the exception of spills and leaks,
Page 126 of 408
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This information could not be located in the draft risk evaluation
under any other COU.
which are outside the scope of the risk
evaluation).
Occupai
tional: EPA lacked or ignored workplace monitoring data; EPA shoulc
use its authority to gather monitoring data
SACC
SACC COMMENTS:
It is concerning that EPA did not find enough reasonably available data
to determine statistical distributions for air concentrations for workers,
ONUs, and consumers exposed to TCE. EPA should use its statutory
authority to request studies to consider in the assessment.
EPA considered the reasonably available data
and provided several opportunities for all
entities to submit workplace monitoring data or
other information for consideration in the risk
evaluation.
As noted in the document entitled EPA's
Responses to Public Comments Received on the
Scope Documents for the First Ten Chemicals
for Risk Evaluation under TSCA (EPA-HO-
OPPT-2016-0723-00671 EPA conducted
extensive and varied data gathering activities for
each of the first 10 chemicals, including:
Extensive and transparent searches of
public databases and sources of scientific
literature, government and industry sector
or other reports;
Searches of EPA TSCA 8(e), Chemical
Data Reporting, and other EPA information
holdings; and CBI submission holdings;
Outreach meetings with chemical
manufacturers, processors, chemical users,
non-governmental organizations, trade
organizations, and other experts, including
other State and Federal Agencies (e.g., Dept
of Defense, NASA, OSHA, NIOSH, FDA
and CPSC); and
Publication of conditions of use documents,
scope documents, and problem formulation
100
PUBLIC COMMENTS:
EPA has ready access to a wealth of occupational exposure data and the
ability to require the production of that data under TSCA. No effort was
made to review that data when preparing the draft risk evaluation.
For several COUs, EPA did not seek or receive any monitoring data,
relying instead on modeling or unsupported extrapolations from other
uses of TCE.
For the use of TCE in spot cleaning, EPA estimates that up to
269,000 workers per year are exposed in up to 63,748 facilities, yet
the draft risk evaluation considered only eight data points to estimate
such exposures. EPA's failure to identify relevant monitoring data
does not mean that such data do not exist.
108
PUBLIC COMMENTS:
When a data gap exists, EPA cannot rationally assume that the absence
of evidence regarding a particular hazard or exposure establishes that the
hazard or exposure is not present. Such assumptions violate EPA's duty
to consider all reasonably available information, which EPA could
generate to fill these data gaps, as well as EPA's duty to use the best
available science.
Page 127 of 408
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documents to solicit information generally
from industry, nongovernmental
organizations, and the public.
108
PUBLIC COMMENTS:
For numerous COUs, EPA lacked adequate monitoring data.
EPA considered the reasonably available data
and provided several opportunities for all entities
to submit workplace monitoring data or other
information for consideration in the risk
evaluation.
SACC,
56,
108,
100
SACC COMMENTS:
EPA does not use the wealth of OSHA data because it may not be
representative (potential for bias). These OSHA data are unlikely to be
any less representative than using monitoring results from a single plant
with a small number of measurements as is used for the exposure
derivation in this draft risk evaluation.
PUBLIC COMMENTS:
EPA appears to have ignored OSHA data and dismisses it as "biased."
EPA only relied on OSHA data for a single COU (metalworking fluids, 3
data points) and incorporated OSHA data into an additional two COUs
(adhesives, sealants, paints, and coatings as well as spot cleaning and
wipe cleaning, <8 data points) despite OSHA having 3,225 air samples
for TCE.
There is a substantial amount of TCE exposure data from OSHA
inspections available online; however, EPA failed to consider the
majority of that data in its draft risk evaluation.
It is unclear why the other OSHA data - which are not even
mentioned in the systematic review supplemental file on
environmental releases and occupational exposure - have not been
incorporated. EPA must acquire all of the relevant OSHA data on
TCE in order to comply with its requirements to consider reasonably
available information and the best available science, in accordance
with TSCA.
EPA's decision to highlight potential bias in OSHA data is
EPA used the highest quality data reasonably
available for all scenarios, including OSHA data.
EPA consulted with and obtained data from
OSHA, whose data are used and cited in the
Risk Evaluation as (OSHA 2017).
EPA consults regularly with its federal partners
and will consult with state agencies if they are
known to have relevant occupational exposure
data. EPA's discussions and consultation with
OSHA are described in section 1.4.5.2 of
Supplemental Information on Releases and
Occupational Exposure Assessment.
Additionally, EPA conferred with OSHA and
NIOSH during interagency review and their
contributions during review are reflected in the
Draft and Final Risk Evaluation.
EPA regularly engages with OSHA along with
its other federal partners. However, it should be
noted that under section 6 of TSCA, EPA is not
mandated to consult with OSHA. Under section
9(a) of TSCA, the Administrator may determine
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unjustified and likely inaccurate.
it is appropriate, after making an unreasonable
risk finding, to refer an action to OSHA, but the
Agency is not mandated to do so. Regarding
monitoring data from state agencies and
industry, EPA has considered the reasonably
available data, including from states, and has
provided several opportunities for all entities to
submit workplace monitoring data or other
information for consideration in the risk
evaluation.
EPA engages with all its federal partners as it
works to conduct and refine its risk evaluations.
EPA is under no obligation to categorically
provide descriptions of its discussions and
consultations with other federal agencies and, in
the interest of continuing to have open and
candid discussions with them, is not intending to
include the content of those discussions in the
risk evaluation. However, input from federal
partners is included as appropriate.
108
PUBLIC COMMENTS:
During the SACC meeting, several reviewers questioned EPA's sparse
use of the OSHA data and EPA's assertion that such data are not
representative. One peer reviewer questioned whether the OSHA data are
at least as representative as the single-site Halogenated Solvents Industry
Alliance (HSIA) data that EPA used. It was suggested that EPA consider
a composite data analysis - combining the OSHA data and the HSIA
data - to increase the confidence compared to relying on data from a
single study/site.
EPA used the highest quality data reasonably
available for all scenarios, including OSHA data.
EPA consulted with and obtained data from
OSHA, whose data are used and cited in the
Risk Evaluation as (OSHA 2017).
EPA consults regularly with its federal partners
and will consult with state agencies if they are
known to have relevant occupational exposure
data. EPA's discussions and consultation with
OSHA are described in section 1.4.5.2 of
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Supplemental Information on Releases and
Occupational Exposure Assessment.
Additionally, EPA conferred with OSHA and
NIOSH during interagency review and their
contributions during review are reflected in the
Draft and Final Risk Evaluation.
EPA regularly engages with OSHA along with
its other federal partners. However, it should be
noted that under section 6 of TSCA, EPA is not
mandated to consult with OSHA. Under section
9(a) of TSCA, the Administrator may determine
it is appropriate, after making an unreasonable
risk finding, to refer an action to OSHA, but the
Agency is not mandated to do so. Regarding
monitoring data from state agencies and
industry, EPA has considered the reasonably
available data, including from states, and has
provided several opportunities for all entities to
submit workplace monitoring data or other
information for consideration in the risk
evaluation.
EPA engages with all its federal partners as it
works to conduct and refine its risk evaluations.
EPA is under no obligation to categorically
provide descriptions of its discussions and
consultations with other federal agencies and, in
the interest of continuing to have open and
candid discussions with them, is not intending to
include the content of those discussions in the
risk evaluation. However, input from federal
partners is included as appropriate.
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100
PUBLIC COMMENTS:
OSHA requires employers to preserve and maintain employee
exposure records including "the sampling results, the collection
methodology (sampling plan), a description of the analytical and
mathematical methods used, and a summary of other background
data relevant to interpretation of the results obtained" for 30 years.
OSHA's respirator standard also requires that employers "evaluate
the respiratory hazards at their workplaces," including a quantitative
determination of potential exposures so the employer can determine
whether respirators are required and, if so, what type of respirator
will adequately protect workers. Therefore, employers would have
significant amounts of workplace exposure data that would be
reasonably available to EPA. If no such data exist, then assumptions
of widespread and health-protective respirator use are wrong.
EPA used the highest quality data reasonably
available for all scenarios, including OSHA data.
EPA consulted with and obtained data from
OSHA, whose data are used and cited in the
Risk Evaluation as (OS ).
EPA assumes for some conditions of use, the use
of appropriate respirators is not a standard
practice, based on best professional judgment
given the burden associated with the use of
supplied-air respirators, including the expense of
the equipment, and the necessity of fit-testing
and training for proper use. The risk evaluation
also presents estimated risk in the absence of
PPE and does not assume that occupational non-
users use PPE.
108,
100
PUBLIC COMMENTS:
In response to previous comments EPA acknowledged its duty to
consider "reasonably available information" and while EPA details its
"data gathering activities," EPA has not established that these activities
will result in EPA obtaining all of the reasonably available information
that EPA could "generate, obtain, and synthesize" if EPA also used its
authorities under TSCA to obtain additional information.
Thus, EPA has not established that it will obtain all reasonably
available information.
EPA appears to recognize that voluntary requests standing alone are
insufficient. Despite that acknowledgement, EPA still has not relied on
its available authorities to obtain additional information.
A voluntary call is much less likely to produce all of the necessary
information than rules mandating that affected parties provide the
requested information.
EPA has provided no empirical evidence establishing that this
As noted in the document entitled EPA's
Responses to Public Comments Received on the
Scope Documents for the First Ten Chemicals
for Risk Evaluation under TSCA CEPA-HO-
OPPT-2016-0723-00671 EPA conducted
extensive and varied data gathering activities for
each of the first 10 chemicals, including:
Extensive and transparent searches of public
databases and sources of scientific literature,
government and industry sector or other
reports;
Searches of EPA TSCA 8(e), Chemical Data
Reporting, and other EPA information
holdings; and CBI submission holdings;
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voluntary approach will result in EPA obtaining all "reasonably
available" information.
Manufacturers and processors of TCE have a vested interest in EPA
finding that TCE does not present an unreasonable risk. It raises
concern that companies by choose to "cherry pick" information, or
not voluntarily provide information at all.
Because of this reality and appearance of partiality, relying solely on
voluntary measures decreases the credibility of this risk evaluation.
If EPA acts under TSCA, the regulations impose some requirements that
will help ensure the accuracy and completeness of the information.
To the extent that it relies on voluntary submissions from industry, EPA
needs to take additional steps to better ensure that the voluntary
information it receives is accurate and complete. EPA would need to
develop a more rigorous and structured process. For example, EPA's
submission process does not appear to require anyone to certify that the
information in their submissions is accurate or complete to the best of
their knowledge. EPA should consider approaches for vetting statements
and assertions, particularly when made by entities with a financial
interest in the outcome of these risk evaluations.
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Searches for Safety Data Sheets (SDSs)
using the internet, EPA Chemical and
Product Categories (CPCat) data, the
National Institute for Health's (NIH)
Household Product Database, and other
resources in which SDS could be found;
Preparation of a market analysis using
proprietary databases and repositories;
Outreach meetings with chemical
manufacturers, processors, chemical users,
non-governmental organizations, trade
organizations, and other experts, including
other State and Federal Agencies (e.g., Dept
of Defense, NASA, OSHA, NIOSH, FDA
and CPSC); and
Publication of conditions of use documents,
scope documents, and problem formulation
documents to solicit information generally
from industry, nongovernmental
organizations, and the public.
EPA requested information on all aspects of risk
evaluations throughout the risk evaluation
process, including opening public dockets for
receipt of such information, conducting outreach
to manufacturers, processors, users and other
stakeholders, as well as conducting tailored data
development efforts for some of the first 10
chemicals. Given the timeframe for conducting
risk evaluations on the first 10 chemicals, use of
TSCA data gathering authorities has been
limited in scope.
-------
EPA had sufficient information to complete the
TCE risk evaluation using a weight of scientific
evidence approach. EPA selected the first 10
chemicals for risk evaluation based in part on its
assessment that these chemicals could be
assessed without the need for regulatory
information collection or development. When
preparing this risk evaluation, EPA obtained and
considered reasonably available information,
defined as information that EPA possesses, or
can reasonably obtain and synthesize for use in
risk evaluations, considering the deadlines for
completing the evaluation. However, EPA will
continue to improve on its method and data
collection for the next round of chemicals to be
assessed under TSCA.
All studies used in the Risk Evaluation,
including industry submissions, are evaluated
using the same data quality criteria under the
TSCA Systematic Review process described in
the document, Application of Systematic Review
in TSCA Risk Evaluations. In consideration of
comments received, EPA is in the process of
updating the TSCA Systematic Review protocol
to improve the transparency of this review
process and further reduce possible bias such
that all studies are appropriately considered.
EPA identifies the uncertainty of
representativeness as a primary uncertainty for
each occupational exposure scenario that
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includes monitoring data. The Uncertainties
section 4.3.2.1 provides detailed discussion of
this potential bias and notes that limited data sets
may potentially underestimate or overestimate
exposures. EPA describes data quality ratings in
its Application of Systematic Review in TSCA
Risk Evaluations.
Occupai
tional: Additional worker monitoring data for EPA to consider
97
PUBLIC COMMENTS:
EPA's preliminary conclusion was based upon a significant over-
estimation of the level of exposure for workers and ONUs to TCE when
processed as a reactant/intermediate in industrial gas manufacturing.
Additional industrial hygiene and emission monitoring data is
provided by the commenter that demonstrates exposure to TCE use
as a refrigerant feedstock is de minimus and does not pose an
unreasonable risk of injury to human health (workers and ONUs).
This new information should be adequate for EPA to conclude that
processing TCE as a reactant/intermediate in industrial gas
manufacturing (e.g., manufacture of fluorinated gases used as
refrigerants, foam blowing agents and solvents) does not present an
unreasonable risk of injury to health workers and ONUs.
Inhalation monitoring data from manufacturing
facilities were used as surrogate for other
conditions of use. This data was chosen as TCE
concentrations for these conditions of use would
be similar to manufacturing, and TCE exposures
during unloading would be comparable in
magnitude to TCE loading following
manufacture.
Following publication of the draft risk
evaluation, one industry stakeholder that uses
TCE as a feedstock in the manufacture of
refrigerants provided occupational exposure
information which was added to the
manufacturing data. As a result, occupational
exposure estimates for three OES have been
revised in the final risk evaluation.
Occupai
tional: EPA's reliance on occupational exposure data from HSIA is invalid
SACC
SACC COMMENTS:
Recommendation: Discuss the implications of using monitoring data
from surrogate scenarios that can differ in the level and extent of
exposure controls.
EPA should discuss that HSIA data could be under better controlled
exposures compared to scenarios in other categories.
HSIA data were provided as part of continuous
IH monitoring programs and were evaluated
using the same criteria as all other data sets.
Following publication of the draft risk
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The link to the HSIA data in the draft risk evaluation is incorrect; it is
not to the exposure monitoring data.
evaluation, one industry stakeholder that uses
TCE as a feedstock in the manufacture of
refrigerants provided occupational exposure
information which was added to the
manufacturing data. As a result, occupational
exposure estimates for three OES have been
revised in the final risk evaluation.
The ranking of data sources in the Risk
Evaluation is reflective of the approaches
outlined in Application of Systematic Review in
TSCA Risk Evaluations. EPA is in the process of
seeking peer review of its Systematic Review
protocol, and potential bias of data sources may
be addressed in future updates. EPA used the
highest quality data reasonably available for all
scenarios, and the combined HSIA and industry-
supplied data are the highest quality data for
three COUs. Independent validation of data is
not available for these COUs.
56,
108,
100
PUBLIC COMMENTS:
EPA inappropriately relies solely on occupational exposure data from the
HSIA for three COUs, "Manufacturing," "Processing as a Reactant," and
"Other Industrial Uses." HSIA is the main trade association for
manufacturers of TCE, and, as such, it has a strong vested interest in
EPA finding the chemical present as low a risk as possible. This vested
interest calls into question the reliability and completeness of the data
voluntarily submitted by HSIA. There is concern over EPA's reliance on
voluntarily submitted industry data. EPA made some questionable
decisions regarding HSIA data.
During systematic review, EPA assigned the data a score of "1" for
Geographic Scope because the data come from U.S. facilities.
However, the data represent only one manufacturing facility, which
HSIA data were provided as part of continuous
IH monitoring programs and were evaluated
using the same criteria as all other data sets.
Following publication of the draft risk
evaluation, one industry stakeholder that uses
TCE as a feedstock in the manufacture of
refrigerants provided occupational exposure
information which was added to the
manufacturing data. As a result, occupational
exposure estimates for three OES have been
revised in the final risk evaluation.
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is unlikely to be representative of the entire country.
EPA scored the HSIA data a "1" for "Sample Size," even though the
dataset is only comprised of 16 samples.
EPA assigned the 2018 data a "3" for Methodology explaining that
"no method provided by the HSIA Industry organization." However,
EPA's approach to weighting criteria, which is inconsistent with best
practices in systematic reviews, results in the "Low" Methodology
score having little impact on the overall score.
EPA fails to acknowledge potential bias and provides insufficient
justification for its exclusive reliance this data without independent
validation and quality assurance reporting.
EPA has not adequately compared HSIA's data to that available
through OSHA.
The ranking of data sources in the Risk
Evaluation is reflective of the approaches
outlined in Aimlication of Systematic Review in
TSCA Risk Evaluations. EPA is in the process of
seeking peer review of its Systematic Review
protocol, and potential bias of data sources may
be addressed in future updates. EPA used the
highest quality data reasonably available for all
scenarios, and the combined HSIA and industry-
supplied data are the highest quality data for
three COUs. Independent validation of data is
not available for these COUs.
100
PUBLIC COMMENTS:
EPA used HSIA manufacturing data as a surrogate to estimate
occupational exposures from the processing of TCE as a reactant and for
other industrial uses of TCE, despite acknowledging that EPA is "unsure
of the representativeness of these surrogate data toward actual exposures
to TCE."
HSIA's data cover 16 data points from a single manufacturing
facility, from which EPA extrapolates exposures for up to 500
facilities nationwide that manufacture TCE, process it as a reactant,
or use it in other industrial operations.
EPA identifies no reason to believe that this sparse data set, is
representative of the industry as a whole.
Moreover, HSIA did not provide any information about the
conditions under which these samples were taken or the sampling
protocols and methodology. EPA relied on the HSIA data without
questioning its reliability or representativeness.
HSIA data were provided as part of continuous
IH monitoring programs and were evaluated
using the same criteria as all other data sets.
Following publication of the draft risk
evaluation, one industry stakeholder that uses
TCE as a feedstock in the manufacture of
refrigerants provided occupational exposure
information which was added to the
manufacturing data. As a result, occupational
exposure estimates for three OES have been
revised in the final risk evaluation.
The ranking of data sources in the Risk
Evaluation is reflective of the approaches
outlined in Aimlication of Systematic Review in
TSCA Risk Evaluations. EPA is in the process of
seeking peer review of its Systematic Review
protocol, and potential bias of data sources may
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be addressed in future updates. EPA used the
highest quality data reasonably available for all
scenarios, and the combined HSIA and industry-
supplied data are the highest quality data for
three COUs. Independent validation of data is
not available for these COUs.
Occupai
tional: Comments on EPA's approaches and use of monitoring or modeled data for exposure assessment
SACC
SACC COMMENTS:
Recommendation: Explore statistical and computational approaches to
better utilize available monitoring data and produce more representative
exposure estimates.
The Committee suggested that EPA identify the drivers for model
exposure estimates (from the Monte Carlo simulations), and how
changing values in these drivers affect differentially the central tendency
and high-end model-based exposure estimates in comparison to estimates
based on measurements. This exercise could provide insights into the
assumptions that need refinement or improved data.
Statistical and computational approaches (such as censored
estimation, Bayesian methods, and Monte Carlo simulation; see for
example Helsel, 2005; Gelman et al., 2004; and Robert and Casella,
2004) can be used to derive better estimates of exposure statistics
(means, medians, variances, interquartile ranges, minimums, and
maximums) from unknown distributions. EPA should use these
techniques in evaluations to overcome limitations in available
monitoring data. The alternative is to use TSCA statutory authority to
mandate and/or implement adequate monitoring programs to fill this
data need.
EPA thanks the commenter for the
recommendation. EPA will investigate methods
to apply to monitoring data, which may include
statistical and computational approaches, for
future risk evaluations.
SACC
SACC COMMENTS:
Monitoring data are not intended to accurately reflect the range of
worker exposures across an industry or a COU and unlikely to account
for the full range of variability of OESs. Typically, too few workers are
monitored, it is done over a short period of time, and collected at only
one or a few sites. Data and associated statistics are likely biased and
EPA used the highest quality data reasonably
available for all scenarios, including monitoring
data. Monitoring data is at the top of the
hierarchy of approaches for occupational
exposure assessments. EPA will seek peer
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there is differential reliability between sets of samples. These are
unlikely true estimates of central tendency.
review of its Systematic Review protocol,
including the hierarchy of approaches to
exposure estimation.
SACC
SACC COMMENTS:
TSCA evaluations should be using a composite approach to
understanding exposure. The draft risk evaluation uses summary central
tendency and high-end descriptors, so compiling all of the data would
provide a broader base.
EPA considered the reasonably available
information and used the best available science
to determine whether to consider aggregate
exposures for a particular chemical. EPA has
determined that using the high-end risk estimate
for inhalation and dermal risks separately as the
basis for the unreasonable risk determination is a
best available science approach. There is low
confidence in the result of aggregating the
dermal and inhalation risks for this chemical if
EPA uses an additive approach, due to the
uncertainty in the data.
EPA will seek peer review of its Systematic
Review protocol, including the hierarchy of
approaches to exposure estimation.
50
PUBLIC COMMENTS:
In several cases, (batch open-top vapor degreasing, conveyorized vapor
degreasing, metalworking fluids, spot cleaning and wipe cleaning, and
other commercial uses), EPA presents both monitoring and modeled data
for inhalation exposures to workers. EPA states, "If both, inhalation
monitoring data and exposure models were reasonably available, where
applicable, EPA presented central tendency and high-end exposures
using both."
The SACC should consider whether EPA's justification of which
OESs warranted both monitoring and modeling approaches is
sufficient, and whether EPA has adequately detailed the
circumstances and process for determining which of these
approaches is ultimately used for risk characterization.
EPA presented two sets of inhalation estimates
only where both inhalation monitoring data and
exposure models were reasonably available.
Presenting both estimates allowed comparability
between the data sets.
EPA will seek peer review of its Systematic
Review protocol, including the presentation of
exposures based on both monitoring and
modeling.
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SACC
SACC COMMENTS:
This Evaluation, as others previously reviewed by the SACC, uses the
Nicas (2009) two-zone box model for estimating occupational inhalation
exposures. The Committee recommended that EPA explore other models
available in the research literature for estimating vapor generation.
EPA thanks the commenter for the
recommendation. EPA will investigate whether
alternative methods to estimate vapor generation
are appropriate for future risk evaluations.
103
PUBLIC COMMENTS:
EPA should use a tiered approach to assessing exposure. By beginning
with screening-level assessments that rely on health-protective
assumptions to estimate exposure values, the resulting risk calculations
will not underestimate risks but will likely overestimate them. This will
allow EPA to recognize COUs with no unreasonable risk quickly and set
these aside as not needing further evaluation. Substances identified by
screening-level analyses as needing additional attention would then
proceed to the next analytical tier using a more sophisticated model.
These higher tiered exposure models are designed to provide more
accurate exposure estimates, so that the higher tiered risk evaluation of
such substances will yield more precise risk estimates.
EPA thanks the commenter for the
recommendation. EPA will investigate whether a
tiered exposure approach can be utilized to
assess exposure for future risk evaluations.
103
PUBLIC COMMENTS:
Future risk evaluations should provide guidance on how EPA plans to
choose between modeled data and monitored data. The TCE risk
evaluation featured five COUs that had both monitoring and modeled
data and these data were largely congruent, but that may not be the case
in other evaluations. Additional clarity regarding what data constitutes
"reasonable availability" would be instructive, particularly if that
involves non-trivial Monte Carlo simulations.
EPA has included the hierarchy of approaches in
Section 2.3.1.2 of the Risk Evaluation. This
section shows the hierarchy has preferences, and
these preferences do not have to be strictly
followed. EPA will seek peer review of its
Systematic Review protocol, including the
hierarchy of approaches to exposure estimation.
Occupational: Assumptions EPA used for exposure estimates for specific COUs are invalid
100
PUBLIC COMMENTS:
EPA estimates TCE exposures from metalworking fluids based on the
expected concentrations in the mist created by the use of such fluids.
EPA acknowledges that "these estimates may underestimate exposures to
TCE during use of metalworking fluids as they do not account for
exposure to TCE that evaporates from the mist droplets into the air."
EPA does not attempt to quantify or correct for this underestimation;
EPA stated this potential exposure underestimate
as an uncertainty. Risk was determined for this
OES using this modeling approach. EPA thanks
the commenter for the information concerning
NIOSH's methodology for sampling and
analysis. EPA consults regularly with its federal
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instead, it says that "[t]his exposure is difficult to estimate and is not
considered in this assessment." The fact that realistic exposure
scenarios may be more "difficult" or less "certain" to estimate does
not permit EPA to rely on inaccurate exposure assumptions that
understate worker risks.
NIOSH has recommended a methodology for the sampling and
analysis of metalworking fluid aerosols (mist).
The draft risk evaluation must account for metalworkers' TCE
inhalation from evaporated mists.
partners and will consult with NIOSH on this
topic for future risk evaluations.
108
PUBLIC COMMENTS:
EPA's analysis of distribution was inadequate in the draft risk
evaluation. EPA stated that: "Activities related to distribution (e.g.,
loading and unloading) will be considered throughout the TCE life cycle,
rather than using a single distribution scenario."
EPA assumes exposure from distribution occurs only during loading
and unloading. It is not clear how, if at all, EPA considered
exposures from loading and unloading under individual COUs, as it
presents no specific analysis of these activities in the context of the
various COUs.
EPA does not appear to address exposures from distribution aside
from those arising from loading and unloading. Does EPA assume
that all distribution occurs through "closed systems" which lead to no
releases or exposure?
EPA provides no evidence or support for any assumption that TCE is
always distributed in closed systems leading to no releases or
exposures. EPA has provided no evidence that exposures and
releases during distribution will be nonexistent.
For the purposes of the risk evaluation,
distribution in commerce is the transportation
associated with moving TCE in commerce.
Unloading and loading activities are associated
with other conditions of use as discussed in the
Supplemental Information File: Environmental
Releases and Occupational Exposure
Assessment. EPA assumes transportation of
TCE is in compliance with existing regulations
for the transportation of hazardous materials,
and emissions are therefore minimal (with the
exception of spills and leaks, which are outside
the scope of the risk evaluation).
Occupai
tional: EPA must identify all occupational exposure pathways
SACC
SACC COMMENTS:
Recommendation: Specifically identify all occupational exposure
pathways with their associated regulatory authority.
The draft risk evaluation should address more specifically those
occupational exposure pathways that are not included because of
EPA provides a list of previous TCE
assessments in Table 1-2 and TCE's regulatory
history is covered in Appendix A. Exposure
pathways addressed by other EPA-administered
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competing areas of regulatory mandate. For example, lace wig and hair
extension glues are excluded because they are considered cosmetics
(Food and Drug Administration [FDA] regulation), but hoof polish, used
for cosmetic purposes and not considered a veterinary medicine under
FDA regulations, remains under TSCA. A table should be included that
specifically lists all the excluded pathways, and which indicates whether
risk assessments are available for these pathways from other regulatory
programs.
statutes are discussed in detail in Section 1.4.2.
Section 1.4.2 has been added to the final risk
evaluation in response to these and other SACC
and public comments.
SACC
SACC COMMENTS:
Recommendation: Provide a rationale for not estimating the separate
vapor and particle-bound fractions of TCE-containing aerosols in the
near field.
It is not clear whether the literature on liquid aerosol modeling has been
examined to see if it would be possible to estimate the vapor
phase/particle-bound fraction of TCE in aerosols generated in close
proximity to the worker applying the product. Despite the rapid
volatilization of TCE from droplets, it is likely that a sizable portion of
the TCE is in the particle-bound phase close to the worker, not
completely in the vapor phase.
In each case where EPA models inhalation
exposures using the NF/FF model, this exposure
is the combined inhalation exposure to vapor
and particulates. The aerosol degreasing model
is the one exception. This model assumes that an
aerosol is formed when sprayed from the can.
The droplets may evaporate TCE vapors into the
air. Also, the degreaser droplets may hit the
brake surface, and some may adhere to the tool
the worker uses to scrape the brake. But EPA
assesses that all such TCE is ultimately released
into the air (and does so rather quickly) such that
the worker is exposed to the airborne
concentration formed by the total mass of TCE
released from the aerosol can. This is a more
protective assumption.
Occupai
tional: EPA's reliance/assumptions about OSHA's Permissible Exposure Limit (PEL) is invalid
56,
108,
61, 100
PUBLIC COMMENTS:
It is inappropriate for EPA to assume that there is compliance with
OSHA's PEL and that it would be health protective.
The data indicate exactly the opposite of what EPA assumes: the
existence of real-world exposure monitoring data above the PEL
demonstrate that non-compliance is both known to occur and is
EPA did not exclude data if it exceeded the
OSHA PEL. Some data were excluded based on
finding the study/data source as unacceptable.
EPA has outlined specific criteria for identifying
a studv as unacceptable in Application of
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reasonably foreseeable.
The OSHA PEL, set at 100 ppm, was adopted in 1971, and is
outdated and inadequate for ensuring protection of worker health.
OSHA acknowledged that "studies have indicated that chronic
exposure to less than 100 ppm TCE is associated with a variety of
nervous disturbances," and EPA found that developmental TCE
exposure is associated with fetal cardiac malformations at
concentrations less of than 1 ppm, and a range of other unreasonable
risks at concentrations less than 10 ppm.
EPA has previously recommended the use of the 2 ppm NIOSH
Recommended Exposure Limit (REL).
EPA also developed a recommendation for an Existing Chemical
Concentration Limit, or "ECEL" of 1 ppb (8-hour time weighted
average) as a more current benchmark for workplace exposures.
However, under the assumption of compliance, in its "PEL-capped"
analysis, EPA ignored/excluded real-world workplace monitoring
data that are above 100 ppm.
It is inappropriate for EPA to consider excluding data points collected in
the real world on the basis of its flawed assumption of universal
compliance with regulatory requirements. EPA must utilize the full
dataset, regardless of whether data points are above or below the PEL.
Systematic Review in TSCA Risk Evaluations.
For the single OES in which modeled exposure
estimates were above the PEL (Batch Open Top
Vapor Degreasing) EPA also presented
exposures and risks based only on estimates
below the PEL. For this OES, risks were
identified whether exposure estimates above the
PEL are excluded or not.
EPA will seek peer review of its Systematic
Review protocol, including the hierarchy of
approaches to exposure estimation.
61
PUBLIC COMMENTS:
The OSHA standard for TCE consists only of the PEL; it is not a
comprehensive standard. OSHA's TCE standard does not require
application of the hierarchy of controls, or the use of PPE, or any sort of
training or education, or medical monitoring.
EPA thanks the commenter for the information.
80
PUBLIC COMMENTS:
In 2009, the Cal/OSHA Health Effects Advisory Committee
recommended that the PEL for TCE be lowered from 25 to 0.4 ppm.
Since that time, EPA, the National Toxicology Program (NTP), and the
International Agency for Research on Cancer (IARC) have classified
TCE as a human carcinogen and based on the IRIS review in 2011,
Cal/OSHA has lowered its recommended PEL for TCE to 0.2 ppm.
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100
PUBLIC COMMENTS:
While employers have a statutory duty to continue to protect workers
against "recognized hazards" at exposures below the PEL, OSHA will
cite an employer for a violation of the general duty clause only when
such exposures have resulted in actual injuries or illnesses to workers.
OSHA has never issued a citation to an employer under the general duty
clause for TCE exposures below the PEL.
NIOSH currently recommends an exposure limit of 25 ppm over a
10-hour period, and the American Conference of Government
Industrial Hygienists (ACGIH) recommends an 8-hour limit of 10
ppm.
EPA acknowledges that the OSHA regulations at
29 CFR 1910.132 require employers to assess a
workplace to determine if hazards are present or
likely to be present which necessitate the use of
personal protective equipment (PPE). If the
employer determines hazards are present or
likely to be present, the employer must select the
types of PPE that will protect against the
identified hazards, require employees to use that
PPE, communicate the selection decisions to
each affected employee, and select PPE that
properly fits each affected employee.
EPA thanks the commenter for the information
from NIOSH and ACGIH.
Dermal exposure assumptions are not valid; impact of assumptions on exposure estimates
SACC
SACC COMMENTS:
The dermal exposure estimates are valid or at least reasonable as a means
of calculating potential dermal exposure. The mean surface areas are as
described in the Exposure Factors Handbook (U.S.EPA, 2011), which
uses data from the National Health and Nutrition Examination Survey
(NHANES). Body weight data from NHANES can be used to construct a
distribution of dermal surface areas for each age category in addition to
central tendency values.
EPA thanks the commenter regarding the
validity of EPA's dermal exposure estimation
methods.
SACC
SACC COMMENTS:
Recommendation: Discuss all parameters that drive all human exposure
estimates based on modeling.
The Committee recommended that EPA provide a clear, specific
discussion about the parameters involved in calculating exposure
estimates based on modeling (dermal parameters recommended by the
SACC for inclusion in the current and future TSCA risk evaluations are
provided in Table 6 of the SACC report) and further consider a limited
EPA conducted a sensitivity analysis for each
model to evaluate how the input parameters
affect modeling results. The default value and
assumptions associated with each input
parameter is explained in detail in the
Supplemental File: TCE Environmental Releases
and Occupational Exposure Assessment, which
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sensitivity analysis to identify those parameters that most influence
(drive) the exposure estimates.
was published along with the Draft Risk
Evaluation.
SACC
SACC COMMENTS:
Recommendation: Consider the potential for dermal exposure to TCE
vapor.
At a minimum, there should be mention and discussion of the vapor
through the skin pathway of exposure, including the potential for vapor
penetration through non-impermeable clothing.
An analysis in Section 2.5.1 of the Problem
Formulation of the Risk Evaluation for TCE
shows that absorption of TCE via skin to be
orders of magnitude lower than via inhalation
and that additional coverage of this topic is not
included in the Risk Evaluation for TCE. EPA
included expanded discussion in 2.3.1.2.5 about
the fabs parameter that accounts for volatilization
in the estimates of dermal exposure to
occupational users.
56,
108,
100
PUBLIC COMMENTS:
EPA failed to explain or justify its assumption of one dermal exposure
event per day for workers.
In an 8-hour workday, it is likely that workers would regularly
engage in activities that could result in multiple exposure events per
day.
In prior risk evaluations, EPA has acknowledged that this assumption
"likely underestimates exposure as workers often come into repeat
contact with [the same chemicals] throughout their work day," but
has chosen not to consider those risks in this draft risk evaluation.
EPA fails to acknowledge that this assumption will underestimate
exposure. EPA has not, but must, account for this underestimation and at
a minimum provide an uncertainty analysis.
EPA did not identify reasonably available
information on how many contact events may
occur and the time between contact events.
Therefore, EPA assumes a single contact event
per day for estimating dermal exposures. EPA
has described events per day (FT) as a primary
uncertainty for dermal modeling in the
discussion of occupational dermal uncertainties
section 2.3.1.3.4 as well as in the Supplemental
File: TCE Environmental Releases and
Occupational Exposure Assessment.
SACC
SACC COMMENTS:
Recommendation: Provide a justification for the assumption that 10% of
the skin surface will be exposed for consumer product users.
The products with impeded evaporation that
were originally modeled using a surface area
corresponding to 10% of hands have been
updated in the final risk evaluation to consider a
dermal contact area for the inside of one hand to
account for the entire hand surface being in
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contact with a rag during cleaning/degreasing
activities. These products now use the same
surface area assumption as the liquid
formulations with impeded dermal contact.
94, 103
PUBLIC COMMENTS:
Both occluded and non-occluded dermal TCE exposure estimates were
likely to be considerably overestimated based on numerous factors,
including (but not limited to):
The absorption factor for non-occluded scenarios used (8-13%),
which is higher than expected under realistic scenarios,
Lack of consideration for saturation of the stratum corneum.
The assumption that the skin surface area that comes in contact with
TCE is one to two full hands, rather than the more likely interior
hand surfaces,
The assumption that TCE exposure occurs continuously for 8 hours
rather than short intermittent exposures; and
The assumption that the worker does not change gloves or wash
hands at all during the work shift.
In the case of the occluded scenarios, additional overestimation likely
occurred based on the assumption that the whole hand (or hands) were
coated with TCE in-glove, and the lack of consideration for possible
permeation back out of the glove and evaporative losses.
EPA should include discussion of the impacts of these assumptions on
the level of confidence in the overall estimates, and the degree to which
the assumptions are more than adequately protective.
The uncertainties and limitations of the dermal
modeling approach are discussed in Appendix H
the Supplemental Information on Releases and
Occupational Exposure Assessment document.
See further discussion on occlusion in Appendix
H of the Supplemental File: TCE Environmental
Releases and Occupational Exposure
Assessment. The occluded scenarios were
presented as a what-if scenario. EPA does not
know the likelihood or frequency of these
scenarios in the workplace; therefore, EPA did
not present risk estimates associated with
occluded exposure in the Risk Evaluation.
SACC
SACC COMMENTS:
The assumed percutaneous absorption of 100% is too high. Twenty to
thirty percent would be a high estimate. Some Committee members
considered the assumption of keeping TCE in contact with the skin under
occluded conditions for an extended period as not a realistic exposure
scenario. One Committee member pointed out that this might happen if a
consumer were using a TCE-containing product without gloves and a
product-soaked rag.
The uncertainties and limitations of the dermal
modeling approach are discussed in Appendix H
the Supplemental Information on Releases and
Occupational Exposure Assessment document.
See further discussion on occlusion in Appendix
H of the Supplemental File: TCE Environmental
Page 145 of 408
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103, 94
PUBLIC COMMENTS:
For occluded exposure scenarios, while some chemical may splash and
spill over the cuff of the glove or permeate through the glove itself over
time, it is unlikely that the TCE would cover the full hand surface. A
more reasonable estimate for surface area of contact would be just the
palm or some fraction of the palm and fingers, rather than the full hand
surface from the wrist down.
The impact of sweat inside the glove that would lower the flux of
TCE through the skin (Cherrie et al., 2004) was not considered. The
contribution of evaporation to the overall dose is not clear, and would
require additional calculations to quantify, outside of the application
of a screening model.
Ungloved hands are washed and gloves are likely removed every few
hours for breaks or to switch tasks, limiting the duration of exposure
events.
The assumption that 100% of the TCE that enters the glove is
absorbed neglects the potential for flux of the TCE back out of the
glove via evaporation during periods of no liquid contact.
Flux of the TCE into the stratum corneum does not occur
instantaneously. Thus, models that assume the total applied dose is
available to be absorbed would overestimate actual uptake.
Releases and Occupational Exposure
Assessment. The occluded scenarios were
presented as a what-if scenario. EPA does not
know the likelihood or frequency of these
scenarios in the workplace; therefore, EPA did
not present risk estimates associated with
occluded exposure in the Risk Evaluation.
108
PUBLIC COMMENTS:
EPA should present fractional absorption and applied flux assumptions
side by side.
EPA default quantities that can remain on skin
are based on experimental data that were
measured. EPA did not find additional
reasonably available actual measurements of
quantity remaining on the skin form TCE, nor
were citations or data provided by the
commenter. The dermal assessment generated
central tendency and high-end doses using
models, and the models incorporated estimates
of evaporation. Central tendency estimates are
less than the maximum default quantity that may
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remain on the skin. EPA did not find reasonably
available empirical data or additional modeling
tools proposed by this comment to inform better
absorption estimates.
94
PUBLIC COMMENTS:
EPA's high-end assumption assumed coverage of two complete hands is
overly conservative and not consistent with industrial hygiene practices
for glove use.
EPA's approach for developing exposure
assessments for workers is to use the reasonably
available information and expert judgement.
When appropriate, in the risk evaluation, EPA
will use exposure scenarios both with and
without engineering controls and/or PPE that
may be applicable to particular worker tasks on a
case-specific basis for a given chemical. Again,
while EPA has evaluated worker risk with and
without PPE, as a matter of policy, EPA does
not believe it should assume that workers are
unprotected by PPE where such PPE might be
necessary to meet federal regulations, unless it
has evidence that workers are unprotected. For
the purposes of determining whether or not a
condition of use presents unreasonable risks,
EPA incorporates assumptions regarding PPE
use based on information and judgment
underlying the exposure scenarios. These
assumptions are described in the unreasonable
risk determination for each condition of use, in
section 5.2. Additionally, in consideration of the
uncertainties and variabilities in PPE usage (e.g.,
dry cleaners), EPA uses the high-end exposure
value when making its unreasonable risk
determination in order to address those
uncertainties. EPA has also outlined its PPE
assumptions in section 5.1. Further, in the final
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risk evaluation for TCE, EPA has determined
that most conditions of use pose an unreasonable
risk to workers even with the assumed PPE.
99
PUBLIC COMMENTS:
EPA acknowledged that estimates of dermal exposure rested on
questionable assumptions and likely understate the magnitude of TCE
exposure by this route.
Instead of relying on test data to quantify dermal absorption rates,
EPA modeled "dermal potential dose rate based on an assumed
amount of liquid on skin during one contact event per day and the
steady-state fractional absorption for TCE based on a theoretical
framework provided by Kasting."
The assumption of rapid volatilization of TCE after skin contact did
not hold true for all worker operations, including cases of occlusion,
repeated contacts, dermal immersion, or activities with a high degree
of splash potential. EPA, however, did not develop alternate
estimates of dermal exposure using higher levels of absorption.
EPA preferentially relies on a variety of test and
analog data. In the absence of suitable test data,
modeling tools may be used.
Because the chemical simultaneously evaporates
from and absorbs into the skin, the dermal
exposure is a function of both the number of
contact events per day and the time between
contact events. EPA did not identify information
on how many contact events may occur and the
time between contact events. Therefore, EPA
assumes a single contact event per day for
estimating dermal exposures.
EPA has described the uncertainties in the
dermal modeling approach in the discussion of
occupational dermal uncertainties section
2.3.1.3.4 as well as in the Supplemental File:
TCE Environmental Releases and Occupational
Exposure Assessment.
56,
108, 99
PUBLIC COMMENTS:
EPA does not have any actual data on glove use and efficacy. EPA
recognizes the potential for occlusion, whereby glove use can increase
skin exposure; in both the draft risk evaluation and the Supplemental
File, however, exposure estimates under occluded conditions are not
actually incorporated at all into the ultimate risk estimates and risk
determinations for the occupational scenarios.
When comparing Table 2-15 to Tables 4-6 through 4-27, the
occluded exposure scenarios disappear from the risk estimates shown
See further discussion on occlusion in Appendix
H of the Supplemental File: TCE Environmental
Releases and Occupational Exposure
Assessment. The occluded scenarios were
presented as a what-if scenario. EPA does not
know the likelihood or frequency of these
scenarios in the workplace; therefore, EPA did
not present risk estimates associated with
Page 148 of 408
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in the latter tables. Likewise, occluded scenarios do not appear in the
Supplemental Information File: Risk Calculator for Occupational
Exposures (e.g., see tab "RR" in EPA's "TCE-Risk Calculator for
Occupational Exposures" spreadsheet).
If EPA did incorporate occlusion into its ultimate risk estimates and
determinations, it needs to be far clearer on how it did so.
occluded exposure in the Risk Evaluation.
108
PUBLIC COMMENTS:
EPA failed to consider exposure via dermal vapor. While this may not
constitute a major exposure route for TCE, EPA needs to conduct the
analysis to determine whether or not it can be considered negligible.
An analysis in Section 2.5.1 of the Problem
Formulation of the Risk Evaluation for TCE
shows that absorption of TCE via skin to be
orders of magnitude lower than via inhalation
and that additional coverage of this topic is not
included in the Risk Evaluation for TCE. EPA
included expanded discussion in 2.3.1.2.5 about
the fabs parameter that accounts for volatilization
in the estimates of dermal exposure to
occupational users.
SACC,
108
SACC COMMENTS:
Recommendation: Discuss skin damage from contact with TCE and how
it affects skin permeability to TCE.
PUBLIC COMMENTS:
EPA relies upon data that do not account for the potential impact of skin
damage. Exposure to neat TCE could cause damage to skin, especially
with chronic exposures, which in turn can allow for higher dermal
penetration of the compound. While human data may not be available,
dermal penetration from damaged skin increases ~25x, according to one
peer reviewer.
The disruption of the stratum corneum leading to
increased absorption is discussed in Section
3.2.2.1. EPA used a human patch test study for
deriving the permeability of neat TCE, and
presumably this data captured the effects of skin
damage increasing absorption in participants.
94
PUBLIC COMMENTS:
A key weakness in the EPA approach for both occluded and non-
occluded exposure scenarios is the lack of consideration of chemical
irritancy and task duration. Dermal exposure to TCE, particularly in neat
concentration, may result in skin irritation. Some degree of skin
sensation would alert the worker to the presence of the chemical; thus, a
EPA's approach for developing exposure
assessments for workers is to use the reasonably
available information and expert judgement.
When appropriate, in the risk evaluation, EPA
will use exposure scenarios both with and
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worker would remove their gloves, wash their hands, and replace their
gloves. Moreover, general industrial hygiene and worker training would
dictate removal and replacement of gloves following spillage into the
glove or to comply with PPE change out schedules designed to limit
breakthrough time.
without engineering controls and/or PPE that
may be applicable to particular worker tasks on a
case-specific basis for a given chemical. Again,
while EPA has evaluated worker risk with and
without PPE, as a matter of policy, EPA does
not believe it should assume that workers are
unprotected by PPE where such PPE might be
necessary to meet federal regulations, unless it
has evidence that workers are unprotected. For
the purposes of determining whether or not a
condition of use presents unreasonable risks,
EPA incorporates assumptions regarding PPE
use based on information and judgment
underlying the exposure scenarios. These
assumptions are described in the unreasonable
risk determination for each condition of use, in
section 5.2. Additionally, in consideration of the
uncertainties and variabilities in PPE usage (e.g.,
dry cleaners), EPA uses the high-end exposure
value when making its unreasonable risk
determination in order to address those
uncertainties. EPA has also outlined its PPE
assumptions in section 5.1. Further, in the final
risk evaluation for TCE, EPA has determined
that most conditions of use pose an unreasonable
risk to workers even with the assumed PPE.
94
PUBLIC COMMENTS:
A number of dermal occupational scenarios in the draft risk
evaluation assuming worst-case scenarios yielded estimates of
unreasonable risk. However, revised scenarios with more appropriate
assumptions result in substantially lower exposure estimates that may
impact the risk characterizations. EPA should consider whether more
refined exposure assessment is warranted for some scenarios in the
EPA's approach for developing exposure
assessments for workers is to use the reasonably
available information and expert judgement.
When appropriate, in the risk evaluation, EPA
will use exposure scenarios both with and
without engineering controls and/or PPE that
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revised risk evaluation using additional information on realistic
workplace scenarios coupled with appropriate modeling.
The inputs and models utilized in the draft risk evaluation resulted in
estimates of exposure, and consequently, estimates of risk, that may
not reflect actual industry working conditions.
may be applicable to particular worker tasks on a
case-specific basis for a given chemical. Again,
while EPA has evaluated worker risk with and
without PPE, as a matter of policy, EPA does
not believe it should assume that workers are
unprotected by PPE where such PPE might be
necessary to meet federal regulations, unless it
has evidence that workers are unprotected. For
the purposes of determining whether or not a
condition of use presents unreasonable risks,
EPA incorporates assumptions regarding PPE
use based on information and judgment
underlying the exposure scenarios. These
assumptions are described in the unreasonable
risk determination for each condition of use, in
section 5.2. Additionally, in consideration of the
uncertainties and variabilities in PPE usage (e.g.,
dry cleaners), EPA uses the high-end exposure
value when making its unreasonable risk
determination in order to address those
uncertainties. EPA has also outlined its PPE
assumptions in section 5.1. Further, in the final
risk evaluation for TCE, EPA has determined
that most conditions of use pose an unreasonable
risk to workers even with the assumed PPE.
94
PUBLIC COMMENTS:
EPA assumptions lead to overestimation of exposure for chemical
manufacturing and in processing TCE as a reactant.
In the majority of the operational time, TCE would only be present in
closed vessels or process equipment with no dermal contact. Small
magnitude exposures during short-term tasks can occur in unit operations
and maintenance activities.
EPA does incorporate the use of gloves into the risk assessment
For the purposes of determining whether or not a
condition of use presents an unreasonable risk,
EPA incorporates assumptions regarding PPE
use based on information and judgment
underlying the exposure scenarios. These
assumptions are described in the unreasonable
risk determination for each condition of use, in
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approach. However, based on typical industrial hygiene practice, the
use of such gloves would achieve much greater protection than the
default assumptions under the scenarios described for due to
vaporization of TCE from the gloves.
Only non-occluded scenarios that consider various levels of glove
use were modeled. For other COUs (e.g., vapor degreasing), EPA
estimated exposures for occluded scenarios. Some of the principles
governing the occluded scenario would apply to the dose permeating
the glove in the un-occluded scenarios and, therefore, are relevant to
the chemical manufacturing environment.
section 5.3. Additionally, in consideration of the
uncertainties and variabilities in PPE usage,
EPA uses the high-end exposure value when
making its unreasonable risk determination in
order to address those uncertainties. EPA has
also outlined its PPE assumptions in section 5.1.
Further, in the final risk evaluation for TCE,
EPA has determined that most conditions of use
pose an unreasonable risk to workers even with
the assumed PPE.
94
PUBLIC COMMENTS:
In the non-occluded scenario, EPA did not account for exposure duration
of industrial scenarios nor the saturation of the skin by TCE. In TCE
manufacturing and use as a reactant, dermal exposures are intermittent
throughout the workday (i.e., 1 hour or less, 4 times per shift with
sufficient time in between exposures for evaporation from, or cleaning
of, skin). Revised analyses using the IHSkinPerm model (provided by
the commenter), in which duration and saturation factors were
appropriately considered, showed that exposure scenarios without PPE in
the draft risk evaluation may have overestimated the absorption fraction
of TCE by 8- to 22-fold for exposure to an ungloved hand, and the total
dermal dose of TCE by 6- to 17-fold for exposure to an ungloved hand
assuming four one-hour exposure events per day.
The dermal model used by EPA considers
competing processes of absorption into the skin
and evaporation. The model does not assume
continuous exposure with liquid TCE, only that
the applied dose (i.e., the amount of chemical
remaining on the skin after contact with the
exposure source) remains on the skin until it is
absorbed or evaporates. Based on the
physiochemical properties of TCE, this duration
may not be very long after initial contact.
Data considered for dermal exposure estimates were invalid or incomplete
SACC
SACC COMMENTS:
Recommendation: Estimate dermal exposure to neat liquid TCE using
experimental in vivo human data described in Stewart and Dodd (1964);
Sato and Nakajima (1978); and Kezic et al. (2001).
TCE is known to cause dermatitis, which implies skin barrier damage.
Data reflecting exposure to neat TCE are needed. Human data show a
maximum flux exceeding the flux estimated from the Poet et al. (2000)
permeability coefficient, and is consistent with the Morgan et al. (1991)
rat study. Based on these data, EPA should conclude that the best
Based on comments from the SACC, EPA
updated dermal permeability modeling for the
final Risk Evaluation to utilize results for neat
permeability from human data in Kezic et al,
2001 as opposed to data from aqueous TCE, as
was used previously.
Page 152 of 408
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estimate of permeation in humans from neat exposure would be an
approximation based on the results of these studies.
108
PUBLIC COMMENTS:
If EPA does not have sufficient information on dermal exposure whether
through measured or modeled data, it should have used its authorities to
obtain them.
EPA believes it had sufficient information to
complete the TCE Risk Evaluation using a
weight of scientific evidence approach. EPA
selected the first 10 chemicals for Risk
Evaluation based in part on its assessment that
these chemicals could be evaluated without the
need for regulatory information collection or
development. When preparing this Risk
Evaluation, EPA obtained and considered
reasonably available information, defined as
information that EPA possesses, or can
reasonably obtain and synthesize for use in Risk
Evaluations, considering the deadlines for
completing the evaluation. 40 CFR 702.33
Given the timeframe for conducting Risk
Evaluations on the first 10 chemicals, use of
TSCA data gathering authorities has been
limited in scope. In general, EPA intends to
utilize TSCA data gathering authorities more
routinely for the next 20 Risk Evaluations.
56,
108, 99
PUBLIC COMMENTS:
EPA assumed a dermal absorption rate of 8% in industrial settings and
13% in commercial settings based on the Kasting and Miller (2006)
model; however, elsewhere, EPA indicates that dermal absorption is
rapid, citing other research.
It is unclear whether EPA considered this latter research when setting
the fractional absorption rates of 8% and 13%. If not, the model used
may underestimate dermal exposure, given the cited human and
excised skin tissue studies specific to TCE.
EPA cited ATSDR (2019), which reviewed a number of studies of
There is a difference between how fast
absorption occurs and how much absorption
occurs. The commenter seems to be confusing
these. There are competing processes of
absorption and evaporation that lead to the
calculated percent absorbed. For other solvents
where experimentally derived percent absorption
values were available, the actual absorption was
lower, not greater, than the model's prediction.
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TCE dermal absorption. EPA failed to consider those studies and
their implications for assumed rates of dermal absorption. This is in
violation of the requirement to base its risk determinations on all
"reasonable available information" and the "best available science."
EPA used the best available science and
reasonably available data to assess exposures for
each COU. EPA appreciates any additional data
from commenters that would improve its
estimates of occupational exposures.
Dermal exposure model is incomplete; modeling improvements/additional moc
eling suggestions
SACC
SACC COMMENTS:
The Committee expressed concerns about the suitability of the
permeability sub-model (P_DER2b). For consumer exposure to liquid
TCE EPA selected a permeability coefficient published by Poet et al.
(2000) and derived from fitting of a PBPK model. Two issues arise with
respect to this modeling approach
PBPK models typically treat skin as a well-mixed compartment
rather than as a membrane. Because the underlying mathematics is
different, the numerical value of the coefficient can be affected (see
Norman et al., 2008).
Such models represent multi-variable fitting exercises. Due to
compensating errors, good fits can be achieved by poor estimates of
more than one parameter.
Parameter values obtained from PBPK fitting should be checked against
values obtained by other means. The permeability coefficient obtained
from Poet et al. (2000) does not appear unreasonable for absorption from
aqueous media. However, the draft risk evaluation pairs an aqueous
phase permeability coefficient with the concentration of the neat liquid.
This approach is invalid.
The maximum concentration that can legitimately be paired with an
aqueous-phase permeability coefficient is that of the saturation
concentration in water. Barring skin damage by the pure solvent, this
should result in an overestimate of the maximum flux (and hence
absorbed dermal dose).
Based on comments from the SACC, EPA
updated dermal permeability modeling for the
final Risk Evaluation to utilize results for neat
permeabilitv from human data in (Kezic et al.
2001) as ODDOsed to data from aciueous TCE, as
was used previously.
99
PUBLIC COMMENTS:
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EPA did not model any repeat contact scenarios. EPA should model a
broader range of dermal contact scenarios based on its own analysis of
variations in dermal exposure conditions and base risk estimates on
multiple dermal exposure events per day. It should also estimate
increases in exposure and risk where occlusion results in higher skin
absorption of TCE during glove use.
EPA did not identify information on how many
contact events may occur and the time between
contact events. Therefore, EPA assumes a single
contact event per day for estimating dermal
exposures. EPA has described events per day
(FT) as a primary uncertainty for dermal
modeling in the discussion of occupational
dermal uncertainties section 2.3.1.3.4 as well as
in the Supplemental File: TCE Environmental
Releases and Occupational Exposure
Assessment.
See further discussion on occlusion in Appendix
H of the Supplemental Information on
Environmental Releases and Occupational
Exposure Assessment document. The occluded
scenarios were presented as a what-if scenario.
EPA does not know the likelihood or frequency
of these scenarios in the workplace; therefore,
EPA did not present risk estimates associated
with occluded exposure in the Risk Evaluation.
108
PUBLIC COMMENTS:
In the problem formulation, EPA states: "EPA anticipates that existing
EPA/OPPT dermal exposure models would not be suitable for
quantifying dermal exposure to highly volatile chemicals such as TCE."
The draft risk evaluation does not acknowledge this concern or make
clear whether or how it was addressed.
Unlike the EPA/OPPT dermal model, the
Dermal Exposure to Volatile Liquids Model
(DEVL) model incorporates the evaporation of
the material from the dermis. The DEVL model
was used to estimate dermal exposures to TCE
for the Risk Evaluation. More information on the
DEVL model can be found in Appendix H of the
Supplemental File: Environmental Releases and
Occupational Exposure.
99
PUBLIC COMMENTS:
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EPA uses different dermal absorption models for consumer and
workplace exposure scenarios - assuming that absorption is on the order
of 8-13% for workers but 0.8% for consumers - without clearly stating
the rationale. The implication that worker dermal exposure is longer in
duration than consumer exposure is inconsistent with EPA's premise that
both exposures involve one-time events.
Differences between occupational and consumer
assessment approaches are addressed in Section
4.3.2.3. The choice of one model over the other
is primarily driven by the exposure scenario that
needs to be assessed and the information that is
reasonably available. For example, EPA does
not know the exact duration of exposure for
occupational loading and unloading hence EPA
used the engineering model for occupational
exposure assessment since it is event based and
does not require a duration input. In contrast, for
consumer applications there is reasonably
available information for duration of use, hence
the CEM permeability model or the fraction
absorbed model can be used for these exposure
scenarios with greater confidence. Overall, the
models are considered appropriate for their
respective uses based on the reasonably
available information.
94
PUBLIC COMMENTS:
The exposure assessment for the dermal route was conducted using the
DEVL model using various scenario centric parameters that are applied
with little justification.
More information on the DEVL model and
associated parameters can be found in Appendix
H of the Supplemental File: Environmental
Releases and Occupational Exposure.
94
PUBLIC COMMENTS:
EPA's approach of assuming all occluded doses cannot be corrected
using IHSkinPerm. In IHSkinPerm, the thickness of the air layer
would have to be greatly increased (towards infinity) or the vapor
pressure of TCE would have to be greatly decreased (towards 0) to
correctly simulate, assuming no ability for TCE to escape the
occluded environment.
Exposure duration becomes even more important for occluded
contact, and a flux-based model assuming that no or negligible
The draft risk evaluation excluded dermal
consumer exposure scenarios without impeded
evaporation. Dermal approaches were revised
for the final draft with additional evaluation
incorporated for whether the condition of use
was expected to have expectation of impeded vs.
unimpeded dermal evaporation. For those
scenarios expecting impeded dermal
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evaporation is recommended as a conservative estimate. IHSkinPerm
is difficult to modify to account for negligible evaporation.
evaporation, EPA utilized the Permeability
submodel within CEM and for those expecting
unimpeded dermal evaporation, EPA utilized the
Fraction absorbed submodel within CEM. This
has been explained more fully within Section
2.3.2.4.1. EPA presents the results for the model
deemed to be most appropriate (permeability for
impeded evaporation, fraction absorbed for
unimpeded evaporation) within the Risk
Evaluation, however results via both methods
are provided for all COUs in the Supplemental
File Exposure Modeling Results and Risk
Estimates for Consumer Dermal Exposures.
EPA has provided a discussion of key sources of
uncertainty for occupational dermal scenarios in
section 2.3.1.3.4. EPA may explore the range of
possible exposures utilizing different models in
future assessments.
99
PUBLIC COMMENTS:
EPA failed to include dermal exposure in risk determinations for several
consumer products. EPA's claim that it can dismiss dermal exposure
because it is de minimis, or unlikely to contribute significantly to overall
exposure, is not consistent with realistic use scenarios for these products
and in conflict with how EPA has quantified dermal exposure by
workers. TSCA does not permit EPA to ignore exposures that it
considers de minimis.
EPA states that "there is low to medium confidence in consumer dermal
exposure modeling due to uncertainties related to absorption and
assumptions regarding impeded evaporation for particular COU." We
agree and believe that EPA should revise this modeling to reflect more
realistic consumer use scenarios.
103
PUBLIC COMMENTS:
EPA should consider providing additional discussion of the uncertainty
in the occupational dermal exposure scenarios, and potentially
calculating the range of possible exposures utilizing different models.
Uncertainties in dermal modeling were not adequately addressed
99
PUBLIC COMMENTS:
EPA admits that its absorption rate modeling was uncertain because
"there is a large standard deviation experimental measurement, which is
indicative of the difficulty in spreading a small, rapidly evaporating dose
of TCE evenly over the skin surface."
As with all modeling assessments, there is some
level of uncertainty. Uncertainties in regards to
dermal modeling are discussed in both the Risk
Evaluation and the Supplemental File:
Environmental Releases and Occupational
Exposure.
The EPA appreciates the submission of this
comment. The EPA will consider additional
alternative model selections, modeling
assumptions and empirical dermal exposure
studies in future assessments.
94
PUBLIC COMMENTS:
The TCE risk evaluation would be strengthened by refinements to the
methodology of the exposure characterization. When utilizing WOE
approaches to develop appropriate input parameters, models may be
more reliable than low-quality monitoring data.
Alternative model selections and more well-informed inputs indicate
that dermal exposures are likely substantially lower in the industry
Page 157 of 408
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than was estimated by EPA.
EPA should consider the incorporation of additional exposure
modeling in the revised risk evaluation that reflects well
characterized industrial handling practices.
At a minimum, the risk evaluation should include discussion of the
impacts of these assumptions on the level of confidence in the overall
estimates, and the degree to which the assumptions are more than
adequately protective.
Given the many uncertainties inherent in the TCE dermal assessment,
EPA should also investigate whether an empirical study of dermal
exposure to TCE can be conducted, and the findings incorporated
into the revised draft.
ONUs:
CPA's assumptions of ONU exposure scenarios and levels of exposure require justification
SACC
SACC COMMENTS:
Recommendation: Clarify the distinction between workers and ONUs for
all COCs.
In Table 2-23, it is not clear why chemists are considered ONUs (even
analytical chemists?), as are engineering technicians, or shoe and leather
workers. In small commercial operations, the same person can be both a
retail worker (ONU) and worker-operator.
EPA has not found additional reasonably
available information or data to explore different
categories of ONUs beyond the ONU categories
presented in this Risk Evaluation.
In Uncertainties section 4.3.2, EPA added the
uncertainty "ONUs are likely a heterogeneous
population of workers, and some could be
exposed more than just occasionally to high
concentrations."
Also, workers at small facilities are not
excluded.
56,
108,
100
PUBLIC COMMENTS:
The commenter supports EPA's decision to assume that ONUs will not
wear respirators; however, EPA may still have underestimated exposure
to ONUs.
EPA assumes central tendency exposures for ONUs in any case
where it does not have monitoring data or modeling specific to
EPA has revised the Risk Evaluation to discuss
uncertainties associated with assumptions related
to ONUs. EPA acknowledges that workers and
ONUs may not stay within their respective work
zones for the entire workday, and that exposures
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ONUs and provides no estimate of high-end risk for ONUs. These
cases are those where the "population" column in Table 4-54
identifies the population as "ONU (upper limit)." EPA then
determines ONUs face an unreasonable risk only if its central
tendency risk estimate for workers (carried over to ONUs) exceeds
its benchmark.
Where EPA does have data to estimate exposure of ONUs
specifically, EPA assumes that they are only present in the "far field
zone" - i.e., outside of the "near field" workers' zone. However,
ONUs may not stay within the "far field zone."
EPA assumes that ONUs will have no dermal exposures, an
assumption that is unfounded for cleaning workers and skilled trade
workers.
Particularly over a short period (e.g., response to a spill or equipment
maintenance), ONU exposures may be as great as or greater than
those of other workers, and ONUs are even less likely to be provided
PPE.
EPA's failure to collect ONU-specific data and its reliance on central
tendency exposure estimates thus understates the risks to ONUs.
for ONUs can vary substantially. Most data
sources do not sufficiently describe the
proximity of these employees to the exposure
source. As such, exposure levels for the "ONU"
category will have high variability depending on
the specific work activity performed. It is
possible that some employees categorized as
"ONU" have exposures similar to those in the
"worker" category depending on their specific
work activity pattern. ONUs are likely a
heterogeneous population of workers, and some
could be exposed more than just occasionally to
high concentrations.
For the risk evaluation, ONUs were defined as
not routinely handling the chemical that is
handled by the workers. Therefore, dermal
exposures for ONUs were excluded.
While spills and leaks generally are not included
within the scope of a TSCA risk evaluation,
maintenance staff are considered a subset of
ONUs and as such are not excluded from the
risk evaluation.
56, 108
PUBLIC COMMENTS:
EPA has provided no empirical basis for its arbitrary assumption that
ONUs will never be exposed at levels higher than the central
tendency exposure workers experience. EPA's approach is at odds
with its obligation under TSCA to conduct risk evaluations that
ensure protection of PESS, which TSCA explicitly defines as
including workers.
EPA represents its high-end estimates as "generally intended to cover
individuals or sub-populations with greater exposure," while its
EPA has revised the Risk Evaluation to discuss
uncertainties associated with assumptions related
to ONUs. EPA acknowledges that workers and
ONUs may not stay within their respective work
zones for the entire workday, and that exposures
for ONUs can vary substantially. Most data
sources do not sufficiently describe the
proximity of these employees to the exposure
Page 159 of 408
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central tendency estimates apply to the "average or typical exposure"
that people experience (p. 655).
TSCA would not permit EPA to protect against only the "average or
typical exposure;" in fact, when it comes to workers, ONUs, and other
PESS, EPA is required to protect all of them.
source. As such, exposure levels for the "ONU"
category will have high variability depending on
the specific work activity performed. It is
possible that some employees categorized as
"ONU" have exposures similar to those in the
"worker" category depending on their specific
work activity pattern. ONUs are likely a
heterogeneous population of workers, and some
could be exposed more than just occasionally to
high concentrations. See also Sections 2.3.3,
3.2.5.2, and 4.4.1 in the risk evaluation for
further discussions of PESS.
EPA disagrees that the potentially exposed or
susceptible subpopulations identified for each
chemical substance must include workers. TSCA
section 3(12) lists examples of human receptors
that may be considered PESS but provides for
EPA to identify the relevant subpopulations for
each chemical substance.
100,
108
PUBLIC COMMENTS:
EPA acknowledges that it has virtually no data on ONU exposures, and
the broad range of workers that EPA defines as ONUs is too large to
support any single classification. For example, supervisors have very
different exposure patterns than skilled trade workers and cleaning
workers, and thus face very different risks from TCE.
Information on activities where ONUs may be present are
insufficient to determine their exposures.
EPA has not found additional reasonably
available information or data to explore different
categories of ONUs beyond the ONU categories
presented in this Risk Evaluation.
ONUs:
CPA should collect additional ONU exposure data
SACC
SACC COMMENTS:
Recommendation: Explore the use of area monitoring samples and
estimates of far field modeling concentrations for deriving ONU
exposure estimates.
Where data was reasonably available, both area
monitoring data and far-field modeling data
were used to estimate ONU exposures.
Page 160 of 408
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Monitoring data reports frequently have area samples (also called static
samples) collected away from the worker's location. These data could be
explored as potential indicators of ONU's exposures.
108
PUBLIC COMMENTS:
During the SACC meeting, several reviewers raised concern over EPA's
lack of sufficient occupational exposure data especially with regards to
ONUs and suggested that EPA undertake a more concerted effort to
acquire data from OSHA, NIOSH, and companies to fill these gaps.
One reviewer suggested that OSHA or NIOSH inspection data could
be helpful in understanding where ONUs are located in facilities,
helping to refine the near field versus far field assumptions. If these
agencies do not have applicable data, EPA could request that they
collect such data moving forward.
Another reviewer noted that the same data gap issues have arisen in
multiple draft risk evaluations and will continue to arise unless
addressed; he suggested that EPA begin looking forward to the next
20 chemicals slated for risk evaluations to proactively fill data gaps
by better collaborating with NIOSH and OSHA.
EPA thanks the commenter for the suggested
data sources. EPA consults regularly with its
federal partners and will consult with OSHA and
NIOSH on this topic for future risk evaluations.
Improved discussion/consideration of hierarchy of engineering controls
SACC
SACC COMMENTS:
Recommendation: Improve the discussion of the exposure control
hierarchy.
The draft risk evaluation's discussion of the exposure control hierarchy
should be more complete, specifically noting the PPE is the third stage of
protection after establishment of proper engineering and administrative
controls. EPA should also present data demonstrating relatively poor
adherence to guidelines and supporting recommendations for worker
protection, not just provide a reference. At a minimum, the discussion
should provide a table summarizing the type of gloves recommended for
TCE by NIOSH, OSHA, and product manufacturers, both for handling
neat TCE and TCE-containing mixtures.
Section 2.3.1.2.6 of the Risk Evaluation
discusses the hierarchy of controls and that PPE
is the last stage of protection.
80, 100
PUBLIC COMMENTS:
A hierarchy of controls is a method for
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The hierarchy of controls has been endorsed by NIOSH, the American
Society of Safety Engineers, the American Industrial Hygiene
Association, ACGIH, the American Public Health Association, the
American Federation of Labor and Congress of Industrial Organizations,
and many others. OSHA has incorporated the hierarchy of controls into
all of its health standards, and EPA has endorsed this risk management
approach. It calls for the use of elimination, substitution, engineering
controls, administrative controls, and lastly PPE. That order is predicated
on well-established observations that PPE is the hardest control to
effectively implement and has the highest failure rate.
While the draft risk evaluation pays lip service to the hierarchy of
controls - stating that PPE should be the "last means of control," to
be used only "when the other control measures cannot reduce
workplace exposure to an acceptable level" - EPA's assumption of
PPE use prior to the consideration of other risk management tools is
fundamentally at odds with this approach.
Given the broad acceptance of this methodology when conducting
occupational risk assessment, EPA's deviation from the hierarchy of
controls violates EPA's obligation to use the best available science in
TSCA risk evaluations.
eliminating workplace hazards. While EPA has
assessed the extent to which certain exposure
reduction tools that it assumes to be in place
may be reducing risks to workers, application of
the methodology of the hierarchy of controls is
not relevant to risk evaluations. EPA will
manage unreasonable risks presented by
chemical substances when the Agency
undertakes regulatory action for COUs
determined to have unreasonable risk.
Utilization of the hierarchy of controls to
recommend or require risk management actions
in the risk evaluation would be premature and
inappropriate.
Consumers: Consumer COU/exposure scenarios/pathways require clarification or are not valid/complete
SACC
SACC COMMENTS:
Recommendations: (1) Include a more detailed description of the process
used for identifying consumer COUs and TCE-containing products. (2)
Review current uses of the 33 reported commercial, industrial, and
consumer COUs and identify all of the TCE-containing products for each
of the consumer use scenarios.
The Committee concluded that there is insufficient description about
the process used for identifying consumer COUs and products
containing TCE. One member of the Committee noted that the draft
risk evaluation is clear in explaining differences between COU
categories and products identified in the draft risk evaluation and
those identified in the problem formulation (U.S. EPA, 2018).
The Risk Evaluation describes the sources used
to identify COUs, including EPA's Use and
Market Profile for Trichloroethvlene. (EPA-HO-
OPPT-2016-073 7-0056). The Use and Market
Profile for Trichloroethylene provides a
description of the process EPA used to identify
COUs (including consumer COUs), including
use the of EPA databases from Chemical Data
Reporting, the Toxic Release Inventory, and the
National Emissions Inventory. Section 3 of the
report further details the process EPA used to
Page 162 of 408
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The draft risk evaluation references the Use and Market Report and
Preliminary Information on Manufacturing, Processing, Distribution,
Use, and Disposal: TCE (U.S. EPA, 2017c), but the report does not
describe how specific consumer products were identified. It is not
clear when this report was updated.
The draft risk evaluation does not describe in enough detail and
specificity how comprehensive and systematic the search was for this
information. On p. 142, the draft risk evaluation states: "Additional
online research was undertaken following problem formulation to
confirm TCE concentrations and compile a comprehensive list of
products that may be available to consumers for household use."
What kind of "online research" was performed?
Similarly, on p. 179 the statement: "Additional sources of product
information were evaluated, including the NIH Household Product
Survey and EPA's Chemical and Products Database (CPDat), as well
as available product labels and safety data sheets (SDSs)" does not
provide enough details to know how comprehensive and systematic
the search was. A Committee member noted that the National
Institutes of Health (NIH) Household Product Survey is no longer
maintained by the NIH, and wondered what steps are being taken
going forward to ensure that products are identified in a systematic
and comprehensive manner.
supplement information from these databases,
including internet searches for consumer
products. In addition, the Risk Evaluation notes
that EPA made use of public meetings, and
meetings with companies, industry groups,
chemical users and other stakeholders to aid in
identifying conditions of use and verifying
conditions of use identified by the EPA.
Statements in the Risk Evaluation implying
"Additional online research" or "Additional
sources" conducted after Problem Formulation
have been rewritten to clarify that research
subsequent to Problem Formulation was
conducted to confirm information identified in
prior searches.
There are limited available product databases
and they are not necessarily complete nor
consistently updated and general internet
searches cannot guarantee entirely
comprehensive product identification. Therefore,
it is possible that the entire universe of products
may not have been identified, or that certain
changes in the universe of products may not
have been captured, due to market changes or
research limitations. EPA has added language
clarifying this in Section 3.2.7.2 of the Risk
Evaluation.
SACC
SACC COMMENTS:
It is unclear if the IRTA (2007) report is a good proxy for TCE-based
spot remover, as the product was prohibited by California Air
Resources Board (CARB, 2019) for that use in 2012. Additional
products may have also been reformulated in part due to California
The IRTA (2007) study was used to develop (for
CalEPA and EPA Region IX) annual per-site use
rate information for an occupational exposure
scenario as described in section 2.14.3.3.2 of the
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Proposition 65.
Another Committee member noted that a surrogate product is used
for film cleaner and toner aid use scenarios, but a simple Google
internet search reveals the commercial availability of TCE-
containing film cleaners {i.e., brands such as Edwal, Tetenal, etc.)
both in liquid and spray forms, and toner aid {e.g., brand Sprayway;
SDS online; see example:
http://www.spraywayinc.com/content/toner-aide).
Supplemental Information File Environmental
Releases and Occupational Exposure
Assessment (Inhalation Exposure Assessment
Results Using Modeling - Spot Cleaning).
All weight fractions used in this evaluation are
derived from SDSs for actual TCE-containing
products. The "surrogate product data" used
from Westat represent the most current,
nationally relevant data source available for a
range of the evaluated conditions of use, namely
for data on length of time a product was used,
the room of use, and the mass of product used.
These durations and amounts are intended to
cover the spectrum of possible users ranging
from low to high intensity users as described in
the document.
SACC
SACC COMMENTS:
Recommendation: Reexamine the pepper spray use scenario.
Committee members indicated that it is unclear whether any of the
pepper spray products remain available in the consumer market. It is
not clear what efforts were taken to ensure the scenario described on
p. 148, footnote 12 in Table 2-28 is reflective of actual usage. EPA
needs to verify and/or determine the concentration of the existing
pepper spray products, and review if this and other product use
patterns appear reasonable.
Another Committee member considered the assumption of only one
gun in the gun scrubber use scenario not well justified and not
sufficiently conservative.
EPA has updated the pepper spray scenario to
include additional variance in user intensity
scenarios based on different mass inputs (Table
2-29), resulting in addition of two additional
scenarios reflective of a higher use amount.
EPA acknowledges that variability exists in
modeling assumptions of user scenarios for gun
scrubber. As stated in Section 2.3.2.6.2, "this
mass input may not appropriately capture
consumers cleaning multiple guns in a day... "
While the Westat product category does not
align closely with this specific use, the duration
data was deemed reasonable for modeling.
SACC
SACC COMMENTS:
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One Committee member suggested including TCE inhalant as a
consumer exposure. However, other members indicated that intentional
misuse of products is not considered a COU under TSCA.
EPA would not generally consider intentional
misuses (e.g., inhalant abuse), as a "known" or
"reasonably foreseen" activity. Without this
exclusion, the concept of "conditions of use"
would likely result in no meaningful limitation
on EPA risk evaluations, and risk evaluations
could present unmanageable challengesan
outcome that EPA does not expect Congress
intended.
56, 108
PUBLIC COMMENTS:
EPA excludes "paints and coatings for consumer use" but continues to
analyze these COUs in the industrial and commercial context.
EPA should analyze consumer uses in these circumstances. TCE's
use in the industrial and commercial context makes it at least
reasonably foreseen that TCE is, or could be, used in the same
manner in the consumer context. Even where a product is "labeled
for industrial use," it may be reasonably foreseeable that the product
may ultimately be used by a consumer.
During the SACC meeting, EPA explained that the exclusion was due to
EPA's promulgation of a SNUR on certain consumer uses of TCE,
implying that the SNUR prohibits consumer use of TCE in paints and
coatings. This is untrue; the SNUR does not place any restrictions on
such use; any actual restriction would require further Agency action
subsequent to review.
The existence of a SNUR is insufficient to conclude that these uses
will not occur or are not "reasonably foreseeable.
EPA has not adequately shown that these circumstances are not
"reasonably foreseen" COUs.
Even if a ban on TCE's use in such consumer products were in place,
absent specific steps to ensure that consumers cannot gain access to
products intended for industrial or commercial uses, such use would
still be "reasonably foreseen."
Non-occupational bystanders may be exposed to industrial or
EPA does not believe that paints and coatings
for consumer use contain TCE. EPA did not
identify any paint and coating products currently
containing TCE through the searches of the
internet, databases, and other sources used to
identify uses and does not consider it an ongoing
use. Furthermore, EPA developed a Significant
New Use Rule (SNUR) on TCE in Certain
Consumer Products (81 FR 20535) that was
cited in the Problem Formulation for TCE.
Persons subject to the SNUR are required to
notify EPA at least 90 days before commencing
any manufacturing or processing of TCE for a
significant new use, including manufacture or
processing of TCE for use in paints and coatings
for consumer use. The required Significant New
Use Notification (SNUN) provides EPA with the
opportunity to evaluate the intended use. If EPA
finds upon review of the Significant New Use
Notice (SNUN) that the significant new use
presents or may present an unreasonable risk (or
if there is insufficient information to permit a
reasoned evaluation of the health and
Page 165 of 408
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commercial uses of paints and coatings containing TCE during
regular use, e.g., during painting of residential spaces or houses or
other buildings.
EPA cannot evade their duty by limiting its analysis to COU with
evidence of current, ongoing use - such an interpretation limits
EPA's analysis to "known" uses.
environmental effects of the significant new
use), then EPA would take action under TSCA
section 5(e) or (f) to the extent necessary to
protect against unreasonable risk. EPA is only
including use of TCE in industrial and
commercial paints and coatings as a condition of
use for TCE.
Because U.S. EPA 2014 was developed prior to
the SNUR and proposed rules for the ban of
TCE in certain uses, it does not reflect ay market
changes that may have occurred subsequent to
its preparation.
Finally, the Use and Market Report states that
the list of products containing TCE within the
report is not exhaustive and has not been
updated. The Use and Market Report is meant to
provide examples of products that contain TCE
and their formulations where possible.
SACC
SACC COMMENTS:
Recommendation: Clarify whether consumer paints and coatings no
longer contain TCE.
It is not clear if referenced U.S. EPA (2014) is reflective of likely market
changes since the significant new use rule (SNUR) on consumer uses for
TCE was implemented as well as the proposed rules for the ban of
aerosol and vapor degreasing.
Based upon a review of the 33 reported commercial, industrial, and
consumer products listed in the Market and Use Report, 17 appear valid,
2 appear to no longer exist, and 13 are unclear as to current status. In
addition, there are products that have not been captured in the draft risk
evaluation. For example, the previously cited hoof polish product now is
labeled as 'extremely flammable' and has likely been reformulated, and
Berryman Products appears to have products formulated with TCE
(www. b erry manproducts. com).
108
PUBLIC COMMENTS:
EPA excludes the oral route of exposure for consumers despite
acknowledging potential for exposure via hand-to-mouth patterns.
As stated in the footnotes for Figure 1-5, mists
of TCE will likely be rapidly absorbed in the
respiratory tract or evaporate and not result in an
oral exposure. Although less likely given the
physical-chemical properties, oral exposure may
also occur from incidental ingestion of residue
on hand/body. Because oral exposure would be a
very minor pathway relative to dermal and
inhalation exposure.
108
PUBLIC COMMENTS:
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EPA excludes exposure to consumers from disposal. Congress
consciously decided to specify that "disposal" is a COU under TSCA.
Page 167 of 408
EPA evaluated and considered the impact of
existing laws and regulations (e.g., regulations
on landfill disposal, design, and operations) in
the problem formulation step to determine what,
if any future analysis might be necessary as part
of the risk evaluation. During problem
formulation EPA analyzed the TRI data and
examined the definitions of elements in the TRI
data to determine the level of confidence that a
release would result from certain types of
disposal to land (e.g., RCRA Subtitle C
hazardous landfill and Class I underground
Injection wells) and incineration. EPA also
examined how TCE is treated at industrial
facilities. EPA did not include emissions to
ambient air from commercial and industrial
stationary sources, which are under the
jurisdiction of and addressed by Section 112 of
the Clean Air Act. EPA did not include
emissions to ambient air from municipal and
industrial waste incineration and energy
recovery units in the risk evaluation, as they are
regulated under section 129 of the Clean Air
Act. EPA did not include disposal to
underground injection, RCRA Subtitle C
hazardous waste landfills, RCRA Subtitle D
municipal solid waste (MSW) landfills, and on-
site releases to land from industrial non-
hazardous waste and construction/demolition
waste landfills in this Risk Evaluation. These
methods of disposal fall under the jurisdiction of
and are addressed by other EPA-administered
statutes and associated regulatory programs.
-------
47
PUBLIC COMMENTS:
One consumer COU was excluded from the final list (lace wig and hair
extension glues) because, after consultation with the FDA, it was
determined that it falls outside the scope of EPA's jurisdiction.
This does not mean that exposure attendant to that use should be
excluded from the exposure assessments for consumers in the
relevant subpopulation.
Under TSCA ง 3(2)(B)(vi), the definition of
"chemical substance" does not include "any
food, food additive drug, cosmetic, or device (as
such terms are defined in section 201 of the
Federal Food, Drug, and Cosmetic Act) when
manufactured, processed, or distributed in
commerce for use as a food, food additive, drug,
cosmetic, or device." EPA has concluded that
lace wig and hair glue is used as a cosmetic, and
has concluded that this use falls within the
aforementioned definitional exclusion and is not
a "chemical substance" under TSCA.
47
PUBLIC COMMENTS:
The current assessment included three consumer uses that had been
excluded from the 2014 TCE Risk Assessment list.
This is seen to be a wise choice because these three COUs were
determined to pose an unreasonable risk to consumers and also to
bystanders, and, therefore, are targets for risk management, most
appropriately a ban on all those uses.
EPA acknowledges this comment.
99
PUBLIC COMMENTS:
EPA concedes that its risk estimates for consumers may be understated
because they do not take into account the continuous presence of TCE in
outdoor and indoor air.
EPA acknowledges this comment and agrees
there may be an underestimation of risk.
Additional discussion of this underestimation is
found in Sections 2.3.2.6.1 and 4.4.2.
Consumers: Additional consumer data considerations
SACC
SACC COMMENTS:
Recommendation: Consider exploring the wealth of information
available in the internet on do-it-yourself (DIY), hobbies, and home-
based production of items for sale to get more data on products used by
consumers who are likely high-frequency users.
Although the Committee could not identify additional sources of data for
specific COU and was not aware of any specific databases, it is likely
As noted in the document entitled EPA's
Responses to Public Comments Received on the
Scope Documents for the First Ten Chemicals
for Risk Evaluation under TSCA (EPA-HO-
OPPT-2016-0723-00671 EPA conducted
extensive and varied data gathering activities for
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that these data exist. Some of the large general population exposure
assessment studies cited in the draft risk evaluation also administered
questionnaires about residential activity patterns and the use of some
types of products. This literature could be explored to obtain information
on product type use, though not specific products.
each of the first 10 chemicals, including:
Extensive and transparent searches of
public databases and sources of scientific
literature, government and industry sector
or other reports;
Searches of EPA TSCA 8(e), Chemical
Data Reporting, and other EPA information
holdings; and CBI submission holdings;
Searches for Safety Data Sheets (SDSs)
using the internet, EPA Chemical and
Product Categories (CPCat) data, the
National Institute for Health's (NIH)
Household Product Database, and other
resources in which SDS could be found;
Preparation of a market analysis using
proprietary databases and repositories;
Outreach meetings with chemical
manufacturers, processors, chemical users,
non-governmental organizations, trade
organizations, and other experts, including
other State and Federal Agencies (e.g., Dept
of Defense, NASA, OSHA, NIOSH, FDA
and CPSC); and
EPA published conditions of use documents,
scope documents, and problem formulation
documents to solicit information generally from
industry, nongovernmental organizations, and
the public.
SACC
SACC COMMENTS:
EPA has conducted public outreach and
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Recommendation: Scrutinize the products included in the ATSDR
(2019) Toxicological Profile for TCE content or reformulation.
A member of the Committee indicated that the ATSDR (2019)
Toxicological Profile for TCE included typewriter correction fluid,
drain cleaners, spray paint, and paint strippers as uses. These should
be considered. It is not clear in the draft risk evaluation whether all
products included in the Toxicological Profile underwent careful
scrutiny (revalidation) by EPA.
literature searches to collect information about
trichloroethylene's conditions of use and has
reviewed reasonably available information
obtained or possessed by EPA concerning
activities associated with trichloroethylene,
including information on uses in the ATSDR
Toxicological Profile. The conditions of use
included in the risk evaluation include uses for
which manufacturing, processing, or distribution
in commerce is intended, known to be occurring,
or reasonably foreseen to occur.
SACC,
108
SACC COMMENTS:
Recommendation: Consider updating the Westat survey data (U.S. EPA,
1987) to verify that use patterns and building-related parameters reflect
current consumer use patterns and housing construction.
The committee was unanimous that at least some consumer use patterns
are likely to have changed since the survey data was collected. The size
of homes has also changed with a trend to larger homes and more open
floor designs, as to increasingly tighter structures that may affect air
exchange rates.
Conducting a national survey of consumer uses
and behaviors was infeasible to support the TCE
risk evaluations. Absent a time-consuming
update, the data used from Westat still represent
the most current, nationally relevant data source
available for a range of the evaluated conditions
of use. EPA notes there are limitations and
uncertainties associated with this Westat dataset.
Consumers: EPA should consider chronic scenarios for consumer exposure
SACC,
99, 108
SACC COMMENTS:
Recommendation: Characterize TCE chronic risk to consumers and add
a discussion of chronic non-cancer risks.
The committee disagrees with EPA's basis for their decision not to
characterize chronic risks. Several Committee members suggested that
some consumers are likely to be exposed more frequently and more
pervasively to emissions from these products than indicated by the
Westat survey data (U.S. EPA, 1987).
Certain high-exposed consumers (hobbyists, home businesses, etc.)
are likely to use more than one TCE-containing product on the same
Scenarios for conditions of use associated with
products containing TCE include a wide range
of usage intensities with ranges in weight
fractions, time of use, and mass of product used.
While the actual use of the product only occurs a
single time during the evaluation period a given
consumer user can encounter inhalation
exposures during both the use period and also
following use through the prescribed movement
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day and/or multiple and consecutive days.
The Westat survey was unlikely to capture the true distribution of use
frequency for high-end users (oversampling would be been required
to obtain a reliable estimate of use patterns).
It is likely that contributions to indoor air concentrations (and,
therefore, exposures) persist for longer periods of time than assumed
by EPA from sources such as carpet spot cleaners and fabric sprays.
Products stored in homes after use may emit low levels of chemical
into the indoor atmosphere resulting in additional chronic exposure.
SACC COMMENTS:
Recommendation: The uncertainty in consumer risks from high-end
periodic exposures combined with background air and water
concentrations should be better characterized and if possible, sensitivity
to assumptions and data uncertainties addressed.
On p. 322, the draft risk evaluation indicates that risks cannot be ruled
out for consumers exposed from high-end frequency of product use that
is periodic. Associated risks could not be estimated due to the
uncertainty in the extrapolation from continuous exposure studies in
animals. The Committee expressed concern that periodic exposures
combined with background exposures may leave consumers with higher
risks than calculated in this draft risk evaluation.
56, 108
PUBLIC COMMENTS:
Other chronic users may be artists who work at home, home
renovators, and consumers who maintain and repair vehicles.
EPA could determine overall exposure levels from recurring consumer
use of multiple TCE-containing consumer products and then estimate
risks of cancer, developmental/reproductive toxicity, kidney effects, and
immunotoxicity to consumers.
PUBLIC COMMENTS:
EPA assumes a single dermal exposure event per day for consumers.
This assumption is particularly problematic for "do-it-yourselfers,r
Page 171 of 408
about the house.
EPA assumes that exposure is not chronic in
nature, the assumption is discussed in Section
2.3.2.2 of the Risk Evaluation. Chronic exposure
scenarios resulting from long-term use of
household consumer products were not
evaluated as these events are likely to be
relatively infrequent with short durations of use.
This assumption is supported by product use
frequencies reported within the Westat survey
( 7) for evaluated conditions of use that give
central tendency frequencies that were
considered to be too low to create chronic risk
concerns. In addition, the short half-life of the
chemicals in the body does not result in
significant accumulation between uses on
different days. EPA directly identifies the
uncertainties, such as the fact that exposure
estimates may underestimate exposure to
individuals who are involved with do-it-yourself
projects as well as recognition that consumer
practices are moving toward more do-it-yourself
work. TSCA Section 6(b)(4)(F)(iv) instructs
EPA to factor into TSCA risk evaluations "the
likely duration, intensity, frequency, and number
of exposures under the conditions of use." This
suggests that activities for which duration,
intensity, frequency, and number of exposures
cannot be accurately predicted or calculated
based on reasonably available information were
not intended to be the focus of TSCA Risk
Evaluation. Since reasonably available
-------
which EPA acknowledged may be exposed more than once per day.
EPA fails to actually address this scenario in calculating exposure and
risk estimates.
information was not identified to inform these
and other parameters, and as recognized by
SACC the absence of data leaves it uncertain
how to develop a worst-case scenario, storage of
consumer products was not evaluated in this
Risk Evaluation.
56,
108, 99
PUBLIC COMMENTS:
EPA fails to assess any chronic exposures to consumers despite
acknowledging in the draft risk evaluation they are expected to occur.
EPA thus fails to address consumer risk for cancer, developmental
toxicity, kidney effects, and immunotoxicity.
While chronic exposure may not be typical for consumers, EPA's
failure to assess DIY users as a "potentially exposed or susceptible
subpopulation" is troubling, particularly because it considered DIY
users as a sentinel exposure.
EPA's assumptions about consumer exposure are likely to significantly
underestimate the risks they face. EPA needs to conduct a sensitivity
analysis regarding these assumptions in the context of this risk
evaluation, which is different than the sensitivity analysis EPA indicates
was done on the model itself.
49, 99
PUBLIC COMMENTS:
EPA's risk evaluation assumes that consumers only have acute exposure
to TCE. However, the evidence of ongoing TCE concentrations in indoor
air indicates that chronic exposure is also occurring and therefore
consumers are at risk for cancer and other chronic health effects that
EPA fails to address.
Since exposure to TCE in ambient air and contaminated drinking
water is continuous, if EPA included these pathways, it could not
limit its evaluation to acute risks to consumers, it would need to
address long-term exposure scenarios.
Consumers: Comments on Consumer Exposure Model (CEM) parameters/estimates; additional suggestions
SACC
SACC COMMENTS:
Recommendation: Consider developing CEM exposure estimates for
bystanders present in Zone 1 for scenarios where it is likely that the
bystander could be in the same room as the user.
EPA acknowledges that consumer bystanders
were not assumed to be exposed in same room
as the users. Additional language has been added
to the uncertainty discussion in Section 2.3.2.6.
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In the CEM model members of the Committee were concerned about the
assumption that bystanders remain in Zone 2 while the product is in use,
without providing adequate justification for this assumption, which could
result in underestimation of bystander exposures.
One Committee member suggested that bystanders should be treated
similarly to how ONUs are treated in the OESs, and was unclear why
"near-field" and "far-field" zone assumptions could not be applied to
consumer users and bystanders in the same room (in addition to the
alternative of assuming the zones correspond to two separate rooms).
EPA will consider this refinement to the
consumer modeling approach for future
evaluations.
SACC
SACC COMMENTS:
Recommendation: Perform a sensitivity analysis on inputs to the
consumer exposure model to address uncertainties in representativeness
of model outputs.
EPA's conclusion that "Certain inputs to which the (consumer exposure)
model outputs are sensitive, such as zone volumes and airflow rates,
were not varied across product-use scenarios. As a result, model
outcomes for extreme circumstances such as a relatively large chemical
mass in a relatively low-volume environment likely are not represented
among the model outcomes. Such extreme outcomes are believed to lie
near the upper end (e.g., at or above the 90th percentile) of the exposure
distribution," represents a source of uncertainty, and the limited
discussion provided to be inadequate.
The overall CEM model had a sensitivity
analysis conducted for evaluation of which
scenario specific inputs influenced inhalation
and dermal exposure results. Within this section,
EPA describe that the full description of this
sensitivity analysis is available in Appendix C of
the CEM User's Guide (U.S. EPA 2019a). As
described in Appendix C, elasticity was
evaluated by altering model input parameters by
a 10% increase. Due to the number of
parameters evaluated, the calculated elasticities
are not included in the risk evaluation but are
available for review in Tables D2-D8 and Figures
D1-D15 in Appendix C of the User's Guide
available here:
httDs://www.eDa.sov/sites/Droduction/files/2017-
06/documents/cem user suide appendices.odf.
Appropriateness of exposure uncertainty discussion
SACC
SACC COMMENTS:
Recommendation: Discuss all of the biases and uncertainties inherent in
OSHA and non-OSHA, and foreign monitoring data for exposure
estimation.
In particular, German data were used as a surrogate for unloading
EPA identifies the uncertainty of
representativeness as a primary uncertainty for
each occupational exposure scenario that
includes monitoring data. The Uncertainties
Page 173 of 408
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and repacking, and degreasing. There is potential for exposures in
Germany to be lower because of tighter controls in response to the
stricter occupational exposure regulations. This issue and
corresponding limitation of using the German data should be
specifically discussed.
section 4.3.2.1 provides detailed discussion of
this potential bias and notes that limited data sets
may potentially underestimate or overestimate
exposures. Foreign data is scored following the
data qualitv ratines in EPA's Application of
Systematic Review in TSCA Risk Evaluations.
103
PUBLIC COMMENTS:
EPA should provide additional discussion of the uncertainty in the
occupational dermal scenarios.
Uncertainty in dermal exposure estimates is
included in Sections 2.3.2.7 and 4.3.2.3 of the
Risk Evaluation.
80
PUBLIC COMMENTS:
EPA should develop uncertainty estimation methods to define potential
distributions of PPE usage and performance. These distributions should
then be included as parameters in the Monte Carlo occupational exposure
assessment modeling. Several studies have proposed methods for
characterizing uncertainty in respirator performance and usage.
EPA appreciates the comment and may consider
potential distributions of PPE usage and
performance as data availability allows.
Appropriateness of exposure confidence ratings
SACC
SACC COMMENTS:
Recommendation: Provide more detail on the confidence ratings used in
the tables for inhalation and dermal exposures.
Committee members liked the framework of variability and
uncertainty for presenting strengths and limitations in risk
characterization estimates for consumers. However, it is unclear how
the final confidence levels are derived. Footnotes in Tables 2-71 and
2-72 do not provide enough detail to clarify the process that leads to
a high, moderate or low confidence for each specific component of
the risk characterization and consumer use in these tables.
One Committee member noted that statements such as: "The
exposure durations modeled could exceed the duration of such
dermal contact, therefore, the higher-end durations may result in an
overestimation of dermal exposure" should acknowledge the
possibility of underestimation unless a specific reason is provided for
why the potential error is one-sided.
Tables 2-85 and 2-86 lay out the factors that
contributed to the overall confidence rating for
each exposure scenario evaluated, such as model
application, default values, and user-selected
inputs (e.g., mass, duration, weight fraction, and
room of use). Consideration of the confidence in
each of these displayed factors underlies the
overall confidence score in a scenario.
Section 2.3.2.7 discuss sources of uncertainty
and assumptions that may lead to overestimation
and underestimation of exposure.
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56, 108
PUBLIC COMMENTS:
The errors in EPA's characterization of exposure monitoring systematic
review ratings call into question EPA's ultimate "overall confidence"
ratings for the inhalation exposure estimates presented in Table 2-26
EPA is in the process of seeking peer review of
its Systematic Review protocol, and the
confidence rating system may be addressed in
future updates.
Exposure - other
56, 108
PUBLIC COMMENTS:
EPA did not establish that the exposures it analyzed represent the
"plausible upper bound of exposure relative to all other exposures"
within the relevant categories.
The purpose of risk evaluation under TSCA is
"to determine whether a chemical substance
presents an unreasonable risk of injury to health
or the environment, without consideration of
costs or other nonrisk factors, including an
unreasonable risk to a potentially exposed or
susceptible subpopulation identified as relevant
to the risk evaluation by the Administrator,
under the conditions of use." TSCA section
6(b)(4)(A). EPA described background exposure
in the uncertainties section acknowledging that
the risk estimations in the Risk Evaluation may
be underestimations, because background
exposures and risk are not incorporated into the
risk estimations for each COU.
47
PUBLIC COMMENTS:
TCE exposure assessments and risk determinations should take into
account cumulative exposures to perchloroethylene (and to the other
chlorinated compounds listed in Table 3.4) where metabolites, endpoints,
COUs, and ambient exposures co-exist. TCE's and perchloroethylene's
COUs have significant potential for overlap; their COU categories are
virtually identical as are many of the subcategories.
TSCA section 6(b)(4)(F)(ii) directs EPA to
"describe whether aggregate or sentinel
exposures to a chemical substance under the
conditions of use were considered, and the basis
for that consideration" in risk evaluations. EPA
defines aggregate exposures as the combined
exposures to an individual from a single
chemical substance across multiple routes (i.e.,
dermal, inhalation, or oral) and across multiple
pathways (i.e., exposure from different sources).
Page 175 of 408
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40 CFR 702.33. EPA defines sentinel exposures
as the exposure from a single chemical
substance that represents the plausible upper
bound of exposure relative to all other exposures
within a broad category of similar or related
exposures. 40 CFR 702.33. EPA considered the
reasonably available information and used the
best available science to determine whether to
consider aggregate or sentinel exposures for a
particular chemical. EPA has determined that
using the high-end risk estimate for inhalation
and dermal risks separately as the basis for the
unreasonable risk determination is a best
available science approach. There is low
confidence in the result of aggregating the
dermal and inhalation risks for this chemical if
EPA uses an additive approach, due to the
uncertainty in the data. EPA does not have data
that could be reliably modeled into the
aggregate, which would be a more accurate
approach than adding, such as through a PBPK
model. Using an additive approach to aggregate
risk in this case would result in an overestimate
of risk. Given all the limitations that exist with
the data, EPA's approach is the best available
approach.
56
PUBLIC COMMENTS:
EPA dismisses unreasonable risk based on bias assessment of exposure
estimates by choosing only to emphasize the potential for data sources to
overestimate exposure, while ignoring the potential for similar factors to
underestimate exposures.
EPA considered the weight of scientific
evidence and presented its assessment of
direction of uncertainty for exposure estimates in
Sections 2.3.1.3 and 2.3.2.6.
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5. Human Health Hazard
Human lleahli lla/artl
Charge Question 5.1: LIW performed a weight of e\ idcncc assessment ibr the endpoint of de\ elopmeiital cardiac delects based on
available epidemiological, in vivo animal, and mechanistic data. EPA concluded that the available literature supported positive
overall evidence that TCE may produce cardiac effects in humans (Section 3.2.4.1.6 and Appendix G.2); however cardiac defects
after developmental exposure were not observed consistently across the available in vivo animal studies. The Charles River
dissection methodology differed from Johnson et. al. (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 al. (2003) study. Please comment on EPA's Weight of Evidence (WOE) analysis
approach and conclusions for this endpoint, including EPA's analysis of the Charles River (2019) and Dawson (1993)/Johnson
(2003) studies.
Charge Question 5.2: Please comment on the assumptions, strengths and weaknesses of the dose-response approaches used to
estimate the non-cancer risks to workers, occupational non-users, and consumers. Please also comment on whether EPA
sufficiently justified its selections of BMRs for BMD modeling results and uncertainty factor values in deriving the PODs and
benchmark margin of exposures (MOEs) (Sections 3.2.5.3.2 and 3.2.5.3.3). As part of this discussion, please comment on EPA's
justification for selecting a 1% BMR for the cardiac malformation endpoint based on the severity of the endpoint {i.e., potential
mortality).
Charge Question 5.3: EPA determined that the immune effects from Selgrade and Gilmour (2010) represent the best
representative dataset to use for evaluating acute effects and the autoimmunity effects from Keil et al (2009) represent the best data
set to use for evaluating chronic non-cancer effects (Section 3.2.6.4).
a. Please comment on EPA's selection of these studies as the best representative endpoints, including consideration of the POD
derivation and benchmark MOEs.
b. 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
{i.e., blood:air partition coefficient 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.
c. EPA acknowledges that in using the Keil et al (2009) study, EPA is relying upon an early clinical marker to account for
susceptibilities, and the endpoint is a precursor to adverse effects for autoimmunity. This LOAEL was considered in this context
and the LOAEL to NOAEL uncertainty factor was reduced from 10 to 3X. In light of this, please comment on EPA's use of a 3x
Uncertainty Factor for human variability and LOAEL to NOAEL extrapolation.
Charge Question 5.4: EPA performed a meta-analysis on the published database for liver cancer, kidney cancer, and non-Hodgkins
lymphoma (NHL), concluding that there was a statistically significant association between TCE exposure and all three cancers when
Page 177 of 408
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accounting for various sensitivity analyses. Please comment on EPA's methodology and conclusions (Sections 3.2.4.2.1 and
Appendix H).
Charge Question 5.5: 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 al, 2006, adjusted upward to also account for the
relative contribution of 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 sufficient 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
justification 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).
Charge Question 5.6: Please comment on EPA's application of the PBPK model to the dose-response analysis for all endpoints.
Was the selection of dose metrics and percentile output selection appropriate when considering the sensitivity, uncertainty, and
variability of the data (Sections 3.2.2 and 3.2.5)?
Charge Question 5.7: Have the most scientifically robust critical health effects and corresponding PODs been identified for
TCE? Are there additional data regarding other 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 (Sections 3.2 and 4.3.2)?
Charge Question 5.8: Please comment on any other aspects of the human health hazard assessment that have not been discussed,
including the data quality evaluation and the characterization of all assumptions and uncertainties (Section 3.2).
Summary of Comments lor Specific Issues Related lo Charge
Question 5
KIW/OPPT Response
Johnson et al. (2003)
SACC
SACC COMMENTS:
Committee members had differences in opinion concerning the adequacy
of the Dawson/Johnson studies. These studies have several significant
problems in their design and execution despite being scored as medium
quality. For example, Johnson et al. (2003) used pooled data for controls
from multiple experiments conducted over 6 years. Some members felt
this study lacked credibility and should not be relied on by EPA. Several
Committee members commented that Johnson et al. (2003) reported
adverse cardiac effects at TCE exposure levels that were orders of
magnitude lower than no-effect levels of other investigators. Other
Committee members said it seems premature to completely dismiss
Johnson et al. (2003), given that there are cardiac malformations (1-2 per
In considering the conflicting evidence and
varied opinions concerning the validity and
relevance of the cardiac heart defects (CHD)
database, EPA has added text throughout the RE
(Appendix F.l, Section 3.2.4.1.6, Section
3.2.5.3.1, Section 3.2.5.1.6, and Section 3.2.6.1)
acknowledging the uncertainties associated with
this endpoint. EPA acknowledges that while
there is qualitative support for the endpoint,
based on uncertainties in the dose-response for
this endpoint and other considerations EPA has
Page 178 of 408
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1,000) in humans that are of unknown etiology. Another Committee
member opined that EPA came to an appropriate conclusion after
assessing the strengths and weaknesses of the Dawson/Johnson studies.
Another member felt that it might not be possible to reach consensus.
The Committee recognized that no systematic review can definitively
answer the question of whether the issues with this study are severe
enough to disallow its use in setting a non-cancer POD. Reasonable
scientists have differed on this, and two reviews came to opposite
conclusions. Wikoff et al. (2018) reviewed Johnson et al. (2003) and
determined it was "not sufficiently reliable for the development of
toxicity reference values." Makris et al. (2016) reviewed all the evidence
for developmental cardiac effects and determined that Johnson et al.
(2003) is "suitable for hazard characterization and reference value
derivation."
selected immune endpoints as the best overall
endpoints for risk conclusions (Sections
3.2.5.4.1, 3.2.6.1.1). However, various
biological factors may lead to increased
susceptibility to CHDs, (e.g., maternal age).
Therefore, CHDs are now classified as a PESS
consideration and the associated POD and risk
estimates are included in the RE in consideration
of PESS groups. However, based on
uncertainties in the dose-response for this
endpoint and other considerations, EPA has
selected immune endpoints as the best overall
endpoints for risk conclusions (Sections
3.2.5.4.1, 3.2.6.1.1).
108, 99
PUBLIC COMMENTS:
The Johnson et al. (2003) study is valid and appropriate for the
derivation of toxicity values and risk estimates. This study has been
repeatedly vetted, reviewed, and discussed by EPA and peer reviewers in
previous assessments, including its limitations; in each case, the study
was found to be sufficient for hazard identification and dose-response
analysis. Its results are also wholly consistent with the findings of many
other studies - including human, in vitro and in vivo studies - that also
indicate congenital heart defects resulting from TCE exposure (see
Makris et al., 2016; Runyan et al., 2019).
105
PUBLIC COMMENTS:
The Johnson et al. (2003) study provides relevant and positive evidence
of that TCE can induce fetal heart defects and should not be discounted.
While there may be issues with the dose-response in the fetal heart
defect study (Johnson et al., 2003), the WOE for fetal heart defects
makes this an important developmental endpoint that should be
considered in the quantitative assessment of the health hazards of
TCE.
There is evidence from studies besides Johnson et al. (2003) that
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TCE-induced developmental cardiac toxicity effects may follow a
non-monotonic dose response relationship, in which lower doses can
produce greater effects than higher doses. In a recent mechanistic
study on TCE-induced changes in gene transcription in the
developing heart, a non-monotonic dose response was observed, and
this is consistent with findings in other studies (Chen et al., 2020 and
references within).
99
PUBLIC COMMENTS:
EPA classifies Johnson et al. (2003) as "medium quality" and suitable
for use in risk determinations. The authors have responded in detail to
the industry concerns, and reliance on the study is based on a careful
review of this additional information. The study is essential for dose-
response assessment without which calculation of MOEs for this
endpoint would be impossible.
80
PUBLIC COMMENTS:
Cal/OSHA notes that while the SACC, in its discussion of fetal cardiac
malformations on March 26, found both the Johnson et al. (2003) and
Charles River Laboratory (CRL) studies problematic for dose response
modeling, most committee members indicated that the Johnson et al.
(2003) study was adequate for hazard assessment.
99
PUBLIC COMMENTS:
The 2016 EPA updated WOE assessment (Makris et al., 2016) reviewed
available scientific literature on TCE developmental cardiac defects,
reporting on the quality, strengths, and limitations of the available
studies. This review concluded that the Johnson studies, augmented by
detailed additional information about study design and conduct, were
sufficient for dose-response analysis and determinations of risk.
The study was considered suitable for use in deriving a POD.
The study has an appropriate design, was conducted by a relevant
route of exposure (drinking water), covered the entire period of
gestation covering the developmental window for the initiation of
cardiac defects, and tested multiple exposure levels.
It had a robust, statistically significant dose-response relationship.
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Also, the highest dose lies at the lower end of doses that elicited
substantial responses in other studies. Thus, "a hypothesis that the
Johnson data represent a false positive or an anomalous dose-
response pattern seems implausible, based on trend tests and
comparison with studies that used higher doses."
Makris et al. (2016) also addressed many of the concerns brought against
the Johnson et al. (2003) study.
Based on a detailed methodological comparison of Johnson/Dawson
and negative animal studies, differences in study methods (e.g., route
of exposure, vehicle, animal source or strain, or other factors) may
have contributed to differences in the detection of cardiac
malformations [between studies],
Concerns about variability among litters were resolved in the method
for data analysis: "The possibility of increased variability among
litters due to temporal drift and perhaps other factors across time
(overdispersion), was dealt with by using a standard method for
clustered data. The dose-response trend was found to be highly
significant after adjusting for overdispersion. Because the maximal
observed response was 10%, models with plateaus of less than 100%
were investigated and were found to not substantially change the
general conclusions and results. Confidence in the dose-response
relationship is supported by the increasing trend in response and by
metabolite studies that demonstrate findings at higher dose levels."
108
PUBLIC COMMENTS:
Criticisms of the Johnson et al. (2003) study were discussed in the SACC
meeting. Although some issues were identified, most members indicated
that the Johnson et al. (2003) study was adequate for hazard assessment.
One SACC member noted that the combination of experimental data
across several years (i.e., pooling) is common, and well-accepted in
epidemiological studies. Another SACC member indicated that
observing the same effects several years apart is similar to replication
and should be viewed as a strength.
One SACC member stated that the use of tap water as the negative
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control in one period of the experiment but the use of distilled water
in another does not matter unless it can be demonstrated that one of
these two types of water is directly causing the cardiac effects, which
is highly unlikely. Another member highlighted that there is no
plausible mechanism by which water would be responsible for
cardiac defects.
76, 79,
103, 72
PUBLIC COMMENTS:
The Johnson et al. (2003) study has serious deficiencies that could not be
corrected by the two published errata (Johnson, 2005, 2014) and one
explanatory letter to the editor (Johnson et al., 2004). These diminish the
reliability of the study for the purposes of risk assessment.
Potential maternal toxicity was not evaluated. Maternal clinical signs,
body weights during gestation, and feed consumption were not
reported; therefore, it is not possible to assess whether any of the
fetal findings were secondary to maternal toxicity.
Potential developmental delay in the fetuses was not evaluated. Fetal
weights were not reported, and it cannot be assessed whether any of
the reported effects were due to the fetuses being at different stages
of maturation than those in the control group.
"Litter effects" were not evaluated. Data were not recorded in a
manner that allowed the laboratory to keep track of littermates. Data
were not evaluated using the litter as the statistical unit.
Data regarding potential loss of TCE was not reported. Due to its
high volatility, TCE likely was lost during the formulation of
drinking water solutions, the transfer of formulations to water bottles,
and during residence of the formulations on cages. In the CRL (2019)
study, substantial TCE loss was observed and mitigated during
formulation of water and transfer to bottles, indicating that this is a
significant confounding factor.
In-life study was conducted over a 6-year period. The TCE treated
groups and controls were not run concurrently, and the higher TCE
dose groups were run 6 years prior to the lower TCE dose groups.
Data for the higher TCE dose groups were first reported in Dawson
Follow-up personal communications from the
studv author (Johnson. 2008) provided maternal
body weight data that show no significant
difference among treatment groups in body
weight gain that would suggest overt maternal
toxicity.
Simple developmental delay would not be
expected to lead to observations of specific
cardiac defects. Hearts were assessed at the time
of birth and incomplete development at the time
of birth would itself be a major endpoint.
EPA acknowledges this issue as an important
limitation of the Johnson lab studies in
Appendix F.2.1 and Table Apx F-l.
(Johnson et al.. 2003) provided data on average
TCE loss across 24 hours, which was
comparable or slightly less than the loss reported
in (Charles River Laboratories. 2019).
Substantial TCE loss would indicate that toxicity
of TCE may have actually been underestimated,
since any observed effects actually occurred at
lower doses than nominally reported.
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et al. (1993) in conjunction with data for 238 control fetuses (232
control hearts). None of the combinations of controls reported in the
Johnson et al. (2005) erratum, however, equate to this initial number
of controls, bringing into question the overall record-keeping related
to this study. The study did not have a positive retinoic acid control.
Reported doses were not verified. It is not clear how doses were
determined. Water consumption was reported to have been
monitored by treatment group and maternal body weights were not
measured. Body weights in pregnant rats are dynamic, and therefore,
dose estimations could be highly inaccurate.
It was not verified that TCE was absorbed into maternal blood.
Cardiac dissection used a novel methodology and evaluation of fetal
hearts was performed using a non-standard procedure.
The long duration of the study period is also
acknowledged in Appendix F.2.1 and
Table Apx F-l. Some control experiments were
run at the same time with treated groups,
however both the authors and the Risk
Evaluation acknowledge that data was pooled
and compared from independent experiments.
The number of controls at the time of (Dawson
et al., 1993) publication mav have included a
partial group, however this is in fact an
uncertainty that adds to the data reporting
concerns, which are acknowledged in the Risk
Evaluation.
EPA agrees that doses were not analytically
verified and this is an uncertainty that affects the
precision of the dose-response analysis. This
uncertainty applies to many studies however and
does not exclude the positive results from
consideration.
Use of a novel dissection methodology that may
have been more sensitive than traditional
techniques is not a negative consideration.
94
PUBLIC COMMENTS:
The extent to which EPA appears to support Johnson et al. (2003) at the
expense of a balanced scientific review is not only inconsistent with the
requirements of the Lautenberg Act but violates the fundamental
principles of science.
The Johnson et al. data has not been replicated by any other
laboratory. California Office of Environmental Health Hazard
Assessment (OEHHA) also rejected the study as deficient for
regulatory consideration.
EPA acknowledges that the original study
publication would have scored lower than a
medium in data quality, however EPA
considered the reasonably available information
for the set of studies in evaluating data quality.
EPA determined that when accounting for
subsequent errata and communications to EPA,
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The transparency problem and fact that an erratum had to be
published should alone disqualify this as a study representing the
"best available science."
Accepting the authors' claim in the 2014 erratum that exposure times
cannot be confirmed for substantial amounts of either control or
treatment data, it can be presumed that it is impossible to reconstruct
a calculation of per litter incidence of cardiac malformations that is
appropriately matched to concurrent controls, an analysis generally
accepted as essential to interpreting outcomes of developmental
toxicity study findings. The lack of data availability and clarity
sufficient to construct key analyses associated with a study should
disqualify the use of that study for regulatory purposes.
the overall strengths and limitations resulted in a
study of medium quality.
94
PUBLIC COMMENTS:
In Johnson et al. (2003), the abnormalities in rats dosed at 1100 ppm
(10.4%) were statistically higher than at 1.5 ppm (5.5%), but those dosed
at 1.5 ppm were not statistically different from the controls. Thus, no
meaningful dose-response relationship was observed in either treatment
group. Data for the 1.5 and 1100 ppm dose groups from Dawson et al.
(1993) was republished and control data from other studies were pooled
to conclude that rats exposed to levels of TCE >250 ppb during
pregnancy have increased incidences of cardiac malformations in their
fetuses. This is an inappropriate statistical practice.
A dose-response relationship does not require
statistical significant at all tested doses. In the
two highest doses of (Johnson et al., 2003)
(orisinallv published in (Dawson et al., 1993)),
incidence of CHDs increases from 3.3% in
controls to 5.5% in the lowest dose and 10.4% in
the highest dose, a clear (albeit shallow) dose-
response. EPA used data from all controls and
dose levels in conducting BMD modeling to
obtain a POD based on a selected BMR and
model fit. Therefore, the original study NOAEL
as determined by authors was not relevant for
the Risk Evaluation.
79, 72
PUBLIC COMMENTS:
Problems with the Johnson et al. (2003) dissection technique.
It requires fixation and manipulation, including immersion or
flooding with a formalin-based fixative prior to examination, which
can both shrink and stiffen fragile tissues, that may result in tissue
damage.
The foramen ovale opening in the atrial septal wall poses a challenge
Any artifacts from this dissection technique
would be expected to be equally observed across
all groups since the investigators were blinded
and required unanimous confirmation of defects.
While (Fisher et al., 2001) did not report a
statistically significant increase in defects, it did
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for examining the atrial septum before birth and supports why the
recommended cardiac dissection methods in EPA guidelines do not
require opening of the atria.
Some SACC members noted the dissection technique was also used
in Fisher et al. (2001) which did not report a significant increase in
fetal cardiac defects either with TCE, or with the metabolites,
trichloroacetic acid (TCA) and dichloroacetic acid (DCA).
report observations of the same set of defects
observed in (Johnson et al., 2003) (Table Adx
F-6). The lack of statistical significance in
Fisher et al. (2001) from TCE treatment may be
due to the elevated incidence in controls, which
used soybean oil instead of water.
79
PUBLIC COMMENTS:
Re. Johnson et al. (2005) EPA staff suggested to the SACC that, while
none of the TCE exposure groups were tested at the same time, each
exposure group did have a respective concurrent control group.
If there is evidence to support this claim, EPA has not shared this
information with the public or the SACC. EPA's claim regarding the
inclusion of concurrent controls is not supported by information
presented by staff in their most robust analysis. Specifically, as
illustrated in Makris et al. (2016), none of the start dates of the
control groups align with any of the four TCE exposure groups over
the 6 years the various studies were conducted prior to the
publication.
If EPA has identified original records that contradict the timing of
the studies by Johnson et al. described by Makris et al., these should
be made public. The post-hoc pooling of controls across time,
including studies that did not involve TCE exposures, artificially
inflates the statistical power making it prone to false positives based
on apparent statistical significance.
While control and treatment group experiments
were not started or completed at the exact same
time, there was substantial overlap in the
timelines for many of the groups. EPA does
acknowledge however that this is not standard
practice and has included the issue as a
significant limitation of the publication (see
TableApx F-l).
79
PUBLIC COMMENTS:
Johnson et al. (2003) provided no documentation to support the claim of
a 35 percent reduction of TCE levels in drinking water over a 24-hour
period or indicate whether that reduction includes loses during
preparation formulations as well as from the water bottle during the 24-
hour period. EPA's analysis of the TCE losses in Johnson et al. appears
to have misinterpreted the study reporting; the percentage difference
between the initial and average concentrations are identical for each of
EPA acknowledges this concern. In evaluation
of Metric 7 for (Johnson et al., 2003), EPA
states: "The rarity of obtaining almost identical
measurements across doses is worth noting,
however equal loss across dose groups mitigates
concerns about dose-response, and may even
suggest underestimation of toxicity depending
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the dose groups, suggesting that the data reflect a general assumption
about TCE losses rather than on empirical data. This concern should
have been reflected in EPA's study quality evaluation and scoring for
this metric.
on calculations."
76
PUBLIC COMMENTS:
The major focus of previous TCE assessments (Makris et al., 2016) was
on the presence of ventricular septal defects (VSDs) in fetuses. In the
current risk assessment, EPA has shifted focus to emphasize atrial septal
defects. Atrial septal defects were reported only in studies in which the
fetal examinations were conducted by Dr. Johnson (Dawson et el., 1993;
Fisher et al., 2001; Johnson et al., 2003). The occurrence of atrial septal
defects in these studies appears to be sporadic. EPA studies (Smith et al.,
1989; Epstein et al., 1992) on metabolites of TCE, that used the sensitive
Wilson sectioning technique, found no ADSs. The Johnson atrial septal
defects, therefore, are suspected to be an artifact. The Johnson dissection
procedure and the presence of fixative may have displaced tissue in some
samples, explaining why atrial septal defects only occurred randomly in
a few embryos.
Any artifacts from this dissection technique
would be expected to be equally observed across
all groups since the investigators were blinded
and required unanimous confirmation of defects.
ASDs were observed in a dose-responsive
manner in (Johnson et al.. 2003), so the defects
were not equally distributed across groups. In
addition to differences in dissection method,
defects that are inconsistently observed across
studies may indicate variations in susceptibility
between strains. Therefore, EPA has classified
CHDs as a PESS concern and not necessarily
likely to present in a large proportion of the
general population.
95
PUBLIC COMMENT
The draft risk evaluation places far too much emphasis rationalizing the
validity of Johnson et al. leaving the impression that this is a useful study
for risk characterization. The draft risk evaluation calculates risk
estimates for fetal cardiac defects for each of the COUs based on the
results from Johnson et al., despite concluding it would not be used to
quantify risk.
The majority of SACC members determined that the quality of
Johnson et al. study data as insufficient for estimating risks.
Several SACC members noted that EPA should have put more focus
on the inhalation studies, since this route of exposure is of greater
relevance to the exposure scenarios evaluated.
EPA should remove all the calculations of risk for fetal cardiac
defects from the risk evaluation. Inclusion based on Johnson et al.
Inclusion of dose-response analysis from
(Johnson et al.. 2003) is not inconsistent with
systematic review guidelines because it scored a
medium in data quality and considered both
weight of scientific evidence and statistical
sensitivity of the data. EPA acknowledges that
there is substantial uncertainty in the
quantitative dose-response for CHDs and the
relevance of these results to the human general
population (Appendix F.l, Section 3.2.4.1.6,
Section 3.2.5.3.1, and Section 3.2.6.1).
Nonetheless, this endpoint is of concern to
susceptible subpopulations (Section 3.2.5.2) and
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study would be inconsistent with EPA's guidelines for systematic
review and create confusion regarding EPA's conclusions about the
risks of TCE exposure.
Only studies that are considered to be of sufficient quality under the
systemic review guidelines should be carried forward to the risk
estimation stage in the final risk evaluation.
consideration of dose responses from studies
that are more sensitive than the more commonly
observed responses observed among relatively
young, healthy, and inbred laboratory rodent
strains is important in accounting for human
susceptibility. Therefore, the results from
(Dawson et al., 1993) and (Johnson et al., 2003)
were considered for dose-response analysis.
56
PUBLIC COMMENTS:
The Dawson et al. (1993) study that reported on two TCE dose groups
that were included in the Johnson et al. (2003) study had initially
received a rating of High, but that rating was downgraded to Medium
based on the study evaluator's professional judgment.
Thank you for your comment.
60
PUBLIC COMMENTS:
EPA scored Johnson et al. (2003) as medium quality, although according
to the guidance, the study would be unacceptable. This is indicative of
inconsistency in conducting data quality assessments (e.g., in this case,
the study authors were contacted to obtain additional information not
found in the published report, while in other cases, e.g., Hardin/Beliles,
studies were disregarded without even considering the full study reports).
(Hardin et al., 1981) did not show exoosure-
related findings for each study group and results
were only briefly described in the text.
Additionally, the study did not report how
animals were allocated to groups. The original
(Johnson et al., 2003) publication reports both
blinding and random allocation to groups along
with summary and defect-specific results for
each group.
51
PUBLIC COMMENTS:
Issues with study quality scoring for Dawson et al. (1993)/Johnson et al.
(2003)
Metric 4: Scored "low", should be "unacceptable" for use of non-
concurrent, pooled controls.
Metric 7: Scored "Med", should be "low" for inadequate reporting of
preparation and storage of highly volatile test compound.
Metric 8: Scored "Med", should be "low" for uncertain TCE solution
exposure concentrations and group housing of animals.
Metric 16: Scored "high", should be "low" for use of unvalidated,
Scoring for each of these metrics was based on
consistent interpretation of the bins across all
studies. In many cases, the scoring for a
particular metric between bins is ambiguous,
however the same interpretations were applied
to all studies in the database.
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non-good laboratory practice (GLP) dissection technique.
Metric 20: Scored "Med", should be "low" for
uncertainties/deficiencies in control responses.
Metric 23: Scored "high" should be "low" or "unacceptable" for
insufficient reporting of statistical methods and uncertain
appropriateness.
Overall: Scored "Med", should be "Unacceptable"
51
PUBLIC COMMENTS:
The result of EPA's biased review and selective and inconsistent
application of TSCA study quality metrics is that EPA ultimately
characterizes what is well-documented to be a clearly flawed, unreliable
and irreproducible rat drinking water study (Dawson et al., 1993/Johnson
et al., 2003) as a reliable study equivalent in study quality to a superior-
designed, GLP study (Charles River, 2019/DeSesso et al., 2019) that
followed the Organisation for Economic Cooperation and Development
(OECD) Guideline protocols utilizing a validated outcome assessment
technique.
The studies end up with the same scores
however for different reasons. Following OECD
Guidelines does not ensure a high score for data
quality because data quality evaluations also
take into account the purpose of the study and
other considerations. While there is substantial
uncertainty about the Johnson et al dose-
response, Charles River 2019 suffers from
inconsistency in data reporting, higher reported
TCE loss, and indications of reduced sensitivity.
HSIA/CRL/DeSesso et al. (2019)
64,
106,
108,
47, 99
PUBLIC COMMENTS:
A study by DeSesso et al. (2019) singularly focuses on refuting the
findings of Johnson et al. (2003) to argue that developmental exposure to
TCE does not induce cardiac malformations.
Cardiac effects were identified, but study authors ignore them by
erroneously deeming the observed effects to be insignificant.
EPA found the methodology was of reduced sensitivity, not a "close
enough replication to Johnson et al. to sway the WOE for the
endpoint on its own," and that the results do not entirely contradict
the conclusions of Johnson et al. (2003).
DeSesso et al. does not negate the body of evidence supporting TCE-
induced cardiac malformations, and itself presents methodological
shortcoming and unsupported conclusions.
Even with its flaws, this study provides evidence of VSDs in the
The full review of (Charles River Laboratories,
2019) (publiclv published as DeSesso et al.
2019) is contained in Appendix F.2 of the Risk
Evaluation which discusses many of these
considerations. EPA agrees that the CRL study
does not refute the findings of (Johnson et al.,
2003), however it was considered as slishtlv
negative for strength and overall grade in the
WOE analysis.
Page 188 of 408
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developing heart, supports the findings of the Johnson et al., and adds
to the overall WOE for this endpoint. Authors dismiss these findings
by proposing, despite evidence to the contrary, that these
developmental defects heal over time "without adverse effects."
78
PUBLIC COMMENTS:
The CRL (2019) study does not negate the Johnson 2003 study and
may support its findings.
The Oregon Health Authority (OH A ) and Department of Quality
(DEQ) disagree with the draft risk evaluation claim that the CRL
(2019) study fails to reproduce the outcomes of the Johnson et al.
(2003) study.
The CRL study did not adequately evaluate the range of heart defects
(including atrial or valvular defects) in test or control groups as in the
Johnson 2003 study. It also did not report on atrial or valvular defects
in retinoic acid-exposed positive controls despite substantial
literature indicating that such defects should have been evident
following retinoic acid exposure.
The degree and direction of change among dose groups between the
two studies was remarkably similar for VSDs. While the CRL (2019)
study did not find a statistically significant increase in these defects
when comparing each dose group against the control independently,
it may have found a statistically significant trend had a trend analysis
been completed and reported.
OHA and DEQ conclude that, to the limited extent to which the CRL
(2019) study evaluated the same endpoints as the Johnson (2003)
study, it may support, rather than refute, the Johnson (2003) study.
The CRL study should not be used as justification to decrease EPA's
confidence in Johnson et al. or the POD derived from it.
Page 189 of 408
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108,
99, 64
PUBLIC COMMENTS:
In Appendix G of the draft risk evaluation, EPA recognized the
limitations of the DeSesso et al. (2019) study. Specifically:
Retinoic acid (the positive control) was administered in a completely
different manner than TCE (gavage on gestation days 6-15 vs.
drinking water on gestation days 1-21), which calls into question the
experimental design and compromises its validity.
The dissection method has reduced sensitivity and no report of valve
defects (including positive control), and no examination of atrial
septal defects.
DeSesso et al. (2019) attempted to downplay the significance of the
small VSDs (<1 mm) that were observed in their study, claiming that
"small VSDs which close spontaneously...should be considered
normal developmental delay." Epidemiological literature indicates
small VSDs can result in adverse effects and evidence does not
support DeSesso et al.'s assertion that small VSDs do not have
clinical significance.
The study was commissioned and supported by the HSIA and the
American Chemistry Council (ACC), companies that have direct and
substantial financial interests in the continued production and use of
TCE as well as with respect to potential liability associated with
releases and exposures to TCE, including from contaminated sites.
There is a risk of bias.
83
PUBLIC COMMENTS:
It is not logical to take the chemical industry backed studies seriously
when there are better, very thorough, long-term scientific studies
available by unbiased, well-respected scientists. There needs to be non-
chemical industry backed studies that genuinely refute the 2003 Johnson
study before backing off on TCE regulations. These studies need to look
at all types of fetal heart defects, not just a carefully selected few.
Page 190 of 408
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108
PUBLIC COMMENTS:
Runyan et al. (2019) point out that DeSesso et al. utilized a static
assessment methodology that captures only a subset of dysmorphologies
and does not evaluate actual function and a study design that ignores the
many studies published in the last 18 years that show TCE toxicity at
exposures (in vitro) lower than 1,000 ppm, as well as evidence that TCE
exhibits nonmonotonic effects. Runyan et al. (2019) argue that the
conclusion of DeSesso et al. that ingestion of TCE in drinking water at
less than 1,000 ppm does not cause heart defects is not supported by their
own data.
64
PUBLIC COMMENTS:
The CRL study conducted a "targeted" analysis, so that it doesn't look at
other developmental malformations, including some that were identified
in the Johnson et al. study (e.g., atrial septal defects). Thus, the CRL
study was only a partial replication of the Johnson study because it didn't
look at all effects; it was designed to be a negative study by not fully
examining TCE-induced developmental malformations that are well-
established in the peer-reviewed literature.
64
PUBLIC COMMENTS:
The CRL study argues that, based on published data, defects in the
membranous septum tend to "resolve postnatally, without adverse effects
on postnatal survival of the animals" and thus should not
be considered adverse, referencing two rat studies to support this claim.
There is another study in rodents, however, that indicates even small and
seemingly healed chemically-induced VSD at birth "may permanently
alter the capacity of the postnatal heart to adapt to pregnancy and this
may have transgenerational effects." There are some supporting data for
this same effect in people. There is no scientific basis to dismiss
evidence of adverse effects.
EPA agrees with the commenter, and this claim
bv the CRL studv (Charles River Laboratories,
2019) is rebutted in Appendix F.2.2.4.
99, 64
PUBLIC COMMENTS:
The statistical analysis in DeSesso et al. is inappropriate.
The unit of analysis is the litter, but with only 20 litters, the analysis
is likely to be statistically underpowered. Statistical analyses should
EPA agrees that a trend analysis would be better,
however pairwise analysis is consistent with
statistical methodology for other studies
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be done using both the litter and the individual fetus.
The study primarily used pairwise statistics instead of trend analysis.
A trend test would be preferable.
The use of two-sided tests is inappropriate; a one-sided test should
have been done, which would increase statistical power and likely
would have resulted in a study outcome showing statistically
significant harmful effects of the treatment.
If the VSDs from this study on an individual animal basis are run
through the Cochran Armitage trend test, the one-sided p-value is
0.0196, which is significant. EPA should provide this analysis,
incorporating an adjustment for litter effect as appropriate, in
Appendix G.
The study misuses statistics as a weapon to cut away evidence of
adverse effects, rather than a tool to identify associations where they
may occur.
including (Johnson et al.. 2003). EPA chose not
to perform dose-response analysis on the results
of the (Charles River Laboratories. 2019) studv
because the methodology from (Johnson et al..
2003) was considered more sensitive and
therefore the results of dose-response analysis
from those results were used for POD
derivation.
99, 64
PUBLIC COMMENTS:
The CRL study misused historical controls.
The Charles River Ashland historical control data range for major
heart vessel variations is 0.0 to 0.86% per litter. The study dismisses
the major blood vessel variations by saying they are within the
historical controls - in fact, they are not. The incidence at the high
dose is 2X the historical control.
The HSIA's use of historical control data is pieced together after-the-
fact (post hoc) from old publications from labs in China in the 1960s
and early 1970s. Per EPA cancer guidelines, the most relevant
historical data come from the same laboratory and the same supplier
and are gathered within 2 or 3 years one way or the other of the study
under review; other data should be used only with extreme caution
due to genetic drift in the laboratory strains, differences in pathology
examination at different times and in different laboratories (e.g., in
criteria for evaluating lesions; variations in the techniques for the
preparation or reading of tissue samples among laboratories), and
comparability of animals from different suppliers.
EPA agrees that the use of decades old post-hoc
historical controls is not appropriate. It is
unclear whv the (Charles River Laboratories.
2019) studv focused on the historical controls
discussion at all, because it is not very relevant
to the comparison with the Johnson et al. study.
The Charles River methodology may have been
highly sensitive to VSDs, and in fact the
incidence of VSDs was very similar to that
observed in Johnson et al. which used a novel
sensitive dissection technique. The primary
concern with the Charles River study is not the
identified incidence of VSDs but the absence of
many other defect types.
Page 192 of 408
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The HSIA report applies a cherry-picked use of historical control
data for some endpoints but not others, with no real rationale
provided. This is inappropriate. The oscillation between using
within-study and historical controls casts doubt on the rigor and
consistency of the statistical analysis, making it appear instead to be
manipulated and biased to dismiss evidence of harm.
The study reports that 2.4% of control fetuses developed VSDs.
However, in Appendix 8, the incidence of various interventricular
septal defects in the historical control database is recorded as 0.01%
with a maximum mean incidence of 0.26%. DeSesso et al. (2019)
comment on these differences, noting that "the mean litter proportion
of VSDs in the control group was more than 9x higher than the
maximum mean value for this parameter in the historical controls.
The extreme discrepancy between the CRL concurrent and historic
control incidence data is surprising and concerning. During the TCE
SACC meeting, several panelists highlighted that this observation
suggests that the animals used by DeSesso et al. (2019) represent an
anomalous population. Overall, this inconsistency increases
skepticism about the applicability and conclusions of this study and
indicates that the findings should be interpreted with extreme
caution.
66, 34
PUBLIC COMMENTS:
Had DeSesso et al. (2019) (supported by HSIA and ACC) been
interested in objectively testing TCE and heart defects, they should have
included ultrasound or other measures of cardiac function, changes in
calcium homeostasis, examination of developmental gene expression, a
more sensitive examination of morphology and a range of exposure that
extended down to 5-10 ppb. All of these approaches have been
developed since the report of Johnson et al. (2003) and are reported in
the literature. It appears that the study was designed only to challenge
Johnson et al. (2003) rather than to objectively test TCE effects on heart
development. This study should be disregarded because of the bias in the
experimental design and the bias identified by the funding source.
EPA has discussed limitations of the Charles
River/DeSesso studv (Charles River
Laboratories, 2019), however it was still overall
a relatively well-conducted study despite
insufficiently addressing its stated goal of
recapitulating the methodolosv of (Johnson et
al., 2003). Therefore, it was considered alone
with all other relevant studies in the overall
WOE analysis.
Page 193 of 408
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64, 54
PUBLIC COMMENTS:
It was proposed that EPA consider presenting a statistical analysis of the
CRL data grouping the two reported cardiac malformations - the
membranous interventricular septal defects and the cardiac major vessels
variations - since the two tissues share the same embryonic tissue origin,
the truncus arteriosus, and developmental deformities in the membranous
septum and variations in the great vessels often present clinically
together.
EPA chose not to perform dose-response
analysis on the results of the (Charles River
Laboratories. 2019) studv because the
methodology from (Johnson et al 2003) was
considered more sensitive and therefore the
results of dose-response analysis from those
results were used for POD derivation.
76, 72
PUBLIC COMMENTS:
There were numerous problems with EPA's evaluation of the positive
control data from the CRL study.
The evaluation was not done in a transparent manner: References
were not provided for the 25 retinoic acid studies that were included;
the doses, routes, and durations of exposure used were not provided
and may be irrelevant to those used in the CRL (2019) study; the
criteria used to include a heart defect in the analysis was not reported
(e.g., did findings have to be statistically associated with retinoic acid
treatment or only observed at least once in an retinoic acid treatment
group)?
The evaluation was done in non-mammalian species. Both zebrafish
and chickens develop outside the material anima and may not be
relevant to what occurs in rats.
Some findings were reported only in mouse/hamster and not rat.
No report on how many heart findings occurred in a single fetus.
20/35 findings were seen in only a single retinoic acid study. Only
11/35 were reported in >2 studies.
In the evaluation, the category of early developmental defects
included endocardial cushion defects and abnormal heart looping.
This terminology is vague, and it is not clear what is meant by these
terms as used by EPA. Those terms are not ones used by contract
laboratories; related defects would have been described by CRL
using terms included in other categories.
Despite limitations, the evaluation shows that the retinoic acid positive
Exclusion of the 25 retinoic acid (RA) studies
was an oversight that has been corrected in the
final Risk Evaluation.
Chicken and zebrafish studies were a minority of
the total studies and were included as to avoid
bias in presenting the results of the retinoic acid
literature search. EPA acknowledges that there
may be differences in the specific defects
observed in these species, however they are both
well-established models for studying
developmental toxicity and cardiac
development. Notably, atrial septal defects were
observed in (Johnson et al.. 2003) and 5
independent RA studies in hamster and rat.
Multiple other defects observed in Johnson et al,
2003 were also observed in at least one RA
study, all of which were on mammals (most on
rats or mice).
EPA has added a table to the final Risk
Evaluation including all identified studies and a
breakdown of defects observed (Table Apx F-
8). A summary of defects identified across all
Page 194 of 408
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control incorporated in the CRL study demonstrated adequate sensitivity
of the model to detect heart findings due to treatment.
studies are provided in Table Apx F-7 and
Table ApxF-9.
76, 72
PUBLIC COMMENTS:
The DeSesso et al. (2019) study was conducted over a single period of
time, using statistically robust group sizes, with all treatment and control
groups run concurrently. Volatility of TCE was taken into consideration.
Maternal toxicity was assessed through weighing of dams throughout
gestation and reporting of clinical signs. Fetal weights and internal
sexing were recorded in order to enable assessment of potential
developmental delays or sex-specific findings. Data were evaluated
using the litter as the experimental unit. Examination of fetal hearts was
done using an approved standard method, and findings were confirmed
by a fetal pathologist and an external teratologist. A toxicokinetic arm
was included to verify internal doses. Using linear extrapolation from the
highest exposure group to the lowest, estimated TCE exposures ranged
between 25 ng/mL to 0.006 ng/mL.
This well-designed study that did not replicate findings of Johnson et
al. (2003), and along with support from Fisher et al. (2001) and
Carney et al. (2006), it provides strong support for the position that
real-world drinking water exposures to TCE (MCL = 5 ppb) are
unlikely to present biologically plausible risks of adverse cardiac
development.
EPA agrees that the study was overall well
conducted. This study is included in the WOE
analysis for cardiac defects and considered along
with all other relevant studies (i.e., the
reasonably available information).
51, 72
PUBLIC COMMENTS:
DeSesso et al. (2019) made the detailed and extensive laboratory report
publicly available, whereas deficiencies in reporting and documentation
are evident in the journal correspondence and errata that followed
Johnson et al. (2003) (Hardin et al., 2004; Johnson et al., 2004, 2005,
2014), showing obvious disparity in transparency and documentation
between these two documents.
Deficiencies in the data reoortins for (Johnson et
al.. 2003) are acknowledged in the Risk
Evaluation, however these concerns were at least
partially addressed in subsequent errata and
communications.
76, 79
PUBLIC COMMENTS:
EPA's criticisms of the CRL (2019)/DeSesso et al. (2019a) study on rats
Page 195 of 408
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are invalid.
EPA incorrectly states that the examination of fetal hearts was
limited to the ventricular septum. The standard operating procedure
describing the methods used includes examination of the semilunar
valve, interventricular septum, bicuspid valve, and walls of the
atrium and ventricle.
EPA states that the study lost an appreciable amount of TCE,
equivalent to that reported by Johnson et al. The lack of description
in Johnson et al. calls into question the accuracy and methodology
used to measure TCE. Conversely, the CRL study took steps to
minimize volatilization or photolysis. Analytical and toxicokinetic
measurements were performed to assure internal exposure had
occurred and all data is well documented.
EPA suggested that the lack of statistically significant effects in the
CRL study was due to a high incidence of findings in the negative
control group. As discussed in DeSesso et al. (2019a), the higher
incidence is considered to be a function of the detailed evaluations of
the heart that were conducted. The CRL historical control database
shows a lower incidence as expected because those studies were done
involving a less-detailed examination of the heart and is similar to
the Johnson et al. (2003) and Fisher et al. (2001) studies.
EPA did not state that the examination was
limited to the ventricular septum, but that the
methodology was likely focused to primarily
identify those types of defects.
The effort taken to minimize volatilization does
not discount the fact that volatilization did take
place, indicating that the analytical dosing was
lower than the nominal dose and potentially
reducing the relative severity of observed
responses.
As indicated by other public comments, the use
of historical controls from decades earlier in
unrelated studies are not very relevant for
comparison to the current study.
79
PUBLIC COMMENTS:
A commenter suggested that the statistical analysis conducted by CRL
was inappropriate. In direct contrast to EPA's guidelines for
developmental toxicity studies, the commenter suggested that the
statistical analysis should have been conducted on a per-fetus, rather than
a per-litter basis.
DeSesso et al. present the CRL study data on both a per-fetus and
per-litter basis.
The commenter also suggested that a trend analysis should have been
conducted to evaluate the data instead of a pairwise comparison to
increase sensitivity.
A SACC member noted that while no clear trend is evident in the
EPA acknowledges this comment. EPA did not
consider the issue raised by the other commenter
in our evaluation of the study.
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CRL data, it would be difficult to assess the significance of a trend
(should it exist) over the four orders of magnitude of exposures in the
study (0.25 to 1000 ppm).
The CRL study report notes that two-tailed statistical tests were
conducted at both the 5% and 1% significance level, which should
address the comment that the analysis lacked statistical power.
51
PUBLIC COMMENTS:
EPA argues that genetic drift could explain why none of the other eleven
reliable TCE-fetal cardiac defect animal studies - including those
designed to replicate their findings - have provided TCE-fetal cardiac
defect evidence in support of the Dawson et al. (1993)/Johnson et al.
(2003) study.
EPA has not provided any supporting citations that might provide
corroboration for this theory.
GLP studies designed to examine TCE-fetal cardiac defect
hypothesis were conducted within a few years of Johnson et al.
(2003), and not 1-2 decades after. Would genetic drift occur over
very short windows of time?
The incidence of common fetal cardiac defects (e.g., VSDs) in
control Sprague-Dawley rats has been shown to be consistent across
multiple breeders located on multiple continents over several decades
(DeSesso et al., 2019). Given this evidence, cardiac development is
highly conserved across vertebrate species and unlikely to be
affected by genetic drift.
Genetic drift is more likely to explain the
increased sensitivitv of the animals in (Johnson
et al., 2003) vs (Dawson et al., 1993). However,
differences in animal sources could explain
varied responses from different experiments
conducted at the same time because genetic drift
would have been occurring for years or decades
in those distinct populations prior to being used
for the experiment.
51
PUBLIC COMMENTS:
The published, Open Access version of the CRL study, provided to EPA,
which addressed many, if not all, of EPA criticisms, was ignored during
the assessment and scoring the quality of this study.
The peer-review published study (DeSesso et al,
2019, available at
httos ://onlinelibrarv. wilev. com/doi/full/10.1002/
bdr2.1531) confirms EPA's assessment that the
study was designed to be more targeted in its
focus on VSDs compared to (Dawson et al.,
1993V
51
PUBLIC COMMENTS:
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Issues with study quality scoring for CRL (2019)/DeSesso et al. (2019)
Metric 5: Scored "low;" should be "Not applicable" - positive
controls are not required, a score was selectively given to downgrade
this study.
Metric 16: Scored "low;" should be "high" for using validated GLP
technique.
Metric 20: Scored "Med;" should be "high" for clearly reported
responses in controls.
Metric 23: Scored "Med;" should be "high" for clearly reported and
appropriate statistical methods.
Metric 24: Scored "Med;" should be "high" for data reporting in
publication and supporting data in publicly available report.
Overall: Was downgraded to "med" should be "high."
Scoring for each of these metrics was based on
consistent interpretation of the bins across all
studies. In many cases, the scoring for a
particular metric between bins is ambiguous,
however the same interpretations were applied
to all studies in the database.
Fisher et al. (2001)
108
PUBLIC COMMENTS:
DeSesso et al. (2019) repeatedly points to the Fisher et al. (2001) study
to support an assertion that TCE does not cause congenital heart defects.
However, the Fisher et al. (2001) study has serious shortcomings in both
its methodology and its characterization of findings that significantly
reduce confidence in its conclusions, and these have been acknowledged
by EPA.
EPA agrees with these comments and discusses
the (Fisher et al., 2001) studv in the Risk
Evaluation. The Fisher study had an elevated
negative control which diminishes the strength
of its negative result, and it is cited in Appendix
F.2 as evidence of (Charles River Laboratories,
2019) having a narrowlv focused dissection and
evaluation methodology.
66
PUBLIC COMMENTS:
TCE is non-monotonic and produces cardiac defects most strongly at
very low exposure levels. Therefore, the failure of the Fisher et al.
(2001) study, which used gavage with high concentrations, to observe
heart defects in their animals is consistent with emerging understanding
of the mechanisms involved.
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76, 72
106
PUBLIC COMMENTS:
Evaluation of the Fisher et al. (2001) data, in which fetuses were
examined using the Johnson dissection method, show that this method is
no more sensitive than the fresh visceral dissection technique used in the
CRL study for detecting cardiovascular defects.
Although EPA's specific language that the Fisher et al. (2001) study
did not find a statistically significant risk is correct, the study did find
an elevated risk, reporting that "[t]he rate of heart malformations
ranged from 3% to 5% across the TCE, TCA, and DCA dose
groups.. .on a per fetus basis. On a per litter basis, the rate of heart
malformations for TCE, TCA, and DCA ranged from 42% to 60%."
The risk for fetal cardiac defects may not have been statistically
significant, but that is not the same as finding no elevated risk.
The high background incidence in the soybean oil control, as
identified by both the study authors and again by EPA in this draft
risk evaluation, likely resulted in less statistical power to detect the
risk, leading to an underestimation of risk.
EPA cites that Fisher et al. "identified a significant number of... defects
that match those identified in (Johnson et al., 2003) and (Dawson et al.,
1993) (including atrial septal and valve defects)," indicating that while
the study may not have been entirely consistent with previous studies on
the particular endpoint of fetal cardiac defects, it was in agreement on
other defects, meaning it was not as contrary to the Johnson et al. (2003)
study as certain parts of the draft risk evaluation indicated.
94
PUBLIC COMMENTS:
Failure to observe cardiac malformations in TCE, TCA, and DCA in the
Fisher et al. (2001) study substantially challenges the conclusion that
TCE in drinking water or by inhalation induces cardiac malformations.
The Fisher et al. (2001) study should be given greater emphasis in the
WOE as it provides important information showing that TCE metabolites
do not plausibly cause fetal heart malformations in rats at doses higher
than what would be considered a lethal or Maximum Tolerated Dose
(MTD).
All assays relevant to potential cardiac toxicity
from TCE exposure were given equal
consideration in the WOE analvsis. The (Fisher
et al., 2001) studv scored (0/-) for TCE and (-)
for metabolites in the cardiac defects WOE
analysis (Table Apx F-l 1), indicating that it did
contribute negative evidence toward the WOE
for cardiac defects.
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94
PUBLIC COMMENTS:
The EPA comment that the Fisher et al. (2001) 300 mg/kg-day TCA
dose was "too low to rule out effects at higher doses" is a dosimetric red
herring in that TCA maximum blood concentrations resulting from this
dose cannot be plausibly attained from TCE administered in drinking
water or by inhalation. Toxicokinetic comparisons indicate that the 300
mg/kg oral TCA dose used in Fisher et al. (2001) produced a maximum
systemic blood concentration of TCA that far exceeded the maximum
TCA blood concentrations resulting from 1,000 ppm TCE drinking water
or 600 ppm inhalation exposures.
EPA agrees that this statement is not appropriate
as written and it has been changed to "but only a
single dose level was used."
Wikoff et al. (2018)
108
PUBLIC COMMENTS:
EPA missed key flaws in Wikoff et al. (2018) that should have reduced
its confidence in the conclusions of that review. The review adapts the
Office of Health Assessment and Translation (OHAT) Risk of Bias
rating tool for human and animal studies to assess the internal validity of
experimental animal and human evidence linking maternal exposure to
TCE to fetal congenital heart defects.
The study authors state that they modified the OHAT framework to
tailor it to the specific research hypothesis under study and took
some of the 11 research questions/domains from OHAT and created
"subdomains" that split out the combined criteria into multiple,
separate considerations. This separation creates additional
opportunities to highlight shortcomings of individual studies. It is not
clear whether the subdomains are quantitatively considered
equivalent to domains (not clearly described), but the visual effect on
risk of bias heatmaps is that studies that perform poorly on individual
subdomains appear to be of even lower quality than they would be if
subdomains were retained as single domains per the OHAT risk of
bias rating tool.
Using this rating scheme, the Johnson et al. (2003) study performs
especially poorly. It would seem that Wikoff worked backwards from
shortcomings in conduct/presentation of the Johnson (2003) to put
EPA agrees that (Wikoff et al., 2018) involved
some subjective decisions, as do all WOE
analyses, and the Risk Evaluation indicates how
the Risk Evaluation's WOE analysis differs
from (Wikoff et al., 2018). However, it was not
the goal of the Risk Evaluation to dissect
specific aspects of other WOE analyses, only to
indicate why the conclusions may have differed.
EPA's WOE analysis incorporated relevance,
data reliability, and strength of response, while
(Wikoff et al., 2018) onlv focused on Risk of
Bias, a measure of data reliability.
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more emphasis on the elements of the OHAT framework that would
devalue that study and cause it to be discarded.
Wikoff et al. (2018) select a bias rating of "Probably High" that there
is indirect evidence that non-treatment-related experimental
conditions were not comparable between study groups without
presenting evidence to support this.
Wikoff et al. (2018) unreasonably scored Johnson et al. (2003) as
"probably high" for risk of bias due to the different cardiac
evaluation methods used. The superiority of certain heart dissection
methods was inappropriately asserted that led to an incorrect poor
risk of bias for Johnson et al. (2003). EPA noted the Johnson method
was sensitive and capable of detecting a variety of septal and valve
defects, as well as atrial, ventricular, and other miscellaneous
abnormalities (many of which were not observable using the methods
employed by the 2019 CRL study).
The completed risk of bias tables were not available from the Wikoff
study. This lack of transparency prevents EPA and the public from
examining the bases and justifications for specific study ratings.
106
PUBLIC COMMENTS:
Study conclusions for Wikoff et al. (2018) likely underestimate risk due
to lack of consideration of mechanistic data.
Wikoff s lack of consideration of mechanistic studies removes from
its evidence base "/// vivo animal studies in rats and chicks [which]
have identified an association between TCE exposures and cardiac
defects in the developing embryo and/or fetus (U.S. EPA, 201 le)"
and "provided strong and consistent supporting information for
effects of TCE and metabolites on cardiac development and
precursor effects."
EPA states in the Risk Evaluation that (Wikoff
et al., 2018) did not account for mechanistic
data. The study also did not assess data on TCE
metabolites.
Toxicokinetic data do not support developmental cardiac defects as an endpoint for TCE
79
PUBLIC COMMENTS:
A comparison of TCE toxicokinetics following drinking water,
inhalation, and gavage administration provides strong evidence that
parent TCE is an implausible source of potential fetal cardiac defects.
The presence of non-detects for TCA does not
indicate that TCE is not a plausible teratogen.
The sensitivity of the assay is an important
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The absence of detectable levels of TCE in maternal blood in rats
exposed to up to 1,000 ppm in drinking water in the CRL study is
consistent with previous drinking water findings. In contrast, TCE would
clearly have been present in maternal blood in the gavage study by
Fisher et al. (2001) and the inhalation study by Carney et al. (2006),
neither of which reported a fetal cardiac defect increase in offspring of
exposed rats.
consideration and it is possible that TCE
metabolites are toxic at very low doses based on
results from (Johnson et al., 2003) and various
mechanistic data (Appendix F.3.3.).
EPA discusses the non-monotonic dose response
of cardiac defects and presents data supporting
the dose-response in Appendix F.3.3. This non-
monotonic dose response in both apical and
molecular responses may explain the differences
in observed responses via different routes and
unexpected results at varying doses.
The WOE analysis assigned reduced relevance
to metabolite studies partially due to
considerations of dosimetry and uncertainty
regarding toxicokinetics via different routes,
however they still contributed consistent support
to the positive weight of scientific evidence.
72, 94
PUBLIC COMMENTS:
The statement by Makris et al. (2016) "[t]he evidence supports a
conclusion that TCE has the potential to cause cardiac defects in humans
when exposure occurs at sufficient doses during a sensitive period of
fetal development" is at odds with toxicokinetic data. Analysis of TCE
exposures and the peak concentrations of TCE and TCA in maternal
blood or plasma from three routes of exposure shows:
TCE Non-Detects in maternal blood in drinking water studies (CRL
and Fisher et al., 1989) indicate parent TCE is not a dosimetrically
plausible teratogen as postulated by Johnson et al. (2003).
TCE is unlikely to reach the fetal heart from exposure via drinking
water because of substantial hepatic first-pass metabolism, in
contrast to routes of exposure involving oral gavage and inhalation.
Higher peak TCA plasma levels are achieved in the gavage and
inhalation developmental toxicity studies (Fisher et al., 2001; Carney
et al., 2006) reporting no increase in cardiac malformations
compared to the drinking water study (Johnson et al., 2003) reporting
cardiac malformations. An absence of cardiac malformations by
these routes was not due to insufficient systemic TCE/TCA dosing.
Oral gavage and inhalation routes failed to show an increase in fetal
heart malformations, even at systemic doses that were considerably
higher than can be achieved by the drinking water route; the findings of
Johnson et al. (2003) cannot be a biologically plausible effect.
72, 94
PUBLIC COMMENTS:
EPA fails to incorporate toxicokinetic data showing minimal systemic
concentrations after oral exposures. It is incomprehensible that EPA
Page 202 of 408
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ignored toxicokinetics in its discussion of the developmental toxicity
data on TCE and its metabolites, and thus biased its conclusions in
support of the poorly designed and reported drinking water findings of
Johnson et al. (2003).
51,68,
79, 95,
103, 94
PUBLIC COMMENTS:
The claim that studies on TCE metabolites (TCE or DCA) provided the
strongest evidence in the animal database supporting the TCE-fetal
cardiac defect hypothesis is not accurate because the dose levels used in
those studies was high. Extrapolating to equivalent TCE concentrations
would result in lethal doses that would likely exceed the LDso in rodents.
EPA's conclusions on the TCE metabolite studies contradicts EPA's
TCA and DCA IRIS assessments.
In the TCE animal studies that measured the levels of metabolites in
blood, it is clear that the levels of TCA are substantially lower than
the doses that were associated with development of fetal cardiac
defects in the metabolite studies cited by EPA.
EPA failed to provide any quantitative perspective on dose plausibility
on whether the low dosages administered in drinking water generate the
necessary TCA and DCA tissue concentration supported by PBPK and
metabolism modeling.
94
PUBLIC COMMENTS:
The draft risk evaluation states that "Both TCA and DCA were
convincingly shown to produce strong dose-related cardiac defects in the
Smith et al., 1992, 1989 studies."
EPA failed to put these studies into perspective for the TCE hazard
assessment by providing an estimate of the TCE exposures that
would be required to attain the same TCA or DCA blood levels
where cardiac defects were observed.
Mechanistic/iVi vitro data supports/does not support developmental cardiac defects as an endpoint for TCE
108
PUBLIC COMMENTS:
The Urban et al. (2020) systematic evaluation of mechanistic data is
flawed and does not negate the strong body of mechanistic data
supporting the link between TCE and congenital heart defects. The NTP-
EPA agrees that Urban et al. 2020 (available at
httDs://Dubmed.ncbi.nlm,nih,ซov73 2145346/)
does not sufficiently discount the weight of
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OHAT method for evaluating a study's internal validity (risk of bias),
adopted by Urban et al. (2020), does not address mechanistic studies, nor
does it have a formal, structured approach to evidence integration for
mechanistic data as it does for animal and human studies. This is a
misappropriation of the NTP-OHAT method.
scientific evidence for mechanistic studies. The
study inappropriately applied TSCA systematic
review data quality metrics, often assigning
Unacceptable based merely on incomplete data
reporting, often for metrics that were assigned
N/A by EPA.
108
PUBLIC COMMENTS:
It appears that Urban et al. (2020) had a desired conclusion in mind when
reviewing mechanistic data regarding TCE-induced congenital heart
defects.
All of the studies inappropriately disqualified provided mechanistic
evidence of the linkage between TCE and congenital heart defects.
This study was supported by the ACC, which represents companies
that have direct and substantial financial interests in the continued
production and use of TCE and potential liability associated with
releases and exposures to TCE. As a general matter, risk of bias from
conflict of interest is an important consideration in conducting
systematic reviews and it should be considered by OPPT.
108, 66
PUBLIC COMMENTS:
Urban et al. (2020) relied on the deeply flawed TSCA systematic review
scoring method for evaluating study quality and to support integration of
evidence across identified mechanistic studies.
The majority of experimental datasets (approximately 70%) were
assigned a score=4 for at least one of the OPPT study quality metrics,
indicating the data sets are unreliable for risk assessment. These
exclusions are unwarranted.
Urban et al. raise issues of substance preparation and storage, data
analysis and testing for potential cytotoxicity as the primary reasons
for rejection of 16 studies that provide mechanistic support for the
link that they challenge. Dr. Raymond Runyan indicated that proper
handling of TCE is a convention in the field that did not require
specification. This information could have been provided if the study
authors had been contacted.
A study by Harris et al. (2018) was downgraded because T tests were
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used rather than analysis of variance (ANOVA) in the analysis.
However, since the authors were not attempting to utilize multiple
independent measures together, ANOVA was not necessary for the
analysis.
Several studies were downgraded because they did not test for
cytotoxicity. Most studies, however, were testing low concentrations
where previous data had shown that there is no cytotoxicity at those
concentrations and therefore, disqualification for this reason is
inappropriate.
No attempt was made to contact authors of the disqualified studies,
many of whom likely would have been able to provide the missing
information.
66
PUBLIC COMMENTS:
The systematic examination of mechanisms in relation to TCE and
congenital heart defects as performed by Urban et al. (2020) is distorted
by a basic asymmetry of resources. There has been no national funding
for research on TCE and heart defects since 2009. The Urban paper
focuses on an adverse outcome pathway (AOP) that was identified 20
years ago. Newer data on alternative mechanisms has only been
produced by very limited local funding and suggests the existence of
additional mechanisms that need more analysis. In contrast, the ACC and
HSIA spend more than $7 million each year lobbying to relax
restrictions on the use of TCE and contracting consultants to write papers
to perpetuate the controversy.
66
PUBLIC COMMENTS:
The Urban et al. (2020) paper suggests that the chick embryo may be
uniquely sensitive to TCE because it has no protective maternal
metabolism and there is no placenta in this non-mammalian model.
However, a recent paper by Chen et al. shows that the non-monotonic
regulation of HNF4a activity by TCE, previously identified in the chick,
is also a component of low dose exposure in the mouse model.
There is substantial overlap in relevant pathways
of cardiac toxicity among developmental
models. Appendix F.3.3 discusses potential
Modes of Action (MOA) and other mechanistic
considerations that support the observed non-
monotonic dose-response, and these are often
observed in varied cell types.
32
PUBLIC COMMENTS:
TCE has been shown to induce a biphasic response in transcription factor
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HNF4a in the developing heart in chick embryos and in mammals (e.g.,
Chen et al., 2020). HNF4a and TCE are each also associated with liver
cancer, kidney cancer and Parkinson's Disease. These pathologies may
be variously related to loss of HNF4a activity (low dose TCE) or over
expression of HNF4a (higher dose TCE).
While there is not strong evidence for any
particular singular AOP, mechanistic evidence
suggests that multiple mechanisms and MOA
may be involved. The involvement of multiple
mechanisms could also explain the diversity of
the observed cardiac defects.
79
PUBLIC COMMENTS:
One SACC member noted that the relevance of the mechanistic
information cannot be critically evaluated until EPA has developed a
mechanistic framework (e.g., an AOP) for the cardiac effect. While
Makris et al. (2016) suggest an AOP for a subset of fetal cardiac defects,
Urban et al. (2020) noted that the mechanistic evidence in mammalian
models either do not support, or contradict, the postulated AOP, and
found no basis for supporting the validity of TCE as an agent capable of
causing such effects.
51,68,
79, 95,
103
PUBLIC COMMENTS:
The EPA conclusion that the mechanistic literature represented the
strongest and most consistent line of evidence in support of the TCE-
fetal cardiac defect hypothesis is in stark contrast with the conclusions of
a systematic review (Urban et al., 2020) that focused on these studies.
EPA rationalized the discrepancy by stating Wikoff et al. (2018) did
not evaluate any mechanistic data, which may explain the difference
in overall conclusions between the two studies.
The study quality review and scoring methods of the TCE-fetal
cardiac defect mechanistic studies reveal several critical oversights
and inconsistencies that violate norms of systematic review. EPA has
overstated the quality of the TCE-fetal cardiac defect mechanistic
literature and the degree to which it can inform the TCE-fetal cardiac
defect hypothesis. For example, three mechanistic studies examined
both TCE and metabolites, so EPA counted these twice.
Overall, EPA's conclusions were surprising given the heterogeneity
and inconsistency in findings between and within species.
EPA disagrees that there is heterogeneity and
inconsistency among mechanistic studies. The
vast majority of mechanistic studies
demonstrated responses supporting induction of
developmental cardiac defects. Additionally, the
non-monotonic dose-responses observed in
(Johnson et al.. 2003) are in agreement with
several studies demonstrating varied responses
at low vs. high doses. While there is not strong
evidence for any particular singular AOP,
mechanistic evidence suggests that multiple
mechanisms and MOA may be involved. The
involvement of multiple mechanisms could also
explain the diversity of the observed cardiac
defects. EPA does agree that mechanistic studies
are of reduced relevance compared to in vivo
animal or human data, and this was accounted
for in the WOE analysis.
76, 68,
95
PUBLIC COMMENTS:
There are problems with the in vitro studies used by EPA to challenge
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the key conclusion of DeSesso et al. (2019) and suggest that TCE may
exhibit low-dose nonmonotonic effects on cardiac development.
In vitro studies are not kinetically equivalent to in vivo exposures.
Based on the toxicokinetic portion of the DeSesso study, blood (and
assumed associated embryo concentrations) are within or
substantially below the doses used in the in vitro studies. Other oral
and inhalation studies (Carney et al., 2006; Fisher et al., 1989) also
found negligible TCE blood concentrations with high dose
exposures.
In ovo or in vitro studies are not physiologically representative of
mammalian embryos. Exposures occur outside maternal organism;
therefore, no maternal metabolism or retardation of transfer to the
embryo occurs.
Most of the studies are hypothesis-generating by design. The
transcriptomics datasets lack any cross-species gene pathway
coherence.
The endpoints used (e.g., changes in gene expression; alterations in
the methylation of DNA; changes in calcium regulatory transcripts of
calcium flux) have not been demonstrated to be causative of cardiac
malformations.
The findings are not relevant to the assessment of potential cardiac
teratogenicity in mammalian embryos.
Overall, EPA resorted to a non-systematic, narrative approach in
which only those datasets suggesting a potential TCE-fetal cardiac
defect association were highlighted, while contradictory datasets
were ignored. This approach fundamentally violates basic systematic
review methodologies.
The WOE analysis assessed biological
plausibility and not quantitative dose-response,
so the use of high doses was only considered
qualitatively as contributing to the reduced
relevance of the studies.
(Harris et al.. 2018) was included in the WOE
analysis for the data on chick embryos. See the
supplemental document Data Table for
Congenital Heart Defects Weight of Evidence
Analysis for full details on the evaluation of each
study.
94
PUBLIC COMMENTS:
The biological relevance of the in vitro studies cited is questionable due
the use of enormously high doses. Even studies that EPA claims support
a non-monotonic dose response, with effects seen at lower, but not,
higher TCE doses, used doses either within or higher than the worst-case
estimates for TCE blood levels in the CRL drinking water study. Since
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cardiac malformations were not increased in the CRL study, the
conclusion that these low-dose effects seen in some of the in vitro studies
are non-monotonic are without merit.
51, 95
PUBLIC COMMENTS:
EPA only scored each of the mechanistic TCE-fetal cardiac defect papers
that it included in its evaluation as a single study despite having multiple
experiments.
Harris et al. (2018) reported TCE effects in three different models:
HepG2 cells, chicken eggs exposed in ovo, and chicken embryos
exposed ex ovo. Each experiment should have been scored separately
as they likely would have unique scoring responses. It is not clear
which experiment EPA was focusing on for their scores.
EPA mischaracterized what is a series of "unacceptable"
experimental datasets as a single "medium quality" study for their
TCE-fetal cardiac defect WOE.
51, 95
PUBLIC COMMENTS:
EPA failed to apply both the data interpretation and cytotoxicity testing
metrics to most of the relevant TCE-fetal cardiac defect mechanistic
studies. In addition, EPA inconsistently applied the Blinding of Outcome
Assessors Metric (#19) to the relevant mechanistic studies, scoring this
metric for some in ovo studies (e.g., Drake et al., 2006a,b; Loeber et al.,
1988), but not others where subjective observations were being reported
and it was thus clearly warranted (Rufer et al., 2010).
(Rufer et al., 2010) used non-subiective
echocardiography for evaluating hearts in
addition to multiple quantitative and qualitative
measures. (Drake et al., 2006a; Drake et al.,
2006b) and (Loeber et al., 1988) focused on
more subiective measures, and (Loeber et al.,
1988) indicated blinding for researchers.
51
PUBLIC COMMENTS:
EPA erroneously applied the in vitro study quality metrics to Collier et
al. (2003), which is an in vivo study. This resulted in a faulty study
quality score. Had the appropriate quality metrics been applied, this
study would have been scored as "unacceptable" because it used an
insufficient number of animals per dose group and did not report any
statistical analysis of their findings.
Exposure occurred in vivo, however the
experiment involved genomics of exposed fetal
embryos. Statistical analysis is included as a
metric in the in vitro mechanistic criteria and
was accounted for in the evaluation.
EPA W<
DE approach and conclusions for cardiac developmental defects
SACC
SACC COMMENTS:
It appeared to the Committee that the WOE assessment and the
This comment incorrectly interprets the role of
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systematic review process used two different rating systems, despite
having overlap in their goals and methods. Figure 3.3 explains that data
interpretation is part of the systematic review process. This suggests that
the draft risk evaluation should not need a separate WOE method, and
the WOE discussion should be considered part of the scoring and
integration components of the systematic review. The systematic review
appropriate for dose-response would be included.
data quality as part of the systematic review
process. Data quality is only one factor in
considering data integration of the reasonably
available data, which accounts for the weight of
scientific evidence and must incorporate both
relevance and strength of study results.
SACC
SACC COMMENTS:
Recommendation: Revise the WOE to integrate strength and relevance
of all in vivo animal and epidemiological study findings with available
mechanistic evidence.
The WOE analysis already accounts for
relevance and strength of all relevant studies, in
addition to data quality (reliability).
SACC
SACC COMMENTS:
Recommendation: Reconsider the scores assigned to the epidemiological
evidence for TCE-induced cardiac anomalies.
Several Committee members felt the epidemiological data showing
suggestive evidence of an association between TCE exposure and
cardiac effects in offspring were weak. For example, none of the
three studies showing positive associations (Brender et al., 2014;
Forand et al., 2012; Wright et al., 2017) accounted for the residential
location of the mothers during the critical period for cardiac
development (3rd to 8th week of pregnancy) or had TCE exposure
data for the study population. Instead, they all used the maternal
location at the time of birth. Other weaknesses were noted as well.
Some Committee members thought that the relevance score of ++
given to Brender et al. (2014), Forand et al. (2012) and most of the
other epidemiological studies in the WOE evaluation was too high,
because they felt that it would be difficult to use the data from any of
the three studies in question to develop a toxicity value, even though
animal to human extrapolation is not needed.
There is some uncertainty in the exposure
domains due to the lack of individual level
exposure assessment, but the environmental
monitoring procedure was well done. If the 22-
32% of women are estimated to move during
pregnancy, then 68-78% are in the same location
during pregnancy, which would include the
critical period for cardiac development. So, this
was accounted for in the study. Potential for
misclassification is accounted for in the
reliability score of each study (+) instead of
(++)
Forand et al.. 2012 - As the author also pointed
out, this move would be true of both cases and
controls. So, this is a non-differential
misclassification which would bias the estimate
towards the null {i.e., resulting in an
underestimate in risk). The sample size was
indeed small, but still sufficient enough to see
biologically relevant and statistically significant
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differences in this population.
Brender et al., 2014 - These limitations are
already accounted for in the reliability score of
the study.
Wrisht et al., 2017 - Maternal location is not the
ideal method and exposure misclassification is
possible, but that's why the authors used a
categorical exposure measure in the analysis
(rather than continuous). It's easier to have
confidence that particular households were
placed in the right exposure group, despite the
averaging that occurred by sampling location.
There is no reason to believe that the results are
unreliable.
SACC
SACC COMMENTS:
Recommendation: Multiple in vivo animal TCE inhalation studies
reporting no heart defects need more consideration in the WOE analysis
of animal data.
Cardiac developmental anomalies have not been described in any of
six TCE inhalation studies in rodents. Patterns in available
developmental inhalation studies should be searched/assessed for
specific endpoints to determine coherence. Particular attention should
be paid to the study by Carney et al. (2006). Several Committee
members said the draft risk evaluation needs to consider the findings
of this study and others by Beliles et al. (1980), Cosby and Dukelow
(1992), and Narotsky et al. (1995) in its WOE analysis. It was noted
that Watson et al. (2006) published an analysis that concluded there
was no causal association between TCE exposure at environmentally
relevant concentrations and congenital heart defects.
For this draft risk evaluation, it appears data for the inhalation route
would be preferred because inhalation exposures are most relevant to
EPA incorporated all relevant studies identified
in previous assessments into the WOE analysis.
Some studies were excluded because there was
no evidence that they specifically examined
cardiac defects. (Cosbv and Dukelow, 1992) did
not investigate heart defects, neither did
(Narotskv et al., 1995). The onlv evidence of
anv heart investigation in (Beliles et al., 1980) is
gross discoloration observed in dams. Watson et
al. 2006 (available at
httDs://www.sciencedirect.com/science/article/Di
i/S0890623805001759?via%3Dihub) is a review
paper that was published well before many of
the later studies incorporated into EPA's WOE
analysis. These and other excluded studies are
now cited in Appendix F.3.1.
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COUs. As a result, findings from studies based on the inhalation
route of exposure offer less uncertainty on POD estimates. PBPK
models are useful; however, they do add uncertainty when
conducting route-to-route extrapolation; hence, data from inhalation
exposures and oral exposures are not equivalent. There are several
high-quality developmental studies conducted with inhalation
exposures. It is recommended that the risk evaluation focus on these
(but not ignore the oral studies).
EPA relies on the peer-reviewed PBPK model
and considers all routes similarly relevant,
however EPA acknowledges uncertainties
associated with route-to-route extrapolation in
Section 3.2.6.2.
51
PUBLIC COMMENTS:
EPA failed to include three oral TCE developmental toxicity animal
studies - Cosby and Dukelow (1992); Narotsky et al. (1995); Narotsky
and Kavlock (1995) - that are of medium quality and thus reliable for
inclusion in the draft TCE-fetal cardiac defect WOE. Notably, none of
these studies observed fetal cardiac defects associated with gestational
TCE exposures, findings that impact EPA's WOE conclusion for animal
studies.
SACC
SACC COMMENTS:
Recommendation: Improve the discussion on the MOA for TCE-induced
fetal cardiac defects and identify gaps in the AOP that need to be filled.
The EPA's WOE approach to scoring evidence for cardiac defects
was considered by the Committee to be overly simplistic and
problematic, in that in the Committee's view, it gave more weight to
incomplete mechanistic data than to in vivo animal evidence.
Mechanistic data are valuable in understanding MO As and assessing
biological plausibility. These data, however, are limited for TCE in
that they primarily involve enzymes and gene induction.
Metabolomic and proteomic evidence was not described.
The draft risk evaluation did not integrate and organize the
mechanistic data into a coherent causal pathway from initial
exposure to adverse outcome. The MOA narrative in the draft risk
evaluation proposes several hypotheses for potential MO As but
concludes that the evidence to date does not identify a specific MOA.
Why then are mechanistic studies assigned a score of'++' in view of
EPA has downgraded the summary score
slightly for mechanistic studies from ++ to +/++
based on the absence of a single, clear AOP.
EPA believes however that there are multiple
contributing MOA for TCE's impact on cardiac
defects.
EPA already accounted for reduced relevance of
mechanistic studies in the WOE analysis scores.
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limited information and no apparent/likely mechanism?
The use of high-dose experiments in in vitro and avian systems limit
their relevance in assessing risks of environmental TCE exposures.
60, 52
PUBLIC COMMENTS:
The approach for data integration and WOE assessment for hazard ID
was not consistent within the TCE draft risk evaluation; the step was
either absent (all endpoints except one) or conducted with a novel
approach designed and implemented only for fetal cardiac defects.
An independent assessment of the overall WOE was not conducted
for any of the endpoints other than fetal cardiac defects. That is, an
independent, structured evaluation of the WOE was absent for the all
endpoints considered except one. This is contrary to standard
systematic review practice.
For all of the endpoints without a WOE evaluation, EPA relied on
conclusions from previous authoritative assessments. This introduces
uncertainty given that the assessments relied upon were not
conducted using systematic review, nor were the WOE conclusions
determined in previous assessments clearly described in the TCE
draft risk evaluation.
o The EPA cites that no new data were identified to alter the
conclusions of such, but presents no clear documentation of all of
the studies that were considered "new" relative to the WOE
conclusions being relied upon for each endpoint.
o Further, EPA conducted data quality assessments for studies
related to these endpoints where a WOE was not conducted - a
significant use of resources - exercises that largely seem to be
unused given that an independent WOE was not conducted.
A de novo WOE approach was designed and implemented only for
fetal cardiac defects. The approach was not part of EPA's Draft
TSCA's Systematic Review guidance, nor has it been applied to any
other chemical. The draft risk evaluation does not provide sufficient
detail to evaluate the rigor and validity of the methods, and there
were no opportunities for peer review. The two pages of bulleted
The detailed WOE analysis was only performed
for cardiac defects because that endpoint
involves a large database of conflicting results.
For other endpoints, the database is relatively
consistent in favor of a weight of scientific
evidence for that endpoint with very little
conflicting evidence. Therefore, only a short
summary of the newer studies was discussed for
how they contributed to or countered the
previous weight of scientific evidence
established in the published 2014 TCE Risk
Assessment. All studies published after the 2011
IRIS Assessment in addition to any key studies
from the IRIS Assessment considered for dose-
response analysis were evaluated for data quality
and described in the Risk Evaluation.
New studies identified in the literature search are
identified in Trichloroethylene (CASRN 79-01-
6) Bibliography: Supplemental File for the
TSCA Scope Document. EPA-HO-OPPT-2016-
0737)
The cardiac defects WOE analysis is based on
existing methodology from the EPA Risk
Assessment Forum ( ). It adds
important considerations of data integration,
relevance and strength, to the data quality
considerations that were imparted by the
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explanation provided are insufficient to understand or reproduce the
WOE assessment as presented in the draft risk evaluation.
The data quality assessment and WOE evaluation methods rely
partially on the same criteria and thus studies are evaluated using the
same criteria multiple times - but with different results. This equates
to "double counting" of criteria, which favors reviewer bias and is
not consistent with the fundamental tenets of systematic review,
o It is difficult to remedy the rationale that the data evaluation
metrics from the systematic review guidance would be used
differently for evaluating the utility for dose-response and also for
potential consideration in the WOE assessment (which seems
"backwards" if the study has already been evaluated for utility in
dose-response).
The de novo WOE approach applied to fetal cardiac defects utilizes
subjectively assigned overall "scores" based on reliability, relevance,
and strength - aspects that are not fully in alignment with traditional
systematic review approaches.
o It is not clear if this approach considers aspects commonly
evaluated as part of determining the certainty or confidence in a
body of evidence in systematic review or those commonly
assessed in causation analyses,
o In particular, an evaluation of the biological plausibility of a
response in humans should be assessed; this is not well-defined in
the WOE approach and is critical to the topic to which it is
applied given that much of the mechanistic data are in non-
mammalian models and are in contrast to findings observed in
mammalian studies,
o The individual scores for reliability, relevance, and strength are
subjectively assigned, as is the overall score for each type of
evidence. The overall score appears to employ weighting by
evidence stream, though the description of this method is not
sufficient such that it can be reproduced. It is not clear what the
overall score means in terms of hazard characterization - i.e., is it
systematic review data quality evaluations. EPA
acknowledges that the systematic review
guidance for the first 10 Risk Evaluations did
not explicitly describe a process for data
integration, however EPA is working with the
National Academies of Science to develop a
more robust process for the future that may
incorporate principles of this WOE analysis.
While expert judgment is part of any WOE
analysis, scores for each study and domain were
consistently applied across all studies. The
methodology and scoring guidance are presented
clearly in Appendix F.3.1. The overall result
indicates the relative support for an association
of TCE exposure with cardiac defects. It
supports that TCE exposure is more likely than
not to increase risk of cardiac defects. It does not
determine the dose-response of the endpoint or
any quantitative assessment of the POD.
The SACC did peer review the WOE analysis as
part of the overall Risk Evaluation and this
analysis has been updated based on public
comments including this comment. It is based on
existing methodology from the EPA Risk
Assessment Forum ( ). The
reliability metric was evaluated with the TSCA
systematic review data quality evaluation in
mind, but with a more focused evaluation of data
quality for the particular outcome at hand. The
reliability scores closely track the TSCA
systematic review data quality scores for all
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a measure of the magnitude of a potential association? Is it
confidence in an effect? The meaning of the overall score should
be defined.
The output of the WOE assessment should be further connected with the
risk evaluation process, particularly as it relates to the differential
approaches for individual study assessment and the requirement to utilize
individual studies to develop PODs for purposes of the risk evaluation.
studies. EPA acknowledges that the systematic
review guidance for the first 10 Risk Evaluations
did not explicitly describe a process for data
integration, however EPA is working with the
National Academies of Science to develop a
more robust process for the future that may
incorporate principles of this WOE analysis. The
methodology and scoring guidance are presented
clearly in Appendix F.3.1.
106
PUBLIC COMMENTS:
EPA has employed a post hoc WOE analysis based on a hierarchy of
preferences against one single endpoint only.
The post hoc method is unvalidated, not empirically based, has not
been subject to peer review nor public comment, and falls short of
the best practice methods in systematic review methods, which is the
codified approach that EPA must take for risk evaluations.
For example, for the metric of reliability, instead of looking at the
overall study quality evaluations already completed by EPA for TCE,
as would be normal practice when assessing the influence of risk of
bias on the quality/certainty of a body of evidence, EPA performed a
separate evaluation focused on "key attributes." This is inconsistent
with how the quality of the evidence should be evaluated based on
the overall risk of bias of the included studies. Additionally, EPA is
not clear in its definition of these referenced "key attributes," lead to
a higher score for metrics such as reliability.
There is no empirical basis for the "grades assigned based on the
number and nature of the specific deficiencies identified." EPA has
continued its pattern of creating a method that is incompatible with
best practice, post hoc.
EPA has not rated the confidence in the body of evidence in any of the
draft risk evaluations that it has completed to date, nor has it
implemented a predefined evidence integration step to come to its final
conclusion on whether the chemical being assessed poses an
unreasonable risk for certain COUs. Therefore, how EPA translates the
available evidence into its final conclusion is unclear and unjustified by
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EPA. We strongly recommend that EPA use the validated, peer review
method of NTP OHAT, which is consistent with best practice, for the
evidence integration step in all risk evaluations it conducts. This method
will allow EPA to transparently demonstrate the process for how the
conclusions are reached in assessing human health hazards for each end
point it assesses.
108
PUBLIC COMMENTS:
EPA adopted the methodology described in Risk Assessment Forum's
WOE in Ecological Assessment to apply the evidence base for
congenital heart defects, but uses a narrative summary in developing a
WOE evidence for all other endpoints.
EPA fails to adequately explain/justify the selection of this particular
methodology.
It is unclear whether EPA intends to apply this method in future risk
evaluations, and the extent to which EPA considered more prominent
GRADE-based structured frameworks for evidence integration used
by analogous chemical assessment approaches {i.e., National
Toxicology Program OHAT health effects evaluations, University of
California at San Francisco [UCSF] Navigation Guide, EPA IRIS
assessments).
EPA highlights the strength criterion as a distinguishing feature and
explains that the strength of a given piece of evidence corresponds to its
"magnitude, dose-response." There is concern that the inclusion of effect
"magnitude" as a criterion for consideration could be interpreted as the
fraction of the affected population, or the effect size of the change in a
measure of outcome. An effect with a small "magnitude" either may
affect a considerable fraction of the exposed population or could be
sufficiently severe to warrant concern. Caution is advised in discounting
evidence from well-designed, relevant studies with a small magnitude.
108
PUBLIC COMMENTS:
In the WOE analyses for congenital heart defects, EPA jointly
considered the evidence for oral and inhalation studies in animals. When
considered independently, the oral studies had an integrated area score of
The WOE analysis considered overall
plausibility and likelihood of TCE exposure
leading to developmental cardiac defects. While
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(+), whereas the inhalation studies had an integrated area score of (-).
Taken together, EPA assigned the in vivo studies via all routes a (0),
which impacts the overall evidence integration for the endpoint (the
quantitative nature of its impact is unclear for this semi-quantitative
integration approach). However, it is not appropriate to consider the oral
and inhalation routes together in this approach. Given potential
differences in toxicokinetics and metabolism across routes, it is plausible
that oral exposures are associated with the endpoint while inhalation
exposures are not. EPA should conduct the WOE analyses separately by
route. Then the in vivo animal toxicity studies score would have been
higher (for oral exposure), which would have likely increased the overall
Integrated Area Score and summary score.
EPA agrees that there may be differences via
different routes, evidence via different routes
together contribute to the overall WOE. It would
be difficult to parse apart specific exposure
routes via animal studies when combined with
epidemiological and mechanistic data that are
not necessarily route-specific.
51
PUBLIC COMMENTS:
The framework used by EPA to integrate the mechanistic data into the
larger WOE skips a critical step after study quality scoring: EPA fails to
integrate the evidence within the mechanistic database - i.e., bringing it
all together to determine the degree to which it is able to provide a
coherent story supportive of the biological plausibility of the TCE-fetal
cardiac defect hypothesis and how it all fits together. Urban et al.
evaluated three approaches for mechanistic data integration:
Hazard-based: Does the mechanistic evidence on its own suggest that
fetal cardiac defects are a potential hazard associated with gestational
exposures to TCE?
AOP-based: Does available mechanistic evidence inform the
biological plausibility of TCE-fetal cardiac defects?
Risk-based: Do any of the mechanistic studies provide a dose-
response dataset that should be considered as candidate studies in
developing toxicity values?
EPA provides a summary of the mechanistic
database both within the WOE analysis itself
(Appendix F.3.2) and in a separate subsection
(Appendix F.3.3) which discusses potential
modes of action.
51, 68
PUBLIC COMMENTS:
EPA's study quality and WOE evaluations for the TCE-fetal cardiac
defect hypothesis contain several errors and examples of inconsistencies
in how EPA interpreted and applied its study quality metrics across the
various evidence bases (human, animal, mechanistic), as well as bias in
EPA applied data quality metrics consistently to
all studies evaluated in the Risk Evaluation,
however interpretations may differ for similar
studies based on the available information. Some
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several key inter-study critiques. There is a noticeable discrepancy in the
level of detail and latitude given studies of the mechanistic and human
evidence base relative to the animal studies, suggesting a problematic
variation in the level of reviewer expertise between these databases that
appears to result in deference to the former at the expense of the latter.
The draft risk evaluation:
Inconsistently applies study quality metrics between studies.
Fails to apply all relevant study quality metrics (e.g., data
interpretation, cytotoxicity metrics for in vitro assays).
Re-scores initial study quality results using a process outside of the
prescribed systematic review protocol and based on subjective
judgment (introducing subjective bias into the evidence base).
Inconsistently follows up with study researchers (introduction of
subjective bias into the evidence base).
Excludes relevant TCE-fetal cardiac defect studies from the
assessment (unexplained exclusion criteria).
metrics were scored as N/A if they were only
required for certain study types/assays. As stated
in Appendix F.3.1, "This analysis was
performed in parallel with the systematic review
data evaluation of the individual studies. The
WOE analysis had a greater focus on relevance
to the specific endpoint while the data evaluation
metrics aimed to evaluate the utility of a study
for dose-response analysis." Usually scores were
aligned between the data quality and WOE
reliability scores. EPA has added the list of
excluded studies to Appendix F.3.1 based on no
indication of direct assessment of cardiac
defects.
As stated above, all metrics may not be
applicable for all studies. The metric for
cytotoxicity was primarily applicable for study
types in which it is required by OECD
guidelines (e.g., Ames assay for genotoxicity).
Expert judgment is considered in all data quality
evaluations when the metrics do not fully
capture the full scope of a study's data quality.
EPA opened communications with authors of
both positive (Johnson et al.. 2003) and negative
(Charles River Laboratories, z ) studies in an
attempt to clarify missing or unclear
information.
51, 68
PUBLIC COMMENTS:
There is evidence of reviewer bias in the systematic review process.
Consistent scoring was not applied to studies that did not report test
substance source (Metric 2).
Two key in vivo studies were scored as "not rated/not applicable" for
Metric 5, but this metric was removed from scoring for all other
animal and mechanistic studies. The discrepancy was not justified.
Metric 19 was scored in less than half of the applicable studies.
Metric 23 "scoring and/or evaluation criteria" were scored as "not
applicable" for in vitro studies without justification.
EPA only scored Metric 24 "cytotoxicity testing" in one cell culture
study while excluding it from study quality scoring for all other in
vitro experiments. All of those not scored did not report cytotoxicity
testing.
There were several instances where study scores were overturned by
an evaluator based on subjective judgment, where the rationale did
not adhere to any framework or protocol decision making tree.
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There was subjective bias (in favor of studies supporting a WOE for
cardiac defects) in which studies correspondence with authors was
cited as supporting evidence for metric scores.
51
PUBLIC COMMENTS:
Lack of quality control measures during systematic review introduces
additional uncertainty into what is already a highly subjective and
questionable WOE evaluation process, further calling into question
EPA's attempt to integrate the TCE-fetal cardiac defect evidence
streams.
All studies were evaluated by two reviewers to
ensure consistency among scoring. For the WOE
analysis, all criteria and summary scores were
additionally reviewed for consistency among
studies and domains.
51,95,
94
PUBLIC COMMENTS:
EPA concluded that "[OJverall, the in vivo animal toxicity studies
provided mixed, ambiguous evidence for an effect of TCE (summary
score of 0)." This conclusion is a mischaracterization of the animal data.
With the exception of Dawson et al. (1993)/Johnson et al. (2003), the
database is comprised of high-quality studies, with relevant routes of
exposure, that failed to demonstrate any association between in utero
TCE exposure and fetal cardiac defects. EPA dismissed an inhalation
study by Carney et al. (2006) that perhaps provides the most definitive
data on the fetal cardiac defect endpoint, because it uses the most
relevant exposure route and underwent a rigorous peer review process by
multiple federal agencies, including EPA, and was given a high quality
data score. The disregard of Carney et al. (2006) points to a bias in
EPA's approach to evaluating the developmental data rather than
supporting an agenda based on the WOE.
EPA did not dismiss the (Carney et al.. 2006)
study. The Carney study scored (+++) for
reliability, higher than any other TCE animal
study. It is included in the WOE analysis and
EPA states that "the summary score for the
inhalation studies was (-), primarily driven by
the weight of the (Carney et al.. 2006) data but
reduced by the weaknesses of the other studies
and the limited number of acceptable studies
with non-ambiguous results."
51
PUBLIC COMMENTS:
The Galba et al. (2012) study is scored as a "High Quality" study;
however, EPA erroneously characterize it as a "Medium Quality" study
in the WOE spreadsheet, without providing justification. This impacts
the human WOE determination because this is a negative study of high
quality, so the unjustified downgrade in study quality reduces its impact
on a weak dataset.
EPA assumes that the commenter is referring to
( )oa et al.. 2012). EPA appreciates this
comment, there was a mistake in the data table
for the WOE analysis. The study has been
updated, and the reliability score has been raised
to +/++, with some remaining limitations due to
potential exposure misclassification. This
change in reliability score does not affect the
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overall grade, which is dictated by the lowest
magnitude of the three scores for reliability,
strength, relevance (strength was scored (-)).
51, 68
PUBLIC COMMENTS:
Wright et al. (2017) was purportedly scored an initial "High Quality,"
but was then downgraded to "Medium Quality" for issues of directness
(e.g., investigating proximity to TCA and DC A, rather than TCE).
However, this study quality downgrade was ignored in the WOE, where
this study was rated as the only high reliability study in the dataset.
As indicated in TCE Data Table for Congenital
Heart Defects Weight of Evidence Analysis, the
study was downgraded in the TSCA data quality
evaluation because TCE was not directly
evaluated, however the reliability is still high
when fit-for-purpose of evaluating TCE
metabolites. As with Gilboa et al. 2012, the
overall grade was dictated by the lowest score
(strength and relevance were both scored (+)).
51
PUBLIC COMMENTS:
EPA over-characterized the outcome strength of the findings of the
Brender et al. (2014) study, which reported weak associations between
proximity to TCE and select fetal cardiac defects. EPA did not reflect
these weak findings in its rating (positive, or "+" vs. weakly positive, or
"0/+").
The finding was statistically significant, despite
the modestly increased OR. Therefore, the study
was scored (+) for strength, as opposed to (0/+)
which suggests ambiguity.
51, 72
PUBLIC COMMENTS:
The CRL study is consistent with the negative TCE-fetal cardiac defect
findings that have been reported in 11 other animal studies (oral and
inhalation), all of which can be characterized as reliable per TSCA study
quality scoring. The Johnson et al. (2003) positive findings remain a
unique outlier in this evidence stream that can reasonably be explained
by the many underlying issues in study design and reporting. EPA does
not properly account for multiple robust apical developmental toxicity
studies that show no increase in heart defects and ultimately minimized
the negative TCE-fetal cardiac defect animal studies (comprising all but
one of the studies in the animal database) while enhancing the single,
relevant positive animal study.
All studies are considered equally for their
contribution to the WOE analysis. While
(Johnson et al.. 2003) and (Dawson et al., 1993)
are the only positive animal studies on parental
TCE, there are several positive studies on TCE
metabolites that contribute to the overall WOE.
51
PUBLIC COMMENTS:
Twelve animal studies demonstrate a lack of association between in
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utero TCE exposure and fetal cardiac defects, including all inhalation
studies, representing the most relevant route of exposure for the human
exposure scenarios evaluated in the TCE draft risk evaluation.
The TCE-fetal cardiac defect animal data do not support the TCE-fetal
cardiac defect hypothesis.
60
PUBLIC COMMENTS:
POD for the cardiac endpoint is based on a single study; there are 12
others reporting lack of effect. The POD selection metrics do not address
negative findings in selecting the POD for an endpoint.
51, 72
PUBLIC COMMENTS:
There is concern about dependence on a single flawed study to conclude
that TCE exposure may cause fetal heart malformations, despite
evidence to the contrary from multiple, well-conducted studies. EPA's
interpretation of the cardiac data has had a profound effect on the
remediation of contamination sites.
Follow-up studies by Fisher et al. (2001) and DeSesso et al. (2019)
did not observe cardiac defects despite repeating as many aspects of
the original study as possible. EPA has offered an expanding list of
possible explanations - exposure route specificity, importance of
mechanistic data, genetic drift, possible role of metabolites, and most
recently, differences in the dissection techniques.
The problems with EPA's consideration of the cardiac defect data can be
seen in several aspects of the draft including inconsistent application of
the TSCA systematic review, mischaracterization of the quality and
reliability of the available cardiac mechanistic literature, failure to relate
the levels of metabolites required to cause heart effects in rats with the
levels generated from typical TCE exposures, and clear evidence of bias
in the consideration of the WOE for cardiac effects.
EPA disagrees with the characterization of
EPA's WOE determination. There are multiple
lines of evidence in support of an association
between TCE exposure and cardiac defects.
However, EPA acknowledges that while there is
qualitative support for the endpoint, based on
uncertainties in the dose-response for this
endpoint and other considerations EPA has
selected immune endpoints as the best overall
endpoints for risk conclusions (Sections
3.2.5.4.1, 3.2.6.1.1).
103
PUBLIC COMMENTS
EPA did not fully consider and integrate all of the relevant literature in
its systematic review of the developmental evidence. EPA paid little
attention to other reproductive/developmental studies that did not
observe increased fetal cardiac malformations. EPA must also adhere to
EPA considered all relevant studies identified in
either previous WOE assessments or the TSCA
literature search. EPA has added a list of studies
excluded as off-topic to Appendix F.3.1. EPA
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systematic review principles that when followed (as shown in the Wikoff
et al., 2018 and Urban et al., 2020 papers), reject TCE as a proven cause
of fetal cardiac malformations.
followed systematic review principles, which
include data integration in addition to data
quality.
103
PUBLIC COMMENTS
It is not clear why EPA presented a hazard and toxicity value assessment
that emphasized the Johnson et al. (2003) study when in the draft
determination, EPA elected not to use the reference dose based on
Johnson et al. (2003). EPA should adjust the WOE discussion for
developmental cardiac effects to reflect the critical deficiencies in the
Johnson et al. (2003) study.
EPA should also further clarify why the WOE does not support use
of this endpoint to provide the representative POD for risk
characterization especially at low environmental concentrations
relevant to the POD and the low (ppb) air concentration that EPA
derived from the Johnson et al. (2003) study.
EPA should reconsider its assessment of the WOE for the developmental
toxicity endpoint and whether it is appropriate to rely on a single study
that is inconsistent with other studies when making its conclusions on
developmental hazard.
EPA has modified the Risk Evaluation to more
consistently emphasize the key immune
endpoints. Additionally, much of the discussion
on cardiac defects has been moved to Appendix
F. The weight of evidence conclusions for the
cardiac defects endpoint have not changed, but
EPA has bolstered its support of selecting the
two immune studies as the basis for risk
conclusions.
51, 68
PUBLIC COMMENTS:
In the WOE evaluation, EPA concludes that human studies, as a group,
provide suggestive evidence for an effect of TCE on cardiac defects in
humans; this is not an accurate reflection of the uncertainty and poor
reliability of this evidence stream, which severely compromise data
interpretation and integration resulting from the well-published high risk
of bias associated with exposure characterization and confounding
factors, as well as inconsistent results.
Considered in the context of largely weak study designs (cross-
sectional and ecological), this evidence stream has been deemed
inadequate for informing the TCE-fetal cardiac defect hypothesis and
does not agree with prior TCE assessments. Earlier EPA assessments
concluded that "overall, these epidemiologic studies are not
sufficient to establish a causal link between TCE exposure and
EPA has accounted for these considerations in
the assessment of study reliability. In most cases
uncertainties surrounding exposure
characterization are either applicable to both
controls and treatment groups, or they lead to an
underestimation of exposure. EPA agrees that
these studies alone are not sufficient for
establishing a causal link, however they do
establish an association between TCE exposure
and increased incidence of cardiac defects.
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cardiac defects in humans."
Wikoff et al. (2018) applied NTP's OHAT risk-of-bias framework to the
TCE-fetal cardiac defect human studies, which focused on the "internal
validity" of the study design and reporting and determined that the
human TCE-fetal cardiac defect data were of insufficient quality to
inform the direction of an effect. Wikoff et al. (2018) found no consistent
evidence of fetal cardiac effects when integrating animal and
epidemiological evidence.
51, 60
PUBLIC COMMENTS:
EPA inappropriately excluded two inhalation studies (Hardin et al.,
1981; Healy et al., 1982).
Hardin et al. (1981) was scored "unacceptable" for Metrics 7 and 2;
however, EPA had all of the study details in the underlying
laboratory report (Beliles et al., 1980), which it scored overall high
quality but failed to include in the WOE evaluation.
Healy et al. (1982) was scored "unacceptable" on Metric 12. It is
clear investigators used a whole body, dynamic, single animal
exposure cage for each test animal, which meets the definition of a
"medium quality" for this metric.
(Beliles et al., 1980) was not included because
the study report did not contain an indication
that cardiac effects were specifically examined
(See Appendix F.3.1). (Hardin et al., 1981) had
several flaws, including an absence of details on
TCE source, storage, and administration. Healy
et al., 1982 scored unacceptable due to an
absence of details on inhalation chamber and
exposure method. This information was not
provided in the study text.
51
PUBLIC COMMENTS:
Due to the inaccurate absence of Beliles et al. (1980)/Hardin et al.
(1981), and Healy et al. (1982) from the draft WOE, the current WOE
conclusions are in error. Ultimately, EPA excluded inhalation studies
from its WOE that would have demonstrated that the animal TCE-fetal
cardiac defect data are strongly negative for the most relevant route of
exposure for the exposure scenarios assessed.
51
PUBLIC COMMENTS:
EPA scored the TSCA Outcome Assessment Metric (#16) as "High
Quality" for all five of the TCA/DCA studies, including the three earliest
studies (Smith et al., 1989, 1992; Epstein et al., 1992); however, none of
the studies observed atrial septal defects following high-dose exposure.
This metric should have been scored "Low Quality" for failure to
observe atrial septal defects. EPA did not score Metric #19, which
The majority of data quality criteria metrics
apply to the overall study of interest and are
independent of any particular endpoint target
unless otherwise indicated by the study design.
Occasionally a study will be split and evaluated
for different outcomes, however all but a few
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should be a scoring requirement for any study with teratogenic
determinations. Study quality scores are inflated and reflect inconsistent
application of scoring methods.
metrics are likely to be the same. All studies
were reviewed by two subject matter experts
with experience reviewing dozens of studies to
ensure consistency in application of data quality
evaluation across studies. EPA stands by its data
quality evaluation of all studies.
51, 68
PUBLIC COMMENTS:
EPA failed to separately score experiments reported in studies testing
multiple animal species, minimizing negative TCE-fetal cardiac defect
findings for most relevant exposure route (inhalation). This
inappropriately reduced the impact of two separate developmental
toxicity studies (Schwetz et al., 1975; Hardin et al., 1981) - each testing
multiple mammalian species, on the TCE-fetal cardiac defect WOE.
94
PUBLIC COMMENTS:
Narotsky et al. (1995) is a flawed study that should have been excluded
from the systematic review for methodological concerns.
The highest dose likely exceeded the metabolic saturation of TCE.
Use of data at supra-saturating doses is problematic because there
may be secondary high-dose specific effects that do not occur at
lower doses where the toxicokinetics are linear.
At oral doses below metabolic saturation where the data can be used
quantitatively to extrapolate to realistic human exposures, the Narotsky
et al. (1995) study found no adverse developmental effects.
51
PUBLIC COMMENTS:
After correcting several study quality scoring issues, and accounting for
all of the relevant TCE-fetal cardiac defect animal experimental studies
appropriately, an updated WOE is strongly negative.
108
PUBLIC COMMENTS:
EPA should also include/consider the following studies supporting a
mechanistic linkage between TCE and developmental cardiac
malformations prior to finalizing the risk evaluation:
Caldwell, Patricia T., et al. "Gene expression profiling in the fetal
cardiac tissue after folate and low-dose trichloroethylene exposure."
Birth Defects Research Part A: Clinical and Molecular Teratology
88.2 (2010): 111-127.
Selmin O.I., Makwana 0., Runyan R.B. (2014) Environmental
The referenced Caldwell study is a follow-up to
(Caldwell et al., 2008), which was included in
the WOE analysis. This study examines gene
expression changes following TCE exposure but
does not provide any relevant novel information
that would influence the WOE beyond what was
alreadv discussed from (Caldwell et al., 2008)
and (Collier et al., 2003). (Selmin et al., 2008) is
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sensitivity to trichloroethylene (TCE) in the developing heart. In:
Gilbert K., Blossom S. (eds) Trichloroethylene: toxicity and health
risks, molecular and integrative toxicology.
Jin, Hongmei, et al. "AHR-mediated oxidative stress contributes to
the cardiac developmental toxicity of trichloroethylene in zebrafish
embryos." Journal of hazardous materials 385 (2020)
Chen, Sheri, et al. "HNF4a transcription is a target of
trichloroethylene toxicity in the embryonic mouse heart."
Environmental Science: Processes & Impacts (2020).
a review paper that does not contain novel data.
The 2020 studies were published well after the
systematic review literature deadline and were
not included in the WOE analysis, however they
also do not contain novel information that was
not already addressed by other studies that were
included in the WOE analysis.
EPA has added a list of studies in Appendix
F.3.1 that were excluded during screening based
on no direct assessment of cardiovascular
outcomes.
51
PUBLIC COMMENTS:
Several mechanistic studies and a few animal studies relevant to the
TCE-fetal cardiac defect database are absent from the draft risk
evaluation's TCE-fetal cardiac defect WOE. This is evidence of a flawed
systematic review protocol, an inadequate integration of the database,
and thus an incomplete risk evaluation.
51
PUBLIC COMMENTS:
EPA ignored the Caldwell et al. (2010) mouse transcriptomics study, not
including it at all in the draft risk evaluation. This study failed to find
any developmental toxicity in mice.
51
PUBLIC COMMENTS:
EPA ignored the in vivo arm of the Palbykin et al. (2011) study and
instead scored the study based on the cell culture data.
(Palbvkin et al., 2011) was not rated because
there is not a direct connection of Sera2 gene
expression to cardiac toxicity, however it was
cited in Appendix F.3.3 as relevant to the non-
monotonic dose response of the cardiac defects
data. These findings were consistent both in ex
vivo and cell culture.
51
PUBLIC COMMENTS:
EPA's human evidence base is missing an occupational study by Tola et
al. (1980), undermining the completeness of their human assessment.
While this was another study of limited quality, it too failed to
demonstrate an association between in utero TCE exposures and fetal
cardiac defects.
This study was not cited in any previous WOE
assessment, which were the basis of EPA's
literature database for the WOE analysis.
51
PUBLIC COMMENTS:
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EPA excluded the ATSDR Camp Lejeune Study by Ruckart et al. (2013)
from the TCE-fetal cardiac defect WOE because no formal analysis was
conducted by the authors for the fetal cardiac defect endpoint, yet the
fact that this exposed population had lower-than-background fetal
cardiac defects should be included in the WOE.
The study authors were unable to perform any
quantitative analysis and therefore conclusions
cannot be made about cardiac endpoints based
on this study.
67
PUBLIC COMMENTS:
EPA seems to have missed the following relevant study:
Trichloroethylene perturbs HNF4a expression and activity in the
developing chick heart. Harris AP, Ismail KA, Nunez M, Martopullo I,
Lencinas A, Selmin 01, Runyan RB. Toxicol Lett. 2018 Mar
15;285:113-120. doi: 10.1016/].toxlet.2017.12.027.)
This study is included in the WOE analysis.
51
PUBLIC COMMENTS:
It is unclear why EPA includes the rat intra-uterine pump exposure
experiment described by Dawson et al. (1990), considering it "positive"
TCE-fetal cardiac defect WOE. The irrelevant exposure route should
have led EPA to disqualify this study from the WOE.
It is relevant for the plausibility of exposure
leading to fetal cardiac effects.
51, 68
PUBLIC COMMENTS:
EPA reviewed and scored two TCE-fetal cardiac defect positive studies
as separate, single studies in their study quality assessment and WOE
evaluation: Dawson et al. (1993) and Johnson et al. (2003). This decision
artificially inflates the positive animal evidence in EPA's WOE
evaluation because these publications represent the same animal study.
EPA then considers them a single study for the dose-response evaluation.
The recent risk of bias assessment by Wikoff et al. (2018) treated these
studies as a single experimental study.
EPA stands by the results of the WOE analysis.
In considering the conflicting evidence and
varied opinions concerning the validity and
relevance of the cardiac heart defects (CHD)
database, EPA has added text throughout the RE
(Appendix F.l, Section 3.2.4.1.6, Section
3.2.5.3.1, Section 3.2.5.1.6, and Section 3.2.6.1)
acknowledging the uncertainties associated with
this endpoint. EPA acknowledges that while
there is qualitative support for the endpoint,
based on uncertainties in the dose-response for
this endpoint and other considerations EPA has
selected immune endpoints as the best overall
endpoints for risk conclusions (Sections
3.2.5.4.1, 3.2.6.1.1). However, various
biological factors may lead to increased
99
PUBLIC COMMENTS:
The Makris et al. review determined that, "despite the recognized
uncertainties and limitations in the TCE database, the evidence supports
a conclusion that TCE has the potential to cause cardiac defects in
humans when exposure occurs at sufficient doses during a sensitive
period of fetal development." This conclusion is warranted by the data
that demonstrate or suggest a potential hazard to cardiac development,
including epidemiological studies, developmental toxicology studies in
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rodents with TCE and its metabolites (DCA and TCA), avian in ovo
studies, in vitro assays, and mechanistic data that form the basis of a
preliminary conceptual model of an AOP for valvulo-septal defects
resulting from TCE exposures.
susceptibility to CHDs, (e.g., maternal age).
Therefore, CHDs are now classified as a PESS
consideration and the associated POD and risk
estimates are included in the RE in consideration
of PESS subset for which it is most applicable
(e.g., older mothers). Based on the inconsistent
results for this outcome, EPA chose more
consistently supported immune endpoints as the
basis for risk conclusions.
78
PUBLIC COMMENTS:
Multiple lines of scientific evidence clearly indicate that TCE increases
the risk of fetal heart malformations. While the Johnson (2003) study
plays an important role as the source of the POD for the fetal heart
malformation endpoint for TCE, it is important to note that there are
multiple lines of evidence that TCE and/or its metabolites increase risk
of fetal heart malformation. These include:
studies in vitro and in multiple animal species that demonstrate a
mechanism by which TCE and its metabolites cause fetal heart
defects,
epidemiological studies suggesting TCE causes fetal heart defects in
humans, and
in vivo animal studies that show a quantitative dose-response
relationship between in utero TCE exposure and fetal heart defects.
The body of science supporting the fetal heart malformation endpoint is
substantial, as EPA acknowledged in its own draft risk evaluation.
108,
99, 64
PUBLIC COMMENTS:
Multiple lines of evidence support the finding that fetal cardiac
malformations result from gestational exposure to TCE, including
epidemiological evidence, laboratory animal studies, metabolism studies,
and mechanistic studies which were indicated in the 2011 EPA IRIS
TCE assessment and the 2016 review by Makris et al. (2017)
Support for TCE-induced fetal cardiac malformations based on WOE
considerations has also been provided by the EPA Science Advisory
Board (SAB) in its review of the IRIS TCEtoxicological review; an
EPA TCE Developmental Cardiac Toxicity Assessment Update
("Update") following the publication of the IRIS toxicological
review; EPA's 2014 Workplan risk assessment, and EPA's response
for a Request for Correction submitted by the HSIA regarding raising
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concerns regarding EPA's reliance on Johnson (2003).
In Chapter 3 of the draft, EPA named developmental toxicity as among
the most sensitive acute health effects associated with TCE exposure.
However, in its risk determination, inconsistent with previous
assessments and with summary statements in the body of the text, EPA
states that the evidence contains uncertainties that decrease confidence in
the endpoint of fetal cardiac defects. The rationale is unclear.
99
PUBLIC COMMENTS:
Even with the changes allegedly demanded by the Inter-Agency
reviewers, the TCE draft risk evaluation presents a strong case for the
sufficiency of the evidence of TCE-related cardiac effects.
It was concluded that "Overall, the database is both reliable and
relevant and provides positive overall evidence that TCE may
produce cardiac defects in humans based on positive evidence from
epidemiology studies, mixed evidence from animal studies, and
stronger positive evidence from mechanistic studies."
As EPA indicated, "the fetal cardiac defects reported in (Dawson et al.,
1993) and (Johnson et al., 2003) were identified as the most sensitive
endpoint within the developmental toxicity domain and across all of the
health effects domains evaluated in the TCE IRIS assessment."
103
PUBLIC COMMENTS:
EPA should utilize an established framework to organize evidence for
MOA and to support decisions based on a side-by-side WOE comparison
of alternative plausible MO As. Examples:
AOPs to organize potential mechanisms into models that describe
how exposure might cause cancer (e.g., using the approach of the
OECD AOP methodology).
The MOA approach initially championed by the World Health
Organization (WHO)/International Programme on Chemical Safety
(IPCS), which is utilized by other EPA program offices.
MOA confidence scores, as described by Becker et al. (2017).
The available mechanistic data on TCE supports
multiple potential mechanisms that may
contribute to developmental cardiac defects.
However, there is not enough evidence for the
majority of these to support development of a
detailed AOP. EPA discusses mode of action
considerations and the relevance to the observed
non-monotonic dose response in Appendix F.3.3
94
PUBLIC COMMENTS:
A systematic approach, such as the procedure developed by Becker et al.
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(2017), which enables side-by side comparison of numerical WOE
confidence scores for different hypothesized MO As, would provide the
kind of scientific rigor in the selection of dose-response models that the
amended TSCA requires in assessing potential cancer risk of TCE.
51
PUBLIC COMMENTS:
The putative AOP proposed by Makris et al. (2016) is incomplete (lacks
empirical data for a molecular initiating event or subsequent early Key
Events), but it provides a helpful approach to organizing the studies and
their findings, as well as integrating in the higher level toxicological
experiments {in vivo) and epidemiology data.
108
PUBLIC COMMENTS:
There is support for EPA's conclusion that "evidence of a single
dominant MO A is not required in order for the data to support a
plausible mechanism of TCE-induced congenital heart defects,"
particularly given that "teratogens may function through a multitude of
pathways, often resulting in a constellation of effects."
While defined MO As are not required for hazard identification, it
should be noted that Makris et al. developed a preliminary AOP
providing biological support for TCE-induced cardiac effects,
specifically valvulo-septal defects, following developmental
exposure.
The WOE for congenital heart defects is robust, with corroborating data
across mechanistic, animal, and human studies. A requirement that a
MOA must be defined to legitimize this evidence is both unscientific and
unprotective of public health.
108
PUBLIC COMMENTS:
EPA appropriately recognizes that developmental studies are relevant for
evaluating acute exposure scenarios.
EPA acknowledges this comment.
66
PUBLIC COMMENTS:
One of the criteria associated with a systematic review is a Risk of Bias.
An element of that criteria is the source of study support. Except for
Fisher et al. (2001), the entire body of literature challenging the link
between TCE and heart defects (including Urban et al.) has been
EPA considered all data equally in evaluating
the cardiac toxicity WOE.
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supported by the HSIA and ACC industry associations. One could view
the entire "controversy" on this link as a construct of these two
organizations.
Immunotoxicity evaluation
SACC
SACC COMMENTS:
One Committee member concluded that the TSCA program is struggling
to integrate immunotoxicity into its chemical risk evaluations, as
evidenced by the poor discussion and justification applied to
inclusion/exclusion criteria used to identify key immunotoxicity studies
and by the imprecision of terms used to discuss immunotoxicity in this
draft risk evaluation.
EPA has improved the discussion of
immunotoxicity in the assessment. Data on
immune enhancement has been separated from
discussion of immunosuppression, and
additional studies have been added to the
immunotoxicity hazard identification section
(3.2.3.1.4). There is strong evidence in support
of both autoimmunity and immune suppression
as indicated throughout the Risk Evaluation.
SACC
SACC COMMENTS:
Recommendation: Use and define more precise terms in discussing
immunotoxicity.
The draft risk evaluation uses imprecise language to discuss
immunotoxicity. For example, the use of terms such as "allergic
respiratory sensitization" and "sensitization/hypersensitivity" need to be
better defined. Although such vague terms are often found in the
literature, they can and should be replaced by more precise and
informative terms (e.g., one Committee member suggested using more
precise designations such as Type I, II, III, or IV hypersensitivity).
SACC
SACC COMMENTS:
Recommendation: Clarifications and corrections are needed.
Section 3.2.3.1.4, pp. 212-214; lines 837-895: In the overview of
immunotoxicity and sensitization, there appears to be confusion
regarding immuno-suppression vs. immuno-stimulation. The statements
in lines 839-840 appear contradictory to the statement in line 868.
SACC
SACC COMMENTS:
Recommendation: Consider separating indicators of immune-
enhancement and immunosuppression and discuss how these indicators
reflect different MO As.
Based on the difference in mechanisms between acute and chronic
immune effects, the draft risk evaluation should be especially careful not
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to suggest some false equivalence. The draft risk evaluation states that in
general, immunotoxic effects in animals and humans were associated
with an enhanced immune response rather than an immunosuppressive
effect (draft risk evaluation, p. 212, lines 839-840). However, the first
paragraph on animal data (draft risk evaluation, p. 213, lines 872-880)
suggests that support for immunotoxicity is provided by decreased
thymus weight and cellularity in mice (Keil et al., 2009). The Committee
recommended that the risk evaluation not put indicators of immune-
enhancement and immunosuppression in the same category and think
more about MOA where these processes and indicators are different.
103
PUBLIC COMMENTS:
EPA should include a more complete discussion of the available
literature on issues affecting immunotoxicity in the WOE section for this
endpoint. Specifically, EPA should add additional explanation of the
overall confidence in and uncertainties across the body of evidence,
including additional discussion of: (1) the difference in risk profiles and
etiology of autoimmune and immune effects, (2) alternative explanations
that may be plausible for some or all of the observed associations, and
(3) the strengths and weaknesses of the available literature. An enhanced
WOE discussion would improve transparency in EPA's conclusions
regarding hazard and its risk characterization.
Choice of best representative POD
SACC
SACC COMMENTS:
Some Committee members commented that there is the impression of
bias in the descriptions of the fetal cardiac malformations in relation to
the literature, especially the Johnson et al. (2003) and the CRL (2019)
studies. The Committee recommended that EPA consider a full and
complete description of the issue (i.e., why is this endpoint so
controversial?) and provide a more complete discussion of other relevant
studies to help explain the results relevant to data coherence between
studies conducted by the same route of administration (e.g., Is there
coherence in the available literature? Is it consistent with oral, inhalation
exposures or both?). Committee members brought up a concern related
EPA has expanded the justification for selection
of the immune studies as the best overall
endpoints. EPA believes these endpoints
represent the "best available science" based on
the weight of scientific evidence in accordance
with TSCA and the use of these endpoints for
risk conclusions was supported by SACC peer
reviewers
(http s: //www. resul ati ons. sov/document?D=EP A
-HO-OPPT-2019-0500-0111). TSCA reciuires to
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to the questions raised publicly regarding alleged changes to the draft
risk evaluation. The claim stated that the draft provided for interagency
review identified fetal cardiac malformations as the most sensitive
endpoint, and used this value to derive the PODs for making
determinations of risk, a decision that was consistent with prior reviews
of TCE (e.g., EPA's 201 1 IRIS review; U.S. EPA, 201 1). This public
allegation in part justified the Committee engaging in an extensive
discussion of the draft risk evaluation's rationale for excluding fetal heart
malformations as the endpoint for setting the POD.
select exposure and hazard values based on the
best available science, not simply the lowest
values. Additionally, EPA has expanded
discussion of the history of (Johnson et al
2003) and the cardiac defects endpoint in
Appendix F.l.
EPA routinely conducts Inter-Agency review of
its TSCA Risk Evaluation before SACC peer
review and public comments. Federal experts in
toxicology, epidemiology, and industrial
hygiene among other disciplines help EPA
develop more comprehensive and rigorous risk
evaluations. In this particular Inter-Agency
review EPA discussed, among other things, the
strengths and weaknesses associated with use of
the cardiac defects endpoint as the basis of the
risk conclusions. Based on these discussions,
EPA concluded that whereas evidence indicates
that CHDs may be of concern for susceptible
subpopulations, the inconsistency of the data and
reduced confidence in dose response results
suggest that it is not the best indicator of TCE
toxicity overall. For purposes of risk evaluations
under TSCA, EPA chose to use immune
endpoints as the indicator of TCE toxicity based
on their consistency, reduced uncertainty, and
robustness of the data. EPA has created a new
subsection identifying and justifying the two
immune endpoints as best overall for use in risk
conclusions (Section 3.2.5.4.1).
100, 34
PUBLIC COMMENTS:
EPA acknowledges an association between TCE and fetal cardiac
malformations occurring at doses lower than those that cause any other
adverse health effect. However, in a departure from prior EPA risk
assessments, EPA fails to base its calculations of TCE's risk on that most
sensitive endpoint. The draft should be revised to restore heart
development as a driver of exposure standards.
78
PUBLIC COMMENTS:
EPA should use the fetal heart malformation endpoint as the critical
endpoint for determining whether various uses of TCE present
unreasonable risk.
OHA and DEQ disagree with the decision to not select fetal heart
malformations as the critical endpoint because of the severity of the
potential health outcome.
EPA stated "Neither the statute nor the framework rule require that EPA
choose the lowest [POD]." The lack of a requirement to use the most
health protective POD does not preclude it, especially when good
science indicates the potential for severe health outcome in a sensitive
population. EPA should not use a less sensitive endpoint in lieu of a
more sensitive endpoint just because the less sensitive endpoint has more
scientific certainty. The available science justifies using the more
sensitive fetal heart malformation endpoint as the POD for TCE.
78
PUBLIC COMMENTS:
OHA and DEQ have grave concerns that EPA has rejected the vvell-
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vetted, peer-reviewed science on fetal hemi malformations as the
basis for making determinations about which types of product-use
exposures (industrial, commercial, domestic, etc.) pose unreasonable
risk in their TSCA draft risk evaluation. The POD for this health
effect (endpoint) is important for the protection of a vulnerable
population - developing human fetuses. The draft risk evaluation
shows that nearly all types of TCE use would pose unreasonable risk
to developing human fetuses, even with the most rigorous use of
PPE. Ignoring this endpoint in making official risk determinations
could allow continued, unsafe TCE exposures to developing fetuses if
any future actions EPA takes to limit exposure do not consider the
more sensitive endpoint of fetal cardiac malformations.
73
PUBLIC COMMENTS:
Study scoring is inappropriately used to support the use of immune-
related endpoints rather than fetal cardiac malformations to derive PODs
for determinations of risk.
47
PUBLIC COMMENTS:
We were struck by the tortured logic being applied to justify the choice
of endpoints for the quantitative assessment of acute and chronic non-
cancer effects, and then learned that Inter-Agency reviewers allegedly
directed EPA not to use fetal heart defects, the most sensitive endpoint,
for determination of unreasonable risk. We view this alleged intervention
into the scientific assessment of a high-profile chemical as one of the
most egregious acts we have witnessed in our collective century-plus
years of experience at the agency. It raises the spectre that less-visible
manipulations have occurred in earlier draft risk evaluations and
prospects of the same for risk evaluations to come. The credibility of the
once-promising amended TSCA risk evaluation program for existing
chemicals is now shattered.
47
PUBLIC COMMENTS:
The PODs derived from the Johnson et al. study should be used in the
assessment of all acute and chronic occupational exposure scenarios and
all acute consumer exposure scenarios.
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As currently articulated in the draft risk evaluation, it would appear
that EPA is employing a new and unvetted policy of selecting the
most "representative" over the most sensitive endpoint, an approach
at odds with longstanding agency-wide risk assessment practices.
The factors selected for consideration under this new policy do not
include sensitivity and appear to be arbitrary and capricious,
designed to provide EPA with complete discretion to ignore the most
sensitive endpoint.
In addition to providing the most sensitive endpoint, congenital heart
defects, the Johnson study has the lowest cumulative uncertainty
factor and highest relevance to the endpoint of interest and human
exposure scenarios of all the studies chosen for derivation of the
POD. The low cumulative uncertainty factor is backed by the
positive WOE supporting this study, with epidemiology and
mechanistic studies compensating for the mixed evidence from
animal studies.
It is critically important that EPA not replace the protective public health
policy of selecting the most sensitive endpoint with this arbitrary and
capricious "representative policy." There is no scientific justification for
this new policy.
88, 86
PUBLIC COMMENTS:
We are gravely concerned with EPA's failure to identify fetal heart
defects, the most sensitive health outcome affecting the most sensitive
group, as the key risk of exposure to TCE. This means that the chemical
will not be regulated at a level to protect against this outcome. This lack
of regulation grants a long-held wish of the chemical industry that
ignores decades of scientific research.
83, 36
PUBLIC COMMENTS:
The studies are pretty clear that fetal cardiac defects occur at doses 500
times lower than the immune diseases that EPA is using for the
maximum allowable exposure. Given that the best information we
currently have strongly supports that TCE is toxic to human fetuses at
much lower doses than EPA is considering for future regulations, then
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we MUST maintain the stricter regulations. It makes no humanitarian
sense to use a 500 times higher maximum exposure dose until proven
wrong.
108
PUBLIC COMMENTS:
EPA presents a rigorous case for the congenital heart defect endpoint
throughout the draft, considering multiple lines of evidence that
converge into an integrated strength area score of (+). EPA highlights the
robust evidence base multiple times. This endpoint should be considered
in the quantitative assessment of the health hazards of TCE.
108
PUBLIC COMMENTS:
EPA's reliance on immune-related endpoints, instead of congenital heart
defects, for its determinations of acute and chronic risk deviates from
scientific best practices, defies requirements under the law, and is not
sufficiently protective of public health and vulnerable subpopulations.
The WOE supports TCE-induced congenital heart defects. Multiple lines
of evidence support the finding that congenital heart defects result from
gestational exposure to TCE, including data from epidemiological, in
vivo, and in vitro studies. This is the conclusion of the draft risk
evaluation, as well as previous peer and SAB-reviewed analyses (e.g.,
2011 EPA IRIS, Makris et al., 2016). Failure to protect against the most
sensitive endpoint, congenital heart defects, is a major concern.
108
PUBLIC COMMENTS:
The SACC meeting indicated that there was not a consensus among
members over EPA's decision to jettison reliance on heart defects as the
key driver for TCE's risks.
Some members believed this was a critical endpoint that was
supported by the WOE, despite acknowledging that there was some
uncertainty in the literature that posed challenges for moving from
hazard identification to dose-response modeling. Other members also
noted the extreme nature of scrutiny paid to studies identifying
congenital heart defects in comparison to that applied to the immune
studies, as well as the changes made in response to political
interference.
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Other members supported EPA's decision, arguing that the heart
defect endpoint was an outlier, emphasizing flaws in supporting
studies, and placing greater weight on studies sponsored by the
chemical industry that did not replicate those effects.
A question posed was: How can EPA protect against risks of a health
endpoint that the WOE indicates is real and that some studies show
occurs at very low doses, if there is a view by some that the data are not
ideal for dose-response modeling? How would reliance instead on a non-
developmental endpoint that shows effects only at higher doses fulfill
EPA's responsibility under TSCA to identity and protect against risks to
the most vulnerable subpopulation? EPA must rely on this endpoint to
ensure protection a vulnerable subpopulation.
106
PUBLIC COMMENTS:
EPA's rationale for changing the representative acute non-cancer
endpoint is unclear and inconsistent within the draft risk evaluation.
Throughout the draft, we found scientifically unsupported, unclear,
and inconsistent statements around the evidence base for fetal cardiac
defects and EPA's choice of representative acute non-cancer
endpoint.
EPA's previous claims in its IRIS assessment and TSCA Work Plan,
and current claims in Chapter 3 of the draft risk evaluation (Hazards),
find that the fetal cardiac defects endpoint was the most sensitive
(thus should be chosen as the representative non-cancer endpoint),
with the support of animal, epidemiological, and mechanistic data.
However, Chapter 5 of the draft risk evaluation (Risk Determination)
rewrites the scientific evaluation of fetal cardiac defects, claiming
that there are uncertainties that decrease EPA's confidence in this
endpoint. This internal inconsistency and rewrite of the scientific
evaluation suggests that there may have been some type of
interference in this document.
EPA chooses the immunosuppression endpoint proposed by Selgrade
and Gilmour (2010), without justification for why the fetal cardiac
defects endpoint was insufficient to serve as the representative endpoint
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and despite just stating that "confidence is raisedfrom the robust WOE
analysis performed on the congenital heart defects endpoint. "
106
PUBLIC COMMENTS:
EPA is inconsistent with its reporting of study conclusions throughout
the draft risk evaluation.
For example, on p. 215, EPA states that Yauck et al. (2004) observed
a strong relative risk estimate for cardiac malformations in infants
born to TCE-exposed mothers aged 38 years or older, but later calls
the Yauck conclusions equivocal or ambiguous, because the study
"reported a positive association between congenital heart defects and
TCE exposure only in older mothers, while younger mothers and the
overall population had a null association," even though it is
previously stated that "Maternal age is known to have a large
influence on the incidence of congenital heart defects" and that
"Among pregnant women, older women may be especially
susceptible to TCE-induced cardiac defects in their offspring."
These inconsistencies threaten the validity of the risk evaluation and
appear to incorrectly downplay the strength of the fetal cardiac defect
endpoint in support of an immunosuppression endpoint whose POD is
orders of magnitude less protective.
The distinct statements are not mutually
exclusive. There is statistically significant risk
identified for older mothers, however there was
a null association for mothers overall. Evidence
such as the (Yauck et al., 2004) data supports the
decision to consider the congenital heart defects
endpoint only applicable to susceptible
subpopulations.
106
PUBLIC COMMENTS:
Chapter 3 of the draft risk evaluation is in conflict with respect to
developmental endpoints. On p. 257, EPA states that "Confidence is
reduced from a high due to the data quality scores, the wide range of
PODs, and controversy over the most sensitive POD (Johnson et al.,
2003). For developmental endpoints, there is some uncertainty
extrapolating from chronic developmental toxicity studies to acute
exposure, especially in assuming a consistent dose-
response. . .Confidence is raised from the robust WOE analysis
performed on the congenital heart defects endpoint (see Appendix G),
the presence of a variety of endpoints including a study using acute TCE
administration, and reduced uncertainty factors due to the use of PBPK
model or allometric scaling." In the next line, EPA chooses the
EPA has added justification for the selection of
the immune PODs as the representative acute
and chronic endpoints and has highlighted their
selection throughout the risk evaluation,
including a new section, 3.2.5.4.1. The
referenced values in IRIS (RfD, RfC) are based
on multiple endpoints, namely the kidney
toxicity endpoint and the autoimmunity endpoint
in addition to fetal cardiac defects. Risk
estimates for each of these endpoints are
included in the risk evaluation, and the
autoimmunity endpoint is the POD from (Keil et
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immunosuppression endpoint proposed by Selgrade and Gilmour (2010)
without providing justification for why the fetal cardiac defects endpoint
was insufficient to serve as the representative endpoint. EPA asserts in
the evaluation that the data for fetal cardiac defects is not robust enough
to represent acute non-cancer endpoints and instead chooses
immunosuppression as the sensitive endpoint for acute inhalation and
dermal exposures as it is . .considered to be the most robust and best
representative POD for acute non cancer scenarios." Although EPA
indicates that the endpoint of fetal cardiac defects was not sufficiently
robust and thus not a good candidate as the non-cancer endpoint for
TCE, this is inconsistent with its IRIS assessment, which found that
regarding fetal cardiac defects, "[tjhere is high confidence in these
noncancer reference values, as they are supported by moderate-to-high
confidence estimates for multiple effects from multiple studies."
al 2009), which was selected as the best overall
chronic endpoint in this risk evaluation. Risk
estimates for the cardiac defects endpoint are
still included in the risk evaluation, however
based on uncertainties in the dose-response for
this endpoint and other considerations EPA has
selected immune endpoints as the best overall
endpoints for risk conclusions (Sections
3.2.5.4.1, 3.2.6.1.1).
EPA does not directly compare numerical
scores, just the overall bin. The metrics are not
designed for that granularity. Additionally, 0.3 is
a relatively large difference (almost no study
scores higher than a 2 without being
unacceptable, with higher scores indicating
lower quality and 1.0 being the best possible
score).
106
PUBLIC COMMENTS:
EPA's choice of a representative acute non-cancer endpoint is less
sensitive, less protective of vulnerable populations, nor consistent with
best practices in scientific evaluation and use.
EPA indicated "... the POD for mortality due to immunosuppression
from Selgrade and Gilmour (2010) is considered to be the most
robust and best representative POD for acute non-cancer scenarios."
However, it fails to sufficiently detail what makes this choice of
endpoint more robust and the best representative.
This choice is in contrast to EPA's IRIS assessment, which derived
its RfD for non-cancer effects of 0.0005 mg/kg/day based on the
critical effect of heart malformations and concluded there was high
confidence in this RfD.
The POD from the Johnson (2003) study is much lower than that
from the Selgrade and Gilmour (2010) study, while data quality
scores from both studies were similar (1.6 vs. 1.9).
EPA has failed to justify why it is unable to use the POD for fetal
cardiac defects, which is orders of magnitude more protective than
the immunosuppression endpoint, as the acute non-cancer endpoint.
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If EPA were to pursue the representative endpoint of
immunosuppression, EPA would be allowing acute exposures that
are significantly greater than the POD for fetal cardiac defects and
would fail to account for the particular sensitivity represented by
developmental endpoints.
Choosing to use the immunosuppression endpoint in comparison to
the fetal cardiac defect endpoint means discarding a more sensitive
endpoint that has evidence of hazard to human health and which
accounts for potential exposure to susceptible subpopulations, such
as fetuses, pregnant women, infants, and children.
Considering the disparities between PODs for the two endpoints and the
potential human health ramifications due to this inadequately
representative non-cancer endpoint for TCE, EPA should use fetal
cardiac defects as the basis of the non-cancer acute health effects and the
subsequent risk assessment.
108
PUBLIC COMMENTS:
During the SACC meeting, one reviewer noted several general
population studies found associations between a variety of TCE exposure
metrics and birth defects (central nervous system [CNS] and neural tube
defects, congenital heart defects, oral clefts) and growth measures such
as small for gestational age and term low birth weight. These studies
involved numerous communities (Woburn, MA; Endicott, NY; northern
NJ; Camp Lejeune, NC; Milwaukee, WI; and Tucson, AZ), state registry
studies (MA, TX), and a national birth defects prevention study. Failing
to include this endpoint in EPA's determination of unreasonable risk
would ignore a documented and serious health concern that should play a
major role in setting limits on TCE exposure and use.
The risk evaluation discusses these
epidemiological studies and associated effects in
Section 3.2.3.1.6. Risk estimates are provided
for multiple developmental endpoints covering
developmental neurotoxicity, developmental
mortality, and congenital defects. EPA has the
discretion to make unreasonable risk
determinations based on other risk benchmarks
or factors as appropriate. EPA's unreasonable
risk determination (Section 5) considers multiple
risk-based factors including the uncertainties in
the analysis (Section 4.3). In considering
uncertainties surrounding these endpoints
(Section 3.2.6.1.1), the immune endpoints were
determined to be the best overall endpoints for
risk conclusions and risk determinations
(Section 3.2.5.5.1).
105
PUBLIC COMMENTS:
Developmental effects are not adequately considered in the draft risk
evaluation. As a result, the evaluation does not sufficiently address the
pregnant woman and her developing fetus, which represent a susceptible
subpopulation. The draft risk evaluation presents evidence that TCE can
cause developmental toxicity, cites studies that can be used for hazard
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identification and dose-response assessment, and concludes that the
WOE indicates TCE produces fetal heart defects. Despite this finding,
the risk determination (Section 5) does not consider this endpoint and
does not provide an adequate rationale for dismissing developmental
studies that were previously used in the peer-reviewed IRIS document
(U.S. EPA, 2011). Developmental effects are often the most sensitive
endpoint. EPA should develop and present toxicity values that are
sufficiently protective against the adverse developmental effects of TCE.
90
PUBLIC COMMENTS:
In previous risk evaluations for TCE under TSCA, EPA has consistently
concluded that the weight of the scientific evidence supports
teratogenicity of TCE exposure and fetal heart malformations. Fetal heart
malformation has been considered the standard for the most sensitive
endpoint for TCE exposures, and consequently these adverse effects
have driven risk determinations for acute and chronic TCE exposure.
Since the last risk assessment for TCE, a WOE analysis of
epidemiological, toxicological, in vitro, in ovo, and mechanistic/AOP
data concluded that TCE has the potential to cause cardiac defects in
humans when exposure occurs at sufficient doses during a sensitive
window of fetal development (Makris, 2016). The study that had formed
the earlier basis for this association by Johnson et al. was reaffirmed as
suitable for hazard characterization. However, this draft risk evaluation
downgrades consideration for these previously accepted studies by
saying that there may be scientific uncertainties associated with TCE
exposures. This is inconsistent with the weight of the scientific evidence
as described by Makris et al. As a result of the downgrade of previously
accepted scientific evidence, this draft risk assessment has chosen a
much less vigorous endpoint that is based on immunotoxicity impacts.
Exposure limits based on immune effects are far higher in this risk
assessment than those for fetal heart malformation and would therefore
inadequately protect developing fetuses. This risk evaluation dismisses
the WOE supported by sound science with defective analysis, even when
the most vulnerable of special populations, the developing fetus, is put at
EPA's WOE analysis is consistent with the
conclusions of (Makris et al., 2016). (Makris et
al., 2016) did acknowledge that the database and
dose-response for the cardiac defects endpoint
had significant uncertainty, however the weight
of the scientific evidence supported the
association between TCE exposure and
developmental cardiac malformations. This risk
evaluation comes to the same conclusion based
on a rigorous, detailed WOE analysis that
considers all relevant studies in the database
scores for reliability, relevance, and strength of
the response. EPA does not consider costs or
other non-risk factors in the risk evaluation.
Page 239 of 408
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higher risk of fetal malformation. Clearly, EPA has replaced the
Precautionary Principle with a Cost-Benefit Analysis calculation. We
strongly urge EPA to revert to a weight-of-the-scientific-evidence
approach for their risk assessment and prioritize vulnerable populations,
in this case fetuses, in the final evaluation for TCE.
99
PUBLIC COMMENTS:
EPA is wrong that its "representative endpoint" of immune effects
"would address other identified risks." The acute HEC99 (99th percentile
for human equivalent concentration [HEC]) for immune system effects is
470 times higher than the acute HEC99 for heart malformations. This
significant disparity translates into large differences in the acute MOEs
for the two endpoints. For example, EPA calculated acute inhalation
MOEs (high-end exposure/no PPE) for workers in batch open top vapor
degreasing operations of 0.000014 for heart defects but 0.67 for immune
effects. Both MOEs are far below the benchmark MOEs for these
endpoints but the MOE for heart defects is over two orders of magnitude
below the MOE for immune effects.
Accordingly, the large number of pregnant women exposed to TCE
would be unprotected from fetal heart defects in their offspring by an
exposure limit based only on immunotoxicity.
EPA has clarified that these risk estimates would
address "most" other identified risks. EPA has
also added additional POD derivations for the
key immune endpoints specific to occupational
scenarios in order to account for increased
exposure due to elevated breathing rates in
workers. For these occupational PODs, the
resulting chronic risk estimates based on (Keil et
al 2009) are within 2.6-fold of the results for
Johnson et al 2003 when accounting for
differences in benchmark MOE. Additionally,
EPA has increased confidence that the (Keil et
al 2009) MOEs are applicable to the entirety of
the population evaluated in the risk evaluation.
99
PUBLIC COMMENTS:
The claim that the data supporting immune effects are significantly more
"certain" than the evidence of heart defects is incorrect and based on a
selective and misleading comparison of the WOE for the two endpoints.
According to EPA, "the POD for mortality due to immunosuppression is
considered to be the most robust and best representative POD for acute
non-cancer scenarios."
However, EPA's considerations for selecting this endpoint also apply
to the heart defect database (e.g., heart malformations are an
extremely "severe" effect; the Johnson study used a "broad dose
range;" the "dose response curve" in Johnson was clear and
consistent; and while Johnson was a repeated-dose study, EPA's
longstanding policy is that a single exposure to a chemical within a
EPA disagrees with the commenter that there is
not increased confidence in the immune
endpoints. While all studies selected for dose-
response analysis are medium or high quality
and contain broad dose ranges and sensitive
endpoints when possible, they still contain
varying uncertainties, resulting in varying
confidence in the resulting POD. EPA agrees
that data quality is only one aspect of
consideration for selecting robust endpoints,
however the immune endpoints involve
significantly less uncertainty in the dose-
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critical window of fetal development can cause adverse effects.) The
different quality scores of the two studies, "medium" for Johnson and
"high" for Selgrade and Gilmour, are unimportant compared to their
strength in demonstrating adverse effects and the overall WOE
supporting their findings.
UFs for immune effects were higher than for the fetal heart
malformations. The UF for fetal heart defects was 10 and for acute
immunosuppression effects was 30 "because the data was not subject
to PBPK modeling and therefore a HEC99/HED99 value was not
applied which would have accounted for human toxicokinetic
variability."
EPA expressed concerns about the Selgrade study in its draft risk
evaluation, observing that a "reliable BMDL could not be obtained
from the percentage infected data because BMDs and BMDLs from
all models were well below the lowest data point and cannot be
considered reliable."
The SACC should recommend that EPA revise the draft to use the heart
defect data for addressing TCE's acute and chronic risks to human health
and, as the most sensitive endpoint, the key driver for determining
whether TCE presents an unreasonable risk of injury.
response results. Additionally, the (Selsrade and
Gilmour, 2010) endooint now also has a UF =10
because EPA has run the study data through the
PBPK model to obtain more accurate dose-
response results, further increasing confidence in
the endpoint. The "percentage infected" data
was not used for POD derivation, so those
results have no impact on confidence in the POD
for mortality. EPA presents reasoning for
selection of the two immune endpoints as the
best overall acute and chronic PODs in Section
3.2.5.4.1.
108
PUBLIC COMMENTS:
It is inappropriate to use study quality as the sole basis for endpoint and
study selection. Study quality is an appropriate consideration of the
adequacy of published research to serve as the basis for dose-response
analyses. After inappropriate studies are eliminated as candidates for
dose-response analyses, other considerations, such as sensitivity, should
form the basis for endpoint selection for dose-response analysis.
EPA erroneously prioritizes study quality above all else in selecting
the immune endpoints as the basis for its risk determinations for
acute and chronic non-cancer risks.
When selecting between studies of the same endpoint EPA reviews
both High and Medium quality studies and chooses to advance the
Medium quality studies to represent those endpoints.
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This approach seems intended to allow EPA to derive less-protective
hazard values and use them to underestimate risk, to the benefit of
industry, allied interests and to the detriment of public health.
105
PUBLIC COMMENTS:
"Medium quality" evidence should not be disregarded. If EPA limits its
evaluations to consider "high quality" information only, then it will
severely impair EPA's ability to develop health protective
determinations or guidelines. For many chemicals, there is a limited
amount of high-quality toxicological information available.
74
PUBLIC COMMENTS:
EPA's numerical scoring plays a nefarious role in this draft, whereby
EPA claims the evidence for fetal cardiac defects are of "medium"
quality while that for immune effects is "high" quality leading EPA to
rely on risk estimates orders of magnitude less than should be the case.
Selgrade and Gilmore (2010) as source of best representative POD for acute efl
'ects
SACC
SACC COMMENTS:
Recommendation: Highlight the uncertainty inherent in relying on one
study to establish the immune endpoint.
The Selgrade and Gilmour (2010) study represents an appropriate
choice for evaluating the acute effects of TCE on the immune
system, although it has not been validated.
The draft risk evaluation must make clear that acute immuno-
suppressive response is based on a single study. It should be
acknowledged that while this study is novel with respect to TCE, it
by no means reports a novel response or study design in the
inhalation toxicology literature. The text should highlight the higher
uncertainty inherent in relying upon a single study in isolation to
evaluate the most sensitive response.
(Selsrade and Gilmour, 2010) is actuallv a
repeat of (Aranvi et al. 1986), which identified a
lower NOAEL but had issues with mortality in
controls. Therefore, it was not a completely
novel study or result and the finding is not only
based on a single study. Additionally, the 25
ppm NOEL is in the same
range as the lowest observable effect for the
vacuolation of Clara cells reported after a single
6-h exposure to TCE concentrations as low as 20
DDm in CD-I mice (Odum et al., 1992).
SACC
SACC COMMENTS:
While six valid criteria were listed in justification of utilizing the
Selgrade and Gilmour data, none of these points really address whether
this endpoint is the most representative or most sensitive and, therefore,
the most protective. This conclusion should be more directly stated.
The selection of the immune endpoints as the
best overall endpoints for risk conclusions has
been made more clear throughout the document
and is established in a new Section 3.2.5.4.1.
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SACC
SACC COMMENTS:
The draft risk evaluation should consider reducing the POD based on
the extrapolation of a reasonable sublethal effect. While the use of
mortality as an endpoint is both clinically relevant and unequivocal, it
brings into question whether this is effective as a protective POD,
because one would expect other functional effects that precede
mortality to occur at even lower doses.
EPA accounts for the severity of the endpoint by
using a 1% BMR. EPA was unable to BMD
model sublethal endpoints from the study,
however any sublethal effects would be subject
to a higher BMR which would be less sensitive
than the 1% BMR that was used. Selection of a
lower BMR based on the severity of an effect
(referred to in the Guidance as a "frank effect")
is consistent with EPA BMD guidance (U.S.
i). Considerations for BMD modeling
are provided in Appendix G.
The committee appears to have confused the
data for number of mice infected with the data
for mortality. EPA ran BMD modeling for both
endpoints. Table Apx F-5 (now labeled
Figure Apx F-5) is the plot for number of mice
infected, which was not considered reliable. The
data for mortality was instead used for dose-
response analysis and POD derivation.
EPA agrees the use of mortality may
underestimate risk, however the use of a
sublethal endpoint would also involve a higher
BMR selection. EPA will acknowledge this in
the uncertainties section. EPA modeled the
number of mice infected as an attempt to
examine sublethal effects, however sample sizes
and dose selection for that and other sublethal
endpoints were insufficient for use in dose-
response.
108
PUBLIC COMMENTS:
A POD based on mortality from the Selgrade and Gilmour study is not
protective of public health.
SACC panelists highlighted that using mortality to derive the POD
results is an underestimation of sublethal effects. There are expected
to be toxic effects on the immune system below the level that causes
death. As such, this mortality endpoint is not expected to be
sufficiently protective against more sensitive, sublethal endpoints
across the population.
EPA guidance directs EPA to choose the most sensitive endpoint, which
is congenital heart defects in the case of TCE.
SACC
SACC COMMENTS:
Selection of a 1% benchmark response [BMR] due to lethality is
consistent with other POD derivation in the document (e.g.,
congenital heart defects), but it is not clear whether this is consistent
with EPA policy or is fully a professional judgment call by the
authors. For the sake of transparency, this should be explained.
The benchmark MOE based on UFs is clearly described; however, a
more detailed description would be preferable relative to the choice
of UFa and UFh based on the fact that such a conservative POD
(based on 1% BMR) is selected.
To several of the Committee, the fit of the data is unclear in the
Benchmark Dose Software (BMDS) Figure (Appendix F, p. 599,
Table-Apx F-5) and the model fit is questionable. The data from
Selgrade and Gilmour (2010; i.e., the doses presented) do not match
up with those described in the text (i.e., 0, 80, 100, 200 ppm
Page 243 of 408
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presented; 0, 5, 10, 25, 50, 100, 200 ppm, but not found in BMDS
model); moreover, measures of variance are not provided in the
paper.
The data used to generate I-bars in the BMDS model were not clear
to some of the Committee. Some on the Committee recommended
not trying to fit those data, instead, but suggested using the no-
observed-effect level (NOEL) of 100 ppm as a POD instead.
95, 103
PUBLIC COMMENTS:
There is some question as to whether the immunosuppression in mice
observed by Selgrade and Gilmour is relevant to assessing acute risks to
human. Mice exhibit a specific lung toxicity to chemical agents like TCE
that may contribute to the observed inflammatory response and resulting
mortality. The response reported could be associated with effects on
Clara cells which are enriched in mice relative to rats and humans and
could make mice uniquely vulnerable to infection. Without confirmation
of a similar response in rats, it is not clear what role mouse lung-specific
toxicity plays in the increased mortality seen in the TCE-exposed mice.
It should be considered whether the dose in this study was of a level that
could cause respiratory irritation.
The observations and dose-response observed in
Selsrade and Gilmour, 2010 are consistent with
those observed in chronic immunosuppression
studies (Sanders et al.. 1982; Woolhiser et al.,
2006) on both mice and rats.
105
PUBLIC COMMENTS:
The assessment of acute exposures should be based on developmental
toxicity.
Although the draft describes how developmental endpoints are
relevant to acute scenarios, consistent with EPA guidelines, a
different endpoint was ultimately chosen (mortality due to
immunosuppression) because "there is some uncertainty
extrapolating from chronic developmental toxicity studies to acute
exposure, especially in assuming a consistent dose-response.. .this
may possibly result in an overestimation of risk for some scenarios."
EPA should include developmental toxicity in the assessment of
acute exposures, since this approach would be health protective and
follow EPA guidance. More specifically, EPA should use the POD
from Kiel et al. (2009), with a total UF of 100, for assessment of
Multiple developmental endpoints are included
in risk estimation of acute exposures. MOEs are
provided for congenital heart defects,
developmental neurotoxicity, and developmental
mortality.
EPA would not consider applying a chronic
POD to an acute scenario when there is a robust
studv evaluating acute exposure. The (Keil et al.,
2009) is not comparable to the (Selsrade and
Gilmour, 2010) studv, as thev evaluated
differing exposure scenarios and observed
different immune outcomes.
Page 244 of 408
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acute exposure scenarios, rather than the endpoint of mortality due to
immunosuppression (Selgrade and Gilmour, 2010). This should be
done to provide better protection of developmental toxicity.
Keil et al. (2009) as source of best representative POD for chronic effects
SACC
SACC COMMENTS:
Recommendation: Reevaluate the quality ratings of the four chronic
immunotoxicity studies by Keil et al. (2009), Kaneko et al. (2000),
Sanders et al. (1982), and Woolhiser et al. (2006). These studies have
significant limitations that should affect their quality rating (all currently
medium or high).
Considerations relevant for evaluating immunotoxicity studies
include: (1) whether the choice of animal model and methodology
are optimal for the scientific question being asked, (2) whether the
proper controls were used, such that the reader can determine
whether the immune assay actually worked, and (3) whether the data
are properly evaluated and the conclusions reached were legitimate.
These criteria need to be incorporated into the study rating.
It is not clear how the Keil et al. (2009) study was assigned a "high"
quality rating when critical information regarding exposure is not
provided (e.g., neither purity, stability, nor homogeneity of TCE
concentration is reported; although water concentrations (actual dose
applied) were analyzed, those data are not provided (only nominal
dose levels reported)) and calibration of the biomarker is not
discussed. Dose levels are misreported in the draft risk evaluation.
Sanders et al. (1982) offers only very brief descriptions of
methodology and statistics that are supposedly required for an
adequate rating. The study used a variety of assays to examine
multiple immune parameters. However, only some of the results
were consistent, and/or associated with adequate controls. Overall, it
is difficult to pick a consistent targeted effect on the immune system
from the Sanders et al. (1982) study.
It is not clear why Woolhiser et al. (2006), which only showed an
effect at one concentration of TCE, should be chosen as a key study.
These factors were already all accounted for in
the data quality evaluation. Details are provided
in supplemental files. A study does not need to
score a high in every individual metric in order
to be scored a High overall. The dose levels are
correct in the Risk Evaluation. It appears that the
dose levels are incorrectly presented in the
abstract of the study, which may have caused the
confusion.
Data quality is not necessarily influenced by the
results, only how well the study was performed
and reported. However, this inconsistent
response among results is further justification
for not choosing (Sanders et al.. 1982) as the
representative study for the immune domain.
(Woolhiser et al.. 2006) was not selected as the
representative study for immunosuppression
((Sanders et al.. 1982) was), but the Woolhiser
study is the only immune study that identifies a
NOAEL. This is a benefit of the study and not a
negative.
(Kaneko et al. 2000) was not selected as the
best studv for autoimmunitv ((Keil et al. 2009)
was), so these considerations were taken into
account.
Page 245 of 408
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The results were re-reported by Boverhof et al. (2013), which should
not be considered a separate evaluation of immunosuppression.
The Kaneko et al. (2000) study, apparently chosen as a key study to
illustrate how chronic TCE exposure causes immunotoxicity in an
autoimmune-prone mouse model, reports on pneumatosis cystoides
intestinalis, which is not, however, an autoimmune disease. In
addition, MRL lpr/lpr mice are not a good model to examine
chemically induced autoimmunity. It is not clear why this paper was
selected over several other papers using superior animal models that
have examined how chronic TCE exposure impacts autoimmune
disease (e.g., Griffin et al., 2000; Gilbert et al., 2009; and Wang et
al., 2012).
SACC
SACC COMMENTS:
Recommendation: Add and discuss autoimmunity studies performed in
different rodent models and with humans.
The Keil et al. (2009) paper is useful for evaluating the effects of
chronic TCE exposure on the development of autoimmune disease in
non-autoimmune-prone mice. However, the draft risk evaluation
should also include at least one study that examined the effects of
chronic TCE exposure on disease progression in autoimmune-prone
mice. Because such mice can represent the human population most
susceptible to the autoimmune-promoting effects of TCE, this
inclusion is important. There are several studies that use models
other than the NZBWF1 mice used in the Keil et al. (2009) study,
including Griffin et al. (2000), Gilbert et al. (2009), and Wang et al.
(2012).
HECs from other studies are markedly different from these
calculated from the Keil et al. (2009) study. How does EPA explain
the large differences in HECs compared with other data investigating
the immunological endpoint? The Committee suggested that EPA
consider as high-quality inhalation studies only those that provide
analytical chemistry results confirming exposure.
The autoimmune response study in rodents is supported by data in
All recommended studies in this comment have
been added to the immunotoxicity Hazard ID
Section, 3.2.3.1.4. The key study of Kaneko et
al, 2000 was already included, which evaluates
autoimmune-prone mice (although previous
comments indicate it may not be the best
model).
The POD from (Keil et al., 2009) is consistent
with the POD from the developmental
immunotoxicitv studv (Peden-Adams et al.,
2006). Additionally, almost all other studies
including the other autoimmunity study were
LOAELs, so it cannot be determined that they
had a higher NOAEL. The other autoimmunity
studv, (Kaneko et al., 2000), was also of much
shorter duration so a higher POD is expected.
Finallv, (Keil et al., 2009) represents a sensitive
clinical marker (hence the smaller UFl) and
would therefore be expected to be observed at a
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humans suggesting there are potential immune hypersensitivity
responses to TCE. Suggested human studies include: Bond (1996),
Chittasobhaktra et al. (1997), Nakajima et al. (2003), Xu et al.
(2009), Liu (2009), and Kang et al. (2018).
lower dose than the more severe effects
observed in other studies.
SACC
SACC COMMENTS:
Recommendation: Provide the scientific rationale for selecting the Keil
et al. (2009) study for evaluating chronic non-cancer effects given its
deficiencies. Several members of the Committee voiced concerns over
the use of Kiel et al. (2009) study.
Doses used are outside the range used in other immunotoxicity
studies.
One Committee member commented that the data are of questionable
significance because there seems to be a lack of dose response.
Normal humans are not well represented by a genetically-prone
strain, the data were generated from another pathway of exposure
(oral) than is considered in the human COU, and only nominal
concentrations were reported.
In Table 3-14, no explanation for the selection anti-ds and ssDNA
antibodies as endpoints is given, and the levels of anti-dsDNA
antibodies at 14,000 ppb in both normal and genetically prone mice
are nearly identical to controls at 36 weeks. Qualification of this
biomarker, along with a lack of justification, suggest that these data
are not appropriate for use in this manner.
The draft risk evaluation suggests that TCE has both immuno-
suppressive and autoimmunity properties. A biologically plausible
explanation for how this might happen should be provided.
The authors also state that there is no statistically significant
difference in thymic cellularity (p. 244, lines 2251-2257). This
equivocal cellularity issue is a recurring problem.
The thymus mass effects measured may not be reliable, given the
subjective nature of the assay, and because the thymus must be
removed and trimmed, which unavoidably introduces technique
related variability in weight determination. TCE-induced thymus
EPA provides justification for the selection of
the best overall studies in Section 3.2.5.4.1.
The POD from (Keil et al.. 2009) was based on
responses in normal mice, not autoimmune-
prone mice. Increased autoantibodies were not
observed in the autoimmune-prone strain
(NZBWF1) tested in parallel .While there was
not a consistent dose-response for
autoantibodies (responses are similar or even
decreased at the higher dose), this inconsistent
dose response is in agreement with results from
autoimmune-orone MRL +/+ mice in (Griffin
et al. 2000). The non-standard dose-response
was also considered in assignment of a UFl of 3
instead of 10. EPA has updated the description
of the POD to indicate that it is no longer based
on thymic changes because those are
insufficiently adverse or reliable.
(Keil et al.. 2009) was assigned UFl = 3 (instead
of 10). Detection of anti-nuclear antibodies
(ANA) is a long-established clinical marker of
autoimmune connective tissue diseases (e.g.,
lupus). Specificity of ANA for autoimmune
disease states can be low, however anti-dsDNA
antibodies have been shown to be quite specific
and are rarely detected at elevated levels in
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weight changes were inconsistently observed between the two mouse
strains.
For dsDNA and ssDNA, one Committee member noted that in all
cases the high-dose groups exhibit a lower (average) response than
the low dose groups, suggesting that the lowest-observed-adverse-
effect level (LOAEL) should be the high-dose group, not the low-
dose group.
Age-dependent differences in responses were observed in NZBWF1
mice, but not in B6C3F1 mice. It was not clear to some Committee
members whether the inconsistent minimal effects observed in the
B6C3F1 non-sensitive mouse have any clinical relevance. Other
Committee members disagreed and pointed to multiple figures in the
Keil et al. paper that show legitimate levels of toxicant-induced
increases in antibodies. While dose responses are not very evident,
TCE effects are evident.
healthy patients (Kavanaugh et al.. 2000;
Wichainun et al.. 2013). Therefore, the results
from (Keil et al.. 2009) do represent an adequate
biomarker of autoimmunity, and the selection of
UFl = 3 is justified due to the observed effect
being considered an early, subclinical or pre-
clinical early marker of disease and the non-
standard dose-response observed in the study.
SACC comments above (p. 249) indicate issues
with the (Sanders et al.. 1982) studv, namelv that
only some of the results were consistent, and/or
associated with adequate controls. Additionally,
both are LOAELs. and (Keil et al.. 2009) tested
a lower dose range so was therefore more
sensitive to effects at lower doses. Therefore,
while both studies were selected for representing
their respective chronic immune endpoints
(immunosuppression for Sanders, autoimmunity
for Keil), (Keil et al. 2009) was selected as the
most robust and sensitive study for both the
immune domain and overall chronic non-cancer
endpoints.
SACC
SACC COMMENTS:
Recommendation: Consider increasing the autoimmunity effect UFl to
account for uncertainties in the clinical significance of autoantibodies.
The Committee was comfortable with using a UFl (LOAEL-to-no-
observed-adverse-effect level [NOAEL] UF) of 3 for the Keil et al.
(2009) study because the LOAEL is based on an early clinical
marker (autoantibodies). Because anti-DNA autoantibodies are often
the precursors for actual autoimmune disease, some Committee
members suggested that a UFl=10 should be assigned to their
detection. Not all Committee members agreed with this increase,
however, depending upon their confidence in the significance of this
pre-clinical endpoint.
95,
103, 94
PUBLIC COMMENTS:
Concerns with using data from Keil et al. to drive a toxicity value.
A few SACC members discussed whether the antibody response
reported by Keil et al. should be considered evidence of an adverse
effect or only a biomarker. It was noted that the response was
reported in the insensitive mouse strain but not in the strain with
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autoimmune sensitivity {i.e., NZBWF1).
With limited histopathology evaluation (only the kidney), the
autoantibody results lack confirmatory adverse response verification
as to other organs and tissues that can be impacted.
The DNA autoantibody response reported by Keil et al. was erratic,
noisy, and did show a non-dose response.
The draft risk evaluation should note that the effects observed by
Keil et al. (2009) do not allow for derivation of a POD or reference
concentrati on/dose.
EPA should reconsider the Sanders et al. (1982) and Woolhiser et al.
(2006) studies as more reliable critical studies for defining PODs and
reference dose/concentration determinations. EPA should base its
analysis of chronic, non-cancer risks on data from studies reporting
immunosuppression rather than on the Keil et al. study.
94
The serum DNA autoantibody responses reported in the study by Keil et
al. (2009) is considered to be unreliable for derivation of a chronic non-
cancer toxicity value. This study had:
Lack of analytical verification of dosing concentrations (the study
indicated that analytical measurements were done by an outside
laboratory, but the data were not provided); descriptions of measures
taken to minimize volatility were also not provided.
Lack of biological plausibility with no accompanying pathological
changes and the same effects not seen in autoimmune-prone mouse
strain.
Lack of dose-response seen for most measurements at most time
points throughout the study.
Inadequate number of dose groups for dose-response modeling.
Additional studies are needed to substantiate the findings, with a clear
link to "disease expression and pathology," before it can be considered
sufficiently reliable to be used for risk assessment purposes.
SACC
SACC COMMENTS:
Recommendation: Consider using Sanders et al. (1982) to set the
immunotoxicity POD.
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Some Committee members suggested that EPA consider using an
immunotoxicity study with a clearer dose-response for evaluating
chronic non-cancer effects. One Committee member suggested using
the study by Sanders et al. (1982) that resulted in suppression of
humoral and cell-mediated immunity in female CD1 mice. Another
Committee member disagreed, finding the Keil study superior to the
Sanders study and hence noted that it is appropriate to use the Keil
study in establishing the POD for immunotoxicity.
94
PUBLIC COMMENTS:
Other concerns with the Kiel et al. (2009) study:
Thymus weights are prone to inaccuracies; therefore, interpretation
of the change observed is uncertain in the absence of any other clear
treatment-related effects.
Lack of a water-only control group to rule out potential effects from
the 1% emulphor.
Lack of information on whether 1% emulphor impacts TCE
toxicokinetics (e.g., absorption and distribution).
94
PUBLIC COMMENTS:
EPA's systematic review of Keil et al. (2009) reflects a naive
understanding of the technical difficulties with administrating TCE in
drinking water in animal studies and is based on presumptions rather
than analytical data; leading to an overestimation of the study quality.
The metrics for "Preparation and Storage of Test Substance" and
"Consistency of Exposure Administration" were given "Medium"
and "High" scores, respectively; and for both metrics, EPA
concluded that "TCE levels were confirmed." Yet, there are no
analytical data in the Keil et al. paper to support that conclusion.
EPA relied on a statement saying that it was done.
EPA gave a "High" score for "Exposure Route and Method" with the
comment "Frequent changing of water with exposure level analysis to
avoid decreased dosing to vaporization."
94
PUBLIC COMMENTS:
EPA is encouraged to consider endpoints from two other immunotoxicity
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studies given "High" data quality scores in the systematic review for the
POD for chronic non-cancer exposures: Sanders et al. (1982) and
Boverhof et al. (2013). Both studies reported treatment-related effects in
conventional assays measuring immunosuppression in mice and rats,
which is consistent with the effects on the immune system seen in acute
TCE exposures by Selgrade and Gilmour (2010).
108
PUBLIC COMMENTS:
EPA has not provided sufficient justification for dismissing decreased
thymus weight from the risk evaluation process.
Departing from the 2014 Work Plan Assessment, EPA did not
consider decreased thymus weight and cellularity (observed in Keil
et al., 2009) in the risk estimation process for immunotoxicity
because it deemed these endpoints to be "insufficiently adverse
compared to other endpoints."
The 2011 IRIS assessment considered this as a candidate critical
effect.
45
PUBLIC COMMENTS:
The TCE safe chronic dose in EPA's IRIS database (a RfD) is based on
the same key study as in this draft (Kiel et al). Yet the IRIS RfD is -10
times lower (safer) than the current draft. EPA must explicitly justify
what factors caused the change.
The cumulative UF for (Keil et al.. 2009) in the
IRIS assessment was higher based on a UFl of
10. EPA evaluated consideration for the UFl and
determined that UFl = 3 was most appropriate
based on autoantibodies representing an early,
subclinical effect. The TCE Risk Evaluation
does not state a reference dose or concentration,
so there is no RfD provided for making a direct
comparison.
(Keil et al., 2009) was assigned UFl = 3 (instead
of 10). Detection of anti-nuclear antibodies
(ANA) is a long-established clinical marker of
autoimmune connective tissue diseases (e.g.,
lupus). Specificity of ANA for autoimmune
disease states can be low, however anti-dsDNA
108,
105
PUBLIC COMMENTS:
A UF of 10 instead of 3 should be used to convert from the LOAEL to a
NOAEL for the autoimmunity endpoint (Kiel et al., 2009). This would
provide better protection against developmental toxicity in the
assessment of chronic exposures.
During the SACC meeting, several panelists criticized EPA's
decision to use a value of "3", rather than the default of "10," UFL for
the Keil et al. autoimmunity endpoint.
EPA justified the decision to use a partial value of 3 rather than a full
factor of 10 by stating that "the observed effect is considered an
early, subclinical or pre-clinical early marker of disease." However,
autoimmunity (i.e., changes in antibody levels that impair the body's
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ability to fight viruses and other infections) should itself be
considered a relevant immune effect rather than only a precursor or
subclinical marker. This scenario could be viewed as analogous to
considering liver enzyme changes as a marker of liver toxicity.
In deciding the appropriate UF, other severe effects of TCE should
be considered, namely the evidence of developmental toxicity and
the low concentrations at which developmental effects were
observed. Since the endpoint from the Kiel et al. study is used as the
critical endpoint for all non-cancer effects, the maximum UFl of 10
should be used (bringing the total UF to 100 for the endpoint), to
ensure that the threshold based on this study will protect against
developmental toxicity.
OEHHA generally does not use a UF smaller than 10 when
converting from a LOAEL to NOAEL for chronic endpoints, even
when the effect is mild. For acute endpoints, a smaller UF may be
justifiable, but for chronic effects this is problematic.
antibodies have been shown to be quite specific
and are rarely detected at elevated levels in
healthv patients CKavanaugh et al.. 2000;
Wichainun et al.. 2013). Therefore, the results
from (Keil et al.. 2009) do represent an adequate
biomarker of autoimmunity, and the selection of
UFl = 3 is justified due to the observed effect
being considered an early, subclinical or pre-
clinical early marker of disease and the non-
standard dose-response observed in the study.
BMR selection
SACC
SACC COMMENTS:
Recommendation: Provide better justification or reference policy to
support the choice of BMR used in computing the BMDL.
For liver, kidney, and male reproductive effects, 10% levels are used; the
1% level is used for the congenital heart defect and immunotoxicity. The
extent to which this is driven by EPA policy should be explained in the
document. A 1% response level could be supported, but more
explanation is needed to ensure full transparency for the basis for this
selection.
Selection of a lower BMR based on the severity
of an effect (referred to in the Guidance as a
"frank effect") is consistent with EPA BMD
guidance (I v << \ . 012a) and standard EPA
practice. Considerations for BMD modeling are
provided in Appendix G.
SACC
SACC COMMENTS:
With a cumulative acute UF of 10 [(interspecies uncertainty factor,
UFa=3 {i.e., extrapolating from laboratory animals to humans) and
intraspecies uncertainty factor, UFh=3 {i.e., human [intraspecies]
variability)], should not one of these be reduced to 1.0 based on the
highly conservative nature inherent in use of a BMDL-0.01 level? These
decisions are based on scientific judgment but require more
BMR selection is independent from uncertainty
factor determination, which is based on
confidence in the dose-response and how it
accounts for variability and uncertainty between
the assay and the human population. The use of
a 1% BMR based on a severe effect does not
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comprehensive justification.
indicate that variability between humans and
animals or among the human population is
reduced.
SACC
SACC COMMENTS:
For cardiac malformations as a developmental effect of TCE exposure, a
BMDLoi value is calculated based on the seriousness of this adverse
effect. While the explanation for using a 1% level is clear and agrees
with standard practice, the use of these data from the Johnson et al.
(2003) study raised concerns due to issues with the experimental design
and replication problems.
A detailed justification for the use of a 1% BMR
for (Johnson et al., 2003) is provided in Section
3.2.5.3.1. A re-run of BMD modeling was
performed to confirm the results of the 2011
dose-response assessment and is presented in
Appendix J.
99
PUBLIC COMMENTS:
Using additional information reported by Johnson et al., EPA revaluated
the BMR used in the 2014 risk assessment using biological and statistical
factors, concluding "that the biological severity of the effect, potentially
lethal heart defects, strongly supported a BMR of 1%." Compared to the
2014 assessment, EPA concluded that "the p-value of = 0.661 from the
updated BMDS nested model run is significantly improved,
demonstrating strong model fit and confirming the 2011 conclusion that
the modeling results for cardiac malformation data are appropriate for
reference value derivation."
Meta-analysis of epidemiological cancer data
SACC
SACC COMMENTS:
With two exceptions, members indicated that the short subsection on
the meta-analysis for TCE-induced cancer is concise and clearly
explains the interpretation of the conclusions of an association with
kidney cancer, liver cancer, and NHL. This section and the analysis
are clear and appropriate. The exclusion of Vlaanderen et al. (2013)
is well discussed and justified.
One member of the Committee had reservations about the association of
TCE with liver cancer (due to conflicting evidence, appearance of
tumors only at high doses, and potential MOA not relevant to humans).
Because the POD is derived from the more definitive kidney cancer data
and modified to account for additional cancer types (liver and NHL), the
All studies considered in EPA's cancer meta-
analyses scored acceptable for data quality and
passed inclusion/exclusion criteria for suitability
of the data. Unacceptable studies were not
considered for inclusion. All details on the data
quality evaluation results for these studies are
provided in supplemental files. EPA provides a
meta-analysis stratified by data evaluation score
in Appendix K.2.2.2 that demonstrates stronger
statistical significance for each tumor type
among high-quality studies compared to overall
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other members of the Committee did not see this as an issue.
summary relative risks (RRs).
94
PUBLIC COMMENTS:
EPA provides no discussion on the study quality details for individual
studies in its meta-analysis and how they could have affected the validity
of individual effect estimates/overall interpretation of results. The degree
to which these methodological limitations may have impacted the
individual effects estimates and interpretability of meta-analysis relative
risk estimates (meta-RRs) needs to be further investigated by EPA.
94
PUBLIC COMMENTS:
EPA's conclusion that there are positive associations of NHL, kidney
cancer, and liver cancer with exposure to TCE do not account for some
serious methodological limitations of individual studies (e.g., exposure
measurement error and confounding), qualitative heterogeneity across
individual studies (ratio measures, exposure measurements and contrasts,
mortality vs. incidence data, and covariate adjustments), and unjustified
adjustments in quality ratings, and the inappropriate removal of the
largest study (Vlaanderen et al., 2013). These limitations are not fully
captured through statistical modeling, which calls into question the
appropriateness of meta-analyzing these results. The meta-analyses
results are not reliable, and EPA's interpretation of the results is not
appropriate. The meta-analyses do not support TCE as a risk factor for
NHL, kidney cancer, or liver cancer.
94
PUBLIC COMMENTS:
EPA inappropriately used both inclusion/exclusion criteria and study
quality criteria to determine which studies to include in the meta-
analyses. Data quality criteria should be applied only to studies that have
been selected for inclusion in the analysis. Data quality criteria were also
inconsistently applied. For example: There is no explanation for
excluding Bahr et al. (2011) (scored Unacceptable), but not Buhagen et
al. (2016) (scored Low), when both studies met the inclusion criteria.
This raises a question of the objectivity of the study selection process.
94
PUBLIC COMMENTS:
EPA changed the study quality rating for a few studies (i.e., Vlaanderen
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et al., 2013; Buhagen et al., 2016; Bahr et al., 2011) after completing an
evaluation based on the predetermined Data Quality. These rating
changes were based on factors that had already been accounted for in the
Data Quality Criteria. It is unclear whether the considerations for re-
rating these studies were consistently evaluated in all of the included
studies, or whether certain studies were singled out. As one example:
Vlaanderen et al. (2013) was initially rated as a "High" quality study
based on the Data Quality Criteria, but then re-rated as a "Medium"
quality study due to 'potential JEM misclassification.' However, this
should have been accounted for in Metric 4, where a "low" score was
given. It is unclear why the same issue was double-counted in the rating.
It is also unreasonable to re-rate the entire study (from "High" to
"Medium" quality) for specific issues that should have been accounted
for by simply re-rating individual aspects/metrics that contribute to the
overall rating of the study. The objectivity and reasonableness of these
are questionable, and likely affected the meta-analyses and results
beyond individual study ratings.
94
PUBLIC COMMENTS:
Several studies in the meta-analysis with overall study quality ratings of
"high" may have had serious limitations:
Exposure measurement errors: due to use of less-established
exposure assessment methods, lack of method validation, or having
limited employment information for job-matrix construction
introduce information bias into the meta-analysis.
Limited exposure ranges (e.g., not adequate for developing an
exposure-response) introduce bias to the meta-RRs because their
effect estimates are not adequate to fully capture the underlying
association between exposure and cancer outcomes.
Confounding: studies rated "low" for covariate adjustment, covariate
characterization, and co-exposure confounding.
EPA should compare results of these studies with methodological
limitations to results of the few studies without limitations in generating
the summary effect estimates (i.e., meta-RRs), particularly when
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stratifying by overall study quality, in order to assess the degree to which
the methodological limitations may have impacted individual effects
estimates and the interpretability of meta-RRs.
94
PUBLIC COMMENTS:
EPA considered all risk ratio measures {i.e., RR, odds ratio [OR], hazard
ratio [HR], standardized mortality ratio [SMR], and standardized
incidence ratio [SIR]) as equivalent. Although this is not an uncommon
approach for meta-analyses, it can introduce bias to results, especially
when conditions where other ratio measures would mathematically
approximate RR are not met in individual studies {e.g., an OR from a
case-control study that is not nested within an underlying cohort).
EPA considered all data from multiple studies
within a single cohort in total, with the most
updated cohort results used in the meta-analyses.
94
PUBLIC COMMENTS:
In the meta-analyses, EPA included studies where a diversity of TCE
exposure measurements were used. While this enabled a large number of
studies to be included, an effect estimate based on one exposure
measurement is not necessarily comparable to the effect estimate based
on another exposure measurement.
EPA considered the best overall effect estimate
for each study, along with stratifications for
"high" vs "low" exposure.
94
PUBLIC COMMENTS:
EPA abstracted effect estimates for contrasts within the study population
and were either comparisons of groups exposed and not exposed to TCE
or comparisons of groups with the highest and lowest level of exposure.
However, the definitions of "exposed" vs. "unexposed" or "high" vs.
"low" exposure levels were not specified and could be widely different
between studies. Diversities in both exposure measurements and
contrasts introduce heterogeneity across the meta-analyzed studies and
hinders the interpretability of the meta-analyses results. Thus, the
appropriateness of meta-analyzing these study results is questionable.
There is always uncertainty associated with
study author classification of study groups,
however EPA attempted to use consistent
parameters when grouping studies.
94
PUBLIC COMMENTS:
EPA inappropriately assumed that meta-RR estimates, which are based
on RR estimates for both cancer mortality and incidence, were
appropriate estimates for cancer incidence ratios. Survival rates for
cancer generally depend on the cancer site and stage at diagnosis,
mortality rates often poorly approximate incidence rates, particularly
The meta-analyses were based on associations
with cancer incidence, not mortality.
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when cancers are diagnosed at an early stage. Kidney cancer and NHL
have high 5-year survival rates; therefore, mortality risk estimates are not
good estimates for incidence risks for these two cancers.
94
PUBLIC COMMENTS:
The most fully adjusted risk estimate from each study was used in each
meta-analysis in the draft risk evaluation. However, each study adjusted
for a unique set of covariates, and even the same covariates were often
defined and measured differently across studies.
EPA's decision on whether fixed-effects or random-effects model results
should be used to represent the summary effect estimates (i.e., meta-
RRs) solely relied on the I2 statistic and visual inspection of the plotted
effect estimates. This evaluation is not a replacement for understanding
the underlying meanings of the values of the effect estimates. Given the
heterogeneity between studies, qualitative evaluation of whether the
effect estimates from individual studies can be considered as estimating
the same underlying effect should be conducted along with the
quantitative examinations. If this is done, it is evident that the fixed-
effects TCE models, which assumed that each of the individual studies
are estimating the same underlying effect, likely are subject to biased
results as a result of this heterogeneity.
EPA's procedure for evaluating heterogeneity
paralleled the methods from the peer-reviewed
2011 IRIS Assessment. EPA agrees that the
random effects model is preferable in cases of
significant heterogeneity and states, "random-
effects models are consequently preferred to
fixed-effects models due to the degree of
heterogeneity" in Section 3.2.4.2.1.
94
PUBLIC COMMENTS:
EPA used a "leave-one-out" approach in the assessment of influential
studies (i.e., conducted each analysis several times, removing one study
each time) in fixed-effects, but not random-effects, models for NHL,
kidney cancer, and liver cancer. In doing so, EPA identified only
Vlaanderen et al. (2013) as an influential study; meta-RRs largely
remained not statistically significant with the removal of any other study.
It is not clear why EPA only used fixed effects models for the "leave-
one-out" analysis when random-effects models are more appropriate for
these data given indications of heterogeneity. EPA's reason for omitting
Vlaanderen et al. is flawed.
Just because the value of I2 statistic was substantially reduced, does
The data ciualitv of (Vlaanderen et al., 2013) was
not downgraded based on meta-analysis
determinations, it was merely omitted from
sensitivity meta-analyses because it was shown
to have overly large influence on the results due
to large sample size and likely low sensitivity
for detecting effects (see Section 3.2.4.2.1). The
meta-analyses plots presented with exclusion of
(Vlaanderen et al., 2013) present an updated I2
score that is reduced, indicating reduced
heterogeneity and mitigating the need for use of
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not mean that there is no underlying qualitative heterogeneity among
the remaining studies.
Using this reasoning for downgrading the study quality once again to
support the omission, without acknowledging the many
methodological strengths and the overall good quality of the study is
not justified.
The next largest studies with the highest influences on the meta-RRs
had similar methodological limitations and their initial study ratings
were worse, and therefore, they are likely more subject to bias.
An important question is whether the effect estimates from Vlaanderen et
al. (2013) or any other study under review can be considered as
estimating the same underlying effect. This was not considered.
the random effects model. Omission of
(Vlaanderen et al., 2013) was onlv one
sensitivity analysis conducted in supporting
EPA's conclusions.
94
PUBLIC COMMENTS:
Stratification of meta-analysis by study quality showed that "For all three
tissues, the meta-RR was greater among the high-quality studies
compared to medium or low-quality studies." It is worth noting that this
finding is likely sensitive to the quality rating of Vlaanderen et al.
(2013). Had this study not been re-rated from "High" to "Medium"
quality, the meta-RR would likely have been greater among the medium-
or low-quality studies compared to the high-quality studies, which would
have led to a completely different conclusion.
The study was not "re-rated." All data
evaluations are subject to expert judgment
adjustments to the overall score, and it is likely
that similar considerations influenced the
manual downgrade and the reduced sensitivity
of the study in the meta-analysis.
94
PUBLIC COMMENTS:
There was a blatant misuse of funnel plots in the draft risk evaluation to
assess publication bias. EPA used funnel plots to visually examine a
comparison of study size and effect size with and without the Vlaanderen
et al. (2013) study. This represents a fundamental misunderstanding of
funnel plots, which are crude measures of whether studies represent a
bias in terms of positive results, and should not be used to determine the
sensitivity of meta-analyses to a particular study.
The funnel plots were presented to demonstrate
publication bias both for the overall meta-
analyses, and for the sensitivity analysis
involving omission of the (Vlaanderen et al.,
2013) studv. Thev were not intended to
determine the sensitivity of the performed meta-
analyses.
94
PUBLIC COMMENTS:
The Draft supports the 2011 IRIS assessment classification of TCE as
"Carcinogenic to Humans," but fails to discuss or recognize that such
classification is inconsistent with a definitive report by the National
The NAS review on TCE human health risks
was published in 2006 (NRC, 2006), prior to
both the IRIS Assessment and the publication
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Academy of Sciences (NAS).
This classification is appropriate only when there is convincing
epidemiologic evidence of a causal association between human
exposure and cancer, or several conditions are met with other lines of
evidence.
Neither the epidemiological data nor animal studies meet the
threshold for classification as carcinogenic to humans.
Based on an analysis by Gradient of the new meta-analyses of TCE
and on NHL, kidney cancer, and liver cancer risks, the meta-analyses
results are not reliable, and EPA's interpretation of the results is not
appropriate. The evidence of an association with cancer is neither
"convincing" or "strong."
The classification of TCE as "Carcinogenic to Humans" is not supported
by the evidence or justified under the 2005 Guidelines.
Risk estimates from individual cohort studies, and the meta-estimates
based on these studies, likely did not properly reflect the true
associations between TCE and these cancers.
date for many of the studies included in the
meta-analyses. Therefore it is missing many
studies that were covered by EPA's analysis in
the 2011 IRIS Assessment (TJ.S. EPA 201 lei
2014 Workplan Risk Assessment (U.S. EPA,
2014b), and this Risk Evaluation. Furthermore,
the confirmation of statistically significant
summary effect estimates across a large group of
studies in all three cancer types as well as
positive results in animal cancer bioassays is
very strong support for the conclusion that TCE
is "Carcinogenic to Humans."
105
PUBLIC COMMENTS:
EPA conducted meta-analyses of epidemiological cancer data and found
consistent positive associations for multiple cancer sites, and
appropriately used the cancer dose response characterization from EPA's
2011 IRIS assessment (U.S. EPA, 2011). In light of this, the executive
summary and the body of the document should clearly state the
conclusion that TCE is "carcinogenic to humans." This was the
conclusion in the IRIS assessment and the draft risk evaluation shows
that the evidence since then has strengthened.
EPA agrees with this comment and the risk
evaluation has been updated accordingly.
Evaluation of animal cancer data
SACC
SACC COMMENTS:
The Committee was unclear of the meaning of the justification of
"confounding mortality" used to score the NCI (1976) female study on
kidney endpoint as unacceptable (p. 211, lines 775-776).
The following clarifying language has been
added to the Risk Evaluation: "due to high
mortality in control mice and rats as well as long
post-exposure period prior to sacrifice that could
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have allowed for recovery..."
SACC
SACC COMMENTS:
Recommendation: Clarifications and corrections are needed.
Section 3.2.3.2-Genotoxicity and Cancer Hazard, p. 218: Improve the
discussion to clarify the sex-dependent differences in cancer
incidence, especially for kidney and liver.
EPA does not believe that sex-specific
difference in cancer incidence for non-
reproductive organs are relevant for this
assessment except for consideration of certain
mode of action (MOA), which are discussed in
Section 3.2.4.2.2.
94
PUBLIC COMMENTS:
EPA seems to overly discount negative animal carcinogenicity data and
to highlight marginal findings.
EPA's conclusion that kidney cancer is evident in rats rests on one
statistically significant finding in over 70 dose/tumor endpoint
comparisons and references to exceedances of historical control
values.
EPA's conclusion that TCE is a known kidney tumorigen is based on
flawed studies and not warranted. The data are inconsistent and do
not meet the criterion of "extensive evidence of carcinogenicity in
animals." Several marginal findings do not constitute "extensive
evidence."
EPA disagrees with this statement, and positive
animal bioassays are consistent with results from
various epidemiological results, including a
meta-analysis for each of the three primary
tumor types assessed.
Genotoxic MOA for cancer
SACC
SACC COMMENTS:
Recommendation: Include a table summarizing what is known on the
genotoxicity of TCE and metabolites.
The Committee noted that the MOA for TCE carcinogenicity is not
well addressed in the draft risk evaluation, because it relies on the
conclusions from the IRIS assessment. The risk evaluation should
include a table of data addressing the genotoxicity (for both in vivo
and in vitro studies) of TCE and metabolites. Because kidney cancer
is the most important driver of the conclusions, the data for this
tissue should be prioritized.
EPA has added a table of data extraction and
evaluation for all identified genotoxicity studies
on TCE and important metabolites as a
supplemental file.
SACC
SACC COMMENTS:
The Committee noted that a genotoxic mechanism (supportive of using a
EPA has improved the discussion of cancer
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linear non-threshold [LNT] model) had been assumed for TCE. There is
some support for this due to the mutagenic potential of the metabolites S-
(l,2-dichlorovinyl)-L-cysteine (DCVC) and S-(l,2-dichlorovinyl)
glutathione (DCVG). While this evidence is greatest with regard to
kidney toxicity and is further supported by relevant data from female
reproductive toxicity, it is far from definitive. Committee members were
concerned with both the low mutagenic potential of these metabolites
and the doses that would be achievable in vivo. It is probably best to
consider the presence of these compounds as providing "biological
plausibility" for a genotoxic mechanism and consistent with an LNT
model rather than conclusive proof. However, there is also no
compelling evidence for other mechanisms, so no reason to specifically
reject a genotoxic mechanism.
MOA in Section 3.2.4.2.2. Improvements
include more detailed discussion and
consideration of other mechanisms. Overall, the
MOA conclusions are not changed, and EPA
determined that TCE exhibits a genotoxic mode
of action that is supported for kidney cancer
while any particular MOA cannot be concluded
for the other tumor types. Some additional
discussion of the uncertainty associated with
GSH metabolism across humans has been added.
108, 99
PUBLIC COMMENTS:
EPA appropriately concludes that TCE is genotoxic, stating "there is
sufficient evidence that TCE-induced kidney cancer operates primarily
through a mutagenic MOA." The conclusion regarding a lack of
evidence for alternative MO As is also consistent with other findings of
authoritative agencies.
62
PUBLIC COMMENTS:
The data in Yoo et al., 2015 (Health and Environmental Research Online
[HERO] ID 2799570; PMID: 25424545; PMCID:PMC4281933) and
Luo et al., 2018 (PMID: 29190187; PMCID: PMC6088749), together,
strengthen the plausibility of the mutagenic MOA for TCE-induced
kidney cancer - initiation through DCVC mutagenicity followed by
promotion through compensatory cell proliferation that may be due to
the effects of both DCVC and TCA. EPA should add this information to
strengthen the conclusions for a mutagenic MOA for kidney cancer.
63
PUBLIC COMMENTS:
The new and analytically robust data showing that glutathione-conjugate
derived metabolism is a very minor metabolic pathway of TCE in rats
and humans challenge the hypothesis that this pathway is plausibly
consistent with a mutagenic MOA in rodents and humans.
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94
PUBLIC COMMENTS:
A role for glutathione conjugate-derived metabolites in TCE kidney
toxicity and cancer risk assessment should be reconsidered. There is
compelling evidence that the glutathione (GSH) conjugation pathway is
an extremely small contributor to TCE metabolism.
Yoo et al. (2015) demonstrated that DCVG and DCVC were only a
small fraction of total metabolites quantitated in kidney.
Trichloroethanol (TCOH) kidney concentrations were 2- to 4-fold
greater than TCA; TCA concentrations were 100- to 1,000- fold
greater than DC A; and DC A concentrations were 100- to 1,000-fold
greater than either DCVG or DCVC, resulting in the conclusion that
TCE oxidative metabolism was up to five orders of magnitude
greater than glutathione conjugate-derived metabolism. These
findings are consistent with Kim et al. (2009) and supported by Luo
et al. (2018) and questions the role of the GSH conjugation pathway
in the kidney cancer MOA.
Estimated levels of DCVC and its reactive metabolites in kidneys of
TCE-exposed mice are insufficient to account for toxicity (see Yoo et al.,
2015, Green et al., 1997, and Luo et al., 2018).
Alternai
tive MOAs for cancer
SACC
SACC COMMENTS:
Some Committee members suggested that alternative MOAs for TCE
in liver carcinogenesis have not been adequately discussed. Multiple
MOAs have been proposed for the carcinogenic action of TCE and its
metabolites in rodents, including activation of peroxisome proliferator
activated receptor alpha (PPARa). The human relevance of PPARa
agonism has been the subject of debate due to the substantial species
differences in response to peroxisome proliferator receptor activation
between rodents and primates, with rodents, especially mice, showing
greater sensitivity than primates. A Committee member suggested that
other, non-PPARa mechanisms, such as cytotoxicity and activation of
other nuclear receptors had not been adequately discussed.
EPA has added an additional subsection on
polyploidization. EPA has additionally expanded
the discussion of PPARa and
cytotoxicity/reparative hyperplasia.
SACC
SACC COMMENTS:
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Recommendation: Clarifications and corrections are needed.
Section 3.2.4-Weight of Scientific Evidence, p. 220, lines 1170-
1174: Regarding the MOA for liver cancer, the consensus is that
while peroxisome proliferation in rodents is well-established, it is not
relevant to humans. This point should be noted here.
EPA disagrees with this statement. The
significance of the PPARa pathway in humans is
debated, and while it may be less active it is not
necessarily irrelevant.
SACC
SACC COMMENTS:
Recommendation: Clarifications and corrections are needed.
Section 3.2.4.2.2-Mode of Action: Kidney Cancer, p. 227: The
document states the following: "the predominant mode of action
(MOA) for kidney carcinogenicity involves a genotoxic mechanism."
Although the next paragraph also discusses alternative MO As, which
include cytotoxicity and dysregulated injury and repair cycles, the
relative importance of each mechanism and the evidence supporting
each mechanism are not appropriately described.
EPA has improved the discussion of cancer
MOA in Section 3.2.4.2.2. Improvements
include more detailed discussion including
addition of some recommended citations and
consideration of other mechanisms. Overall, the
MOA conclusions are not changed, and EPA
determined that TCE exhibits a genotoxic mode
of action that is supported for kidney cancer
while any particular MOA cannot be concluded
for the other tumor types. The SACC directly
refuted written and oral comments citing Zhang
et al, 2018 (available at
httos://www.sciencedirect.com/science/art.icle/oi
62
PUBLIC COMMENTS:
It is surprising that PPARa activation is elevated in the draft when it has
been concluded by IARC that there are a number of other equally
plausible mechanisms. Rusyn et al. (2014) indicates that "TCE and its
oxidative metabolites have been shown to induce several non-genotoxic
effects that may contribute to hepatocellular tumors. These include
epigenetic alterations; cytotoxicity and secondary oxidative stress;
alteration of proliferation and apoptosis, and clonal expansion; and
PPARa activation," and that "several data gaps reduce the confidence in
the conclusion that TCA induces hepatocarcinogenesis solely through a
PPARa-activation mechanism." EPA should not provide specific
emphasis on PPARa activation as among the "strongest" potential
mechanisms for liver cancer induced by TCE and instead more directly
state that multiple MO As may be responsible for liver cancer effects of
TCE.
) suggesting that the assay
methods used in the 2011 PBPK model for
measuring DCVG were inappropriate or gross
overestimations.
103
PUBLIC COMMENTS:
EPA should fully evaluate and discuss the plausibility of the alternative
cancer MOA and weigh the scientific evidence of this alternative
approach as part of the risk characterization.
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EPA should utilize an established framework to organize evidence
for MOA based on side-by-side WOE comparison of alternative
plausible MO As.
EPA is obligated to calculate potential risks from alternative
plausible MO As, and the default option, and to characterize each
fully, both narratively and quantitatively, for the risk manager.
103, 94
PUBLIC COMMENTS:
MOA analysis should be updated to include additional studies:
Zhang et al. (2018): This study identified the potential for the GSH
metabolite pathway, which EPA identified as a potential MOA for
kidney cancer, to be overestimated if the non-specific
difluoronitrobenzene derivatization analytical method is used. EPA
should reconsider whether this quantitatively changes the kidney
cancer risk attributed to TCE exposure.
Studies conducted with structurally similar perchloroethylene that is
metabolized to structurally similar compounds through identical
metabolic pathways.
Luo et al. (2018), reported that for TCE, concentrations of
metabolites formed by oxidative biotransformation were several
orders of magnitude higher than concentrations of metabolites
formed by the GSH pathway, suggesting a lack of support for the
conclusion that the GSH metabolites are responsible for TCE-
induced kidney tumors in rodents.
Transcriptomic studies including Zhou et al. (2017); Cichocki et al.
(2017), and Venkatratnam et al. (2017). The latter two suggest that
PCE and TCE exposure are associated with PPAR-a, which indicates
that these findings may not be relevant to humans.
The current available scientific information is not consistent with the
conclusion that the MOA for TCE-induced kidney cancer in rats involves
DNA-reactive metabolites from the GSH conjugation pathway as a key
event. EPA needs to incorporate the evidence from these recent studies
into the TSCA draft risk evaluation for TCE and produce alternative
cancer toxicity values based on a threshold approach.
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94
PUBLIC COMMENTS:
EPA has failed to include any of the more recent published studies that
undermine the validity of EPA's assumptions in the estimation of human
kidney toxicity and cancer risks including Zhang et al. (2018)
Linear extrapolation for cancer dose-response assessment
SACC
SACC COMMENTS:
Although following an LNT dose-response model for cancer assessment
would seem to follow standard practice, support for it remains weak.
Two caveats here that should be considered: While the TCE
metabolite DCVC is clearly mutagenic, it is a relatively weak
mutagen, and while there is evidence that mutagenicity does play a
role, it is clearly not the only MOA. Moreover, its relative
contribution as compared to cytotoxicity and proliferation is unclear.
EPA provides multiple lines of justification for
its application of LNT dose-response model, in
addition to the assumed genotoxicity of kidney
cancer (Section 3.2.4.2.2). Application of this
model is consistent with EPA Guidelines for
Carcinogen Risk Assessment.
108, 99
PUBLIC COMMENTS:
There is agreement with EPA's justification in adopting a linear, no-
threshold approach for TCE carcinogenicity.
There is strong support for TCE's cancer classification and a
mutagenic MOA. EPA correctly concludes that TCE is linked to
NHL, kidney, and liver cancer.
EPA's decision to affirm TCE's carcinogenicity and carry forward
cancer hazard for dose-response modeling is wholly consistent with
numerous other classifications.
EPA's conclusion in the draft is also aligned with EPA's 2014 Work
Plan Chemical Risk Assessment of TCE as well as the recent 2019
ATSDR toxicological profile of TCE.
There is support for EPA's decision to adhere to the EPA Guidelines
for Carcinogen Risk Assessment and use the approach of linear non-
threshold extrapolation in the cancer risk modeling for TCE,
indicating that this is the most scientifically sound and health-
protective approach in cancer dose-response modeling for TCE.
Even were the evidence deemed insufficient to identify with certainty
a genotoxic MOA, there is longstanding EPA policy guidance and
precedent supporting a default to a no-threshold, linear extrapolation
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method for cancer dose-response modeling.
108
PUBLIC COMMENTS:
EPA must employ health-protective approaches to dose-response
modeling. The National Research Council's report, Science and
Decisions: Advancing Risk Assessment discusses the need to conduct a
linear extrapolation at the population level, even where a threshold might
theoretically exist indicating that:
"Human variability with respect to the individual thresholds for a
nongenotoxic cancer mechanism can result in linear dose-response
relationships in the population."
"In the laboratory, nonlinear dose-response processes ... may be
found to cause cancer in test animals. However, given the high
prevalence of these background processes, given cancer as an end
point, and given the multitude of chemical exposures and high
variability in human susceptibility, the results may still be manifested
as low-dose linear dose-response relationships in the human
population."
The 2016 amendments to TSCA made explicit and strengthened
EPA's obligation to consider risks to and protect subpopulations that
may be more exposed or more susceptible to the effects of chemical
exposure than the general population. To meet this statutory
requirement, EPA must use a linear non-threshold modeling
approach. Given: (1) existing EPA guidance, (2) the many sources of
variability in the human population, (3) TSCA's mandate to protect
"potentially exposed or susceptible subpopulations," and (4) the clear
presence of individuals with preexisting health conditions, metabolic
or genetic variability, or other factors that make them more
susceptible, the use of the linear extrapolation is the only appropriate
option for cancer dose-response modeling. EPA also must use this
approach comply with EPA's duty to consider the "best available
science" under TSCA.
99
PUBLIC COMMENTS:
Building on previous determinations, and following the guidelines, the
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draft risk evaluation has correctly determined that TCE is a genotoxic
carcinogen and that hypothesized MO As that assume a threshold are
unsupported. At the SACC meeting, some industry presenters urged EPA
to base cancer risk estimates on a non4inear MOA. A non-threshold
linear extrapolation is the correct approach to estimate risk.
94
PUBLIC COMMENTS:
Cases have been made that the scientific foundations of the linear non-
threshold single-hit model are seriously flawed due to default
assumptions and policy-based analytic procedures. These include:
Weight vs. surface area; maximum or average likelihood vs. upper
95% confidence; malignant tumors vs. malignant plus benign tumors;
average animal sensitivity vs. most sensitive; pharmacodynamics vs.
effective dose; and risks at shorter than equilibrium buildup time.
Using alternatives could result in a reduction in risk estimates.
To demonstrate that this approach constitutes "best available science"
EPA should consider these criticisms and evaluate the appropriateness of
assuming a linear non-threshold model on a case-by-case basis.
94
PUBLIC COMMENTS:
It should be noted that in characterizing the upper confidence limit value
generated by the current methodology, EPA does not refer to the impact
on the risk estimate of the policy chosen dose-response model, the
linearized multistage model (LMS). Alternative models would give risk
values several orders of magnitude lower than the LMS model.
Derivation of the IUR
99
PUBLIC COMMENTS:
EPA's overall conclusions of a mutagenic MOA for TCE-induced
kidney cancer were consistent with conclusions in the 2011 IRIS
assessment; therefore, EPA utilized the same IUR and oral slope.
EPA examined non-linear MO As but correctly concluded that although
the WOE also supports involvement of processes of cytotoxicity and
regenerative proliferation in the carcinogenicity of TCE, data were
lacking and the support was not as strong as a mutagenic MOA. EPA
indicated that any possible involvement of a cytotoxicity MOA would be
EPA followed the peer-reviewed process for
cancer dose-response analysis developed in the
2011 IRIS Assessment, including using the IUR
for (Charbotel et al. 2006) and adjusting based
on relative risk for other tumor tvpes. (Charbotel
et al. 2006) received a Hish in EPA's data
quality evaluation and the meta-analysis
concluded that the epidemiological database
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additional to mutagenicity, and the dose-response relationship would
nonetheless be expected to be linear at low doses. Therefore, the
additional involvement of a cytotoxicity MOA does not provide evidence
against the use of linear extrapolation from the POD. The final
evaluation should retain the unit risks in the draft.
supported an association between TCE exposure
and kidney cancer as well as the other two tumor
sites. EPA has discussed uncertainty in the
cancer dose response based on adjustment of the
IUR for all three tumor sites in Section 3.2.6.4
and acknowledges that it likely represents an
upper bound value, however differences from
the true value are unlikely to vary by more than
~2-fold.
94
PUBLIC COMMENTS:
Based on the new meta-analysis with epidemiology studies on kidney
cancer risk, TCE is not a risk factor for kidney cancer; therefore, it is not
appropriate to derive the IUR using Charbotel et al. (2006), which only
investigated RCC. The study's author concluded that the study only
"suggests that there is a weak association between exposures to TRI
[TCE] and increased risk of RCC," which is not supportive of a robust
relationship. Problems with Charbotel et al. (2006):
The study has evidence of misclassification of exposure and
confounding from cutting fluid exposure, resulting in considerable
uncertainty in the outcome.
Methodological limitations include attrition bias, small sample size,
and limited confounder adjustment.
Selection bias: the study selected controls among patients of the same
urologist or general practitioner as the cases. These controls might
have systematically higher or lower odds of TCE exposure than the
underlying true base population that gave rise to the cases, thus
biasing the study results.
All participants of Charbotel et al. (2006) resided in a particular
geographic area they may share certain characteristics that limit the
generalizability of study results to other populations.
EPA should follow the recommendation of the NAS, which indicated
there was insufficient epidemiologic data to support quantitative dose-
response modeling for TCE and cancer.
94
PUBLIC COMMENTS:
There are serious concerns about the scientific appropriateness of
adjusting the IUR derived from kidney cancer data to account for NHL
and liver cancer because epidemiology data are not sufficiently robust to
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allow such calculations and the data that are available indicate that the
IUR for kidney cancer is protective for all three cancer types. The RR
estimates from the 2011 IRIS meta-analyses do not accurately reflect the
relative contributions from different cancers.
94
PUBLIC COMMENTS:
In an alternative approach to the IUR calculation, EPA relied on SIRs for
kidney cancer, liver cancer, and NHL reported by Raaschou-Nielsen et
al. (2003) to calculate extra cancer risks. Because only SIRs were
assessed in this study, key confounders for liver cancer, such as smoking,
heavy alcohol consumption, and chronic viral hepatitis, and kidney
cancer confounders like smoking and body mass index, were not
adjusted for. Therefore, the SIRs from Raaschou-Nielsen et al. (2003)
should not be used in a regulatory human health risk assessment.
94
PUBLIC COMMENTS:
There are considerable uncertainties in the quantitative analyses in which
EPA adjusted the IUR estimate for multiple cancer sites.
For the approach using the meta-RR estimates, EPA assumed that
populations of the underlying studies in the meta-analyses had
similar TCE exposures. This assumption was likely not true, as the
underlying epidemiology studies were conducted in different
counties, industries, and time periods.
Diagnosis and classification of NHL have changed over time; this
likely led to errors in outcome ascertainment in epidemiology
studies. It is difficult, however, to estimate the direction and extent of
this bias.
Uncertainties in exposure assessment and confounder adjustments in
Raaschou-Nielsen et al. (2003), undermining the validity of the RR
estimates reported in this study.
EPA did not acknowledge that the assumption that lifetime
background incidence rates for each cancer site in the U.S. general
population proportionally approximate the age-specific background
incidence rates in the study populations likely does not hold, because
the epidemiology study populations, generally consisting of workers
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with occupational exposure to TCE, often differed from the U.S.
general population with regard to several lifestyle factors such as
smoking, obesity, and socioeconomic status. These factors could
have impacted the background cancer incidence rates in worker
populations, making them different from the background rates in the
U.S. general population.
EPA assumed that the dose-response relationships for NHL and liver
cancer were similar to the linear one for kidney cancer; however,
because of the use of dichotomous exposure in the underlying data, it
is not possible to know with any degree of confidence that the dose-
response relationships for NHL and liver cancer are linear.
EPA failed to acknowledge the assumption that the dose-response
between TCE exposure and NHL and liver cancer would yield the
same POD as that of kidney cancer. Even if NHL and liver cancer
had identical dose-response curves as kidney cancer, which is
unlikely, the PODs based on 1% extra risks of NHL or liver cancer
would be different from that of kidney cancer because these cancers
have different incidence rates in the general population.
EPA did not demonstrate that any potential risks of kidney cancer, NHL,
or liver cancer from TCE exposures are additive. Even if all three
cancers were causally associated with TCE exposure, and had identical
dose-response relationships, both of which are highly unlikely, this does
not necessarily mean effects were additive.
99, 108
PUBLIC COMMENTS:
Rather than summarily dismissing acute cancer risks because they are
harder to estimate, EPA should have quantified these risks using the
framework outlined by the National Research Council (NRC), which
reflects the best available science.
PBPK model/dose metric and/or cross-species scaling approach
SACC
SACC COMMENTS:
Recommendation: Better discuss/justify the selection of each selected
dose metric.
The text lacks transparency relative to the basis for selection of dose
Some language has been added to section
3.2.5.3.2 justifying use of oxidative metabolites
based on data from (Buben and O'Flahertv,
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metrics, and a number of questions remain to be answered. For
example, how strong is the evidence that liver effects are driven by a
metabolite? Is it merely that early studies show diminution of hepatic
effect with a cytochrome P450 (CYP) inhibitor and enhancement
with CYP inducers? Is this evidence particularly strong? Does this
evidence clearly indicate that it is an oxidative CYP metabolite
versus some other pathway? This might be a relatively
straightforward discussion relative to the liver. However, the basis
for this assumption relative to neurotoxicity, male reproductive
toxicity, or congenital heart defects (only oxidative, not total
metabolism?) is not clear. The short, vague statements in the text
such as evidence suggests a metabolite important or the like, lacks
detail and, therefore, lacks adequate transparency. An enhanced
discussion should be provided in the text and in the uncertainty
discussions. For example, if a single metabolite is responsible for an
effect, is it truly best to use total metabolite as the dose metric?
Would that not introduce more uncertainty than using parent
compound, for example? What if the critical metabolite is a minor
metabolite and the PBPK parameter TotMetabBW34 is overwhelmed
by non-relevant metabolites?
One Committee member suggested that the risk evaluation might
look to using the PBPK model as a more scientific approach to
extrapolating long-term (chronic) exposures from short-term (acute)
exposure data than extrapolating using Haber's Law that multiplies
the exposure concentration (c) by the duration time (t) of exposure.
1985). In that studv toxicity was linear with total
urinary metabolites (and changing kinetics
suggest consistent effects of metabolites even as
parent TCE plateaus). General language
justifying the use of TotMetabBW3/4 and
AUCBld was added to Section 3.2.5.3.
Uncertainties surrounding dose metric selection
are covered in Section 3.2.6.2.
There is too much uncertainty to extrapolate
from acute to chronic exposure data. EPA does
not use Haber's rule for acute to chronic
exposures, only for adjusting hours/day or
days/week exposure. EPA did use the PBPK
model to provide additional occupational
HEC/HEDs for the two key acute and chronic
immunotoxicity studies.
SACC
SACC COMMENTS:
Recommendation: Discuss why the PBPK model could not be used to
examine a dose metric of total absorbed dose of parent TCE for the
Selgrade and Gilmour (2010) study.
It was not clear to some Committee members why this was not done.
If the toxicity is due to the parent compound, then this is the most
appropriate dose metric. Moreover, because the level of any
metabolite must be in some way proportional to the delivery of
Data from (Selgrade and Gilmour. 2010) has
been run through the PBPK model and PBPK
model outputs have replaced the previous
HEC/HED values that were used in the draft risk
evaluation. Based on other immune effects,
TotMetab3/4 is the selected dose metric based
and AUCBld is the alternative dose metric,
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parent compound, then this would still be a potentially valuable dose
metric. The decision to not use this or similar dose metric should be
described.
which is similar to total absorbed dose.
EPA additionally used the PBPK model to
derive HECs/HEDs for occupational exposure
for the two key acute and chronic
immunotoxicity studies.
SACC
SACC COMMENTS:
Although it is not stated in the text, presumably the HEC determination
from Selgrade and Gilmour (2010) is based on the reference
concentration (RfC) methodology assuming TCE is a category 3 gas.
This should be explicitly stated.
Based on the partition coefficient of TCE, it is not clear whether in
short-term exposure the whole body is in steady state (likely not) and
it is not clear the extent to which TCE is recirculated in the venous
blood (thus limiting respiratory tract uptake). Thus, it is not clear that
the standard chronic RfC category 3 assumption is valid.
Because a PBPK model is available and validated (according to the
document), it is unclear why simulations are not performed to
determine if the category 3 assumption is valid.
Methods used for cross-species scaling should be more prominent in
the text rather than in the footnotes of a table.
SACC
SACC COMMENTS:
Recommendation: Expand the discussion on the PBPK model, including
results of sensitivity analyses to identify key inputs.
The discussion of PBPK modeling and its use in dose-response
assessments is too limited and lacks sufficient clarity for most
readers to understand what this model is and how it can be used to
reduce uncertainty relating external chemical exposure to internal
{i.e., blood and target tissue) doses, and in turn to the extent of injury.
Point out the large number of PBPK models and the inordinate time
and effort expended by many scientists to develop the present
version.
Expand description to include the basic model structure and key
input parameters, including physical/chemical properties and
physiological and biochemical indices. Add a table listing the
parameters and referencing the sources of the values. Describe the
Additional discussion has been added
throughout Section 3.2.2.5, however the model
structure was already provided in Figure 3-4 and
a high-level introduction to PBPK modeling was
provided in the first few paragraphs of the
section.
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utility of PBPK models in route-to-route, species-to-species, high-to-
low dose, duration-to-duration, and human-to-human extrapolations.
Emphasize that validated animal and human PBPK models allow one
to make scientifically based predictions of target tissue doses of the
toxicologically active form of TCE to monitor {i.e., the dose metric).
A clear explanation should be given of how the PBPK model is used
to predict/simulate the exposure conditions required to produce the
same blood or target tissue dose in animals and humans by outlining
the basic steps.
Sensitivity analyses are frequently conducted with PBPK models to
determine how much impact variance in each input parameter has on
model output/simulations. Sensitivity analysis of models facilitates
identification of factors, including personal characteristics, that have
the largest impact on systemic deposition and adverse effects in
organs of interest. This method of analysis allows researchers to
learn how characteristics of different individuals or subpopulations
may influence internal dosimetry, and in turn their susceptibility to
particular chemical health effects.
SACC
SACC COMMENTS:
The draft risk evaluation assumes that the same tissue chemical level/
concentration will cause the same degree of injury in each species. It was
not clear to all Committee members that this assumption is valid for all
metabolites.
This uncertainty is accounted for by the 3x
component of UFa that accounts for
toxicodynamic variation and uncertainty. The
PBPK model can only account for toxicokinetic
differences.
SACC
SACC COMMENTS:
Recommendation: Discuss TCE metabolites in more detail including
available evidence on links from metabolites to fetal heart
malformations.
The draft risk evaluation notes that TCE metabolites, not the parent
compound, are suspected as being responsible as the causative agent
for fetal heart malformations. The PBPK model used in the EPA
draft risk evaluation can be used to model the effects of TCE
metabolites such as chloral hydrate, TCOH, trichloroacetic acid,
The consistent positive findings demonstrating
developmental cardiac effects with TCA and
DCA suggest that oxidative metabolism is
important for TCE-induced heart malformations.
All relevant studies are described by the WOE
analysis in Appendix F.3.
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dichloroacetic acid, and others. The experiments by Dawson et al.
(1990, 1993) and Johnson et al. (2003), were not specific or
definitive as to the responsible metabolite(s). The risk evaluation
should provide additional information on all metabolites modeled
and discuss the available evidence on the link from metabolites to
fetal heart malformations.
SACC
SACC COMMENTS:
Recommendation: Include more discussion on uncertainties in the PBPK
model and with route-to-route extrapolation from oral to inhalation.
The cited section (3.2.6) inadequately addresses the uncertainties/
data limitations of PBPK modeling approaches. Toxicity data from
oral exposures are treated as equivalent with data collected from
inhalation exposures, ignoring the uncertainties inherent when
conducting route-to-route extrapolation, even when using a PBPK
model.
One Committee member suggested that EPA re-evaluate the relevance
and quality of toxicity data based on route of exposure. It is not clear that
pathways of exposure in key animal studies are appropriate for human
extrapolation. Is greater weight given to inhalation studies? Is
absorption, distribution, metabolism, and excretion different for
inhalation and oral exposures and could this explain the differences
between fetal heart malformation and immunosuppression findings?
There are sufficient data on TCE to allow proper assessment of health
endpoints via inhalation.
EPA has added a statement to Section 3.2.6.2.
indicating that despite the model being peer
reviewed and the selection of dose metrics that
minimize uncertainties in route-to-route
extrapolation, "there is likely to be remaining
unaccounted uncertainties associated with route-
to-route extrapolation as opposed to relying on
data from the same exposure route as is being
assessed." Despite this uncertainty, EPA relies
on the peer-reviewed PBPK model for
adequately deriving equivalent internal dose
estimates via either inhalation or oral routes.
SACC
SACC COMMENTS:
Recommendation: Consider breathing rates, alcohol consumption and
other models for vapor generation in the inhalation assessment.
Heavy alcohol consumption is known to interact and aggravate some of
the symptoms of TCE exposure. Workers who consume alcohol on a
regular basis, before or after they're exposed to TCE constitute a
vulnerable sub-population.
In response to SACC and public comments,
EPA used the PBPK model to derive
HECs/HEDs for occupational exposure for the
two key acute and chronic immunotoxicity
studies. These model outputs accounted for
elevated breathing rate of workers compared to
the default at-rest assumptions of the model. The
56,
PUBLIC COMMENTS:
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EPA gives insufficient consideration of potential elevated respiration
rates in exposed workers. EPA states that it expects that variability in
human physiological parameters (e.g., breathing rate, body weight, tidal
volume), which may affect internal delivered concentration or dose, is
sufficiently accounted for in the PBPK model although some differences
among lifestages or between working and at-rest individuals may not
have been accounted for.
EPA does not state the basis of this expectation or identify precisely
which "differences . . . between working and at-rest individuals" are
not considered in EPA's model.
The use of HEC99/HED99 (99th percentile for human equivalent
dose [HED]) values is expected to account for the vast majority of
physiological differences among individuals.
It is unclear whether the PBPK model sufficiently addresses potential
elevated respiratory rates in workers.
Workers are a crucial vulnerable subpopulation with respect to TCE,
and EPA must therefore fully and accurately characterize and
account for potential elevated respiratory rates among active
workers.
EPA should not use a resting breathing rate for workers, but rather an
exercise breathing rate, or at least something in between the two.
The recent National Academies of Sciences, Engineering, and
Medicine (NASEM) Review of DOD's Approach to Deriving an
Occupational Exposure Level for TCE, the NAS highlighted that all
PBPK-based derivations of HECs performed using resting ventilation
and associated cardiac output physiological profiles may be
appropriate for clerical or other office workers (e.g., vapor intrusion
within an office building), but for other occupations where
ventilation and cardiac output are elevated by more strenuous
exertion for extended durations, resulting HECs may not be
protective.
For workplace exposure cases, the committee recommended
incorporating exercise (work) physiology and realistic durations from
Page 275 of 408
derived occupational HEC/HED values are
provided in Section 3.2.5.4.1, and they were
used for occupational risk estimates instead of
the default PBPK outputs that were used in the
draft risk evaluation. Alcoholism has been added
as a PESS factor in Section 3.2.5.2, especially in
the context of increased susceptibility due to
enhanced CYP2E1 expression.
EPA identified both workers and ONU as a
PESS in Section 2.3.3.
-------
actual job profiles into PBPK simulations for selected end points
most likely to drive the observed effect level.
EPA is charged with examining the risks to workers in addition to
clerical or other office workers. If EPA did use resting cardiac profiles,
this analysis must be enhanced to provide more realistic estimates of
exposure levels for active workers. If EPA used respiration rates
appropriate for active workers, this should be clearly communicated.
100
Pregnant workers are faced with several physiological burdens, including
elevated cardiac output, heart rate, oxygen consumption, and total air
moved in and out of the lungs, all of which can increase TCE exposure
to the developing fetus. In order to adequately assess risk to the
developing fetus, EPA must take these factors into account and employ
PBPK models that reflect exposure burden in the fetal compartment.
There is no available PBPK model that accounts
for a fetal compartment. EPA believes that use
of 99th percentile outputs will sufficiently
account for toxicokinetic sensitivities of
pregnant women. A statement acknowledging
increased uncertainty due to the lack of a fetal
compartment has been added to Sections 3.2.6.2
and 4.4.1.
108
PUBLIC COMMENTS:
EPA acknowledges important pathways - CYP oxidation pathway and
GSH conjugation pathway - that are involved in TCE metabolism and
lead to the generation of known toxic metabolites including DC A and
TCA. EPA further acknowledges variability across the human population
with regard to these pathways.
EPA's PBPK model attempts to account for these metabolic
differences. However, data gaps introduce uncertainty regarding the
extent to which the PBPK model sufficiently addresses these
variabilities that make individuals differentially susceptible. EPA
should more fully address the extent to which the PBPK model
addresses the acknowledged uncertainty and does so in a manner that
is health-protective, including specifically for susceptible
populations.
EPA states that "[f]or developmental toxicity endpoints, the TCE
PBPK model did not incorporate a pregnancy model to estimate the
internal dose of TCE in the developing fetus." At a minimum, EPA
should explicitly discuss, with supporting evidence, the implications
of the absence of a pregnancy model in the PBPK model with regard
to deriving PODs and ultimately estimating risk.
Page 276 of 408
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EPA should describe how the protection of vulnerable populations,
including the developing fetus, is ensured given EPA's reliance on
the existing PBPK model that does not incorporate a pregnancy
component.
94
PUBLIC COMMENTS:
The kinetic parameters in the PBPK model for the P-lyase enzyme in rats
and humans originating from Clewell et al., 2000 have not been
documented and pre-date the values that were developed by Green et al.
(1997) from in vitro studies. The activity of P-lyase in the metabolism of
DCVC to the reactive metabolites in the kidney was lower in humans
compared to rats.
Additional discussion and citations have been
added to Sections 3.2.2.4, 3.2.6.2, and others
throughout the document concerning uncertainty
around the relative amount of GSH metabolism
occurring in rodents compared to humans.
108
PUBLIC COMMENTS:
EPA should apply an UF of 10 to account for uncertainties for route-to-
route extrapolation. The PBPK model used does not account for dermal
exposure. EPA's decision to rely on inhalation-to-dermal extrapolation
contributes substantial uncertainty to its risk calculations.
Application of oral HED values to dermal
exposure is a conservative assumption that is
unlikely to underestimate risk. Therefore, an
additional UF is not required or appropriate.
62
PUBLIC COMMENTS:
A population-based PBPK model has been published and showed great
similarity in TCE toxicokinetics between humans and mice. The
following studies should be reviewed and considered in the assessment
as relevant toxicokinetics information: Bradford et al. (2011); Chiu et al.
(2014); Yoo et al. (2015a,b,c); and Luo et al. (2018a,b).
EPA's PBPK model is already peer reviewed
and was well-supported by the SACC.
Therefore, EPA is not making any updates to the
model at this time.
34
PUBLIC COMMENTS:
As heart development appears to be the most sensitive marker of TCE
toxicity and Chen et al. (2020) (in the journal "Environmental Science:
Processes & Impacts") and other papers have identified a number of
appropriate markers in the developing heart (e.g., HNF4a transcription
factor), the SACC should recommend that a relative comparison of
exposures be obtained by comparing marker expression in the heart and
changes in cardiac output between oral and inhalation exposures. At a
minimum, this would test the modeling approach used to establish
appropriate levels of inhalation exposure.
Almost all mechanistic data on cardiac heart
effects were in vitro and based on elevated
concentrations. Therefore, a direct extrapolation
to applied doses/concentrations to exposed
human receptors is not possible.
ADME
Page 277 of 408
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SACC
SACC COMMENTS:
Recommendation: Make corrections in statements or provide additional
justification about TCE absorption.
Section 3.2, line 537: It was assumed that systemic absorption of
inhaled TCE is 100%. Dallas et al. (1991) reported systemic uptake
of about 60% of inhaled TCE by rats, with the proportion dependent
upon vapor concentration and duration of exposure. Absorption of
ingested TCE, in contrast, was relatively complete. More than 90%
of TCE given in water by gavage was absorbed by fasted rats
(D'Souza et al., 1985). It should be recognized that the majority of
low oral doses of TCE are removed from the portal blood by first-
pass hepatic and pulmonary elimination, such that very little TCE
reaches the arterial circulation (Liu et al., 2009; Mortuza et al.,
2018).
Section 3.2, line 549: The assumed percutaneous absorption of 100%
is too high. Twenty to thirty percent would be a high estimate. Some
Committee members considered the assumption of keeping TCE in
contact with the skin under occluded conditions for an extended
period as not a realistic exposure scenario. One Committee member
pointed out that this might happen if a consumer were using a TCE-
containing product without gloves and a product-soaked rag.
EPA has added a statement clarifying that more
specific absorption data was incorporated into
the PBPK model to 3.2.2.1. Metabolism of TCE
including first-pass metabolism is described in
Section 3.2.2.3.
EPA does not assume 100% dermal absorption
except under occluded occupational exposure
scenarios, which were not used for risk
estimation. As described in Section 3.2.2.1, both
occupational and consumer assessments
accounted for evaporation in calculating fraction
absorbed of TCE under non-occluded (or non-
impeded evaporation) conditions. Permeability
flux was used in accounting for TCE absorption
for consumer scenarios with impeded
evaporation.
SACC
SACC COMMENTS:
Recommendation: The document needs to provide more accurate and
complete discussion regarding some key aspects of TCE metabolism and
the role of key metabolites in adverse effects caused by TCE.
Section 3.2, lines 595-602, d. 205: Regarding soecies differences in
gamma-glutamytransferase (GGT) activity, the text is incorrect;
mice are higher than humans. See Hinchman and Ballatori (1990) for
information on species differences. Total rat and mouse kidney GGT
levels are similar.
Section 3.2.3, p. 210-Hazard Identification: Gender- and species-
dependent differences, which can be quite prominent, should be
mentioned here.
The statement on GGT activity is accurate as
written according to Table 3-26 of the IRIS
assessment, which cites Lash et al. (1999a;
1998aY
Species-specific differences are discussed in
Toxicokinetics (Section 3.2.2) and PESS
(3.2.5.2) sections. The hazard ID section is
purposely kept succinct and full details of all
studies are not discussed. A reference to sex-
specific differences in GSH conjugation has also
Page 278 of 408
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3.2.3.1.2, p. 211-Kidney Toxicity, lines 779-780: The text states:
"this toxicity is likely caused by DCVC formation, with possible
roles for TCOH and TCA..." There are no data supporting a role for
TCOH or TCA in kidney toxicity.
been added to PESS section 3.2.5.2.
EPA deleted "with possible roles for TCOH and
TCA."
SACC
SACC COMMENTS:
Recommendation: The document should cite recent reviews of TCE
metabolism that have appeared after release of the EPA TCE IRIS
assessment in 2011.
See Lash et al. (2014), Cichocki et al. (2016), and Luo et al. (2018)
for comprehensive reviews of TCE toxicokinetics and mechanisms of
toxicity and carcinogenicity.
These have been added where relevant to the
toxicokinetics section in 3.2.2. (Cichocki et al.
2016) was also cited in the PESS section, while
the (Cichocki et al. 2016) and several Lash
studies were incorporated into the MOA
(3.2.4.2.2) and Metabolism (3.2.2.3) sections.
SACC
SACC COMMENTS:
The committee commented on the written and oral comments from Dr.
James Bus (Commenter 63) at the public meeting focusing primarily on
a new study he co-authored (Zhang et al., 2018) on the relevance of the
glutathione-dependent metabolism pathway for TCE and its role in TCE
induced kidney toxicity and kidney cancer.
Generally, the committee viewed the key points raised by Dr. Bus to
be un-substantiated and long resolved, and the point of the comments
unclear since dismissing the kidney as a target organ for TCE would
have no impact on the TSCA hazard assessment for TCE.
EPA agrees with the SACC and the results of
Zhang et al, 2018 (available at
httDs://www.sciencedirect.com/science/article/Di
i/S0378427418314905) were not incorporated
into the risk evaluation.
63, 94
PUBLIC COMMENTS:
The non-specific HPLC spectrophotometric method used in several
studies that report levels of DCVG has a substantial potential for
chromatographic overlap with peaks of endogenous metabolites that can
result in an overestimation. This was shown in Zhang et al. (2018) using
a side-by-side comparison of a TCE metabolite-specific HPLC MS/MS
method, and indicates that DCVG concentrations reported in the earlier
literature are not reliable for modeling human kidney cancer. A
structure-specific HPLC electrospray ionization (ESI)-MS/MS method is
also available. None of the data using these updated approaches were
incorporated in the draft.
62
PUBLIC COMMENTS:
Page 279 of 408
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The toxicokinetics section, based on EPA (201 le), is incomplete. Data
are now available on organ-, sex-, and strain-specific metabolism of TCE
(gavage) through both oxidative and conjugation pathways. These
studies provide strong evidence that GSH conjugation metabolites are
produced in vivo upon exposure to TCE and reveal organ-specific
information on the levels of these mutagenic species. Information on
inter-organ pathways for metabolism of TCE by the GSH conjugation
pathway is provided in the reviews by Lash et al. (2014; PMID:
25484616 PMCID: PMC4254735) and Rusyn et al. (2014; PMID:
23973663 PMCID: PMC3867557). These reviews cite other relevant
studies.
EPA has added additional detail to the
toxicokinetics and PBPK modeling sections
under Section 3.2.2.
Liver and kidney toxicity
SACC
SACC COMMENTS:
Recommendation: Modify overstatements in Section 3.2.3.1.1 and
3.2.4.1.3.
The Committee felt that several statements are too broad or overstate
the case for liver or kidney toxicity. These include: Section 3.2.3.1.1
p. 210, line 713 that "Animals and humans exposed to TCE
consistently experience liver toxicity," and lines 729-730 "Several
human studies.. .reported an association between TCE exposure and
significant changes in serum liver function tests... ." and Section
3.2.4.1.3, p. 220, line 1180 "Both animal and human studies
consistently observe induction of kidnev toxicity.. .and progression
of existing kidney disease."
It was noted that serum enzyme changes indicative of liver toxicity in
rodents occurred at high doses and that hepatotoxicity was rarely
reported in patients for whom it was used as an anesthetic. It was also
noted that nephrotoxicity has not been consistently observed in
occupational exposure studies, and that evidence of renal proximal
tubular damage is usually mild and limited to increases in certain
cytoplasmic enzymes in urine, and that such effects typically require
chronic TCE exposures.
EPA has modified statements indicating that
studies "consistently" show liver or kidney
toxicity. The statements indicating that multiple
studies demonstrate toxicity are true however
and those have not been modified.
SACC
SACC COMMENTS:
Page 280 of 408
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Recommendation: Clarify what information from Kjellstrand et al.
(1983) is used to calculate the POD for liver toxicity.
It is not clear what inhaled concentration examined in the study by
Kjellstrand et al. (1983) was used in the draft risk evaluation to calculate
the POD. It is difficult to tell from the publication what the NOAEL
and/or LOAEL are for increased liver weight. It appears that 75 ppm was
the LOAEL for liver weight, but 150 ppm was required to cause
cytoplasmic vacuolization. It is not clear whether the vacuolization was
due to lipid, glycogen or water accumulation. Any of these could
contribute to increased liver weight, which is said in line 2115 to be
"merely adaptive," as opposed to cytotoxic. The quality of the
Kjellstrand data needs to be better assessed and more discussion
provided as to whether the observed effect was adverse or adaptive.
Clarification has been added that vacuolization
and inflammatory infiltration occurred at
150ppm and above, and increased liver weight
occurred at ALL dose groups and durations
Inflammatory cell infiltrates would definitely be
considered adverse, and likely are related to
immunotoxicity effects since hepatitis is often
observed as an outcome of hypersensitivity
responses.
SACC
SACC COMMENTS:
There was concern regarding the evaluation of liver toxicity. The
Woolhiser et al. study was excluded because increased liver weight was
not accompanied by other indications of toxicity despite an almost
identical BMLDio value in the Kjellstrand et al. study. The conclusion
that the increased liver weight observed in Woolhiser et al. is an adaptive
response rather than an indicator of toxicity seems speculative and needs
better support.
Liver weight changes alone without any other
indications of toxicity is considered adaptive.
Both (Buben and O'Flahertv. 1985) and
(Kjellstrand et al.. 1983) demonstrated other
liver effects, but (Woolhiser et al. 2006)onlv
showed liver weight increases.
SACC
SACC COMMENTS:
Recommendation: Address the utility/limitation of using the rat data of
Maltoni et al. (1986) to extrapolate to human kidney risk, in view of the
substantially greater metabolic activation of TCE via the GSH pathway
in rats than in humans.
The Committee expressed concern with the use of the rat data of
Maltoni et al. (1986) to establish the POD for nephrotoxicity,
considering the relatively high metabolic activation of TCE in rats, as
demonstrated by Green et al. (1997a,b), Bernauer et al. (1996),
Cooper (1994), and Lash et al. (1990, 2014).
It was also noted that Lash (2001) demonstrated that cultured rat renal
cells were more sensitive to DCVC than human renal cells.
This comment is not specific to the study and
merely expresses uncertainty about extrapolation
of rat kidney data to humans in general. These
differences should be accounted for in the PBPK
model, although uncertainties about GSH
conjugation parameters in the model are
acknowledged in 3.2.6.2. (Bernauer et al. 1996)
actually concluded that you cannot compare the
data between rats and humans, only that they
both do use the pathway. The following text has
been added to the section:
Page 281 of 408
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"There is additional uncertainty in extrapolation
to humans based on evidence suggesting that
metabolic formation of the reactive conjugative
metabolites may be an order of magnitude
greater in rats than humans (Green et al. 1997b;
Lash et al. 1990) and that renal toxicity mav not
be directly related to the rate of DCVC
formation (Green et al. 1997a, b). These
metabolites are indeed formed in both rats and
humans, however, (Bernauer et al. 1996) and in
vitro data suggests that human GSH conjugation
activity may actually be higher than rodents in
some cases (Table 3-23 and 3-26 of (U.S. EPA,
201 le)). Additionally, their slow elimination
kinetics relative to oxidative species indicate
that even lower relative concentrations may
contribute to sustained chronic toxicity
(Bernauer et al. 1996)."
108
PUBLIC COMMENTS:
EPA dismisses an NTP study of kidney toxicity without sufficient
justification.
EPA selects Maltoni et al. (1986) as the representative study for the
kidney toxicity endpoint, a departure from the 2014 Work Plan
Assessment, in which the NTP (1988) study was selected because it
provided the lowest POD.
Both studies were rated as "medium" quality, and the HEC99 for
Maltoni et al. (1986) is nearly 5 times higher.
EPA justifies the decision stating "elevated doses in the NTP study
resulted in massive nephrotoxicity and introduce large uncertainty in
BMD modeling the effects at low doses well below the tested doses
with a BMR well below the observed effect incidence in the study;"
this issue was directly addressed in the 2011 IRIS assessment and
deemed not to represent a concern to warrant not relying on the NTP
Consideration of dose levels in a study
compared to the extrapolated BMDL is
discussed in EPA's Benchmark Dose Technical
Guidance Document (U.S. EPA, 2012a). The
(NTP, 1988) studv itself includes a statement at
the beginning indicating that the doses were
recognized as too high for sensitive evaluation
of effects.
Page 282 of 408
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study.
Given that (1) the NTP study provides the lowest HEC99 on the most
severe kidney toxicity endpoint and (2) modeling challenges did not
present concerns in prior assessments, EPA should select the POD from
the NTP 1988 study rather than the Maltoni et al. (1986) study to
represent the kidney toxicity endpoint.
62
PUBLIC COMMENTS:
EPA stated that it did not identify any new repeat-dose experimental
studies in animals or human epidemiological studies that would
contribute significant additional hazard information for kidney toxicity.
However, there are additional informative studies. For example, a study
by Yoo et al. (2015; HERO ID 2799570; PMID: 25424545; PMCID:
PMC4281933) examined TCE metabolite levels and toxicity phenotypes
in kidneys in mice of various strains after subacute and subchronic
exposures. Data from the subchronic experiment should be extracted for
dose-response analysis.
This study is primarily examining toxicokinetics
in kidney and does not include any novel
endpoints or dose-response information.
62
PUBLIC COMMENTS:
Tables 22-24 in the Data Quality Evaluation document provide results of
the review of the study quality of two companion studies by Yoo et al.
(2015) [HERO IDs 2799569 and 2799570], These studies report data for
liver and kidney effects in two separate manuscripts; however, the data
were collected in the same set of in vivo studies and the same strengths
and weaknesses should apply. The document included separate
evaluations of the subacute and subchronic experiments for liver
endpoints, but not kidney endpoints. It is recommended that for
consistency, the data on renal outcomes should be evaluated separately
between subacute and subchronic study arms, as was done for the liver.
This will be taken into account for consideration
in future Risk Evaluations.
Developmental toxicity (other than fetal cardiovascular defects)
SACC
SACC COMMENTS:
One Committee member indicated that the draft risk evaluation (and the
TSCA program in general) need to define the term "developmental
toxicity." It is not clear whether this refers to toxicity that is induced by
developmental exposure, but which may manifest at any time during life,
Developmental toxicity refers to endpoints
affecting fetal or neonatal outcomes. This
definition has been added to Section 3.2.3.1.6.
Page 283 of 408
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or refer only to pathologies that occur during infancy and childhood.
SACC
SACC COMMENTS:
Recommendation: Justify why developmental toxicity was not given
more consideration in the risk characterization.
There is evidence from both epidemiological and animal studies that
developmental toxicity may be an especially sensitive endpoint for
TCE. The draft risk evaluation discounts investigations describing
these effects, because some did not demonstrate dose-dependency,
some were mouse strain-specific, or some were not of adequate
quality. Studies from Camp Lejeune indicate adverse developmental
effects may occur in response to TCE exposures lower than those
required to cause toxicity in adults. Assessment of this endpoint is
especially important.
The study by Peden-Adams et al. (2006) exhibited one of the lowest
PODs among developmental toxicity studies but was scored Low and not
considered for risk characterization. This was considered unacceptable
by at least one Committee member, who noted that other immunotoxicity
studies of inferior quality received higher quality ratings and were
considered key studies.
Developmental toxicity is thoroughly considered
in the risk evaluation, and three developmental
endpoints are included for risk estimation. While
(Peden-Adams et al.. 2006) did receive a Low
rating, EPA notes in the document that the POD
from (Keil et al., 2009) is almost identical to the
(Peden-Adams et al.. 2006) POD and would
therefore be expected to be protective of those
developmental effects.
SACC
SACC COMMENTS:
Recommendation: Clarifications and corrections are needed.
Section 3.2.3.1.6, pp. 215-216: The draft risk evaluation states (lines
950-952) that aside from congenital heart defects, it does not identify any
repeat-dose experimental studies in animals or human epidemiological
studies that would contribute significant additional information for
developmental effects. Then the draft risk evaluation goes on to describe
numerous papers (including studies from Camp Lejeune exposure) that
associate developmental TCE exposure to various developmental
outcomes in humans such as spontaneous abortion, developmental
neurotoxicity, and childhood cancers. This is very confusing and needs
to be clarified.
EPA has clarified that the statement applies to
"new" studies, as in studies published after
previous EPA assessments (e.g., IRIS
Assessment, 2014 Risk Assessment).
SACC
SACC COMMENTS:
Recommendation: Describe and discuss the findings of recent
An endpoint for developmental neurotoxicity
Page 284 of 408
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investigations of adverse effects of TCE on the developing nervous
system.
EPA adequately addresses acute neurotoxic effects such as CNS
depression, but should consider recent investigations of developmental
neurotoxicity (Salama et al., 2018; Blossom et al., 2017).
from (Fredriksson et al., 1993) is included as a
representative POD for developmental toxicity
and risk estimation. EPA has also added hazard
information from (Blossom et al. 2016) (correct
citation for Blossom et al., 2017) and (Salama et
al. 2018) as recommended to Section 3.2.3.1.6.
100
PUBLIC COMMENTS:
EPA ignores evidence of TCE's developmental effects.
In its 2014 risk assessment of TCE's degreasing, spot cleaning and
arts and crafts uses, EPA wrote "the available studies collectively
suggest that the developing brain is susceptible to TCE
toxicity...studies have reported an association with TCE exposure
and CNS birth defects and postnatal effects such as delayed newborn
reflexes, impaired learning or memory, aggressive behavior, hearing
impairment, speech impairment, encephalopathy, impaired executive
and motor function and attention deficit."
Since 2014, several additional studies have reported further evidence of
TCE's neurodevelopmental effects. However, EPA fails to consider
those more recent studies in its evaluation, and therefore, fails to
adequately evaluate the neurodevelopmental risk of exposure throughout
pregnancy, a likely scenario for pregnant workers.
105,
108
PUBLIC COMMENTS:
The study by Peden-Adams et al. (2006) provides a sensitive
developmental toxicity endpoint for the dose-response assessment of
TCE. The IRIS toxicology review of TCE used Peden-Adams et al.
(2006) to support the derivation of the TCE RfD, indicating that "[f]or
adult and developmental immunological effects, there is high confidence
in the evidence of immunotoxic hazard from TCE." Yet, for the draft risk
evaluation, Peden-Adams et al. (2006) was excluded by EPA in its dose-
response assessment and a POD was not derived. EPA explained "while
this endpoint exhibits one of the lower PODs among developmental
studies, the study scored a "Low" in EPA's data quality evaluation due
While (Peden-Adams et al., 2006) did receive a
Low rating, EPA notes in the final risk
evaluation that the POD from (Keil et al.,
2009) is almost identical and would therefore be
expected to be protective of those developmental
effects. EPA often uses expert judgement to
downgrade or upgrade studies from the
calculated scores when the metrics do not
sufficiently account for all considerations of data
quality. The evaluation for this study was
Page 285 of 408
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to concerns over statistical reliability and dose precision."
However, the systematic review evaluation resulted in a score of
"Medium" quality. The "Medium" rating appears crossed out (i.e.,
strikethrough text) and changed to "Low." The footnote provides, as
the rationale for the rating change, the same criteria that supported
the "Medium" quality rating. This study should receive the same
"Medium" rating consistently throughout the document. The
conclusions of study quality should be scrutinized due to a
problematic systematic review method.
EPA also stated that this study could not be accurately PBPK modeled
because exposure occurred in utero, through nursing, and after weaning.
The fact that the PBPK model cannot accommodate the exposure
scenario in the Peden-Adams et al. (2006) study is an issue with the
model, not a flaw in the study.
The earlier EPA IRIS analysis for the RfD (U.S. EPA, 2011) was
able to calculate doses for the Peden-Adams et al. (2006) study,
based on information from the authors. That analysis calculated a
LOAEL of 0.37 mg/kg-day (1.4 ppm) TCE.
This study should not have been excluded due to the erroneous "Low"
rating or because the data could not be used in an existing PBPK model.
reviewed several times by EPA subject matter
experts who agreed with the final score.
89
PUBLIC COMMENTS:
Links between TCE and specific cancers and to birth defects must be
taken more seriously. The following studies suggest a strong link
between exposure to low levels of TCE and certain cancers and
developmental effects: Chiu et al. (2013); Forand et al. (2012); Caldwell
et al. (2008); Drake et al. (2006); and Peden-Adams et al. (2007).
These studies were all included in the draft Risk
Evaluation and have been retained in the final
version. Multiple endpoints for developmental
toxicity and cancer at multiple tumor sites were
included in risk estimation.
Other endpoints
SACC
SACC COMMENT
Recommendation: Clarifications and corrections are needed.
Section 3.2.3.1.4, p. 212: In discussing TCE-induced neurotoxicity in
humans, the document needs to make it clear that TCE exposures for
neurological effects are generally at quite high doses.
At least one Committee member considered the statement in Section
The commenter must mean Section 3.2.3.1.3.
EPA disagrees that neurotoxicity effects are only
at high doses, as PODs for the key neurotoxicity
endpoints are all based on LOAELs ranging
from 12-47 mg/kg-day.
Page 286 of 408
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3.2.4.1.5 p. 220, lines 1212-1214 to be inaccurate. The declaration
that there is strong evidence from human and animal data of male
reproductive effects is, in their opinion, overstated. The statement
about insufficient evidence for TCE-induced female reproductive
toxicity is incorrect.
Section 3.2.3.1.5 -Reproductive toxicity, p. 214: Six studies
published in 2016, 2018, 2019, and 2020 by R. Loch-Caruso and
colleagues that provide evidence of female reproductive toxicity of
TCE in vivo and DCVC in vitro are not identified or discussed. See
Hassan et al. (2016); Elkin et al. (2018); Elkin et al. (2019); Hassan
et al. (2019); and Elkin et al. (2020).
"Strong" has been changed to "consistent," since
multiple epidemiological and animal studies
have observed male reproductive effects.
The 2020 Elkin review (Elkin et al. 2020) and
the cited 2019 animal studv ((Loch-Caruso et al.
2019), cited here as Hassan 2019) have been
cited in the hazard ID section, 3.2.3.1.5,
however it is noted that the significance of
DCVC to reproductive tox is unclear.
The 2016 study was identified in the literature
search but did not pass PECO because except for
cardiac malformations or other developmental
toxicity outcomes, mechanistic studies
(especially on metabolites) were excluded. The
other studies were all published after the lit
search cutoff date in 2017.
In the WOE section (3.2.4.1.5), the WOE for
female reproductive effects was also upgraded
from "insufficient information" to "limited
information" supporting the outcome.
Foreign language studies are outside the scope
of EPA's PECO statements as published in the
Problem Formulation document.
108
PUBLIC COMMENTS:
SACC members raised additional concerns around the absence of studies
on specific topic areas. One panelist noted the absence of sufficient
information on female reproductive toxicity. Another indicated that
TCE-induced occupational dermatitis is prevalent but that much of the
relevant literature is published in a foreign language. EPA should include
relevant studies published in languages other than English when
pertinent to a risk evaluation and employ necessary resources to have
them translated to ensure these studies are captured.
60
PUBLIC COMMENTS:
For endpoints other than fetal cardiac defects, the rationale for selection
of studies for use in risk evaluation from those available was not
transparent.
Section 3.2.5.1 in the Risk Evaluation lists the
acceptable studies containing adequate dose-
response information. Among those studies,
detailed considerations for the studies and PODs
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selected among that group are provided in
Section 3.2.5.3.
81
PUBLIC COMMENTS:
Is TCE linked with Parkinson's disease, and if yes, how can we
decelerate the disease and prevent the manifestation of clinical
symptoms?
This comment is beyond the scope of the TCE
Risk Evaluation.
General
SACC
SACC COMMENT
Recommendation: Make sure that broad terminology that may be unclear
to some readers is defined.
Section 3.2, lines 487-488, p. 202: What exactly does "acute overt
toxicity" mean? This is an odd term that needs to be explained.
The term has now been defined in the section
(3.2.3.1.7).
SACC
SACC COMMENT
Recommendation: Clarifications and corrections are needed.
Section 3.2.5.2, p. 233, lines 1822-1862: NRC (2009) reviewed
factors influencing susceptibility of human populations to TCE
toxicity and carcinogenicity. This comprehensive review might be
cited here.
EPA has added a reference to the NRC
assessment, which was actuallv in 2006 (NRC,
2006).
91
PUBLIC COMMENTS:
Current research shows that TCE is linked to liver cancer, kidney cancer,
Parkinson's Disease, congenital heart defects, and other diseases. EPA
has not adequately evaluated available data and is not justified in taking
this action. Please conduct a thorough review of the existing literature
and reevaluate. A reliable risk evaluation of TCE cannot be made using a
fraction of the relevant scientific information.
EPA has performed a thorough systematic
review on the reasonably available literature for
TCE as of February 2017. EPA does not believe
that it missed any relevant studies and has
identified each of the health effects mentioned in
the comment within the Risk Evaluation.
Additionally, EPA has added select relevant
individual studies identified to EPA that were
published after that date (Harris et al 2018;
Charles River Laboratories, 2019).
32
PUBLIC COMMENTS:
There has been no federal support for the investigation of TCE and
congenital heart defects since 2009 and a recommendation in this area by
the SACC could be useful.
EPA always encourages additional research that
may yield more useful information.
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32
PUBLIC COMMENTS:
Despite the substantial data referenced in the draft document showing
that TCE produces congenital heart defects, the draft recommendations
do not reference this issue in any affected population. I would argue that
any and all uses of TCE, as described in the draft, should be
accompanied by an explicit warning that low levels of TCE can cause
heart defects and that women who are pregnant or who might be
pregnant should avoid any and all exposure to the solvent.
Per the statute (see TSCA section 6(b)(4)(A))
and the implementing regulations for risk
evaluations (40 CFR part 702, subpart B), during
risk evaluation, EPA must determine whether
the chemical substance presents unreasonable
risk under its conditions of use. Upon finding
unreasonable risk, EPA will apply risk
management actions to the extent necessary so
that the chemical no longer presents such risk, in
accordance with TSCA section 6(a). Warning
labels are one of the regulatory management
components that EPA considers during risk
management.
45
PUBLIC COMMENTS:
The following relevant studies were not included in the draft risk
evaluation:
Alterations in immune and renal biomarkers among workers
occupationally exposed to low levels of trichloroethylene below
current regulatory standards. Lee KM, Zhang L, Vermeulen R, Hu
W, Bassig BA, Wong JJ, Qiu C, Purdue M, Wen C, Walker DI, Jones
DP, Li L, Huang Y, Rothman N, Smith MT, Lan Q. Occup Environ
Med. 2019 Jun;76(6):376-381. doi: 10.1136/oemed-2018-105583.
Epub 2019 Apr 10.
Trichloroethylene perturbs HNF4a expression and activity in the
developing chick heart. Harris AP, Ismail KA, Nunez M, Martopullo
I, Lencinas A, Selmin 01, Runyan RB. Toxicol Lett. 2018 Mar
15;285:113-120. doi: 10.1016/j.toxlet.2017.12.027. Epub 2018 Jan 4.
[Role of complement regulatory protein CD55 in the liver immune
injury of trichloroethylene-sensitized mice], Wang X, Zhang C, Yang
XD, Li BD, Zang DD, Yang P, Zhang JX, Zhu QX. Zhonghua Lao
Dong Wei Sheng Zhi Ye Bing Za Zhi. 2017 Apr 20;35(4):246-250.
The 2019 study was published after the
conclusion of EPA's literature search and would
not add any significant new information to
hazard conclusions since kidney toxicity was
already included in risk estimations. (Harris et
al 2018) was included in the cardiac defects
WOE analysis. (Gilbert et al 2017) was
included in the on topic literature but not cited
in the RE because it did not include any
significant information beyond what was already
discussed. EPA did add discussion of (Gilbert et
al. 2014) covering developmental
immunotoxicitv. (Meadows et al. 2017) was not
included in the literature search and was not
cited for the same reason as above. Jiang et al.
2017 (actually (Jiang et al.. 2016)) also was
outside the window of the literature search and
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doi: 10.3760/cma.j.issn. 1001-9391.2017.04.002. Chinese. did not add significant novel information that
Exposure cessation during adulthood did not prevent immunotoxicity would affect the conclusions of the Risk
caused by developmental exposure to low-level trichloroethylene in Evaluation.
drinking water. Gilbert KM, Bai S, Barnette D, Blossom SJ. Toxicol
Sci. 2017 Jun l;157(2):429-437. doi: 10.1093/toxsci/kfx061.
A single dose of trichloroethylene given during development does
not substantially alter markers of neuroinflammation in brains of
adult mice. Meadows JR, Parker C, Gilbert KM, Blossom SJ, DeWitt
JC. J Immunotoxicol. 2017 Dec;14(l):95-102. doi:
10.1080/1547691X.2017.1305021.
The role of miR-182-5p in hepatocarcinogenesis of trichloroethylene
in mice. Jiang Y, Chen J, Yue C, Zhang H, Tong J, Li J, Chen T.
Toxicol Sci. 2017 Mar 1; 156(l):208-216. doi:
10.1093/toxsci/kfw246.
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6. Risk Characterization
Uisk CharacU'ri/alion
Charge Question 6.1: Please comment on whether the information presented to the committee 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 risk estimates within the context of the requirements stated in EPA's Final Rule, Procedures for Chemical Risk
Evaluation Under the Amended Toxic Substances Control Act (82 FR 33726) (Section 4).
Charge Question 6.2: EPA presented overall human health risk conclusions (Section 4.5.2) based on risk estimates for the endpoints
that it believes are best representative of acute and/or chronic scenarios (see Question 5.3 - immunosuppression for acute exposure,
autoimmunity for chronic exposure). Please comment on EPA's approach including any alternative considerations for determining
and presenting risk conclusions including the risk summary tables (Table 4-54 and 4-55).
Charge Question 6.3: Please comment on the calculation of risk derived from different exposure data sources (e.g., modeling tools
and monitored datasets) and how they account for variability in environmental and human exposure. Please provide specific
recommendations as needed for improving the risk characterization and references to support any recommendations (Section 4).
Charge Question 6.4: 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 (Section 4.3).
Charge Question 6.5: Please comment on the clarity and validity of specific confidence summaries presented in Section 4.3.
Charge Question 6.6: Has a thorough and transparent review of the available information been conducted that has led to the
identification and characterization of all PESS (Sections 2.3.3, 3.2.5.2, and 4.4.1)? Do you know of additional information about
PESS that EPA needs to consider? Additionally, has the uncertainty around PESS been adequately characterized?
Charge Question 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 (exposure - Sections 2.3.1.2.6 and
2.3.1.3, Table 2-20; risk - Sections 4.2.2 and 4.3.2.1).
Charge Question 6.8: Please comment on any other aspect of the environmental or human health risk characterization that has not
been mentioned above (Section 4).
#
Summary of Comments lor Specific Issues Related to Charge
Question 6
KPA/OPPT Response
Cancer risk benchmark is not valid
56, 108
PUBLIC COMMENTS:
EPA's unprecedented use of 1 in 10,000 as the cancer risk benchmark
for workers underestimates risk and violates EPA's long-standing
policy "that it should reduce risks to less than 1 x 10"6 for as many
exposed people as reasonably possible." Workers are specifically
As noted in the draft risk evaluation, EPA relied
on Agency precedent and NIOSH guidance when
choosing the 10"4 cancer risk benchmark to
evaluate risks to workers from TCE exposure.
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identified under TSCA as a vulnerable subpopulation warranting special
protection.
The standard cancer benchmarks used by EPA
and other regulatory agencies range from 1 in
1,000,000 to 1 in 10,000 {i.e., lxlO"6 to lxlO"4)
depending on the subpopulation exposed.
Generally, EPA considers lxlO"6 to lxlO"4 as the
appropriate benchmark for the general
population, consumer users, and non-
occupational PESS.
EPA, consistent with 2017 NIOSH guidance,
used lxlO"4 as the benchmark for the purposes of
this unreasonable risk determination for
individuals in industrial and commercial work
environments, including workers and ONUs.
EPA has consistently applied a cancer risk
benchmark of lxlO"4 for assessment of
occupational scenarios under TSCA. lxlO"4 is
not a bright line and EPA has discretion to make
unreasonable risk determinations based on other
benchmarks as appropriate. See Section 5.1.1.2
of the risk evaluation for additional information.
56, 69,
108
PUBLIC COMMENTS:
EPA's use of a 1 in 10,000 cancer risk level as reasonable is flawed.
EPA cites this benchmark for workers to NIOSH (under OSHA) and the
Benzene decision despite indicating that TSCA has different standards.
There is no basis in TSCA (including 2016 amendments) for EPA to
provide less protection to workers than to any other potentially
exposed or susceptible subpopulation.
EPA's reliance on the Benzene decision is unfounded because EPA
cannot point to statutory language in TSCA evoking the same
standard to regulate significant risks (under the Occupational Safety
and Health Act) rather than unreasonable risks (under TSCA).
In implementing TSCA, EPA has generally sought to reduce
population risks from chemicals in commerce that are carcinogens
to one case per million people {i.e., lxlO"6 risk level).
EPA mentions uses of a lxlO"4 risk level based on the "two-step
approach" under the CAA; however, that level reflects the limit on
maximum individual lifetime cancer risk (rather than a level set to
protect the vast majority of the population).
EPA erroneously invokes the risk level lxlO"4 to numerous COUs so
that no risk is identified for workers, subjecting workers to cancer risks
that are two orders of magnitude higher than warranted. This approach
must be rejected on scientific and legal grounds.
56, 69,
74, 108
PUBLIC COMMENTS:
EPA's use of a lxlO"4 risk level failed to identify risk as unreasonable in
numerous cases and understates the magnitude of the cancer risk even
where it is identified as unreasonable.
Using a benchmark of lxlO"5 or lxlO"6, unreasonable cancer risk
would have been identified in 11 or 12 additional cases (identified in
79 of 91 cases using lxlO"4).
Where unreasonable risk was identified, use of the appropriate
benchmark would have established the need to reduce exposure by
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10-fold via TCE regulations to eliminate unreasonable risk.
74
PUBLIC COMMENTS:
EPA applied a cancer risk benchmark up to two orders of magnitude
less protective than warranted. EPA's benchmark of 1 in 10,000 means
that it provides far less protection to workers than the general
population, let alone other vulnerable subpopulations, directly
contravening TSCA. The only support that EPA cites is policy and
practice under other laws or by other agencies, ignoring the fact that
their standards differ fundamentally from that of TSCA.
99
PUBLIC COMMENTS:
EPA used a cancer risk of lxlO"4 as the benchmark for determining
unreasonable risk to workers. This benchmark results in a significantly
smaller number of worker exposure scenarios that present unreasonable
risks than under cancer risk levels of lxlO"5 and lxlO"6. The SACC has
stated that EPA has not provided "adequate explanation and
justification" for this reduced threshold and that the TCE draft risk
evaluation fails to justify EPA's approach. Despite reserving discretion
to make case-by-case decisions within the range, however, EPA has
identified lxl0"6 as its goal for public health protection. However,
EPA's recent draft risk evaluations deviate from this approach for
worker exposures, maintaining that risks smaller than lxlO"4 will be
considered "reasonable" under TSCA because, "consistent with case
law and 2017 NIOSH guidance," this risk level applies to "industrial
and commercial work environments subject to Occupational Safety and
Health Act (OSHA) requirements." However, the Occupational Safety
and Health Act precedent does not control decision-making under
TSCA, a separate law with different purposes and wording.
The cancer risk threshold applied by NIOSH and OSHA is rooted in
the Benzene decision and is based on the finding that significant
risks are present.
TSCA is anchored in the concept of "unreasonable risk" (a lower
risk threshold than "significant risk"); no provision of TSCA
provides that workers should receive less protection than other
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exposed populations or that well-established benchmarks for
unacceptable cancer risks would be inapplicable to workers.
TSCA protects workers from exposures in the workplace as well as
from other sources, such as environmental releases and consumer
products. Since the draft risk evaluation assesses worker exposures
in isolation from other pathways, risks are already understated.
EPA must apply to workers the same benchmarks for determining
unreasonable cancer risk that it uses for other populations. For all
populations, EPA should consider increased cancer risk exceeding
lxlO"6 to be unreasonable and to require action under TSCA.
100
PUBLIC COMMENTS:
When measuring cancer risks for non-workers potentially exposed or
susceptible to a chemical, EPA considers a range of one increased
incidence of cancer in every 10,000 to 1,000,000 people as evidence of
unreasonable risk. For workers, however, EPA uses only the lowest end
of the range, characterizing increased cancer risks of up to 1 in 10,000
workers as reasonable and not warranting regulation. Although EPA
cites NIOSH for this benchmark, NIOSH is not required to set risk
management limits at levels that avoid unreasonable risk to PESS. EPA
also cites AFL-CIO v. American Petroleum Institute 448 U.S. 607 (the
"Benzene decision") to support its decision, even though it has no
bearing on EPA's duty to identify and manage unreasonable risks under
TSCA. Consistent with NIOSH recommendations, EPA should reduce
exposure to occupational carcinogens as much as possible, the extent of
which should be decided during risk management, and not risk
evaluation.
When TSCA was amended in 2016, a requirement was added that risk
evaluations analyze risks to PESS including workers. Despite this
mandate, EPA's draft risk evaluation accepts greater risks to workers
than the general population. Whereas 1 in 10,000 to 1,000,000 was used
as a measure of unreasonable cancer risk for non-workers potentially
exposed or susceptible, EPA uses the lowest range for workers,
Page 294 of 408
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characterizing risks of up to 1 in 10,000 as reasonable and not
warranting regulation. There is not valid reason to accept such high
risks to workers.
Cancer risk estimates should be calculated for acute exposure
56, 108
PUBLIC COMMENTS:
EPA failed to include estimates of acute cancer risk to workers and
consumers.
EPA states that the "extrapolation of lifetime theoretical excess
cancer risks to single exposures has great uncertainties" and that
"the relationship between a single short-term exposure to TCE and
the induction of cancer in humans has not been established in the
current scientific literature."
NRC guidance recommends applying the linearized multistage
model to assessing carcinogenic risks based on exposures of short
duration, and that the decision to conduct such extrapolation and
modeling should be based on the "sound biological and statistical
principles."
There is concern that EPA did not sufficiently consider such
principles related to MOA in deciding not to model acute cancer
risk. In particular, given that: (1) EPA recognizes that "there is
sufficient evidence that TCE-induced kidney cancer operates
primarily through a mutagenic mode of action" and (2) a mutagenic
MOA suggests a role for "a single direct reaction, specifically, a
single hit in a single target," a linear low-dose extrapolation from
chronic to acute exposures would be the appropriate approach to
take for TCE.
EPA's current approach assumes that acute exposures to TCE, including
to consumers, pose zero cancer risk - an assumption not warranted
based on the WOE. EPA needs to apply an extrapolation that provides a
scientifically sound estimate for cancer risk from acute and short-term
exposures to TCE.
Standard Operating Procedures for Developing
Acute Exposure Guideline Levels for Hazardous
Chemicals notes the significant uncertainty in
extrapolating risks from lifetime exposures to
shorter (once in a lifetime) exposures. The SOP
specifically points out the complex nature of
biological mechanisms related to cancer and
possible differences in such mechanisms when
considering them for acute vs. chronic exposures.
Krewski et al. (2004) further notes that there are
often limited single-exposure inhalation toxicity
data to consider such an extrapolation from
lifetime exposures.
For these reasons, EPA doesn't consider use of
short-term cancer risk estimates to be appropriate
for the current risk evaluation.
99
PUBLIC COMMENTS:
It is recognized that genotoxic carcinogens like TCE can induce cancer
Page 295 of 408
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following a limited acute exposure event and methods are available to
estimate such risks. As stated in the 2011 NRC report, there is
methodology for extrapolating findings of carcinogenicity in long-term
studies to exposures of short duration. EPA acknowledges the
possibility of calculating acute cancer risks in the draft risk evaluation
but declines to do so owing to "uncertainties" in the methodology.
Rather than dismissing acute cancer risks because they are harder to
estimate, EPA should have quantified these risks using the framework
outlined by NRC, which reflects the best available science.
Use of unified linear risk approach instead of MOE approach
56, 108
PUBLIC COMMENTS:
In accordance with the NAS report (Science and Decisions: Advancing
Risk Assessment), EPA must employ health-protective approaches to
dose-response modeling, including the recommendation that cancer and
non-cancer responses be assumed linear as a default. The MOE
approach provided in the draft risk evaluation fails to provide a measure
of population risk at a given exposure level, which limits its utility for
risk managers.
The NAS Committee on Improving Risk Analysis Approaches
concluded that separation of cancer and non-cancer outcomes in
dose-response analysis is artificial, because non-cancer endpoints
can occur without a threshold or low-dose nonlinearity at the
population level; background exposures and underlying disease can
contribute to background risk and lead to linearity at population
doses of concern.
EPA should implement the recommendation by NAS to develop a
unified approach to presenting dose-specific population risks for cancer
and non-cancer endpoints.
EPA relied on existing accepted guidance (e.g.,
(EPA 2012a, 2005a, 2002)) to evaluate
noncancer and cancer endpoints in the current
risk evaluation of trichloroethylene. These
methods include PBPK models for TCE-specific
distributional information on toxicokinetics
among rodents and humans; appropriate
uncertainty factors for non-cancer endpoints; and
a linear low-dose extrapolation to model risk
from cancer, based on a likely genotoxic MOA.
EPA believes that these methods adequately
account for variability and susceptibility within
the population, a concern raised bv NRC (2009).
However, EPA will investigate additional
scientific approaches for our next set of TSCA
risk evaluations.
99
PUBLIC COMMENTS:
The draft risk evaluation, building on previous determinations,
concluded that TCE is genotoxic and uses linear extrapolation.
However, at the SACC meeting, some industry presenters urged that
EPA base cancer risks on a non-linear MOA. We strongly recommend
EPA used a linear no-threshold model for
calculating cancer dose-response. The SACC
agreed with the use of a linear model based on
the MOA and EPA Guidelines for Carcinogen
Page 296 of 408
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against this approach. EPA's Guidelines for Carcinogen Risk
Assessment emphasizes that a high level of evidence is necessary to
deviate from the presumption of linearity.
Risk Assessment.
Descripl
tion of uncertainties and data limitations in Section 4.3 is incomplete
SACC
SACC COMMENTS:
Recommendation: Clarify how the results of exposure uncertainty
analysis are used in the characterization of consumer risk, and consider
performing a more comprehensive uncertainty analysis (i.e., varying
parameters instead of using defaults, for example).
The Committee was unclear about how the results of the limited (i.e.,
only some inputs were varied) uncertainty analysis for consumer
exposure were incorporated into the risk characterization and why a
more comprehensive uncertainty analysis was not performed.
EPA varied key parameters governing the known
product range of weight fractions and user
behavior (mass and duration) in order to present
a range of potential exposures (referred to as
"user intensity levels") in the RE. Risk estimates
were presented at low, medium, and high user
intensity levels for each consumer COU. EPA
incorporated uncertainty and confidence in
consumer scenarios into the overall risk estimate
confidence scores in Section 4.3.2.4.
SACC
SACC COMMENTS:
Recommendation: Better organize the discussion on assumptions and
uncertainties in Section 4.3 and summarize (tabulate) more of the
exposure and hazard uncertainties in this section rather than referring to
previous sections.
The uncertainty and data limitation sections lack balance, are
incomplete, and should be expanded.
More than 2 pages are devoted to exposure and only one paragraph
to human health hazard (p. 350). The issues of greatest
uncertainties/limitation pertaining to human hazard should be
highlighted here, rather than referring the reader to Section 3.2.6.
The summary of uncertainties is too limited (reader is referred to
Section 2.3.1.3). One would expect to see a complete summary of
uncertainties in this section. A table format would be helpful.
Concerns and issues with congenital heart defects as a non-cancer
endpoint are ignored in this section and should be summarized.
Uncertainties in exposure and hazard estimates translate into
uncertainties in the risk characterization. A recurrent issue in this
EPA is considering different formats for
presenting uncertainty in risk estimates. The
SACC proposed varying options without
consensus, and EPA will need to determine the
most efficient yet informative way to incorporate
uncertainties across the different aspects of the
risk evaluation. These changes may be
incorporated into future risk evaluations.
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draft risk evaluation is lack of transparency about how the
uncertainties and sensitivity analysis get integrated into a balanced
evaluation of uncertainty in risk characterization. The Committee
believes that an integrated evaluation of uncertainty in the risk
characterization would be valuable. This involves risk propagation
of uncertainties across the characterization of risk done at least
semi-quantitatively (e.g., high, medium, low) with accompanying
statements of why each is rated as it is. The summary table should
provide annotation and an integrated, semi-quantitative description
of uncertainty in the risk characterization.
One Committee member suggested using confidence summary
slides similar to Slide #48 in the EPA OPPT technical presentation
to SACC; other Committee members indicated that other slides in
this presentation (# 13, 24, 27) were useful and should be included
in the risk evaluation.
Section 3.1.7 has a more detailed discussion of uncertainties and
limitations in environmental hazard identification than that provided
in Section 4.3.1. One Committee member suggested either
expanding Section 4.3.1 or cross-referencing much of Section 4.3.1
back to Section 3.1.7.
More discussion is needed on the uncertainties in the PBPK model
including route-to-route extrapolation (oral to inhalation).
SACC
SACC COMMENTS:
Recommendation: Integrate sensitivity analysis findings with the
discussion of uncertainties.
Although confidence summaries are presented clearly, it is less clear
how assumptions and uncertainties are weighted to arrive at overall
confidence summaries. The validity of confidence summaries is
difficult to assess without a numerical measure of uncertainty and/or
finding from a sensitivity assessment.
The Committee recommends that the draft risk evaluation consider
uncertainty and sensitivity analyses concurrently. For instance, a
finding with high uncertainty but low sensitivity suggests the lack of
EPA does account for the sensitivity of risk
conclusions (i.e., relative to benchmark) to
variance across the absolute risk estimates in
Section 4.3.2.4. Confidence in risk estimates
incorporates the "totality of uncertainties,
including confidence levels for each exposure
scenario/COU, strength of the human health
hazard information, and range of risk estimates
provided for the different aspects of the risk
evaluation relative to the benchmark."
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confidence in the estimate for a parameter that has little impact on
the ultimate risk estimate, whereas a result with medium uncertainty
but high sensitivity suggests that the large associated variability for
an impactful parameter implies large uncertainty in the final risk. In
the latter case, there is greater need to get better information on the
parameter to decrease uncertainty in the final risk. This
recommendation is valid for the entire risk evaluation, given the
degree of uncertainty and data gaps encountered.
PESS - intrinsic susceptibility (gender/age/genetics/health, etc.)
SACC
SACC COMMENTS:
Recommendation: Provide more information for risk assessment of
susceptible populations with non-alcoholic fatty liver disease or non-
alcoholic steatohepatitis because a large proportion (>30%) of the
general population is obese or overweight and have higher levels of fat
in their body.
Numerous factors including race/ethnicity, life stage, sex differences,
lifestyle, nutrition, genetic polymorphisms, and pre-existing health
conditions (i.e., obesity, kidney and liver disease) could affect the
susceptibility of exposed persons but no substantive discussion is found
on susceptible subpopulations in Section 2.3.3. For example, large
amounts of fat in the liver may change the toxicokinetics of TCE.
EPA has added non-alcoholic fatty liver disease
as a PESS factor in Section 3.2.5.2, and those
other factors are also listed as PESS
considerations. Section 2.3.3. deals with
exposure PESS considerations (i.e., higher
exposure) as opposed to biological susceptibility.
SACC
SACC COMMENTS:
Recommendation: Provide a more detailed risk assessment focused on
susceptible subpopulations, particularly pregnant women, their
developing fetuses, and people with specific health conditions.
Section 3.2.5.2 of the draft risk evaluation provides few details on
identified susceptible populations, including pregnant women their
developing fetuses, and people with kidney and liver illness. TSCA-
relevant potentially exposed sub-populations within workers, ONUs,
consumers, product users and bystanders associated with consumer use
are also addressed. It is not clear to all Committee members that risks to
PESS are adequately covered by the uncertainty factors applied. When
are expected PESS responses great enough to require explicit risk
EPA has added a paragraph to Section 4.4.1
acknowledging PESS considerations that could
not be directly accounted for in risk estimations
and the uncertainty around whether the 99th
percentile outputs of the PBPK model
sufficiently account for all susceptible
subpopulations. EPA has quantified risk
estimates for particular PESS groups when
possible, including susceptible mothers, those
with increased enzymatic activity, and pre-
existing infection. Additionally, risk estimates
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calculations or additional uncertainty factor adjustments? A more
accurate estimation of risk to potentially exposed and susceptible sub-
populations should be obtained by aggregating exposures with other
factors.
were provided for three developmental endpoints
in order to account for the PESS group of
pregnant mothers and women of childbearing
age. Consideration of aggregate exposures are
provided in Section 4.4.2.
As stated above, EPA acknowledges that the
PBPK model cannot account for the entirety of
human variability, however the 99th percentile
output of the model (based on parameters that
can be accounted for) was used for risk estimates
to account for the most susceptible proportion of
the population. EPA acknowledges that the
model does not contain a fetal compartment and
the uncertainty this adds in Section 3.2.6.2.
While EPA used average adult worker values for
exposure estimates, as stated above EPA used
toxicity values based on the most
toxicokinetically sensitive 1% of the population.
Presentation of dermal exposure estimates for
women of childbearing age would not have had
any effect on risk determination for any
occupational Condition of Use, all of which
presented Unreasonable Risk (except for
Distribution which is covered by regulations for
Transportation of hazardous chemicals).
SACC
SACC COMMENTS:
Recommendations: (1) Provide more details to support the conclusion
that the 99th percentile for human equivalent concentration/dose
(HEC99/HED99) is sufficient to account for the susceptible
populations. (2) Run the PBPK model to understand effects on
individuals with abnormal values from pre-existing health conditions
such as obesity and hepatitis.
Section 4.4.1 includes approximate differences between some groups
and what is accounted for in the PBPK model. EPA assumes that by
relying on "the 99th percentile output of the PBPK model, [the
HEC99/HED99 POD values] are expected to be protective of
particularly susceptible subpopulations," but no further discussion is
provided. The draft risk evaluation should mention that the PBPK
model does not account for pregnancy or lactation. Further, the Fisher
PBPK models for fetal component should be included. Although the
draft risk evaluation discusses uncertainties with respect to susceptible
populations, the Committee was unable to find where the draft risk
evaluation quantitatively assesses the impacts of sensitivity to
assumption and related uncertainty on risk estimates for susceptible
populations.
56, 108
PUBLIC COMMENTS:
EPA insufficiently considered the susceptibility of pregnant women and
the developing fetus. Under TSCA, EPA has a mandate to protect
vulnerable populations.
The prevalence of pregnant women and their fetuses is 4 million per
year in the U.S (including 1% with a congenital heart defect).
Dermal risk estimates were presented only for average adult
workers, since exposures between this population and women of
childbearing age vary by only about 10% (considered by EPA to be
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relatively insignificant).
EPA must use exposure values applicable to subpopulations with
elevated exposure, even if EPA believes that the overall risk conclusion
would not be impacted. Ignoring these data fails to identify actual risks
to potentially exposed or susceptible populations and makes it more
likely that EPA will not identify unreasonable risk where it should or to
address that risk in subsequent regulation under TSCA section 6.
Ignoring risk deemed "relatively insignificant" also fails to consider the
contribution of such risks to overall risks faced by individuals or
subpopulations from additional exposures they experience.
56, 108
PUBLIC COMMENTS:
EPA did not sufficiently acknowledge that TCE can readily cross the
blood-brain barrier. The 2019 ATSDR Toxicological Profile for TCE
states: "Trichloroethylene crosses the blood-brain barrier, and the extent
of transfer could possibly be greater in young children, although
trichloroethylene is expected to readily cross the blood-brain barrier in
all age groups." This is essential to emphasize given the evidence for
neurotoxicity, including developmental neurotoxicity.
EPA discusses neurological effects of TCE as
well as developmental neurotoxicity, both
involving central nervous system dysfunction.
Therefore, the Risk Evaluation makes it clear
that TCE can impact the brain.
56, 73,
108
PUBLIC COMMENTS:
EPA should acknowledge additional PESS, including individuals with
compromised liver or kidney function, cardiac arrhythmias, obesity
(based on distribution of TCE to body fat and liver), multiple chronic
conditions (e.g., heart, kidney, and liver disease), and co-exposures to
other chemicals that interact with TCE metabolism (e.g., chlorinated
hydrocarbons, ethanol, phenobarbital).
In Section 3.2.5.2 EPA describes PESS factors
that cover all of the considerations included in
the comment including variation in cardiac
output, socioeconomic status, increased body
mass, non-alcoholic fatty liver disease, and
diminished health status in general.
56, 108
PUBLIC COMMENTS:
EPA did not provide, in adequate detail, the extent of genetic variation
in key metabolic pathways, which contributes to human susceptibility to
TCE toxicity. Further information on and analysis of the potential
variability in CYP oxidation across the human population should be
provided (including quantitative information when possible).
In Section 3.2.5.2 EPA discusses various genetic
susceptibilities including increased CYP2E1
activity and mutations in the VHL tumor
suppressor gene. The section also explains that
variation in oxidative and conjugative
metabolism is accounted for by the use of the
99th percentile PBPK outputs for risk estimation.
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88
PUBLIC COMMENTS:
EPA must comprehensively assess exposures to TCE and consider its
detrimental impacts on fetal development to protect health, including
the health of the most vulnerable among us.
EPA agrees with the commenter. These
considerations are discussed in Section 3.2.5.2.
104
PUBLIC COMMENTS:
Tribes must be considered a potentially exposed or susceptible
subpopulation under TSCA, because many factors place them at
differential risk due to multiple exposure pathways not experienced by
the general population, including diet (e.g., increased fish consumption),
substandard housing, less stringent worker safety protocols, and water
use (drinking, hygiene, ceremonial, artisanal, subsistence, recreational).
For the 1,4-dioxane and hexabromocyclododecane (HBCD) risk
evaluations, SACC recommended that specific populations (such as
tribal populations) be specially considered and that EPA provide
quantitative estimates of extra risks for these populations. Special
consideration of tribal lifeways and the resulting multiple exposures
must be analyzed to determine the risks that Native Americans face.
Populations exposed through pathways excluded
from the risk evaluation were not identified as
PESS. EPA disagrees with public and scientific
advisory committee comments on the draft risk
evaluation that suggest tribal communities
should be identified as PESS. TSCA provides
EPA with the discretion to identify the PESS that
are relevant to the chemical-specific risk
evaluation [TSCA section 6(b)(4)(A)], General
population exposure pathways were not included
in the scope of the risk evaluation evaluated as
discussed in Section 1.4.2. Commenters note that
the HBCD risk evaluation identified tribal
communities as well as subsistence fishermen as
PESS; however, HBCD is classified as a
persistent bioaccumulative toxic (PBT)
compound and expected to bioaccumulate
through the food chain. TCE is not a PBT and
has low bioaccumulation potential. Therefore,
TCE is not a significant concern for communities
with elevated fish ingestion and the consumption
of fish along with other trophic transfer pathways
were not included in the scope of the risk
evaluation.
EPA recognizes that Native Americans have
unique lifeways and has considered established
differences in patterns in relevant exposure
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pathways (e.g., increased fish consumption).
However, general population exposure pathways
were not included in the scope of the risk
evaluation evaluated as discussed in Section
1.4.2 and a review of reasonably available
information did not produce data for establishing
a differential experience for the evaluated
exposure pathways, namely occupational and
consumer activities. An additional statement
about the uncertainty associated with
subpopulations patterns of use has been added to
Section 2.3.2.6.2.
105
PUBLIC COMMENTS:
OEHHA is concerned that the draft risk evaluation ignores
developmental toxicity in the concluding risk determination, despite
evidence described in other sections of the report. The draft risk
evaluation should protect susceptible subpopulations, including the
pregnant woman and her fetus, against health effects for which there is
substantial evidence.
EPA has the discretion to make unreasonable
risk determinations based on other risk
benchmarks or factors as appropriate. EPA's
unreasonable risk determination (Section 5)
considers multiple risk-based factors, including
the uncertainties in the analysis (Section 4.3). In
considering the uncertainties surrounding these
endpoints, the immune endpoints were
determined to be the best overall endpoints for
risk conclusions and risk determinations.
Pregnant women are discussed as a PESS group
throughout the PESS sections of the document,
and risk estimates are provided for three
developmental endpoints.
PESS - exposure to workers
56, 108
PUBLIC COMMENTS:
EPA's risk estimation failed to consider workers with compromised
health and active workers with elevated respiratory rates. Assuming that
all workers are healthy is counter to the TSCA mandate, which directs
In response to SACC and public comments, EPA
used the PBPK model to derive HECs/HEDs for
occupational exposure for the two key acute and
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EPA to protect vulnerable populations.
chronic immunotoxicity studies. These model
outputs accounted for elevated breathing rate of
workers compared to the default at-rest
assumptions of the model. The derived
occupational HEC/HED values are provided in
Section 3.2.5.4.1, and they were used for
occupational risk estimates instead of the default
PBPK outputs that were used in the draft risk
evaluation. EPA acknowledges that individuals
with diminished health status are PESS groups in
Section 3.2.5.2.
100
PUBLIC COMMENTS:
Workers exposed to TCE include women of childbearing age. EPA's
failure to consider the latest neurodevelopment toxicity data or to use
the available data on fetal cardiac malformations leaves those workers
and their children exposed to unreasonable risk.
EPA provides risk estimates for both
developmental neurotoxicity and congenital heart
defects. While these developmental endpoints
present more sensitive PODs, (Tredriksson et al.,
1993), (Johnson et al.. 2003), there is lower
confidence in the dose-response results for those
studies.
To determine whether or not a condition of use
presents unreasonable risks, EPA incorporates
assumptions based on information and judgement
underlying the exposure scenarios. These
assumptions are described in the unreasonable
risk determination for each condition of use, in
Section 5.2. It is important to note that the
benchmarks for cancer and noncancer risk
estimates are not bright lines, and EPA has
discretion to make unreasonable risk
determinations based on other risk benchmarks or
factors as appropriate.
PESS - exposure due to proximity (residence near hazardous waste site, manufacturing facility, spill, etc.)
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SACC
SACC COMMENTS:
Recommendation: Include discussion of air emissions, contaminated
groundwater, and drinking water in human risk characterization
discussion.
The draft risk evaluation does not consider the implications of some
TCE releases that may result in air emissions, contaminated
groundwater, and drinking water that could add to the exposure of
TSCA-related populations. Some Committee members continue to state
that not including estimates of these exposures is unacceptable in the
larger framework of risk assessment. The exclusion of these releases
implicitly assumes that these potential exposures result in low and
acceptable risks or are appropriately managed. In addition, exclusion
makes is impossible to assess cumulative and aggregate risk to worker,
ONU, and consumer subpopulations exposed simultaneously via
multiple pathways.
During Problem Formulation, EPA
acknowledged that general population exposures
may occur through air, water, soil, and other
environmental pathways. However, in the Risk
Evaluation EPA did not include pathways under
the jurisdiction of other EPA-administered
environmental statutes and associated regulatory
programs.
EPA identified exposure pathways under other
environmental statutes administered by EPA, i.e.,
the Clean Air Act (CAA), the Safe Drinking
Water Act (SDWA), the Clean Water Act
(CWA), the Resource Conservation and
Recovery Act (RCRA), and the Comprehensive
Environmental Response, Compensation, and
Liability Act (CERCLA). As explained in more
detail in Section 1.4.2 of the Final Risk
Evaluation, EPA believes it is both reasonable
and prudent to tailor TSCA Risk Evaluations
when other EPA offices have expertise and
experience to address specific environmental
media, rather than attempt to evaluate and
regulate potential exposures and risks from those
media under TSCA. EPA believes that
coordinated action on exposure pathways and
risks addressed by other EPA-administered
statutes and regulatory programs is consistent
with statutory text and legislative history,
particularly as they pertain to TSCA's function as
a "gap-filling" statute, and also furthers EPA
aims to efficiently use Agency resources, avoid
39
PUBLIC COMMENTS:
Persons at Camp Lejeune in Jacksonville, NC (now an active Superfund
site) are exposed to TCE as a drinking water contaminant and
subsequently are at risk for cancer and death.
49, 99
PUBLIC COMMENTS:
Some subpopulations are exposed to TCE via multiple pathways
simultaneously {i.e., TCE in indoor/outdoor air, consumption of
contaminated drinking water, reside near TCE-contaminated National
Priority List [NPL] sites). Because their exposures levels are higher than
for the general population, they face elevated risks of TCE-related
health effects (cancer, fetal heart malformations, immunotoxicity). A
comprehensive risk evaluation as required by TSCA would identify and
quantify these subpopulations, estimate total exposure, and characterize
this increased risk. However, the draft risk evaluation fails to provide
this analysis and therefore presents an incomplete picture of TCE's risks
to the public.
56, 74,
108
PUBLIC COMMENTS:
EPA must identify those who face greater exposure due to proximity to
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COUs as a "potentially exposed or susceptible subpopulation" who, due
to exposure, may be at greater risk of adverse health effects. Only a
passing reference to such exposures was made. EPA acknowledged that
consumer exposure was underestimated by failing to consider or
aggregate background exposures (specifically mentioning populations
living near facilities emitting TCE). EPA does not identify these
subpopulations and does not analyze the extent by which living in
proximity to COUs {i.e., Superfund sites and disposal sites associated
with ongoing or prospective manufacturing, processing, distribution, or
use) contributes to greater risk. EPA does not provide a justification for
excluding such exposures. EPA should analyze the associated risks to
these potentially exposed subpopulations and the environmental
pathways that lead to their exposure.
duplicating efforts taken pursuant to other
Agency programs, and meet the statutory
deadline for completing Risk Evaluations. EPA
has therefore tailored the scope of the Risk
Evaluation for TCE using authorities in TSCA
Sections 6(b) and 9(b)(1).
Because stationary source releases of TCE to
ambient air are covered under the CAA, EPA did
not evaluate emission pathways to ambient air
from commercial and industrial stationary
sources or associated inhalation exposure of the
general population. Because the drinking water
exposure pathway for TCE is covered in the
SDWA regulatory analytical process for public
water systems, EPA did not include this pathway
in the risk evaluation for TCE under TSCA. In
Problem Formulation, EPA also found general
population exposures to TCE via underground
injection, RCRA Subtitle C hazardous waste
landfills, RCRA Subtitle D municipal solid waste
(MSW) landfills, and on-site releases to land
from industrial non-hazardous waste and
construction/demolition waste landfills are under
the jurisdiction of and addressed by other EPA-
administered statutes and associated regulatory
programs. EPA did not include Superfund on-site
releases to the environment (which may lead to
vapor intrusion), as they are under the jurisdiction
of CERCLA. Lastly, EPA did not include
emissions to ambient air from municipal and
industrial waste incineration and energy recovery
units in the risk evaluation, as they are regulated
65, 74
PUBLIC COMMENTS:
EPA limits its analysis of PESS to those that might face greater
susceptibility. Except for workers and consumers, EPA does not
consider whether the general population or specific subpopulations face
a greater risk due to greater exposure. EPA does not consider people
who work or live near manufacturing, processing, use, or disposal sites,
or provide any analysis to the extent to which they are at greater risk.
This includes people living near active Superfund sites (731 of which
are contaminated with TCE).
93
PUBLIC COMMENTS:
Residents of Manufacturers Place, as community members who are at
greater risk of adverse health effects from exposure to TCE due to their
long-term, sustained exposure to the chemical, qualify as a "potentially
exposed or susceptible subpopulation" under TSCA. In addition,
Manufacturers Place is a former TCE disposal site, making its residents
among those EPA identified as a target subpopulation. They also meet
the definition of a potentially exposed or susceptible subpopulation
based on their greater susceptibility to harm from TCE, because they,
like other members of the greater Ironbound community, are historically
low-income, people of color that have been disproportionally exposed
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to high levels of pollution with the accompanying potential for
increased public health impacts, and often facing problems beyond
environmental issues (e.g., health risks and housing challenges).
Over 3,300 facilities with environmental permits are located within
the two zip codes that cover Ironbound (source: NJDEP's Data
Miner website)
There are >200 facilities that store and use hazardous materials on
site; over 70 store large enough volumes to require hazardous
chemical inventory forms.
EPA's environmental justice mapping and screening database
(EJSCREEN) indicates that Ironbound is in the 80th and 90th
percentiles for nearly every environmental justice variable.
Because of these high levels of exposures to pollutants, Ironbound
residents have greater susceptibility to adverse effects from TCE
exposure than the general population. Despite this, EPA's draft risk
evaluation ignores risks to those in Manufacturers Place and Ironbound
from a known harmful use of TCE by entirely excluding analysis of
vapor intrusion. This inadequate treatment of susceptible communities
is inconsistent with TSCA mandates and must be corrected.
under section 129 of the Clean Air Act.
EPA-OPPT acknowledges that it did not consider
background exposure from the environment that
workers, ONUs, consumers, or bystanders using
products containing TCE might be exposed to in
addition to exposures from the conditions of use
in the scope of the risk evaluation because there
is insufficient information reasonably available as
to the likelihood of this scenario or the relative
distribution of exposures from each pathway.
This may result in an underestimation of risk, and
EPA acknowledges that risk is likely to be
elevated for individuals who experience TCE
exposure in multiple contexts. Additional
discussion of this issue has been added to
Sections 2.3.2.6.1, 2.3.2.2.1, and 4.4.2.
TSCA section 6(b)(4)(A) requires EPA to
conduct risk evaluations "to determine
whether a chemical substance presents an
unreasonable risk of injury to health or the
environment, without consideration of costs or
other nonrisk factors, including an unreasonable
risk to a potentially exposed or susceptible
subpopulation identified as relevant to the risk
evaluation by the Administrator, under the
conditions of use'' (emphasis added) Therefore,
TSCA does require that the identified PESS are
linked to a COU. Additionally, EPA did not
assess exposures to the general population
because these exposure pathways and risks are
addressed by other EPA-administered statutes.
104
PUBLIC COMMENTS:
EPA needs to analyze those PESS that face greater exposure due to their
proximity to COUs, particularly disposal. In the draft risk evaluation,
EPA did not identify these populations and did not provide any analysis
of whether those living in proximity to COUs are at a greater risk due to
higher exposure. Many tribal communities live near a disposal site or
transfer station. The multiple exposure scenarios associated with
proximity to unlined disposal site releases to environmental media must
be analyzed so that risk determinations can be made for these vulnerable
populations. EPA should identify all populations living near disposal
and other waste management sites as PESS. Groups living near existing
or proposed NPL sites should also be included.
108
PUBLIC COMMENTS:
EPA correctly recognized that a potentially exposed or susceptible
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subpopulation may include groups of individuals who experience
greater exposures due to their proximity to COUs (e.g., near disposal
sites). However, EPA ignores the pathways that lead to enhanced
exposure (releases to air, water, and land) and provides no explanation
for how risk faced by these subpopulations will be evaluated. EPA
largely fails to analyze the risks posed to this PESS. EPA should
analyze these subpopulations in the final risk evaluation.
108
PUBLIC COMMENTS:
EPA should identify people living near COUs, including disposal sites,
as PESS, and these subpopulations should be analyzed in the final risk
evaluation.
108
PUBLIC COMMENTS:
EPA should identify people living in proximity to sources of
contamination (e.g., contaminated groundwater) as potentially exposed
or susceptible populations, even if these sites are not linked to a specific
COU.
108
PUBLIC COMMENTS:
EPA cannot exclude legacy uses and associated disposals. EPA has
excluded the pathways leading to this exposure from analysis without
providing a rationale for how risks will be evaluated for these
subpopulations.
EPA should be analyzing communities who work or live near
past manufacturing processing, distribution, or use sites, even if
those activities have ceased.
The use of TCE in the past are not "legacy" uses.
As described in EPA's Risk Evaluation Rule (82
FR 33726 (July 20, 2017)), a legacy use is an
ongoing use of a chemical substance in a
particular application where the chemical
substance is no longer being manufactured,
processed, or distributed in commerce for that
application. The example provided in the Rule is
insulation, which may be present in buildings
after a chemical substance component is no
longer being made for that use. EPA did not
identify any "legacy uses" or "associated
disposals" of trichloroethylene, as those terms
are described in EPA's Risk Evaluation Rule, 82
FR 33726 (July 20, 2017). Therefore, no such
uses or disposals were added to the scope of the
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risk evaluation for trichloroethylene following
the issuance of the opinion in Safer Chemicals,
Healthy Families v. EPA, 943 F.3d 397 (9th Cir.
2019). In exercising its discretion under TSCA
section 6(b)(4)(D) to identify the conditions of
use that EPA expects to consider in a risk
evaluation, EPA believes it is important for the
Agency to have the discretion to make
reasonable, technically sound scoping decisions.
EPA did not include legacy disposals, (i.e.,
disposals that have already occurred), because
they do not fall under the definition of conditions
of use under TSCA section 3(4).
108
PUBLIC COMMENTS:
Under Executive Order 12898, EPA is required to ensure that
environmental justice is appropriately considered, analyzed, and
addressed in the draft risk evaluation and has failed to do so. EPA's
identification of potentially exposed and susceptible populations is not
sufficient to comply with this order.
EPA must consider the disparate impacts of pollution on "minority
populations and low-income populations."
Some subpopulations, including low-income, minority, and
indigenous communities are disparately exposed to sources of
chemical contamination.
EPA's exclusions of exposure pathways linked to disposal sites and
legacy use underestimate exposures of environmental justice
communities.
EPA must consider whether these communities will face an
unreasonable risk of injury from TCE.
TSCA ง 6(b)(4)(A) requires that EPA conduct a
risk evaluation to "determine whether a chemical
substance presents an unreasonable risk of injury
to health or the environment, without
consideration of cost or other non-risk factors,
including an unreasonable risk to a potentially
exposed or susceptible subpopulation identified
as relevant to the risk evaluation by the
Administrator, under the conditions of use."
TSCA ง 3(12) states that "the term 'potentially
exposed or susceptible subpopulation' means a
group of individuals within the general
population identified by the Administrator who,
due to either greater susceptibility or greater
exposure, may be at greater risk than the general
population of adverse health effects from
exposure to a chemical substance or mixture,
such as infants, children, pregnant women,
workers, or the elderly." EPA believes that the
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statutory directive to consider potentially
exposed or susceptible subpopulations (PESS)
and the statutory definition of PESS inherently
include environmental justice populations. Thus,
EPA's consideration of PESS in this risk
evaluation addresses the requirements of the
Executive Order.
EPA seeks to achieve the fair treatment and
meaningful involvement of any group, including
minority and/or low-income populations, in the
development, implementation, and enforcement
of environmental laws, regulations, and policies.
To this end, the Agency has already sought input
from specific populations and public health
experts in implementing TSCA and will continue
to do so. EPA will also consider environmental
justice populations in accordance with the
Executive Order as it develops risk management
actions based on final TSCA section 6(b) risk
evaluations.
PPE assumptions and effects on risk estimates
SACC
SACC COMMENTS:
Recommendation: Identify COUs having very low expectation of
appropriate PPE use and incorporate this information in the risk
characterization and final risk determination statements.
The Committee continues to be concerned over EPA's inclusion of
calculations based on the use of PPE in occupational scenarios when
EPA has no confidence that PPE is appropriately used by workers in
these scenarios. For example, the likelihood of PPE adherence in
commercial use OES is so low that EPA should consider not presenting
risk estimates with PPE. Alternatively, these risk estimates could be
EPA has outlined its PPE assumptions in Section
5.1 and EPA's assumptions are described in the
unreasonable risk determination for each
condition of use, in Section 5.2. EPA does not
assume that it is a standard industry practice that
workers in some small commercial facilities
(e.g., those performing spot cleaning, wipe
cleaning, shoe polishing, or hoof polishing;
commercial printing and copying) have a
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presented in a separate section or table that describes clearly why EPA
is presenting risks with PPE despite EPA's belief that use of exposure
controls is unlikely. EPA needs to explain why PPE and "hierarchy of
hazard control" are not better considered as mitigation alternatives in
response to a determination of "unreasonable risk."
respiratory protection program or regularly
employ dermal protection. Therefore, the use of
respirators and gloves is unlikely for workers in
these facilities.
For the purpose of this Risk Evaluation, EPA
makes assumptions about potential PPE use
based on reasonably available information and
expert judgment. EPA considers each condition
of use and constructs exposure scenarios with
and without engineering controls and /or PPE
that may be applicable to particular worker tasks
on a case-specific basis for a given chemical.
Again, while EPA has evaluated worker risk with
and without PPE, as a matter of policy, EPA
does not believe it should assume that workers
are unprotected by PPE where such PPE might
be necessary to meet federal regulations, unless it
has evidence that workers are unprotected. For
the purposes of determining whether or not a
condition of use presents unreasonable risks,
EPA incorporates assumptions regarding PPE
use based on information and judgment
underlying the exposure scenarios. These
assumptions are described in the unreasonable
risk determination for each condition of use, in
section 5.2. Additionally, in consideration of the
uncertainties and variabilities in PPE usage,
including the duration of PPE usage, EPA uses
the high-end exposure value when making its
unreasonable risk determination in order to
address those uncertainties.
SACC
SACC COMMENTS:
A hierarchy of controls is a method for
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Although risks are presented with and without PPE, it is inappropriate
to consider these as the universe of possibilities in occupational
exposure control. Protective equipment is described and quantified with
simple (but usually not supportable) assumptions; however, the
hierarchy of controls stipulates that PPE should only be invoked after
engineering and administrative controls.
eliminating workplace hazards. While EPA has
assessed the extent to which certain exposure
reduction tools that it assumes to be in place may
be reducing risks to workers, application of the
methodology of the hierarchy of controls is not
relevant to risk evaluations. EPA will manage
unreasonable risks presented by chemical
substances when the Agency undertakes
regulatory action for COUs determined to have
unreasonable risk. Utilization of the hierarchy of
controls to recommend or require risk
management actions in the risk evaluation would
be premature and inappropriate.
SACC
SACC COMMENTS:
The adequate use of PPE cannot be assumed. Many on the Committee
support removing the use of PPE in the risk characterization section. If
this is not possible, expectations or evidence of PPE under all COUs,
and PPE use impacts on risk characterization should be a separate
discussion and tied to tables separate from non-PPE values.
EPA's approach for developing exposure
assessments for workers is to use the reasonably
available information and expert judgement.
When appropriate, in the risk evaluation, EPA
will use exposure scenarios both with and
without engineering controls and/or PPE that
may be applicable to particular worker tasks on a
case-specific basis for a given chemical. Again,
while EPA has evaluated worker risk with and
without PPE, as a matter of policy, EPA does not
believe it should assume that workers are
unprotected by PPE where such PPE might be
necessary to meet federal regulations, unless it
has evidence that workers are unprotected. For
the purposes of determining whether or not a
condition of use presents unreasonable risks,
EPA incorporates assumptions regarding PPE
use based on information and judgement
underlying the exposure scenarios. These
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assumptions are described in the unreasonable
risk determination for each condition of use, in
section 5.2. Additionally, in consideration of the
uncertainties and variabilities in PPE usage (e.g.,
dry cleaners), EPA uses the high-end exposure
value when making its unreasonable risk
determination in order to address those
uncertainties. EPA has also outlined its PPE
assumptions in section 5.1. Further, in the final
risk evaluation for TCE, EPA has determined
that most conditions of use pose an unreasonable
risk to workers even with the assumed PPE.
EPA will review how the risk values are
presented (PPE vs non-PPE), and determine
whether an alternative presentation approach
should be taken in future risk evaluations.
SACC
SACC COMMENTS:
The primary assumption that exposure control recommendations are
followed considering evidence to the contrary should be addressed
directly. EPA should make a decision as to whether the lack of specific
data on PPE use and having no confidence that it is used as
recommended results in a decision to not characterize risks with PPE.
Alternatively, EPA should transparently and clearly explain why
exposure and risk estimates with PPE are provided in all cases despite
evidence of poor adherence to such use and EPA's recognition of
uncertainty about the proper use of PPE in many scenarios. Is PPE use
being considered a COU, or as many of the Committee consider it, a
risk modifier?
EPA's approach for developing exposure
assessments for workers is to use the reasonably
available information and expert judgement.
When appropriate, in the risk evaluation, EPA
will use exposure scenarios both with and
without engineering controls and/or PPE that
may be applicable to particular worker tasks on a
case-specific basis for a given chemical. Again,
while EPA has evaluated worker risk with and
without PPE, as a matter of policy, EPA does not
believe it should assume that workers are
unprotected by PPE where such PPE might be
necessary to meet federal regulations, unless it
has evidence that workers are unprotected. For
the purposes of determining whether or not a
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condition of use presents unreasonable risks,
EPA incorporates assumptions regarding PPE
use based on information and judgement
underlying the exposure scenarios. These
assumptions are described in the unreasonable
risk determination for each condition of use, in
section 5.2. Additionally, in consideration of the
uncertainties and variabilities in PPE usage (e.g.,
dry cleaners), EPA uses the high-end exposure
value when making its unreasonable risk
determination in order to address those
uncertainties. EPA has also outlined its PPE
assumptions in section 5.1. Further, in the final
risk evaluation for TCE, EPA has determined
that most conditions of use pose an unreasonable
risk to workers even with the assumed PPE.
SACC
SACC COMMENTS:
Although PPE and Protection Factors (PFs) have been discussed at
length in previous draft risk evaluations reviewed by the SACC, one
Committee member raised a new concern that the factor that had the
greatest impact on the final risk determination is PPE PFs as
categorical constants in risk determination calculations. This
reviewer cited the comments by the Environmental Defense Fund
(EDF) and their analysis, which indicates that the factor that had the
greatest impact on the risk determination was the application of PPE
PFs for respirators and gloves. This reviewer noted that the factor
that impacts the risk determination the most has only one page of
text dedicated to discussion.
EPA must provide an expanded justification for applying various
PFs to reduce the risk determination as constants applied to whole
populations in the equations. It was hard to discern on p. 120 of the
draft risk evaluation that OSHA only requires respiratory PPE be
used when the PEL continues to be exceeded after implementing the
EPA appropriately applied the glove PFs within
the framework used in the TCE risk evaluation.
EPA will consider further refinements to the
dermal approaches in future risk evaluations.
The hierarchy of controls discussed is a method
for eliminating workplace hazards. While EPA
has assessed the extent to which certain exposure
reduction tools that it assumes to be in place may
be reducing risks to workers, application of the
methodology of the hierarchy of controls is not
relevant to risk evaluations. EPA will manage
unreasonable risks presented by chemical
substances when the Agency undertakes
regulatory action for COUs determined to have
unreasonable risk. Utilization of the hierarchy of
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higher priority controls in the exposure control strategy. Assuming
that PPE is required for all workers and used continuously is,
therefore, not likely to be correct. This leads to the conclusion that
application of PFs in risk determination for TCE is inappropriate
unless the entire worker group is exposed at levels above the PEL.
EPA's use of these various PFs thus serve to inappropriately and
systematically reduce the calculated risk. There is a lack of
substantial discussion about exposure controls and use of PPE in
actual practice. EPA references some of the NIOSH HHEs and
should review those to see what was being done in the businesses
inspected by NIOSH and the corresponding exposure levels. Nearly
all were below the PEL. Modification of risk estimates by applying
PFs for PPE seemed to many on the Committee as inappropriate
when there is no regulatory reason to compel the use of such PPE.
Page 315 of 408
controls to recommend or require risk
management actions in the risk evaluation would
be premature and inappropriate.
EPA's approach for developing exposure
assessments for workers is to use the reasonably
available information and expert judgement.
When appropriate, in the risk evaluation, EPA
will use exposure scenarios both with and
without engineering controls and/or PPE that
may be applicable to particular worker tasks on a
case-specific basis for a given chemical. Again,
while EPA has evaluated worker risk with and
without PPE, as a matter of policy, EPA does not
believe it should assume that workers are
unprotected by PPE where such PPE might be
necessary to meet federal regulations, unless it
has evidence that workers are unprotected. For
the purposes of determining whether or not a
condition of use presents unreasonable risks,
EPA incorporates assumptions regarding PPE
use based on information and judgement
underlying the exposure scenarios. These
assumptions are described in the unreasonable
risk determination for each condition of use, in
section 5.2. Additionally, in consideration of the
uncertainties and variabilities in PPE usage, EPA
uses the high-end exposure value when making
its unreasonable risk determination in order to
address those uncertainties. EPA has also
outlined its PPE assumptions in section 5.1.
Further, in the final risk evaluation for TCE,
EPA has determined that most conditions of use
-------
pose an unreasonable risk to workers even with
the assumed PPE.
56, 74,
108
PUBLIC COMMENTS:
EPA assumed universal use and effectiveness of PPE for most COUs
throughout the value chain and lifecycle. Workers at any facility where
effective use of PPE cannot be documented should be considered
vulnerable subpopulations as per TSCA requirements.
For the purpose of this Risk Evaluation, EPA
makes assumptions about potential PPE use
based on reasonably available information and
expert judgment. EPA considers each condition
of use and constructs exposure scenarios with and
without engineering controls and /or PPE that
may be applicable to particular worker tasks on a
case-specific basis for a given chemical. Again,
while EPA has evaluated worker risk with and
without PPE, as a matter of policy, EPA does not
believe it should assume that workers are
unprotected by PPE where such PPE might be
necessary to meet federal regulations, unless it
has evidence that workers are unprotected. For
the purposes of determining whether or not a
condition of use presents unreasonable risks, EPA
incorporates assumptions regarding PPE use
based on information and judgment underlying
the exposure scenarios. These assumptions are
described in the unreasonable risk determination
for each condition of use, in section 5.2.
Additionally, in consideration of the uncertainties
and variabilities in PPE usage, including the
duration of PPE usage, EPA uses the high-end
exposure value when making its unreasonable
risk determination in order to address those
uncertainties. EPA has also outlined its PPE
assumptions in Section 5.1 and EPA's
assumptions are described in the unreasonable
risk determination for each condition of use, in
49, 99
PUBLIC COMMENTS:
EPA's risk determinations for workers calculate MOEs assuming the
use of gloves and respirators and the absence of protective equipment.
MOEs for scenarios where workers reliably use PPE are below
benchmarks for all COUs; however, EPA's MOEs are significantly
lower for no PPE scenarios. As SACC has repeatedly underscored and
EPA has recognized, the expectation of universal PPE is contrary to the
realities of workplace. As EPA is required to consider 'reasonably
foreseen' COUs, and universal PPE use is not reasonably foreseeable,
the no PPE scenario is the only defensible baseline for determining risk
levels and defining additional worker protections necessary to eliminate
risk.
49, 99
PUBLIC COMMENTS:
EPA's unreasonable risk determinations for workers should not assume
protection via PPE. In each of its reviews of draft risk evaluations,
SACC has raised concerns about EPA's reliance on PPE for
determinations of unreasonable risk. SACC concluded that assumptions
about PPE use are likely unrealistic for many of the scenarios so that
risk determinations should be based on no PPE use.
Page 316 of 408
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Section 5.2.
EPA is required to conduct risk evaluations to
determine whether chemical substances present
unreasonable risk "under the conditions of use,"
TSCA section 6(b)(4)(A). "Conditions of use"
include intended, known, or reasonably foreseen
activities associated with a chemical substance,
TSCA section 3(4). Occupational exposure
scenarios and assumptions are not the same as
COUs.
49, 99
PUBLIC COMMENTS:
EPA's unreasonable risk determinations for workers should not assume
that they will be protected by PPE. There is evidence that workers are
not meaningfully protected by PPE.
Most worker exposure to TCE is in small, poorly controlled
operations. EPA found in its 2017 proposal to ban vapor degreasing
that nearly all vapor degreasing "open-top" degreasers [resulted in
risk],
The OSHA PEL is 100 ppm, three orders of magnitude higher than
the level that current TCE health effects data warrant. Without a
health-protective OSHA limit, it is inconceivable that OSHA is
enforcing, or employers are implementing, stringent PPE
requirements.
In the proposal to ban vapor degreasing, EPA noted that worker
comprehension of warnings and labels was poor. Many operations lack
effective training and hazard communication programs. Occupational
bystanders mat not even encounter warnings and labels.
EPA agrees that there are challenges associated
with use of PPE; they are described in section
5.1.1.3. By providing risk estimates assuming
use of PPE, EPA is not recommending or
requiring use of PPE. EPA's approach for
evaluating risk to workers and ONUs is to use
the reasonably available information and
professional judgment to construct exposure
scenarios that reflect the workplace practices
involved in the conditions of use of the
chemicals and address uncertainties regarding
availability and use of PPE. EPA uses exposure
scenarios both with and without engineering
controls and/or PPE that may be applicable to
particular worker tasks on a case-specific basis
for a given chemical. Again, while EPA has
evaluated worker risk with and without PPE, as a
matter of policy, EPA does not believe it should
assume that workers are unprotected by PPE
where such PPE might be necessary to meet
federal regulations, unless it has evidence that
Page 317 of 408
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workers are unprotected.
EPA acknowledges that there is a PEL but did
not use it as a benchmark for either risk
assessment or unreasonable risk determination.
EPA provided the PEL as a point of comparison
only to help readers understand EPA's workplace
exposure and risk estimates compared to a
familiar exposure concentration, as expressed in
the PEL. EPA did not use the PEL in the
development of the risk estimates or as part of
making an unreasonable risk determination.
TCE is the subject of an OSHA standard. OSHA
has established a permissible exposure limit
(PEL) of 100 ppm for TCE. However, as noted
on OSHA's website, "OSHA recognizes that
many of its permissible exposure limits (PELs)
are outdated and inadequate for ensuring
protection of worker health. Most of OSHA's
PELs were issued shortly after adoption of the
Occupational Safety and Health (OSH) Act in
1970, and have not been updated since that
time." OSHA provides an annotated list of PELs
on its website, including alternate exposure
levels. For TCE, the alternates provided are the
California OSHA PEL of 25 ppm and the
ACGM TLV of 25 ppm.
(https://www.osha.gov/dsg/annotated-
pels/tablez-2.html).
For the purposes of determining whether or not a
condition of use presents unreasonable risks,
Page 318 of 408
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EPA incorporates assumptions regarding PPE
use based on information and judgment
underlying the exposure scenarios. These
assumptions are described in the unreasonable
risk determination for each condition of use, in
section 5.2 and in the risk characterization
section in Table 4-9. Additionally, in
consideration of the uncertainties and
variabilities in PPE usage, including the duration
of PPE usage, EPA uses the high-end exposure
value when making its unreasonable risk
determination in order to address those
uncertainties.
56, 69,
74, 108
PUBLIC COMMENTS:
EPA's risk determination relied on unsupported assumptions that
workers will use PPE and that it will be universally effective. EPA
states that risk determinations "incorporate consideration of expected
PPE" (frequently a respirator of an assigned protection factor [APF] 25
or 50 and gloves with PF 5-20.) Statements that there are little to no
actual data on PPE use are provided only in the Supplemental File:
Environmental Releases and Occupational Exposure. While EPA still
finds unreasonable risk for most COUs, PPE assumptions dramatically
underestimate the extent and magnitude of risks (both in cases where
EPA did find a COU presented an unreasonable risk and in cases where
it did not). Worker exposure to TCE in the absence of PPE must be
considered reasonably foreseen.
EPA's approach for developing exposure
assessments for workers is to use the reasonably
available information and expert judgement.
When appropriate, in the risk evaluation, EPA
will use exposure scenarios both with and
without engineering controls and/or PPE that
may be applicable to particular worker tasks on a
case-specific basis for a given chemical. Again,
while EPA has evaluated worker risk with and
without PPE, as a matter of policy, EPA does not
believe it should assume that workers are
unprotected by PPE where such PPE might be
necessary to meet federal regulations, unless it
has evidence that workers are unprotected. For
the purposes of determining whether or not a
condition of use presents unreasonable risks,
EPA incorporates assumptions regarding PPE
use based on information and judgement
underlying the exposure scenarios. These
Page 319 of 408
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assumptions are described in the unreasonable
risk determination for each condition of use, in
section 5.3.
56, 69,
74, 108
PUBLIC COMMENTS:
EPA assumed without evidence that respirators or glove use would
result in levels of protection based on hypothetical PPE scenarios. The
reliance on PPE does not reflect the best available science and policy.
EPA only identified unreasonable risk when the most stringent PPE
use (to protect against inhalation and dermal exposures) was
insufficient to mitigate risk or when EPA could not justify any
assumption that PPE would be used.
EPA relies on PPE despite evidence of its limitations. For example,
OSHA notes limitations associated with respirator use (e.g., fit,
physiological burden).
EPA's reliance on PPE is counter to OSHA's Hierarchy of Controls
(HOC), which prioritizes measures to reduce or eliminate the
presence of a hazard over measures that place the burden on the
worker (warning labels and reliance on PPE).
During the TCE SACC meeting, a peer reviewer noted that measures
higher up in the HOC, including whether a chemical is needed at all as
well as protection afforded by engineering controls, should be
considered first. The HOC puts PPE as the last resort.
The hierarchy of controls is a method for
eliminating workplace hazards. While EPA has
assessed the extent to which certain exposure
reduction tools that it assumes to be in place may
be reducing risks to workers, application of the
methodology of the hierarchy of controls is not
relevant to risk evaluations. EPA will manage
unreasonable risks presented by chemical
substances when the Agency undertakes
regulatory action for COUs determined to have
unreasonable risk. Utilization of the hierarchy of
controls to recommend or require risk
management actions in the risk evaluation would
be premature and inappropriate.
EPA's approach for developing exposure
assessments for workers is to use the reasonably
available information and expert judgement.
When appropriate, in the risk evaluation, EPA
will use exposure scenarios both with and
without engineering controls and/or PPE that
may be applicable to particular worker tasks on a
case-specific basis for a given chemical. Again,
while EPA has evaluated worker risk with and
without PPE, as a matter of policy, EPA does not
believe it should assume that workers are
unprotected by PPE where such PPE might be
necessary to meet federal regulations, unless it
has evidence that workers are unprotected. For
Page 320 of 408
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the purposes of determining whether or not a
condition of use presents unreasonable risks,
EPA incorporates assumptions regarding PPE
use based on information and judgement
underlying the exposure scenarios. These
assumptions are described in the unreasonable
risk determination for each condition of use, in
section 5.2. Additionally, in consideration of the
uncertainties and variabilities in PPE usage, EPA
uses the high-end exposure value when making
its unreasonable risk determination in order to
address those uncertainties. EPA has also
outlined its PPE assumptions in section 5.1.
Further, in the final risk evaluation for TCE,
EPA has determined that most conditions of use
pose an unreasonable risk to workers even with
the assumed PPE.
56, 108
PUBLIC COMMENTS:
EPA frequently assumes that PPE is also used and effective in order to
find no unreasonable risk to workers even though EPA also states that it
does not have data on use/effectiveness of gloves or the existence of
comprehensive respiratory protection programs.
EPA's approach for developing exposure
assessments for workers is to use the reasonably
available information and expert judgement.
When appropriate, in the risk evaluation, EPA
will use exposure scenarios both with and
without engineering controls and/or PPE that
may be applicable to particular worker tasks on a
case-specific basis for a given chemical. Again,
while EPA has evaluated worker risk with and
without PPE, as a matter of policy, EPA does not
believe it should assume that workers are
unprotected by PPE where such PPE might be
necessary to meet federal regulations, unless it
has evidence that workers are unprotected. For
the purposes of determining whether or not a
Page 321 of 408
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condition of use presents unreasonable risks,
EPA incorporates assumptions regarding PPE
use based on information and judgement
underlying the exposure scenarios. These
assumptions are described in the unreasonable
risk determination for each condition of use, in
section 5.2. Additionally, in consideration of the
uncertainties and variabilities in PPE usage, EPA
uses the high-end exposure value when making
its unreasonable risk determination in order to
address those uncertainties. EPA has also
outlined its PPE assumptions in section 5.1.
Further, in the final risk evaluation for TCE,
EPA has determined that most conditions of use
pose an unreasonable risk to workers even with
the assumed PPE.
56, 108
PUBLIC COMMENTS:
Analysis of the risk estimates summarized in EPA's Table 4-54,
performed to characterize the impact of EPA's PPE assumptions, found
that:
EPA identified a risk estimate for a COU represented an
unreasonable occupational risk only when the risk estimate was so
high that it could not go away even after assuming workers would
use the most protective PPE that EPA considered or where EPA
could not assume any use of respirators.
For nearly all COUs where EPA found that its risk estimates for
acute, chronic, or cancer risks to workers did not represent an
unreasonable risk, in order to reach that finding, EPA had to assume
that all of the workers were using PPE.
Even where EPA did find unreasonable risk to workers, EPA has
grossly understated both the extent and magnitude of those risks by
assuming use of PPE.
EPA's approach for developing exposure
assessments for workers is to use the reasonably
available information and expert judgement.
When appropriate, in the risk evaluation, EPA
will use exposure scenarios both with and
without engineering controls and/or PPE that
may be applicable to particular worker tasks on a
case-specific basis for a given chemical. Again,
while EPA has evaluated worker risk with and
without PPE, as a matter of policy, EPA does not
believe it should assume that workers are
unprotected by PPE where such PPE might be
necessary to meet federal regulations, unless it
has evidence that workers are unprotected. For
the purposes of determining whether or not a
condition of use presents unreasonable risks,
56, 69,
PUBLIC COMMENTS:
Page 322 of 408
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74, 108
EPA's assumption that PPE use is universally used and effective results
in risk estimates not being carried into final risk determinations and
subsequently regulated, forgoing EPA's only opportunity to ensure PPE
is used and workers are protected. Although EPA finds all occupational
COUs present unreasonable risk, risk estimates that are understated
because of PPE assumptions means that subsequent regulation EPA
promulgates under TSCA will be under-protective. The magnitude of
underestimation is large even using EPA's 500-fold more lenient
immunosuppression endpoint (16-, 34-, and 23-fold for acute, chronic,
and cancer risks, respectively) based on detailed analyses of COUs,
exposure routes (inhalation and dermal), and exposure levels (high-end
or central tendency) for acute, chronic, and cancer risks.
EPA incorporates assumptions regarding PPE
use based on information and judgement
underlying the exposure scenarios. These
assumptions are described in the unreasonable
risk determination for each condition of use, in
section 5.2. Additionally, in consideration of the
uncertainties and variabilities in PPE usage, EPA
uses the high-end exposure value when making
its unreasonable risk determination in order to
address those uncertainties. EPA has also
outlined its PPE assumptions in section 5.1.
Further, in the final risk evaluation for TCE,
EPA has determined that most conditions of use
pose an unreasonable risk to workers even with
the assumed PPE.
80
PUBLIC COMMENTS:
By assuming 100% compliance with and effectiveness of PPE, EPA
miscalculates risks to workers (a conclusion supported by SACC).
OSHA inspection results indicate that this level of PPE adherence is not
achieved in workplaces that use TCE, as evidenced by citations to the
Automotive Body, Paint, and Interior Repair and Maintenance citations
(in 2018 and 2019), an industry classification that overlaps with TCE
with respect to occupational exposure scenarios. In addition, a recent
study of workplace safety practices in the auto collision industry found
declines in respiratory protection and right-to-know training.
100
PUBLIC COMMENTS:
For all but 5 of 29 occupational COUs, EPA assumes that all directly
exposed workers are provided appropriate PPE along with the fit
testing, medical examinations, and training required to properly use
such equipment. EPA assumes that workers will universally wear
respirators with an average PF of up to 50 and chemical-resistant gloves
with a protectiveness factor of up to 20. Even where EPA finds
unreasonable risk, it calculates the workers' MOEs and cancer risks
based on its assumption of PPE use, such that any subsequent
regulations of TCE under TSCA will not be sufficient to protect those
workers who are not provided with or cannot consistently use PPE.
Page 323 of 408
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100
PUBLIC COMMENTS:
EPA's assumption of PPE use violates TSCA's requirement to use the
best available science, since the best available science for occupational
risk assessment requires measurements of worker exposures and risks
without PPE. These non-PPE measurements permit OSHA and other
agencies to determine whether risks can be mitigated via engineering
controls and hazard elimination before the consideration of PPE,
consistent with the occupational hierarchy of controls.
100
PUBLIC COMMENTS:
EPA's PPE assumptions conflate risk evaluation and management.
TSCA requires EPA to complete a risk evaluation and to make
determinations of unreasonable risk before it considers how those risks
be managed. PPE may be considered, if at all, only during the risk
management stage. By assuming PPE use at the risk evaluation stage,
EPA ignores the significant limitations on widespread PPE use. Because
EPA need only regulate TCE to eliminate unreasonable risks, the
inclusion of PPE in risk evaluations means that subsequent TSCA
regulations will not protect workers who do not use PPE. EPA's
assumption of PPE preempts the required consideration of alternate
regulatory tools during the risk management stage.
102
PUBLIC COMMENTS:
EPA makes several assumptions regarding the need for, and the use of,
PPE. Those assumptions often do not include the use of all PPE as
required by NIOSH and/or EPA. The automotive industry maintains
procedures and worker requirements that meet or exceed the
recommended safety protections and PPE. It is therefore important that
EPA base its risk evaluations on manufacturing scenarios where the
automotive sector is fully utilizing all required PPE.
104
PUBLIC COMMENTS:
EPA has significantly underestimated occupational exposures by
assuming proper use of effective PPE without evidence. OSHA has
informed EPA that respirators are the least satisfactory approach to
exposure control, and the SACC report on 1,4-dioxane expressed
Page 324 of 408
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concern that smaller facilities are less likely to require routine PPE use
or to employ engineering controls. Tribal communities, in particular,
often have smaller facilities and are subject to OSHA exemptions and
OSHA reporting and inspection requirements. In the case of TCE, EPA
found unreasonable risk to workers for all COUs considered. However,
EPA's risk determination is based on assumptions that workers will use
PPE (both gloves and respirators) at most times when working with
TCE, which means that actual risks to workers are substantially
underestimated. A risk analysis for workers without PPE also must be
included. For accurate risk characterization of tribal members, NTTC
would like to see a risk determination for workers and ONUs, both self-
employed and in small businesses, that incorporates OSHA's
exemptions and practical exceptions. In these communities, take-home
exposures are also likely.
PPE - respirator/APF assumptions are not valid
49, 99
PUBLIC COMMENTS:
EPA's proposal to ban vapor degreasing conceded that respirators could
not be relied on to protect TCE-exposed workers owing to documented
limitations to successful implementation (including individuals with
impaired lung function, problems associated with adequate fit, and
issues with respect to communication, vision, fatigue, and decreased
efficiency). In addition, there are difficulties with implementing an
effective respirator program (which requires training, respirator
selections, medical evaluations, etc.) in small establishments.
The purpose of risk evaluation under TSCA is
"to determine whether a chemical substance
presents an unreasonable risk of injury to health
or the environment, without consideration of
costs or other nonrisk factors, including an
unreasonable risk to a potentially exposed or
susceptible subpopulation identified as relevant
to the risk evaluation by the Administrator, under
the conditions of use." TSCA section 6(b)(4)(A).
Implementation of respiratory protection
programs at facilities is not a component of a risk
evaluation under TSCA.
56, 108
PUBLIC COMMENTS:
Assumptions that respirators are effective are unsupported. Exposure to
TCE may occur even when respirators are used, and this may occur
without providing any indication to the user that it is no longer
functioning.
EPA assumes for some conditions of use, the use
of appropriate respirators is not a standard
practice, based on best professional judgment
given the burden associated with the use of
Page 325 of 408
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supplied-air respirators, including the expense of
the equipment, and the necessity of fit-testing
and training for proper use. The risk evaluation
also presents estimated risk in the absence of
PPE and does not assume that occupational non-
users use PPE.
100
PUBLIC COMMENTS:
EPA improperly assumes the use of respirators by workers exposed to
TCE. EPA identifies no data concerning the respirator use, but rather
relies on a 2003 NIOSH survey of respirator use across private sector
employers. This survey directly undermines EPA's PPE assumptions.
With respect to the TCE draft risk evaluation, an EPA risk assessor
indicated that the NIOSH study highlights the potential uncertainty
associated with widespread use of respiratory protective equipment. In
addition, respirators cannot be assumed to be protective even when they
are used (as this is dependent on fit, training, and other factors).
Therefore, EPA cannot assume that workers provided respirators will be
adequately protected. EPA has previously acknowledged limitations on
respirator use in its December 2016 proposal to ban aerosol degreasing
uses of TCE. However, EPA now assumes that all workers exposed to
TCE from aerosol degreasing will be provided with and protected by
APF 50 respirators. OSHA and NIOSH have likewise indicated that
there is only a "nominal possibility" that respirators will be worn
properly owing to the limitations of their use (heat stress, discomfort,
and other hazards). Because EPA is required to evaluate chemicals as it
is "reasonably seen" to be manufactured, processed, distributed, used, or
disposed, EPA must make risk determinations about TCE use under the
foreseen and known circumstances where respirators are not worn.
EPA has outlined its PPE assumptions in section
5.1 and has supplemented some sources and
information on respirator use in Section 2.4.1.1.
of the Risk Evaluation and Section 1.4.6 of the
Supplemental Information on Releases and
Occupational Exposure Assessment. EPA has
also added a table in Section 4.2.2.1 to make the
PPE assumptions made for each COU clearer.
For the purposes of determining whether or not a
condition of use presents unreasonable risks,
EPA incorporates assumptions regarding PPE
use based on information and judgment
underlying the exposure scenarios. These
assumptions are described in the unreasonable
risk determination for each condition of use, in
section 5.2. Additionally, in consideration of the
uncertainties and variabilities in PPE usage, EPA
uses the high-end exposure value when making
its unreasonable risk determination in order to
address those uncertainties.
108
PUBLIC COMMENTS:
EPA completely failed to acknowledge data on respirator use into the
draft risk evaluation. The SACC Peer Review Report on Methylene
Chloride recommended that EPA incorporate data from the NIOSH and
Bureau of Labor Statistics joint survey on "Respirator Usage in Private
The risk evaluation does acknowledge the work
completed by NIOSH and the BLS on respirator
use in Section 2.3.1.2.6.
Page 326 of 408
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Sector Firms," which provides industry estimates of respirator program
effectiveness and additional data from other published sources. Based
on these data, it was concluded in the draft carbon tetrachloride risk
evaluation that "the likelihood of respirator use may not be
widespread."
PPE-g
ove assumptions are not valid
56, 108
PUBLIC COMMENTS:
Assumptions that gloves are effective are unsupported. Gloves may
provide limited protection from TCE exposure, and protection varies
based on glove materials. EPA does not provide data on the
effectiveness of gloves, assumes default glove PFs, and disregards the
potential for occlusion to increase exposure.
EPA's approach for developing exposure
assessments for workers is to use the reasonably
available information and expert judgement.
EPA considers each condition of use and uses
exposure scenarios with and without PPE that
may be applicable to particular worker tasks on a
case-specific basis for a given chemical. For the
purposes of determining whether or not a
condition of use presents unreasonable risks,
EPA incorporates assumptions regarding PPE
use based on this information and judgment
underlying the exposure scenarios. These
assumptions are described in the unreasonable
risk determination for each condition of use, in
section 5.3. While EPA has evaluated worker
risk with and without PPE, as a matter of policy,
EPA does not believe it should assume that
workers are unprotected by PPE where such PPE
might be necessary to meet federal regulations,
unless it has evidence that workers are
unprotected. In consideration of these
uncertainties and variabilities in PPE usage, EPA
uses the high-end exposure value when making
its unreasonable risk determination in order to
address those uncertainties. Assumptions for
glove PFs are based on (Marciuart et al.. 2017).
Page 327 of 408
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56, 108
PUBLIC COMMENTS:
EPA used default glove PFs (5x, lOx, and 20x), ignoring the elevated
dermal exposures of workers in occluded scenarios. EPA does this
without empirical data to account for the complexities of glove use
(e.g., contamination or increased absorption due to increased skin
temperature). EPA fails to acknowledge the uncertainties and
deficiencies in its glove use assumptions in the Risk Determination
section of this draft risk evaluation.
For consumers, EPA fails to consider improper glove use and its
potential to lead to occlusion and potentially higher exposure than
the no gloves/soaked rag assumption on which EPA relies.
For workers, glove limitations are acknowledged but 5x, lOx, or 20x
PFs are still assumed despite the potential for occlusion and in the
absence of evidence. In cases where EPA did not identify
unreasonable risks based on the assumption of glove use, risks to
workers will occur whenever a worker uses anything less than the
assumed gloves or when there is occlusion.
See further discussion on occlusion in Section
2.3.1.1 of the Risk Evaluation and Appendix H of
the Supplemental Information on Releases and
Occupational Exposure Assessment document.
The occluded scenarios were presented as a what-
if scenario. EPA does not know the likelihood or
frequency of these scenarios in the workplace;
therefore, EPA did not present risk estimates
associated with occluded exposure in the Risk
Evaluation however a breakdown of the exposure
scenarios for which this was considered can be
found int the [Risk Calculator for Occupational
Exposures. Docket: EPA-1 '/
EPA has acknowledged in Section 4.3.2.1 that
risks under occluded exposure conditions may be
higher than estimated under no-glove conditions.
94
PUBLIC COMMENTS:
EPA's approach of applying a glove PF is appropriate for accounting
for contact with a gloved hand. However, the PFs should be applied to
the non-occluded ungloved estimates following a revised analysis, not
the original estimates presented in the risk assessment (which were
likely 6- to 17-fold too large).
EPA appropriately applied the glove PFs within
the framework used in the TCE risk evaluation.
EPA will consider further refinements to the
dermal approaches in future risk evaluations.
EPA used the best available science and
reasonably available data to assess exposures for
each COU. EPA appreciates any additional data
from commenters that would improve its
estimates of occupational exposures.
99
PUBLIC COMMENTS:
EPA's assumption that gloves will provide any level of protection is
speculative. EPA acknowledges that there are limited data on glove use
and admitted in other evaluations that glove PFs are highly uncertain.
Even when used, gloves may not be effective (some types lack
EPA considers each condition of use and uses
exposure scenarios with and without PPE that
may be applicable to particular worker tasks on a
case-specific basis for a given chemical. For the
Page 328 of 408
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impermeability for certain chemicals or fail to fully prevent exposure).
There are scenarios in which glove use may increase skin absorption.
The draft risk evaluation states that "dermal exposure may be
significant in cases of occluded exposure." Risk determinations for PPE
scenarios are based on default glove PFs and do not reflect the increase
from glove occlusion scenarios. This is a serious omission. If EPA
assumes glove use in the final risk evaluation (and it should not), EPA
must also base in its risk determinations on the foreseeable occlusion
scenarios that glove use would create.
purposes of determining whether or not a
condition of use presents unreasonable risks,
EPA incorporates assumptions regarding PPE
use based on this information and judgment
underlying the exposure scenarios. These
assumptions are described in the unreasonable
risk determination for each condition of use, in
section 5.3. While EPA has evaluated worker
risk with and without PPE, as a matter of policy,
EPA does not believe it should assume that
workers are unprotected by PPE where such PPE
might be necessary to meet federal regulations,
unless it has evidence that workers are
unprotected. In consideration of these
uncertainties and variabilities in PPE usage, EPA
uses the high-end exposure value when making
its unreasonable risk determination in order to
address those uncertainties. As stated in a
previous response, EPA does not know the
likelihood or frequency of these scenarios in the
workplace; therefore, EPA did not present risk
estimates associated with occluded exposure in
the Risk Evaluation. EPA has acknowledged in
Section 4.3.2.1 that risks under occluded
exposure conditions may be higher than
estimated under no-glove conditions.
100
PUBLIC COMMENTS:
EPA improperly assumes that all workers will use protective gloves,
even though they acknowledge that data to support this assertion are
limited.
Absent a recognized dermal hazard, OSHA does not mandate glove
use.
EPA has no information on how many workers who are exposed
EPA's approach for developing exposure
assessments for workers is to use the reasonably
available information and expert judgement.
When appropriate, in the risk evaluation, EPA
will use exposure scenarios both with and
without engineering controls and/or PPE that
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wear gloves, or how protective such gloves would be if worn.
If gloves are provided, EPA has little to no information about the
types of gloves worn, a critical omission given that not all gloves are
protective against TCE.
SDS recommendations are not binding.
EPA has no basis for assuming specific glove PFs. The TSCA SACC
notes that improper glove use can also lead to increased worker
exposures due to contamination on the inside surface (if workers are not
properly trained) or by "acting as a reservoir" for contaminants (if the
gloves are not impermeable). EPA notes that the effectiveness of gloves
is dependent upon training but provides no data about training
programs. In the draft risk evaluation, EPA conducts a separate glove
"occlusion" analysis, which found dermal exposures up to several fold
higher than under no-glove scenarios. In its final risk calculations,
however, EPA ignores the foreseeable exposure scenarios in which
employees are not provided protective gloves, or are provided
inadequate gloves or are not adequately trained and thus face even
greater dermal exposures due to glove contamination and the occlusion
of TCE close to the skin. EPA's assumption that all workers will be
properly wear chemical-resistant gloves is unfounded and contrary to
TSCA.
may be applicable to particular worker tasks on a
case-specific basis for a given chemical. Again,
while EPA has evaluated worker risk with and
without PPE, as a matter of policy, EPA does not
believe it should assume that workers are
unprotected by PPE where such PPE might be
necessary to meet federal regulations, unless it
has evidence that workers are unprotected. For
the purposes of determining whether or not a
condition of use presents unreasonable risks,
EPA incorporates assumptions regarding PPE
use based on information and judgment
underlying the exposure scenarios. These
assumptions are described in the unreasonable
risk determination for each condition of use, in
section 5.2. Additionally, in consideration of the
uncertainties and variabilities in PPE usage, EPA
uses the high-end exposure value when making
its unreasonable risk determination in order to
address those uncertainties. EPA has also
outlined its PPE assumptions in section 5.1.
Further, in the final risk evaluation for TCE,
EPA has determined that most conditions of use
pose an unreasonable risk to workers even with
the assumed PPE.
Interpretation of OSHA requirements for PPE
49, 99
PUBLIC COMMENTS:
EPA repeatedly suggested that OSHA regulations obligate employers to
implement PPE where necessary to provide protection against chemical
risks. OSHA regulations do not require employers to follow the
recommendations in an SDS, and the preamble to OSHA's hazard
communication rule expressly states that "there is no requirement for
employers to implement the recommended controls." Moreover, OSHA
For the purpose of this Risk Evaluation, EPA
makes assumptions about potential PPE use
based on reasonably available information and
expert judgment. EPA considers each condition
of use and constructs exposure scenarios with
and without engineering controls and /or PPE
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regulations give employers latitude to interpret evidence of workplace
risks and to select worker protection measures they deem appropriate.
There is no evidence that employers uniformly implement PPE or
workplace controls sufficient to eliminate these risks in the absence of
any legal obligation to do so. In addition, the draft risk evaluation
explains OSHA's HOC for protecting workers. Consistent with the
HOC and the SACC's consistent recommendations, EPA's risk
determinations should assume no PPE use. How to eliminate TCE's
unreasonable risks to workers should be decided in the TSCA risk
management phase and PPE should be considered as a last resort, only
after other means of control such as chemical substitution and
engineering controls have been shown to be inadequate.
that may be applicable to particular worker tasks
on a case-specific basis for a given chemical.
Again, while EPA has evaluated worker risk with
and without PPE, as a matter of policy, EPA
does not believe it should assume that workers
are unprotected by PPE where such PPE might
be necessary to meet federal regulations, unless it
has evidence that workers are unprotected. For
the purposes of determining whether or not a
condition of use presents unreasonable risks,
EPA incorporates assumptions regarding PPE
use based on information and judgment
underlying the exposure scenarios. These
assumptions are described in the unreasonable
risk determination for each condition of use, in
section 5.2. Additionally, in consideration of the
uncertainties and variabilities in PPE usage,
including the duration of PPE usage, EPA uses
the high-end exposure value when making its
unreasonable risk determination in order to
address those uncertainties.
56, 80,
108
PUBLIC COMMENTS:
EPA mischaracterizes OSHA regulations (29 CFR ง 1910.134)
throughout the draft risk evaluation.
The OSHA PPE standard is rendered unprotective by the outdated
TCE PEL; OSHA cannot require respirators at TCE levels below the
100 ppm PEL. The OSHA respiratory protection standard requires
an entire program {i.e., fit testing and medical exams) if respirators
are provided; therefore, there is a disincentive.
OSHA regulations do not require compliance with SDSs (which are
non-binding). Not only do OSHA regulations not require
compliance (but rather leaves this decision to the employer), but
even if mandatory, reliance on them would be insufficient to ensure
protection because SDSs are often inaccurate, incomplete, and too
technical for many workers to understand.
OSHA's database of inspections demonstrates significant non-
compliance with respiratory protection requirements such as those that
apply to TCE. Cal/OSHA submitted comments to the TCE docket
indicating that an industry classification with many of the same
occupational exposure scenarios covered by the TCE draft risk
evaluation (Automotive Body, Paint, and Interior repair and
Maintenance; North American Industry Classification System [NAICS1
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Code 81121) was the second most cited for respiratory protection in
2018.
61
PUBLIC COMMENTS:
OSHA's hierarchy of controls is clear that it is unacceptable to use PPE
as the primary means to protect workers; rather, the most effective way
to control hazards is through engineering controls. EPA's draft risk
evaluation bases hazard estimates on the assertion that workers will be
protected from exposure via PPE use. The underlying assumptions
(which are likely not true) are that workers will be provided PPE, that
workers will be able to properly use PPE (having no medical conditions
that preclude use), and that PPE will be effective. Recommendations in
SDSs are not required to be followed by employers under OSHA, and
many employers do not follow recommendations and/or OSHA legal
requirements. Existing OSHA regulations will not result in appropriate
PPE use. EPA continues to produce risk evaluations that ignore long-
standing worker protection policies. EPA's risk draft evaluation
assumes that employers will offer PPE when there are incentives not to
(e.g., expense of medical monitoring, fit testing requirements). Despite
this, EPA assumed PPE use, leading to incorrect estimates of exposure,
and drastically underestimating risks by order of magnitude. EPA must
go back and make determinations of unreasonable risk assuming that
many workers will not be using appropriate PPE.
Section 2.3.1.2.6 of the Risk Evaluation
discusses the hierarchy of controls and that PPE
is the last stage of protection.
EPA considers each condition of use and uses
exposure scenarios with and without PPE that
may be applicable to particular worker tasks on a
case-specific basis for a given chemical. For the
purposes of determining whether or not a
condition of use presents unreasonable risks,
EPA incorporates assumptions regarding PPE
use based on this information and judgment
underlying the exposure scenarios. These
assumptions are described in the unreasonable
risk determination for each condition of use, in
section 5.3. While EPA has evaluated worker
risk with and without PPE, as a matter of policy,
EPA does not believe it should assume that
workers are unprotected by PPE where such PPE
might be necessary to meet federal regulations,
unless it has evidence that workers are
unprotected. In consideration of these
uncertainties and variabilities in PPE usage, EPA
uses the high-end exposure value when making
its unreasonable risk determination in order to
address those uncertainties.
100
PUBLIC COMMENTS:
EPA improperly assumes the use of respirators at levels far below the
TCE permissible exposure limit. EPA is simply wrong to assume that
employers have a duty under OSHA to provide PPE to workers at
EPA agrees that there are challenges associated
with use of PPE; they are described in section
5.1.1.3. By providing risk estimates assuming use
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exposure levels below 100 ppm and EPA has no evidence to suggest
that employers voluntarily do so. OSHA does not require workers to be
provided with or to use PPE when exposures fall below the PEL, and
EPA cites no evidence that workers have or will voluntarily provide
expensive and burdensome PPE in circumstances where OSHA does not
require it. Respirators with an APF of 50 are often bulky, inhibit a
worker's ability to safely do their job, and require extensive fit testing,
medical examinations, filter change schedules, cleaning, and
maintenance. EPA nowhere accounts for these serious limitations in the
practical use of, or employer willingness to supply this type of PPE.
of PPE, EPA is not recommending or requiring
use of PPE. EPA's approach for evaluating risk to
workers and ONUs is to use the reasonably
available information and professional judgment
to construct exposure scenarios that reflect the
workplace practices involved in the conditions of
use of the chemicals and address uncertainties
regarding availability and use of PPE. EPA uses
exposure scenarios both with and without
engineering controls and/or PPE that may be
applicable to particular worker tasks on a case-
specific basis for a given chemical. Again, while
EPA has evaluated worker risk with and without
PPE, as a matter of policy, EPA does not believe
it should assume that workers are unprotected by
PPE where such PPE might be necessary to meet
federal regulations, unless it has evidence that
workers are unprotected.
EPA acknowledges that there is a PEL but did not
use it as a benchmark for either risk assessment
or unreasonable risk determination. EPA
provided the PEL as a point of comparison only
to help readers understand EPA's workplace
exposure and risk estimates compared to a
familiar exposure concentration, as expressed in
the PEL. EPA did not use the PEL in the
development of the risk estimates or as part of
making an unreasonable risk determination.
Information reasonably available to EPA,
including data submitted by chemical
manufacturers and processors, indicates that PPE
100
PUBLIC COMMENTS:
EPA relies on OSHA's Hazard Communication Standard to support its
expectation that workers will be provided appropriate PPE consistent
with applicable SDSs; however, employers are not obligated under
OSHA to follow SDS recommendations. In addition, information in
SDSs is often vague and inconsistent so that they are not effective
hazard communication tools. In the absence of a requirement for
employers to implement the recommended controls, there is no basis in
EPA's assumption that the Hazard Communication Standard will result
in uniform use of appropriate PPE.
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is generally used. EPA does not assume that the
inclusion of PPE on SDSs is sufficient to ensure
PPE use. While EPA considers the information
on SDSs, EPA does not make PPE use
assumptions based solely on SDSs.
TCE is the subject of an OSHA standard. OSHA
has established a permissible exposure limit
(PEL) of 100 ppm for TCE . However, as noted
on OSHA's website, "OSHA recognizes that
many of its permissible exposure limits (PELs)
are outdated and inadequate for ensuring
protection of worker health. Most of OSHA's
PELs were issued shortly after adoption of the
Occupational Safety and Health (OSH) Act in
1970, and have not been updated since that
time." OSHA provides an annotated list of PELs
on its website, including alternate exposure
levels. For TCE, the alternates provided are the
California OSHA PEL of 25 ppm and the
ACGM TLV of 25 ppm.
(https://www.osha.gov/dsg/annotated-
pels/tablez-2.htmQ.
For the purposes of determining whether or not a
condition of use presents unreasonable risks,
EPA incorporates assumptions regarding PPE
use based on information and judgment
underlying the exposure scenarios. These
assumptions are described in the unreasonable
risk determination for each condition of use, in
section 5.2 and in the risk characterization
section in Table 4-9. Additionally, in
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consideration of the uncertainties and
variabilities in PPE usage, including the duration
of PPE usage, EPA uses the high-end exposure
value when making its unreasonable risk
determination in order to address those
uncertainties.
Human health risk characterization
SACC
SACC COMMENTS:
The Committee recommends that the evaluation base the risk
characterization on aggregation of inhalation and dermal risks.
EPA has added to the discussion of aggregate
and sentinel exposures in Section 4.4.2. In short,
without a PBPK model containing a dermal
compartment to account for toxicokinetic
processes the true internal dose for any given
exposure cannot be determined. Aggregating
exposures could inappropriately overestimate
total exposure, as simply adding exposures from
different routes without an available PBPK
model for those routes would compound
uncertainties.
SACC
SACC COMMENTS:
Recommendation: Risks from oral exposures should be discussed and
its exclusion justified in the draft risk evaluation.
Worker and Consumer Risk Summary Tables (Tables 4-54 and 4-55)
present benchmark values for dermal and inhalation exposure but oral
exposure may also occur. The only reference to oral exposures in the
draft risk evaluation occurs in 'footnote b' to Figure 1-3 - TCE
Conceptual Model for Consumer Activities and Uses. Even though oral
exposure is expected to be small, the risk evaluation should discuss why
it is excluded.
As stated in the footnotes for Figure 1-5, mists of
TCE will likely be rapidly absorbed in the
respiratory tract or evaporate and not result in an
oral exposure. Although less likely given the
physical-chemical properties, oral exposure may
also occur from incidental ingestion of residue
on hand/body. Because oral exposure would be a
very minor pathway relative to dermal and
inhalation exposure, evaluation of risks via those
routes is protective of any potential lesser risk
from oral exposure.
SACC
SACC COMMENTS:
Recommendation: Explain why risk characterizations for ONUs are
The "upper limit" notation indicated that the
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appropriately identified as high-end exposures despite being based on
central tendency exposure levels of workers.
In Table 4-54, ONU exposures are estimated based on workers' central
tendency exposure estimates, which are assumed to represent the high
end of potential exposures to ONUs. The notation under the Population
column for these ONUs is labeled as "upper limit." This notation is
consistent with the expectation that ONU's exposures would be lower
than the workers' exposures. Thus, it would be expected that these
ONU exposure estimates correspond to the expected high end, not the
central tendency {i.e., they are derived from the central tendency
estimate for the worker, but they represent the high-end exposure for
the ONU).
ONU risk estimate was not based on actual data
but was an extrapolation from worker central
tendency values, which are expected to serve as a
reasonable surrogate for upper-limit ONU
exposure. To improve clarity the notation has
been modified from "upper limit" to "worker
estimate."
90
PUBLIC COMMENTS:
Pushing through this draft risk evaluation in an expedited fashion would
be a disservice to the American people and a violation of EPA's
mandate to protect human health. This draft risk evaluation seems to
prioritize boosting the use/sale of TCE regardless of personal risks to
affected populations. We hope that EPA will abandon this expedited
and incomplete analysis in favor of a comprehensive risk evaluation that
meets the requirements of TSC A and provides what the public deserves.
EPA is finalizing the risk evaluation in a manner
consistent with statutory and regulatory
requirements and deadlines. Consistent with
TSCA, EPA has evaluated unreasonable risk
without consideration of costs or other non-risk
factors.
Per the statute (see TSCA section 6(b)(4)(A))
and the implementing regulations for risk
evaluations (40 CFR part 702, subpart B), during
risk evaluation, EPA must determine whether the
chemical substance presents an unreasonable risk
under its conditions of use. Upon finding
unreasonable risk, EPA will apply risk
management actions to the extent necessary so
that the chemical no longer presents such risk, in
accordance with TSCA section 6(a).
In Section 2.3.3, EPA addresses the potentially
exposed or susceptible subpopulations identified
108
PUBLIC COMMENTS:
TSCA's standard requires EPA to resolve risks without consideration of
costs or other non-risk factors. Other EPA-administered statutes allow
consideration of non-risk factors and do not explicitly require
consideration of vulnerable subpopulations. EPA cannot assume that
regulatory efforts that meet the standards of these statutes also meet
TSCA's requirement to eliminate unreasonable risks to PESS.
Page 336 of 408
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as relevant based on greater exposure. EPA
addresses the subpopulations identified as
relevant based on greater susceptibility in
Section 3.2.5.2. In developing the draft risk
evaluation, the EPA analyzed the reasonably
available information to ascertain whether some
human receptor groups may have greater
exposure than the general population to the
hazard posed by TCE.
EPA believes that coordinated action on
exposure pathways and risks addressed by other
EPA-administered statutes and regulatory
programs is consistent with statutory text and
legislative history, particularly as they pertain to
TSCA's function as a "gap-filling" statute, and
also furthers EPA aims to efficiently use Agency
resources, avoid duplicating efforts taken
pursuant to other Agency programs, and meet the
statutory deadline for completing risk
evaluations.
Ecological risk characterization
SACC
SACC COMMENTS:
Several committee members were concerned that overall environmental
risks were not determined; only risks from TCE released to surface
water and only risks posed to aquatic organisms were assessed. This
limitation should be clearly restated in the risk characterization section.
In the draft risk evaluation, sediment-dwelling
species were assessed qualitatively. However, in
response to SACC comments a quantitative
assessment of sediment organisms was added to
the TCE risk evaluation in Section 4.1.3.
For the terrestrial pathway, the environmental
exposure pathways covered under the jurisdiction
of other EPA-administered statutes and
regulatory programs are not within the scope of
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the risk evaluation. Emissions to ambient air from
commercial and industrial stationary sources, and
associated inhalation exposures of terrestrial
species, are under the jurisdiction of the Clean
Air Act (CAA). Clarifying language about what
pathways are addressed under other statutes has
been added to Section 1.4.2 of the Risk
Evaluation.
During problem formulation EPA determined
risks would not be evaluated for land-applied
biosolids because based on fate properties, TCE
is not anticipated to partition to biosolids during
wastewater treatment. Any TCE present in the
water portion of biosolids following wastewater
treatment and land application would be expected
to rapidly volatilize into air.
In addition, TCE is not expected to
bioaccumulate in tissues, and concentrations will
not increase from prey to predator in either
aquatic or terrestrial food webs. Lastly, based on
the Guidance for Ecological Soil Screening
Levels (EPA 2003a, b) document, for terrestrial
wildlife, relative exposures associated with
inhalation and dermal exposure pathways are
insignificant, even for volatile substances,
compared to direct ingestion and ingestion of
food (by approximately 1,000-fold). EPA has
added language to the final risk evaluation
document in Section 4.1.4 explaining this
rationale.
SACC
SACC COMMENTS:
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Recommendation: Ensure environmental risk characterization
statements are consistent with limitations imposed on the environmental
risk assessment. Conclusions on environmental risk cannot consistently
represent releases from >6000 facilities due to insufficient data;
therefore, the evaluation cannot conclude that there are no risks to
aquatic organisms. The draft risk evaluation underestimates TCE
releases by a factor of 1.5 to 130, depending on multiple assumptions.
Some facilities and species have an estimated RQ>1, but this is not
translated in the risk determination or linked to a mode of use.
EPA modified the language in the risk
characterization and conclusion section to read
"EPA did not identify risks" where RQs were <1
or chronic and algae RQs were greater than or
equal to 1 and? days of exceedance were less
than 20 days.
SACC
SACC COMMENTS:
Recommendation: Report the fraction of estimated TCE releases
captured by monitoring data and improve the discussion of how total
release time is determined.
The Committee understands the modeling process used to determine
days of exceedance from commercial uses (Appendix C) but was unable
to follow the analysis that produced the days of exceedance. There are
many instances in which the 7Q10 surface water concentration (SWC)
exceeds the COC. If the mean SWC exceeds the COC, a description is
required to demonstrate how fewer than 50% of the release days exceed
the benchmark. If the explanation hinges on a log-normal distribution
skewed toward higher concentrations, a quantitative verification is
needed that none of the modeled concentrations exceed the acute
toxicity COC.
The comment is unclear as to what the submitter
defines as "monitoring data." Releases to water
for all OES were based on TRI and DMR data
where available. The assumptions and
methodology used to estimate release days for
each OES is described in Section 2.2.2.3. The
uncertainties with these assumptions are
described in Section 2.2.2.3.
The E-FAST documentation manual provides
more details on how the days of exceedance are
estimated (TJ.S. EPA 2007). E-FAST's PDM
uses probability distributions as inputs to reflect
that streams follow a highly variable seasonal
flow pattern and there are numerous variables in
a manufacturing process that can affect the
chemical concentration and flow rate of the
effluent.
SACC
SACC COMMENTS:
Recommendation: Improve the justification for not assessing ambient
air emissions and impacts from commercial and stationary sources.
It is concerning that these sources were excluded on a statutory
basis, even though it is expected that most TCE will be removed in
For the terrestrial pathway, the environmental
exposure pathways covered under the jurisdiction
of other EPA-administered statutes and
regulatory programs are not within the scope of
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wastewater treatment by volatilization during aeration. It is not
appropriate to assume ambient exposure risks are managed by the
CAA.
EPA did not quantitatively assess exposure to sediment organisms
because TCE is not expected to partition to sediment. Section 4.1.4
concludes that "physical-chemical properties do not support an
exposure pathway through water and soil pathways to terrestrial
organisms." However, Section 4.1.4 does not consider that soil
invertebrates and burrowing mammals in functionally confined
spaces may be exposed to TCE through vapor intrusion from
contaminated underground water.
the risk evaluation. Emissions to ambient air from
commercial and industrial stationary sources, and
associated inhalation exposures of terrestrial
species, are under the jurisdiction of the Clean
Air Act (CAA). Clarifying language about what
pathways are addressed under other statutes has
been added to Section 1.4.2 of the Risk
Evaluation. As explained in more detail in
Section 1.4.2 of the Final Risk Evaluation, EPA
believes it is both reasonable and prudent to tailor
TSCA Risk Evaluations when other EPA offices
have expertise and experience to address specific
environmental media, rather than attempt to
evaluate and regulate potential exposures and
risks from those media under TSCA. EPA
believes that coordinated action on exposure
pathways and risks addressed by other EPA-
administered statutes and regulatory programs is
consistent with statutory text and legislative
history, particularly as they pertain to TSCA's
function as a "gap-filling" statute, and also
furthers EPA aims to efficiently use Agency
resources, avoid duplicating efforts taken
pursuant to other Agency programs, and meet the
statutory deadline for completing Risk
Evaluations. EPA has therefore tailored the scope
of the Risk Evaluation for TCE using authorities
in TSCA Sections 6(b) and 9(b)(1).
SACC
SACC COMMENTS:
Recommendation: Add worst-case scenarios from wastewater
contaminated streams and add data on environmental vertebrate
receptors for reproductive and developmental effects.
Because hazard is identified but risk characterization is not conducted
EPA used the best available science and the
reasonably available information during the data
integration process. Hazard data did include
developmental effects observed in amphibians.
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for aquatic receptors, additional discussion regarding uncertainty is
warranted. "Worst-case scenarios" are missing from the Risk
Characterization section. From the exposure aspect of the RQ
evaluation, monitoring data from NPDES should be used to represent a
"worst-case" exposure, particularly in wastewater dominated streams.
From the effects/hazard side of the risk equation, data are absent for
vertebrate reproduction and development in aquatic vertebrates.
Additionally, EPA considered surface water
concentrations in receiving water bodies from
wastewater treatment plants (WWTPs) based on
TRI indirect release estimates or DMR reporting.
56, 74,
108
PUBLIC COMMENTS:
EPA identified unreasonable risk to aquatic organisms using RQs
and dismissed this risk owing to uncertainty and relying on a
dubiously calculated COC for algae. This approach is arbitrary and
capricious because EPA refuses to accept the outcomes of its own
analyses and conclusions run contrary to the evidence. Based on the
analysis presented, EPA should find an unreasonable risk to the
environment presented by certain COUs.
EPA identified risks (e.g., to the most sensitive species of algae) but
did not make risk findings. Unreasonable risk for some COUs were
dismissed based on "uncertainties in the data" and on selective
monitoring data that exclude contaminated environments and ranged
across 5 orders of magnitude.
Uncertainties in the dataset were not explicitly specified.
Uncertainty increases the chances of unreasonable risk. Uncertainty
does not justify a finding of no unreasonable risk when EPA's own
analysis supports a finding of unreasonable risk.
EPA had more confidence in the probabilistic
approach used to derive the COC from the SSDs,
and the SACC generally agreed with EPA's
approach for algae. The SACC suggested using a
higher assessment factor, and EPA agreed. From
draft to final version of the TCE Risk Evaluation
EPA changed the assessment factor from 1 to 5
to account for the uncertainties around using
ECsos rather than ChVs. If sufficient ChVs had
been available EPA would have used them
instead of ECsos. This change has been made in
Section 3.1.5.
EPA considers the uncertainties associated with
each condition of use, and how the uncertainties
may result in a risk estimate that overestimates or
underestimates the risk. Based on such analysis,
EPA determines whether or not the identified
risks are unreasonable.
56, 108
PUBLIC COMMENTS:
Although EPA's analysis showed that TCE presents an unreasonable risk
to aquatic organisms (based on releases from certain disposal and
recycling facilities generating surface water concentrations above the
COC for TCE), the analysis underestimated this risk, especially for
algae. EPA's calculation of a COC for algae used SSD; algae "as a
EPA had more confidence in the probabilistic
approach used to derive the COC from the SSDs,
and the SACC generally agreed with EPA's
approach for algae. The SACC suggested using a
higher assessment factor, and EPA agreed. From
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whole" were represented by nine species. EPA should use the most
sensitive species as its indicator organism to develop protective COCs.
draft to final version of the TCE Risk Evaluation
EPA changed the assessment factor from 1 to 5 to
account for the uncertainties around using ECsos
rather than ChVs. If sufficient ChVs had been
available EPA would have used them instead of
EC50S. This change has been made in Section
3.1.5.
65
PUBLIC COMMENTS:
The draft risk evaluation demonstrates unreasonable risk to aquatic
organisms, yet EPA dismisses unreasonable risk by invoking
uncertainty.
EPA considers the uncertainties associated with
each condition of use, and how the uncertainties
may result in a risk estimate that overestimates or
underestimates the risk. Based on such analysis,
EPA determines whether or not the identified
risks are unreasonable.
108
PUBLIC COMMENTS:
The use of assessment factors in the development of COCs cannot be
construed as "safety factors" that yield conservative estimates. In
evaluating risks, EPA should recognize that assessment factors ensure
greater accuracy rather than rendering the evaluation conservative.
EPA is in the process of evaluating the body of
reasonably available literature on the subject in
order to determine whether to revise standards for
application of AF and the acute to chronic ratio
for the next 20 high-priority substances
undergoing risk evaluation. Until the body of
scientific evidence for assessment factors is
evaluated, EPA will continue to use OPPT
methodology as cited in the risk evaluation (U.S.
EPA 2013, 2012c) and aoolv an AF of 5 for acute
and 10 for chronic aquatic invertebrate data. EPA
considers these AFs to be protective of aquatic
invertebrates from acute and chronic exposures to
neutral organic substances such as TCE, which
produce toxicity from simple narcosis.
Risk management/mitigation (including proposed ban)
38
PUBLIC COMMENTS:
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Request that rules for use and regulation of TCE not be relaxed from the
TCE ban. Safer, alternative engineered solvents are available as
cleaning fluids for manufacturing applications (e.g., cleaning post
soldering and ionic residues from electronic assemblies). TCE should
not be used or sold without regulation and formal instructions for
handling and disposal.
Per the statute (see TSCA section 6(b)(4)(A)) and
the implementing regulations for risk evaluations
(40 CFR part 702, subpart B), during risk
evaluation, EPA must determine whether the
chemical substance presents an unreasonable risk
under its conditions of use. Upon finding
unreasonable risk, EPA will apply risk
management actions to the extent necessary so
that the chemical no longer presents such risk, in
accordance with TSCA section 6(a).
47
PUBLIC COMMENTS:
In EPA's 2014 TCE TSCA Work Plan Risk Assessment, risks were
assessed for its use in large/small commercial operations and consumer
solvent degreasing, consumer use as a spray-applied protective coating
for arts and crafts, and commercial use as a spot remover at dry cleaning
facilities. This risk assessment was used to support two proposed rules
under TSCA ง 6 (81 FR 91592; December 12, 2016; 82 FR 7432;
January 19, 2017) to ban these uses of TCE:
Notice in December 2016 to prohibit TCE's manufacture,
processing, and distribution in commerce for use in aerosol
degreasing and spot cleaning at dry cleaning facilities.
Notice in January 2017 to prohibit TCE's manufacture (including
import), processing, and distribution in commerce for use in vapor
degreasing, prohibit use of TCE in vapor degreasing.
Both notices also required downstream notifications of prohibitions
throughout the supply chain and some form of limited
recordkeeping.
After the change in administration, both proposals were withdrawn, and
no risk mitigation was implemented. The updated risk evaluation
identified unreasonable risk for workers (and in most cases, ONUs) for
every commercial COU. Unreasonable risk was identified for all but
one consumer COU, and for the vast majority of uses, to bystanders. All
but one trivial COU has been shown to pose a danger to the public
health. It is time to proceed directly to rulemaking with a proposal to
ban all further import, manufacture, and distribution of TCE for
commercial and consumer uses in the U.S., followed by promulgation
of the ban on all uses on an expedited timeline.
Page 343 of 408
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108
PUBLIC COMMENTS:
EPA proposed to ban the use of TCE in aerosol degreasing and spot
cleaning in dry cleaning facilities in 2016 and vapor degreasing in 2017
owing to excessive risks to workers, bystanders, and/or consumers.
EPA's 2014 TCE Work Plan risk assessment and supplemental
technical reports (based on peer review, best science available, and
WOE) indicated that these uses present an unreasonable risk.
EPA's decision to re-evaluate risks associated with these uses was
unnecessary and inappropriate. This action will delay or deny
critical actions to protect workers and consumers.
EPA should promptly act to finalize these bans even as it proceeds to
finalize its risk evaluation focusing on risks from other COUs and
exposures that would remain after banning these COUs.
49
PUBLIC COMMENTS:
It is critical for EPA to fully account for all TCE pathways of exposure
and COUs, accurately and fully identify all health endpoints
contributing to TCE's risks, and ensure that its risk evaluation and risk
management actions protect vulnerable populations.
EPA thoroughly reviews all health endpoints
associated with TCE in Section 3.2. Vulnerable
populations are covered by accounting for PESS,
as described in Sections 2.3.2.8, 3.2.5.2, and
4.4.1.
56
PUBLIC COMMENTS:
EPA has contended that some issues discussed at previous SACC
meetings were in the realm of policy and not relevant to SACC's
charge, including EPA's decisions to: (1) exclude all general population
risks from exposure releases to land, air, and water based on the
assumption that this is addressed by other statutes; (2) assume that PPE
is always used and effective; and (3) use a benchmark cancer risk level
of lxlO"4 to define unreasonable risk to workers. EDF strongly
disagrees that these issues are beyond the scope of the SACC. These
decisions have major direct scientific consequences, as they clearly lead
to underestimations of chemicals' risk to the environment, the general
population, workers, and vulnerable subpopulations. In the Final SACC
Reports for 1,4-dioxane, 1-bromopropane, and methylene chloride, the
SACC appropriately addressed some of these issues and should
EPA considers all comments from the public and
SACC when updating science policy
determinations. Nevertheless, decisions such as
benchmarks to use within established ranges and
what pathways are in scope remain within the
realm of EPA's policy decision-making
authority.
Page 344 of 408
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continue doing so in future reports with a particular emphasis on how
those determinations affect the scientific accuracy and legitimacy of the
risk evaluations.
56, 108
PUBLIC COMMENTS:
TSCA divides risk evaluation and management processes so that
regulatory measures are considered after determinations of unreasonable
risk. EPA's choice to make risk determinations based on an assumption
of PPE conflates risk evaluation and management, leading EPA to not
find an unreasonable risk or to underestimate the extent and magnitude
of these risks. EPA's failure to make unreasonable risk determinations
could potentially deny itself the opportunity to impose mandatory
requirements to control workplace exposures.
For the purpose of this Risk Evaluation, EPA
makes assumptions about potential PPE use
based on reasonably available information and
expert judgment. EPA considers each condition
of use and constructs exposure scenarios with
and without engineering controls and /or PPE
that may be applicable to particular worker tasks
on a case-specific basis for a given chemical.
Again, while EPA has evaluated worker risk with
and without PPE, as a matter of policy, EPA
does not believe it should assume that workers
are unprotected by PPE where such PPE might
be necessary to meet federal regulations, unless it
has evidence that workers are unprotected. For
the purposes of determining whether or not a
condition of use presents unreasonable risks,
EPA incorporates assumptions regarding PPE
use based on information and judgment
underlying the exposure scenarios. These
assumptions are described in the unreasonable
risk determination for each condition of use, in
section 5.2. Additionally, in consideration of the
uncertainties and variabilities in PPE usage,
including the duration of PPE usage, EPA uses
the high-end exposure value when making its
unreasonable risk determination in order to
address those uncertainties.
81
PUBLIC COMMENTS:
Are there any new legal obligations, so as, to assure safe and healthful
Per the statute (see TSCA section 6(b)(4)(A))
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living conditions {water consumption - in public} and working
conditions by an approved state plan or standard regulations, to provide
people with recognized hazards likely to cause death or serious physical
harm. How valuable will the draft risk evaluation for TCE be if not legally
supported? Will it be enough to help identify risk levels and to determine
any appropriate control measures to implement?
and the implementing regulations for risk
evaluations (40 CFR part 702, subpart B), during
risk evaluation, EPA must determine whether the
chemical substance presents unreasonable risk
under its conditions of use. Upon finding
unreasonable risk, EPA will apply risk
management actions to the extent necessary so
that the chemical no longer presents such risk, in
accordance with TSCA section 6(a).
84
PUBLIC COMMENTS:
TCE poses a high risk of exposure to the end-user of the chemical, is a
suspected carcinogen, and has been detected in groundwater.
Commercially available alternatives exist to replace TCE. Honeywell
currently offers a better alternative to TCE for at least three uses,
including vapor/immersion degreasing, aerosol cleaning, and adhesives.
EPA appreciates the information on the
alternatives to TCE and will consider them
during risk management.
86
PUBLIC COMMENTS:
Major problems in the draft risk evaluation will result in families being
left unprotected. We are very concerned that EPA's draft risk evaluation
for TCE, if finalized without major improvements, will fail to protect
public health. Our families and our communities are among those that
have been significantly impacted by TCE; this process is not theoretical
for us.
EPA has improved the final Risk Evaluation
based on public and SACC comments. The Risk
Evaluation for TCE evaluates all associated
conditions of use. For any conditions of use
where unreasonable risk was identified, EPA will
proceed to risk management during which EPA
will consider all available regulatory options.
88
PUBLIC COMMENTS:
There is concern regarding EPA's decision to abandon the previously
proposed bans on high-risk uses of TCE.
Regulatory actions to address unreasonable risks
are outside the scope of this risk evaluation. EPA
has decided to re-evaluate TCE uses from the
proposed TSCA section 6(a) rules in order to
assess them under the updated TSCA statute.
92
PUBLIC COMMENTS:
The effort to replace the previous rule should be scrapped. Independent
scientists agree that TCE is highly toxic, and that even trace amounts
can damage developing hearts of human beings. The rule previously in
place was founded on science responsible to data, not to chemical
industry interests, and should remain in effect.
Risk characterization other
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SACC
SACC COMMENTS:
Recommendation: Clearly and explicitly state in Section 4 the
fundamental objective of the environmental or human health risk
characterization.
The following issues and questions need more emphasis:
What is the most sensitive endpoint for each exposure route and use,
for both acute and chronic non-cancer effects and cancer? Also,
explicitly define what is meant by "most sensitive."
Limitations and data gaps need to be presented in a more
highlighted and obvious manner.
Areas of controversy should be highlighted.
Section 4.1 and 4.4.1 (for environmental risks)
and 4.2.1 (for human health risks) describe the
risk characterization process, which integrates
exposure and hazard in order to determine
whether there is risk for the chemical based on
scientifically established benchmarks.
Section 4.2.1.1 presents the endpoints used for
risk estimates in the Risk Evaluation, including
the most sensitive chronic POD for each hazard
domain. Limitations, data gaps, and controversies
are discussed throughout the Risk Evaluation in
the "Assumptions and Key Sources of
Uncertainty" sections.
Risk del
ermination (unreasonable risk/no unreasonable risk)
SACC
SACC COMMENTS:
Recommendation: Clarify why Pepper Spray, given that its MOE is
below the benchmark MOE, does not present an unreasonable risk.
One Committee member noted that the results for Pepper Spray (Table
4-51) show that its MOEs for consumer users are below the benchmark
MOE and also below the MOE for the congenital heart defects
endpoint. This is an important point to include in the discussion because
it is the only consumer COU that is found to not present an
unreasonable risk to this higher (but controversial) benchmark.
While Pepper Spray does indicate risk for
developmental neurotoxicity and congenital heart
malformations, EPA has reduced confidence in
the dose-response results for those studies
(Fredriksson et al 1993), (Johnson et al 2003).
Therefore, risk conclusions are based on the
robust and sensitive acute immune endpoint from
(Selsrade and Gilmour, 2010) which was the best
overall acute endpoint based on the best available
science and weight of scientific evidence.
56, 108
PUBLIC COMMENTS:
EPA underestimates occupational risk leading to "no unreasonable risk"
findings or understatements of the extent and magnitude of
unreasonable risks. Occupational risks were underestimated by:
EPA's assumption that PPE will be used in most scenarios to avoid
finding risk estimates represent unreasonable risk or to understate
For the purpose of this Risk Evaluation, EPA
makes assumptions about potential PPE use
based on reasonably available information and
expert judgment. EPA considers each condition
of use and constructs exposure scenarios with and
Page 347 of 408
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the extent.
EPA finding cancer risk unreasonable only if it exceeds a level of 1
in 10,000, which is as much as 100 times higher a risk than warrants
regulation under TSCA.
For ONUs, EPA fails to identify unreasonable risks for the most highly
exposed/most vulnerable based on risk determinations that relied
exclusively on central tendency estimates of exposure.
Page 348 of 408
without engineering controls and /or PPE that
may be applicable to particular worker tasks on a
case-specific basis for a given chemical. Again,
while EPA has evaluated worker risk with and
without PPE, as a matter of policy, EPA does not
believe it should assume that workers are
unprotected by PPE where such PPE might be
necessary to meet federal regulations, unless it
has evidence that workers are unprotected. For
the purposes of determining whether or not a
condition of use presents unreasonable risks, EPA
incorporates assumptions regarding PPE use
based on information and judgment underlying
the exposure scenarios. These assumptions are
described in the unreasonable risk determination
for each condition of use, in section 5.2.
Additionally, in consideration of the uncertainties
and variabilities in PPE usage, including the
duration of PPE usage, EPA uses the high-end
exposure value when making its unreasonable
risk determination in order to address those
uncertainties.
EPA, consistent with 2017 NIOSH guidance,
used lxlO"4 as the benchmark for the purposes of
this unreasonable risk determination for
individuals in industrial and commercial work
environments, including workers and ONUs.
EPA has consistently applied a cancer risk
benchmark of lxlO"4 for assessment of
occupational scenarios under TSCA. lxlO"4 is
not a bright line and EPA has discretion to make
unreasonable risk determinations based on other
-------
benchmarks as appropriate. See Section 5.1.1.2
of the risk evaluation for additional information.
Where EPA had monitoring or modeled data
specific to ONUs, unreasonable risk
determinations where made based on high-end
exposures. For conditions of use where the data
did not distinguish between worker and ONU
inhalation exposures, there was uncertainty
regarding ONU exposure. ONU inhalation
exposures are assumed to be lower than
inhalation exposures for workers directly
handling the chemical substance. To account for
this uncertainty, EPA considered the workers'
central tendency risk estimates from inhalation
exposures when determining ONUs'
unreasonable risk (rather than the high-end
inhalation exposures), when data specific to
ONUs was not available.
98
PUBLIC COMMENTS:
Pursuant to TSCA Section 6(b), EPA must determine if TCE presents
an unreasonable risk under the COUs as a single determination (rather
than for each condition). EPA concluded that most COUs of TCE
present an unreasonable risk. However, EPA needs to make an overall
determination as to whether TCE presents an unreasonable risk. The
evidence that EPA has already reviewed in its draft risk evaluation
compels a finding of yes.
Per 40 CFR 702.47 ".. EPA will determine
whether the chemical substance presents an
unreasonable risk of injury to health or the
environment under each condition of use within
the scope of the risk evaluation...." This
approach in the implementing regulations for
TSCA risk evaluations, is consistent with
statutory text in TSCA section 6(b)(4)(A), which
instructs EPA to conduct risk evaluations to
determine whether a chemical substance presents
an unreasonable risk "under the condition of
use."
99
PUBLIC COMMENTS:
EPA's determinations that individual COU of TCE pose no
unreasonable risk violate TSCA. This "use-by-use" approach to risk
determinations is unlawful and threatens to prevent EPA from
eliminating the unreasonable risks posed by TCE. TSCA commands
that EPA determine whether "a chemical substance" (not particular uses
Page 349 of 408
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of a chemical substance) presents an unreasonable risk in a single,
comprehensive determination. This holistic risk determination must
reflect EPA's evaluation of all TCE's COUs considered in combination.
EPA must revise its risk evaluation for TCE to make a single risk
determination for the chemical substance. Based on EPA's findings that
some COUs present unreasonable risks to health, EPA must conclude
under TSCA section 6(b)(4)(A) that TCE presents an unreasonable risk
to human health.
102
PUBLIC COMMENTS:
Under the Lautenberg Chemical Safety Act, a 'use' receives federal
preemption only if it is included in the scope of the risk evaluation and
if EPA makes a definitive determination as to risk. For this reason, it is
critical that EPA clearly make determinations of unreasonable risk and
no unreasonable risk. EPA made no determination related to general
population risk (but rather relied on other statutes to manage exposure
to the general population). We request that EPA clarify how regulation
of "conditions of use" covered by other EPA statutes is considered
adequate to meet the Lautenberg Chemical Safety Act finding of "no
unreasonable risk" and preclude state preemption of EPA's findings.
Similarly, we request that EPA articulate the legal argument as to how
other COUs that EPA has determined are adequately regulated by other
federal agencies cannot be preempted by states.
As explained in more detail in Section 1.4.2 of
the Risk Evaluation, EPA believes it is both
reasonable and prudent to tailor TSCA Risk
Evaluations when other EPA offices have
expertise and experience to address specific
environmental media, rather than attempt to
evaluate and regulate potential exposures and
risks from those media under TSCA. EPA
believes that coordinated action on exposure
pathways and risks addressed by other EPA-
administered statutes and regulatory programs is
consistent with statutory text and legislative
history, particularly as they pertain to TSCA's
function as a "gap-filling" statute, and also
furthers EPA aims to efficiently use Agency
resources, avoid duplicating efforts taken
pursuant to other Agency programs, and meet the
statutory deadline for completing Risk
Evaluations. EPA has therefore tailored the scope
of the Risk Evaluation for TCE using authorities
in TSCA Sections 6(b) and 9(b)(1).
Under TSCA section 18(a)(1)(B) and (c)(3),
federal preemption over certain State actions
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applies to chemical substances for which a
determination of 'no unreasonable risk' has been
made pursuant to TSCA section 6(i)(l) or for
which a final risk management rule is
promulgated pursuant to TSCA section 6(a) and
does not extend to those hazards, exposures,
risks, and uses or conditions of use not included
in that final determination or rule. Pursuant to
TSCA section 18(c)(3), if uses or exposure
pathways are not "included in any final action the
Administrator takes pursuant to section [6(a) or
6(i)(l)]," (e.g., because EPA determines the use
or exposure pathway to be outside of the scope of
the risk evaluation (such as uses or exposure
pathways regulated by EPA or other Federal
agencies under other federal laws)), then TSCA
permanent preemption does not apply. As the
commenter notes, EPA clearly stated in the risk
evaluation for TCE that it did not evaluate
exposures to the general population, and as such
the unreasonable risk determinations for relevant
conditions of use do not account for exposures to
the general population. Thus, exposures to the
general population are not included in any final
determinations of 'no unreasonable risk' for TCE
and TSCA preemption based on those 'no
unreasonable risk' determinations does not apply
to those exposures.
102
PUBLIC COMMENTS:
The International Material Data System (IMDS) is used by many in the
automotive sector as a first screen to identify potential uses of chemical
substances. The IMDS has been adopted as the global standard for
reporting material content throughout the automotive supply chain and
The request by the commenter is outside the
scope of EPA's risk evaluation. This may be
addressed during the risk management phase only
for those conditions of use that present
Page 351 of 408
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for identifying which COCs to human health and the environment are
present in finished materials and components. The threshold for
reporting in this system is 0.1% by weight, a threshold that has been
almost universally adopted by international regulatory bodies and many
states within the United States. The presence of any chemical below this
threshold is not required to be reported in IMDS based on a low
underlying expected risk of exposure from de minimis quantities. We
request that EPA identify a de minimis level for TCE and other TSCA
chemicals below which EPA has no reasonable basis to conclude that
there is an unreasonable risk.
unreasonable risk.
106
PUBLIC COMMENTS:
EPA finds that TCE presents risks of concern for many COUs across
workers, ONUs, consumers, and bystanders. However, we assert that
critical scientific flaws in EPA's risk assessment approach led to
underestimation of risk; the actual risks are of greater magnitude than
that stated by EPA and additional COUs present unreasonable risks.
EPA has made determinations of unreasonable
risk based on the best available science while
considering high-end exposure estimates and
sensitive and robust health endpoints.
108
PUBLIC COMMENTS:
Deficiencies in the draft risk evaluation (including exclusion of known
uses and exposures, insufficient consideration of susceptible
populations, underestimation of occupational risks, dismissal of risk by
invoking uncertainty, failure to adequately evaluate environmental risks
of TCE release and exposure, and use of a flawed systematic review
process) compromise risk determinations for individual COUs presented
in Table 5-1 and Section 5.3 of the draft risk evaluation.
These factors lead to a systematic underestimation of risks from
individual COUs, including risks to human health (specifically
vulnerable populations) and the environment.
Flaws in the draft risk evaluation mean that EPA has clearly not
provided support for any assertion that TCE, across all its COUs,
does not present unreasonable risk.
EPA's determinations that many COUs do present unreasonable risk
supports the conclusion that the chemical as a whole presents
unreasonable risk.
EPA makes determinations of unreasonable risk
on a COU-basis, not for the chemical as a whole.
EPA has performed a thorough risk evaluation
covering all associated COUs based on the best
available science including the results of
systematic review. Unreasonable risk was found
for all but two out of 54 COUs.
Per 40 CFR 702.47 ".. EPA will determine
whether the chemical substance presents an
unreasonable risk of injury to health or the
environment under each condition of use within
the scope of the risk evaluation..This
approach outlined in the implementing
regulations for TSCA risk evaluations is
consistent with the statutory text in TSCA section
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108
PUBLIC COMMENTS:
In violation of TSCA, EPA failed to consider if TCE "as a whole" (i.e.,
all hazards, exposures, and COUs) presents an unreasonable risk. EPA
should change the final risk evaluation to assess the reasonably
available information on all hazards and exposures for TCE, and that
information should inform EPA's evaluation of the risks of this
chemical.
6(b)(4)(A), which instructs EPA to conduct risk
evaluations to determine whether a chemical
substance presents an unreasonable risk "under
the conditions of use."
108
PUBLIC COMMENTS:
The plain text, overall structure, purpose, and legislative history of
TSCA indicate that EPA must determine whether a chemical substance
presents an unreasonable risk comprehensively (i.e., for the chemical as
a whole). EPA is required under TSCA to consider all reasonably
available information regarding hazards, exposures, and COUs, without
limitation and without the discretion to ignore any of this information.
Moreover, TSCA requires that EPA evaluate a chemical's risk without
consideration of costs or other non-risk factors; by excluding certain
hazards, exposures, or COUs, EPA is considering non-risk factors. The
requirement to consider chemical substances as a whole expressly
requires EPA to address risks when risks arise from combined sources
of exposure. EPA must analyze all exposures and assess whether any
combination presents an unreasonable risk. In addition, if the risk
evaluation fails to address all hazards and exposures, it undermines the
purpose of TSCA and the requirement that EPA rely on the best
available science. Finally, the legislative history of TSCA requires EPA
to integrate exposure and hazard information to assess risk.
Selection of key endpoints for risk conclusions/determination
SACC
SACC COMMENTS:
Recommendation: Revise and expand the justification for not using fetal
cardiac malformations as the unreasonable risk driver.
Exposure to TCE during pregnancy linked to heart defects is
controversial, and the discussion in the draft risk evaluation does not
resolve the topic. The Committee agreed that heart malformations
could be used for hazard identification but was divided on the use of
EPA has expanded the justification for selection
of the immune studies as the best overall
endpoints. While congenital heart defects may be
of concern to particular susceptible
subpopulations, the inconsistency of the data
suggests that it is not the best overall endpoint for
Page 353 of 408
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this endpoint for risk characterization. The risk evaluation needs to
better discuss the rationale for excluding fetal heart malformations
given that the 2011 IRIS evaluation computed a POD for this
endpoint.
The Committee also noticed a disconnect between the extensive
discussion of fetal heart malformation data and the controversy
surrounding these findings. The draft risk evaluation presents a
dose-response analysis of the data but ultimately dismisses it in
favor of the immunosuppression POD. Some Committee members
felt that the risk evaluation should better explain why fetal cardiac
malformation data are not used as the unreasonable risk driver. It
appeared to some Committee members that basing unreasonable
risks on immunosuppression rather than fetal heart malformations is
an acceptance of less protective concentration levels.
TCE toxicity overall. EPA acknowledges that
while there is qualitative support for the endpoint,
based on uncertainties in the dose-response for
this endpoint and other considerations EPA has
selected immune endpoints as the best overall
endpoints for risk conclusions (Sections 3.2.5.4.1,
3.2.6.1.1). Additionally, EPA has expanded
discussion of the history of Johnson et al, 2003
and the cardiac defects endpoint in Appendix F. 1.
EPA has moved a significant portion of the
detailed discussion on cardiac malformations to
Appendix F in order to avoid too heavily
focusing on an endpoint other than the best
overall ones in the main body.
EPA routinely conducts Inter-Agency review of
its TSCA Risk Evaluation before SACC peer
review and public comments. Federal experts in
toxicology, epidemiology, and industrial hygiene
among other disciplines help EPA develop more
comprehensive and rigorous risk evaluations. In
this particular Inter-Agency review EPA
discussed, among other things, the strengths and
weaknesses associated with use of the cardiac
defects endpoint as the basis of the risk
conclusions. Based on these discussions, EPA
concluded that whereas evidence indicates that
CHDs may be of concern for susceptible
subpopulations, the inconsistency of the data and
reduced confidence in dose response results
suggest that it is not the best indicator of TCE
toxicity overall. For purposes of risk evaluations
under TSCA, EPA chose to use immune
SACC
SACC COMMENTS:
Recommendation: Improve the justification for immunosuppression
over congenital heart defects as the unreasonable risk driver for acute
non-cancer risks.
Outside parties claimed that an early version of the draft risk
evaluation identified fetal cardiac effects as the most sensitive
endpoint/risk driver (consistent with prior TCE reviews) but that
non-scientific pressures caused EPA to shift to immune findings.
Both endpoints are discussed in the hazard section. Although some
justification is provided for the selection of immunosuppression as
the risk driver, the rationale for this decision (different than that
used in the 2011 IRIS evaluation) should be further discussed.
Greater transparency is warranted in the rationale for selection of
the "best" representative sensitive responses. Some Committee
members would like an explanation as to whether the decision to use
immunosuppression over congenital heart defects was based on
uncertainty. There is a disconnect between the decision to exclude
congenital heart defect data and the amount of text given to support
the decision to use these data in earlier sections.
Page 354 of 408
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The draft risk evaluation presents human health risk conclusions
based on key studies in Tables 4-55 and 4-56, including derivations
based on the Johnson data. Some Committee members suggest not
including heart defect risk values in these tables to allow focus on
the immunosuppression risk.
endpoints as the indicator of TCE toxicity based
on their consistency, reduced uncertainty, and
robustness of the data.
SACC
SACC COMMENTS:
Some Committee members called for this draft risk evaluation to
consider and discuss differences between health effect values derived
from this risk evaluation with those derived and/or used by other EPA
regulatory programs, federal regulatory agencies, and non-federal
entities. The discussion could provide support for the new TSCA health
effect levels or for more protective levels currently established under
other programs. EPA should consider adding information about the key
drivers in the setting of other exposure guidelines to provide context and
improve understanding of the various occupational/consumer/public
exposure mandates and guidelines.
EPA indicates throughout Section 3.2 where the
Risk Evaluation differs and agrees with previous
assessments by EPA and other organizations.
Notably, the updated TSCA statute has different
requirements and considerations than the old law
or other EPA statutes, and therefore "protective
levels" should not be directly compared across
assessments.
SACC
SACC COMMENTS:
One Committee member suggested that approaching the setting of
health effect levels more in the manner of a meta-analysis might provide
a more robust approach than basing the value on a single study and a
most sensitive endpoint. This approach might provide a firmer
foundation on which to base future risk management decisions.
TSCA considers both best available science and
protection of PESS groups in selecting PODs to
use for risk estimation. Based on these
considerations, EPA utilizes PODs representing
the most sensitive endpoints from among the
most robust and well-supported studies.
SACC
SACC COMMENTS:
The draft risk evaluation identifies many COUs that pose unreasonable
risk. These conclusions follow estimated risks exceeding the MOE for
particularly sensitive endpoints that some Committee members consider
outliers, and which are the focus of controversy. Consequently, the
derived occupational exposure levels are orders of magnitude below
those currently used to protect workers by industrial hygienists (e.g.,
ACGIH Threshold Limit Values [TLVs], time weighted averages;
NIOSH RELs, and OSHA PELs).
EPA agrees that many of these occupational
exposure thresholds (e.g., TLVs, OSHA PELs)
are above exposure levels that would be
protective of risks identified in this Risk
Evaluation.
36
PUBLIC COMMENTS:
Page 355 of 408
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The draft risk evaluation changes the method of the assessment, from
levels that will cause abnormalities in fetal cardiac tissue to the levels of
TCE found to trigger no immunosuppression. Given that the study used
in the current draft risk evaluation uses an exposure level 500 times
higher than the exposure found to trigger heart defect in the Johnson et
al. (2003) study, this information needs careful consideration. It may
potentially impact on the future children of the United States.
EPA has expanded the justification for selection
of the immune studies as the best overall
endpoints. EPA believes these endpoints
represent the "best available science" based on
the weight of scientific evidence in accordance
with TSCA and the use of these endpoints for risk
conclusions was supported by SACC peer
reviewers
(httDs://www.reeulations.eov/document?D=
37
PUBLIC COMMENTS:
Extensive revisions were made to EPA's draft risk evaluation of TCE
during the interagency review process. The draft provided for
interagency review identified fetal cardiac malformations as the most
sensitive endpoint and used it to derive the PODs for making
determinations of risk. The draft released to the public and provided to
the SACC for peer review significantly downgrades this endpoint and
bases its risk determinations of acute and chronic risks on immune
endpoints. The implications are significant as evident from the orders-
of-magnitude differences in the MOEs calculated for fetal cardiac
effects versus the selected immune endpoints and given the differing
subpopulations at risk. It is essential that EPA make available the draft
of the risk evaluation prior to the revisions that was submitted for
interagency review. Additionally, EPA must provide a complete
explanation of the basis for the revisions. Absent this information, the
SACC's ability to peer-review the draft TCE risk evaluation will be
significantly impaired.
1 ) TSCA requires
EPA to select exposure and hazard values based
on the best available science, not simply the
lowest values.
EPA routinely conducts Inter-Agency review of
its TSCA Risk Evaluation before SACC peer
review and public comments. Federal experts in
toxicology, epidemiology, and industrial hygiene
among other disciplines help EPA develop more
comprehensive and rigorous risk evaluations. In
this particular Inter-Agency review EPA
discussed, among other things, the strengths and
weaknesses associated with use of the cardiac
defects endpoint as the basis of the risk
conclusions. Based on these discussions, EPA
concluded that whereas evidence indicates that
CHDs may be of concern for susceptible
subpopulations, the inconsistency of the data and
reduced confidence in dose response results
suggest that it is not the best indicator of TCE
toxicity overall. For purposes of risk evaluations
under TSCA, EPA chose to use immune
endpoints as the indicator of TCE toxicity based
47
PUBLIC COMMENTS:
As articulated in the draft risk evaluation, it appears that EPA is using a
new and unvetted policy to select the most "representative" (rather than
the most sensitive) endpoint, which is at odds with long-standing
agency-wide risk assessment practices. The Environmental Protection
Network (EPN) is deeply concerned about this new policy, which
provides EPA with the discretion to ignore the most sensitive endpoint.
On p. 257, EPA documents how this policy was used to select a less
sensitive endpoint than congenital heart defects as the basis for acute
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and chronic non-cancer PODs. A few factors of this policy were used to
justify the selection of immune endpoints for acute and chronic effects,
but congenital heart defects were not evaluated based on the same
factors. It is critically important that EPA not replace the protective
health policy of selecting the most sensitive endpoint with this
"representative policy." There is no scientific justification for this new
policy, which could have a wide range of effects, undermining the
reference doses and cancer potency factors developed for all chemicals.
on their consistency, reduced uncertainty, and
robustness of the data. EPA has created a new
subsection identifying and justifying the two
immune endpoints as best overall of risk
conclusions (Section 3.2.5.4.1). EPA's
conclusions are based on the best available
science and weight of scientific evidence. EPA
used the best overall endpoints as the basis of risk
conclusions (Section 4.5) and unreasonable risk
determinations (Section 5.2).
The draft risk evaluation underwent numerous
rounds of revisions both from internal and
external reviewers throughout the development of
the published draft. The development of the draft
risk evaluation is an ongoing deliberative process
and EPA is not obligated to provide descriptions
of predecisional and deliberative discussions or
consultations with other federal agencies. In the
interest of continuing to have open and candid
discussions with our interagency partners, and as
a matter of policy, EPA does not publicly release
internal deliberative drafts or intend to include
the content of those discussions in the risk
evaluation.
It is unclear whether the totality of the scientific
database examining immune-related endpoints is
larger or smaller than the database for cardiac
effects, however the database for immune-related
endpoints is certainly more consistent.
Indications of both immunosuppression and
autoimmunity were consistently observed in
47, 73,
74, 108
PUBLIC COMMENTS:
The initial draft risk evaluation relied on fetal heart defects as the most
sensitive endpoint. Outside parties allegedly forced EPA career staff to
make fundamental changes to the draft risk evaluation before it was
released to the public and presented to SACC for peer review; namely, a
change in the key health endpoint for risk determinations from
congenital heart defects to immune endpoints. The notion of political
interference was initially uncovered by Elizabeth Shogren of the Center
for Investigative Reporting and was also noted by a member of the peer
review panel at the TCE SACC meeting. This sorry episode heavily
taints the scientific integrity and credibility of EPA's draft risk
evaluation. The decision not to rely on congenital heart defects for
EPA's determinations of TCE's acute and chronic risks deviates from
scientific best practices, defies requirements under the law, and is not
sufficiently protective of public health, particularly the health of
especially vulnerable subpopulations.
49, 99
PUBLIC COMMENTS:
In the past (including EPA's 2011 IRIS and 2014 Workplan
assessments), EPA consistently concluded that the weight of scientific
evidence supports the link between TCE and fetal heart malformations,
and as the most sensitive endpoint, should be used to drive risk
determinations for acute and chronic exposures. This formed the basis
of the proposal in 2016/2017 to ban vapor and aerosol degreasing and
spot removal uses of TCE under TSCA. The original draft risk
evaluation (December 2019) used the study by Johnson et al. (2003) for
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49, 99
determination of MOEs for TCE workers and consumers; however,
investigative reporting (by Elizabeth Shogren) indicates that outside
parties allegedly directed EPA not to use this endpoint (based on
uncertainty and decreased confidence in the endpoint) but rather use
immune-related endpoints. The revised draft suggests that exclusion of
heart defects is inconsequential from a health perspective because
unreasonable risk determinations remain the same for most COUs. This
is misleading because immune effects occur at significantly higher dose
levels than heart malformations. For example, the acute HEC99 based
on immune effects is 470 times higher than that for heart
malformations, resulting in MOEs that are two orders of magnitude
higher than for heart defects. Therefore, exposure limits based on
immune effects expose women to TCE levels that would leave their
offspring at risk for heart malformations. There is no scientific
justification for this decision.
EPA repeatedly finds that the WOE demonstrates that TCE causes
heart malformations, and data are sufficient for dose-response
analysis and subsequent risk determinations.
The only change since the earlier assessments is a study by the
HSIA, which indicated that TCE does not cause heart
malformations. However, the risk draft evaluation notes that
methods were less sensitive, a full range cardiac effects were not
examined, and a dose-related increase on heart malformations was
observed.
The selection of immune effects as a representative endpoint should
drive risk determinations at the exclusion of other more sensitive
endpoints. The choice of this endpoint over heart defects based on
confidence violates long-standing public health policy to protect
against the most sensitive health endpoints.
The implication that data supporting immune effects are more 'certain'
than evidence for heart defects is an invention of outside parties with no
support elsewhere in the draft risk evaluation.
PUBLIC COMMENTS:
epidemiological and animal studies, in both
adults and developmental contexts, and in both
normal and autoimmune-prone rodents (Sections
3.2.3.1.4 and 3.2.3.1.6. In contrast, cardiac effects
are supported mechanistically however
epidemiological support is strong only for select
subpopulations and the animal database (which
would be most suitable for dose-response)
provides overall ambiguous conclusions
(Appendix F.3).
From the EPA Guidelines for Developmental
Toxicity Risk Assessment: "the hazard
identification/ dose-response evaluation and the
exposure assessment for given populations are
combined to estimate some measure of the risk
for developmental toxicity. As part of risk
characterization, a summary of the strengths and
weaknesses in each component of the risk
assessment is discussed along with major
assumptions, scientific judgments, and, to the
extent possible, qualitative and quantitative
estimates of the uncertainties. The Guidance does
describe using the most sensitive effect for
deriving the RfD, however TSCA does not use
RfDs for risk characterization. EPA under TSCA
uses an MOE approach instead of a hazard
index/reference concentration approach because
benchmarks for cancer and non-cancer risk
estimates are not bright lines, and EPA has
discretion to make unreasonable risk
determinations based on other risk benchmarks or
factors as appropriate. The RfC defines an
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The revised risk evaluation indicated that while congenital heart defects
were identified as the most sensitive endpoint, there were uncertainties
that decreased confidence on this endpoint.
These uncertainties and the rationale for decreased confidence in the
endpoint were not further discussed.
Based on EPA's "weight of the scientific evidence" for this
endpoint, EPA indicated that TCE-related cardiac effects in animals
was 'independently verified' in epidemiology and mechanistic
studies, the database was reliable, and that it provided positive
evidence that TCE may cause heart defects in humans.
Based on EPA's evaluation of the "best available science," the key
study used for dose-response analysis (Johnson et al., 2003) was
scored medium, and therefore acceptable for inclusion in the risk
evaluation.
EPA reached the same conclusions on the validity of the heart
defects endpoint in 4 separate assessments that have been reviewed
by the SAB and NAS.
This draft disavows a decade of scientific work based on 'uncertainty;'
this is the opposite of the "best available science" EPA is obligated to
use under TSCA. To achieve this, outside parties allegedly directed
EPA to apply the novel approach of selecting a "representative
endpoint" to determine unreasonable risk; ignoring more sensitive
endpoints that present greater risk. This approach is without precedent,
is not health-protective, and would be contrary to EPA's obligation to
determine whether TCE presents an unreasonable risk to a potentially
exposed or susceptible subpopulation.
exposure that is "likely to be without an
appreciable risk of deleterious effects during a
lifetime." In contrast, TSCA uses unreasonable
risk determinations that incorporate many
considerations and the risk evaluation does not
set a goal of determining an all-encompassing
"safe" exposure level. EPA does consider risks to
infants and children and presents risk estimates
for multiple developmental endpoints, however
the basis for unreasonable risk determinations are
different than the basis for establishing an
RfD/RfC. As explained in the preamble to the
Risk Evaluation Rule, "to make a risk
determination, EPA may weigh a variety of
factors in determining unreasonable risk. The
Administrator will consider relevant factors
including, but not limited to: The effects of the
chemical substance on health and human
exposure to such substance under the conditions
of use (including cancer and non-cancer risks);
the effects of the chemical substance on the
environment and environmental exposure under
the conditions of use; the population exposed
(including any susceptible populations), the
severity of hazard (the nature of the hazard, the
irreversibility of hazard), and uncertainties." 82
FR at 33735.
56, 108
PUBLIC COMMENTS:
EPA based its determinations of acute and chronic unreasonable risk on
immune-related endpoints rather than fetal cardiac defects. This
decision is counter to the preponderance of scientific evidence that TCE
induces fetal cardiac malformations and reflects an agency choice at
odds with scientific policy and practice, statutory requirements to
protect potentially exposed and susceptible subpopulations, and the
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mission of protecting human health.
56, 108
PUBLIC COMMENTS:
EPA's rationale for making risk determinations based on immune-
related endpoints raises significant concerns. The decision to use
"mortality due to immunosuppression" as the selected acute noncancer
endpoint (Selgrade and Gilmour, 2010) and "autoimmunity" as the
chronic non-cancer endpoint (Keil et al., 2009) was based on its rating
of these studies as "High" quality per the TSCA systematic review
method, whereas EPA rated the Johnson (2003) study, used in previous
EPA assessments to derive a point of departure, as "Medium." This
scientifically unsupported and contradictory decision results in EPA
relying its risk determinations on risk estimates across various TCE
exposure scenarios that are orders of magnitude more lenient than those
risks estimates associated with the most sensitive endpoint, fetal cardiac
malformations.
56, 108
PUBLIC COMMENTS:
Although EPA recognizes that developmental studies are relevant for
evaluating acute exposure scenarios, EPA chose to rely its MOE values
based on immunosuppression. This decision is flawed and contradicts
long-standing policy and previous EPA assessments of TCE that require
basing risk assessment and protection on the most sensitive endpoint.
Previous assessments (EPA 2014 TCE work plan assessment and TSCA
section 6 proposed rules for the use of TCE in vapor degreasing, and in
spot cleaning and dry cleaning facilities) relied on developmental
endpoints for assessing the health risks of TCE from acute exposure.
56, 108
PUBLIC COMMENTS:
EPA's decision not to take a health-protective approach to assessing
acute TCE risks is at odds with TSCA's requirement to protect
potentially exposed or susceptible populations, which explicitly
includes pregnant women and children.
TSCA's requirement that EPA assess risks to susceptible
populations demands that EPA base its risk determinations on the
endpoint (congenital heart defects) that specifically impacts
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pregnant women, infants, and children.
EPA acknowledges that congenital heart defects were the most
sensitive endpoint, and this endpoint is relevant to potentially
exposed or susceptible populations of pregnant women, infants, and
children, and instead relies on a far less sensitive endpoint not
relevant to those subpopulations for its risk determinations.
This decision results in EPA making risk determinations based on a
more lenient benchmark and failing to carry out its mandate under
TSCA 6(b)(4)(A). EPA cannot adequately protect against risks specific
to pregnant women (and their developing fetuses), infants, or children
by selecting immune effects as the basis for its determinations. EPA
must develop risk determinations that address the endpoint (congenital
health defects) that specifically impacts this subpopulation.
56, 108
PUBLIC COMMENTS:
EPA's decision to make risk determinations based on immune-related
endpoints represents a break with decades of agency scientific policy
and practice designed to protect human health. EPA's determinations of
unreasonable risks based on immune endpoints results in a significantly
higher POD (e.g., based on Selgrade and Gilmour, 2010), indicating that
the selected endpoint is orders of magnitude less sensitive than the
congenital heart defects endpoint. With this decision, EPA has chosen
not to protect against the most sensitive endpoint, for which there is
strong scientific support. The overall database for immune-related
endpoints is far more limited than the congenital heart defects endpoint,
and this endpoint is less sensitive and not subjected to the same WOE
analysis to which the congenital heart defects data were subjected.
56, 74,
108
PUBLIC COMMENTS:
In defiance of public health protection and statutory requirements under
TSCA to protect PESS, EPA chose immune effects as its basis for risk
determinations rather than fetal cardiac malformations. EPA indicated
that the choice was based on the highest quality information for which
EPA has the greatest confidence. EPA's decision to ignore strong
scientific evidence that TCE induces fetal cardiac malformations at
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levels of exposure lower than immune-related effects is scientifically
unsupported and contrary to EPA's mission to protect health and to
protect a critical susceptible subpopulation (pregnant women and the
developing fetus). EPA's choice also contradicts previous assessments
of TCE and existing EPA guidance to protect sensitive subpopulations
and to protect against the most sensitive endpoint, including:
EPA's Guidelines for Developmental Toxicity Risk Assessment,
which indicates that risk characterizations should be based on the
most sensitive indicator of toxicity.
EPA Risk Assessment Task Force's Staff Paper on Risk Assessment
Principles and Practices, which indicates that cancer and non-cancer
risks should be based on the most sensitive animal data.
EPA's A Review of the Reference Dose and Reference
Concentration Processes, which indicates that the critical effect is
defined as the first adverse effect that occurs to the most sensitive
species as the dose rate of an agent increases.
EPA's policy on evaluating risks to children, which indicates that it
is EPA policy to consider risks to infants and children.
Documents by NAS (Science and Decisions: Advancing Risk
Assessment; and Science and Judgment) also reiterate the need to
protect the most sensitive subpopulations and to protect against the most
sensitive endpoint. EPA's proposed risk determinations fail on both
accounts. EPA asserts without evidence that "it is expected that
addressing risks for these [immune system] effects would address other
identified risks." EPA should be ashamed of itself.
56, 108
PUBLIC COMMENTS:
The TSCA requirement that EPA assess risks using the best available
sciences necessitates that EPA base its risk determinations on congenital
heart defects.
EPA scored studies of heart defects (Johnson et al., 2003 and
Dawson et al., 1993) as "Medium" and has relied on Medium
studies in its draft risk evaluations.
EPA indicated that congenital heart defects are the most sensitive
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endpoint and did not identify contrary studies that were stronger or
more reliable than the Johnson et al. (2003) study.
EPA's decision to ignore this endpoint in its final analysis based on
the "best available science" is non-scientific and illogical; this
decision was based on greater confidence in other endpoints
(evidence that has no bearing on congenital heart defects).
The best available science supports the use of the Johnson et al. (2003)
study. EPA's approach of selecting the endpoint with the greatest
confidence does not address other identified risks; it leaves risks from
congenital heart defects insufficiently addressed, as indicated by the
lower levels of exposure to TCE that cause those defects relative to
exposure required to cause immune effects.
56, 108
PUBLIC COMMENTS:
EPA's decision to dismiss key immunotoxicity endpoints (decreased
thymus weight and cellularity from Keil et al., 2009) and its decision to
dismiss the Johnson et al. (2003) study as a representative chronic non-
cancer study and using an alternative endpoint of autoimmunity from
Keil et al. (2009) results in an approximately 9-fold underestimation of
risk compared to what would have been calculated from the Johnson et
al. (2003) study.
69, 74
PUBLIC COMMENTS:
The choice of immunosuppression (a 500-fold less sensitive endpoint)
rather than fetal heart defects to assess risk fails to protect the most
sensitive subpopulations, contradicts previous EPA assessments of
TCE, existing EPA guidance, and expert advice of NAS, and promotes
the false claim that risks for immune effects would address other
identified risks.
71,73,
74
PUBLIC COMMENTS:
The decision not to base risk determinations on fetal cardiac
malformations is problematic because:
It is a departure from thoroughly peer-reviewed science, based on
evidence of fetal cardiac malformations from the Johnson et al.
(2003) and other epidemiological, in vivo, and in vitro studies. EPA
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and other scientific authorities (including the EPA SAB) have
examined and affirmed the importance of fetal cardiac
malformations.
It fails to protect sensitive populations because fetal cardiac
malformations are directly relevant to the PESS of pregnant women,
infants, and children.
It represents a deviation from EPA policies based on previous
assessments of TCE and existing EPA guidance to use the most
sensitive endpoint and protect the most sensitive group. EPA and
NAS documents indicate that if EPA protects against the most
sensitive endpoint, it will protect against other effects.
A recommendation by SACC to support the decision to use immune
endpoints rather than fetal cardiac endpoints for risk determinations on
TCE is counter to the WOE and years of peer review, ignores TSCA's
mandate to protect sensitive subpopulations, and disregards EPA
policies on the selection of the most sensitive endpoints for modeling.
The public health consequences of this choice will be substantial,
allowing EPA to develop regulations 500-fold less protective for acute
risks and 10-fold less protective of chronic risks.
83
PUBLIC COMMENTS:
Regulate to prevent TCE exposure now, refuting the Johnson (2003)
study later, if possible. The two agencies that attempt to refute the
findings of the Johnson study are associated with the chemical industry
and could profit by being able to sell more TCE. Available data indicate
that fetal cardiac defects occur at doses 500 times lower than the
immune diseases that EPA is using for the maximum allowable
exposure; therefore, stricter regulations must be maintained. The use of
a 500 times higher maximum allowable exposure is putting corporate
profit above human health. Regulation of EPA by the chemical industry
(rather than the reverse) is not a new phenomenon, but it is strikingly
more blatant.
86
PUBLIC COMMENTS:
We are gravely concerned with EPA's failure to identify fetal heart
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defects as the key risk of exposure to TCE, which will mean that when a
woman's exposure to TCE during pregnancy is high enough to increase
the risk of fetal heart defects, the chemical will not be regulated at a
level to protect against that outcome. We demand that EPA address the
major flaws it its draft risk evaluation to ensure that any future
regulation of TCE protects the health of communities, including our
most vulnerable, across the country.
100
PUBLIC COMMENTS:
In a departure from prior EPA risk assessments, EPA fails to base its
calculations of TCE's risk on that most sensitive endpoint. As a result,
any regulation of TCE under TSCA will not adequately protect against
fetal cardiac malformations or neurodevelopmental impairment.
106
PUBLIC COMMENTS:
EPA's rationale for changing the representative acute non-cancer
endpoint is unclear and inconsistent in the draft risk evaluation. EPA's
choice of a representative acute non-cancer endpoint is less sensitive,
less protective of vulnerable populations, and not consistent with best
practices in scientific evaluation and use.
106
PUBLIC COMMENTS:
By pursuing the representative endpoint of immunosuppression, EPA
would be allowing acute exposures significantly greater than the POD
for fetal cardiac defects. While EPA still concluded that TCE presented
an unreasonable risk for many COUs, the use of a more sensitive
endpoint would have resulted in more protective unreasonable risk
determinations for workers, ONUs, consumers, and bystanders.
Choosing an immune endpoint would also fail to account for the
sensitivity represented by developmental endpoints, as "... certain
developmental effects may result from a single exposure during a
critical window of development." It is a health-protective assumption
that repeated exposure is not required for the manifestation of
developmental toxicity. Choosing the immune endpoint in comparison
to the fetal cardiac defects means discarding a more sensitive endpoint
that has evidence of hazard to human health and which accounts for
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potentially exposure to susceptible subpopulations (fetuses, pregnant
women, infants, and children). Considering the disparities between
PODs for the two endpoints and the potential health ramifications due
to this inadequately representative non cancer endpoint for TCE, EPA
should use fetal cardiac defects as the basis of the non-cancer acute
health effects and the subsequent risk assessment. EPA needs to give
deference to the nature of this endpoint, and the sensitive nature as it
impacts a vulnerable developmental period. This is particularly relevant
as EPA's has a mandate under TSCA to ensure the protection of
vulnerable populations such as these from unreasonable risks.
108
PUBLIC COMMENTS:
EPA justifies its selection of immunosuppression based on the highest
quality evidence, the "best available science," independent
verification, and weight of the scientific evidence.
EPA strayed from the requirements of Section 26 TSCA by basing
selection on the quality of the Selgrade and Gilmour (2010) study.
There was an extensive consideration of the WOE supporting the
congenital heart defects endpoint (and scrutiny of the Johnson et al.,
2003 study), but the immunosuppression endpoint and other studies
were not similarly scrutinized.
With respect to the independent verification requirement of TSCA,
there is as much evidence for congenital heart defects as there is for
immune effects. On p. 220, the draft risk evaluation concedes that
there are no other data on respiratory immunosuppression and
provides no supporting data for immunosuppression. For congenital
heart defects, EPA notes that a HSIA-funded study showed a partial
replication of results consistent with heart defects. These data and
supporting epidemiological and mechanistic data make a strong case
for congenital heart defects as a real, sensitive endpoint, protection
against which is likely to be protective of other TCE-induced
endpoints.
108
PUBLIC COMMENTS:
The use of these immune endpoints for POD derivation and subsequent
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risk determination would not protect against a constellation of more
sensitive health effects that have been demonstrated in the literature to
occur close to the range of the POD for congenital heart defects derived
from the Johnson et al. (2003) study. Existing evidence and EPA
precedent indicate that using the Johnson et al. (2003) study for POD
derivation is well-justified and would protect against these numerous
additional effects.
As noted in the IRIS 2011 Toxicological Review of TCE, the POD
from the Johnson et al. (2003) study supported an RfD (of 0.0005
mg/kg-day, based on multiple effects) within 20% of candidate
RfDs for other critical effects, including developmental
immunotoxicity, decreased thymus weights, and kidney effects.
108
PUBLIC COMMENTS:
In the draft risk evaluation (p. 235), EPA presents six criteria for
evaluation of candidate health domains, studies, and PODs (data quality
evaluation score, species, exposure duration, dose range, cumulative
uncertainty factor, and relevance to the endpoint of interest and human
exposure scenarios).
EPA does not justify its endpoint/POD selection (especially given
the difference in sensitivity between immunosuppression and
congenital heart defects endpoints) because it addresses only some
of these criteria {i.e., data quality) for immunosuppression but does
not provide a comparable evaluation for other health domains,
studies, or PODs.
EPA would be best served by considering both the WOE supporting the
endpoint and its sensitivity. Immunosuppression and congenital heart
defects endpoints were of adequate quality for dose-response modeling;
subsequently, endpoint sensitivity should be expected to drive POD
selection to best protect public health.
108
PUBLIC COMMENTS:
EDF strongly believes that the evidence for congenital heart defects is
both compelling and amendable to dose-response modeling. EDF also
believes that EPA must rely on this endpoint to ensure that it is in fact
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protecting the most vulnerable subpopulation from the risks of TCE
exposure.
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7. Overall Content and Organization
Overall Content and Organization
Charge Question 7.1: Please comment on the overall content, organization, and presentation of the TCE draft risk evaluation. Please
provide suggestions for improving the clarity of the information presented.
Charge Question 7.2: Please comment on the objectivity of the information used to support the risk characterization and the
sensitivity of the agency's conclusions to analytic decisions made.
#
Summary of Comments for Specific Issues Related to Charge
Question 6
EPA/OPPT Response
Clarity and completeness of report
SACC
SACC COMMENTS:
Not all committee members agreed that the report structure is the easiest
format to follow.
These organizational comments are appreciated
and will be considered in a revised template for
the next round of chemicals to be evaluated
under TSCA section 6.
SACC
SACC COMMENTS:
Recommendation: Implement the following revisions to improve clarity
of the draft risk evaluation:
Cite original sources instead of referring to documents in the docket
or to the EPA Web Application Access database where the public
may not have easy access.
On Table 2-3 where estimates for the number of facilities for each
OES are provided, the estimation of the number of facilities could
be enhanced by adding a sense of uncertainty +/- X percent or X
facilities.
The choice of a tornado graph in Figure 2-1 does not seem to be the
best one to promote clarity. It is suggested that a set of pie charts or
sectioned bar graph may better illustrate the point.
Section 2.2.5 mentions surface water concentration maps that are
not provided. The color coding is provided but the maps themselves
not provided nor is there a link or reference to their source.
Section 5.1.3 is simply not clear on the final environmental risk
determination. From Section 4.1, one can deduce that no
With respect to citing original sources and using
links in table to link to other tables, these
organizational comments are appreciated and
will be considered in a revised template for the
next round of chemicals to be assessed under
TSCA section 6.
EPA does not have reasonably available data to
conduct such an analysis for TCE. EPA's
analvsis uses TRI (U.S. EPA 2017s) and DMR
(U.S. EPA 2016a) to estimate the highest local
per site water releases of TCE.
The tornado graph noted by the commenter did
not communicate anything in addition to the text
and therefore has been removed.
Section 2.2.5 has been updated to include the
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unreasonable risk to aquatic organisms in surface water was
concluded. There are some risks with RQ >1 associated with
specific facilities and species, but there is no summary of either in
the final risk determination. It is recommended that the risk
evaluation summarize the approach and determination for each
cou.
Expand use of links in tables to other tables and include links to
items in the docket.
surface water maps, which were previously only
included in the environmental risk
characterization sections.
SACC
SACC COMMENTS:
Committee members commented that the SSD diagram (a scatterplot) is
a good visualization tool to display the potential relative impact of
chemical exposure on different species buts its utility depends on
understanding the ecology of the aquatic environment.
EPA agrees with this comment and added further
explanation around the SSD analysis in section 3
of the Risk Evaluation.
SACC
SACC COMMENTS:
Recommendation: Provide more clarity on how cancer risks were
estimated by showing computation details.
A Committee member noted the development of cancer risk is
difficult to ascertain. In this section (p. 250, lines 2463-2476), the
draft risk evaluation states that the IUR is "adjusted by a factor of 4 to
account for estimating risk from all three cancer types," yet later
suggests that lifetime cancer risks are first calculated and then
summed across all three types. Which is it?
From Section 3.2.5.3.3 of the Risk Evaluation,
for the IUR "extra lifetime cancer risks were
summed across the three cancer types and the
ratio of the sum of the extra risks to the extra risk
for kidney alone was derived." This ratio
rounded to 4 from two different calculation
methods. For the oral slope factor, "individual
IUR estimates were first obtained for each site
based on the ratios of extra risk relative to
kidney. Those site-specific IUR estimates were
then extrapolated to the equivalent OSFs using
site-specific dose metrics, and those individual
OSFs were summed to obtain a ratio of 5.0
relative to kidney cancer alone." Full details are
available in Section 5.2.2 of the 2011 IRIS
Assessment (U.S. EPA 201 le).
SACC
SACC COMMENTS:
The draft risk evaluation states that, in general, immunotoxic effects in
animals and humans were associated with an enhanced immune
EPA has clarified that the thymus findings are
not adverse and are not considered as a basis for
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response rather than an immunosuppressive effect (draft risk evaluation,
p. 212, lines 839-840). However, the first paragraph on animal data
(draft risk evaluation, p. 213, lines 872-880) suggests that support for
immunotoxicity is provided by decreased thymus weight and cellularity
in mice, although the cellularity effect is not significant (Keil et al.,
2009). The Committee recommended the risk evaluation not put
indicators of immune-enhancement and immunosuppression in the same
category and think more about MOA where these processes and
indicators are different.
the POD from Keil et al., 2009.
106
PUBLIC COMMENTS:
Not only is Chapter 3 (Hazards) in conflict with Chapter 5 (Risk
Determination), it is also in conflict with itself within Chapter 3 of the
draft risk evaluation for TCE.
EPA respectfully disagrees with this comment.
Section 5 uses language and hazard
determinations that are consistent with
conclusions from Section 3.
Insufficient time to review
44
PUBLIC COMMENTS:
Even before the COVID-19 crisis, the time frame EPA provided for
getting meaningful expert review of this important document was
already questionable. Now it is simply untenable. Proceeding with a
virtual meeting is asking far too much of SACC members and their
families and will clearly lead to a severely compromised peer review.
We cannot let the current crisis result in a weakening of the quality and
credibility of scientific input on other important public health issues.
EPA needs to promptly postpone the SACC peer review of TCE and
reschedule it at a time and in a manner that respects the critical role the
SACC plays.
Thank you for expressing your concern. Due to
the outbreak of the novel coronavirus,
SARS-CoV-2, the cause of COVID-19, the
agency implemented this change out of an
abundance of caution and in response to travel
restrictions imposed by some SACC members'
employers and other members' concerns
regarding travel, as communicated in the Federal
Register on March 20, 2020 (85 FR 16096)
(FRL-10006-79Y
51
PUBLIC COMMENTS:
The health effects information available for cardiac effects related to
TCE exposure raises fundamental scientific questions that require
careful deliberation and that can be informed by stakeholder input. We
hope that you will take the necessary time to receive input from the
ACC and others. EPA should resist pressure to expedite SACC's review
of the draft.
Thank you for your comment. EPA will consider
stakeholder inputs provided during the comment
period.
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52
PUBLIC COMMENTS:
Because of the limited time allowed for public comment, a critical
review of the search strategy described in the 2017 document relative to
that reported in the draft risk evaluation could not be conducted. Thus,
at this time, comments are limited to examples (emphasizing that this is
not a comprehensive list) of aspects that highlight the lack of
transparency and reproducibility.
Thank you for your comment. EPA provides a
60-dav public comment period on draft TSCA
risk evaluations.
52
PUBLIC COMMENTS:
Given the voluminous nature of the assessment, and the aggressive
timeline provided for peer review, it is impossible to fully evaluate this
aspect of the TCE draft risk evaluation (i.e., scoring criteria not
implemented as described in guidance) given that it would require a
fully independent review of each study quality evaluation.
Thank you for your comment. EPA provides a
60-dav Dublic comment Deriod on draft TSCA
risk evaluations.
82, 86
PUBLIC COMMENTS:
We request that EPA suspend the public comment period for the TCE
draft risk evaluation while President Trump's national emergency
declaration remains in effect and provide at least 60 days for comment
once the national emergency is lifted. There is no capacity to focus on
the draft TCE risk evaluation until the national emergency is over.
Thank you for your comment. EPA provided a
60-day public comment period on the draft TCE
risk evaluation and due to the outbreak of the
novel coronavirus, SARS-CoV-2, the cause of
COVID-19, the agency implemented a virtual
public meeting out of an abundance of caution
and in response to travel restrictions imposed by
some SACC members' employers and other
members' concerns regarding travel, as
communicated in the Federal Register on March
20. 2020 (85 FR 16096) (FRL-10006-79).
86, 87
PUBLIC COMMENTS:
EPA's refusal to hold a public meeting or to extend the comment period
is deeply concerning. We renew our request for a public meeting on
TCE and request that it be scheduled at a time and in a manner and
venue that accounts for disruptions caused by COVID-19 (fully
accessible virtual meeting may be an option). The SACC meeting is not
an appropriate venue for robust community participation.
Thank you for expressing your concern. Due to
the outbreak of the novel coronavirus,
SARS-CoV-2, the cause of COVID-19, the
agency implemented this change out of an
abundance of caution and in response to travel
restrictions imposed by some SACC members'
employers and other members' concerns
Page 372 of 408
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regarding travel, as communicated in the Federal
Register on March 20, 2020 (85 FR 16096)
(FRL-10006-79).
47
PUBLIC COMMENTS:
The 2-day lead time before a virtual prep meeting and the ~3 weeks
granted for public comments to reach the peer review committee before
it meets is inadequate. This reinforces the view that the current EPA
approach values a calendar deadline for a decision over the integrity of
the information going into the decision. Furthermore, the process
appears to be a mechanism to discourage comments from the
stakeholder community.
Thank you for your comment. EPA provided a
60-day public comment period on the draft TCE
risk evaluation and due to the outbreak of the
novel coronavirus, SARS-CoV-2, the cause of
COVID-19, the agency implemented a virtual
public meeting out of an abundance of caution
and in response to travel restrictions imposed by
some SACC members' employers and other
members' concerns regarding travel, as
communicated in the Federal Register on March
20. 2020 (85 FR 16096) (FRL-10006-79).
104
PUBLIC COMMENTS:
We believe that the comment deadline provided by EPA for this
chemical is too short under normal circumstances to expect substantial
tribal comment for reasons expressed previously by us regarding other
TSCA-related comment opportunities. At this time in history, the
comment periods for TCE and other draft evaluations out under TSCA,
which so impact tribes, clearly are inadequate.
Thank you for your comment. EPA provides a
60-dav public comment period on draft TSCA
risk evaluations
Concerns regarding virtual SAAC meeting
57, 74,
108
PUBLIC COMMENTS:
EPA's decision to hold the meeting as a virtual meeting during the
Covid-19 public health crisis, poses a number of serious obstacles and
challenges to ensuring that the peer review is conducted in a manner
that complies with the Federal Advisory Committee Act.
Thank you for expressing your concern. Due to
the outbreak of the novel coronavirus,
SARS-CoV-2, the cause of COVID-19, the
agency implemented this change out of an
abundance of caution and in response to travel
restrictions imposed by some SACC members'
employers and other members' concerns
regarding travel, as communicated in the Federal
Register on March 20, 2020 (85 FR 16096)
Page 373 of 408
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(FRL-10006-79Y
70, 74,
108
PUBLIC COMMENTS:
Some panel members were not able to participate in portions of the
meeting. Panel members with unique/particular expertise were not able
to participate on certain days or in certain sessions over the course of
the week. EPA should make this information on participation available
in the docket. There is specific concern that absence of some members
could result in skewing of the panel.
Thank vou for vour comment. The Final Report
and Meeting Minutes of the TCE TSCA SACC
virtual public meeting are available for your
review.
71, 108
PUBLIC COMMENTS:
The SACC peer review panel lacked anyone with specific expertise in
heart development. This is a serious omission that taints the strength of
the peer review of the draft.
Thank vou for vour comment. The Final Report
and Meeting Minutes of the TCE TSCA SACC
virtual public meeting are available for your
review.
References/data not publicly available (includes confidential business information fCBIl)
52, 60
PUBLIC COMMENTS:
EPA has not made critical information related to the identification and
selection of information available in the TCE draft risk evaluation.
There is no (publicly available) HERO project for TCE under OPPT,
which is a significant limitation to the transparency related to the
selection and tagging of data. The use of the HERO platform and library
that is specific to the TSCA risk evaluation should be clarified and all
records and libraries made publicly available.
EPA made the full studies available to peer
reviewers and included a list of the studies and
their results in the docket in accordance with
TSCA section 26(j) and 40 CFR 702.51. Data
quality evaluations for each study are available in
the supplemental files.
108
PUBLIC COMMENTS:
In developing this draft risk evaluation, a large fraction of the
information that EPA relied upon constituted health and safety studies.
All such information not subject to two narrow exceptions needs to be
made public.
EPA made the full studies available to peer
reviewers and included a list of the studies and
their results in the docket in accordance with
TSCA section 26(j) and 40 CFR 702.51. Data
quality evaluations for each study are available in
the appendix and supplemental files.
51
PUBLIC COMMENTS:
HSIA's attempts to obtain the raw data that formed the basis of the
Johnson et al. (2003) study report have been unsuccessful. Examination
of the spreadsheet provided by EPA (Johnson, 2009; HERO ID 783484)
Dates for the range of experiments performed are
provided in (Johnson et al., 2005). Details are not
available on the dates for individual animal
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reveals an absence of certain critical information, including, most
importantly, dates for any of the individual treatment/control animals.
measurements. EPA acknowledges this
deficiency in Appendix F. 1.2.
Primary references not reviewed - using data from other assessments (e.gIB
US, AT SDR)
SACC
SACC COMMENTS:
The Committee commented in general, the draft risk evaluation does a
good job of explaining how the TSCA assessment differs in scope and
focus from the IRIS assessment. Moreover, it is mentioned in multiple
places that the hazard and risk assessments done previously are used as
a starting point and then updated for the present assessment. However, a
more informative summary could be provided, for example, that lists
the critical endpoints for acute and chronic non-cancer and cancer
effects, and the critical studies identified for each endpoint and/or those
that were used to determine POD values.
These organizational comments are appreciated
and will be considered in a revised template for
the next round of chemicals to be evaluated under
TSCA section 6.
33
PUBLIC COMMENTS:
It is recommended that charge questions be added to address the
following systematic review elements as applied in the TCE draft
risk evaluation:
The appropriateness and transparency of partially relying on
previous EPA assessments for selected aspects of the risk
evaluation {e.g., hazard characterization) but not others {e.g.,
POD selection)
These comments with respect to additional
charge questions are appreciated and will be
considered in the next round of chemicals to be
assessed under TSCA section 6.
52, 60
PUBLIC COMMENTS:
There is a significant amount of ambiguity as to how studies identified
in previous assessments were "leveraged." Such assessments were also
described as a "starting point," which seems to be in contrast with that
which is leveraged from previous assessment.
For human health hazard studies, the systematic
review literature search only covered the period
following publication of the IRIS assessment
after 2010, because EPA leveraged the
previously-peer reviewed analysis performed for
that assessment which identified key and
supporting studies. These studies were combined
with relevant data published after the IRIS
assessment and considered together in the Risk
Evaluation.
Biased presentation of results
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SACC
SACC COMMENTS:
Recommendations: (1) Provide support for the statement on kidney
cancer MOA or modify the statement to reflect the lack of consensus.
(2) Provide more discussion in the body of the draft risk evaluation to
support the statement in the Executive Summary on the kidney cancer
MOA.
The Executive Summary, p. 30, lines 1237-1240 states: "A linear non-
threshold assumption was applied to the TCE cancer dose-response
analvsis because there is sufficient evidence that TCE-induced kidnev
cancer operates Drimarilv through a mutagenic mode of action while it
cannot be ruled out for the other two cancer types." One Committee
member was uncertain that this is a correct statement, being unaware
that there is consensus on the kidney cancer MOA. This may have
arisen from the fact that the discussion in Section 3.2.4.2.2 - Kidney
Cancer MOA only references the TCE 2011 IRIS assessment but
provides no details in support of the statement above.
EPA has added some references acknowledging
uncertainty in the genotoxic MOA for kidney
cancer, however EPA believes it is the most
likely mechanism. EPA has inserted the word
"likely" in front of "operates." EPA also copied
language into the Executive Summary from
Section 3.2.4.2.2 which states that the linear
assumption is also supported by "the positive
associations observed via meta-analysis for all
three cancers in epidemiological studies based on
low-level, environmental exposure levels."
Concerns about TSCA systematic review approach/process
SACC
SACC COMMENTS:
Several Committee members commented that overall, it seems that EPA
judges study quality, but it is difficult to understand how study
relevance factors into any conclusion in choosing a particular study
from which to develop a POD and resulting value to carry through the
risk assessment.
EPA describes the factors considered when
selecting studies and PODs to represent each
endpoint in Section 3.2.5.3, of which "relevance
to the endpoint of interest and human exposure
scenarios" is included.
33,47,
49, 99
PUBLIC COMMENTS:
It is recommended that charge questions be added to address the
following SR elements as applied in the TCE draft risk evaluation:
The soundness and reproducibility of the approach to identify
and select studies for the underlying evidence base; specifically,
the transparency, objectivity , and consistency of the approach
implemented (e.g., use of a bibliography to split studies into " on-
topic" and "off-topic" categories).
The appropriateness of using the TSCA systematic review tool to
evaluate individual study quality in one step of the assessment and a
These comments with respect to additional
charge questions are appreciated and will be
considered in the next round of chemicals to be
evaluated under TSCA section 6.
Page 376 of 408
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completely different (and novel) tool to assess relevance and
reliability in the WOE assessment.
The consistency in outreach to study authors to address questions in
reporting.
The appropriateness of applying study quality criteria related to use
of a positive control for some studies but not all, specifically the
soundness of downgrading studies that did use a positive control,
while not scoring this element for studies that lacked a positive
control.
The appropriateness of deviating from the TSCA systematic review
guidance on scoring to categorize in vitro studies that did not
evaluate cytotoxicity and scored them as "NA" instead of
"unacceptable."
The appropriateness, transparency, and consistency of subjective
judgments to up- or down-grade study quality.
The soundness of the novel WOE approach utilized in the draft risk
evaluation relative to standard systematic review approaches, such
as GRADE, that have been previously recommended to EPA by the
NAS.
The appropriateness of applying the novel WOE framework to
assess hazard potential of only one of the several endpoints assessed
in the draft risk evaluation.
The completeness of data integration; specifically, the adequacy
of the evaluation of consistency, coherence, and biological
plausibility as part of the data integration step for each endpoint
(as is described in Figure 3-3 of the TCE draft risk evaluation).
47, 49,
99
PUBLIC COMMENTS:
Feedback on the draft systematic review guidance is needed now;
however, the NAS review of this guidance is not yet available. As the
NAS belatedly reviews the guidance, EPA should cease using it in final
risk evaluations but instead apply one of the recognized systematic
review methodologies.
EPA's systematic review is currently based on
Application of Systematic Review in TSCA Risk
Evaluations. Revisions to systematic review are
under development {Systematic Review Protocol
Supporting the TSCA Risk Evaluations)', EPA
anticipates feedback from the NASEM TSCA
49, 99
PUBLIC COMMENTS:
Page 377 of 408
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The TSCA method departs radically from accepted scientific principles
for systematic review adopted by the Institute of Medicine (IOM), NTP
and IRIS and endorsed by the NAS and other peer review bodies. The
SACC has "noted problems with both the systematic review design and
consistent implementation of its protocols." At a minimum, EPA's final
risk evaluations must respond fully to the SACC's comments.
Committee on its systematic review process,
including the epidemiological data quality
criteria.
EPA/OPPT's quality evaluation method was
developed following identification and review of
various published qualitative and quantitative
scoring systems to inform our own fit-for-
purpose tool. The development process involved
reviewing various evaluation tools/frameworks
(e.g., OHAT Risk of Bias tool, CRED, etc.; see
Appendix A of the Application of Systematic
Review in TSCA Risk Evaluations document and
references therein), as well as soliciting input
from scientists based on their expert knowledge
about evaluating various data/information
sources specifically for risk assessment
purposes.
The epidemiologic criteria were later revised to
more stringently distinguish between High,
Medium and Low studies. After additional
piloting of the criteria, EPA found that the initial
iteration of the epi data quality criteria (as
published in the Application of Systematic
Review in TSCA Risk Evaluations) was
inadvertently skewing quality scores toward the
tail ends of the scoring spectrum (High and
Unacceptable). In order to have the criteria
represent a more accurate depiction of the quality
levels in the epi literature, the criteria were
revised using two methods.
56, 73,
74, 99
PUBLIC COMMENTS:
Ratings are based on a profoundly, and fundamentally, flawed
systematic review method. Those flaws include the lack of any
empirical support for the scoring system devised, use of numerical
scores to characterize study quality as a general matter, and lack of a
defined procedure for data integration, among others. The use of
numerical study scoring defies consistent recommendations in the field
of systematic review including those made in the 2014 Academies
review of the IRIS program.
106
PUBLIC COMMENTS:
EPA's scoring method wrongly downgrades or excludes a study based
on a reporting deficiency, conflating how well a study is reported with
how well the underlying research was conducted. Although EPA has
posted its "Updates to the Data Quality Criteria for Epidemiological
Studies," EPA's TSCA method still uses reporting measures in its
scoring of the quality of human studies; this includes incorporating
reporting guidelines into the rationales for scoring studies "low quality"
(Metrics 1 and 15) or "unacceptable for use" (Metrics 3, 4, 6, 7). Using
STROBE reporting guidelines to score individual studies is contrary to
the recommendations given by the authors of the STROBE guidelines,
who specifically note that the guidelines are not a measure of the quality
of the underlying research.
The inclusion of numerous reporting items irrelevant to bias in a
quality scoring rule (e.g., an indicator of whether power calculations
were reported), will disproportionately reduce some of the resulting
scores and erroneously undervalue the study quality.
106,
PUBLIC COMMENTS:
Page 378 of 408
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49, 99
The use of a scoring system that excludes a study based on only one
criterion/metric directly contradicts widely accepted systematic review
methodological approaches (e.g., NTP OHAT, UCSF Navigation
Guide), and it will almost certainly result in flawed conclusions and
threaten the protection of the public's health. This approach is also
inconsistent with TSCA mandates to use the "best available science"
and "reasonably available information," while discussing its "strengths
and limitations."
The first method was to make the unacceptable
metrics less stringent. This was accomplished by
either rewording the metrics to allow for more
professional judgement in the interpretation of
the unacceptable criterion, or in some cases,
completely removing the unacceptable bin from
metrics that EPA determined were not influential
enough to completely disqualify a study from
consideration (mostly metrics in the Analysis and
Biomonitoring domain). EPA found that these
criteria changes greatly reduced the type one
error in the Unacceptable scoring. No acceptable
studies were inaccurately classified as
Unacceptable.
The second method was to reduce the number of
studies that received an overall High rating. The
majority of overall scores in EPA's initial
evaluations during piloting tended to be High.
Therefore, EPA strived to revise the criteria to
provide more degradation in the scoring to more
accurately and objectively distinguish studies of
the highest quality from medium and low quality
studies. To do this, EPA removed the High
criterion from some metrics, particularly in
dichotomous metrics (High/Low or
High/Unacceptable) that were primarily being
binned as High by reviewers across the majority
of the studies. These dichotomous metrics were
contributing to the overall quality scores being
skewed towards High. To address this, EPA
shifted some of the dichotomous metrics such
that the highest metric score possible (for all
106,
49, 99
PUBLIC COMMENTS:
We strongly urge EPA to remove the option to rate a study
"Unacceptable" from every metric as the underlying assumptions of
EPA's "serious flaws" metrics are not evidence-based, specifically:
EPA's list of "serious flaws" are not all equal indicators of study
quality.
EPA's list of "serious flaws" are not all related to real flaws in the
underlying research (i.e., reporting guidelines are wrongly equated
with serious flaws in study quality.
Analysis is equated with a "serious flaw" in study quality, but statistical
power is not a valid measure of study quality and should not be used to
disqualify studies from consideration. EPA's Metric 13 statistical
power/sensitivity confuses bias with imprecision. Individual studies that
are "underpowered" (e.g., because in the real world, the exposed
population may not be large enough for statistical purposes even if they
are health-impacted) can still be potentially valuable to evidence-based
decision-making. Underpowered studies that find a health effect to be
present may be indicative of a larger effect size than anticipated;
omitting or downgrading such studies due to being underpowered would
severely bias the conclusions of the review.
56
PUBLIC COMMENTS:
OPPT provides neither an explanation nor empirical support for its
revisions to the systematic review data quality criteria for
epidemiological studies, which makes it more difficult for
epidemiological studies to be scored overall as high quality. This
Page 379 of 408
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underscores that the study quality evaluation strategy that OPPT
developed is not evidence-based.
studies) is a Medium. The change led to the
dichotomous metrics having less significant
impact to the numerical scoring and the overall
quality rating for each study.
With the aforementioned changes to the criteria,
EPA observed fewer studies with Unacceptable
ratings and more studies shifting from High to
Medium, with only the highest quality studies
receiving a High overall rating. Out of the -200
relevant epidemiologic studies and cohorts
evaluated for data quality for the first 10 TSCA
chemicals, the majority (-80%) still scored as
High or Medium. The remaining -20% of studies
scored Low or Unacceptable. EPA is confident
that no studies of acceptable quality were
inappropriately assigned as Unacceptable. EPA
is also confident that the revised criteria bins the
quality levels of these epi studies more
appropriately than the previous iteration.
Additional refinements to the epidemiologic data
evaluation criteria are likely to occur as EPA's
validation and process improvement efforts
continue.
56, 108
PUBLIC COMMENTS:
At least six metrics in EPA OPPT's updated epidemiological criteria
can no longer receive a score of High, including Metric 5 (Exposure
Levels) and Metric 15 (Statistical Models). Since these individual
metrics can at best be rated as Medium (a change from the earlier
epidemiological criteria), epidemiological studies are thus less likely to
be considered high quality overall, and as a result, may be given more
limited consideration than other types of evidence (animal and in vitro
studies), where it is remains possible to score High across every data
quality metric.
56, 108
PUBLIC COMMENTS:
EPA should consider other study evaluation tools that are more
appropriate for the consideration of the quality of observational
epidemiologic studies. Examples include the Conducting Systematic
Reviews and Meta-Analyses of Observational Studies of Etiology
(COSMOS-E) tool and the Navigation Guide.
Inappropriate application of systematic review for TCE
52
PUBLIC COMMENTS:
The TCE draft risk evaluation was not compliant with systematic
review. Only two of the key elements were completed by EPA in their
systematic review (a clearly stated set of objectives and
interpretation of results/presentation of a summary of findings);
other key elements were either completely absent or were
inconsistent/incomplete.
Because EPA was developing the systematic
review process while simultaneously
implementing the process for ten chemicals, there
were some challenges with maintaining
consistency. However, EPA did implement
several steps to ensure consistency and reduce
bias. EPA used calibration steps among multiple
Page 380 of 408
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screeners during a pilot phase for both the data
screening and data evaluation processes.
Furthermore, instructions were prepared for
various aspects of the systematic review (e.g.,
data screening, data evaluation, and data
extraction) to guide the reviewers and provide
consistency across reviews. Finally, most studies
received two data quality evaluations with
reviewers working together to resolve conflicts,
sometimes with a single arbiter across similar
types of studies. EPA has implemented additional
calibration steps and internal guidance documents
for the next 20 chemicals going through the
systematic review process now.
Any single set of data quality criteria, even for a
given category of studies (e.g., animal toxicity
studies), cannot necessarily address all aspects of
quality relevant for an individual study in the
category. Thus, EPA allowed reviewers the
ability to adjust the final score based on
professional judgment. This approach has been
used in other established tools, including the
ToxRTool (Toxicological data Reliability
Assessment Tool) developed by the European
Commission (https://eurl-
ecvam.irc.ec. europa. eu/ab out-ecvam/archi ve-
publications/toxrtool).
EPA implemented a literature search process for
the first ten chemicals that included a
comprehensive set of key words to capture as
much of the literature for a given discipline as
Page 381 of 408
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possible. However, even with a comprehensive
literature search, some important studies may be
missed. For instance, an abstract may not identify
the chemical of interest by name (e.g., if a
genotoxicity test was conducted on many
chemicals) and thus might be screened out from
further consideration. In addition, some targeted
searching for topics not anticipated at the
beginning of the risk evaluation process (e.g.,
generic inputs needed for an exposure model)
might be needed. Therefore, such backwards
searching (or snowballing) and targeted searching
remain important aspects of the systematic
review process.
EPA will publish a protocol document for the
next TSCA risk evaluations. Furthermore, EPA
anticipates feedback from the NASEM TSCA
Committee on its systematic review process and
will carefully review their recommendations for
the next 20 chemicals.
52, 56,
108,
49, 99
PUBLIC COMMENTS:
The lack of a protocol resulted in numerous arbitrary and inconsistent
decisions, lack of structured and systematic syntheses, and lack of
transparency throughout the risk evaluation. No protocol was
developed for TCE, rather, planning documents were limited to a
scoping document, a strategy for literature search, and a bibliography
file. OPPT has not provided a pre-established methodology for its
approach to evidence integration. OPPT needs to develop full
protocols for each of its risk evaluation and should consult with the
IRIS program on how best to do so in consideration of requirements
under TSCA.
Because EPA was developing the systematic
review process while simultaneously
implementing the process for ten chemicals, there
were some challenges with maintaining
consistency. However, EPA did implement
several steps to ensure consistency and reduce
bias. EPA used calibration steps among multiple
screeners during a pilot phase for both the data
screening and data evaluation processes.
Furthermore, instructions were prepared for
various aspects of the systematic review (e.g.,
Page 382 of 408
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data screening, data evaluation, and data
extraction) to guide the reviewers and provide
consistency across reviews. Finally, most studies
received two data quality evaluations with
reviewers working together to resolve conflicts,
sometimes with a single arbiter across similar
types of studies. EPA has implemented additional
calibration steps and internal guidance documents
for the next 20 chemicals going through the
systematic review process now.
Any single set of data quality criteria, even for a
given category of studies (e.g., animal toxicity
studies), cannot necessarily address all aspects of
quality relevant for an individual study in the
category. Thus, EPA allowed reviewers the
ability to adjust the final score based on
professional judgment. This approach has been
used in other established tools, including the
ToxRTool (Toxicological data Reliability
Assessment Tool) developed by the European
Commission (https://eurl-
ecvam.jrc.ec. europa. eu/ab out-ecvam/archi ve-
publications/toxrtool).
EPA implemented a literature search process for
the first ten chemicals that included a
comprehensive set of key words to capture as
much of the literature for a given discipline as
possible. However, even with a comprehensive
literature search, some important studies may be
missed. For instance, an abstract may not identify
the chemical of interest by name (e.g., if a
Page 383 of 408
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genotoxicity test was conducted on many
chemicals) and thus might be screened out from
further consideration. In addition, some targeted
searching for topics not anticipated at the
beginning of the risk evaluation process (e.g.,
generic inputs needed for an exposure model)
might be needed. Therefore, such backwards
searching (or snowballing) and targeted searching
remain important aspects of the systematic
review process.
EPA will publish a protocol document for the
next TSCA risk evaluations. Furthermore, EPA
anticipates feedback from the NASEM TSCA
Committee on its systematic review process and
will carefully review their recommendations for
the next 20 chemicals.
52
PUBLIC COMMENTS:
There are many aspects of EPA's systematic review approach that are
not reproducible - a reflection of the lack of compliance with
systematic review methodologies and extensive subjective and
inconsistent actions. These include the lack of transparency and
systematic method for identifying evidence, lack of consistency in
applying the data quality tool, lack of adherence to the criteria in
applying the data quality tool, subjective decisions to up- and down-
grade studies after applying the study quality tool, and developing and
implementing a WOE approach during the conduct of the TCE risk
evaluation.
Because EPA was developing the systematic
review process while simultaneously
implementing the process for ten chemicals, there
were some challenges with maintaining
consistency. However, EPA did implement
several steps to ensure consistency and reduce
bias. EPA used calibration steps among multiple
screeners during a pilot phase for both the data
screening and data evaluation processes.
Furthermore, instructions were prepared for
various aspects of the systematic review (e.g.,
data screening, data evaluation, and data
extraction) to guide the reviewers and provide
consistency across reviews. Finally, most studies
received two data quality evaluations with
Page 384 of 408
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reviewers working together to resolve conflicts,
sometimes with a single arbiter across similar
types of studies. EPA has implemented additional
calibration steps and internal guidance documents
for the next 20 chemicals going through the
systematic review process now.
Any single set of data quality criteria, even for a
given category of studies (e.g., animal toxicity
studies), cannot necessarily address all aspects of
quality relevant for an individual study in the
category. Thus, EPA allowed reviewers the
ability to adjust the final score based on
professional judgment. This approach has been
used in other established tools, including the
ToxRTool (Toxicological data Reliability
Assessment Tool) developed by the European
Commission (https://eurl-
ecvam.jrc.ec. europa. eu/ab out-ecvam/archi ve-
publications/toxrtool).
EPA implemented a literature search process for
the first ten chemicals that included a
comprehensive set of key words to capture as
much of the literature for a given discipline as
possible. However, even with a comprehensive
literature search, some important studies may be
missed. For instance, an abstract may not identify
the chemical of interest by name (e.g., if a
genotoxicity test was conducted on many
chemicals) and thus might be screened out from
further consideration. In addition, some targeted
searching for topics not anticipated at the
Page 385 of 408
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beginning of the risk evaluation process (e.g.,
generic inputs needed for an exposure model)
might be needed. Therefore, such backwards
searching (or snowballing) and targeted searching
remain important aspects of the systematic
review process.
EPA will publish a protocol document for the
next TSCA risk evaluations. Furthermore, EPA
anticipates feedback from the NASEM TSCA
Committee on its systematic review process and
will carefully review their recommendations for
the next 20 chemicals.
52, 60,
106
PUBLIC COMMENTS:
The approach for identification of evidence is not systematic,
transparent, or readily reproducible. For example:
There is a large time lag between searches described in the strategy
and the conduct of the actual risk evaluation.
The generic flow charts in Figures 1-5 through 1-9 do not provide
transparent documentation of how data were identified, nor do they
align with the multitude of approaches described in the 2017
literature search strategy document. Documentation should be made
publicly available for all records, by tag, in the figures.
Appendix B is missing almost 1000 'on-topic' study reports from
the supplemental bibliography from the TCE scoping document, and
there are an additional 35 studies which go missing between the 215
study reports in the cited supplemental bibliographies for the draft
risk evaluation, and the 180 studies referenced in Figure 1-9. Such
inconsistencies are deeply concerning and threaten the validity of
the draft risk evaluations.
In Figure 1-8, EPA includes the appropriate additional step of
reporting the number of studies screened at the 'Title/Abstract' stage
and the number at the 'Full Text Screening' stage while Figure 1-9
Because EPA was developing the systematic
review process while simultaneously
implementing the process for ten chemicals, there
were some challenges with maintaining
consistency. However, EPA did implement
several steps to ensure consistency and reduce
bias. EPA used calibration steps among multiple
screeners during a pilot phase for both the data
screening and data evaluation processes.
Furthermore, instructions were prepared for
various aspects of the systematic review (e.g.,
data screening, data evaluation, and data
extraction) to guide the reviewers and provide
consistency across reviews. Finally, most studies
received two data quality evaluations with
reviewers working together to resolve conflicts,
sometimes with a single arbiter across similar
types of studies. EPA has implemented additional
calibration steps and internal guidance documents
Page 386 of 408
-------
does not.
The draft risk evaluation does not describe how multiple platforms
(DRAGON, DistillerSR, and HERO) were utilized to facilitate
various aspects of the review. The 2017 document indicates that
information from DRAGON was being migrated to DistillerSR, but
it is not clear which platform was used for steps outside of the initial
title and abstract screening for "on topic" and "off topic" selections.
All of these platforms provide audit trails and produce output that
could transparently document the identification and selection
process. Such documentation should be made publicly available.
The articles identified by backwards searching should be clearly
identified, and a narrative on the types and number of studies that
were not identified in the initial search should be discussed. The
2017 document describes a process to evaluate the performance of
the search strategies, though the results of such are not described in
the draft risk evaluation.
The decision to skip data screening is unclear and should be clarified
as to which data were not subject to screening as such an approach is
not consistent with systematic review.
Page 387 of 408
for the next 20 chemicals going through the
systematic review process now.
Any single set of data quality criteria, even for a
given category of studies (e.g., animal toxicity
studies), cannot necessarily address all aspects of
quality relevant for an individual study in the
category. Thus, EPA allowed reviewers the
ability to adjust the final score based on
professional judgment. This approach has been
used in other established tools, including the
ToxRTool (Toxicological data Reliability
Assessment Tool) developed by the European
Commission (https://eurl-
ecvam.irc.ec. europa. eu/ab out-ecvam/archi ve-
publications/toxrtool).
EPA implemented a literature search process for
the first ten chemicals that included a
comprehensive set of key words to capture as
much of the literature for a given discipline as
possible. However, even with a comprehensive
literature search, some important studies may be
missed. For instance, an abstract may not identify
the chemical of interest by name (e.g., if a
genotoxicity test was conducted on many
chemicals) and thus might be screened out from
further consideration. In addition, some targeted
searching for topics not anticipated at the
beginning of the risk evaluation process (e.g.,
generic inputs needed for an exposure model)
might be needed. Therefore, such backwards
searching (or snowballing) and targeted searching
-------
remain important aspects of the systematic
review process.
EPA will publish a protocol document for the
next TSCA risk evaluations. Furthermore, EPA
anticipates feedback from the NASEM TSCA
Committee on its systematic review process and
will carefully review their recommendations for
the next 20 chemicals.
45, 67
PUBLIC COMMENTS:
Based on a simple PubMed Search, it was estimated that there was
-2,200 published findings of toxicity on TCE; however, EPA finds only
419 ecotox and 170 human hazard. It was also suggested that the search
query was too general, and that EPA should start again at the literature
review stage or it will not be performing systematic review. Six studies
were listed that were considered relevant, but were not included by EPA
including a study on congenital heart effect (Harris et al., 2018). EPA
should verify that none of the excluded studies from previous risk
assessments were key studies.
Thank you for your comment. However, as
shown in Figures 1-10 and 1-11, EPA identified
8,500+ and 6,000+ literature results for
Environmental and Human Health Hazard,
respectively. The majority of these studies were
identified as off-topic and not relevant to the
TCE Risk Evaluation based on title/abstract
screening. The literature search ended in early
2017, so studies published after this date would
not have been identified. (Harris et al., 2018) was
included in the Risk Evaluation, however and is
incorporated into the WOE analysis for cardiac
malformations.
52
PUBLIC COMMENTS:
Many studies that were relevant to the Populations, Exposures,
Comparators, and Outcomes (PECO) statement and initially categorized
as "on topic" were not considered in the TCE draft risk evaluation. The
documentation is insufficient to understand why clearly relevant studies
that were initially included were, at some later point, disregarded in the
TCE draft risk evaluation (six studies were listed).
Cosby, NC; Dukelow, WR. (1992). Toxicology of maternally
ingested trichloroethylene (TCE) on embryonal and fetal
development in mice and of TCE metabolites on in vitro
EPA did consider the majority of these studies in
the Risk Evaluation in the context of the cardiac
defects WOE. EPA has added a clarification to
Appendix F.3.1 that the following studies were
screened out as off-topic for the cardiac defects
WOE specifically because the study reports did
not indicate direct assessment of cardiac defects,
cardiovascular effects, or any related outcomes:
(Beliles et al., 1980; Bross et al., 1983; Cosbv
Page 388 of 408
-------
fertilization. Fundam Appl Toxicol. 19: 268-274.
Narotsky, MG; Kavlock, RJ. (1995). A multidisciplinary approach
to toxicological screening: II. Developmental toxicity. J Toxicol
Environ Health. 45: 145-171.
http://dx.doi.org/10.1080/15287399509531987.
Caldwell, PT; Manziello, A; Howard, J; Palbykin, B; Runyan, RB;
Selmin, O. (2010). Gene expression profiling in the fetal cardiac
tissue after folate and low-dose trichloroethylene exposure. Birth
Defects Res A Clin Mol Teratol. 88: 111-127. http://dx doi org/10
1002/bdra 20631.
Bross, G; Difranceisco, D; Desmond, ME. (1983). The effects of
low dosages of trichloroethylene on chick development. Toxicology.
28: 283-294. http://dx doi org/10 1016/0300-483X(83)90002-l.
Elovaara, E; Hemminki, K; Vainio, H. (1979). Effects of methylene
chloride, trichloroethane, trichloroethylene, tetrachloroethylene and
toluene on the development of chick embryos. Toxicology. 12: 111-
119. http://dx.doi.org/10.1016/0300-483X(79)90037-4.
Tola, S; Vilhunen, R; Jarvinen, E; Korkala, ML. (1980). A cohort
study on workers exposed to trichloroethylene. J Occup Environ
Med. 22: 737-740.
and Dukelo\\ rsฐ2; Dorfmueller et a 1 9;
Elovaara et al 1979; Narotskv and Kavlock.
1995; Narotskv et al 1995). The referenced
Caldwell studv is a follow-uo to (Caldwell et al
2008). which was included in the WOE analysis.
This study examines gene expression changes
following TCE exposure but does not provide any
relevant novel information that would influence
the WOE beyond what was already discussed
from (Caldwell et al 2008) and (Collier et al
2003). The (Tola et al 1980) studv was not
included in (Makris et al.. ) or the 2014 TCE
Work Plan Chemical Risk Assessment (U.S.
ป), which were the sources for older
studies {i.e., would not have been captured in the
literature search which only searched 2010-2017
studies) relevant to cardiac toxicity (as described
in Appendix F3.1). It was also not identified as a
key study from the 201 1 IRIS Assessment (U.S.
) because it did not contain dose-
response information. Therefore, this study was
not included in the risk evaluation for cardiac
defects or other effects.
56
PUBLIC COMMENTS:
EPA's use of studies here that are otherwise excluded through the PECO
statement raises concern that EPA has introduced bias and inconsistency
in the risk evaluation process. EPA should develop general guidance for
when these allowances may be considered, and clearly identify, with
supporting justification, those specific instances where studies excluded
during systematic review or other processes can be referenced and relied
on in developing the risk evaluation.
Because EPA was developing the systematic
review process while simultaneously
implementing the process for ten chemicals, there
were some challenges with maintaining
consistency. However, EPA did implement
several steps to ensure consistency and reduce
bias. EPA used calibration steps among multiple
screeners during a pilot phase for both the data
screening and data evaluation processes.
Page 389 of 408
-------
Furthermore, instructions were prepared for
various aspects of the systematic review (e.g.,
data screening, data evaluation, and data
extraction) to guide the reviewers and provide
consistency across reviews. Finally, most studies
received two data quality evaluations with
reviewers working together to resolve conflicts,
sometimes with a single arbiter across similar
types of studies. EPA has implemented additional
calibration steps and internal guidance documents
for the next 20 chemicals going through the
systematic review process now.
Any single set of data quality criteria, even for a
given category of studies (e.g., animal toxicity
studies), cannot necessarily address all aspects of
quality relevant for an individual study in the
category. Thus, EPA allowed reviewers the
ability to adjust the final score based on
professional judgment. This approach has been
used in other established tools, including the
ToxRTool (Toxicological data Reliability
Assessment Tool) developed by the European
Commission (httDs://eurl-
ecvam.irc.ec. europa. eu/ab out-ecvam/archi ve-
Dublications/toxrtool).
52, 60
PUBLIC COMMENTS:
Data quality evaluations were not conducted in a systematic or
reproducible manner - aspects of which will not be apparent to the
SACC members without conducting an independent review of each
study quality evaluation and, as such, it will be practically impossible
for the SACC to critically evaluate the consistency across studies and
evidence streams.
Because EPA was developing the systematic
review process while simultaneously
implementing the process for ten chemicals, there
were some challenges with maintaining
consistency. However, EPA did implement
several steps to ensure consistency and reduce
Page 390 of 408
-------
The scoring criteria were not implemented as described in the Draft
EPA Systematic Review guidance; thus, entries are either inaccurate
or intentionally scored differently than that described in the draft
guidance without explanation to such (e.g., Metric 9 for HERO ID
65163; Metric 6 for HERO ID 62111).
Data quality scores were applied inconsistently across studies
(specific examples and HERO IDs were provided). Examples
included Metric 2 (test substance source; 2 studies that failed to
report source, one was rated medium, one was rated low), Metric 5
(positive controls; should not be not rated for teratogenicity studies)
and Metric 19 (blinding; should not be scored for initial
histopathology). Inconsistency in metric scoring is a re-occurring
feature across the score sheets, suggesting insufficient reviewer
oversight and quality control measures in the scoring process.
Scoring inconsistencies introduce additional uncertainty into what is
already a highly subjective evaluation process, further calling into
question EPA's attempt at integrating the evidence streams related
to in utero exposures to TCE and development of fetal cardiac
defects into a coherent conclusion.
Data quality scores were subjectively altered based on judgments for
aspects not addressed by the data quality criteria (i.e., were altered
for reasons, such as relevance, which should be addressed in a
different step of the systematic review). There were many instances
in the data quality evaluation that TSCA relied on quality elements
related to relevance and applicability (which relate to construct and
external validity) rather than assessing the quality based on internal
validity as described in the guidance. That is, many subjective
judgments were made based on data quality criteria that were not
actually part of the data quality tool. These subjective judgments
were not consistent within and across the evidence base, nor are they
reproducible (two examples were provided in a table).
Data quality scores were subjectively altered based on the results of
the study rather than the methodological and reporting quality,
Page 391 of 408
bias. EPA used calibration steps among multiple
screeners during a pilot phase for both the data
screening and data evaluation processes.
Furthermore, instructions were prepared for
various aspects of the systematic review (e.g.,
data screening, data evaluation, and data
extraction) to guide the reviewers and provide
consistency across reviews. Finally, most studies
received two data quality evaluations with
reviewers working together to resolve conflicts,
sometimes with a single arbiter across similar
types of studies. EPA has implemented additional
calibration steps and internal guidance documents
for the next 20 chemicals going through the
systematic review process now.
Any single set of data quality criteria, even for a
given category of studies (e.g., animal toxicity
studies), cannot necessarily address all aspects of
quality relevant for an individual study in the
category. Thus, EPA allowed reviewers the
ability to adjust the final score based on
professional judgment. This approach has been
used in other established tools, including the
ToxRTool (Toxicological data Reliability
Assessment Tool) developed by the European
Commission (https://eurl-
ecvam.irc.ec.europa.eu/about~ecvam/archive~
publications/toxrtooO.
EPA implemented a literature search process for
the first ten chemicals that included a
comprehensive set of key words to capture as
-------
which is regarded as a significant bias in evidence-based practice.
The direction of result should not impact the objective assessment of
methodological rigor and reporting quality (three examples were
provided in a table).
Inconsistencies speak to insufficient reviewer oversight and quality
control measures in the scoring process, including failure to get all
reviewers on "the same page" with respect to interpreting and
applying the metric scoring criteria.
Data quality scores demonstrate bias in reviewer evaluation (two
examples were provided in a table).
much of the literature for a given discipline as
possible. However, even with a comprehensive
literature search, some important studies may be
missed. For instance, an abstract may not identify
the chemical of interest by name (e.g., if a
genotoxicity test was conducted on many
chemicals) and thus might be screened out from
further consideration. In addition, some targeted
searching for topics not anticipated at the
beginning of the risk evaluation process (e.g.,
generic inputs needed for an exposure model)
might be needed. Therefore, such backwards
searching (or snowballing) and targeted searching
remain important aspects of the systematic
review process.
EPA will publish a protocol document for the
next TSCA risk evaluations. Furthermore, EPA
anticipates feedback from the NASEM TSCA
Committee on its systematic review process and
will carefully review their recommendations for
the next 20 chemicals.
56
PUBLIC COMMENTS:
EPA's selective inclusion of studies otherwise excluded as part of its
systematic review process raises concern around inconsistency and bias.
EPA fails to identify which "unacceptable" studies were referenced for
hazard identification and weight-of-the-scientific-evidence assessment,
for which endpoints, and on what basis. Absent any explanation, let
alone guidance, for when and how "unacceptable" studies may be
considered during risk evaluation, EPA's ad hoc use of unacceptable
studies introduces significant risk for arbitrary, biased, and inconsistent
treatment of scientific evidence.
Because EPA was developing the systematic
review process while simultaneously
implementing the process for ten chemicals, there
were some challenges with maintaining
consistency. However, EPA did implement
several steps to ensure consistency and reduce
bias. EPA used calibration steps among multiple
screeners during a pilot phase for both the data
screening and data evaluation processes.
Furthermore, instructions were prepared for
Page 392 of 408
-------
various aspects of the systematic review (e.g.,
data screening, data evaluation, and data
extraction) to guide the reviewers and provide
consistency across reviews. Finally, most studies
received two data quality evaluations with
reviewers working together to resolve conflicts,
sometimes with a single arbiter across similar
types of studies. EPA has implemented additional
calibration steps and internal guidance documents
for the next 20 chemicals going through the
systematic review process now.
Any single set of data quality criteria, even for a
given category of studies (e.g., animal toxicity
studies), cannot necessarily address all aspects of
quality relevant for an individual study in the
category. Thus, EPA allowed reviewers the
ability to adjust the final score based on
professional judgment. This approach has been
used in other established tools, including the
ToxRTool (Toxicological data Reliability
Assessment Tool) developed by the European
Commission (https://eurl-
ecvam.irc.ec. europa. eu/ab out-ecvam/archi ve-
publications/toxrtool).
EPA implemented a literature search process for
the first ten chemicals that included a
comprehensive set of key words to capture as
much of the literature for a given discipline as
possible. However, even with a comprehensive
literature search, some important studies may be
missed. For instance, an abstract may not identify
Page 393 of 408
-------
the chemical of interest by name (e.g., if a
genotoxicity test was conducted on many
chemicals) and thus might be screened out from
further consideration. In addition, some targeted
searching for topics not anticipated at the
beginning of the risk evaluation process (e.g.,
generic inputs needed for an exposure model)
might be needed. Therefore, such backwards
searching (or snowballing) and targeted searching
remain important aspects of the systematic
review process.
EPA will publish a protocol document for the
next TSCA risk evaluations. Furthermore, EPA
anticipates feedback from the NASEM TSCA
Committee on its systematic review process and
will carefully review their recommendations for
the next 20 chemicals.
56
PUBLIC COMMENTS:
OPPT's approach taken to evidence integration in the TCE draft risk
evaluation does not align with best practices as reflected and shared by
leading systematic review methods for chemical assessment (e.g.,
OHAT, NavGuide, IRIS).
EPA's systematic review is currently based on
Application of Systematic Review in TSCA Risk
Evaluations. Revisions to systematic review are
under development (Systematic Review Protocol
Supporting the TSCA Risk Evaluations)', EPA
anticipates feedback from the NASEM TSCA
Committee on its systematic review process,
including the epidemiological data quality
criteria, and will carefully review and implement
relevant recommendations.
Conduc
additional sensitivity analyses
SACC
SACC COMMENTS:
The assumptions and uncertainties associated
with our consumer exposure evaluation is fully
The Committee strongly supports the use of a sensitivity assessment of
the consumer exposure model.
Page 394 of 408
-------
described in Section 2.3.2.6. A description of the
sensitivity analysis on the overall CEM model is
described in Appendix D.3. Consumer exposures
were evaluated across a range of user intensities
by varying weight fraction of a product and the
time and amount of a product used. These user
intensities were expected to cover a range of
possible consumer exposures.
106
PUBLIC COMMENTS:
There is no empirical evidence demonstrating how each risk-of-bias
domain should be weighted and the exclusion of studies based on an
arbitrary rating of the evidence is not supported. If studies are to be
excluded from a body of evidence, it is more appropriate to evaluate
their influence on the overall effect estimates quantitatively using meta-
analysis. Strategies including conducting sensitivity analyses which
calculate overall effect estimates among high quality studies only or
stratifying results based on overall study quality. Researchers may also
choose to present all studies and qualitatively discuss the risk of bias
using structured approaches, similar to OHAT and GRADE.
Because EPA was developing the systematic
review process while simultaneously
implementing the process for ten chemicals, there
were some challenges with maintaining
consistency. However, EPA did implement
several steps to ensure consistency and reduce
bias. EPA used calibration steps among multiple
screeners during a pilot phase for both the data
screening and data evaluation processes.
Furthermore, instructions were prepared for
various aspects of the systematic review (e.g.,
data screening, data evaluation, and data
extraction) to guide the reviewers and provide
consistency across reviews. Finally, most studies
received two data quality evaluations with
reviewers working together to resolve conflicts,
sometimes with a single arbiter across similar
types of studies. EPA has implemented additional
calibration steps and internal guidance documents
for the next 20 chemicals going through the
systematic review process now.
Any single set of data quality criteria, even for a
given category of studies (e.g., animal toxicity
Page 395 of 408
-------
studies), cannot necessarily address all aspects of
quality relevant for an individual study in the
category. Thus, EPA allowed reviewers the
ability to adjust the final score based on
professional judgment. This approach has been
used in other established tools, including the
ToxRTool (Toxicological data Reliability
Assessment Tool) developed by the European
Commission (https://eurl-
ecvam.irc.ec. europa. eu/ab out-ecvam/archi ve-
publications/toxrtool).
EPA implemented a literature search process for
the first ten chemicals that included a
comprehensive set of key words to capture as
much of the literature for a given discipline as
possible. However, even with a comprehensive
literature search, some important studies may be
missed. For instance, an abstract may not identify
the chemical of interest by name (e.g., if a
genotoxicity test was conducted on many
chemicals) and thus might be screened out from
further consideration. In addition, some targeted
searching for topics not anticipated at the
beginning of the risk evaluation process (e.g.,
generic inputs needed for an exposure model)
might be needed. Therefore, such backwards
searching (or snowballing) and targeted searching
remain important aspects of the systematic
review process.
EPA will publish a protocol document for the
next TSCA risk evaluations. Furthermore, EPA
Page 396 of 408
-------
anticipates feedback from the NASEM TSCA
Committee on its systematic review process and
will carefully review their recommendations for
the next 20 chemicals
Content
/organization
SACC
SACC COMMENTS:
Recommendation: Add very concise summary tables that highlight
previous hazard assessments and risk assessments (e.g., EPA IRIS
document, ATSDR, NTP, IARC, etc.) with their main conclusions.
For example, Section 1.3 on regulation and assessment history does
not have enough detail in the main report and instead refers to other
documents and Appendix A.
EPA references previous government
assessments where relevant, however EPA
decided not to add any additional tables
containing results of other assessments to the
main body in order to avoid further expansion of
the large Risk Evaluation document.
SACC
SACC COMMENTS:
Recommendation: One Committee member recommended adding the
Global Harmonization System (GHS) classification to Section 1.1 on
physical-chemical properties.
Including the GHS classification for the substance here as reference
makes sense because this is the first description of the
characteristics of the chemical. GHS classification provides a
standardized way to look at the hazards across chemicals and is the
most common way to communicate on hazards of chemicals to
industrial users.
GHS classification has not been included in other
finalized EPA Risk Evaluations. EPA will
consider adding GSH classification to future
Risk Evaluations.
SACC
SACC COMMENTS:
Recommendation: Enhance Table 1-1 to include additional properties
and property variability.
The Committee had several comments on the physical-chemical
properties in Table 1-1. Other properties should be added to the table,
including properties related to dermal absorption (see Table 6 for
dermal parameters recommended by the SACC for inclusion in the
current and future TSCA risk evaluations). Include all properties that
are used either explicitly or implicitly in modeling. Concern was
expressed with the over-reliance on EPI Suite, a tool that is no longer
being supported (e.g., the databases are not being updated). The
EPA has added dermal permeability parameters
to Table 1-1 as recommended by the SACC.
Other properties included are consistent with
other Risk Evaluations.
Page 397 of 408
-------
variability associated with each property estimates should be included.
Adding variability estimates allows for quantitative assessment of how
this uncertainty impacts risk evaluation findings.
SACC
SACC COMMENTS:
Recommendation: Consider including a table or figure that shows mass
balance information.
The SACC recommended in previous assessments of TSCA chemical
evaluations to include more information on the chemical manufacture,
uses, and releases, which the Committee has referred to as the "mass
balance" approach. This is a consolidation and expansion of several
tables in the Problem Formulation, main report, and appendices.
Committee members had differing opinions on the reasonableness of
this approach and what it might entail. No consensus was reached on
whether such a table would be useful or even able to be created.
Problems with fulfilling the needs of a mass balance table include CBI,
delays between manufacturing and use, and changing uses/formulations.
The Committee recommended that EPA investigate possible solutions,
such as using a multi-year average and aggregating information to avoid
disclosure of CBI. Committee members provided Table 7 as one
example of what a mass-balance table might look like.
One Committee member point out that the draft risk evaluation
purported 2 million pounds of TCE lost. This is 2% of the total
product volume and a mass balance approach would show where
this loss is coming from. It would be a higher percentage if the loss
came from the approximately 15% used to make TCE-containing
products.
The estimates should also be updated for both the newer reports to
EPA, as EPA has stated it will do, and for the market study.
Some Committee members commented that the TRI estimated
releases are under-reported, while another Committee member
commented that they are over-reported. The Committee agrees that
TRI estimated releases are not accurate, although reporters try to
report all their releases.
EPA's analvsis uses TRI (U.S. EPA 2017s) and
DMR (U.S. EPA 2016a) to estimate the highest
local per site water releases of TCE. EPA has
added a mass balance analysis as suggested to
Appendix R of the Risk Evaluation.
Page 398 of 408
-------
SACC
SACC COMMENTS:
Recommendation: Use figures instead of tables for production volume
(Table 1-2) and uses (p. 42-43, lines 1659-1665). Sample figures were
provided.
EPA has added figures for production volume
and has removed the production volume tables.
SACC
SACC COMMENTS:
EPA uses table structures consistent with the
2014 Workplan Risk Assessment of TCE, which
EPA believes most succinctly and informatively
presents endpoints under consideration for dose-
response analysis.
Recommendation: Consider using table structures in the TSCA draft
risk evaluation that are similar to those used in the associated IRIS
assessment.
In the draft risk evaluation, Tables 3-7 to 3-14 report dose-response
analysis results for selected studies and present PODs, HECs, HEDs
and Uncertainty Factor values used. In the 2011 TCE IRIS report (U.S.
EPA, 201 lb), Table 5-13 provides the same information but in a
different format. In this case, the IRIS table is clearer. One Committee
member strongly recommend the use of the IRIS report format for
these tables, if for no other reason than for consistency.
SACC
SACC COMMENTS:
Recommendation: Move exposure estimates based on workers central
tendency exposures from Section 4 Risk Characterization to Section 2
Exposures.
EPA chose to discuss ONUs' exposure estimates based on modeling or
measurements in Section 2 - Exposures, but to discuss the central
tendency exposure estimates based on workers in Section 4 - Risk
Characterization. This is problematic because the estimates for ONUs
based on workers are also exposure estimates, although with different
levels of assumptions, uncertainty, and confidence. They should be
included in Section 2 with the appropriate justification, description of
uncertainties, caveats, etc.
EPA thanks the commenter for the
recommendation. EPA will investigate the
organization of exposure estimates and risk
characterization discussions for future risk
evaluations.
SACC
SACC COMMENTS:
Recommendation: Provide more consistent and detailed discussion of
PPE usage in the main draft risk evaluation document. PPE use is a
critical issue that should have more information in the main document
rather than referring the reader to the NIOSH memorandum.
Presentation of PPE issues in Section 2 is organized awkwardly.
EPA thanks the commenter for the
recommendation. EPA has added a summary
table (Table 4-9) presenting assumptions on
respirator and glove usage for each OES. EPA
will investigate the organization of exposure
Page 399 of 408
-------
PPE for dermal exposures appears as part of subsection section
2.3.1.3.5 - Modeled Dermal Exposures, while for inhalation
exposures it is presented in the next subsection, 2.3.1.3.5 -
Consideration of Engineering Controls and Personal Protective
Equipment, which discusses respirators, but inhalation exposures are
described in Sections 2.3.1.2.1 through 2.3.1.2.4, well before dermal
exposures.
Either the presentations of dermal and inhalation protection are
made separately for each route of exposure in both cases, or there
should be a separate subsection that discusses exposure controls and
presents both types of PPE.
estimates and discussion of PPE for future risk
evaluations.
SACC
SACC COMMENTS:
EPA has updated definitions and references
throughout the document for consistency in
defining adults vs. adolescents and children. The
line in Section 2.3.3 has been clarified as
referring to adults or children age 11 and up.
Recommendation: Use the Department of Health and Human Services
(DHHS) definition of adults consistently.
Throughout the document, there is a need to be consistent and correct
about the age cut-off for "adults." The draft risk evaluation should
follow the DHHS guideline of adults being age >18 years. In some
places, the draft risk evaluation uses either age 16 or 21 years as a cut-
off; it is unclear why there is a lack of consistency. Page 186, lines
3128-3129 has a particularly odd definition of adults as age >11 years.
52
PUBLIC COMMENTS:
It is notable that WOE is not addressed in the methods section of the
draft risk evaluation (Section 1.5.3).
Section 1.5.3 of the TCE risk evaluation states
"EPA considers quality, consistency, relevancy,
coherence and biological plausibility to make
final conclusions regarding the weight of the
scientific evidence."
Presentation of uncertainty and conclusions
SACC
SACC COMMENTS:
These organizational comments are appreciated
and will be considered in a revised template for
the next round of chemicals to be evaluated
under TSCA section 6.
Recommendation: Present uncertainty and confidence as in Table 2-26
throughout the draft risk evaluation.
One Committee member commented they liked the presentation of
uncertainty and overall confidence in a table format such as Table 2-26:
Summary of overall confidence in inhalation exposure estimates by
Page 400 of 408
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OES. If the descriptions are systematized better, it would be a good
model to follow for summarizing uncertainties and confidence
throughout the risk evaluation, including summarizing PESS.
Errors
SACC
SACC COMMENTS:
The dose levels used in the (Keil et al.. 2009)
study were not misreported. The dose levels
stated by the commenter are actually misreported
in the Abstract of the original publication, which
presumably is the basis for the comment.
The dose levels in the Keil et al. (2009) study are misreported in the
draft risk evaluation. They were 0.001, 0.4, or 14 ppm (0, 1, 400, or
14,000 ppb) TCE in water.
56
PUBLIC COMMENTS:
Errors in Table 2-26:
Batch Open-Top Vapor Degreasing
EPA states on p. 129: "These monitoring data include 123 data
points from 16 sources, and the data quality ratings from systematic
review for these data were medium
Based on the description on p. 705, the referenced data sources
appear to be from these 10 studies: Daniels et al., 1988; Ruhe et al.,
1981; Barsan, 1991; Ruhe, 1982; Rosensteel and Lucas, 1975; Seitz
and Driscoll, 1989; Gorman et al., 1984; Gilles et al., 1977;
Vandervort and Polakoff, 1973; and Lewis, 1980.
In the document "Systematic Review Supplemental File: Data
Quality Evaluation of Environmental Releases and Occupational
Exposure Data," all 10 studies received an overall quality
determination of high, not medium.
Spot Cleaning and Wipe Cleaning
EPA states on p. 133: "These monitoring data include 8 data points
from 2 sources, and the data quality ratings from systematic review
for these data were medium
Based on the description on p. 732, the referenced data sources
appear to be Burton and Monesterskey (1996) and NIOSH (1997).
In the document "Systematic Review Supplemental File: Data
Quality Evaluation of Environmental Releases and Occupational
EPA agrees that the data quality ratings of the
sources from systematic review were all scored
as high. This has been corrected in the text.
However, the overall confidence statements in
Table 2-26 involve more than just the data
quality. For the overall confidence statements,
EPA considered the assessment approach, the
quality of the data and models, and uncertainties
in assessment results to determine an overall
level of confidence. All these factors together
yield an overall confidence factor of medium for
the three occupational exposure scenarios (OES)
described by the commenter.
Additional description of how the overall
confidence statements are determined is provided
in the Appendix titled Data Integration Strategy
for Occupational Exposure and Release
Data/Information of the Supplemental
Information on Releases and Occupational
Exposure Assessment document.
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Exposure Data," both Burton and Monesterskey (1996) and NIOSH
(1997) received an overall quality determination of high (1.6 and
1.4, respectively; see p. 159 and 172 of the systematic review
supplemental file), not medium.
Commercial Printing and Copying:
EPA states on p. 134: "These monitoring data include 20 data points
from 1 source, and the data quality ratings from systematic review
for these data were medium."
Based on the description on p. 737, the referenced data source
appears to be Finely and Page (2005).
In the document, "Systematic Review Supplemental File: Data
Quality Evaluation of Environmental Releases and Occupational
Exposure Data," Finely and Page (2005) received an overall quality
determination of high (1.6) and had 23 samples (see p. 126 of the
systematic review supplemental file), not medium.
96
PUBLIC COMMENTS:
Table Apx C-l is incorrect:
The Occidental Chemical Corporation, Wichita, KS NPDES:
KS0096903 facility does not release TCE to surface water or to a
POTW (off-site wastewater treatment). All process wastewater and
stormwater that falls on process areas is collected and disposed to a
permitted deepwell system. TCE is a constituent detected in
remediation extraction wells located on the manufacturing site; thus,
any TCE waste resulting from extraction activities is disposed in the
deepwell system.
The Occidental Chemical Corporation, Niagara Plant, Niagara
Falls, NY NPDES: NY0003336 facility does not use TCE as an
industrial processing aid. TCE is not used as an industrial process
aid at the facility; TCE measured, if any, is from legacy disposal
remediation at the site.
The Oxy Vinyls LP - Deer Park PVC, Deer Park, TX NPDES:
TX0007412 facility does not use TCE in other industrial uses.
TCE measured, if any, is from legacy remediation at the site.
Based on re-evaluation of TRI and DMR data,
EPA has revised the Risk Evaluation to indicate
the Occidental Chemical Corporation facility in
Wichita, KS does not release TCE to surface
water or off-site wastewater treatment.
The SIC for the Occidental Chemical
Corporation Niagara Plant reported in DMR (SIC
2812) (U.S. EPA 2016a) translates to a NAICS
code of 325180. This facility has been grouped
with other facilities with the same/similar
NAICS codes that have listed TCE use as an
industrial processing aid in TRI.
The TRI submission from the Oxy Vinyls LP
facility in Deer Park. TX fU.S. EPA 2017a)
indicates "Ancillary of other use of TCE" which
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EPA classified under the Other Industrial Use
OES.
96
PUBLIC COMMENTS:
TableApx E-3 is incorrect: The Occidental Chemical Corp, Wichita,
Wichita KS NPDES: KS0096903 facility does not release TCE to
surface water or to a POTW. Any TCE waste resulting from our
remediation extraction activities is disposed in the deepwell system.
The comment is noted and this surface water
release was removed from final risk evaluation.
96
PUBLIC COMMENTS:
Table Apx E-3 is incorrect: The Oxy Vinyls LP - Deer Park PVC, Deer
Park, TX NPDES: TX0007412 facility does not use TCE in other
industrial uses. TCE measured, if any, is from legacy disposal
remediation at the site.
The TRI submission from the Oxy Vinyls LP
facility in Deer Park, TX indicates "Ancillary of
other use of TCE" which EPA classified under
the Other Industrial Use OES.
96
PUBLIC COMMENTS:
Table Apx E-3 is incorrect: The Occidental Chemical Corp, Niagara
Plant, Niagara Falls, NY NPDES: NY0003336 facility does not use
OES as an industrial processing aid. TCE is not used as an industrial
process aid at the facility; TCE measured, if any, is from legacy
disposal remediation at the site.
The SIC for the Occidental Chemical
Corporation Niagara Plant reported in DMR (SIC
2812) (U.S. EPA 2016a) translates to a NAICS
code of 325180. This facility has been grouped
with other facilities with the same/similar
NAICS codes that have listed TCE use as an
industrial processing aid in TRI.
96
PUBLIC COMMENTS:
Table Apx 1-3 is incorrect: The Occidental Chemical Corp,
Wichita, Wichita KS does not produce TCE in the annual volume at
or greater than the production volume listed in Table_ApxI-3. The
daily production volume in the table is also inaccurate and is greater
than actual daily production values. Finally, there are no wastewater
flows to surface water or a POTW from the site that contain TCE.
Table Apx P-4 is incorrect: The Occidental Chemical Corp,
Wichita, Wichita KS does not produce TCE at or greater than the
annual or daily production volume listed in Table_Apx-P-4. There
are no wastewater flows to surface water or a POTW from the site
that contain TCE so the maximum, average, and annual release
The 2015 annual production volumes in the 2016
CDR (U.S. EPA 2016c) for this site was either
claimed as CBI or withheld. EPA estimated the
production volume by subtracting known site
production volumes from the national production
volume and averaging the result over all the sites
with CBI or withheld production volumes and
converting from pounds to kilograms.
The SIC for the Occidental Chemical Corporation
Niagara Plant reported in DMR (SIC 2812) (U.S.
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columns should be zero (0).
Table Apx P-30 is incorrect: The Occidental Chemical Corp,
Niagara Plant, Niagara Falls, NY NPDES: NY0003336 facility does
not use OES as an industrial processing aid. TCE is not used as an
industrial process aid at the facility; TCE measured, if any, is from
legacy disposal remediation at the site.
EPA 2016a) translates to a NAICS code of
325180. This facility has been grouped with other
facilities with the same/similar NAICS codes that
have listed TCE use as an industrial processing
aid in TRI.
Editorial comments
SACC
SACC COMMENTS:
General:
All references to documents should also include a link to the
appropriate record in the EPA HERO database.
Be mindful to use the proper number of significant figures.
There are problems with formats in several tables.
Add a footnote to tables listing HE and CT indicating what they
mean.
Acronyms and labels used in the draft risk evaluation should be
sufficiently long and distinct enough to perform searches: acronyms
such as "El" and "E3" are insufficient.
Use the word "sex" instead of "gender," since sex refers to
biological difference whereas gender is a social construct.
Supplemental document references are now all
linked to the docket where they are contained.
Significant figures have been reviewed, however
inconsistencies in significant figures result from a
preference for providing additional clarity when
presenting values that can differ by several orders
of magnitude. EPA has corrected any problematic
formats in tables; HE = high-end, CT= central
tendency. EPA attempts to use acronyms that are
consistent throughout the document and with
other Risk Evaluations. "Gender" has been
changed to "sex" throughout the document.
SACC
SACC COMMENTS:
Specific:
Pages 115-116, lines 1250-1256: provide citations to OSHA and
NIOSH hierarchy of exposure controls.
Page 119: protect workers from exposure; line 1354 add citations.
Page 119, lines 1359-1361: something is missing in the sentence,
suggest alternative with commas: "Respirator selection provisions
are provided in ง 1910.134(d) and require that appropriate
respirators are (be) selected based on the respiratory hazard(s) to
which the worker will be exposed, and (including) workplace and
user factors that affect respirator performance and reliability."
Page 120, line 1371: provide the reference to the ACGIH TLVs, not
to ATDSR, which is a secondary source. Unclear why primary
Citations have been added to the document as
requested.
The text has been revised accordingly to fix any
errors.
For page 259, EPA has added clarifying
language to indicate whether toxicity values are
ECsos, LCsos or NOECs or LOECs. As
mentioned earlier, EPA derived the geometric
mean, because the hazard values for all three
species were similar, and because EPA had more
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sources of information or data are sometimes not used.
Page 240, line 2110: "kidney" needs to be changed to "liver."
Page 259, lines 25-26 states: "For acute exposures to invertebrates,
toxicity values ranged from 7.8 to 33.85 mg/L (integrated into a
geometric mean of 16 mg/L). For chronic exposures, toxicity values
for fish and aquatic invertebrates were as low as 7.88 mg/L and 9.2
mg/L, respectively." The Committee was uncertain as to what these
values are. Are they median lethality values? ECsos? NOAELs?
LOAELs? What is the justification for using a geometric mean? The
second sentence discusses chronic values for fish and invertebrates;
what do these values represent?
Figures in Appendix F are captioned as "tables."
confidence in a COC derived from a geometric
mean for three species than a COC derived from
one value from one species. EPA added a
justification for using the geometric mean in
calculating an acute COC in the 3.1.5 Section of
the Risk Evaluation.
SACC
SACC COMMENTS:
Recommendations: (1) Modify Tables 2-7, 2-8, and 2-9 to make it clear
they refer to estimated concentrations. (2) Modify Table 2-2 to clarify
that it applies to water releases.
A Committee member had difficulty finding an estimate of the total
pounds of TCE released to waterways. The problem formulation
lists 52 pounds for 2015 (Problem Formulation, p. 31 Table 2-7,
U.S. EPA, 2018). Later in that document, there is a release value
from DMR data of 1,564 pounds (p. 34, Section 2.3.4).
The Committee recommended that EPA make it clear that Table 2-
7, 2-8, and 2-9 present estimated aqueous concentrations. Table
titles and figure captions should "stand alone." The captions should
better distinguish between estimated and measured aqueous
concentrations. Similarly, it is not clear that Table 2-2 refers to
water releases.
Additional comments on Table 2-2 and associated text noted by
members:
Estimated daily releases per COU depend heavily on TRI and DMR
data for 2016 and assumes 260 days of operation per year.
Impact on TRI data comes only from those manufacturers/
processors having 10 full-time employees, and that handle greater
Regarding the recommendations, (1) The three
table titles have been edited as recommended, (2)
Table 2-2 has been updated to clarify that it
refers to water releases.
The total mass of TCE released to water was not
presented as EPA's analvsis uses TRI (U.S. EPA
2017s) and DMR (U.S. EPA 2016a) to estimate
the highest local per site water releases of TCE.
The assumptions and uncertainties associated
with using TRI and DMR data sources are
discussed in Section 2.2.2.3 and Section 4.3.
Page 405 of 408
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than 25,000 pounds (manufacturers) or 10,000 pounds (processors).
Impact on DMR data of requirement to load major discharger data,
but optional to load minor discharger data, and the fact that
distinction between major/minor is set independently by each state.
SACC
SACC COMMENTS:
Recommendation: Correct issues with Figure 3-1.
The green algae Raphidocelis subcapitata is formally called
Pseudokirchneriella subcapitata. In the environmental hazard data
extraction table for TCE (U.S. EPA, 2020b), the label
Pseudokirchneriella subcapitata is used. In Figure 3-1, the newer
name Raphidocelis subcapitata is used. The Committee suggested
using the most recent taxonomic nomenclature consistently
throughout.
The green algae (Raphidocelis subcapitata) has a toxicity value
from the Data Extraction Table of logl0(411.5) = 2.61 [Medium
quality (Lubra et al., 2010) and high quality (Tsai and Chen, 2007)]
whereas in Figure 3-1, the toxicity value for Raphidocelis
subcapitata is shown at a value below 2.
Value for the diatom (Skeletonema costatum) in Figure 3-1 is below
2, whereas the value should be logl0(122.5) = 2.088 [Medium
quality (Ward et al., 1986)].
The value for green algae (Parachlorella kessleri) in Figure 3-1 at
toxicity value of logl0(640) = 2.8 [Medium quality (Lukavsky et
al., 2011)] is not included in the figure.
The value for the green algae (Chlamydomonas reinhardtii) in
Figure 3-1 at a toxicity value of logl0(24.4) = 1.39 [High quality
72-hour (Brack and Rottler, 1994)] is not included in the figure.
Other specific comments:
Genus previously Rana is now Lithobates (draft risk evaluation p.
190, lines 9293 and throughout).
Also note that developmental effects could result in premature
mortality in these aquatic organisms (p. 191, lines 98-102).
Please be specific regarding the term "mild intoxication." If this is
Scientific name updates have been made in their
respective sections.
EPA double checked on the toxicity values listed
in Figure 3-1. Some values were used because
they were either more relevant or of higher
quality than others. Each toxicity value used in
the SSDs were listed in Appendix El for full
transparency.
A mention of developmental effects potentially
resulting in premature death was added to
Section 3.1.2.
In terms of describing "mild intoxication"
further, the original study, Ward et al. (1986), did
not specify what behaviors were included in this
description.
Page 406 of 408
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narcosis or lethargy, please state as such (draft risk evaluation p.
192, line 144).
56, 108
PUBLIC COMMENTS:
The scheme used to calculate the overall rating for a particular study is
not clearly presented in either the updated criteria document or the draft
risk evaluation. For the following equation, the subscripts of i and j are
not defined, and the final subscript of 0.1 is not explained. From this
description, it is not possible to see how EPA OPPT calculated its
overall ratings.
EPA's systematic review is currently based on
Application of Systematic Review in TSCA Risk
Evaluations. Revisions to systematic review are
under development {Systematic Review Protocol
Supporting the TSCA Risk Evaluations) , EPA
anticipates feedback from the NASEM TSCA
Committee on its systematic review process,
including the epidemiological data quality
criteria, and will carefully review and implement
relevant recommendations.
94
PUBLIC COMMENTS:
In the text: "contrasts within the study population and were either
1) comparisons of groups exposed and not exposed to [TCE]..," there
appears to be a typographical error, because the sentence refers to
perchloroethylene instead of TCE.
EPA appreciates the commenter pointing out this
error. The paragraph should refer to TCE, not
perchloroethylene.
Miscellaneous
31
PUBLIC COMMENTS:
Restriction of such a substance would be in violation of free-trade, and
could therefore pose, an unmitigated threat to our capitalist society. As
such, TCE should be allowed as an intermediate in the process of
manufacturing hydrofluorocarbon HFC-134a.
Thank you for your comment. Per 15 U.S.C
ง 2605, EPA is required to prioritize, evaluate
and manage unreasonable risks of chemical
substances and mixtures.
35
PUBLIC COMMENTS:
Why isn't there any mention of fetal heart defects or warnings for
pregnant women? There should be warnings. We don't want to cause
birth defects unknowingly.
89
PUBLIC COMMENTS:
The petro-chemical industry has a vested interest in seeing the
allowable levels of TCE made very high; banning of TCE would require
Page 407 of 408
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finding an alternative to this very powerful (and very toxic) chemical.
We cannot continue to put the interests of the petro-chemical industry
ahead of the value of human lives. Please maintain stricter levels of
presence of TCE in ground and drinking water, vapor intrusion levels,
and dermal contact.
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