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CDA United States Office of Chemical Safety and
v/tm Environmental Protection Agency Pollution Prevention
Summary of External Peer Review and Public Comments and
Disposition for C.I. Pigment Violet 29 (PV29)
(Anthra[2,l»9-def:6,5,10-d'eT]diisoquinoline-
l,3,8,10(2H,9H)-tetrone)
Response to Support the Revised Draft Risk Evaluation of
C.I. Pigment Violet 29
CASRN: 81-33-4
October 2020
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Contents
Contents 2
Introduction 6
List of Comments Submissions 7
Comment Summary 10
Overall Content, Organization, and Presentation of the Draft Risk Evaluation 10
Draft was sufficiently clear and transparent 10
Need to improve clarity, transparency, and organization of rationale and conclusions 10
Need to improve clarity and transparency of study quality evaluations 12
Include measures and discussion of uncertainty and variability with numerical values 14
Need to improve transparency of risk evaluation process and procedures 14
Report would be improved by adding graphics, figures, and/or tables 16
Need to improve transparency of external review processes 17
Need to improve access to information sources 17
Need to improve transparency of occupational exposure data and PV29 uses 19
Need to improve clarity and transparency of study quality evaluations 21
EPA did not use its legal authority under TSCA to collect data, and it should 22
Violation of TSCA by not releasing full studies due to CBI claims 23
Support for EPA's handling of CBI 25
Update risk evaluation to reflect availability of studies that were previously redacted 26
Include description of the ramifications of the final risk statement 26
Systematic Review Approaches and Clarity 28
Need to describe the rationale for developing a systematic review method specific to
TSCA 28
Need to initiate an external peer review of the TSCA systematic review protocol 28
Need to develop, peer review, and publish systematic review protocols prior to conducting
TSCA risk assessments 29
Concerns that the TSCA systematic review method does not follow best scientific
practices and should be replaced 30
Need to more clearly describe the systematic review protocol and procedures 32
Need to provide a more thorough discussion of data integration 34
Insufficient data concerns and handling of lack of data 35
Concerns about the quality of the body of evidence for PV29 36
Concerns relating to the personal communication from Sun Chemical 37
Need for public access to data 38
Study quality evaluation and scoring concerns 39
TSCA systematic review method was effective for PV29 42
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Include discussion of toxicity of byproducts of manufacturing and impurities in PV29 43
Physical Chemical Properties and Environmental Fate 45
Concerns about water solubility study and value EPA used 45
Remove statements that low aqueous solubility precludes oral bioavailability 46
Use alternative methods to generate information to evaluate bioavailability 46
Concerns about use of EPI Suite 46
Lack of clarity and data to support conclusions regarding bioaccumulation potential 48
Supportive of conclusion that PV29 is poorly absorbed 48
Ensure consistency or justify differences among physicochemical properties across the
assessment 48
Consider metabolic pathway prediction software to identify intermediates 48
Concerns about environmental persistence and fate evaluation and lack of data 50
Exposure and Releases 51
Supportive of EPA's occupational exposure assessment 51
Incorporate uncertainty analysis and screening-level fugacity modeling in life cycle safety
assessment 52
EPA did not consider full range of uses and exposure pathways 52
EPA failed to consider workers experiencing multiple routes of exposure 56
Deficiencies in exposure data and analysis 56
Opposition to EPA's reliance on personal communication from Sun Chemical 58
Concern regarding EPA's approach to evaluate only highest anticipated exposure 59
Supports tiered approach that incorporates PPE in the exposure assessment 61
Opposes assumption of PPE use in the exposure assessment 61
EPA should not rely on the presence of and compliance with safety data sheets (SDS) 62
EPA should prioritize engineering controls over PPE or warning labels to reduce exposure63
Concerns about lack of release data 64
Support for EPA's engagement with industry to obtain data 64
Concerns about occupational inhalation exposure assessment assumptions and parameters64
Concerns about occupational dermal exposure analysis and clarity 65
EPA should revisit its decision not to assess occupational oral exposure 66
EPA did not properly assess exposure of downstream processors and users 67
Concerns about the environmental release characterization 68
EPA did not consider environmental release of PV29 when used as an intermediate 71
Concern about assumption that PV29 remains "bound" in downstream use 71
EPA was right to remove conditions of use it was unable to support 72
Evaluation lacks information on conditions of use 72
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Inadequate characterization of potentially exposed or susceptible sub-populations (PESS) 74
Support for and request for clarity regarding quantitative screening-level exposure
assessment 75
EPA did not address exposures in pregnant women, children, and other downstream users 76
EPA was correct to focus on sentinel exposure 77
Support for aggregate exposure vs. sentinel exposure assessment 77
EPA should pursue exposure and releases information from a wider range of organizations78
Other SACC comments related to physical chemical properties 78
Environmental Effects 79
Need for more data to evaluate hazard to aquatic ecological receptors 79
Do not ignore Topkat-predicted acute LC50 for fathead minnow 80
Need to better describe how log Koc was determined 81
Concerns about ecological hazards for sediment-dwelling invertebrates 81
Need for more data to evaluate hazard to terrestrial ecological receptors 82
Concerns about citing the Canadian Ecological Risk Classification for PV29 as support for
determination 83
Support for EPA's characterization of hazard to ecological receptors 84
Concerns about studies where observed exposures exceed water solubility limit 85
Human Health 86
Support for EPA's approach and conclusions regarding human health risk 87
Make hazard conclusions specific to routes of exposure 87
Clarify value of the screening reproductive/developmental toxicology study and highlight
data gaps 88
The toxicity studies EPA used are unreliable 88
EPA improperly disregarded intraperitoneal studies 89
EPA did not use data from similar substances 90
EPA should acquire additional studies due to insufficient data 90
Increase transparency of evidence used to determine carcinogenic risk 92
Concerns about route-to-route extrapolation and lack of uncertainty factor 92
MPPD model requires size distribution of PV29 in workplace aerosols 93
Present models or NAMs to improve understanding of absorption potential 93
Concerns about lack of scientific evidence for EPA's conclusion regarding absorption
potential 93
Consumer hazard is not fully investigated 94
Obtain more occupational hazard data 95
Clarify uncertainties and justify conclusions regarding susceptibility 96
There are no vulnerable subpopulations 98
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Risk Characterization/Risk Determination 98
Support for the conclusions in the draft risk characterization 98
The conclusions in the draft risk characterization are flawed due to lack of data 100
EPA should order the development and submission of additional information 102
EPA's reliance highly uncertain fate and persistence information casts doubt on its risk
conclusions 102
Criticism of the margin of exposure (MOE) approach and clarity 103
Supports EPA's use of the MOE approach 104
Concerns about CBI affecting the risk characterization 105
Need to apply additional uncertainty factors 105
Use of intraspecies uncertainty factor was conservative 106
Occupational risk characterization is flawed 107
Need to expand the risk characterization narrative 108
Need additional guidance on when higher-tier assessments will be triggered for future risk
evaluations 108
Supplemental Analysis 110
EPA needs more current and/or accurate inhalation exposure data 110
Supplemental inhalation analysis improves risk evaluation, but clarify sources of
uncertainty Ill
Supplemental inhalation analysis is inadequate Ill
Peer Review Comments on Whether or Not Information in the CBI Materials Was
Accurately Reflected in the Publicly Available Summaries 112
Include justifications for redactions by companies 112
Provide summaries of differences between full and redacted study reports 113
Allow certain parties to examine full study reports 114
Other Peer Review Comments 114
Cited References 114
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Introduction
EPA published the Draft Risk Evaluation for C.I. Pigment Violet 29 (PV29) on November 15, 2018 and
accepted public comments until January 14, 2019. EPA accepted additional public comments from April
17, 2019 until May 17, 2019 following the release of 24 studies used in the draft risk evaluation of C.I.
Pigment Violet 29, as well as the updated systematic review documents. EPA accepted a third round of
public comments from June 10 to July 10, 2019 due to the publication of the PV29 Inhalation Risk
Characterization Summary and the Updated Charge Questions for the peer review meeting of EPA's
Science Advisory Committee on Chemicals (SACC) on the draft risk evaluation on June 18 to 21, 2019.
Materials on the draft risk evaluation are available at www.regulations.gov in docket EPA-HQ-OPPT-
2019-0437.
This document summarizes the external peer review and public comments that EPA's Office of Pollution
Prevention and Toxics (OPPT) received for the risk evaluation of C.I. Pigment Violet 29 (PV29). It also
provides EPA/OPPT's response to the comments received from the peer review panel and the public.
EPA/OPPT appreciates the valuable input provided by the peer review panel and the public. 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 ten main themes.
1. Overall Content, Organization, and Presentation of the Document
2. Systematic Review Approaches and Clarity
3. Physical Chemical Properties and Environmental Fate
4. Exposure and Releases
5. Environmental Effects
6. Human Health
7. Risk Characterization and Risk Determination
8. Supplemental Analysis
9. Peer Review Comments on Confidential Business Information (CBI) Material
10. Other Peer Review Comments
All peer review comments for the nine charge questions are presented first, organized by charge question
in the following section. These are followed by the public comments.
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 Submissions
#
Docket File
Submitter
8
EP A-HO-OPPT-2018-0604-0008
Stacy Tatman, Director, Environmental Affairs, Alliance of Automobile
Manufacturers (Alliance)
9
EP A-HO-OPPT-2018-0604-0009
Michelle Roos, Executive Director, Environmental Protection Network
(EPN)
10
EP A-HO-OPPT-2018-0604-0010
Georges C. Benjamin, Executive Director on behalf of American Public
Health Association (APHA)
11
EP A-HO-OPPT-2018-0604-0011
David Michaels, Epidemiologist, Professor, Environmental and
Occupational Health, Milken Institute School of Public Health, George
Washington University
12
EP A-HO-OPPT-2018-0604-0012
Jonathan Kalmuss-Katz, Staff Attorney, Earthjustice and Randy
Rabinowitz, Executive Director, Occupational Safety & Health Law
Project
13
EP A-HO-OPPT-2018-0604-0013
Richard A. Denison, PhD, Lead Senior Scientist, on behalf of
Environmental Defense Fund (EDF)
14
EP A-HO-OPPT-2018-0604-0014
Veena Singla, Associate Director, Science and Policy, Program on
Reproductive Health and the Environment, University of California, San
Francisco (UCSF) et al.
15
EP A-HO-OPPT-2018-0604-0015
Brett Fox, International Union, United Automobile, Aerospace, and
Agricultural Implement Workers of America (UAW)
16, 16(S)
EP A-HO-OPPT-2018-0604-0016
Liz Hitchcock, Acting Director, Safer Chemicals Healthy Families et al.
17
EP A-HO-OPPT-2018-0604-0017
Suzanne Hartigan, Senior Director, Regulatory and Technical Affairs,
American Chemistry Council (ACC)
18
EP A-HO-OPPT-2018-0604-0018
Rebecca L. Reindel, Senior Safety & Health Specialist, AFL-CIO
19
EP A-HO-OPPT-2018-0604-0019
David Wawer, Executive Director, Color Pigments Manufacturers
Association (CPMA)
20
EP A-HO-OPPT-2018-0604-0020
Ansje Miiller, Director of Policy and Partnerships, Center for
Environmental Health et al.
37
EP A-HO-OPPT-2018-0604-003 7
Jennifer Sass, Senior Scientist, Natural Resources Defense Council
(NRDC)
43
EP A-HO-OPPT-2018-0604-0043
Hanna Vesterinen, Research Consultant to UCSF PRHE et al.
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#
Docket File
Submitter
44
EP A-HO-OPPT-2018-0604-0044
Jonathan Kalmuss-Katz, Staff Attorney, Earthjustice and Randy
Rabinowitz, Executive Director, Occupational Safety & Health Law
Project
45
EP A-HO-OPPT-2018-0604-0045
David Wawer, Executive Director, Color Pigments Manufacturers
Association, Inc. (CPMA)
46, 46(S)
EP A-HO-OPPT-2018-0604-0046
Richard A. Denison, Environmental Defense Fund (EDF)
47
EP A-HO-OPPT-2018-0604-0047
Suzanne Hartigan, Senior Director, Regulatory and Technical Affairs,
American Chemistry Council (ACC)
48
EP A-HO-OPPT-2018-0604-0048
Liz Hitchcock, Acting Director, Safer Chemicals Healthy Families
(SCHF) et al.
49
EP A-HO-OPPT-2018-0604-0049
Kathy Pope, Environmental Protection Network (EPN)
55
EP A-HO-OPPT-2018-0604-005 5
Liz Hitchcock, Safer Chemicals Healthy Families (SCHF) et al.
71
EP A-HO-OPPT-2018-0604-0071
Richard A. Denison, Environmental Defense Fund (EDF)
72
EP A-HO-OPPT-2018-0604-0072
Suzanne Hartigan and Christina Franz, Senior Directors of Regulatory
& Technical Affairs, American Chemistry Council (ACC)
73
EP A-HO-OPPT-2018-0604-0073
Suzanne Hartigan, Senior Director of Regulatory & Technical Affairs,
American Chemistry Council (ACC)
74
EP A-HO-OPPT-2018-0604-0074
David Michaels, Department of Environmental and Occupational
Health, The George Washington University
75
EP A-HO-OPPT-2018-0604-0075
Gary E. Timm, Environmental Protection Network (EPN)
76
EP A-HO-OPPT-2018-0604-0076
Jennifer Sass, Natural Resources Defense Council (NRDC)
77
EP A-HO-OPPT-2018-0604-0077
Georges C. Benjamin, Executive Director, American Public Health
Association (APHA)
78
EP A-HO-OPPT-2018-0604-0078
Jonathan Kalmuss-Katz, Staff Attorney, Earthjustice et al.
79
EP A-HO-OPPT-2018-0604-0079
Suzanne Hartigan, Senior Director, Regulatory and Technical Affairs,
American Chemistry Council (ACC)
80
EP A-HO-OPPT-2018-0604-0080
Michelle Roos, Environmental Protection Network (EPN)
81
EP A-HO-OPPT-2018-0604-0081
Swati Rayasam et al., Science Associate, Program on Reproductive
Health and the Environment, Department of Obstetrics, Gynecology and
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#
Docket File
Submitter
Reproductive Sciences, University of California, San Francisco (UCSF
PRHE)
82
EP A-HO-OPPT-2018-0604-0082
Natural Resources Defense Council (NRDC) and Safer Chemicals
Healthy Families (SCHF)
SACC
N/A
Science Advisory Committee on Chemicals (SACC)
(S) = Supplemental documents were provided with the comment and included in the summary
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Comment Summary
Overall Content, Organization, and Presentation of the Draft Risk Evaluation
Charge Question 1: Please comment on the overall content, organization, and presentation of the draft risk evaluation of PV29. Please
provide suggestions for improving the clarity and transparency of the information presented in the documents.
#
Summary of Comments for Specific Issues Related to
Charge Question 1
EPA/OPPT Response
Draft was sufficiently clear and transparent
8, 17
PUBLIC COMMENTS:
EPA's draft risk evaluation for PV29 is
transparent in areas where the evaluation diverged
from the problem formulation document, and in
most cases, provided reasoning for changes. (8 1,
17_5) (note to reviewers, these parentheticals are
used for EPA internal comment tracking purposes
and will be removed from the final Response to
Comment Document).
EPA clearly indicates that the conditions of use
have been modified slightly since the problem
formulation phase of the assessment. (8 7)
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.
Need to improve clarity, transparency, and organization of rationale and conclusions
SACC,
8, 17
SACC COMMENTS:
Carefully review and revise the Evaluation to
ensure a logical and coherent flow to the
discussion, and, to ensure that justifications are
near their associated conclusions. The Committee
noted that throughout the document, conclusions
are stated without referencing the appropriate
source or analysis that supports it. Sometimes
these conclusions occur due to how the Evaluation
is organized, forcing the reader to search a later
part of the document or an entirely different
document for the justification of the conclusion.
An example of this occurs in Section 2.4.2
Conceptual Models (page 14) that assumes that
EPA has updated the risk determination format for increased
clarity regarding the unreasonable risk determination and the
risk considerations for each condition of use. 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.
While EPA believes that discussions of the rationale for the
determination of unreasonable risk is outside the scope of the
SACC, EPA is committed to providing the public with
sufficient information on the basis for that determination.
TSCA requires EPA to determine whether chemicals in the
marketplace present unreasonable risks to health or the
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PV29 has low hazard and limited exposures (a
conclusion) to justify the model before hazard
(Section 3) and exposure (Section 4) have been
discussed.
Clearly state preliminary suppositions in the final
risk determination and ensure that the hazard
statement contains associated limitations and
uncertainties. The Committee noted that there is
information reported in EPA's Problem
Formulation document that is referenced in the
risk assessment. This information represents
preliminary suppositions not discussed in a
definitive manner in the Evaluation. Of most
concern to the Committee were the preliminary
suppositions that impacted Human Exposures
(Section 3.3). The Committee concluded that
broad statements such as "low hazard was
reported for all routes of exposure in human health
testing" did not adequately portray the associated
uncertainty due to limited data and endpoints
considered. The hazard statement at a minimum
should identify the animal models and endpoints
used.
Define unreasonable risk under the TSCA
legislative requirement and describe in general
how the threshold between reasonable and
unreasonable risk is determined.
Consider using the slide presentation given by
EPA on Thursday as a guide for organizing the
draft risk assessment document.
PUBLIC COMMENTS:
At present, OPPT does not sufficiently describe its
rationale for the conclusion of "no unreasonable
risk" for PV29. While we support this
determination, we have concerns about how this
method will be applied to future chemical risk
environment. While the law does not specifically define this
term, during the risk evaluation process EPA weighs a variety
of factors including the effects of the chemical on human health
or the environment, who are exposed (including any sensitive
subpopulations), the severity of the hazard, and uncertainties.
This approach is outlined in EPA's 2017 Procedures for
Chemical Risk Evaluation Under the Amended Toxic
Substances Control Act rule ("Risk Evaluation Rule") preamble
on how risk evaluations will be conducted. [82 FR 33726, at
33735 (July 20, 2017)] Each draft risk evaluation details those
factors and describes for the public which conditions of use
were preliminarily identified to have unreasonable risk for a
chemical. For PV29, these factors included workplace
exposures based on monitoring information from the sole U.S.
manufacturer, Sun Chemical. When appropriate, in the risk
evaluation, EPA will consider exposure scenarios both with and
without engineering controls and personal protective equipment
(PPE) that may be applicable to particular worker tasks on a
case-specific basis for a given chemical. These assumptions are
described in the uncertainties sections that were added
throughout the final Risk Evaluation to more adequately discuss
uncertainties and their effect on the unreasonable risk
determination for each condition of use in Section 5.2.
TSCA requires EPA to use reasonably available information
and best available science in its risk evaluation. Utilizing the
systematic review process, EPA used reasonably available data
and best available science in a weight of the scientific evidence
analysis. EPA identified uncertainties regarding the information
that is reasonably available to characterize PV29's solubility
and occupational worker inhalation exposure in Section 2.3.4 of
the final Risk Evaluation. These uncertainties resulted in EPA
requiring testing of PV29 to develop and submit new
information in order for EPA to increase certainty in the final
Risk Evaluation of PV29 under TSCA section 6(b). Test data
has been reviewed for data quality according to the relevant
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#
Summary of Comments for Specific Issues Related to
Charge Question 1
EPA/OPPT Response
evaluations. We request that OPPT expand the
narrative in the risk evaluation document to more
clearly describe how the available information
supports its findings. (8 6)
EPA should consider making clear how it
determined the existing data set was sufficient to
develop a risk characterization and determination.
(17 1)
data quality evaluation metrics and incorporated into the final
Risk Evaluation.
Need to improve clarity and transparency of study quality evaluations
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17, 46
PUBLIC COMMENTS:
More detail in the risk evaluation regarding how
EPA evaluated study quality would improve
transparency. (1714)
EPA should always make study reviewer
comments public in order for the public to
understand the rationale behind its study quality
scoring decisions and to have a transparent record
of when and why changes to scores are made.
(4611)
Along with publishing the problem formulation for PV29, EPA
published the inclusion/exclusion criteria statements used
during full text screening for each chemical in appendices to
those documents as well as a separate document titled
Application of Systematic Review in TSCA Risk Evaluations that
described the data quality criteria used for each discipline and
outlined data integration strategies which are being used for the
risk evaluations.
EPA initially released the SR Supplemental File without the
EPA reviewer's comments due to concerns that the comments
might contain information claimed CBI. The Updated SR
Supplemental File, released on April 4, 2019, made publicly
available the EPA reviewer's comments related to the data
quality evaluation of the physical chemical characteristics,
environmental fate, environmental hazard and human health
studies (EPA-HO-OPPT-2018-0604-0040). EPA is making
reviewer comments public with the release of the Systematic
Review Companion documents for the final Risk Evaluation to
increase transparency. In addition, an ad hoc committee of the
National Academies of Sciences, Engineering, and Medicine is
reviewing EPA's guidance document on Application of
Systematic Review in TSCA IToxic Substances and Control Actl
Risk Evaluations (EPA 2018) and associated materials
developed subsequent to its issuance. The committee is
considering public comments on the document, EPA's
responses to public comments, and enhancements to the
systematic review process reflected in documentation of the
first 10 chemical risk evaluations. The committee will
determine whether EPA's process is comprehensive, workable,
objective, and transparent. Recommendations for enhancements
to EPA's 2018 guidance document will be made. More
information and details about the NAS review effort are
available here: httDs://www.nationalacademies.or«/our-
work/review-of-epas-tsca-svstematic-review-mii dance-
document
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#
Summary of Comments for Specific Issues Related to
Charge Question 1
EPA/OPPT Response
Include measures and discussion of uncertainty and variability with numerical values
SACC,
46
SACC COMMENTS:
Include measures and discussion of uncertainty
and variability with all numerical values. The
SACC Committee noted that in the Evaluation,
numerical values are presented without associated
statements of confidence or measures of
variability, especially the physical-chemical
values. The Committee noted that risk
assessments typically include discussions of
uncertainty and variability with reported values.
The scientifically reasoned basis for inclusion,
exclusion or selection of data values is also
expected. For example, is the indirect
photodegradation half-life of 7 hours listed in
Table 3-1 consistent with overall conclusions that
the chemical is very persistent? Estimates of water
solubility of PV29 are also inconsistent.
PUBLIC COMMENTS:
Major data gaps have not been acknowledged or
addressed by EPA. EPA needs to forthrightly
address the data gaps and uncertainties including
those flagged by EU authorities. (46_27)
EPA has made an effort to increase the discussion of
uncertainty surrounding the numerical values used in the
assessment in Section 4 of the final Risk Evaluation. Where
applicable, the use of a particular value over another is
explained and justified with a discussion of uncertainties.
EPA identified uncertainties regarding what information was
reasonably available to characterize PV29's solubility and
occupational worker inhalation exposure in Section 2.3.4, as
well as EPA responses to the submitted information from the
Section 4 Test Order in the Test Order docket (EP A-HQ-OPPT-
2020-0070-0008). These uncertainties resulted in EPA
requiring testing of PV29 to develop new information in order
for EPA to increase certainty in the final Risk Evaluation of
PV29 under TSCA section 6(b). Test data has been reviewed
for data quality according to the relevant data quality evaluation
metrics and incorporated into the final Risk Evaluation so that
uncertainty is reduced.
Need to improve transparency of risk evaluation process and procedures
SACC,
8,13,
17, 49
SACC COMMENTS:
Include a short history or basis on why PV29 was
originally selected for inclusion on EPA's Work
Plan and discuss how those concerns have been
addressed in the assessment. The Committee felt
that this section is important in establishing the
justification for the risk evaluation and provides
In the Introduction (Section 1) of the final Risk Evaluation EPA
incorporated a narrative explaining the basis for the inclusion of
PV29 on the TSCA Work Plan, which was developed as a
screening tool prior to full risk assessment. The final Risk
Evaluation also describes the current understanding of the
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context and importance for the final risk
determination.
PUBLIC COMMENTS:
Guidance documents that detail the internal
processes and procedures for risk evaluation under
TSCA should be generated and made publicly
available. (17_27)
EPA's description of its approach to data
integration in its draft risk evaluation for PV29 is
severely lacking. (13 231)
EPA should provide more detail on the tiered
approach used in this risk evaluation. This should
include developing guidance detailing its tiered
assessments process, especially on how EPA will
conduct higher-tier assessments triggered by
lower-tier outcomes. (1710, 17_28)
Recommend that EPA provide additional
information regarding why a quantitative
screening-level exposure assessment was added.
(8 8, 17 6)
EPA should clarify why PV29 was poorly
characterized for the Work Plan, and how the
lessons from that characterization might inform
EPA's prioritization process for the TSCA Active
Inventory. (17 22)
The lack of transparency in this risk evaluation
will create a precedent of making "no
unreasonable risk" determinations based on
proprietary information. (491)
chemical's risks as a result of the full TSCA risk evaluation
EPA has finalized and made publicly available a document
Application of Systematic Review in TSCA Risk Evaluations to
provide the public with continued transparency regarding how
EPA plans to evaluate scientific information. This document
outlines EPA's initial work on systematic review. This
document can be accessed at: https://www.epa.gov/assessing-
and-managing-chemicals-under-tsca/application-svstematic-
In addition, EPA anticipates feedback from the National
Academy of Sciences (NAS) on its systematic review process
and will carefully review and implement relevant NAS
recommendations as appropriate. EPA has incorporated
references to this process in the final Risk Evaluation document
in Section 1.6 of the final Risk Evaluation
EPA continues to improve upon its data integration strategies,
which are expected to be more formal and structured for the
next set of TSCA chemical risk evaluations. The anticipated
feedback from the NAS on EPA's systematic review process
will inform this.
EPA is not implementing a fixed approach concerning tiered
risk evaluations as suggested by the commenter. As evidenced
by the Risk Evaluations for each of the first 10 chemicals
evaluated under TSCA, EPA is adopting a fit-for-purpose
approach which makes the determination based on the
reasonably available data characterizing the conditions of use,
hazards and exposures. The decision to adopt a screening-level
approach for the Risk Evaluation of PV29 was made as a result
of reasonably available information indicating hazards for all
routes of exposure except for inhalation are low, and exposures
through all routes except manufacturing, processing and
industrial/commercial uses are expected to be limited.
process.
review-tsca-risk-evaluations
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#
Summary of Comments for Specific Issues Related to
Charge Question 1
EPA/OPPT Response
With regard to the comment pertaining to proprietary
information, the Agency has made a final determination on the
CBI claims made for PV29 and this can be accessed at
FOIAonline at: https://foiaonline.sov/foiaonline/action/public
/submissionDetails?trackinsNumber=EPA-HO-2019-
001853 &tvpe=request
In all instances, non-CBI versions of the study reports were
made available to the Agency and can now be accessed in the
public docket.
Report would be improved by adding graphics, figures, and/or tables
SACC
SACC COMMENTS:
Develop a flowchart/decision tree to more
adequately describe the risk evaluation. The
Committee concluded that uncertainty in decisions
could be more transparently communicated and
evaluated using appropriate graphics. The
Committee discussed decision tree diagrams as
well as logic model diagrams. Such diagrams
could be adapted to display associated confidence
at each decision point in order to clarify overall
confidence in the conclusion (see also discussion
in Question 2).
Describe in more and better detail the systematic
review process (Section 2.5) and its results. The
results of systematic review are discussed in prose
where one or two diagrams would significantly
improve the clarity and transparency of the
process. Graphical and/or tabular summaries are
needed of the number of abstracts, reports and
manuscripts reviewed, and reports and
manuscripts accepted and rejected and at what
stage in the review process.
In response to these comments, EPA has integrated flow-charts
outlining the various steps of the literature search and the
number of references that were identified at each step of the
literature search and screening processes in Section 2.5.1. These
literature flow diagrams have also been incorporated into the
other evaluations for the first 10 chemicals evaluated under
TSCA. For additional information about how the literature
search strategy for PV29 was conducted, please consult the
document entitled, "Strategy for conducting literature searches
for Pigment Violet 29 (PV29): Supplemental document to the
TSCA scope document," available at:
httDs://www.eDa.sov/sites/Droduction/files/2017-
06/documents/pv29 lit search strategy 053017 O.pdf
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EPA/OPPT Response
Need to improve transparency of external review processes
16(S),
17, 82
PUBLIC COMMENTS:
Coordination with other federal agencies and other
EPA program offices should be clearly described.
(17 11)
The final Risk Evaluation should include all peer
reviewer comments and how EPA responded to
them. (16(S)_23)
EPA did not provide any means for the public to
know about and have confidence in the extent of
EPA CBI reviews, the determinations being
reached, and the provision of access to
information the law requires be provided. (82 6)
EPA's discussions and consultation with NIOSH are reflected
in the updated screening-level assessment of risks from
inhalation exposure in Section 4.4 of the final Risk Evaluation.
EPA does not share internal deliberative comments from the
interagency review process.
All EPA responses to SACC recommendations are provided in
this Response to Comment document. A final report of the
proceedings of the TSCA Scientific Advisory Committee on
Chemicals (SACC) meeting held on lune 18-21, 2019 has been
made oubliclv available in the docket (EPA-HO-OPPT-2018-
0604).
As explained in a March 21, 2019 transmittal memorandum
available in the docket, the Agency made a final determination
on the CBI claims of the studies used in this assessment which
can be accessed at FOIAonline at:
https://foiaonline.sov/foiaonline/action/public/
submissionDetails ?trackinsNumber=EPA-HO-2019-
001853&tvpe=request. In all instances, non-CBI versions of the
study reports were made available to the Agency and were
added to the public docket.
Need to improve access to information sources
SACC,
13, 17
SACC COMMENTS:
Provide cross references to relevant documents
and associated information. The Committee
understood that in order to keep the Evaluation
relatively short and concise, EPA chose to not
repeat information available in other documents or
information sources, primarily other EPA
documents that provide relevant guidelines. To
assist the reader, the risk evaluation document
EPA has made every effort to update the final Risk Evaluation
to provide links to accommodate easier access to all publicly
available information, data and guidance referenced in the risk
evaluation. This includes Safety Data Sheets, information
received from manufacturing stakeholders of C.I. Pigment
Violet 29 and the full study reports used in the evaluation. All
of these materials have been made publicly available in the
docket for C.I. Pigment Violet 29 ffiPA-HO-OPPT-2018-0604)
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should provide easy reference, and, where
possible, internet links to these key documents or
information sources. For example, reviewing the
section on "environmental release and exposure,"
a reader should be able to click on a link to
relevant EPA guidance documents on this topic.
The SACC noted that recent TSCA legislation
established that public review of (including access
to) supporting data is part of the process ensuring
transparency in the evaluation of health risk from
large quantity manufactured chemicals in the US.
All documentation and studies used for the
assessment, especially health and safety
information, should be made available to the
public. Access to certified CBI is still problematic.
PUBLIC COMMENTS:
EPA needs to link directly to the Safety Data
Sheets (SDSs) used in reviewing engineering
controls and PPE, or directly provide them.
(13172)
EPA should provide access to the SDS and
industry statements on which it relies to discount
potentially relevant routes of exposure. (13 172)
Sun Chemical's SDS is not available to the public;
without this SDS, it is not possible to assess the
accuracy of EPA's claims regarding engineering
controls and PPE. (13 173)
Most information obtained from industry should
have been made public, particularly the
approximate maximum workplace air
concentration and daily discharge rate from Sun
Chemical. (13 34)
EPA must immediately make public the details of
the Mott 2017 personal communication, and all
other personal communications relevant to the risk
evaluation. (13 170, 15 9)
in a supplement entitled, Supplemental File: Information
Receivedfrom Manufacturing Stakeholders U.S. EPA (2020a).
EPA has included copies of the Safety Data Sheets (SDSs) as
well as information received via correspondence with
manufacturing stakeholders that contain data used to
characterize occupational and environmental exposures to PV29
(including the Mott 2017 personal communication). These data
are available in a supplemental file in the docket for the final
Risk Evaluation entitled, "Supplemental File: Information
Receivedfrom Manufacturing Stakeholders" U.S. EPA (2020a)
EPA has worked with the data owners of the studies
summarized in the ECHA database and has included fully
unredacted or partially redacted versions of these studies in the
public docket for PV29 (EPA-HQ-QPPT-2018-06041 A
summary of the redaction status of each study report can be
found at https://www.regulations.gov/document?D=EPA-HQ-
QPPT-2018-0604-0021. The inclusion of the full study reports
increases the transparency of the Risk Evaluation process as it
relates to PV29.
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Summary of Comments for Specific Issues Related to
Charge Question 1
EPA/OPPT Response
The exposure sampling data and detailed
information should be available for public review
so that commenters can provide their own
interpretations to the docket. The public should
not have to rely on the judgment of the
manufacturer and the Agency that this is indeed
the maximum exposure level. (15 10, 15 15)
EPA should consider more clearly linking the
robust study summaries available on ECHA's
website to the outcome of the risk evaluation, to
enhance clarity in how the data were applied.
(17 8)
Need to improve transparency of occupational exposure data and PV29 uses
SACC,
13, 15,
16, 17,
18
SACC COMMENTS:
Include more information on production volume
and derivative products. The Committee discussed
the need for better discussion of PV29 production
volume in the report. Missing was a discussion of
how the quantity of PV29 produced makes this a
high production volume chemical, or how the
quantity produced relates to production volumes
of other priority chemicals or high production
chemicals. The Evaluation reports that 90% of
PV29 production is used to make another
pigment. This, combined with the observation that
the European Union (EU) is assessing risks of
both pigments together, suggested that the
assessment should discuss both pigments in a
single assessment. Needed is the rationale for why
EPA has chosen to assess PV29 alone. The
Committee would have also liked a
summary/comparison of the structure, toxicity
As indicated above, EPA has included a narrative explaining
the inclusion of PV29 on the TSCA Work Plan. Included in this
narrative is an explanation of how the total production volume
of the chemical relates to the current understanding of the
conditions of use. In particular, the vast majority of overall
production volume is consumed at the manufacturing site as an
intermediate for the production of other pigments. EPA also
notes that production volume of this chemical, -600,000 lbs. in
2015, falls well below the threshold for a high production
volume chemical which EPA considers to be 1,000,000 lbs;
therefore, a discussion of PV29 being a high production volume
chemical is not warranted. The risks of another pigment
produced using Pigment Violet 29 as an intermediate is outside
the scope of this risk evaluation. This chemical, if identified to
meet the criteria for assessment through the prioritization would
be considered in its own risk evaluation. PV29 was included in
the prioritization list without other perylene pigments because
information specific to PV29 were identified during the
prioritization process that indicated that it was potentially
hazardous to aquatic organisms. As explained in Section 1 of
the final Risk Evaluation, review of the data led EPA to
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concerns, and exposure profiles for both
chemicals.
PUBLIC COMMENTS:
EPA does not detail the efforts it made to research
all reported PV29 uses and explain why uses it
initially identified were dropped. (16 41)
EPA should provide information on how it
determines what conditions of use are in/out of
scope. (17_30)
This draft risk evaluation on PV29 is incomplete
and not transparent about the information it relied
on to assess health risk to working people.
(1816)
conclude that these aquatic toxicity data as well as other data
used in the prioritization process are no longer applicable to C.I.
Pigment Violet 29.
Regarding the decision to assess PV29 alone, EPA incorporated
a narrative explaining the basis for the inclusion of PV29 on the
2012 Work Plan in the Introduction (Section 1) of the final Risk
Evaluation.
A list of "other uses" was compiled during EPA's initial search
for PV29 conditions of use. This list of other uses included the
following: Applications in odor agents, cleaning/washing
agents, surface treatment, absorbents and adsorbents, laboratory
chemicals, light-harvesting materials, transistors, molecular
switches, solar cells, optoelectronic devices, paper, architectural
uses, polyester fibers, adhesion, motors, generators, vehicle
components, sporting goods, appliances, agricultural equipment
and oil and gas pipelines (EPA-HQ-OPPT-2016-0725-0004).
However, no further evidence was found or submitted during
the scope, problem formulation and draft risk evaluation steps
to support these "other uses" as intended, known, or reasonably
foreseen conditions of use for C.I. Pigment Violet 29. As a
result, these uses were determined to not be intended, known, or
reasonably foreseen conditions of use.
As stated in C.I. Pigment Violet 29's Problem Formulation, to
determine the current conditions of use of C.I. Pigment Violet
29 and inversely, activities that do not qualify as conditions of
use, EPA conducted extensive research and outreach. This
included EPA's review of published literature and online
databases including the most recent data available from EPA's
Chemical Data Reporting program (CDR) and Safety Data
Sheets (SDSs). EPA also conducted online research by
reviewing company websites of potential manufacturers,
importers, distributors, retailers, or other users of C.I. Pigment
Violet 29 and queried government and commercial trade
databases. EPA also received comments on the Scope of the
Risk Evaluation for Pigment Violet 29 U.S. EPA (2017) that
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Summary of Comments for Specific Issues Related to
Charge Question 1
EPA/OPPT Response
were used to determine the current conditions of use. In
addition, EPA convened meetings with companies, industry
groups, chemical users, states, environmental groups, and other
stakeholders to aid in identifying conditions of use and
verifying conditions of use identified by EPA.
TSCA Section 3(4) grants EPA the authority to determine what
constitutes a condition of use for a particular chemical
substance. In the case of PV29, as described in the preceding
response, there were a group of "other uses" that were
identified early in the process with poor quality references.
Subsequent to the publication of the scope document, no further
information was found or received by EPA that substantiated
any of the uses with limited and poor-quality references that
had been characterized as "other uses". As a result, these uses
were determined to not be intended, known, or reasonably
foreseen and are not conditions of use.
Following the publication of the Draft Risk Evaluation, EPA
communicated with the manufacturing stakeholders to clarify
the uncertainties indicated by the commenters related to a lack
of information characterizing the full range of job tasks, chronic
health/exposure studies, workplace air monitoring data across
shifts and tasks, assumptions about volumes handled by
downstream processors/users, and PPE assumptions. The results
of this information gathering have been compiled and released
to the docket in a supplement entitled, Supplemental File:
Information Received from Manufacturing Stakeholders U.S.
EPA (2020a).
Need to improve clarity and transparency of study quality evaluations
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Summary of Comments for Specific Issues Related to
Charge Question 1
EPA/OPPT Response
17, 46,
47
PUBLIC COMMENTS:
More detail in the risk evaluation regarding how
EPA evaluated study quality would improve
transparency. (17 14, 47 2)
EPA should always make study reviewer
comments public in order for the public to
understand the rationale behind its study quality
scoring decisions and to have a transparent record
of when and why changes to scores are made.
(4611)
On April 4th- 2019, EPA released an updated version of the
systematic review documents for the PV29 risk evaluation. The
systematic review materials for PV29 were updated following
the release of study reports to include the reviewer's comments
and a reevaluation of several human health studies (EPA-HO-
OPPT-2018-0604-0040). These updated systematic review data
quality evaluation results were also released as supplemental
documents to the final Risk Evaluation. This enhances the
transparency of the systematic review portion of the risk
evaluation.
EPA did not use its legal authority under TSCA to collect data, and it should
13, 16,
IB, 44,
75
PUBLIC COMMENTS:
EPA did not use its full authority to collect the
relevant toxicity and exposure data. (1814)
EPA must consider "reasonably available"
information, and thus EPA must use its authorities
under TSCA 4 and 8 to obtain additional
information, this includes relying on more than
voluntary data submissions. EPA is still relying
solely on "readily" available information, not all
reasonably available information. Relying solely
on voluntary requests for information, may result
in limited, biased, inaccurate, or incomplete
information on the chemicals. (13 268)
Rather than relying on voluntary requests for
information which are often limited, biased,
inaccurate, or incomplete (e.g., submissions by
Sun Chemical Corporation and Color Pigments
Manufacturers Association), EPA should use its
mandatory authorities to collect the relevant
toxicity and exposure data, and reissue for public
Uncertainties were identified in the draft Risk Evaluation
regarding reasonably available information characterizing
PV29's solubility and occupational inhalation exposure. To
address these uncertainties and respond to comments received,
EPA used its Test Order authority under TSCA section 4(a)(2)
to requiring testing of PV29 to develop new information to
increase certainty in the final Risk Evaluation of PV29 under
TSCA section 6(b). EPA required the following testing to be
conducted for PV29:
1) Solubility of PV29 in water
2) Solubility of PV29 in octanol
3) A workplace dust monitoring study of particles not
otherwise regulated, conducted according to the
NIOSH 0600 guideline available
Test data has been received and reviewed for data quality
according to the relevant data quality evaluation metrics and
incorporated into the final Risk Evaluation. More information
about the Section 4 Test Order for PV29 can be found in the
Section 4 Test Order docket (EPA-HO-OPPT-2020-0070-
0008).
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Summary of Comments for Specific Issues Related to
Charge Question 1
EPA/OPPT Response
comment. (13 274, 13 284, 13 286, 18 16,
18 16, 44 4)
Necessary information includes conditions of use,
exposures, workplace monitoring, environmental
releases, hazards, potentially exposed or
susceptible subpopulations, ecotoxicity. (13 80,
13 84, 13 89, 13 244, 13 284, 16 3, 16 104,
16-110, 75_2) [For specific data requests, see
comment summary sections 4.5, 5.1, and 6.7.]
Violation of TSCA by not releasing full studies due to CBI claims
9,11,
12, 13,
14, 16,
20, 44,
46,
46(S),
48, 49,
55, 75,
76, 82
PUBLIC COMMENTS:
Failure to release the 24 CBI studies violates
section 14 of TSCA, reflects a troubling lack of
transparency, and will frustrate the ability of
interested parties to review and submit comments
on the science EPA cites to support its risk
evaluation and to participate meaningfully in the
peer review process. (13 32, 20 1) (55 9)
TSCA restrictions on disclosure of CBI do not
apply to health and safety studies that are
submitted for chemical substances which have
been offered for commercial distribution [TSCA
section 14(b)(2)], TSCA defines "health and
safety study" broadly. EPA should immediately
release all of the full study reports to the public
under TSCA 14b. (9 8, 12 16, 12 36, 13 16-20,
13 11,13 32,14 5,16 15-17,20 1-9,44 6,
46_5, 48_2, 49_3, 55_7-9, 76_2, 82_6)
Threats from industry cannot justify
compromising the transparency that Congress
required under TSCA section 14(b). (46(S)_6)
Withholding the full study reports
violates requirements of public notice and
On March 21, 2019, EPA released copies of the 24 study
reports claimed as CBI to the public docket. Fifteen study
reports were completely released without redactions, while nine
reports remain partially CBI with certain information redacted.
Consistent with Agency regulations concerning the review of
confidential business information claims located at 40 CFR Part
2, Subpart B, the Agency, in December 2018, requested
substantiation of the CBI claims from the affected businesses.
Subsequently these entities provided responses to the
substantiation request. In fifteen instances, the CBI claims
associated with the study reports were removed in full by the
data owners. In nine instances, the CBI claims were reduced in
scope. For the reasons explained in the final confidentiality
determination, EPA concluded that TSCA section 14 did not
govern these studies and determined that the information
redacted in the nine studies at issue is entitled to confidential
treatment. The Agency made a final determination on the CBI
claims and this can be accessed at FOIAonline at:
httDs://foiaonline.sov/foiaonline/action/Dublic/
submissionDetails ?trackinsNumber=EPA-HO-2019-
001853&tvDe=reciuest. In all instances, these studv reports were
made available to the Agency and can now be accessed in the
public docket. The study reports as well as a summary of the
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comment in section 6 of TSCA and hinders the
peer review process. Providing summaries of
study reports does not adequately meet these
requirements. Only access to the full studies will
allow a meaningful opportunity to comment
whether the studies support EPA's claim that
PV29 does not present unreasonable risk. (9 9,
112, 12_37, 13_26-27, 14_5, 1619, 20_6, 46_5,
5 5 7, 82 6)
It is ironic that EPA believes it can base
regulatory decisions on PV29 on data that are
unavailable to the public while taking a
diametrically opposite position in its recent
proposed rule purportedly promoting
"transparency" in regulatory science. Federal
Register 18768 (April 30, 2018). (20_8)
The heavy data redactions from the
reproductive/developmental toxicity screening
study are so extensive as to preclude the ability of
the public to have any confidence at all in EPA's
many decisions in the draft risk evaluation that are
based on it. (44_9, 46_2-3, 55_8, 75_6)
EPA's indication that it will allow members of the
SACC to review the 24 studies but deny access to
the public only compounds this lack of
transparency. (13 25, 16 19, 20 7)
EPA has not described the claims of
confidentiality that would justify withholding all
or parts of the PV29 health and safety studies.
Under TSCA, the only portion of a health and
safety study that can be treated as CBI is
information "that discloses processes used in the
manufacture or processing of a chemical
substance." The studies available for PV29 are
unlikely to contain this type of information.
(13 21, 16 18, 20 4)
redaction status of each study report can be found in the PV29
docket (EP A-HQ-QPPT-2018-0604-0021).
As a result of the release of this information and input from the
public about the application of the data quality evaluation
process, EPA re-evaluated the studies and updated the data
evaluation scoring sheets based on public comments. These
updated systematic review scoring sheets also contain the
reviewer comments which were previously not included
because of concerns about the CBI status of the studies. The
updated SR Supplemental File, available in the public docket
for PV29 (EPA-HQ-OPPT-2018-0604). provides a more
transparent approach than previously provided by including the
metric scores, weighting, reviewer's comments and the study's
overall score.
The information provided in the public docket for PV29
enabled a meaningful opportunity to comment on the draft risk
evaluation and was consistent with TSCA 26(j) and 40 CFR
702.51 provisions on public availability of information.
EPA reviews confidentiality claims asserted for information
that is reported to, or otherwise obtained by, EPA under TSCA
in accordance with TSCA section 14(f) and (g). Confidentiality
claims asserted for business information that is not subject to a
specific statutory review requirement are reviewed in
accordance with 40 CFR 2.204(a).
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Summary of Comments for Specific Issues Related to
Charge Question 1
EPA/OPPT Response
EPA should have reviewed all confidentiality
claims asserted in at least approximately one-
fourth of the information submissions it received.
(13_33)
Support for EPA's handling of CBI
19, 45,
47, 72
PUBLIC COMMENTS:
EPA is correct to protect the CBI status of health
and safety studies that are voluntarily submitted.
The language in TSCA section 14 does not require
EPA to publish confidential health and safety
studies. (19_19-20)
EPA determined correctly that studies owned by
foreign companies submitted voluntarily to EPA
qualify for CBI protection under FOIA, and that
analysis under TSCA is inapplicable. (47 4, 72_1)
However, EPA significantly overstates what is
required of the Agency under TSCA section
14(b)(2) in its March 14, 2019, Final
Confidentiality Determination letter. If Congress
had intended to require EPA to disclose all
information contained within or underlying health
and safety studies, it would have used the word
"shall" or "must." TSCA section 14(b)(1)
provides that when confidential information is
mixed with information that is not protected from
disclosure, the confidential information does not
lose its confidential status merely because it is
contained within information that is otherwise
disclosed. While the health and environmental
results of a study can never be CBI, the underlying
data that has commercial value can and should be
protected from disclosure with EPA's discretion.
EPA should amend its analysis and recognize that
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. As discussed above, following
substantiation of the CBI claims from the affected businesses,
EPA has released fully unredacted or partially redacted versions
of all of the studies discussed in the draft risk evaluation in the
oublic docket for PV29 (EPA-HO-OPPT-2018-0604). The
Agency does not intend to amend its 2019 final confidentiality
determination.
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Summary of Comments for Specific Issues Related to
Charge Question 1
EPA/OPPT Response
TSCA section 14 provides EPA with discretion to
protect CBI. (47 4)
Publishing confidential product data, such as
valuable health and safety studies, would
discourage companies from voluntarily expending
resources on expensive toxicology studies.
(1922)
EPA's practice of protecting CBI in health and
safety studies is consistent with past EPA
practices and other chemical regulatory agencies
around the world, including ECHA. (19 23)
Robust study summaries, as defined in the
REACH regulation, provide "sufficient
information to make an independent assessment of
the study minimizing the need to consult the full
study report." (19_24)
The SACC independent review minimizes the
need to publicly release full study reports and
provides the public with additional basis for
confidence in the studies. (19 24)
Update risk evaluation to reflect availability of studies that were
jreviously redacted
SACC
SACC COMMENTS:
Update the Evaluation to reflect recent changes in
CBI availability. The Committee noted that there
had been significant changes to CBI redacted
information upon which the Draft Risk Evaluation
relied. These formerly redacted studies are now
publicly available for review.
EPA has updated the risk evaluation to reflect the public release
of the studies with CBI claims.
Include description of the ramifications of the final risk statement
SACC
SACC COMMENTS:
The Public needs to know that if a substance is
determined to pose an "unreasonable risk," the
Agency will address the identified risk(s) through
The final Risk Evaluation was modified to include detailed risk
determinations for each condition of use in order to improve the
understanding of the impact of the risk evaluation and if any
risk management activities will follow the evaluation. Any
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Summary of Comments for Specific Issues Related to
Charge Question 1
EPA/OPPT Response
a risk management process. At a minimum,
reference should be made to Agency guidance on
how this next step would proceed.
Any finding of no unreasonable risk is tied to
limitations of currently available data and uses,
including industrial hygiene practices, then the
Evaluation should so state. A finding of "no
unreasonable risk" should not preclude additional
review. Substantial changes in use of the
substance under review, and/or the development
of new data that alters substantially knowledge of
chemical properties, exposures and or toxicity,
will alter exposures, toxicity, and will ultimately
alter the overall risk.
The Committee expressed concerned that a
finding of "no unreasonable risk" indicates to the
public that nothing further will be done to evaluate
or regulate the substance under review (in this
case PV29). On the other hand, the prior
designation of PV29 as a high priority chemical
may suggest to many in the public that additional
risk management measures will be enacted
regardless of outcome. Additional clarification
would be helpful so that manufacturers, state
regulators, and the public will understand how the
risk assessment finding will impact their current
and future activity related to this substance. This
statement is needed to clarify report findings and
increase transparency of EPA intent following the
report finding.
changes to risk determinations from the draft risk evaluation
will be clearly stated.
TSCA section 6 requires EPA to make a determination that a
chemical substance undergoing risk evaluation presents or does
not present an unreasonable risk of injury to health or the
environment, under the conditions of use. In carrying out
section 6, EPA must take into consideration information "that is
reasonably available to the Administrator." TSCA section
26(k). A determination that a condition of use of a chemical
substance does not present an unreasonable risk of injury is a
final agency action. See TSCA section 6(i). Federal preemption
of certain State actions regarding that chemical substance would
apply only to the hazards, exposures, risks, and uses or
conditions of use of such chemical substance included in that
final agency action. See TSCA section 18(c)(3).
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Systematic Review Approaches and Clarity
Charge Question 2.1: Please comment on the approaches and/or methods used to support and inform the gathering, screening,
evaluation, and integration of information used in the draft risk evaluation of PV29 and the updated Pigment Violet 29 (81-33-4)
Systematic Review: Supplemental File for the TSCA Risk Evaluation (Published April 17, 2019). Please also comment on the clarity
of the information as presented related to systematic review and suggest improvements as it applies to PV29.
#
Summary of Comments for Specific Issues Related to
Charge Question 2
EPA/OPPT Response
Need to describe the rationale for developing a systematic review method specific to TSCA
SACC,
82
SACC COMMENTS:
Describe clearly the rationale for developing a
systematic review specific to TSCA risk
evaluations.
Describe clearly the rationale for the differences in
the TSCA systematic review relative to other peer-
reviewed systematic review approaches currently
in use.
PUBLIC COMMENTS:
EPA was not forthcoming during the SACC
meeting when queried as to why it chose to
develop its own method of systematic review for
TSCA. (82_6)
EPA/OPPT's quality evaluation method was developed
following identification and review of various published
qualitative and quantitative scoring systems to inform EPA's
specific 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.
While EPA's/OPPT's systematic review process may differ
from other procedures or guides, it was developed
specifically for the TSCA risk evaluation process and
included certain protocols and processes. Based on
comments received and challenges experienced with
EPA's/OPPT's process for the first round of risk evaluations,
EPA is refining it systematic review process for added
transparency and clarity. Additionally, the refinement
process includes more detail, specificity, and data integration
than previously applied as well as developing clearer, more
transparent processes and practices to be applied in future
risk evaluations. The refined systematic review process is
being reviewed by the National Academy of Sciences.
Need to initiate an external peer review of the TSCA systematic review protocol
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Summary of Comments for Specific Issues Related to
Charge Question 2
EPA/OPPT Response
SACC,
13, 16,
46, 48,
80, 82
SACC COMMENTS:
As soon as practical have NAS conduct a peer
review of the TSCA systematic review protocol.
PUBLIC COMMENTS:
EPA should immediately initiate an external,
independent peer review of its TSCA systematic
review protocol. Until external reviews are
completed, EPA should not use the TSCA
systematic review protocol. (13 242,16 109,
46_25, 48_16, 80_1, 82_6)
An ad hoc committee of the National Academies of Sciences,
Engineering, and Medicine is reviewing EPA's guidance
document on Application of Systematic Review in TSCA
[Toxic Substances and Control Act] Risk Evaluations (EPA
2018) and associated materials developed subsequent to its
issuance. The committee is considering public comments on
the document, EPA's responses to public comments, and
enhancements to the systematic review process reflected in
documentation of the first 10 chemical risk evaluations. The
committee will determine whether EPA's process is
comprehensive, workable, objective, and transparent.
Recommendations for enhancements to EPA's 2018 guidance
document will be made. More information and details about
the NAS review effort are available here:
httos://www. national academies, ory/our-work/revi ew-of-
eDas-tsca-svstematic-review-yui dance-document
Need to develop, peer review, and publish systematic review protocols prior to conducting TSCA risk assessments
SACC,
13,43
SACC COMMENTS:
Develop, peer review and publish SRs for
substances undergoing TSCA risk assessment prior
to conducting the actual risk assessment.
PUBLIC COMMENTS:
EPA failed to establish an upfront protocol for
PV29, which violates a basic principle of
systematic review under TSCA. Developing
systematic review protocols for each chemical in
advance reduces bias and ensures transparency in
decision-making. (13 217, 43 4)
Insufficient time is not an acceptable justification
for EPA's failure to develop protocols. (13 221)
The systematic review protocols should be
available and subject to public comment prior to
Systematic review and evaluation of reasonably available
data for a chemical substance forms a major part of the risk
evaluation process. In the interest of meeting the statutory
deadlines set forth under TSCA for the completion of the risk
evaluations, the systematic review process was conducted as
the risk evaluations were being developed. To address
systematic review best practices, EPA developed criteria for
screening and evaluating reasonably available information
before these specific systematic review processes occurred.
For future risk evaluations, EPA will work to implement
procedures to identify and fill critical data deficiencies at the
beginning of the risk assessment process.
EPA/OPPT's systematic review and data quality evaluation
methods were developed in part by consulting various
published qualitative and quantitative scoring systems. The
development process involved reviewing various evaluation
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Summary of Comments for Specific Issues Related to
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EPA/OPPT Response
initiating subsequent steps of the risk evaluation
process. (13_221)
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. Based on
comments received and challenges experienced with
EPA's/OPPT's process for the first round of risk evaluations,
EPA is revising it systematic review process for added
transparency and clarity. Additionally, the revision process
includes more detail, specificity, and data integration than
previously applied as well as developing clearer, more
transparent protocols and practices to be applied in future
risk evaluation processes. The revised systematic review
process also went through a National Academy of Sciences
in August, 2020. The recommendations resulting from this
review are being summarized and will be made publicly
available and incorporated into the process as needed.
Concerns that the TSCA systematic review method does not follow best scientific practices and should be replaced
9,13,
14, 16,
IB, 43,
44, 46,
48, 55,
80
PUBLIC COMMENTS:
The TSCA systematic review method does not
follow best scientific practices for systematic
reviews. (9 5, 13 222, 14 2, 16 2, 43 1, 44 20,
46_12, 48_1, 55_4, 801)
Another example is that EPA has adopted a rigid,
numerical scoring approach with weighted metrics
to grade the quality of studies while other
systematic review systems holistically evaluate and
compare different studies and data sources, without
relying on numeric scores. The National Academy
of Sciences has cautioned against the use of scores
EPA will work with the National Academy of Sciences,
Engineering, and Medicine (NASEM) TSCA Committee to
consider revisions to the data quality evaluation criteria and
options regarding integrating evidence within and across
evidence streams (human, animal, mechanistic data). EPA
proposes to use a more structured framework for evidence
integration for the next set of chemicals evaluated under
TSCA.
Appendix A of the Application of Systematic Review in
TSCA Risk Evaluations explains the basis for EPA/OPPT's
development of a numerical scoring system to inform the
characterization of the data/information sources during the
data integration phase. The intent is to provide transparency
and consistency to the evaluation process along with creating
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in systematic review. (1310, 16_107, 44_20,
46_23, 48_14)
The TSCA approach focuses on one limited aspect
of systematic review, study quality, but fails to
address other critical elements that the Agency
itself recognizes are essential for science-based risk
judgments, such as identifying and evaluating each
stream of evidence and integrating evidence as
necessary and appropriate based on strengths,
limitations, and relevance. (16 107)
EPA should use a peer-reviewed, validated
systematic review method for chemical evaluations
instead of the TSCA method even if that delays
development and completion of some risk
evaluations. Examples include the NTP Handbook
for Conducting a Literature-Based Health
Assessment Using OHAT Approach for Systematic
Review and Evidence Integration; the EPA
Handbook for Developing IRIS Assessments; the
Preamble to the IARC Monographs; and the
Navigation Guide Systematic Review Method
(Woodruff and Sutton, 2014). (13_313, 43_1,
48 16, 55 16)
Unlike the aforementioned approaches to
systematic review, the TSCA protocol fails to
address the steps TSCA risk evaluations will take
to determine the strengths and relevance of
individual studies, group them into streams of
evidence and integrate these streams into a set of
judgments about the weight of the evidence as a
whole. (1814)
evaluation strategies that meet the TSCA science standards
for various data/information streams. 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., NTP's Office of Health Assessment
and Translation (OHAT) Risk of Bias tool, Criteria for
Reporting and Evaluating Ecotoxicity Data (CRED), etc.; see
Table 1 and Appendix A of the Application of Systematic
Review in TSCA Risk Evaluations and references therein), as
well as soliciting input from scientists based on their expert
knowledge about evaluating various data/information sources
for risk assessment purposes. While there are many
published systematic review tools available for human health
and environmental health hazard assessment, no systematic
review tools were identified that encompass either exposure
assessment (e.g., general population exposures, occupational
exposures and industrial releases) or fate and transport
assessment. The published data quality evaluation results
provided the lists of references EPA/OPPT evaluated for the
first 10 TSCA risk evaluations.
In order to ascertain the quality of the available data,
EPA/OPPT used a numerical scoring system to assign a
qualitative rating. The goal of this approach was to add
consistency and transparency to the evaluation process.
Scores were used for the purpose of assigning the confidence
level rating of High, Medium, Low, or Unacceptable, and
informed the characterization of data/information sources
during the data integration phase. The data quality evaluation
results for the first ten TSCA Risk Evaluations are posted on
chemical specific websites (see Table 1). In all evaluation
strategies, professional judgment was employed to determine
the adequacy or appropriateness of the qualitative rating
assigned by the numerical scoring system.
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Summary of Comments for Specific Issues Related to
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EPA/OPPT Response
The TSCA evaluation strategies consider methodological
design and implementation and reporting within the existing
domains and metrics. Since it is difficult to have high
confidence in data where the underlying methods are
unreported or poorly reported, EPA assesses reporting and
methodological quality simultaneously. However, EPA
recognizes the challenge of discerning between a deficit in
reporting and a problem in the underlying methodological
quality of the data/information source. Developing a
reporting checklist, guidance document or a separate
reporting quality domain may be a future solution for
consideration in optimizing the evaluation strategies. EPA
also designed evaluation criteria that consider risk of bias
and Bradford Hill aspects when assessing the quality of
animal toxicity and epidemiological studies. Refer to
Appendices F, G and H of the Application of Systematic
Review in TSCA Risk Evaluations for more information.
EPA will consider other existing approaches as part of the
process of developing the methods and/or approaches for
integrating exposure and hazard evidence supporting the
TSCA risk evaluations. Due to the variety of chemicals being
evaluated under TSCA, EPA expects variations in the
integration methods and/or approaches across different
evidence streams as part of the process of developing fit-for-
purpose risk evaluations that meet the TSCA science
standards.
Need to more clearly describe the systematic review protocol and procedures
SACC
SACC COMMENTS:
Describe clearly the explicit populations,
exposures, comparators, and operators (PECO or
According to the Application of Systematic Review in TSCA
Risk Evaluations U.S. EPA (2018a), systematic reviews
typically describe the study eligibility criteria in the form of
PECO statements or a modified framework. PECO stands for
Population, Exposure, Comparator and Outcome. The
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problem formulation) used in the systematic
review.
Describe clearly how the TSCA systematic review
is updated and describe the rationale for decisions
applied in the systematic review for specific
substances.
approach is used to formulate explicit and detailed criteria
about those characteristics in the publication that should be
present in order to be eligible for inclusion in the review
(e.g., inclusion of studies reporting on the effects of chemical
exposure to potentially exposed or susceptible
subpopulations).
EPA developed PECO statements to guide the screening of
the environmental and human health hazard data or
information sources for each of the TSCA risk evaluations.
However similar guides for screening were developed for
data and information of different disciplines using generic
RESO and PESO statements. In the case of C.I. Pigment
Violet 29, EPA did not exclude and populations, exposures,
comparators or operators during the data search and
screening process for C.I. Pigment Violet 29.
Various PECO or PECO equivalent documents have been
created to document the eligibility criteria for various data or
information streams informing the TSCA risk evaluations:
physical chemical properties; environmental fate and
transport; engineering and occupational exposure; exposure
to the environment, the general population and consumers;
and environmental and human health hazards.
It is important to mention that PECO/RESO/PESO
statements can be modified once they are drafted and
implemented, through a calibration process. Calibration is
when screeners jointly screen 10-40 studies to identify points
of confusion or chemical-specific considerations.
More information about the use of specific populations used
in the systematic review of PV29 are outlined in the
Application of Systematic Review in TSCA Risk Evaluations
available at:
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#
Summary of Comments for Specific Issues Related to
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EPA/OPPT Response
httDs://www.eDa.sov/sites/Droduction/files/2018-
06/documents/final application of sr in tsca 05-31-18.pdf
EPA anticipates feedback from the NAS on its systematic
review process and will carefully review and implement
relevant NAS recommendations, as appropriate.
Need to provide a more thorough discussion of data integration
SACC,
8,13,
48, 55
SACC COMMENTS:
Include a more thorough and inclusive data
integration discussion in the TSCA systematic
review for PV29. The discussion should include
descriptions of how the human health experience,
mechanistic information, in vitro data, and
controlled laboratory animal data are used to
support conclusions. Include in the discussion how
chemical structural considerations, read across, and
other information including finding from New
Approach Methodologies (NAMs) add to the
evidence for potential PV29 toxicity. The
discussion should also address data uncertainties.
PUBLIC COMMENTS:
The TSCA systematic review protocol does not
include methods for evidence synthesis and
integration as required by EPA regulation under
TSCA. (48 14, 55 15)
The draft risk evaluation simply states that "EPA
analyzed and synthesized" available evidence,
without specifying its strategy for data integration.
The discussion does not detail how individual
EPA appreciates the comments and is currently in the
process of updating its Systematic Review protocol. In
addition, EPA is seeking feedback from the National
Academies of Science (NAS) on its Systematic Review
process, including data evaluation criteria and data quality
rating methods used in TSCA Risk Evaluations. The NAS
webinars occurred from June through August, 2020. EPA
will consider all comments and feedback received in
updating its Protocol.
In response to comments, EPA has made several editorial
changes in multiple sections within the final Risk Evaluation
document to increase the transparency of its systematic
review process and methodologies used. In addition to the
data evaluation criteria published in the Application of
Systematic Review in TSCA Risk Evaluations, EPA has
updated the systematic review components of the final Risk
Evaluation which revises or adds data quality evaluation
reviews for all available data for human health,
environmental hazard, environmental fate, physical chemical
property data, environmental release occupational exposure
data quality evaluation reviews in the assessment. The
updated systematic review scoring sheets, released on April
17. 2019 (EPA-HO-OPPT-2018-0604-0040) with undated
data quality evaluation scores and reviewer comments, are
reflected in Systematic Review Companion Documents
released with the final Risk Evaluation. EPA is developing
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Summary of Comments for Specific Issues Related to
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EPA/OPPT Response
study scores were used in this step of the review
process for PV29. (13 234)
EPA should describe its general approach to
evidence integration, referring to established
systematic review approaches. (13 235)
If OPPT relied directly on SAR evaluations or
other data used in international agency assessments
of PV29, OPPT should indicate this and describe
how the other evaluations were evaluated to
determine their robustness. (816)
and implementing more formal and structured data
integration, analysis and synthesis strategies for the next set
of TSCA chemical risk evaluations.
There EPA utilized SAR tools in its assessment, EPA
evaluated these tools for data quality. The results of the data
quality evaluation of the EPIsuite modeling program is
available in the supplemental file, Systematic Review
Supplemental File: Data Quality Evaluation of
Environmental Fate and Transport Studies'" U.S. EPA
(2020b)
Insufficient data concerns and handling of lack of data
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Summary of Comments for Specific Issues Related to
Charge Question 2
EPA/OPPT Response
SACC,
10, 12,
13, 15,
16, 18,
44, 46,
49, 82
SACC COMMENTS:
Discuss why an "indeterminate" designation is not
needed in the TSCA systematic review to account
for situations where there is significant lack of
data.
Improve the discussion on why available study data
are adequate to reach the conclusions of "no
unreasonable risk" from exposure to PV29. This
discussion should also justify why additional
testing is not necessary to confirm this conclusion.
PUBLIC COMMENTS:
The systematic review did not gather all
appropriate data and EPA should use its authorities
under TSCA to obtain additional information.
(10 13, 12 3, 13 73, 15 22, 16 13, 18 5,44 5,
46 1, 49 2, 82 2)
The updated study quality scores for the two BASF
acute inhalation toxicity studies as Unacceptable
further highlights the lack of sufficient information
available to evaluate PV29's risks. (13 227,
46 14)
EPA did not include a review of, or reference to, a
90-day repeated dose dietary study in rats that also
is in the REACH database for this chemical. (49 4)
In response to uncertainties resulting from lack of data
identified in public and SACC comments, as well as in the
risk evaluation, EPA issued a TSCA Section 4(a)(2) Test
Order for PV29 on February 28, 2020. The Test Order was
issued to the one U.S. manufacturer, Sun Chemical
Corporation, and one U.S. importer, BASF, and required the
generation and submission of three studies to address critical
data gaps identified in the risk evaluation. More information
about the Section 4 Test Order for PV29 can be found in the
docket (EPA-HO-OPPT-2020-0070-0008). EPA is currently
developing a procedure to identify data deficiencies earlier in
the risk evaluation process so an indeterminate designation is
not necessary.
As indicated above, EPA issued a TSCA Section 4(a)(2) Test
Order for PV29 on February 28, 2020 to the one U.S.
manufacturer, Sun Chemical Corporation, and one U.S.
importer, BASF, that required the generation and submission
of three studies to address critical data gaps identified in the
risk evaluation. More information on this Test Order can be
found on its docket (EPA-HO-OPPT-2020-0070-0008).
In the absence of reasonably available data to characterize
inhalation toxicity of PV29, EPA has used analog toxicity
data to characterize the risks to human health from
occupational exposure to PV29.
EPA did not identify a US data owner for these studies. As
the full study reports could not be obtained for these study
summaries, EPA did not utilize the results in the assessment,
although they appeared to be consistent with the
Reproduction/Developmental Toxicity Screening Test
discussed in the assessment.
Concerns about the quality of the body of evidence for PV29
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43, 47,
48, 55
PUBLIC COMMENTS:
Applying the Navigation Guide risk of bias tool to
the 15 PV29 animal toxicity studies indicates that
the overall quality of the body of evidence is low.
(43_7, 48 11, 55_13)
Based on the partial disclosure of reports of the 24
PV29 studies, the limitations and deficiencies of
these studies in assessing PV29's acute and chronic
health effects have been further demonstrated,
providing more evidence that EPA's lacks any
justification for its conclusion that PV29 "presents
a low hazard to human health across all routes of
exposure". (47_2)
All studies and information used in the Risk Evaluation,
including those submitted through correspondences with
manufacturing stakeholders of PV29, 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. As indicated in the final Risk Evaluation, EPA
issued a TSCA Section 4(a)(2) Test Order for C.I. Pigment
Violet 29 on February 28, 2020. This test order compelled
the creation and submission of three studies by the sole US
manufacturer of PV29, Sun Chemical, as well as BASF, an
importer of PV29 to address critical data gaps identified in
the risk evaluation.
In an effort to increase transparency, EPA has released all
data that were used to conduct the risk evaluation, with some
redactions for CBI. CBI in several study reports prevented
the release of fully unredacted versions of these studies.
Fully unredacted versions of these studies were made
available to the SACC members and their input on the
quality of the studies and the effect of the remaining
redactions on the ability of the general public to interpret the
studies was recorded in the Transmittal of Meeting Minutes
and Final Report for the TSCA Science Advisory Committee
on Chemicals Meeting Held Jane 18-21, 2019, which was
made available in the public docket for PV29 (EPA-HO-
OPPT-2018-0604-0089Y
Concerns relating to the personal communication from Sun Chemical
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Summary of Comments for Specific Issues Related to
Charge Question 2
EPA/OPPT Response
SACC,
12, 13,
14, 15,
16, 17
SACC COMMENTS:
Perform a quality assessment of the exposure data
for occupational exposures to PV29 that was
provided to the Agency as a personal
communication from the manufacturer of PV29.
PUBLIC COMMENTS:
EPA's characterization of human health risk is
based on the suspect and undocumented workplace
exposure estimates privately provided to EPA by
the chemical's manufacturer. (12 3,13 8,14 17,
15 10, 16 20)
EPA heavily and inappropriately relied upon
unsubstantiated industry correspondence to inform
its exposure analysis, but this correspondence was
exempted from quality review under its systematic
review approach. (13 236)
The Sun Chemical Corporation communication as
reported by EPA fails to meet the minimal
requirements for poor quality data, and it should be
classified as unacceptable. (1513)
This personal communication does not constitute
the "best available science" showing worker
exposures and it does not meet the scientific
standards of industrial hygiene. Therefore, it cannot
reasonably form the basis of EPA's conclusion that
PV29 does not pose an unreasonable risk to
workers. (1212)
If EPA receives data from a manufacturer, the data
should be reviewed for accuracy, quality, relevancy
and suitability. EPA should specify how it
evaluated these sources for PV29. (1715)
As part of the final Risk Evaluation, EPA has conducted a
data quality evaluation for all environmental release and
occupational exposure data received for PV29 through
correspondences with manufacturing stakeholders and has
made this information publicly available in the companion
document to the final Risk Evaluation titled, "Supplemental
File: Information Receivedfrom Manufacturing
Stakeholders." In cases where data were insufficient or
inadequate to meet the minimum validity criteria, EPA has
made efforts to clarify the information. In the case of
occupational exposure data, EPA compelled the creation and
submission of a workplace monitoring study of particle not
otherwise regulated, conducted according to the NIOSH
0600 by the sole US manufacturer of PV29, Sun Chemical as
well as BASF, an importer of PV29.
Need for public access to data
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EPA/OPPT Response
SACC,
13,46
SACC COMMENTS:
Ensure that Confidential Business Information
(CBI) requirements do not prevent important
health-based data from being made available to the
public.
PUBLIC COMMENTS:
Systematic review practices require access to full
studies. The lack of study detail in the study
summaries calls into question EPA's ability to
reliably evaluate study quality. (13_24, 46_4)
EPA should make such information public and
easily searchable through online portals such as the
Health and Environmental Research Online
(HERO) database. (13 24)
On March 21, 2019, EPA released copies of the 24 study
reports claimed as CBI to the public docket for PV29 (EPA-
HO-OPPT-2018-0604). Fifteen studv reports were
completely released without redactions, while nine reports
remain partially CBI with certain information redacted. As
indicated above, on April 4th- 2019, EPA released an updated
version of the systematic review documents for the PV29
risk evaluation. The systematic review materials for PV29
were updated following the release of study reports to
include the reviewer's comments and a reevaluation of
several human health studies (EPA-HO-OPPT-2018-0604-
0040). These updated systematic review data qualitv
evaluation results were also released as supplemental
documents to the final Risk Evaluation. EPA hopes that this
enhances the transparency of the systematic review portion
of the risk evaluation.
Study quality evaluation and scoring concerns
SACC,
8,13,
16, 17,
43, 46,
47, 48,
55
SACC COMMENTS:
Describe clearly the justification for using a
weighted scoring system and the rationale for the
metrics selected for differential weighting in its
evaluation of studies.
Provide additional rationale to the TSCA
systematic review justifying NR codes for certain
metrics that are not typical of animal studies and
improve discussions on how an NR code impacts
the quality score.
Include data quality criteria in the TSCA
systematic review for evaluating personal
communications and other information types not
already identified in the TSCA systematic review
Appendix A of the Application of Systematic Review in
TSCA Risk Evaluations explains the basis for EPA/OPPT's
development of a numerical scoring system to inform the
characterization of the data/information sources during the
data integration phase. The intent is to provide transparency
and consistency to the evaluation process along with creating
evaluation strategies that meet the TSCA science standards
for various data/information streams.
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., NTP's
Office of Health Assessment and Translation (OHAT) Risk
of Bias tool, Criteria for Reporting and Evaluating
Ecotoxicity Data (CRED), etc.; see Table 1 and Appendix A
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that might be considered critical in a risk
evaluation.
PUBLIC COMMENTS:
The numerical scoring approach was not effective
for evaluating study flaws. Overall scores can mask
flaws that might otherwise cause a study's
conclusions to be questioned. (13 222)
The scoring system could result in many studies
being arbitrarily classified as "poor" or
"unacceptable" based on a small number of
reporting or methodology limitations that do not
negate their overall value for assessing health risks.
(16 107)
The study quality scoring system is highly
questionable in the absence of any external
validation phase or thorough pilot testing. (4811)
EPA should provide more explicit criteria and
descriptions for the Not Rated/Applicable score
determination. (46 20)
There were many changes in the study quality
metric ratings for the animal toxicity studies
between the initially released and updated
systematic review documents. This suggests the
criteria for the metrics are not clear and it reveals
numerous inconsistencies and inaccuracies in the
scoring sheets. (43_4, 46_21, 4811)
It appears that different reviewers were used for the
second round of scoring than the first, suggesting
that the scores depend heavily on the subjective
judgement of the reviewer. (48 11, 55 11)
It seems that there was one reviewer for each study,
although best scientific practice is to have two
independent reviewers. (43 6, 46 22, 48 11)
The scoring sheets provide the quality scores but
do not provide information regarding the rationale
for scores. EPA should make the reviewer
of the Application of Systematic Review in TSCA Risk
Evaluations and references therein), as well as soliciting
input from scientists based on their expert knowledge about
evaluating various data/information sources for risk
assessment purposes. While there are many published
systematic review tools available for human health and
environmental health hazard assessment, no systematic
review tools were identified that encompass either exposure
assessment (e.g., general population exposures, occupational
exposures and industrial releases) or fate and transport
assessment. The data quality evaluation results published
with each risk evaluation provides the lists of references
EPA/OPPT evaluated for the first 10 TSCA risk evaluations.
In order to ascertain the quality of the available data,
EPA/OPPT used a numerical scoring system to assign a
qualitative rating. The goal of this approach was to add
consistency and transparency to the evaluation process.
Scores were used for the purpose of assigning the confidence
level rating of High, Medium, Low, or Unacceptable, and
informed the characterization of data/information sources
during the data integration phase. The data quality evaluation
results for the first ten TSCA Risk Evaluations are posted on
chemical specific websites. In all evaluation strategies,
professional judgment was employed to determine the
adequacy or appropriateness of the qualitative rating
assigned by the numerical scoring system.
The TSCA data evaluation strategies consider
methodological design and implementation and reporting
within the existing domains and metrics. Since it is difficult
to have high confidence in data where the underlying
methods are unreported or poorly reported, EPA assesses
reporting and methodological quality simultaneously.
However, EPA recognizes the challenge of discerning
between a deficit in reporting and a problem in the
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comments publicly available or provide more detail
on the rationales behind the scores. (811, 13 6,
17 14)
EPA should continue to update its systematic
review guidance to provide greater clarity and
transparency in regard to study quality criteria. It
remains unclear how EPA will address the quality
of more disparate study types that may be
encountered for other chemistries. (8 5, 47 3)
EPA must ensure that its scientists and contractors
are appropriately trained and equipped and given
the scientific independence to conduct robust
evaluations of study quality. (46 12)
EPA had failed to empirically document the link
between its scoring metrics and the overall value of
a study in a holistic evaluation of risk. (4812)
underlying methodological quality of the data/information
source. Developing a reporting checklist, guidance document
or a separate reporting quality domain may be a future
solution for consideration in optimizing the evaluation
strategies. EPA also designed evaluation criteria that
consider risk of bias and Bradford Hill aspects when
assessing the quality of animal toxicity and epidemiological
studies. Refer to Appendices F, G and H of the Application
of Systematic Review in TSCA Risk Evaluations for more
information.
Relevant data sources are evaluated for data quality
following title/abstract and full-text screenings, after a pilot
period to calibrate criteria and revise as needed. Generally,
each study evaluation is conducted by at least two reviewers,
with a process for comparing and resolving differences. This
helps ensure quality assurance. However, based on
assessment needs, the assessment team should make
decisions about how many reviewers are needed. While more
than one reviewer is ideal, there may be times when one
reviewer is acceptable, such as when the assessment needs to
be conducted under a rapid timeframe and the outcome being
reviewed is unlikely to be a driver for the assessment. These
quality assurance methods are the same as used by EPA's
IRIS Program. Other EPA Offices (such as Office of
Research and Development and the Office of Science
Coordination and Policy) partnered with OPPT in developing
innovations in searching and screening for the next 20
chemical evaluations (see response to Q5) and continue to
support OPPT in scoping and SR efforts.
The data evaluation is conducted in a tool (e.g., Excel,
Access, DistillerSR) that tracks and records the evaluation
for each data/information source including reviewer's
comments. EPA initially released the SR Supplemental File
without the EPA reviewer's comments due to concerns that
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the comments might contain information claimed CBI. The
Updated SR Supplemental File, released on April 4, 2019,
now makes publicly available the EPA reviewer's comments
related to the data quality evaluation of the physical chemical
characteristics, environmental fate, environmental hazard and
human health studies (EPA-HO-OPPT-2018-0604-0040).
EPA will make reviewer comments public with the release of
the Systematic Review Companion documents for the final
Risk Evaluation to increase transparency. This
documentation approach also increased transparency of
professional judgment calls to stakeholders and the public for
the first 10 TSCA risk evaluations. EPA/OPPT plans to use
these evaluation strategies, including pre-determined criteria,
documented in EPA's Application of Systematic Review in
TSCA Risk Evaluations document, for the next 20 TSCA
risk evaluations. However, refinements to the evaluation
strategies are likely to occur. EPA already made changes to
the physical chemical properties, environmental hazard, and
epidemiological criteria since the Application of Systematic
Review in TSCA Risk Evaluations document was published.
These changes were due to validation and improvement
efforts to ensure that the most relevant studies were included
in the TSCA risk evaluations, and the most up-to-date data
quality evaluation criteria are used for the next 20 TSCA risk
evaluations.
Use of an NR rating for a score is up to the scientific
judgement of the reviewer. This rating should be applied
when the metric or domain is not relevant to the scoring
criteria. If this rating of NR is applied, then the metric is not
counted towards the overall data quality evaluation score of
the study.
TSCA systematic review method was effective for PV29
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8,17,
19, 47
PUBLIC COMMENTS:
EPA appropriately gathered and considered all of
the available and relevant data for PV29. (8 9,
17 17, 19 11)
EPA's use of data generated for other regulatory
programs is important and encouraged. (17 7)
EPA completed a thorough review to verify the
quality of the submitted studies. (19 11)
ACC commends EPA on its approach to using
inhalation exposure data provided by a
manufacturer as a means to obtain useful data in an
expedient manner. (17 17)
The updated systematic review increased
transparency in regard to study quality evaluation
and is a marked improvement over EPA's original
PV29 systematic review document. (47_1)
EPA acknowledges these comments and has made no change
Include discussion of toxicity of byproducts of manufacturing and impurities in PV29
SACC,
12, 13,
46
SACC COMMENT:
Include a discussion on the potential toxicity of
byproducts of manufacturing and impurities in
PV29.
PUBLIC COMMENT:
EPA did not review studies on chemical residuals
of the PV29 manufacturing process. (12_26, 46_6)
In the problem formulation, EPA identifies
naphthalimide as a residual of PV29 as
manufactured. Workers are potentially exposed to
naphthalimide. EPA has dropped all mention of
this chemical in the draft risk evaluation. EPA must
conduct a much more extensive review of the
extent of presence and the potential risks of
naphthalimide in PV29 before reaching a decision
EPA's exclusion of naphthalimide impurities of reactions in
the production of other chemicals from the scope of this risk
evaluation is a policy decision. In exercising its discretion
under 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
anticipates that any risks presented by the presence of
naphthalimide impurities will be considered in the scope of
any risk evaluation of those chemicals. EPA believes that,
rather than evaluate one aspect of the risk that may be
presented by naphthalimide, a more sensible approach is to
consider that risk while evaluating the risks that may be
presented by the naphthalimide itself. Naphthalimide
generated as a byproduct of the production of PV29 is
outside the scope of this risk evaluation. EPA believes that
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to do no further analysis. (12 26,13 213-215,
46_6)
its regulatory tools under TSCA section 6(a) are better suited
to addressing any unreasonable risks that might arise from
naphthalimide as a byproduct of the production of PV29.
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Physical Chemical Properties and Environmental Fate
Charge Question 3.a: Please comment on the characterization of Log Kow, Koc and bioaccumulation for PV29, including any
suggestions for alternative sources or methods to obtain or derive better estimates of the properties (e.g., use of specific analogs).
Charge Question 3.b: Please comment on characterization of the physical chemical properties of PV29, especially with regard to the
determination by the European Chemicals Agency (ECHA) to include PV29 on the 2019-2021 Community Rolling Action Plan
(CoRAP) update as a "suspected PBT/vPvB [Potentially Persistent, Bioaccumulative and Toxic/very Persistent and very
Bioaccumulative substance]" The CoRAP justification document for PV29 is available at:
https://echa.europa.eu/documents/10162/13628/corap justification 201-344-6 226-866-1 be 12079 en.pdf/cf312ff9-6bl8-8b76-
bc66-d86320faa24a
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Summary of Comments for Specific Issues Related to
Charge Question 3
EPA/OPPT Response
Concerns about water solubility study and value EPA used
13,45,
55, 78
PUBLIC COMMENTS:
EPA did not explain why the water solubility value
provided in the 2017 PV29 scoping document was
discarded in the draft risk evaluation. (13 38)
The study used to determine water solubility failed
to consider pH and its influence on water solubility.
(13 37)
Measured values for relatively poorly soluble
substances are highly uncertain. (13 41)
EPA used an incomplete data set and selected
lowest solubility estimate available. (78 6)
While the water solubility estimate is higher than
the actual measured solubility for PV29, it is still
more than 10 times lower than the estimate
provided in the CoRAP Justification Document.
(4515)
The CoRAP Justification Document failed to
incorporate the output of the most recent EPA
ECOSAR estimation program. (4516)
Studies provided in the ECHA dossier for PV29
reported higher solubility values. (13 39, 55_17)
The structure of PV29 is unique. Not only does it have the
chromophore to give its color, it is also entirely planar and
has multiple hydrogen bonding groups to give it high
stability. The highly symmetric nature of the structure
allows for efficient molecular packing and strong
intermolecular hydrogen bonding at both ends to give a
closely packed herringbone or stair-step type manner. As a
result, the substance has a very high melting point (> 500
deg C) for an organic substance and low water solubility.
The value that was 16.9 times higher was inconsistent with
the expected solubility due to its highly stable
intermolecular structure. The value from EPI allows for the
input of a melting point value.
The standard protocol values EPA reports include the water
solubility. The water solubility test guidelines call for testing
the substance in deionized water and recording the pH of the
test solution during the test. The study performed by BASF
determined the pH to be 6 during the water solubility study.
Also, it should be noted that PV 29 was found to be
insoluble in most solvents except for concentrated sulfuric
acid which was used to perform the UV studies. Therefore,
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the substance is soluble under highly acidic conditions
(though the exact value was not determined).
EPA issued a test order to require the sole manufacturer of
PV29 to submit additional testing to measure the solubility
of PV29 in water and octanol. The results of this testing are
incorporated into the final Risk Evaluation. This testing was
conducted with a modified protocol that accommodates the
particular physical-chemical characteristics ofPV29 and
EPA has high confidence in the study results.
Remove statements that low aqueous solubility precludes oral bioavailability
SACC
SACC COMMENTS:
Remove statements that claim that an aqueous
solubility of < 11 [j,g/L precludes oral
bioavailability.
EPA has updated the final Risk Evaluation to remove these
statements.
Use alternative methods to generate information to evaluate bioavailability
SACC COMMENTS:
Use alternative property estimation methods to
generate the additional information needed to
strengthen the weight of evidence to conclude that
PV29 is not bioavailable.
EPA has utilized several in-silico methods to strengthen the
available body of evidence that discusses the bioavailability
of PV29 where possible.
SACC
Concerns about use of EPI Suite
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SACC,
13,45
PUBLIC COMMENTS:
EPA should clarify and address the appropriateness
of using EPI Suite estimates in evaluating PV29's
risks. (13 52)
EPA altered its prior characterization questioning
the reliability of estimates derived using EPI
(Estimation Programs Interface) Suite. (13 53)
Using modelled estimations for water solubility
from EPI Suite is inconsistent with the REACH
guidance. (45 1)
Significant problems remain with EPI Suite, but
versions linked to the PBT Profiler were improved
in their accuracy with respect to organic pigments.
(45_12)
Models like EPI Suite historically have tended to
predict a much higher solubility than experimental
results determine for substances outside the
calibration range of the models. (4513)
In the absence of measured data, estimating chemical
properties can be used to obtain approximate values to get
an idea of the chemical behavior. The model limitations
should be taken into consideration when evaluating the
results. For PV29, the chemical substance does not contain
structural elements that would lead EPA to believe that the
model would not provide a good estimated value.
As discussed in the assessment, Log Kow is not a relevant
property for PV29 because it demonstrates a low solubility
in octanol and water and behaves more like an insoluble
particle. As such, it is not expected to absorb into organisms
or tissues.
As discussed above, EPA has required the submission of
measured data to characterize the solubility of PV29 in
water and octanol. Therefore, the result of this testing was
utilized in the final Risk Evaluation. EPA routinely relies on
modeled predictions of physical chemical properties when
measured values cannot be obtained due to the nature of the
substance.
PBT Profiler is no longer available at the EPA web site. Fate
and transport data extracted from the Systematic Review and
submitted testing reports were used as the base of PV29's
fate assessment.
EPA required the development and submission of measured
data to characterize the solubility of PV29 in water and
octanol. While EPA chose to rely on the measured solubility
data, a comparison with these values and the EPI-estimated
solubility values (estimated to be 0.01 mg/L with an input of
400 deg C as the Melting Point and 0.001 mg/L with an
input of 500 deg C) indicates that EPI-estimated values were
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higher than the measured values, but still indicates low
water solubility.
Lack of clarity and data to support conclusions regarding bioaccumulation potential
13, 16
PUBLIC COMMENTS:
EPA did not indicate the methods used in deriving
its BAF and BCF values. (13 49)
EPA relies on incomplete and uncertain data to
conclude that PV29 does not bioaccumulate.
(13 46)
The evidence for solubility and bio-accumulation
potential is inconclusive. (16_45, 16_62)
The solubilities of PV29 in both water and Octanol were
confirmed by EPA from recent studies submitted by Sun
Corporation under the TSCA section 4 order. Therefore, the
BCF and BAF values calculated by EPI Suite using
estimated Kow value will not be used in the final PV29 Risk
Evaluation.
Supportive of conclusion that PV29 is poorly absorbed
19, 45
PUBLIC COMMENTS:
Based on physicochemical properties of PV29,
EPA correctly classified PV29 as poorly absorbed
by all routes of exposure. (19 7)
Measured values for octanol and water solubility
using the ETAD method, which were submitted to
ECHA under science-based guidance adopted by
ECHA for assessments under REACH, and
submitted to EPA for its Draft Risk Evaluation,
accurately indicate that PV29 is not
bioaccumulative. (451)
EPA classified PV29 as poorly absorbed because of the low
solubility and the relatively large molecular weight, which
hinders PV29's particles ability to penetrate through
membranes.
Ensure consistency or justify differences among physicochemical properties across the assessment
SACC
SACC COMMENTS:
Ensure that the physical-chemical properties used
throughout the Evaluation are consistent or note the
reasons for discrepancies.
EPA has reviewed the physical chemical properties used
throughout the document for consistency
Consider metabolic pathway prediction software to identify intermediates
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SACC
SACC COMMENTS:
Consider using metabolic pathway prediction
software to look for potentially problematic
intermediates for PV29. Despite the fact that PV29
seems to have minimal ready biodegradation, the
production of toxic and persistent metabolites is
always a concern especially for any compound
having structure similar to PAHs.
Develop and justify high-quality estimates for log
Kow or fat solubility to solidify the argument that
PV29 is not bioavailable or likely to be absorbed
into organisms or tissues.
Improve the discussion supporting the importance
of Koa and better illustrate its implications on
determinations of environmental distribution of
PV29 and resulting exposure to humans and other
organisms.
The lack of biodegradation and low solubility of PV29 in
water and octanol means that the chemical is out of the
bounds of the metabolic prediction software. In addition,
PV29 is not expected to be metabolized due to low potential
for absorption, so the production of metabolites is not
expected.
As discussed in the assessment, LogKow is not a relevant
property for PV29 because it demonstrates a low solubility
in octanol and water and behaves more like an insoluble
particle. As such, it is not expected to absorb into organisms
or tissues.
EPA issued a test rule Order under TSCA section 4(a)(2)
requiring the Sun Chemical Corporation and BASF to
conduct solubility testing for PV29. These tests were
required to address the uncertainties identified by EPA and
members of the Science Advisory Committee on Chemicals
(SACC) regarding PV29's water and octanol solubility. EPA
issued this test rule Order because, for an insoluble
particulate substance such as PV29, the octanol and water
solubility should be considered separately to give a useful
estimate for the Log Kow and an indication of its
bioavailability. The Sun Chemical Corporation conducted
these studies under protocols reviewed by EPA and based on
OECD Test No. 105 for water solubility and the Ecological
and Toxicological Association of Dyes and Organic
Pigments (ETAD) method for octanol solubility. The study
results, which are available on regulations.sov at (EPA-HO-
OPPT-2020-0070-0008), were conducted under Good
Laboratory Practices according to provisions in 40 CFR part
792. The solubilities were determined for PV29 after being
ground into a fine powder and mixed in water or octanol for
24, 48, or 72 hours at room temperature. To determine the
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concentration of PV29 dissolved in water or octanol,
samples were passed through filters to remove any
suspended PV29 particles. The concentration of PV29
dissolved in water or octanol was below the analytical
quantitation limit of 0.003 mg/L in every sample tested.
These studies confirm that PV29 is an insoluble particulate
substance and there is no expectation that PV29 will be
taken up by fat solubility.
The octanol-air partitioning coefficient (Koa) describes the
distribution of a substance between octanol and air. The
results of the octanol solubility experiment, where PV29 was
not detected in any sample above the analytical quantitation
limit of 0.003 mg/L, demonstrates that PV29 does not
dissolve in octanol. Therefore, there is no expectation that
PV29 will be taken up by terrestrial organisms through fat
solubility.
Concerns about environmental persistence and fate evaluation and lack of data
SACC,
13, 55
SACC COMMENT:
Projection of environmental fate based on one-at-a-
time examination of physical properties is
unscientific.
PUBLIC COMMENTS:
EPA downplays the level of environmental
persistence for PV29. (13 44)
The Belgian Competent Authority issued a
document that elaborates on why PV29 should be
considered a potential PBT, observing that "[i]n
view of the structure of the substances, it is
reasonable to expect that the persistent and the very
persistent criterion are met for these substances and
QSAR estimations support this concern." The
Document adds that, for bioaccumulation potential,
EPA issued a Section 4 Test Order to require the
manufacturer of PV29, as well as an imported to generate
and submit additional testing to measure the solubility of
PV29 in water and octanol (more information can be found
in the Test Order docket (EPA-HO-OPPT-2020-0070-0008).
The results of this testing are incorporated into the final Risk
Evaluation. This testing was conducted with a modified
protocol that accommodates the particular physical-chemical
characteristics of PV29 and was determined to be high
quality after review with the data quality evaluation criteria
for physical chemical property studies Nicolaou (2020). The
results of the data quality evaluation of the physical
chemical property studies can be found in the supplemental
file, "Systematic Review Supplemental File: Data Quality
Evaluation ofPhvsical-ChemicalProperty Studies U.S. EPA
(2020c)." EPA also identified articles on similar organic
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"the log Kow and log Koa-values are important
metrics" and indicate a "high potential for
bioaccumulation in air breathers" and that "the
substance may accumulate in terrestrial organisms
and in mammals. The Document underscores that
significant additional testing is needed to better
define PV29's P and B properties, in marked
contrast to the draft PV29 evaluation, which
presumes that PV29 is not a PBT based on the data
available. (55_17)
pigments and used the research results as references to
support EPA's fate assessment on PV29.
EPA agrees with the assessment that PV29 is a persistent
substance. The Belgian assessment relied on experimental
results for Kow and Koa which EPA determined to be
unacceptable. EPA issued a test rule Order and Sun
Chemical Corporation conducted solubility testing showing
that PV29 does not dissolve in octanol or water. Therefore,
PV29 is considered not bioaccumulative for purposes of
TSCA risk evaluation.
Exposure and Releases
Charge Question 4.a: Please comment on the characterization of occupational exposures (inhalation and dermal) for the
manufacturing workers. Is the panel aware of other additional relevant information, including PV29 specific data, that could be
considered?
Charge Question 4.b: Please comment on the environmental release characterization for the manufacturing and use as a site limited
intermediate. Is the panel aware of other relevant additional information, if any, that could be considered?
Charge Question 4.c: Please comment on the exposure and release characterization for the downstream processors and users. Is the
panel aware of other PV29 specific data and/or information that could be considered?
Charge Question 4.d: Please comment on the screening level approach used in the context of the conclusions associated with
potentially exposed susceptible subpopulations (e.g., to children, workers, or pregnant women). Please comment on other additional
information or analyses that could be conducted, if any, in light of the screening level approach used in this case?
Charge Question 4.e: Please comment on the conclusion regarding the need for aggregate exposure.
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Summary of Comments for Specific Issues Related to
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EPA/OPPT Response
Supportive of EPA's occupational exposure assessment
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17, 45
The PV29 estimation of occupational exposure is
evidence of the utility of EPA's risk assessment
approach in appropriate cases. (17 4)
The current regulatory standards applicable to inert
nuisance dusts such as PV29, as well as the limited
U.S. production and use of the material, adequately
restrict reasonably foreseeable worker exposures.
(451)
EPA acknowledges these comments and encourages the
commenters to consult the final Risk Evaluation to note
changes to the occupational exposure.
Incorporate uncertainty analysis and screening-level fugacity modeling in life cycle safety assessment
SACC
SACC CCOMMENTS:
Incorporate uncertainty analysis into the life cycle
safety assessment (LCSA) risk evaluations and, at
a minimum, present screening-level calculations
when dismissing exposure pathways.
For non-ionizable organics, EPA should adopt a
screening level fugacity modeling approach as a
default under LCSA.
EPA included screening level occupational exposure
estimates for processing and downstream users
According to the developers of the fugacity model, for
substances like PV29 with no solubility in octanol or air, this
model mav not be useful Mackav et al. (1996). This is
because particulate substances like PV29 do not dissolve in
water, air, or octanol like molecular chemicals. Instead,
particulate substances will adsorb to solid surfaces and
undergo particle transport rather than partition between air,
water, and organic Mackav et al. (1996). To model
particulate substances, EPA would need to determine the
rates of attachment and detachment of PV29 particles to
environmental surfaces. EPA, under TSCA, has not
conducted such a modeling effort to date.
EPA did not consider full range of uses and exposure pathways
12, 13,
17, 18
PUBLIC COMMENTS:
EPA failed to identify or evaluate PV29's full
range of uses by ignoring many uses identified in
the 2012 TSCA Work Plan and uses that other
reliable sources consider "intended" and
"reasonably foreseen." (12 8)
EPA has dismissed a wide range of uses for PV29
and erroneously suggests that its risk
TSCA Section 3(4) grants EPA the authority to determine
what constitutes a condition of use for a particular chemical
substance. In the case of PV29, there were a group of "other
uses" that were identified early in the process with poor
quality references. Subsequent to the publication of the scope
document, no further information was found or received by
EPA that substantiated any of the uses with limited and poor-
quality references that had been characterized as "other uses".
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characterization should be limited to "actual use"
of PV29. However, TSCA requires EPA to
evaluate a chemical's risk under its conditions of
use and reasonably foreseen conditions of use. Any
circumstances that have been known to have
occurred in the past are reasonably foreseen
conditions of use and EPA must consider them in
the risk evaluation. (13 59-68).
The risk characterization did not account for the
full range of occupational uses and exposures.
Workers are potentially exposed by multiple routes
including dermal absorption, inhalation, and
possibly oral ingestion. (1216, 13_8, 1816)
EPA must revise its evaluation to reflect all
occupational uses and exposures, use its authority
to collect data, and reissue for public comment.
(18 16)
EPA lacks sufficient information to evaluate
potential uses of PV29, including the likely
duration, intensity, frequency, and number of
exposures under all conditions of use. The
omission of even a single condition of use is fatal
to EPA's risk evaluation. (1210, 13187)
EPA has not fully evaluated conditions of use for
consumers. (12_8, 13_244)
EPA has ignored reasonably foreseeable uses and
uses with evidence that the use is occurring or has
recently occurred, particularly with PV29 as an
intermediate. (13 5, 13 59, 13 79)
EPA did not consider all relevant exposures under
the conditions of use (e.g., as an intermediate,
import), as required under TSCA. Moreover,
EPA's arguments for excluding certain conditions
of use cannot simply be extended to exclude
consideration of exposures and hazards (13 5,
13 6, 13 287, 13 244, 13 261).
As a result, these uses were determined to not be intended,
known, or reasonably foreseen and are not conditions of use.
EPA does not believe that it is appropriate to categorically
consider all activities that occurred in the past but are not
currently occurring to constitute reasonably foreseen
conditions of use. As explained in the Procedures for
Chemical Risk Evaluation Under the Amended Toxic
Substances Control Act rule preamble, 82 FR 33726, 33730-1
(July 20, 2017), "[i]t is reasonable to foresee a condition of
use, for example, where facts suggest the activity is not only
possible but, over time under proper conditions, probable."
EPA's risk evaluation includes all known, intended, and
reasonably foreseen conditions of use. During EPA's initial
PV29 use investigation, a search was conducted to create the
use document (EPA-HQ-OPPT-2016-0725-0004). This use
document was not limited to only TSCA uses or information
of a particular level of quality. Subsequent to the publication
of the scope document, no further information was found or
received by EPA that substantiated any of the uses with
limited and poor-quality references that had been
characterized as "other uses". As a result, these uses were
determined to not be intended, known, or reasonably foreseen
conditions of use. This list included the following:
Applications in odor agents, cleaning/washing agents, surface
treatment, absorbents and adsorbents, laboratory chemicals,
light-harvesting materials, transistors, molecular switches,
solar cells, optoelectronic devices, paper, architectural uses,
polyester fibers, adhesion, motors, generators, vehicle
components, sporting goods, appliances, agricultural
equipment and oil and gas pipelines (EPA-HQ-QPPT-2016-
0725-0004).
Furthermore, EPA does not believe that it is appropriate to
categorically consider all activities that occurred in the past
but are not currently occurring to constitute reasonably
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EPA refused to analyze certain exposure pathways
in depth. (13 262)
EPA should not dismiss exposure pathways on a
cursory basis and must consider those exposures
when evaluating the combined exposures, not
make unjustified exclusions and cursory analyses
(13 264, 13 266).
When EPA declines to analyze an exposure
pathway further, EPA must have a sound, rational
basis for the assessment of that exposure and
consider how it may combine with other exposure
sources (13_263).
foreseen conditions of use. As explained in the Procedures
for Chemical Risk Evaluation Under the Amended Toxic
Substances Control Act rule preamble, 82 FR 33726, 33730-1
(July 20, 2017), "[i]t is reasonable to foresee a condition of
use, for example, where facts suggest the activity is not only
possible but, over time under proper conditions, probable."
EPA considered all potential routes of exposure. Based on the
physical chemical properties of PV29 and available data
about the potential hazards and exposures of PV29, EPA
determined that inhalation exposure from manufacturing and
processing is the primary route of concern, so this route of
exposure was assessed quantitatively. EPA included a
screening level assessment of risks to workers as a result of
inhalation exposures in the final Risk Evaluation. EPA
determined that oral exposure was not a relevant route of
exposure, as eating, drinking and smoking are prohibited in
the PV29 production facility, with the low hazard reported in
all oral toxicity studies and the low potential for absorption
meant that no risk concerns were identified from oral
exposure for all conditions of use.
All occupational uses and exposures have been included and
evaluated (Refer to Section 2.3.1). Uncertainties were
identified regarding reasonably available information
characterizing PV29's occupational worker inhalation
exposure. These uncertainties resulted in EPA requiring
testing of PV29 to develop new information in order for EPA
to increase certainty in the final Risk Evaluation of PV29
under TSCA section 6(b). Test data has been reviewed for
data quality according to the relevant data quality evaluation
metrics and incorporated into the final Risk Evaluation. Since
that data collected was in direct response to comments on the
draft risk evaluation, EPA has determined that it is not
warranted for this risk evaluation to be reissued for public
comment.
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EPA/OPPT Response
EPA does not lack information - EPA has used reasonably
available information and used test order authority where
there were uncertainties. Refer to section 2.3.1 in the risk
evaluation for the occupational exposures for the conditions
of use. EPA has not excluded any condition of use for this
evaluation. Each condition of use is intended, known, or
reasonably foreseen.
The only identified consumer condition of use of PV29 was
use in artistic paints and watercolors (Section 3.3.2).
Exposures from this condition of use are expected to be low
based on physical chemical properties and/or well below
those exposures likely to occur compared to occupational
users.
There were no uses determined to be reasonably foreseeable.
As described in a preceding response, there were a group of
"other uses" that were identified early in the process with
poor quality references. Subsequent to the publication of the
scope document, no further information was found or
received by EPA that substantiated any of the uses with
limited and poor-quality references that had been
characterized as "other uses". As a result, these uses were
determined to not be intended, known, or reasonably foreseen
and are not conditions of use. PV29 as an intermediate is
included as a condition of use. Once PV29 is used as an
intermediate, it is no longer present; therefore, end products
formed following reactions using PV29 as an intermediate
are not conditions of use of PV29 and thus are not evaluated.
General population and consumer exposures were evaluated
to the degree possible given the reasonably available data and
expected routes of exposure.
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EPA/OPPT Response
There is low confidence in the result of aggregating
exposures and risks for this chemical if EPA uses an additive
approach due to the uncertainty of the data. EPA does not
have data that could be reliably modeled for the aggregate
exposure.
EPA failed to consider workers experiencing multiple routes of exposure
8, 12,
13
EPA failed to account for multiple routes of
occupational exposure, such as cleaning paint
booths and other locations. (13 8, 13 211, 12 9)
EPA's "screening-level analysis of sentinel
exposure (dermal and inhalation) to workers" is
inadequate because it fails to mention the potential
that a worker might be exposure by both inhalation
and dermal routes. (13 197)
EPA repeatedly understates the risks to exposed
workers when calculating dermal and inhalation
exposures by ignoring the fact that many workers
will face both; EPA does not evaluate whether
PV29 is safe for workers who both touch and
inhale it. (12 16)
EPA's series of rationales for dismissing the
significance of worker exposures are weak and
based on little actual data or analysis. (13161)
EPA was unclear in its assumptions regarding
dermal exposure levels (812)
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. 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.
EPA has updated its assumptions regarding dermal exposure
levels in the final Risk Evaluation.
Deficiencies in exposure data and analysis
8,13,
16, 18,
75
PUBLIC COMMENTS:
EPA lacks critical exposure information for PV29
and took no steps to require the submission or
development of any more exposure data. As a
TSC A requires EPA to use reasonably available information
and best available science in its risk evaluation. Utilizing the
systematic review process, EPA used reasonably available
data and best available science in a weight of scientific
evidence analysis. EPA identified uncertainties regarding
reasonably available information characterizing the solubility
and occupational inhalation exposure (including duration,
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result, the evaluation has major exposure data
deficiencies (13_80).
EPA lacks substantial evidence on occupational
exposures from the inhalation and dermal routes.
(13_90)
EPA did not comply with TSCA because it did not
consider the likely duration, intensity, frequency,
or number of exposures for PV29 (13 187,
13 310).
EPA should require the following data: (13 284)
Use data
- Range of concentrations in industrial, commercial,
and consumer products
- Measured levels of residual PV29 left in products
made using PV29 as an intermediate, where PV29
is a reactant or where PV29 is added to adjust the
color of other pigments
- Empirical data on frequency of product use for
industrial, commercial, and consumer products
- Empirical data on duration of product use for
industrial, commercial, and consumer products
Fate data
- Measured data on absorption by inhalation, dermal,
and oral routes, for PV29:
- as produced in solid (powder) form
- as produced in solution form
- in each type of formulation in which it is present
- Measured water solubility in a reliable study that
accurately accounts for pH
- Measured bioconcentration factor (BCF) and
bioaccumulation factor (BAF)
- Appropriate values to assess
bioconcentration/bioaccumulation directly from air
Environmental release and exposure data
intensity, frequency, or number of exposures for PV29) for
PV29. These uncertainties resulted in EPA requiring testing
of PV29 to develop new information, in order for EPA to
increase certainty in the final Risk Evaluation of PV29 under
TSCA section 6(b). Test data has been received, reviewed for
data quality according to the relevant data quality evaluation
metrics and incorporated into the final Risk Evaluation. For
all data elements, except when it relates to solubility or
inhalation exposure, EPA determined that it has sufficient
reasonably available information. With the generation and
submission of the additional testing under TSCA section 4,
EPA now has sufficient reasonably available information for
all data elements relevant to PV29. Where assumptions were
used in the final Risk Evaluation as a result of deficiencies in
the available data, these were explained clearly in the final
Risk Evaluation.
Where EPA received additional data from the manufacturing
stakeholders of PV29 to reduce uncertainties about the
manufacturing practices and environmental releases of PV29,
in the form of. correspondences with manufacturing
stakeholders, this was made publicly available in the docket
in the Supplemental File: Information Receivedfrom
Manufacturing Stakeholders U.S. EPA (2020a). This
information includes SDSs as well as updates to the
Environmental release information (described in Section 3.2)
New occupational exposure estimates were added for the
manufacturing workers. These estimates were prepared using
recent monitoring data and several conservative assumptions.
The new screening level occupational exposure for the down-
stream processors and users were added. These estimates use
several conservative assumptions which will cover the worst-
case scenarios.
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- Measured data for air, water, and waste releases
from sites of manufacture, processing, and
industrial or commercial use; wastewater treatment
(both effluent and sludges/biosolids); landfill
leachate and effluent and sludges/biosolids from
leachate treatment
- Measured data for presence/concentration in
environmental media and organisms (air, water,
sediment; aquatic, sediment-dwelling, and
terrestrial organisms) near manufacturing,
downstream processing and use, and disposal and
land (biosolids) application sites
- Occupational exposure data (for all manufacturing
and downstream processing and use sites)
- Monitoring of air concentrations, for dust, mists,
aerosols, vapors (75_2)
- Monitoring of dust on surfaces and concentrations
in solutions in all settings where skin contact with
the surfaces or solutions could potentially occur
- Numbers of workers potentially exposed in each
activity/setting, at each site
- Specific engineering controls, PPE and workplace
practices in place at each site/setting, and data on
their extent of use and efficacy
- SDSs: If EPA plans to rely on SDSs, then EPA
needs empirical data on extent of their availability
and comprehension to all potentially exposed
workers; their completeness, accuracy and
currency; extent of compliance with protective
measures they specify
Opposition to EPA's reliance on personal communication from Sun Chemical
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9,10,
12, 13,
15, 18
PUBLIC COMMENTS:
EPA should not have relied on the single personal
communication with Sun Chemical Corporation to
obtain "air monitoring data" and the "maximum air
concentration value." (911, 10_5, 1212, 13_86,
13 93, 15 9, 18 8) Sun Chemical Corporation is
an entity with a strong interest in having EPA find
its chemical safe. (13 93)
By relying on this personal communication with
the potentially regulated manufacturer, EPA failed
to include the full range of job tasks, chronic
health/exposure studies, and representative
monitoring data necessary to evaluate occupational
exposure. (18 8)
While EPA uses this value, the Agency knows
nothing about the data quality, how the
concentration was determined, or what this
workplace air value actually represents. This
personal communication does not constitute the
"best available science." (9 11,12 12,15 9,
105)
OSHA refuses to rely on undocumented exposure
measurements offered by industry without study
details and requires employers to preserve
exposure records; EPA should have requested
these monitoring data and protocols from
employers (i.e., Sun Chemical Corporation) in
order to evaluate their data submission. (1214)
EPA should take steps to allow workers to provide
input in a manner that reduces the risks of any
potential retaliation from management. (13 297)
EPA acknowledges the uncertainty related to the use of a
point estimate to describe potential workplace exposure to
PV29 dust as a result of workplace activities. In response to
these uncertainties as well as public and SACC comments,
EPA issued a TSCA Section 4(a)(2) Test Order for PV29 on
February 28, 2020. This Test Order required the generation
and submission of a workplace air monitoring study of
particles not otherwise regulated, conducted according to the
NIOSH 0600 guideline available at:
https://www.cdc.sov/NIOSH/DOCS/2003-
154/Ddfs/0600.Ddf.
This study takes into account a full range of job tasks and
representative monitoring of actual PV29 production at the
sole U.S. manufacturing facility of PV29. This study has
been evaluated for data quality and the results are
incorporated into the final Risk Evaluation for PV29. More
information about the Section 4 Test Order for PV29 can be
found in the docket (EPA-HO-OPPT-2020-0070-0008V
During the data collection phase of the Risk Evaluation
process, EPA welcomed comments and information on
occupational exposure. The Agency did not receive any
comments considered.
Concern regarding EPA's approach to evaluate only highest anticipated exposure
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13
PUBLIC COMMENTS:
EPA's assertion that it need only account for the
highest anticipated exposure ignores the potential
that multiple sources of exposure (e.g., at work and
at home) may engender a risk greater than the risk
from the highest exposure alone. (13 196, 13 198)
EPA's decision to conduct only a screening-level
assessment of certain workers and claim that it can
serve as the sole sentinel exposure for all other
human exposures is scientifically corrupt and fails
to meet TSCA's mandates. (13_200)
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 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 risks separately from other
pathways as the basis for the unreasonable risk determination
is a best available science approach. There is low confidence
in the result of aggregating the risks from various exposure
pathways 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 available
data, EPA's approach is the best available science.
Available data for PV29 indicate low hazard and low
potential for exposures. As a result, it was determined that a
mix of quantitative assessment and qualitative, screening-
level assessment, was the most optimal approach to focus
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efforts on the exposure pathways that are most likely to result
in potential risks.
Supports tiered approach that incorporates PPE in the exposure assessment
17
PUBLIC COMMENTS:
EPA should use a tiered approach to exposure
assessment that incorporates PPE. Margin of
exposure (MOE) calculations did not account for
PPE (which is acceptable in this case), but EPA
should use higher tier methods that account for
worker protections when necessary. (1719)
In the final Risk evaluation, EPA calculated risks to workers
without PPE and with PPE.
Opposes assumption of PPE use in the exposure assessment
11,12,
13, 15,
16, 18,
44, 77,
82
PUBLIC COMMENTS:
EPA should not use the baseline assumption that
PPE is used, and used correctly, when assessing
occupational exposure. (18 12,13 166,12 18,
152)
EPA makes incorrect assumptions regarding
absence of data, extrapolation of data to alternate
exposure routes, exposure characteristics, use of
PPE, adherence/enforcement to workplace policies
(i.e., no-eating-or-smoking policy), model inputs,
and similarities between PV29 and other
chemicals. (11 6, 12 18, 13 7, 13 98, 13 99,
13 101, 13 103, 13 167, 15 2; 16 37, 16 94,
1811, 44_5, 77_4, 82_3)
There appear to be no empirical data to document
the extent of use or effectiveness of any of
Through correspondences with Sun Chemical, and by
consulting the SDSs available for PV29, EPA has gathered
information about the types of PPE utilized throughout the
manufacturing process for PV29. This information is being
made publicly available in the Supplemental File:
Information Received from Manufacturing Stakeholders U.S.
EPA (2020a).
Statements on SDS and use of PPE used by the downstream
processors and users were updated to indicate the
uncertainties.
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
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industrial hygiene controls, such as PPE or SDS
adherence. (13 169)
EPA should use its authority to require data in
order to have empirical data on actual use of PPE.
(13 284)
No information is provided on the type of PPE
used and whether it is sufficiently protective to
reduce oral exposure. (13 168)
Given that EPA has not identified the workplaces
where PV29 is used, it has no basis for assuming
the use or effectiveness of unspecified PPE.
(1218)
EPA has an obligation to evaluate exposures and
risks for the subset of people for whom
engineering controls are not in place or do not
reach 100% efficiency. (13 302)
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. 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 and EPA's assumptions are described in the
unreasonable risk determination for each condition of use. In
the case of PV29, risks were not identified for oral exposure
because of low exposure and low hazard for oral exposure.
Therefore, use of workplace practices prohibiting eating,
drinking and smoking in manufacturing and processing
facilities is important but not an ultimate determining factor
in whether risks are expected for oral exposure.
EPA should not rely on the presence of and compliance with safety data sheets (SDS)
11,12,
13, 15,
18
PUBLIC COMMENTS:
It is unacceptable for EPA to rely on the presence
of accurate, well-understood SDSs and that
workers and employers will comply with SDSs as
a means to minimize occupational exposure.
(1813, 13166, 11 7, 1514)
EPA provides no evidence to support this
assumption that workers will read and understand
Statements on PPE use by the downstream processors and
users were updated to include a discussion of the
uncertainties.
As stated above, 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
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SDS; in fact, there is extensive evidence it is
incorrect in many instances. (117)
SDSs should not be a substitute for a workplace
control plan to eliminate and mitigate PV29
occupational exposure. (18 13)
EPA assumes without evidence that engineering
controls and PPE described in unpublished
industry SDSs are universally used in all
workplaces. (13_172)
Manufacturer admonitions on SDSs are not
enforceable and cannot support a determination
that PV29 presents no unreasonable risk. (1218)
Workers and small employers often have a great
deal of trouble understanding SDSs. Employers
often ignore not only SDS recommendations, but
basic, common-sense safety rules. (1111)
SDSs often contain inaccuracies and are
incomplete, as concluded by a review study of 24
SDSs. (1113)
EPA appears to be operating under a significant
misunderstanding of OSHA's Hazard
Communication Standard (HCS); a
recommendation on a safety data sheet by itself
would not trigger the need to implement new
controls. (118, 119)
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. 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.
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 should prioritize engineering controls over PPE or warning labels to reduce exposure
11,12,
13, 15,
18
PUBLIC COMMENTS:
Under OSHA Hierarchy of Controls, PPE is the
least effective form of protection; EPA should use
this hierarchy and prioritize measures to reduce
occupational exposure, not rely on PPE or warning
As indicated above, 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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labels to reduce exposure (18 14,13 307,15 16,
12 19)
There is widespread support, including in court, for
the hierarchy of control. (18 15)
The most effective way to control dust in the
workplace is through engineering controls, rather
than PPE; reliance on PPE rather than engineering
controls is unacceptable. (11_4)
that may be applicable to particular worker tasks on a case-
specific basis for a given chemical.
Concerns about lack of release data
13
PUBLIC COMMENTS:
EPA has no actual data on the levels of PV29
released to or present in workplaces, products, or
environmental media and has not used its
authorities to require these data. (13 84)
EPA requested additional info detailing possible releases of
PV29 to the environment. That information is communicated
in Section 3.2 and the Supplemental File: Information
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CPMA submitted a comment noting use of PV29
in downstream applications involving high heat
(could generate vapors) or spraying (could
generate mists or aerosols), yet EPA fails to
mention or analyze the potential for inhalation
of forms other than powder or dust. (13 95,
13 97)
EPA should clarify the procedure through which
PV29's particle size distribution was calculated,
and, if bulk material was tested, redo its analysis to
reflect the size distribution for the airborne
particles to which workers are exposed. (7810)
information used in the assessment that was provided by the
US manufacturing stakeholders for PV29 can be found in the
Supplemental File: Information Received from
Manufacturing Stakeholders U.S. EPA (2020a).
Workers may be exposed to mist (paint and ink) Downstream
exposure estimate using OSHA PEL is applicable for mist
exposure and a statement on possible mist exposures for the
relevant conditions of uses was included.
Particle size distribution data is available in the Supplemental
File: Information Receivedfi'om Manufacturing Stakeholders
U.S. EPA f2020a).
Concerns about occupational dermal exposure analysis and clarity
13
PUBLIC COMMENTS:
To assess dermal occupational exposure, EPA
relied on modeling, even though EPA itself
acknowledges that measured workplace exposure
data is preferable to modeling. (13 91)
Some aspects of the modeling are conservative
(e.g., a "high" default for the amount of solid
material contacting skin, assumed no use of
gloves) and others are not (e.g., assumed single
exposure event per worker per day, assumed a
single worker is exposed per day) even though the
range of activities to which the model applies
would clearly have the potential to involve
multiple exposures per day or exposure of multiple
workers. (13 99)
EPA presented only a single dermal exposure
scenario that it claims represents the "theoretical
Input parameters and assumption for the inhalation and
exposure modeling are consistent with those used in other
OPPT assessments including the TSCA New Chemicals
program.
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maximum exposure" with no basis for this
characterization. (13 99)
EPA's dermal exposure analysis assumed only
PV29 in solid form, yet PV29 is also produced in
the form of a high-concentration solution. (13 6,
13_96, 13101)
EPA hand-waves away dermal exposure in part by
assuming that PPE is always used and used
effectively. (13 182)
EPA should revisit its decision not to assess occupational oral exposure
12, 13,
15
PUBLIC COMMENTS:
EPA's argument assumes that oral exposure only
occurs if workers eat contaminated food or smoke
is incorrect. (13 167)
This argument assumes without any documentation
that there is 100% compliance with the no-eating-
or-smoking policy. Research has revealed that
incidental ingestion from hand-to-mouth contact
occurs in the workplace. (13167)
EPA should more closely assess the potential for
oral exposure via pathways beyond ingestion of
contaminated food. (13168)
Dermal and inhalation exposures make oral
ingestion likely in a workplace. (1216)
EPA hand-waves away oral exposure in part by
assuming that PPE is always used and used
effectively. (13182, 1218)
EPA's blanket rejection of the oral route of
exposure is not supported by science; it has been
estimated that approximately one in six workers
may be involved in tasks in which inadvertent
ingestion exposure could contribute to their total
body burden. (1514)
EPA agrees that oral exposures are possible other than from
contaminated food or smoking. EPA's inhalation exposure
estimate included oral exposure via incidental ingestion of
inhaled mist/dust. However, EPA currently does not have
data or methods to fractionate the total PV29 inhaled into the
amount of PV29 that deposits in the upper respiratory system
and the amount of PV29 that goes into the lung.
EPA generally does not separately evaluate occupational
exposures through the oral route. Workers may inadvertently
transfer chemicals from their hands to their mouths or ingest
inhaled particles that deposit in the upper respiratory tract.
The frequency and significance of this exposure route are
dependent on several factors including the physical-chemical
properties of the substance during worker activities, the
visibility of the chemicals on the hands while working,
workplace training and practices, and personal hygiene that is
difficult to predict Cherrie et al. (2006).
EPA may consider the relevance of oral exposure route on a
case-by-case basis, taking into consideration the
aforementioned factors and any reasonably available
information, and may assess oral exposure for workers for
certain COUs and worker activities where warranted. For
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PV29, EPA did not find any information indicating
significant oral exposure during the systematic review of the
materials found.
EPA did not properly assess exposure of downstream processors and users
11, 12
13, 15,
16, 44,
55
PUBLIC COMMENTS:
EPA assumes that downstream processors and
users are at low risk of exposures because they
wear PPE, which is an incorrect way to assess
health risk. (13 11,15 21)
EPA restricts its occupational exposure analysis to
the site of manufacture, failing to account for
worker exposures at downstream processing and
use sites. (13154)
EPA does not appear to have received or obtained
significant information from the processors of
PV29, only the sole manufacturer. (13 288)
EPA's analysis is based on the unsupported
assertion that downstream worker exposure and
industrial uses will be less than manufacturing
exposure because volume handled is less and the
manufacturing exposure represents a "worst case";
there is no basis for this. (13 6,11 16,15 19,
167)
It is inappropriate for EPA to discount exposure at
processing and use sites since EPA has no data on
the of use or efficacy of engineering controls, SDS,
and PPE downstream. (13 156)
EPA inappropriately used the approximate
maximum workplace air concentration reported in
a personal communication from Sun Chemical to
The new screening level occupational exposure for the down-
stream processors and users were added. These estimates use
several conservative assumptions which will cover the worst-
case scenarios.
Statements on SDS and PPE use by the down-stream
processors and users were updated to indicate the
uncertainties.
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estimate downstream worker exposure. (12 13,
44 11-13, 55 5-6, 55 18, 15 9, 16 7)
Downstream occupational exposure may
significantly exceed manufacturing site exposure
given the potentially different activities and
controls that might be in place. (1116, 13107)
EPA has failed to use the best available science for
downstream exposure. (13 161, 15 19)
EPA lacks data on potential exposure of
downstream workers at processing and use sites,
number of sites involved, and number of
potentially exposed workers. (13104)
Without evaluating downstream exposures, PA has
no basis for comparing risks faced by
manufacturing workers to those who work with or
use downstream products. (1210, 13187)
EPA has failed to use its authority to collect data
on downstream exposure. (13_284)
Concerns about the environmental release characterization
13, 16
PUBLIC COMMENTS:
EPA fails to include basic information about
environmental release critical for a meaningful
assessment of PV29's risks to the environment, as
required by TSCA. (16_32)
No calculation or data are presented to support the
conclusion that approximately 1-2% of the
production volume is released into the
environment. (16 46)
EPA relies on industry determination that use is
restricted to a single site; as a result, sources of
exposure are overlooked. (13 77, 13 78)
The only remotely "quantitative" element
regarding exposures is the manufacturer's asserted
EPA requested additional info detailing possible releases of
PV29 to the environment and based its environmental risk
characterization on the best reasonably available information.
The information received from communications with Sun
Chemical is communicated in Section 3.2 and 2 and the
Supplemental File: Information Received from
Manufacturing Stakeholders with resultant releases to surface
water beins
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estimate for water discharges from its facility, but
this value is unreliable and insufficient. (13188)
EPA does not properly analyze distribution and
gives no attention to potential releases and
exposures resulting from accidental releases.
(13 268,13 269)
EPA's analysis of biosolids is particularly lacking;
a thorough analysis of biosolids would be
appropriate given that PV29 is poorly
biodegradable. (13 266)
environment and felt it was worth including due to the
absence of other information.
Accidental releases Spills and leaks generally are not
included within the scope of a TSCA risk evaluation. EPA is
exercising its authority under TSCA to tailor the scope of the
risk evaluation for PV29, rather than evaluating activities
which are determined not to be circumstances under which
PV29 is intended, known or reasonably foreseen to be
manufactured, processed, distributed, used, or disposed of, or
environmental exposure pathways addressed by another
EPA-administered statute and associated regulatory program.
First, EPA does not identify PV29 spills or leaks as
"conditions of use." EPA does not consider PV29 spills or
leaks to constitute circumstances under which PV29 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 MC 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 PV29 could be
considered part of the listed lifecycle stages of PV29, EPA
has "determined" that spills and leaks are not circumstances
under which MC 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 exercising its discretionary authority to exclude
MC spills and leaks from the scope of the MC risk
evaluation. The exercise of that authority is informed by
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EPA's expertise 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
expertise 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, 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 PV29 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
PV29 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
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cannot be accurately predicted or calculated based on
reasonably available information, including spills and leaks,
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."
EPA qualitatively assessed discharges of PV29 in biosolids
based on its physical chemical and fate properties. Based on
its low solubility (<0.003 mg/L), PV29 in land-applied
biosolids is not expected to leach to soil or groundwater.
PV29 is not expected to bioaccumulate in tissues, and
concentrations will not increase from prey to predator in
either aquatic or terrestrial food webs.
EPA did not consider environmental release of PV29 when used as an intermediate
13
PUBLIC COMMENTS:
EPA asserts without evidence that use of PV29 as
an intermediate does not result in environmental
releases and exposures and does not mention the
potential for PV29 to remain in products generated
from its use as an intermediate. (13 71)
EPA leaves open the question of whether
intermediate use of PV29 is restricted to a single
site or may involve more than one site, which
would involve storage, transport, and transfer and
thus greater risk of release and exposure. (13 76)
EPA does not have information one the residual PV 29 after
it is used as a chemical intermediate for the manufacture of
other pigments. However, release and exposure from any
residual PV29 is expected to be lower than the exposure and
releases from use of PV29.
Concern about assumption that PV29 remains "bound" in downstream use
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13,
16(S)
PUBLIC COMMENTS:
There are reasons to question the notion that PV29
is "bound in a matrix" once in consumer products,
including at end-of4ife. (16(S) 9)
EPA failed to consider the disposition of PV29
when products, including plastics, enter the waste
and recycling streams, where any "encapsulated"
compound may be released. (16(S)_11)
EPA should not rely on a food additives petition to
FDA that is not publicly available to conclude
that PV29 will not leach from plastics or paints.
(13171)
As stated in the risk evaluation, PV29 is not expected to leach
out of plastics when it is encapsulated. PV29 demonstrates
negligible solubility in both octanol and water, and no
toxicity effects were observed following oral or dermal
exposure. Additional data, submitted to fulfil the conditions
of the Section 4 test order confirm that PV29 exhibits a low
solubility in octanol and water (<0.003 mg/L). This reduces
the uncertainties about whether PV29 would be expected to
leach from plastics once it is encapsulated. Furthermore, risks
were not identified at the highest exposure concentrations
during manufacturing, so risks are not expected to result from
exposure to PV29 in plastics, as these potential exposures are
negligible.
EPA is not relying on the results of the food additive petition
to draw conclusions about the potential for PV29 to leach
from plastics. The same data are used in this assessment as
well as in the food additive petition and as a result, similar
conclusions were drawn in both documents regarding the
potential for leaching from plastics.
EPA was right to remove conditions of use it was unable to support
8,17,
45
EPA was right to remove "other uses" and
"import" as conditions of use due to the inability to
support these uses. If there were no data of concern
or all uses were already covered and non-standard
uses were not anticipated, EPA should make such a
statement. (8_7, 17_5, 45_3)
Based on information provided in public comments, EPA has
included import as a condition of use of the evaluation (see
section 1.5 of the final Risk Evaluation).
Evaluation lacks information on conditions of use
12, 13,
16,
16(S),
82
PUBLIC COMMENTS:
The draft risk evaluation lacks crucial information
on the conditions of use of PV29. In particular,
EPA ignored the presence of PV29 in products
made using PV29 as an intermediate even though
Intermediates are evaluated in the risk evaluation. EPA
prepared exposure estimates using OSHA PEL for total and
respirable dust which results in a protective approach and
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represents all downstream processors and users who might be
exposed to dust or mist containing PV29 in products.
Following the publication of the Draft Risk Evaluation,
information was received from a group of NGOs indicating
that BASF Corporation imports C.I. Pigment Violet 29 in
volumes less than 25,000 pounds per year (EP A-HQ-OPPT-
2018-0604-0016). Therefore, import of C.I. Pigment Violet
29 is included as a condition of use.
A list of "other uses" was compiled during EPA's initial
search for PV29 conditions of use. This list of other uses
included the following: Applications in odor agents,
cleaning/washing agents, surface treatment, absorbents and
adsorbents, laboratory chemicals, light-harvesting materials,
transistors, molecular switches, solar cells, optoelectronic
devices, paper, architectural uses, polyester fibers, adhesion,
motors, generators, vehicle components, sporting goods,
appliances, agricultural equipment and oil and gas pipelines
(EPA-HQ-OPPT-2016-0725-0004). However, no further
evidence was found or submitted during the scope, problem
formulation and draft risk evaluation steps to support these
"other uses" as intended, known, or reasonably foreseen
conditions of use for C.I. Pigment Violet 29. As a result,
these uses were determined to not be intended, known, or
reasonably foreseen conditions of use.
EPA disagrees that it made no effort to further identify
unknown uses or dismissed certain conditions of use based
on little evidence. EPA conducted extensive research and
outreach including review of published literature and online
databases including the most recent data available from
EPA's Chemical Data Reporting program (CDR) and Safety
Data Sheets (SDSs). EPA also conducted online research by
reviewing company websites of potential manufacturers,
importers, distributors, retailers, or other users of C.I.
Pigment Violet 29 and queried government and commercial
trade databases. EPA also received comments on the Scope of
the evidence in the record establishes that PV29
often remains present in such products. (13 5)
EPA has provided no analysis explaining why
"import" and the "other" uses are no longer
considered reasonably foreseen, especially given
that PV29 has a domestic market and is sold to
downstream processors and users, so may be
imported in the future. It is reasonably foreseeable
that persons might use PV29 in those same
circumstances in the United States if persons
already use PV29 for those purposes abroad.
(13 63 & 66)
EPA made no effort to further identify "unknown"
uses. (16 41)
By dismissing certain conditions of use based on
little evidence, EPA violates its duty under the
statutory language to consider all conditions of use,
exposures, and hazards. (13_244)
By excluding downstream conditions of use (e.g.,
candles, carpet fibers, paint, coatings), EPA failed
to evaluate downstream worker and consumer
exposure. (12 9, 16(S) 8)
The risks of these additional activities, in
combination with those from the originally
intended activities, could well increase to a point
where EPA would find that the chemical "presents"
or "may present" an unreasonable risk. Hence it is
vital that EPA consider both intended and
reasonably foreseen conditions of use in its initial
review. (82_4)
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the Risk Evaluation for Pigment Violet 29 (U.S. EPA, 2017c)
that were used to determine the current conditions of use. In
addition, EPA convened meetings with companies, industry
groups, chemical users, states, environmental groups, and
other stakeholders to aid in identifying conditions of use and
verifying conditions of use identified by EPA. Those
meetings included a February 14, 2017 public meeting with
such entities and a September 15, 2017 meeting with several
representatives from trade associations.
In any event, EPA disagrees that it has a statutory duty to
consider all conditional of use in each risk evaluation. As
explained in the final rule for Procedures for Chemical Risk
Evaluation Under the Amended Toxic Substances Control
Act, TSCA section 6(b)(4)(D) requires EPA to identify "the
hazards, exposures, conditions of use, and the potentially
exposed or susceptible subpopulations the Administrator
expects to consider" in a risk evaluation, suggesting that EPA
may exclude certain activities that EPA has determined to be
conditions of use on a case-by-case basis. (82 FR 33736,
33729; July 20, 2017). For example, EPA may exclude
conditions of use that the Agency has sufficient basis to
conclude would present only de minimis exposures or
otherwise insignificant risks (such as use in a closed system
that effectively precludes exposure or use as an intermediate)
or that have been adequately assessed by another regulatory
agency.
EPA has included a more detailed discussion of potential
risks to downstream conditions of use in the final Risk
Evaluation. EPA plans to consider all reasonably foreseen
uses as they apply to PV29.
Inadequate characterization of potentially exposed or susceptible sub-populations (PESS)
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11,13,
14, 16
PUBLIC COMMENTS:
EPA dismissed concerns about exposures of
vulnerable subpopulations, distorting the law's
definition and failing to meet TSCA's
requirements. (13190, 16_3 7)
EPA's approach of accounting for the highest
anticipated exposure ignores the potential that a
lower exposure may result in greater risk to a
member of a vulnerable subpopulation. (13 196,
1414)
EPA should identify people living near disposal
sites, sources of contamination, and other
conditions of use as PESS. (13 298)
EPA should always evaluate exposures scenarios
without engineering controls and PPE in order to
assess exposures and risks to those subpopulations
not subject to such controls. (13 301)
Workers are a relevant PESS, and EPA has not
provided adequate evidence that it has made an
accurate determination as required by TSC A.
(11_17)
EPA assertions that the risk evaluation is
protective of workers, consumers and the general
population are not supported by data. (14 20)
EPA uses the high-end exposure value when making its
unreasonable risk determination in order to address
uncertainties around PPE usage as well as to capture
exposures for PESS. Because EPA is making its
unreasonable risk determinations on the high-end exposure
value for workers and either the high-end exposure value or
central tendency for ONUs, depending on the data, and
factoring in the uncertainties due to UF factors, it is unclear
how this is a flawed approach. Additionally, EPA makes an
unreasonable risk determination and makes no determination
on reasonable risk.
Support for and request for clarity regarding quantitative screening-level exposure assessment
8, 17
PUBLIC COMMENTS:
Two commenters generally support the
quantitative screening level exposure assessment
approach used by EPA. (1716, 8 8)
EPA should explain why a quantitative screening-
level exposure assessment was added, given that it
EPA initially proposed the screening level-approach in the
assessment for human health to incorporate available data to
create a high-end risk estimate for the most highly exposed
subpopulation, which was determined to be workers at the
sole US manufacturing facility of PV29. Where data were not
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was not anticipated in the problem formulation and
scoping phase. (17 16, 8 8)
EPA should explain how quantitative exposure
assessment data were obtained and checked for
their reliability and accuracy. (8 8)
available, monitoring data received from the manufacturer for
respirable dust to represent a worst-case exposure scenario.
After problem formulation, EPA chose to perform additional
quantitative analysis to increase confidence in the results of
its screening-level assessment. In response to comments
received from the public as well as the SACC, EPA has
worked to obtain additional exposure information for PV29
in order to refine and enhance the conclusions made in the
initial screening-level risk calculations.
EPA did not address exposures in pregnant women, children, and other downstream users
9,10,
12, 16,
16(S)
PUBLIC COMMENTS:
EPA's evaluation of PES S does not cover
populations that are known to be more susceptible
to chemical hazards, such as pregnant women or
children, particularly workers who could be
pregnant. (12_20)
EPA fails to consider downstream exposure of
users of products such as paints, art supplies, toys,
food packaging, plastics, candles, and carpets
containing PV29, which particularly significant
because PV29-containing products can be used by
pregnant women and children who are more
susceptible to environmental hazards. (9 12, 12 8,
12_9, 1210, 16(S)_6, 16(S)_7, 16(S)_8)
EPA cannot assume that pregnant women or
children exposed during downstream use have
lesser exposures and are adequately protected.
(16 37)
Children crawling on carpets containing PV29 can
potentially be exposed through dermal contact and
ingestion. PV29 can also become dispersed into the
indoor environment through routine abrasion and
cleaning. (16 39)
As stated in the risk evaluation, the reasonably available data
does not indicate increased susceptibility for any particular
group or subpopulation. In addition, based on available data
for high end exposure to workers handling PV29 in an
occupational setting, EPA is confident that this presents a
high-end exposure scenario.
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EPA was correct to focus on sentinel exposure
17, 19
PUBLIC COMMENTS:
EPA was correct to focus on sentinel exposure for
PV29, but if the Agency conducts aggregate
exposure assessments in the future, it must be clear
about how and what it considered and show that it
was appropriate to do so. (17 18)
EPA's conservative assumptions with regard to
inhalation and dermal exposures are protective and
appropriate. (19 9)
EPA acknowledges these comments and encourages the
submitters to consult the final Risk Evaluation for
refinements made since the publication of the draft risk
evaluation.
Support for aggregate exposure vs. sentinel exposure assessment
SACC,
10, 13
SACC COMMENTS:
Aggregate exposures should be considered
including use of PV29 in food packaging.
PUBLIC COMMENTS:
EPA should combine all routes of
exposure (including dermal, oral, and
inhalation) when making a risk
determination. (10 14)
EPA's rationale for adopting a sentinel over
aggregate exposure assessment approach is
inadequate, distorts the meaning of sentinel
exposure assessment, and is not a science-based
approach. (13195)
The presence of PV29 in food packaging is under the
purview of the Food and Drug Administration and no
information was identified to understand the production and
uses of PV29 as a result of these pathways.
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 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 risks from other routes of
exposure separately as the basis for the unreasonable risk
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determination is a best available science approach. There is
low confidence in the result of aggregating the inhalation
risks and other routes of exposure 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.
EPA should pursue exposure and releases information from a wider range of organizations
SACC
SACC COMMENTS:
More aggressively pursue information from
manufacturer(s) of life cycle sustainability
assessment (LCSA) targets, purchasers/users of
those chemicals, trade associations, and other
federal and state regulatory agencies that may have
specialized knowledge.
When preparing this Risk Evaluation, EPA obtained and
considered reasonably available information, defined in 40
CFR 702.33 as information that EPA possesses, or can
reasonably obtain and synthesize for use in risk evaluations,
considering the deadlines for completing the evaluation. EPA
also communicated with manufacturing stakeholders of C.I.
Pigment to better understand the production and uses of
PV29.
Other SACC comments related to physical chemical properties
SACC
SACC COMMENTS:
Refrain from making sweeping generalizations
especially when based on limited and/or uncertain
information regarding physical chemical
properties or toxicological testing.
Include Jmax. ss (maximum steady-state dermal
flux) estimates in their list of physical chemical
properties routinely reported in TSCA risk
assessments.
By definition, the maximum steady-state dermal flux is
calculated using the dermal permeability coefficient (Kp) and
the solubility of a substance both in the same vehicle. Since
PV29 is not soluble in any solvents except strong acids, this
value cannot be estimated.
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Charge Question 5.a: Please comment on the evidence used to support the characterization of hazard to ecological receptors from
acute and chronic exposure as presented in the document.
Charge Question 5.b: Strong sorption to sediment is indicated as a result of the estimated Koc of 5.0 based on estimations from EPI
Suite. While this indicates that exposures to aquatic organisms in the water column are likely to be low, this also indicates that
potential water releases could result in exposure to sediment-dwelling organisms. EPA assumed low hazard to these organisms due to
the lack of toxicity observed in the tests conducted with all other aquatic species, particularly Daphnia magna. Given the acute hazard
profile for this chemical, limited releases, and the physical-chemical characteristics of PV29, please comment on the risk
characterization for sediment-dwelling invertebrates.
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Need for more data to evaluate hazard to aquatic ecological receptors
13, 16,
46
PUBLIC COMMENTS:
There is insufficient data to evaluate potential
ecological hazards and risks. EPA has no
information on chronic aquatic toxicity or toxicity
to sediment-dwelling organisms. (13 7,13 109-
110, 16 101-103, 46_6)
EPA could have required the generation of more
ecotoxicity data for PV29 during this risk
evaluation, and therefore has failed to consider
reasonable available information about ecological
hazards. (13110, 16104)
EPA bases its conclusion that PV29 presents no
environmental hazard solely on acute aquatic
toxicity data. According to EPA's Appendix C
listings, those studies only examined one endpoint,
mortality. (13 140).
EPA should require the following data (13 284)
- Acute toxicity to sediment-dwelling organisms
- Chronic toxicity including to aquatic organisms
including aquatic plants, fish, and aquatic
invertebrates
EPA acknowledged the uncertainties regarding the lack of
environmental hazard data characterizing the effects of
chronic exposure to aquatic organisms and hazard data for
sediment-dwelling aquatic organisms. Available
environmental hazard data for acute exposure indicated a low
hazard and the low solubility and low potential for aquatic
releases of PV29 led EPA to conclude that additional
environmental hazard data is not a critical data need. To
reduce the level of uncertainty in the assessment, EPA
included Ecological Structure Activity Relationships
(ECOSAR; v.2.0) predictive modeling outputs in the final
Risk Evaluation to understand the potential hazards of
chronic exposure to PV29 to aquatic organisms. The results
of this modeling indicate that environmental hazards
following chronic exposure are not expected to result at
concentrations below the limit of solubility. This provides an
additional indication that hazard data for chronic exposure
are not a critical data need. While PV29 is expected to be
persistent, it is not expected to bioaccumulate, and additional
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- Chronic toxicity to terrestrial organisms (including
sediment-dwelling organisms)
EPA and Environment Canada relied on acute
studies. EPA should not presume that toxic levels
will not be reached due to low solubility of PV29.
This line of argument cannot rule out that there are
chronic effects at lower levels. There is no
indication that Environment Canada had any
chronic toxicity data for the other pigments.
(13_127)
EPA should not assume that data from acute
aquatic studies can sufficiently address potential
chronic aquatic effects for the same chemical.
Many chemicals have been shown to exhibit
significantly different acute and chronic toxicity
values, and these can differ across species for the
same chemical. Among other testing, long-term
aquatic toxicity testing is needed for PV29 given
its persistence, lack of evidence that it is not
bioaccumulative, and concerns from EU member
countries that it may be PBT or very persistent and
very bioaccumulative (vPvB). (13 111-113,
13_284)
data submitted indicate a low solubility in octanol, further
indicating a low bioaccumulation potential.
In addition to the discussion above about the critical data
needs for chronic ecotoxicity data, EPA disagrees with some
of the information presented in the ECHA Community
Rolling Action Plan (CoRAP) justification document where
PV29 is determined to be a potentially Persistent,
Bioaccumulative and Toxic (PBT) substance. The
justification document
(https://echa.europa.eu/documents/10162/c607549c-lc07-
c5d6-d6e2-8dl8bff91f3a) categorizes PV29 as a ootentiallv
bioaccumulative substance because of uncertainties related to
the water solubility, LogKow. and LogKoa of the chemical
substance that stems from discrepancies in the predictive
modeling outputs, namely between EpiSuite and
ACD/Percepta 14.2.0 predictive models. While EPA does
agree that PV29 is a persistent chemical, it determined that
water and octanol solubility data were critical data needs in
order to finalize the Risk Evaluation. As a result, EPA issued
a TSCA Section 4(a)(2) Test Order for C.I. Pigment Violet
29 on February 28, 2020. This test order compelled the
creation and submission of solubility data to clarify these
uncertainties. These studies concluded that PV29 exhibits an
extremely low solubility in both water and octanol (<0.003
mg/L), which led EPA to conclude that LogKowis not a
relevant property for PV29 Nicolaou (2020). In addition, the
substance is a solid with a high melting point, so log Koa is
not a relevant property for this compound. As indicated
above in the "Physical Chemical Properties and
Environmental Fate" section, EPA has clarified these
uncertainties and does not consider PV29 a PBT substance.
Do not ignore Topkat-predicted acute LC50 for fathead minnow
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13
EDF located Environment Canada's specific
categorization results for PV29. Those results
reveal that the pivotal value Environment Canada
used for predicted acute toxicity of PV29 to fathead
minnow was an LC50 value of 0.115 mg/L (as
predicted by Topkat v6.1). This is lower than water
solubility estimates for PV29 that EPA provided in
the scoping document (0.169 mg/L). This means
that PV29 could reach levels in water sufficient to
kill 50% or more of fathead minnows exposed to it,
not to mention exerting other non-lethal aquatic
effects. EPA should not ignore this pivotal toxicity
value. (13120-125)
EPA does not typically rely on modeled toxicity values when
empirically-measured toxicity information are available. In
the case of PV29, the acute toxicity study with fish indicated
that no mortality was observed in test organisms up to the
limit of solubility. In addition, the toxicity value used in the
screening-level approach described by Environment Canada
of 0.169 mg/L is >100x larger than the limit of solubility
reported in the water solubility study submitted to EPA in
resDonse to the Section 4 Test Order (0.003 ms/L) Nicolaou
(2020).
Need to better describe how log Koc was determined
SACC
SACC COMMENT:
Provide better description of how log Koc was
determined in key studies.
The Koc value was derived by using EPI suite estimation
software in the Draft Risk Evaluation document. This
estimated log Koc using the Kow which has been determined
not to be an applicable property for PV29 based on the low
solubility in water and octanol. As a result, LogKoc will not
be relied upon in the final Risk Evaluation.
Concerns about ecological hazards for sediment-dwelling invertebrates
SACC,
13, 75,
80
SACC COMMENT:
Include a level of confidence statement with
judgements of toxicity to sediment dwelling
organisms.
PUBLIC COMMENTS:
EPA's conclusion that PV29 is "unlikely to present
an unreasonable risk to sediment-dwelling, aquatic
invertebrates" is unscientific and unreasonable.
(13132)
EPA noted that PV29 was expected to partition to
soil and sediment. Therefore, it cannot conclude
there is no unreasonable risk to the environment
The assessment discusses the uncertainties regarding the risk
evaluation to sediment-dwelling organisms. The final Risk
Evaluation includes an expanded discussion to help
understand the level of confidence in the environmental risk
assessment for sediment-dwelling aquatic organisms.
EPA believes it has adequate hazard data to evaluate the
environmental risks of PV29 to aquatic organisms. EPA used
the reasonably available data to assess sediment
invertebrates. Because PV29 is not expected to sorb to
sediment and demonstrates low solubility indicates, the
presence in pore water will be low. Daphnia, which feed
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without data on biodegradation and toxicity to
benthic organisms. (75 3, 80 5)
Data from a single acute Daphnia magna study
cannot be used as a proxy to evaluate potential
hazards to all sediment-dwelling invertebrates or
other organisms. (13129)
Anklev et al. (1993) provides guidance on
assessing the toxicity of sediment-associated
contaminants. "For example, many researchers use
upper-water-column test species, such as
cladocerans (which includes Daphnia) and fishes,
to assess the toxicity of contaminated sediments;
however, these organisms are not relevant if
species of concern are benthic, particularly in terms
of adequately addressing all possible routes of
exposure." (13 131)
See also U.S. EPA, Methods for Measuring the
Toxicity and Bioaccumulation of Sediment-
associated Contaminants with Freshwater
Invertebrates (Mar. 2000) (13 131)
through the entire water column were deemed to be an
acceptable surrogate species for sediment invertebrates
consistent with EPA/OPP guidance, which lists several
considerations for determining the likelihood of exposure
and toxicological relevance of exposure to sediment-dwelling
organisms (https://www.epa.gov/pesticide-science-and-
assessing-Desticide-risks/toxicitv-testing-and-ecological-risk-
assessment).
EPA appreciates the submission of the sediment-dwelling
organism testing guidance (USEPA, 2000). This reference
outlines testing procedures for testing with benthic organisms
rather than proposing criteria to determine whether this
testing is necessary. As EPA did not determine that toxicity
data with sediment-dwelling organisms is a critical data
need, so this reference was not relevant.
Need for more data to evaluate hazard to terrestrial ecological receptors
13, 16,
46
PUBLIC COMMENTS:
EPA has not identified any studies of potential
terrestrial and avian toxicity for PV29, despite the
fact that this substance is persistent and released
into the environment, including to landfills where it
has potential to leach and contaminate soil.
(13 133, 13 109-110, 16 101-103, 46 6)
Toxicity to terrestrial organisms may differ from
aquatic organisms. A 2014 ECHA report notes,
"Especially for substances with low water
solubility toxic effects may not be detectable
through acute aquatic toxicity tests whereas
EPA acknowledged the uncertainties in the assessment with
regard the lack of hazard data for terrestrial organisms. EPA
does not consider this a critical data need because conditions
of use are expected to result in limited exposure to terrestrial
organisms. Potential exposure to terrestrial organisms
resulting from disposal to landfills is expected to be low, as
the low solubility of PV29 indicates that leaching from
landfill is not likely. In addition, the low bioaccumulative
potential of PV29 indicates that releases to water are not
expected to biomagnify up the food chain, so exposures to
terrestrial organisms under the conditions of use of the
assessment are not expected.
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prolonged aquatic exposure and/or tests with
terrestrial organisms exposed through soil or food
may result in toxic effects." (13 134-135)
Similarly, a 2014 National Academies report states,
"Relative chemical hazards to terrestrial organisms
do not necessarily follow the same patterns as that
seen with aquatic organisms, necessitating separate
testing and assessment schemes." (13136)
Therefore, the lack of any terrestrial toxicity data
for PV29 is a major data gap leading to significant
uncertainty. (13137)
Concerns about citing the Canadian Ecological Risk Classification for PV29 as support for determination
13
PUBLIC COMMENTS:
EPA has asserted that PV29 has a low potential for
aquatic hazard. In support of this assertion, EPA
cited the Canadian Ecological Risk Classification
for PV29 (Environment Canada, 2006); however,
upon further examination of that source, it does not
appear to support EPA's assertion. Canada's
categorization exercise was intended only to
identify chemicals of potentially high concern, not
to also identify chemicals of low concern. In
addition, Canadian officials made do with whatever
information they already had or could develop
rapidly through predictive models. No attempts
were made to fill data gaps. Chemicals that Canada
found not to meet the categorization criteria should
not be characterized as affirmatively low concern.
Given the different purpose and limited nature of
Environment Canada's analysis, EPA should not
The determinations of potential environmental hazard of
PV29 made by EPA and Environment Canada are consistent.
Due to the limited nature of the Canadian Categorization
results that are publicly available, EPA has removed all
reference to the determination by Environment Canada
regarding ecological hazard from the final Risk Evaluation.
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rely on that screening process to support a finding
of no unreasonable risk for PV29. (13 115-128)
In EPA's draft risk evaluation, there is mention that
Environment Canada made its final ecological risk
determination for PV29 using a combination of
QSAR modeling and hazard data for analogous
pigments with low solubility (e.g., Pigment Red
149). However, neither EPA nor Environment
Canada have provided any predicted or measured
data for the similar pigments. (13124)
Support for EPA's characterization of hazard to ecological receptors
17, 19
PUBLIC COMMENTS:
No effects were observed in three acute toxicity
studies up to the limit of solubility of the chemical.
The lines of evidence clearly support EPA's
conclusion of low hazard potential to
environmental receptors. (17 24-25, 19 8-10)
There are substantial details on ecological hazard
data in the studies initially submitted to ECHA and
cited by EPA. To enhance clarity in how the data
were applied, EPA should consider more clearly
linking the robust study summaries available on
ECHA's website to the outcome of the risk
evaluation. (17 8)
EPA's use of a qualitative approach for ecological
exposure assessment is appropriate given the low
volume of PV29 material used in finished products
(<100,000 pounds) and infrequent use in consumer
products. The final risk evaluation should provide
additional information on EPA's process for
determining the tiered approach it used and why.
(1721)
This is consistent with the approach presented in the final
Risk Evaluation.
The full study reports for the environmental hazard studies
for PV29 have been made publicly available in the docket for
PV29, so EPA has removed the references to the ECHA
study summaries and has based the conclusions of the risk
evaluation on the results of the full study reports.
EPA does not have a set guidance for when a risk evaluation
utilizes a quantitative or qualitative approach. Instead, the
determination is made on a case by case basis as a result of
reasonably available data and the potential for a given route
of exposure to result in a concern. According to TSC A
702.41(a)(6)-(7):
"(6) The extent to which EPA will refine its evaluations for
one or more condition of use in any risk evaluation will vary
as necessary to determine whether a chemical substance
presents an unreasonable risk of injury to health or the
environment.
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(7) To the extent a determination as to the level of risk
presented by a condition of use can be made, for example,
using assumptions, uncertainty factors, and models or
screening methodologies, EPA may determine that no further
information or analysis is needed to complete its risk
evaluation of the condition(s) of use. "
In the case of PV29, a comparison of the high-end exposures
of PV29 to the available environmental hazard data indicated
that risks were not expected and additional quantitative
analysis is not necessary.
Concerns about studies where observed exposures exceed water solubility limit
SACC
SACC COMMENT:
Improve explanations for estimates of toxicity
benchmarks developed from those studies where
observed exposures exceed the water solubility
limit.
The reporting of the solubility limit across the environmental
hazard studies is inconsistent. For example, the solubility
limit in the Zebrafish studv BASF (1988) is reported as 670
mg/1. while the studv with Davhnia magna BASF (2012)
reports a limit of solubility of 0.001 mg/L. This is an
uncertainty that is discussed in the final Risk Evaluation.
Following the publication of the draft risk evaluation U.S.
EPA (2018b), EPA identified the uncertainty regarding the
limit of solubility of PV29 in octanol and water as a critical
data gap for the assessment and issued a TSCA Section
4(a)(2) Test Order for C.I. Pigment Violet 29 on February
28, 2020. These data were submitted to the agency and
confirm the low solubility of PV29 in both octanol and water
(<0.003 mg/L). The submission of these data clarifies the
uncertainties regarding the solubility.
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Human Health
Charge Question 6.a: Please comment on the toxicological study which was used to identify the endpoint of concern and derive the
associated point of departure (POD). Also, please comment on alternative approaches to estimate the potential for lung effects using
analogs for poorly absorbable particles to calculate an inhalation toxicity POD and the screening-level calculation to estimate the
potential for lung overload. Please comment on this approach and whether this analog represents useful information to quantify risk
for the inhalation route and whether oral developmental study is appropriate for all routes of exposure. If not, please describe what
other alternative approaches could be used in lieu of these approaches to serve as the basis for completing the hazard assessment and
subsequent risk evaluation for PV29.
Charge Question 6.b: Please comment on the use and interpretation of Multiple-Path Particle Dosimetry Model (MPPD v. 3.04),
which has not been formally peer-reviewed, to predict lung deposition of aerosolized PV29.
Charge Question 6.c: Please comment on the evidence available to support the agency's conclusion of negligible absorption via oral,
dermal, and inhalation routes.
Charge Question 6.d: Given the varied nature of the consumer uses, please comment on the agency's characterization of hazard to
consumers via inhalation and dermal exposure for different durations of exposure.
Charge Question 6.e: Similarly, please comment on the Agency's characterization of hazard to workers via inhalation and dermal
exposure for different durations of exposure.
Charge Question 6.f: Please comment on the Agency's consideration of health hazard concerns for potentially exposed susceptible
subpopulations given the constraints of the available information (e.g., children, workers, or pregnant women).
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Support for EPA's approach and conclusions regarding human health risk
19, 47,
49
PUBLIC COMMENTS:
EPA's health hazard determination and decision
that guideline studies for each human health
endpoint are not necessary for risk determination
are adequately supported with data regarding
genotoxicity, SARs, and poor absorption. (19 8,
1913)
EPA appropriately concluded that it did not need
to possess a guideline study of PV29 regarding
every conceivable human health endpoint. (1913)
EPA's cross-route extrapolation of oral route
exposure to derive other no-observable adverse
effect levels (NOAELs) to address systemic
effects is appropriate and is a typical convention
of risk assessment practice. (47 2)
The summaries of the 10 short-term assays
provided sufficient information and show
compliance with OECD test guidelines. (49 7)
EPA acknowledges these comments and encourages the
commenters to consult the final Risk Evaluation for the most
updated risk characterization.
Make hazard conclusions specific to routes of exposure
SACC
SACC COMMENTS:
Wherever in the Evaluation the statement "PV29
has low hazard potential across all possible routes
of exposure" occurs, the statement should be
replaced with one that is specific and limited to
the routes of exposure observed in the available
study datathus allowing new data, as it becomes
available, to add to and expand hazard conclusions
regarding PV29.
EPA acknowledges this and has updated the language in the
final Risk Evaluation to better tie the risk determinations ot
the specific conditions of use of PV29. Statements on low
exposure when EPA lacks the data were updated where
necessary.
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Clarify value of the screening reproductive/developmental toxicology study and highlight data gaps
SACC
SACC COMMENTS:
Include a table in the Evaluation that compares the
endpoints reported in the screening
reproductive/developmental toxicological study
used in the Evaluation to endpoints typically
reported in a 90-day subchronic toxicity study or
to compare what's available for PV29 versus a
basic SIDS data set-to clarify the value of the
screening reproductive/devel opmental
toxicological study and highlight data gaps in the
toxicity assessment.
EPA did not make this change. There is no minimum data set
for risk evaluations conducted under TSCA. EPA obtained
all reasonably available data for C.I Pigment Violet 29 and
issued a TSCA Section 4(a)(2) Test Order for C.I. Pigment
Violet 29 to address critical data gaps in the assessment.
Other data gaps, such as environmental hazard testing with
aquatic species and inhalation toxicity testing, were
addressed by using analogue toxicity data or with QSAR
modeling.
The toxicity studies EPA used are unreliable
8,10,
12, 13,
14, 16,
46, 48
PUBLIC COMMENTS:
EPA uses unacceptable and unreliable studies that
present risk of bias to determine inhalation
toxicity and chronic health effects and the
measurements use for PV29 levels are unreliable.
(10_2, 16_84, 48_10, 4815)
The OECD 421 screening test utilized is flawed
and unreliable. It cannot be used to estimate
human risk. (12 27, 13 148, 13 191, 14 8,
14 16, 16 84)
EPA cannot determine reproductive toxicity
hazard based on the current data available and
should provide more discussion on reproductive
toxicity screening limitations. (817, 10_9, 1412)
There are concerns with the quality ratings of the
oral toxicity studies due to inadequacies,
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 believes that OECD 421 is adequate to determine whether
additional reproductive testing is necessary. As no significant
adverse effects were observed in the study, EPA believes that
this provides justification that no additional reproductive testing
is necessary.
To alleviate concerns about the oral toxicity studies, EPA has
released the partially redacted study reports and the updated
systematic review data quality evaluation scoring sheets to the
PV29 Docket (EPA-HO-OPPT-2018-0604)
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information gaps, and a protocol that is no longer
available online for evaluation. (48 8)
Multiple studies utilized by EPA are inadequate,
such as the 10-page report prepared by BASF
providing summaries for 10 studies which lack
supporting data, and the developmental toxicity
study which involved a small number of rats from
a single species. (12_28, 14_8, 46_2)
EPA acknowledges that the study reports are often truncated
and overly summarized. As this represents the best available
data to understand the potential health effects of PV29, EPA
utilized the study report results to understand the human health
hazards of PV29 and issued a Section 4 Test Order where
critical data were considered insufficient.
EPA improperly disregarded intraperitoneal studies
12, 13,
16
PUBLIC COMMENTS:
EPA improperly disregarded intraperitoneal
studies reporting clinical effects and death. These
two studies should not have been rejected as
irrelevant but instead treated as reliable because
there is a strong scientific basis for treating
intraperitoneal dosing studies similarly to oral
dosing studies. (12 25, 16 8, 16 57, 16 63,
16 70)
EPA swiftly discounts evidence of hazard. Toxic
effects were observed in intraperitoneal studies,
but EPA invoked its problematic low solubility
argument. EPA cannot rely on a deeply flawed
low solubility4ow absorption argument to dismiss
the observed effects those studies. (13147)
EPA released an update to the systematic review
supplemental file that provided the reviewer comments and
updated systematic review data quality evaluation scores in
response to comments received from the public. These files
are available on the docket for PV29 at:
httDs://beta.resulations.sov/document/EPA-HO-OPPT-2018-
0604-0040
The result of this data quality evaluation found that the
intraperitoneal injection studies were of low quality but were
not used qualitatively in the evaluation. As stated in the final
Risk Evaluation, the studies were not used in the screening
level risk evaluation because the route of exposure
(intraperitoneal injection) is not a relevant route of exposure
for PV29, so there is a great deal of uncertainty about how
this exposure pathway relates to the routes of exposure
expected for C.I. Pigment Violet 29. In addition, the
concentrations where adverse effects were observed in the
test animals (LDso= 7000-9000 mg/kg-bw) is far greater than
the NOAEL for reproductive/developmental toxicity of 1000
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mg/kg-bw that was used in the screening-level risk
evaluation.
EPA did not use data from similar substances
13, 15
PUBLIC COMMENTS:
EPA failed to utilize data on similar substances.
(15 2)
An analysis of PV29 through ToxTree provides a
structural alert for PV29 given its structural
similarity to polycyclic aromatic hydrocarbons
(PAHs). EPA completely fails to analyze this
structural alert or consider this evidence
suggesting that PV29 may be a carcinogen as a
result of this similarity. (13152)
EPA has updated its approach in the final Risk Evaluation to
incorporate analogue toxicity data into the screening level
risk evaluation for inhalation exposure.
Empirical data indicates that C.I. Pigment Violet 29 is
negative for genotoxicity and Structural activity relationships
(SAR) considerations support EPA's conclusion that C.I.
Pigment Violet 29 is unlikely to be a carcinogen. Given the
low potential for biodegradability, the relevance of PAHs as
a predictor of carcinogenicity are low.
EPA should acquire additional studies due to insufficient data
SACC,
10, 12,
13, 14,
15, 16,
IB, 22,
43, 46,
49, 74,
75, 76,
82
SACC COMMENTS:
Request an appropriate study to adequately
determine bioavailability or bolster the evidence
for poor water and octanol solubility in a well-laid
out manner to support the agency's conclusions.
The utility of the screening
reproductive/developmental toxicological study
for deriving the POD would benefit from
additional and better estimates of
physical/chemical properties and ADME studies
to further strengthen support that PV29 has low
bioaccessibility/bioavailability and therefore,
decreased risk for absorption and inhalation.
PUBLIC COMMENTS:
There is insufficient data to make a human health
hazard determination due to CBI and insufficient
To address the uncertainties identified in the assessment,
EPA has issued a TSCA Section 4(a)(2) Test order for the
development and submission of additional solubility testing
of C.I. Pigment Violet 29 in water and octanol. This
solubility testing has been submitted to EPA, and it was
determined to be high quality and acceptable for use in this
risk evaluation. This reduces the uncertainty about the
preliminary determination that the low solubility of C.I.
Pigment Violet 29 results in a low potential for absorption.
To further reduce uncertainties related to the screening-level
risk analysis of inhalation exposure, EPA decided to use
analogue toxicity data to better characterize the hazards to
workers from chronic inhalation of C.I. Pigment Violet 29.
While there are uncertainties regarding the available data for
C.I. pigment Violet 29, EPA has determined that sufficient
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testing, including the following topics: PV29
levels, exposure characteristics, absorption, and
chronic toxicity. (13 6, 13 7, 13 90, 13 98,
13101, 13165, 1416, 15_2, 16_74, 46_6, 74_2,
76 3, 82 1)
EPA has authority to acquire more "reasonably
available data" by requiring additional studies by
manufacturers to evaluate human hazard. (103,
12_4, 13_90, 13 146, 13 194, 14 14)
Specific suggested study types that should need to be
included are:
- High-quality, reliable experimental test results for
acute inhalation toxicity. (16 9)
- A 90-day repeated dose toxicity study for oral,
inhalation, and dermal routes of exposure. (16 9,
49_4, 10_3, 13_284)
- Chronic mammalian health studies sufficient to
account for exposures via dermal, inhalation, and
oral routes. (188, 10_3, 13_284)
- Carcinogenicity studies. (10_3, 12_22, 1414,
169)
- Respiratory/inhalation sensitization studies.
(12_22, 10_3, 16 88)
- Tests for genetic toxicity/mutagenesis/gene
mutation, including in vivo tests for chromosome
damage, cytotoxicity, and other relevant
endpoints. (10_3, 1414, 16_9)
- Neurotoxicity studies, including developmental
stages. (10_3, 12_22, 1414, 16_88, 16-9)
- Two generation reproduction toxicity studies.
(10 3, 12 22, 16 9)
data exist to make a risk determination for C.I. Pigment
Violet 29 under the conditions of use of the assessment. 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.
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- Studies for acute and chronic endocrine effects.
(10_3, 12_22, 14 14, 16 9)
- Pharmacokinetic study measuring distribution in
blood and fat and toxicokinetic studies. (10 3,
16 88, 75 2)
Increase transparency of evidence used to determine carcinogenic risk
8, 17
PUBLIC COMMENTS:
EPA should provide more detail on the in vitro
carcinogenicity assessment, including a
description of the structure-activity relationship
(SAR) data/programs that were used, how they
were evaluated, and why the data strengthens
confidence in a low likelihood of carcinogenic
risk. In addition, EPA could further describe how
the assessment of carcinogenicity includes
consideration of other available in vivo toxicity
studies, in particular, the evaluation of
histopathology in repeat dose studies. (17 23,
815)
The SAR determination for carcinogenicity was based on
expert judgement about the carcinogenic potential of
functional groups to elicit carcinogenic potential. This
determination is supported by the available data for C.I.
Pigment Violet 29, which was considered in the assessment.
This information has been captured in the OncoLogic
predictive model which is available at:
https://www.epa.sov/tsca-screenins-tools/oncolosictm-
comDuter-svstem-evaluate-carcinosenic-Dotential-chemicals
Concerns about route-to-route extrapolation and lack of uncertainty factor
10, 12
PUBLIC COMMENTS:
EPA incorrectly determined low hazard across all
routes of exposure and used an oral exposure
study to calculate the point of departure for its
analysis of dermal and inhalation risks, but this
extrapolation ignores the potential that PV29's
absorption rate is lower for oral exposures than for
inhalation and an uncertainty factor should have
been applied. (1011, 12_33)
EPA acknowledges the uncertainties inherent in utilizing a
route-to-route extrapolation to assess the risks from
inhalation exposure. As a result, EPA has updated the risk
characterization for inhalation exposure to use chronic
inhalation toxicity data for carbon black to represent the
inhalation toxicity for C.I. Pigment Violet 29 following
chronic exposure.
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MPPD model requires size distribution of PV29 in workplace aerosols
77
PUBLIC COMMENTS:
The MPPD model depends on the particle size
distribution, but EPA lacks data on the size
distribution of PV29 particles in workplace
aerosols. (77_3)
Through correspondences with the sole US manufacturer of
C.I. Pigment Violet 29, EPA has obtained additional
characterizations of the particle size of C.I. Pigment Violet
29 dust that can represent the potential workplace exposure
of C.I. Pigment Violet 29 dust. These particle size
distributions have been be made public with the final Risk
Evaluation as a supplemental file, titled, "Supplemental File:
Information Received from Manufacturing Stakeholders U. S.
EPA (2020a)."
Present models or NAMs to improve understanding of absorption potential
SACC
SACC COMMENTS:
Given the low confidence in absorption potential
based on limited physical-chemical data, present
models based on several solubility scenarios or
NAM in vitro testing using tissue adsorption
models.
To address the uncertainties identified in the assessment
regarding the assumptions made about the absorption
potential of C.I. Pigment Violet 29 from its solubility, EPA
issued a TSCA Section 4(a)(2) Test order for the
development and submission of additional solubility testing
of C.I. Pigment Violet 29 in water and octanol. This testing
was received and reviewed by the agency and found to be of
high quality. As a result, EPA has high confidence that the
data received as a result of the Section 4 Test Order
represents the true limit of solubility of PV29.
Concerns about lack of scientific evidence for EPA's conclusion regarding absorption potential
8, 12,
13, 16,
IB, 46,
55, 77,
78
EPA has no scientific basis for using low
solubility to conclude there would be no
absorption through the dermal and inhalation
routes of exposure, but did not provide
confirmatory data, which could have been readily
obtained using EPA's section 4 testing authority.
As indicated above, EPA issued a TSCA Section 4(a)(2) Test
Order for the submission of water and octanol solubility
studies to reduce uncertainties about the available data used
in the Draft Risk Evaluation.
EPA determined that the low solubility in water and octanol
initially reported in the assessment and confirmed by the
studies submitted as a result of the Section 4 Test Order was
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(12 25, 13 6, 13 102, 13 162, 13 165, 16 7,
16 45, 16 62, 18 11, 46 6, 77 3, 78 6, 55J)
EPA should consider basic physicochemical
information (i.e., molecular mass and
lipophilicity) when determining dermal
absorption. EPA ignored the multiple mechanisms
by which chemicals, including poorly soluble
substances, may be absorbed. EPA should have
obtained actual absorption information instead of
simply assuming that low solubility will
necessarily result in low absorption. (13 103)
EPA did not consider how the presence of other
constituents in a PV29 formulation, such as
surfactants, can significantly alter the
absorbability of PV29. (13 164)
EPA assumes that a lower fraction of PV29 is
dermally absorbed than the source it cites as
support recommends based on the chemical's
properties. (13 8)
Given the inconsistency in the way exposure
potential is described, OPPT should clarify
exposure assumptions, specifically with regards to
applying a consistent approach regarding potential
for dermal absorption. (812)
adequate evidence to conclude that absorption of PV29 is
low.
As there are limited data to indicate that components of the
formulations can affect the absorbability of PV29, EPA
acknowledges that there are uncertainties about this issue.
Given the difficulty of finding a solvent for PV29, it is likely
that the stability of the compound is high in all but highly
acidic conditions.
EPA has updated the final Risk Evaluation to remove the
screening level risk evaluation for dermal exposure presented
in the Draft Risk Evaluation. The overly conservative nature
of the assumptions in that approach and the route to route
extrapolation using the subchronic NOAEC to calculate an
MOE for dermal and inhalation hazard meant that the results
were of limited utility to actual exposure scenarios,
especially for a substance that is as poorly absorbed as PV29.
Therefore, the discussion of the inputs used in that approach
are no longer relevant.
Consumer hazard is not fully investigated
SACC
12, 13
SACC COMMENTS:
Improve the discussion of the uncertainty
surrounding exposures for the general population.
Explain clearly why it was initially determined
that there were widespread consumer exposures to
EPA acknowledges the uncertainties in its conclusion that
risks are not expected for the general population. EPA has
high confidence in this conclusion, as a high percentage of
PV29 is used as an intermediate and is therefore converted
into other chemical substances and is therefore not released
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PV29 but that this did not need to be addressed in
the final risk assessment. Clearly acknowledge
that there may be certain consumers that receive
higher acute and chronic exposures and explain
why this is not considered important for this risk
assessment.
PUBLIC COMMENTS:
EPA does not provide evidence to support the
expectation that consumer and general population
exposures will be lower than worker exposures.
(12 20, 13 6)
EPA has not fully evaluated hazards to consumers.
(12_8, 13_244)
EPA cannot expect that consumers exposed to
PV29 will wear protective gear. (13185)
into the environment. Therefore, PV29 exposure is primarily
expected to result in a manufacturing setting and not as a
result of exposures to consumers and the general population
from downstream uses.
Based on the available data to characterize consumer
exposures to PV29, the consumer uses are not expected to
result in long term inhalation exposure to PV29 dust, which
is the primary route of concern for PV29. Exposures from
this pathway are expected to result from manufacture,
processing and industrial/commercial uses to workers.
Regardless, the risk evaluation is updated to better explain
potential risks to consumers.
EPA calculated risks from occupational exposures with and
without the use of PPE. EPA does not assume that consumers
will use PPE.
Obtain more occupational hazard data
SACC
13
SACC COMMENTS:
Clearly acknowledge that there are few data to
support a confident conclusion that workers would
not be exposed, and therefore, not experience
human health hazards via dermal and/or inhalation
routes.
Obtain and incorporate into the Evaluation better
(e.g., collected using standard measurement
techniques with adequate temporal and spatial
coverage) data/documentation from the
Uncertainties were identified regarding reasonably available
information characterizing PV29's occupational worker
inhalation exposure. These uncertainties have resulted in
EPA requiring testing of PV29 to develop new information
in order for EPA to increase certainty in the final Risk
Evaluation of PV29 under TSCA section 6(b). Test data was
reviewed for data quality according to the relevant data
quality evaluation metrics and incorporated into the final
Risk Evaluation.
This information includes information that measures
exposures to workers from the sole US manufacturer of C.I.
Pigment Violet 29.
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manufacturer on conditions of use, exposures, and
potential for worker exposures.
Regardless of whether PV29 is bioavailable, more
justification is needed to conclude that exposures
to dusts in occupational settings do not cause lung
depositional events or immunological responses
sufficient to cause injury.
PUBLIC COMMENTS:
Manufacturers must submit all available
information on occupational hazard and exposure
under the identified conditions of use because
EPA must consider all hazards and exposures
when preparing risk evaluations. (13_258)
The updated human health risk evaluation for C.I. Pigment
Violet 29 calculates an updated POD based on the potential
for lung depositional events based on lung overload observed
in an analogue, carbon black Elder et al. (2005).
All information gathered from correspondences with industry
stakeholders regarding PV29 is being made publicly
available with the final Risk Evaluation as a supplemental
file, titled, "Supplemental File: Information Receivedfrom
Manufacturing Stakeholders U.S. EPA (2020a). In addition,
where occupational exposure information was judged to be
insufficient, EPA issued a Section 4 Test Order for the
generation of workplace dust monitoring data. These data are
used in the final Risk Evaluation to estimate workplace
exposure to PV29 dust.
Clarify uncertainties and justify conclusions regarding susceptibility
SACC
8, 9,
10, 12,
13, 14,
16, 77,
78, 82
SACC COMMENTS:
Clarify the statement in 3.4.1, "there is no
evidence of increased or decreased susceptibility
for any given population" to acknowledge that
there are large data gaps that preclude coming to
confident conclusions regarding certain
subpopulations.
Do not make statements without additional
clarifications and justifications that children or
other susceptible populations would be protected.
The current data as discussed in the data
integration does not clearly support this
conclusion and the committee has recommended
EPA acknowledges the uncertainties regarding this
conclusion and has updated the final Risk Evaluation to
explain these uncertainties
EPA has identified critical data needs and issued a Section 4
Test Order to fulfill these needs. As a result, EPA received
additional information and incorporated it into the
evaluation. EPA has modified the risk characterization
approach to better represent the expected effects of exposure
to PV29. While there are remaining uncertainties, EPA is
confident that its risk determination is protective of
potentially exposed or susceptible subpopulations identified
in this risk evaluation.
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additional data needs and rationale to address this
uncertainty. Some committee members
recommended EPA consider an "indeterminate"
categorization and qualify with data that may
suggest low toxicity. Methods to address this
would include using more uncertainty factors in
MOE calculations or developing multiple
modeling scenarios including best case to worst
case and presenting these models in the text.
Improve transparency by acknowledging in the
evaluation that there are no data supporting the
determination of hazards or exposures to children
or other susceptible populations on which to make
confident conclusions regarding risk to these
susceptible subpopulations.
PUBLIC COMMENTS:
EPA has not met the TSCA mandate to consider
risks to PESS and needs to require additional
studies and data collection. (10 12,13 7,13 191,
13 287, 14 20, 77 5)
The agency did not adequately consider pregnant
women, children, and other vulnerable
subpopulations, those vulnerable in the workplace,
and should apply uncertainty factors in their
hazard assessment. (8 18, 9 2, 10 12, 12 20,
12_34, 13 191, 78_8, 82_3)
A factor of 10 is applied for risk assessments on
dietary pesticide ingestion for PESS. (1012)
EPA should seek the advice of its Children's
Health Protection Advisory Committee. (16 22)
EPA has updated the risk evaluation to discuss uncertainties
resulting from lack of data for specific susceptible
subpopulations including children and other susceptible
populations outlined in Section 2.4.1.
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There are no vulnerable subpopulations
45
PUBLIC COMMENTS:
There are no vulnerable subpopulations with
reasonably foreseen exposures to harmful
quantities of PV29. Workers in U.S.
manufacturing facilities do not constitute a
vulnerable subpopulation. (45 7)
EPA has updated the risk evaluation to discuss uncertainties
resulting from lack of data for specific subpopulations.
Risk Characterization/Risk Determination
Charge Question 7.a: Please comment on whether the information presented to the panel supports these conclusions outlined in the
draft risk characterization section concerning PV29. If not, please suggest alternative approaches or information that could be used to
develop a risk finding in the context of the requirements of EPA's final rule, Procedures for Chemical Risk Evaluation Under the
Amended Toxic Substances Control Act (82 FR 33726).
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Summary of Comments for Specific Issues Related to
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EPA/OPPT Response
Support for the conclusions in the draft risk characterization
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17, 19,
47
PUBLIC COMMENTS:
The risk evaluation relies on conservative, lower-
tier screening approaches to risk assessment to
support the determination that PV29 does not pose
an unreasonable risk of harm to human health or the
environment under reasonably foreseeable
conditions of use. This is appropriate due to PV29's
evidence of low toxicity, largely industrial
conditions of use, and low volume of material used
in finished products. (17 3, 19 3)
EPA appropriately considered the full body of
toxicity studies, physical-chemical properties, use
patterns and relevant routes of exposure, addressed
uncertainties, and used an established health-
protective approach to calculate risks that accounts
for the different routes of exposure. EPA utilized
conservative assumptions and highly protective
default values for risk characterization. Even so,
EPA found no unreasonable risk. (17 26,19 7-10)
EPA collected more than enough data to support its
risk evaluation and appropriately concluded that a
guideline study is not needed for every conceivable
human health endpoint. EPA's conclusions confirm
those contained in the published EU Registration,
Evaluation and Authorization of Chemicals
(REACH) summaries. Further assessment of PV29
would not yield any benefit for EPA, consumers,
industry or workers. EPA's limited risk evaluation
resources should be directed to substances for which
EPA acknowledges the comments and has incorporated the
suggestions received in these comments where applicable.
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reasonably foreseeable conditions of use pose a high
potential for unreasonable risk. (19 11-15)
Despite the changes to these quality scores [after the
first round of comments], the risk evaluation is not
impacted for the following reasons. First, high-
quality studies also exist for both acute oral toxicity
and eye irritation. Second, EPA has evaluated the
remainder of the studies used for the risk evaluation
to be of medium- and high-quality, including
biodegradation and aquatic toxicity studies, which
address the limited water solubility. Third, EPA
uses the high-quality reproduction/developmental
toxicity study to identify the no-observed-adverse
effect level (NOAEL) that is used in the MOE
calculations. (47_1)
The conclusions in the draft risk characterization are flawed due to lack of data
SACC,
10,11,
12, 13,
14, 16,
44, 46,
55, 74,
75, 77,
80
SACC COMMENTS:
Saying that no unreasonable risks for PV29 were
identified may reflect the weakness and limitations
of the database.
Lack of evidence isn't evidence. [Note: refers to
data gaps.]
PUBLIC COMMENTS:
EPA relied on inadequate hazard and exposure data
to determine that PV29 does not present an
unreasonable risk of injury to human health or the
environment. In addition, the draft risk evaluation
EPA had sufficient information to complete the PV29 risk
evaluation using a weight of 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
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contains numerous logical flaws and unwarranted
assumptions, rendering its final conclusion
unsupported by substantial evidence, as required
under TSCA. The resulting draft risk evaluation
fails to consider reasonably available information or
to use the best available science. (10 2, 11 17,
12 22, 13 3, 13 55, 13 110, 13 144-146, 14 6,
16 25,16 65,16 110,44 18,46 6,46 27,55 10,
74_2, 77_2, 80_2)
A lack of information does not mean that there is no
or low exposure or hazard. EPA improperly inferred
the absence of risk from the absence of information.
(12 4, 13 14, 13 146)
EPA has based its conclusion of "no unreasonable
risk" on claims of low exposure, low bioavailability,
and low toxicity observed only in short-term
studies. These data seem to support a hypothesis of
low risk but are woefully insufficient to establish it.
(75_2)
EPA concludes that PV29 is not carcinogenic on the
basis of insufficient information and unsupported
assumptions. (12 22, 13 7, 13 151, 14 13, 16 68-
69, 46 6)
The new information that has now been made
available [referring to the release of the full studies]
further demonstrates the poor quality and limited
scope of the data in the draft evaluation and
underscores the lack of evidence to support a
finding that PV29 does not present an unreasonable
risk of injury. (55 1)
improve on its method and data collection for the next
round of chemicals to be assessed under TSCA.
To address the uncertainties identified in the assessment
regarding the assumptions made about the absorption
potential of C.I. Pigment Violet 29 from its solubility, EPA
issued a TSCA Section 4(a)(2) Test order for the
development and submission of additional solubility testing
of C.I. Pigment Violet 29 in water and octanol. This testing
has been received and reviewed by the agency and found to
be of high quality.
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EPA should order the development and submission of additional information
SACC,
9,55,
76, 77,
80, 82
SACC COMMENTS:
If it is not possible to arrive at an "indeterminate"
conclusion, EPA could conclude that the limitations
in the data are sufficient to conclude an
"unreasonable risk" and, as a regulatory response,
order the manufacturer to develop a limited set of
new data, the development of which would not be
time limited.
The Agency needs to compel answers to these
questions if they are to accurately assess the
potential human and environmental hazards. Such
questions include long-term effects of PV29
exposure, apparent lack of consensus regarding
PV29 solubility, and data gaps regarding
characteristics and fate of PV29.
PUBLIC COMMENTS:
The Agency had ample opportunity to use TSCA
authorities to obtain additional hazard and exposure
data that could have supported a defensible risk
evaluation - as Congress intended - yet refused to
do so, instead reaching categorical conclusions
about the absence of risk that simply cannot be
supported by the inadequate data in the record. (9 2,
55 1, 76_4, 77_1, 80_4, 82_2-3)
In response to uncertainties resulting from lack of data
identified in public and SACC comments, as well as in the
risk evaluation, EPA issued a TSCA Section 4(a)(2) Test
Order for C.I. Pigment Violet 29 on February 28, 2020.
This test order compelled the creation and submission of
three studies by the sole U.S. manufacturer of PV29, Sun
Chemical Corporation to address critical data gaps
identified in the risk evaluation. EPA is currently working
to identify data deficiencies earlier in the prioritization/risk
evaluation process. TSCA section 6 requires EPA to
determine within a specified period of time whether a
chemical substance presents an unreasonable risk of injury
to health or the environment. The uncertainties identified
were in regard to reasonably available information
characterizing PV29's solubility and occupational worker
inhalation exposure. Test data were received and reviewed
for data quality according to the relevant data quality
evaluation metrics and incorporated into the final Risk
Evaluation. The studies received by EPA in response to this
Section 4 order included solubility of PV29 in water and
octanol, as well as a workplace monitoring study of
particles not otherwise regulated, conducted according to
the NIOSH 0600 guideline. More information about this
test order can be found at:
httDs://beta.resulations.sov/document/EPA-HO-OPPT-
2020-0070-0008
EPA's reliance highly uncertain fate and persistence information casts doubt on its risk conclusions
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13, 46,
55
PUBLIC COMMENTS:
EPA fails to acknowledge and address serious
limitations and uncertainties associated with several
of its characterizations of PV29's physical-chemical
and environmental fate properties that it relies on to
conclude low risk. (13 4)
EPA relies heavily on a single, poorly documented
value for water solubility while failing to account
for other available data on water solubility. This
reliance on a highly uncertain value casts major
doubt on all of EPA's risk conclusions. (13 4,
13 36, 55_17)
EPA's risk conclusions fail to address the
implications of the very high persistence of PV29 in
the environment. EPA relies upon modeled values
derived using an estimation program lacking
sufficient data on similar chemicals. (13 4, 46 6,
55_17)
As discussed above, EPA issued a TSCA Section 4(a)(2)
test order to generate more data that address uncertainties
related to the physical-chemical properties of C.I. Pigment
Violet 29, particularly the uncertainty regarding the
solubility studies. These solubility data were used to reduce
uncertainties stemming from the low confidence ratings of
the solubility data presented in the draft Risk Evaluation.
EPA acknowledges the persistence of PV29, but based on
the low potential for bioaccumulation and low toxicity, the
persistence does not result in specific risk concerns.
Criticism of the margin of exposure (MOE) approach and clarity
SACC
8,10,
12, 14,
16, 46,
48, 77
SACC COMMENTS:
Either do not perform MOE calculations or clearly
qualify assumptions used in the MOE calculation
based on the limited data.
PUBLIC COMMENTS:
EPA should not use MOE as an analysis method in
the risk evaluation process. MOE is not an estimate
of risk, it is a single number that is a version of the
"bright line" approach. This approach does not
provide information about the magnitude of the
risks above, at, or below the line. Further, it implies
EPA acknowledges these comments and has attempted to
explain the additional assumptions used in the calculations
of the MOEs used in the final Risk Evaluation. This
includes selecting uncertainty factors that are more
appropriate given the limitations of the reasonably
available data for PV29.
To increase transparency, EPA has compiled the available
data received from the sole US manufacturer, Sun
Chemical, and used in the risk evaluation into a single
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that there is a "safe" level of exposure below which
no harm will occur. While this may be true for a
select few chemicals, the NAS Science and
Decisions report recognizes that this is not a valid
assumption for all chemicals and has recommended
moving away from such "bright line" approaches
which do not establish risk estimates across the full
range of exposures. Additionally, the MOE will not
provide the necessary information for future
analysis of risks and benefits that will be critical for
decision-making on these chemicals. We
recommend that EPA utilize available analytical
methods, such as PODs based on a Benchmark
Dose, to develop quantified estimates of risk.
(1415-19)
The results from the MOE approach does not
adequately account for humans that may be more
susceptible to chemical toxicity, and an uncertainty
factor should be considered. (10 7, 12 34, 16 37)
EPA incorrectly relied on a single studies or data
points to base elements of their risk determination.
(46 6, 77 5)
In response to FOIA requests and our initial
comments, EPA has failed to provide any
supporting data or other justification for the critical
workplace air concentration on which its MOE
calculation is based, further weakening its assertion
that workers and other exposed populations are not
at risk of harm. (48 1)
supplemental file. This supplemental file has been uploaded
to the docket with the final Risk Evaluation.
Supports EPA's use of the MOE approach
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17
The PV29... MOE assessment is evidence of the
utility of EPA's risk assessment approach in
appropriate cases. (17 4) This commenter supports
EPA's use of an MOE approach to assess non-
cancer risk. (17 26)
EPA acknowledges the comment and encourages the
commenter to consult the updated risk characterization
approaches in the final Risk Evaluation.
Concerns about CBI affecting the risk characterization
SACC
SACC COMMENTS:
EPA should continue to encourage data submitters
to review CBI claims closely prior to submission.
EPA should consider novel ways to make full study
reports available to interested members of the public
without compromising the investment of the data
owner.
EPA understands the uncertainties that arise when data are
not publicly available due to CBI claims. EPA will work
with stakeholders to ensure that relevant data are made
available while adhering to the applicable legal
requirements regarding confidential business information.
Need to apply additional uncertainty factors
8,10,
12, 13,
77, 80
SACC COMMENTS:
Include the subchronic-to-chronic uncertainty factor
in the calculations of the MOE or significantly
improve the justification/qualifications in the
Evaluation for why this uncertainty factor should
not be used.
PUBLIC COMMENTS:
EPA failed to apply the necessary uncertainty
factors to account for the many data gaps in the
PV29 human hazard database of studies. (10 6,
12_29, 13 8, 77_6-7)
Additional 10-fold uncertainty factors that EPA
should have considered include: database
deficiencies, extrapolation from short-term to
chronic exposures, extrapolation from oral to
EPA updated the risk evaluation so that the route to route
extrapolation used to characterize risks from inhalation and
dermal exposure of PV29 presented in the Draft Risk
Evaluation is no longer included in the final Risk
Evaluation for human health. In place of this assessment,
which was determined not to be appropriate based on
feedback provided through public and interagency
comments, EPA has chosen to focus on the effects of lung
overload following chronic exposure to PV29. Based on
available data characterizing the effects of particles with a
similar size, density and solubility, the most relevant effect
from inhalation of PV29 is the overloading of lung
clearance mechanisms. As a result, the discussion of the
application of uncertainty factors to the subchronic oral
NOAEC to calculate an MOE is no longer relevant.
Discussions about the use of assessment factor in this
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inhalation and dermal exposures, and vulnerable
subpopulations (pregnant women, infants and
children). (10_9-12, 12_30-34, 80_3)
EPA OPPT should use an adjustment factor for
intraindividual variability. (818)
EPA used an oral exposure study to calculate the
point of departure for its analysis of dermal and
inhalation risks, but this extrapolation ignores the
potential that PV29's absorption rate is lower for
oral exposures than for inhalation and an
uncertainty factor should have been applied. (10 11,
12 33)
Even adding a single additional uncertainty factor
would result in a benchmark value exceeding the
MOE that EPA calculated for worker dermal
exposure. (13 8)
If EPA had applied all of the appropriate uncertainty
factors, the benchmark MOE would have far
exceeded the acceptable margins of exposure and
EPA would have concluded that PV29 presents an
unreasonable risk to human health. (10 13, 12 35)
assessment have been included in Section 4 of the final
Risk Evaluation where necessary.
Use of intraspecies uncertainty factor was conservative
8
PUBLIC COMMENTS:
The point of departure (POD) was selected from a
reproductive and developmental screening study.
Considering this study design evaluates hazards to
potentially sensitive subpopulations, an additional
factor for interindividual variability may not be
necessary. We request OPPT acknowledge the
conservatism of this approach and consider potential
EPA acknowledges the uncertainties regarding this
approach as well as the potential for conservative
assumptions.
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redundancy in adjustments for sensitive populations
via an adjustment factor for intraindividual
variability. (818)
Occupational risk characterization is flawed
11,12,
13, 18
PUBLIC COMMENTS:
It is wrong and inconsistent to use personal
protective equipment (PPE) and safety data sheets
(SDSs) as a baseline for risk determination. Risk
should be assessed on the basis of health impacts.
PPE is not a basis for risk; it is a means to control
the risk. There is no OSHA requirement for
employers to follow the recommendations of SDSs.
(117-8, 18 12)
EPA should mandate worker protections for PV29
consistent with agencies specializing in
occupational safety and health regulation and
research (e.g., OSHA and NIOSH). (18 5)
Even with using one uncertainty factor for dermal
exposure, EPA cannot conclude that PV29 does not
present an unreasonable risk to workers. (13 208)
EPA's approach for developing exposure assessments for
workers is to use reasonably available information and
expert judgement. EPA considers each condition of use and
constructs 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 a condition of use presents
unreasonable risks, EPA incorporates assumptions
regarding PPE use based on this 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. 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.
EPA has consulted with NIOSH to update the inhalation
risk characterization to ensure that the evaluation follows
the best practices for risk assessment.
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EPA updated the approach to characterize the risks of
dermal exposure to PV29. This screening level assessment
of risks from dermal exposure presented in the draft Risk
Evaluation were extremely conservative and not
representative of actual exposure under the conditions of
use of the assessment.
Need to expand the risk characterization narrative
8
PUBLIC COMMENTS:
EPA did not sufficiently describe the thought
process and rationale that led to the conclusion of
no unreasonable risk for PV29. There are concerns
about how this method will be applied to future
chemical risk evaluations. OPPT should expand the
narrative in the risk evaluation document to more
clearly describe how the available information
supports its findings, particularly with regard to
determining that the evidence was sufficient for a
risk determination. (8 6-19)
To increase the transparency and clarity of the process used
to arrive at the risk determinations, EPA tied each risk
determination in the final Risk Evaluation for PV29 to a
condition of use and explained the uncertainties involved.
Need additional guidance on when higher-tier assessments will be triggered for future risk evaluations
17
PUBLIC COMMENTS:
Additional guidance, developed with stakeholder
engagement, would be helpful for future risk
evaluations, especially regarding tiered approaches
to assessment, occupational exposure assessment,
and systematic review. In particular, additional
guidance from the Agency on how and when
higher-tier assessments will be triggered would be
helpful for future risk evaluations. (17 26-31)
As discussed above, in Section 4, EPA is not planning to
develop a guidance for a tiered approach to Risk
Evaluation. Each chemical is assessed using a fit-for-
purpose approach that depends on the reasonably available
information and conditions of use specific to each
chemical. This is consistent with the flexibility afforded to
EPA for this risk evaluation process, as explained in 40
CFR 702.41(a)(6) and (7), which explains:
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(6) The extent to which EPA will refine its evaluations for
one or more condition of use in any risk evaluation will
vary as necessary to determine whether a chemical
substance presents an unreasonable risk of injury to health
or the environment.
(7) To the extent a determination as to the level of risk
presented by a condition of use can be made, for example,
using assumptions, uncertainty factors, and models or
screening methodologies, EPA may determine that no
further information or analysis is needed to complete its
risk evaluation of the condition(s) of use.
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Supplemental Analysis
Charge Question 8.a: Please comment on whether the use of point of departure from analog data used in conjunction with the
adjusted NIOSH-recommended exposure limit or the Occupational Safety and Health Administration (OSHA) standard for Particles
Not Otherwise Regulated (PNOR) to develop an MOE provides utility in risk characterization concerning PV29. If not, please suggest
alternative approaches or information that could be used to incorporate these values into the human health risk characterization.
Charge Question 8.b: Please comment on whether the screening-level estimate for the potential for lung overload with the NIOSH-
recommended exposure limit or the Occupational Safety and Health Administration (OSHA) standard for Particles Not Otherwise
Regulated (PNOR) and the predicted deposition fraction to the alveolar region predicted by the MPPD model (v3.04) from
Orberdorster (1994), and whether this provides utility in risk characterization concerning PV29.
Oberdorster, G. (1994). Lung particle overload: implications for occupational exposures to particles. Regulatory Toxicology and
Pharmacology, 27(1), 123-135
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Summary of Comments for Specific Issues Related to
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EPA/OPPT Response
EPA needs more current and/or accurate inhalation exposure data
SACC
SACC COMMENTS:
Given that no acceptable inhalation toxicity studies
are available for PV29, a properly designed
inhalation study (e.g., 28-day, aerosol, nose only,
inhalable fraction with the high dose achieving
toxicity which may be lung overload) would be
needed to fill this data gap.
PV29 is assumed to not be bioavailable or readily
absorbed by any applicable route of exposure since
it may have poor water and lipid solubility. No
absorption, distribution, metabolism, elimination
(ADME)/toxicokinetic data were presented.
However, mouse skin staining was observed after
dosing by intra-peritoneal injection, gavage, and
dermal application. The mechanism for this has not
been ascertained. NAMs such as Organ on a Chip
EPA agrees that there are uncertainties inherent in making a
determination about respiratory hazard without available
inhalation toxicity data for C.I. Pigment Violet 29. However,
as discussed in the final Risk Evaluation, with the new data
obtained through the Section 4 test order to evaluate the
solubility of C.I. Pigment Violet 29, EPA has a greater
degree of confidence that it is poorly absorbed and therefore
not metabolically active. Therefore, based on evidence that
suggests chronic inhalation of such particles can trigger lung
overload, EPA has determined that lung overload is the
relevant effect for C.I. Pigment Violet 29 U.S. EPA (2019).
As chronic inhalation data are available for Carbon Black,
another pigment with low solubility and a similar particle
diameter and relative density, EPA determined that these
data are adequate to understand the potential hazards of
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(lung) or skin permeability in vitro assay should be
considered.
Supplement available data by requesting personal
monitoring data from the manufacturer which
should include both respirable dust fraction and
total dust.
chronic inhalation of C.I. Pigment Violet 29 and no
additional inhalation toxicity data are needed.
The staining effects are poorly explained in the assessments.
However, with the submission of the new solubility data that
confirms the low solubility of C.I. Pigment Violet 29 in
water and octanol and as a result, the low potential for
absorption, it is determined that these staining effects (which
are inconsistently reported) are not representative of the
chemical, but of issues with the way the studies are
conducted. Regardless, these staining events did not result in
adverse effects to the test organisms in the cases of oral and
dermal exposure.
EPA requested and received additional respirable dust
monitoring data.
Supplemental inhalation analysis improves risk evaluation, but clarify sources of uncertainty
73
PUBLIC COMMENTS:
EPA's updated inhalation risk characterization of
PV29 provides additional rigor to the risk
evaluation demonstrating low risk in occupational
settings. EPA could, however, provide additional
clarity by tabulating sources of uncertainty within
the different MOE calculations. (731)
EPA has added language to the final Risk Evaluation to
better describe the sources of uncertainty.
Supplemental inhalation analysis is inadequate
55,
78, 82
PUBLIC COMMENTS:
The New Inhalation Analysis is inadequate to
evaluate PV29's inhalation risks and rests upon
EPA agrees that the inhalation analysis presented in update
to the Draft Risk Evaluation is inadequate based on data
received to characterize the inhalation potential of PV29.
EPA has updated the final Risk Evaluation to better explain
the assumptions and modeling approach. EPA will be
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Summary of Comments for Specific Issues Related to
Charge Question 8
EPA/OPPT Response
unsupported assumptions and an unvalidated, non-
peer reviewed model. (78 5-11)
EPA assumes that Pigment Violet 29 is non-toxic
and not absorbed via inhalation without providing
adequate empirical data to support such
assumptions and because of these major data gaps,
EPA's new occupational inhalation analysis fails to
demonstrate that PV29 is not risky. (821)
EPA's New Inhalation Analysis does not explain
why EPA selected the screening-level lung overload
calculation or discuss any uncertainties associated
with the formula and its application to
PV29. (55_2)
EPA's inhalation risk calculations based on the
barium sulfate study are unsupported and
underestimated. (7813)
conducting an external peer review of Technical Support
Documentation and User's Guide to accompany an EPA
version (2020 v. 1.01) of the MPPD model for use in Agency
assessments at the end of FY20.
EPA acknowledges that the lack of inhalation toxicity data is
an uncertainty. EPA is confident that, based on the physical
chemical properties of the analogue Carbon Black, it is
sufficiently similar to C.I. Pigment Violet 29 to be able to
adequately describe the inhalation hazards of the chemical.
EPA has updated the explanation of why it selected the
screening-level lung overload calculation and has expanded
the discussion of any uncertainties associated with this
approach in the final Risk Evaluation.
EPA has updated the inhalation approach in the final Risk
Evaluation with an analogue that is more representative of
the physical chemical properties of C.I. Pigment Violet 29.
Peer Review Comments on Whether or Not Information in the CBI Materials Was Accurately Reflected in
the Publicly Available Summaries
Charge Question 9: Please comment on whether or not the information contained in the CBI materials provided to the panel is
accurately reflected in the sanitized data that are made publicly available and robust summaries used in the risk evaluation for PV29.
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Summary of Comments for Specific Issues Related to
Charge Question 9
EPA/OPPT Response
Include justifications for redactions by companies
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Summary of Comments for Specific Issues Related to
Charge Question 9
EPA/OPPT Response
SACC
SACC COMMENTS:
The Committee suggested EPA develop a protocol
to include justifications [of redactions by
companies] when providing the CBI materials.
For information reported to or otherwise obtained by EPA
under TSCA, EPA currently requires CBI claims to be
substantiated in accordance with TSCA sec. 14(c)(3) at the
time the information is submitted, unless the information is
exempt from upfront substantiation under TSCA sec.
14(c)(2). For information that is not reported to or otherwise
obtained by EPA under TSCA, EPA requires CBI claims to
be substantiated in accordance with the procedures set forth
in 40 CFR Part 2, Subpart B.
Provide summaries of differences between full and redacted study reports
SACC
SACC COMMENTS:
The Committee suggested providing, for each study
involving CBI, a summary of the differences
between the full study report and the redacted study
report, with a focus on what information/data is
critical to the assessment and how redactions could
affect this information.
EPA acknowledges that this approach would be useful in
future assessments where critical data are not publicly
available as a result of CBI determinations. In the case of the
data available for C.I. Pigment Violet 29, this is not
necessary. Of the 24 studies initially claimed in full as CBI,
15 were released completely without redactions, and 8 study
reports were released with partial redactions that do not
affect the study details (redactions were only applied to the
contact information of the laboratory staff and company). In
the instance of the sub chronic toxicity study, the CBI claims
were applied to the individual animal data tables and not the
result summaries. Upon comparison of the fully unredacted
and partially redacted study reports, EPA determined that the
redactions did not apply to critical study details and therefore
did not affect the ability of a reviewer to understand the
results of the study. The study reports can be found in the
docket for PV29 (EPA-HO-OPPT-2018-0604Y
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Summary of Comments for Specific Issues Related to
Charge Question 9
EPA/OPPT Response
Allow certain parties to examine full study reports
SACC
SACC COMMENTS:
The Committee suggested that EPA come up with a
means to allow certain parties to examine full
(unredacted) studies.
EPA will explore this in cases where future assessments rely
on information protected by CBI claims.
Other Peer Review Comments
Charge Question 10: Comments that do not fit into the other charge questions.
#
Summary of Comments for Specific Issues Related to
Charge Question 10
EPA/OPPT Response
82
The implementation of the Lautenberg Act has
deviated dramatically from Congress' intent and the
new law's requirements. (82_1)
EPA is committed to effectively implementing the
Lautenberg Act's amendments to TSCA. EPA will
incorporate meaningful and relevant feedback received
during this public period into its future risk evaluations.
Cited References
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evaluation of test methods for benthic invertebrates and sediments: Effects of flow rate and feeding on water quality and
exposure conditions. Arch Environ Contam Toxicol 25: 12-19.
BASF. (1988). Testing the acute toxicity in the fish model Zebra danio (brachydanio rerio) over the course of 96 hours. Germany:
Hoechst AG, Pharma Research Toxicology and Pathology.
BASF. (2012). H-28548: Paliogen violet 5011, Daphnia magna, acute immobilization test. Pszczyna, Poland: Institute of Industrial
Organic Chemistry, Branch Pszcyna Department of Ecotoxicology.
Cherrie. JW; Semple. S; Christopher. Y; Saleem. A; Hughson. GW; Philips. A. (2006). How important is inadvertent ingestion of
hazardous substances at work? Ann Occup Hyg 50: 693-704.
Elder. A; Gelein. R; Finkelstein. JN; Driscoll. KE; Harkema. J; Oberdorster. G. (2005). Effects of subchronically inhaled carbon black
in three species I Retention kinetics, lung inflammation, and histopathology. Toxicol Sci 88: 614-629.
http://dx.doi.org/10.1093/toxsci/kfi327.
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Mackav. D; Di Guardo. A; Paterson. S; Cowan. CE. (1996). Evaluating the environmental fate of a variety of types of chemicals using
the EQC model. Environ Toxicol Chem 15: 1627-1637.
Nicolaou. C. (2020). Determination of the Solubility of C.I. PV29 in 1-Octanol and Water. Colors Technology Analytical Laboratory.
https://beta.regulations.gov/document/EPA-HO-OPPT-2020-0070-00Q8.
U.S. EPA. (2017). Scope of the risk evaluation for Pigment Violet 29 (Anthra[2,l,9-def:6,5,10-d'e'f]diisoquinoline-l,3,8,10(2H,9H)-
tetrone): CASRN: 81-33-4 [EPA Report], (740-R1-7011). U.S. EPA, Office of Chemical Safety and Pollution Prevention,
Office of Pollution Prevention and Toxics, https://www.epa.gov/sites/production/files/2017-06/documents/pv29 scope 06-22-
17.pdf.
U.S. EPA. (2018a). Application of systematic review in TSCA risk evaluations. (740-P1-8001). Washington, DC: U.S. Environmental
Protection Agency, Office of Chemical Safety and Pollution Prevention, https://www.epa.gov/sites/production/files/2018-
06/documents/final application of sr in tsca 05-31-18.pdf.
U.S. EPA. (2018b). Draft Risk Evaluation for C.I. Pigment Violet 29.
U.S. EPA. (2019). U.S. EPA Integrated Science Assessment for particulate matter [EPA Report], (EPA/600/R-19/188).
https://cfpub.epa. gov/ncea/isa/recordisplav.cfm?deid=347534.
U.S. EPA. (2020a). Final Risk Evaluation for C.I. Pigment Violet 29, Supplemental File: Information Received from Manufacturing
Stakeholders.
U.S. EPA. (2020b). Final Risk Evaluation for C.I. Pigment Violet 29, Systematic Review Supplemental File: Data Quality Evaluation
of Environmental Fate and Transport Studies.
U.S. EPA. (2020c). Final Risk Evaluation for C.I. Pigment Violet 29, Systematic Review Supplemental File: Data Quality Evaluation
of Physical-Chemical Property Studies.
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