vyEPA
United States Environmental Protection Agency
Office of Chemical Safety and 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 Final Risk Evaluation of
C.I. Pigment Violet 29
CASRN: 81-33-4
°^N^°
January 2021
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Contents
Contents 2
Introduction 6
Comments on the Draft Risk Evaluation for C.I. Pigment Violet 29 8
List of Comments Submissions 8
Overall Content, Organization, and Presentation of the Draft Risk Evaluation 11
Draft was sufficiently clear and transparent 11
Need to improve clarity, transparency, and organization of rationale and conclusions 11
Need to improve clarity and transparency of study quality evaluations 13
Include measures and discussion of uncertainty and variability with numerical values 13
Need to improve transparency of risk evaluation process and procedures 14
Report would be improved by adding graphics, figures, and/or tables 15
Need to improve transparency of external review processes 15
Need to improve access to information sources 16
Need to improve transparency of occupational exposure data and PV29 uses 18
Need to improve clarity and transparency of study quality evaluations 20
EPA did not use its legal authority under TSCA to collect data, and it should 21
Violation of TSCA by not releasing full studies due to CBI claims 21
Support for EPA's handling of CBI 23
Update risk evaluation to reflect availability of studies that were previously redacted 25
Include description of the ramifications of the final risk statement 25
Systematic Review Approaches and Clarity 27
Need to describe the rationale for developing a systematic review method specific to
TSCA 27
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 28
Concerns that the TSCA systematic review method does not follow best scientific
practices and should be replaced 29
Need to more clearly describe the systematic review protocol and procedures 31
Need to provide a more thorough discussion of data integration 32
Insufficient data concerns and handling of lack of data 34
Concerns about the quality of the body of evidence for PV29 35
Concerns relating to the personal communication from Sun Chemical 36
Need for public access to data 37
Study quality evaluation and scoring concerns 37
TSCA systematic review method was effective for PV29 40
Page 2 of 180
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Include discussion of toxicity of byproducts of manufacturing and impurities in PV29 41
Physical Chemical Properties and Environmental Fate 42
Concerns about water solubility study and value EPA used 42
Remove statements that low aqueous solubility precludes oral bioavailability 43
Use alternative methods to generate information to evaluate bioavailability 43
Concerns about use of EPI Suite™ 43
Lack of clarity and data to support conclusions regarding bioaccumulation potential 44
Supportive of conclusion that PV29 is poorly absorbed 44
Ensure consistency or justify differences among physicochemical properties across the
assessment 44
Consider metabolic pathway prediction software to identify intermediates 45
Concerns about environmental persistence and fate evaluation and lack of data 46
Exposure and Releases 48
Supportive of EPA's occupational exposure assessment 48
Incorporate uncertainty analysis and screening-level fugacity modeling in life cycle safety
assessment 48
EPA did not consider full range of uses and exposure pathways 49
EPA failed to consider workers experiencing multiple routes of exposure 52
Deficiencies in exposure data and analysis 53
Opposition to EPA's reliance on personal communication from Sun Chemical 55
Concern regarding EPA's approach to evaluate only highest anticipated exposure 56
Supports tiered approach that incorporates PPE in the exposure assessment 57
Opposes assumption of PPE use in the exposure assessment 57
EPA should not rely on the presence of and compliance with safety data sheets (SDS) 59
EPA should prioritize engineering controls over PPE or warning labels to reduce exposure60
Concerns about lack of release data 60
Support for EPA's engagement with industry to obtain data 61
Concerns about occupational inhalation exposure assessment assumptions and parameters61
Concerns about occupational dermal exposure analysis and clarity 62
EPA should revisit its decision not to assess occupational oral exposure 62
EPA did not properly assess exposure of downstream processors and users 63
Concerns about the environmental release characterization 65
EPA did not consider environmental release of PV29 when used as an intermediate 68
Concern about assumption that PV29 remains "bound" in downstream use 68
EPA was right to remove conditions of use it was unable to support 69
Evaluation lacks information on conditions of use 69
Page 3 of 180
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Inadequate characterization of potentially exposed or susceptible sub-populations (PESS) 71
Support for and request for clarity regarding quantitative screening-level exposure
assessment 72
EPA did not address exposures in pregnant women, children, and other downstream users 72
EPA was correct to focus on sentinel exposure 73
Support for aggregate exposure vs. sentinel exposure assessment 73
EPA should pursue exposure and releases information from a wider range of organizations74
Other SACC comments related to physical chemical properties 75
Environmental Effects 76
Need for more data to evaluate hazard to aquatic ecological receptors 76
Do not ignore Topkat-predicted acute LC50 for fathead minnow 78
Need to better describe how log Koc was determined 78
Concerns about ecological hazards for sediment-dwelling invertebrates 78
Need for more data to evaluate hazard to terrestrial ecological receptors 79
Concerns about citing the Canadian Ecological Risk Classification for PV29 as support for
determination 80
Support for EPA's characterization of hazard to ecological receptors 81
Concerns about studies where observed exposures exceed water solubility limit 82
Human Health 83
Support for EPA's approach and conclusions regarding human health risk 84
Make hazard conclusions specific to routes of exposure 84
Clarify value of the screening reproductive/developmental toxicology study and highlight
data gaps 84
The toxicity studies EPA used are unreliable 85
EPA improperly disregarded intraperitoneal studies 86
EPA did not use data from similar substances 86
EPA should acquire additional studies due to insufficient data 87
Increase transparency of evidence used to determine carcinogenic risk 88
Concerns about route-to-route extrapolation and lack of uncertainty factor 88
MPPD model requires size distribution of PV29 in workplace aerosols 89
Present models or NAMs to improve understanding of absorption potential 89
Concerns about lack of scientific evidence for EPA's conclusion regarding absorption
potential 90
Consumer hazard is not fully investigated 91
Obtain more occupational hazard data 91
Clarify uncertainties and justify conclusions regarding susceptibility 92
There are no vulnerable subpopulations 93
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Risk Characterization/Risk Determination 94
The conclusions in the draft risk characterization are flawed due to lack of data 95
EPA's reliance highly uncertain fate and persistence information casts doubt on its risk
conclusions 97
Criticism of the margin of exposure (MOE) approach and clarity 97
Supports EPA's use of the MOE approach 99
Concerns about CBI affecting the risk characterization 99
Need to apply additional uncertainty factors 99
Use of intraspecies uncertainty factor was conservative 100
Occupational risk characterization is flawed 100
Need to expand the risk characterization narrative 101
Need additional guidance on when higher-tier assessments will be triggered for future risk
evaluations 102
Supplemental Analysis 103
EPA needs more current and/or accurate inhalation exposure data 103
Supplemental inhalation analysis improves risk evaluation, but clarify sources of
uncertainty 104
Supplemental inhalation analysis is inadequate 104
Peer Review Comments on Whether or Not Information in the CBI Materials Was
Accurately Reflected in the Publicly Available Summaries 106
Include justifications for redactions by companies 106
Provide summaries of differences between full and redacted study reports 106
Allow certain parties to examine full study reports 107
Other Peer Review Comments 108
Comments on the Revised Draft Risk Evaluation for C.I. Pigment Violet 29 (PV29) 109
List of Comments Submissions 109
Response to Public Comments Received 110
Response to Peer Review Comments 159
Cited References 179
Page 5 of 180
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Introduction
Draft Risk Evaluation for C.I. Pigment Violet 29
EPA published the Draft Risk Evaluation for C.I. Pigment Violet 29 ( .Q-OPPT-2018-0604-0007)
("draft risk evaluation") on December 11, 2018. As per EPA's final Risk Evaluation Rule, Procedures
for Chemical Bisk Evaluation Under the Amend >c Substances Control Act (82 PR 33726). the
draft risk evaluation was subject to both public comments and peer review, which are distinct but related
processes. EPA provided 60 days for public comment on all aspects of the draft risk evaluation,
including the submission of any additional information that might be relevant to the science underlying
the risk evaluation. This satisfied TSCA Section 6(b)(4)(H), which requires EPA to provide public
notice and an opportunity for comment on a revised draft risk evaluation prior to publishing a final risk
evaluation.
EPA accepted public comments on the draft risk evaluation 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 as well as the updated systematic review documents. EPA accepted a
third round of public comments from June 10 to July 10, 2019 after publication of the C.I. Pigment
Violet 29 Inhalation Risk Characterization Summary and Updated Charge Questions for the Science
Advisory Committee on Chemicals (SACC) peer review of the draft risk evaluation held June 18-21,
2019. A report of the SACC peer review results was published in September . Materials on the draft
risk evaluation are available at www.regulations.gov in docket EPA-HQ-OPPT-2019-0437.
EPA appreciates the valuable input provided by the SACC peer review panel and the public. The first
portion of this document summarizes the SACC peer review and public comments received by EPA on
the draft risk evaluation and provides EPA's responses to the comments received. The SACC peer
review Updated Charge Questions1 are used to categorize the peer review and public comments on the
draft risk evaluation into specific issues related to ten main themes.
Overall Content, Organization, and Presentation of the Document
Systematic Review Approaches and Clarity
Physical Chemical Properties and Environmental Fate
Exposure and Releases
Environmental Effects
Human Health
Risk Characterization and Risk Determination
Supplemental Analysis
Peer Review Comments on Confidential Business Information (CBI) Material
Other Peer Review Comments
Revised Draft Risk Evaluation for C.I. Pigment Violet 29
On June 6, 2019, EPA released a quantitative human health inhalation risk characterization approach.
This approach used toxicity information for an analogue, barium sulfate to estimate risks to workers
from inhalation of C.I. Pigment Violet 29 dust in a manufacturing facility. This approach is described
in a summary document released to the docket ( Q-OPPT-2018-0604-0052).
1 These are the questions that EPA/OPPT submitted to the panel to guide the peer review process.
Page 6 of 180
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In the draft risk evaluation, EPA preliminarily concluded that C.I. Pigment Violet 29 does not pose
unreasonable risks to public health or the environment. During the review of the draft risk evaluation by
the SACC, uncertainties were identified concerning C.I. Pigment Violet 29 solubility and occupational
worker inhalation exposure. EPA gathered additional data to address critical uncertainties identified in
the draft risk evaluation indicated by the SACC and in public comments. Where data received from the
manufacturing stakeholders was determined to be deficient, EPA utilized its information gathering
authorities under TSCA Section 4. On February 28, 2020, EPA issued a TSCA Section 4(a)(2) Test
Order for the generation and submission of solubility testing in water and octanol, as well as a respirable
dust monitoring study. More information can be found in the TSCA Section 4 Test Order docket (I
HO-OPPT-2020-007QY
In October of 2020, EPA published a Revised Draft Risk Evaluation for C.I. Piment Violet 29 ( Q~
OPPT-2018-0604-0007) ("revised draft risk evaluation") on October 30, 2020. EPA accepted public
comments on the revised draft risk evaluation from October 30 to November 30, 2020 and extended the
public comment period for an additional 20 days to December 19, 2020. EPA also conducted a Letter
Peer Review of the revised draft risk evaluation from October 30 to November 30, 2020. The charge
questions for the external peer reviewers are found here. The Letter Peer Review report on the revised
draft risk evaluation can be found here: EPA-HQ-QPPT-2018- Materials on the revised draft
risk evaluation are available at www.regulations.gov in docket EPA-HQ-OPPT-2018-0604.
EPA appreciates the valuable input provided by the Letter Peer Review and the public. The second
portion of this document summarizes the Letter peer review and public comments received by EPA on
the revised draft risk evaluation and provides EPA's responses to the comments received. EPA's
responses to comments received from the general public and the Letter Peer Reviewers are provided in
separate sections. Responses to the Letter Peer Review are organized by Charge Questions, while
responses to public comments are organized into specific and general issues.
Page 7 of 180
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Comments on the Draft Risk Evaluation for C.I. Pigment Violet 29
List of Comments Submissions
#
Docket File
Submitter
8
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-
001 I
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-
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-
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-
Jennifer Sass, Senior Scientist, Natural Resources
Defense Council (NRDC)
43
EP A-HO-OPPT-2018-0604-
Hanna Vesterinen, Research Consultant to UCSF
PRHE et al.
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)
Page 8 of 180
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#
Docket File
Submitter
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-
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-
Gary E. Timm, Environmental Protection Network
(EPN)
76
EP A-HO-OPPT-2018-0604-
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 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)
Commciils Received During Public ( onimcnl Period Kndiii" on 12/19/2020
105
* r \ nO-OPPT-2018-060 1-010*
EP A-HO-OPPT-2018-0604-0103
David Wawer, Executive Director, Color Pigments
Manufacturers Association, Inc. (CPMA)
Page 9 of 180
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#
Docket File
Submitter
106
EP A-HO-OPPT-2018-060
Jared Rothstein, Society of Chemical Manufacturers &
Affiliates (SOCMA)
108
EP A-HO-OPPT-2018-060*
Julia M. Rege, Vice President, Energy & Environment,
Alliance for Automotive Innovation
109
EP A-HO-OPPT-2018-0604-
0109
Riaz Zaman, Counsel, Government Affairs, American
Coatings Association (ACA)
110
EP A-HO-OPPT-2018-060
Liz Hitchcock, Director, Safer Chemicals Healthy
Families (SCHF) & National Resources Defense
Council (NRDC)
111
EP A-HO-OPPT-2018-0604-
01 1 1
Swati Rayasam, et al., Program on Reproductive Health
and the Environment Department of Obstetrics,
Gynecology and Reproductive Sciences University of
California, San Francisco
112
E
P A-HO-OPPT-2018-0604-
Suzanne Hartigan, American Chemistry Council (ACC)
0
l .1 »
113
E
P A-HO-OPPT-2018-0604-
Michelle Roos, Environmental Protection Network
(EPN)
1 13
119
E
P A-HO-OPPT-2018-0604-
Richard A. Denison, Environmental Defense Fund
(EDF)
120
E
P A-HO-OPPT-2018-0604-
Brett Fox, International Union, UAW
120
121
E
P A-HO-OPPT-2018-0604-
Jen Jackson, Toxics Reduction & Healthy Ecosystems
Program Manager, San Francisco Department of the
Environment
10 1
1 1
(S)= Supp
emental documents were providec
with the comment and included in the summary
Page 10 of 180
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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
Drill"! was sufficiently clear ami 1 r;inspiircnl
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.
EPA clearly indicates that the conditions of use have been
modified slightly since the problem formulation phase of
the assessment.
These organizational comments are appreciated and were
considered in the final risk evaluation.
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 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
These organizational comments are appreciated and were
considered in the final risk evaluation. EPA has updated the risk
evaluation and determination format for increased clarity
regarding the unreasonable risk determination and the risk
considerations for each condition of use.
While EPA believes that discussions of the rationale for the
determination of unreasonable risk are 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
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, populations who are exposed (including
any sensitive subpopulations), the severity of the hazard, and
uncertainties. This approach is outlined in EPA's 2017
Page 11 of 180
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#
Summary of Comments for Specific Issues Related to
Charge Question 1
EPA/OPPT Response
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 evaluations. We request that OPPT expand
the narrative in the risk evaluation document to more
clearly describe how the available information supports
its findings.
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 risk evaluation details
those factors and describes for the public which conditions of
use were 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
considers exposure scenarios both with and without engineering
controls and personal protective equipment (PPE). These
assumptions are described in the risk characterization and risk
determination sections of the final risk evaluation including
uncertainties and their effect on the unreasonable risk
determination for each condition of use.
TSCA requires EPA to use reasonably available information
and best available science in its risk evaluation. EPA identified
uncertainties regarding the information that is reasonably
available to characterize PV29's solubility and occupational
worker inhalation exposure. These uncertainties resulted in
EPA requiring testing of PV29 for use in the final risk
evaluation under TSCA section 6(b). Test data has been
reviewed for data quality and incorporated into the final risk
evaluation.
Page 12 of 180
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#
Summary of Comments for Specific Issues Related to
Charge Question 1
EPA/OPPT Response
EPA should consider making clear how it determined the
existing data set was sufficient to develop a risk
characterization and determination.
Need to improve clarity and transparency of study quality c\ ;iln;il ions
17, 46
PUBLIC COMMENTS:
More detail in the risk evaluation regarding how EPA
evaluated study quality would improve transparency.
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.
Along with publishing the problem formulation for PV29, EPA
Dublished a guidance document titled Application of Systematic
Review in TSCA Risk Evaluations that describes the data qualitv
criteria used for each discipline and outlines 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 revised draft and
final risk evaluation increases transparency by inclusion of
supplemental files that provide the details of the systematic
review of all studies used.
Include men suits 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:
EPA included further discussion of uncertainty surrounding the
numerical values used in the final risk evaluation. Where
applicable, the use of a particular value over another is
explained and justified.
EPA identified uncertainties regarding what information was
reasonably available to characterize PV29's solubility and
occupational worker inhalation exposure in the final risk
evaluation. These uncertainties resulted in EPA requiring
testing of PV29 to develop new information for EPA to
decrease uncertainty in the final risk evaluation under TSCA
section 6(b).
EPA has added text to the final risk evaluation to identify data
gaps in the information available for PV29 including human
hazard information and particle size distribution information as
well as dust exposure information for workers and processors.
Page 13 of 180
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#
Summary of Comments for Specific Issues Related to
Charge Question 1
EPA/OPPT Response
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.
Need to improve transparency of risk c\ :iln:ilion 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 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.
EPA's description of its approach to data integration in its
draft risk evaluation for PV29 is severely lacking.
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.
Recommend that EPA provide additional information
regarding why a quantitative screening-level exposure
assessment was added.
EPA should clarify why PV29 was poorly characterized
for the Work Plan, and how the lessons from that
The final risk evaluation describes the history of PV29 risk
evaluation from problem formulation through draft, revised
draft and final risk evaluations. EPA incorporated narratives
explaining the concerns associated with worker exposure to
dust particles. The final risk evaluation also describes the
current understanding of the chemical's risks as a result of the
full TSCA risk evaluation process.
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
evaluates the scientific information. The final risk evaluation
includes supplemental files that provided the detailed
evaluation of data quality for each study used.
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.
Information has been added to the final risk evaluation to
substantiate why evaluation of risks associated with inhalation
exposures to PV29 dust was added.
Page 14 of 180
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#
Summary of Comments for Specific Issues Related to
Charge Question 1
EPA/OPPT Response
characterization might inform EPA's prioritization
process for the TSCA Active Inventory. The lack of
transparency in this risk evaluation will create a precedent
of making "no unreasonable risk" determinations based
on proprietary information.
With regard to the comment pertaining to proprietary
information, 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 he improved In adding graphics. figures. and/or l:ihies
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 1.5. 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:
httos://www.eoa.8ov/sites/oroduction/files/z
06/documents/t»v29 lit search stratt f
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.
The final Risk Evaluation should include all peer
reviewer comments and how EPA responded to them.
EPA's discussions and consultation with other federal agencies
and other EPA program offices are reflected in both the revised
draft risk evaluation and the final risk evaluation. EPA does not
share internal deliberative comments from the interagency
review process.
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EPA/OPPT Response
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.
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 June 18-21, 2019 has been
made publiclv available in the docket (EPA-HO-GPPT-2018-
0604). The Letter Peer Review report on the revised draft risk
evaluation is available at EPA-H< T-2018-0604-0107 and
the comments are provided as part of this Response to
Comment (RTC) document.
In all instances, non-CBI versions of study reports were made
available to the Agency and were added to the public docket.
The revised draft and final risk evaluation increases
transparency by inclusion of supplemental files that provide the
details of the systematic review of all studies used.
Need to improve access lo 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 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
EPA has made every effort to update the revised draft and 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 and full
study reports.
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. These data are available in a supplemental file in the
docket for the final Risk Evaluation entitled, "Supplemental
File: Information Receivedfrom Manufacturing Stakeholders."
(US. EPA. 2020a)
EPA has worked with the data owners of the studies
summarized in the ECHA database and has included fully
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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.
EPA should provide access to the SDS and industry
statements on which it relies to discount potentially
relevant routes of exposure.
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.
Most information obtained from industry should have
been made public, particularly the approximate maximum
workplace air concentration and daily discharge rate from
Sun Chemical.
EPA must immediately make public the details of the
Mott 2017 personal communication, and all other
personal communications relevant to the risk evaluation.
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.
EPA should consider more clearly linking the robust
study summaries available on ECHA's website to the
unredacted or partially redacted versions of these studies in the
public docket for PV29 (EPA-HO-OPPT-2018-0604V A
summary of the redaction status of each study report can be
found at htto s: //www. reeul ati on s. gov/docum ent?D=EP A-HO -
OPPT-2018-0604-0021. The inclusion of the full studv reports
increases the transparency of the Risk Evaluation process as it
relates to PV29. The revised draft and final risk evaluation
increases transparency by inclusion of supplemental files that
provide the details of the systematic review of all studies used.
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outcome of the risk evaluation, to enhance clarity in how
the data were applied.
Need lo improve transparency <>!'occnp:ilion:il exposure (InIn ami P\ 29 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 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.
EPA should provide information on how it determines
what conditions of use are in/out of scope.
This draft risk evaluation on PV29 is incomplete and not
transparent about the information it relied on to assess
health risk to working people.
As indicated abo\ e, EPA has included a narrali\ e 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 was 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
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.
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Summary of Comments for Specific Issues Related to
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EPA/OPPT Response
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
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.
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EPA/OPPT Response
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.
)20a).
Need to improve clarity and transparency of study (|ii:ilil\ c\ ;ilunlions
17, 46,
47
PUBLIC COMMENTS:
More detail in the risk evaluation regarding how EPA
evaluated study quality would improve transparency.
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.
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 reviewers' comments
and a reevaluation of several human health studies CEPA-HO-
OPPT-2018-0604-0040). These undated systematic review data
quality evaluation results were also released as supplemental
files to the revised draft and final risk evaluation. This enhances
the transparency of the systematic review portion of the risk
evaluation.
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EPA/OPPT Response
EPA did not use its legal authority under TSCA to collect data, and it should
13, 16,
18, 44,
75
PUBLIC COMMENTS:
EPA did not use its full authority to collect the relevant
toxicity and exposure data.
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.
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
comment.
Necessary information includes conditions of use,
exposures, workplace monitoring, environmental releases,
hazards, potentially exposed or susceptible
subpopulations, ecotoxicity. [For specific data requests,
see comment summary sections 4.5, 5.1, and 6.7.]
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 require testing of PV29 to develop new information to
increase certainty in the final risk evaluation. EPA required the
following testing to be conducted for PV29:
Solubility of PV29 in water
Solubility of PV29 in octanol
A workplace dust monitoring study of respirable particles not
otherwise regulated, conducted according to the NIOSH 0600
guideline.
Test data has been received and reviewed for data quality 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 ( !0-OPPT-2020-0070-
0008).
Violation of TSCA by not releasing lull studies due to C'IS 1 claims
II.
12, 13,
14, 16,
20, 44,
46,
IM liLIC 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
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
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46(S),
48, 49,
55, 75,
76, 82
risk evaluation and to participate meaningfully in the peer
review process.
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.
Threats from industry cannot justify compromising the
transparency that Congress required under TSCA section
14(b).
Withholding the full study reports violates requirements
of public notice and 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.
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).
The heavy data redactions from the
reproductive/developmental toxicity screening study are
so extensive as to preclude the ability of the public to
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. In all instances, these study reports were made available
to the Agency and can now be accessed in the public docket
ffiP A-HO-OPPT-2018-0604-0021).
As a result of the release of this information, 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 CBI status.
The updated SR Supplemental File, available in the public
docket for PV29 (EPA-HO-OPPT-2018-06041 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
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have any confidence at all in EPA's many decisions in the
draft risk evaluation that are based on it.
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.
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.
EPA should have reviewed all confidentiality claims
asserted in at least approximately one-fourth of the
information submissions it received.
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).
Support lor KPA's handling ol'Clil
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.
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.
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
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
supplemental files to the final risk evaluation. 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
in the public docket for PV29 (EPA-HO-OPPT-2018-0604V
The Agency does not intend to amend its 2019 final
confidentiality determination.
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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 TSCA section 14
provides EPA with discretion to protect CBI.
Publishing confidential product data, such as valuable
health and safety studies, would discourage companies
from voluntarily expending resources on expensive
toxicology studies.
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.
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."
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.
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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 miMick a\ailaMe lor re\ ieu
Data quality evaluations for each study are available in
supplemental files to the final risk evaluation. 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
in the nuMic docket lor PY21) ( )
Include description of 1 lie 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 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
The final Risk Evaluation was modified to include detailed risk
determinations for each condition of use in order to improve the
understanding of the final risk evaluation results and if any risk
management activities will follow the evaluation. EPA has
identified in the final risk evaluation any changes to risk
determinations from the draft risk evaluation.
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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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.
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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.
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.
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Need lo inili:ile mi cxlernsil peer review of (lie TSCA systematic review protocol
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.
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 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://w ww.nationalacademies.org/our-work/review-of~
Need lo develop, peer review. :ind publish systematic review protocols prior lo conducting TSCA risk sisscssmcnts
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.
Insufficient time is not an acceptable justification for
EPA's failure to develop protocols.
The systematic review protocols should be available and
subject to public comment prior to initiating subsequent
steps of the risk evaluation process.
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. 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's/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
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
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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.
C oncerns llisil (lie TSCA systematic review method does not follow hest scientific prnctices sind should he replsiced
9,13,
14, 16,
18, 43,
44, 46,
48, 55,
80
PUBLIC COMMENTS:
The TSCA systematic review method does not follow best
scientific practices for systematic reviews.
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 in systematic review.
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.
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
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's/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's/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
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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).
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.
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.
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.
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
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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 elesirlv describe (lie system;ilie review proloeol nnd procedures
SACC
SACC COMMUNIS.
Describe clearly the explicit populations, exposures,
comparators, and operators (PECO or 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.
According to the Application oj Systematic Review in 1SCA
Risk Evaluations ( 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
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.
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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:
https://www.epa.gov/sites/production/files/2018-
06/documents/final application of sr in ts
EPA anticipates feedback from the NAS on its systematic
review process and will carefully review and implement
relevant NAS recommendations, as appropriate.
Need lo provide 21 more thorough discussion ol'dnlsi inK'
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48, 55
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 findings 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.
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 study scores were used in this step of the
review process for PV29.
EPA should describe its general approach to evidence
integration, referring to established systematic review
approaches.
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.
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 fEPA-HO-OPPT-2018-0604-0040") with updated
data quality evaluation scores and reviewer comments, are
reflected in Systematic Review Companion Documents
released with the final risk evaluation. EPA is developing
and implementing more formal and structured data
integration, analysis and synthesis strategies for the next set
of TSCA chemical risk evaluations.
Where 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
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Environmental Fate and Transport Studies" (
2020b)
Insufficient diiln concerns iiihI hsimlling of hick ol'dsitsi
SACC,
10, 12,
13, 15,
16, 18,
44, 46,
49, 82
SACC COMNIUM'S.
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.
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.
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.
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 fEPA-HO-OPPT-2020-0070-0008Y 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 ffiPA-HO-C)PPT-2020-0070-0008V
In the absence of reasonably available data to characterize
inhalation toxicity of PV29, EPA has used analogue 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,
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although they appeared to be consistent with the
Reproduction/Developmental Toxicity Screening Test
discussed in the assessment.
Concerns sihonl (lie qiisililv of the hotly of evidence lor P\ 29
43, 47,
48, 55
PUBLIC COMMUNIS.
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.
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."
All studies and information used in the final risk e\ aluation.
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 final 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 June 18-21, 2019, which was
made available in the public docket for PV29 (EPA-HO-
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OPPT-2018-0604-00891
C oncerns rchiling lo (lie porsonnl com 1111111 ic:ilion IVoin Sun (hcmicsil
SACC,
12, 13,
14, 15,
SACC COMMUNIS.
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.
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.
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 respirable
particles 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.
16, 17
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.
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.
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.
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Need for public across to data
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.
EPA should make such information public and easily
searchable through online portals such as the Health and
Environmental Research Online (HERO) database.
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 ( O-OPPT-2018-0604-0040). These
updated systematic review data quality evaluation results are
included as supplemental documents to the final risk
evaluation and enhances the transparency of the systematic
review portion of the final risk evaluation.
Study quality evaluation and scoring ronrrrns
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 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
Appendix A of the Application of Systematic Review in
TSCA Risk Evaluations explains the basis for EPA's/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's/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
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might otherwise cause a study's conclusions to be
questioned.
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.
The study quality scoring system is highly questionable in
the absence of any external validation phase or thorough
pilot testing.
EPA should provide more explicit criteria and descriptions
for the Not Rated/Applicable score determination.
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.
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.
It seems that there was one reviewer for each study,
although best scientific practice is to have two independent
reviewers.
The scoring sheets provide the quality scores but do not
provide information regarding the rationale for scores.
EPA should make the reviewer comments publicly
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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available or provide more detail on the rationales behind
the scores.
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.
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.
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.
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
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comments. 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,
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-2018-0604-0040Y
EPA has made reviewer comments public as Supplemental
Files released with the revised draft and final risk evaluation.
This documentation increases the transparency of
professional judgment calls to stakeholders and the public for
the final risk evaluation for PV29.
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.
TSC'A systematic review method \v:is effective for PY29
PUBLIC COMMENTS:
EPA appropriately gathered and considered all of the
available and relevant data for PV29.
EPA acknowledges these comments.
8,17,
19, 47
EPA's use of data generated for other regulatory programs
is important and encouraged.
EPA completed a thorough review to verify the quality of
the submitted studies.
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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.
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.
Include discussion ol'toxicity of byproducts of 111:11111 l':icttiring nnd impurities in P\ 29
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.
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 to do no further analysis.
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 has added a discussion of chemical residuals of the
PV29 manufacturing process to the final risk evaluation. In
particular, Naphthalic acid/anhydride is considered to be a
dermal and inhalation sensitizer. Risks are not quantified for
the chemical residuals, but their presence is discussed in
terms of increasing potential risks associated with the
chemical of interest.
Naphthalimide generated as a byproduct of the production of
PV29 is outside the scope of this risk evaluation.
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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/cf312ff9-6b!8-8b76-
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Concerns iihonl wsilcr solubility slnriv iinri value KPA 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.
The study used to determine water solubility failed to
consider pH and its influence on water solubility.
Measured values for relatively poorly soluble substances
are highly uncertain.
EPA used an incomplete data set and selected lowest
solubility estimate available.
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.
The CoRAP Justification Document failed to incorporate
the output of the most recent EPA ECOSAR estimation
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 PV29 was found to be insoluble
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Summary of Comments for Specific Issues Related to
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EPA/OPPT Response
program. Studies provided in the ECHA dossier for PV29
reported higher solubility values.
in most solvents except for concentrated sulfuric acid which
was used to perform the UV studies. Therefore, the
substance is soluble under highly acidic conditions (though
the exact value was not determined).
EPA issued a TSCA Section 4 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 of PV29 (Nicolaou. 2020). The results of the
solubility in water and solubility in octanol tests were
determined to be high quality and are used support EPA's
conclusion that PV29 is insoluble.
Remove slsilciiienls llinl low ;h|iic»iis solubility precludes orsil hio:i\:iil:ihilil\
SACC
SACC COMMENTS:
Remove statements that claim that an aqueous solubility of
<11 |ig/L precludes oral bioavailability.
EPA has updated the final risk evaluation to remove these
statements.
I se ;illcrn;ili\c methods lo "cncrsile inlbnnnlion lo e\:iln:ile hiosivsiihihililv
SACC
SACC COMMUN I S
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 se\ oral in-silico methods to strengthen the
available body of evidence that discusses the bioavailability
of PV29 where possible.
Concerns sihoul use ol' KPI Suite™
SACC,
13,45
PUBLIC COMMENTS:
EPA should clarify and address the appropriateness of
using EPI Suite estimates in evaluating PV29's risks.
EPA altered its prior characterization questioning the
reliability of estimates derived using EPI (Estimation
Programs Interface) Suite™.
EPA acknowledges the limitations of EPI Suite™ modeling
to predict the solubility of PV29. The model limitations
were taken into consideration when evaluating the results. In
response to uncertainties about the quality of EPI predictions
for PV29, EPA required the submission of water and octanol
solubility data through the submission of a Section 4 Test
Order.
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Using modelled estimations for water solubility from EPI
Suite is inconsistent with the REACH guidance.
Significant problems remain with EPI Suite, but versions
linked to the PBT Profiler were improved in their accuracy
with respect to organic pigments.
Models like EPI Suite historically have tended to predict a
much higher solubility than experimental results determine
for substances outside the calibration ranee of the models
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
higher than the measured values, but still indicates low
water solubility
l.sick of chirilv nild to support conclusions regarding hioncciiniuhilion potcnlinl
13, 16
PUBLIC COMMENTS:
EPA did not indicate the methods used in deriving its BAF
and BCF values.
EPA relies on incomplete and uncertain data to conclude
that PV29 does not bioaccumulate.
The evidence for solubility and bio-accumulation potential
is inconclusive.
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 tlisil PV29 is poorly sihsorhed
19, 45
PUBLIC COMMENTS:
Based on physicochemical properties of PV29, EPA
correctly classified PV29 as poorly absorbed by all routes
of exposure.
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.
EPA classified PV29 as poorly absorbed because of the low
solubility and the relatively large molecular weight, which
hinders absorption of PV29 as particles into the bloodstream
by all routes of exposure. However, inhalation of PV29 as
particles may result in the accumulation of the particles in
the pulmonary system. PV29 is also reported by Sun
Chemical Corporation to be present in the workplace at a
particle size in the nanometer range. These particles can
potentially migrate through tissues after inhalation and could
be deposited into other tissues.
Knsurc consistency or justify differences siniong physicochcmiciil properties sicross (lie sisscssnienl
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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 metsiholic psilhwnv prediction software to identify inlermedinles
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. The exception may be deposition of particles in
the respiratory system after inhalation.
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
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Summary of Comments for Specific Issues Related to
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EPA/OPPT Response
and Toxicological Association of Dyes and Organic
Pigments (ETAD) method for octanol solubility. The study
results, which are available on regulations.gov at CEPA-HO-
OPPT-2020-0070-00081 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
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 sihonl cnvironincnliil persistence iintl Isile evsilnsilion sind hick <>!'
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.
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 ( 0-OPPT-2020-0070-0008Y
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
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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, "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.
characteristics of PV29 and was determined to be high
quality after review with the data quality evaluation criteria
for Dhvsical 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 of Physical-Chemical Property Studies (U.S.
)20c)." EPA also identified articles on similar
organic 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 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.
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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.
#
Summary of Comments for Specific Issues Related to
Charge Question 4
EPA/OPPT Response
Supportive of EPA's occupational exposure assessment
17, 45
The PV29 estimation of occupational exposure is
evidence of the utility of EPA's risk assessment approach
in appropriate cases.
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.
EPA acknowledges these comments.
Incorporate uncertainly analysis and screening-level I'ugacily modeling in lile cycle salely 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.
EPA included occupational exposure estimates for inhalation
of PV29 for processing and downstream users in the final risk
evaluation.
According to the developers of the fugacity model, for
substances like PV29 with no solubility in octanol or air, this
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For non-ionizable organics, EPA should adopt a screening
level fugacity modeling approach as a default under
LCSA.
model mav not be useful CMackav 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 CMackav 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.
KPA did not consider lull rsingc of uses nnd exposure pnlhwnvs
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."
EPA has dismissed a wide range of uses for PV29 and
erroneously suggests that its risk 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.
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.
EPA must revise its evaluation to reflect all occupational
uses and exposures, use its authority to collect data, and
reissue for public comment.
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."
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
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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.
EPA has not fully evaluated conditions of use for
consumers.
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.
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.
EPA refused to analyze certain exposure pathways in
depth.
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.
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.
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-HO-GPPT-^
5-0004Y
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
quantitative 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
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Summary of Comments for Specific Issues Related to
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EPA/OPPT Response
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 to decrease
uncertainty 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.
EPA believes it now has sufficient information to assess risk
- EPA has used reasonably available information and used
TSCA Section 4 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 2.2.3).
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
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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.
In this risk evaluation, EPA determined that aggregating
exposure pathways would be inappropriate because the only
route of concern is chronic inhalation to PV29, and the lungs
are the site of the adverse effects. Chronic exposure to
PV29is expected to increase lung burden, overwhelm the lung
clearance mechanisms over time, and ultimately result in
adverse effects. Exposure via dermal and oral routes is
expected to be low due to workplace practices, including use
of PPE such as gloves; and any absorption from dermal or
oral exposure is expected to be negligible based on the
insolubility of PV29. Therefore, these exposure pathways are
not expected to influence the toxicity in the respiratory tract".
EPA determined that sentinel exposure via inhalation was the
most appropriate approach for risk characterization
KPA foiled 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.
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.
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. In this risk evaluation,
EPA determined that aggregating exposure pathways would
be inappropriate because the only route of concern is chronic
inhalation to C.I. Pigment Violet 29, and the lungs are the site
of the adverse effects. Exposure via dermal and oral routes is
expected to be low due to workplace practices, including use
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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.
EPA's series of rationales for dismissing the significance
of worker exposures are weak and based on little actual
data or analysis.
EPA was unclear in its assumptions regarding dermal
exposure levels
of PPE such as gloves; and any absorption from dermal or
oral exposure is expected to be negligible based on the
insolubility of C.I. Pigment Violet 29. Therefore, these
exposure pathways are not expected to influence the toxicity
in the respiratory tract. EPA determined that sentinel exposure
via inhalation was the most appropriate approach for risk
characterization.
EPA has updated its assumptions regarding dermal exposure
in the final risk evaluation. Dermal exposures are not
quantitatively evaluated as it is an insoluble particle that is not
expected to be absorbed across the skin.
Deficiencies in exposure sind sis
8,13,
16, 18,
75
PUBLIC C 0M\II:M S:
EPA lacks critical exposure information for PV29 and
took no steps to require the submission or development of
any more exposure data. As a result, the evaluation has
major exposure data deficiencies.
EPA lacks substantial evidence on occupational exposures
from the inhalation and dermal routes.
EPA did not comply with TSCA because it did not
consider the likely duration, intensity, frequency, or
number of exposures for PV29.
EPA should require the following data:
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
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 scientific
evidence analysis. EPA identified uncertainties regarding
reasonably available information characterizing the solubility
and occupational inhalation exposure (including duration,
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 and toxicity, 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 enough reasonably available
information for most data elements relevant to PV29. Where
assumptions were used in the final risk evaluation as a result
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- 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, forPV29:
- 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
- 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,
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 ( 20a). This
information includes SDSs as well as updates to the
Environmental release information (described in Section 2.2)
New occupational exposure estimates were added for the
manufacturing workers. These estimates were prepared using
recent monitoring data and several conservative assumptions.
An occupational exposure for the down-stream processors and
users were added. These estimates use several conservative
assumptions which will cover the reasonable high-end
exposure scenarios.
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aerosols, vapors
- 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 thev specify
Opposition lo KPA's rcliiincc on porsonsil coniniiiniciilion IVoni Sun C'hemic:il
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." Sun Chemical Corporation is an
entity with a strong interest in having EPA find its
chemical safe.
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.
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
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 breathing zone air monitoring
study of respirable particles not otherwise regulated,
conducted according to the NIOSH 0600 guideline available
at: httos://www.cdc. eov/NIGSB/DOCS/2003 -
i»dfs/0600.t»df. This studv takes into account a range of
job tasks as reported by the Sun Chemical Corporation (sole
U.S. manufacturing facility) and representative monitoring of
PV29 dust in the breathing zone. This study has been
evaluated for data quality and the results are incorporated into
the final risk evaluation. More information about the Section
4 Test Order for PV29 can be found in the docket ( O-
OPPT-2020-0070-0008). As a result, the point estimate value
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represents. This personal communication does not
constitute the "best available science."
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.
EPA should take steps to allow workers to provide input
in a manner that reduces the risks of any potential
retaliation from management.
of 0.5 mg/m3 presented in the draft risk evaluation is no
longer used in the risk evaluation.
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 to consider.
Concern regarding KPA's sipprouch l» evsilnsile only highest iinlicipsileri exposure
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.
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.
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 PV29. EPA has
determined that using the high-end exposure for inhalation
risks separately from other pathways as the basis for the
unreasonable risk determination is a best available science
approach.
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EPA determined that aggregating exposure pathways would
be inappropriate because the only route of concern is chronic
inhalation to PV29, and the lungs are the site of the adverse
effects. Chronic exposure to C.I. Pigment Violet 29 is
expected to increase lung burden which may result in kinetic
lung overload, a pharmacokinetic phenomenon, which is not
due to the overt toxicity of the chemical, but rather the
possibility that C.I. Pigment Violet 29 dust overwhelms the
lung clearance mechanisms over time and ultimately result in
adverse effects.. Exposure via dermal and oral routes is
expected to be low due to workplace practices, including use
of PPE such as gloves; and any absorption from dermal or
oral exposure is expected to be negligible based on the
insolubility of PV29. Therefore, these exposure pathways are
not expected to influence the toxicity in the respiratory tract.
Therefore, EPA determined that sentinel exposure via
inhalation was the most appropriate approach for risk
characterization.
Available data for PV29 indicate low hazard and low
potential for exposures for oral and dermal exposures. As a
result, it was determined that a mix of quantitative assessment
and qualitative assessment, was the most optimal approach to
focus efforts on the exposure pathways that are most likely to
result in potential risks.
Supports liered sipprosich 1 hill incorporules PPK in the exposure sissessnienl
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.
In the final risk evaluation, EPA calculated risks (MOEs)
without PPE and with PPE.
Oppose
s iissiiill pi ion of PPK use in (lie exposure sissessnienl
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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.
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.
There appear to be no empirical data to document the
extent of use or effectiveness of any of industrial hygiene
controls, such as PPE or SDS adherence.
EPA should use its authority to require data in order to
have empirical data on actual use of PPE.
No information is provided on the type of PPE used and
whether it is sufficiently protective to reduce oral
exposure.
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.
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.
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 by the downstream
processors and users were updated to indicate the
uncertainties.
For the purpose of the final risk evaluation, EPA makes
assumptions about potential PPE use based on reasonably
available information and expert judgment. EPA considers
each condition of use and constructs exposure scenarios with
and without engineering controls and /or PPE that may be
applicable to particular worker tasks on a case-specific basis
for a given chemical. Again, while EPA has evaluated worker
risk with and without PPE, as a matter of policy, EPA does
not believe it should assume that workers are unprotected by
PPE where such PPE might be necessary to meet federal
regulations, unless it has evidence that workers are
unprotected. For the purposes of determining whether or not a
condition of use presents unreasonable risks, EPA
incorporates assumptions regarding PPE use based on
information and 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
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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.
KPA should not relv on (lie presence ol'snul compliance willi ssilelv sheets (SI)S)
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.
EPA provides no evidence to support this assumption that
workers will read and understand SDS; in fact, there is
extensive evidence it is incorrect in many instances.
SDSs should not be a substitute for a workplace control
plan to eliminate and mitigate PV29 occupational
exposure.
EPA assumes without evidence that engineering controls
and PPE described in unpublished industry SDSs are
universally used in all workplaces.
Manufacturer admonitions on SDSs are not enforceable
and cannot support a determination that PV29 presents no
unreasonable risk.
Workers and small employers often have a great deal of
trouble understanding SDSs. Employers often ignore not
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 final risk evaluation, EPA
makes assumptions about potential PPE use based on
reasonably available information and expert judgment. EPA
considers each condition of use and constructs exposure
scenarios with and without engineering controls and /or PPE
that may be applicable to particular worker tasks on a case-
specific basis for a given chemical. Again, while EPA has
evaluated worker risk with and without PPE, as a matter of
policy, EPA does not believe it should assume that workers
are unprotected by PPE where such PPE might be necessary
to meet federal regulations, unless it has evidence that
workers are unprotected. For the purposes of determining
whether or not a condition of use presents unreasonable risks,
EPA incorporates assumptions regarding PPE use based on
information and 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
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only SDS recommendations, but basic, common-sense
safety rules.
SDSs often contain inaccuracies and are incomplete, as
concluded by a review study of 24 SDSs.
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.
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.
KPA should prior it ixc engineering controls over PIT. or wsirning hihels lo reduce exposure
11,12,
13, 15,
18
PUBLIC COMMUN I S
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 labels to reduce
exposure.
There is widespread support, including in court, for the
hierarchy of control.
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.
As indicated abo\ c, for the purpose of this final 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.
Concerns nboul hick ol'relesise (InIn
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.
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
Receivedfrom Manufacturing Stakeholders with resultant
releases to surface water being
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Other PV29 that may be captured in wastewater sludge is
disposed of via permitted landfills.
EPA issued a TSCA Section 4 Test Order to measure PV29
respirable dust in the breathing zone of workers in the Sun
Chemical Corporation workplace.
Support lor KPA's engagement with industry lo ohlsiin (InIn
19
PUBLIC COMMENTS:
EPA did the right thing by engaging with industry and
seeking actual data to answer its questions, i.e., for
working with Sun Chemical to understand the
manufacturing conditions and potential for worker
exposures and environmental releases.
EPA acknowledges the comment.
Concerns sihoul omipsilioiiiil inhsilsilion exposure sissessmenl sissuniplions mid psirsimelers
13, 78
PUBLIC COMMENTS:
EPA calculated a potential dose rate based on a NIOSH
inhalation exposure rate that is over 40 years old, which is
inadequate, or EPA should provide empirical evidence
supporting its use.
EPA assumes without explanation or justification that
workers could inhale PV29 only in dust form. 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.
EPA has updated the final risk evaluation to incorporate
actual monitoring information collected from the sole US
manufacturer of PV29, Sun Chemical Corporation. Through
communications with Sun Chemical, EPA obtained
monitoring data information used to assess if measures of
total dust in the worker breathing zone was below the
associated regulatory limit. This information along with all
information used in the assessment that was provided by the
US manufacturing stakeholders for PV29 can be found in the
Supplemental File: Information Receivedfrom Manufacturing
Stakeholders (l v < < \ 2020a). The NIOSH inhalation
exposure rate is not used in the final risk evaluation.
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.
Downstream workers may be exposed to PV29 in mist (paint
and ink). In the final risk evaluation, EPA estimated
exposures based on dust measurements in the original Sun
Chemical Workplace to estimate exposures for downstream
workers.
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Available Particle size distribution data for PV29 is described
in the final risk evaluation based on information in the
Supplemental File: Information Receivedfrom Manufacturing
Siakclioklcrs ( )
C oncerns iihoul occupnlionnl dermsil exposure sis sind chirilv
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.
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.
EPA presented only a single dermal exposure scenario
that it claims represents the "theoretical maximum
exposure" with no basis for this characterization.
EPA's dermal exposure analysis assumed only PV29 in
solid form, yet PV29 is also produced in the form of a
high-concentration solution.
EPA hand-waves away dermal exposure in part by
assuming that PPE is always used and used effectively.
EPA has updated its approach in the final risk evaluation. No
quantitative dermal modeling was carried out in the final risk
evaluation because of the low potential for exposure due to
low solubility of the chemical. As a result, the discussion of
exposure scenarios has been updated in the final risk
evaluation in Section 2.3.1.3.
KPA should revisit its decision not to nssoss occnp:ilion:il or:il exposure
12, 13,
15
PUBLIC COMMENTS:
EPA's argument assumes that oral exposure only occurs if
workers eat contaminated food or smoke is incorrect.
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
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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.
EPA should more closely assess the potential for oral
exposure via pathways beyond ingestion of contaminated
food.
Dermal and inhalation exposures make oral ingestion
likely in a workplace.
EPA hand-waves away oral exposure in part by assuming
that PPE is always used and used effectively.
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.
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
PV29, EPA did not find any information indicating significant
oral exposure during the systematic review of the materials
found.
KPA did not properly sissess exposure of downs!renin processors mid 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.
EPA restricts its occupational exposure analysis to the site
of manufacture, failing to account for worker exposures at
downstream processing and use sites.
The final risk evaluation includes evaluation of risks
associated with inhalation of PV29 dust for downstream
occupational processors and users. These estimates use
several conservative assumptions based on exposures in the
original Sun Chemical Corporation workplace.
Statements on SDS and PPE use by the downstream
processors and users were updated to indicate the
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EPA does not appear to have received or obtained
significant information from the processors of PV29, only
the sole manufacturer.
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.
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.
EPA inappropriately used the approximate maximum
workplace air concentration reported in a personal
communication from Sun Chemical to estimate
downstream worker exposure.
Downstream occupational exposure may significantly
exceed manufacturing site exposure given the potentially
different activities and controls that might be in place.
EPA has failed to use the best available science for
downstream exposure.
EPA lacks data on potential exposure of downstream
workers at processing and use sites, number of sites
involved, and number of potentially exposed workers.
uncertainties.
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Without evaluating downstream exposures, EPA has no
basis for comparing risks faced by manufacturing workers
to those who work with or use downstream products.
EPA has failed to use its authority to collect data on
downstream exposure.
C oncerns iihoul (lie cnvironiiicnlsil rclcsisc chnrnclcri/nlion
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.
No calculation or data are presented to support the
conclusion that approximately 1-2% of the production
volume is released into the environment.
EPA relies on industry determination that use is restricted
to a single site; as a result, sources of exposure are
overlooked.
The only remotely "quantitative" element regarding
exposures is the manufacturer's asserted estimate for
water discharges from its facility, but this value is
unreliable and insufficient.
EPA does not properly analyze distribution and gives no
attention to potential releases and exposures resulting
from accidental releases.
EPA's analysis of biosolids is particularly lacking; a
thorough analysis of biosolids would be appropriate given
that PV29 is poorly biodegradable.
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 included in the Supplemental File: Information
Receivedfrom Manufacturing Stakeholders with resultant
releases to surface water being < 1 lb/dav ( )20a).
Other PV29 that may be captured in wastewater sludge is
disposed of via permitted landfills. EPA concedes the
uncertainty associated with this information and has added
language discussing this uncertainty. Nevertheless, it was the
best reasonably available information concerning possible
releases of PV29 to the environment.
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
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"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 PV29
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 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,"
and EPA is exercising its discretionary authority to exclude
PV29 spills and leaks from the scope of the PV29 risk
evaluation. The exercise of that authority is informed by
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
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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. Inclusion of spills
and leaks as part of the risk evaluation, could result in
potentially expansive and potentially boundless impacts
making the conduct of the risk evaluation untenable within
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
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.
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PV29 is not expected to bioconcentrate in aquatic organism
tissues, and concentrations will not increase from prey to
predator in either aquatic or terrestrial food webs.
KPA did not consider environment;)! release of P\ 29 when used sis ;in inlerniedisile
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.
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.
Release and exposure to any incidental residual PV29 present
in products where it is used as an intermediate is expected to
be lower than the exposure and releases from the production
and handling of pure PV29. The vast majority of the total
manufactured volume of PV29 is consumed at the
manufacturing facility as an intermediate for the production
of other pigments. The residual PV29 in these finished
pigments is low due to the reaction efficiency, and any
exposure to residual amounts of residual PV29 that will result
from the handling of these other pigments is expected to be
negligible. As a result, the final concentration of PV29 as a
residual, in coatings and plastics will be negligible in
comparison to the exposure expected to result from the
handling of PV29.
Concern iihoul nssiiniplion llinl P\ 29 reninins "hound** in downslresini use
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-of-life.
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.
As stated in the risk e\ alualion, PY29 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 fulfill 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 concerning possible leaching of PV29 from
plastics once it is encapsulated.
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.
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 used in the final risk evaluation
is also used the food additive petition and as a result, similar
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conclusions were drawn in both documents regarding the
potential for leaching from plastics.
KPA wns right to remove conditions of use il \v;is unsihle to support
8,17,
45
EPA was right to remo\ e "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.
Based on information provided in public comments, EPA has
included import as a condition of use in the final risk
evaluation.
Kv2ilu;itiou hicks inCorin:!!ion 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 the evidence in the record
establishes that PV29 often remains present in such
products.
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.
EPA made no effort to further identify "unknown" uses.
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.
The final risk evaluation includes more detailed information
on the conditions of use of PV29. The vast majority of the
total manufactured volume of PV29 is consumed at the
manufacturing facility as an intermediate for the production
of other pigments. The residual PV29 in these finished
pigments is low due to the reaction efficiency, and any
exposure to residual amounts of residual PV29 that will result
from the handling of these other pigments is expected to be
negligible. As a result, the final concentration of PV29 as a
residual, in coatings and plastics will be negligible in
comparison to the exposure expected to result from the
handling of PV29.
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 oer vear CEPA-HO-OPPT-
2018-0604-0016). Therefore, import of C.I. Pigment Violet
29 is included as a condition of use in 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
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Summary of Comments for Specific Issues Related to
Charge Question 4
EPA/OPPT Response
By excluding downstream conditions of use (e.g., candles,
carpet fibers, paint, coatings), EPA failed to evaluate
downstream worker and consumer exposure.
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.
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
Risk Evaluation for Pigment Violet 29 (U.S. EPA, 2017c) that
were used to identify the current conditions of use. EPA also
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.
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Summary of Comments for Specific Issues Related to
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EPA/OPPT Response
EPA disagrees that it has a statutory duty to consider all
conditions 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
for downstream conditions of use in the final risk evaluation
Insulequiile chnnu'leri/iilion of polenlisillv exposed or susceptible suh-popiihilions (PKSS)
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.
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.
EPA should identify people living near disposal sites,
sources of contamination, and other conditions of use as
PESS.
PV29 is manufactured (as a solid) in one workplace in the
U.S and is either used to produce other pigments in their
workplace or sold as a solid to other processors. EPA
identified workers and occupational non-users, as well as
consumers and bystanders to consumer use, as relevant PESS
due to their greater potential exposure and evaluated whether
PV29 presents an unreasonable risk to those groups.
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 the
upper end of exposures which would include PESS.
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Summary of Comments for Specific Issues Related to
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EPA/OPPT Response
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.
Workers are a relevant PESS, and EPA has not provided
adequate evidence that it has made an accurate
determination as required by TSCA.
EPA assertions that the risk evaluation is protective of
workers, consumers and the general population are not
supported by data.
EPA is making an unreasonable risk determination in the final
risk evaluation based on the high-end exposures for workers
and factoring in the uncertainties by retaining the full
Uncertainty Factor (UFh) of 10; thereby considering
variability among the human population, including PESS, for
risk evaluation.
Support lor nntl request lor chiritv regarding (|ii;inlil;ili\e screening-level exposure sisscssmcnl
8, 17
PUBLIC COMMUN I S
Two commenters generally support the quantitative
screening level exposure assessment approach used by
EPA.
EPA should explain why a quantitative screening-level
exposure assessment was added, given that it was not
anticipated in the problem formulation and scoping phase.
EPA should explain how quantitative exposure
assessment data were obtained and checked for their
reliability and accuracy.
LPA initially used the screening level-approach in the
assessment of possible risks for worker exposures to PV29
dust by inhalation. The concern was for workers as a highly
exposed population within the sole US manufacturing facility
of PV29.
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
analyses of inhalation of exposures for occupational
exposures and risks made in the initial screening-level risk
calculations.
KPA did not suldress exposures in pre^iiiinl women, children, sind oilier downslresini users
9,10,
12, 16,
16(S)
PUBLIC COMMENTS:
EPA's evaluation of PESS 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.
EPA fails to consider downstream exposure of users of
products such as paints, art supplies, toys, food packaging,
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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Summary of Comments for Specific Issues Related to
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EPA/OPPT Response
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.
EPA cannot assume that pregnant women or children
exposed during downstream use have lesser exposures
and are adequately protected.
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.
KPA wns correct to locus 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.
EPA's conservative assumptions with regard to inhalation
and dermal exposures are protective and appropriate.
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 lor siggregsite exposure vs. sentinel exposure iissessnienl
SACC,
10, 13
SACC COMMENTS:
Aggregate exposures should be considered including use
of PV29 in food packaging.
PUBLIC COMMENTS:
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
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Summary of Comments for Specific Issues Related to
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EPA/OPPT Response
EPA should combine all routes of exposure (including
dermal, oral, and inhalation) when making a risk
determination.
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.
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 determination is a best
available science approach. In this risk evaluation, EPA
determined that aggregating exposure pathways would be
inappropriate because the only route of concern is chronic
inhalation to C.I. Pigment Violet 29, and the lungs are the site
of the adverse effects. Chronic exposure to C.I. Pigment
Violet 29 is expected to increase lung burden, overwhelm the
lung clearance mechanisms over time, and ultimately result in
adverse effects. Exposure via dermal and oral routes is
expected to be low due to workplace practices, including use
of PPE such as gloves; and any absorption from dermal or
oral exposure is expected to be negligible based on the
insolubility of C.I. Pigment Violet 29. Therefore, these
exposure pathways are not expected to influence the toxicity
in the respiratory tract". Therefore, EPA determined that
sentinel exposure via inhalation was the most appropriate
approach for risk characterization.
KPA should pursue exposure siud releases iiirorinsilioii IVoin :i wider muge of or«;iniz;ilions
SACC
SACC COMMENTS:
When preparing this Risk Evaluation, EPA obtained and
considered reasonably available information, defined in 40
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EPA/OPPT Response
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.
CFR 702.33 as information that EPA possesses or can
reasonably generate, 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.
Oilier SACC comincnls rclsilcd lo physicnl clicmic:il proper!ics
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.
Page 75 of 180
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Environmental Effects
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.
#
Summary of Comments for Specific Issues Related to
Charge Question 5
EPA/OPPT Response
Need for in ore lo evsilusile li;iz:irtl lo ;i(| mil ic ecological receptors
13, 16,
46
PUBLIC COMMUN I S
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.
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.
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.
EPA should require the following data
- Acute toxicity to sediment-dwelling organisms
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
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Summary of Comments for Specific Issues Related to
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EPA/OPPT Response
- Chronic toxicity including to aquatic organisms
including aquatic plants, fish, and aquatic
invertebrates
- 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.
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).
are not a critical data need. While PV29 is expected to be
persistent, it is not expected to bioaccumulate, and additional
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
(httos://echa.eurooa.eu/documents/10162/c607549c-lc07-
c5d6~d6e2~8dl8bfP91f3a) categorizes PV29 as a potentially
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, EPA 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.
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Summary of Comments for Specific Issues Related to
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EPA/OPPT Response
Do not ignore Topksil-predicled sicule 1.(50 lor l:il lieiicl in in now
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.
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 mg/L) (Nicolaou.
2020).
Need lo heller describe how log Iw wsis 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, log Koc will not
be relied upon in the final risk evaluation.
Concerns sihonl ecological h;i/;irds lor sediment-dwelling inveiiehrsiles
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.
EPA noted that PV29 was expected to partition to soil and
sediment. Therefore, it cannot conclude there is no
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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Summary of Comments for Specific Issues Related to
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EPA/OPPT Response
unreasonable risk to the environment without data on
biodegradation and toxicity to benthic organisms.
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.
(Anklev et; 3) provides guidance on assessing the
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.eDa. gov/oesticide-science-and-
assessing-oesticide-risks/toxicitv-testing-and-ecological-risk-
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."
See also U.S. EPA, Methods for Measuring the Toxicity
and Bioaccumulation of Sediment-associated
Contaminants with Freshwater Invertebrates (Mar. 2000)
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, this reference was not relevant.
Need lor more risitii lo evsiliisile li;i/:irri lo lerreslrisil ecologicsil 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.
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
prolonged aquatic exposure and/or tests with terrestrial
organisms exposed through soil or food may result in toxic
effects."
EPA acknowledged the uncertainties in the assessment with
regard to 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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Summary of Comments for Specific Issues Related to
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EPA/OPPT Response
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."
Therefore, the lack of any terrestrial toxicity data for PV29
is a major data gap leading to significant uncertainty.
C oncerns sihoul citing 1 lie (nnndhin Ixologienl Kisk (Inssiricnlion lor P\ 29 sis support lor (Iclcrniiniilion
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 rely on that screening process to support a
finding of no unreasonable risk for PV29.
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
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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Summary of Comments for Specific Issues Related to
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EPA/OPPT Response
nor Environment Canada have provided any predicted or
measured data for the similar pigments.
Support lor KPA's ehnnieleri/ntion ol'hnznrd lo eeolo«ie;il 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.
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.
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.
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 40 CFR
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.
(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
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Summary of Comments for Specific Issues Related to
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EPA/OPPT Response
that risks were not expected and additional quantitative
analysis was not necessary.
Concerns iibonl studies where observed exposures exceed wsilcr solubility limil
SACC
SACC COMMI-VI
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 study ( 8) is reported as 670
mg/1, while the studv with Daphnia 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.
3), 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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Summary of Comments for Specific Issues Related to
Charge Question 6
EPA/OPPT Response
Support lor KIW's iipproiicli siml conclusions regarding hiininn henllli risk
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.
EPA acknowledges these comments and encourages the
commenters to consult the final risk evaluation for the most
updated risk characterization.
19, 47,
49
EPA appropriately concluded that it did not need to
possess a guideline study of PV29 regarding every
conceivable human health endpoint.
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.
The summaries of the 10 short-term assays provided
sufficient information and show compliance with OECD
test guidelines.
M:ikc hn/nrtl conclusions specific to routes of exposure
SACC
SACC COMMEjSi IS
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 data—thus 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 to
the specific conditions of use of PV29. Qualitative
statements were replaced with specific statements based on
the availability of data.
( hil ily value of (lie screening rcprodiiclivc/dcvclopmcnlul toxicology study mid hi«hli«ht d;il:i "sips
SACC
SACC COMMENTS:
Include a table in the Evaluation that compares the
endpoints reported in the screening
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
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Summary of Comments for Specific Issues Related to
Charge Question 6
EPA/OPPT Response
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/developmental toxicological
study and highlight data gaps in the toxicity assessment.
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 inhalation toxicity testing, were
addressed by using analogue toxicity data and basic exposure
assumptions. The final risk evaluation discusses the
limitations of data and data gaps as part of the uncertainty
analyses.
The toxicity studies KPA used sire 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.
The OECD 421 screening test utilized is flawed and
unreliable. It cannot be used to estimate human risk.
EPA cannot determine reproductive toxicity hazard based
on the current data available and should provide more
discussion on reproductive toxicity screening limitations.
There are concerns with the quality ratings of the oral
toxicity studies due to inadequacies, information gaps,
and a protocol that is no longer available online for
evaluation.
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.
The available PV29 human health hazard studies are
evaluated bv the guidance and criteria in the Application of
Systematic Review in TSCA Risk Evaluations.
The results of EPA's data quality evaluation of each study is
provided in detail in a Supplemental file to the final risk
evaluation.
EPA agrees that the available inhalation toxicity study for
PV29 is unacceptable. However, EPA considers the OECD
421 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.
In the final risk evaluation, EPA assessed the potential
inhalation of PV29 dust particles by workers using an
analogue chemical (carbon black). Using this analogue and a
sub-chronic inhalation study as well as additional
information on PV29 dust concentrations in the Sun
Chemical Manufacturing workplace, unreasonable risk was
identified for several conditions of use.
EPA acknowledges that the study reports are often truncated
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Summary of Comments for Specific Issues Related to
Charge Question 6
EPA/OPPT Response
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. EPA has released the full study
reports to the PV29 Docket ffiPA-HO-OPPT-2018-0604}
KPA iinproperly disregarded inlrnperilonenl studios
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
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:^eta.reeulations.eov/document/EPA-HO-OPPT-2018-
dosing studies.
0604-0040
12, 13,
16
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 solubility-low absorption
argument to dismiss the observed effects in those studies.
The result of this data quality evaluation found that the
intraperitoneal injection studies were of low quality and they
were not used qualitatively in the final risk evaluation. The
studies were not used because the route of exposure
(intraperitoneal injection) is not considered by EPA to be a
relevant route of exposure for PV29. There is a great deal of
uncertainty about how this type of exposure relates to those
associated with the conditions of use expected for PV29. 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 mg/kg-bw that was used in the screening-
level risk evaluation.
KPA did not use from simihir substances
13, 15
PUBLIC COMMENTS:
EPA failed to utilize data on similar substances.
EPA has updated its approach in the final risk evaluation to
incorporate analogue toxicity data into the risk
characterization for inhalation exposure.
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Summary of Comments for Specific Issues Related to
Charge Question 6
EPA/OPPT Response
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.
Empirical data indicates that C.I. Pigment Violet 29 is
negative for genotoxicity and structural activity relationships
(SAR) considerations support EPA's conclusion that PV29 is
unlikely to be a carcinogen. Given the low potential for
absorption/ uptake and biodegradability, the relevance of
PAHs as a predictor of carcinogenicity are low.
KPA should :ic(|iiire nddilionnl studies due 1» insulTicienl dsilsi
SACC,
10, 12,
13, 14,
15, 16,
18, 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 testing,
including the following topics: PV29 levels, exposure
characteristics, absorption, and chronic toxicity.
EPA has authority to acquire more "reasonably available
data" by requiring additional studies by manufacturers to
evaluate human hazard.
Specific suggested study types that should need to be
included are:
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 the
final 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
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
evaluated without the need for regulatory information
collection or development. When preparing this risk
evaluation, EPA obtained and considered reasonably
available information, defined as information that EPA
possesses, or can reasonably obtain and synthesize for use in
risk evaluations, considering the deadlines for completing the
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Summary of Comments for Specific Issues Related to
Charge Question 6
EPA/OPPT Response
- High-quality, reliable experimental test results for
acute inhalation toxicity.
- A 90-day repeated dose toxicity study for oral,
inhalation, and dermal routes of exposure.
- Chronic mammalian health studies sufficient to
account for exposures via dermal, inhalation, and
oral routes.
- Carcinogenicity studies.
- Respiratory/inhalation sensitization studies.
- Tests for genetic toxicity/mutagenesis/gene
mutation, including in vivo tests for chromosome
damage, cytotoxicity, and other relevant
endpoints.
- Neurotoxicity studies, including developmental
stages.
- Two generation reproduction toxicity studies.
- Studies for acute and chronic endocrine effects.
- Pharmacokinetic study measuring distribution in
blood and fat and toxicokinetic studies.
evaluation. However, EPA will continue to improve on its
method and data collection for the next round of chemicals to
be assessed under TSCA.
1 no reuse Irnnspnrenev of evidence used lo 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.
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 PV29,
which was considered in the assessment. This information
has been captured in the OncoLogic™ predictive model
which is available at: httos://www.eoa.80v/tsca-screenin8-
tools/oncologictm-comDuter-svstem-evaluate-carcinosenic-
potential-chemicals
Concerns iihoul roulc-to-roiile extrapolation :ind Isick of uncerlsiinlv I'siclor
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Summary of Comments for Specific Issues Related to
Charge Question 6
EPA/OPPT Response
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.
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 PV29 following chronic exposure.
MPPD model requires si/e distribution of P\ 29 in workplace nerosols
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.
Through correspondences with the sole US manufacturer of
PV29, 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 made public
with the final Risk Evaluation as a supplemental file, titled,
"Supplemental File: Information Receivedfrom
Manufacturing Stakeholders ( 20a)."
77
For the final risk evaluation the MPPD model was not used
due to the uncertainties and incomplete information on the
particle size distribution of PV29 in the workplace. The
MPPD model also does not have the ability to calculate
human equivalent concentrations (HEC) for the hamster. The
RDDR dosimetry model was instead used to estimate a
HECs based on a carbon black inhalation toxicity study for
rats, mice, and hamsters.
Present models or NA.Ms to improve understanding of sihsorption potenti:il
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
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Summary of Comments for Specific Issues Related to
Charge Question 6
EPA/OPPT Response
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 PY29
Concerns sihonl hick of scicnlifio evidence lor KIW's conclusion regarding sihsorplion potenti:il
8, 12,
13, 16,
18, 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.
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.
EPA did not consider how the presence of other
constituents in a PV29 formulation, such as surfactants,
can significantly alter the absorbability of PV29.
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.
Given the inconsistency in the way exposure potential is
described, OPPT should clarify exposure assumptions,
specifically in applying a consistent approach for
potential dermal absorption.
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
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
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Summary of Comments for Specific Issues Related to
Charge Question 6
EPA/OPPT Response
are no longer relevant.
C onsumer hnznrtl is not lull} invcsli»;iK'(l
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 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.
EPA has not fully evaluated hazards to consumers.
EPA cannot expect that consumers exposed to PV29 will
wear protective gear.
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 not released 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.
Ohliiin more omipsilionsil h;i/:ird
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
EPA in the final risk evaluation identified and considered
uncertainties regarding reasonably available information
characterizing occupational worker exposures to PV29 dust.
The updated human health risk characterization in the final
risk evaluation calculates an updated POD based on alveolar
inflammatory and proliferative responses following
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Summary of Comments for Specific Issues Related to
Charge Question 6
EPA/OPPT Response
adequate temporal and spatial coverage)
data/documentation from the 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.
inhalation observed in an analogue, carbon black (Elder et
al. 2005).
EPA gathered some information as suggested on the
conditions of use, exposures and potential for worker
exposures from correspondences with industry stakeholders.
In the final risk evaluation this information is included as a
supplemental file, titled, "Supplemental File: Information
Received from 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 worker
exposure to PV29 dust.
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.
( hil ily iinccrlsiinlics sind justify conclusions rcgsirriing 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
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
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.
EPA has updated the risk evaluation to discuss uncertainties
resulting from lack of data for specific susceptible
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Summary of Comments for Specific Issues Related to
Charge Question 6
EPA/OPPT Response
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.
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.
A factor of 10 is applied for risk assessments on dietary
pesticide ingestion for PESS.
EPA should seek the advice of its Children's Health
Protection Advisory Committee.
subpopulations including children and other susceptible
populations outlined in Section 2.4.1.
here sire no vulnersihle snhpopuhitions
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.
EPA has updated the risk evaluation to discuss uncertainties
resulting from lack of data for specific subpopulations.
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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
#
Summary of Comments for Specific Issues Related to Charge
Question 7
EPA/OPPT Response
Support for the conclusions in the draft risk characterization
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.
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.
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 reasonably foreseeable conditions of use
pose a high potential for unreasonable risk.
This comment was received on the draft risk evaluation. The
revised and final risk evaluations by EPA have found
unreasonable risk associated with PV29.
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Summary of Comments for Specific Issues Related to Charge
Question 7
EPA/OPPT Response
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.
The conclusions in (lie drsil'l risk chsimctcri/iilion sire Unwed due lo hick ol'dsilsi
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 contains numerous logical flaws and
unwarranted assumptions, rendering its final conclusion
unsupported by substantial evidence, as required under TSCA.
When preparing the draft, revised draft and final risk
evaluations, EPA obtained and considered reasonably available
information, defined as information that EPA possesses or can
reasonably generate, obtain and synthesize for use in risk
evaluations, considering the deadlines for completing the
evaluation. Along this process, EPA continued to improve the
methods and data collection.
The resulting final risk evaluation considers reasonably
available information and the use of the best available science.
Unreasonable risk was identified for several conditions of use
for occupational exposures to PV29 via inhalation.
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Summary of Comments for Specific Issues Related to Charge
Question 7
EPA/OPPT Response
The resulting draft risk evaluation fails to consider reasonably
available information or to use the best available science.
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.
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.
EPA concludes that PV29 is not carcinogenic on the basis of
insufficient information and unsupported assumptions.
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.
l-P.\ should order the di*\ clopmcni 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
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. 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
Page 96 of 180
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#
Summary of Comments for Specific Issues Related to Charge
Question 7
EPA/OPPT Response
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.
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.reeulations.eov/document
KIW's relinnee highly uncertnin I'silo :iihI persistence i 11 form;ilion csisls riouhl on its risk conclusions
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.
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.
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.
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 PV29, 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 (lie m;ir«in of exposure (MOK) sipprosich iiml chirily
SACC
8,10,
SACC COMMENTS:
EPA acknowledges these comments and has attempted to
explain the additional assumptions used in the calculations of
the MOEs in the final Risk Evaluation. This includes selecting
Page 97 of 180
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#
Summary of Comments for Specific Issues Related to Charge
Question 7
EPA/OPPT Response
12, 14,
16, 46,
48, 77
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 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.
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.
EPA incorrectly relied on a single studies or data points to base
elements of their risk determination.
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
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
and correspondence received from the sole US manufacturer,
Sun Chemical Corporation into a single supplemental file. This
supplemental file has been uploaded to the docket with the
revised draft and final risk evaluation.
Page 98 of 180
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#
Summary of Comments for Specific Issues Related to Charge
Question 7
EPA/OPPT Response
calculation is based, further weakening its assertion that
workers and other exposed populations are not at risk of harm.
Supports KPA's use of 1 lie MOT. sipprosich
17
The PV29 MOE assessment is evidence of the utility of EPA's
risk assessment approach in appropriate cases. This commenter
supports EPA's use of an MOE approach to assess non-cancer
risk.
EPA acknowledges the comment and encourages the
commenter to consult the updated risk characterization
approaches in the final risk evaluation.
Concerns sihoul CIJI ;ilTcc(in« the risk chnrsu'lcri/iilion
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 lo iipplv siririilionsil unccrlsiinly I'nclors
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.
Additional 10-fold uncertainty factors that EPA should have
considered include: database deficiencies, extrapolation from
short-term to chronic exposures, extrapolation from oral to
inhalation and dermal exposures, and vulnerable
subpopulations (pregnant women, infants and children).
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 PV29 particle inhalation following chronic exposure.
Based on available data characterizing the effects of particles
using an analogue with a similar size, density and solubility as
PV29, the most relevant effect from inhalation of PV29 is the
inflammation and proliferative responses in the alveolar region
of the lung following overloading of lung clearance
mechanisms. As a result, the discussion of the application of
uncertainty factors to account for the subchronic oral NOAEC
to calculate an MOE is no longer relevant.
Page 99 of 180
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#
Summary of Comments for Specific Issues Related to Charge
Question 7
EPA/OPPT Response
EPA OPPT should use an adjustment factor for intraindividual
variability.
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.
Even adding a single additional uncertainty factor would result
in a benchmark value exceeding the MOE that EPA calculated
for worker dermal exposure.
There is no universal list of hazard data required when
evaluating chemical risks under TSCA. Furthermore, for
PV29, EPA has sufficient, reasonably available hazard data
and included the use of an analogue to support the use of the
chosen hazard endpoints and conduct the risk evaluation.
Therefore, EPA did not use a database uncertainty factor in the
PV29 risk evaluation. Discussions about the use of uncertainty
factors in this assessment have been included in Section 4 of
the final risk evaluation.
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.
I so of inlmspecies iincerhiinlv Isiclor wsis 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 redundancy in adjustments for sensitive populations
via an adjustment factor for intraindividual variability.
This comment is related to an earlier draft prior to the use of
carbon black as an analogue and the selection of a POD based
on the subchronic inhalation studv bv Elder et al. (2005). It is
acceptable standard practice in risk assessment to have a
composite UF of 100 based on interspecies and intraspecies
UF of 10 each. In order to reduce the UFh (intraspecies), you
would need confidence that your POD is relevant to the most
sensitive PESS. While it may be that it is based on the most
sensitive endpoint in the most sensitive species tested, that
may not equate to the lowest PESS among the human
population. Therefore, the UFh of 10 is retained.
Occii|);ilion;il risk ch;ir:u'leri/:ilion is llsiwed
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
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
Page 100 of 180
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#
Summary of Comments for Specific Issues Related to Charge
Question 7
EPA/OPPT Response
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.
EPA should mandate worker protections for PV29 consistent
with agencies specializing in occupational safety and health
regulation and research (e.g., OSHA and NIOSH).
Even with using one uncertainty factor for dermal exposure,
EPA cannot conclude that PV29 does not present an
unreasonable risk to workers.
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
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
if 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 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 was
extremely conservative and not representative of actual
exposure under the conditions of use. Dermal exposures were
not quantitatively evaluated in the final risk evaluation based on
PV29's insolubility, no adverse effects at 1000 mg/kg/day via
oral dosing and probable poor absorption across the skin.
Need lo cxpsiml (lie risk chsirsu'lcri/silion nsirrsilivo
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
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.
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#
Summary of Comments for Specific Issues Related to Charge
Question 7
EPA/OPPT Response
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.
Need ;i(l(lhion;il "ukIiiikt on when hi«hcr-licr sisscssnicnls will he triggered lor I'nlnrc risk cviiliinlions
PUBLIC COMMUN I S
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.
As discussed abo\ c, in Section 4, JiPA 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:
17
(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, 21(1), 123-135
#
Summary of Comments for Specific Issues Related to
Charge Question 8
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 (lung) or skin
permeability in vitro assay should be considered.
EPA agrees that there are uncertainties inherent in making a
determination about respiratory hazard without available
inhalation toxicity data for PV29. However, as discussed in
the final risk evaluation, with the new data obtained through
the Section 4 test order to evaluate the solubility of PV29,
EPA has a greater degree of confidence that it is poorly
absorbed by dermal or oral ingestion exposures.
Therefore, based on evidence that suggests chronic
inhalation of particles can accumulate in different pulmonary
regions, EPA has determined that inflammatory and
proliferative responses to lung particle accumulation is a
relevant effect for PV29 ( ) As chronic
inhalation data are available for Carbon Black, another
pigment with low solubility, a similar particle diameter and
relative density, EPA determined that these data are adequate
to understand the potential hazards of chronic inhalation of
Page 103 of 180
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#
Summary of Comments for Specific Issues Related to
Charge Question 8
EPA/OPPT Response
Supplement available data by requesting personal
monitoring data from the manufacturer which should
include both respirable dust fraction and total dust.
PV29 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 PV29 in water and octanol and
as a result, the low potential for absorption. EPA determined
that the observed 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 from the Sun Chemical Corporation. This
data has been incorporated into the final risk evaluation
Snpplcnienl;i 1 inh:il:ilioii sis improves risk cviiliiiilion. hul chirily sources of unccrlsiinlv
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.
EPA has added language to the final risk evaluation to better
describe the sources of uncertainty.
Siipplciiicnlsil illion sis is in;ulc(|ii;ilc
55,
78, 82
PUBLIC COMMENTS:
The New Inhalation Analysis is inadequate to evaluate
PV29's inhalation risks and rests upon unsupported
assumptions and an unvalidated, non-peer reviewed model.
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.
EPA agrees that the inhalation analysis presented in the
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 acknowledges that the lack of inhalation toxicity data
for PV29 is an uncertainty. EPA is confident that, based on
the physical chemical properties of the analogue Carbon
Black, it is sufficiently similar to PV29 to be able to
Page 104 of 180
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#
Summary of Comments for Specific Issues Related to
Charge Question 8
EPA/OPPT Response
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.
EPA's inhalation risk calculations based on the barium
sulfate study are unsupported and underestimated.
adequately describe the inhalation hazards.
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 PV29.
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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.
#
Summary of Comments for Specific Issues Related to
Charge Question 9
EPA/OPPT Response
Include jlistillciilions lor reductions by compsuiies
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 sum inn lies of differences between Cull ;ind 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 PV29, 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
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Summary of Comments for Specific Issues Related to
Charge Question 9
EPA/OPPT Response
docket for PV29 (EP A-HO-OPPT-2.018-0604),
Allow ccrlsiin psirlios lo examine lull 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.
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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.
EPA is committed to implementing the Lautenberg Act and
welcomes continued specific input to improve the process
of implementation.
Page 108 of 180
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Comments on the Revised Draft Risk Evaluation for C.I. Pigment Violet 29 (PV29)
List of Comments Submissions
Comments Received During Public ( onimcnl Period Km
ingon 12/19/2020
105
EP A-HO-OPPT-2018-0604-0105
EP A-HO-OPPT-2018-0
David Wawer, Executive Director, Color Pigments Manufacturers
Association, Inc. (CPMA)
106
EPA-HO-OPi I -im • o 0 1 010
Jared Rothstein, Society of Chemical Manufacturers & Affiliates (SOCMA)
108
EP A-HO-OPPT-2018-0604-0108
Julia M. Rege, Vice President, Energy & Environment, Alliance for
Automotive Innovation
109
EP A-HO-OPPT-2018-0604-0109
Riaz Zaman, Counsel, Government Affairs, American Coatings Association
(ACA)
110
EP A-HO-OPPT-2018-0
Liz Hitchcock, Director, Safer Chemicals Healthy Families (SCHF) &
National Resources Defense Council (NRDC)
111
EP A-HO-OPPT-2018-0
Swati Rayasam, et al., Program on Reproductive Health and the Environment
Department of Obstetrics, Gynecology and Reproductive Sciences University
of California, San Francisco
112
EP A-HG-GPPT-20
18-06
12
Suzanne Hartigan, American Chemistry Council (ACC)
113
EP A-HO-OPPT-20
18-0604-0
Michelle Roos, Environmental Protection Network (EPN)
119
EP A-HO-OPPT-20
18-0604-0
Richard A. Denison, Environmental Defense Fund (EDF)
120
EP A-HO-OPPT-20
18-06
20
Brett Fox, International Union, UAW
121
EP A-HO-OPPT-20
o
1
°xf
o
o
o
oc
21
Jen Jackson, Toxics Reduction & Healthy Ecosystems Program Manager, San
Francisco Department of the Environment
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Response to Public Comments Received
#
Summary of Public Comment
Panicle Size Distributions in the Assessment Are Not
EPA/OPPT Response
Repi esentati\ e of the lieha\ ior of PY21)
105
The smallest particle size evaluated in the draft risk
evaluation is not representative of PV29 dust particles in the
workplace. It is physically impossible for such particles to
remain separate without complex engineering.
It is physically impossible for PV29 to be present in the
workplace in the predominant form of such small dust
particles. Like virtually any solid material, very small
particles of PV29 will naturally form agglomerates that are
more accurately characterized by the two larger particle
sizes evaluated in the draft risk evaluation (10.4 and 46.9
|im).
The second particle size analysis was designed and
conducted specifically to measure the types of the particles
that might be present in workplace dust. This was generated
very simply: a sample of dry pigment, unprepared, was
charged directly into an instrument, compressed air was
blown through it to simulate the effect of being released into
turbulent workplace air, and a laser was shined through the
cloud to measure particle size. This measurement thus more
closely represents the sort of PV29 particles that might be
found in the workplace environment at a manufacturing or
processing site. EPA did not give CPMA or Sun any
indication that it did not understand the information
provided by Sun, or that EPA was uncertain about its
relevance to workplace conditions.
The information provided by CPMA to explain the
discrepancies observed in the particle size measurements in
the workplace provides no additional information or
evidence beyond what was provided to EPA in earlier
correspondence (available in the Supplemental File:
Information Received from Manufacturing Stakeholders
( 2020a). CPMA simplv reiterated its previous
inadequately-substantiated claims that, The smaller
particle size initially supplied by CPMA and relied on in
the risk evaluation is not representative ofPV29 in
workplace dust," and, "By contrast, the larger particle size
measurements subsequently provided by CPMA, and
previously supplied by BASF, are representative of the
agglomerated PV29 particles that might be found in
workplace dust" Simply stating that one dataset is more
representative of workplace dust without actually
presenting any empirical support to verify these claims is
not sufficient for EPA to discount the existing particle size
information. Additional information that actually measures
the particle size of airborne particles found in the
workplace would provide sufficient evidence to clarify the
uncertainties about workplace dust characteristics.
The explanation about the design of the sample used to
calculate the 10.4 um particle diameter sample is
inadequate. "This was generated very simply: a sample of
dry pigment, unprepared, was charged directly into an
instrument, compressed air was blown through it to
simulate the effect of being released into turbulent
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#
Summary of Public Comment
EPA/OPPT Response
The smaller particle size initially supplied by CPMA and
relied on in the risk evaluation is not representative of PV29
in workplace dust and is not physically self-sustaining in the
ambient workplace environment. Because workplace
exposure is limited to agglomerated pigment particles, there
is no condition of use which could result in a significant
exposure to primary PV29 crystals. By contrast, the larger
particle size measurements subsequently provided by
CPMA, and previously supplied by BASF, are
representative of the agglomerated PV29 particles that
might be found in workplace dust. It would be arbitrary and
capricious for EPA to rely on that smaller particle size in the
final risk evaluation.
Finally, we note that the inherent tendency of particles to
form agglomerates that are 2-3 orders of magnitude larger
than the primary particles is true of pigments generally;
indeed, it is true of any chemical substance which forms
very small, stable particles.
workplace air, and a laser was shined through the cloud to
measure particle size.'" This provides context but it does
not provide adequate empirical evidence to conclude that
this sample is representative of dust encountered in
manufacturing settings. EPA also agrees with several other
comments received by other commenters as well as
members of the SACC that 1) the dust samples analyzed by
Sun Chemical are taken from the product bags and may not
be representative of the PV29 PSD in the workplace
breathing zone and 2) smaller particle sizes are more likely
to occur within the breathing zone and potentially remain
suspended in air compared to larger particle diameter sizes.
In addition, this claim that the diameter of PV29 particles
found in the workplace is most accurately represented by
the larger measurements (10.4 and 46.9 |im) ignores the
median particle diameter measurement of 0.5 |im presented
in the BASF Safety Data Sheet (available in the
Supplemental File: Information Received from
Manufacturing Stakeholders ( :0a). The
particle diameter presented in this SDS is also inconsistent
with CPMA's assertion that 10.4 and 46.9 |im are
representative of workplace dust.
As a result, EPA will not change its determination that
PV29 is potentially represented by all particle size
information identified and received during the risk
evaluation process. EPA has updated its modeling
approach in the final risk evaluation. The particle size
information is used primarily to judge the appropriateness
of the carbon black analogue used to describe the potential
hazards of PV29 inhalation. The MPPD model presented in
the earlier draft of the risk evaluation to estimate the %
deposition of PV29 based on the different particle size
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distribution data is no longer part of the final risk
evaluation.
112
The significant efforts that are necessary to produce these
smallest particles are not conditions that occur normally in a
plant setting and should not be considered reasonably
foreseeable conditions of use. Thus, best available science
indicates that the smallest particle size is not representative
of dust that workers would be routinely exposed to, and
therefore should not be used as the driver for unreasonable
risk.
As discussed above, the justification provided by CPMA to
explain the relative applicability of the PV29 particle size
distribution data provided by Sun Chemical and CPMA are
lacking empirical data. Therefore, there is insufficient
evidence for EPA to disregard the potential occupational
exposures to PV29 dust at the smallest particle sizes
(diameter of 0.043 |im; as provided by Sun Chemical)). As
explained in Section 3.2.3.1 of the final risk evaluation,
EPA has updated its modeling approach so that the
potential exposures are not calibrated for the % deposition
as predicted by MPPD based on particle size distribution.
Instead, the particle size distribution data are used to justify
the use of carbon black as an analogue and to describe the
"respirable" size of the particles.
119
Given this enormous range and the continuing uncertainty
associated with the levels in and physical forms of PV29 in
workplace air across the lifecycle, EPA appears quite
appropriately to have based its risk determinations on the
smallest particle size from among these widely varying
industry estimates.
EPA agrees with the commenter and has not changed in the
final risk evaluation, its assumptions about the possibility
for exposure to the smallest particle size diameter particles
of PV29 in the workplace. Please see Section 3.2.3.1 of the
final risk evaluation for the updated hazard discussion.
119
EPA should not discount the smaller particle size diameter
measurements in its risk calculations.
EPA agrees with the commenter and has not changed in the
final risk evaluation, its assumptions about the possibility
for exposure to the smallest particle size diameter particles
of PV29 in the workplace. Please see Section 3.2.3.1 of the
final risk evaluation for the updated hazard discussion.
1 .iinu ()\ crlocKl as llic ("l ilical Ijulpoinl li>r ()cciipiili«.>iiiil Inhalation l-\posiiiv
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111
EPA must consider all relevant health endpoints of its
analogue, Carbon Black, not just lung overload.
The EPA agrees with this comment. The Agency has
edited the text of the final risk evaluation in Section 3.2.
EPA describes that particle overload is a kinetic
phenomenon and the term does not necessarily describe an
adverse effect. The definition of overload and how it is
used to create context for the evaluation of any observed
toxicities has also been provided in the final risk evaluation
in Section 3.2.3.1.
EPA has updated the human health hazard section to
discuss the non-cancer adverse effects observed in rats,
mice and hamsters as a result of inhalation of carbon black
particles (the analogue for PV29) including alveolar
hyperplasia, inflammatory and morphological changes in
the lungs.
105
Lung overload is not relevant to humans, and workplace
exposure to PV29 does not cause chronic lung disease.
The revised draft risk evaluation bases all of its
determinations of unreasonable risk on "lung overload," a
health effect nowhere discussed in the initial draft. At the
outset, CPMA notes that PV29 particles are not present in
the workplace in respirable sizes (i.e., <10 |im), and so this
effect is not relevant to this evaluation.
The revised draft considers lung overload strictly as a "non-
cancer effect." By doing so, EPA is implicitly excluding
lung overload as a precursor event, with cancer as the
endpoint of concern. Rather, the draft risk evaluation merely
describes lung overload "as when the exposure
concentration is sufficiently high or the duration sufficiently
long to overwhelm alveolar macrophage (AM)-mediated
clearance." This implies workers with different patterns of
intensity of exposure (concentration) and duration of
The Agency has corrected the text to provide clarification
of the kinetic effects observed in the chronic inhalation
study conducted with carbon black (alveolar hyperplasia,
inflammatory and morphological changes in the lungs in
rats). The definition of overload and how it is used to
create context for the evaluation of any observed toxicities
has also been provided. As indicated above, available
evidence provided to describe the particle size of PV29 is
insufficient to conclude that particles <10 |im will not be
present in the workplace.
This physical chemical properties of PV29 (particle size,
solubility, solid state) support the conclusion that concerns
for potential effects resulting from lung overload by poorly
soluble particulate matter, are key hazard concerns for this
chemical.
There is a lack of scientific consensus about whether lung
overload causes cancer in humans. However, inhalation of
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exposure are assumed to have the same risk if the product of
intensity of exposure (concentration) and duration of
exposure are the same.
The toxicological literature shows that rat data on lung
overload is not relevant to humans. Elder et al. (2005) does
not evaluate what other adverse health effects might follow
from impaired lung clearance, nor its relevance to humans.
Elder et al. (2005) and other relevant publications were
reviewed, with the following conclusions: Target organ
effects at higher doses are lung inflammation, hyperplasia,
and fibrosis (Carter et al., 2006; Elder et al., 2005; Driscoll
et al., 1996). However, this response in rats under
conditions of lung overload is principally a species-specific
response that is not relevant to humans...
There is no evidence of lung overload in the epidemiological
literature or in the color pigments industry's experience.
CPMA and its members are not aware of any evidence of
dust exposure to primary pigment particles in workers
resulting in lung overload in the pigment manufacturing
industry or downstream industries after over 50 years of
production. Therefore, it is not plausible to hypothesize that
continued use of a chemical substance that has been in
commerce for a half-century will suddenly give rise to a
previously unrecognized category of illness, and it would
be extraordinarily unreasonable to speculate that color
pigments could, at some future time, present an "emerging"
risk like lung overload.
respirable poorly soluble particulate matter is associated
with other adverse effects in humans, such as fibrosis,
asthma, Chronic Obstructive Pulmonary Disease, etc., and
that rodents are a good model for these effects in humans.
In the chronic carbon black studv bv Nikula et al., (1995),
fibrosis and tumors were observed in rats. Rats have a 10X
faster clearance rate for particles than humans, thus EPA
has interpreted that humans are also susceptible to adverse
effects for particulate matter ( ).
Furthermore, as no employee health data have been
provided, it is not possible for EPA to verify the validity of
the claims about employee health.
The Elder (2005) carbon black sub-chronic inhalation
study female rat NOAEC HEC is 0.28 mg/m3 or 8 times
lower than the Nikula et al., carbon black chronic
inhalation studv (1995) female rat LOAEC HEC of 2.23
mg/m3 based on lung hyperplasia, fibrosis and tumors in
this 24-month study (a major duration of the lifetime of a
rat). If overload is demonstrated to occur, especially when
considering rat tumors, then these effects may be less
relevant for human risk assessment. However, as noted,
several other "noncancer" events such as inflammation and
hyperplasia are related to other adverse outcome pathways
and should be evaluated as relevant to humans (U.S. EPA.
2019). Overall, tumor formation from PV29 is not
expected at the rat NOAEC HEC value of 0.28 mg/m3, a
concentration that does not cause inflammation and
hyperplasia precursor events in animal models.
113
Page 70 of the revised draft risk evaluation states "MOE
calculations and equations are provided in Appendix G and
Appendix H." Appendix G has MOEs listed in a column of
the first table for both central tendency and high-end
EPA has added the risk equations to the text in the final
risk evaluation as well as the resulting MOEs to clarify the
calculations of non-carcinogenic risk for both central
tendency and high-end inhalation exposures of PV29.
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exposure scenarios, but no calculations or equations.
Appendix H has nothing to do with human health (but also
contains neither MOE calculations nor equations).
Please see Table 4-3 in Section 4.2.1 of the final risk
evaluation for the updated table of MOE calculations
Appendix G has been removed from the final risk
evaluation.
Occupational l-xposuivs lo Dow n si ream I scrs of PY21)
105
Industrial and commercial uses of PV29 do not expose
workers to greater risks than manufacturing or processing.
Workers in Downstream Industries Cannot Be Exposed to
Free PV29 Particles. Cutting, grinding, and similar physical
processing of molded plastic parts or fibers could
conceivably cause a release of plastic particles, but it does
not release pigment particles, nor does application of paint
or ink containing PV29. Even spray applications of paint
containing PV29 cause the release of paint particles, in
which PV29 crystals are bound up with binders, liquids and
additives. As a result, these workers have essentially no
potential exposures to PV29 particles.
Workers in Downstream Industries Wear Dust Masks When
Warranted. The revised draft risk evaluation agrees that
workers in manufacturing, importing and processing
workplaces will wear APF 10 respiratory protection.
However, it assumes that workers in industrial and
commercial uses (other than automotive coatings) will not.
This assumption is unfounded.
APF 10 respirators are half-masks; essentially, the dust
masks that, until March of this year, anyone could buy at
Home Depot... Finally, the Sun Chemicals safety data sheet
EPA agrees that the potential exposures to respirable PV29
particles after it has been incorporated into a plastic or
rubber matrix are expected to be low. As a result, the
unreasonable risk concerns identified for the manufacture
and processing of PV29 only apply to scenarios where
workers are handling PV29 as a solid (powder). This
scenario includes processing steps where powdered
pigment is mixed into paint products or incorporated into
the plastic and rubber products. The unreasonable risk
determinations are not meant to indicate that finished
plastic, rubber or paint applied products are expected to
result in an unreasonable risk concern for industrial and
commercial users. This point is clarified in the final risk
evaluation. In the final risk evaluation, EPA changed its
determinations to no unreasonable risk for
industrial/commercial use in plastic & rubber products.
During the spray application, workers may be exposed to
respirable PV29 however, the size of the spray particle and
the fraction of PV29 bound up with other chemicals is not
clear. In addition, this condition of use encompasses the
potential for applicators to be exposed to PV29 as a result
of sanding cars painted with paint containing PV29
pigments. There is unreasonable risk determined for
industrial and commercial users in the paint and coatings
sector.
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for PV29 recommends use of respiratory protection where
warranted.
The Agency stands by the assumption that most industrial
and commercial users (except application of paints) of
PV29 containing material are not expected to use PPE as
these uses involve the handling of finished products where
release of PV29 is not expected. This is clarified in the
assessment, where risks to commercial/industrial uses are
not expected to result, except in the case of auto paint use.
120
EPA has no valid basis for concluding that processing
exposures will not exceed manufacturing exposures. EPA
estimated the highest full-shift exposure to occupational
users at Sun Chemical at 0.37 mg/m3 and reported that
workers at Sun Chemical handle PV29 at nearly 100%
concentration. However, sampling of repair technicians
engaged in orbital sanding of automobile paint (see citation)
has found total dust concentrations as high as 12 mg/m3.
Under this condition of use exposures could exceed those in
manufacturing if the concentration of PV29 in the paint
exceeds 3.08%.
Citation: Enander, R. T., Cohen, H. J., Gute, D. M., Brown, L. C.,
Desmaris, A. M. C., & Missaghian, R. (2004). Lead and methylene
chloride exposures among automotive repair technicians. Journal of
Occupational and Environmental Hygiene, 1(2), 119-125.
The air concentrations EPA used for the risk estimates are
for the respirable particulates. The OSHA PEL for
respirable fraction is 5 mg/ m3 and it is not reasonable to
assume that 12 mg/ m3 of dust measured in the study is
entirely composed of respirable particles of PV29.
EPA has revised its estimations for exposures to PV29 as a
result of downstream processing and use activities. As
explained in Section 4.2.3 of the assessment, the updated
exposure concentrations for downstream processors are the
same central tendency and high-end workplace
concentrations that are expected to result from
manufacturing activities. EPA determined that this is a
more appropriate approach given the lack of data
characterizing exposures to downstream processors and
users.
112
The revised draft risk evaluation states that approximately
90% of that volume is consumed as a site-limited
intermediate, so it should be expected that significantly less
of the PV29 produced is used for other processing
applications. Therefore, the assessment of occupational
exposures in the revised draft risk evaluation does not
reflect reasonably foreseen conditions of use in context of
the information that EPA has, including use patterns and
consideration of the stable annual production volumes.
The final risk evaluation considers all known, intended and
reasonably foreseen conditions of use. The volume
expected in the processing of PV29 is the remaining 10%
manufactured, not that which is used as a site-limited
intermediate.
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108
The assumptions made by EPA as to similarity in exposures
between manufacture workers and other downstream
activities skew the exposure assessment towards
overestimation. The same is true for the assumption that no
PPE is used during industrial and commercial use of plastic
and rubber products and in automobile plastics.
AAI member facilities comply with OSHA standards:
grinding or milling of rubber or plastic articles impregnated
with small amounts of PV29 does not release pigment
particles.
AAI conducted a survey of its members that indicated
preliminarily that in paints and coatings used in the
automotive industry, any addition of PV29 would take place
at the supplier level. This survey also would indicate that
spray painting of coatings is primarily applied in controlled,
robotic environments.
Workers use respirators, chemical gloves, and overalls. AAI
automotive facilities strive to ensure that workers have PPE
designated to address the most rigorous OSHA standards
that would apply.
EPA has updated its descriptions of conditions of use to
indicate that exposures are expected to be negligible from
the handling of finished plastic and rubber products as a
result of industrial/commercial uses where PV29 is not
handled directly or applied as a paint. As a result, there are
no risk concerns identified for industrial/commercial uses
except for application/use of auto paint.
EPA appreciates the information regarding PPE use at AAI
member facilities. However, considering that not all
facilities are AAI members the Agency accounts for
possible exposures in non-member facilities. EPA stands
by its assumption that not all industrial and commercial
users use PPE in order to derive a risk determination
because there is no PV29 OSHA requirement. There is the
exception for automobile OEM & refinishing for which
EPA assumes use of respirators with APF of 25. Although
the assumptions may skew towards overestimating risk, the
conservative high-end exposure approach is appropriate for
the reasonably available data.
119
EPA solicited information about exposures of PV29 to
downstream processors, but data were insufficient and
indicate that downstream processers handle PV29. No
information about use of PPE by downstream processers
and users was provided to EPA.
EPA appreciates the information provided to the Agency
that describes the downstream processor activities and
resulting exposures. The Agency did receive limited
information from Sun Chemical Corporation about their
processors' use of PPE. This information is available in the
supplemental file, titled, "Supplemental File: Information
Receivedfrom Manufacturing Stakeholders (
2020a). The Agencv is using this information in a limited
fashion for risk characterization purposes and
acknowledges uncertainties regarding the assumption that
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the use of PPE are applicable across all downstream
processors.
119
EPA erroneously assumed that dust concentrations in
downstream processing industries are never higher than
those from manufacturing at Sun Chemical.
EPA appreciates that potential for exposure to total dust
may be higher in processing facilities than in the
manufacturing facility, but EPA does not agree that
downstream processing activities are likely to result in
exposure to PV29 at levels higher than in the
manufacturing facility. EPA has made a number of
conservative assumptions when describing the high end
exposure estimate for manufacturing exposure that leads
the EPA to conclude that 1.2 mg/m3 represents the true
high end exposure across all conditions of use. First, EPA
has assumed that the highest exposure concentration to
total workplace dust, as presented in Table 2-4 is
comprised of 100% PV29. Second, EPA is assuming that
employees will be exposed to this high-end concentration
for the entire shift. In addition, during these activities,
workers are handling material that is comprised of 100%
PV29, which is assumed to be the activity which results in
the highest potential for exposure, as it is not encapsulated
in plastic or other matrices. As a result of these
assumptions, EPA is confident that the high-end exposure
concentration used to describe exposure through
downstream processing activities is sufficiently protective
to describe the exposure through these activities.
109
ACA is concerned that data related to particle size is not
incorporated into the risk evaluation in a manner that
reflects realistic practices during paint formulation and
downstream use of paint, and is concerned that unwarranted
assumptions have led to findings of unreasonable risk for
two conditions
As explained in the final risk evaluation, reasonably
available data indicates PV29 can be formulated into a
powder of varying particle sizes. The conflicting
information provided by the manufacturing stakeholders
regarding the particle size data for PV29 and the lack of
adequate explanation or characterization of particle size
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of use: (1) Processing into formulation - Incorporation into
formulation, mixture or reaction products in paints and
coatings; and (2) Industrial and Commercial Use, paints and
coatings, coatings and basecoats.
Even without PPE, it is ACA's understanding, from PV-29
manufacturers that exposure is physically impossible since
PV-29 particles at the nanoscale would agglomerate.
PV-29 manufacturers further state that industrial and paint
applicators would not handle PV-29 in the powder from, but
instead in a pellet, bound in a matrix, as noted in comments
filed by CPMA.
ACA also asserted that engineering controls and PPE use
further reduces exposures, including use of closed and
automated systems by most manufacturers of automotive
paint, and common PPE and engineering controls
implemented by paint formulators, including ventilation and
respirators of higher protection factor than the assumed PF
10 respirators.
distribution information of actual workplace dust led EPA
to consider the distribution of all available particle size
data and its relevance to PV29 dust found in the workplace.
Further conflicting information is provided in this
comment by CPMA. Earlier in their comment, they
indicate that pigments are only "deagglomerated" into the
primary (smallest) particles following dispersion in inks,
plastics or paints, yet later in the comments, they are
indicating that paint applicators who are presumably
handling these stable dispersions are only exposed to
agglomerates or plastic pellets. The conflicting and
unsubstantiated information provided by Sun Chemical
only serves to bolster the need for particle size
measurements taken from actual workplace dust in order to
clarify the potential for exposure. In the absence of such
empirical evidence, EPA assumes that potential exposure
to PV29 of all particle size diameters described in the
reasonably available data is possible. Regardless, EPA has
updated the approach regarding the use of particle size
information. Due to the deficiencies in the particle size
data, EPA is no longer using particle size information to
estimate the % deposition of the particles in the lung, but
now only using this information to judge the adequacy of
the carbon black analogue. Please refer to Section 3.2.3.1
of the final risk evaluation for a discussion of the
comparative particle diameters of carbon black and PV29.
EPA has updated its assumptions about PPE usage for
automotive paint applicators. In the final risk evaluation,
an APF of 25 is assumed to account for the practices
described in this comment received from CPMA.
Assumptions About OSI1A Rcc|iiircmcnis Regarding Workplace l-\posure Controls aiicl Safety Data Sheets (SI)Ss). and Personal
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Protective Equipment (PPE)
120
The use of an assigned protection factor (APF) of 10 is
supported only by a report from Sun Chemical that workers
wear "dust masks" during manufacturing activities. EPA
does not report whether the wearing of "dust masks" is
voluntary or mandatory. Nor does EPA report how it
determined that it was appropriate to assign a protection
factor of 10 to these "dust masks." Dust masks do not
appear to be filtering facepiece respirators and should not
receive an APF of 10.
EPA believes that information provided from the only
domestic manufacturer about the dust masks used in its
manufacturing facility supports the Agency's assumption
for PPE use. The air-purifying respirators with an APF of
10 were assumed (Refer to Table 2-7 in the final risk
evaluation).
120
Access to respirator PPE is likely reduced as a result of the
COVID-19 pandemic. In a pandemic, during which there
are not enough such respirators for health care, the
assumption that they would be available in manufacturing is
utter nonsense.
In the risk evaluation EPA maintains its assumption that
PPE is being used during manufacturing and processing of
PV29. The PPE assumptions from the Agency are not
limited to PPE use during this pandemic, but practices
before and after as well.
119
EPA continues to apply the unwarranted assumptions that
many workers engaged in manufacturing, processing, using
and disposing of PV29 will wear personal protective
equipment (PPE) and that such equipment is fully effective
in protecting them from exposure to the chemical.
Elsewhere in these comments and in EDF's prior comments
on the initial draft risk evaluation, we have rebutted these
assumptions in great detail. EPA should base its occupational
risk estimates and risk determinations on the exposures absent
use of PPE that workers face.
For the majority of the conditions of use EPA examined, it
assumed workers would wear PPE providing an APF of 10
(and in one case, for auto paints, an APF of 25).
EPA believes that information provided by the only
domestic manufacturer about the use of PPE (i.e. half face
dust masks) in its manufacturing facility supports the
Agency's assumption of PPE use. In addition, for
processing, recycling, and disposal conditions of use, air-
purifying respirators with an APF of 10 were assumed. For
one condition of use, paints and coatings for automobile
(e.g., Original Equipment Manufacturer (OEM) and
refinishing), EPA assumed the use of a supplied-air
respirator (continuous flow mode) with an APF of 25. For
the remaining industrial, commercial, and consumer
conditions of use, EPA assumed no use of a respirator
because there is no PV29-specific OSHA requirement and
no reasonably available data to support a use of PPE under
these uses.
The PPE assumptions for all the conditions of use did not
affect the unreasonable risk determinations made. Only an
Information provided by the manufacturers regarding use of
PPE failed to identify any specific activities as requested by
EPA, and no information on quantified effectiveness other
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than a general specification for the type of paper mask used,
which does not reflect performance in actual use. The
response's use of the subjunctive case ("would be") casts
doubt on the reliability of the information being provided.
The "detailed work instructions" referred to were not
provided (or if they were, EPA has not made them publicly
available).
assumption of PPE with APF of 50 would eliminate
unreasonable risk; however, the final risk evaluation does
not use that assumption for any condition of use.
113
EPA has not justified the assumption that respirators will be
used either in PV29 manufacture or in downstream
conditions of use. OSHA regulations do not require
respirators for PV29-exposed workers, and EPA has
repeatedly acknowledged that respirator use in many
workplaces is sporadic and often ineffective. EPA should
assume no PPE (in this case, respirators) in calculating
MOEs for PV29.
Please refer to comment directly above for discussion of
PPE assumptions and justifications.
119
Many major limitations of the PV29 SDSs as a means of
worker protection, which is discussed in more detail in
subsection C. of the comment. EPA's reliance on them as a
basis for assuming proper and effective use of PPE is even
more far-fetched.
BASF SDS (see PV29 Supplemental file) has no
information regarding precautions or use of PPE.
Sun Chemical SDSs (see PV29 Supplemental file) state in
section 8 that there are no applicable occupational exposure
limits, while EPA claims and relies on OSHA's respirable
dust PEL as one of the bases for claiming workers would be
required to wear PPE. The SDSs make no mention of this
PEL and hence the user of the SDS would have no idea of
the existence of the standard on which EPA relies.
EPA believes that information provided by the only
domestic manufacturer about the dust mask used in its
manufacturing facility supports the Agency's assumption
of PPE use.
The Agency only assumes PPE use by manufacturers and
processors with an APF of 10. No PPE is assumed for
industrial and commercial users, except auto paint
refinishers. Even with the PPE assumptions for
manufacturers and processors, unreasonable risk is
determined. Reducing the PPE to none would not change
the risk determinations for manufacturers or processors and
would be inconsistent with reasonably available
information regarding PPE usage at manufacturing and
processing facilities.
Refer to response directly below for discussion about the
OSHA standards for PV29.
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TCI America SDS does not indicate adequate instructions
for use of PPE.
Given this lack of evidence as well as the lack of any
binding requirement on employers to ensure workers are
protected through use of PPE, EPA should assume workers
do not wear PPE in making its risk determinations.
119
To justify assumptions about PPE use, EPA grossly distorts
and mischaracterizes OSHA requirements, including with
respect to PPE use. First, EPA acknowledges - and then
dismisses - the fact that the agency does not have
"reasonably available information" on use of PPE for each
condition of use. Contrary to EPA's assertion that, "in the
absence of such information," it can simply assume
compliance - especially where there is no clear and
universally applicable requirement regarding PPE use for
this chemical - EPA should instead assume no use of PPE.
Second, EPA implies that OSHA worker protection
standards are in place for PV29, while in fact there is no
OSHA PEL for PV29. EPA goes onto invoke three OSHA
regulations relating to employers' obligation to provide
respiratory protection from exposure. Its hazard
communication standard, 29 C.F.R. § 1910.1200, its
respiratory protection standard, 29 CFR § 1910.134, and its
standard and PEL for respirable dust, 29 CFR § 1910.1000.
None of these consistently requires employers to provide
respiratory protection from PV29. Significant evidence
demonstrates that SDSs are often of insufficient quality to
be useful and are frequently not understood.
Assuming use of PPE conflates risk evaluation and risk
management and significantly understates risk.
EPA disagrees that the OSHA standards for worker
protection are not applicable to PV29 particulate exposures
in the manufacturing and processing workplace. Although
there is no chemical specific OSHA PEL for PV29, the
OSHA PEL for general and respirable nuisance dust
applies to all solids including PV29.
EPA generally assumes compliance with OSHA
requirements for protection of workers, including the
implementation of the hierarchy of controls. In support of
this assumption, EPA used reasonably available
information indicating that some employers, particularly in
the industrial setting, are providing appropriate
engineering, or administrative controls, or PPE to their
employees consistent with OSHA requirements. EPA does
not have reasonably available information to either support
or contradict this assumption for each condition of use;
however, EPA does not believe that the Agency must
presume, in the absence of such information, a lack of
compliance with existing regulatory programs and
practices. Rather, EPA assumes there is compliance with
worker protection standards unless case-specific facts
indicate otherwise, and therefore existing OSHA
regulations for worker protection and hazard
communication will result in use of appropriate PPE in a
manner that achieves the stated APF or PF. EPA's
decisions for unreasonable risk to workers are based on
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high-end exposure estimates, in order to account for the
uncertainties related to whether or not workers are using
PPE. EPA believes this is a reasonable and appropriate
approach that accounts for reasonably available
information and professional judgement related to worker
protection practices, and addresses uncertainties regarding
availability and use of PPE.
The PPE assumptions for all the conditions of use did not
affect the unreasonable risk determinations made. Only
with an assumption of PPE with APF of 50 would be
protective to eliminate unreasonable risk; however, the
final risk evaluation does not use that assumption for any
condition of use; therefore, no PPE assumptions conflated
the risk evaluation or understated the risk of PV29.
111
EPA continues to make assumptions about PPE which are
scientifically unsupported.
EPA believes that information directly from the only
domestic manufacturer about the dust mask used in its
manufacturing facility supports the Agency assumption for
PPE use. EPA further stands by the assumption that
industrial and commercial users (except auto refinishers)
do not use PPE.
l-l\\ Makes Ikoad. Sweeping Conclusions 011 Risks I-need hy Occupational \onuseis (OM )
119
EPA also relied on several unsubstantiated assumptions.
First, the agency assumed that all ONUs would be subject to
lower exposures than occupational users - even those ONUs
engaged in potentially high-exposure activities such as
maintenance, repair and cleaning. Second, in the absence of
any data on downstream processing, the agency assumed
that dust concentrations in downstream processing
industries are never higher than those from manufacturing at
Sun Chemical.
EPA has updated the assumptions in the final risk
evaluation regarding downstream exposure. EPA is now
assuming that downstream users and processors that handle
PV29 are exposed equally to workers at the manufacturing
facility.
EPA assumes that workers at the manufacturing facility are
handling PV29 directly. Based on anticipated uses of
PV29, EPA believes that it is reasonable to assume that this
represents the highest-end potential for exposure, as this is
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the only activity where workers will encounter scenarios
where 100% of respirable dust is comprised of PV29. For
downstream users and processors, the highest expected
exposure scenario involves processes where workers are
handling PV29 in a powder form. As such, it is reasonable
to assume that inhalation exposure from these activities is
not higher than scenarios where manufacturing workers
will be handling PV29 dust.
I sing Suhmiiiecl Data Characterizing PY2l> Concentration in the lirealhinu /one. N\\ Miscalculated Airborne Ia|">osuic
Concentrations in ils Calculation of l-\posurc
105
Sun complied with the test order. EPA cannot assume llial
exposure assessments for batch operations can and will
operate sampling equipment for longer periods of time than
the batch requires.
The exposure assessment was performed in accordance with
the order given by the EPA and the sampling strategy that
EPA agreed to and approved. The final risk evaluation
should incorporate all of the test results, not just the results
of the solubility testing.
In particular, EPA represented the high-end of worker
exposure by using 1.2 mg/m3, derived from data supplied
by Sun in 2019, rather than data from the test order
sampling.
The method EPA's test order required has maximum sample
volume of 400 liters of air, and sampling air flow rate
specific for the sampling device. NIOSH 0600 measures the
mass concentrations of all non-volatile respirable dust in the
air, and it cannot differentiate between PV29 and dusts
generated from other processes or tasks performed in the
workplace. If these parameters were unacceptable for the
EPA appreciates the submission of the lesl dala in response
to the Section 4 Test Order. While the air monitoring test
was conducted by following the NIOSH 0600 test
guideline, there were several deficiencies noted by EPA
with the submitted test data. These deficiencies, as outlined
in the risk evaluation, affected the ability to accurately
characterize the inhalation exposure for a full
manufacturing shift producing PV29. For example, fine
particulate matter can remain suspended in the air long
after a process has ceased, drift to other areas of the
facility, and be carried by the ventilation system. Thus, the
inhalation exposure duration to workers or bystanders can
be far longer than the actual process duration which
generated the dust. In addition, this assumption that
exposure is negligible when PV29 is not being produced
ignores the possibility that ambient dust can be inhalable
when it is disturbed during cleaning. This factor must be
considered in the exposures to workers and in the risk
assessment. As explained in the assessment, as a result of
the short duration of the sampling, EPA must make
assumptions to ensure that the exposure concentrations do
not underestimate exposure to workers in a manufacturing
facility.
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purposes of EPA's risk assessment, then a different method
should have been specified in the order.
Indeed, the sampling plan was amended to specify use of
the PPI device, to lower the flow rate from 2.5 1pm to 2.0
1pm, to require discard of samples where the pre- or post-
flow rate variance exceeded 10% of the average, and to
raise the maximum sample run time from 160 to 200
minutes. It would be particularly unfair and unreasonable
for EPA now to fault the work for following specifications
that were added at EPA's direction.
The NIOSH protocol which is a key part of the test order
includes discretion. The discretion ensures that the protocol
can accommodate different workplace settings/conditions
and that the study result is informative. The expressed
purpose of the test order was to reduce uncertainties in
assessing PV29 occupational inhalation exposures.
However, as noted above, and as outlined in Appendix I of
the final risk evaluation, the study deficiencies precluded
the ability of EPA to accurately characterize workplace
inhalation exposures. As a result, EPA had to make several
assumptions for the final risk evaluation.
The approved study plan included a total of 43 samples, 30
worker Occupational User (OU) samples and 13
Occupational Non-User (ONU) samples. Instead, 23 OU
samples and six ONU samples were collected. Concerns
are described further below.
In addition, the samples were collected in a sub-optimal
manner such that results are not representative of OU
exposures and ONU exposures:
- Based on IH study, workers were in the PV29 area
over multiple samples. Samples were collected for
short periods of time back to back instead of
collecting each sample for a longer period of time
to better represent the full duration of the PV29
tasks performed. The short-sampled durations
contributed to nearly every sample result being
below the limit of detection.
- EPA approved the Sun-requested modification to
use a Parallel Particle Impactor (PPI), although the
flow rate was not specified. The lowest flow rate
PPI was used for the sampling, which resulted in
most samples being below the limit of detection.
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Based on the low measured concentrations; a higher
flow PPI would have allowed a higher volume of
sample resulting in a better characterization of the
worker and ONU exposures.
Area samples were collected right next to open bay
doors, which may not have been representative of
exposures to ONUs. Sun stated that they monitored
in that area with bay doors open because that was
the best representation of ONU exposures.
- Lastly, there were three instances of pump failures
which resulted in samples being lost.
A good industrial hygiene (IH) survey requires sampling
practices that consistently provide information supporting
the purpose of the project. It is important that the limit of
quantitation (LOQ) (i.e., the actual airborne respirable dust
concentration that can be reliably quantified by the
laboratory) and limit of detection (LOD) be lower than the
level of interest, which should be defined during the
planning phase of the project. There are several accepted
industrial hygiene procedures that, when followed, can
limit the number of sample results that are below the LOQ
or the LOD. As a starting point, the sampling team should
understand the purpose and priorities of the project. Shorter
task-based samples can be used to better understand
exposure sources and plan more targeted sampling
strategies, while full-shift samples best characterize
employees' daily workplace exposure. Airborne
contaminant levels should be estimated and used to
calculate the sample air volume needed to achieve the
desired detection level. If the contaminant concentration
cannot be estimated in advance, preliminary screening
samples may be collected and analyzed to determine the
contaminant concentration range and permit sampling
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teams to make informed choices when designing the
survey. An additional consideration for sampling teams
planning to obtain quantifiable or detectable respirable dust
sample results is that total dust concentrations tend to be
substantially higher than the respirable dust fraction, since
total dust includes more large particles and more mass, so
airborne concentrations (in mg/m3) are almost always
appreciably higher for total dust than respirable dust.
Sampling teams should use great caution if attempting to
use total dust sample results as information to design a
respirable dust survey. In all cases, sampling a larger air
volume improves the likelihood of obtaining sample results
above the LOQ or LOD. Higher air sampling volumes can
be achieved by choosing higher sampling pump airflow
rates (if permitted by the sampling equipment and method)
or by increasing the length of the sampling time (to the
extent practical for the project goals). Therefore, the
quality and accuracy of information obtained from an
industrial hygiene sampling survey is improved when the
sampling team collects concurrent personal samples of
different lengths (task-based and half-day, in addition to
full-shift) and high-flow area samples. The most
meaningful workplace exposure sample results are
obtained from full shift personal breathing zone sampling
methods; however, if contaminant levels are truly
miniscule and unable to be detected by personal sampling
methods, supplemental high-flow area sampling is likely
the best way to confirm that airborne contaminant
concentrations are well below the level of interest.
105
EPA cannot assume that PV29 workers will be exposed for
10.5 hours/day at concentrations of 1.2 mg/m3. EPA
assumed that the unsampled portion of the work shift had
the same average exposure to PV29 as the sampled portion.
The OSHA Technical Manual (2014) describes the
importance of full-shift sampling when determining
compliance with a full-shift TWA PEL. The Sun IH study
failed to include any full-shift air measurements, resulting
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Assuming that exposure for the unsampled portion of the
work shift was the same as the sampled portion
overestimates potential exposure. This approach is incorrect
and inconsistent with standard industrial hygiene practice
for this type of batch process operation.
The reality of batch manufacture of PV29, as noted by the
revised draft, is that "employees at Sun Chemical only spent
a fraction of their shift (approximately V2 hour to 2 hours)
actually handling C.I Pigment Violet 29." It is not a
"deficiency" of the study that they did not have longer
exposures, it is an unavoidable artifact of batch
manufacture.
EPA's risk evaluation processes need to accommodate this
commercial reality, not force it onto a Procrustean bed that
assumes continuous manufacture.
These assumptions are individually implausible, and
collectively they exceed the realm of the possible.
in most measurements being below the LOD. As a result,
EPA had to make several assumptions including the
duration of exposure explained in Section 2.3.1.2 of the
final risk evaluation. To estimate high-end exposure to
occupational users (OUs), EPA assumed that workers in
the manufacturing facility were exposed at the maximum
dust concentration as presented in Table 2-4. To estimate
central tendency inhalation exposure for OUs, EPA used
the results of the dust monitoring study to calculate an
average monitored concentration. This involved creating an
average of the LOQ/2 for each shift operator. Of these
values, the central tendency was determined to be the
highest average of these monitored concentrations.
Similarly, for the occupational non-users (ONUs), EPA
estimated central-tendency exposure by taking an average
of the LOQs/2 for all operators determined to be ONUs in
the dust monitoring report, while high-end for ONUs was
estimated using the maximum detected concentration
reported in the dust monitoring study. To calculate an
MOE for both OUs and ONUs, these concentrations are
converted to an average daily concentration according to
the approach outlined in Table 4-3.
Due to the short duration of the sampling, there is
insufficient information for EPA to conclude that
inhalation exposures to OUs and ONUs are negligible
when they are not performing activities where they are
handling PV29 directly. This ignores the potential for dust
in the workplace to be re-entrained through cleaning and
incidental contact. This also potentially overestimates the
effectiveness of ventilation present in the facilities, for
which no information was provided. As a result of the lack
of data, EPA assumes that there is the potential for
exposure between PV29 production activities.
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106
EPA's assumptions for sentinel exposure are individually
implausible and collectively exceed the realm of the
possible. It is assumed that 100% of dust in the workplace at
the highest level ever recorded (1.2 mg/m3) would be PV29
and that workers would be exposed throughout their shifts.
Other materials besides PV29 are handled at Brushy Park,
and so dust particles will never be 100% PV29. The vast
majority of PV29 production at Brushy Park is also
transferred mechanically directly into equipment for
producing other pigments and is not sold to customers
without potential for worker exposure.
As indicated above, the respirable dust monitoring study
provided by Sun Chemical lacked full-shift monitoring to
allow EPA to adequately understand workplace exposure
to dust. As the Sun IH study failed to include any full-shift
air measurements and most measurements are below the
limit of detection, EPA made conservative assumptions
using reasonably available data in order to understand the
potential exposures to PV29 during manufacturing
activities. See Section 2.3.1 for an explanation of the
occupational exposure methodology and Section 4.2.2 for a
summary of the methodology used in the risk calculation.
113
We believe the test order data can be used, in the near term,
for exposure estimates but also agree with EPA that the data
have substantial limitations, leading to a number of
uncertainties (see pages 53-54 of the revised draft). The Sun
Chemical studies provide support for risk determinations in
the absence of better information, but over the long term,
they should be replaced with new data collected in a manner
consistent with the test order study plan and fully compliant
with the NIOSH 0600 test guideline.
The EPA appreciates the commenter's suggestion to
replace the TSCA Section 4 Test Order data, but the time
required to repeat the testing is not feasible in order to
complete the final risk evaluation. The Agency also
believes that the risk evaluation can be completed even
with the deficiencies in the test data.
113
Over the longer term, EPA should get better data by having
Sun Chemical conduct another study that is in compliance
with the test order study plan and NIOSH test guideline,
resolving the Limitations and Uncertainties described on
pages 53-54 of the revised draft.
Refer to comment above. The Agency also believes that
the risk evaluation can be completed even with the
deficiencies in the test data.
112
EPA used personal breathing zone (PBZ) monitoring data to
estimate the average air concentration of PV29 for the
purposes of calculating the LADC. Data from two studies
were summarized in Table 2-5 and Table 2-6. The first study
used the NIOSH 0500 method for total (inhalable) dust, which
typically uses a 5-(im filter (Table 2-5). Inexplicably, EPA
only used the value from the higher sample (14-0941902) to
establish the value for the high end exposure calculations. It
The highest measurement is not a full shift measurement.
EPA made a decision to use this highest measurement as
the high-end exposure level and was used for the risk
calculation. As this was the highest value actually reported
in the manufacturing facility, EPA determined that this,
rather than using a regulatory limit such as the OSHA PEL
of 5.0 mg/m3 for respiratory dust, is a more appropriate
value to represent high-end exposure. As explained in
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is not clear why there are two values for one worker in one
shift. If these samples are sequential samples for the same
worker during the same shift, the combined weighted
average of 0.72 mg/m3 should be used to represent exposure
across the entire shift.
Section 2.3.1 and Section 4.2.2, in order to better
understand the potential occupational exposures, EPA
calculated central tendency exposures using the data
provided in the dust monitoring study. The risks from this
central tendency exposure is presented in the risk
calculation for additional context.
112
The second study used the NIOSH 0600 method for
respirable dust, which would capture PV29 dust across the
particle size range it realistically would occur. Of the 22
samples collected, 20 were below the limit of quantitation
(LOQ) for respirable dust. EPA estimated that the dust
concentration in air associated with below-LOQ samples
was half the limit of quantitation of the method, or LOQ/2.
There is a robust body of literature representing the best
available science for applying modern statistical approaches
to handle exposure data, including monitoring data with
values below the limits of detection (LOD), i.e., left-
censored data. EPA should apply the methods for analyzing
the left-censored occupational air monitoring data that are a
common component of the risk evaluations they are
developing (e.g., maximum likelihood estimation), as these
are the current state-of-the-science methods.
As indicated above, the Sun Chemical IH study did not
include any full-shift air measurements and most of
measurements are below the limit of detection. EPA
followed EPA guidelines for analysis to process non-
detects. EPA has determined that given the deficiencies in
the dust monitoring study, EPA has made reasonable
assumptions to calculate central tendency and high-end
inhalation exposure to PV29. Given the small sample size
presented for each operator, many statistical tools proposed
to analyze left-censored data may not be appropriate.
112
EPA's calculation of an LADC, which is typically used for
cancer risk, is inconsistent with the revised draft risk
evaluation where EPA determined that C.I. Pigment Violet
29 is not likely to be carcinogenic (p. 80). For chronic non-
cancer effects, EPA should calculate an average daily
concentration (ADC). This would be consistent with EPA's
approach in other risk evaluations.
EPA agrees and has calculated an ADC instead of an
LADC to estimate exposure in the final risk evaluation.
112
As shown in Appendix G of the revised draft risk
evaluation, EPA used the same ED and EF parameters for
both central tendency and high end exposure estimates; that
is, ED of 10.5 hr/day and EF of 190 hr/yr. Specifically,
For the manufacturing workers, EPA assumed 190 days
year exposure based on the following:
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currently available data collected by EPA indicate that the
exposure duration and exposure frequency are substantially
lower for both the manufacturing and processing conditions
of use.
For manufacturing, the data from the Sun 2020 IH Survey
(EI Group 2020 HERO: 6656714) show that workers
perform multiple tasks during their shifts and the duration of
PV29 tasks range from 1 hour to 5 hours per day. Therefore,
the agency should use a central tendency exposure duration
between 1 to 5 hours per day, and a high end exposure
duration of 5 hours per day for the manufacturing condition
of use.
For processing, Sun indicated that approximately 350 lbs of
PV29 are processed per batch and 8,800 lbs are processed
per year at these processing facilities for paint plastics (e.g.,
nylon fibers for carpets). Sun indicated, "[wjorkers are only
exposed during the short weigh up and transfer process of a
couple minutes. Extruder time depends on batch size and
equipment size, but can take up to 30 minutes for the entire
process" (EPA 2020b, p. 44). Therefore, 30 minutes should
be representative of central tendency exposure duration, and
a multiple of 30 minutes, perhaps 2X or 3X, would then be a
reasonable high end exposure duration.
Information from Sun indicates PV29 is manufactured in
batches ranging from roughly 1,000 lbs to 7,000 lbs; the
average batch size for four batches reported is 4,048 lbs.
Data from the Sun IH Survey (EI Group 2020, p. 26)
suggest that multiple smaller batches may be manufactured
in a single day/shift. Therefore, a reasonable central
tendency annual manufacturing frequency should be
approximately 125 batches/yr (500,000 lbs/4,000 lbs per
The batch sizes during the industrial hygiene survey ranged
from 2,000 lb to 7,000 lb. Based on IUR submission from
Sun, the production volume is 600,000 lbs/year: 600,000
lb/year / (2,000 ~ 7,000 lbs/batch) = 86 ~ 300 batches/year.
Assuming 1 day/batch, this would be 86 to 300 days/year
for the manufacture of PV29. In addition, the company
stated that PV29 is manufactured and/or used "362
days/year" (This information is available in the
supplemental file, titled, "Supplemental File: Information
Receivedfrom Manufacturing Stakeholders (
2020aV).
Based on this information provided by the manufacturer,
EPA assumed the following for a typical manufacturing
worker: 2,000 work hours per year and 10.5 hours per day
(2000/10.5 = 190 days/year)for the duration of exposure,
the company did not provide any information which
showed that the workers are not exposed during the non-
sampled period. EPA assumed workers are exposed at the
same level as ONU during the non-sampled period.
Due to the low and inconsistent quality of the data
received, EPA made conservative assumptions to assure
that all potential exposure scenarios are accounted for and
to ensure that the high-end scenario actually represents
potential high-end scenarios for manufacturing and
downstream exposures. EPA appreciates that this approach
may lead to some overestimation of potential exposure for
some exposure scenarios and has provided both high-end
and central tendency estimates of exposure in the risk
characterization to account for this.
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batch); given that there are two shifts per day, any
individual employee is not likely to work on every batch
throughout a given year. Of the five operators on Shift A at
the Sun facility who worked on the three days for which
respirable dust monitoring data was collected, only one
(Operator #1) worked on PV29 production on more than
one day. For Shift B, two operators are identified who each
work on only one shift. Consequently, a reasonable central
tendency annual exposure frequency would be 60-65 days
per year (125 batches/2 shifts). A reasonable high end
annual manufacturing frequency would be 80-85 days per
year (500,000 lbs/3,000 lbs per batch per day divided by 2
shifts per day).
For processing, Sun Chemicals indicated that processing of
PV29 into plastics and paint only 6 to 12 days/yr typically.
Therefore, the logical central tendency and high-end
exposure frequency would be 6 days and 12 days,
respectively. Based on the data provided by Sun regarding
worker shift activity patterns and batch production sizes, it
appears the maximum hours of total annual production is
approximately 350 to 400 hours per year. The total ED-EF
should not exceed this value on the high end.
113
After the SACC raised numerous concerns about the initial
draft, EPA issued a narrow test order under TSCA section 4
requiring only solubility studies in water and octanol and
dust monitoring at the Sun Chemical workplace (the sole
U.S. manufacturing site). The agency did not, however,
require a 90-day subchronic study and other health effects
studies recommended by commenters, including EPN.
EPA appreciates the commenter's request for a 90-day
subchronic study on PV29 in the TSCA Section 4 Test
Order; however, the test was not requested by the Agency
because the Agency believes that the risk evaluation could
still be completed without the information.
112
EPA did not provide any explanation for the averaging time
calculation used in the revised draft risk evaluation that
appears to deviate from normal practice. The value used in
EPA agrees with this comment and has updated the
approach to calculate an ADC to represent potential
exposure to workers.
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the revised draft is classified as an ATLADC and the value
used is 155,610 hours, described as being derived from 78
years x 10.5 hours/day x 190 days/year. As stated above at
the beginning of Section III, ADC and LADC are used to
estimate air concentrations associated with chronic
workplace exposures for non-cancer and cancer risks,
respectively. The averaging time used for occupational
exposure to a non-carcinogen should be "living hours" for
the duration of a career (e.g., working years x 24 hours/day
x 365 days/year), and for a carcinogen, the average lifetime
of 78 years is used, consistent with the approach used in the
risk evaluation for carbon tetrachloride.
119
EPA has generally relied on its high-end estimates of
occupational inhalation exposure for its risk determinations.
This, too, is appropriate - indeed necessitated - by the
insufficient quantity, poor quality, and high variability of
the inhalation hazard and exposure information EPA has.
EPA acknowledges the comment.
119
High end exposure may not be representative of
downstream exposures.
In the absence of robust information for downstream
exposures, the Agency stands by its conservative approach
to assess exposures.
I sc of Carbon IJIack as an Analogue
105
CPMA indicated that the smallest particle size of PV29 is
not representative of pigment dust found in the workplace as
it does not take into account the potential for the chemical to
form agglomerates. Therefore, it is not appropriate to use
carbon black as an analog for evaluating the toxicity of
PV29. Rather, a more appropriate analog would be one
involving the larger particle sizes considered in the
evaluation. Examples for which data are available include
Barium sulfate and Diketopyrrolopyrroles (DPP) pigment,
which is closer to PV29 than inorganic carbon black in
terms of chemical structure, properties and use.
As discussed in prior responses, EPA disagrees that the
smallest particle size of PV29 is not representative of
possible workplace exposures. Sun Chemical has not
provided sufficient empirical evidence to discount the
possibility that PV29 in the air may exist at the smallest
particle sizes. As a result, EPA used all of the particle size
distribution information provided by Sun Chemical and
BASF to describe possible exposures in the workplace.
The diketopyrrolopyrrole pigments DPP inhalation study
by Hoffman et al. has been carefully considered by the
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Agency (Hofmann et ai. 2016). The study is only 5 days in
duration for particle exposure, thus not appropriate for
evaluating sub-chronic and chronic particulate matter
exposure durations for PV29.
Data characterizing the inhalation toxicity of Barium
sulfate was considered an appropriate analogue to
characterize the inhalation hazard of PV29 in the "
Updated Risk Characterization for Occupational
Inhalation of PV2 9 Based on Updated Approach because
of similar particle diameter. Based on the updated particle
size information provided by Sun Chemical, BaSC>4 is not
an appropriate chemical substance to understand the
potential chronic effects of PV29 inhalation at the smallest
particle size, as it is much larger and more dense
(MMAD=4.3 [j,m vs 0.043 for PV29).
In contrast, the DPP analogs proposed by CPMA contain
only two conjugated rings and also contains halogens, thus
carbon black with multiple conjugated aromatic rings
without halogenation is a much better analogue for PV29
with similar structures.
Carbon black is a suitable analogue for PV29 because both
compounds are pigments and are respirable, poorly soluble
particulate matter that are expected to cause increased lung
burden via inhalation exposures and potentially kinetic
lung overload at higher exposure concentrations Elder et al.
(2005). Both compounds are expected to cause adverse
effects to the respiratory tract such as irritation,
inflammation, and proliferation. Carbon black also is
structurally similar to PV29 in that both compounds
contain conjugated polyaromatic ring structures. DPP
pigments are not considered good analogues for PV29
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because they only contain two ring structures that are not
aromatic in nature and, DPP is a halogenated compound,
unlike carbon black and PV29 (Hofmann et al.. 2016).
112
The carbon black analog studv Elder et al. (2005)also
indicated that particle surface area was an "important
determinant of target tissue dose and, therefore, effects."
Based on effects observed at 7 mg/m3 high surface area
carbon black (HSCb) in all three species, EPA selected the
NOAEC of 1 mg/m3 HSCb as the point of departure for
chronic non-cancer hazards. However, the revised draft risk
evaluation does not contemplate whether PV29 has a
surface area sufficiently similar to HSCb that would support
the use of carbon black as an analog.
EPA does not have sufficient data to characterize several
properties of PV29, including surface area. As a result,
EPA did not use surface area as a criterion to understand
carbon black's suitability as an analogue for the purposes
of this risk evaluation. EPA has updated the discussion of
carbon black's suitability as an analogue in the final risk
evaluation.
The Sun Chemical Corporation provided limited and
unsubstantiated information on the properties of PV29
including particle size distributions and surface area.
119
While Carbon Black is a more appropriate analogue to
represent the inhalation toxicity of PV29, EPA must provide
greater detail for the selection of this particular study given
the broader body of evidence available for carbon black.
EPA has updated the discussion of carbon black's
suitability as an analogue in the final risk evaluation
including the selection of the particular study for
identification of the POD in Section 3.2.3.1 of the final risk
evaluation.
113
As in the Elder et al., (2005) studv, the focus should be on
particle retention kinetics, but in the whole respiratory tract,
with special attention given to examining the potential for
pulmonary inflammation and histopathology, as well as the
standard evaluation of systemic toxicity in other tissues.
While there are notable differences in the respiratory
systems of rodents and humans, these have received much
attention with other chemical substances. The lessons
learned can be applied in this case.
EPA has updated the discussion of the effects from
inhalation exposure to include additional discussion about
the potential for pathological effects such as pulmonary
inflammation, increased BAL cell numbers, and increased
polymorphonuclear leukocytes. Please refer to Section
3.2.3.1 of the final risk evaluation.
113
Some of the inhalable PV29 particles are nanoscale.
Nanoscale particles have the propensity to be translocated
systemically or to the brain, circumventing the blood-brain
barrier (e.g., (Oberddrster et al.. 2009)). Some types of
EPA agrees and has added a discussion in the final risk
evaluation of potential for nanoscale exposures to PV29
with unknown consequences in the hazard characterization
uncertainty analyses. The Elder (2005) studv did not assess
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nanoparticles have significant toxicity potential beyond lung
inflammation and pathogenesis and could pose other risks of
concern if there is sufficient exposure.
the systemic effects or the upper respiratory tract effects.
Similarly, the referenced study by Oberdorster did not
specifically assess the potential for blood-brain barrier
transfer of PV29 (Oberdorster et al.. 2009). This studv does
not provide direct evidence of this phenomenon in PV29
and the EPA has no reason to assume that the
organometallic nanoparticle compounds with distinct
update mechanisms such as those referenced in the study
would demonstrate this for PV29, which is a nonmetallic
particle.
113
EPA reconsidered the appropriateness of barium sulfate as a
surrogate to PV29 for purposes of evaluating potential
pulmonary system damage and lung overload. Instead, EPA
selected carbon black, which has particle sizes closer to
those of PV29, to understand the risks from inhalation of
PV29 dust. EPN agrees with this decision because smaller-
size particles could lead to a greater potential for toxicity,
and carbon black is more similar than barium sulfate to
PV29 with respect to this and other characteristics
EPA acknowledges the comment. Please see Section
3.2.3.1 of the final risk evaluation for the most updated
approach regarding the use of carbon black as an analogue.
113
EPN supports the unreasonable risk determination to the
health of workers for 11 of PV29's 14 COUs based on
EPA's selection of Elder's (2005) toxicitv studv of carbon
black to assess inhalation effects of PV29.
EPA acknowledges the comment. Please see Section
3.2.3.1 of the final risk evaluation for the most updated
approach regarding the use of carbon black as an analogue
and the unreasonable risk determinations for PV29.
110
Based on new information showing that PV29 particles are
significantly smaller and more capable of lung toxicity than
previously believed, EPA has selected carbon black as an
appropriate surrogate for PV29 and used rodent sub-chronic
studies on this substance to determine the risk of harmful
lung effects to PV29-exposed workers. This is a sound and
defensible approach. The suitability of carbon black as an
analogue, evidence that PV29 dust contains particles of
respirable size, and findings of severe lung damage in
Please see Section 3.2.3.1 of the final risk evaluation for
the most updated approach regarding the use of carbon
black as an analogue and the unreasonable risk
determinations for PV29.
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studies on carbon black all weigh strongly in favor of
providing additional protection to workers from the
disabling consequences of lung overload - a goal that can be
accomplished by making an unreasonable risk determination
for PV29 based on these effects and triggering risk
management under section 6(a) of TSCA.
l.iinu Cancer I-llccls of Carbon lilaek
113
EPA's conclusion that PV29 is not likely to be
carcinogenic is contradicted by the observed carcinogenicity
of carbon black in rodent studies. If this substance is an
appropriate analogue to PV29 with regard to lung toxicity,
then it must also be used to evaluate other health effects. As
carbon black is a carcinogen when inhaled, PV29 should be
assumed to be one, too.
EPA asserts that there is insufficient information for PV29
to classify it as a carcinogen. EPA has added a discussion
to the hazard characterization and uncertainty section
(Section 3.2.3.2 of the final risk evaluation) concerning
potential carcinogenic effects of the carbon black analogue.
Tumors were not observed in the Elder et al.. (2005) studv
of carbon black used to identify the POD. The relevance of
particle overload to humans, and even to species other than
laboratory rats and mice, is not clear.
While it likely to be of little relevance for most "real
world" ambient exposures of humans, it is of concern in
interpreting some long-term experimental exposure data. It
may also be of concern to humans occupationally exposed
to some particle tvpes (Mohr et al.. 1994), since overload
may involve all insoluble materials and affect all species if
the particles are deposited at a sufficient rate (Pritchard.
1989). i.e., if the deposition rate exceeds the clearance rate.
In addition, the relevance to humans is also clouded by the
suggestion that macrophage-mediated clearance is
normally slower and perhaps less important in humans than
in rats (Morrow. 1994). and that there will be significant
differences in macrophage loading between the two
species. The inherent toxicity of the compounds should be
considered as well and there are no chronic oral or
inhalation studies available for PV29. EPA calculated the
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HEC values for both the Elder et al.. (2005) sub-chronic
and Nikula et al., chronic inhalation studies. In
comparison, the Elder study female rat NOAEC HEC is
0.28 mg/m3 or 8 times lower than the Nikula female rat
LOAEC HEC of 2.23 mg/m3. The Elder et al., (2005) study
LOAEC HEC in female rats is a similar value of 1.95
mg/m3. Lung cancer hazard is not anticipated at
concentrations in which chronic active inflammation and
cell proliferation are not present. Additional
characterization has been added to the risk evaluation on
this topic.
If, indeed, the two substances have similar characteristics as
EPA concluded, PV29 and carbon black should be deemed
While EPA considers the noncancer effects of lung
overload such as inflammation and hyperplasia observed in
carbon black studies to be relevant to PV29, EPA did not
conclude the same for lung tumor formation. As discussed
in Section 3.2.3.2 of the final risk evaluation, the NOAEC
value of 1.1 mg/m3 from Elder et al.. (2005). used to
calculate the HEC of 0.28 mg/m3 is below the LOAEC
HEC of 2.23 mg/m3 where tumor formation and precursor
events such as lung hyperplasia, fibrosis were observed
(Elder et al.. 2005; Nikula et al.. 1995). EPA has added a
discussion to the hazard characterization and uncertainty
section of the final risk evaluation (see Section 3.2.3.2)
concerning potential carcinogenic effects of the carbon
black analogue.
113
to share not only physical-chemical and particle size and
dimension characteristics, but also toxicity profile
characteristics, including carcinogenicity.
119
The available data for PV29 does not meet an acceptable
level to indicate a lack of carcinogenicity. An analysis of
PV29 through ToxTree provides a structural alert for PV29
given its structural similarity to PAHs. A more
comprehensive genotoxicity evaluation is necessary to
address this structural flag. Additionally, there are many
EPA has determined that inhalation of PV29 is not likely to
produce carcinogenic effects as a result of genotoxicity or
inhalation of particles. EPA calculated the HEC values for
both the Elder and Nikula studies (Elder et al.. 2005;
Nikula et al.. 1995). In comparison, the Elder et al., (2005)
study female rat NOAEC HEC used in the risk calculation
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potential mechanisms by which cancer may arise beyond
genotoxicity and clastogenicity. For example, PV29 could
potentially present a concern for inhalation carcinogenicity
due to chronic inflammation resulting from particle
deposition. It is worth highlighting that the surrogate
proposed by EPA, carbon black, is classified by IARC as a
potential human carcinogen. Further studies are required
before EPA can conclude that PV29 lacks carcinogenicity
potential.
is 0.28 mg/m3 or 8 times lower than the Nikula (1995)
female rat LOAEC HEC of 2.23 mg/m3 where tumor
formation and cancer precursor events were observed. The
Elder study LOAEC HEC in female rats is a similar value
of 1.95 mg/m3. Lung cancer hazard is not anticipated at
concentrations in which chronic active inflammation and
cell proliferation are not present. Additional
characterization has been added to the risk evaluation on
this topic. Neither tumors, nor tumor precursor events were
observed at the rat NOAEC in the Elder et al.. (2005) with
carbon black that was used to identify the POD. in Section
3.2.3.2 of the final risk evaluation discussion regarding
carcinogenicity of PV29.
111
.. .the data on Pigment Violet 29 and this analogue [carbon
black] are inadequate to conclude that Pigment Violet 29 is
not a carcinogen.
Please see the previous comment as well as Section 3.2.3.2
of the final risk evaluation for additional discussion of the
carcinogenicity of PV29. EPA asserts that based on
available data, both genotoxic and based on tumor
formation observed in studies with the carbon black
analogue, PV29 lung cancer hazard is not expected. EPA
has added a discussion to the hazard characterization for
PV29 in Section 3.2.3.2 concerning potential carcinogenic
effects of the carbon black analogue as they relate to PV29.
Neither tumors, nor tumor precursor events were observed
at the level of the rat NOAEC reported in the Elder et al.,
(2005) studv with carbon black that was used to identify
the POD.
110
While relying on the carbon black database to assess
PV29's lung toxicity, EPA's revised draft incorrectly
reaffirms its earlier conclusion that PV29 lacks
carcinogenicity potential. This conclusion ignores the fact
that that carbon black has produced lung tumors in animal
studies and is classified as a likely carcinogen by the
International Agency for Research on Cancer (IARC). The
Please see the previous comments as well as Section
3.2.3.2 of the final risk evaluation for additional discussion
of the carcinogenicity of PV29. EPA asserts that based on
available genotoxic and carbon black analogue data, PV29
lung cancer hazard is not expected. EPA has added a
discussion to the hazard characterization for PV29 in
Section 3.2.3.2 concerning potential carcinogenic effects of
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mechanism for carbon black carcinogenicity in rodents -
impaired lung clearance resulting in particle accumulation
and inflammation - is the same mechanism EPA has
identified for its non-cancer lung toxicity. If EPA believes
that carbon black is an appropriate surrogate for PV29 for
one endpoint, it should be a surrogate for other endpoints
involving the same target organ and mechanism of action.
While additional testing may well provide further insight
into PV29's carcinogenicity, the extensive data-base on
carbon black now supports a determination of elevated
cancer risk from inhalation exposure to PV29. EPA should
include this determination in its final evaluation and, as it
has done for non-cancer lung effects, use the carbon black
cancer studies to estimate cancer risk to PV29-exposed
workers.
the carbon black analogue as they relate to PV29. Lung
cancer hazard is not anticipated at concentrations in which
chronic active inflammation and cell proliferation are not
present. Neither tumors, nor tumor precursor events were
observed at the rat NOAEC in the Elder et al., (2005) studv
with carbon black that was used to identify the POD.
Potentially Imposed or Susceplihie Siihpopulalions
119
EPA's reliance on Stark et al., 2013 to assert a lack of
increased susceptibility for any subpopulation is entirely
inappropriate. Stark et al., 2013 is a gavage study that does
not examine pulmonary effects resulting from inhalation of
PV29—a primary concern identified by EPA. The millions
of individuals in the U.S. with respiratory conditions are
undeniably a relevant susceptible subpopulation and EPA's
risk evaluation of PV29 must reflect the risks to these
individuals.
The OECD 421 reproductive-developmental study did not
detect significant effects at the limit dose of 1000
mg/kg/day. However, oral data may not adequately address
concerns via the inhalation route. EPA believes that the
information provided in the Stark et al., ( ) study
provides adequate evidence that additional chronic oral
toxicity data are not needed, as the information provided in
the reproductive and developmental screening study do not
indicate that toxicity following chronic oral exposures to
PV29 is not expected.
111
EPA does not have sufficient evidence to determine that
Pigment Violet 29 does not have reproductive/
developmental toxicity due to the methodological
inadequacy of BASF's test protocol, the unjustified
dismissal of potentially impactful findings in its study, and
the lack of power of the OECD 421 screening method to
determine lack of toxicity.
The OECD 421 reproductive-developmental study did not
detect significant effects at the limit dose of 1000
mg/kg/day. As indicated in earlier comments, EPA
believes that the information provided in the Stark et al.,
) study provides adequate evidence that additional
chronic oral toxicity data are not needed, as the
information provided in the reproductive and
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developmental screening study do not indicate that chronic
toxicity is expected to result from oral exposure to PV29.
111
EPA still fails to consider pregnant workers and consumers
who are at higher risk, despite listing them as a PESS.
The OECD 421 reproductive-developmental study did not
detect significant effects at the limit dose of 1000
mg/kg/day. The inhalation POD is based on the effects of
the analogue carbon black on the lungs (alveolar
inflammation & hyperplasia, etc). The physical-chemical
properties of carbon black and PV29 indicate that they are
insoluble and not likely to be absorbed into the
bloodstream via the lungs and therefore not distributed
throughout the bloodstream so the potential to cross the
placenta and expose the fetus of a pregnant worker or
consumer is negligible.
I-PA l-'uils lo Apply All Rdc\ anl I ncu'lainly I'aclors in Chaiacluixinu PY2lJ Risk
EPA applies only the following uncertainty factors in
deriving a point of departure when characterizing the risks
of PV29
EPA has updated its justification for the use of uncertainty
factors in Section 4.2.1 of the final risk evaluation. EPA
has utilized an Animal-to-Human uncertainty factor (UFa)
of 3 and an Inter-individual uncertainty factor (UFh) of 10.
119
Animal-to-Human extrapolation (UFA) - 3 (to account for
toxicodynamic variability)
Inter-individual variation (UFH) - 10
By EPA's own admission the MPPD model only accounts
for a portion of toxicokinetic uncertainty. In the absence of
any measured toxicokinetic data on PV29, the UFA
uncertainty factor should be revised to 10.
EPA also argues that a sub-chronic to chronic uncertainty
factor is unnecessary because "the available information in
animal studies support pulmonary system effects at similar
concentrations following chronic exposures to carbon black
particles" and "...[EJxposures in longer-term animal studies
EPA disagrees that it is necessary to increase the UFa from
3 to 10. The UFa accounts for the uncertainties in
extrapolating from rodents to humans. In the absence of
data, the default UFa of 10 is adopted which is the product
of a factor of 3 for toxicokinetic variability and a factor of
3 for toxicodynamic variability. There is no PBPK model
for PV29 to account for the interspecies extrapolation
using rodent toxicokinetic data in order to estimate internal
doses. In this assessment, a portion of the interspecies
uncertainty is accounted for by use of the RDDR model for
estimating the deposited particle fraction in the alveolar
region of the lung (internal dose) which accounts for
toxicokinetics, thereby reducing the factor for toxicokinetic
variability from a 3 to a factor of 1. An UFa of 3 is retained
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are not reasonably expected to cause equivalent nervous
system effects at a lower concentration than the 13-day
study by Elder et al., (2005)" (p. 72). This rationale is an
unsupported assertion and is incorrect. As described in
subsection C., the ECHA dossier for PV29 describes a 2-
year rat study of carbon black in which effects were
observed at concentrations lower than the POD EPA
selected from the Elder et al. 2005 study. The dossier notes:
Severe lung damage (including lung tumours) was seen in
Fischer 344 rats of both sexes exposed for 2 years to 2.5 and
6.5 mg/m3 (16 hrs/day, 5 days/week) (see section on
carcinogenicity for full details). The lung weights of all
exposure groups increased in an almost linear manner
throughout the exposure period. Exposure-related lesions
consisted of alveolar macrophage hyperplasia, alveolar
epithelial hyperplasia, chronic-active inflammation, septal
fibrosis, alveolar proteinosis, bronchiolar alveolar
metaplasia, focal fibrosis with alveolar epithelial
hyperplasia, squamous metaplasia and squamous cysts
(Nikula etal 19951
EPA reliance on Elder et al. 2005 requires at a minimum
that the agency apply a sub-chronic to chronic uncertainty
factor of 10 barring more robust data.
Lastly, given the dearth of available data for PV29, in
particular for inhalation toxicity, EPA should include an
additional uncertainty factor of 10 for database uncertainty.
The Elder et al. 2005 study, for example, did not examine
potential effects in the upper respiratory system. EPA is
relying on analog data (carbon black) exclusively to
characterize inhalation toxicity for PV29 and the uncertainty
engendered by this decision on top of lack of any inhalation
to account for toxicodynamic differences between the test
species and humans. Several non-carcinogenic effects
associated with the inhalation exposure of carbon black
(the analogue for PV29), including alveolar hyperplasia,
inflammation and morphological changes in the lungs of
rats, mice and hamsters, are adverse effects considered by
EPA to be relevant to humans and require the retention of
the UFa of 3 for toxicodynamics for use in this final risk
evaluation.
Similarly, EPA disagrees that an additional uncertainty
factor to account for sub chronic to chronic duration is
necessary; and a UFs of 1 was used by EPA in this final
risk evaluation. EPA considered the chronic toxicity study
bv Nikula et al., (1995) cited bv the commenter, and has
included a discussion of that paper in the final risk
evaluation in Section 3.2. However, the Nikula et al.,
(1 °°5) study was not used for selection of the POD
because, although the LOAEC was lower (2.5 mg/m3)
compared to the Elder study (7.6 mg/m3), a NOAEC was
established in the Elder study (1.1 mg/m3) which provides
a lower POD and more certainty regarding the threshold of
effects. Using the LOAEC in the Nikula et al., (1995)
study would require the incorporation of additional UF
because a NOAEC was not established. Specifically, the
rat NOAEC HEC of 0.28 mg/m3 for PV29 risk calculations
are based on the no-effect concentrations for precursor
events such as inflammation and hyperplasia in the Elder et
al., (2005) studv, thus, a POD for downstream events in a
longer duration study is not warranted, and a UFs of 1 was
utilized by EPA in this final risk evaluation.
Similarly EPA is not including an uncertainty factor for the
conversion of a LOAEL to a NOAEL. The noncancer POD
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toxicity data for PV29 itself warrants the application of a
database uncertainty factor.
for the carbon black analogue for PV29 is a NOAEC.
Therefore, a UFl of 1 is used by EPA in this final risk
evaluation.
There is no universal list of hazard data required when
evaluating chemical risks under TSCA. Furthermore, for
PV29, EPA has sufficient, hazard data and included the
use of an analogue to support the use of the chosen hazard
endpoints and conduct the risk evaluation. Therefore, EPA
did not use a database uncertainty factor in the PV29 risk
evaluation.
While EPA acknowledges the uncertainty introduced by
using an analogue to estimate the risks of PV29, the
assessment uses many highly conservative assumptions in
its risk calculations and additional uncertainty factors
beyond those that are presented in the final risk evaluation
are not needed.
113
The uncertainty factors (UFs) EPA has used to determine its
Benchmark MOE of 30
are inadequate; a more defensible Benchmark MOE would
be at least 1,000 and, arguably, 3,000
because of lack of data on PV29 itself. As a result, EPN is
concerned that the updated EPA evaluation still understates
PV29's risk to workers.
EPA disagrees that use of a benchmark MOE of 30 is
inadequate. Please see the previous comment for a
discussion of the uncertainty factors used in the final risk
evaluation to determine the benchmark MOE and EPA's
rationale for selecting the uncertainty factors. Additional
discussion about these UFs is available in Section 4.2.1.
111
EPA's use of a hazard test is unsuitable for use in risk
assessment, and fails to account for numerous uncertainties,
such as potential differences between inhalation and oral
exposure routes. Further, EPA should not use MOE (Margin
of Exposure) as an analysis method in the risk evaluation
process.
EPA has updated its approach to utilize analogue toxicity
data characterizing inhalation hazards from PV29 instead
of using a route-to-route extrapolation approach presented
in earlier versions of the risk evaluation.
110
Although we support EPA's proposed unreasonable risk
determination for PV29, we are concerned that EPA's
EPA disagrees that use of a benchmark MOE of 30 is
inadequate. Please see the previous comment for a
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methodology for calculating Margins of Exposure (MOEs)
systematically understates the magnitude of PV29's risks to
workers in two respects: (1) the uncertainty factors (UFs)
EPA has used to determine its Benchmark MOE of 30 are
inadequate and, properly calculated, would require a
Benchmark MOE of at least 3,000 and arguably 10,000; and
(2) EPA has improperly increased its MOEs to account for
the protection provided by respirators despite the limited
evidence for respirator use at PV29 manufacturing and
processing facilities and the Agency's misinterpretation of
OSHA policies and regulations to require respiratory
protection for PV29 exposure. If these flaws were corrected,
MOEs would be well below the benchmark MOE for high-
end and central-tendency exposure scenarios and two of the
three median particle sizes for all 14 of the PV29 conditions
of use. Thus, an unreasonable risk determination would be
required for all PV29 uses.
discussion of the uncertainty factors used in the final risk
evaluation to determine the benchmark MOE and EPA's
rationale for selecting the uncertainty factors. Additional
discussion about these UFs is available in Section 4.2.1.
113
EPA's rationale for selecting a UFsof 1 to account for
extrapolation from a subchronic to chronic exposure
duration is unconvincing, particularly in light of identifying
a potential for carcinogenicity following long-term
inhalation exposure to the surrogate, carbon black. In this
instance, the UFS should be at least 3.
EPA disagrees that use of a benchmark MOE of 30 is
inadequate. Please see the previous comment for a
discussion of the uncertainty factors used in the updated
risk evaluation to determine the benchmark MOE and
EPA's rationale for selecting the uncertainty factors.
Additional discussion about these UFs is available in
Section 4.2.1.
113
EPA selected a UFA of 3 to account for animal-to-human
extrapolation, stating that a portion of the toxicokinetic
component of this extrapolation may be accounted for by
use of the MPPD model for estimating the retained particle
fraction in the alveolar region of the lung, and converting
the animal dose (1 mg/m3) to a Human Equivalent
Concentration (HEC). There is nothing in the text or
appendices that describes and illustrates mathematically the
derivation of HEC, particularly the one which should be
EPA disagrees that use of a benchmark MOE of 30 is
inadequate. Please see the previous comment for a
discussion of the uncertainty factors used in the final risk
evaluation to determine the benchmark MOE and EPA's
rationale for selecting the uncertainty factors. The
calculation of the HEC from the RDDR model is available
in Section 3.2.3. Additional discussion about these UFs is
available in Section 4.2.1.
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serving as the POD in determining whether or not the MOE
for each COU is adequate. This assessment step needs better
documentation in the text - it was initially thought that this
step had not been performed and only discovered by
accident.
113
We are in agreement that the Inter-individual variation UFh
should remain at 10.
EPA acknowledges the comment.
113
There is a missing UF that accounts for data deficiencies
(UFd) OPPT claims they don't use this UF, however the
omission runs counter to agency guidance in (
2002) and (U.S. EPA. 2005). In this case, the database for
PV29 is so lacking that this UF should be set to its
maximum default of 10X.
EPA does not utilize a database uncertainty factor in its
risk evaluations as a matter of policy. Please see previous
comment for discussion of the lack of EPA using a
database uncertainty factor. There is no universal list of
hazard data required when evaluating chemical risks under
TSCA. Furthermore, for PV29, EPA has sufficient,
reasonably available hazard data and included the use of an
analogue to support the use of the chosen hazard endpoints
and conduct the risk evaluation. Therefore, EPA did not
use a database uncertainty factor in the PV29 risk
evaluation.
113
Calculating the total Uncertainty Factor results in a
Benchmark MOE of at least 1,000,or 3,000, if one employs
the full default for extrapolation of subchronic data to a
chronicexposure scenario.
As discussed above, EPA disagrees that an additional
uncertainty factor to account for subchronic to chronic is
necessary. Specifically, the ratNOAEC HEC of 0.28
mg/m3 for PV29 risk calculations are based on the no-
effect concentrations for precursor events such as
inflammation and hyperplasia in the Elder et al.. (2005)
study, thus, a POD for downstream events in a longer
duration study is not warranted, and a UFs of 1 was utilized
by EPA in this final risk evaluation.
113
With a more appropriate Benchmark MOE of 1,000, there
are no acceptable MOEs for workers without respirators for
any COU; no acceptable MOEs for Occupational Non-Users
(ONUs) without respirators, except those with central
EPA disagrees that use of a benchmark MOE of 30 is
inadequate. Please see the previous comment for a
discussion of the uncertainty factors used in the updated
risk evaluation to determine the benchmark MOE and
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tendency exposures to the 46.4 ug/m3 particle size; no
acceptable MOEs to workers using Assigned Protection
Factor (APF) 10 or 25 Personal Protective Equipment
(PPE), except those with central tendency exposures to the
46.4 ug/ m3 particle size; and no acceptable MOEs for
workers using APF 50 PPE, except those with high-end or
central tendency exposures to the 46.4 ug/m3 particle size.
With a Benchmark MOE of 3,000, there are no acceptable
MOEs for any COU except for workers using APF 50 PPE
with central tendency exposures to the 46.4 ug/m3particle
size.
EPA's rationale for selecting the uncertainty factors.
Additional discussion about these UFs is available in
Section 4.2.1 of the final risk evaluation. EPA
acknowledges that changing the MOEs would result in
different risk determinations, but using the benchmark
MOE of 30 still results in unreasonable risk determinations
for 10 conditions of use.
Point of Departure
113
The POD is generally defined as the measured or modeled
dose administered in a toxicity study that did not result in
adverse effects of concern. In Table 4-1 on page 71 of the
revised draft, EPA presents a POD of 1.0 mg/m 3 as the
NOAEC based upon the "lung particle increased burden and
inflammation" at the next higher dose (7.6 mg/m3) reported
in the Elder et al. (2005) study. Respiratory tract particle
burden is NOT a measure of toxicity. It is a measure of
exposure dosimetry. If 1 mg/m3 is the highest dose at which
no adverse changes such as inflammatory and
morphological changes in the lungs are observed, then that
dose is the appropriate NOAEC to serve as the POD (once
converted to an HEC). Whether or not there is coincident
particle overload is irrelevant.
EPA has updated its approach to convert the NOAEC into
an HEC and describe effects in terms of physiological
effects rather than in terms of kinetic lung overload.
Risk I'Slimalion and Characterization
113
We agree with Ecological Structure Activity Relationships
(ECOSAR) (ver. 2.0) guidance for predicting acute and
chronic effects to aquatic organisms that PV29 may not be
sufficiently soluble to measure predicted effects for each
EPA agrees with the comment and has made no change to
this analysis in the final risk evaluation
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species, and that, if effect levels exceeded the water
solubility by 10-fold, typically "no effects at saturation" is
reported. This approach is consistent with standard practices
in the testing industry.
113
Given its low solubility in water, its limited environmental
releases, and lack of environmental hazard, EPA determined
that PV29 does not present an unreasonable risk to aquatic
species in the water column and sediment, and to terrestrial
species. We agree with EPA's determination that there is no
unreasonable risk of injury to the aquatic and terrestrial
environment from all conditions of use of PV29.
EPA agrees with the comment and has made no change to
this analysis in the final risk evaluation
113
Based on PV29's low vapor pressure and volatility and low
solubility, exposures to terrestrial species through air and
water are not expected, so risk concerns for terrestrial
species are not identified.
EPA agrees with the comment and has made no change to
this analysis in the final risk evaluation
113
Given the expanded discussion in the revised draft risk
evaluation, we agree with the agency's assessment that no
adverse effects were observed in results from laboratory
testing for acute exposure to microorganisms, aquatic
plants, aquatic invertebrates, and fish up to the limit of
PV29 solubility, 3 (J,g/L.
EPA agrees with the comment and has made no change to
this analysis in the final risk evaluation
113
On Page 75 of the document, EPA states "Because the
exposure estimates and hazard assessment for inhalation
exposures to C.I. Pigment Violet 29 are considered to be of
high uncertainty and low confidence, the confidence in the
risk estimation is considered to be low."
EPN agrees with this conclusion but believes that there is an
adequate basis for a determination of unreasonable risk.
EPA should require additional studies to provide greater
certainty in its risk estimates.
EPA believes that sufficient data (both hazard and physical
chemical property data) exist for PV29 to make a
determination that risks are not expected for environmental
receptors under the conditions of use of this risk
evaluation.
I-PA Lacks Critical Data
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105
Solubility: CPMA defines color pigments as colored or
fluorescent particulate organic or inorganic solids that
usually are insoluble in, and essentially physically and
chemically unaffected by, the vehicle or substrate in which
they are incorporated. This insolubility is key to the
functioning of color pigments, which as noted earlier retain
a crystalline or particulate structure in the larger matrix in
which they are encapsulated and impart color by selective
absorption or by scattering of light. The revised draft finds
that the solubility tests performed under the Section 4 test
order "confirm that C.I. Pigment Violet 29 is an insoluble
particulate substance; that there is no expectation that C.I.
Pigment Violet 29 will be taken up by fat solubility; and
confirms that C.I. Pigment Violet 29 is not expected to
bioaccumulate." These test results thus confirm previous
findings regarding other color pigments. Taken together
with those other findings, they add further support to the
weight of evidence conclusion that color pigments, in
general, are not bioavailable, do not bioaccumulate and do
not bioconcentrate in the food chain, due to their extremely
low solubility, in both lipids and water.
EPA agrees with this comment and has presented similar
points in the final risk evaluation.
119
Data voluntarily submitted to EPA by manufacturing
stakeholders is insufficient and speaks volumes about the
limitations faced by EPA when it relies on voluntary
information requests instead of using its TSCA authorities
to require companies to submit such information
EPA acknowledges the comment on information
collection. In February 2020 EPA did use its TSCA
authority to collect new data on PV29. The Section 4 Test
Order required solubility in water, solubility in octanol and
inhalation monitoring at the manufacturing facility tests.
Results from these data are discussed in the final risk
evaluation.
106
The revised draft risk evaluation sets a problematic
precedent for chemicals manufactured in batch processes,
with respect to the monitoring data test order. It is not
reasonable to expect workplaces to conduct sampling for
Prior to the initiation of any testing, EPA recommends
engaging in discussions to clarify any uncertainties and
ensure that the testing plan accounts for all limitations in a
mutually agreeable manner. In the case of the NIOSH 0600
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periods longer than are required by NIOSH 0600. To
assume otherwise would bias the risk evaluation process
whenever chemicals are manufactured in batch processes.
test conducted by Sun Chemical, several deficiencies were
identified in the final study that were not identified in the
study plan or properly communicated to EPA. These issues
resulted in significant uncertainties in the study that
impacted the usability of the results of this study.
106
Sun Chemical went to great expense to comply with the
Section 4 test order. It is surprising and unfortunate that
EPA propose not to use some of the information generated
by the test order. The final risk evaluation should
incorporate all of the test results, not just the results of the
solubility testing. That "employees.. .only spent a fraction of
their shift (approx. 0.5-2 hrs) actually handling [PV29]" is
not a "deficiency" of the study, it is an unavoidable
condition of batch manufacture.
These issues were not communicated to EPA prior to the
initiation of the test. These resulted in significant
uncertainties that impacted the utility of the testing. EPA is
utilizing the information presented in the dust monitoring
study but because of deficiencies with the study, EPA
needed to make several assumptions in order to understand
the potential exposures during a full work shift. Prior to the
initiation of any testing, EPA recommends engaging in
discussions to clarify any uncertainties and ensure that the
testing plan accounts for all limitations in a mutually
agreeable manner.
106
EPA's risk evaluation needs to accommodate the
commercial reality that batch manufacturing allows
facilities to maintain flexible and responsive commercial
operations to handle specialized chemistries and meet
diverse customer demands.
Prior to the initiation of any testing, EPA recommends
engaging in discussions to clarify any uncertainties and
ensure that the testing plan accounts for all limitations in a
mutually agreeable manner. In the case of the realities of
batch manufacturing, as EPA indicated in its review of the
final respirable dust monitoring study provided by Sun
Chemical (available in Appendix I of the final risk
evaluation), extending the respirable dust collection period
beyond the activities where PV29 was being produced
would have allowed EPA to adequately characterize full
shift exposure without needing to rely on the assumptions
outlined in the exposure section of the final risk evaluation
(see Section 2.3.1 of the final risk evaluation).
106
EPA's assumption that the unsampled portion of the work
shift had the same average exposure to PV29 as the sampled
portion overestimates potential exposure. This approach is
As indicated above, the deficiencies of the NIOSH 0600
respirable dust monitoring study conducted by Sun
Chemical meant that EPA needed to make several
assumptions to model the potential full-shift exposure to
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incorrect and inconsistent with standard industrial hygiene
practice for this type of batch process operation.
PV29. If the study authors extended the sampling period
beyond the times where PV29 was being manufactured, it
would have provided a quantitative estimate of exposure.
Instead, in the absence of such data, EPA assumed that
potential exposure reported in the monitoring study
extended throughout the length of the shift. The only
alternate assumption, the exposure between batches of
PV29 is essentially zero, is not appropriate because it
would ignore the presence of ambient dust, as well as
reaerosolization of workplace dusts from activities such as
cleaning. Additional information, as well as a full review
of the respirable dust monitoring study with a full
discussion of the deficiencies is available as an Appendix I
of the final risk evaluation.
119
Based on ECHA-REACH recommendations, toxicokinetic
studies as well as static and dynamic dissolution assays
should be performed to support their claims of poor
absorption and low bioavailability. Solubility is not
sufficient to make a determination of a lack of
bioavailability via oral and dermal pathways.
While toxicokinetic studies as well as static and dynamic
dissolution assays are optimal studies to understand the
potential for these processes to occur, the solubility studies
available for PV29 are sufficient to make a determination
that solubility and bioavailability are low for PV29.
113
EPN disagrees with EPA's argument that, because of its
purported lack of solubility, PV29 lacks the potential for
inducing acute and chronic health effects (with the
exception of lung toxicity following inhalation based upon
its comparison with carbon black). The evidence of
insolubility is not clear-cut; there are suggestions of toxicity
in the limited number of studies on PV29, and it cannot be
assumed that insolubility definitively rules out the
possibility that PV29 will be distributed to tissues and
organs within the body and cause toxic effects, especially
when inhaled. EPA therefore lacks a basis to determine that
PV29 is without health effects other than lung toxicity
following inhalation and must require testing to make
EPA acknowledges the commenter's request for a 90-day
subchronic study on PV29 in the TSCA Section 4 Test
Order; however, the test was not requested by the Agency
because the Agency believes that the risk evaluation could
still be completed without the information, as reasonably
available data are sufficient to make a risk determination.
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informed judgments on the issue. At a minimum, required
testing should include a 90-day subchronic inhalation study
along with appropriate shorter-term in vivo and/or in vitro
studies designed to characterize the mode of action of the
lung effects and examine the potential for carcinogenicity.
119
EPA lacks acute inhalation toxicity studies for PV29, since
the two identified in the ECHA database were found to be
unacceptable. EPA should require acute, sub-acute, and
chronic inhalation toxicity studies of PV29.
EPA acknowledges the commenter's request for a 90-day
subchronic study on PV29 in the TSCA Section 4 Test
Order; however, the test was not requested by the Agency
because the Agency believes that the risk evaluation could
still be completed without the information, as reasonably
available data are sufficient to make a risk determination.
111
EPA still does not have adequate information to conclude
that Pigment Violet 29 does not pose an unreasonable risk
and still failed to assess all relevant health hazards.. .Using
its full authorities under TSCA sections 4 and 8, EPA must
request additional test data (compliant with established
standards) to fill critical health data gaps for Pigment Violet
29.
EPA acknowledges the commenter's request for additional
information; however, the Agency believes that the risk
evaluation could still be completed without the
information, as reasonably available data are sufficient to
make a risk determination.
111
EPA still assumes that Pigment Violet 29 is non-toxic and
not absorbed via inhalation without providing adequate
empirical data to support such assumptions.
Additional data generated as a result of the Section 4 test
order provides additional evidence that solubility in both
octanol and resulting absorption potential is low. EPA is
using carbon black as an analogue for PV29 which has
adverse effects in the lower respiratory tract.
110
In our initial comments, we argued that the many data-gaps
for PV29 required EPA to use its TSCA section 4 authority
to reliably characterize its toxicological properties.
Unfortunately, the revised draft evaluation continues to
dismiss concerns for any health endpoint other than
inhalation toxicity on the unsupported basis that PV29's
purported lack of solubility and bioavailability prevent its
systemic absorption and distribution throughout the body. In
fact, PV29's insolubility has not been clearly established by
EPA acknowledges the commenter's request for additional
information; however, the Agency believes reasonably
available data are sufficient to conduct a risk evaluation
and make a risk determination. The EPA has determined
that the studies indicated by the commenter are not
necessary because EPA has sufficient data to reach a
conclusion regarding the potential absorption, uptake, and
inhalation effects of PV29. As indicated in the final risk
evaluation, these effects are characterized through the
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available studies and in any case lack of solubility is
insufficient in itself to rule out uptake of PV29 and systemic
toxicity. We therefore urge that EPA use its section 4
authority to require studies to (1) examine whether there is
absorption and uptake of PV29 by all routes (oral, dermal
and inhalation) and, if so, whether PV29 causes systemic
toxicity, and (2) further elucidate PV29's cancer and non-
cancer inhalation effects by testing PV29 directly for these
endpoints Once this testing is completed, a supplemental
risk evaluation and/or additional risk management may be
warranted. In the interim, EPA should finalize unreasonable
risk determinations for PV29 based on the known lung
toxicity and carcinogenicity of the carbon black surrogate
solubility information provided in response to the Section 4
test order, which confirms the low solubility of PV29 in
water and octanol, as well as the toxicity information
available on the analogue carbon black.
121
EPA's proposed determination of no unreasonable risk to
the environment from all uses of Pigment Violet 29 is based
on limited analysis, fails to examine chronic impacts of a
persistent chemical, and relies on a broad assumption that
environmental releases and concentrations are limited.
EPA disagrees with the comment. EPA has sufficient data
to determine that, under the conditions of use in the risk
evaluation, environmental risks are not identified. In
Section 3.1 of the final risk evaluation, EPA incorporated
modeling approaches to confirm the preliminary
conclusions from the draft risk evaluation.
121
EPA's proposed determination of no unacceptable risks to
the public and to consumers is not supported by adequate
testing or monitoring data and not based on a
comprehensive assessment of potential exposures to
Pigment Violet 29 from products, building materials, and
the environment.
Monitoring of PV29 exposure to the public is not necessary
because of the few consumer products available and the
nature of the pigment in these products. As discussed in the
final risk evaluation, use of finished plastic or rubber
products containing PV29 are not expected to result in risk,
as the pigment particle is confined to a matrix such as
plastic or rubber, thereby making it unlikely to leach out.
The only activities where potential risks are expected as a
result of PV29 uses are activities where PV29 is handled
directly as a powder or spray applied as part of a paint, or
if the pigment is released during sanding of automotive
paints. EPA did not identify uses of PV29 in building
materials.
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121
EPA's apparent focus on respirators to mitigate
occupational exposure risks from use of Pigment Violet 29
is not adequately informed by comprehensive toxicological
testing or by exposure assessments in downstream
processing facilities and industrial/commercial sites.
EPA has received information outlining PPE usage by
manufacturing stakeholders of PV29. EPA determined that
this information is suitable to understand the potential PPE
use in a typical production facility. To further understand
potential risks, EPA has calculated risks with and without
PPE.
For most conditions of use of PV29 with an identified risk
for workers, EPA evaluated the use of a respirator.
However, EPA assumes that for some conditions of use,
the use of appropriate respirators is not a standard industry
practice, based on best professional judgement given the
burden associated with the use of respirators, including the
expense of the equipment and the necessity of fit-testing
and training for proper use. For manufacturing, processing,
recycling, and disposal conditions of use, air-purifying
respirators (e.g. half face dust masks) with an APF of 10
were assumed. For one condition of use, paints and
coatings for automobile (e.g., Original Equipment
Manufacturer (OEM) and refinishing), EPA assumed the
use of a supplied-air respirator (continuous flow mode)
with an APF of 25. For the remaining industrial,
commercial, and consumer conditions of use, EPA
assumed no use of a respirator.
The PPE assumptions for all the conditions of use did not
affect the unreasonable risk determinations made. Only
with an assumption of PPE use with APF of 50 would
eliminate unreasonable risk; however, the final risk
evaluation does not use that assumption for any condition
of use.
121
EPA's evaluation of risks to workers during recycling and
disposal of Pigment Violet 29-containing materials is not
EPA has a limited understanding of the potential recycling
activities for PV29. EPA determined that there is potential
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sufficiently detailed to inform its future risk management
determinations. EPA's determination that recycling
(processing) and disposal of Pigment Violet 29 presents
unreasonable risks to human health are of particular interest
to local agencies that provide or contract for these services.
However, the revised draft risk evaluation identifies no
specific data on exposures or Pigment Violet 29 releases in
recycling and waste facilities. Further analysis or direct
testing is needed to verify EPA's assumption that Pigment
Violet 29 remains irreversibly encapsulated in the matrices
of materials during different recycling processes and waste
disposal methods. Without additional analysis, it is unclear
how EPA can develop evidence-based recommendations for
its subsequent risk management actions to ensure workers
are protected and environmental releases are prevented.
for exposure to PV29 if plastic products are recycled
through grinding or milling and PV29 is released. As a
result, EPA made several assumptions to estimate exposure
through these activities. EPA acknowledges that there are
uncertainties with this approach.
I se i>T\lnlliplc-Piilh Particle Dosimetry (MPPD) Model was not Appropriate lor the Risk Ia aluation
105
EPA supported its use of carbon black as a surrogate by
predicting the retained mass in the pulmonary region of rats
using Multiple-Path Particle Dosimetry (MPPD) modeling,
incorporating the characteristics and administered doses of
carbon black in Elder et al. (2005). However, EPA does not
appear to have calculated a relative ratio of the retained dose
for rats relative to humans. As discussed in detail by the
European Centre for Ecotoxicology and Toxicology of
Chemicals (ECETOC), there are critical differences in
particle lung translocation patterns between rats and
humans, and humans are less sensitive to developing
comparable lung overload conditions. Thus, the rat lung
model is an unreliable predictor for risk to the human lung
from chronic exposures to particles.
EPA recognizes that particle overload is a kinetic
phenomenon and not an adverse effect per se. The Agency
has revised the text in the final risk evaluation to provide
this clarification. In addition, the definition of overload and
how it is used to create context for the evaluation of any
observed toxicities has been provided. The final risk
evaluation discusses several other "noncancer" events such
as inflammation and hyperplasia, and how they are relevant
and related to other adverse outcome pathways and should
be evaluated as relevant to humans (U.S. EPA. ^ V
EPA could not calculate a relative ratio of the retained dose
using the MPPD model due to a lack of adequate
information on particle size distribution data for PV29.
Therefore, EPA used the RDDR model instead. However,
this model calculates the deposited dose ratio, not the
retained dose ratio, in various regions of the respiratory
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tract between rats and humans. EPA has updated its
approach to calculate a human equivalent concentration
(HEC) for carbon black in the final risk evaluation utilizing
the RDDR model. The carbon black study compared the
results of rats, mice and hamsters to determine the most
sensitive species after exposure to carbon black via
inhalation. The RDDR model was utilized as a dosimetry
refinement to the risk evaluation since the MPPD model
does not model hamster data in the Elder et al. (2005)
study relative to the rats and mice data.
("151 Delhi Access Issues
113
'I'd obtain heller (and \ alid) partition coefficient data and
particle size information, EPA issued a test order under
TSCA section 4 to obtain new data on PV29's solubility in
water and octanol and exposure data in the work setting.
Information on these parameters was provided. Regrettably,
it is not possible to answer the question of EPA's initial
conclusion of "no unreasonable risk," as the Nicolaou
(2020) study is restricted access (presumably meaning
Confidential Business Information (CBI)) and cannot be
independently evaluated, and the link EPA (2012c) leads to
no data on this chemical. However, even if we had access to
the details of the Nicolaou study, it would not show that
PV29 lacks the potential to produce adverse health effects in
the absence of additional, relevant toxicity testing.
The Nicolaou ( ) sludv contains no confidential
business information. The restrictions on the full study
report and some attachments in the public docket is from
copyright claims. Anyone from the public can request full
access to the restricted documents in the docket's reading
room. Reasonable accommodations as a result of the
pandemic can be arranged on a case-by-case basis by
contacting the reading room staff.
EPA disagrees that this study is not informative of
potential health effects from PV29. While this study is not
a hazard study, the lack of solubility in water and octanol
can inform the potential for absorption from oral, dermal,
and inhalation exposure.
119
EPA has no basis for not providing full public access to the
solubility study (Nicolaou, 2020). The reading room where
the study is available is currently closed due to the global
pandemic.
The reading room is open by appointment only. For further
guidance visit the EPA's reading room webpage:
httDs://www. eDa.gov/dockets/eoa-docket-center-and-
reading-room-closed-oublic-limited-exceotions. Uoon
request, reasonable accommodation can be made for
access.
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105
EPA properly allowed study owners to redact some
confidential business information (CBI).
The owners of 24 toxicological study reports that had
previously been claimed as CBI ultimately allowed EPA to
release the full study reports, evidently to prevent EPA from
refusing to consider them. The revised draft indicates that
for nine reports, however, EPA allowed the redaction of
"personal information relating to laboratory personnel,
certain company-related information and, in one instance,
individual test animal data tables." This is a positive
precedent for future risk evaluations. CPMA has
consistently argued that, even as EPA requires the release of
health and safety data, EPA can and should allow study
report owners to claim as CBI the sort of identifying
information that does not bear on interpretation of the study,
but does affect the ability of non-owners to submit the study
to approving agencies in other countries
EPA acknowledges the comment. EPA will continue to
update its approach for handling CBI information received
for future risk evaluations.
IVer Re\ ieu Process
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113
The extension notice does not state whether or not the peer
review comment period was extended for 20 days as well.
Completing the peer review comment period before the
public comment period is a backward approach to peer
review and inconsistent with EPA's own agency peer
review guidance.
The revised risk evaluation is essentially a brand new
document and therefore should be sent back to the peer
review panel in a public setting, not to a small group of
individuals in a closed, non-transparent letter-review
process.
The agency would be better served if it sought consultation
with the full SACC, adding a person or two in the key area
of inhalation toxicology.
An earlier draft risk evaluation underwent peer review by
the full SACC in 2018-2019. The final risk evaluation
incorporates changes in response to those comments and
before finalization underwent a further 30-day letter peer
review and a public comment period of 45 days. The peer
review comments, and EPA's responses are transparently
documented in this Response to Comment document. The
revised draft risk evaluation that was reviewed by the letter
peer reviewers incorporated responses and comments
proposed by previous rounds of public comments as well
as key recommendations of the SACC. EPA utilized
members of the previous SACC panel and other subject
matter experts relevant to the areas that were revised in
response to input provided by the SACC.
110
EPA is seeking a limited "letter review" of the revised draft
evaluation by a small subset of its Science Advisory
Committee on Chemicals (SACC) and eliminating the
public comment process normally part of SACC review.
EPA should reconvene the entire SACC to review the
revised draft and afford the public an opportunity to submit
comments and make presentations to the SACC.
As stated above, the comments received by the SACC
were incorporated into the final risk evaluation. Major
changes made to the risk evaluation since the SACC were
subject to a letter peer review.
Concerns thi.il llic TSCA systematic ie\iew method does not follow best seienlille practices
UCSF
EPA should use a peer-reviewed, validated systematic
review method for chemical evaluations instead of
"Application of systematic review in TSCA risk
evaluations."
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
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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.
UCSF
The Pigment Violet 29 evaluation still does not use a pre-
established protocol as required by EPA regulation under
TSCA.
EPA appreciates the comments and is currently in the
process of updating its Systematic Review protocol. In
addition, EPA has sought 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
UCSF
The TSCA method does not have a pre-established protocol
or methods for evidence integration as required by EPA
regulation under TSCA.
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Response to Peer Review Comments
Charge Question 1: Based on the available data, do you agree with the conclusion that C.I. Pigment Violet 29 has extremely low solubility in
octanol and water? Do you also agree with EPA's determination that log Kow is not a relevant property for this chemical? Please explain your
answers and provide any other information that would inform EPA on the physical/chemical properties of C.I. Pigment Violet 29.
Charge Question 2: Does EPA's approach to inhalation exposure estimates make appropriate use of the received test data? Have
uncertainties associated with the inhalation exposure estimates been adequately addressed? Please provide a rationale to your answer.
Charge Question 3: Do you have any specific recommendations to improve EPA's calculation of inhalation exposures for C.I. Pigment
Violet 29 based on the two available sets of breathing zone data?
Charge Question 4: Please provide any additional suggestions or additional factors that EPA should consider in estimating central tendency
and high-end exposures for C.I. Pigment Violet 29 in the manufacturing workplace air.
Charge Question 5: Is EPA's determination that carbon black matches the critical properties of C.I. Pigment Violet 29 and is an appropriate
surrogate reasonable? If not, please provide suggestions of surrogates that may be better as a surrogate for C.I. Pigment Violet 29, along with
additional justification for why the alternative surrogate is better than carbon black.
Charge Question 6: Are there other critical characteristics that should be considered in the selection of a surrogate? If so, provide detailed
additional substantive information that EPA should consider.
Charge Question 7: Please provide any additional recommendations that EPA should consider for estimation of risk for conditions of use
downstream from the original manufacturing site. What alternative assumptions could EPA make considering the lack of specific
measurements of C.I. Pigment Violet 29 in air in downstream processing facilities?
Charge Question 8: EPA combined data for particle size from data sets that are independent of the data sets for concentrations measured in
the breathing zone. Considering this, EPA calculated risks using the range of reported median particle sizes from small (0.043 |im), medium
(10.4 |im) and large (46.9 jam) for both central tendency and high-end exposures. Is this matrix appropriate for estimation of the range of risks
for OUs and ONUs? If not, please provide specific recommendations concerning alternatives that would provide less uncertainty in the risk
characterization.
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1
In the TSCA. Section 4 Test Order studv results (Nicolaou.
2020)no test material was observed in either water
(Organisation for Economic Co-operation and Development
(OECD) 105 flask method) or octanol (ETAD method,
2005) (Table 1-1). Again, Log Kow could not be determined.
The revised draft risk evaluation states, "Due to low
solubility of C.I. Pigment Violet 29, Log Kow was
determined not to be an irrelevant property for C.I. Pigment
Violet 29." The statement should be revised as follows,
"Due to low solubility of C.I. Pigment Violet 29, LogKow
could not be included in the risk assessment process."
Purity and solubility data in Table 1-1 use new data.
Henry's Law Constant is included. Overall, information
pertaining to the physical and chemical properties has been
improved to some extent.
Per the Revised Draft Risk Evaluation, EPA now views log
Kow as irrelevant for PV29. It would be better classified as
indeterminant. If log Kow could be determined, it would at
least be of interest. It may well be that log Kow cannot be
accurately determined for this compound given available
analytical methodologies.
EPA incorporated the suggested revision to characterize log
Kow as "indeterminant" into the final risk evaluation. The
solubility determination was limited by the sensitivity of the
equipment used to carry out the experiment. In this case, and
for the purposes of the Test Order and final risk evaluation,
EPA determined that the methodology used in this
assessment were sufficient to fulfill the requirements of the
Test Order.
2
This Letter Peer Reviewer concurs that based on the
available data, PV29 has extremely low solubility in both
octanol and water. Based on this data, it is highly unlikely
to partition into either a hydrophilic or lipophilic media,
thus negating the usefulness of the log Kow for predictive
purposes. Predicting the log Kowfrom the independent
solubility assays also has the potential, depending on the
ratio of the two, to give the wrong prediction with regards
to bioaccumulation (e.g., should octanol solubility be
EPA agrees with the comment and has not predicted the log
Kow from the solubility assays in the final risk evaluation.
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significantly lower than water solubility, even when both
are of extremely low solubility, the log of that ratio can still
be high enough to predict bioaccumulation or vice versa),
further making the use of individual solubility data
inappropriate for this effort.
3
PV29 likely has very low water solubility. The new data
submitted represents a reasonable amount of work.
However, the data provided do not necessarily support the
claim of unmeasurable water solubility or unmeasurable
octanol solubility.
The solubility data provided to the EPA indicate that PV29
is functionally insoluble down to the limits of detection of
the instruments used to conduct the experiment. Given the
low limits of detection reported for the instruments, EPA has
determined that this information is sufficient to make a
solubility determination for this chemical.
4
The available information does indicate that PV29 is poorly
soluble in both water and octanol and has a high melting
point. However, that information appears to have been
generated within the manufacturer's facilities rather than in
an independent testing laboratory. Given that some
information provided by the manufacturer in the course of
the review has been superseded or otherwise judged
unacceptable, an independent determination would have
been preferable.
The methods used to determine solubilities are described in
detail (YNicolaou. 2020 and appendices) and appear
appropriate, but this reviewer is not an analytical chemist
and may have overlooked some important detail. A claim of
GLP is stated. Thq Revised Draft Risk Evaluation does not
explicitly state whether EPA agrees that the laboratory
practices were consistent with GLP and meet requirements
under TSCA Section 4. EPA should clarify this point.
Generally, substances that are poorly soluble in water and
in octanol and are characterized by high melting point are
As part of the section 4 Test Order, the EPA indicated that
the testing organization was required to, "For purposes of
satisfying the requirements of this Order, you are required to
follow the Good Laboratory Practice (GLP) standards
described in 40 CFR part 792 as specified in the Code of
Federal Regulations on the day this order is signed. You are
also required to provide a statement of compliance with
these standards when submitting information to the EPA
pursuant to this Order." The testing submitted to fulfil this
test order included a GLP claim and was therefore
determined to fulfil this requirement.
EPA acknowledges the uncertainties surrounding the
determination that low solubility precludes absorption.
Where appropriate, EPA has modified the statements to
more accurately describe the properties of PV29.
Regarding the high-quality rating of the EPI Suite™ QSAR
software package, EPA acknowledges that this does not
apply specifically to PV29, but to the model. EPA will
update the confidence statements in the assessment to
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expected to have poor absorption characteristics in
mammals. However, poor solubility in only water or only
octanol does not preclude efficient absorption. As was
pointed out during the SACC Review of the PV29 Draft
Risk Evaluation, many pollutants of concern possess very
low aqueous solubility (i.e., lower than the original estimate
for PV29 of <11 ug/L), but are well known to be efficiently
absorbed via the human gut (e.g., all seven of the polycyclic
aromatic hydrocarbons (PAHs) EPA currently designates as
carcinogens). In the Response to Support the Revised Draft
Risk Evaluation of C.I. Pigment Violet 29 on page 46, EPA
acknowledges this criticism and claims that "EPA has
updated the final [sic] Risk Evaluation to remove these
statements." Nevertheless, in at least three places in the
Revised Draft Risk Evaluation, inappropriate claims are
made:
Page 45: "Any C.I. Pigment Violet 29 incidentally ingested
is unlikely to be absorbed from the digestive tract into the
bloodstream based on its low water solubility (<0.003
mg/L) (Nicolaou. 2020)."
Page 60: "Absorption of C.I Pigment Violet 29 after oral
ingestion is expected to be limited due to the low water
solubility (0.003 mg/L) and dermal and oral absorption are
estimated to be poor for the neat material (because it is a
solid with low solubility) (Nicolaou, 2020)."
Page 61: "Additionally, physical and chemical properties
indicate that, if found in these media and ingested,
absorption would be expected to be poor due to low water
solubility."
In the revised Table 1-1, (page 20) EPA asserts "high
confidence" in the estimated Henry's Law constant for
PV29. This evaluation is based on a general evaluation of
EPA's EPI Suite™ QSAR software package, rather than a
acknowledge uncertainties about PV29 and the use of the
model. Similarly, a footnote on Pg 20 of the final risk
evaluation will be added to better describe the uncertainties
related to the calculation of Henry's Law Constant.
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specific result for PV29. Quantitative structure-activity
relationship (QSAR) packages are calibrated against and
work best for compounds that fall into well-studied
chemical classes and that do not exhibit extremely low
solubilities in air, water or common solvents. PV29 is
apparently an outlier. Confidence in properties predicted
for PV29 by QSAR should be low. Footnote #3 (on page
21) should revised accordingly.
For compounds that are liquids at room temperature, a good
estimate of Henry's constant can be generated by dividing
vapor pressure by aqueous solubility. For solids this method
is less reliable and provides only a first approximation. For
PV29, neither vapor pressure nor aqueous solubility are
well characterized. Log Kowis now found to be
indeterminant and the prior EPI Suite™ estimate included
in the Draft Risk Evaluation has now been rejected. The
EPI Suite™ Henry's constant estimate (10"21 atmm3/mol)
should be treated similarly. The EPI Suite™ estimate could
easily be (and likely is) wrong by multiple orders of
magnitude.
5
I agree with the EPA's assessment of solubility and the
partition coefficient for PV29. However, in addition to the
properties already mentioned, I suggest addressing the
chemical reactivity of the test substance. Carboxamide
functional group as a structural feature may have the
potential to react locally with the respiratory tissues. The
need for this information here is further addressed in
answers to questions 5 and 6.
The functional group is an imide. However, there is SDS
information that residual anhydride content is present in
PV29 which is a concern for dermal and respiratory
sensitization. The assessment has been updated to include a
discussion of the potential for residuals to cause respiratory
sensitization.
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Summary of Comments for Specific Issues Related to Charge
Question 2
EPA/OPPT Response
1
The data source for occupational exposure was ranked at the high
confidence level. The occupational exposure assessment covers
manufacturing, processing and distribution in commerce.
Personal breathing zone data (NIOSH 0500) were used to
estimate occupational exposure. Various protection factors in
different scenarios were assigned. Time-weighted average
exposure concentrations considering shift and breaktime were
determined. I have a couple of comments. First, the sample sizes
(i.e., numbers of individuals tested) tend to be small, which may
lead to statistical uncertainties. Second, the air sampling
experimental design has a flaw due to low concentrations in the
air; the sampling duration needs to last longer with a higher flow
rate. This deficiency might have compromised the data
confidence level. Third, due to the sampling issues, the accuracy
of using LOQ/2 remains uncertain.
The consumer exposure assessment includes consumers and
bystanders. Users of products that contain C.I. Pigment Violet 29
(PV29) include watercolor artists and acrylic painters. It was
determined that inhalation is not an issue to consumers and
bystanders as the chemical is not volatile from paints due to its
low vapor pressure. Absorption via oral ingestion is unlikely due
to insolubility in water. General population exposure was
determined to be negligible due to engineering controls on
manufacturing releases, low volatilization rates that limit air
releases in incineration process, as well as high removal
efficiency of PV29 during the wastewater treatment process.
Consumer exposure was assumed to be negligible because it is
not present in a dust form and therefore not respirable. Further it
was assumed not to leach out products due to the insoluble
nature. Collectively, although no monitoring data exists, these
assumptions are reasonable and associated uncertainties is low
EPA agrees with the reviewer's comments regarding the
deficiencies identified in the personal breathing zone study
used to estimate occupational exposure as well as the
potential for exposure to consumers and commercial users
from finished products containing PV29. EPA has added
an in-depth discussion about the uncertainties regarding
the use of the personal breathing zone data in Section
4.2.3 of the final risk evaluation.
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Summary of Comments for Specific Issues Related to Charge
Question 2
EPA/OPPT Response
due to the obvious chemical nature of PV29. EPA places medium
confidence in the strength of the conclusion is understandable.
2
I concur with EPA's approach to inhalation exposure estimates
based on the received data. EPA has done its best to address the
uncertainties based on these data. It is unfortunate that longer
sampling periods for workers were not available, or alternatively,
that a 12-hour sample at the point of exposure was not available
(placed approximately where a worker would stand but left for
the entire processing day). With these limitations, and the limited
material to sample, EPA has adequately accounted for exposures.
EPA acknowledges the reviewer comment.
4
The preface to Question #2 contains the following statements:
"Individual exposures of respirable dust for six workers in the
Sun Chemical 2019 Study ranged from 0.22 to 1.2 mg/m3." and
"For further information on the Sun Chemical 2019 Study refer to
Table 1-2 in Section 1.1 of the revised draft risk evaluation."
These statements are incorrect and may confuse members of the
public. They should be corrected when responses are compiled.
As was discussed at the June 2019 SACC review for the Draft
Risk Evaluation, the relevant particle size for assessment of risk
of inhalation exposure is the size of the particles suspended in the
breathing zone, not the size of the particles in the product
package. Handling of powders generally results in preferential
suspension of finer particles. Therefore, the inhaled particle
median is likely to be finer (and present greater risk) than the
package median. Nevertheless, EPA continues to use bulk
material particle size in its analysis.
In the Supplemental File: Information Receivedfrom
Manufacturing Stakeholders, three Particle Size Distribution
(PSD) estimates can be found. They are summarized (as median
values) in the following table along with the corresponding
EPA agrees with the reviewer's comment. The updated
preface to the comment should read, "Individual
exposures of total dust for five workers in the Sun
Chemical 2019 Study ranged from 0.22 to 1.2 mg/m3."
and "For further information on the Sun Chemical 2019
Study refer to Table 2-4 in Section 2.3.1.2 of the final risk
evaluation." EPA has clarified in the final risk evaluation
that in order to estimate high-end exposure in the
workplace, EPA has conservatively assumed that 100% of
the measured dust concentration is comprised of PV29.
The particles size demonstrates a polydisperse distribution
of sizes, from low nm to um sizes, presumably from
grinding of the PV29 for various applications. EPA did
not receive particle size distribution for actual workplace
dust collected in the manufacturing facility. In an attempt
to capture uncertainties and capture all information
provided to the EPA to characterize the particle size
distribution of the chemical, EPA included all particle size
distributions in the analysis presented in the draft Risk
Evaluations. EPA did not specifically discuss the PSD
estimates from the BASF SDS because they were within
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Summary of Comments for Specific Issues Related to Charge
Question 2
EPA/OPPT Response
statistic reported by BASF that was utilized in the Draft Risk
Evaluation. Three of the four values were utilized in EPA's
modeling of potential lung overload. For unexplained reasons,
EPA included an older value from a published BASF Safety Data
Sheet (SDS) in the Supplemental File (page 55) but did not use
that value in the Revised Draft Risk Evaluation.
EPA should determine why the original submittal for the PV29
review (BASF, 2013) does not correspond to the SDS (which is
apparently still considered current?).
(EPA should also consider whether it is helpful to label the
second (laser diffraction) PSD study received by EPA as Sun
Chemical #1 and the first (TEM) study as Sun Chemical #2 in
Table 1.2 of the Revised Draft Risk Evaluation).
Regarding the four PSD medians, gross differences among them
suggest high uncertainty that is further compounded by
uncertainty generated by using bulk packaged product median
particle diameter rather than suspended particle median diameter.
Indeed, the NIOSH 0600 Respirable Particle method used to
collect the Test Order workplace data set has an estimated
median cut point of 4 |im, making the Test Order results simply
incompatible with the two larger medians applied to the lung
overload calculations.
The smallest particle size assumed is more conservative
(although perhaps not conservative in an absolute sense since
suspended dust might be finer still). Given limited and
inconsistent data, EPA is justified in making conservative
assumptions.
the range of the existing particle data provided by Sun
Chemical. In addition, EPA has updated its use of particle
size information to use primarily as a judge for the
appropriateness of the carbon black analogue. This is
primarily based on the smallest particle size measurement
of 0.043 |im provided by Sun Chemical.
EPA agrees that workers in a manufacturing facility will
be exposed to respirable dust. Particle sizes below 10 |im
are considered respirable in humans and are likely the
main component of the personal breathing zone data
provided to the EPA in response to the Section 4 Test
Order. In the final risk evaluation, the EPA is removing
the discussion of particle size as it relates to the modeled
deposition in the lungs. As a result, it is expected that
respirable particles will be deposited in the lungs and the
particle size data received for PV29 has been used
primarily to determine whether carbon black is an
appropriate analogue to characterize the inhalation hazards
of PV29. Inhalation of respirable, poorly soluble particles
can increase their lung burden. Particles are retained in the
lungs when the deposition rate exceeds the clearance rate.
Depending on the exposure magnitude, retained particles
may cause kinetic lung overload.
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Summary of Comments for Specific Issues Related to Charge
Question 2
EPA/OPPT Response
6
EPA appears to have reasonably utilized the PV29 concentration
data from the Test Order Study provided by the Sun Chemical.
The central tendency is based on the average of PV29
concentrations (or TWAs). All but one sample of the Test Order
Study were below LOQ. The true sampled value is somewhere
below LOQ along a (truncated) probability distribution; the
distribution however is unknown. In addition to LOQ/2, other
values such as a/L0Q/2 or LOQ have also been used in the
literature. The choice of such a value to replace the unobserved
true value that is below LOQ can lead to a different central
tendency value. Although in the case PV29, the resultant
variation in the central tendency is small and is less likely to bear
significant consequence, a consistent and systematic approach is
relevant in view of TSCA risk evaluation approach. Looking
beyond PV29, it is helpful that EPA develops and adopts a
consistent and systematic approach to the situation where
samples are below LOQ.
In addition to central tendency, it is also useful to report key
percentiles (e.g. median, 95-percentile and maximum) based on
the two available datasets for the Test Order Study. The use of
maximum of the Test Order Study as the high-end estimate
should be considered.
In view of the high-end estimate, the use of the highest value of
total respirable dust concentration does not serve to enhance
consistency in EPA's approach to exposure assessment in TSCA
risk evaluation. It is difficult to imagine that EPA would always
use total dust concentration as the high-end estimate when in fact
only exposure to the specific chemical is of relevance.
EPA's use of the average of the LOQ/2 for each operator
to generate a central-tendency estimate of exposure is
consistent with agency practices given the distribution of
the data (TI.S. EPA. 1994). In light of the deficiencies in
the dataset, particularly regarding the predominance of
non-definitive {i.e.
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Summary of Comments for Specific Issues Related to
Charge Question 3
EPA/OPPT Response
1
Two sets of Personal Breathing Zones (PBZ) (Table 2-3,
Table 2-5, Table 2-6) were used for calculation of inhalation
exposure. The air monitoring experiment should have been
conducted with longer sampling durations and higher air
flow rates. Because these two actions were not taken, it is
likely that concentrations in the air might have been
underestimated. The usual EPA method of estimating
central tendency and high-end exposures might result in
underestimated risk. Can an additional safety factor be built
into the calculations? Or can the sampling experiments be
performed again with improved methods?
EPA acknowledges these deficiencies and took what it
determined to be a conservative approach by considering the
highest total dust concentration as representative of a
potential exposure to workers. As this measured value may
capture not only workplace concentrations of PV29, but also
other workplace respirable dusts, and therefore EPA
determined that this approach is conservative. As a result,
EPA is not taking additional measures to account for
potential uncertainties such as adding additional uncertainty
factors. Additionally, EPA has calculated both a central
tendency and high-end exposure estimation and is
incorporating both values in the risk determination.
4
The (two) available data sets are each somewhat limited in
scope. EPA is constrained by the data. Heroic interpretation
is not warranted.
On page 50 of th q Revised Draft Risk Evaluation, EPA
States that".. EPA determined that the study [The E.I.
Group, 2020] did not meet the terms of study plan set forth
in the Test Order." The text then references a HERO
citation that yields a "Content Restricted" message. More
discussion of the inadequacies of the study as reported
should be included in the Revised Draft Risk Evaluation or
in an Appendix. Is EPA now satisfied with the response to
the Section 4 request?
EPA has bolstered the discussion of the uncertainties and
deficiencies identified in the submitted personal breathing
zone data as a full review of the dust monitoring study in
Appendix I of the final risk evaluation.
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Summary of Comments for Specific Issues Related to Charge
Question 4
EPA/OPPT Response
1
Central tendency and high-end exposure were calculated based
upon two air monitoring study data. Three reported median
particles from the PSD data sets (0.043, 10.4, and 46.9 [j,m) and
associated estimated deposition fraction in the pulmonary
region of the lungs were considered. The estimation follows
the typical EPA protocol. I have no additional suggestions over
this question.
EPA acknowledges the comment
5
The only other area for consideration is if there is a need to
distinguish between solid aerosols and liquid aerosols for
PV29. That would be important if there is a potential for
reacting with the local respiratory tissues
EPA assumed that exposure of PV29 from solid
and liquid aerosols (from spray application of
paints containing PV29) are the same as exposure
to respirable PV29 dust from manufacturing
activities.
#
Summary of Comments for Specific Issues Related to Charge
Question 5
EPA/OPPT Response
1
Carbon black is used as a surrogate for C.I. Pigment Violet 29
(PV29) in the revised draft risk evaluation document. The
rationales of choice are 1) the range of carbon black particle
sizes (0.014 [^m - 0.070 (j,m) brackets the particle size of PV29
(0.08 [j,m at 90 percentile), 2) both have similar physical and
chemical properties such as density ((1.97 g/cm3 for carbon
black vs 1.69 g/cm3 for PV29) and insolubility, 3) both have
limited absorption and metabolism, and 4) both are being used as
pigments and inks. Collectively, the use of carbon black as a
surrogate chemical is a scientifically sound decision. The use of
the study by Elder et al. (2005) is appropriate as multiple
species, exposure concentrations and lung overload were
assessed.
Carbon black is an appropriate analogue for PV29
due to the similar organic conjugated aromatic ring
structure and its poor solubility in water to replicate
the lung overload PK phenomenon in inhalation
studies. Carbon black has two reliable inhalation
studies for risk assessment purposes, the sub-chronic
Elder et al.. (2005) studv and the chronic Nikula et
al.. studv (1995).
2
I concur with EPA's assessment that carbon black is an
appropriate surrogate based on its physical- chemical properties
and functional use. I had briefly considered suggesting other
EPA acknowledges the reviewer comment
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Summary of Comments for Specific Issues Related to Charge
Question 5
EPA/OPPT Response
Violet pigments, however upon investigating their physical-
chemical properties, the carbon black comparison was still more
appropriate, outside of the similarity of the functional groups.
The other violet pigments have similar functional groups to
PV29, which could inform toxicity, however they are more
likely to be readily absorbed due to much higher solubility.
4
EPA's justification for using carbon black rather than barium
sulfate as a surrogate for PV29 appears well founded to this
reviewer.
EPA acknowledges the reviewer comment.
#
Summary of Comments for Specific Issues Related to Charge
Question 6
EPA/OPPT Response
1
The criteria of surrogate choice are well described and justified
in the revised document (page 21 and page 67). No additional
information is needed.
EPA acknowledges the reviewer comment.
2
EPA should place further consideration of the potential for
carcinogenicity by a non-genotoxic mechanism. Carbon Black is
a Group 2B (possibly carcinogenic to human beings) compound
according to IARC (2006). The mechanism through which
carbon black is suspected to cause tumors is non-genotoxic and
is instead thought to be through impaired lung clearance
(overloading) and most likely induction of inflammatory
reactions, increased reactive oxygen species, and ultimately
tumor formation. As carbon black is the preferred surrogate for
CI Pigment Violet 29 (PV29), due to its similar critical
properties, this too should be considered. Both PV29 and carbon
black are poorly soluble and both are negative in genotoxicity
assays, likely due to the low solubility (ECHA 2020). Both are
considered to cause their toxic effects through lung overload.
Thus, if carbon black is acceptable for use in the estimation of
chronic exposure and lung overloading, the potential of a
The chronic Nikula et al.. (1995) carbon black studv
cited in the IARC document reported fibrosis and
tumors. The relevance of particle overload to humans,
and even to species other than laboratory rats and
mice, is not clear. While it likely to be of little
relevance for most "real world" ambient exposures of
humans, it is of concern in interpreting some long-
term experimental exposure data. And it may be of
concern to humans occupationally exposed to some
particle tvpes (Mohr et al.. 1994), since overload mav
involve all insoluble materials and affect all species if
the particles are deposited at a sufficient rate
(Tmchan! Ps\9), i.e.. if the deposition rate exceeds
the clearance rate. In addition, the relevance to
humans is also clouded by the suggestion that
macrophage-mediated clearance is normally slower
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Summary of Comments for Specific Issues Related to Charge
Question 6
EPA/OPPT Response
carcinogenetic effect due to this overloading should not be
ignored.
and perhaps less important in humans than in rats
(Morrow. 1994) and that there will be significant
differences in macrophage loading between the two
species. The inherent toxicity of the compounds
should be considered as well and there are no chronic
oral or inhalation studies available for PV29. EPA
calculated the HEC values for both the Elder et al.,
(2005) sub-chronic and Nikula et al.. (1995) chronic
inhalation studies. In comparison, the Elder et al.,
(2005) studv female rat NOAEC HEC is 0.28 mg/m3
or 8 times lower than the Nikula et al., (1995) female
rat LOAEC HEC of 2.23 mg/m3. The Elder et al.,
(2005) studv LOAEC HEC in female rats is a similar
value of 1.95 mg/m3. Lung cancer hazard is not
anticipated at concentrations in which chronic active
inflammation and cell proliferation are not present.
Thus, tumor formation by carbon black is not expected
at the rat NOAEC HEC value of 0.28 mg/m3, a
concentration that does not cause inflammation and
hyperplasia precursor events in animal models. EPA
asserts that there is insufficient information for PV29
to classify it as a carcinogen. EPA has added a
discussion to the hazard characterization and
uncertainty section (Section 3.2.3.2 of the final risk
evaluation) concerning potential carcinogenic effects
of the carbon black analogue. Tumors were not
observed in the Elder et al. (2005) studv of carbon
black used to identify the POD. Additional
characterization has been added to the risk evaluation
on this topic and as well as the Nikula (1995) studv
discussion in Section 3.2.3 of the final risk evaluation
regarding the findings of fibrosis and tumors as a
result of chronic exposure to carbon black.
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Summary of Comments for Specific Issues Related to Charge
Question 6
EPA/OPPT Response
Aspect ratio of the particles is critical. The measured "particle
size" maxima in BASF data represents only axial 3 lengths
(imine to imine) of the PV29 molecule. Different light scattering
instruments can be configured to measure particle aspect ratios.
The brand use by BASF for their particle counting is one of
them. Carbon black normally has an amorphous shape so it is
unlikely that carbon black will have a high aspect ratio, while it
is quite possible for PV29. High aspect ratios of PV29 particles
relative to carbon black would make carbon black an inadequate
surrogate.
Compound aspect ratios at the molecular level are not
relevant to the aspect ratio of particles which can be
ground to any size. In addition, the discussion of
particle size as it relates to exposure has been updated
in the final assessment. The assumption that different
particle sizes will result in different deposition
percentages in the lungs has been updated.
5
Carbon black can exist at the elemental level as well as a
compound of several carbon atoms, which is very different from
the PV29 molecule. The differences in the particle size between
PV29 and CB may be due to the tendency of CB particles to
form agglomerates. It is important to compare the chemical
reactivity potential for both the target and the surrogate analog.
The presence of potentially reactive functional groups in PV29
and their absence in CB structure needs to be addressed. This
informs the potential for local respiratory effects that would be
observed much earlier than the increased bioburden in the lung
due to accumulating insoluble particles. At the nanoscale, PV29
and CB are very different substances with non-comparable
Physico-chemical properties. Given the structural complexity of
PV29, it is acknowledged that finding a suitable surrogate is
difficult (if not impossible). Therefore, it would be helpful to
highlight these differences and add justification as to why these
may or may not be important in the current assessment.
The appropriateness of carbon black as an analogue
for PV29 is discussed in greater detail in Sections
3.2.3 of the final risk evaluation. Both PV29 and
carbon black are respirable, poorly soluble pigments
composed of conjugated aromatic rings that are
expected to cause similar PK effect of increased lung
burden and adverse effects on the respiratory tract.
There are similarities between the two compounds in
terms of physical chemical properties that led the EPA
to consider this a suitable analogue. The uncertainties
of this approach are discussed in Section 4.2.4 of the
risk evaluation.
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Summary of Comments for Specific Issues Related to
Charge Question 7
EPA/OPPT Response
4
[The preface to Question 7 includes the statement: "Dust
particles less than 100 urn are considered non- respirable. "
This statement is incorrect and may confuse members of the
public. It should be corrected when responses are compiled.]
The absence of data in downstream facilities is a significant
shortcoming. If downstream operations are relatively small
economic enterprises, occupational hygiene may be
substandard. In the absence of air sampling data and worker
exposure factors specific to downstream facilities, EPA is
justified in assuming downstream exposures are the same as
production facility exposures.
EPA did not include this statement on dust particles
in the final risk evaluation.
#
Summary of Comments for Specific Issues Related to
Charge Question 8
EPA/OPPT Response
1
The three median particle sizes vary significantly. The highest
and the lowest have a difference of 1,079 folds. No values of
ONU without a respirator are below the benchmark MOEs. On
the other hand, some values of workers without a respirator or
workers with APF 10 are below the benchmark MOEs. These
differences originate from three median particle sizes of large
variations. There is no way to reduce the high uncertainty in the
risk characterization, unless more accurate PSD data is collected.
Page 79, Line 13-14, Section 3.2.3.2 presents the MOEs for
cancer effects.
Page 50: the first row of Table 2-6 was duplicated in page 50. It
should be removed.
EPA has updated the discussion of inhalation risks
from PV29. The EPA recommends reviewers consult
the updated discussion of inhalation risks to workers
that does not incorporate assumptions of deposition
based on particle size (see Section 4.2.1). In addition,
the errors indicated by the reviewer have been
updated in the final risk evaluation.
4
As noted above, a 46.9 |im median particle diameter (and even a
10.4 jam median) is inherently inconsistent with OSHA 0600
Respirable Particle data. Given two other potential sources of
information (Sun Chemical #2 and BASF SDS 4081884) that
EPA has updated the discussion of inhalation risks
from PV29. EPA agrees that workers in a
manufacturing facility will be exposed to respirable
dust. Particle sizes below 10 |im are considered
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Summary of Comments for Specific Issues Related to
Charge Question 8
EPA/OPPT Response
suggest much finer particles and that larger particles are less
likely to be suspended, EPA would be justified in
rejecting/discarding the 46.9 |im data point.
ONUs cannot be distinguished from OUs by guesswork. In the
absence of ONU specific data, use of OU data as a surrogate is
justifiable. The regulated community can prevent imposition of
excessively conservative ONU exposure assumptions by
collecting data.
respirable in humans and are likely the main
component of the personal breathing zone data
provided to the EPA in response to the Section 4 Test
Order. In the final risk evaluation, the EPA is
removing the discussion of particle size as it relates
to the modeled deposition in the lungs. As a result, it
is expected that all respirable particles will be
deposited in the lungs and the particle size data
received for PV29 will be used primarily to
determine whether carbon black is an appropriate
analogue to characterize the inhalation hazards of
PV29.
The updated discussion of inhalation risks from
exposures reflects this change in approach and can be
found in Table 2.6 of Section 2.3.1 of the final risk
evaluation.
In the absence of available data to describe risks to
ONUs, EPA made assumptions using reasonably
available data. While there are uncertainties in this
approach, EPA believes that this represents a fair and
conservative approach to describe exposure to ONUs
in the absence of available data.
6
EPA's "matrix" (or grid) approach of using medium particle size
of (0.043 um, 10.4 um, and 46.9 um) is reasonable. A more
probabilistic alternative would be to pull the three PSD datasets
from BASF and Sun Chemical together and determine the
overall median, mean, quartiles, higher percentiles such as 95
and 99 percentiles, and calculate the corresponding MOEs. By
doing so, there would be a distribution of MOEs which in turn
inform uncertainty and variability in a way that is more
quantitative and probabilistic, which in turn supports risk
characterization.
EPA has updated the discussion of inhalation risks
from PV29. The EPA recommends reviewers consult
the updated discussion of inhalation risks to workers
that does not incorporate assumptions of deposition
based on particle size (see Section 4.2.1 of the final
risk evaluation).EPA agrees that workers in a
manufacturing facility will be exposed to respirable
dust. Particle sizes below 10 |im are considered
respirable in humans and are likely the main
component of the personal breathing zone data
provided to the EPA in response to the Section 4 Test
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Summary of Comments for Specific Issues Related to
Charge Question 8
EPA/OPPT Response
Order. In the final risk evaluation, the EPA is
removing the discussion of particle size as it relates
to the modeled deposition in the lungs. As a result, it
is expected that all respirable particles will be
deposited in the lungs and the particle size data
received for PV29 will be used primarily to
determine whether carbon black is an appropriate
analogue to characterize the inhalation hazards of
PV29.
The updated discussion of inhalation risks from
exposures reflects this change in approach and can be
found in Section 2.3.1 of the final risk evaluation.
#
Other SACC Comments not included in the Charge
Questions
EPA/OPPT Response
The nuances of comments made in response to question
clearly indicate why careful attention is needed by the
agency and in SACC reviews of these TSCA mandated Risk
Evaluations. EPA has allocated an insufficient number of
staff to review details in supporting documents and those
who assigned to this National Need are overstretched.
Timelines that the SACC has been given for these reviews
are inadequate for such detailed reviews. This situation has
compounded itself during the early rounds of TSCA
reviews. The situation also clearly highlights the need for
full peer review of TSCA mandated Risk Evaluations at
critical stages to allow refinement of assessments by
improving modeling approaches and data quality for those
models.
It is positive to note that Figure 1-1 depicts all
environmental media to be "in scope" for this evaluation.
EPA acknowledges the efforts of the letter peer reviewers to
provide a thorough review on such a short timeline. The
difficulties encountered by the letter peer reviewers in light
of the abbreviated timeline will be incorporated into the
future review schedules of the documents. In this case, the
decision to do a letter peer review resulted from the
significant changes in the document as a result of the original
peer reviewer recommendations, new information, and new
agency analysis by EPA.
The final letter peer review report can be found in the docket
at the following link:
httos ://www.reeulations. gov/documen t °n 1 IP A-HO-OPPT -
2018-0604-0!07
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Other SACC Comments not included in the Charge
Questions
EPA/OPPT Response
This is a major improvement relative to other TSCA related
Risk Evaluations that EPA recently presented to the SACC.
No environmental data are presented to justify the omission
of all environmental media from consideration as shown in
Figure 1-4. No measurements are provided in waste waters
or in air exhausts. Thus, Figure 1-4 and the premise of the
assessment are in question.
EPA acknowledges the uncertainties resulting from a lack of
empirical monitoring studies to measure actual PV29
concentrations in discharges from the manufacturing facility.
EPA disagrees that no data are available to assess the
potential releases to aquatic and terrestrial media. As
indicated in the final risk evaluation, EPA has determined
that it has sufficient information to conclude that releases
and resulting exposure to aquatic media to PV29 are
negligible. Section 2.2 of the final risk evaluation outlines
the release information EPA has used to reach this
conclusion. To summarize, available discharge information
received from the primary US manufacturer indicates that
0.8 lb/day of PV29 is being discharged to wastewater.
Data screening that removes 96% of available data requires
more justification. Return to page 37 and access citation for
Systemic review.
EPA would like to clarify the results of the data search
process. 96% of the references identified during the data
search and screening process were found not to contain
relevant information pertaining to PV29. Therefore, it is
inaccurate to conclude that 96% of available data were
removed, as these data sources did not contain any
information relevant to PV29. As a result, 100% of
reasonably available data were considered in the assessment,
with the exception of the acute inhalation toxicity studies
which were determined to be unacceptable following data
quality evaluation.
Page 23 Table 1-3: It is troubling to have 5 yr old
production data in an assessment of this magnitude. Also, it
is noted that the production is increasing and that imports
are improperly excluded from this table. The data should be
more current, and the import should be added to the
production to develop a table of total use. This type of table
EPA has used the most recent production volume data that
was reasonably available and has noted that, although PV29
is being imported, data on import volume was not identified
and therefore no information on import volume was included
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Other SACC Comments not included in the Charge
Questions
EPA/OPPT Response
could have rows for production, import, and total, or it
could simply provide a total.
Table 2.1. The footnote a must say ESTIMATED unless
otherwise noted. Four values are estimated, one is not
determined, and one is measured. Careful review of the foot
notes in this table is needed.
EPA has updated the footnote at the suggestion of the
reviewer. The EPA has made the studies in Appendix D
available in the docket for PV29 (numbered as studies 18,
19, and 20):
htto s://b eta. r egul ati on s. gov/docket/EP A410-GPP T-2018-
None of the studies in Appendix D are accessible in the
Hero Data Base and as such cannot be assessed. The
inaccessibility of these data makes it impossible to ascertain
the validity of these data. Further the data purport to be
testing but based on BASF data the limit value would be
well above solubility. It would be useful to use the
dissolution approach mentioned in my physical properties
comments (Ql) and repeat these studies at or near the
solubility. Adding the sulfuric acid solution would not pose
a problem as the toxicity tests are likely to be performed in
moderately hard water which is buffered and contains
sulfate. The sulfate amounts in the test system salts could be
altered to accommodate the sulfate from sulfuric acid if
needed. Likewise, hydroxide could be added to balance the
equivalents of proton from the acid.
0604/document
The acute ecotoxicity testing submitted for PV29 were found
to be acceptable for use in risk assessment. Given the low
solubility of the compound, the approach of dissolving the
substance in sulfuric acid, as proposed by the reviewer,
would exceed the reported solubility as reported in the
solubility testing and would therefore not be representative
of actual environmental concentrations expected to result
from discharges of PV29 to wastewater.
In Section 2.2, EPA makes an erroneous assumption that
there is extremely limited potential for releases from
chemical reactions in the manufacture of other pigments. No
data describe reaction efficiencies, reaction byproducts, or
product purification effluents are presented. Without such
data, this statement cannot be validated.
As shown in the supplemental file, the reaction efficiency
from the use of PV29 as an intermediate is >99%, so the
potential for release of PV29 is low. The potential for release
of other chemicals created as a result of these reactions are
outside of the scope of this risk evaluation.
Section 3.1, Page 64: The solubility of 670 mg/L is higher
than measured by others, but the other ecotox studies did
While it is accurate to describe the 0.003 mg/L "solubility
limit" as a method quantification limit, The EPA has
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#
Other SACC Comments not included in the Charge
Questions
EPA/OPPT Response
measure 6-7 [j,g/L in test solutions. That should be added to
this section and the 0.003 mg/L "solubility limit" should be
removed. That is not a solubility limit; it is not a method
quantification limit; it is an instrument limit of
quantification. If reference to a solubility limit is retained
the more appropriate 0.004 mg/L estimate of instrument
LOQ should be used, as noted above.
determined 0.003 mg/L to be the limit of solubility because
of the nature of the study where it was determined. This
study was conducted specifically to measure the limit of
solubility of the chemical. The study details included in the
ecotoxicity testing regarding the solubility limits are helpful,
but these studies did not contain sufficient details to verify
the methods for determining the solubility limit.
Given the sensitive coastal and estuarine ecosystems near
the production facility on the Cooper River, important
estuarine species should have been tested.
Section 4: EPA has too little data to support the statement of
low hazard to environmental receptors.
EPA used all reasonably available data to characterize the
environmental hazards of PV29. These data were determined
to be sufficient to characterize the environmental hazards of
the chemical substance.
Section 5.5.2: The inadequate data sets assembled for the
environmental assessment is a common theme in the vast
majority of EPA's TCSA Risk Determinations, thus far.
3
Section 5.3: EPA should be praised for gathering the new
information about particle sizes to refine the human health
risk assessment. This type of refinement is needed whether
it the inclusion produces a risk determination that is
suggests more risk or less risk. The refinement increases the
certainty that a proper determination has been made.
EPA acknowledges the comment.
P. 44 LL5 weight should be omitted from the phrase
.. .mean weight diameter of particles...
P. 55 there is a font shift just above section 2.3.1.6.
EPA has updated the final risk evaluation to correct the
errors indicated by the reviewer.
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