MC RESPONSE TO COMMENT
4>EPA
EPA Document# EPA-740-R2-0022
Office of Chemical Safety and
United States Pollution Prevention
Environmental Protection Agency
June 2020
Summary of External Peer Review and Public Comments and Disposition for Methylene Chloride (MC)
Response to Support Risk Evaluation of
Methylene Chloride (MC)
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June 2020
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MC RESPONSE TO COMMENT
Table of Contents
Environmental Fate and Exposure 9
Environmental Releases and Exposure 25
Environmental Hazard 42
Occupational and Consumer Exposure 52
Human Health Hazard 123
Risk Characterization 152
Overall Content and Organization 214
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EPA published the Draft Risk Evaluation for Methylene Chloride (Dichloromethane, DCM) in
October of 2019, and accepted public comments until December 30, 2019. Materials on the draft
risk evaluation are available at www.regulations.gov in docket EPA-HQ-OPPT-2019-0437. EPA
held a peer review meeting of EPA's Science Advisory Committee on Chemicals (SACC) on the
draft risk evaluation for this chemical's conditions of use on December 3-4, 2019.
This document summarizes the public and external peer review comments from the SACC that
the EPA's Office of Pollution Prevention and Toxics (OPPT) received for the risk evaluation of
methylene chloride (MC). It also provides EPA/OPPT's response to the comments received from
the public and the peer review panel.
EPA/OPPT appreciates the valuable input provided by the public and peer review panel. The
input resulted in numerous revisions to the risk evaluation document.
The peer review and public comments are categorized by the MC peer review charge questions,
which align with the seven themes listed below. Additionally, within each theme comments that
cover similar issues are presented together.
1. Environmental Fate and Exposure
2. Environmental Releases and Exposure
3. Environmental Hazard
4. Occupational and Consumer Exposure
5. Human Health Hazard
6. Risk Characterization
7. Overall Content and Organization
ABBREVIATIONS
l-BP
1-Bromopropane
ACC
American Chemistry Council
ACE
Acute-to-Chronic Estimation
ADC
Average daily concentration
AF
Assessment factor
AFL-CIO
American Federation of Labor and Congress of Industrial Organizations
AEGL
Acute Exposure Level Guidelines
AIHA
American Industrial Hygiene Association
AOP
Adverse outcome pathway
APF
Assigned protection factor
APHA
American Public Health Association
APHL
Association of Public Health Laboratories
AQMD
Air Quality Management District
ASD
Autism Spectrum Disorder
AT SDR
Agency for Toxic Substances and Disease Registry
BCF
B i oconcentrati on F actor
BMDL
Benchmark dose lower bound
BMDS
Benchmark Dose Software
BW
Bodyweight
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CAA
Clean Air Act
CalEPA
California Environmental Protection Agency
CASRN
Chemical Abstracts Service Registry Number
CEM
Consumer Exposure Model
COU
Condition of use
CFD
Computational fluid dynamics
ChV
Chronic value
CNS
Central Nervous System
coc
Concentration of concern
CWA
Clean Water Act
DMR
Discharge Monitoring Report
EC50
Effect Concentration at which 10% of test organisms
exhibit the effect
ECEL
Existing Chemical Concentration Limit
EDF
Environmental Defense Fund
E-FAST
Exposure and Fate Assessment Screening Tool
EIA
Environmental Investigation Agency
EPI Suite
Estimation Programs Interface suite of models
EPN
Environmental Protection Network
EXAMS
Exposure Analysis Modeling System
GHS
Globally Harmonized System
GST
Glutathione S-transferase Tl-1
HAP
Hazardous air pollutant
HBCD
Cyclic aliphatic bromide cluster
HEC
Human equivalent concentration
HEI
Health Effects Institute
HERO
Health & Environmental Research Online
HSIA
Halogenated Solvents Industry Alliance
HUC
Hydrologic unit code
IARC
International Agency for Research on Cancer
IUR
Inhalation unit risk
Koa
Octanol-Air Partition Coefficient
Koc
Soil Organic Carbon-Water Partitioning Coefficient
LA DC
Lifetime average daily concentrations
LC01
Lethal Concentration at which 1% of test organisms die
LC10
Lethal Concentration at which 10% of test organisms
die
LC50
Lethal Concentration at which 50% of test organisms
die
LOAEL
Lowest Observed Adverse Effect Level
LOD
Limit of detection
MC
Methylene chloride
MOA
Mode of Action
MOE
Margin of Exposure
NAICS
North American Industry Classification System
NAS
National Academies of Science
NATA
National Air Toxics Assessment
NEI
National Emissions Inventory
NESHAP
National Emission Standards for Hazardous Air Pollutants
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NF
Near-field
NHANES
National Health and Nutrition Examination Survey
NIOSH
National Institute for Occupational Safety and Health
NMP
N-Methylpyrrolidone
NOAEL
No Observed Adverse Effect Level
NOEC
No Observed Effect Concentration
NPDES
National Pollutant Discharge Elimination System
NTP
National Toxicology Program
OECD
Organisation for Economic Co-operation and Development
OES
Occupational exposure scenario
OPERA
Open Structure-activity/property Relationship App
OPPT
Office of Pollution Prevention and Toxics
ONU
Occupational non-user
OSHA
Occupational Safety and Health Administration
PBPK
Physiologically based pharmacokinetic
PEL
Permissible exposure limits
PDM
Probabilistic Dilution Model
PF
Protection factor
POD
Point of departure
POTW
Publicly owned treatment works
PPE
Personal protective equipment
QSAR
Quantitative Structure-Activity Relationship
REL
Reference Exposure Level
RIOPA
Relationship between Indoor, Outdoor, and Personal Air
ROS
Regression on Order Statistics
RQ
Risk quotient
SACC
Science Advisory Committee on Chemicals
SCHF
Safer Chemicals Healthy Families
SDS
Safety Data Sheet
SIR
Standard incidence rates
SOCMA
Society of Chemical Manufacturers & Affiliates
STORET
STOrage and RETrieval database
TNO
The Netherlands Organisation for Applied Scientific Research
TRI
Toxics Release Inventory
TSCA
Toxic Substances Control Act
TURI
Toxics Use Reduction Institute
TWA
Time-weighted average
UCSF PRHE
University of California, San Francisco Program on Reproductive Health and the
Environment
UF
Uncertainty factor
U.S. BLS
United States Bureau of Labor Statistics
USGS
U.S. Geological Survey
VOC
Volatile organic compound
WASP
Water Quality Analysis Simulation Program
WHO
World Health Organization
WOE
Weight-of-evidence
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List of Com incuts
#
Docket l;ilc
Sn hm it lor
SACC
N/A
Science Advisory Committee on Chemicals (SACC)
28
EP A-HO-OPPT-2019-043 7-0028
Tamara Fox, Vertex Pharmaceuticals, Inc.
33
EPA-HI
Mass Comment Campaign sponsored by Environmental Defense Fund
(EDF) (web)
34
EP A-HO-OPPT-2.019-043 7-0034
Melvin Andersen, Andersen ToxConsulting LLC
41
EP A-HO-OPPT-2019-043 7-0041
Suzanne Hartigan, Senior Director, Regulatory and Technical Affairs,
American Chemistry Council (ACC)
42
EP A-HO-OPPT-2.019-043 7-0042
Richard A. Denison, Lead Senior Scientist, Environmental Defense
Fund (EDF)
43
EP A-HO-OPPT-20
19-0437-0043
Sebastian Irby, Environmental Protection Network (EPN)
44
EP A-HO-OPPT-20
19-0437-0044
Bob Sussman, Counsel, Safer Chemicals Healthy Families (SCHF)
45
EP A-HO-OPPT-20
19-0437-0045
Andrew Maier, Senior Managing Health Scientist, Cardno ChemRisk
46
EP A-HO-OPPT-2.0
19-0437-0046
Kenneth A. Mundt, Senior Principal Health Scientist, Cardno
ChemRisk
47
EP A-HO-OPPT-2019-043 7-0047
Anonymous
48
EP A-HO-OPPT-2019-043 7-0048
Laura Reinhard, Vice President and General Manager, Foam and
Industrial Products, Honeywell
49
EP A-HO-OPPT-2019-043 7-0049
Jonathan Kalmuss-Katz, Staff Attorney, Earthjustice
50
EP A-HO-OPPT-2019-043 7-0050
Richard A. Denison, Lead Senior Scientist, Environmental Defense
Fund (EDF) (Attachment to OPPT-2019-043 7-0042)
51
EP A-HO-OPPT-20
19-0437-0051
Gustav A. Ruggiero, Johnson Matthey Inc. (JMI)
52
EP A-HO-OPPT-2.0
19-0437-0052.
Eric Kendall, R&D Director, Adhesives Division, Wilsonart LLC
53
EP A-HO-OPPT-20
19-0437-0053
W. A. Chiu
54
EP A-HO-OPPT-20
19-0437-0054
Bob Sussman, Counsel, Safer Chemicals Healthy Families (SCHF)
55
EP A-HO-OPPT-20
19-0437-0055
Jennifer Sass, Senior Scientist, Natural Resources Defense Council
(NR. DC)
56
EP A-HO-OPPT-2.019-043 7-0056
Suzanne Hartigan, Senior Director, Regulatory and Technical Affairs
Department, American Chemistry Council (ACC)
57
EP A-HO-OPPT-2019-043 7-005 7
Penelope Fenner-Crisp, Environmental Protection Network (EPN)
58
EP A-HO-OPPT-2019-043 7-005 8
Tracey Woodruff, Professor and Director, Program on Reproductive
Health and the Environment, School of Medicine, University of
California, San Francisco
59
EP A-HO-OPPT-2019-043 7-0059
Melvin E. Andersen, Andersen ToxConsulting, LLC
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List of Com incuts
#
Docket l;ilc
Sn hm it lor
60
EPA-HG-GPr i -2019-043 7-0060
Julia M. Rege, Senior Director, Environment & Energy, Association
of Global Automakers, Inc
61
EP A-HO-OPPT-2019-043 7-0061
Mass Comment Campaign sponsored by Environmental Defense Fund
(EDF)
62
EP A-H0-OPPT-2019-043 7-0062.
Christina Starr, Environmental Investigation Agency (EIA)
63
EP A-HO-OPPT-2019-043 7-0063
Eric Berg, Deputy Chief, California Division of Occupational Safety
and Health (Cal/OSHA)
64
EP A-HO-OPPT-2019-043 7-0064
Philip M. Fine, Deputy Executive Officer, Planning, Rule
Development & Area Sources, South Coast Air Quality Management
District (AQMD)
65
EP A-HO-OPPT-2019-043 7-0065
Jared Rothstein, Senior Manager, Regulatory Affairs, Society of
Chemical Manufacturers & Affiliates (SOCMA)
66
EP A-HO-OPPT-2.019-043 7-0066
S. Abbott et al.
67
EP A-HO-OPPT-2019-0437-0067
Faye Graul, Executive Director, Halogenated Solvents Industry
Alliance, Inc. (HSIA)
68
EP A-HO-OPPT-2019-043 7-0068
Suzanne Hartigan, Senior Director, Regulatory and Technical Affairs,
American Chemistry Council (ACC)
69
EP A-HO-OPPT-2.019-043 7-0069
Swati Rayasam, Science Associate, Program on Reproductive Health
and the Environment, University of California, San Francisco (UCSF
PRHE) et al.
70
EP A-HO-OPPT-2019-043 7-0070
Massachusetts Toxics Use Reduction Institute (TURI)
71
EPA-HI
Georges C. Benjamin, Executive Director, American Public Health
Association (APHA)
72
EP A-HO-OPPT-2019-043 7-0072
Randy Rabinowitz, Executive Director, Occupational Safety & Health
Law Project and Jonathan Kalmuss-Katz, Staff Attorney, Earthjustice
on behalf of American Federation of Labor and Congress of Industrial
Organizations (AFL-CIO) et al.
73
EP A-HO-OPPT-2019-043 7-0073
Stephanie Schwarz, Legal Fellow, Environmental Defense Fund
(EDF)
74
EP A-HO-OPPT-2019-043 7-0074
Randy Rabinowitz, Executive Director, Occupational Safety & Health
Law Project and Jonathan Kalmuss-Katz, Staff Attorney, Earthjustice
on behalf of American Federation of Labor and Congress of Industrial
Organizations (AFL-CIO) et al. (Exhibits to OPPT-2019-0437-0072)
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List of Com incuts
#
Docket l;ilc
Sn hm it lor
75
EPA-HG-GPr i -2019-043 7-0075
Liz Hitchcock, Director, Safer Chemicals Healthy Families (SCHF) et
al.
76
EP A-HO-OPPT-2019-043 7-0076
Letitia James, Attorney General of New York et al.
77
EP A-HO-OPPT-2019-043 7-0077
Amy McCamphill, Senior Counsel and Amy Chyao, Assistant
Corporation Counsel, Environmental Division, Law Department, City
of New York
79
EP A-HO-OPPT-2019-043 7-0079
Anonymous
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Knviromncnlal I nto and Exposure
EPA qualitatively analyzed the sediment, land application, and biosolids pathways based on methylene chloride's physical/chemical
and fate properties. Exposure estimates to the environment were developed for the conditions of use for exposures to aquatic
organisms.
Charge Question 1.1. Please comment on EPA's qualitative analysis of pathways based on physical/chemical and fate properties.
Charge Question 1.2. Please comment on the data, approaches and'or methods used to characterize exposure to aquatic receptors
#
Summary of Comments lor Specific Issues
Related to Charge Qucslion 1
EPA Response
Need to describe in more detail the selection of environmental pathways and receptors
SACC
SACC COMMENTS:
Clarify to what extent excluded environmental
pathways (e.g., groundwater, soil) are addressed
by other regulations and add this information to
the conceptual model (Figure 2-1).
Clarify why no terrestrial pathways and receptors
were considered, especially since soil discharges
were at least as likely as discharges via publicly
owned treatment works (POTWs).
The conceptual models only included exposure pathways that are
within the scope of the risk evaluation. The environmental
exposure pathways covered under the jurisdiction of other EPA-
administered statutes and regulatory programs are not within the
scope of the risk evaluation. Emissions to ambient air from
commercial and industrial stationary sources, and associated
inhalation exposures of terrestrial species, are under the
jurisdiction of of the Clean Air Act (CAA), Safe Drinking Water
Act (SDWA), Clean Water Act (CWA), and Resource
Conservation and Recovery Act (RCRA). Clarifying language
about what pathways are addressed under other statutes has been
added to Section 1.4.2 of the Risk Evaluation.
During problem formulation EPA conducted a screening level
analysis to consider whether pathways of exposure for terrestrial
organisms should be further analyzed and determined that
terrestrial organism exposures to MC was not of concern partially
based on estimates of soil concentrations several orders of
magnitude below concentrations observed to cause effects in
terrestrial organisms. In addition, methylene chloride is not
expected to bioaccumulate in tissues, and concentrations will not
increase from prey to predator in either aquatic or terrestrial food
webs. This language was brought forward to discussion of
conceptual model in risk evaluation.
Additional environmental pathways and receptors that shou
d be considered
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SACC
SACC COMMENTS:
Seabirds may be impacted by MC volatilizing
from surface waters near points of discharge.
This pathway should be analyzed for risk.
Based on the Guidance for Ecological Soil Screening Levels
(EPA. 2003a, b) document for terrestrial wildlife, relative
exposures associated with inhalation and dermal exposure
pathways are insignificant, even for volatile substances, compared
to direct ingestion and ingestion of food (by approximately 1,000-
fold). MC is not expected to bioaccumulate in tissues, and
concentrations will not increase from prey to predator in either
aquatic or terrestrial food webs. EPA has added language to the
final risk evaluation document in Section 4.1.4 explaining this
rationale.
Additionally, based on its vapor density (2.93 relative to air) and
persistence in the atmosphere (photolysis half-life by OH* reaction
= 79 days), MC vapor may accumulate under specific conditions,
but typically will disperse readily into the air. For these reasons,
the final risk evaluation does not include further analysis of this
pathway for risk, and EPA was able to assess risk based on
qualitative analysis.
SACC,
70, 73
SACC AND PUBLIC COMMENTS:
EPA omits consideration of a number of possible
sources of MC exposure. MC is present in air,
soil, and sediment and will likely expose
terrestrial and sediment-dwelling organisms. EPA
noted that MC was found in 20% of sediment
samples in the STORET database (p. 26, Problem
Formulation). The rationale for not considering
exposures to sediment-dwelling organisms is
unclear. The risk evaluation states that MC in
sediment is expected to be in the porewater rather
than sorbed to the sediment organic matter.
However, the log Koc of 1.4 indicates that the
concentration in sediment organic matter will be
25 times higher than porewater (without
considering volatilization or sediment
degradation rates).
Clarifying language about what pathways are addressed under
other statutes has been added to Section 1.4.2 of the Risk
Evaluation.
Additionally, the STORET data showing detections in 20% of
samples was summarized by Staples et al., 1985, and quoted by
ATSDR ChttDs://www.atsdr.cdc.eov/toxorofiles/tD I4.pdf). Staples
et al. stated that the median concentration measured in sediment
was 13 (J,g/kg, equivalent to 13 ppb, which is more than 2 orders of
magnitude below the chronic (1,800 ppb) and acute concentration
of concern (COC) (36,000 ppb) values estimated for sediment
invertebrates by read-across from COCs reported for aquatic
invertebrates.
Although the log Koc indicates that MC will partition to sediment
organic carbon, organic matter typically comprises 25% or less of
sediment composition (e.g.,
httDs://oubs.uses.8ov/of/2006/1053/downloads/odf/of-2006-
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If) of which approximately 40-60% is organic carbon
(Schwarzenbach et al 2003). Based on these values, the
sediment-water Kd (where Kd = Koc*/oc) is expected to be equal
to or less than 3.8, indicating that at equilibrium, concentrations in
sediment would be expected to be less than four times higher than
in porewater. However, biodegradation can be expected to be rapid
in anaerobic sediments and the porewater also interacts with
overlying surface water from which MC may be lost via
volatilization and/or aerobic biodegradation. Thus, concentrations
in sediment and pore water are expected to be equal to or less than
concentrations in overlying water. A narrative to this effect has
been added to the final risk evaluation (Section 2.1).
54, 73
PUBLIC COMMENTS:
EPA disregarded pathways of exposure to
sediment and terrestrial organisms based on
estimated partition coefficients that assume that
chemical equilibrium has been established.
However, chemicals of concern can occur in high
concentrations in different environmental
compartments prior to reaching equilibrium. A
better approximation approach might be the
Level III Fugacity model, as suggested by the
SACC, which predicts that 11% of MC will be
distributed to soil, 44.1% to air, 44.8% to water,
and the remainder (0.13%) to sediment, as
calculated using EPI Suite 4.11. An 11%
distribution to soil cannot be dismissed as de
minimis.
Because of its high volatility and use as a solvent
in many open operations, a large fraction of the
total amount of MC produced is lost to the
atmosphere. Estimates of total emissions are high
and MC has been widely found in ambient air.
SACC has previously criticized EPA's failure to
include all environmental exposure pathways in
its determinations of health risk, and the MC
During problem formulation EPA conducted a screening level
analysis to consider whether pathways of exposure for
sediment and terrestrial organisms should be further analyzed
and determined that terrestrial organism exposures to MC was
not of concern partially based on estimates of soil
concentrations being several orders of magnitude below
concentrations observed to cause effects in terrestrial
organisms. See prior response for more information on the
sediment pathway.
EPA did not include the emission pathways to ambient air
from commercial and industrial stationary sources, because
releases of methylene chloride from stationary source to
ambient air are under the jurisdiction of and addressed by
Section 112 of the Clean Air Act (CAA). Resulting exposure
were out of scope as described in the problem formulation for
MC. Clarifying language about what pathways are addressed
under other statutes has been added to Section 1.4.2 of the
Risk Evaluation.
Spills/leaks
Spills and leaks generally are not included within the scope of
a TSCA risk evaluation. EPA is exercising its authority under
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evaluation has the same weakness. The
contribution of air emissions to total should be
accounted for, particularly in areas near emitting
facilities, and should be combined with other
routes of exposure.
Due to its high volatility, MC spills and leaks
will likely lead to soil vapor intrusion as a
potential exposure pathway. This pathway should
be considered but was not addressed in the draft
risk evaluation.
In addition to the fact that several million pounds
of MC are released annually into the air due to its
volatility, disposal to water may also create a
route of exposure to organisms living at the
water-atmosphere interface (e.g., aquatic plants,
amphibians, and/or shorebirds). These organisms
may be disproportionally impacted by MC. In its
literature review, EPA dismissed a study that not
only identified a BCF of 577 in water moss
(Thiebaud et al., 1994), but also found that
concentrations at the water-atmosphere interface
may be more significant than aquatic
concentrations.
EPA unjustifiably disregarded Theibaud et al.
(1994). According to the Systematic Review
Supplemental File: Data Quality Evaluation of
Environmental Hazard Studies, EPA determined
the study to be of unacceptable quality, despite
giving it a mean score of 1.5 (defined as "high"
quality) because one metric, the outcome
assessment methodology (Metric 17), was rated
as "unacceptable" because, according to the
comments, there was "[n]o adverse outcome.
This study analyzed the bioaccumulation/
concentration factors of DCM" (p. 64). As such,
this metric should have been rated as "not
TSCA to tailor the scope of the risk evaluation for MC, rather
than evaluating activities which are determined not to be
circumstances under which MC 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 MC spills or leaks as "conditions
of use." EPA does not consider MC spills or leaks to
constitute circumstances under which MC is manufactured,
processed, distributed, used, or disposed of, within TSCA's
definition of "conditions of use." Congress specifically listed
discrete, routine chemical lifecycle stages within the statutory
definition of "conditions of use" and EPA does not believe it is
reasonable to interpret "circumstances" under which MC is
manufactured, processed, distributed, used, or disposed of to
include uncommon and unconfined spills or leaks for purposes
of the statutory definition. Further, EPA does not generally
consider spills and leaks to constitute "disposal" of a chemical
for purposes of identifying a COU in the conduct of a risk
evaluation.
In addition, even if spills or leaks of MC could be considered
part of the listed lifecycle stages of MC, EPA has
"determined" that spills and leaks are not circumstances under
which MC is intended, known or reasonably foreseen to be
manufactured, processed, distributed, used, or disposed of, as
provided by TSCA's definition of "conditions of use," and
EPA is therefore exercising its discretionary authority to
exclude MC spills and leaks from the scope of the MC risk
evaluation. The exercise of that authority is informed by
EPA's experience in developing scoping documents and risk
evaluations, and on various TSCA provisions indicating the
intent for EPA to have some discretion on how best to address
the demands associated with implementation of the full TSCA
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applicable" because the study did not seek to
determine whether there was a hazard outcome
and should rather have been considered a study
of the chemical's environmental fate and
transport.
risk evaluation process. Specifically, since the publication of
the Risk Evaluation Rule, EPA has gained experience by
conducting ten risk evaluations and designating forty chemical
substances as low- and high-priority substances. These
processes have required EPA to determine whether the case-
specific facts and the reasonably available information justify
identifying a particular activity as a "condition of use." With
the experience EPA has gained, it is better situated to discern
circumstances that are appropriately considered to be outside
the bounds of "circumstances... under which a chemical
substance is intended, known, or reasonably foreseen to be
manufactured, processed, distributed in commerce, used, or
disposed of' and to thereby meaningfully limit circumstances
subject to evaluation. Because of the expansive and
potentially boundless impacts that could result from including
spills and leaks as part of the risk evaluation, which could
make the conduct of the risk evaluation untenable within the
applicable deadlines, spills and leaks are determined not to be
circumstances under which MC is intended, known or
reasonably foreseen to be manufactured, processed,
distributed, used, or disposed of, as provided by TSCA's
definition of "conditions of use."
Exercising the discretion to not identify spills and leaks of MC
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
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intended to be the focus of TSCA risk evaluations. And, as
noted in the preamble to the Risk Evaluation Rule, EPA
believes that Congress intended there to be some reasonable
limitation on TSCA risk evaluations, expressly indicated by
the direction in TSCA section 2(c) to "carry out [TSCA] in a
reasonable and prudent manner."
For these reasons, EPA is exercising this discretion to not
consider spills and leaks of MC to be COUs.
Second, even if MC spills or leaks could be identified as
exposures from a COU in some cases, these are generally not
forms of exposure that EPA expects to consider in risk
evaluation. TSCA section 6(b)(4)(D) requires EPA, in
developing the scope of a risk evaluation, to identify the
hazards, exposures, conditions of use, and potentially exposed
or susceptible subpopulations the Agency "expects to
consider" in a risk evaluation. As EPA explained in the
"Procedures for Chemical Risk Evaluation Under the
Amended Toxic Substances Control Act" ("Risk Evaluation
Rule"), "EPA may, on a case-by-case basis, exclude certain
activities that EPA has determined to be conditions of use in
order to focus its analytical efforts on those exposures that are
likely to present the greatest concern, and consequently merit
an unreasonable risk determination." 82 FR 33726, 33729
(July 20, 2017).
In the problem formulation documents for many of the first 10
chemicals undergoing risk evaluation, EPA applied the same
authority and rationale to certain exposure pathways,
explaining that "EPA is planning to exercise its discretion
under TSCA 6(b)(4)(D) to focus its analytical efforts on
exposures that are likely to present the greatest concern and
consequently merit a risk evaluation under TSCA...." The
approach discussed in the Risk Evaluation Rule and applied in
the problem formulation documents is informed by the
legislative history of the amended TSCA, which supports the
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Agency's exercise of discretion to focus the risk evaluation on
areas that raise the greatest potential for risk. See June 7, 2016
Cong. Rec., S3519-S3520.
In addition to TSCA section 6(b)(4)(D), the Agency also has
discretionary authority under the first sentence of TSCA
section 9(b)(1) to "coordinate actions taken under [TSCA]
with actions taken under other Federal laws administered in
whole or in part by the Administrator." TSCA section 9(b)(1)
provides EPA authority to coordinate actions with other EPA
offices, including coordination on tailoring the scope of TSCA
risk evaluations to focus on areas of greatest concern rather
than exposure pathways addressed by other EPA-administered
statutes and regulatory programs, which does not involve a risk
determination or public interest finding under TSCA section
9(b)(2).
Following coordination with EPA's Office of Land and
Emergency Management (OLEM), EPA has found that
exposures of methylene chloride from spills and leaks fall
under the jurisdiction of RCRA. See 40 CFR 261.33(d)
(defining in part a hazardous waste as "any residue or
contaminated soil, water or other debris resulting from the
cleanup of a spill into or on any land or water of any
commercial chemical product or manufacturing chemical
intermediate having the generic name listed [40 CFR 261.33(e)
or (f)], or any residue or contaminated soil, water or other
debris resulting from the cleanup of a spill, into or on any land
or water, of any off-specification chemical product and
manufacturing chemical intermediate which, if it met
specifications, would have the generic name listed in [40 CFR
261.33(e) or (f)]"); 40 CFR 261.33(f) (listing methylene
chloride as hazardous waste no. U080). As a result, EPA
believes it is both reasonable and prudent to tailor the TSCA
risk evaluation for methylene chloride by declining to evaluate
potential exposures from spills and leaks, rather than attempt
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to evaluate and regulate potential exposures from spills and
leaks under TSCA.
Thiebaud et al. (1994) was evaluated in the Supplemental File:
Data Quality Evaluation of Environmental Fate Studies with a
"high" quality rating for its assessment of bioaccumulation
potential. It has been incorporated into the fate narrative
(Section 2.1.2). The study remains unacceptable for evaluating
environmental hazards; it was incorrectly categorized in
environmental hazards, as a hazard endpoint was not assessed,
so there were no data to evaluate from a hazard perspective.
The draft risk evaluation ignores regulation under the Clean Water Act (CWA)
68
PUBLIC COMMENTS:
The decision to evaluate risk to aquatic life of
MC exposure doesn't account for the Office of
Water's extensive and long-standing regulation
of MC under the CWA and CWA's water quality
criteria and standard setting processes. EPA
OPPT should include in the draft risk evaluation
a summary of any discussions with Office of
Water related to this issue.
Communication and coordination between program offices within
EPA occurs regularly on TSCA-related efforts. While EPA has
recommended water quality criteria for protection of human health
for MC ffiPA-H0-0\* ). it has not developed CWA
section 304(a) recommended water quality criteria for the
protection of aquatic life for MC. Therefore, EPA evaluated
exposures and risks to aquatic life in this TSCA risk evaluation.
Need for tiered exposure assessment approach
68
PUBLIC COMMENTS:
EPA needs a tiered approach to environmental
exposure assessment. The agency should better
explain and provide more transparency into its
approach. EPA applied a number of
conservatisms to its estimates of environmental
exposures, and specifically, surface water
concentrations. While this approach may suffice
for screening-level assessments, it does not
represent real world situations.
In response to comments received from the SACC and the public,
EPA included additional analysis of surface water concentrations,
for the 5 facilities that show risk in Section 4.1 (Environmental
Risk Characterization). The analysis now includes modeling of all
facilities with known releases of MC to surface water according to
Toxics Release Inventory (TRI) and Discharge Monitoring Report
(DMR) data. Any facilities that show risk then go through an
additional analysis with surface water concentrations estimated
using fugacity models in EPI Suite, which take volatilization
into account, and water body information from EXAMS. The
results show that environmental conditions can produce a wide
range of surface water concentrations; however, that range
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encompasses concentrations estimated in E-FAST. Given this
variation, EPA found that E-FAST surface water concentrations
best represent estimated concentrations evaluated in this risk
evaluation may best represent concentrations found at the point of
discharge. The farther from the facility, the more uncertainty, and
the lower the confidence EPA has in the concentration.
Need to consider climate change impact on physical/chemical parameters
49, 75
PUBLIC COMMENTS:
Climate change may influence choice of vapor
pressure, water solubility, and air-water partition
coefficients to use in an assessment.
To the extent that specific impacts of climate
change are difficult to predict, EPA may account
for that uncertainty via sensitivity analyses, use
of a broader range of temperature-related
assumptions, or additional uncertainty factors
(UFs).
Generally, the predicted increases in atmospheric temperatures
will not modify physical-chemical or fate properties sufficiently to
impact the risk evaluation. Based on its vapor pressure (435
mmHg at 25°C) MC is expected to volatilize from dry surfaces.
Increasing temperatures from standard test conditions at 25°C to
30°C would increase vapor pressure by approximately 20%, which
would generally increase MC volatilization and shift MC from soil
and other dry media compartments to the air. Water solubility
would increase, but MC is soluble in water (13 g/L at 25°C). MC's
enthalpy of solvation, needed to correct its air-water partition
coefficient for an increase in temperature, is not readily available;
thus, EPA cannot at this time assess how increasing temperatures
will change air-water partitioning and whether it will increase
volatilization from water to air.
Release of MC to the environment
SACC
SACC COMMENTS:
In the statement "37.8 million pounds were
treated," it is unclear what is meant by "treated."
One Committee member was concerned that this
uncertainty implies that some "treated" MC could
eventually be released to the environment.
One Committee member indicated that the
reported releases on p. 79 seem too low, unless
significant unassessed releases occur through the
atmosphere.
This reference, in the Problem Formulation document, refers to
treatment of waste documented in the TRI data. In TRI treatment
refers to waste containing MC that is treated for destruction on-site
or is sent to a POTW or other off-site location for treatment for
destruction. If waste is ultimately released to the environment, it
would be reported to TRI as a release. EPA clarified in Section
2.2.3 (Summary of Water Release Assessment) that the
magnitudes of annual per site releases are "of MC to water."
Releases through the atmosphere are not assessed in this section.
Dischar
ge flow data
SACC
SACC COMMENTS:
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It is unclear how the hydrologic unit code (HUC)
flow data are used, and the description of the
numbers of facilities releasing to different HUCs
is confusing. Specifically, it is unclear whether
the total flow value used an estimate for the basin
or was measured flow at the discharging facility.
It was suggested that geometric means should be
used instead of arithmetic means as the
appropriate descriptor.
The hydrologic unit codes are used as an organizing landscape unit
of measure to see where known discharging facilities are co-
located with known monitoring locations. For the purposes of this
assessment, a HUC8 and HUC 12 represent the proximate
watershed areas of known releases. The HUC units themselves do
not have specific flow values associated with them. The flow
values used for estimating instream concentrations of MC
represent stream reach specific 7Q10 values associated with the
discharging facility (where possible through aNPDES permit) or
averages across industry codes. Section 2.3.1 has been edited to
make the use of HUC units clearer.
With regard to geometric means or arithmetic means descriptors, if
the commenter is referring to the flow values, the EFAST
modeling program uses various flow metrics in its calculations
including 7Q10s, harmonic means, 30Q5s and IQIOs depending
on the desired output. For surface water quality modeling, a 7Q10
flow value is typically used instead of a mean flow value since the
EFAST model uses it as an input to calculate days of exceedance
of an input concentration of concern for aquatic wildlife endpoints.
Similarly, for drinking water exposures, a 30Q5 flow value is
used.
Inconsistencies/errors in landfill or biosolids release assumptions
SACC
SACC COMMENTS:
It is unclear whether biosolid application is the
only route of discharge to the soil environment
that can be considered under TSCA.
Typically, the primary release pathway directly to soil through
land application of biosolids or as leachate from landfills.
Landfills are under the jurisdiction of RCRA (see section 1.4.2 of
the risk evaluation). Land application of biosolids is not covered
under other statutes so it was included the scope of this risk
evaluation.
49
PUBLIC COMMENTS:
"If methylene chloride is placed in a landfill or
discharged to soil, it can seep into groundwater
and contaminate nearby wells." MC has been
detected in the soil and groundwater at numerous
federal Superfund sites. In the draft risk
Landfill exposures were not included in the environmental
exposure conceptual model or assessed because disposal of
methylene chloride via underground injection, RCRA Subtitle
C hazardous waste landfills, RCRA Subtitle D municipal solid
waste (MSW) landfills, and on-site releases to land from
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evaluation, however, EPA states that "[sjtudies
clearly associated with releases from Superfund
sites ... and landfills were considered out of
scope ... and excluded from data evaluation and
extraction." EPA also ignored available data on
MC in leachate.
MC is present in biosolids from wastewater
treatment, which are then applied to land as
fertilizer. The MC risk evaluation should include
an evaluation of available data that identify
where these types of applications are made,
numbers of people exposed, and
presence/numbers of sensitive biological
receptors exposed by this pathway.
industrial non-hazardous waste and construction/demolition
waste landfills are covered under the jurisdiction of RCRA.
EPA qualitatively assessed discharges of MC in biosolids
based on its physical chemical and fate properties. Based on its
vapor pressure (435 mmHg at 25°C ) and Henry's law constant
(0.00291 atm-m3/mole), MC in land-applied biosolids is
expected to primarily volatilize to air, where it will disperse
into the atmosphere. Additionally, based on the Guidance for
Ecological Soil Screening Levels ( 33a. b) document
for terrestrial wildlife, relative exposures associated with
inhalation and dermal exposure pathways are insignificant,
even for volatile substances, compared to direct ingestion and
ingestion of food (by approximately 1,000-fold). MC is not
expected to bioaccumulate in tissues, and concentrations will
not increase from prey to predator in either aquatic or
terrestrial food webs.
Physica
/chemical property and fate values and interpretation
SACC
SACC COMMENTS:
Adding values for environmental partition
coefficients and relative rates of transport and
transformation to Figure 2-1 (p. 65) would
provide a more quantitative description of the
pathways.
Add octanol-air partition coefficient (Koa) values
to the physical-chemical property table.
Henry's Law values should be reported as
dimensionless air-water partition coefficients
since partition coefficients directly relate
chemical concentrations in the two phases that
are in equilibrium.
Be more precise in how equilibrium properties
are used to describe relative concentrations. For
The environmental fate diagram was updated with partition
coefficients and degradation rates.
The Koa value reported in the PhysProp database in EPI Suite
has been added to the physical chemical properties table.
The Henry's law constants with the units atm-m3/mol was
converted to the dimensionless value and added to the p-chem
properties table.
The language of the risk evaluation has been modified to clarify
the issue of equilibrium concentrations versus rates of transport or
degradation. The quoted statement on biosolids was amended to
read, "Based on the results of the Sewage Treatment Plant [STP]
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example, the risk evaluation states (p. 64):
"Based on high volatilization, negligible
adsorption, and possible biodegradation,
concentrations of methylene chloride in land-
applied biosolids are expected to be lower than
concentrations in wastewater treatment plant
effluents." This statement is true only if
volatilization and/or biodegradation rates are
rapid relative to sorption.
Review the risk evaluation for incorrect
environmental fate statements associated with
implied rates to equilibrium of physical-chemical
properties. For example, equilibrium properties
such as Henry's law and vapor pressure do not
inform volatilization rates in the environment.
Henry's law constant is an equilibrium value not
a rate.
The photolysis process referred to in Table 2-1
should be clearly identified as "atmospheric
oxidation via the OH radical."
The term 'sorption,' which includes both
adsorption and absorption, is preferred over
'adsorption' when discussing the interaction of
an organic chemical with an environmental solid
(see review by Doucette, 2003).
The risk evaluation assumes that all sediment
environments are anaerobic (e.g., p. 299). This is
not likely to be true in many shallow, rapid flow
rivers.
The following statement (p. 64) is incorrect:
"Based on its vapor density (2.93 relative to air),
volatilized methylene chloride is expected to
remain near ground level." This would only be
true for a very short period of time after release.
model, in which removal of methylene chloride from wastewater
is dominated by volatilization, in combination with possible
biodegradation, concentrations of methylene chloride in land-
applied biosolids are expected to be lower than concentrations in
wastewater treatment plant effluents."
The risk evaluation document has been revised to avoid implying
rates from Henry's Law constants (e.g., 'rapidly' was removed
from the discussion of volatilization potential on pg 68 of the
revised risk evaluation). However, it is noted that volatilization
rates are controlled by resistances to mass transfer. In two-film
theory, the mass-transfer coefficient associated with volatilization
is directly related to the Henry's law constant.
The suggested change has been made.
The suggested change has been made throughout the document.
The text has been edited to clarify that not all sediments are
anaerobic.
The text has been edited to specify that MC will remain near
ground level in very calm conditions but disperse readily with
mixing.
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At low concentrations and under most
environmental conditions, MC would rapidly mix
with air.
66
PUBLIC COMMENTS:
There is a lack of clarity about inputs chosen for
the modeling. For example, there was a high
variation in the hydrolysis half-life value (Table
2-1); there is also an inconsistency in the
standard temperature used.
The inputs for EPI Suite model runs are described in Appendix
C of the risk evaluation. To summarize, the inputs were chemical
name, CASRN number, and structure; and physical-chemical
property values (water solubility, melting point, boiling point, log
Kow, vapor pressure, and Henry's law constant) as presented in
Table 1-1 of the risk evaluation. Hydrolysis half-life (as presented
in Table 2-1) was not entered as a model input in EPI Suite.
73
PUBLIC COMMENTS:
In its assessment of biodegradation studies to
understand fate and transport of MC through the
environment, EPA states that "[sufficient
numbers of high-confidence biodegradation
studies were available" for this endpoint (p. 62).
However, of the three aerobic biodegradation
studies, one of the high-confidence studies cited
by EPA indicates that for aerobic activated
sludge there was 0% degradation of MC in 28
days, whereas a second study found 100%
degradation in 7 days (Table 2-1, p. 63).
According to the authors of the first study, MC is
non-biodegradable and causes cellular lyses
(Lapertot and Pulgarin, 2006). The second study,
in contrast, showed rapid degradation (Tabek et
al., 1981). The stark difference between the
biodegradation rates reported in these studies is
not examined further by EPA and is instead
simply reported as having a range "depending on
the microorganisms present and previous
adaptation to methylene chloride" (p. 63). This is
an important caveat; without proper microbial
consortia and environmental conditions,
biodegradation may not occur, stall out, or
proceed slowly enough to expose receptors.
Discussion of this issue has been added to the fate uncertainties
Section (2.1.3) and to the environmental exposure assessment
uncertainties and assumptions section (4.4.1). As it relates to
EFAST not taking into account fate parameters like
biodegradation, language describing additional analysis and
evaluation on the effect water depth, wind speed and water
velocity played on the volatilization rate of MC from surface water
was described and added to the evaluation. Not taking these fate
parameters into account may lead to an over estimation of risk.
However, in response to this comment and others, EPA included
additional analysis of surface water concentrations, for the 5
facilities that showed risk in the environmental risk
characterization section. The analysis now includes modeling of
all facilities with known releases of MC to surface water according
to TRI and DMR data. Any facilities with risk then go through an
additional analysis with surface water concentrations estimated
using higher tier fugacity models in EPI Suite, which take
volatilization into account, and information from EXAMS. The
results show that environmental conditions can produce a wide
range of surface water concentrations which encompasses
concentrations estimated in E-FAST.
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The agency used a conservative assumption of no
biodegradation in its E-FAST modeling. This
conservative assumption should be carried
throughout the evaluation because, the potential
of slow or minimal biodegradation of MC is
important in other aspects of environmental fate
and transport, beyond what may occur in
wastewater treatment facilities.
Data quality, variability and uncertainty for physical/chemical and fate properties
SACC
SACC COMMENTS:
The Committee suggested expanding the
discussion on data quality assessment. Generally,
physical-chemical properties can be considered
high in quality if experimentally measured
(unless there are obvious procedural or analytical
problems), medium in quality if derived from
other experimental data or relationships (e.g., by
algorithm), and low if determined by in silico
models (e.g., quantitative structure property
relationships [QSPRs]; Hansch et al., 1995).
However, EPA rated the hydrolysis value from
Dilling et al. (1975) as "low" in Table 2-1 (even
though Dilling et al. 1975 is rated as "high" in the
data quality evaluation supplemental file) while
an estimated value was ranked "high."
The Committee suggested adding more
discussion of variability in physical/chemical
properties obtained from EPI Suite and other
references. For example, the aerobic activated
sludge biodegradation data (Table 2-1, p. 63)
show variability. The values from Lapertot and
Different data quality evaluation metrics are used for experiments
or models, because the metrics are designed to identify possible
issues with specific aspects of the studies. Thus, the data quality
ratings for experimental results are not directly comparable to
those for model results. The data are selected for use based on a
data integration exercise in which the assessor weighs the study
types (experimental, modeling), details of the studies, and their
overall data quality ratings. High-quality measured data are
selected for use first, and if they are unavailable the assessor will
choose from among estimated values and lower-quality measured
data.
The error in the Dilling et al., 1975 data quality rating has been
corrected so that Table 2-1 and the supplemental file agree.
Discussion of the range of reported biodegradation rates has been
added to the fate uncertainties section (2.1.3). Regarding the
variability of the Lapertot and Pulgarin (2006) results, study
quality scores were assigned according to the criteria outlined in
Application of Systematic Review in TSCA Risk Evaluations and
without respect to the reported values themselves. The results of
the EPI Suite BIOWIN models, which estimate biodegradation
rates, were presented in the MC problem formulation and have
been added to the fate section of the risk evaluation.
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Pulgarin (2006) were considered high quality,
even though these results were highly variable.
EPA should provide a short discussion of why
the values were dissimilar and present an
estimated value(s) for comparison.
For values estimated within EPI Suite, EPA
should identify the estimation method used, rank
values based on the reliability of the estimation
method and provide the rationale for selecting
one estimation method over another.
EPA should incorporate a description of the
uncertainty associated with the measured and
estimated physical-chemical and fate properties
into the draft risk assessment. Several Committee
members suggested estimating confidence
intervals around each property and conducting a
sensitivity analysis to determine whether
potential variability would significantly change
the outcome of the qualitative pathway analysis.
The bioconcentration factor, log Koc, and aerobic biodegradability
were the only values estimated with EPI Suite for which the
program contains multiple calculation techniques. In each of these
cases, the various techniques estimated values similar enough to
result in equivalent fate assessments. The result of each technique
is now presented in Table 2-1 or in the fate discussion.
The rate of aerobic biodegradation is the key area of uncertainty in
the fate assessment for MC. A description of this has been added
to the fate section (2.1.3). Due to the differences among study
conditions, generating confidence intervals for each property
would be very complex. However, the range and quality of
available data were considered in the fate assessment of MC.
73
PUBLIC COMMENTS:
Physical-chemical property models in EPI
Suite that were used to derive environmental
fate characteristics (Table 2-1) lack transparency
in performance and applicability.
EPI Suite has undergone peer review and the models contained
in EPI Suite have been published in peer-reviewed journals as
described in the EPI Suite documentation. The training set for
each QSAR model is available for the user to assess applicability
of a given input structure, and the performance of the models is
summarized in the EPI Suite help files and in the relevant
published articles (see https://www.epa.gov/tsca-screening-
tool s/epi-suitetm -estim ation-program -interface#peer).
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Henry's Law constant, provided in Table 1-1,
which was sourced from the literature, is not the
value that EPA used in its evaluation. Without
explanation, EPA instead used the Henry's Law
constant that was estimated using EPI Suite
(see pp. 63, 299, Section 4.1.4 Risk Estimation
for Terrestrial).
It is important to be judicious in sourcing
physical-chemical property values, justify
reliance on particular sources and address any
variability and uncertainty associated with the
values, including ramifications for conclusions
regarding environmental fate. Many of the values
presented in the draft risk evaluation (Table 1-1,
p. 39) were sourced from textbooks, which are
not original data. The quality of the studies (or
models) and the underlying data must be
evaluated before they are used in a risk
evaluation.
It is unclear why EPA did not use the newer,
more transparent QSPR model, OPEn structure-
activity/property Relationship App (OPERA), for
its estimation of environmental fate
characteristics. OPERA includes the reporting of
a chemical-specific applicability domain and was
built using a newer database of physical-chemical
parameters.
The inconsistencies have been corrected (Section 2.1.2, pg. 70;
Section 4.2.4, pg. 354).
The sources used to collect physical-chemical property data for
MC were all subjected to data quality evaluations based on metrics
presented in the Application of Systematic Review in TSCA Risk
Evaluations document, and the full data aualitv assessments are
presented in a supplemental file.
OPERA-estimated values have been added to the discussion of
fate characteristics where measured values were not available.
Other comments
67
PUBLIC COMMENTS:
The risk evaluation for MC cannot be considered
complete without assessing the toxicity and
flammability risks of alternative products. MC-
based paint remover products were developed
and became dominant because of their
effectiveness and because they are not
flammable. The draft risk evaluation does not
Under TSCA section 6(b), EPA is required to determine whether a
chemical substance presents unreasonable risks without
consideration of costs or other non-risk factors. Consideration of
technically and economically feasible alternative substances is a
step that may occur as part of a potential risk management action
developed pursuant to TSCA section 6(c)(2)(C). This type of
analysis could be considered as part of a subsequent risk
management action if unreasonable risk are determined and
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consider the significant health risks of
alternatives (e.g., acetone, methanol, toluene) in
confined spaces used in a similar manner to MC.
regulatory considerations are pursued.
Environmental Releases ;intl Exposure
EPA evaluated releases to water and aquatic exposures for conditions of use in industrial and commercial settings. EPA used Toxics
Release Inventory (TRI) and Discharge Monitoring Report (DMR) data to provide a basis for estimating releases. EPA used these
releases and associated inputs within EFAST 2014 to estimate instream chemical concentrations and days of exceedance. EPA also
evaluated monitored values of methylene chloride in surface water and where possible compared those values to estimated release
concentrations.
Charge Question 2.1: Please comment on the approaches, models, and data used in the water release assessment including
comparison to monitored data.
Charge Question 2.2: Please provide any specific suggestions or recommendations for alternative data or estimation methods,
including modeling approaches, that could be considered by the Agency for conducting or refining the water release assessment and
relation to monitored data.
#
Summary of Comments for Specific Issues Related
to Charge Question 2
EIW/OPPT Response
Use of E-FAST to predict surface water concentrations
SACC
SACC COMMENTS:
The Committee considered comparisons between
E-FAST-generated surface water concentrations
and monitoring data as inappropriate since the
model is not applicable for volatile compounds
like MC.
o Modeled values generated from E-FAST were
as high as 17,000 (J,g/L, which is inconsistent
with the highest measured concentration
reported at 134 [j,g/L and most measured
values around 5 [j,g/L or less,
o Even if the model were applicable to MC, the
number of samples collected was too small to
draw definitive conclusions on possible
associations between measured concentrations
in surface water and predicted concentrations
from facility releases.
In response to comments received from the SACC and the
public, EPA included additional analysis of surface water
concentrations for the 5 facilities that indicated risk in the
environmental risk characterization section. The analysis
now includes modeling of all facilities with known
releases of MC to surface water according to TRI and
DMR data. Any facilities with indicated risk then went
through an additional analysis with surface water
concentrations estimated using higher tier fugacity models
in EPI Suite, which take volatilization into account, and
information from EXAMS. The results show that
environmental conditions can produce a wide range of
surface water concentrations which encompasses
concentrations estimated in E-FAST.
EPA agrees that the lack of colocation between monitored
values of MC and estimated surface water concentrations
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Modify the E-FAST model to include
volatilization or use a more appropriate model for
MC that incorporates volatilization, such as the
EPA WASP model (Ambrose, 1987) or Exposure
Analysis Modeling System (EXAMS).
Use surface water monitoring data available for
other similar chlorinated volatile solvents having
larger databases to evaluate models and model
predictions.
At a minimum, the half-lives predicted in the EPI
Suite program could be used to adjust the E-
FAST predicted surface water concentrations.
from known releases for the majority of results makes it
difficult to draw definitive conclusions and stated this in
Section 2.3.2. Nevertheless, the evaluated monitoring data
within the United States showed that the majority of
samples were at non-detectable levels and those with
detectable levels of MC were below identified COCs.
EPA appreciates the suggestion to do modeling across
similar classes of chemicals to evaluate model
performance and predictive ability and will entertain those
suggestions for future risk evaluations. However, absent
monitoring programs designed to measure these
concentrations proximal to discharging facilities, the co-
location of monitoring information with known facility
releases is expected to be small thereby limiting model
verification with actual monitored values.
41, 68
PUBLIC COMMENTS:
EPA used its E-FAST model to predict surface
water concentrations at the TRI/DMR facilities
based on facility-specific emissions and
wastewater treatment removal. The PDM was used
to predict the number of days a stream
concentration may exceed the designated COC. It
is unclear whether EPA used the dilution factor for
the site-specific receiving water body or the
national 7Q10 dilution factor, which is equivalent
to 1.0. The SACC should consider whether EPA
should be using the 7Q10 value for the facility-
specific receiving water body associated with the
facilities discharge, rather than the E-FAST PDM
7Q10 for dilution.
o Surface water dilution estimates calculated
using E-FAST for a still water body (i.e., bays,
lakes, and estuaries) typically range from 1
(representing no dilution) to 200 (p. 82).
Wherever possible, EPA used site specific 7Q10 flow
metrics to estimate flows at waterbodies receiving known
facility releases. For still water bodies, a dilution factor
approach is applied since no available 7Q10 metric is
available. If neither of these metrics are available a flow
associated with the industry sector of the discharging
facility was chosen to approximate the instream flow (p.
84 of draft).
The Long Beach facility does discharge into a tidal
estuary and has a given dilution factor of 1 within the
EFAST model (see Supplemental File: Supplemental
Information on Surface Water Exposure Assessment;
(HPA, 2019b)). The uncertainties and assumptions of
these estimates are discussed in Section 4.3 and while the
commenter may be correct that such a waterbody would
lead to greater dilution, EPA used the best available
science to evaluate this facility. There was no better
estimate of possible dilution occurring within this specific
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However, these assumptions are unrealistically
low and do not reflect the reality of the
facilities evaluated. For example, the Long
Beach Water Pollution Control Plant (New
York; Table 4-1, p. 289) discharges into a tidal
estuary of the southern Long Island Sound and
is likely to experience significantly greater
dilution than assumed. EPA should conduct a
more realistic, site-specific analysis for the
limited number of distinct facilities that appear
to show unacceptable risk quotients.
waterbody that was found.
Use of a mass balance approach to estimate discharges to the environment
SACC, 73
SACC AND PUBLIC COMMENTS:
The Committee recommended performing a mass
balance analysis to describe the disposition of all
of the MC produced or imported to its ultimate
disposal, in order to provide a more realistic
estimate of environmental discharges and to
ensure that the risk evaluation addresses all major
exposure opportunities.
EPA relies on the CDR and TRI to compile
estimates of discharges, but there are limitations
on both of those reporting schemes that result in an
incomplete picture. In the case of MC, over 260
million pounds of MC are manufactured in or
imported into the United States annually (p. 40),
yet less than 3 million pounds of MC were
identified as released to the air and less than 3,000
pounds to surface water. One Committee member
suggested that using the National Emission
Standards for Hazardous Air Pollutants
(NESHAP) might be another approach to estimate
releases to water since it contains purchase
records, disposal records and air releases. The
remainder could be interpreted as releases to
water.
EPA does not have reasonably available mass balance
data to conduct such an analysis for MC. EPA's analysis
uses TRI and DMR to estimate the highest local per site
water releases of MC.
NESHAPs are air regulations that require companies to
keep certain records; however, these records are retained
by individual sites and companies and would need to be
requested from each company/facility individually. These
records could not be obtained in the timeframe for the risk
evaluation. This comment may be in reference to the
National Emissions Inventory (NEI), which is compiled
every 3 years for the purpose of supporting residual risk
evaluations as required by Section 112 of the CAA. NEI
contains air emission estimates, which sites estimate using
a variety of methods, such as emission factors, mass
balance, stack monitoring. Purchase and disposal records
are not reported to NEI. However, NEI could not be used
to reasonably estimate water releases as it only includes
air releases from larger facilities and would not include
releases from many smaller shops that use methylene
chloride.
The EFAST modeling program used in this assessment
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One Committee member suggested the mass
balance calculation be performed for each assessed
facility, considering intake and documented
disposal plus water and air releases. Another
suggested releases from multiple facilities located
in the same hydrologic unit be combined.
The Committee recommended that discharges
estimated from the mass balance approach be used
as input to a Fugacity level 3 or similar model to
compare with (and supplement) any available
environmental monitoring data.
does not offer the ability to model multiple releases within
the same hydrologic unit or stream reach. While the
majority of evaluated hydrologic units at the HUC8 level
have a single releasing facility ( 73%), EPA recognizes
this uncertainty and has added the following language to
Section 4.4.1, "EPA did not consider releases' combined
impact on concentrations in the same waterbody. This
may lead to an underestimation of surface water
concentrations in waterbodies with multiple releases
coming from one facility or waterbodies with multiple
facilities contributing releases."
Limitations of using TRI and DMR data to estimate releases
SACC
SACC COMMENTS:
The lack of surface water monitoring data for MC
was a concern, as was the insufficiency of just
looking at TRI and DMR data for releases. Given
that only facilities of a certain size are required to
submit these reports, it is likely that overall release
data are underestimated.
SACC members questioned why the quantitative
environmental assessment is limited only to the
measured water concentrations from the 2016
dataset and recommended that the discussion be
expanded to better justify why all of the available
data were not used.
The Committee expressed concern that monitoring
data were obtained far away from the discharging
facility.
The environmental assessment was limited to 2016 to
better harmonize with the estimated releases from the
2016 TRI and DMR releases. EPA's analysis uses TRI
and DMR to estimate the highest local per site water
releases of MC and is not intended to estimate overall
releases. EPA's analysis uses TRI and DMR to estimate
the highest local per site water releases of MC. A mass
balance calculation for each assessed facility, considering
intake and documented disposal plus water and air
releases, is not useful for EPA's analysis, which is to
estimate the highest local per site water releases of MC.
EPA used reasonably available data concerning monitored
concentrations and reported releases of MC. The
assumptions and uncertainties associated with using these
data sources are discussed in Section 4.3. Included in
those uncertainties is the distance and possible time of
sampling in comparison to known releasers of MC.
62, 66, 73,
75
PUBLIC COMMENTS:
Using the TRI and DMR to estimate releases into
the environment is not health-protective and
EPA used the best available science and reasonably
available data concerning known releases of MC. EPA's
analysis uses TRI and DMR to estimate the highest local
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underestimates the true release of MC into the
environment.
Reporting requirements limit the amount of
entities providing information to the TRI. A
facility is only required to report if it has ten or
more full-time employees, is included in an
applicable NAICS code, and manufactures,
processes, or uses the chemical in quantities
greater than a certain threshold. Companies
producing, manufacturing, and using MC on a
smaller scale are overlooked.
There are potential sources of emissions from
sectors not covered by TRI reporting, such as oil
and gas extraction.
For DMR, the EPA used the Water Pollutant
Loading Tool within EPA's Enforcement and
Compliance History Online to attain MC point
source water discharge. States are only required to
load "major" discharger data into DMR, at the
discretion of the state. This is a massive
uncertainty and flaw in the reporting system.
per site water releases of MC. The assumptions and
uncertainties associated with using these data sources,
such as limitations on required reporters, are discussed in
Section 4.4.
Use of additional data sources for monitoring and release data
SACC,
70, 73
SACC AND PUBLIC COMMENTS:
Consider exploring other potential data sources for
monitoring and release data, such as the
Association of Public Health Laboratories
(APHL), the National Emission Standards for
Hazardous Air Pollutants (NESHAP), and the
Toxic Use Reduction Act (TURA).
Analytical data for soil, vapor, and water samples
collected during subsurface or remediation
investigations of regulated chemicals like MC are
often required to be submitted in electronic data
formats to state or regional regulatory agency;
EPA should obtain and use these data.
EPA did not find readily available information from
APHL or TURA.
NESHAPs are air regulations that require companies to
keep certain records; however, these records are retained
by individual sites and companies and would need to be
requested from each company/facility individually. These
records could not be obtained in the timeframe for the risk
evaluation. This comment may be in reference to the
National Emissions Inventory (NEI), which is compiled
every 3 years for the purpose of supporting residual risk
evaluations as required by NESHAPs. NEI contains air
emission estimates, which can be estimated by sites using
a variety of methods, such as emission factors, mass
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Some Committee members were concerned that
EPA did not have adequate MC production use
and discharge data and had to rely on industry data
(e.g., from market reports). They were concerned
that market reports and other industry data have
not been evaluated for quality.
balance, stack monitoring. Purchase and disposal records
are not reported to NEI. However, NEI could not be used
to reasonably estimate water releases as it only includes
air releases from larger facilities and would not include
releases from many smaller shops that use methylene
chloride.
Industry data covers a wide range of data EPA reviewed
in developing the COU and subsequent exposure scenarios
included in the Risk Evaluation. Some data is self-
reported by industry directly to EPA such as CDR and
TRI. Both sources require a signed certification statement
confirming that all information submitted on the form is
complete and accurate to the best knowledge of the
submitter. CDR and TRI also go through data quality
processes to help reduce the issue of misreports. Other
industry data have not been used directly for the water
release assessment for MC. EPA also consults trade
publications and technical references that go through a
vetting and review process prior to publication.
Information also is collected through direct
communication with industry, trade associations, or other
stakeholders (including our federal partners). The
information collected from these sources is helpful in
refining EPA's understanding of the information
submitted by industry through CDR and TRI and often
provides much needed context to those data.
Model inputs and assumptions
SACC
SACC COMMENTS:
Better document the uncertainty of model inputs
and assumptions and perform sensitivity analysis
to categorize the impact of this uncertainty on
exposure estimates. For example, the removal
from wastewater treatment was estimated to be
Possible uncertainties in the WWTP removal estimates
include confidence in the physical-chemical properties, the
range of reported aerobic biodegradation rates, and variation
in performance among wastewater treatment plants. The
physical-chemical properties reported in Table 1-1 and used
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57% and this value was used in the model with no
variation or uncertainty considered.
in the STPWIN model are reported in high-quality data
sources and align with expected values for MC, and thus are
of high-confidence. The uncertainty in biodegradation rates is
discussed in Section 2.1.3, and MC removal from wastewater
by biodegradation was assessed to range from negligible to
complete depending on the conditions in a given WWTP. The
MC removal performance may vary among WWTP, but the
STPWIN model is designed to estimate removal from a
model, conventional WWTP. The removal estimated by
STPWIN for abiotic processes alone (57%) aligns with the
measured overall removal reported by TRI (54%).
68
PUBLIC COMMENTS:
EPA noted that due to its high Henry' s law
constant and vapor pressure, MC is expected to
volatilize rapidly from wastewater (p. 64).
However, it did not consistently or appropriately
apply this aspect to its exposure estimations. For
example, a number of the active releasers
identified in Table Apx E-4 (pp. 572-591) are
indirect releasing facilities, meaning that their
wastewater is piped and sent to another treatment
facility, typically a POTW. The EPA analysis does
not consider dissipation in the sewers prior to
wastewater treatment, also referred to as
"pipeloss" (Matthjis et al., 1995). In addition, EPA
estimated that the half-life of MC in a model river
will be 1.1 hours (p. 64); however, it did not
appear to apply that half-life when considering
effluent discharges to a receiving stream and the
impact on downstream concentrations.
EPA stated that, "[tjwenty days of release was
modeled as the low-end release frequency at which
possible ecological chronic risk could be
determined (pp. 79-80)."
o The 20-day release assumption should be
better justified. While it may seek to replicate a
As other comments have pointed out, Henry's law
constants and vapor pressures indicate partitioning
directions but not rates. Thus, the risk evaluation has been
edited and no longer states that MC will volatilize
"rapidly."
Pipe loss was not considered in our estimated releases due
to lack of information about the rates that would occur for
a chemical such as MC or the distances between
transferring facilities to indirect dischargers.
EPA added more explanation about the 20-day release
assumption to Section 2.3.1.2.1 E-FAST Calculations in
the Risk Evaluation. The 20-day chronic risk criterion is
derived from partial life cycle tests (e.g., daphnid chronic
and fish early life stage tests) that typically range from 21
to 28 days in duration. Additionally, EPA included
additional analysis of surface water concentrations, for the
5 facilities that showed risk in the environmental risk
characterization section. The analysis now includes
modeling of all facilities with known releases of MC to
surface water according to TRI and DMR data. Any
facilities with risk then go through an additional analysis
with surface water concentrations estimated using
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worst-case situation, there is no basis in fact
that any particular facilities discharge their
effluents accordingly,
o The 20-day release scenario is coupled with
7Q10 dilution. The odds of the 20 days falling
within the 7Q10 window are small and overly
conservative. EPA should assume mean flow if
it is going to apply an arbitrary, conservative,
limited release scenario,
o If this arbitrary assumption results in
exceedance of the COC, EPA should not
conclude that the situation constitutes an
unreasonable risk but that additional analysis
at a higher tier would be justified.
fugacity models in EPI Suite, which take volatilization
into account, and information from EXAMS. The results
show that environmental conditions can produce a wide
range of surface water concentrations which encompasses
concentrations estimated in E-FAST.
The use of the 7Q10 flow value is intended to represent a
protective evaluation of low flow conditions where
environmental and human populations may be most
affected. The predicted concentrations associated with
different flow metrics are available in supplementary
materials, but the modeling with EFAST does not allow
for evaluation of days of exceedance outside use of the
7Q10 flow metric.
73
PUBLIC COMMENTS:
EPA found that releases from certain disposal and
recycling facilities would result in surface water
concentrations well above the COC for MC (pp.
427-28). ButEPA's analysis may still have
underestimated the total risk from these releases.
For example, when estimating the releases from
one facility where the surface water concentration
exceeded the COC, EPA "assumed 57% removal
of methylene chloride before it was released to
surface water" (p. 288). EPA did not establish that
this assumed removal actually occurs, so EPA may
be underestimating the total risk presented by
releases from this facility.
Releases were not considered together and
combined when appropriate. For example, three of
the facilities where modeled surface water
concentrations exceed the chronic COC engaged
in transfers to the same facility - Clean Harbors
Baltimore (p. 287). Particularly given that the
modeled results for each of the three facilities
The EPI Suite model that estimates removal during
wastewater treatment (STPWIN) estimated that 57% of
MC in influent water will be removed via abiotic
processes (sorption to sludge and volatilization to air) in a
conventional wastewater treatment plant (WWTP) with
secondary treatment via activated sludge. This does not
include possible biodegradation, but because there is a
range of reported aerobic biodegradation rates EPA
assessed that removal via biodegradation may range from
negligible to complete depending on factors such as the
microbial consortium in a given WWTP, its pre-
adaptation to MC, and biomass concentration in the
activated sludge stage. Discussion of this uncertainty has
been added to Section 2.1.3. Thus, 57% removal was
expected to be the more protective value to use. The
estimated 57% removal aligns with the WWTP removal
efficiency for MC reported by TRI (54%), which was
used in exposure calculations.
As mentioned, EPA did not consider releases' combined
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indicate a risk when analyzed separately, EPA
should have considered how they may combine to
present an even greater risk.
impact on concentrations in the same waterbody. EPA
added language to the Key Assumptions and Uncertainties
Section describing how this may lead to an
underestimation of surface water concentrations in
waterbodies with multiple releases coming from one
facility or waterbodies with multiple facilities contributing
releases.
Climate change impact on stream flow rates
49, 75
PUBLIC COMMENTS:
Climate change is likely to affect stream flow rates
(EPA used 15-30-year-old stream flow data to
calculate surface water concentrations for MC),
contaminant fate and transport, human sensitivity
to chemical stressors, and even the use of personal
protective equipment (PPE) (which can be even
more burdensome in higher temperature). To the
extent that specific impacts are difficult to predict,
EPA should account for that uncertainty through
sensitivity analyses, a broader range of
temperature-related assumptions, or additional
UFs.
As mentioned, climate change is anticipated to affect a variety
of factors considered in this assessment. The stream flow data
used represents the most comprehensive and accurate
nationwide datasets available for evaluation and analysis. The
assumptions and uncertainties of this dataset are discussed in
full within Section 4.3. EPA did not find reasonably available
information on impacts of climate change on use of PPE, and
EPA does not have methods to conduct such sensitivity
analyses on use of PPE. EPA agrees that there are challenges
associated with use of PPE; they are described in Section
5.1.1.3. By providing risk estimates assuming use of PPE,
EPA is not recommending or requiring use of PPE. Rather,
these risk estimates are part of EPA's approach for
developing exposure assessments for workers that use the
reasonably available information to construct exposure
scenarios that are anchored in the real-world use of chemicals.
When appropriate, in the risk evaluation, EPA will use
exposure scenarios both with and without engineering
controls and/or PPE that may be applicable to particular
worker tasks on a case-specific basis for a given chemical.
Again, while EPA has evaluated worker risk with and without
PPE, as a matter of policy, EPA does not believe it should
assume that workers are unprotected by PPE where such PPE
might be necessary to meet federal regulations, unless it has
evidence that workers are unprotected. For the purposes of
determining whether or not a condition of use presents
unreasonable risks, EPA incorporates assumptions regarding
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PPE use based on information and judgement underlying the
exposure scenarios. These assumptions are described in the
unreasonable risk determination for each condition of use, in
section 5.2. Additionally, in consideration of the uncertainties
and variabilities in PPE usage (e.g., the burden associated
with the use of supplied-air respirators, including the expense
of the equipment and the necessity of fit-testing and training
for proper use), EPA uses the high-end exposure value when
making its unreasonable risk determination in order to address
those uncertainties. EPA has also outlined its PPE
assumptions in section 5.1. Further, in the final risk
evaluation for MC, EPA has determined that most conditions
of use pose an unreasonable risk to workers even with the
assumed PPE.
Generally, the predicted increases in atmospheric
temperatures will not modify physical-chemical or fate
properties sufficiently to impact the environmental fate and
transport assessment. Based on its vapor pressure (435 mmHg
at 25°C) MC is expected to volatilize from dry surfaces.
Increasing temperatures from standard test conditions at 25°C
to 30°C would increase vapor pressure by approximately
20%, which would generally increase MC volatilization and
shift MC from soil and other dry media compartments to the
air. Water solubility would increase, but MC is soluble in
water (13 g/L at 25°C). MC's enthalpy of solvation, needed to
correct its air-water partition coefficient for an increase in
temperature, is not readily available; thus, EPA cannot at this
time assess how increasing temperatures will change air-water
partitioning and whether it will increase volatilization from
water to air.
No requirement that release be tied to conditions of use
73
PUBLIC COMMENTS:
Under TSCA, EPA must conduct risk evaluations
that consider all "reasonably available"
information relating to a chemical substance,
EPA has considered releases that are not attributable to
specific conditions of use, and these releases are addressed in
Section 2.2.2.22.
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including information that may not be tied to a
specific condition of use, 15 USC § 2625(k).
There is no basis in TSCA for EPA to ignore
environmental releases of a chemical simply
because it has not determined or cannot determine
how much of the exposure is attributable to a
particular condition of use.
Consider disposal and spill related releases
66, 49, 75
PUBLIC COMMENTS:
The draft MC risk evaluation does not evaluate the
risks associated with disposal-related releases,
including reasonably foreseen spills and leaks
during production, use, distribution, and disposal.
In its report on the 1,4-dioxane and HBCD risk
evaluations, the SACC noted EPA's failure to
consider releases associated with disposal,
including "the movement and breakdown of
disposed materials from soils and in particular
from landfills into air and waterways" and
recommended that "EPA should also include a
spill scenario as potential and probable
occurrences in the occupational environment."
Since then, the Ninth Circuit has affirmed that
"TSCA's "definition of'conditions of use' clearly
includes uses and future disposals of chemicals,"
as well as "spills, leaks, and other uncontrolled
discharges" emanating from landfills, Superfund
sites, and other disposal locations.
Household disposal is neglected. It is not
reasonable to assume all containers on the
consumer end are treated properly. There will be a
significant amount of aerosol containers end up in
landfills or other places. Thus, it will increase the
amount of MC in the soil or water.
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 MC,
rather than evaluating activities which are determined not to
be circumstances under which MC 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 MC spills or leaks as "conditions
of use." EPA does not consider MC spills or leaks to
constitute circumstances under which MC is manufactured,
processed, distributed, used, or disposed of, within TSCA's
definition of "conditions of use." Congress specifically listed
discrete, routine chemical lifecycle stages within the statutory
definition of "conditions of use" and EPA does not believe it
is reasonable to interpret "circumstances" under which MC is
manufactured, processed, distributed, used, or disposed of to
include uncommon and unconfined spills or leaks for
purposes of the statutory definition. Further, EPA does not
generally consider spills and leaks to constitute "disposal" of
a chemical for purposes of identifying a COU in the conduct
of a risk evaluation.
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In addition, even if spills or leaks of MC could be considered
part of the listed lifecycle stages of MC, EPA has
"determined" that spills and leaks are not circumstances
under which MC is intended, known or reasonably foreseen
to be manufactured, processed, distributed, used, or disposed
of, as provided by TSCA's definition of "conditions of use,"
and EPA is therefore exercising its discretionary authority to
exclude MC spills and leaks from the scope of the MC risk
evaluation. The exercise of that authority is informed by
EPA's experience in developing scoping documents and risk
evaluations, and on various TSCA provisions indicating the
intent for EPA to have some discretion on how best to
address the demands associated with implementation of the
full TSCA risk evaluation process. Specifically, since the
publication of the Risk Evaluation Rule, EPA has gained
experience by conducting ten risk evaluations and
designating forty chemical substances as low- and high-
priority substances. These processes have required EPA to
determine whether the case-specific facts and the reasonably
available information justify identifying a particular activity
as a "condition of use." With the experience EPA has gained,
it is better situated to discern circumstances that are
appropriately considered to be outside the bounds of
"circumstances... under which a chemical substance is
intended, known, or reasonably foreseen to be manufactured,
processed, distributed in commerce, used, or disposed of'
and to thereby meaningfully limit circumstances subject to
evaluation. Because of the expansive and potentially
boundless impacts that could result from including spills and
leaks as part of the risk evaluation, which could make the
conduct of the risk evaluation untenable within the applicable
deadlines, spills and leaks are determined not to be
circumstances under which MC is intended, known or
reasonably foreseen to be manufactured, processed,
distributed, used, or disposed of, as provided by TSCA's
definition of "conditions of use."
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Exercising the discretion to not identify spills and leaks of
MC 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."
For these reasons, EPA is exercising this discretion to not
consider spills and leaks of MC to be COUs.
Second, even if MC spills or leaks could be identified as
exposures from a COU in some cases, these are generally not
forms of exposure that EPA expects to consider in risk
evaluation. TSCA section 6(b)(4)(D) requires EPA, in
developing the scope of a risk evaluation, to identify the
hazards, exposures, conditions of use, and potentially
exposed or susceptible subpopulations the Agency "expects
to consider" in a risk evaluation. As EPA explained in the
"Procedures for Chemical Risk Evaluation Under the
Amended Toxic Substances Control Act" ("Risk Evaluation
Rule"), "EPA may, on a case-by-case basis, exclude certain
activities that EPA has determined to be conditions of use in
order to focus its analytical efforts on those exposures that
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are likely to present the greatest concern, and consequently
merit an unreasonable risk determination." 82 FR 33726,
33729 (July 20, 2017).
In the problem formulation documents for many of the first
10 chemicals undergoing risk evaluation, EPA applied the
same authority and rationale to certain exposure pathways,
explaining that "EPA is planning to exercise its discretion
under TSCA 6(b)(4)(D) to focus its analytical efforts on
exposures that are likely to present the greatest concern and
consequently merit a risk evaluation under TSCA...." The
approach discussed in the Risk Evaluation Rule and applied
in the problem formulation documents is informed by the
legislative history of the amended TSCA, which supports the
Agency's exercise of discretion to focus the risk evaluation
on areas that raise the greatest potential for risk. See June 7,
2016 Cong. Rec., S3519-S3520.
In addition to TSCA section 6(b)(4)(D), the Agency also has
discretionary authority under the first sentence of TSCA
section 9(b)(1) to "coordinate actions taken under [TSCA]
with actions taken under other Federal laws administered in
whole or in part by the Administrator." TSCA section
9(b)(1) provides EPA authority to coordinate actions with
other EPA offices, including coordination on tailoring the
scope of TSCA risk evaluations to focus on areas of greatest
concern rather than exposure pathways addressed by other
EPA-administered statutes and regulatory programs, which
does not involve a risk determination or public interest
finding under TSCA section 9(b)(2).
Following coordination with EPA's Office of Land and
Emergency Management (OLEM), EPA has found that
exposures of methylene chloride from spills and leaks fall
under the jurisdiction of RCRA. See 40 CFR 261.33(d)
(defining in part a hazardous waste as "any residue or
contaminated soil, water or other debris resulting from the
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cleanup of a spill into or on any land or water of any
commercial chemical product or manufacturing chemical
intermediate having the generic name listed [40 CFR
261.33(e) or (f)], or any residue or contaminated soil, water
or other debris resulting from the cleanup of a spill, into or on
any land or water, of any off-specification chemical product
and manufacturing chemical intermediate which, if it met
specifications, would have the generic name listed in [40
CFR 261.33(e) or (f)]"); 40 CFR 261.33(f) (listing methylene
chloride as hazardous waste no. U080). As a result, EPA
believes it is both reasonable and prudent to tailor the TSCA
risk evaluation for methylene chloride by declining to
evaluate potential exposures from spills and leaks, rather than
attempt to evaluate and regulate potential exposures from
spills and leaks under TSCA.
Finally, EPA notes that the Ninth Circuit in Safer Chemicals
Healthy Families v. EPA presented examples of
circumstances that may qualify as disposal but did not
establish a "precise meaning of 'disposal.'" 943 F.3d 397,
426 (9th Cir. 2019). The Court also did not opine on EPA's
authority to determine the circumstances under which a
chemical substance is intended, known, or reasonably
foreseen to be manufactured, processed, distributed in
commerce, used or disposed of.
Releases from municipal landfills are regulated under RCRA.
As explained in more detail in Section 1.4.2, EPA believes
that coordinated action on exposure pathways and risks
addressed by other EPA-administered statutes and regulatory
programs is consistent with statutory text and legislative
history, particularly as they pertain to TSCA's function as a
"gap-filling" statute, and also furthers EPA aims to
efficiently use Agency resources, avoid duplicating efforts
taken pursuant to other Agency programs, and meet the
statutory deadline for completing risk evaluations.
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EPA does not expect exposure to consumers from disposal of
consumer products. It is anticipated that most products will
be disposed of in original containers, particularly those
products that are purchased as aerosol cans. As described in
section 1.4.2 EPA is not evaluating on-site releases to land
from RCRA Subtitle D municipal solid waste (MSW)
landfills or exposures of the general population from such
releases in the TSCA evaluation because they are adequately
addressed by other EPA statutes.
Disposal of household waste to municipal landfills is covered
under the jurisdiction of RCRA as discussed in section
1.4.2. Additionally, the following has been added to
Section 2.4.2.2 discussing possible consumer Exposure
Routes: "EPA does not expect exposure to consumers from
disposal of consumer products. It is anticipated that most
products will be disposed of in original containers,
particularly those products that are purchased as aerosol
cans."
Coordination with other statutes
SACC
SACC COMMENTS:
Several Committee members expressed concern
that large quantities of MC are volatilized to
ambient air from diverse and disperse uses and
that there is no condition of use that provides a
basis for setting any limit on these emissions.
While EPA asserts that the CAA can be used to
control these emissions, Committee members
thought the CAA would address only a fraction of
total emissions, i.e., only from Major Sources as
defined by the 1990 CAA Amendments.
Emissions to ambient air from commercial or industrial
stationary sources, or inhalation exposures of terrestrial
species are under the jurisdiction of the Clean Air Act (CAA).
Additionally, based on its vapor density (2.93 relative to air)
and persistence in the atmosphere (photolysis half-life by
OH* reaction = 79 days), MC vapor may accumulate under
specific conditions, but typically will disperse readily into
the air.
75, 77, 73,
33 (3)
PUBLIC COMMENTS:
EPA's exclusion of all environmental releases
violates TSCA and disregards additional human
Clarifying language about what pathways are addressed
under other statutes has been added to Section 1.4.2 of the
Risk Evaluation.
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exposure pathways that contribute to aggregate
exposure and risk. This approach is an unlawful
interpretation of TSCA, has twice been rejected by
SACC and overlooks the widespread presence of
MC in environmental media to which millions of
people are exposed. Congress designed TSCA to
fill "regulatory gaps" through a comprehensive
approach to chemical risk management that
considered "the full extent of human or
environmental exposure," H.R. Rep. No. 94-1341.
TSCA's role in assessing these aggregate risk and
exposure pathways is unique and not duplicated in
other statutes and must be reflected in the MC risk
evaluation. The legislative history of the original
law confirms that Congress recognized that then-
existing environmental laws were "clearly
inadequate" to address the "serious risks of harm"
to public health from toxic chemicals. While other
federal environmental laws focused on specific
media, such as air or water, none gave EPA
authority to "look comprehensively" at the hazards
of a chemical "in total." S. Rep. No. 94-698.
Despite recognizing MC's high volatility, high
vapor density, and long-range transport in air (p.
64) - all factors that increase potential air
exposures to terrestrial organisms - EPA ignored
inhalation exposures to terrestrial species, stating:
"stationary source releases of MC to ambient air
are adequately assessed and any risks effectively
managed under the jurisdiction of the Clean Air
Act (CAA)" (p. 299). This exclusion is illegal.
MC's status as a CAA HAP does not justify
ignoring air emissions in the draft evaluation. Title
III of the CAA initially mandates technology-
based - not risk-based - emission limits. Once
these limits are in place, the law gives EPA at least
The purpose of risk evaluation under TSCA is to
determine whether a chemical substance presents an
unreasonable risk to health or the environment, under a
TSCA conditions of use. EPA described background
exposure in the uncertainties section acknowledging that
the risk estimations in the Risk Evaluation may be
underestimations, because background exposures and risk
are not incorporated to the risk estimations for each COU.
Emissions to ambient air from commercial or industrial
stationary sources, or inhalation exposures of terrestrial
species are managed under the jurisdiction of the Clean
Air Act (CAA).
Based on the Guidance for Ecological Soil Screening
Levels (EPA, 2003a, b) document, for wildlife, relative
exposures associated with inhalation and dermal exposure
pathways are insignificant, even for volatile substances,
compared to direct ingestion and ingestion of food (by
approximately 1,000-fold).
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eight more years to evaluate residual risks and
potentially set risk-based emission standards under
CAA Section 112(f). However, these standards
only consider emission-related risks, and thus do
not take into account aggregate health risks from
all sources of exposure. Moreover, the CAA
mandates emission standards for "major" sources,
which are defined as facilities that emit more than
10 tons per year of any single HAP or 25 tons per
year of all HAPs. This definition would not cover
the thousands of smaller establishments that in the
aggregate account for substantial MC air
emissions. These facilities may be regulated as
"area sources" under the CAA but would not be
subject to mandatory, chemical-specific, risk-
based standards.
68
PUBLIC COMMENTS:
EPA OPPT's decision to "scope in" the ambient
water pathway and to conduct an aquatic life risk
evaluation in the MC draft TSCA risk evaluation
raises serious questions about the overlapping
jurisdiction of TSCA and other environmental
laws, the TSCA Section 9 coordination
requirements, and EPA's ability to efficiently
conduct risk evaluations in the longer term.
Communication and coordination between program offices
within EPA occur regularly on TSCA-related efforts. While
EPA has recommended water quality criteria for protection of
human health for MC ffiPA-HO-OW-2014-0135}. it has not
developed CWA section 304(a) recommended water quality
criteria for the protection of aquatic life for MC. As a result,
the ambient water pathway underwent aquatic life risk
evaluation under TSCA.
Additionally, clarifying language about what pathways are
addressed under other statutes has been added to Section 1.4.2
of the Risk Evaluation.
K11 \ i ro 11 in oil t;i I 11 a/a I'd
EPA evaluated environmental hazards for aquatic species from acute and chronic exposure scenarios.
Charge Question 3.1. Please comment on EPA's approach for characterizing environmental hazard for each risk scenario (e.g.
acute aquatic, chronic aquatic). What other additional information, if any, should be considered?
Summary of Peer Review Comments lor Specific Issues
Related lo Charge Question 3
EPA/OPPT Response
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Key study not publicly available, lack of adequate data
49
PUBLIC COMMENTS:
TSCA expressly prohibits EPA from withholding health
and safety studies, including studies of a chemical's
ecological toxicity, but EPA has not provided public
access to all studies it relied on for its environmental risk
evaluations (e.g., 1987 study by E I Dupont de Nemours
& Co. Flow-Through Acute 96-Hour LC50 of Methylene
Chloride to Rainbow Trout, has not been made available
online). All of the cited references in the risk evaluation
should be made available for public review.
The EI Dupont de Nemours & Co study is publicly
available with the HERO ID of #4213817. All cited
references are available for public review.
49, 75
PUBLIC COMMENTS:
EPA lacks adequate data to evaluate ecological risk. EPA
does not have any studies of MC's effects on terrestrial
or sediment-dwelling species (p. 299). EPA also has no
"chronic studies that encompassed amphibian
metamorphoses and adult reproductive stages of the
amphibian life-cycle" (p. 204) and "no acceptable
chronic exposure aquatic invertebrate studies" (p. 205).
Without these data, EPA cannot fully evaluate MC's
environmental risks.
EPA believes it has adequate hazard data to evaluate
the environmental risks of MC to aquatic organisms.
MC is not expected to bioaccumulate in tissues, and
concentrations will not increase from prey to predator
in either aquatic or terrestrial food webs.
Based on the Guidance for Ecological Soil Screening
Levels (EPA. 2003a. b) document for wildlife, relative
exposures associated with inhalation and dermal
exposure pathways are insignificant, even for volatile
substances, compared to direct ingestion and ingestion
of food (by approximately 1,000-fold). EPA
characterized terrestrial organism exposures to MC as
"not of concern" based on estimates of soil
concentrations several orders of magnitude below
concentrations observed to cause effects in terrestrial
organisms during Problem Formulation. Therefore,
EPA had adequate information to conclude that
terrestrial species would not be a concern. EPA has
added language to the final risk evaluation document in
Section 4.1.4 explaining this rationale.
EPA used the reasonably available data to assess
sediment invertebrates. Because MC is not expected to
sorb to sediment and will instead remain in pore water,
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daphnia which feed through the entire water column
were deemed to be an acceptable surrogate species for
sediment invertebrates consistent with EPA/OPP
guidance, which lists several considerations for
determining the likelihood of exposure and
toxicological relevance of exposure to sediment-
dwelling organisms (https://www.epa.gov/pesticide-
science-and-assessing-pesticide-risks/toxicity-testing-
and-ecological-risk-assessment). Therefore, EPA did
not view this as a data need.
Additionally, Staples et al. (1985) stated that the
median concentration measured in sediment was 13
Hg/kg, equivalent to 13 ppb, which is more than 2
orders of magnitude below the chronic (1,800 ppb) and
acute COC (36,000 ppb) values estimated for sediment
invertebrates by read-across from COCs reported for
aquatic invertebrates.
Selection of point of departure (POD) for acute environmental hazard
SACC
SACC COMMENTS:
The Committee considered the LC50 endpoint not
protective of environmental receptors and argued that it
is incorrect to use the geometric mean of LC50 values
from multiple species as the measure of lethality. The
committee recommended instead that EPA develop LC01
values for different species where possible and select the
lowest value as the POD. In that light, the Committee
considered the LC01 of 9.7 [j,g/L for the common
European frog (Rana temporaria) to be a more easily
justified POD than the LC50 for Northern salamander
(Ambystoma gracile) of 23.03 mg/L, while noting that
the LC50 of 23.03 mg/L for A. gracile would still be
more appropriate than the value proposed in the current
risk evaluation, because this lowest measured LC50
In accordance with EPA guidance, LC50s are
commonly used as a measure of acute hazard to
aquatic organisms (EPA. 2013. 2012b). After
considering this comment, EPA determined that no
change is needed. LC01 values were only
reasonably available fori?, catesbeiana (0.09 mg/L)
and R temporaria (0.07 mg/L), which were the
most sensitive species tested. Toxicity data for
other amphibian and fish species was not sufficient
to calculate LCOls, and/or LClOs. EPA added
LC01 values for the two Rana species to the hazard
table and summary, but used the geometric mean of
the LClOs (0.9 mg/L from LClOs of 0.98 mg/L and
0.82 mg/L, respectively) as the lowest value for the
concentration of concern because, as both Birge, et
al. (1980) and Black et al., (1982) noted, it is more
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represents 17% of amphibian species in a species
sensitivity distribution.
The Committee further recommended that if calculation
of LC01 values is not considered a viable approach, then
an assessment factor of 100 (see Kienzler et al., 2017)
should be applied to the daphnia toxicity estimate
proposed in the current risk evaluation.
likely to have substantial reproductive impairment
resulting in population-level effects.
EPA is in the process of evaluating the body of
reasonably available literature on the subject in
order to determine whether to revise standards for
application of AF and the acute to chronic ratio for
the next 20 high-priority substances undergoing risk
evaluation. EPA will consider the Kienzler et al.,
2017 study in its assessment. Until the body of
scientific evidence for assessment factors is
evaluated, EPA will continue to use OPPT
methodology as cited in the risk evaluation (EPA.
2013, 2012b) and applv an AF of 5 for acute and 10
for chronic aquatic invertebrate data. EPA considers
these AFs to be protective of aquatic invertebrates
from acute and chronic exposures to neutral organic
substances such as MC, which produce toxicity
from simple narcosis.
49, 75,
73
PUBLIC COMMENTS:
EPA's toxicity assessment methodology for MC leaves
the most sensitive species at risk. EPA does not select
COCs based on the most sensitive species and the most
sensitive endpoint, as it has done in other risk
evaluations. Instead, EPA averages data across studies of
different species and different endpoints and sets the
COC based on their geometric mean (e.g., for acute
toxicity in freshwater fish, EPA used LC50 = 242.41
mg/L, calculated as geometric mean of available studies,
rather than LC50 = 108 mg/L, based on the most
sensitive species, rainbow trout).
EPA used reasonably available data for estimating
lethality and overall effects to aquatic organisms. EPA
used a geometric mean using toxicity values from more
than one species of amphibian, because the toxicity
values were very close to one another, and taking more
than one toxicity value into consideration from more
than one species gave EPA higher confidence in the
value that EPA used to calculate its COC. To account
for species that may be more sensitive that are not
included in the COC calculation EPA used an
assessment factor (AF) of 10, consistent with OPPT
methodology cited in the risk evaluation (EPA, 1
2012b) This AF is higher than the AF of 5 normally
used to calculate acute COCs for aquatic invertebrates
and fish, because EPA wanted to incorporate the added
uncertainty around amphibians into the COC.
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49, 75
PUBLIC COMMENTS:
The commenters disagreed with EPA's assessment of
toxicity in algae. EPA selected a COC of 33.09 mg/L,
based on a study of C. reinhardtii, even though, in
another study that EPA assigned an overall quality level
of medium, MC killed V. steinii, a different algal species,
at a much lower concentration, 0.002 mg/L (p. 206).
EPA stated that "[t]he study supports the need for
assessment factors to establish the hazard values to
account for more sensitive species," but the 10-fold
"assessment factor" applied by EPA is not nearly large
enough to account for the more than 10,000-fold
difference in results between the studies.
The 2003 studv bv Ando. et al. (2003) referred to bv
the commenter used an indirect measurement of algal
cell growth, chlorophyll a, that is not relevant for
hazard evaluation. The study also did not have critical
details, such as analytical measurement of test
concentrations, chemical substance source or purity, or
an EC50 calculated from the relative absorbance
results, so EPA used this value qualitatively in the risk
evaluation. EPA added clarifying language to the risk
evaluation to address this issue.
SACC
SACC COMMENTS:
Evaluation of the aquatic invertebrate toxicity data
showed that the geometric mean for aquatic invertebrates
(i.e., 179.98 mg/L; p. 207) or the underlying values for
aquatic invertebrate toxicity (p. 204) seem to be in error.
The geometric mean for aquatic invertebrates included
definitive values only.
Use of I
>aphnia as a surrogate species for estimating hazard in sediment invertebrates
SACC,
73
SACC AND PUBLIC COMMENTS:
Daphnia was used as a surrogate species for estimating
hazard in sediment invertebrates (p. 205).
o Since daphnia feed through the entire water column
and in sediment, it is improper to consider daphnia as
representative of sediment-dwelling organisms,
o If daphnia must be used, then the assessment factor or
UF should be higher, as noted by Keinzler et al.
(2017).
o EPA should have identified this as a data gap and
taken steps to address it using its information
authorities under TSCA.
EPA used the reasonably available data to assess
sediment invertebrates. Because MC is not expected to
sorb to sediment and will instead remain in pore water,
daphnia which feed through the entire water column
were deemed to be an acceptable surrogate species for
sediment invertebrates. Therefore, EPA did not view
this as a data need.
Additionally, Staples et al. (1985) stated that the
median concentration measured in sediment was 13
[j,g/kg, equivalent to 13 ppb, which is more than 2
orders of magnitude below the chronic (1,800 ppb) and
acute COC (36,000 ppb) values estimated for sediment
invertebrates by read-across from COCs reported for
aquatic invertebrates.
Chronic toxicity to aquatic invertebrates
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73
PUBLIC COMMENTS:
EPA states "there were no acceptable chronic exposure
aquatic invertebrate studies, so EPA applied the acute-to-
chronic ratio (ACR) of 10... to estimate the freshwater
aquatic invertebrate chronic exposure toxicity value" (p.
205).
o EPA provided no justification for its application of an
'acute-to-chronic ratio' or its specific value of 10. A
search of the literature indicated that an ACR of at
least 100 may be needed to be sufficiently protective,
o EPA should have identified this as a data gap and
taken steps to address it using its information
authorities under TSCA.
In the absence of chronic aquatic invertebrate data,
EPA applied an ACR of 10 to the acute aquatic
invertebrate data to estimate a chronic toxicity value
according to current EPA methods under TSCA (EPA.
-01 2012b). EPA decided to do this, because aquatic
invertebrates were not the most sensitive taxa
represented in the acute data. Therefore, EPA did not
view this as a data need.
Selection of POD for chronic hazard to amphibians
SACC,
73
SACC AND PUBLIC COMMENTS:
A 9-day exposure (p. 212) is not a chronic exposure for
salamander.
These durations fall far short of the recommended length
of amphibian assays according to OECD test guidelines
and accepted practice. The Amphibian Metamorphosis
Assay (OECD 231) calls for an exposure duration of 21
days, whereas the Larval Amphibian Growth and
Development Assay guideline (OECD 241) requires the
assessment be run for 16-17 weeks.
An additional AF of 10 should be applied with the
existing AF of 10 to produce a value of 0.09 mg/L that
would seem to be consistent with the conclusions of the
authors (Black et al., 1982).
Calculating an acute-to-chronic estimate using the Acute-
to-Chronic (ACE) tool could provide corroborative
evidence in support of this value.
A benchmark dose lower bound (BMDL) could be
estimated using the Black et al. (1982) data.
In the absence of chronic amphibian studies, EPA
viewed the amphibian study 4-days post-hatch (8-9
days total) as sub-chronic and applied an AF of 10
to derive a chronic hazard value per current OPPT
methodoloav ffiPA. 2013. 2012bY
EPA is in the process of evaluating the body of
reasonably available literature on AF in order to
determine whether to revise standards for
application of AF and the acute to chronic ratio for
the next 20 high-priority substances undergoing
risk evaluation but will use current OPPT
methodology for the first 10 priority chemicals,
including MC. Neutral organic substances such as
MC produce toxicity from simple narcosis. EPA
applies an AF of 10 to chronic toxicity values to
derive chronic hazard values for aquatic organisms
exposed to this class of chemicals under current
OPPT methodoloav (EPA. 2013. 2012bY EPA feels
confident that the AF of 10 applied to the sub-
chronic toxicity value for amphibians is adequately
protective of these species. The amphibian chronic
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hazard value of 0.9 mg/L is similar to but more
protective than the fish chronic hazard value of 1.5
mg/L and more protective than the amphibian
chronic value of 2.6 mg/L (derived by applying the
ACR of 10 to the geometric mean of amphibian
acute hazard values).
EPA will consider the ACE tool in its effort to
evaluate the body of available literature on AF
(including ACR ratios) in the future, but used
current OPPT methodology for the first 10 priority
chemicals, including MC. EPA examined whether
benchmark dose modeling could be applied to the
toxicity data from Birge, et al. (1980) and Black et
al., (1982) used to derive the acute and chronic
Concentrations of Concern using the peer-reviewed
Benchmark Dose Software (BMDS)
(https://www.epa.gov/bmds/about-benchmark-
dose-software-bmds). Benchmark dose modeling is
the preferred method used in human health fields to
predicting toxicity effect values for a given
endpoint and study. Its utility translates to
ecotoxicity studies, where its use in generating LCx
or ECx values can help to remove biases due to
experimental design {i.e. what concentrations are
chosen), allow for the inclusion of all toxicity data
points, and allow for model fitting specific to the
shape of different dose-response curves, as
compared to traditional LOEC/NOEC
methodologies. EPA found that benchmark dose
modeling was not possible with the data provided
in Birge, et al. (1980) and Black et al., (1982). This
is because it was not possible to back-calculate a
measure of error (STD/STE) for either paper
because the experiments utilized one tank replicate
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per concentration, and the BMDS requires a
measure of error for model calculation. However,
EPA has high confidence in the toxicity values
provided by both papers because the study authors
did apply an appropriate modeling technique (log-
probit analysis) to generate their LC10 and LC50
estimates for fish and amphibian species.
Selection of POD for chronic hazard to fish
SACC
SACC COMMENTS:
The Committee did not agree with the selection of 5.55
mg/L as the no-observed-effect concentration (NOEC)
for teratic larvae in the rainbow trout study (p. 207) since
teratogenic effects were observed at this value.
Black et al. (1982) corrected survival numbers for
control survivals (p. 205). Therefore, the 85% survival
was relative to control survival. Thus, there is no
rationale for excluding low concentration effects. A
NOEC cannot reasonably be defined as a concentration,
0.41 mg/L, in which 15% mortality occurred.
There was a lower concentration of 0.042 mg/L, which
demonstrated a 93% survival. The value of 0.041 mg/L
would be the more appropriate NOEC for this study.
Immobile fish (p. 203) in this study could be considered
mortalities in current testing protocols. The Agency
should justify not considering immobile fish as
mortalities.
The authors did not establish a NOEC, LOEC, or
LC10 for fish for MC as they did for other
substances in the study. As a result, these values
were not extracted during data extraction (only
LC50s were established by the authors for MC).
EPA agrees that the percent larval survival at 0.042
mg/L (92%) and 0.41 mg/L (85%) suggest (by
calculating with geometric mean) a LC10 falling
around 0.13 mg/L. However, in the absence of a
NOEC/LOEC for MC by the authors and resulting
uncertainty in the statistical significance of the
values, EPA established the NOEC as 0.41 mg/L
and the LOEC as 5.55 mg/L (the next highest
concentration) in order to not be over-conservative.
The geometric mean fish ChV of 1.51 mg/L is also
in line with the amphibian ChV of 0.9 mg/L,
therefore EPA has greater confidence in this value
for the fish ChV.
EPA determined that fish immobilization may be a
temporary narcosis from which fish may recover
after exposures. Although predation may occur as a
result of immobilization, it is not necessarily
mortality.
A hazard assessment for terrestrial organisms is needed
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SACC,
73
SACC AND PUBLIC COMMENTS:
The Committee disagreed with the characterization of
environmental hazard in the risk evaluation and
recommended addition of an assessment of potential
exposures to terrestrial vertebrates through inhalation and
soil contact, pathways that were dismissed without
sufficient justification in the risk evaluation.
MC is not expected to bioaccumulate in tissues, and
concentrations will not increase from prey to predator
in either aquatic or terrestrial food webs.
Based on the Guidance for Ecological Soil Screening
Levels (EPA. 2003a. b) document for wildlife, relative
exposures associated with inhalation and dermal
exposure pathways are insignificant, even for volatile
substances, compared to direct ingestion and ingestion
of food (by approximately 1,000-fold). EPA
characterized terrestrial organism exposures to MC as
"not of concern" based on estimates of soil
concentrations several orders of magnitude below
concentrations observed to cause effects in terrestrial
organisms during Problem Formulation. EPA has
added language to the final risk evaluation document in
Section 4.1.4 explaining this rationale.
The assessment needs to consider threatened and endangered species, especially amphibians
SACC
SACC COMMENTS:
The Committee recommended that the risk evaluation
include an analysis of how home ranges of threatened
and endangered species, including amphibians, overlap
with known source areas impacted by MC releases, e.g.
by use of U.S. Geological Survey (USGS) maps
(Zogorski et al., 2006) and overlays of species ranges
from E-FAST.
The TSCA risk evaluation focuses on exposures to
particular species and environmental receptors, and
appropriately considered impacts to affected
species.
Environmental hazard - general comments
SACC
SACC COMMENTS:
The risk evaluation citation "Wilson, JEH. (1988)" is
incomplete. It does not contain the name of the journal or
the book.
Even though the purity of the test substance was not
specified in this paper, the Committee questioned
whether the purity could be assigned or assumed using
the average purity of MC on the market.
The full citation (Wilson. 1998) was updated in
HERO read: Wilson, J.E.H., "Developmental Arrest
in Grass Shrimp Embryos Exposed to Selected
Toxicants," Environmental Toxicology and Risk
Assessment: Seventh Volume, ASTM STP 1333,
E.E. Little, A.J. DeLonay, and B.M. Greenberg,
Eds., American Society for Testing and Materials,
1998.
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EPA considered converting the Wilson study using
a range of purity assumptions but determined that
these would add to the uncertainty for the test
results. Therefore, the paper was used qualitatively.
SACC
SACC COMMENTS:
The summary of environmental hazard in Section 3.1.5
needs one or two concluding sentences that compare
effects of MC across different trophic levels.
Concluding sentence added.
SACC
SACC COMMENTS:
The EC50 values of 242.41 and 135.81 mg/L (p. 203)
cannot be known to this level of precision.
Rounding to 3 significant figures where possible in
the risk evaluation.
SACC
SACC COMMENTS:
The species and LC50 values for each study used should
be listed along with an indication of whether measured or
nominal data were used.
Many of these LC50 values are from studies that do not
report any measured or nominal concentrations for
exposures.
Species and whether studies report nominal or
measured concentrations are included in the hazard
summaries and in the Systematic Review
Supplemental File: Data Quality Evaluation of
Environmental Hazard Studies.
All LC50 values were from studies that reported
these values, as indicated in the hazard summaries.
SACC
SACC COMMENTS:
The Committee concurred that amphibians are likely
among the most sensitive aquatic species for MC (Risk
Evaluation, pp. 29, 285).
This conclusion suggests that obtaining toxicity data on
amphibians and/or accounting for amphibian sensitivity
should be a part of all TSCA risk evaluations.
Manufacturers and users of chemicals considered for
regulation under TSCA should be required to provide
data on amphibian toxicity.
EPA considered amphibian data by using
amphibian toxicity data to calculate the
concentration of concern. Variation in species
sensitivity was accounted for by using an
assessment factor of 10. EPA considers reasonably
available data on a chemical by chemical basis and
would exercise any necessary information
gathering in a fit-for-purpose manner, as was the
case for PV29. As part of the consideration of
reasonably available information, EPA considers
data gaps and the need for additional information as
appropriate.
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Omipalional mid Consumer Kxposure
EPA evaluated acute and chronic exposures to workers for conditions of use in industrial and commercial settings. For exposure via
the inhalation pathway, EPA quantified occupational exposures for both workers and occupational non-users based on a combination
of monitoring data and modeled exposure concentrations. For exposure via the dermal route, EPA modeled exposure for workers,
accounting for the effect of volatilization. EPA assumed dermal contact with liquids would not occur for occupational non-users.
EPA assumed that workers and occupational non-users would be adults of both sexes (>16 and older, including women of
reproductive age).
Charge Question 4.1. Please comment on the approaches and estimation methods, models, and data used in the occupational
exposure assessment.
Charge Question 4.2. Please provide any specific suggestions or recommendations for alternative data or estimation methods that
could be considered by the Agency for conducting the occupational exposure assessment.
Charge Question 4.3. EPA assumed the following default surface area value for modeling dermal exposures for occupational
exposure scenarios for which surface area data were not available: a high-end value of 1070 cm2, which represents two full hands
(mean value for males) in contact with a liquid. Please provide input on data sources and specific alternative values relevant to the
uses.
To estimate ONU inhalation exposure, EPA reviewed personal monitoring data, area monitoring data and modeled far-field exposure
concentrations. When EPA did not identify personal or area data on or parameters for modeling potential ONU inhalation exposures,
EPA assumed ONU inhalation exposures could be lower than worker inhalation exposures however relative exposure of ONUs to
workers could not be quantified. When exposures to ONUs were not quantified, EPA considered the central tendency from worker
personal breathing zones to estimate ONU exposures.
Charge Question 4.4. Please comment on the assumptions and uncertainties of this approach.
Charge Question 4.5. Are there other approaches or methods for assessing ONU exposure for the specific condition of use?
Consumer exposure estimates were developed for the conditions of use for inhalation and dermal exposures to consumers. EPA did
systematic review, collected data from available sources and conducted modeling for estimating consumer inhalation and dermal
exposures using the CEM model.
Product specific consumer monitoring information was not identified during the systematic review process, therefore, model inputs
related to consumer use patterns (duration of use, mass of product used, room of use, and similar inputs) are based on survey data
found in the literature as described and referenced within the methylene chloride draft risk evaluation. Weight fraction of chemical
within products are based on product specific safety data sheets (SDS). Default values utilized within the models are based on
literature reviewed as part of model development as well as EPA's Exposure Factors Handbook.
Charge Question 4.6. Please comment on the approaches, models, exposure or use information and overall characterization of
consumer inhalation exposure for users and bystanders for each of the identified conditions of use. What other additional
information, if any, should be considered?
Charge Question 4.7. Please comment on the approaches, models, exposure or use information and overall characterization of
consumer dermal exposure for each of the identified conditions of use. What other additional information or modeling approaches, if
any, should be considered?
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Charge Question 4.8. Dermal exposure was evaluated using the absorption method submodel within CEM. Please comment on the
suitability and use of this modeling approach for this evaluation. Please provide any suggestions or recommendations for alternative
approaches, dermal methods, models or other information which may guide EPA in developing and refining the dermal exposure
estimates.
#
Summary ol" Peer Review Comments lor
Specific Issues Related to Charge Question
4
KPA/OPPT Response
Conditions of use
49, 72,
73, 75,
76,
SACC
SACC COMMENTS:
Several conditions of use described under
both consumer and "industrial and
commercial" were not evaluated under
consumer uses. Ensure that these
conditions of use do not exist in the
consumer space and evaluate the condition
of use if they are reasonably foreseen to
exist.
PUBLIC COMMENTS:
EPA excluded consumer uses such as
metal products not covered elsewhere,
apparel and footwear care products, and
laundry and dishwashing products from its
analysis of consumer uses; EPA included
these conditions of use as industrial and
commercial uses.
Given MC's industrial and commercial
uses, the potential for these uses to be
expanded to consumer use is reasonably
foreseeable.
EPA also excluded reasonably foreseen
conditions of use in the workplace
including exposure from spills and leaks,
"take-home exposures", exposures to
maintenance staff, and exposure to workers
EPA's risk evaluation addresses consumer uses. EPA has
determined that there is no known, intended, or reasonably
foreseen consumer use of certain conditions of use, including
metal products not covered elsewhere, apparel and footwear care
products, and laundry and dishwashing products. There are only
industrial and commercial uses of methylene chloride for these
conditions of use, and these conditions of use were assessed.
EPA included ONUs who are defined in section 2.4.1 as "working
in the general vicinity of workers but do not handle chemical
substances and do not have direct dermal contact with chemicals
being handled by the workers." Maintenance staff are a subset of
ONUs and as such are not excluded from the risk evaluation. Also,
workers at small facilities are not excluded, and the PPE use
expectation is applicable to all facilities (OSHA regulations cover
small facilities).
The frequency and magnitude of take-home exposure is dependent
on several factors, including personal hygiene and visibility of the
chemical on skin or clothing. EPA does not have methods to
reliably predict take-home exposure.
Spills/leaks
Spills and leaks generally are not included within the scope of a
TSCA risk evaluation. EPA is exercising its authority under TSCA
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at small facilities where routine PPE use is
less likely to be valid.
EPA should clarify its treatment of these
conditions of use.
to tailor the scope of the risk evaluation for MC, rather than
evaluating activities which are determined not to be circumstances
under which MC 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 MC spills or leaks as "conditions of
use." EPA does not consider MC spills or leaks to constitute
circumstances under which MC is manufactured, processed,
distributed, used, or disposed of, within TSCA's definition of
"conditions of use." Congress specifically listed discrete, routine
chemical lifecycle stages within the statutory definition of
"conditions of use" and EPA does not believe it is reasonable to
interpret "circumstances" under which MC is manufactured,
processed, distributed, used, or disposed of to include uncommon
and unconfined spills or leaks for purposes of the statutory
definition. Further, EPA does not generally consider spills and
leaks to constitute "disposal" of a chemical for purposes of
identifying a COU in the conduct of a risk evaluation.
In addition, even if spills or leaks of MC could be considered part
of the listed lifecycle stages of MC, EPA has "determined" that
spills and leaks are not circumstances under which MC is
intended, known or reasonably foreseen to be manufactured,
processed, distributed, used, or disposed of, as provided by
TSCA's definition of "conditions of use," and EPA is therefore
exercising its discretionary authority to exclude MC spills and
leaks from the scope of the MC risk evaluation. The exercise of
that authority is informed by 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
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designating forty chemical substances as low- and high-priority
substances. These processes have required EPA to determine
whether the case-specific facts and the reasonably available
information justify identifying a particular activity as a "condition
of use." With the experience EPA has gained, it is better situated
to discern circumstances that are appropriately considered to be
outside the bounds of "circumstances... under which a chemical
substance is intended, known, or reasonably foreseen to be
manufactured, processed, distributed in commerce, used, or
disposed of' and to thereby meaningfully limit circumstances
subject to evaluation. Because of the expansive and potentially
boundless impacts that could result from including spills and leaks
as part of the risk evaluation, which could make the conduct of the
risk evaluation untenable within the applicable deadlines, spills
and leaks are determined not to be circumstances under which MC
is intended, known or reasonably foreseen to be manufactured,
processed, distributed, used, or disposed of, as provided by
TSCA's definition of "conditions of use."
Exercising the discretion to not identify spills and leaks of MC 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
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prudent manner."
For these reasons, EPA is exercising this discretion to not consider
spills and leaks of MC to be COUs.
Second, even if MC spills or leaks could be identified as exposures
from a COU in some cases, these are generally not forms of
exposure that EPA expects to consider in risk evaluation. TSCA
section 6(b)(4)(D) requires EPA, in developing the scope of a risk
evaluation, to identify the hazards, exposures, conditions of use,
and potentially exposed or susceptible subpopulations the Agency
"expects to consider" in a risk evaluation. As EPA explained in
the "Procedures for Chemical Risk Evaluation Under the
Amended Toxic Substances Control Act" ("Risk Evaluation
Rule"), "EPA may, on a case-by-case basis, exclude certain
activities that EPA has determined to be conditions of use in order
to focus its analytical efforts on those exposures that are likely to
present the greatest concern, and consequently merit an
unreasonable risk determination." 82 FR 33726, 33729 (July 20,
2017).
In the problem formulation documents for many of the first 10
chemicals undergoing risk evaluation, EPA applied the same
authority and rationale to certain exposure pathways, explaining
that "EPA is planning to exercise its discretion under TSCA
6(b)(4)(D) to focus its analytical efforts on exposures that are
likely to present the greatest concern and consequently merit a risk
evaluation under TSCA...." The approach discussed in the Risk
Evaluation Rule and applied in the problem formulation
documents is informed by the legislative history of the amended
TSCA, which supports the Agency's exercise of discretion to
focus the risk evaluation on areas that raise the greatest potential
for risk. See June 7, 2016 Cong. Rec., S3519-S3520.
In addition to TSCA section 6(b)(4)(D), the Agency also has
discretionary authority under the first sentence of TSCA section
9(b)(1) to "coordinate actions taken under [TSCA] with actions
taken under other Federal laws administered in whole or in part by
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the Administrator." TSCA section 9(b)(1) provides EPA authority
to coordinate actions with other EPA offices, including
coordination on tailoring the scope of TSCA risk evaluations to
focus on areas of greatest concern rather than exposure pathways
addressed by other EPA-administered statutes and regulatory
programs, which does not involve a risk determination or public
interest finding under TSCA section 9(b)(2).
Following coordination with EPA's Office of Land and
Emergency Management (OLEM), EPA has found that exposures
of methylene chloride from spills and leaks fall under the
jurisdiction of RCRA. See 40 CFR 261.33(d) (defining in part a
hazardous waste as "any residue or contaminated soil, water or
other debris resulting from the cleanup of a spill into or on any
land or water of any commercial chemical product or
manufacturing chemical intermediate having the generic name
listed [40 CFR 261.33(e) or (f)], or any residue or contaminated
soil, water or other debris resulting from the cleanup of a spill, into
or on any land or water, of any off-specification chemical product
and manufacturing chemical intermediate which, if it met
specifications, would have the generic name listed in [40 CFR
261.33(e) or (f)]"); 40 CFR 261.33(f) (listing methylene chloride
as hazardous waste no. U080). As a result, EPA believes it is both
reasonable and prudent to tailor the TSCA risk evaluation for
methylene chloride by declining to evaluate potential exposures
from spills and leaks, rather than attempt to evaluate and regulate
potential exposures from spills and leaks under TSCA.
45
PUBLIC COMMENTS:
Some of the conditions of use evaluated,
such as pesticides and polyurethane foam
applications, may not be current uses. For
other uses, the use patterns and practices
have likely changed to reflect better
Pesticides are not a chemical substance under TSCA and therefore outside
the scope of this evaluation, which means that any pesticidal use of
methylene chloride was not evaluated. Rather, EPA evaluated the
processing of methylene chloride as a reactant (as an intermediate for
pesticide, fertilizer, and other agricultural chemical manufacturing. See
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exposure control. EPA should consider
reassessing the relevance of these uses that
are no longer current.
section 5.2.1.3). EPA relied on reasonably available information
throughout the risk evaluation process for use patterns and practices and,
unless otherwise indicated in the evaluation, the conditions of use
identified in the risk evaluation (e.g., industrial/commercial use as a
propellent and blowing agent in polyurethane foam manufacturing) are
considered intended, known or reasonably foreseen. These are conditions
of use and are therefore evaluated in the risk evaluation.
77
PUBLIC COMMENTS:
EPA's identified conditions of use overlap,
leading to internally inconsistent
conclusions. EPA concludes that the
industrial and commercial use of MC for
paints and coatings presents an
unreasonable risk, but simultaneously
concludes that the distribution of MC in
commerce does not present an
unreasonable risk.
If EPA believes that only some uses of MC
warrant regulation, such a determination is
only appropriate at the Section 6(a) stage -
not at the TSCA Section 6(b) stage, which
charges EPA with the yes-or-no
determination of whether a chemical
presents an unreasonable risk.
TSCA section 6(b)(4)(D) requires EPA to conduct risk evaluations to
determine whether a chemical substance presents unreasonable risk of
injury to health or the environment, under the conditions of use.
Therefore, TSCA section 6(b) risk evaluations can and should make
unreasonable risk determinations for each condition of use included
within the scope. While there may be connections between conditions of
use, EPA distinguishes between them such that they do not overlap.
Specifically, regarding the comment on distribution in commerce, for the
purposes of the risk evaluation, distribution in commerce is the
transportation associated with moving methylene in commerce. Unloading
and loading activities are associated with other conditions of use. EPA
assumes transportation of methylene chloride is in compliance with
existing regulations for the transportation of hazardous materials, and
emissions are therefore minimal (with the exception of spills and leaks,
which are outside the scope of the risk evaluation).
Per the statute (see TSCA section 6(b)(4)(A)) and the implementing
regulations for risk evaluations (40 CFR part 702, subpart B), EPA must
make the unreasonable risk determination at the time of the risk
evaluation. Upon finding unreasonable risk, EPA will apply risk
management actions to the extent necessary so that the chemical no longer
presents such risk, in accordance with TSCA section 6(a).
73
PUBLIC COMMENTS:
EPA did not address the presence of MC as
a disinfectant byproduct in water as a
condition of use.
EPA identified multiple on-topic literature
sources addressing disinfection byproducts
in the bibliography search results for MC
Methylene chloride generated as a byproduct of the disinfectant process
for drinking water treatment is outside the scope of this risk evaluation.
This activity would be considered in the scope of the risk evaluation for
those drinking water treatment chemicals. EPA believes that its regulatory
tools under TSCA section 6(a) are better suited to addressing any
unreasonable risks that might arise from methylene chloride as a
byproduct of the disinfectant process for drinking water treatment through
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but did not provide any rationale or
scientific basis for excluding this condition
of use.
As required by TSCA, EPA cannot exclude
this condition of use based on its presence
as a byproduct rather than being
intentionally used.
regulation of the activities that generate methylene chloride as an impurity
or cause it to be present as a contaminant than addressing them through
direct regulation of methylene chloride. EPA expects that a risk
evaluation of drinking water treatment chemicals would consider the
requirements and existing regulations under the Safe Drinking Water Act
as described in section 1.4.2.
79
PUBLIC COMMENTS:
[ ] reports a condition of use where MC is
imported as part of a formulation. This
proprietary blend, containing [ ] MC, is
imported in drums for an industrial
chemical customer in the United States [ ],
which does not transfer material or
otherwise open the imported drums, and
ships the formulation in the original
containers to the customer.
EPA appreciates the additional information regarding this specific
importing scenario. In general, the occupational exposure scenario for
import (which includes repackaging activities and exposures) is most
suitable for the import of methylene chloride. Additionally, the scenario
provided by the commenter is the distribution in commerce of methylene
chloride, which is considered the transportation associated with the
moving of methylene chloride in commerce with the unloading and
loading activities associated with other conditions of use.
52
PUBLIC COMMENTS:
MC is used as a solvent for adhesive
systems. The reported level of exposure
workers using MC as a solvent for
adhesive systems in commercial shops (p.
71) is likely incorrect because engineering
controls can be too expensive for shops to
install and proper PPE is often not worn.
EPA does not report a level of worker exposure on page 71. Page 71
covers releases to water and this is not associated with the worker
exposure assessment.. EPA assesses adhesives and sealants use
industrially and commercially in three sub-scenarios: spray, non-spray,
and unknown application method. Monitoring data are used in each
subscenario to estimate inhalation exposures, and modeling is used to
estimate dermal exposures.
73
PUBLIC COMMENTS:
EPA does not explain why the finding of
unreasonable risk would not equally extend
to the distribution in commerce of MC as
parts of these conditions of use.
Distribution in commerce was not
separately analyzed as parts of these
conditions of use.
EPA assumes that distribution in
commerce does not result in any exposures
beyond those already related to a given
Distribution in-commerce is a distinct and separate condition of use. Some
activities related to preparing the chemical or products for distribution,
such as loading, unloading, and repackaging, are included in the relevant
condition of use or evaluated separately (e.g. repackaging methylene
chloride, Section 5.2.1.5). For the purposes of the unreasonable risk
determination, distribution in commerce of methylene chloride is the
transportation associated with moving methylene chloride in commerce.
Unloading and loading activities are associated with other conditions of
use. EPA assumes transportation of methylene chloride is in compliance
with existing regulations for the transportation of hazardous materials, and
emissions are therefore minimal (with the exception of spills and leaks,
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condition of use. EPA provides no analysis
or evidence supporting this assumption. Is
EPA assuming that all distribution occurs
through "closed systems," which lead to no
releases or exposure? EPA has provided no
evidence indicating exposures and releases
during distribution will be nonexistent.
which are outside the scope of the risk evaluation). Based on the limited
emissions from the transportation of chemicals, EPA determines EPA's
determination that there is no unreasonable risk of injury to health
(workers and ONUs) from the distribution in commerce of methylene
chloride.
28
PUBLIC COMMENTS:
Are exceptions to the rule being considered
for academic labs, private industry,
Biotech, Pharma, and manufacturers when
appropriate engineering controls, work
practices, and required personal protective
clothing and equipment are used to prevent
or reduce worker exposures below
established Occupational Safety and
Health Administration (OSHA)
Permissible Exposure Limits (PELs),
Short-Term Exposure Limits (STELs),
etc.?
EPA should consider this comment in the
rulemaking evaluation for the exemption
for restrictions on the use of MC for
certain industries.
EPA is unclear what the commenter means by "exceptions to the rule"
and it appears the commenter may be referencing entities that could be
subject to potential future risk management regulatory action. For
purposes of estimating occupational exposures, based on the OSHA
methylene chloride standard at 29 CFR 1910.1052, the only respirators
that can be considered by EPA are supplied-air respirators (i.e., APF of 25
would be the lowest APF that could be considered), further discussed in
section 2.4.1.1. As such, EPA assumes, as a baseline, the use of a
respirator with an APF of 25. However, EPA is assuming that for some
conditions of use, the use of appropriate respirators is not a standard
practice, based on best professional judgment given the burden associated
with the use of supplied-air respirators, including the expense of the
equipment, and the necessity of fit-testing and training for proper use. The
risk evaluation also presents estimated risk in the absence of PPE and
does not assume that occupational non-users use PPE.
EPA must evaluate the conditions of use it expects to consider under
TSCA in the risk evaluation and propose risk management for any
condition of use which the Agency determines presents unreasonable risk.
Risk management activities will only occur after EPA has completed the
risk evaluation. As the commenter indicated, for any condition of use
determined to have unreasonable risk, EPA will consider this and other
public comments during risk management.
65
PUBLIC COMMENTS:
The use of MC to manufacture
pharmaceuticals is excluded from TSCA
regulation and should not be within the
scope of the risk evaluation.
While use of methylene chloride as a functional fluid in a closed system
during pharmaceutical manufacturing was included in the problem
formulation and draft risk evaluation, upon further analysis of the details
of this process, EPA has determined that this use falls outside TSCA's
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EPA should be explicit about what
constitutes a chemical substance under
TSCA. EPA may not regulate non-TSCA
uses in a risk management rule under
Section 6(a).
Neither the problem formulation, nor the
prior scope document, nor the draft risk
evaluation, discusses the fact that MC's
use in pharmaceutical manufacture is a
non-TSCA use.
EPA is obligated to revise the draft risk
evaluation to exclude all discussion of
MC's use in pharmaceutical manufacturing
- except to explain the basis for its
exclusion.
definition of "chemical substance." Under TSCA § 3(2)(B)(vi), the
definition of "chemical substance" does not include any food, food
additive, drug, cosmetic, or device (as such terms are defined in section
201 of the Federal Food, Drug, and Cosmetic Act) when manufactured,
processed, or distributed in commerce for use as a food, food additive,
drug, cosmetic, or device. EPA has found that methylene chloride use as
a functional fluid in a closed system during pharmaceutical manufacturing
entails use as an extraction solvent in the purification of pharmaceutical
products, and has concluded that this use falls within the aforementioned
definitional exclusion and is not a "chemical substance" under TSCA
(section 5.3)
Consideration of exposure from accidental release
73, 72
PUBLIC COMMENTS:
The draft risk evaluation and problem
formulation do not consider potential
releases and exposures resulting from
accidental releases which should be
considered to be "reasonably foreseen",
particularly in cases of flooding, and other
natural disasters.
Releases from accidents
Releases from accidents generally are not included within the scope of a
TSCA risk evaluation. First, EPA does not identify accidental releases as
"conditions of use." EPA does not consider MC releases from accidents
to constitute circumstances under which MC is manufactured, processed,
distributed, used, or disposed of, within TSCA's definition of "conditions
of use." Congress specifically listed discrete, routine chemical lifecycle
stages within the statutory definition of "conditions of use" and EPA does
not believe it is reasonable to interpret "circumstances" under which MC
is manufactured, processed, distributed, used, or disposed of to include
uncommon and unconfined releases from accidents for purposes of the
statutory definition. Further, EPA does not generally consider accidental
releases to constitute "disposal" of a chemical for purposes of identifying
a COU in the conduct of a risk evaluation.
In addition, even if accidental releases of MC could be considered part of
the listed lifecycle stages of MC, EPA has "determined" that such releases
are not circumstances under which MC is intended, known or reasonably
foreseen to be manufactured, processed, distributed, used, or disposed of,
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as provided by TSCA's definition of "conditions of use," and EPA is
therefore exercising its discretionary authority to exclude releases from
accidents from the scope of the MC risk evaluation. The exercise of that
authority is informed by EPA's experience in developing scoping
documents and risk evaluations, and on various TSCA provisions
indicating the intent for EPA to have some discretion on how best to
address the demands associated with implementation of the full TSCA
risk evaluation process. Specifically, since the publication of the Risk
Evaluation Rule, EPA has gained experience by conducting ten risk
evaluations and designating forty chemical substances as low- and high-
priority substances. These processes have required EPA to determine
whether the case-specific facts and the reasonably available information
justify identifying a particular activity as a "condition of use." With the
experience EPA has gained, it is better situated to discern circumstances
that are appropriately considered to be outside the bounds of
"circumstances... under which a chemical substance is intended, known,
or reasonably foreseen to be manufactured, processed, distributed in
commerce, used, or disposed of' and to thereby meaningfully limit
circumstances subject to evaluation. Because of the expansive and
potentially boundless impacts that could result from including accidental
releases as part of the risk evaluation, which could make the conduct of
the risk evaluation untenable within the applicable deadlines, MC releases
from accidents are determined not to be circumstances under which MC is
intended, known or reasonably foreseen to be manufactured, processed,
distributed, used, or disposed of, as provided by TSCA's definition of
"conditions of use."
Exercising the discretion to not identify MC releases from accidents 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
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on reasonably available information, including accidental releases, were
not intended to be the focus of TSCA risk evaluations. And, as noted in
the preamble to the Risk Evaluation Rule, EPA believes that Congress
intended there to be some reasonable limitation on TSCA risk evaluations,
expressly indicated by the direction in TSCA section 2(c) to "carry out
[TSCA] in a reasonable and prudent manner."
For these reasons, EPA is exercising this discretion to not consider MC
releases from accidents to be COUs.
Second, even if MC releases from accidents could be identified as
exposures from a COU in some cases, these are generally not forms of
exposure that EPA expects to consider in risk evaluation. TSCA section
6(b)(4)(D) requires EPA, in developing the scope of a risk evaluation, to
identify the hazards, exposures, conditions of use, and potentially exposed
or susceptible subpopulations the Agency "expects to consider" in a risk
evaluation. As EPA explained in the "Procedures for Chemical Risk
Evaluation Under the Amended Toxic Substances Control Act" ("Risk
Evaluation Rule"), "EPA may, on a case-by-case basis, exclude certain
activities that EPA has determined to be conditions of use in order to
focus its analytical efforts on those exposures that are likely to present the
greatest concern, and consequently merit an unreasonable risk
determination." 82 FR 33726, 33729 (July 20, 2017).
In the problem formulation documents for many of the first 10 chemicals
undergoing risk evaluation, EPA applied the same authority and rationale
to certain exposure pathways, explaining that "EPA is planning to
exercise its discretion under TSCA 6(b)(4)(D) to focus its analytical
efforts on exposures that are likely to present the greatest concern and
consequently merit a risk evaluation under TSCA..." The approach
discussed in the Risk Evaluation Rule and applied in the problem
formulation documents is informed by the legislative history of the
amended TSCA, which supports the Agency's exercise of discretion to
focus the risk evaluation on areas that raise the greatest potential for risk.
See June 7, 2016 Cong. Rec., S3519-S3520.
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In addition to TSCA section 6(b)(4)(D), the Agency also has discretionary
authority under the first sentence of TSCA section 9(b)(1) to "coordinate
actions taken under [TSCA] with actions taken under other Federal laws
administered in whole or in part by the Administrator." TSCA section
9(b)(1) provides EPA authority to coordinate actions with other EPA
offices, including coordination on tailoring the scope of TSCA risk
evaluations to focus on areas of greatest concern rather than exposure
pathways addressed by other EPA-administered statutes and regulatory
programs, which does not involve a risk determination or public interest
finding under TSCA section 9(b)(2).
Following coordination with EPA's Office of Land and Emergency
Management (OLEM), EPA has found that exposures of methylene
chloride from accidental spills fall under the jurisdiction of RCRA. See
40 CFR 261.33(d) (defining in part a hazardous waste as "any residue or
contaminated soil, water or other debris resulting from the cleanup of a
spill into or on any land or water of any commercial chemical product or
manufacturing chemical intermediate having the generic name listed [40
CFR 261.33(e) or (f)], or any residue or contaminated soil, water or other
debris resulting from the cleanup of a spill, into or on any land or water,
of any off-specification chemical product and manufacturing chemical
intermediate which, if it met specifications, would have the generic name
listed in [40 CFR 261.33(e) or (f)]"); 40 CFR 261.33(f) (listing methylene
chloride as hazardous waste no. U080). As a result, EPA believes it is
both reasonable and prudent to tailor the TSCA risk evaluation for
methylene chloride by declining to evaluate potential exposures from
accidental releases, rather than attempt to evaluate and regulate potential
exposures from accidental releases under TSCA.
Releases from floods/natural disasters
For the same reasons noted above, releases of MC from floods and natural
disasters were not included within the scope of the MC risk evaluation.
EPA does not identify releases from floods and other natural disasters as
"conditions of use." Based on the circumstances surrounding chemical
releases from floods and natural disasters, which are uncommon and
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outside the control of regulated entities or other persons, EPA does not
consider such acts to be reasonably viewed as known, intended, or
reasonably foreseen forms of chemical manufacture, processing,
distribution, use, or disposal. In particular, EPA does not consider an
uncommon and uncontrolled event like a flood or natural disaster to be a
"probable" part of the chemical lifecycle described in the definition of
"conditions of use," and believes this is a reasonable approach to
meaningfully limit activities within the scope of EPA risk evaluations.
In addition, even if releases of MC from floods or natural disasters could
be considered part of the listed lifecycle stages of MC, EPA has
"determined" that MC releases from floods and natural disasters are not
circumstances under which MC is intended, known or reasonably foreseen
to be manufactured, processed, distributed, used, or disposed of, as
provided by TSCA's definition of "conditions of use," and EPA is
therefore exercising its discretionary authority to exclude releases of MC
from floods or natural disasters from the scope of the MC risk evaluation.
For instance, an analysis of natural disasters like floods could entail
evaluation primarily on the basis of skewed exposure assumptions and the
chemical's hazards (e.g., an assumption of 100% chemical release,
resulting in theoretical, maximal exposure to any nearby populations),
contrary to what might be contemplated for evaluation of a condition of
use under TSCA section 6(b)(4)(F). EPA does not believe that Congress
intended the Agency to evaluate circumstances such as natural disasters
where the evaluation would cover only half of the risk calculation (hazard
but not exposure) for the scenario at issue.
Exercising the discretion to not identify releases of MC from floods and
other natural disasters 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 2(c), 3(4),
3(12), 6(b)(4)(D), 6(b)(4)(F).
For these reasons, EPA is exercising this discretion to not consider floods
and other natural disasters to be COUs of MC.
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Second, even if MC releases from floods or other natural disasters could
be identified as a COU, or a form of exposure from a COU, in some cases,
these are not COUs or exposures that EPA "expects to consider" in the
MC risk evaluation per TSCA section 6(b)(4)(D), and EPA is exercising
its authority under TSCA to tailor the conditions of use and exposures
evaluated in the MC risk evaluation. Given the rare , unpredictable, and
uncontrollable nature of floods and other natural disasters, EPA does not
believe that Congress intended the Agency to evaluate such acts during
TSCA risk evaluation.
Exclusion of exposure pathways subject to other regulation
33, 42,
44, 70,
73, 76,
77
PUBLIC COMMENTS:
"EPA plans to exclude exposure pathways
for methylene chloride that allegedly are
addressed under other statutes although
these pathways have been identified for
regulation precisely because they are
known or suspected to pose a serious
concern..
EPA excludes all general population risks
arising from exposures from releases to
land, air, and water based on the
assumption that other statutes adequately
address the exposures i.e., the Clean Air
Act ("CAA")" (p. 428).
EPA has failed to provide any scientific
rationale for this assumption and this strays
from basic risk assessment principles by
omitting well known exposure routes such
as water consumption by all occupationally
and non-occupationally-exposed humans
as well as similar exposures to other
biological receptors.
The problem formulation included less
than four pages to justify EPAs decision to
eliminate entire pathways and provided no
data or analysis of the exposures and risks
Clarifying language about what pathways are addressed under other
statutes has been added to Section 1.4.2 of the Risk Evaluation.
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that remain and their contribution to total
exposure and risk. The draft risk evaluation
provided no additional analysis. See MC
problem formulation pp. 54-57 and the
draft risk evaluation p. 33.
44, 73
PUBLIC COMMENTS:
EPA has excluded environmental releases
from its risk determinations. Due to its
exclusion of all exposures via
environmental releases to air, water, and
land, EPA has not considered all non-
occupational baseline exposures workers
experience. The agency needs to take these
into account as baseline exposures for
workers.
EPA did not consider background exposure that workers and consumers
using products containing MC might be exposed to in addition to
exposures from TSCA-regulated conditions of use. This may result in an
underestimation of risk, and additional discussion of this underestimation
has been added to the document in the uncertainties section 4.3.2 for
occupational exposure.
Additionally, clarifying language about what pathways are addressed
under other statutes has been added to Section 1.4.2 of the Risk
Evaluation.
Need to aggregate exposure/risk across conditions of use
44, 49,
66, 72,
73, 75,
77
PUBLIC COMMENTS:
EPA failed to assess "the combined
exposures to an individual from a single
chemical substance across multiple routes
and across multiple pathways" which
contravenes EPA's mandate under TSCA
Section 6(b).
This includes risk from aggregate
exposures such as concurrent workplace,
consumer product, and environmental
exposures, which are common occurrences
for many individuals and communities.
EPA acknowledges, "[s]ome products
[containing methylene chloride] are used in
both commercial and consumer
applications such as adhesives and
sealants"; however, EPA did not conduct a
EPA has determined that using the high-end risk estimate for
inhalation and dermal risks separately as the basis for the
unreasonable risk determination is a best available science approach.
There is low confidence in the result of aggregating the dermal and
inhalation risks for this chemical if EPA uses an additive approach,
due to the uncertainty in the data. EPA does not have data that could
be reliably modeled for the aggregate exposure, which would be a
more accurate approach than adding, such as through a PBPK model.
Using an additive approach to aggregate risk in this case could result
in an overestimate of risk. Given all the limitations that exist with the
data, EPA's approach is the best available science. EPA has added
language to the Key Assumptions and Uncertainties section describing
these assumptions and uncertainties.
EPA did not consider background exposure that workers and
consumers using products containing MC might be exposed to in
addition to exposures from TSCA-regulated conditions of use. This
may result in an underestimation of risk, and additional discussion of
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cumulative risk assessment taking this
information into consideration.
EPA is not authorized to identify particular
conditions of use and make individualized
determinations as to whether each
condition of use, rather than each
chemical, presents an unreasonable risk.
TSCA requires EPA risk evaluations to
"describe whether aggregate or sentinel
exposures to a chemical substance under
the conditions of use were considered, and
the basis for that consideration." The MC
draft indicates that EPA used an
"aggregate exposure" methodology by
estimating dermal and inhalation risks for
each condition of use (even though it failed
to combine them) but ignores the
possibility of concurrent exposure to MC
across conditions of use.
EPA is not authorized to identify particular
conditions of use and make individualized
determinations as to whether each
condition of use, rather than each
chemical, presents an unreasonable risk.
Aggregation of multiple pathways that
contribute to individual exposure would
result in even smaller margins of exposure
(MOEs) for acute and non-cancer chronic
effects and larger carcinogenicity risks
under MC's conditions of use.
this underestimation has been added to the document in the Key
Assumptions and Uncertainties section.
Per 40 CFR 702.47 ".. EPA will determine whether the chemical
substance presents an unreasonable risk of injury to health or the
environment under each condition of use within the scope of the risk
evaluation...". This approach in the implementing regulations for
TSCA risk evaluations, is consistent with statutory text in TSCA
section 6(b)(4)(A), which instructs EPA to conduct risk evaluations to
determine whether a chemical substance presents an unreasonable risk
"under the condition of use."
TSCA section 6(b)(4)(F)(ii) directs EPA to "describe whether
aggregate or sentinel exposures to a chemical substance under the
conditions of use were considered, and the basis for that
consideration" in risk evaluations. EPA defines aggregate exposures
as the combined exposures to an individual from a single chemical
substance across multiple routes (i.e., dermal, inhalation, or oral) and
across multiple pathways (i.e., exposure from different sources). 40
CFR 702.33. EPA defines sentinel exposures as the exposure from a
single chemical substance that represents the plausible upper bound of
exposure relative to all other exposures within a broad category of
similar or related exposures. 40 CFR 702.33. EPA considered the
reasonably available information and used the best available science
to determine whether to consider aggregate or sentinel exposures for a
particular chemical. EPA has determined that using the high-end risk
estimate for inhalation and dermal risks separately as the basis for the
unreasonable risk determination is a best available science approach.
There is low confidence in the result of aggregating the dermal and
inhalation risks for this chemical if EPA uses an additive approach,
due to the uncertainty in the data. EPA does not have data that could
be reliably modeled into the aggregate, which would be a more
accurate approach than adding, such as through a PBPK model. Using
an additive approach to aggregate risk in this case would result in an
overestimate of risk. Given all the limitations that exist with the data,
EPA's approach is the best available approach.
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EPA did not consider background exposure that workers and
consumers using products containing MC might be exposed to in
addition to exposures from TSCA-regulated conditions of use. This
may result in an underestimation of risk, and additional discussion of
this underestimation has been added to the document in the Key
Assumptions and Uncertainties section.
Occupational exposure estimates - vapor degreasing
45, 66
PUBLIC COMMENTS:
Regarding the open top vapor degreasing
scenario (p. 123), EPA had no monitoring
data and thus performed modeling of near-
field and far-field exposure concentrations.
It may be possible to use surrogate data
and correct for vapor pressure and vapor
density using data from other common
solvents to add to the empirical validation
of the model estimates.
Some of the data are of limited quality; for
example, p. 374: "The emission rate for
conveyorized vapor degreasing is based on
equipment at a single site and the emission
rates for web degreasing are based on
equipment from two sites. It is uncertain
how representative these data are of a
'typical' site."
Because MC-specific emission rates were available for modeling of
open top vapor degreasing, EPA did not pursue modeling for this use
using surrogate data for other chemicals. Such surrogate modeling
would unnecessarily add additional uncertainties that would prevent
usefulness toward validation. Regarding the limited data for
conveyorized and web degreasing, the limited number of sites does
not impact data quality but does impact representativeness. This
impact on representativeness is noted as an uncertainty in section
4.3.2.2.1.
Occupational exposure estimates - cold cleaning
45, 68,
56
PUBLIC COMMENTS:
For cold cleaning (p. 125), the exposure
estimates based on historical data versus
the model were very different (280-fold for
the central tendency estimate). EPA
ultimately chose the central tendency
estimate based on monitoring. This
specific value was chosen because EPA
did not have underlying data, rather only a
EPA has added explanation to section 2.4.1.2.7 to explain that
monitoring data have higher weight of evidence due to higher
relevance than modeling results for this use for several reasons: (1)
monitoring data are known to be relevant to this use; and (2) the
modeled results cannot be validated and do not capture the full range
of possible exposure concentrations identified by the monitoring data
for this use. For example, the 95th percentile modeling results appear
equal to about the 25th percentile of monitoring data. Also, EPA uses
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reported air concentration range of 14-
1,000 mg/m3, as reported by TNO (CIVO)
1995. This difference in estimated
exposure, and the resulting choice made by
EPA to use the measured yet uncertain and
old monitoring data, represent the selection
of hierarchy rather than weight-of-
evidence (WOE) approaches. Methods
should be informed by both the empirical
data and models - not individually in a
hierarchy.
For the cold cleaning occupational
condition of use, EPA utilized inhalation
data from the published literature dating to
1998. These data were rated as low quality,
in line with EPA's systematic review
guidelines, yet EPA also ran Monte Carlo
simulations for this condition of use,
arriving at values that differed by an order
of magnitude (Section 2.4.1.2.7, p. 126).
Despite the published data's low-quality,
EPA used these because the modeled data
"[did] not capture the full range of possible
exposure concentrations identified by the
monitored data." It is not clear from the
draft risk evaluation what ranges EPA
believes the monitored data captured that
the modeled data did not. Further, given
the available inputs in the Monte Carlo
model, EPA does not explain why this
model could not accommodate these
ranges, or how it came to the conclusion to
use low quality monitoring data.
the occupational exposure data with the highest quality rating, and
sometimes the highest quality data available have a low quality rating.
Occupational exposure estimates - manufacturing, reactant, processing
SACC
SACC COMMENTS:
EPA added text to Section 2.4.1.2.15 of the Risk Evaluation and
Section 2.15.3.2 of the Supplemental Information on Releases and
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The exposure concentrations for
polyurethane foam manufacturing are
highly variable (Tables 2-65 and 2-66).
Therefore, a clearer presentation of
resulting uncertainty in exposure estimates
is important.
Occupational Exposure Assessment to discuss variability in exposure
concentrations for polyurethane foam manufacturing.
SACC
SACC COMMENTS:
The Committee was concerned about how
the risk evaluation characterizes
occupational inhalation exposure of MC as
used in manufacturing (domestic
manufacture), processing (as a reactant)
distribution, industrial, and commercial use
as a laboratory chemical for all other
chemical product and preparation
manufacturing.
EPA takes note of the SACC concerns about these conditions of use.
EPA has described the risks and its assumptions and uncertainties. It
has provided additional justification for using high-end exposure
estimates in its upper bound risk estimation
66
PUBLIC COMMENTS:
Although exposure data were used to
calculate 8-hour time-weighted averages
(TWAs) for manufacturing (p. 114),
processing as a reactant (p. 116), and
processing (p. 118), the data are very
limited and most likely not representative
of true exposure. For instance, for
manufacturing only data from one facility
was provided, and for processing, only
data from two facilities were given.
EPA states the uncertainty of representativeness as a primary
uncertainty for each occupational exposure scenario that includes
monitoring data and in the Uncertainties section 4.3.2. EPA has also
obtained additional monitoring data from OSHA to bolster the
monitoring data base for many COUs.
66, 68,
75, 49,
72, 73
PUBLIC COMMENTS:
EPA inappropriately relies solely on
occupational exposure data from the
Halogenated Solvents Industry Alliance
(HSIA) for two conditions of use and
ignores available data from OSHA to
support its determinations of no
unreasonable risk.
Dr. Adam Finkel provided information to
EPA used the highest quality data reasonably available for all
scenarios, including the HSIA data. EPA consulted with and obtained
data from OSHA, whose data are used and cited in the Risk
Evaluation as OSHA, 2019. EPA added pretreated 8-hr TWA data
from Dr. Finkel into the exposure assessment in 12 occupational
exposure scenarios (OESs). The new data added for each OES ranged
from 12 to 468 points. The Commercial Aerosol Products OES
previously had only modeling but now has monitoring data as well.
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EPA on 12,152 air samples that OSHA
collected on MC. EPA references only 15
of those samples (<0.2%) in its draft risk
evaluation, solely for the spot cleaning and
fabric finishing conditions of use.
EPA does not explain why the remaining
data in Dr. Finkel's submission (which
received a "medium" data quality score in
EPA's systematic review) were not used.
Nor does EPA address whether OSHA was
in possession of additional MC monitoring
data and, if so, explain why it did not
contact OSHA directly to request access.
EPA made no effort to compare the HSIA
data with the air samples submitted by Dr.
Finkel or other monitoring data for the two
conditions of use in the possession of
OSHA or state agencies.
HSIA is the main trade association for
manufacturers of MC, and, as such, it has a
strong vested interest in EPA finding no
unreasonable risk from the chemical. It
appears to be a lobbying group. This calls
into question the reliability and
completeness of the data voluntarily
submitted by HSIA.
For the manufacturing of MC and the
processing of MC as a reactant, EPA relied
exclusively on exposure data from three
facilities provided by the HSIA. HSIA did
not provide any information about the
conditions under which these samples were
taken or the sampling protocols and
methodology. EPA relied on the HSIA data
without questioning its reliability or
representativeness.
The Adhesives and Sealants OES has a new Unknown Application
Method subcategory (added to Spray and Non-spray categories)
HSIA data were provided as part of continuous IH monitoring
programs and were evaluated using the same criteria as all other data
sets. The only other reasonably available data readily attributable to
manufacturing and processing of MC were limited and contained their
own deficiencies, such as the age of the studies, lack of discrete data
points, and no metadata information, resulting in low quality ratings.
EPA consults regularly with its federal partners and will consult with
state agencies if they are known to have relevant occupational
exposure data. EPA's discussions and consultation with OSHA are
described in section 1.4.4.4 of Supplemental Information on Releases
and Occupational Exposure Assessment. Additionally, EPA conferred
with OSHA and NIOSH during interagency review and their
contributions during review are reflected in the Draft and Final Risk
Evaluation.
EPA regularly engages with OSHA along with its other federal
partners. However, it should be noted that under section 6 of TSCA,
EPA is not mandated to consult with OSHA. Under section 9(a) of
TSCA, the Administrator may determine it is appropriate, after
making an unreasonable risk finding, to refer an action to OSHA, but
the Agency is not mandated to do so. Regarding monitoring data from
state agencies and industry, EPA has used all reasonably available
data, including from states, and has provided several opportunities for
all entities to submit workplace monitoring data or other information
for consideration in the risk evaluation.
EPA engages with all its federal partners as it works to conduct and
refine its risk evaluations. EPA is under no obligation to categorically
provide descriptions of its discussions and consultations with other
federal agencies and, in the interest of continuing to have open and
candid discussions with them, is not intending to include the content
of those discussions in the risk evaluation. However, input from
federal partners is included as appropriate.
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EPA is mandated under TSCA to consult
with OSHA. In finalizing the MC risk
evaluation, EPA should make every effort
to obtain additional workplace monitoring
data from OSHA, state agencies, and
industry and should use all data in its
possession to determine unreasonable risks
to workers.
Descriptions of discussions and
consultation with OSHA should be
documented and included in the risk
evaluation.
Occupational exposure estimates - pharmaceutical production
45, 65
PUBLIC COMMENTS:
The draft risk evaluation cites a World
Health Organization (WHO) publication
for MC exposures in the pharmaceutical
manufacturing industry. The WHO
publication (1996b) is actually a secondary
reference that in turn cites Zahm et al.
(1987) and HSE (1992). Zahm (1987)
reports MC exposures that range from 7.1
to 3749 mg/m3 (on an 8-hour TWA basis)
and it appears that these data were used by
EPA in its risk calculations. The Zahm
(1987) report is very old and based on
metadata collected at a time when
pharmaceutical manufacturing was often
done in open vessels. That is no longer the
case, and thus, data from Zahm (1987) are
not representative of current practices.
Further, the dermal estimate is flawed, as
gloves would be worn for product quality.
Under EPA's TSCA systematic review
guidance, these data should be rated "low"
for the temporality metric of
EPA has removed assessment of Pharmaceutical Production from the
risk evaluation because this use is not a TSCA use.
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representativeness (>15 years old). They
should not be used for exposure
assessment, particularly when more timely
(and thus more representative) data are
available.
In contrast to Zahm (1987), the other
primary source discussed in the WHO
study - HSE (1992) - reported MC
exposure data from pharmaceutical
manufacturing (0-18 mg/m3, 8-hour TWA)
that are consistent with recent data
provided to EPA. EPA should thus rely on
this study, and not Zahm (1987), in its final
risk evaluation.
A comparison of recent data (from a
modern pharmaceutical manufacturing
site) to the data used by EPA in its draft
risk evaluation was made, and there was no
instance in which current exposure levels
exceeded EPA de minimis risk levels or
the PEL (25 ppm = 86.8 mg/m3).
Occupational exposure estimates - waste handling
66
PUBLIC COMMENTS:
Very few exposure data are available for
waste handling. The available data might
not truly represent worker exposure
concentrations (p. 160). Three data points
are not enough to make a statistical
determination of exposure (p. 161).
As stated in the first 10 Draft Risk Evaluations, EPA makes statistical
estimates of 50th and 95th percentiles for exposure scenarios with 6 or
more data points, and this scenario has 22 full shift data points. The
uncertainty of representativeness is included as a primary uncertainty
towards confidence in the section 2.4.1.2.21 covering Waste
Handling, Disposal, Treatment, and Recycling.
Occupational exposure estimates - repackaging
45
PUBLIC COMMENTS:
When historical data were used, it is
sometimes unclear whether the source
reported the associated exposure
conditions, including the use of personal
protective equipment and local exhaust
EPA has clarified in section 2.4.1.2 that EPA could not determine
whether PPE or engineering controls were used for some settings
where monitoring was conducted.
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ventilation (e.g., in the repackaging use
with the 1976 Unocal data from an
American Industrial Hygiene Association
(AIHA) report (p. 120).
Occupational exposure estimates - painting and coating
45
PUBLIC COMMENTS:
The painting and coating industrial hygiene
data demonstrate how variable the data are
among studies and applications,
emphasizing the role of local scenario
factors (p. 132). As such, there are
questions regarding whether these data are
sufficiently representative for decision-
making.
Such data variability are common in many OESs, and EPA believes
that data variability may improve representativeness. EPA has been
transparent about the uncertainty of representativeness towards
confidence in each OES section of 2.4.1.2 and overall in the
Uncertainties section 4.3.2.1.
Near-field wind speed and use of ventilation in estimating occupational inhalation exposure
SACC
SACC COMMENTS:
Clarify the issues related to near-field air
wind speed and use of additional
ventilation in the scenario,
o It is unclear from the text of the report
why the near-field indoor air speed is
not related to the air exchange rate and
the volume of the room,
o It is also unclear why the speed of air
movement in the near-field would not
be the same as for the rest of the room
unless some type of additional
ventilation (i.e., a fan) was used in the
near-field. The use of additional
ventilation was not mentioned in the
text.
o It is also unclear why movement of the
chemical in the air was modeled using
air speed rather than diffusion between
the near-field and far-field.
PUBLIC COMMENT:
There is no additional ventilation (e.g., fan) modeled in this scenario.
The scenario is as described in Figure F-l. Air does not necessarily
move through a workplace in plug flow. While the air exchange rate
(and air volumetric flow rate) is a function of the ventilation system's
air moving capacity, the air speed is a function more of the
configuration of the air ventilation system, moving or rotating
equipment that may cause air currents, and the movement of people.
Air moves in multiple, swirling directions with variations in localized
air speeds. Workplaces are generally expected to have turbulent air
flow, with air moving in turbulent eddy currents. While air speed can
vary spatially depending on the geometry, configuration, and
placement of equipment and other objects in the workspace, the model
uses a mean air speed. This is the mean air speed throughout the
workplace and is modeled using a distribution derived from the mean
air speeds calculated by Baldwin and Maynard (1998) based on their
measured air speeds in workplaces. Therefore, the model uses a single
value of air speed for the near-field and far-field (this value varies
from iteration to iteration following its distribution).
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None of the exposure estimates (including
modelled scenarios) considered the use of
active ventilation controls. This is a major
limitation that likely yields significant
overestimates of exposure. Consideration
of modern handling practices and presence
of engineering controls (e.g., ventilation)
can be built into modeling scenarios.
Under these circumstances, diffusion is a weak form of mass transfer
compared to convection. If we were to approximate the Peclet number
for the near-field, using the NF's radius (1.5 m), the median mean air
speed (8.78 cm/s), and an approximate diffusivity of water vapor in air
(0.282 cm2/s), we calculate a Peclet number of approximately 4,700.
Since this number is orders of magnitude greater than one, this
confirms that convection is of much greater importance than diffusion
to mass transfer. A more rigorous approach would use computational
fluid dynamics (CFD) to discretize the workplace volume and solve
the mass and momentum balances, calculate the various length scales
of the eddy currents, and calculate local Peclet numbers. Higher
energy eddy currents are expected to show convection (or turbulent
"diffusivity") more important than molecular diffusion. As eddy
currents dissipate energy and become smaller, there may be small
length scales (i.e., Kolmogorov microscale) where molecular diffusion
becomes more important. These domains are of negligible importance
to the overall mass transfer of chemical through the workplace.
Characterization of important exposure determinants in occupational exposure assessment approach
SACC
SACC COMMENTS:
Provide a better characterization of
important exposure determinants (i.e.,
number of tasks/occupations, number of
companies sampled, date range of samples,
conditions under which measurements
were taken) when describing the exposure
data and exposure assessment approach in
the occupational exposure scenarios in
Section 2.4.1.2 of the risk evaluation.
The mathematical approach used to
estimate the central tendency and high-end
percentiles when the distribution of
exposure samples is unknown does not
account for all sources of variability in
exposure, nor does it account for
representativeness of exposure estimates
EPA has added these important exposure determinants when known. Full
details of available data are in Appendix A of the Supplemental
Information on Releases and Occupational Exposure Assessment.
Representativeness of data is discussed in Section 4.3.2.1 of the Risk
Evaluation and Section 4.2.2 of the Supplemental Document.
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within each occupational exposure
scenario.
For example, the data provided by the
HSIA for worker exposure during
manufacturing (Tables 2-28 and 2-29) are
based on 136 samples, coming from only 2
companies.
Occupational exposure estimates - general
SACC
SACC COMMENTS:
Possible values of Fabs should be
discussed when this parameter is first
defined in the text. This is typically done
for a number of the other parameter values.
EPA has added discussion to Key Dermal Exposure Dose Models
section of Section 2.4.1.1 in the Risk Evaluation to include the
possible values of Fabs and reference to the Supplemental Information
on Releases and Occupational Exposure Assessment for more details.
SACC
SACC COMMENTS:
EPA should not refer to the 95th percentile
value as a 'high-end estimate' of exposure.
It is misleading to suggest that the 95th
percentile value is an upper bound on
exposure since exposure distributions are
typically skewed and as a result, higher
percentile values (e.g., the 99th percentile
value) can often be an order of magnitude
or higher than the 95th percentile value.
EPA has included in 2.4.1.1 the definition of the term "high-end"
taken from EPA's Guidelines for Exposure Assessment (HERO
90324) and shown in the Supplemental Information on Releases and
Occupational Exposure Assessment. These Guidelines define high-
end as an exposure value above the 90th percentile but below the
exposure of the individual with the highest exposure. The Guidelines
also recommend not using higher values in the high-end, such as 98th
or higher. EPA does not suggest or use the term "upper bound."
SACC
SACC COMMENTS:
SACC indicated the need to determine and
describe occupational exposure scenarios
where the industry standard is to provide
dedicated ventilation.
While EPA has learned of some exposure scenarios where dedicated
ventilation was in use, EPA did not find reasonably available information
to determine and describe occupational exposure scenarios where the
industry standard is to provide dedicated ventilation.
73
PUBLIC COMMENTS:
In its systematic review process, EPA rated
the 2018 HSIA data as 1.6, or "High."
However, it appears that the data represent
only four manufacturing facilities and it is
unclear how representative of the entire
country the data are.
EPA states the uncertainty of representativeness which is included as a
primary uncertainty towards confidence in section 2.4.1.2.1 covering
Manufacturing. EPA estimates between 4 and 14 sites for this COU.
EPA does not believe that its weighting criteria for occupational exposure
data are inconsistent with best practices in systematic reviews.
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EPA's approach to weighting criteria,
which is inconsistent with best practices in
systematic reviews, results in the "Low"
Methodology score for the 2018 HSIA
having little impact on its overall score.
EPA's systematic review protocol does not
take into consideration the potential for
bias based on the data source.
EPA provides insufficient justification for
its exclusive reliance upon this potentially
biased data without independent validation
and quality assurance reporting.
The ranking of data sources in the Risk Evaluation is reflective of the
approaches outlined in Application of Systematic Review in TSCA Risk
Evaluations. EPA is in the process of seeking peer review of its
Systematic Review protocol, and potential bias of data sources may be
addressed in future updates. EPA used the highest quality data reasonably
available for all scenarios, and the HSIA data are the highest quality data
for two COUs. Independent validation of data is not available for these
COUs.
49, 72
PUBLIC COMMENTS:
EPA determined that MC presents no
unreasonable risk without considering the
vast majority of that data. In so doing, EPA
violated its statutory obligation to consider
"reasonably available information" when
evaluating chemical risks.
EPA fails to consider readily available data
on occupational exposures to MC, and thus
lacks sufficient information to support its
proposed determinations of no
unreasonable risk.
EPA has considered all reasonably available data on occupational
exposures to MC. Some data did not have sufficient metadata such as
more specific industry codes and worker activities needed for
incorporation in the risk evaluation. When sufficient metadata is not
reasonably available, EPA cannot utilize the underlying dataset. For
example, some data do not have the metadata to associate it with a
particular industry or use or to associate it with a particular time
averaging. EPA has added hundreds of additional data pointsfrom
previously underutilized sources of OSHA data.
Occupational exposure estimates - combining pre and post OSHA PEL (1997)
SACC,
41,45,
65, 67
SACC COMMENTS:
The risk evaluation groups MC area and
exposure measurement data pre- and post-
revision of the PEL from 500 to 25 ppm in
1997, which could lead to overestimation
of exposure.
The analysis of these OSHA inspection
data suggests that exposure levels did not
change dramatically before and after 1997,
so that the data could be combined for the
purpose of exposure estimation.
In section 4.3.2.1, EPA states the uncertainty of the use of data from
before the PEL revision and that use of some older data may overestimate
some exposures. EPA revised text in 2.4.1.1 to expand upon adequacy of
older data and summarize EPA's new statistical analysis, which is
included as a new appendix in the Supplemental Information on Releases
and Occupational Exposure Assessment. EPA added text to 2.4.1.1 noting
that some producers and users of MC may have started implementing
changes before the PEL revision became effective, which could also be a
factor in the relatively limited reduction in exposures between the pre-
and post-revision of the PEL periods. EPA analyzed 8-hr TWA exposures
measured prior to April 10, 1997 (pre-rule) and after April 10, 2000 (post-
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The statement that"... incremental general
exposure reductions due to the PEL
change..." indicate that"... exposure data
from before the PEL are adequate"
(Section 2.4.1.1, p. 108, lines 1852-1854)
needs to be expanded.
The argument for combining the two
periods could be strengthened by an
expanded discussion of the mix of
products, processes, and/or worker
practices before and after 1997, about
which EPA claims to not have received
information. It is not clear whether EPA
contacted users proactively to obtain this
information.
It is likely that producers and users of MC
started implementing changes before 1997,
in advance of the expected promulgation of
the 25 ppm PEL. This could also
contribute to explain the relatively limited
reduction in exposures between the two
periods.
The Committee noted that data collected
after the PEL should simply be given more
weight.
rule), respectively. Several distributional statistics showed consistent
reductions of about 30% to 35% following a reduction in the PEL of 95%.
Hence, a twentyfold reduction in the PEL resulted in only an
approximately 1.5-fold reduction in actual exposures. Due to the small
reduction in exposures relative to the reduction in PEL, EPA included the
pre-rule samples in the occupational exposure assessment to provide a
more robust data set. While EPA's new analysis justifies the use of the
pre-PEL change data, EPA weighted use of pre-PEL change data through
changes in overall confidence ratings. Strength of overall confidence in
monitoring data is reduced depending upon the reliance of use of
monitoring data that had been sampled before the OSHA PEL for
methylene chloride was reduced (effective after transition in 2000).
SACC
SACC COMMENTS:
Analyze the OSHA data using appropriate
statistical methods for each use category
and cite the results to justify that the old
monitoring data remains relevant for
assessing exposures in 2019.
EPA revised text in 2.4.1.1 to summarize EPA's new statistical analysis,
which is included as a new appendix in the Supplemental Information on
Releases and Occupational Exposure Assessment. The new analysis uses
appropriate statistical methods and shows changes in exposures for each
use category for which data are available. EPA found a range of exposure
reductions across eight industry sectors and increases for two sectors. The
largest decreases were for spot cleaning (94.5%), fabric finishing (93.4%),
and use of adhesives (50.6%). On the other hand, exposures increased for
plastics manufacturing (617%) and aerosol degreasing (130%). The
results justify use of the pre-PEL change data but with lower weight in
some use categories. EPA weighted use of pre-PEL change data through
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ONSE TO COMMENT
changes in overall confidence ratings. Strength of overall confidence in
monitoring data is reduced by having a portion of a use's monitoring data
that had been sampled before the OSHA PEL for methylene chloride was
reduced (effective after transition in 2000).
Data quality of Finkel (2017) commentary
45
PUBLIC COMMENTS:
EPA did not assess the methodological
validity or reliability of the Finkel (2017)
commentary, which was critical to
assumptions in the risk evaluation.
EPA assessed the analysis in Dr. Finkel's commentary to determine
potential improvements. EPA revised text in 2.4.1.1 to summarize EPA's
new statistical analysis, which is included as a new appendix in the
Supplemental Information on Releases and Occupational Exposure
Assessment. The new analysis has improvements in validity and
reliability than the analysis in the commentary. For example, EPA's
analysis excluded samples that were not personal samples or had unit of
measure denoted "X" or were blank, and apparent duplicate samples. EPA
also combined samples with the same sample number (but different values
of sample time and sample result), which were assumed to be samples
taken on the same worker to calculate an 8-hr TWA. EPA investigated
and found that the analysis is not sensitive to values of the level of
detection used.
Concerns with Finkel analysis of pre- and post-1997 occupational exposure data
67, 45
PUBLIC COMMENTS:
Several public commenters summarized
Finkel's letter comparing airborne
occupational MC concentrations pre- and
post- implementation of the 1997 OSHA
standard. Two of the commenters pointed
out limitations of his analysis including: a
lack of transparency in the dataset (i.e.,
not publicly available, not from an
identifiable peer-reviewed source,
durations were not provided, missing
units of measurement). All exposure
concentrations should be converted to the
same unit of measure for appropriate
comparison. There is also uncertainty
whether compliance-driven data that is
not randomly sampled adequately
EPA assessed the analysis in Dr. Finkel's commentary to determine
potential improvements. EPA revised text in 2.4.1.1 to summarize EPA's
new statistical analysis, which is included as a new appendix in the
Supplemental Information on Releases and Occupational Exposure
Assessment. EPA's new analysis supersedes and replaces the Finkel
analysis and has improvements in validity and reliability and uses
appropriate statistical methods. For example, EPA's analysis excluded
samples that were not personal samples or had unit of measure denoted
"X" or were blank (thereby using the same unit of measure), and apparent
duplicate samples. EPA also combined samples with the same sample
number (but different values of sample time and sample result), which
were assumed to be samples taken on the same worker to calculate an 8-hr
TWA. EPA investigated and found that the analysis is not sensitive to
values of the level of detection used. Also, EPA analyzed by NAICS
codes to show differences among industry classes. The new analysis
shows changes in exposures for each use category for which data are
available. EPA found a range of exposure reductions across most industry
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represent the full range of exposure, and
there is lack of appropriate statistical
analysis to support his claim.
Specifically, it is clear that the data do
not approximate a normal distribution
(i.e., do not fall closely along the
centerline on the probability plot);
therefore, any statistical comparisons
should be made using transformed data
with comparison between the geometric,
rather than arithmetic means. This allows
more weight to be placed upon the
majority of the data that falls at lower
concentrations.
A commenter suggested EPA re-assess
the use of Finkel's analysis for the risk
evaluation, because he grouped all
available OSHA personal monitoring data
from MC to calculate trends without
stratification by different uses/scenarios,
and OSHA data are not representative of
the industry as a whole.
sectors and increases for several sectors. The largest decreases were for
spot cleaning (94.5%), fabric finishing (93.4%), and use of adhesives
(50.6%)). On the other hand, exposures increased for plastics
manufacturing (617%>) and aerosol degreasing (130%>). The results justify
use of the pre-PEL change data but with lower weight in some use
categories. EPA weighted use of pre-PEL change data through changes in
overall confidence ratings. Strength of overall confidence in monitoring
data is reduced by having a portion of a use's monitoring data that had
been sampled before the OSHA PEL for methylene chloride was reduced
(effective after transition in 2000). These OSHA data are adequately
representative to use for this analysis.
67
PUBLIC COMMENTS:
Cardno ChemRisk performed a de novo
analysis of the publicly available OSHA
dataset. This included a review of all field
definitions. The differences observed in
this simplified analysis illustrate the
importance of proper data sub setting
when analyzing the appropriateness of
empirical data for exposure estimation.
Overall, the Cardno ChemRisk evaluation
concluded that there is indeed a reduction
in MC exposures before and after the
implementation of the OSHA standard,
and that this difference was statistically
EPA assessed the analysis by Cardno to determine potential
improvements. EPA revised text in 2.4.1.1 to summarize EPA's new
statistical analysis, which is included as a new appendix in the
Supplemental Information on Releases and Occupational Exposure
Assessment. EPA's new analysis has improvements in validity and
reliability and uses appropriate statistical methods. For example, EPA's
analysis excluded samples that were not personal samples or had unit of
measure denoted "X" or were blank (thereby using the same unit of
measure), and apparent duplicate samples. EPA also combined samples
with the same sample number (but different values of sample time and
sample result), which were assumed to be samples taken on the same
worker to calculate an 8-hr TWA. EPA investigated and found that the
analysis is not sensitive to values of the level of detection used. Also,
EPA analyzed by NAICS codes to show differences among industry
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significant. In addition to a significant
lowering of workplace exposures as a
result of the OSHA Standard, there were
also significant differences in the
reported exposure values across business
types when the OSHA dataset was
separated by NAICS code. Aggregating
the data from all commercial/industry
uses, as done in the Finkel report,
increased the overall variability in the
dataset, thus reducing the ability to detect
any trends by industry or date.
EPA should consider re-evaluating the
appropriateness of its use of aggregated
historical data and increase emphasis on
recent exposure monitoring data
supplemented by model estimates for the
revised risk evaluation.
classes. EPA re-evaluated and confirmed the appropriateness of its use of
aggregated historical data using a new analysis. The new analysis uses
appropriate statistical methods and shows changes in exposures for each
use category for which data are available. EPA found a range of exposure
reductions across most industry sectors and increases for several sectors.
The largest decreases were for spot cleaning (94.5%), fabric finishing
(93.4%), and use of adhesives (50.6%). On the other hand, exposures
increased for plastics manufacturing (617%) and aerosol degreasing
(130%>). The results justify use of the pre-PEL change data but with lower
weight in some use categories. EPA weighted use of pre-PEL change data
through changes in overall confidence ratings. Strength of overall
confidence in monitoring data is reduced by having a portion of a use's
monitoring data that had been sampled before the OSHA PEL for
methylene chloride was reduced (effective after transition in 2000). EPA
has exhausted all modeling opportunities with the data that are reasonably
available.
Approach to handling non-detect values in exposure measurements
SACC,
67
SACC COMMENTS:
A Committee member pointed that there
are different approaches for handling
non-detect values beyond replacement by
'/2 the detection limit, 0, or the detection
limit. The selection of non-detect
replacement method can affect estimates
of central tendency and 95th percentiles.
A substantial body of literature on the
treatment of non-detects for estimating
population parameters has been
developed including studies and guidance
by EPA. The EPA should consider these
methods. As a start, Helsel (2010)
provides a critical review of some
methods for dealing with non-detects.
PUBLIC COMMENTS:
EPA used its documented approach for occupational exposure data that
were reported as below the limit of detection. This approach has been
used consistently across the Risk Evaluations and is summarized in
section 1.4.4.2 of the Supplemental Information on Releases and
Occupational Exposure Assessment. For datasets including exposure data
that were reported as below the limit of detection (LOD), EPA estimated
the exposure concentrations for these data, following EPA/OPPT's
Guidelines for Statistical Analysis of Occupational Exposure Data (1994)
which recommends using the LOD / 2°5 if the geometric standard
deviation of the data is less than 3.0 and LOD / 2 if the geometric standard
deviation is 3.0 or greater (EPA, 1994).
For environmental and consumer exposures, limits of detection were
reported as stated within the evaluated reviewed literature and evaluated
monitoring information. As explained, those limits of detection varied
amongst studies based on differences in sampling routine, methodology,
and precision in available analysis tools. No values using relevant limits
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The dataset did not report the limit of
detection (LOD) associated with each of
the samples. Without the actual analytical
limits of detection, a substitution for the
limit of detection (such as
LOD/SQRT(2)) is not feasible.
The ProUCL 5.1 User Guide (Singh and
Maichle, 2015), and Regression on Order
Statistics (ROS) methods are used to fill
in non-detect values in alignment with the
lognormal distribution as determined
from the non-censored concentrations.
of detection were incorporated into the consumer or environmental
modeling outputs.
Occupational exposure comparisons to PEL
67
PUBLIC COMMENTS:
In 1997, OSHA lowered the workplace
exposure limit for MC from 500 to 25
ppm as an 8-hour TWA. In addition, it
established a STEL (15-minute) of 125
ppm and an action level for
concentrations of airborne MC of 12.5
ppm (8-hour TWA) resulting in a 95%
reduction in acceptable exposures.
There is no basis for EPA to assume that
MC is being used at levels that would be
in violation of the OSHA standard.
Nevertheless, the draft risk evaluation
uses incorrect baselines for exposure to
MC, particularly the occupational
exposure scenarios.
This OSHA workplace exposure limit reduction is noted in section 2.4.1.1
of the risk evaluation. Reasonably available data indicates that
exceedances of the limits can occur in some scenarios. EPA is not aware
of any incorrect baselines.
73
PUBLIC COMMENTS:
The current draft risk evaluation does not
mention EPA's 2017 recommended
Existing Chemical Concentration Limit
(ECEL).
If EPA were to compare its workplace
exposure estimates to the ECEL - as
EPA did not recommend this ECEL in the 2017 proposed rule for
methylene chloride in paint and coating removal (82 FR 7464, January 19,
2017). Rather, the ECEL was one possible risk management approach
outlined in the rulemaking that proposed to prohibit the use of methylene
chloride in most commercial paint and coating removal. This ECEL was
not finalized and thus, there is no ECEL for methylene chloride. EPA
provided the PEL as a point of comparison only to help readers
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opposed to OSHA's PEL - a very
different picture would emerge. For
example, under the manufacturing
condition of use, the high-end 8-hour
TWA exposure concentration (4.6 mg/m3
or 1.32 ppm) would just exceed the
ECEL of 1.3 ppm.
understand EPA's workplace exposure and risk estimates compared to a
familiar exposure concentration, as expressed in the PEL. EPA did not use
the PEL in the development of the risk estimates or as part of making an
unreasonable risk determination.
Use of limited data sets to extrapolate exposure among broader worker groups
SACC,
67
SACC COMMENTS:
There is concern over the use of limited
data sets to extrapolate exposure among
broader worker groups. While there is a
mathematical approach to identify the
central tendency and high-end values
when the distribution is unknown, the
current data quality assessment does not
take into account whether the data are
generalizable to the exposures among the
entire set of workers that the data are
being used to represent.
The risk evaluation does not provide
sufficient information on the reasons used
by OSHA to collect data at targeted sites,
and therefore, the potential for
overestimation or bias of general
exposures for a specific use is not easily
determined.
EPA should include additional
information on the basis and purpose of
data collection to provide better
understanding about why the data
reported by OSHA were collected.
EPA states the uncertainty of representativeness as a primary uncertainty
for each occupational exposure scenario that includes monitoring data and
in the Uncertainties section 4.3.2.
EPA added text to Section 2.4.1.1 of the Risk Evaluation and Section
1.4.4.4 of the Supplemental Information on Releases and Occupational
Exposure Assessment to add additional information from the OSHA
website about why monitoring data were collected.
SACC
SACC COMMENTS:
For use categories where EPA analysis
determined exposure above the PEL, an
additional analysis could be conducted
EPA shows reductions of exposures associated with respirator use in the
Risk Characterization. EPA also compares exposures to the OSHA PEL
and STEL. EPA does not have an approach of setting the maximum
exposure based on data for those companies that are following EPA
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based on the approach of setting the
maximum exposure based on data for
those companies that are following either
OSHA and/or EPA NESHAP regulations.
Evaluate the representativeness of data
sets or express the uncertainty in the
extrapolated exposures.
NESHAP regulations. EPA has addressed representativeness of data sets
and limited data sets in the list of limitations in each subsection of 2.4.1.2
and holistically in the Uncertainties section 4.3.2.1. {Note: This is a repeat
response to several similar comments}
Modeling versus monitoring data for occupational exposure estimates
SACC
SACC COMMENTS:
Include a comparison of the exposure
model predictions to the monitoring data
("Supplemental Information on Releases
and Occupational Exposure Assessment",
Section 4.2.3, p. 123) or include an
explanation as to why this was not done.
EPA compared monitoring data to model predictions for the one OES,
Cold Cleaning (Section 2.7.3 of the Supplemental Information on
Releases and Occupational Exposure Assessment), for which both were
available. EPA has added explanation to section 2.4.1.2.7 showing this
comparison and to explain that monitoring data have higher weight of
evidence due to higher relevance than modeling results for this use for
several reasons: (1) monitoring data are known to be relevant to this use;
and (2) the modeled results cannot be validated and do not capture the full
range of possible exposure concentrations identified by the monitoring
data for this use.
67,
SACC
SACC COMMENTS:
The hierarchy of approaches to exposure
estimation is not always appropriate. The
Agency should develop a protocol for
deciding when measurement data of good
quality are available in sufficient
quantities to derive reliable estimates. If
they are not sufficient, modeling could be
a preferable approach to available
measurements.
PUBLIC COMMENTS:
When empirical sampling data are
outdated or sparse, supplementing such
data with modeling would improve the
exposure estimates and increase the
likelihood that the risk characterization is
founded on the best available science.
EPA has included the hierarchy of approaches in Appendix G of the
Supplemental Information on Releases and Occupational Exposure
Assessment. This appendix shows that the hierarchy has preferences, and
these preferences do not have to be strictly followed. EPA will seek peer
review of its Systematic Review protocol, including the hierarchy of
approaches to exposure estimation. EPA used a model and relevant
parameter data for one occupational exposure scenario, Cold Cleaning.
EPA did not find reasonably available data for modeling of other
Occupational Exposure Scenarios (OESs).
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67
PUBLIC COMMENTS
EPA provides detailed occupational
model descriptions in the draft risk
evaluation for MC that appear to be
sufficient to reproduce the exposure and
MOE estimates (EPA, 2019). However,
there are a number of issues regarding the
occupational modeling approaches that
could be strengthened in the final risk
evaluation.
To the degree that modeling has not been
completed for MC specifically, existing
modeling can be leveraged. Models that
have been applied to other volatile
organic compounds (VOCs) for well-
defined scenarios can be reapplied for
MC after adjusting for chemical-specific
input parameters (e.g., vapor pressure,
usage volumes, etc.). This methodology
is consistent with EPA's endorsement of
read-across approaches for data gap
filling and is appropriate for exposure
characterization.
When modelers utilize WOE approaches
to develop appropriate input parameters,
models may be more appropriate than
low-quality monitoring data.
EPA should consider the incorporation of
additional modeling in the revised risk
evaluation using scenario definitions that
are consistent with modern uses and peer
review by occupational exposure
assessment professionals familiar with
current handling practices.
EPA has utilized all modeling opportunities with the reasonably available
data, and this includes the use of near-field/ far-field modeling in several
well-defined degreasing and brake servicing scenarios. EPA is not aware
of other well-defined scenarios that could be reapplied.
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41,45, PUBLIC COMMENTS:
66, 67, EPA's modeling results could be
68 improved by using model inputs that
represent more realistic data - such as
workplace volumes, weight fraction, and
amount used - this is a necessary step.
Available monitoring data can be used for
risk modeling inputs rather than using
assumptions or defaults. For most uses
however, the described empirical data
sets are very limited in the number of
samples and descriptions of the
conditions under which the samples were
collected. Because such data should be
considered of limited confidence, an
alternative evidence integration approach
should be considered. In this approach,
for each scenario, methods should be
informed by the empirical data and
models used as a package - not
individually in a hierarchy.
Use tiered approaches to exposure
modeling to verify model outputs and
ensure they represent exposure levels in
line with real-world conditions.
A tiered approach to exposure assessment
will necessarily outline how EPA chooses
which data to include in its analysis and
will provide helpful guideposts when
choosing between multiple problematic
data.
EPA needs to outline a tiered approach
towards exposure assessment. In this
instance, there are two competing data
sets (monitoring data and modeled data)
and a cursory justification. A tiered
EPA used reasonable available model input data for modelling
occupational exposures in several OESs. EPA considered both monitoring
and modeling for the one OES, Cold Cleaning, for which both were
available. Monitoring data and thus modeling were not reasonably
available for other OESs. EPA does not have tiered approaches or other
data necessary to verify any of the occupational models used in this Risk
Evaluation.
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approach could provide a scientifically
based path forward, and, if needed,
suggest further steps such as a Tier 2
exposure model to achieve higher quality
data. A tiered approach to exposure
assessment would be more consistent
with TSCA's Section 26(h) requirement
for EPA to rely upon best available
science in its risk evaluations.
EPA should gather additional monitoring data
SACC
SACC COMMENTS:
Include personal monitoring sampling
data provided in OSHA (2019) and
Finkel (2019) to better characterize MC
exposures in a number of occupational
exposure scenarios.
While the OSHA (2019) data are used for
three exposure scenarios, this data set
includes important exposure data that can
supplement exposure data used in other
scenarios.
Sampling data from the NAICS 325199
code (summarized in Table MC4-1 of the
SACC report) should also be
incorporated into the occupational
inhalation exposure summary metrics
presented in Tables 2-28 and 2-29 of
worker exposure to MC during
manufacturing.
SIC codes provided within Finkel (2019)
can be matched with occupational
exposure scenarios to provide additional
exposure data for a number of scenarios.
EPA added text to Section 2.4.1.1 of the Risk Evaluation and Section
1.4.4.4 of the Supplemental Information on Releases and
Occupational Exposure Assessment to add additional information
about OSHA and data provided by Dr. Finkel.
While the values presented in Table MC4-1 are classified as
"Manufacturing," these were designated by OSHA and correspond
only to NAICS code 325199, which may be applicable to any
chemical manufacturing, not specifically MC manufacturing.
EPA added pretreated 8-hr TWA data from Dr. Finkel into the
exposure assessment in 11 OESs. The new data added for each OES
ranged from 12 to 468 points. The Commercial Aerosol Products OES
previously had only modeling but now has monitoring data as well.
The Adhesives and Sealants OES has a new Unknown Application
Method subcategory (added to Spray and Non-spray categories).
SACC
SACC COMMENTS:
State environmental and health agencies
can be queried about the availability of
EPA did not find additional reasonably available information for these
sources including Washington state, which was contacted. EPA
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monitoring and exposure data relevant to
this chemical. These data should be
obtained and incorporated into the
assessment. Washington State was
mentioned as likely having such data that
could be shared.
believes that state OSHA data is included in the OSHA Chemical
Exposure Health Data set.
49, 72,
73, 75,
76,
SACC
SACC COMMENTS:
EPA should develop a process to identify
critical missing information on uses, PPE,
or area and personal monitoring data.
Some of the measurement data available
to EPA were not used because critical
sample collection information (e.g.,
duration of sample collection) was not
reported by the source of the data.
It is not clear whether EPA exhausted all
reasonable means to obtain the missing
information; for example, by contacting
the authors of a publication or company
report, or the laboratory that analyzed the
sample.
Indicate clearly whether all proactive
venues for obtaining necessary and/or
missing information (including uses, PPE,
or specific information on monitoring
samples) were exhausted and whether
indeed there was no way of obtaining
these data.
The process of requesting missing
information should take place early in the
risk evaluation process to allow sufficient
time for relevant stakeholders to provide
the missing information to fill data gaps
and/or strengthen the available
information already present.
PUBLIC COMMENTS:
EPA added new text about modeling in Section 2.4.1.1 to indicate that
beyond the modeling conducted for this Risk Evaluation, EPA did not
find reasonably available models and associated parameter sets to do
additional modeling. EPA has not found additional reasonably
available information or data to explore different categories of ONUs
beyond the ONU categories presented in this Risk Evaluation.
EPA requested information on all aspects of risk evaluations
throughout the risk evaluation process, including opening public
dockets for receipt of such information, conducting outreach to
manufacturers, processors, users and other stakeholders, as well as
conducting tailored data development efforts for some of the first 10
chemicals. Given the timeframe for conducting risk evaluations on the
first 10 chemicals, use of TSCA data gathering authorities has been
limited in scope. In general, EPA intends to utilize TSCA data
gathering authorities more routinely for the next 20 risk evaluations.
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EPA has failed to ask employers to share
the workplace monitoring data that they
are required to preserve under OSHA
regulations, or asked OSHA and other
state and federal agencies to provide
access to the extensive exposure
information in their direct possession or
made use of the exposure information that
is in EPA's possession.
Selection of sites for collection of occupational exposure monitoring data
SACC
SACC COMMENTS:
It was unclear exactly what EPA meant
by .. sites used to collect occupational
exposure monitoring data for workers
were not selected randomly" (lines 1850-
1851) and this appears to be indicating
that bias was included in monitoring data.
Provide more context and added
justification for how the OSHA
monitoring data collected post-1997 are
used, describe clearly biases in the OSHA
data and any associated uncertainties in
the exposure estimates.
EPA revised text in 2.4.1.1 to remove the unclear sentence and to
summarize EPA's new statistical analysis, which is included as a new
appendix in the Supplemental Information on Releases and
Occupational Exposure Assessment. The new analysis has
improvements in validity and reliability and uses appropriate
statistical methods. In section 4.3.2.1, EPA states the uncertainty of
the use of data from before the PEL revision and that use of some
older data may overestimate some exposures.
SACC
SACC COMMENTS:
Facilities with fewer than 10 employees
are not required to report to TRI.
Consider using NPDES data to estimate
the number of facilities employing fewer
than 10 workers and use these data to
assess the potential degree of under-
estimation in the current assessment.
EPA's analysis uses TRI and DMR to estimate the highest local per
site water releases of MC and is not intended to estimate overall
releases. EPA's analysis uses TRI and DMR to estimate the highest
local per site water releases of MC. EPA does not expect that this
suggested approach would improve upon EPA's approach or provide
higher local per site releases compared to estimates provided using
TRI and DMR data. The proposed assumption is that a site that
monitors MC discharges per their NPDES permit but does not report
to TRI has fewer than 10 full-time equivalent workers. This proposed
assumption does not seem reasonable or likely to be valid.
Clarification of calculations for occupational exposure
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SACC
SACC COMMENTS:
The value for Yderm in Table 2-33 is
used for the calculations, but the
calculated numbers don't match those in
the Table 2-57, p. 138. It appears that this
is because the value for Yderm should be
0.9 instead of 1.0. The summary table for
dermal exposure estimates (Table 2-85, p.
165) shows a value of 0.9 for this worker
category.
Reconcile this discrepancy and adjust the
text accordingly.
EPA should verify the dermal dose
calculations for the commercial, adhesive
and caulk removers, and spot cleaning
scenarios were performed with
Yderm = 0.9.
EPA corrected Yderm in Table 2-57 for Adhesive and Caulk
Removers to be 0.9 instead of 1.0. Values in Table 2-33 are correct
and not related to Table 2-57. EPA has verified that the dermal dose
calculations for the commercial, adhesive and caulk removers, and
spot cleaning scenarios were performed with Yderm = 0.9.
SACC
SACC COMMENTS:
Clarify how the minimum, maximum and
mean values from the Ukai et al. (1998)
study are used to estimate the TWA for
calculating the average daily
concentration (ADC) and lifetime
average daily concentrations (LADC)
(Section 2.4.1.2.19, p. 156, lines 3138-
3145).
EPA added clarifying text to both Section 2.4.1.2.19 of the Risk
Evaluation and Section 2.19.3.2 of the Supplemental Information on
Releases and Occupational Exposure Assessment.
SACC
SACC COMMENTS:
Ensure that ADC and LADC estimates
are correct and explain discrepancies
between estimates derived using Equation
2.5 and estimates derived from the 8-hour
TWA measurements.
The Committee was unable to duplicate
estimates for ADCs and LADCs
presented in Tables 2-39, 2-41, and 2-45
(pp. 122, 124, and 128) using the
EPA originally calculated ADC and LADC values directly within the
Monte Carlo model but revised the Risk Evaluation and the
Supplemental Information on Releases and Occupational Exposure
Assessment to use Equation 2.5 for consistency with other scenarios.
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approach and equations of Section 2.4.1.1
(p. 107) and the available 8-hour TWA
exposure concentrations. These estimates
differ enough that they do not appear to
be due to rounding in the calculations.
These tables were the only instances
where the exposure estimates are from
modeling the data rather than calculated
directly from monitoring data. If the
estimates derived from modeling were
handled differently from direct estimates
the text should discuss this.
SACC
SACC COMMENTS:
The mean and standard deviation should
be included in the parameter distribution
tables for the specific lognormal
distributions used. Parameters used to
define the other distributions are
included.
In the Supplemental Information on Releases and Occupational
Exposure Assessment document, the mean and standard deviation for
the lognormal distributions are included in the text sections (e.g.,
Sections F. 1.2.3 and F. 1.2.11). EPA removed the values in the Lower
Bound and Upper Bound columns in Table F-l for the lognormal
distributions (indoor air speed and operating hours per week). EPA
included the mean and standard deviation in the Comments column.
Assumptions made in Monte Carlo analysis used in occupational exposure assessment
SACC
SACC COMMENTS:
Expand the discussion on the selection of
distributions for the Monte Carlo
analysis, particularly for specification of
the uniform distributions as the most
appropriate choice for an input parameter.
Expand the description and rationale for
setting an input parameter to a constant or
investigate whether a distribution
provides a better description of the
exposure range.
It is unclear why the number of spray
applications per brake job was set to a
constant in the Monte Carlo analysis
rather than as a variable with associated
The specificity of more complex distributions (e.g., triangular,
lognormal) requires adequate data to demonstrate the distribution. If
only an overall range is known, then a uniform distribution is the only
possible distribution to use. There may be some cases where a uniform
distribution is appropriate if data indicate it as such. But generally, for
EPA's modeling, uniform distributions were used because no data
were found to demonstrate a more sophisticated distribution. EPA
added text in Appendix F.1.2 of the Supplemental Information on
Releases and Occupational Exposure Assessment for clarification.
EPA defined distributions for model parameters where EPA had data
or information to justify the distribution. Model parameters kept as
constants were generally cases where EPA did not have reasonably
available data to describe the variability or uncertainty of the
parameter value (e.g., number of brake jobs per site-year, number of
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distribution. The comment in Table Apx
F-l of the risk evaluation for number of
applications per job (NA) is
uninformative
ounces of aerosol degreaser used per job). Some model parameters
were kept as constants by choice (i.e., temperature and pressure are
constant as the model is isothermal and isobaric) and some were kept
as constants appropriately (i.e., the molecular weight of MC is
appropriately kept constant). EPA added text in Appendix F.1.2 of the
Supplemental Information on Releases and Occupational Exposure
Assessment for clarification.
Recommending alternative occupational risk approaches
SACC
SACC COMMENTS:
One Committee member suggested a
Monte Carlo approach to ensure that
variability and uncertainty are handled
within one consistent framework.
It was suggested that EPA use a
probabilistic approach in the risk
calculation derivation by providing each
parameter (including fate properties,
amount of MC discharged directly or
indirectly in water sources, number of
facilities that use or discharge MC,
frequency of release, assigned protection
factor (APF), extent of use of PPE, and
UF used) with distributions derived from
previous studies, rather than using a
mixed approach where certain parameters
are kept fixed, while others are sampled
from uniform distributions with ranges
derived from the literature.
By using a Monte Carlo approach, it
would be easier to make probability
statements regarding both optimistic and
pessimistic projections, which the
Committee member believed were hard
to quantify directly from the risk
evaluation.
EPA incorporated probabilistic modeling in several analyses in the Risk
Evaluation. EPA conducted probabilistic assessments for occupational
exposure using the Near-Field / Far-field model when parameter values
were reasonably available. Deterministic assessments were only used
when lack of parameter distributions prevented probabilistic assessments.
For the human health hazard, EPA also used probabilistic models (Monte
Carlo analyses) for the dose-response models for chronic non-cancer and
cancer endpoints.
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Recommending alternative occupational exposure assumptions
SACC
SACC COMMENTS:
For chronic exposure, extended working
years should be factored into the
assessment, since workers continue to
work past the traditional retirement age,
including ages 65-74 and 75 and older.
Information on employed persons, by
occupation and industry and age, is
provided by the U.S. BLS and can be
used to inform industry specific working
age for chronic exposure calculations
(BLS, 2019).
EPA used BLS data to develop a distribution of working years. The
max of the distribution is 44 years and the calculated 95th percentile is
40 years. The distribution included low tenure to reflect workers who
change industries. Appendix C of the Supplemental Information on
Releases and Occupational Exposure Assessment contains a more
detailed explanation on how the distribution was derived.
66
PUBLIC COMMENTS:
EPA was not clear about which age
groups were included in the occupational
exposure assessment; inhalation exposure
was not presented by age group.
EPA should indicate when reproductive
age ends for men.
The health effects of women >50 years of
age, and the elderly was not considered,
this is not health protective and does not
take into account that this population is
vulnerable (p. 105).
Line 6823: Calculate adults but define
them as >16 years of age. Also, calculate
40 years working when the retirement age
(16+40 years) would be 56 years.
p. 300: Include 16-year-olds because they
are able to obtain permits, even though
most workers are adults.
At the beginning of section 2.4.1, EPA states that for the purpose of
this assessment, EPA considered occupational exposure of the total
workforce of exposed users and non-users, which include but are not
limited to male and female workers of reproductive age who are >16
years of age. Female workers of reproductive age are >16 to less than
50 years old. Adolescents (>16 to <21 years old) are a small part of
this total workforce. The occupational exposure assessment is
applicable to and covers the entire workforce who are exposed to MC.
There was no upper limit on male reproductive age assumed for this
evaluation.
72,
SACC
SACC COMMENTS:
For high-end acute exposure scenarios,
the risk evaluation should incorporate
longer shift lengths (exposure periods)
EPA added the 12- hr shift data from HSIA for the Manufacturing
OES and updated the corresponding equation defaults in Section
2.4.1.1 of the Risk Evaluation and Appendix C of the Supplemental
Information on Releases and Occupational Exposure Assessment, as
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informed with data from the HSIA
surveys (up to 12 hours).
This is relevant to each exposure scenario
as well as to the calculation of the acute
exposure concentration (equations 2-4
and 2-5) as it relates to exposure duration,
and averaging time.
The U.S. BLS provides industry-specific
data on weekly hours worked, which, on
average, are beyond 40 hours for the
manufacturing industry (BLS, 2019).
PUBLIC COMMENTS:
EPA should clarify whether its 8-hour
TWA values for manufacturing account
for the longer work shifts indicated by
HSIA, and, if not, should revise its
calculations to reflect those workers'
increased exposures, as well as those for
any other workers who work shifts longer
than 8 hours.
HSIA indicated that 12-hr shifts were also common. 12-hr data are
presented separately and no changes were made to the 8-hour shift
data.
Uncertainty and recommended probabilistic assessment
SACC
SACC COMMENTS:
The potential for introducing bias when
classifying uses and type of worker
activities into these categories is not
transparent. If the exposure estimate is
based on reported measurement data, and
those data are for one or very few worker
activities within the user/occupational
exposure scenario (OES) category, it
could potentially underestimate or
overestimate exposures for other worker
activities included in the same OES.
A more detailed description of this
potential bias is needed.
EPA identifies the uncertainty of representativeness as a primary
uncertainty for each occupational exposure scenario that includes
monitoring data. The Uncertainties section 4.3.2.1 provides detailed
discussion of this potential bias and notes that limited data sets may
potentially underestimate or overestimate exposures. EPA describes data
quality ratings in its Application of Systematic Review in TSCA Risk
Evaluations. EPA describes the data integration approach and factors
considered in determining levels of confidence for the occupational 8- or
12-hr TWA data and estimates and dermal potential dose estimates in an
appendix added to the Supplemental Information on Releases and
Occupational Exposure Assessment.
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While EPA describes the sources of
uncertainty in exposure estimates
(including PPE), it is not clear how these
uncertainties translate into data quality
and overall confidence designations.
Describe in a transparent manner how
EPA derives data quality ratings and
overall confidence levels, so it is clear
how uncertainties are reflected into these
evaluations
66
PUBLIC COMMENTS:
EPA should consider conducting a
probabilistic risk assessment for exposure
data. The EPA considered the central
tendency and high-end exposures to
conduct deterministic risk assessments
for the different exposure scenarios.
When performing a deterministic
analysis, only one value is inserted per
parameter, which results in a single point
estimate. However, single point estimates
may not provide an accurate or realistic
depiction of the exposure scenario, and
less is understood about variability and
uncertainty.
EPA conducted probabilistic assessments using the Near-Field / Far-field
model when parameter values were reasonably available. Deterministic
assessments were only used when lack of parameter distributions
prevented probabilistic assessments.
Consumer exposure assumptions
SACC
SACC COMMENTS:
The Agency does not consider that there
is an increasing number of people that
engage in activities using products, such
as adhesives, more frequently and for
longer periods than the typical occasional
user.
EPA should recognize that a sector of the
population could be at increased risk
from exposure than the typical consumer
The uncertainties associated with the use of USEPA (1987) are discussed
in Section 4.3.3. A sentence has been added to explain that an increasing
trend in do-it-yourself type activities may lead to an underestimate in
exposures. Nevertheless, the range of use patterns evaluated (10th to 95th
percentile) is expected to cover the reasonable range of possible
exposures.
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because they engage in hobby-type
activities for both pleasure and profit.
Essentially, they could be considered
home-based workers.
The Agency should consider developing
methods for assessing the size and risk
from exposure for this subpopulation.
SACC
SACC COMMENTS:
Clearly define the brush cleaner condition
of use in the risk evaluation.
This is a condition of use that was not
considered in the 2014 risk evaluation,
which has much lower use percentages
and differing use patterns when compared
to paint rem overs/strippers into which
EPA categorizes this product.
This is significant since it was the only
consumer condition of use that met the
"does not present an unreasonable risk"
criteria.
As noted by the commenter, brush cleaning products contain methylene
chloride in lower concentrations than paint removal products and were not
included in the 2014 risk assessment. In the case of methylene chloride,
EPA considers use as a brush cleaner to be distinct from use in paint and
coating removal more broadly, as reflected by its inclusion in the risk
evaluation. Due to the potential for brush cleaning to have impeded
dermal evaporation from dermal immersion, this condition of use was re-
evaluated using the CEM Permeability submodel in our revised dermal
evaluation. In the revised evaluation, risk was identified, resulting in a
determination of unreasonable risk in the final evaluation.
SACC
SACC COMMENTS:
One Committee member mentioned that
while MC is a solvent that may be used in
some children's product manufacturing
processes (e.g., metal component
degreasing, solvent bonding, paint/ink
carriers), due to its high volatility,
significant concentrations are unlikely to
remain in products as received by
consumers.
Some manufacturers are reporting this
substance under state reporting statutes at
concentrations of up to 10,000 ppm.
The informed Committee member
considered reported concentrations this
high are very unlikely to be accurate, and
EPA appreciated these comments as they give context to possible MC
concentrations in consumer products. All consumer products were
evaluated based on current conditions of use and known consumer
product properties as reported on their SDSs. No known products that
were expected to be used by children specifically were identified .
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instead reflect over-reporting, which is
common.
SACC
SACC COMMENTS:
One Committee member noted that a
comprehensive accounting of MC in
consumer products may be obtained from
the California Air Resources Board
which collects this information, including
weight-percent and estimated emissions.
A summary of these data was provided to
EPA for the docket.
EPA appreciates the potential source of information. EPA is aware and
uses CARB as a data source in developing the COUs for chemicals and to
help ensure the COUs analyzed in the Risk Evaluation is comprehensive.
In practice, for products, the Agency prefers to cite information directly
from the company (often in the form of SDS) to ensure it is the most
current formulation and the product is still available in the marketplace.
SACC
SACC COMMENTS:
Pratt et al. (2005) reported method
detection limits for MC that are
representative for the studies by Adgate
et al. (2004) and Sexton et al. (2007)
because measurements were made with
the same sampler and sampling/analysis
protocol, and the analysis was performed
by the same laboratory in all these
studies.
These values could be reported in Tables
2-120 and 2-121 (pp. 194-195) with an
appropriate footnote.
Table 2-121 appears to reference the
Adgate et al. (2004) study twice as the
corresponding text refers to only two
studies and the Adgate et al. (2004) study
rows only differ by the Detection
Frequency (DFq) values.
EPA appreciates these citations as relevant sources of information.
Adgate et al. (2004) was re-reviewed for mention of detection limits (DL)
and while the article does not include quantitative DLs it does include
mention of an article that better describes the methodology used in the
study. That study (Chung et al. (1999)) was reviewed and found to have
representative DLs. A footnote has been added to tables where Adgate is
discussed citing the relevance of the DL found within Chung et al. (1999)
73, 75
PUBLIC COMMENTS:
It is not realistic to assume that
consumers are only exposed once to
consumer products containing this
substance in view of how these products
are used.
Scenarios for conditions of use associated with products containing MC
include a wide range of usage intensities with ranges in weight fractions,
time of use, and mass of product used. While the actual use of the product
only occurs a single time during the evaluation period a given consumer
user can encounter inhalation exposures during both the use period and
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The MC problem formulation commits
EPA to evaluate risks to "subsets of
consumers who may use commercially-
available products or those who may use
products more frequently than typical
consumers" (p. 65), however the draft
evaluation does not follow through on
this commitment.
EPA's final evaluation must address
chronic cancer risks to consumers based
on scenarios of recurring and/or multiple
consumer product use.
EPA's assumption about consumer
exposure seems likely to significantly
underestimate the risks they face. EPA
needs to conduct a sensitivity analysis
regarding these assumptions in the risk
evaluation, which is different than the
sensitivity analysis that EPA indicates
was done on the model itself (p. 179).
also following use through the prescribed movement about the house.
Chronic exposure scenarios resulting from long-term use of household
consumer products were not evaluated as these events are likely to be
relatively infrequent with short durations of use. This assumption is
supported by product use frequencies reported within US EPA (1987) for
evaluated conditions of use that give central tendency frequencies that
were considered to be too low to create chronic risk concerns. In addition,
the short half-life of the chemicals in the body does not result in
significant accumulation between uses on different days. Although high-
end frequencies of consumer use are up to 50 times per year, reasonably
available toxicological data is based on either single or continuous MC
exposure and it is unknown whether these use patterns are expected to be
clustered or intermittent (e.g. one time per week). There is uncertainty
regarding the extrapolation from continuous studies in animals to the case
of repeated, intermittent human exposures. Therefore, EPA cannot fully
rule out that consumers at the high-end frequency of use could possibly be
at risk for chronic hazard effects, however it is expected to be unlikely.
Bystanders exposures would be expected to be appreciably lower than
user scenarios. This uncertainty on frequency of use patterns is mentioned
within Section 4.3.3 as an uncertainty within the consumer exposure
evaluation and notes that the possibility of more DIY-type consumer users
may underestimate exposure, but that US EPA (1987) is the currently the
most up-to-date, nationally comprehensive resource available for
evaluating consumer use patterns.
The evaluation of subsets of consumers that may be high-end users is
addressed in Section 4.4.3. The uncertainties and assumptions have
been edited to better describe uncertainties associated with high use
consumer like hobbyist and do-it-yourself consumers by adding,
".. .consumer movement towards more do-it-yourself projects with
products containing the chemical may lead to an underestimate of
consumer use patterns described within the survey in some instances.
Nevertheless EPA assumes that the use pattern data presented in U.S.
EPA (1987) reflects reasonable estimates for current use patterns of
similar product type. These estimates were deemed to be reasonable
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due to the range of use patterns evaluated (e.g., ranging from 10th to
95th percentile) and that this dataset represents the most recent,
relevant and nationally-representative data available for use pattern
data in most cases."
The assumptions and uncertainties associated with our consumer
exposure evaluation is fully described in Section 4.4.3. A description
of the sensitivity analysis on the overall CEM model is described in
Section 2.4.2.3.3 and Appendix G. It is unclear as to which
assumptions about consumer exposure the commenter is referring to
that would lead to an underestimate in risk, but consumer exposures
were evaluated across a range of user intensities by varying weight
fraction of a product and the time and amount of a product used.
These user intensities were expected to cover a range of possible
consumer exposures.
73,
SACC
SACC COMMENTS:
EPA should consider carefully the
assumption that the bystander(s) will
remain in a different room (Zone 2 for
modeling) during use of a product.
Depending on the actual use, product, and
specific application, the assumption of
far-field location for the bystander(s)
during use may not be sufficiently
conservative.
Reconsider whether bystanders are
always located in a different zone than
the user for the consumer use scenarios,
independent of the type of product.
At a minimum, EPA should specifically
address the uncertainty about bystander
location depending on specific product
use.
As explained in Section 2.4.2.3.1, EPA states that the bystander was
assumed to remain outside the room of use as a bystander entering the
room of use would be expected to approximate the exposures associate
with a user. As a way to better communicate this assumption it has been
added to the Assumptions and Uncertainties for Consumer Exposure
Section (Section 4.3.3)
It has been clarified in Section 2.4.2.3.1 that a user or bystander may
enter/re-enter the room of use depending on the modeled room of use and
prescribed activity patterns.
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73
PUBLIC COMMENTS:
EPA recognizes that "[residential
bystanders for consumer uses are
expected to be indirectly exposed to
methylene chloride and may be of any
age" (p. 275), but the Agency does not
appear to have actually assessed exposure
to all age groups.
EPA provides no rationale for excluding
infants and children under the age of 3
years in its evaluation. Infants, relative to
older children and adults, have a higher
breathing rate per unit body weight and,
as acknowledged by EPA, may be
particularly susceptible to the neurotoxic
effects of MC due to their higher residual
levels of fetal hemoglobin that has a
higher affinity for carbon monoxide (CO)
(P. 32).
As described in Section 2.4.2.3.2, dermal exposure results are presented
for users of three possible age groups: adults and two youth age groups
(16-20 years and 11-15 years).
Inhalation exposures are presented as concentrations encountered for
users and non-user bystander populations and are independent of age
group.
In developing the hazard assessment, EPA described human
subpopulations that may have greater susceptibility than the general
population to hazards of MC (Section 4.4).
As described in Section 3.2.5 (Dose-Response Modeling), EPA used
PBPK models for toxicokinetic differences (for chronic risk) and
intraspecies UFs in the risk evaluation. The intraspecies UF was
established to account for uncertainty and variability that includes
susceptible subpopulations ( 02). Research indicates that a factor
of 10 (when including both toxicokinetics and toxicodynamics) is
sufficient in most cases ( '02).
77
PUBLIC COMMENTS:
Bystanders may experience elevated
inhalational exposures if they live or
work adjacent to a workplace where MC-
containing products are used. EPA
assumes that bystander inhalation
exposures would be acute, these
exposures can, in fact, be chronic.
Chronic bystander exposures should be
systematically studied and appropriately
addressed by EPA under TSCA.
This is especially important given EPA's
conclusion that "[cjonsumer and
bystander inhalation exposure ... is
expected to be the most significant route
of [consumer] exposure through the
Chronic exposure scenarios resulting from long-term use of household
consumer products were not evaluated as these events are likely to be
relatively infrequent with short durations of use. This assumption is
supported by product use frequencies reported within US EPA (1987) for
evaluated conditions of use that give central tendency frequencies that
were considered to be too low to create chronic risk concerns. In addition,
the short half-life of the chemicals in the body does not result in
significant accumulation between uses on different days. Although high-
end frequencies of consumer use are up to 50 times per year, reasonably
available toxicological data is based on either single or continuous MC
exposure and it is unknown whether these use patterns are expected to be
clustered or intermittent (e.g. one time per week). There is uncertainty
regarding the extrapolation from continuous studies in animals to the case
of repeated, intermittent human exposures. Therefore, EPA cannot fully
rule out that consumers at the high-end frequency of use could possibly be
at risk for chronic hazard effects, however it is expected to be unlikely.
Bystanders exposures would be expected to be appreciably lower than
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direct inhalation of sprays, vapors, and
mists."
user scenarios due to greater distance from and less time spent in the room
of use. This uncertainty on frequency of use patterns is mentioned within
Section 4.3.3 as an uncertainty within the consumer exposure evaluation
and notes that the possibility of more DIY-type consumer users may
underestimate exposure, but that US EPA (1987) is the currently the most
up-to-date, nationally comprehensive resource available for evaluating
consumer use patterns.
66
PUBLIC COMMENTS:
The consumer exposure modeling
parameters shown in Table 2-87 indicates
a background MC concentration of 0
mg/m3. However, from Table 2-121, the
baseline concentration is not 0.
Consumer modeling for specific condition of use scenarios was modeled
with a background concentration of zero since documented concentrations
referenced in Table 2-121 could not be tied to a specific condition of use.
This uncertainty has been added to Section 4.3.3
41,68,
SACC
SACC COMMENTS:
Section 3.2.5.2 states "A 1-hour value is
used for consumer settings, which is
similar to the length of time (1.5 hours)
after which effects were observed by Putz
etal., (1979)."
One hour seems too short to estimate
consumer exposures, even just based on
the few fatality case studies described in
Appendix J.
In estimating consumer exposure for
specific uses, different time lengths were
used; hence, the risk evaluation does not
rely exclusively on the 1-hour
assumption.
The exposure time for consumer
exposures for all uses (scenarios) should
be detailed in Section 3.2.5.2 or in an
associated appendix/supplemental file.
PUBLIC COMMENTS:
EPA should ensure that duration and
product amounts within the conditions of
use represent realistic values. In modeling
As described in Section 2.4.2.3.1, exposure inhalation consumer durations
are presented as maximum 1-hour and 8-hour TWAs over the course of
the 72-hour model run. Most of the timing related to deaths is not known
but one occurred within 2 hours 20 minutes, as stated in Appendix J of the
risk evaluation. The effect being used in the risk evaluation occurred after
1.5 hours of exposure.
The data used from Westat represent the most current, nationally relevant
data source available for a range of the evaluated conditions of use.
Westat was used principally as support for the length of time a product
was used and the mass of product used. These durations and amounts are
intended to cover the spectrum of possible users ranging from low to high
intensity users as described in the document. All weight fractions used in
this evaluation are derived from SDSs for products that are available to or
marketed to consumer users. EPA notes there are limitations and
uncertainties associated with this Westat dataset. Those limitations and
uncertainties are discussed fully in Section 2.4.2.6
With regard to clarity in concentrations assumed by EPA the evaluated
weight fractions associated with products of a particular condition of use
are available in Table 2-90. In addition, estimated dermal and inhalation
exposure concentrations, are found in Section 2.4.2.4
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consumer exposures, for example, EPA
estimated the duration and product
amount corresponding to the 10th, 50th,
and 95th percentile values based on data
from the 1987 EPA publication,
Household Solvent Products: A National
Usage Survey. Certain durations,
however, seem excessive for consumer
exposures.
Likewise, certain mass of product use
assumptions for consumer exposures
seem excessive. EPA should develop
and/or use more current and/or relevant
exposure scenarios/data to estimate the
duration of use and amount of use of
consumer products containing MC.
EPA used historic data (WESTAT, 1987)
for information regarding duration of use
and quantity of use. In some cases, the
scenarios do not seem plausible. They
have assumed that consumers use high-
concentration, industrial products, that
are not intended for consumer use.
EPA should consider the validity of
certain exposure scenario data and the
relevance of historic data used to describe
current consumer exposure scenarios.
The concentrations that EPA is assuming
are not clear. This information is not
discussed specifically for the individual
products.
EPA's exposure values for consumer use
scenarios include peak concentrations
that appear to overpredict levels,
including levels are in excess of 7000
mg/m3, a level that is immediately
The reported consumer exposure evaluations are anticipated to cover a
plausible range of possible exposure conditions ranging from a low-
intensity to a high-intensity user. The referenced scenario where this value
occurs represents a condition of use where the evaluated product has a
weight fraction of 100% MC, thereby providing support for the estimated
high value.
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dangerous to life or health according to
NIOSH.
Use and market profile
SACC
SACC COMMENTS:
In the Use and Market Profile for
Methylene Chloride (EPA 2017),
reconfirm product links and update
profiles, eliminating products that no
longer contain MC.
The Use and Market Profile contributed to the basis of EPA's
identification of the conditions use for the purposes of the scope and
problem formulation documents for methylene chloride. The document
presented publicly available information as of the date of the document on
the manufacturing (including importing), processing, distribution in
commerce, use, and disposal of methylene chloride and was used to
inform decisions regarding conditions of use. The document does not
reflect information received directly from other sources such as
manufacturers, processors, etc., which has further informed EPA's
understanding of the conditions of use. As such, the uses and products
identified in the document may differ from EPA's current understanding.
If any of the products are associated with conditions of use determined to
have unreasonable risk, EPA will reconfirm product links and profiles
during the risk management process.
Consumer exposure model
SACC
SACC COMMENTS:
The potential exposures of the general
public to MC need to be clarified further
and/or expanded.
The CEM assumes zero baseline
concentration of MC. Despite not
considering aggregate exposures, EPA
should indicate that this assumption is not
conservative; population exposure data
show that there are measurable
concentrations of MC in the indoor air of
homes as well as in the personal
breathing zone of the occupants.
On the other hand, blood concentrations
of MC were undetectable in 2,878
individuals measured as part of the 2009-
2010 National Health and Nutrition
Examination Survey (NHANES). These
During Problem Formulation, EPA acknowledged that general population
exposures may occur through inhalation, oral, and dermal. However, in
the Risk Evaluation EPA did not include pathways under programs of
other environmental statutes, administered by EPA, for which long-
standing regulatory and analytical processes already exist. Because
stationary source releases of methylene chloride to ambient air are
adequately assessed and any risks covered under the CAA, EPA did not
evaluate emission pathways to ambient air from commercial and
industrial stationary sources or associated inhalation exposure of the
general population. Because the drinking water exposure pathway for
methylene chloride is currently addressed in the SDWA regulatory
analytical process for public water systems, EPA did not include this
pathway in the risk evaluation for methylene chloride under TSCA. In
Problem Formulation, EPA also found general population exposures to
methylene chloride via underground injection, RCRA Subtitle C
hazardous waste landfills, RCRA Subtitle D municipal solid waste
(MSW) landfills, and on-site releases to land from industrial non-
hazardous waste and construction/demolition waste landfills are under the
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findings are not discussed in detail in the
risk evaluation and these observations
should be better explained.
jurisdiction of and addressed by other EPA-administered statutes and
associated regulatory programs. Lastly, EPA did not include emissions to
ambient air from municipal and industrial waste incineration and energy
recovery units in the risk evaluation, as they are regulated under section
129 of the Clean Air Act.
SACC
SACC COMMENTS:
The rationale for setting the modeling
inputs for the weight fraction (Section
2.4.2.3, p. 168, lines 3449-3452) is
unclear.
Explain why only the maximum and
minimum were used to determine
modeling inputs if the weight fraction
was <40% but the maximum, minimum,
and midpoint were used if the weight
fraction was >40%.
Weight fractions were derived from product specific SDSs. Depending
on the product information and number of found products, those weight
fractions could end up encompassing a range of possible weight fractions.
The midpoint weight fraction was evaluated for ranges >40% to better
evaluate the range of possible exposures. Language has been added to
this section to clarify these points.
SACC
SACC COMMENTS:
Further justification is required for
current approaches used to characterize
consumer dermal exposure.
There is concern that the dermal surface
area for exposure indicated in Table 2-88
seems low - 10% for activities that
involve spray and inside of both hands
for some of the cleaning surveys.
o The only justification of this assumption
is provided in footnote 6, p. 176 of the
risk evaluation, which indicates "Selected
dermal SA/BW ratio used is based on
CEM scenario used or best professional
judgment for Generic Scenario." The
justification would be strengthened by
including additional supporting
information, not limited to an indicator of
which scenarios use dermal surface area
Dermal approaches were revised for the final draft with additional
evaluation incorporated for whether the condition of use was expected to
have expectation of impeded vs. unimpeded dermal evaporation. For
those scenarios expecting impeded dermal evaporation, EPA utilized the
Permeability submodel within CEM and for those expecting unimpeded
dermal evaporation, EPA utilized the Fraction absorbed submodel within
CEM. This has been explained more fully within 2.4.2.3.
Included in that re-evaluation is description and revision to the SA/BW
ratios used in EPA's evaluation. For those evaluations using the
Permeability approach, EPA used either full hand or both hands SA/BW
ratios since those conditions could involve wiping with a chemical soaked
rag that would be expected to cover the whole hand. Meanwhile, those
offering unimpeded dermal exposure tended towards continued use of the
10%) of hands SA/BW ratios. Those selected SA/BW ratios are identified
in Table 2-90.
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based on the CEM scenario and which are
based on professional judgment. The
justification should also discuss if the
dermal surface area of exposure
assumptions include dermal exposure
from the product application as well as
dermal exposures through rags containing
product or spills on clothing, which likely
occur in these consumer scenarios and
which could increase the dermal surface
area to which consumers are exposed.
The Committee recommends that EPA
document the dermal surface area
assumed for each occupational condition
of use exposure scenario indicate which
estimate is based on CEM and which is
based on best professional judgment and
indicate whether the dermal exposure
estimate includes application exposures,
rag exposures, and spills to clothing.
45, 66
PUBLIC COMMENTS:
The consumer assessments utilized
EPA's CEM (relied merely on CEM,
without real simulation data). There was
high confidence in this model, without
supporting justification for its use. EPA
should justify the CEM and perhaps
benchmark its results with another model.
CEM was used for the evaluation of both dermal and inhalation consumer
exposures. As outlined in Section 2.4.2.3.1, there are several reasons for
the selection, use, and confidence in this model including aspects such as
it has undergone peer review. Thus, there was high confidence in the
selection of this model. Particular confidence in the results of this model
ranged from low to high depending on the route and available information
informing parameterization which is discussed in Section 2.4.2.6. There
was no other model suggested that could be used to benchmark these
results.
68
PUBLIC COMMENTS:
EPA indicated that it has run sensitivity
models for the CEM, EPA did not supply
elasticity values for specific inputs. This
information would help EPA focus data
collection efforts on inputs that have
greater impact on the model results.
As described in Section 2.4.2.3.3, the overall CEM model had a
sensitivity analysis conducted for evaluation of which scenario specific
inputs influenced inhalation and dermal exposure results. Within this
section, EPA describe that the full description of this sensitivity analysis
is available in Appendix C of the CEM User's Guide. As described in
Appendix C, elasticity was evaluated by altering model input parameters
by a 10% increase. Due to the number of parameters evaluated, the
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calculated elasticities are not included in the risk evaluation but are
available for review in Tables D2-D8 and Figures D1-D15 in Appendix C
of the User's Guide.
68
PUBLIC COMMENTS:
Data that EPA incorporates as input
values into consumer models must
undergo a review to determine whether
they reasonably depict real world
conditions. EPA should implement a
quality review system for SDSs it might
consider in TSCA risk evaluations,
removing SDSs and associated weight
fraction values that do not represent real
world conditions. Improper input values
can lead to grossly overestimated
exposure levels, as is the case with the
coil cleaner condition of use.
Input values for modeling purposes uses actual product or scenario values
wherever possible to represent use scenarios as accurately as possible.
The evaluated weight fraction for the coil cleaner scenario was a value
given within the specific product SDS (60-100%). Since the value is given
as a range, EPA evaluated the product as if it could be both at the low and
high end of that range to cover the range of possible exposures. It was
assumed the given industry was reporting their product accurately so there
is no evidence it does not represent a real world condition or would result
in an overestimation in exposure.
General
population exposure
SACC
SACC COMMENTS:
The data provided by EPA is incomplete
and suggest EPA is in possession of other
data. As part of the Total Exposure
Assessment Methodology (TEAM)
studies, EPA measured concentrations of
MC in residential indoor and exhaled
breath (Wallace et al., 1991) before the
lowering of the PEL.
The Agency and the Health Effects
Institute (HEI, Boston, MA) also
sponsored the Relationship between
Indoor, Outdoor, and Personal Air
(RIOPA) study (Weisel et al., 2005a, b,
c).
Phillips et al. (2005) also monitored
indoor and personal air for selected
VOCs, including MC, in four Oklahoma
EPA reviewed the suggested references. In the case of Phillips et al.
(2005) and Weisel et al (2005a), the studies were reviewed and not found
to have any extractable quantitative information for MC. Wallace et al.
(1991) was reviewed and received a medium quality rating. Extracted
information was added to Table 2-120. Measured indoor concentrations
in this study were in the range of other reported values within Table 2-
120 of the Risk Evaluation.
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cities.
Occupational short-term sample duration ranges
SACC
SACC COMMENTS:
It is unclear why the 15- and 30-minute
samples (Section 2.4.1.2.1, p. 115, Table
2-29) are categorized using the bounds of
15-29 and 30-59 minutes, respectively,
given that, for instance, a 29-minute
exposure is closer to a 30-minute sample
than a 15-minute sample.
EPA must justify the time ranges used or
adjust ranges of 15-22.5 minutes and
22.5-45 minutes for the 15- and 30-
minute samples, respectively.
EPA globally adjusted short-term groupings as recommended and to be
consistent included the short-term groupings in Section 2.4.1.2.1 of the
Risk Evaluation and in Section 2.1.3 of the Supplemental Information on
Releases and Occupational Exposure Assessment.
Dermal exposure assessment
SACC
SACC COMMENTS:
Include a discussion of uncertainty
related to dermal exposure assessment in
Section 4.3.7 of the risk evaluation.
A discussion of uncertainty related to dermal exposure assessment was
added to Section 4.3.7 of the risk evaluation.
45, 73
PUBLIC COMMENTS:
The dermal exposure assessment appears
to be based on the maximum default
quantity that can remain on the skin,
rather than actual measurements.
Given the chemical properties (e.g.,
volatility) and industry uses of MC, this
methodology is not justified. Empirical
data are available that might inform better
absorption estimates and should be
considered. EPA should provide
additional justification for such
assumptions and consider modeling tools
for better estimations.
EPA default quantities that can remain on skin are based on experimental
data that were measured. EPA did not find additional reasonably available
actual measurements of quantity remaining on the skin form MC, nor
were citations or data provided by the commenter. The dermal assessment
generated central tendency and high-end doses using models, and the
models incorporated estimates of evaporation. Central tendency estimates
are less than the maximum default quantity that may remain on the skin.
EPA did not find reasonably available empirical data or additional
modeling tools proposed by this comment to inform better absorption
estimates.
41,49
PUBLIC COMMENTS:
EPA's approach to dermal exposure
modeling for MC includes fraction
For consumer dermal exposure modeling, the assessment has been revised
to incorporate both fraction absorbed and permeability based approaches
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absorbed models for both consumer and
occupational exposures. This contrasts
with prior draft risk evaluations that have
used permeation models for consumer
exposures. EPA acknowledges that
"fractional absorption may vary and is
dependent on various factors ..." EPA's
should further justify use of this
approach.
dependent on how the particular COU is expected to be used. That
revised approach is discussed in Section 2.4.2.3.
63
PUBLIC COMMENTS:
Significant dermal absorption, even with
the use of gloves, is expected for many of
the occupational exposure scenarios listed
in Table 4-104. Dermal absorption should
be accounted for in a cumulative risk
assessment of all exposure routes. This
would be useful to the risk management
phase by identifying dermal exposures
that cause the risk estimate to exceed the
MOE.
Regarding cumulative risk assessment by all routes, there is low
confidence in the result of aggregating the dermal and inhalation risks for
this chemical if EPA uses an additive approach, due to the uncertainty in
the data. EPA does not have data that could be reliably modeled into the
aggregate, which would be a more accurate approach than adding, such as
through a PBPK model. Using an additive approach to aggregate risk in
this case would result in an overestimate of risk. Given all the limitations
that exist with the data, EPA's approach is the best available approach. .
72, 73,
SACC
SACC COMMENTS:
Exposure modeling in the risk evaluation
assumes dermal exposure limited to one
event/day - even in the high-end
exposure scenario. This assumption may
underestimate potential exposures. EPA
should provide a more thorough
explanation of why the assumption of a
single dermal exposure per day was used.
EPA should also consider the possibility
of more than one exposure per day per
worker since workers are likely to
encounter the chemical throughout their
workday. Multiple exposure events are
even more likely in high-end exposure
scenarios.
EPA has described events per day (FT) as a primary uncertainty for
dermal modeling in the discussion of occupational dermal Uncertainties
section 4.4.2.3. This discussion also notes that this assumption likely
underestimates exposure as workers often come into repeat contact with
the chemical throughout their workday.
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PUBLIC COMMENTS:
EPA acknowledges that this assumption
"likely underestimates exposure as
workers often come into repeat contact
with the chemical throughout their work-
day," but did not account for this
underestimation or provide any sort of
uncertainty analysis.
EPA would need to have robust data
demonstrating only a single exposure
event occurs per day before incorporating
such an assumption into its models. EPA
has not provided any such data.
68
PUBLIC COMMENTS:
EPA must implement a tiered dermal
modeling approach to ensure the dermal
values considered in the assessment
accurately reflect occupational
conditions. Modeling programs such as
IHSkinPerm can produce needed detail
during the exposure assessment process
and ACC encourages EPA to incorporate
this model into future assessments.
EPA has not found reasonably available data and models to conduct tiered
modeling for occupational dermal exposures to MC. IHSkinPerm does not
have necessary parameters for the uses of MC and requires the user to
input parameters (e.g., deposition rates and frequencies) for which EPA
does not have reasonably available data.
49, 73
PUBLIC COMMENTS:
EPA indicates that it "considered
potential dermal exposure in cases where
exposure is occluded," referencing the
Supplemental Information on Releases
and Occupational Exposure Assessment
document (p. 111). That document found
exposures that are 8-37 times higher than
the no-glove scenarios. These exposure
scenarios were not incorporated into the
risk characterizations.
For example, when comparing Table 2-85
in the draft risk evaluation (p. 165) to
See further discussion on occlusion in Appendix E of the Supplemental
Information on Releases and Occupational Exposure Assessment
document. The occluded scenarios were presented as a what-if scenario.
EPA does not know the likelihood or frequency of these scenarios in the
workplace; therefore, EPA did not present risk estimates associated with
occluded exposure in the Risk Evaluation.
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Table 3-3 in the Supplemental
Information on Releases and
Occupational Exposure Assessment
document (pp. 118-119), they present
identical exposure estimates with the
exception that all of the columns for
occluded exposures have been removed
from Table 2-85.
Default surface area values used for modeling dermal occupational exposures
73,
SACC
SACC COMMENTS:
EPA should indicate why an upper bound
for hand surface area was not used. The
Agency should indicate how the dermal
exposure and risk evaluation would have
changed had they decided to use an upper
percentile value for hand surface instead
of the average.
Expand the discussion of hand surface
area to more adequately describe the
exposed surface and include dermal
exposure to forearm to better describe the
high-end exposure scenarios. The Agency
clarified at the face to face meeting, that
this area likely represented more than just
hand surface.
PUBLIC COMMENTS:
The two-hand assumption may
underestimate exposure because other
areas of the body may be exposed to the
chemical either through splashes or via
deposition of vapor.
EPA has clarified in section 2.4.1.1 regarding the assumption of contact
surface area of 1,070 cm2 as an input parameter for estimating high-end
dermal exposure to liquids. This clarification includes that value is
equivalent to the 50th percentile surface area of two-hands for males, the
highest exposed population. The clarification also includes discussion that
EPA has no reasonably available information on actual surface area of
contact with liquid and that the value is assumed to represent an adequate
proxy for a high-end surface area of contact with liquid that may
sometimes include exposures to much of the hands and also beyond the
hands, such as wrists, forearms, neck, or other parts of the body, for some
scenarios.
Consideration of vapor exposure in dermal occupational exposure estimates
73,
SACC
SACC COMMENTS:
Discuss the potential of the vapor to the
skin exposure route, including
penetration of the vapor through clothing
An analysis in Section 2.5.1 of the Problem Formulation of the Risk
Evaluation for MC shows that absorption of MC via skin to be orders of
magnitude lower than via inhalation and that additional coverage of this
topic is not included in the Risk Evaluation for MC. EPA included
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fabrics, and incorporate it in the dermal
exposure estimates if suitable data are
available to estimate the contributions to
exposures. This pathway should be
mentioned for occupational users and
ONUs, and EPA should indicate why it
was not considered.
EPA should contact ASTM-International
and the NFPA about test data for
penetration of MC vapor and revise the
sources of dermal exposure appropriately,
if needed.
The assumption that volatilization is
accounted for in the estimates of dermal
exposure to occupational users needs
further clarification/justification.
expanded discussion in 2.4.1.1 about the fabs parameter that accounts for
volatilization in the estimates of dermal exposure to occupational users.
Need to aggregate exposure across inhalation and dermal pathways
SACC
43, 54,
57, 66,
72, 73,
75, 77
SACC COMMENTS:
The committee discussed the need to
aggregate exposures through multiple
routes and perform a risk evaluation on
overall exposure, not only components
through specific route and the need to
assess and indicate whether one route of
exposure is clearly more important than
another in order to prioritize mitigation
approaches.
PUBLIC COMMENTS:
Because both inhalation and dermal
exposure result in systemic distribution of
MC, it is essential to evaluate exposures
from both of these routes in combination,
including simultaneously, to assess total
body burden and the associated effects.
The rationale that the dominant exposure
pathway is inhalation due to MC's
MC has a PBPK model for inhalation but not dermal exposure. EPA
chose to assess the inhalation pathway for human health, as it is the driver
of risk for human health. EPA has added language to uncertainties section
explaining how this could lead to an underestimation of risk, as dermal
exposure was not incorporated into that analysis.
TSCA section 6(b)(4)(F)(ii) directs EPA to "describe whether aggregate
or sentinel exposures to a chemical substance under the conditions of use
were considered, and the basis for that consideration" in risk evaluations.
EPA defines aggregate exposures as the combined exposures to an
individual from a single chemical substance across multiple routes (i.e.,
dermal, inhalation, or oral) and across multiple pathways (i.e., exposure
from different sources). 40 CFR 702.33. EPA defines sentinel exposures
as the exposure from a single chemical substance that represents the
plausible upper bound of exposure relative to all other exposures within a
broad category of similar or related exposures. 40 CFR 702.33. EPA
considered the reasonably available information and used the best
available science to determine whether to consider aggregate or sentinel
exposures for a particular chemical. EPA has determined that using the
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physical-chemical properties is
insufficient, given that EPA found
significant risk from dermal exposure
alone for many conditions of use,
including for some where it assumed use
of gloves with a protection factor (PF) 5
or 10 (pp. 344-349).
Combining dermal and inhalation
exposure would clearly provide a more
realistic picture of actual risk.
high-end risk estimate for inhalation and dermal risks separately as the
basis for the unreasonable risk determination is a best available science
approach. There is low confidence in the result of aggregating the dermal
and inhalation risks for this chemical if EPA uses an additive approach,
due to the uncertainty in the data. EPA does not have data that could be
reliably modeled into the aggregate, which would be a more accurate
approach than adding, such as through a PBPK model. Using an additive
approach to aggregate risk in this case would result in an overestimate of
risk. Given all the limitations that exist with the data, EPA's approach is
the best available approach.
Uncertainty is not rationale for failing to aggregate inhalation and dermal
43, 44,
49, 63,
72, 73,
75
PUBLIC COMMENTS:
EPA states that it "chose not to employ
simply additivity of exposure [routes] at
this time ... because of the uncertainties
present in the current exposure estimation
procedures."
The "uncertainties" were associated with
its physiologically based pharmacokinetic
(PBPK) model that lacks a dermal
compartment and therefore "a PBPK
model for aggregating inhalation and
dermal exposures is not reasonably
available."
It is not clear what "uncertainties" EPA is
referring to. In fact, EPA derived dermal
PODs by extrapolation from inhalation
PODs, using toxicokinetic information to
MC has a PBPK model for inhalation but not dermal exposure. EPA
chose to assess the inhalation pathway for human health, as it is the driver
of risk for human health. EPA has added language to uncertainties section
explaining how this could lead to an underestimation of risk, as dermal
exposure was not incorporated into that analysis.
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
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estimate dermal doses at which the
effects seen in inhalation studies would
occur. Since EPA had sufficient
confidence in route-to-route extrapolation
to base estimates of dermal risk on the
results of inhalation studies, it is hard to
understand why this same approach could
not be used to determine overall exposure
by the two routes combined.
These uncertainties do not provide a basis
for ignoring realistic exposure scenarios.
available science to determine whether to consider aggregate or sentinel
exposures for a particular chemical. EPA has determined that using the
high-end risk estimate for inhalation and dermal risks separately as the
basis for the unreasonable risk determination is a best available science
approach. There is low confidence in the result of aggregating the dermal
and inhalation risks for this chemical if EPA uses an additive approach,
due to the uncertainty in the data. EPA does not have data that could be
reliably modeled into the aggregate, which would be a more accurate
approach than adding, such as through a PBPK model. Using an additive
approach to aggregate risk in this case would result in an overestimate of
risk. Given all the limitations that exist with the data, EPA's approach is
the best available approach.
Failure to aggregate exposure pathways leads to underestimate of risks
44, 72,
75, 77,
66, 43,
57
Although the draft evaluation
demonstrates that MC presents serious
and unreasonable risks to health, its risk
determinations examine individual
sources of exposure in isolation and fail
to estimate the overall risks to consumers
and workers from these exposure sources
combined.
Aggregation of multiple pathways that
contribute to individual exposure would
result in even smaller MOEs for acute
and non-cancer chronic effects and larger
carcinogenicity risks under MC's
conditions of use. The lack of
aggregation may also lead the declaration
of "no unreasonable risk" when one
actually exists.
By failing to analyze aggregate
exposures, EPA underestimates the health
hazards posed by MC. Even if there are
uncertainties inherent in the estimation of
aggregate exposures, EPA should
consider aggregate exposures and, if
EPA has determined that using the high-end risk estimate for
inhalation and dermal risks separately as the basis for the
unreasonable risk determination is a best available science approach.
There is low confidence in the result of aggregating the dermal and
inhalation risks for this chemical if EPA uses an additive approach,
due to the uncertainty in the data. EPA does not have data that could
be reliably modeled into the aggregate, which would be a more
accurate approach than adding, such as through a PBPK model. Using
an additive approach to aggregate risk in this case would result in an
overestimate of risk. Given all the limitations that exist with the data,
EPA's approach is the best available science. EPA has added
language to the Key Assumptions and Uncertainties section describing
these assumptions and uncertainties.
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
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needed, append a discussion of the
associated uncertainties or potential for
estimation errors.
exposure relative to all other exposures within a broad category of
similar or related exposures. 40 CFR 702.33. EPA considered the
reasonably available information and used the best available science
to determine whether to consider aggregate or sentinel exposures for a
particular chemical. EPA has determined that using the high-end risk
estimate for inhalation and dermal risks separately as the basis for the
unreasonable risk determination is a best available science approach.
There is low confidence in the result of aggregating the dermal and
inhalation risks for this chemical if EPA uses an additive approach,
due to the uncertainty in the data. EPA does not have data that could
be reliably modeled into the aggregate, which would be a more
accurate approach than adding, such as through a PBPK model. Using
an additive approach to aggregate risk in this case would result in an
overestimate of risk. Given all the limitations that exist with the data,
EPA's approach is the best available approach.
EPA did not consider background exposure that workers and
consumers using products containing MC might be exposed to in
addition to exposures from TSCA-regulated conditions of use. This
may result in an underestimation of risk, and additional discussion of
this underestimation has been added to the document in the Key
Assumptions and Uncertainties section.
49, 73,
42, 70,
75, 69,
72
PUBLIC COMMENTS:
EPA draft risk evaluations have assessed
worker exposure in isolation from other
pathways and this approach understates
risks. EPA should combine exposures
from all relevant pathways and determine
an aggregate risk reflecting the
contribution of each source. This is a
further reason why setting a higher cancer
risk threshold for workers than other
populations is unjustified under TSCA.
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
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to determine whether to consider aggregate or sentinel exposures for a
particular chemical. EPA has determined that using the high-end risk
estimate for inhalation and dermal risks separately as the basis for the
unreasonable risk determination is a best available science approach.
There is low confidence in the result of aggregating the dermal and
inhalation risks for this chemical if EPA uses an additive approach,
due to the uncertainty in the data. EPA does not have data that could
be reliably modeled into the aggregate, which would be a more
accurate approach than adding, such as through a PBPK model. Using
an additive approach to aggregate risk in this case would result in an
overestimate of risk. Given all the limitations that exist with the data,
EPA's approach is the best available approach.
EPA did not consider background exposure that workers and
consumers using products containing MC might be exposed to in
addition to exposures from TSCA-regulated conditions of use. This
may result in an underestimation of risk, and additional discussion of
this underestimation has been added to the document in the Key
Assumptions and Uncertainties section.
Estimation of ONU exposures
SACC
SACC COMMENTS:
EPA should consider the different
categories of ONUs potentially at risk
from exposure to MC at the different
conditions of use (e.g., workers who do
not handle MC directly, but whose job
requires them to be in the same area as
users; cleaning staff who can be exposed
after hours to residues present in the work
area, or office/managerial workers who
could be incidentally exposed when
visiting a work area but are not at risk
from exposure routinely) because their
potential exposure risk likely varies.
EPA does not have reasonably available information and data to
consider different categories of ONUs or to develop additional
scenarios for ONU exposures.
EPA has included all modeling opportunities with the data reasonably
available. We do not have reasonably available info to further
differentiate ONU population for the purpose of risk assessment. More
data are required to pursue additional modeling options.
In Uncertainties section 4.3.2.1, EPA added the uncertainty "ONUs
are likely a heterogeneous population of workers, and some could be
exposed more than just occasionally to high concentrations."
For full shift exposures, EPA assumes 8 hours of exposure except
when 12-hour shifts apply.
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Develop scenarios for ONU conditions of
use that are amenable to modeling their
exposures using assumptions informed by
professional judgment and/or information
provided by users.
ONUs are likely a heterogeneous
population of workers, and some could be
exposed more than just occasionally to
high concentrations. This possibility
should be included explicitly as a source
of uncertainty.
Several Committee members suggested
EPA assume 8 hours of exposure duration
for central tendency workers and ONUs.
SACC,
72, 75
SACC COMMENTS:
In Section 2.4.1.2.2 (p. 117, lines 2114-
2119), ONU area monitoring data were
available, but were not used. Instead
modeling was used to estimate ONU
exposures.
ONU monitoring data should have been
compared to the modeled estimates and
justification provided if it is not possible
to do a comparison. Additional discussion
is needed on the representativeness or
lack thereof of the data. When both
monitoring and modeling estimates are
available, the most conservative estimate
should be used.
PUBLIC COMMENTS:
EPA has no ONU-specific data and
calculates ONU risks based on the central
tendency (50th percentile) of worker
inhalation exposures as opposed to
collecting ONU-specific data or using the
In Section 2.4.1.2.2, EPA clarified that the area monitoring data were
not appropriate surrogates for ONU exposure due to lack of necessary
metadata, such as monitor locations and distance from worker
activities, to justify its use.
EPA compared monitoring data to model predictions for the one OES,
Cold Cleaning (Section 2.7.3 of the Supplemental Information on
Releases and Occupational Exposure Assessment), for which both
were available. EPA has added explanation to section 2.4.1.2.7 to
explain that monitoring data have higher weight of evidence due to
higher relevance than modeling results for this use for several reasons:
(1) monitoring data are known to be relevant to this use; and (2) the
modeled results cannot be validated and do not capture the full range
of possible exposure concentrations identified by the monitoring data
for this use. For example, the 95th percentile modeling results appear
equal to about the 25th percentile of monitoring data.
For most occupational exposure scenarios, ONU-specific data and
modeling are not available; in these OESs, EPA assumes ONU
exposures are equal to central tendency (50th percentile) of worker
inhalation exposures.
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higher end exposure estimates as EPA
does for other workers.
SACC,
66, 72,
73, 70
SACC COMMENTS:
Unless use of MC is physically
sequestered from other MC-releasing jobs
in the same area, the assumption that
ONUs are less exposed than users is not
sufficiently supported.
The evaluation should expand the
descriptions to show physical
sequestration of MC from other sources
in the same work area or add UFs for
these scenarios where more than one user
is present.
PUBLIC COMMENTS:
There are scenarios where ONUs may
have almost equal exposure including
handling MC in small areas that are
poorly ventilated.
The ONUs exposure is underestimated.
There might be an interaction between
occupational exposure and consumer
exposure.
The TURA program reports several
instances where ONUs were in close
proximity to workers, and without the
protection of PPE.
Particularly over a short period (e.g.,
response to a spill or equipment
maintenance), ONU exposures may be as
great as or greater than those of other
workers, and ONUs are even less likely
to be provided PPE.
EPA states "The assumption that ONUs
are present only in the far-field could
result in underestimates for ONUs
EPA does not have reasonably available data or information on
physical sequestration of MC from other sources in the same work
area. EPA also has no method to quantify uncertainty factors for
scenarios where workers and ONUs are both present.
EPA does not have reasonably available data or information on
scenarios where ONUs may have almost equal exposure including
handling MC in small areas that are poorly ventilated.
TSCA section 6(b)(4)(F)(ii) directs EPA to "describe whether
aggregate or sentinel exposures to a chemical substance under the
conditions of use were considered, and the basis for that
consideration" in risk evaluations. EPA defines aggregate exposures
as the combined exposures to an individual from a single chemical
substance across multiple routes (i.e., dermal, inhalation, or oral) and
across multiple pathways (i.e., exposure from different sources). 40
CFR 702.33. EPA defines sentinel exposures as the exposure from a
single chemical substance that represents the plausible upper bound of
exposure relative to all other exposures within a broad category of
similar or related exposures. 40 CFR 702.33. EPA considered the
reasonably available information and used the best available science
to determine whether to consider aggregate or sentinel exposures for a
particular chemical. EPA has determined that using the high-end risk
estimate for inhalation and dermal risks separately as the basis for the
unreasonable risk determination is a best available science approach.
There is low confidence in the result of aggregating the dermal and
inhalation risks for this chemical if EPA uses an additive approach,
due to the uncertainty in the data. EPA does not have data that could
be reliably modeled into the aggregate, which would be a more
accurate approach than adding, such as through a PBPK model. Using
an additive approach to aggregate risk in this case would result in an
overestimate of risk. Given all the limitations that exist with the data,
EPA's approach is the best available approach.
Employees doing equipment maintenance are considered by EPA to
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present in the near-field" (p. 373). It is
unclear then, why EPA ignores this
potential in characterizing ONU
exposures.
In lines 1811-1818, EPA stated that the
near field does not accurately represent
the ONU workers because the ambient
concentration of MC closer to them is
lower compared to those who directly
work with MC. EPA instead modeled
ONU exposures using a combination of
far-field modeling and area sampling
data, since this would more accurately
represent ONU exposures. A
contradictory conclusion was then made
in lines 2125-2127 that "relative exposure
of ONUs to workers cannot be
quantified."
be workers and not ONUs. Response to a spill would generally be
covered by shorter-term exposures. EPA clarified in section 2.4.1.2.2
that relative exposure of ONUs to workers cannot be quantified using
modeling.
Exposures for occupational non-users can vary substantially. Most
data sources do not sufficiently describe the proximity of these
employees to the exposure source. As such, exposure levels for the
"occupational non-user" category will have high variability depending
on the specific work activity performed. It is possible that some
employees categorized as "occupational non-user" have exposures
similar to those in the "worker" category depending on their specific
work activity pattern. ONUs are likely a heterogeneous population of
workers, and some could be exposed more than just occasionally to
high concentrations.
SACC
SACC COMMENTS:
In the absence of measurements, the
Agency could use modeling for
estimating ONUs exposures. Models used
in industrial hygiene (AIHA, 2009) could
be adapted for this purpose using
assumptions based on professional
judgment and input from users.
EPA has exhausted all modeling opportunities for ONUs with the data
that are reasonably available. The specified AIHA models are too
limited and do not have necessary parameter sets, particularly use-
specific emission rates and zonal volumes and air flow rates, for ONU
exposure assessment.
SACC,
72, 73,
70,
SACC COMMENTS:
The risk evaluation should examine how
ONU risk changes if exposure is
estimated using the distance from ONUs
to users and the inverse square law.
This method is considered to be a better
estimate of ONU exposure than the use of
central tendency for occupational users.
Assigning the occupational users central
tendency exposure may not be
ONU distance from users are accounted in the uses with Near-Field/
Far-Field modeling, which is superior to a method that would use the
inverse square law. EPA does not have a method to account for air
exchange rates for potential use of the inverse square law nor the
reasonably available data or information to estimate distance of ONUs
from users in the other assessed uses.
Where EPA had monitoring or modeled data specific to ONUs,
unreasonable risk determinations where made based on high-end
exposures. For conditions of use where the data did not distinguish
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sufficiently conservative, depending on
the specific use scenario and the location
of the ONU with respect to the user(s).
PUBLIC COMMENTS:
EPA ignored exceedances of its risk
benchmarks for acute, chronic and/or
cancer effects by high-end exposures to
ONUs for at least 19 of its 65 conditions
of use (for examples, see pp. 431, 436,
449).
between worker and ONU inhalation exposures, there was uncertainty
regarding ONU exposure. ONU inhalation exposures are assumed to
be lower than inhalation exposures for workers directly handling the
chemical substance. To account for this uncertainty, EPA considered
the workers' central tendency risk estimates from inhalation exposures
when determining ONUs' unreasonable risk (rather than the high-end
inhalation exposures), when data specific to ONUs was not available.
Sentinel exposure assessment
73
PUBLIC COMMENTS:
EPA did not establish that its so-called
sentinel exposure assessments actually
reflect "the plausible upper bound of
exposure," as required by EPA's
regulation, and EPA did not rely on those
assessments in its risk characterizations.
While EPA stated that the sentinel
exposure was the high-end exposure with
no gloves, EPA does not address whether
it considers the sentinel exposure to be
the high-end exposure with no respirator
as well.
To accurately assess "the plausible upper
bound of exposure," EPA should consider
exposures without any PPE unless EPA
can establish that PPE is always used for
the particular condition of use. As
discussed in Section l.B, EPA
acknowledged that it does not have data
sufficient to establish this, and EPA has
further acknowledged that it cannot make
such an assumption for at least certain
occupational exposure scenarios (see
Supplement on Releases and
Language better describing the consideration of sentinel exposure for
consumer use evaluations has been added to Section 4.6. It is as
follows: For consumer exposures, a range of consumer inhalation and
dermal estimates for each consumer condition of use were provided
by varying duration of use per event, amount of chemical in the
product and mass of product used per event, while retaining central-
tendency inputs for exposure factors and exposure setting
characteristics. In presenting the inhalation results, high intensity use
was characterized by the model iteration that utilized the 95th
percentile duration of use and mass of product used (as presented in
U.S. EPA (1987)) and the maximum weight fraction derived from
product specific SDS, when available. Dermal exposures for high
intensity use were characterized by the model iteration that utilized
the 95th percentile duration of use and maximum weight fraction."
The EPA defines sentinel exposure as "the exposure to 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)." In terms of this risk
evaluation, the EPA considered sentinel exposure the highest
exposure given the details of the conditions of use and the potential
exposure scenarios. Sentinel exposures for workers are the high-end
no PPE scenario within each OES.
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Occupational Exposure, e.g., pp. 115,
116).
Coordination with CAA
67
PUBLIC COMMENTS:
EPA itself has adopted a number of
national emission standards that limit
emissions of MC, which is a HAP listed
in CAA § 112. Under CAA § 112, these
standards must ensure an "ample margin
of safety to protect public health." Thus,
if the risk of concern was significant,
EPA would have to adopt more protective
standards under the CAA.
These standards include, notably, the
NESHAP for paint stripping and
miscellaneous surface coating operations
at area sources.
The draft risk evaluation is deficient in
that it fails to draw on the information
available to EPA to evaluate use and
exposure information. EPA has adopted
NESHAPs for many applications
restricting emissions of MC, for which it
relied on exposure assessments showing
concentrations below 25 ppm.
The exposure data in the draft risk
evaluation also predate the compliance
dates of the NESHAPs (mostly ranging
from 2008 to 2011). It is remarkable that
the draft risk evaluation was apparently
compiled without utilizing the data
already in the hands of EPA and other
permitting authorities.
NESHAPs are air regulations that require companies to keep certain
records; however, these data are retained at the company sites and are
not available in a centralized database. This comment may be in
reference to the National Emissions Inventory (NEI), which is
compiled every 3 years for the purpose of supporting residual risk
evaluations as required by Section 112 of the CAA. NEI contains air
emission estimates, which can be estimated by sites using a variety of
methods, such as emission factors, mass balance, stack monitoring. A
site could use purchasing records and disposals to estimate air
emissions, but these purchasing records and disposals are not reported
to NEI.
Exposure characterization needs sensitivity analysis
66, 67
PUBLIC COMMENTS:
The MC exposure characterization would
Regarding occupational inhalation exposure modeling, qualitative
sensitivity analysis sections were added to Appendix F of in the
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be strengthened by qualitative and/or
quantitative sensitivity analysis. A
qualitative assessment would help
explore potentially influential exposure
factors and justify EPA's approach. A
quantitative analysis would allow for
interpretation of the contribution of
individual parameters to the predicted
exposure concentrations.
Supplemental Information on Releases and Occupational Exposure
Assessment.
Tables in Appendix F of "Supplemental Information on Releases and Occupational Exposure Assessment"
SACC
SACC COMMENTS:
Table Appendix F-l of "Supplemental
Information on Releases and
Occupational Exposure Assessment" (p.
270) shows that a discrete distribution
was used for weight fraction. However,
the actual text reads as if the weight
fraction was determined by sampling
from two separate distributions with the
sampling from the second dependent on
the sampling from the first distribution.
Additionally, this table does not show a
distribution for New Jersey (number of
brake jobs per work shift). No
justification is provided as to why this
was not considered a variable with an
appropriate discrete distribution assumed.
Table Apx F-l of "Supplemental
Information on Releases and
Occupational Exposure Assessment"
should be updated to more clearly
represent what was actually done.
Table Appendix F-3 of "Supplemental
Information on Releases and
Occupational Exposure Assessment" (p.
280) shows a lower bound for the vapor
The aerosol product weight fraction of MC was modeled using a two-
dimensional sampling technique. A uniform distribution is used to
simulate the weight fraction of MC in each aerosol product. Due to
lack of data on volumes or market penetration of each individual
aerosol product, EPA assumes each aerosol product has an equal
probability of being used at any given shop. Therefore, a discrete
distribution is used to model the frequency of occurrence of each
product, where each product has a probability of occurrence of 10%
(there is a total of 10 products). On each iteration of the simulation,
the model executes each product's weight fraction distribution and the
product frequency distribution. The model then reads the product
selected from the product frequency distribution and selects the
weight fraction that was generated from the corresponding product's
weight fraction distribution. EPA added additional clarification in
Section F.l.2.7 and the table.
The number of brake jobs per shift is calculated from the fixed
average number of brake jobs per year per shop (this is the only data
EPA identified). To calculate NJ, the model uses a constant 936
jobs/site-yr, a constant 8 hr/shift, a constant 52 weeks/year, and a
distribution for the number of operating hours per week. Therefore, NJ
is varied according to a distribution dictated by the distribution of
operating hours per week. This is calculated in situ in the model.
Tables F-3 and F-7 show the value for vapor generation rate at
different levels of precision, but the model stores the value at 15 digits
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generation rate of 0.015, but the text
describing this parameter (p. 285) gives a
value of 0.02.
This table and/or associated text should
be updated to represent the correct value.
EPA should revise the risk evaluation and
supplemental documents to verify that
values for parameters in tables and the
text are all reported to the same precision
as used in calculations and models.
The distribution for the exposure duration
parameter in Tables Appendix F-3, F-4
and F-5 (in Appendix F of "Supplemental
Information on Releases and
Occupational Exposure Assessment," pp.
280, 281, and 282) is given as being a
discrete distribution; however, the text
describes this parameter as being
determined based on the number of
operating hours per day. Both could more
accurately be listed as a constant or as a
calculated value based on the number of
operating hours.
of precision. EPA updated the value in Table F-7 to 0.015.
EPA revised the tables to clarify exposure duration is calculated from
operating hours per day.
Human lleahli lla/artl
EPA used the acute point of departure (POD) to use to estimate risks from the human controlled experiment described by Putz et
al. (1979). This study was rated as a medium quality study; it was a double-blind design but used a single exposure, which
prevented the use of dose-response modeling. Given uncertainty regarding concentrations and exposure durations and the potential
for a steep dose-response leading to death as suggested by these case reports and the analysis by Benignus et al. (2011), EPA
considers Putz et al. (1979) to be the most relevant study for this risk evaluation.
Charge Question 5.1. Please comment on the appropriateness of the approach, including the data quality evaluation, and the
approach's underlying assumptions, strengths and weaknesses.
Charge Question 5.2. Please provide any specific suggestions or recommendations for alternative approaches that should be
considered by the Agency in characterizing the acute inhalation risks.
Charge Question 5.3. Please provide relevant data or documentation and rationale for including other studies and endpoints for
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consideration.
Charge Question 5.4. Please comment on the severity of the response used as the basis of the POD as well as the use of the result
at 1.5 hours rather than at 4 hours.
For methylene chloride, exposure-versus-time data are limited. Therefore, EPA considers the Ten Berge equation using n = 2 as a
valid method to convert the 1.5-hr POD value from Putz et al. (1979) to the 15-min, 1-hour and 8-hr PODs.
Charge Question 5.5. Please comment on the conversion of the 1.5 h time point in Putz to 15 min, 1-hour and 8-hour PODs.
EPA used PODs and cancer slope factors (i.e. human equivalent concentration (HEC), inhalation unit risk (IUR) and dermal slope
factor) for evaluating the non-cancer and cancer risks, respectively, for chronic exposures to methylene chloride.
5.6. Please comment on the appropriateness of the approach, including its underlying assumptions, strengths and weaknesses.
Charge Question 5.6. Please comment on the appropriateness of the approach, including its underlying assumptions, strengths and
weaknesses.
Charge Question 5.7. Please provide any specific suggestions or recommendations for alternative approaches that should be
considered by the Agency in characterizing the chronic inhalation risks to workers.
Charge Question 5.8. Please provide relevant data or documentation and rationale for including other studies and endpoints for
consideration.
EPA used a linear low-dose extrapolation for evaluating potential cancer risks from chronic exposures to methylene chloride.
Charge Question 5.9. Please comment on the appropriateness of using a linear low-dose extrapolation versus a non-linear or
threshold approach, recognizing that methylene chloride is predominantly metabolized by cytochrome P450 2E1 to carbon
monoxide at low concentrations (a high affinity, low capacity pathway) and by glutathione S-transferase Tl-1 to two reactive
intermediates (i.e., S-(chloromethyl)glutathione) and formaldehyde) at high concentrations (a low affinity, high capacity pathway).
EPA calculated a cancer slope factor by using a PBPK model that accounts for the internal dose of the amount of methylene
chloride metabolized through the glutathione S-transferase Tl-1 (GST) pathway.
Charge Question 5.10. Please comment on the appropriateness of applying the PBPK model and assumptions within the model,
specifically using the internal dose metric of daily mass of methylene chloride metabolized via the GST pathway as the basis for
performing a linear low-dose extrapolation for quantifying potential cancer risks from chronic exposures to methylene chloride.
Summary of Peer Review Comments lor
Specific Issues Related to Charge Question 5
KPA/OPPT Response
Acute PODs
SACC
SACC COMMENTS:
The Committee was generally satisfied with
the approach of using the 1.5-hour result
from Putz et al. (1979) as the basis of the
acute POD; however, one Committee
member felt that the modest CNS effects are
more useful in establishing a LOAEL and
recommended the Agency use the 4-hour
EPA believes that effects at the 1.5-hr time point are important; this
was the first time point that a statistically significant change was
observed. Although the effect was a 7% change in a visual response
as part of a dual performance task, EPA adjusted the LOAEL to
NOAEL uncertainty factor to 3 (from a default of 10) to account for
the lower severity of effect.
Longer studies are described in the MC risk evaluation. Although
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exposure level of 200 ppm to convert to the
15-minute, 1-hour and 8-hour PODs.
The Committee suggested the risk evaluation
should support conclusions by including data
from other human studies measuring CNS
effects from longer duration exposures than
are summarized in this risk evaluation.
studies are available for longer durations and do suggest effects on
the nervous system associated with MC, they were not adequate for
risk evaluation. Lash et al. (1991) identified a lower score on
attention tasks and complex reaction time from MC exposure, but
this effect was not statistically significant and could have been
affected bv other pollutants. Cherry et al. (1983) also identified
neurological changes but received an unacceptable data quality
rating. General Electric Co (1990) found a statistically significant
effect associated with 49 ppm MC but did not control for other
chemical exposures. These studies are already described in the risk
evaluation.
67
PUBLIC COMMENTS
While this Putz et al. (1979) was considered
to be of medium quality in the systemic
review, only one exposure concentration was
tested, which is a significant issue for
assessing the acute neurobehavioral effects of
MC because the dose-response curve cannot
be determined.
Although EPA would have preferred to use a study with multiple
exposure concentrations, Putz et r9) was superior to the other
studies for several important reasons. First Stewart et al. (1972) also
used only one concentration per experiment, but with higher
concentrations than Putz et al. f 1979). Second, Wimmel
provided only limited dose-response information (one or two
concentrations per experiment), and the responses at 300 ppm were
similar to or sometimes more pronounced than at 500 ppm.
Although Gamberale ei al i lcr5) conducted their experiment using
four concentrations, effects were observed only at 1000 ppm; yet,
Gamberale et a received a 'low' data quality rating and
among all of the acute human experimental studies, the majority of
individual experiments at lower concentrations showed some effect
of visual and auditory responses.
For these reasons, EPA considered it important to use Putz et al.
(1979), which did report the lowest concentration associated with an
adverse effect. In addition, CNS depression is identified in multiple
studies in humans and animals. Furthermore, serious effects
(including lethality) are observed at higher concentrations, with
limited information regarding the concentrations where lethality
occurs.
45, 67
PUBLIC COMMENTS:
EPA's acute toxicity assessment is
EPA applied risk assessment methods tailored to the needs of TSCA
implementation. TSCA compels EPA to evaluate risk associated
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inconsistent with existing occupational
exposure limits (OELs) (8-30-fold lower than
the current range of widely accepted 8-hour
TWA OELs from 25 to 100 ppm).
Neurological effects were not reported in
occupational cohort studies, with MC
exposures in the range of OELs.
Human kinetic studies by DiVincenzo and
Kaplan (1981) indicate that exposure to 100
ppm MC for 8 hours would result in a COHb
blood level of approximately 3%, which is
the NOAEL for neurobehavioral effects
based on Putz et al. (1976).
Data indicate that exposure to OEL levels
would not increase COHb levels above
background or result in COHb above the
NOAEC for CO, including for susceptible
individuals lacking the GST-T1 enzyme.
with specific conditions of use without consideration of cost or other
non-risk factors. Occupational risk assessments and conclusions are
performed for a different purpose using a different set of
assumptions and considerations. OSHA specifically notes that they
considered issues of feasibility in choosing both the PEL of 25 ppm
and 15 min STEL of 125 ppm and acknowledges that there are still
risks associated with both of these values (OSHA. 1997).
Actually, some indications of neurological effects have been seen in
multiple longer-term studies. General Electric Co (1990) identified
dizziness and vertigo associated with 49 ppm MC. Lash et al,ij
found some association between MC and lower scores on attention
and reaction time tasks; there was a lack of statistical significance
but sample sizes were low. Although considered unacceptable due to
participants' loss to follow-up, Cherry et al. (1983) identified
sleepiness, tiredness, mood change and deterioration on digit symbol
tests associated with MC. Finally, although Silver et al. (2014) did
not identify deaths from malignant or non-malignant diseases of the
nervous system, this endpoint is much more severe compared with
responses used for the acute timepoint.
EPA expects that direct exposure to the parent compound MC will
also result in CNS effects, based on human experimental studies.
Two studies (Putz et al. 1979; Winneke. 1974) separately tested MC
and CO concentrations (with both MC and CO expected to result in
the same COHb levels) and had identified more CNS effects
associated with MC (and no CNS effects were associated with CO in
one study). Thus, COHb is not the only compound producing CNS
effects associated with MC exposure.
EPA agrees that COHb levels even down to 2% may result in
exacerbation of cardiotoxicity. For example, in Section 3.2.4.1,
(Weight of Scientific Evidence, Non Cancer), EPA identified studies
of COHb levels ranging from 2 to 4.5% that have resulted in
decreased time to onset of angina pain during exercise among
individuals with coronary artery disease. Because there is little
evidence of this effect directly associated with MC but because it
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may occur as a result of increased COHb concentrations from MC
exposure, EPA has included an uncertainty factor to account for
possible exacerbation of cardiac effects.
73,
SACC
SACC COMMENTS:
The Committee questioned the conclusion in
the risk evaluation that the MC-induced CNS
effects are concentration-dependent with a
steep dose-response curve.
Recommendation: Use the data from the
Winneke et al. (1974) study to confirm the
assumption used in the dose-response
modeling of the Putz et al. (1979) study.
PUBLIC COMMENTS:
The commenter supported use of Putz et al.
(1979) because it provides better study
quality and a more health-protective POD for
the draft risk evaluation.
Response to SACC Comments:
EPA evaluated information within Winneke (1974) more fully and
also reviewed other information to more fully consider the steepness
of the dose-response curve. Information from the human
experimental studies is inconclusive/not supportive of a steep dose-
response curve in the range of concentrations from these studies (see
Appendix B, below). However, lethality data in animals is
supportive of a steep dose-response curve because these studies
show an increase in mortality from 0 to 100% within an
approximately twofold increase in exposure concentration, with
death primarilv preceded bv CNS effects (Nac/Aegl. 2.008). In
addition, although EPA doesn't have definitive information on
concentrations associated with human deaths, information suggests
that in one report, lower exposures (e.g., down to 100 ppm or lower)
might have been associated with lethality. In conclusion, the
lethality data in animals and the potential that human lethality may
occur within the range of concentrations associated with less severe
effects still support EPA's statement regarding the fact that there
may be a steep dose-response leading to lethality. The study used for
the POD has only one concentration so there is no dose-response
information within that study.
Response to Public Comments:
Agreed.
Comments on use of Ten Berge approach for acute POD
SACC
SACC COMMENTS:
Check calculations for the 1- and 8-hour
PODs to ensure that no impactful rounding is
occurring.
EPA has updated the process used for rounding and has also updated
the risk estimates.
SACC,
67, 73,
45
SACC COMMENTS:
One committee member supported the use of
the ten Berge equation but noted there are
additional relevant models. Committee
EPA understands the uncertainties in using any model, including the
use of lethality data for non-lethal effects. However, when weighing
the scientific evidence, EPA chose the use of the ten Berge equation
of C 11 *T, where n = 2 instead of other approaches because even
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discussion pointed out that the ten Berge
equations have limitations. The work of ten
Berge (1986) was limited to data on lethality
and often does not accurately reflect dose-
response relationships for very short periods
of exposure, as well as for longer durations
(Bruckner et al., 2004). Use of the Cnxt
approach can underestimate longer AEGLs
and thereby overestimate risks.
Recommendation: Use the PBPK model for
acute exposures or justify why it is not
suitable for this task.
The Committee described the PBPK model
as both more scientifically justifiable and
more protective of human health.
Additional advantages were identified for
using PBPK modeling over the ten Berge
equation. It should be recognized that blood
and brain concentrations of MC increase
rapidly upon initiation of inhalation
exposure, approaching near steady-state, or
equilibrium within 1.5-2 hours. CNS
depression is directly attributable to the
parent compound. Human PBPK modeling
and monitoring data show gradual,
progressive increases in blood MC levels
over the next 6 hours of exposure (Bos et al.,
2006). For duration adjustments, NAS (2009)
used a PBPK model based on a modification
of the model of Andersen et al. (1987, 1991)
and by Reitz et al. (1997). NAS (2009)
utilized the same modeling to simulate
COHb levels for derivation of AEGL-2
values.
PUBLIC COMMENTS:
EPA's use of the ten Berge et al. (1986)
though the lethality data are not ideal, they do represent an
empirically-derived value from inhalation data for solvents that can
be used for n. There are also several reasons that EPA did not use
the PBPK model, as described below.
Although the PBPK model described by Bos et al. (2006) and used
to set AEGLs seems appropriate for these higher emergency
guideline values, EPA believes that there are enough uncertainties
regarding both the assumptions used in the model and the validation
of the model that don't warrant using it instead of the ten Berge
equation for the lower acute PODs in the current risk evaluation.
Although the model accounts for P-450 saturation and thus, a switch
to metabolism/conjugation by GSTT1, P450 saturation occurs at
approximately 500 ppm, which is higher than the POD for the
current evaluation. In addition, the model includes the distribution of
GSTT1 in the population; this refinement may not be entirely
necessary when using human volunteers (especially at lower MC
concentrations). Furthermore, the parent compound has been shown
to result in CNS effects that are in excess of CO/COHb
concentrations, as identified by Putz et al. (1979) and Winneke
However, Bos et al. (2006) acknowledge that there are no
adequate data on MC in rat or human brains and also assumes that at
longer exposures, the more relevant endpoint is COHb only. OSHA,
when considering a similar PBPK model for acute effects for
derivation of the 1997 PEL, had similar concerns the about lack of
experimental validation of the predicted brain MC concentrations
and the level of brain concentrations that would produce detectable
CNS depression (OSHA. 1997).
Although EPA understands that the COHb concentrations may be
maintained for several hours after exposure ceases (and a primary
reason to consider this type of PBPK model), this effect is not as
pronounced at lower concentrations. Finally, Bos et al. (2006) state
that the model overpredicts MC and COHb concentration by up to
50%; thus, the lower POD predicted by the model for longer
exposure durations may be partially due to this overprediction.
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equation and UFs is untenable in light of the
MC human kinetic data and the PBPK
models. EPA's assertion that the values
derived from differing methods (i.e., ten
Berge equation vs. PBPK model) are
"similar" is inaccurate and fails to
acknowledge that the differences are non-
negligible. The application of time averaging
in the ten Berge calculation may not fully
consider the toxicokinetic data for MC or the
concentration-response data for the selected
endpoints.
Because the human behavioral effects can be
caused by both hypoxia (COHb levels) and
by the MC brain concentrations, which
exhibit different kinetics and thus different
dose-response relationships over time, a
PBPK model (published by Bos et al., 2006)
was used to derive ATSDR's acute oral
Minimal Risk Level (MRL) and EPA's
AEGL values (Reitz et al., 1997; AEGL,
2009). The PBPK model also incorporates
the impact of the GST-T1 polymorphism in
humans. In the draft risk evaluation,
however, EPA did not use these models.
For the final risk evaluation, EPA added a 12-hr time point; to
consider the sensitivity of using n = 2 in the ten Berge equation for
this longer time point, EPA extrapolated to this time point using
both a value of n = 1 and n = 2.
In conclusion, although the PBPK model may be an important way
to account for the time-course of sustained COHb levels at higher
AEGL values, EPA believes that it doesn't add enough value over
the use of the Ten Berge et al. (1986) approach for the current risk
evaluation. EPA has added more information to the risk evaluation
to describe uncertainties related to the PBPK model as well as any
uncertainties in not using the model.
Acute exposure and cancer
73, 75
PUBLIC COMMENTS:
EPA's risk evaluation should account for
acute cancer risks to workers and consumers.
It is widely recognized that genotoxic
carcinogens like MC can induce cancer
following a limited acute exposure event and
that methods to estimate such risks are
available (NRC 1993a).
As stated in this NRC report, the decision to
conduct extrapolation and modeling should
For the current MC risk evaluation, there is a significant database of
positive mutagenicity results for the MC metabolites of the GST
pathway, particularly related to the GSTT1 isozyme. EPA believes
that these data are strong enough to model cancer using a linear low
dose extrapolation. However, there are still some uncertainties
regarding the strength of the information relate to this MOA.
Standard Operating Procedures for Developing Acute Exposure
Mine Levels for Hazardous Chemicals notes the significant
uncertainty in extrapolating risks from lifetime exposures to shorter
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be based on the "sound biological and
statistical principles." There is concern that
EPA did not sufficiently consider such
principles related to mode-of-action in
deciding not to model acute cancer risk based
on chronic exposure data. A linear low-dose
extrapolation from chronic to acute
exposures would be the appropriate approach
to take for MC.
(once in a lifetime) exposures. The SOP specifically points out the
complex nature of biological mechanisms related to cancer and
possible differences in such mechanisms when considering them for
acute vs. chronic exposures. Krewski et al. (2004) further notes that
there are often limited single-exposure inhalation toxicity data to
consider such an extrapolation from lifetime exposures.
For these reasons, EPA doesn't consider use of short-term cancer
risk estimates to be appropriate for the current risk evaluation.
Non-cancer hazards not considered for chronic POD
SACC,
49, 55,
70
SACC COMMENTS:
The Committee considered the potential
immunotoxicity of MC to be underestimated,
even based on the somewhat equivocal
results.
There are a few epidemiological studies
included in the risk evaluation that show a
weak association, and this is supported with
data from short-term animal models. The
evidence, especially the results from Arayni
et al. (1986), fulfill the NTP criteria for
"clear evidence of toxicity to the immune
system (NTP 2009)."
The Committee disagrees with study quality
rating for the Arayni et al. (1986) study,
which was not rated more highly because of
a lack of information about test substance
preparation and animal group allocation.
Recommendation: Add a conclusion
statement to Section 3.2.3.1.3, Immune
System Effects, stating that this summarizes
the equivocal results while acknowledging
the strong potential for MC immunotoxicity
based on the Aranyi et al. (1986) study.
PUBLIC COMMENTS:
In its MC risk evaluation, EPA "did not carry
Response to SACC comments:
After closely reviewing the NTP (2009) criteria and the information
on immunotoxicity related to MC exposure, EPA considers there to
be some evidence of immunotoxicity from MC. Although Aranyi et
6) identified a statistically significant decrease in bacterial
resistance accompanied by increased mortality at the highest of two
MC concentrations, there is a lack of information on the dose-
response gradient simply because the effect was seen only at the
highest concentration and there are no other similar bacterial
resistance studies to show the effects at different concentrations.
One human study identified increased mortality from infection, and
another identified increased mortality from non-specific chronic
bronchitis, but the results are not consistent across studies. Also,
other subchronic and chronic animal studies did not identify
increased infection rates associated with MC exposure. (N I P (i °86)
measured this and found an infection in only one low-dose female,
and the functional IgM assay was negative.
Although EPA did consider the NTP (2009) criteria, EPA also used
an evidence integration framework to consider the evidence on
MC's association with immunotoxicity (see Appendix A, below).
EPA has applied consistent data quality evaluation criteria across
studies and considers Aranyi et al. (1986) to be a medium quality
study, which is an acceptable confidence rating.
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immune system effects forward for dose-
response" analysis "due to a limited
database" of immunotoxicity studies. The
evidence that EPA does have, however,
indicates that MC is immunotoxic.
EPA added more information to the conclusion section for the
immunotoxicity endpoint.
Response to public comments:
EPA considers the database to show some evidence of
immunotoxicity and has revised the hazard identification and weight
of the scientific evidence sections.
PUBLIC COMMENTS:
The agency should present a more defensible
rationale for dismissing the ASD endpoint
based on a single study limited to one county
in one state when four other studies
consistently present evidence of an effect.
Lack of a link to specific conditions of use
does not provide a basis for exclusion of
studies for use in dose-response assessment.
The lack of an animal model for ASD should
not preclude the inclusion of epidemiologic
evidence, given that humans are the species
of interest.
EPA acknowledges the hazard associated with the ASD endpoint,
including the low air concentrations that are associated with
consistently positive odds ratios (e.g., several hundred ng/m3).
However, given uncertainties already described regarding the
models, EPA has chosen not to calculate risks for ASD.
EPA agrees with this statement. Lack of a link with specific
conditions of use should not be a basis for exclusion because animal
toxicity studies are used in risk evaluations and they cannot be
linked to specific conditions of use. However, the risk evaluation
doesn't make this claim. The weight of scientific evidence section
(Section 3.2.4) for the ASD studies does, however, note that the
studies do not provide exposure estimates for workers (e.g., nurses)
or indoor exposure estimates for consumer products or indoor
exposure estimates for the general population. This statement refers
to the fact that these other possible MC exposures may suggest that
these studies may not fully account for all MC exposures. EPA
added clarifying language to the Sections 3.2.4.1.4 and 4.3.5
(Weight of Scientific Evidence and Key Assumptions sections).
EPA agrees that the ASD studies can be considered on their own
merit. Yet, EPA has considered the available information in drawing
conclusions regarding this endpoint and has noted the lack of
applicable animal data for MC.
73
PUBLIC COMMENTS:
EPA's decision to ignore human evidence of
hematologic effects results in a less
protective risk metric. The California EPA
Two human experimental studies found greater CNS effects from
the parent compound MC than from CO (both resulting in the same
COHb concentration). Therefore, EPA doesn't recommend basing a
value on modeling only COHb. (See a more complete response
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(CalEPA) based its 2008 chronic Reference
Exposure Level (REL) on a human study
(DiVincenzo and Kaplan, 1981) and arrived
at a more protective result than did the draft
risk evaluation's approach.
regarding COHb in the second row - commenters 67, 73, 45 - under
"Comment on use of ten Berge approach for acute POD.")
EPA chose an intraspecies uncertainty factor to address individuals
with cardiac disease who may have decreased time to angina at
COHb levels lower than those associated with the acute POD for
MC.
49, 55,
72
PUBLIC COMMENTS:
In a risk evaluation, a decision not to further
analyze an endpoint has the same effect as a
finding of unreasonable risk. EPA's risk
management rules for MC will not address
immune system, developmental, or
reproductive effects because EPA has
neglected its responsibility to evaluate
whether and at what levels those risks are
unreasonable.
EPA presented and analyzed the reasonably available information
for immune system, developmental, and reproductive effects in the
hazard identification and weight of evidence sections in the risk
evaluation. Based on the weight of the scientific evidence, EPA
decided not to advance these data to the dose-response analysis.
Unless otherwise indicated, an endpoint subject to "no further
analysis" in risk evaluation may be included in the risk evaluation
and when EPA makes its unreasonable risk determinations as to
whether methylene chloride presents unreasonable risk under the
conditions of use based on an endpoint this also includes other
endpoints.
55, 73
PUBLIC COMMENTS:
MC has enough toxicity data to show that it
exhibits developmental toxicity and
neurotoxicity. EPA should regulate it as a
developmental neurotoxic agent, with
potential lasting adverse effects on
neurological functioning.
EPA must act immediately to fill the data gap
for developmental neurotoxicity.
As noted, some studies have identified neurotoxicity and some
developmental toxicity. EPA considers the database to be adequate
for evaluation and used reasonably available information to assess
these endpoints in a weight of scientific evidence analysis to identify
a developmental neurotoxicity hazard but did not bring the
information forward to dose-response for a variety of reasons
discussed in Section 3.2.4 of the Risk Evaluation.
49, 55
PUBLIC COMMENTS:
EPA does not evaluate endocrine effects in
either of the draft risk evaluations and has
not determined whether MC presents an
unreasonable risk of endocrine disruption, or
otherwise addressed in the risk evaluation, as
a data gap.
EPA evaluated the outcomes from existing epidemiological and
toxicity studies of MC that might be related to endocrine disruption
and considers the database adequate for risk evaluation without the
need to separately address endocrine effects on their own.
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SACC,
55
SACC COMMENTS:
Include more information on irritation and
burns. One Committee member dnoted an
additional source of information: King
County, Washington analyzed poison center
data for 2007-2016 for MC (Fisk and
Whittaker, 2018).
PUBLIC COMMENTS
Failing to address irritation and burns will
lead to underestimations of risk and leave the
public - including families and workers - at
risk from illness and disease due to exposure
to this toxic solvent.
EPA added information on irritation and burns from Fisk and
Whittaker (2018) to the risk evaluation. Air concentrations leading
to eye and respiratory tract irritation are not well established. Eye
irritation has occurred in rabbits, but this is after direct instillation in
the eye. Burns have occurred upon direct contact with skin and eyes,
including one worker that experienced severe corneal burns and
other anecdotal information that 1st through 3rd degree burns may
occur after direct contact
EPA added the following statement to Section 4.2 (human health
risk characterization) to address the possibility of irritation and
burns: "Although irritation and burns may result from exposure to
methylene chloride, air concentrations leading to eye and respiratory
tract irritation are not well established, nor are concentrations
resulting in direct contact burns to skin or eyes."
Chronic
*OD not protective
55
PUBLIC COMMENTS:
MC chronic toxicity is underestimated. EPA
should consider the potential effects of MC at
levels much lower than the POD, including
effects that may be biologically significant,
even if they are not statistically significant.
The commenter refers to increased COHb,
which was observed down to 50 ppm in
Nitschke et al. (1988), the 2-year bioassay
used for chronic liver effects.
It may be appropriate to re-calculate the risk
estimate using a lower POD or add additional
adjustment factors to provide a margin of
safety for adverse effects at lower exposures.
EPA evaluated the reasonably available epidemiological and animal
toxicity studies for multiple health outcomes and chose the PODs
considered to be most appropriate given the data quality evaluations,
amount of data reasonably available and integration of the data.
EPA considers both biological and statistical significance equally
when evaluating adverse effects and conducting dose-response
modeling. This is highlighted in Benchmark Dose Technical
Guidance (EPA, 2012a), which notes the need for a statistical or
biological trend when considering dose-response modeling and even
on EPA's website (www.eoa.gov/ri sk/con ductin g-human-health-
risk-assessment), which defines the NOAEL as "the highest level at
which no statistically or biologically significant increases are seen in
the frequency or severity of adverse effect."
Even though biological significance is of importance, however, it
cannot always be easily established (e.g., the percent response of a
given endpoint that is adverse is not always well established).
EPA agrees that increased COHb levels may result in exacerbation
of cardiotoxicity (decreased time to angina pain) and increased
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levels are expected to contribute to CNS depression, although the
exact contribution is unclear (see Putz et al. (1979) and (Winneke.
4), showing less or no CNS effects from CO). Therefore, EPA
uses the intraspecies uncertainty factor to account for susceptible
subpopulations associated with this effect (e.g., decreased time to
angina for individuals with cardiac disease).
55
PUBLIC COMMENTS:
How will EPA treat data where a dose-
response trend includes lower doses that do
not achieve statistical significance? How will
EPA treat an outcome that may not have
statistical significance, but has biological
significance? How will EPA treat data that
are limited by some potential confounding
factors, but show consistence across studies?
How will EPA include studies with outcomes
that are difficult to quantify, but have
biological significance?
In the face of scientific uncertainty, rather
than obtaining the data needed to answer
pending questions as the law requires, EPA
has instead disregarded and dismissed
evidence of harm.
When conducting benchmark dose (BMD) modeling, EPA fits data
from all doses in a study, regardless of whether they all were
statistically significantly different from the control response.
Therefore, the doses that were not statistically significant are
included and inform the modeling. EPA relies heavily on the
biological significance by choosing a priori the response that will be
the basis of the BMDL, although oftentimes the response level that
would be considered adverse is not available so a standard response
level is used.
EPA evaluates studies to determine whether confounding factors
could substantially affect the outcome of a study; if so, the study
might still be considered in the weight of evidence to the extent it
can be used but would likely not be relied upon for dose-response
modeling.
For irritation and burns (endpoints that are difficult to quantify),
EPA has identified the possibility that they may result from
methylene chloride exposure (see Section 4.2, Human Health Risks)
. However, they are not modeled in the risk evaluation due to lack of
quantitative information.
EPA relied on reasonably available information and considers the
database for MC to be adequate for risk evaluation. In particular, the
hazard database for MC is fairly robust, but some of the information
in the studies is not easily modeled quantitatively.
Reconsider liver POD
67
PUBLIC COMMENTS:
HSIA considers hepatocyte vacuolation in
female rats from the 2-year inhalation study
EPA considers hepatocyte vacuolation to be an adverse outcome
relevant for humans. Therefore, the study is appropriate for
inclusion in the risk evaluation of MC.
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by Nitschke et al. (1988) an inappropriate
endpoint for EPA's POD for chronic non-
cancer inhalation exposure.
Perhaps a more appropriate endpoint for a
POD for chronic non-cancer inhalation
exposure is the genomic changes associated
with circadian rhythms observed in liver and
lungs of mice exposed by inhalation to MC
in the Andersen et al. (2017) study.
EPA has evaluated the information on genomic changes and
determined that it is premature to use this information without a
more complete understanding of the key events associated with
adverse outcomes. EPA added discussion of Andersen et al. (1
to the cancer weight of scientific evidence section.
Use of body weight scaling on BMDL10 predictions
SACC
SACC COMMENTS:
One Committee member questioned use of
body weight scaling on animal BMDL10
predictions. Given that there is uncertainty
regarding differences in clearance, then it
seems that using an UF of 3 for
pharmacokinetic differences would be a more
consistent approach to addressing this
uncertainty.
Even if body weight scaling is used, it should
be applied after the model is used to get the
human external doses.
It would be useful if more detail was added
on how the sampling for the GST-T1
polymorphism was conducted (Appendix I,
p. 659, lines 11601-11603).
EPA doesn't apply uncertainty factors when using the cancer slope
factor derivation; therefore, BW3/4 is considered the only approach
to address animal to human extrapolation uncertainties when data
are limited.
For non-cancer, BW3/4 was applied (table 3-19) to the animal
BMDLio to obtain a value of 130.0 (see Table 3-19). Because the
relationship (as shown in the Toxicological Review; Fig 5-7) is
linear, applying BW3/4 before or after the HEC calculations doesn't
make a difference. EPA BW3 4 policy gives preference to BW3 4
rather than an uncertainty factor of 3 to account for animal to human
TK extrapolation. Using a 3x uncertainty factor results in a similar,
slightly lower POD.
EPA added details regarding the GST-T1 sampling to the risk
evaluation.
Evaluation of cancer epidemiology data
SACC
SACC COMMENTS:
Limitations in the evaluation of
epidemiological studies and the "healthy
worker effect" were noted.
However, the other biases, namely the
healthy worker survivor bias, can occur when
workers with poorer health status continue to
leave the workforce or switch jobs and as a
result incur lower exposures. Unlike the
EPA added details regarding the healthy worker survivor bias to the
weight of evidence section for human health.
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healthy hire bias, this cannot be addressed
using internal reference groups.
Recommendation: Add further details to the
evaluation of the epidemiology studies to
fully describe the "healthy worker effect."
46, 67,
68
PUBLIC COMMENTS:
The lack of consistency and absence of
associations in well-defined cohorts having
experienced high exposures suggest that the
carcinogenic hazard of MC to man is low or
non-existent. It should not be classified as
"likely carcinogenic in humans."
EPA relied on the 2005 Cancer Guidelines (EPA. 2005b) to
determine the classification, which considers results from both
epidemiological and animal toxicity studies to determine the
likelihood of carcinogenicity in humans. In addition, several of the
epidemiological studies did identify associations between MC and
various cancers. Finally, EPA identified methodological issues in
epidemiological studies (both more generally and specifically for
MC). Several of these issues make it difficult to determine an
association between MC and cancer in humans, even if an
association may exist.
46, 68,
73
PUBLIC COMMENTS:
EPA dismisses human epidemiological
studies and disregards their well-accepted
value in public health risk assessment. EPA's
attempt to summarize specific criticisms and
project them upon the broader body of
human evidence is unhelpful and misleading.
The constellation of inherent limitations
presented in the draft risk evaluation appears
to lean toward an interpretation that true
positive associations somehow were missed.
The agency should instead apply specific
criticisms where applicable to its discussion
of individual studies and focus its
assessments of the WOE on the strengths and
limitations on the entire study database.
EPA added more information to the risk evaluation (Section 3.3.4.2)
to address the epidemiological database as a whole including
discussion of the healthy worker effect (survivor bias). EPA believes
there is value in describing possible limitations that may make it
difficult to discern positive associations. However, EPA has also
described situations where possible positive associations may
actually be overstated due to confounding by other chemicals.
67
PUBLIC COMMENTS:
EPA is to be congratulated for a much more
realistic interpretation of the epidemiology
data base for MC. We question the
characterization of "inconclusive" results as
Thank you for your comment.
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"limited" evidence of anything, but otherwise
commend EPA's recognition that the cohort
studies do not show a cancer risk.
67
PUBLIC COMMENTS:
The cohort studies have many features that
make them useful for evaluating potential
health effects associated with MC.
Considered as a whole, the available
epidemiological evidence does not indicate a
cancer risk associated with occupational
exposures to MC. The studies consistently
demonstrate no excess mortality for all
causes of death, total cancer, and the cancers
that were observed in the one positive mouse
bioassay (lung and liver cancers).
Moreover, a recently published
comprehensive study of chlorinated solvents
and brain cancer found no association
between exposure to any of six chlorinated
solvents, including MC, and glioma risk
(Ruder et al., 2013).
In conclusion, the absence of associations in
well-defined cohorts having experienced
high exposures suggests that the carcinogenic
hazard of MC to man is extremely low or
non-existent, as summarized in the review by
Dell et al. (1999). The strong and consistent
cohort studies showing no increase in cancer
risk should accordingly be determinative in
characterizing that risk.
EPA agrees that it is important to consider the cohort studies.
However, several epidemiological studies did identify associations
between MC and various cancers. Also, EPA identified
methodological issues that may make it difficult to measure the
association between MC and cancer in humans as identified in the
risk evaluation.
EPA described the results of Ruder et al. (2013) in this risk
evaluation.
EPA has considered all of the studies, including the cohort and case-
control studies. As noted in the risk evaluation, most of the cohort
studies used SMRs or standard incidence rates (SIRs), which use
rates from the full population; therefore, there are possible important
differences between the workers and the comparison group. Thus,
even though the cohort studies have some strong attributes, EPA
doesn't believe that they are determinative by themselves and need
to be considered with the case-control studies as well as the animal
and mechanistic data.
Epidemiological data - application of systematic review
SACC
SACC COMMENTS:
The Committee recommends improvement of
the systematic review process, including the
definition and use of "unacceptable" studies
in TSCA risk evaluations. The Committee
EPA has outlined specific criteria for identifying a study as
unacceptable in Application of Systematic Review in TSCA Risk
Evaluations. Note that EPA considered single dose studies as not
relevant (vs. unacceptable from a quality perspective) when
considering studies for the dose-response process; they were
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reiterates that single dose studies can contain
useful information and should not be ranked
"unacceptable" just for having a single dose.
Recommendation: Develop quality
assessment criteria for human studies to be
included in its systematic review methods
prior to review by NAS.
excluded during the screening steps. However, previous studies in
authoritative sources (e.g., the IRIS assessment) were sent forward
for data evaluation regardless of whether they were a single dose
study.
EPA will develop criteria for human experimental studies for
upcoming assessments.
73
PUBLIC COMMENTS:
The rationale presented for certain ratings
within influential criteria is inadequate or
flawed, thus negatively influencing the
agency's confidence rating of particular
studies. For example, the agency concluded
that relying on National Air Toxics
Assessment (NATA) data for exposure
measurements was insufficient with respect
to the relationship between exposure and
autism spectrum disorder for four
epidemiological studies.
EPA revised the discussion of the NATA data in the weight of
scientific evidence section (Section 3.2.4.1.4) to focus primarily on
the concern related to some of the studies that used multiple years of
NATA data. Although EPA had previously suggested that exposure
data specific to individual months as used bv von Ehrenstein et al.
(2014) might be more closelv aligned with vulnerable exposure
periods, stronger associations have been identified for the first year
of life in one study of pesticide exposure compared with prenatal
exposures, suggesting the potential that a full year (and the first year
of life) mav be an important developmental period (von Ehrenstein
et al. 2019).
Cancer hazard evidence integration
SACC
SACC COMMENTS:
The lack of evidence for cancer risk in
epidemiological studies is not compelling.
Humans are so genetically variable, with so
many other exposures and complicating
issues, that it is difficult and often rare to find
associations in epidemiological studies.
Animal studies reveal a clear association
with liver cancer. In terms of lung cancer,
there is clear evidence of a link in animals
exposed via inhalation, and some evidence
for oral exposure. There is some evidence of
a link between MC exposure and breast
cancer in animals. Consequently, it made
sense to use the animal data for the risk
evaluation.
Thank you for your comment. EPA agrees that the use of animal
data is appropriate in this risk evaluation.
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41,45,
46, 56,
68, 44
PUBLIC COMMENTS:
Regarding potential cancer risks, there are
several medium to high-quality
epidemiological studies available for
occupational populations, which do not
demonstrate evidence of carcinogenic hazard.
Yet, these studies were deemed "uncertain"
and "inconclusive" by EPA and largely
discarded in the hazard assessment for MC.
Where animal and human (and possibly
mechanistic) evidence fail to align, it is clear
that more objective and verifiable methods
are needed for evidence integration.
EPA has comprehensively evaluated the human and animal studies
for MC. Although many epidemiological studies may have been
conducted adequately, there are still inherent aspects of some of
these studies, such as lack of control for co-exposure to other
chemicals that are associated with the same outcome, that make it
difficult to either fully understand the true relationship between MC
and cancer or use the studies quantitatively in a risk evaluation.
However, EPA clearly identified relevant issues and described the
logic regarding which endpoints and studies would be considered for
dose-response in the weight of evidence section.
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.
The human relevance of mouse tumor data is uncertain
SACC,
67
SACC COMMENTS:
The decision to base the risk assessment on
mouse data was questioned, since mice have
greater GST-T1 activity than rats or humans
and this may make mice more susceptible to
getting these types of tumors.
Recommendation: Add information on the
relevance of mouse data to humans.
Recommendation: Include a discussion of the
issue of whether MC itself or its metabolites
(or both) are causing the observed effects.
PUBLIC COMMENTS:
In light of the draft risk evaluation's sound
interpretation of the cancer epidemiology
data, its continued characterization of MC as
"likely carcinogenic in humans," based on
the mouse lung and liver tumors observed in
EPA added more details about the relevance of mouse data to
humans and the fact that metabolites are expected to be the toxic
moiety.
Upon review of the evidence, EPA considers MC to be "likely
carcinogenic in humans." Because 1) metabolites of MC via the
GSTT1 pathway are genotoxic; 2) GSTT1 activity is not likely to be
completely absent at lower concentrations; and 3) no alternate MOA
has adequate support, EPA followed the recommendation of the
2005 Guidelines for Carcinogen Risk Assessment CEP A, 2005b) to
use linear low dose extrapolation. EPA already discusses
uncertainties regarding whether genotoxicity will be observed at
lower concentrations (see Section 4.3.5: Key Assumptions and
Uncertainties in the Human Health Hazards).
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a high-dose bioassay, is no longer
appropriate.
A mutagenic MO A for MC cannot be
scientifically justified when there appears to
be a kinetic threshold at 500 ppm where
genotoxicity (and thus tumors) is unlikely to
occur. If the best available science is to be
used in the risk evaluation for MC, EPA must
take into account the dose-response changes
for both the kinetics of MC metabolism and
the genotoxicity, which together point to a
threshold dose-response being the most
appropriate for estimating human cancer risk.
IUR POC
>/modeling
73
PUBLIC COMMENTS:
EPA should default to classifying acidophilic
and basophilic cell foci from Aiso et al.
(2014) as preneoplastic and thus also include
them in the Benchmark Dose Software
(BMDS) multi-tumor model.
EPA disagrees. Aiso et al. (2014) identified acidophilic and
basophilic foci in rats but not mice after chronic inhalation exposure.
An oral study also identified altered liver foci (Serota et al., 1986).
Because one study identified them in rats and not mice and saw few
tumors in rats and because both studies showed that liver foci were
not correlated with tumors, EPA considers them most likely to be
non-neoplastic.
The IUR calculations are not transparent
SACC
SACC COMMENTS:
The inhalation unit risk values developed for
this MC risk evaluation are less protective
than previous dose-response assessments by
EPA and OSHA, all of which relied on the
same underlying data. The risk evaluation
should mention this, explain why new
inhalation unit risks were derived, and
describe exactly how they differ from
previous assessments.
In addition, more discussion is needed to
support the decision to estimate risk using
liver and lung tumors when the calculation of
IUR based on mammary tumors gives the
EPA has added more information to explain the difference between
the IRIS assessment and the current MC risk evaluation. Because the
IUR is based on the lower 95% confidence limit, EPA considered
that this adequately covers the risk for the GSTT1 +/+ population
and that previous assessments were more conservative than
necessary by combining both the GSTT1 +/+ population and the
lower 95% confidence limit.
EPA has discussed the reasons that the mammary tumors were not
used to quantitate risk (See Section 4.3.5).
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highest unit risk.
Recommendation: Add rationale for not
using mammary tumors as an endpoint as
other evaluations have done.
73
PUBLIC COMMENTS:
Despite the fact that Aiso et al. (2014)
identified evidence of carcinogenicity at a
lower dose (1000 ppm) than NTP 1986,
OPPT (Table 3-20, p. 281) presents
calculations suggesting that the IUR based on
the NTP study is actually higher than that
based on the Aiso et al. (1986) study. EPA
must address these apparent inconsistencies
as well as explain the details of these crucial
calculations much more transparently, as
they serve as the basis for its cancer IURs.
Although Also et al. (1 identified carcinogenicity at a lower
concentration, the BMD modeling results were nearly identical for
both studies resulting in similar IURs. EPA added clarifying
language in the dose-response section (Section 3.2.5.2.2).
Furthermore, Appendix I includes details regarding the steps used to
determine the IUR, and the supplemental file Methylene Chloride
Benchmark Dose and PBPK Modeling Report (EPA. 2019a)
presents more details on the models used.
IUR - Consideration of GST
73
PUBLIC COMMENTS:
EPA's IUR calculation gives insufficient
consideration to susceptible subpopulations,
because EPA sampled from the "full
distribution of GST-T genotypes in the
human population". This approach was
rejected by EPA in its 2011 IRIS assessment.
EPA should follow the IRIS-recommended
approach in its final evaluation and adjust the
IUR accordingly.
It should also provide a fuller explanation of
all the differences in the IUR calculation in
the draft risk evaluation as compared to the
2011 and 2014 IURs and how they impacted
the estimates of cancer risk.
EPA did sufficiently consider susceptible subpopulations. EPA has
added more information to explain the difference between the IRIS
assessment and the current MC risk evaluation. Because the IUR is
based on the lower 95% confidence limit, EPA considered that this
adequately covers the risk for the GSTT1 +/+ population and that
previous assessments (which modeled the GSTT +/+ directly) were
more conservative than necessary by combining both the GSTT1
+/+ population and the lower 95% confidence limit. The previous
IUR is 75%) higher than the updated IUR.
73
PUBLIC COMMENTS:
EPA selected the "whole-body GST metric"
(i.e., not tissue-specific values) in estimating
the combined liver and lung tumor IUR.
The whole-body GST metric is based on a combination of individual
liver and lung tissue specific values and is necessary when
combining the lung and liver tumors in a single dose-response
relationship. This is explained in the risk evaluation (Section
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There is inadequate explanation for the
crucial decision to select the whole-body
rather than tissue-specific metric. EPA must
provide further details on the scientific
rationale for this choice, which directly
affects the IUR estimate.
3.2.5.2.2).
IUR does not account for other cancers identified from epidemiological data
SACC,
55, 75
SACC COMMENTS:
Recommendation: Model the dose responses
from epidemiological studies and compare
these with the dose-response models from the
rodent studies to confirm HEC and IUR for
chronic and cancer effects, respectively, are
sufficiently conservative and health
protective.
PUBLIC COMMENTS:
SACC should recommend to EPA that it
quantitatively include the NHL and biliary
cancer risks from MC exposure, and other
cancer risks, with additional adjustment
factors.
Based on the variability in results of the epidemiological studies,
EPA determined that the studies are appropriately used qualitatively
to support the hazard endpoint in a weight of scientific evidence
analysis.
75
PUBLIC COMMENTS:
Despite the evidence of breast cancer risks,
EPA failed to base the IUR on this endpoint
for the following three reasons: (1) only a
small number of tumors in animal studies
progressed to malignancy; (2) the dose-
metric was not certain; and (3) data on
mutagenicity in these tissues is lacking.
These considerations are inappropriate,
unscientific, and inconsistent with EPA's
Guidelines.
EPA cited information in the risk evaluation that identified the low
conversion from benign to malignant tumors (see Section 4.3.5, Key
Assumptions and Uncertainties in the Human Health Hazards).
Specifically, with respect to mammarv tumors. Russo (
indicates that 0.1% of fibroadenomas lead to carcinomas. Therefore,
EPA considers our conclusion to be appropriate.
Genotoxicity data
SACC
SACC COMMENTS:
Recommendation: Conduct a data quality
evaluation on all in vivo and in vitro
EPA conducted data quality evaluations for all genotoxicity studies
and described the results in the risk evaluation (Section 3.2.3.2.1;
Appendix K).
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genotoxicity studies included in the MC risk
evaluation as described in the application of
systematic review in TSCA risk evaluations.
SACC,
68
SACC COMMENTS:
Recommendation: For in vitro genotoxicity
studies, provide an in vitro to in vivo
exposure extrapolation assessment to
estimate equivalent in vivo exposures needed
to produce genotoxicity based on in vitro
genotoxicity observations.
PUBLIC COMMENTS:
EPA should consider all possible MO As
using the I PCS/WHO framework and
methods to consider confidence in the MO As
(Becker et al. 2017).
EPA acknowledges that this type of extrapolation does have merit.
Because there are several in vivo genotoxicity studies available for
MC, EPA will not consider in vitro to in vivo extrapolation for MC.
EPA has considered multiple modes of action and revised the risk
evaluation to include more discussion of multiple MOAs.
Support
'or mutagenic MOA/linear low dose extrapolation and alternate MOAs
34, 56,
59, 67,
68, 73
SACC COMMENTS:
Recommendation: Include models based on
alternative updated MOAs developed by
Andersen et al. (2017) and others applying
the PBPK model and assumptions within the
model, specifically using the internal dose
metric of daily mass of MC metabolized into
COHb per Andersen et al. (2017) and other
alternative MOAs identified by EPA.
Recommendation: Include the alternative
updated MO A developed by Andersen et al.
(2017) and all other likely mechanisms and,
through WOE evaluations, provide the
rationale justifying the MOA for MC-
induced mouse liver and lung tumors.
The risk evaluation should include dose-
response modeling under both the mutagenic
and the non-genotoxic mechanisms, and then
provide justification for the choice of model
used.
Although Andersen et al. (2017) provides an interesting hypothesis
regarding a possible MOA, EPA believes that specific mechanisms
that might be possible haven't been demonstrated for MC.
Furthermore, to EPA's knowledge, an adverse outcome pathway
(AOP) describing the molecular initiating and key events hasn't
been well established for hypoxia leading to changes in the circadian
clock and then subsequently to cancer. For example, EPA found no
AOP in development on the AOP wiki (fattps://aopwiki.org/) or any
articles describing relevant MOAs or AOPs in a brief search on
PubMed.
EPA still considers a mutagenic MOA related to the metabolism of
MC by the GSTT1 isoenzyme as having the most support and
relevance to human health risk, despite some uncertainties. EPA has
added more discussion of these uncertainties to the risk evaluation.
Details regarding the MOA suggested bv Andersen et al. f
include identified changes in gene expression in mice exposed to
MC, with marked changes occurring in several genes associated
with circadian clocks. Results indicate that liver and lung tumors
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One Committee member commented on
interspecies extrapolation and developing the
human-equivalent dose metric and stated the
risk evaluation provided no reason for using
the default ratio in the model.
PUBLIC COMMENTS:
Several public commenters representing the
HSIA and the American Chemistry Council
(ACC) and some SACC members urged EPA
to consider a 2017 study by Anderson et al.,
which uses transcriptomics to evaluate
pathways activated in response to MC
exposure, arguing it provides evidence for a
non-mutagenic cancer MOA. EPA should
consider these speculative findings within the
context of the extensive and strong evidence
base (from epidemiological, in vivo, and in
vitro studies) supporting a mutagenic MOA
(pp. 245-246).
It is time to reexamine the evidence
supporting this genotoxic MOA for MC,
especially in light of the toxicogenomic
studies and identification of altered oxygen-
utilizing pathways and circadian cycle
disruption as key events in cancer
development.
Risk assessments for MC should focus on
elevations in COHb rather than presumptions
of a linear, no-threshold risk model based on
production of glutathione-pathway
metabolites for which there is only limited
evidence of mutagenicity in engineered
bacterial assays.
At the very least, the present draft TSCA risk
from MC exposure appear to be related to core changes in circadian
processes in liver and lung tissue. Andersen et al. (2 also link
circadian rhythms to metabolism showing different patterns in lung
versus liver tissue. The common circadian clock effects are for
genes that code for regulatory proteins. The authors also identified
decreased tissue oxygenation from elevated COHb and the altered
association of reduced oxygenation to both circadian cycle proteins
and tissue metabolism as the likely mode of action (MOA) for tissue
responses to MC, but they note that this conclusion is tentative.
In other research, changes in circadian rhythm have been associated
with cancer, and some research also links hypoxia to changes in the
circadian clock, tare (2 assigned night shift work as Group 2A,
probably carcinogenic to humans, based on "limited evidence of
cancer in humans, sufficient evidence of cancer in experimental
animals, and strong mechanistic evidence in experimental animals."
Iarc ( also briefly described the mechanistic evidence
regarding association between changes in the circadian clock and
cancer. Enhanced inflammation was observed in rats. In addition,
studies that evaluated changes in light-dark schedules directly
measured increased cell proliferation in transplanted tumors.
Furthermore, immune suppression was identified in nocturnal rats,
mice and Siberian hamsters. Finally, altered tumor glucose
metabolism was observed in female nude rats, consistent with the
Warburg effect (glucose fermentation in cancer cells). In addition to
the link between changes in the circadian clock and cancer, hypoxia
has been shown to result in some changes in the circadian clock
(Andersen et al.. 2017).
Some of the mechanistic steps identified in the Iarc (2019) review
regarding the induction of tumors via changes in the circadian clock
have not been established for MC. In particular, enhanced cell
proliferation was either not observed in livers of mice after 78 weeks
(Foley et al.. 1993) as cited in U.S. EPA. (2011). or proliferation
from acute and short-term exposure was not sustained after longer
(83-93 days) exposure (Casanova et al.. 1996; Foster et al... 1992) as
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evaluation for MC should acknowledge the
more recent MOA studies - including both
toxicogenomic evaluations and improved
PBPK models - that cast considerable doubt
on the role of short-lived, reactive
glutathione pathway metabolites as causative
for mouse lung and liver tumors.
EPA should more clearly and transparently
present biologically robust, MOA
assessments where the weight of the
evidence is integrated fully. EPA should
carry any biologically plausible alternative
MO As and the default MOA option through
the entire assessment and present all risk
calculations in the risk characterization
section.
cited in In addition, although MC has been
associated with immunosuppression (Aramyi et al. 1986), EPA has
concluded that the evidence is limited.
In addition to the MOA suggested bv Andersen, et al. f! , no
other information was robust enough to consider as a biologically
plausible MOA with enough support to carry forward in a
comparison with the genotoxic MOA.
For interspecies extrapolation to develop the human equivalent
concentration, EPA applied a value of BW3 4 based on a lack of MC-
specific information on the pharmacokinetic differences between
laboratory animals (mice and rats for MC) and humans. Use of
BW3/4 represents our general understanding that metabolic clearance
scales allometrically across species. EPA added this reason to
Section 3.2.5.2.2 (dose-response for chronic endpoints) of the risk
evaluation. The reason is already in Appendix I.
73,75
PUBLIC COMMENTS:
Given: (1) existing agency guidance, (2) the
many sources of variability in the human
population, (3) TSCA's mandate to protect
"potentially exposed or susceptible
subpopulations," and (4) the clear presence
of individuals with preexisting health
conditions, metabolic or genetic variability,
or other factors that make them more
susceptible to MC exposure (see, for
example, pp. 275, 386), the use of the linear
extrapolation is the only appropriate option
for cancer dose-response modeling. EPA also
must use this approach to cancer dose-
response modeling to comply with EPA's
duty to consider the "best available science"
under TSCA§ 26(h).
Thank you and EPA agrees with this comment.
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EPA should use established framework for alternative MOA evaluation
68
PUBLIC COMMENTS:
EPA should utilize an established framework
to organize evidence for MOA based on side-
by-side WOE comparison of alternative
plausible MO As (e.g., OECD AOP
methodology, WHO/IPCS MOA framework,
MOA confidence scores, as described by
Becker et al., 2017). Standard MOA
templates, such as the dose/temporal
concordance and species concordance
templates, can be utilized.
EPA evaluated all available evidence, including mechanistic
information, related to MO As and presented the information in
Section 3.3.4. EPA considered aspects of the MOA framework (e.g.
related to Bradford Hill criteria, whether information was available
that indicates key events) when evaluating the available data for
methylene chloride.
Route-to-route extrapolation for dermal POD
SACC
SACC COMMENTS:
Recommendation: Add further justification
for inhalation-to-dermal extrapolation.
Schenk et al. (2018) recently measured the
permeability coefficient and steady-state flux
of 38 VOCs, including MC, for newborn pig
skin in static diffusion cells.
EPA has added more justification to the use of inhalation data for
the route-to-route extrapolation to the dermal route to Section
3.2.5.2.3 (Route to Route Extrapolation for Dermal PODs). Note
that the specific information on adjustment for any
absorption/permeation is described in the exposure sections.
EPA used the permeability coefficient from Schenk et al. (2018) in
the dermal calculations.
73
PUBLIC COMMENTS:
EPA has made inappropriate assumptions
about activity rates in its route-to-route
extrapolation for dermal PODs. By assuming
only "light activity" in this draft risk
evaluation, EPA ignores the potential
elevated risk faced by high-activity
individuals.
To extrapolate dermal PODs from inhalation PODs, EPA calculated
human equivalent doses based on an inhalation rate of 1.25m3/hr as
recommended in EPA's Engineering Manual (cited in an EPA
internal document titled Chemical Engineering Branch Manual for
the Preparation of Engineering Assessments, 1991). That value is
based on a standard estimate that the typical worker inhales 10m3
over the course of an 8 hour workday (Nuclear Regulatory
Commission, 2007) and is taken from Niosh (1976). This is the
same breathing rate assumption that is used for occupational
exposure limits. The daily average value of 1.25m3/hr is slightly
higher than the inhalation rate for light work (1.18m3/hr) and below
the inhalation rate for moderate work (1.75m3/hr) estimated by
NIOSH (1976).
Note also that assuming a higher inhalation rate based on moderate
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intensity work for the purposes of route-to-route POD extrapolation
would result in a higher POD that may not be appropriate or
adequately health protective for all exposure scenarios.
68
PUBLIC COMMENTS:
EPA should expand the discussion of the
uncertainty associated with the route-to-
route extrapolation for dermal hazard
evaluation. Several points to clarify in the
hazard assessment section could include
regulatory precedent, toxicokinetics, route
dosimetry and irritation hazard.
EPA has added more information on the uncertainties to Section 4.3,
Assumptions and Key Sources of Uncertainty.
Due to the dermal contact effects, which include irritation and burns,
direct dermal contact with liquid MC should be avoided. Gloves and
protective clothing are required in the OSHA standard for workers
and when we assume dermal PPE is used, risks to workers are not
identified, even with the conservative dermal POD.
75
PUBLIC COMMENTS:
Uncertainty relating to the absence of
toxicity data for the dermal route of exposure
could be considered a "data-base deficiency"
warranting an additional UF in determining a
benchmark MOE for acute and chronic
dermal exposure.
There is no universal list of hazard data required when evaluating
chemical risks under TSCA. Furthermore, for methylene chloride,
EPA has sufficient, reasonably available hazard information to
conduct a risk evaluation and support the use of the chosen hazard
endpoints. Therefore, EPA did not use a database uncertainty factor
in the methylene chloride risk evaluation.
Consistency with TSCA requirements
67
PUBLIC COMMENTS:
The criteria for interpretation and analysis
are policy choices resulting in the regulatory
use of an upper confidence limit value
calculated using only a selected part of the
data. This is not in accordance with TSCA §
26(h) and (i).
The draft risk evaluation's reliance on the
2011 IRIS Assessment is inappropriate in
light of the intervening passage of the
Lautenberg Act with its requirements that
EPA use the best available science and base
its decisions on the weight of the scientific
evidence. Indeed, the IRIS Assessment used
a "strength of the evidence" approach,
whereas TSCA § 26(i) expressly requires
"decisions under sections 4, 5, and 6 [to be]
EPA used the lower 95th confidence bound of the dose-response to
choose a POD to estimate the cancer slope factor for use in the risk
evaluation. As suggested by EPAs' 2005 Guidelines for Carcinogen
Risk Assessment (EPA. 2005b) this lower bound can be used to
account for uncertainties in the assessment. EPA considered the use
of this lower bound to be appropriate for the current assessment.
EPA re-evaluated studies identified in the IRIS assessment and also
applied a systematic review process developed specifically for the
TSCA risk evaluations, including our own data quality criteria. EPA
has added more information to the weight of scientific evidence
section to explain EPA's consideration of other possible MO As,
namely the one suggested by Andersen et al. (2.017) and thus has
based its decisions on the weight of the scientific evidence.
EPA disagrees with departing from application of the 2005
Guidelines for Carcinogen Risk Assessment (EPA. 2005b) because
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based on the weight of the scientific
evidence."
The Guidelines recognize that there may be
scientific advances not consistent with the
policy-based assumptions and the Guidelines
accordingly authorize departure in certain
cases from the policy default options. A
departure is authorized, indeed necessary, in
the case of MC.
no scientific advances that would lead the Agency to depart from the
assumptions used have been identified for MC.
Expand toxicokinetics section
SACC
SACC COMMENTS:
Recommendation: Add more explanation to
the toxicokinetics section. Pertinent
information on interspecies differences in the
metabolism and TK of MC needs to be
presented (i.e., GST metabolism in the liver,
CYP in the lung).
EPA added more summary and comparative information to the
toxicokinetics section (Section 3.2.2).
73
PUBLIC COMMENTS:
In the discussion of toxicokinetics (Section
3.2.2), EPA has neglected to acknowledge
the potential for placental transfer of MC, as
documented in the 2011 IRIS assessment.
EPA has added more information on placental transfer to the
toxicokinetics section (Section 3.2.2).
Present t
ose-specific risks for cancer and non-cancer
73
PUBLIC COMMENTS:
EPA should implement the recommendations
of the NAS and develop a unified approach
to presenting dose-specific population risks
for both cancer and non-cancer endpoints.
EPA relied on existing accepted guidance (e.g., (EPA. 2012a, 2005a.
2002)) to evaluate noncancer and cancer endooints in the current
risk evaluation of methylene chloride. These methods include PBPK
models for chronic endpoints that use MC-specific distributional
information on toxicokinetics among rodents and humans;
appropriate uncertainty factors for non-cancer endpoints; and a
linear low-dose extrapolation to model risk from cancer, based on a
likely genotoxic MOA. EPA believes that these methods adequately
account for variability and susceptibility within the population, a
concern raised by NRC (2009). However, EPA will investigate
additional scientific approaches for our next set of TSCA risk
evaluations.
General
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SACC
SACC COMMENTS:
The prediction from Benignus et al. (2011)
that the frequency of fatal car accidents may
increase at exposures <1 ppm is questionable,
and data from other studies included in the
risk evaluation could be used to establish a
LOAEL of 200-300 ppm.
The risk evaluation misinterpreted the
rationale of NAS (2009) in setting its 8-hour
AEGL-2 at 60 ppm.
Decrements in performance in humans
inhaling up to 751 ppm for 230 minutes were
not considered severe enough to significantly
impair one's ability to escape a dangerous
environment, and thus were not used as the
basis of the AEGL-2 derivation.
The values were instead based upon PBPK
model simulations of COHb levels at
selected exposure times.
The main reason that Benignus et al. (2011) was discussed was to
underscore the potential for the association with increased car
accidents related to solvent use (which could be a surrogate for
workplace accidents); reference to specific concentrations from the
study was removed. Reference to the NAS AEGL-2 value in Section
3.2.3.1.1 was removed.
AEGL-2 is a level to protect against disabling effects whereas EPA
is protecting against effects of lower severity as well. Furthermore,
EPA has reviewed all studies and has determined that Putz et al.
'9) can be used to set the POD.
See response to commenters # 67, 73 and 45 in the second row in
section "Comments on use of ten Berge approach for acute POD"
SACC
SACC COMMENTS:
The risk evaluation needs to justify why its
analysis approach differs from the EPA's
National Center for Environmental
Assessment (NCEA) recommendation to use
trend tests over pairwise tests.
EPA described the reasons in the supplemental file Methylene
Chloride Benchmark Dose and PBPK Modeling Report. The
endpoints not chosen generally also had unclear dose-response
relationships and/or had incidences that noticeably lower than liver
and lung tumors.
SACC
SACC COMMENTS:
Additional discussion is needed regarding
direct vs. indirect (i.e., systemic or blood-
based) endpoints due to the acknowledged
requirement for metabolism for toxic effect.
See response to commenters # 67, 73 and 45 in the second row in
section "Comments on use of ten Berge approach for acute POD"
SACC
SACC COMMENTS:
Add more details to Table 3-20 (i.e., spell out
what the models are, include how long the
simulations were run).
EPA has added more details to Table 3-20
SACC
SACC COMMENTS:
EPA added this information to Section 3.2.5.2.1 of the risk
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p. 274, lines 6275-6278: EPA fails to
mention that exercise increases the rates of
respiration (alveolar ventilation) and cardiac
output, two factors important in increasing
systemic uptake of VOCs such as MC.
evaluation.
SACC
SACC COMMENTS:
The Agency has not adequately addressed the
topic of adverse myocardial effects of VOCs.
EPA added information on cardiac effects in dogs to the hazard
identification section on non-cancer effects from acute/short-term
exposure (Section 3.2.3.1.1). These studies identify effects (such as
cardiac sensitization - ventricular tachycardia or fibrillation and
other effects) at 15,000 ppm or higher after very short-term
exposures.
In answer to the SACC question regarding whether such data are
relevant to hypoxia-induced angina, the answer is less clear. COHb
levels of 2-4.5% that have been identified as being associated with
decreased time to angina are applicable to much lower MC
concentrations (< 195 ppm) than the concentrations used in the MC
cardiac sensitization studies.
EPA considers that the uncertainty factor of 10 for intra-individual
variability to account for this effect in individuals with cardiac
disease. Use of an uncertainty factor is appropriate to protect the
susceptible subpopulation of individuals with cardiac disease and
because the direct effects of MC on this population have not been
systematically studied.
67
PUBLIC COMMENTS:
The draft risk evaluation contains no
discussion of scientific issues raised by HSIA
and other commenters on both the draft IRIS
Assessment and the draft MC Work Plan
Assessment released for review in 2014.
EPA responded to comments on the draft IRIS assessment in the
final IRIS assessment. EPA also summarized and responded to
comments on the draft MC work plan assessment and provided
those responses to the public
(https://www.em.gov/sites/i3rQduction/ftles/2015-
09/documents/dcm resDonsetocomments final.odf). Finally, EPA
has added details to various sections of the current risk evaluation to
further elaborate on scientific issues raised by the comments on the
current draft risk evaluation.
43
PUBLIC COMMENTS:
It would be helpful to have better information
Bornschein et £ 0) found delayed rates of behavioral
habituation to novel environments in offspring from female rats
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on development neurotoxicity in order to
determine if the acute PODs based upon
adult data are protective of the fetus, infants,
and children.
exposed to 4500 ppm MC via inhalation before and/or during
gestation. No similar studies with multiple and lower exposure
concentrations are available. However, five studies on autism found
positive associations with MC (not always statistically significant).
For various methodological reasons that include confounding by
other chemicals and lack of temporal specificity, EPA did not use
these studies in the risk evaluation, but they do identify a
neurodevelopmental hazard for humans.
66
PUBLIC COMMENTS:
One concern in evaluating this document was
a lack of discussion of potential bias of some
sourced material. The use and inclusion of
corporate sponsored studies could influence
how health protective this section and the
EPAs recommendations are.
EPA evaluated the merits of the individual studies in the data quality
evaluations for each study. The specific metrics within the data
quality evaluation domains address several types of biases. EPA
considered this approach to be appropriate so that each study,
regardless of sponsorship, can be evaluated in a consistent manner.
SACC,
44, 49,
72, 75,
69
SACC COMMENTS:
Increase use of the human lethality data. MC
has been linked to more than 60 deaths
nationwide since 1980 (reference: Safer
Chemicals, Healthy Families). One
Committee member suggested that the few
case reports in Appendix J address this issue
insufficiently.
PUBLIC COMMENTS:
Fatality reports from OSHA and the
Massachusetts Department of Public Health
are attached to these comments as Exhibit B.
Data from a comprehensive review of 10
sources, all of which are reasonably available
to EPA, identified 85 unique deaths related to
acute methylene chloride exposure from
1980-2018.
EPA reviewed the sources cited in the SACC and public comments
and has updated the text of Appendix J appropriately including
reference to the updated compilation of 85 deaths. Note that the
same fatalities are often described in multiple data sources. Exhibit
B was mentioned in the submitter's comment but was not included
as an attachment/available in the docket; therefore, EPA could not
review the information.
Editorial
SACC,
49
SACC and PUBLIC COMMENTS:
The SACC and public comments provided
many suggestions for editorial comments that
EPA considered and revised many of the editorial suggestions and
comments provided by the SACC and the public.
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EPA will consider.
Risk CharacU'ri/alion
EPA calculated em ironmeiilal risk using exposure data (e.g. modeling tools and monitored dalasels) and em ironmental toxicity
information, accounting for variability within the environment. EPA concludes that methylene chloride poses a hazard to environmental
aquatic receptors, with amphibians being the most sensitive taxa identified for aquatic exposures. Risk Quotients (RQs) and the number
of days a concentration of concern (COC) was exceeded were used to assess environmental risks. The risk characterization section
provides a discussion of the risk and uncertainties around the risk calculations.
EPA calculated human health risks for acute and chronic exposures. For non-cancer effects EPA used a margin of exposure (MOE),
which is the ratio of the hazard value to the exposure to calculate human health risks. Using an acute non-cancer POD, EPA evaluated
potential acute risks for workers for certain scenarios, consumer users and bystanders/non-users (e.g., children, women of childbearing
age). A benchmark MOE of 30 was used with the acute POD based on central nervous system (CNS) effects. For chronic occupational
risks, EPA used a POD for liver effects as the basis of the chronic non-cancer MOE calculations. A benchmark MOE of 10 was used to
interpret chronic risks for workers. An IUR for liver and lung tumors was used to evaluate potential chronic risks to cancer endpoints
for the worker exposure scenarios. The risk characterization also provides a discussion of the uncertainties surrounding the risk
calculations.
Charge Question 6.1. Please comment on the characterization of uncertainties and assumptions including whether EPA has presented a
clear explanation of underlying assumptions, accurate contextualization of uncertainties and, as appropriate, the probabilities associated
with both optimistic and pessimistic projections, including best-case and worst-case scenarios.
Charge Question 6.2. Please provide information on additional uncertainties and assumptions that EPA has not adequately presented.
Charge Question 6.3. Please comment on whether the information presented supports the findings outlined in the draft risk
characterization section.
Charge Question 6.4. Please comment on the objectivity of the underlying data used to support the risk characterization and the
sensitivity of the agency's conclusions to analytic assumptions made.
Risk Characterization: The EPA risk characterization of human health risk from inhalation exposure to workers includes estimates of
risk for respirator use. These estimates are calculated by multiplying the high end and central tendency MOE or extra cancer risk
estimates without respirator use by the respirator assigned protection factors (APFs) of 25 and 50 (air-supplied respirators). EPA did not
assume occupational non users (ONUs) or consumers used personal protective equipment in the risk estimation process.
Charge Question 6.5. Please comment on whether EPA has adequately, clearly, and appropriately presented the reasoning, approach,
assumptions, and uncertainties for characterizing risk to workers using air-supplied respirators and to ONUs and consumers who would
not be expected to use PPE.
#
Summary ol*Comments lor Specific Issues Related
to Charge Question 6
KPA/OPPT Response
Overall characterization of uncertainties and assumptions
SACC
SACC COMMENTS:
EPA has added language to uncertainties section describing
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One Committee member stated that there are many
lingering uncertainties still pervasive in many
aspects of the exposure assessment and the risk
characterization.
Recommendation: Add more UFs or better explain
the rationale for not doing so.
multiple analyses including for the exposure analysis and
risk characterization.
EPA considers the current UFs to be sufficient to cover
uncertainty and variability in the PODs that have been
chosen. EPA added more discussion of the choice of UFs in
the risk evaluation.
SACC, 53,
73
SACC COMMENTS:
The Committee members observed that increased
monitoring efforts (occupational and
environmental), coupled with a Bayesian
framework could help reduce uncertainty.
Recommendation: Consider following NRC
recommendations to use Bayesian UFs in the
development of criteria for risk assessment
purposes.
PUBLIC COMMENTS:
There are fundamental flaws in the Simon et al.
(2016) implementation of Bayesian/probabilistic
methods. A more comprehensive and rigorous
framework for probabilistic analysis that already
exists in the form of a WHO/IPCS guidance
document (WHO/IPCS, 2017b). Other references
that can be consulted include Chiu and Slob (2015),
Chiu et al. (2018), the APROBA tool on the WHO
website, APROBAweb, and the Bayesian
Benchmark Dose online web system
(benchmarkdose.org).
EPA must provide justification for their decision to
deviate from a Bayesian approach.
EPA used reasonably available information for the Risk
Evaluation of methylene chloride. In the current risk
evaluation, probabilistic models (Monte Carlo analyses)
were used in the dose-response models for chronic non-
cancer and cancer endpoints. Due to time and resource
constraints associated with the deadline for completing the
MC Risk Evaluation, EPA cannot implement a Bayesian
framework comprehensively for this risk evaluation;
however, EPA will consider incorporating more
probabilistic modeling into future risk evaluations under
TSCA.
66
PUBLIC COMMENTS:
It is unclear in some cases why a given UF was
chosen, and why a more health protective UF was
not used (e.g., Table 4-7; perhaps this was human
study, but not explained).
EPA explained the choice of uncertainty factors in Section
3.2.5.2 Derivation of PODs and UFs for Benchmark Margins
of Exposures (MOEs). Human data were used for the acute
POD.
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Interspecies and intraspecies UFs
SACC
SACC COMMENTS:
Several Committee members suggested that UFs
should account for differences among people that
arise from unknown factors, and not be used to
account for differences from known factors, such as
GST alleles. One Committee member noted GST
variation results in known subpopulations that
should be taken into consideration separately, and
not considered part of the general intraspecies UF.
The PBPK model does not consider breastfeeding
infants (a potentially exposed or susceptible
subpopulation), which Committee members
suggested may be an issue especially since cited
studies have found concentrations of MC in breast
milk (Pellizzari et al., 1982). Many felt this is a
justification for using an additional or larger UF.
EPA does not use uncertainty factors to account for the
GSTT1 +/+ polymorphism in the cancer assessment.
Regarding the cancer slope factor, the distribution of GSTT
+/+ was modeled using data, and a level of conservatism has
already been included in the cancer slope factor by using the
lower 95% confidence interval; this was the primary reason
that EPA did not add another level of conservatism by basing
the risk evaluation only on the GSTT1 +/+ population. Using
the 95th confidence interval can be quantitively understood
and can also encompass other uncertainties in addition to
differences in the presence of the GSTT1 isoenzyme.
EPA understands that the GSTT1 polymorphism can also
affect individuals' non-cancer responses. For the chronic
endpoint of liver toxicity, PBPK modeling relied on
metabolites of the CYP2E1 pathway and although the
GSTT1 polymorphism may affect the outcome, it is not well
understood. For the acute non-cancer CNS endpoint, the
GSTT1 polymorphism might influence the amount of CO
metabolite available leading to differences in COHb;
however, the effect was measured in humans so some
GSTT1 distributions should be represented, even given the
small sample sizes.
Overall, EPA believes that for the non-cancer endpoints, the
intraspecies uncertainty factor of 10 is adequate to protect
susceptible populations including the GSTT1 polymorphism
as well as breastfeeding infants.
45, 49, 55,
44, 72, 75,
PUBLIC COMMENTS:
EPA fails to apply certain necessary UFs and
departs from its recommended values for others
without an adequate explanation.
EPA has identified specific subgroups with
biological characteristics that make it likely that
they will experience adverse acute effects at lower
In previous assessments (e.g., the new chemicals program),
EPA has applied uncertainty factors of 3 instead of 10 when
effects are less severe. Furthermore, IRIS assessments have
used default uncertainty factors of 3 (EPA, 2002). The risk
evaluation states that this value was applied based on the
more limited severity of the effect (i.e., the 7% change in just
one part of a dual performance task).
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concentrations than healthy adults. To provide
protection to these groups, an UF beyond the
default intraspecies 10X factor should be applied, as
EPA has done for other susceptible groups such as
infants and children. An UF of at least 20X,
consistent with the EPA Supplemental Cancer
Guidance is suggested.
EPA should re-evaluate the approach applied and
the appropriateness of assumptions in light of extant
occupational assessments that have relied on the
same data and reached different conclusions.
EPA used an intraspecies UF of 10 in the risk evaluation,
which is expected to protect individuals with cardiac disease
that may experience decreased time to angina as well as
other susceptible populations. The intraspecies UF was
established to account for uncertainty and variability that
includes susceptible subooDulations (EPA. 2002). Research
indicates that a factor of 10 (when including both
toxicokinetics and toxicodynamics) is sufficient in most
cases (EPA. 2002), and EPA expects this factor to account for
the identified subpopulations applicable to methylene
chloride.
Occupational assessments may have other goals. For
example, OSHA, in their 1997 PEL document,
acknowledged that the PEL of 25 ppm considered feasibility
of meeting the level and that the PEL was associated with a
level resulting in a risk of 3.62 cancer deaths per 1000
population. Furthermore, OSHA notes this level is "clearly
well above any plausible upper boundary of the 'significant
risk' range defined by the Supreme Court, used by OSHA in
its prior rulemakings, and reported in the scientific/economic
literature on risk" (OSHA. 1997). In contrast amended
TSCA directs EPA to conduct the risk evaluation without
consideration for non-risk factors, such as feasibility of
meeting an applicable level.
49, 73, 75,
57
PUBLIC COMMENTS:
EPA has failed to justify its deviations from its
standard inter- and intra-species UFs.
Reducing the interspecies variability UF is
warranted only where there is evidence of
correspondence between human and animal
response.
EPA guidance likewise cautions against reductions
in the 10X UF for intraspecies variability.
For the non-cancer chronic liver endpoint, the portion of the
intraspecies uncertainty factor associated with toxicokinetics
(3) is not needed because EPA used the 1st percentile of the
distribution related to toxicokinetic differences in a PBPK
model. Using data derived factors is preferable to applying a
default uncertainty factor and EPA expects the use of the 1st
percentile to be protective of human health.
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Similarly, the portion of the interspecies uncertainty factor
that accounts for toxicokinetic differences between rats and
humans was accounted for by the PBPK model.
55
PUBLIC COMMENTS:
Because the MC chronic risk estimates are based on
liver toxicity, they do not address the risk of
neurological effects. It is suggested that EPA use
additional adjustment factors to address
neurological effects from chronic exposure to MC.
For methylene chloride, EPA has sufficient, reasonably
available hazard information to conduct a risk evaluation and
support the use of the chosen hazard endpoints.
43,41
PUBLIC COMMENTS:
The SACC should consider why EPA uses the first
percentile (HEC99) used for non-cancer effects,
particularly since an intraspecies UF of 3 is used.
EPA has not provided adequate evidence to show
that variability in sensitivity of specific
subpopulations (fetuses, workers and consumers
engaged in vigorous activity, individuals with
higher CYP2E1 enzyme levels, smokers and
individuals with heart disease/cardiac patients) is
accommodated by the UFH of 3X. A larger UFH,
perhaps 4.5X, should be applied.
EPA used the 1st percentile from the PBPK model to account
for variability and uncertainty in toxicokinetic differences
among humans; this chemical-specific modeled information
is preferable to using a default uncertainty factor. However,
there may also be toxicodynamic differences among humans.
Therefore, EPA considered that an intraspecies UF of 3 is
still appropriate, according to guidance and standard practice
(EPA. 2.002).
The commenter does not provide a quantitative reason for
suggesting 4.5 vs. 3 as the portion of UFh to account for
toxicodynamic differences among humans. Research
indicates that a factor of 10 (when including both
toxicokinetics and toxicodynamics) is sufficient in most
cases (EPA, 2002). Therefore, because the toxicokinetics
portion of the UF (rounded to 3) has been accounted for by
PBPK modeling, EPA considers that the toxicodynamic UF
of 3 is adequate. Furthermore, at least one of the susceptible
subpopulations identified by the commenter (individuals with
higher CYP2E1) would be accounted for by the use of the 1st
percentile from the PBPK modeling. EPA expects that the
PBPK modeling and UF of 3 to is sufficient for the identified
subpopulations applicable to methylene chloride.
SACC, 73
SACC COMMENTS:
There is no universal list of hazard data required when
evaluating chemical risks under TSCA. Furthermore, for
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The Committee questioned why a database UF
wasn't included, even if it is not historically used in
TSCA evaluations.
Recommendation: Improve the justification for the
UFs and/or changes to the UFs and consider
including a database UF.
PUBLIC COMMENTS:
Given potential deficiencies in the study database
for MC unrelated to study duration, we assert that
the Agency should use a database UF in the MOE
derivation.
In addition to identifying toxicity information that is
lacking, review of existing data may also suggest
that a lower reference value might result if
additional data were available.
Consequently, in deciding to apply this factor to
account for deficiencies in the available data set and
in identifying its magnitude, the assessor should
consider both the data lacking and the data available
for particular organ systems as well as life stages.
methylene chloride, EPA has sufficient, reasonably
available hazard information to conduct a risk evaluation
and support the use of the chosen hazard endpoints.
Therefore, EPA did not use a database uncertainty factor in
the methylene chloride risk evaluation.
49, 73, 75,
55, 43, 44,
72
PUBLIC COMMENTS:
EPA acknowledges that it lacks data about immune
system, reproductive, and/or developmental
endpoints for MC. Moreover, for the endpoint that
EPA used to calculate MC's acute risks
(neurological effects), EPA acknowledges
"uncertainty regarding concentrations and exposure
durations that may lead to severe effects and death
from inhalation of methylene chloride."
A database UF is further warranted given the
potential for hematologic effects (e.g., increased
COHb levels), an effect not acknowledged at all in
this draft risk evaluation.
The lack of endocrine effects data is another area of
data insufficiency for MC.
There is no universal list of hazard data required when
evaluating chemical risks under TSCA. Furthermore, for
methylene chloride, EPA has sufficient, reasonably
available hazard information to conduct a risk evaluation
and support the use of the chosen hazard endpoints.
Therefore, EPA did not use a database uncertainty factor in
the methylene chloride risk evaluation.
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EPA's final risk evaluation should apply a database
UF in determining the benchmark MOE for MC's
non-cancer chronic effects.
43, 73
PUBLIC COMMENTS:
EPA needs to apply an UF to account for lack of
dermal toxicity data.
EPA's decision to rely on inhalation-to-dermal
extrapolation contributes substantial uncertainty to
its risk calculations. Therefore, as is recommended
for route-to-route extrapolation generally, EPA
should apply an additional UF of 10 to account for
these uncertainties.
There are concerns about the adequacy of the acute
benchmark MOE. EPN would argue that a third UF
(UFD) should be incorporated into the derivation of
the MOE to accommodate for the incomplete
information on neurodevelopment. This third UF
could be set at either 1.5X or 2X. The resulting
MOE would then be either 45 or 60 (10X (UFH) x
3X (UFL) x 1.5X (UFD) = 45 or (10X (UFH) x 3X
(UFL)x 2X (UFD) = 60).
There is no universal list of hazard data required when
evaluating chemical risks under TSCA. Furthermore, for
methylene chloride, EPA has sufficient, reasonably
available hazard information to conduct a risk evaluation
and support the use of the chosen hazard endpoints.
Therefore, EPA did not use a database uncertainty factor in
the methylene chloride risk evaluation.
EPA added more discussion of the uncertainty in the
inhalation-to-dermal extrapolation in the Key Assumptions
and Uncertainties in the Human Health Risk Estimation
(Section 4.3.7).
LO A EC-to-NO A EC UF
SACC, 49,
73, 75
SACC COMMENTS:
The selection of a LOAEC-to-NOAEC UF of 3 was
not well justified. The reasons for reducing the UF
from 10 to 3 based on the magnitude of the effect
was unclear, and the Committee noted that other
agencies have not done this (e.g., the California
OEHHA used 6). One Committee member
suggested that a LOAEC-to-NOAEC UF was not
needed, since the observed effect (7% decrease)
was essentially aNOAEC.
PUBLIC COMMENTS:
The effects observed in that study are not "of a
small magnitude." In addition to a reduction in
peripheral vision, which presents serious risks to
In previous assessments (e.g., the new chemicals program),
EPA has applied uncertainty factors of 3 instead of 10 for the
LOAEC to NOAEC UF when effects are less severe.
Furthermore, IRIS assessments have used default uncertainty
factors of 3. The risk evaluation states that this value was
applied based on the more limited severity of the effect (i.e.,
the 7% change in just one part of a dual performance task).
EPA used an intraspecies UF of 10 in the risk evaluation for
effects resulting from acute exposure, which is expected to
protect individuals with cardiac disease that may experience
decreased time to angina as well as other susceptible
populations. The intraspecies UF was established to account
for uncertainty and variability that includes susceptible
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many of the commercial and consumer users of
MC, the study reported a COHb level in exposed
subjects of 5.1%.
The AEGL analysis of MC reports that COHb
levels of 4% can lead to "disabling" effects, and
EPA's draft risk evaluation states that "at COHb
levels of 2 or 4%, patients with coronary artery
disease may experience a reduced time until onset
of angina (chest pain) during physical exertion."
The LOAEC-to-NOAEC UF of 3 does not seem to
be based on any official agency guidance and
actually deviates from prior evaluations. An UF of 3
is insufficiently protective of acute inhalation risks.
subooDulations (EPA, 2002). Research indicates that a factor
of 10 (when including both toxicokinetics and
toxicodynamics) is sufficient in most cases (EPA, 2002).
EPA expects this factor to account for the identified
subpopulations for methylene chloride.
PPE - general comments
SACC
SACC COMMENTS:
The risk evaluation should highlight those scenarios
where safety margins are dependent on proper PPE
usage.
EPA outlined its assumptions regarding PPE in section 5.1.
Within the unreasonable risk determination for each
condition of use, EPA describes assumptions regarding PPE
(respirators and gloves), including when use of PPE is not
assumed, and the contribution of PPE assumptions to each
unreasonable risk determination in section 5.2. EPA has also
added a table in Section 4.2.2.1 to make the PPE
assumptions made for each occupational exposure scenario
clearer. Additionally, EPA uses the high-end exposure value
when making its unreasonable risk determination in order to
address uncertainty as to whether or not workers are using
PPE and using it properly.
SACC
SACC COMMENTS:
Emphasis on the insufficient information on
appropriate PPE use should be strengthened. It is
not clear how lack of knowledge about appropriate
use of PPE, or of components in products
containing MC (which could synergistically or
additively reduce PPE effectiveness) is reflected in
the level of confidence on exposures without PPE
as compared to PPE use. EPA should be more
transparent in this regard.
EPA has outlined its PPE assumptions in section 5.1 and has
supplemented some sources and information on respirator
use in Section 2.4.1.1. of the Risk Evaluation and Section
1.4.6 of the Supplemental Information on Releases and
Occupational Exposure Assessment. EPA has also added a
table in Section 4.2.2.1 to make the PPE assumptions made
for each COU clearer. These assumptions incorporate
available information on PPE use, including OSHA
violation reports and the BLS and NIOSH respirator use
surveys.
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EPA should increase efforts at obtaining specific
information on PPE use from users in future risk
evaluations. The Agency could reach out to
producers and distributors of PPE to determine if
they could provide useful information.
EPA's approach for developing exposure assessments for
workers is to use reasonably available information and
expert judgement to construct exposure scenarios that are
anchored in the real-world use of chemicals. EPA considers
each condition of use and uses exposure scenarios with and
without PPE that may be applicable to particular worker
tasks on a case-specific basis for a given chemical. For the
purposes of determining whether or not a condition of use
presents unreasonable risks, EPA incorporates assumptions
regarding PPE use based on this information and 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. In consideration of these uncertainties and
variabilities in PPE usage, EPA uses the high-end exposure
value when making its unreasonable risk determination in
order to address those uncertainties.
EPA will also increase its effort to obtain information on
PPE use for future risk evaluations.
SACC
SACC COMMENTS:
The Agency's reliance on appropriate use of PPE,
including both respirators and gloves, is not
supported by current research literature or industrial
hygiene practice.
The mere presence of a regulation requiring
respirators does not mean that they are used or used
effectively. Inadequacies in respirator programs are
documented. Respirators require multiple
EPA has outlined its PPE assumptions in section 5.1 and
has supplemented some sources and information on
respirator use in Section 2.4.1.1. of the Risk Evaluation
and Section 1.4.6 of the Supplemental Information on
Releases and Occupational Exposure Assessment.
EPA has also added a table in Section 4.2.2.1 to make the
PPE assumptions made for each COU clearer. These
assumptions incorporate available information on PPE
use, including OSHA violation reports and the BLS and
NIOSH respirator use surveys.
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respiratory protection (RP) compliance factors in
order to perform as certified.
Brent et al. (2005) used data from the NIOSH and
BLS joint survey on Respirator Usage in Private
Sector Firms (BLS, 2001) to examine the adequacy
of respirator protection programs in private
industries. They found "large percentages of
establishments requiring respirator use [under
OSHA or the Mine Safety and Health
Administration (MSHA) regulations] had indicators
of potentially inadequate respirator programs."
Later, Janssen et al. (2014) reported that "APFs do
not apply to RPD used in the absence of a fully
compliant RP program; less than the expected level
of protection is anticipated in these situations."
The frequency of proper use of gloves and
respirators is largely unknown.
There is variability in use of PPE across
manufacturing facilities, with larger and better-
funded manufacturing industries and facilities often
having industrial hygiene compliance programs.
The Committee encouraged EPA to look for
existing literature on PPE use and recommends that
EPA consider OSHA violation reports on glove and
respirator use which may provide data on the
frequency or extent of usage in the industry.
The Committee suggested that the NIOSH BLS
respirator usage survey can be used to provide
industry-based estimates of respirator program
effectiveness, which could then be employed to set
the best APF for an industry.
One Committee member indicated that the high-end
exposure scenarios do not include PFs derived from
assumed respirator use.
EPA's approach for developing exposure assessments for
workers is to use reasonably available information and
expert judgement to construct exposure scenarios that are
anchored in the real-world use of chemicals. EPA
considers each condition of use and uses exposure
scenarios with and without PPE that may be applicable to
particular worker tasks on a case-specific basis for a
given chemical. For the purposes of determining whether
or not a condition of use presents unreasonable risks,
EPA incorporates assumptions regarding PPE use based
on this information and 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. In consideration of these uncertainties
and variabilities in PPE usage, EPA uses the high-end
exposure value when making its unreasonable risk
determination in order to address those uncertainties.
73
PUBLIC COMMENTS:
EPA's approach for developing exposure assessments for
workers is to use the reasonably available information to
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EPA has adopted a flawed assumption - absent any
empirical evidence to support it - that workers
under many conditions of use of MC will always
wear effective PPE, including gloves.
construct exposure scenarios that are anchored in the real-
world use of chemicals. When appropriate, in the risk
evaluation, EPA will use exposure scenarios both with and
without engineering controls and/or PPE that may be
applicable to particular worker tasks on a case-specific basis
for a given chemical. Again, while EPA has evaluated
worker risk with and without PPE, as a matter of policy,
EPA does not believe it should assume that workers are
unprotected by PPE where such PPE might be necessary to
meet federal regulations, unless it has evidence that workers
are unprotected. Additionally, in consideration of the
uncertainties and variabilities in PPE usage, EPA uses the
high-end exposure value when making its unreasonable risk
determination in order to address those uncertainties. EPA
has also outlined its PPE assumptions in section 5.1. Further,
in the final risk evaluation for MC, EPA has determined that
most conditions of use pose an unreasonable risk to workers
even with the assumed PPE.
EPA's assumption that workers are typically protected by
PPE is based on consideration of the OSHA regulations at
29 CFR 1910.1052, which sets the methylene chloride
standard, including which circumstances necessitate the use
of personal protective equipment (PPE). Thus, 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.
66
PUBLIC COMMENTS:
Draft risk evaluation (line 8109): what type of
gloves are being used? Some materials amplify the
dermal exposure from gloves; verify with the glove
standard.
Protective gloves in this table are either PF5, PF10, or PF20.
Use of PF > 1 means that the gloves are protective and have
permeation data to support the greater protection factor and
possibly various levels of training. Gloves that are not
protective have PF = 1.
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52
PUBLIC COMMENTS:
From p. 181; For consumer usage, it is expected
that proper PPE is rarely worn with the exception of
gloves for dermal exposure (still expect low usage
of PPE). I do not know how best to comment on the
data in Tables 2-94 and 2-95 other than the concern
for lack of PPE being used.
Modeled consumer exposures (both inhalation and dermal)
are evaluated based on the reasonable assumption that
consumers and bystanders would not be wearing PPE.
52
PUBLIC COMMENTS:
From p. 319; Focus on the data from the "No
Respirator" values as this is more in line with usage
that is observed in practice.
EPA's approach for developing exposure assessments for
workers is to use the reasonably available information to
construct exposure scenarios that are anchored in the real-
world use of chemicals. When appropriate, in the risk
evaluation, EPA will use exposure scenarios both with and
without engineering controls and/or PPE that may be
applicable to particular worker tasks on a case-specific basis
for a given chemical. Again, while EPA has evaluated
worker risk with and without PPE, as a matter of policy,
EPA does not believe it should assume that workers are
unprotected by PPE where such PPE might be necessary to
meet federal regulations, unless it has evidence that workers
are unprotected. Additionally, in consideration of the
uncertainties and variabilities in PPE usage, EPA uses the
high-end exposure value when making its unreasonable risk
determination in order to address those uncertainties. EPA
has also outlined its PPE assumptions in section 5.1. Further,
in the final risk evaluation for MC, EPA has determined that
most conditions of use pose an unreasonable risk to workers
even with the assumed PPE.
EPA's assumption that workers are typically protected by
PPE is based on consideration of the OSHA regulations at 29
CFR 1910.1052, which sets the methylene chloride standard,
including which circumstances necessitate the use of
personal protective equipment (PPE). Thus, 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
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to meet federal regulations, unless it has evidence that
workers are unprotected.
69
PUBLIC COMMENTS:
EPA continues to inappropriately assume that
workers wear both respirators and protective gloves
in its risk calculations.
"Based on the protection standards, inhalation
exposures may be reduced by a factor of 25, 50,
1,000, or 10,000, if respirators are required and
properly worn and fitted."
EPA's approach for developing exposure assessments for
workers is to use the reasonably available information to
construct exposure scenarios that are anchored in the real-
world use of chemicals. When appropriate, in the risk
evaluation, EPA will use exposure scenarios both with and
without engineering controls and/or PPE that may be
applicable to particular worker tasks on a case-specific basis
for a given chemical. Again, while EPA has evaluated
worker risk with and without PPE, as a matter of policy,
EPA does not believe it should assume that workers are
unprotected by PPE where such PPE might be necessary to
meet federal regulations, unless it has evidence that workers
are unprotected. For the purposes of determining whether or
not a condition of use presents unreasonable risks, EPA
incorporates assumptions regarding PPE use based on
information and judgement underlying the exposure
scenarios. These assumptions are described in the
unreasonable risk determination for each condition of use, in
section 5.2. Additionally, in consideration of the
uncertainties and variabilities in PPE usage (e.g., dry
cleaners), EPA uses the high-end exposure value when
making its unreasonable risk determination in order to
address those uncertainties. EPA has also outlined its PPE
assumptions in section 5.1. Further, in the final risk
evaluation for MC, EPA has determined that most conditions
of use pose an unreasonable risk to workers even with the
assumed PPE.
EPA's assumption that workers are typically protected by
PPE is based on consideration of the OSHA regulations at
29 CFR 1910.1052, which sets the methylene chloride
standard, including which circumstances necessitate the use
of personal protective equipment (PPE). Thus, as a matter of
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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.
73, 66
PUBLIC COMMENTS:
EPA makes clear that its risk determinations
"incorporate consideration of expected PPE
(frequently estimated to be a respirator of APF 25
or 50 and gloves with PF 5-20)" (p. 33).
Given the types of respirators used to be able to
achieve an APF 25 or 50, a more protective
consideration would be to lower the limit rather
than rely on personal protective equipment.
Line 8117: for gloves with PFs of 10 not being
protective enough, levels should be lowered.
EPA has outlined its PPE assumptions in section 5.1 and has
supplemented some sources and information on respirator
use in Section 2.4.1.1. of the Risk Evaluation and Section
1.4.6 of the Supplemental Information on Releases and
Occupational Exposure Assessment. EPA has also added a
table in Section 4.2.2.1 to make the PPE assumptions made
for each COU clearer. Additionally, in consideration of the
uncertainties and variabilities in PPE usage, EPA uses the
high-end exposure value when making its unreasonable risk
determination in order to address those uncertainties.
PPE assumptions - respirator use
SACC, 49,
73, 57, 43,
44, 72, 75,
SACC COMMENTS:
Several Committee members questioned the use of
APFs to indicate protectiveness of PPE, and others
noted that the actual use of PPE as well as the
proper use of PPE in affected occupations had not
been sufficiently investigated.
PUBLIC COMMENTS:
EPA assumes that workers wear respirators and
protective gloves for the entirety of their work shift,
every day throughout their careers.
Because TSCA requires risk management only after
EPA has made an unreasonable risk determination,
and only to the extent needed to address the risks
that EPA has found unreasonable, EPA's PPE
assumptions leave millions of workers unprotected
or under-protected.
EPA has outlined its PPE assumptions in section 5.1 and has
supplemented some sources and information on respirator
use in Section 2.4.1.1. of the Risk Evaluation and Section
1.4.6 of the Supplemental Information on Releases and
Occupational Exposure Assessment. EPA has also added a
table in Section 4.2.2.1 to make the PPE assumptions made
for each COU clearer. 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.
72, 73, 42,
63
PUBLIC COMMENTS:
EPA incorrectly assumes that all workers in many
conditions of use will be provided and will use PPE,
without any supporting evidence. Even within a
EPA has outlined its PPE assumptions in section 5.1 and has
supplemented some sources and information on respirator
use in Section 2.4.1.1. of the Risk Evaluation and Section
1.4.6 of the Supplemental Information on Releases and
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given condition of use (e.g., the commercial use of
lubricants and greases containing MC), there often
are a wide range of employers and workplaces.
EPA should more clearly specify precisely which
conditions of use workers are presumed to wear
PPE and how it determined whether workers
exposed from a given condition of use were
expected to use PPE.
Occupational Exposure Assessment. EPA has also added a
table in Section 4.2.2.1 to make the PPE assumptions made
for each COU clearer. For the purposes of determining
whether or not a condition of use presents unreasonable
risks, EPA incorporates assumptions regarding PPE use
based on information and judgement underlying the
exposure scenarios. These assumptions are described in the
unreasonable risk determination for each condition of use, in
section 5.2. Additionally, in consideration of the
uncertainties and variabilities in PPE usage, EPA uses the
high-end exposure value when making its unreasonable risk
determination in order to address those uncertainties.
SACC, 49,
73, 72, 75,
33, 77
SACC COMMENTS:
The assumptions and uncertainties with regard to
respirator use and the assumed protection are not
discussed in Sections 4.3.2 and 4.3.7.
Recommendation: Discuss more thoroughly all the
assumptions made with respect to respirator use and
its protective effect.
PUBLIC COMMENTS:
EPA made it clear that it does not have any actual
data on respirators or gloves, such as types used and
frequency. EPA assumed without evidence various
levels of protection from different purely
hypothetical PPE scenarios.
EPA's risk evaluations must be supported by
"substantial evidence" in the administrative record.
Not only do EPA's unsupported assumptions of
PPE use fall far short of that standard, but in many
instances, they are directly contrary to EPA's prior
findings and analyses.
EPA has outlined its PPE assumptions in section 5.1 and has
supplemented some sources and information on respirator
use in Section 2.4.1.1. of the Risk Evaluation and Section
1.4.6 of the Supplemental Information on Releases and
Occupational Exposure Assessment. EPA has also added a
table in Section 4.2.2.1 to make the PPE assumptions made
for each COU clearer. For the purposes of determining
whether or not a condition of use presents unreasonable
risks, EPA incorporates assumptions regarding PPE use
based on information and judgement underlying the
exposure scenarios. These assumptions are described in the
unreasonable risk determination for each condition of use, in
section 5.2. Additionally, in consideration of the
uncertainties and variabilities in PPE usage, EPA uses the
high-end exposure value when making its unreasonable risk
determination in order to address those uncertainties.
SACC, 49,
73, 42, 44,
72, 75, 63,
77, 83
SACC COMMENTS:
The Committee expressed concern that long-term
repeated inhalation exposures to MC can lead to
other respiratory illnesses, such as asthma, which
EPA has not identified reasonably available information
associating asthma with MC.
EPA's approach for developing exposure assessments for
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has been reported with long-term exposures to
VOCs in general.
Discussion of PPE use in the risk evaluation did not
address known factors that affect workers' or
ONUs' use of PPE, such as discomfort, limitations
in movement, sensory perception (i.e., hearing,
vision, touch). These factors are exacerbated as
task-time and temperature increase, implying that
even under the best-case scenario of proper use of
PPE at the beginning of a work shift, use of PPE
will degrade over time, both within a daily work
shift and over the course of a worker's career
because of increasing reluctance to use PPE.
PUBLIC COMMENTS:
EPA's PPE assumptions are also contrary to EPA's
prior findings concerning MC (January 2017
proposal to ban consumer and commercial uses of
MC paint strippers). Individuals with impaired lung
function due to asthma, emphysema, or chronic
obstructive pulmonary disease, for example, may be
physically unable to wear a respirator.
There are clear differences in the size and
sophistication of employers, workplace
demographics and language barriers, and working
conditions that may make PPE more burdensome, if
not prohibitive.
OSHA and NIOSH have similarly found that
respirators can cause discomfort, skin irritation,
heat stress, communication difficulties, and vision
limitations, and that they often create other hazards
for workers, such as trips, falls, and "struck by"
hazards.
The increased heat hazard associated with respirator
use is a significant limitation of the draft risk
evaluation, given that many users of MC are likely
to work outside or in non-air-conditioned spaces.
workers is to use the reasonably available information to
construct exposure scenarios that are anchored in the real-
world use of chemicals. When appropriate, in the risk
evaluation, EPA will use exposure scenarios both with and
without engineering controls and/or PPE that may be
applicable to particular worker tasks on a case-specific basis
for a given chemical. Again, while EPA has evaluated
worker risk with and without PPE, as a matter of policy,
EPA does not believe it should assume that workers are
unprotected by PPE where such PPE might be necessary to
meet federal regulations, unless it has evidence that workers
are unprotected. For the purposes of determining whether or
not a condition of use presents unreasonable risks, EPA
incorporates assumptions regarding PPE use based on
information and judgement underlying the exposure
scenarios. These assumptions are described in the
unreasonable risk determination for each condition of use, in
section 5.2. Additionally, in consideration of the
uncertainties and variabilities in PPE usage, EPA uses the
high-end exposure value when making its unreasonable risk
determination in order to address those uncertainties. EPA
has also outlined its PPE assumptions in section 5.1.
The OSHA regulations at 29 CFR 1910.1052 set forth the
methylene chloride standard, including which circumstances
necessitate the use of personal protective equipment (PPE).
Thus, 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.
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Moreover, with warming conditions globally due to
climate change, it is "reasonably foreseen" that PPE
which imposes additional heat stress will be even
less frequently used.
The 2017 proposal also recognized that effective
use of PPE requires clear and understandable hazard
warnings and directions for safe use together with
adequate employee training and oversight. Absent
such warnings and a requirement that workers use
approved PPE when handling MC, EPA's
assumption that workers are using the "expected"
PPE is likely false.
52
PUBLIC COMMENTS:
Our experience is that engineering controls can be
too expensive for commercial shops to install and
proper PPE is often, if not usually, not worn.
EPA's approach for developing exposure assessments for
workers is to use the reasonably available information to
construct exposure scenarios that are anchored in the real-
world use of chemicals. When appropriate, in the risk
evaluation, EPA will use exposure scenarios both with and
without engineering controls and/or PPE that may be
applicable to particular worker tasks on a case-specific basis
for a given chemical. Again, while EPA has evaluated
worker risk with and without PPE, as a matter of policy,
EPA does not believe it should assume that workers are
unprotected by PPE where such PPE might be necessary to
meet federal regulations, unless it has evidence that workers
are unprotected. For the purposes of determining whether or
not a condition of use presents unreasonable risks, EPA
incorporates assumptions regarding PPE use based on
information and judgement underlying the exposure
scenarios. These assumptions are described in the
unreasonable risk determination for each condition of use, in
section 5.2. Additionally, in consideration of the
uncertainties and variabilities in PPE usage, EPA uses the
high-end exposure value when making its unreasonable risk
determination in order to address those uncertainties. EPA
has also outlined its PPE assumptions in section 5.1. Further,
in the final risk evaluation for MC, EPA has determined that
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most conditions of use pose an unreasonable risk to workers
even with the assumed PPE.
The OSHA regulations at 29 CFR 1910.1052 set forth the
methylene chloride standard, including which circumstances
necessitate the use of personal protective equipment (PPE).
Thus, 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.
63, 70, 75,
77
PUBLIC COMMENTS:
It should be noted that many of the subcategories in
Table 4-104 (p. 395) involve multi-task cleaning
and repair operations that may require close worker
examination of treated metals and materials, which
may not be possible with the types of respirators
permitted for MC.
The Massachusetts TURA program staff have
observed workers using MC without appropriate
PPE.
It is very likely that smaller establishments and
family owned businesses (e.g., dry cleaners) will
not likely use or properly utilize PPE (ie., Blando et
al., 2010; CDC, 2008).
EPA's approach for developing exposure assessments for
workers is to use the reasonably available information to
construct exposure scenarios that are anchored in the real-
world use of chemicals. When appropriate, in the risk
evaluation, EPA will use exposure scenarios both with and
without engineering controls and/or PPE that may be
applicable to particular worker tasks on a case-specific basis
for a given chemical. Again, while EPA has evaluated
worker risk with and without PPE, as a matter of policy,
EPA does not believe it should assume that workers are
unprotected by PPE where such PPE might be necessary to
meet federal regulations, unless it has evidence that workers
are unprotected. For the purposes of determining whether or
not a condition of use presents unreasonable risks, EPA
incorporates assumptions regarding PPE use based on
information and judgement underlying the exposure
scenarios. These assumptions are described in the
unreasonable risk determination for each condition of use, in
section 5.2. Additionally, in consideration of the
uncertainties and variabilities in PPE usage (e.g., dry
cleaners), EPA uses the high-end exposure value when
making its unreasonable risk determination in order to
address those uncertainties. EPA has also outlined its PPE
assumptions in section 5.1. Further, in the final risk
evaluation for MC, EPA has determined that most conditions
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of use pose an unreasonable risk to workers even with the
assumed PPE.
The OSHA regulations at 29 CFR 1910.1052 set forth the
methylene chloride standard, including which circumstances
necessitate the use of personal protective equipment (PPE).
Thus, 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.
73, 66
PUBLIC COMMENTS:
Organic solvents like MC may breakthrough the
carbon or other medium in organic vapor cartridge
respirators, and this can occur without providing
any indication to the user that the respirator is no
longer functioning.
EPA has acknowledged ensuring protection
necessitates use of air-supplied respirators.
Thank you for your comment.
73, 66, 44,
72, 75, 63
PUBLIC COMMENTS:
EPA's deviation from the hierarchy of controls
violates the obligation to use the best available
science in TSCA risk evaluations.
The hierarchy of controls should be followed to
eliminate workplace hazards. PPE has the highest
failure rate and is the least effective control, since it
does not eliminate the hazard and is subject to
human error. OSHA and NIOSH manage chemical
risks using the "hierarchy of controls."
NIOSH states the following regarding PPE: "PPE
(e.g., respirators, gloves, protective clothing) is the
least desired option for controlling worker
exposures to hazardous substances. PPE is used
when engineering and administrative controls are
not feasible or effective in reducing exposures to
acceptable levels or while controls are being
OSHA's hierarchy of controls is a method for eliminating
workplace hazards. While EPA has assessed the extent to
which certain exposure reduction tools that it assumes to be
in place may be reducing risks to workers, application of the
methodology of the hierarchy of controls is not relevant to
risk evaluations. EPA will manage unreasonable risks
presented by chemical substances when the Agency
undertakes regulatory action for COUs determined to have
unreasonable risk. Utilization of the hierarchy of controls to
recommend or require risk management actions in the risk
evaluation would be premature and inappropriate.
EPA agrees that there are challenges associated with use of
PPE; they are described in Section 5.1.1.3. By providing risk
estimates assuming use of PPE, EPA is not recommending or
requiring use of PPE. Rather, these risk estimates are part of
EPA's approach for developing exposure assessments for
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implemented. It is the last line of defense after
engineering controls, work practices, and
admini strative control s."
OSHA has also highlighted the major limitations of
reliance on PPE. In 2016, OSHA informed EPA
that respirators are the "least satisfactory approach
to exposure control," stating that respirator
effectiveness ultimately relies on the practices of
individual workers who must wear them. EPA
affirmed its agreement with OSHA's conclusions in
its proposed TSCA Section 6 rule to ban MC-based
paint strippers in both consumer and commercial
settings.
workers that use the reasonably available information to
construct exposure scenarios that are anchored in the real-
world use of chemicals. When appropriate, in the risk
evaluation, EPA will use exposure scenarios both with and
without engineering controls and/or PPE that may be
applicable to particular worker tasks on a case-specific basis
for a given chemical. Again, while EPA has evaluated
worker risk with and without PPE, as a matter of policy,
EPA does not believe it should assume that workers are
unprotected by PPE where such PPE might be necessary to
meet federal regulations, unless it has evidence that workers
are unprotected. For the purposes of determining whether or
not a condition of use presents unreasonable risks, EPA
incorporates assumptions regarding PPE use based on
information and judgement underlying the exposure
scenarios. These assumptions are described in the
unreasonable risk determination for each condition of use, in
section 5.2. Additionally, in consideration of the
uncertainties and variabilities in PPE usage (e.g., the burden
associated with the use of supplied-air respirators, including
the expense of the equipment and the necessity of fit-testing
and training for proper use), EPA uses the high-end exposure
value when making its unreasonable risk determination in
order to address those uncertainties. EPA has also outlined
its PPE assumptions in section 5.1. Further, in the final risk
evaluation for MC, EPA has determined that most conditions
of use pose an unreasonable risk to workers even with the
assumed PPE.
EPA's assumption that workers are typically protected by
PPE is based on consideration of the OSHA regulations at
29 CFR 1910.1052, which sets the methylene chloride
standard, including which circumstances necessitate the use
of personal protective equipment (PPE). Thus, while EPA
has evaluated worker risk with and without PPE, as a matter
of policy, EPA does not believe it should assume that
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workers are unprotected by PPE where such PPE might be
necessary to meet federal regulations, unless it has evidence
that workers are unprotected.
PPE assumptions - gloves
SACC
SACC COMMENTS:
Committee members were unclear as to how PPE
use is factored into the human health risk
calculations (e.g., MC can penetrate gloves
necessitating frequent changing of gloves).
Recommendations: Add the use of respirator and
personal gloves as both a key assumption and as a
source of uncertainty. And acknowledge that
workers do not wear gloves continuously over their
work shift and incorporate this assumption into
calculations of risk for certain categories of
workers.
EPA added a table in Section 4.2.2.1 to make the PPE
assumptions made for each COU clearer. EPA has also
supplemented some sources and information on respirator
use in Section 2.4.1.1. of the Risk Evaluation and Section
1.4.6 of the Supplemental Information on Releases and
Occupational Exposure Assessment. Additionally, Section
4.3.2.3 Occupational Dermal Exposure Dose Estimates
mentions glove protection factors, based on the ECETOC
TRA model as described in Section 2.4.1.1, are "what-if'
assumptions and are uncertain. EPA does not know the
actual frequency, type, and effectiveness of glove use in
specific workplaces of the OESs.
SACC
SACC COMMENTS:
Regarding the statement in the risk evaluation,
"Initial literature review suggests that there is
unlikely to be sufficient data to justify a specific
probability distribution for effective glove use for a
chemical or industry" (p. 110, lines 1918-1922), the
EPA should present and/or reference the literature
reviewed and should be clear when they believe that
PPE will be used within an industry and present the
appropriate justification. The EPA should indicate
when/if the assessment of PPE use was made based
on professional judgment.
EPA added a table in Section 4.2.2.1 to make the PPE
assumptions made for each COU clearer.
73, 44, 72,
75, 70, 74
PUBLIC COMMENTS:
EPA acknowledges that protection varies greatly
with different glove materials; however, the agency
cites no data on actual use of specific glove types,
and instead simply assumes default glove PFs.
EPA indicated that it does not have any actual data
on gloves, such as the types used and frequency, or
For the purposes of determining whether or not a condition
of use presents unreasonable risks, EPA incorporates
assumptions regarding PPE use based on information and
judgement underlying the exposure scenarios. These
assumptions are described in the unreasonable risk
determination for each condition of use, in section 5.2.
Additionally, in consideration of the uncertainties and
variabilities in PPE usage (e.g., dry cleaners), EPA uses the
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data on the proper use of effective gloves in
industrial settings.
OSHA makes specific recommendations about MC-
resistant gloves. TURA program staff have
observed workers using non-recommended gloves
in some cases. At a furniture refinishing facility,
TURA program staff did observe the use of more
protective, multiple-layer laminate gloves; however,
the same pair of gloves was used over a long period
of time. TURA program staff have observed that
many workers are unfamiliar with the concepts of
breakthrough and degradation time for gloves.
high-end exposure value when making its unreasonable risk
determination in order to address those uncertainties. EPA
has also outlined its PPE assumptions in section 5.1.
EPA's assumption that workers are typically protected by
PPE is based on consideration of the OSHA regulations at
29 CFR 1910.1052, which sets the methylene chloride
standard, including which circumstances necessitate the use
of personal protective equipment (PPE). Thus, 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.
Regarding the comment about TURA program staff
observing in some instances that there is proper glove use
while not at other times, because EPA uses the high-end
exposure values to account for uncertainties and variabilities
in PPE usage, this is accounted for in its unreasonable risk
determinations.
49, 72, 70,
73
PUBLIC COMMENTS:
Improper glove use can lead to increased worker
exposures due to "contamination of the interior of
the glove" (if workers are not properly training in
glove use and replacement) or by "acting as a
reservoir" for contaminants (if the gloves are not
impermeable).
Notably, "EPA has not found information that would
indicate specific activity training (e.g., procedure for
glove removal and disposal) for tasks where dermal
exposure can be expected to occur in a majority of
sites ..."
TURA program staff have observed that MC users
do not necessarily use gloves when handling the
EPA's approach for developing exposure assessments for
workers is to use the reasonably available information to
construct exposure scenarios that are anchored in the real-
world use of chemicals. When appropriate, in the risk
evaluation, EPA will use exposure scenarios both with and
without engineering controls and/or PPE that may be
applicable to particular worker tasks on a case-specific basis
for a given chemical. Again, while EPA has evaluated
worker risk with and without PPE, as a matter of policy,
EPA does not believe it should assume that workers are
unprotected by PPE where such PPE might be necessary to
meet federal regulations, unless it has evidence that workers
are unprotected. For the purposes of determining whether or
not a condition of use presents unreasonable risks, EPA
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chemical; users also lack information on correct
choice of gloves, and even sometimes re-use
contaminated gloves.
EPA must therefore consider the foreseeable
exposure scenarios in which employees are not
provided protective gloves, or, worse, are provided
inadequate gloves or are not adequately trained and
thus face even greater dermal exposures due to glove
contamination and the occlusion of MC close to the
skin.
incorporates assumptions regarding PPE use based on
information and judgement underlying the exposure
scenarios. These assumptions are described in the
unreasonable risk determination for each condition of use, in
section 5.2. Additionally, in consideration of the
uncertainties and variabilities in PPE usage (e.g., dry
cleaners), EPA uses the high-end exposure value when
making its unreasonable risk determination in order to
address those uncertainties. EPA has also outlined its PPE
assumptions in section 5.1. Further, in the final risk
evaluation for MC, EPA has determined that most conditions
of use pose an unreasonable risk to workers even with the
assumed PPE.
EPA's assumption that workers are typically protected by
PPE is based on consideration of the OSHA regulations at
29 CFR 1910.1052, which set the methylene chloride
standard, including which circumstances necessitate the use
of personal protective equipment (PPE). Thus, 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.
Regarding the comment about TURA program staff
observing in some instances that there is proper glove use
while not at other times, because EPA uses the high-end
exposure values to account for uncertainties and variabilities
in PPE usage, this is accounted for in its unreasonable risk
determinations.
SACC, 73
SACC COMMENTS:
The Committee recommends that for high-end
exposure scenarios where workers are expected to
be exposed for longer duration at higher chemical
EPA's approach for developing exposure assessments for
workers is to use the reasonably available information to
construct exposure scenarios that are anchored in the real-
world use of chemicals. As stated in section 5.1.1.3, EPA
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concentrations, the glove PF should be limited to
five or one, regardless of industry.
PUBLIC COMMENTS:
EPA appears to want to have it both ways: To
acknowledge the limitations of gloves and their
potential to increase skin absorption, but then to
simply assume that gloves actually provide 5x, lOx,
or 20x levels of protection over no gloves -
regardless of the potential for occlusion - without
citing any evidence to support these values.
This approach will allow clear risks to occur
whenever a worker uses anything less than the most
protective gloves (or no gloves), or when there is
occlusion; these scenarios are quite likely - and
certainly reasonably foreseen - to occur in the real
world.
assumes the use of gloves with PF of 5 and 10 in
commercial settings and gloves with PF of 5 and 20 in
industrial settings. For the exposure scenarios referenced by
the Committee, EPA determined it is appropriated to assume
glove PFs of 5, 10, 02 20 (with specific assumptions
described in the unreasonable risk determination for each
condition of use, in Section 5.2). EPA does not factor in
duration of dermal exposure in the occupational exposure
scenarios because the durational of dermal exposure for
different occupational exposure activities across various
workplaces are often not known (see Section 2.4.1.1). 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. Once EPA has applied the
appropriate PPE assumption for a particular condition of use
in each unreasonable risk determination, in those instances
when EPA assumes PPE is used, EPA also assumes that the
PPE is used in a manner that achieves the stated APF or PF.
EPA agrees that there are challenges to achieving full
protection from PPE. In consideration of the uncertainties
and variabilities in PPE usage, EPA uses the high-end
exposure value when making its unreasonable risk
determination in order to address those uncertainties.
73
PUBLIC COMMENTS:
Gloves can also increase skin temperature and
humidity, which can increase absorption. Therefore,
the assumption that PFs can only range as low as lx
(no gloves) is erroneous; rather, the range should
include PFs below lx.
EPA's assumptions and methodology for estimating dermal
risks are described in section 2.4.1.1, including assumptions
about glove use and associated protection factors. The data
about the frequency of effective glove use - that is, the
proper use of effective gloves - is very limited in industrial
settings. Initial literature review suggests that there is
unlikely to be sufficient data to justify a specific probability
distribution for effective glove use for a chemical or
industry. Instead, the impact of effective glove use is
explored by considering different percentages of
effectiveness. EPA also considered potential dermal
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exposure in cases where exposure is occluded. See further
discussion on occlusion in Appendix E of the Supplemental
Information on Releases and Occupational Exposure
Assessment document.
OSHA - assumptions and regulations
49, 72, 75,
63
PUBLIC COMMENTS:
EPA misrepresents OSHA regulations with respect
to the use of PPE. OSHA regulations do not require
employers to follow the recommendations in an
SDS, and the preamble to OSHA's hazard
communication rule expressly states that "there is
no requirement for employers to implement the
recommended controls."
With respect to MC, OSHA's regulators expressly
require employee exposures and risks to be
measured without the use of respiratory protection.
OSHA permits the use of respirators only if
"engineering controls and work practices" cannot
achieve OSHA's PEL on their own.
EPA's approach for developing exposure assessments for
workers is to use the reasonably available information to
construct exposure scenarios that are anchored in the real-
world use of chemicals. When appropriate, in the risk
evaluation, EPA will use exposure scenarios both with and
without engineering controls and/or PPE that may be
applicable to particular worker tasks on a case-specific basis
for a given chemical. Again, while EPA has evaluated
worker risk with and without PPE, as a matter of policy,
EPA does not believe it should assume that workers are
unprotected by PPE where such PPE might be necessary to
meet federal regulations, unless it has evidence that workers
are unprotected. For the purposes of determining whether or
not a condition of use presents unreasonable risks, EPA
incorporates assumptions regarding PPE use based on
information and judgement underlying the exposure
scenarios. These assumptions are described in the
unreasonable risk determination for each condition of use, in
section 5.2. Additionally, in consideration of the
uncertainties and variabilities in PPE usage (e.g., the burden
associated with the use of supplied-air respirators, including
the expense of the equipment and the necessity of fit-testing
and training for proper use), EPA uses the high-end exposure
value when making its unreasonable risk determination in
order to address those uncertainties. EPA has also outlined
its PPE assumptions in section 5.1. Further, in the final risk
evaluation for MC, EPA has determined that most conditions
of use pose an unreasonable risk to workers even with the
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assumed PPE.
EPA's assumption that workers are typically protected by
PPE is based on consideration of the OSHA regulations at 29
CFR 1910.1052, which sets the methylene chloride standard,
including which circumstances necessitate the use of
personal protective equipment (PPE). Thus, 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.
73, 49, 69
PUBLIC COMMENTS:
OSHA's database of inspections demonstrates
significant noncompliance with OSHA respiratory
protection requirements (e.g., 2,892 violations of
the respiratory protection standard identified in
1,281 separate inspections in 2018).
EPA thus has no basis for assuming that employers
will voluntarily exceed OSHA requirements and
provide respirators even in circumstances where it
is not required.
OSHA data are collected as part of compliance inspections at
carious types of facilities. Certain industries are typically
targeted based on national and regional emphasis programs.
Other inspections may be prompted based on complaints or
referrals. As a result, OSHA data may underrepresent PPE
usage throughout the affected industry. Additionally,
because EPA uses the high-end exposure values to account
for uncertainties and variabilities in PPE usage, this is
accounted for in its unreasonable risk determinations.
EPA's approach for developing exposure assessments for
workers is to use the reasonably available information to
construct exposure scenarios that are anchored in the real-
world use of chemicals. When appropriate, in the risk
evaluation, EPA will use exposure scenarios both with and
without engineering controls and/or PPE that may be
applicable to particular worker tasks on a case-specific basis
for a given chemical. Again, while EPA has evaluated
worker risk with and without PPE, as a matter of policy,
EPA does not believe it should assume that workers are
unprotected by PPE where such PPE might be necessary to
meet federal regulations, unless it has evidence that workers
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are unprotected. For the purposes of determining whether or
not a condition of use presents unreasonable risks, EPA
incorporates assumptions regarding PPE use based on
information and judgement underlying the exposure
scenarios. These assumptions are described in the
unreasonable risk determination for each condition of use, in
section 5.2. Additionally, in consideration of the
uncertainties and variabilities in PPE usage (e.g., the burden
associated with the use of supplied-air respirators, including
the expense of the equipment and the necessity of fit-testing
and training for proper use), EPA uses the high-end exposure
value when making its unreasonable risk determination in
order to address those uncertainties. EPA has also outlined
its PPE assumptions in section 5.1. Further, in the final risk
evaluation for MC, EPA has determined that most conditions
of use pose an unreasonable risk to workers even with the
assumed PPE.
EPA's assumption that workers are typically protected by
PPE is based on consideration of the OSHA regulations at
29 CFR 1910.1052, which sets the methylene chloride
standard, including which circumstances necessitate the use
of personal protective equipment (PPE). Thus, 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.
72
PUBLIC COMMENTS:
OSHA has recognized atmosphere-supplying
respirators are a relatively expensive type of
respiratory equipment, requiring the employer not
only to purchase the respirators themselves but also
to install an air compressor and associated ductwork
or rent cylinders containing breathing air.
Thank you for your comment. For the purposes of
determining whether or not a condition of use presents
unreasonable risks, EPA incorporates assumptions regarding
PPE use based on information and judgement underlying the
exposure scenarios. These assumptions are described in the
unreasonable risk determination for each condition of use, in
section 5.2. Additionally, in consideration of the
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In the case of MC, the situation is complicated by
the predominance of relatively small companies
among the employers whose employees are
currently exposed above the 8-hour TWA PEL.
uncertainties and variabilities in PPE usage (e.g., the burden
associated with the use of supplied-air respirators, including
the expense of the equipment and the necessity of fit-testing
and training for proper use), EPA uses the high-end
exposure value when making its unreasonable risk
determination in order to address those uncertainties. EPA
has also outlined its PPE assumptions in section 5.1.
42
PUBLIC COMMENTS:
To fully evaluate EPAs assumptions regarding PPE
use, EPA should provide any feedback it has
received from OSHA and NIOSH on its assumption
regarding PPE use, and more generally, any input
they have provided EPA regarding the extent and
sufficiency of OSHA's authorities.
EPA does not share internal deliberative comments from the
interagency review process. However, other agencies can
make their comments public by submitting their comments
to the docket.
73, 75, 69,
11,49, 66,
72
PUBLIC COMMENTS:
EPA inappropriately invokes the OSHA PEL as a
benchmark. The OSHA PEL for MC is not health-
protective and EPA identified unreasonable risks at
concentrations five times below the PEL (i.e.,
chronic liver toxicity at <5 ppm). OSHA calculated
a cancer risk of 3.62 deaths per 1,000 workers
exposed to the PEL over a working lifetime, a level
of risk several times above that which EPA deems
acceptable.
In the 2017 proposed ruling, EPA developed a
recommendation for an ECEL as a more current
benchmark for workplace exposures (1.3 ppm 8-
hour TWA). Under the manufacturing condition of
use, the high-end 8-hour TWA exposure
concentration (4.6 mg/m3 or 1.32 ppm) would just
exceed the ECEL of 1.3 ppm.
In Chapter 2, exposures were compared to the PEL because
exposures above the PEL would require mitigation under the
OSHA standard.
EPA acknowledges that there is a PEL but did not use it as a
benchmark for either risk assessment or unreasonable risk
determination. EPA provided the PEL as a point of
comparison only to help readers understand EPA's
workplace exposure and risk estimates compared to a
familiar exposure concentration, as expressed in the PEL.
EPA did not use the PEL in the development of the risk
estimates or as part of making an unreasonable risk
determination.
EPA did not recommend this ECEL in the 2017 proposed
rule for MC in paint and coating removal (82 FR 7464,
January 19, 2017). Rather, the ECEL was one possible risk
management approach outlined in the rulemaking that
proposed to prohibit the use of methylene chloride in most
commercial paint and coating removal. This ECEL was not
finalized and thus, there is no ECEL for methylene chloride.
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65
The de minimis occupational cancer risk policy
levels between OSHA and EPA differ by one order-
of- magnitude, exactly as does the OSHA PEL
when converted using the EPA IUR. This means
that at the PEL, EPA's "no unreasonable risk"
criteria are met for cancer endpoint (and for non-
cancer endpoints, for which EPA's risk levels are
only exceeded at higher exposures). Thus, no
unreasonable risk exists in OSHA-compliant
manufacturing facilities.
As noted in the draft risk evaluation, EPA relied on NIOSH
guidance when choosing the 10"4 cancer risk benchmark to
evaluate risks to workers from methylene chloride exposure.
Furthermore, OSHA, in their 1997 PEL document,
acknowledged that the PEL of 25 ppm considered feasibility
of meeting the level and that the PEL was associated with a
level resulting in a risk of 3.62 cancer deaths per 1000
population. OSHA notes this level is "clearly well above any
plausible upper boundary of the 'significant risk' range
defined by the Supreme Court, used by OSHA in its prior
rulemakings, and reported in the scientific/economic
literature on risk." (()! ). In contrast TSCA
compels EPA to evaluate chemicals without consideration of
non-risk factors (such as feasibility of meeting a standard) to
determine whether they present unreasonable risk under the
conditions of use.
EPA's "no unreasonable risk" standard has not necessarily
been met at the PEL.
68
PUBLIC COMMENTS:
To satisfy Section 9's coordination requirements, as
well as TSCA's call for increased transparency in
decision-making, EPA should provide more
information about how it determines whether
existing regulations under other statutes are
adequate to address potential risks associated with a
TSCA chemical under certain conditions of use.
As part of the problem formulation for methylene chloride,
EPA identified exposure pathways under other
environmental statutes administered by EPA, i.e., the Clean
Air Act (CAA), the Safe 9892 Drinking Water Act (SDWA),
the Clean Water Act (CWA) and the Resource 9893
Conservation and Recovery Act (RCRA). The Office of
Chemical Safety and Pollution Prevention works closely
with EPA offices that administer and implement the
regulatory programs under these statutes. EPA believes that
the TSCA risk evaluation should focus on those exposure
pathways associated with TSCA uses that are not subject to
the regulatory regimes discussed above because these
pathways are likely to represent the greatest areas of concern
to EPA. Clarifying language about what pathways are
addressed under other statutes has been added to Section
1.4.2 of the Risk Evaluation.
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The impact of PPE assumptions on risk determination
SACC, 57,
43, 72, 73,
44, 69
SACC COMMENTS:
One Committee member thought that PPE use
should not be considered when determining risk.
Rather, it should be considered only in a risk
management phase, except for conditions of use
where EPA ascertains the proper use of PPE and
other exposure controls at least 95% of the time.
EPA should consider any scenarios that present
unreasonable risks without assuming PPE use,
while the risk management process should be
focused on designing and ensuring appropriate PPE
use and other controls.
PUBLIC COMMENTS:
While EPA may assess and characterize worker risk
with and without the use of PPE, it should make its
unreasonable risk determinations based upon the
"no PPE" scenarios. Lacking the guarantee of
consistent use of PPE, EPA should focus its
regulatory options on mitigating risk to the
unprotected individual.
By assuming extensive use of PPE at the risk
evaluation stage, EPA conflates risk evaluation with
risk management and preempts the required
consideration of alternate regulatory tools during
the risk management stage, in violation of TSCA.
PPE assumptions are the key driver of a large
fraction of EPA's inhalation risk determinations for
workers - both in cases where EPA did find
unreasonable risk and in cases where it did not. If
EPA's PPE assumptions erase unreasonable risks,
then EPA will not regulate the chemical under
TSCA and will forgo its only opportunity to ensure
that PPE is actually used and workers are protected.
For the purposes of unreasonable risk determinations, EPA is
assuming the use of PPE on a case-by-case basis for each
COU and how it is used (i.e., industrial, commercial,
consumer) in contrast to the approach EPA would take in
any regulatory action, which is to eliminate workplace
hazards by requiring certain actions occur to address the
unreasonable risk.
EPA's approach for developing exposure assessments for
workers is to use the reasonably available information to
construct exposure scenarios that are anchored in the real-
world use of chemicals. When appropriate, in the risk
evaluation, EPA will use exposure scenarios both with and
without engineering controls and/or PPE that may be
applicable to particular worker tasks on a case-specific basis
for a given chemical. Again, while EPA has evaluated
worker risk with and without PPE, as a matter of policy,
EPA does not believe it should assume that workers are
unprotected by PPE where such PPE might be necessary to
meet federal regulations, unless it has evidence that workers
are unprotected. For the purposes of determining whether or
not a condition of use presents unreasonable risks, EPA
incorporates assumptions regarding PPE use based on
information and judgement underlying the exposure
scenarios. These assumptions are described in the
unreasonable risk determination for each condition of use, in
section 5.2. Additionally, in consideration of the
uncertainties and variabilities in PPE usage, EPA uses the
high-end exposure value when making its unreasonable risk
determination in order to address those uncertainties. EPA
has also outlined its PPE assumptions in section 5.1. Further,
in the final risk evaluation for MC, EPA has determined that
most conditions of use pose an unreasonable risk to workers
even with the assumed PPE.
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EPA's assumption that workers are typically protected by
PPE is based on consideration of the OSHA regulations at
29 CFR 1910.1052, which sets the methylene chloride
standard, including which circumstances necessitate the use
of personal protective equipment (PPE). Thus, 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.
SACC
SACC COMMENTS:
Some Committee members appreciated that Table
4-104 presented an evaluation of human health risk
without the use of PPE and its reduction due to PPE
use, and found the table to be effective in
communicating results.
Other Committee members felt that the table was
too detailed to navigate easily. One suggestion was
that the Table show results only for three
categories: no unreasonable risk, no unreasonable
risk under condition of proper PPE use, and
unreasonable risk even under conditions of proper
PPE use.
Table 4-104 provides information to summarize the risk
characterization, not the unreasonable risk determination.
The format of this table and the unreasonable risk
determination have both been updated for greater clarity.
73
PUBLIC COMMENTS:
EPA finds no unreasonable risk for acute (15-
minute) non-cancer effects from inhalation during
processing of MC as a reactant - despite the fact
that its MOE is substantially lower than its
benchmark MOE (4.9 and 30, respectively); it does
so only by assuming universal and effective use of a
respirator with an APF of 25 (see Table 4-9, p.
307).
Based on the OSHA standard for methylene chloride at 29
CFR 1910.1052, the only respirators that can be considered
by EPA are supplied-air respirators (i.e., APF of 25 would
be the lowest APF that could be considered), further
discussed in section 2.4.1.1. Therefore, for each condition of
use of methylene chloride with an identified risk for
workers, EPA assumes, as a baseline, the use of a respirator
with an APF of 25 or 50.
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
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judgement underlying the exposure scenarios. These
assumptions are described in the unreasonable risk
determination for each condition of use, in section 5.2.
Additionally, in consideration of the uncertainties and
variabilities in PPE usage, EPA uses the high-end exposure
value when making its unreasonable risk determination in
order to address those uncertainties. EPA has also outlined
its PPE assumptions in section 5.1.
75
PUBLIC COMMENTS
EPA calculates cancer risks above its "benchmark"
of 1 x 10"4 for several workplace exposure scenarios
in the absence of respirators and gloves but then
determines that use of PPE would lower the risk
below the benchmark. If finalized, EPA's
determinations of no unreasonable risk would mean
that these workers receive no protection against
cancer risk under Section 6(a) of TSCA.
EPA uses the same approach in assessing non-
cancer risks to workers. Numerous worker
categories have highly unprotective MOEs in the
absence of PPE but would be adequately protected
if PPE is used. As a result, workers at risk of serious
acute and non-cancer chronic effects (including
death and severe incapacitation) would receive no
protection under Section 6(a) based on the
unrealistic "expectation" that use of PPE would
prevent harm.
EPA's approach is not grounded in data, departs
from established workplace protection policy and is
contrary to the realities of worker exposure to
unsafe chemicals.
EPA considers the uncertainties associated with each
condition of use, and how the uncertainties may result in a
risk estimate that overestimates or underestimates the risk.
Based on such analysis, EPA determines whether or not the
identified risks are unreasonable. Such consideration carries
extra importance when the risk estimates are close to the
benchmarks for acute, chronic non-cancer risks, and cancer
risks.
EPA's approach for developing exposure assessments for
workers is to use reasonably available information and
expert judgement to construct exposure scenarios that are
anchored in the real-world use of chemicals. EPA considers
each condition of use and uses exposure scenarios with and
without PPE that may be applicable to particular worker
tasks on a case-specific basis for a given chemical. For the
purposes of determining whether or not a condition of use
presents unreasonable risks, EPA incorporates assumptions
regarding PPE use based on this information and 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. Additionally, in consideration of the
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uncertainties and variabilities in PPE usage, EPA uses the
high-end exposure value when making its unreasonable risk
determination in order to address those uncertainties. EPA
has also outlined its PPE assumptions in section 5.1.
73
PUBLIC COMMENTS:
For each of the 29 conditions of use where EPA
assumed routine use of respirators, EPA's
assumption of respiratory PPE use "eliminated" or
"understated" 74% of the risk estimates calculated
for the conditions of use.
Of the 29 conditions of use, EPA made a final risk
determination that 19 of them presented
unreasonable risk to workers, while 10 did not.
In at least the 19 cases just noted, EPA took the
wholly unjustifiable approach of finding a risk to be
unreasonable only if the risk from both the high-end
and the central tendency exposures exceeded its
acceptable risk levels. In contrast, in its draft risk
evaluation for 1-BP, EPA took the far more
justifiable approach of finding a risk to be
unreasonable even when the risks from only the
high-end exposure exceed its acceptable risk levels.
That approach is necessary to ensure that those
experiencing high-end, i.e., sentinel, exposures will
always be protected. For EPA not to do so would be
inconsistent with its own definition of sentinel
exposure in the risk evaluation rule. See 40 CFR §
702.33.
EPA examines the totality of risk estimates for a condition
of use when making a determination of unreasonable risk.
EPA makes one determination for each condition of use and
describes the basis in terms of risks to workers and ONUs,
with specificity to what kind of risks.
For worker exposures, 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. Additionally, in consideration of the
uncertainties and variabilities in PPE usage, EPA uses the
high-end exposure value when making its unreasonable risk
determination in order to address those uncertainties. EPA
has also outlined its PPE assumptions in section 5.1. Further,
in the final risk evaluation for MC, EPA has determined that
most conditions of use pose an unreasonable risk to workers
even with the assumed PPE.
Regarding the use of central tendency and high-end risk
estimates, in the draft and final risk evaluations for
methylene chloride, EPA used the high-end exposure value
when considering worker risks in order to address the
uncertainties and variability in PPE usage. In both the draft
and final risk evaluations, EPA used the central tendency
exposure value when considering ONU exposures when the
data did not distinguish between worker and ONU
exposures.
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EPA assumed that all ONU exposures should not be
presented as identical to exposures of workers directly
handling or using the chemical. EPA has, where possible,
estimated far-field ONU exposures and described the risks
separately. To account for those instances where monitoring
data or modeling did not distinguish between worker and
far-field ONU inhalation exposure estimates, EPA
considered the worker central tendency risk estimate when
determining far-field ONU risk.
73, 70
PUBLIC COMMENTS:
For every occupational exposure scenario EPA
examined, EPA found no unreasonable risk from
dermal exposure only by assuming that workers
wear gloves delivering a level of protection
sufficient to protect against dermal exposures
(examples were provided).
For all 23 scenarios, EPA found that the exposures,
absent glove use, present unreasonable risks for
both acute and chronic, non-cancer health effects.
EPA then assumed that all workers under all those
scenarios would routinely wear the right gloves that
always provided effective dermal protection and
never led to situations of chemical breakthrough or
occluded exposures.
Through this assumption, EPA effectively
eliminated from consideration all of its no-glove
risk estimates, each of which yielded an MOE
falling below EPA's benchmarks MOEs, indicating
unreasonable risk.
Based on the OSHA standard for methylene chloride at 29
CFR 1910.1052, the only respirators that can be considered
by EPA are supplied-air respirators (i.e., APF of 25 would
be the lowest APF that could be considered), further
discussed in section 2.4.1.1. Therefore, for each condition of
use of methylene chloride with an identified risk for
workers, EPA assumes, as a baseline, the use of a respirator
with an APF of 25 or 50. Similarly, EPA assumes the use of
gloves with PF of 5 and 10 in commercial settings and
gloves with PF of 5 and 20 in industrial settings.
For the purposes of determining whether or not a condition
of use presents unreasonable risks, EPA incorporates
assumptions regarding PPE use based on information and
judgement underlying the exposure scenarios. These
assumptions are described in the unreasonable risk
determination for each condition of use, in section 5.2.
Additionally, in consideration of the uncertainties and
variabilities in PPE usage, EPA uses the high-end exposure
value when making its unreasonable risk determination in
order to address those uncertainties. EPA has also outlined
its PPE assumptions in section 5.1.
51
PUBLIC COMMENTS:
We request that EPA revise Section 4.2.2.1.20 -
and all risk estimates and conclusions derived in or
While use of methylene chloride as a functional fluid in a
closed system during pharmaceutical manufacturing was
included in the problem formulation and draft risk
evaluation, upon further analysis of the details of this
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from that section - to reflect pharmaceutical
manufacturers actual current practices.
JMI uses respirators of 1000 APR or higher in all
situations involving potential worker exposures to
MC during pharmaceutical production processes
and believes that this is widely (and perhaps
universally) the case within the industry.
EPAs current assumptions substantially overstate
the risks to workers and should be revised to reflect
actual practices in the industry. Those practices do,
in fact, protect workers against exposure to
unreasonable health risks.
process, EPA has determined that this use falls outside
TSCA's definition of "chemical substance." Under TSCA §
3(2)(B)(vi), the definition of "chemical substance" does not
include any food, food additive, drug, cosmetic, or device
(as such terms are defined in section 201 of the Federal
Food, Drug, and Cosmetic Act) when manufactured,
processed, or distributed in commerce for use as a food,
food additive, drug, cosmetic, or device. EPA has found
that methylene chloride use as a functional fluid in a closed
system during pharmaceutical manufacturing entails use as
an extraction solvent in the purification of pharmaceutical
products, and has concluded that this use falls within the
aforementioned definitional exclusion and is not a "chemical
substance" under TSCA (section 5.3).
Clarity in the use of PPE assumptions for risk characterization is needed
73, 66
PUBLIC COMMENTS:
In the "Risk Considerations" section for each entry
in Table 5-1, the following statement: "EPA does
not expect routine use of respiratory PPE sufficient
to mitigate risk" appears for several conditions of
use. However, in some cases, later in the same
"Risk Considerations" section, EPA states that its
risk estimates "do not indicate risk when expected
use of PPE was considered". These statements
appear contradictory and clarity is needed.
The meaning of parenthetical statements such as
"(respirator APF 25)" or "(for central tendency,
respirator APF 25)" was not explained and is
unclear.
In Table 5-1, a number of the risk estimates are
presented with PPE (pp. 430-431, for example).
This seems to go against the discussion earlier,
which appeared to state that risk estimates would be
done without PPE to be more health protective and
also contradicts the initial statement that EPA does
not expect routine use of respiratory PPE.
In response to these comments, EPA has revised and
clarified the language used in the unreasonable risk
determinations in section 5. The details of the considerations
in the unreasonable risk determinations for each condition of
use now more clearly state when EPA assumes use of PPE,
what APF or PF is assumed, and how the risk estimates
support or do not support a determination of unreasonable
risk for that condition of use. EPA also describes the other
factors considered when making determinations of
unreasonable risk.
While Table 5-1 in the final risk evaluation presents
different information than in the draft risk evaluation, EPA
is consistent in incorporation of assumptions regarding PPE
use based on information and judgement underlying the
exposure scenarios. These assumptions are described in the
unreasonable risk determination for each condition of use, in
section 5.2. Additionally, in consideration of the
uncertainties and variabilities in PPE usage, EPA uses the
high-end exposure value when making its unreasonable risk
determination in order to address those uncertainties. EPA
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In some cases, the risk estimates EPA listed for
workers (and ONUs) in Table 5-1 fail to include
those for cancer, which frequently indicate
excessive risk relative to EPA's 10"4 cancer risk
benchmark when respiratory PPE is not assumed.
It is essential that EPA's risk determinations
accurately reflect the risk estimates that EPA
derived for each exposure scenario and health
endpoint where EPA found excessive risk relative
to its benchmarks. Accurate accounting of the risk
estimates that EPA used to determine whether it
found unreasonable risk and to characterize the
nature, magnitude and extent of the risk EPA found
is vital for the transparency of EPA's decisions.
has also outlined its PPE assumptions in section 5.1. Further,
in the final risk evaluation for MC, EPA has determined that
most conditions of use pose an unreasonable risk to workers
even with the assumed PPE.
Regarding the cancer risk estimates, all risk estimates are
now presented in Table 4-2 for workers and 4-3 for
consumers, and were considered along with other factors
during the determinations of unreasonable risk.
73
PUBLIC COMMENTS:
For 8 of its 65 conditions of use, EPA dismissed an
unreasonable risk to workers by invoking PPE that
the Agency had already stated is not expected to be
used. Conversation with EPA staff indicate this
contradictory approach appears to have been a
mistake, but they are presented here to ensure that
they are corrected. All of these cases involved
cancer risks.
In each case, EPA's risk estimation tables in
Chapter 4 of the draft risk evaluation identified and
boldfaced a risk estimate that exceeded EPA's risk
benchmark; yet, these risks were not identified in
the corresponding section of Table 5-1 in EPA's
risk determinations. Instead, EPA appears to have
invoked expected use of PPE as the explanation.
In two other cases, EPA dismisses an unreasonable
risk with no explanation.
In all 10 of these, EPA's conclusions run contrary
to the evidence before the Agency. Based on the
analysis presented in the draft risk evaluation, EPA
EPA has reviewed all the risk determinations in the draft
risk evaluation to correct any inconsistencies in the approach
for determining unreasonable risk, including considering the
use of PPE in each condition of use. In response to this
comment, EPA has revised the structure of the unreasonable
risk determination section and the presentation of the
unreasonable risk determination for each condition of use,
for greater clarity and to prevent the appearance of any
contradictions.
EPA's approach for developing exposure assessments for
workers is to use the reasonably available information to
construct exposure scenarios that are anchored in the real-
world use of chemicals. When appropriate, in the risk
evaluation, EPA will use exposure scenarios both with and
without engineering controls and/or PPE that may be
applicable to particular worker tasks on a case-specific basis
for a given chemical. Again, while EPA has evaluated
worker risk with and without PPE, as a matter of policy,
EPA does not believe it should assume that workers are
unprotected by PPE where such PPE might be necessary to
meet federal regulations, unless it has evidence that workers
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should find an unreasonable risk to workers or
ONUs presented by these conditions of use.
are unprotected. For the purposes of determining whether or
not a condition of use presents unreasonable risks, EPA
incorporates assumptions regarding PPE use based on
information and judgement underlying the exposure
scenarios. These assumptions are described in the
unreasonable risk determination for each condition of use, in
section 5.2. Additionally, in consideration of the
uncertainties and variabilities in PPE usage, EPA uses the
high-end exposure value when making its unreasonable risk
determination in order to address those uncertainties. EPA
has also outlined its PPE assumptions in section 5.1. Further,
in the final risk evaluation for MC, EPA has determined that
most conditions of use pose an unreasonable risk to workers
even with the assumed PPE.
EPA's assumption that workers are typically protected by
PPE is based on consideration of the OSHA regulations at
29 CFR 1910.1052, which sets the methylene chloride
standard, including which circumstances necessitate the use
of personal protective equipment (PPE). Thus, 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.
General potentially exposed or susceptible subpopulation considerations
SACC, 66
SACC COMMENTS:
Several Committee members requested additional
clarification on the handling of potentially exposed
or susceptible subpopulations within the TSCA risk
evaluation approach and especially with respect to
the setting of UFs.
The risk evaluation should define and assess worker
subpopulations that would be expected to have
EPA describes potentially susceptible subpopulations in
Section 4.4 (Potentially Exposed or Susceptible
Subpopulations), including tobacco smokers. EPA uses
PBPK models for toxicokinetic differences (for chronic risk)
and intraspecies UFs in the risk evaluation; the intraspecies
UF was established to account for uncertainty and variability
that includes susceptible subpopulations (EPA. 2002).
Research indicates that a factor of 10 (when including both
toxicokinetics and toxicodynamics) is sufficient in most
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enhanced inhalation intake, such as tobacco
smokers.
PUBLIC COMMENTS:
Section 4.3 has a good discussion of potentially
vulnerable populations, but it's not clear in this
section how some of those vulnerabilities (genetic
polymorphisms, current smoking, etc.) are factored
into the risk assessment.
Fetuses, infants, and toddlers are briefly mentioned,
but it's not clear that their risk was modeled at all in
the risk assessment.
cases ( )02), and EPA expects that the UFs and PBPK
models used in the risk evaluation are sufficient for the
identified subpopulations applicable to methylene chloride.
54
PUBLIC COMMENTS:
The draft evaluation underscores the greater
vulnerability of certain population groups to the
risks of CNS depression, coma, and death from
acute exposure to MC. These groups include
pregnant women, the elderly, fetuses, children,
people engaged in vigorous physical activity, users
of alcohol, and individuals suffering from lung and
heart disease. EPA argues that it has accounted for
the higher susceptibility of these groups by applying
a default intraspecies uncertainty/variability factor
(UF) of 10. However, this UF is normally used for
expected variations in response among a healthy
population and may not be protective for subgroups
known to be a risk of acute effects at lower levels of
exposure than healthy adults.
EPA considers the intraspecies UF of 10 for the CNS
endpoint from acute exposure to be sufficient; this UF was
established to account for uncertainty and variability that
includes susceptible subpopulations (EPA, 2002). Research
indicates that a factor of 10 is sufficient in most cases (EPA.
2002), and EPA expects that the UFs and PBPK models used
in the risk evaluation are sufficient for the identified
subpopulations applicable to methylene chloride.
73, 44, 75,
72, 55, 43
PUBLIC COMMENTS:
EPA has not met its mandatory duty under TSCA to
thoroughly identify and evaluate the risks to
vulnerable subpopulations.
Due to the developmental neurotoxicity risks,
pregnant women, fetuses, and children should all be
specifically included. EPA could have been more
health-protective by considering non-regular
exposures to MC for infants and toddlers.
EPA uses PBPK models for toxicokinetic differences (for
chronic risk) and intraspecies UFs in the risk evaluation. The
intraspecies UF was established to account for uncertainty
and variability that includes susceptible subpopulations
(EPA, 2002). Research indicates that a factor of 10 (when
including both toxicokinetics and toxicodynamics) is
sufficient in most cases (EPA, 2002), and EPA expects that
the UFs and PBPK models used in the risk evaluation are
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Due to the reproductive risks, reproductive aged
men and women should be included.
Due to the risks for neurotoxicity, immunotoxicity
and other risks, elders and people with health
conditions should be included. Because of MC's
conversion to CO, people engaged in vigorous
physical activity, users of alcohol and individuals
suffering from lung and heart disease should be
included.
sufficient for the identified subpopulations applicable to
methylene chloride.
At the beginning of section 2.4.1, EPA states that for the
purpose of this assessment, EPA considered occupational
exposure of the total workforce of exposed users and non-
users, which include but are not limited to male and female
workers of reproductive age who are >16 years of age.
Female workers of reproductive age are >16 to less than 50
years old. Adolescents (>16 to <21 years old) are a small
part of this total workforce. The occupational exposure
assessment is applicable to and covers the entire workforce
who are exposed to MC. There was no upper limit on male
reproductive age assumed for this evaluation.
For methylene chloride consumer exposure evaluation,
inhalation exposures are presented as concentrations
encountered by users and bystanders independent of age-
group considerations, while dermal exposures are presented
for users in three age groups that would be inclusive of
reproductive aged men and women (ages 11-15; ages 16-20,
and 21+)
Potentially exposed or susceptible subpopiilation considerations for the general population
SACC
SACC COMMENTS:
The impact of MC emissions to the ambient air,
including population exposures living in close
proximity to large and small emission sources of
MC. These populations can be considered
potentially exposed subpopulations in the context of
potentially exposed or susceptible subpopulations.
EPA evaluated and considered the impact of existing laws
and regulations (e.g., regulations on landfill disposal, design,
and operations) in the problem formulation step to determine
what, if any future analysis might be necessary as part of the
risk evaluation. During problem formulation EPA analyzed
the TRI data and examined the definitions of elements in the
TRI data to determine the level of confidence that a release
would result from certain types of disposal to land (e.g.
RCRA Subtitle C hazardous landfill and Class I
underground Injection wells) and incineration. EPA also
examined how methylene chloride is treated at industrial
facilities. EPA did not include emissions to ambient air from
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commercial and industrial stationary sources, which are
under the jurisdiction of and addressed by Section 112 of the
Clean Air Act. EPA did not include emissions to ambient air
from municipal and industrial waste incineration and energy
recovery units in the risk evaluation, as they are regulated
under section 129 of the Clean Air Act. EPA did not include
disposal to underground injection, RCRA Subtitle C
hazardous waste landfills, RCRA Subtitle D municipal solid
waste (MSW) landfills, and on-site releases to land from
industrial non-hazardous waste and construction/demolition
waste landfills in this Risk Evaluation. These methods of
disposal fall under the jurisdiction of and are addressed by
other EPA-administered statutes and associated regulatory
programs.
64, 73, 75,
44
PUBLIC COMMENTS:
Long-term exposure to MC through the ambient air
pathway is an area of concern for the South Coast
Air Quality Management District (AQMD),
especially for residents and sensitive receptors
located close to facilities using MC or temporary
worksites where there is use of MC-containing
materials.
ATSDR emphasizes that "groups within the general
population that could have potentially high
exposures... include individuals living in proximity
to sites where MC was produced or sites where
methylene chloride was disposed, and individuals
living near 1 of the 1,569 NPL hazardous waste
sites where methylene chloride has been detected in
some environmental media (HazDat 1996)."
In the 2018 MC Problem Formulation document,
EPA stated that it expects to consider in the risk
evaluation "other groups of individuals within the
general population who may experience greater
exposures due to their proximity to conditions of
use. Such consideration was not presented in the
EPA did not consider background exposure that workers
and consumers using products containing MC might be
exposed to in addition to exposures from TSCA-
regulated conditions of use. This may result in an
underestimation of risk, and additional discussion of this
underestimation has been added to the document in the
uncertainties section.
See section 1.4.2 of the risk evaluation regarding EPA's
approach to exposure pathways and risks addressed by
other EPA-administered statutes.
EPA evaluated and considered the impact of existing
laws and regulations (e.g., regulations on landfill
disposal, design, and operations) in the problem
formulation step to determine what, if any future analysis
might be necessary as part of the risk evaluation. During
problem formulation EPA analyzed the TRI data and
examined the definitions of elements in the TRI data to
determine the level of confidence that a release would
result from certain types of disposal to land (e.g. RCRA
Subtitle C hazardous landfill and Class I underground
Injection wells) and incineration. EPA also examined
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draft risk evaluation document, and instead, the
EPA assumed that its other environmental statutes -
such as the CAA - adequately assess and
effectively manage these other exposure pathways.
We disagree with this assumption and are
concerned that risks to individuals living or working
near manufacturing, processing, use or disposal
sites could be substantial.
EPA provides no analysis of whether those living in
proximity to the conditions of use are at greater risk
due to greater exposure. EPA should analyze these
exposures and should analyze these potentially
exposed subpopulations.
EPA should also identify people living near all
disposal sites as potentially exposed or susceptible
subpopulations. These groups include (but are not
limited to) those living near Superfund sites. Many
disposal sites are associated with activities that
reflect ongoing or prospective manufacturing,
processing, distribution, or use, so EPA must also
analyze those disposals and disposal sites and
populations living in proximity to them.
how methylene chloride is treated at industrial facilities.
EPA did not include emissions to ambient air from
commercial and industrial stationary sources, which are
under the jurisdiction of and addressed by Section 112 of
the Clean Air Act. EPA did not include emissions to
ambient air from municipal and industrial waste
incineration and energy recovery units in the risk
evaluation, as they are regulated under section 129 of the
Clean Air Act. EPA did not include disposal to
underground injection, RCRA Subtitle C hazardous
waste landfills, RCRA Subtitle D municipal solid waste
(MSW) landfills, and on-site releases to land from
industrial non-hazardous waste and
construction/demolition waste landfills in this Risk
Evaluation. These methods of disposal fall under the
jurisdiction of and are addressed by other EPA-
administered statutes and associated regulatory
programs.
66
PUBLIC COMMENTS:
Chapter 5 (p. 425) notes that high-end risk estimates
(i.e., 95th percentile) are generally intended to
cover individuals or sub-populations with greater
exposure. This may be the best available alternative
but may not address smaller subpopulations that
have very different risk profiles.
To address potentially exposed subpopulations, the range of
use patterns evaluated (10th to 95th percentile) is expected to
cover the reasonable range of possible exposures. To address
susceptible subpopulations, EPA has relied in PBPK models
(for chronic risks) as well as uncertainty factors (for
noncancer acute and chronic risks), and the lower 95th
percent confidence limits on the dose-response model (for
cancer), in accordance with existing guidance (EPA. 2005b.
2002).
Workers are a potentially exposed or susceptible subpopulation
73, 69, 72
PUBLIC COMMENTS:
EPA is required to protect workers, both generally
and as a "potentially exposed or susceptible
subpopulation," under TSCA, not under OSHA.
EPA recognizes that the PEL is a technology-based limit,
rather than a risk-based limit and that there may be health
risks in some cases from exposures below the PEL.
As noted in the draft risk evaluation, EPA relied on
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There are considerable gaps in the OSHA standard
that leave some particularly vulnerable workers
unprotected (e.g., small businesses or individual
contractors). EPA cannot claim the OSHA standard
is sufficient to remove unreasonable risks to
workers as it does not improve workplace
compliance over time, allows an appreciable cancer
risk that is unreasonable as per EPA standards, and
does not protect all worker populations. EPA is
obligated under TSCA to take action to mitigate
unreasonable risks.
The 2016 amendments to TSCA strengthened
EPA's already-existing mandate to protect workers.
TSCA's new definition of "potentially exposed or
susceptible subpopulation" has no asterisk next to
workers, and there is no basis in TSCA for EPA to
provide less protection to workers than any other
such subpopulation, let alone than the general
population. Yet that is exactly what EPA has done
here.
EPA represents its high-end estimates as "generally
intended to cover individuals or sub-populations
with greater exposure," while its central tendency
estimates apply to the "average or typical exposure"
that people experience (p. 425). TSCA would not
permit EPA to protect against only the "average or
typical exposure;" in fact, when it comes to workers
and other "potentially exposed or susceptible
subpopulations," EPA is required to protect all of
them.
NIOSH guidance when choosing the 10"4 cancer risk
benchmark to evaluate risks to workers from methylene
chloride exposure.
The range of use patterns evaluated (10th to 95th
percentile) is expected to cover the reasonable range of
possible exposures.
EPA considers each condition of use and uses exposure
scenarios with and without PPE that may be applicable
to particular worker tasks on a case-specific basis for a
given chemical. For the purposes of determining
whether or not a condition of use presents unreasonable
risks, EPA incorporates assumptions regarding PPE use
based on this information and 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. Additionally, in consideration
of the uncertainties and variabilities in PPE usage, EPA
uses the high-end exposure value when making its
unreasonable risk determination in order to address
those uncertainties as well as to capture exposures for
PESS. EPA has also outlined its PPE assumptions in
section 5.1.
Consideration of potentially exposed or susceptible subpopulations and genetic polymorphisms
SACC
SACC COMMENTS:
GST-T1 genotype plays an important role in
individual response to MC exposures. This defines
(genetically and proportionately) a specifically
EPA added more information to the risk evaluation to
explain that this population is expected to be protected based
on use of the 95% lower confidence limit on the cancer slope
factor.
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susceptible subpopulation that should be further
discussed in the risk evaluation.
44, 49, 72,
75
PUBLIC COMMENTS:
In particular people with the GST-T1 +/+ genotype
- who comprise approximately 1/3 of the U.S.
population, and thus also represent a significant
proportion of the workforce - "are expected to be
more susceptible to cancer endpoints. EPA failed to
protect these sensitive subpopulations in its risk
characterization."
EPA added more information to the risk evaluation to
explain that this population is expected to be protected based
on use of the 95% lower confidence limit on the cancer slope
factor.
Consideration of potentially exposed or susceptible subpopulations and cardiovascular disease
69, 49, 44,
75, 72
PUBLIC COMMENTS
EPA's quantitative calculations of risk do not
account for the increased susceptibility of those
with cardiovascular disease to MC acute toxicity,
including higher risk of myocardial infarction and
fatality. In addition, MC's metabolite, CO, has well-
documented ischemic and arrhythmogenic cardiac
effects. MC can also directly sensitize the
myocardium to arrhythmias.
This risk group constitutes a large proportion of the
population and EPA should add a data-derived or
default adjustment factor to its risk calculations.
EPA considers the intraspecies UF of 10 for the CNS
endpoint from acute exposure to be sufficient; this UF was
established to account for uncertainty and variability that
includes susceptible subooDulations (EPA. 2002). Research
indicates that a factor of 10 is sufficient in most cases (EPA.
2002). and EPA expects that the UFs used in the risk
evaluation are sufficient for the identified subpopulations
applicable to methylene chloride.
Sensitization of the myocardium to ventricular tachycardia
occurs at concentrations of 25,000 ppm, and therefore the
POD of 195 ppm is expected to protect against this effect.
Potentially exposed or susceptible subpopulations and developmental toxicity/neurotoxicity
55, 73, 44,
75, 57
PUBLIC COMMENTS:
EPA does not evaluate risks to fetuses and infants
or calculate its PODs with them in mind.
Neurotoxic and cardiovascular effects may be
exacerbated in fetuses and infants with higher
residual levels of fetal hemoglobin when exposed to
high concentrations of methylene chloride;
however, developmental neurotoxicity risks are not
addressed.
With regard to the acute MOE, the Bornschein et al.
(1980) neurodevelopmental study revealed effects
EPA uses PBPK models for toxicokinetic differences (for
chronic risk) and intraspecies UFs in the risk evaluation. The
intraspecies UF was established to account for uncertainty
and variability that includes susceptible subpopulations
(EPA. 2002). Research indicates that a factor of 10 (when
including both toxicokinetics and toxicodynamics) is
sufficient in most cases (EPA, 2002). and EPA expects that
the UFs used in the risk evaluation are sufficient for the
identified subpopulations applicable to methylene chloride.
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but did not identify a NOAEL. This calls into
question whether the hazard values (PODs) for
acute exposure occupational and consumer
scenarios are adequately protective for the fetus (in
the case of exposures to pregnant women) as well as
infants and children.
EPA did not apply any additional UFs to address
sensitive developmental neurotoxicity endpoints,
which can be much more sensitive than systemic
impacts like fecundity and fetal resorption.
Conclusion: Based on these findings, we assert that
the current system in the United States for
evaluating scientific evidence and making health-
based decisions about environmental chemicals is
fundamentally broken. To help reduce the
unacceptably high prevalence of
neurodevelopmental disorders in our children, we
must eliminate or significantly reduce exposures to
chemicals that contribute to these conditions. We
must adopt a new framework for assessing
chemicals that have the potential to disrupt brain
development and prevent the use of those that may
pose a risk. This consensus statement lays the
foundation for developing recommendations to
monitor, assess, and reduce exposures to neurotoxic
chemicals. These measures are urgently needed if
we are to protect healthy brain development so that
current and future generations can reach their fullest
potential.
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 science in a weight of scientific evidence
analysis.
75
PUBLIC COMMENTS:
The draft MC evaluation does not mention placental
transfer as an additional risk factor for fetuses.
Because fetuses are already more vulnerable to the
neurotoxic effects of elevated CO than healthy
adults, even where fetal exposures may be lower
EPA uses PBPK models for toxicokinetic differences (for
chronic risk) and intraspecies UFs to account for variation in
sensitivity within the human population. The intraspecies UF
was established to account for uncertainty and variability
that includes susceptible subpopulations (EPA. 2002).
Research indicates that a factor of 10 (when including both
toxicokinetics and toxicodynamics) is sufficient in most
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than maternal exposures, the effects on the fetus are
likely to be much more severe and even deadly.
Use of an additional UF to address to address
greater susceptibility to MC's CNS effects during
early-life exposure is consistent with the similarly
enhanced UFs recommended in EPA's
Supplemental Guidance for Assessing
Susceptibility from Early-Life Exposure to
Carcinogens.
cases ( 02), and EPA expects that the UFs used in the
risk evaluation are sufficient for the identified subpopulations
applicable to methylene chloride, including fetuses.
Cancer risk benchmark
49, 73, 42,
70, 75, 69,
72
PUBLIC COMMENTS:
EPA cites NIOSH guidance and the Benzene
decision for support of the cancer risk benchmark
(p. 426, footnote 23), but that guidance and that
case pertain to how the standard for health
protection is applied under OSHA, not under
TSCA.
The 2016 amendments to TSCA also explicitly
preclude EPA from considering feasibility or other
non-risk factors when determining whether a
chemical presents an "unreasonable risk," including
to workers; see TSCA Section 6(b)(4)(A). Yet EPA
invokes standards under other statutes that lack this
prohibition in an effort to claim precedent for its 1 x
10"4 benchmark (p. 426, footnote 22).
EPA invokes the "two-step approach" used under
the CAA, where EPA includes a "limit on
maximum individual lifetime [cancer] risk (MIR) of
approximately 1 in 10 thousand" (p. 426 n. 22,
citing 54 Fed. Reg. 38,045 (September 14, 1989))
and consideration of whether emissions standards
provide an ample margin of safety to protect public
health "in consideration of all health information,
including the number of persons at risk levels
higher than approximately 1 in 1 million, as well as
other relevant factors."
As noted in the draft risk evaluation (Section 5.1.1), EPA
relied on NIOSH guidance fWhittaker et aL 2016) when
choosing the 10"4 cancer risk benchmark to evaluate risks to
workers from methylene chloride exposure. NIOSH's
mandate, on ds iii of Whittaker et al. (2016), is to: "...
describe exposure levels that are safe for various periods of
employment, including but not limited to exposure levels at
which no employee will suffer impaired health or functional
capacities or diminished life expectancy as a result of his
work experience." Although NIOSH guidance, p. 20, states
that: "exposures should be kept below a risk level of 1 in
10,000, if practical [emphasis added]" EPA adheres to the 1
in 10,000 benchmark during the risk evaluation stage for
TSCA chemicals.
Note that other precedents (e.g., Office of Water; Office of
Air) are the basis for cancer benchmarks to be used for risks
to the general population, but EPA did not evaluate such
scenarios for MC.
EPA has considered susceptible subpopulations when
evaluating these risks, as directed by TSCA. Specifically,
EPA used the lower 95th confidence bound on the cancer
slope, which accounts for variability and uncertainty in
individuals' tumor responses, including susceptible
subpopulations.
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EPA likewise uses a risk range of 1 x 10"4 to 1 x 10"
6 to set cleanup goals at CERCLA hazardous waste
sites. EPA's recent draft risk evaluations deviate
from this approach for worker exposures,
maintaining that risks smaller than 1 x 10"4 will be
considered "reasonable" under TSCA because,
"consistent with case law and 2017 NIOSH
guidance," this risk level applies to "industrial and
commercial work environments subject to
Occupational Safety and Health Act (OSHA)
requirements" (p. 426).
EPA fails to explain why OSHA precedent should
control decision-making under TSCA. In contrast to
OSHA, TSCA provides protections to workers not
just from chemical exposure in the workplace, but
also from air emissions and other environmental
releases as well as exposures to consumer products.
In this risk evaluation, EPA has set a risk level for
the entire worker population that is the same as the
level EPA elsewhere set for the most exposed
individual in a population. EPA then erroneously
invokes this level repeatedly to find a number of
conditions of use of MC to pose no risk to any
workers, thereby subjecting many tens of thousands
of workers to cancer risks that are as much as two
orders of magnitude higher than warranted. This
approach must be rejected on scientific as well as
legal grounds.
The cancer risk benchmark level EPA uses for
workers that fails to protect them as a vulnerable
subpopulation as required by TSCA. EPA must
apply to workers the same benchmarks for
determining unreasonable cancer risks that it uses
for other populations. For all exposed populations,
the goal should be to protect against cancer risks
exceeding 1 x 10"6.
Consistent with 2017 NIOSH guidance, EPA used lxlO"4 as
the benchmark for the purposes of this unreasonable risk
determination for individuals in industrial and commercial
work environments. It is important to note that lxlO"4 is not
a bright line and EPA has discretion to make unreasonable
risk determinations based on other benchmarks or factors as
appropriate. See section 5.1.1.2 of the risk evaluation for
additional information.
For the purposes of unreasonable risk determinations, EPA is
assuming the use of PPE on a case-by-case basis for each
COU and the context of how it is used (i.e., industrial,
commercial, consumer), in contrast to the approach EPA
would take in a regulatory action, which would protect
against workplace hazards by requiring certain actions to
address the unreasonable risk. EPA also distinguished
between the methods for risk evaluation and the "protection"
measures that are the goal of risk management actions.
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73, 75
PUBLIC COMMENTS:
EPA's occupational risk estimates were
dramatically impacted by EPA's selection of 10"4 as
the cancer risk benchmark.
To determine how large the impact is, EPA's cancer
risk estimates for each of its 65 conditions of use
involving inhalation exposures to workers and
ONUs and each of its 23 OESs involving potential
dermal exposures to workers were examined.
Collectively, this analysis shows that EPA's draft
risk evaluation has dramatically understated the
occupational cancer risks of MC (specific examples
were given).
As noted in the draft risk evaluation, EPA relies on NIOSH
guidance when choosing the 10"4 cancer risk benchmark to
evaluate risks to workers from methylene chloride exposure.
EPA, consistent with 2017 NIOSH guidance, used lxlO"4 as
the benchmark for the purposes of this risk determination for
individuals in industrial and commercial work
environments. EPA, consistent with 2017 NIOSH guidance,
used lxlO"4 as the benchmark for the purposes of this
unreasonable risk determination for individuals in industrial
and commercial work environments. It is important to note
that lxlO"4 is not a bright line and EPA has discretion to
make unreasonable risk determinations based on other
benchmarks or factors as appropriate. See section 5.1.1.2 of
the risk evaluation for additional information.
Risk to ON
Js
SACC,
49, 73, 72,
75
SACC COMMENTS:
In its review of the resulting risk estimate for
chronic exposure of ONU for two scenarios
(repackaging and plastic and rubber product
manufacturing), the risk evaluation reports: "... In
consideration of the uncertainties in the exposures
for ONUs for this condition of use, EPA has
determined the non-cancer risks presented by
chronic inhalation are not unreasonable" (pp. 432
and 436).
The justification for this statement is the use of the
pre-1997 updated OSHA PEL exposure data. This
justification seems arbitrary, given that pre-1997
data was used to estimate exposure for fabric
finishing and spot cleaning. Since the risk
evaluation establishes the need and utility of the
pre-1997 data in one case, it should also use all the
data for repackaging and plastic and rubber product
In section 4.3.2.1, EPA states the uncertainty of the use of
data from before the PEL revision and that use of some older
data may overestimate some exposures. EPA revised text in
2.4.1.1 to expand upon adequacy of older data and
summarize EPA's new statistical analysis, which is included
as a new appendix in the Supplemental Information on
Releases and Occupational Exposure Assessment. This
supplemental document also presents all data found for each
use and provides rational for whether data were acceptable or
not.
EPA considers occupational non-users (ONUs) to be a subset
of workers for whom the potential inhalation exposures may
differ based on proximity to the exposure source. For the
majority of MC conditions of use, the difference between
ONU exposures and workers directly handling the chemical
cannot be quantified. EPA assumed that, in most cases, ONU
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manufacturing. Alternatively, the risk evaluation
should explicitly state under what conditions data
do not represent exposure (or hold too much
uncertainty) prior to the risk determination stage.
Recommendation: Be more explicit and consistent
with respect to what data are deemed usable for the
determination of exposure and risk.
PUBLIC COMMENTS:
EPA fails to properly account for risks to so-called
ONUs, because the range of workers defined by
EPA as ONUs (supervisors, managers, engineers,
and other personnel in nearby production areas) is
too broad to warrant a single categorization
EPA applied the flawed approach that even if it
found excessive risks in some cases for high-end
exposures, it could still determine that the risk was
not unreasonable as long as the risks of the
corresponding central tendency exposures did not
exceed its benchmarks.
This assumption alone, which has no support in the
record, resulted in multiple determinations of no
unreasonable risk for ONUs. If EPA treated ONUs
similarly to other workers, the risks presented by
this condition of use would be nearly 20 times
lower than the benchmark MOE.
This is not theoretical: EPA has ignored
exceedances of its risk benchmarks for acute,
chronic and/or cancer effects by high-end exposures
to ONUs for at least 19 of its 65 conditions of use;
for examples, see pp. 431, 436, 449.
inhalation exposures are assumed to be lower than inhalation
exposures for workers directly handling the chemical
substance. In several instances, monitoring data or modeling
did not distinguish between worker and ONU inhalation
exposure estimates. To account for this uncertainty, EPA
considered the workers' central tendency risk estimates from
inhalation exposures when determining ONU unreasonable
risk. For dermal exposures, EPA assumed that ONUs do not
have direct contact with methylene chloride; therefore, non-
cancer effects and cancer from dermal exposures from
methylene chloride generally were not identified. For
inhalation exposures, EPA, where possible, estimated ONU
exposures and described the risks separately from workers
directly exposed.
66
PUBLIC COMMENTS:
In chapter 5, line 9910 on p. 431, the article stated
that it poses an unreasonable risk to occupational
non-users that would be exposed to it. Protective
measures should be in place or lowering of the
standard would be in order, rather than risk people
During the risk management process, which follows the risk
evaluation, EPA identifies and proposes risk management
options for the unreasonable risks EPA has determined are
presented.
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in an occupational health setting to this exposure
without their knowledge.
Exclusions in the MC draft risk evaluation
75
PUBLIC COMMENTS:
EPA's position that other environmental laws
should displace TSCA risk evaluations arbitrarily
assumes that these laws provide equivalent
protection of public health and the environment and
that there is no added benefit in evaluating the risks
presented by environmental pathways of exposure
under TSCA.
TSCA's strict risk-based framework for chemical
risk management is not mirrored in most
environmental laws that govern releases to air,
water, and soil and disposal of waste.
Clarifying language about what pathways are addressed
under other statutes has been added to Section 1.4.2 of the
Risk Evaluation.
49, 73, 64
PUBLIC COMMENTS:
In the problem formulation for MC (pp. 43-44),
EPA explicitly relies on the CAA to dismiss the
need to assess exposures to MC from air emissions.
MC is regulated as a HAP under the CAA, but the
standards under the CAA for HAPs are set for
individual source categories, meaning that the
exposures to MC from all sources in combination
are never considered.
Unlike considerations under TSCA, EPA is required
to consider cost in establishing standards for HAPs,
resulting in a less stringent risk analysis under CAA
authority than that under TSCA review.
It is recommended that the EPA establish clear
enforcement mechanisms for its standards and
allow state and local regulatory agencies the
authority to enforce them.
Clarifying language about what pathways are addressed
under other statutes has been added to Section 1.4.2 of the
Risk Evaluation.
66, 76, 33,
49, 73, 77
PUBLIC COMMENTS:
EPA's ongoing failure to consider all contexts in
which exposure to MC create the risk of cancer,
injury to the reproductive system, or other harms to
Clarifying language about what pathways are addressed
under other statutes has been added to Section 1.4.2 of the
Risk Evaluation.
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human health and the environment puts our
residents at risk, contradicts TSCA's requirements,
and fails to satisfy reasonableness standards.
EPA is thus required to evaluate all of the risks
associated with a chemical's known, intended, and
reasonably foreseen conditions of use, regardless of
whether such risks are or may be regulated under
another statute. Even if other statutes can address
some of these risks to some extent, EPA cannot
evaluate, as it purports to do here, the total,
cumulative risk to public health and the
environment from these chemicals if it excludes
exposures through these other pathways To do so
would render any evaluation partial and incomplete.
This assault on TSCA is illegal, and goes against
the science that informs what we know about how
chemicals like MC can affect our health and the
environment. EPA's delegated authority under
TSCA does not allow it to focus only on "the
greatest areas of concern to EPA." EPA must
evaluate all exposure pathways, including those
regulated by other statutes.
SACC, 49,
55, 72, 73,
75
SACC COMMENTS:
The Committee discussed the need for data on
neurotoxicity on outcomes such as CNS depression
and cognitive deficits.
PUBLIC COMMENTS:
EPA's decision not to develop risk estimates for
reproductive/development effects, developmental
neurotoxicity, immunotoxicity, and endocrine
effects is effectively a recognition that it cannot
make unreasonable risk determinations under TSCA
Section 6(b) for these endpoints using currently
available data.
EPA had sufficient information to complete the MC risk
evaluation using a weight of scientific evidence approach.
Data are available for the endpoints identified were not
recommended for use in the dose-response analysis. EPA
selected the first 10 chemicals for risk evaluation based in
part on its assessment that these chemicals could be assessed
without the need for regulatory information collection or
development. When preparing this risk evaluation, EPA
obtained and considered reasonably available information,
defined as information that EPA possesses, or can
reasonably obtain and synthesize for use in risk evaluations,
considering the deadlines for completing the evaluation.
However, EPA will continue to improve on its method and
data collection for the next round of chemicals to be
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EPA's obligation under TSCA is to address all
conditions of use, hazards and routes of exposure in
its risk evaluations.
EPA did not use its information-gathering authority
when preparing the draft MC risk evaluation, even
in circumstances where EPA itself described the
existing data as inadequate and despite identifying
the absence of data for critical endpoints in its 2011
IRIS assessment and 2014 Work Plan risk
assessment.
Any risk evaluation that EPA now finalizes without
sufficient data for all endpoints would be
incomplete and inadequate. EPA must act
expeditiously to require the necessary testing under
Section 4 and make an unreasonable risk evaluation
for the health effects it is now unable to address.
assessed under TSCA. EPA addresses all conditions of use
for MC.
Environmental risk characterization
SACC, 73,
49, 75, 66
SACC COMMENTS:
Five out of 21 (23.8%) manufacturing facilities
examined in the assessment were found to pose risk
to aquatic organisms. Given that in 2019 there were
81,654 facilities reporting disposal of MC, it is
quite possible that many these facilities, if
examined, would also be found to pose an
unreasonable risk.
This admittedly simplistic extrapolation suggest that
MC releases pose an unreasonable risk for
environmental/aquatic receptors simply because of
the large numbers and geographical spread of
manufacturing facility releases.
EPA should acknowledge the implications of this
extrapolation in its environmental risk
characterization.
PUBLIC COMMENTS:
EPA cannot reasonably dismiss its findings of
environmental risk merely by invoking uncertainty.
EPA considered facilities that release methylene chloride
and did not find unreasonable risk to the environment for
any condition of use based on risks to aquatic, sediment-
dwelling, and terrestrial organisms.
It should be noted that it is unclear where the SACC
member identified 81,654 facilities reporting disposal of
MC. The number is not in the methylene chloride risk
evaluation.
EPA modeled the TRI data and considered the waste
treatment of the facilities, the ambient water
concentrations, the biological relevance of the species
(e.g. for one facility it releases to an estuarian
environment, and the acute RQ is based on amphibian
data. Because amphibians reside in freshwater
environments, acute risk to amphibians is unlikely at this
facility), and frequency and duration of the exposure
(e.g., in many instances the releases were indirect) to
determine if the RQs indicated risk.
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For environmental risk, EPA's own analyses
showed that MC presents an unreasonable risk to
aquatic organisms (pp. 389, 286-87), but EPA
dismisses this unreasonable risk by invoking
uncertainty without further explanation (pp. 32,
428).
This approach is arbitrary and capricious because
EPA refuses to accept the outcomes of its own
analyses, and EPA's conclusions run contrary to the
evidence before the agency. Based on the analysis
presented in the draft risk evaluation, EPA should
find an unreasonable risk to the environment
presented by certain disposal and recycling
conditions of use.
EPA also discounts the results of its own
calculations that indicate unreasonable
environmental risks. Despite its exclusions of data
and averaging of results, EPA still calculated
multiple RQs >1, the general threshold for
unreasonable risk (p. 425).
In its draft risk evaluation, EPA concludes that MC
does not pose an unreasonable risk to the
environment. However, it reaches this conclusion by
excluding the studies that demonstrate the greatest
environmental risk, obscuring the results of the
studies that it does consider, and disregarding RQs
more than 100 times greater than EPA's
unreasonable risk threshold.
EPA also dismisses the evidence of harmful
contamination with the following: "No acute or
chronic risks to aquatic organisms were identified in
ambient water; therefore, the risks identified for the
five facilities mentioned above are likely localized
to surface water near the facility" (p. 389). EPA
provides no information on how large an area it
considers to be 'ambient' or 'localized' or - most
At the suggestion of the SACC, because the E-FAST
model does not consider chemical fate or hydrologic
transport properties and may not consider dilution in
static water bodies, EPA conducted an analysis of
fugacity modeling and a more robust discussion of these
uncertainties was added to the risk evaluation. Given the
uncertainties about waterbody depth, flow, temperature,
etc. there is some uncertainty about how long the half-life
of MC will be in various water bodies (section 4.4.6).
The analysis indicated that model outputs may best
represent concentrations found at the point of discharge,
and there is lower confidence in concentration estimates
the farther they are from the facility. Additionally, EPA
added more discussion of how large an area is considered
"ambient" and "localized." Discussion of other
uncertainties was also included, such as limitations in
data, since monitoring data were not available near
facilities where methylene chloride is released, TRI does
not capture release data for facilities with fewer than 10
employees, and only one year of release data was
evaluated.
While some site-specific RQs, calculated from modeled
release data from particular facilities conducting
recycling, disposal, and waste water treatment plant
activities, are greater than or equal to 1, indicating risk,
uncertainties related to these particular estimates
(discussed broadly above and specifically in section
4.2.2) support a determination of unreasonable risk for
the environment.
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importantly - why risks to aquatic species in
contaminated waters near facilities can be
disregarded in determining unreasonable risks to the
environment under TSCA.
Is the draft risk evaluation protective?
SACC, 49,
73, 66, 75
SACC COMMENTS:
One Committee member suggested that very likely
the Evaluation underestimates risk during the
process of risk characterization.
The target MOEs were not sufficiently large to
capture the uncertainties in the assessment (such as
e.g., GST polymorphisms, database UFs) and thus
conclusions of no unreasonable risk, for example
for ONUs, cannot be adequately supported.
In the spirit of protecting public health, the
Committee member invited the Agency to
acknowledge the unaccounted sources of
uncertainty and as a result include more scenarios in
the unreasonable risk category.
In several parts of the risk evaluation, the possibility
of both overestimation and underestimation are
discussed. One Committee member cautions that
overestimation in one part of the risk
characterization calculation and underestimation in
another part do not cancel each other out. The two
errors are not the same and do not carry the same
weight in terms of human health risk assessment.
PUBLIC COMMENTS:
In its draft risk evaluations, EPA has not only
understated MC risks, but also mischaracterized the
risks that it has calculated. EPA repeatedly finds
that risks that fall below the benchmark MOE or
that exceed EPA's cancer threshold are nonetheless
reasonable and need not be managed under TSCA.
In this risk evaluation EPA has re-instituted a
flawed approach, under which it can still deem a
EPA uses PBPK models for toxicokinetic differences (for
chronic risk) and intraspecies UFs (for non-cancer risks) in
the risk evaluation. The intraspecies UF was established to
account for uncertainty and variability that includes
susceptible subpopulations (EPA. 2002). Research indicates
that a factor of 10 (when including both toxicokinetics and
toxicodynamics) is sufficient in most cases (EPA. 2002). and
EPA expects that the UFs used in the risk evaluation are
sufficient for the identified subpopulations applicable to
methylene chloride.
EPA considers the uncertainties associated with each
condition of use, and how the uncertainties may result in a
risk estimate that overestimates or underestimates the risk.
Based on such analysis, EPA determines whether or not the
identified risks are unreasonable. Such consideration carries
extra importance when the risk estimates are close to the
benchmarks for risks from acute and chronic non-cancer
health effects and cancer.
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risk to be reasonable even though it exceeds the
applicable acceptable level, as long as it is "close"
to the acceptable level.
EPA applies this in only one direction in the draft
risk evaluation. Even where EPA's estimated MOEs
are only slightly greater than the benchmark MOE,
EPA still finds no unreasonable risk.
To determine whether or not a condition of use presents
unreasonable risks, EPA incorporates assumptions based on
information and judgement underlying the exposure
scenarios. These assumptions, which include assumptions
regarding PPE use, are described in the unreasonable risk
determination for each condition of use, in section 5.2. It is
important to note that the benchmarks for cancer and non-
cancer risk estimates are not bright lines, and EPA has
discretion to make unreasonable risk determinations based
on other risk benchmarks or factors as appropriate.
EPA uses the high-end exposure value when making its
unreasonable risk determination in order to address
uncertainties around PPE usage as well as to capture
exposures for PESS. Because EPA is making its
unreasonable risk determinations on the high-end exposure
value for workers and consumers and either the high-end
exposure value or central tendency for ONUs, depending on
the data, and factoring in the uncertainties due to UF factors,
it is unclear how this is a flawed approach. Additionally,
EPA makes an unreasonable risk determination and makes
no determination on reasonable risk.
69
PUBLIC COMMENTS:
Our research on MC fatalities finds current policies
inadequate to protect workers and recommends
elimination of MC use in commercial settings.
Thank you for your comment.
73
PUBLIC COMMENTS:
Of particular concern is that EPA's current draft
risk evaluation is less health-protective than its
2014 MC Work Plan risk assessment. EPA's risk
estimates backslides by a factor of 2 (relying on a
benchmark MOE = 30 as opposed to 60).
EPA also uses the far less health-protective cancer
risk benchmark of 10"4 instead of 10"6 (see Section
9.A.ii).
In previous assessments (e.g., the new chemicals program),
EPA has applied uncertainty factors of 3 instead of 10 when
effects are less severe. Furthermore, IRIS assessments have
used default uncertainty factors of 3. In the current risk
evaluation, EPA adjusted the LOAEL to NOAEL uncertainty
factor to 3 (from a default of 10) to account for the lower
severity of effect.
As noted in the draft risk evaluation, EPA relied on NIOSH
guidance when choosing the 10"4 cancer risk benchmark to
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evaluate risks to workers from methylene chloride exposure.
66
PUBLIC COMMENTS:
In datasets where there was insufficient data to
generate a mean or 95th percentile, EPA made up
their own. This could either be too protective or not
protective enough.
In Section 4.3.2.1, the potential for overestimation
by using the few available air concentration datasets
was discussed, and it was difficult to determine
whether or not those high values represented actual
occupational exposures. This section does not
appear to have substantial enough data to be health
protective.
EPA had sufficient information to complete the MC risk
evaluation using a weight of evidence approach. EPA
selected the first 10 chemicals for risk evaluation based in
part on its assessment that these chemicals could be assessed
without the need for regulatory information collection or
development. When preparing this risk evaluation, EPA
obtained and considered reasonably available information,
defined as information that EPA possesses, or can
reasonably obtain and synthesize for use in risk evaluations,
considering the deadlines for completing the evaluation.
However, EPA will continue to improve on its method and
data collection for the next round of chemicals to be
assessed under TSCA.
66, 73
PUBLIC COMMENTS:
If the EPA is attempting to be health protective for
the vulnerable populations that would be exposed at
higher levels than the general population on a more
regular occurrence, these assumptions should be
laid out more transparently.
Workers at any facility - whether small, medium, or
large - where use of effective PPE cannot be
thoroughly documented should be considered
vulnerable subpopulations and the risk they face be
specifically assessed. For these subpopulations,
EPA must determine risk based on exposures
without assuming any use of PPE.
The range of use patterns evaluated (10th to 95th percentile)
covers the reasonable range of possible exposures.
Risk characterization - general
73
PUBLIC COMMENTS:
EPA failed to analyze distribution in commerce and
made unsupported risk findings about this condition
of use without a supporting analysis.
EPA's finding on this condition of use has no
factual support. It is not supported by substantial
evidence or the best available science, and EPA's
For the purposes of the final unreasonable risk
determination, distribution in commerce of methylene
chloride is the transportation associated with the moving of
methylene chloride in commerce. Unloading and loading
activities are associated with other conditions of use.
EPA assumes transportation of methylene chloride is in
compliance with existing regulations for the transportation
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analysis is arbitrary and capricious because it fails
to consider this important part of the problem - one
of the conditions of use specifically identified by
Congress.
of hazardous materials, and emissions are therefore minimal
(with the exception of spills and leaks, which are outside the
scope of the risk evaluation). Based on the limited emissions
from the transportation of chemicals, EPA determines that
there is no unreasonable risk of injury to health (workers
and ONUs) from the distribution in commerce of methylene
chloride.
44, 75
PUBLIC COMMENTS:
The draft evaluation addresses 15 consumer
products that contain MC. It concludes that these
products present acute risks similar in nature and
magnitude to the paint remover risks on which EPA
based its consumer use ban.
The risk evaluation incorporates verbatim large
portions of EPA's 2014 risk assessment and thus
reaffirms the rationale for the proposed ban on
commercial use of these products that EPA failed to
finalize earlier this year.
Thank you for your comment.
69, 77, 71
PUBLIC COMMENTS:
EPA has concluded that the vast majority of the
conditions of use of MC present an unreasonable
risk. But EPA needs to make a determination, under
Section 6(b), as to whether MC itself presents an
unreasonable risk. The evidence that EPA has
already reviewed in its draft risk evaluation compels
a finding of yes.
Per 40 CFR 702.47 ".. EPA will determine whether the
chemical substance presents an unreasonable risk of injury
to health or the environment under each condition of use
within the scope of the risk evaluation..This approach
outlined in the implementing regulations for TSCA risk
evaluations is consistent with the statutory text in TSCA
section 6(b)(4)(A), which instructs EPA to conduct risk
evaluations to determine whether a chemical substance
presents an unreasonable risk "under the conditions of use."
71
PUBLIC COMMENTS:
EPA's risk evaluation must address commercial use
and occupational conditions of use and exposures.
Well-documented occupational risks from
commercial uses are not adequately being addressed
by EPA as required by TSCA. In March 2019, the
Agency also proposed to reassess the feasibility of a
training, certification, and limited access program
for commercial uses of MC paint and coating
EPA evaluated all conditions of use of methylene chloride
under TSCA, including commercial and industrial uses that
result in occupational exposures. Risk management
activities are outside the scope of the risk evaluation. As the
commenter indicated, as appropriate for any condition of
use determined to have unreasonable risk, EPA will
consider feasibility and implementation of any risk
management actions that are proposed to address the
unreasonable risks that EPA has determined are presented.
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removal, options that were already analyzed and
rejected by the Agency due to inability of these
techniques to mitigate unreasonable risks.
In that context, EPA intends to analyze the applicability of
any training, certification, and limited access programs.
45
PUBLIC COMMENTS:
The use of TWA extrapolation from toxicology
studies to schedules for the occupational scenarios
is specific to TSCA risk evaluations. The duration
averaging approaches for each risk assessment
scenario definition should be closely evaluated
considering chemical-specific MOA and
toxicokinetic data.
As noted in a previous response, EPA understands the
uncertainties in using any model but EPA chose the use of
the ten Berge equation because even though the lethality data
they are based on are not ideal, they do represent an
empirically-derived value from inhalation data for solvents.
Also, there are several assumptions and uncertainties in the
PBPK model described by Bos et al. (2006) that don't
warrant using it instead of the ten Berge equation: 1) The
model accounts for P-450 saturation but P450 saturation
occurs at approximately 500 ppm, a value higher than the
POD for the current evaluation; 2) The model includes the
distribution of GSTT1 in the population but a human study
was already used; 3) the parent compound MC has been
shown to result in CNS effects in excess of CO/COHb
concentrations and Bos et al. (2006) acknowledge that there
are no adequate data on MC in rat or human brains; and 4)
Bos et al. (2006) state that the model overoredicts MC and
COHb concentration by up to 50%.
66
PUBLIC COMMENTS:
On several occasions, sources used had likely
conflicts of interest from industry making chemical
or lobbying group. Other assumptions were made
based off one source and from studies made greater
than 30 years ago. It would be more prudent to put
out a request for more information, especially
amongst industrial hygiene groups to assess
occupational health exposure limits that monitor
hazardous chemicals.
EPA had sufficient information to complete the MC risk
evaluation using a weight of evidence approach. EPA
selected the first 10 chemicals for risk evaluation based in
part on its assessment that these chemicals could be
assessed without the need for regulatory information
collection or development. When preparing this risk
evaluation, EPA obtained and considered reasonably
available information, defined as information that EPA
possesses, or can reasonably obtain and synthesize for use in
risk evaluations, considering the deadlines for completing
the evaluation. However, EPA will continue to improve on
its method and data collection for the next round of
chemicals to be assessed under TSCA.
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49, 73
PUBLIC COMMENTS:
TSCA requires EPA to make a determination as to
whether MC, as a whole, presents an unreasonable
risk of injury to health or the environment. The
extent and magnitude of the flaws in this draft risk
evaluation, and the resulting underestimation of
risk, mean that EPA has clearly not provided
support for any assertion that MC, across all of its
conditions of use, does not present unreasonable
risk.
Indeed, EPA's determinations that many conditions
of use of the chemical do present unreasonable risk
can only support a conclusion that the chemical
presents unreasonable risk. Moreover, the flaws we
have identified make clear that EPA has
significantly understated the extent and magnitude
of the chemical's unreasonable risk, both overall
and for specific conditions of use.
Per 40 CFR 702.47 ".. EPA will determine whether the
chemical substance presents an unreasonable risk of injury
to health or the environment under each condition of use
within the scope of the risk evaluation..This approach
outlined in the implementing regulations for TSCA risk
evaluations is consistent with the statutory text in TSCA
section 6(b)(4)(A), which instructs EPA to conduct risk
evaluations to determine whether a chemical substance
presents an unreasonable risk "under the conditions of use."
66
PUBLIC COMMENTS:
The risk assessment only looks at a subset of
exposures (acute CNS effects for acute exposure),
liver effects, and cancer risks for chronic exposure -
although it recognizes that there may be many other
health-related effects of MC. The decision was
made to focus on these effects due to data
limitations, but at least a qualitative discussion of
other risks would have provided a fuller picture.
EPA added more information on these uncertainties to
Section 4.3.5. - Assumptions and Key Uncertainties in the
Human Health Hazards. The risk evaluation also discusses
the weight of scientific evidence related to these other
effects, including why they were not carried forward to
dose-response modeling.
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66
PUBLIC COMMENTS:
p. 394: The assessment notes that some cancer risks
were "very nearly at the benchmarks" for MOE,
which both makes the selection of MOE (discussed
above) very important, and the characterization of
uncertainty very important. These close cases were
generally presented as not posting an unreasonable
risk, which is not the most health-protective
approach.
Chapter 4 Section 2 (related to occupational health
exposure): The way it is presented, the set points for
the risk estimated were stated but the logic as to
how they were calculated was not explained.
EPA considers the uncertainties associated with each
condition of use, and how the uncertainties may result in a
risk estimate that overestimates or underestimates the risk.
Based on such analysis, EPA determines whether or not the
identified risks are unreasonable. Such consideration carries
extra importance when the risk estimates are close to the
benchmarks for acute, chronic non-cancer risks, and cancer
risks.
The uncertainty factors are described in Section 3.2.5.2 and
Tables 4-3 through 4-5 identify that the uncertainty factors
are used to set the benchmark MOEs. Page 304 also
describes how the uncertainty factors are used to set the
benchmark MOE.
68
PUBLIC COMMENTS:
EPA should also be more transparent about its
consultation and coordination with OSHA when the
Agency addresses worker exposures in the risk
evaluations, as well as the degree of coordination
EPA OPPT had with the Office of Water as
required by TSCA Section 9.
A longer term re-thinking of EPA OPPT's approach
to coordinating with other EPA program offices,
and the establishment of a better process, is in order
- both to ensure protection of our air, water and soil
and to enable EPA OPPT to meet its statutory
obligations to conduct TSCA risk evaluations of
high priority chemicals efficiently and in
accordance with the best available science.
Thank you for your comment. EPA engages with its federal
partners such as OSHA as well as with other offices across
EPA to ensure its risk evaluations are well informed and
coordinated. EPA will consider this comment for future
Risk Evaluations.
EPA's discussions and consultation with OSHA are
described in section 1.4.4.4 of Supplemental Information on
Releases and Occupational Exposure Assessment.
Additionally, EPA conferred with OSHA during
interagency review and their comments are reflected in the
Draft and Final Risk Evaluation
67
PUBLIC COMMENTS:
EPA notes in numerous scenarios that their methods
likely "overestimate the exposure" based on the
data used. However, how this overestimation was
considered in the final risk evaluation decision
within the MOE calculation is not clear.
EPA considered the key assumptions and uncertainties
when determining the overall confidence for the risk
estimates.
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66
PUBLIC COMMENTS:
Sections 4.2 and 4.3 contain some vague statements
that make it hard to assess the appropriateness of
the decisions (e.g., p. 303: "Different adverse
endpoints were determined to be appropriate based
on the expected exposure durations;" p. 380: "EPA
did not carry immune system effects forward for
dose-response because epidemiological, animal and
mechanistic data are limited and inconclusive for
several reasons.")
Within sections 4.2 and 4.3, EPA added references to other
sections (Section 3.2.3, Hazard Identification and Section
3.2.4, Weight of the Scientific Evidence) that contain more
detail regarding these decisions.
66
PUBLIC COMMENTS:
The tables in Sections 4.6 and 5 - as with those in
previous parts of Chapter 4 - are not very
transparent. The risk estimates are presented, but it
is impossible to follow the calculations without
more information.
EPA has added information explaining the data behind
several of the risk tables in section 4 and a table explaining
PPE assumptions in section 4. Additionally, EPA has
reformatted section 5 to increase clarity and transparency.
Suggestions for improving clarity and readability
SACC
SACC COMMENTS:
To aid readability, present findings (e.g., "Risk
Conclusion" in Section 4.6) at the beginning of the
Risk Characterization section rather than at the end.
EPA has made this change in the MC risk evaluation.
SACC
SACC COMMENTS:
Clarification of the statement in p. 383 is requested:
"... Because of this the results of risk
characterization were generally not sensitive to the
individual estimates of the central tendency and
high-end separately but rather were based on
considering both central tendency and high-end
exposure which increase the overall confidence in
the risk characterization."
This statement suggests that considering the risks
from central tendency and the high-end exposures
separately somehow increases confidence in results.
Recommendation: Be more transparent with respect
to the decision of using estimates of central
In Section 4.3.2 EPA added a statement saying that where
the central tendency and high-end exposure scenarios both
had risk, EPA had higher confidence in the risk
characterization.
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tendency and high-end jointly as a way to increase
confidence in the risk characterization.
SACC
SACC COMMENTS:
Refrain from using the expression "no risk" and use
instead the expression "no unacceptable risk" in
recognition of the inherent variability and estimator
uncertainty associated with assessing even low-risk
scenarios. We can never be certain that the true risk
is zero.
Unreasonable risk is only used in the unreasonable risk
determination section, because it is a legal term under
TSCA. Everywhere else EPA states that it identified risk, or
it did not identify risk.
Other comments
62
PUBLIC COMMENTS:
There is support for EPA's finding of unreasonable
risk of MC in the oil and gas extraction sector and
we urge EPA to further investigate and require
reporting of emissions from this sector as well.
EPA evaluated the industrial and commercial use of
methylene chloride for oil and gas drilling, extraction, and
support activities. EPA determined that this condition of use
presents an unreasonable risk of injury to health (Section
5.2.1.37). During risk management, EPA will consider
which regulatory approaches would address this
unreasonable risk, which may include requirements for
reporting and recordkeeping.
45
PUBLIC COMMENTS:
Flexible foam operation (discussed on p. 144)
provides a good example of the issues that arise
with grouping non-similar tasks together. This is an
example of a failure to use best available science,
and it might misinform the risk characterization for
"industry application."
EPA did not find reasonably available data to completely
prevent grouping of non-similar tasks in many OESs
including this OES.
65
PUBLIC COMMENTS:
The draft risk evaluation's overstatement of the
risks of MC is already discouraging beneficial
reclamation of spent MC and encouraging its
incineration, contrary to the goals of RCRA. EPA
should revise the risk evaluation to more accurately
characterize MC's foreseeable TSCA conditions of
use and the risks associated with them.
EPA does not agree that there is a need to revise the MC
EPA has evaluated all known, intended, or reasonably
foreseen conditions of use of methylene chloride and
determined whether they present unreasonable risks of
injury to health or the environment. EPA's evaluation of
these conditions of use, including the reasonably foreseen
uses and the recycling that the commenter describes, are
based on reasonably available information and best
available science. While EPA does not consider non-risk
factors for the unreasonable risk determinations in this risk
evaluation, the impacts of any risk management actions will
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be considered during any rulemaking to address those
unreasonable risks.
62
PUBLIC COMMENTS:
EPA has authority to further restrict MC and other
VSLS where a substance is listed as Acceptable for
end-uses covered by the Significant New
Alternatives Policy (SNAP) Program including for
solvents, and coatings (see Appendix I). However,
this Title VI authority is limited and does not cover
risks from the full lifecycle of substances,
intermediate uses such as feedstocks, or other end-
uses in which Class I and Class II substances were
not historically used.
Thank you for your comment.
68
PUBLIC COMMENTS:
It is recommended that EPA OPPT convene a
broader discussion with other EPA program offices
about how - in the longer term - it should seek to:
o better understand the regulatory requirements
and processes of the various environmental
statutes under EPA's purview;
o reach agreement on the value (or not) of EPA's
potential use of TSCA risk evaluations to
address air, water, and other waste pathways
under the TSCA disposal condition of use; and
o establish better approaches for coordinating
what each program office (including EPA
OPPT) can provide the others to improve
environmental protection under their respective
statutory authorities more efficiently and
without duplication.
EPA communicated with other program offices within the
agency throughout the assessment process, including at
scoping, problem formulation, and risk evaluation. These
discussions included regulatory requirements and processes
of the various environmental statues. EPA will continue to
have these conversations with other offices at the Agency for
the next round of chemicals to be evaluated under TSCA
Section 6. See section 1.4.2 of the risk evaluation regarding
EPA's approach to exposure pathways and risks addressed
by other EPA-administered statutes.
67
PUBLIC COMMENTS:
The "applicable requirements of TSCA § 6," with
which the Lautenberg Act mandates that a
completed risk assessment must comply before it
can support § 6 rulemaking, include taking into
account exposure under the conditions of use,
EPA believes that the MC risk evaluation is sound and has
met the requirements of TSCA § 26(h), (i) and (k) to use the
best available science in a weight of scientific evidence
approach using reasonably available information.
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describing the weight of the scientific evidence for
the identified hazard and exposure, using scientific
information employed in a manner consistent with
the best available science, considering variability
and uncertainty in the information, and ensuring
independent verification or peer review of the
information.
The draft risk evaluation is more of a screening
level assessment. Its hazard assessment is not based
on the best available science; it uses "strength of
evidence" as opposed to "weight of evidence;" its
exposure assessment is mostly based on workplace
limits in effect 20 years ago that were 20 times
higher than current limits; it ignores available EPA
data; and it includes no formal or informal
uncertainty analysis. To maintain the credibility of
its regulatory efforts under TSCA, it is imperative
that EPA build upon available information to
construct a more realistic risk assessment before
proceeding with rulemaking.
Overall ( onleiil :iii(I Organization
EPA's Final Rule, Procedures for Chemical Risk Evaluation Under the Amended Toxic Substances Control Act (82 FR 33726)
stipulates the process by which EPA is to complete risk evaluations under the Frank R. Lautenberg Chemical Safety for the 21st
Century Act. As part of this draft risk evaluation for methylene chloride, EPA evaluated potential environmental, occupational and
consumer exposures. The evaluation considered reasonably available information, including manufacture, use, and release
information, and physical chemical characteristics. It is important that the information presented in the risk evaluation and
accompanying documents is clear and concise and describes the process in a scientifically credible manner.
Charge Question 7.1. Please comment on the overall quality and relevance of the resources used in this draft risk evaluation;
describe data sources or models that could improve the risk evaluation.
Charge Question 7.2. Please comment on the overall content, organization, and presentation of the draft risk evaluation of
methylene chloride.
Charge Question 7.3. Please provide suggestions for improving the clarity of the information presented in the documents.
Summary of Comments lor Specific Issues Related
lo Charge Question 7
KPA/OPPT Response
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Organization and clarity of presentation
SACC,
68
SACC COMMENTS:
Committee members requested more clarity about
the rationale for choices that influence the risk
evaluation, and clearer presentation of
assumptions.
PUBLIC COMMENTS:
Increased clarity is requested in the presentation of
supporting data and analyses supporting the risk
characterization and risk determination.
EPA has added more information to the uncertainties
sections and more explanation and detail to the risk
characterization section.
SACC
SACC COMMENTS:
Committee members suggested EPA standardize
first- and second-level headings for the risk
evaluations and provide a subsection at the
beginning of each section to summarize that
section, as well as conclusion sentences.
The use of additional summary graphics was
suggested.
One Committee member suggested organizing the
report to present information about consumer
exposure for each COU and after that to present
information about bystander exposure for each
consumer COU.
These organizational comments are appreciated and will be
considered in a revised template for the next round of
chemicals to be assessed under TSCA section 6.
SACC
SACC COMMENTS:
Committee members suggested modifying links to
external documents as well as internal links within
the document to increase transparency.
Some Committee members stated that the risk
evaluation should concisely summarize
information taken from external documents, rather
than only providing links, while other Committee
members requested additional links to external
supporting materials to improve readability and
shorten the risk evaluation.
EPA made an effort to include more summaries of
information referenced in other documents. This comment
will also be considered in future risk evaluations.
SACC
SACC COMMENTS:
A regulatory history of MC is included in Appendix A of the
draft and final risk evaluation.
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A short summary of MC's regulatory status under
EPA, OSHA, and FDA should be included.
66
PUBLIC COMMENTS:
Details of the human health hazards section were
not clear until the data summary. It is suggested
that an introductory paragraph be added that
provides an outline and sets up the flow of the
section.
EPA could also give a brief overview of the quality
rating criteria in this section.
EPA has revised parts of the human health hazard section for
better clarity based on other comments. EPA is developing
an updated template for future TSCA risk evaluations.
73, 68
PUBLIC COMMENTS:
EPA's risk determinations in Table 5-1 do not
accurately incorporate the risk estimates from
Chapter 4.
In general, Table 5-1 is lacking organization and
clarity. For example, some risk estimates are
presented only for medium intensity users, while
others are presented for high intensity users,
without an explanation.
EPA should consider including a modified table
(e.g., use of boldface for "presents" and "does not
present", color-coding of endpoints that exceed
benchmarks, citation to regulatory requirements).
EPA has updated the unreasonable risk determination format
for increased clarity regarding the unreasonable risk
determination and the risk considerations for each condition
of use.
68
PUBLIC COMMENTS:
EPA should consider using Health and
Environmental Sciences Institute's (HESI's)
Risk21 Project and Web Tool application to create
a plot of exposure and toxicity data, overlaying a
risk matrix represented as a heat map.
EPA will investigate the methods and principles behind the
HESI Risk 21 application and consider using its
visualizations in future risk evaluations.
66
PUBLIC COMMENTS:
Clarification is requested for the following:
pp. 65-66: The "other" category of facilities failing
to report a NAICS or SIC code is unclear.
Table 2-28, p. 114: It is unclear which central
tendency was used.
p. 218: Were there 2878 people who participated or
Regarding the "other" category discussion in section 2.2.1 on
pages 65-66, the discussion did not indicate that these
facilities failed to report NAICS or SIC codes. The
discussion indicates that EPA cannot map the codes reported
by these facilities to a specific occupational exposure
scenario or condition of use.
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did 2878 people have levels below detection?
p. 226: Does use of menthol refer to menthol
cigarettes?
Table 3-12, p. 256: No explanation is provided for
downgrading Gold et al. from a high to medium
rating.
p. 425: It is not clear what is meant by determining
cancer risk "based on other benchmarks as
appropriate".
Section 2.4.2: Further explanation of the use of
"default parameters" is requested.
Sections 4.2 and 4.3 and tables in Sections 4.2, 4.3,
4.6, and 5: Increased transparency is required.
Section 5: Confidence ratings are presented
without any discussion. The origin of these ratings
is unclear.
The 8-hr TWA exposure concentration from Table 2-28 was
used to calculate risk, which is made clear in the risk
characterization section.
The 2878 individuals were those who participated and who
had their blood monitored for methylene chloride; methylene
chloride was not detected in the blood of this sample.
Menthol was used only to disguise the odor of MC in a
human experimental studv (Gamberale et al.. 1975), as stated
in the human health hazard section of the risk evaluation.
EPA added the explanation for downgrading Gold et al.
(2010) to Table 3-12.
Confidence ratings are explained earlier in the document, and
the final version of the document does not list confidence
ratings in Section 5.
66
PUBLIC COMMENTS:
The sensitivity analysis (p. 179) should be made
available to readers.
The CEM sensitivity analysis is available to the public and
referenced in the MC RE. It is also available in Appendix C
at the following link.
https://www.eDa.eov/sites/Drodiiction/files/
Addition of Globally Harmonized System (GH.S) classification information
SACC
SACC COMMENTS:
One committee member suggested including GHS
classification information on the subject chemical.
EPA did not locate any existing U.S. GHS classifications for
methylene chloride. EPA doesn't rely on GHS for labelling
chemicals under TSCA and therefore has also not separately
classified methylene chloride based on the results of this risk
evaluation.
Addition ofOSHA and/or NIOSH representatives to SACC
SACC
SACC COMMENTS:
Consider adding representatives from OSHA
and/or NIOSH to the SACC since many of the
COUs are worker exposures.
OSHA and NIOSH were able to comment on this document
during interagency review. EPA will consider adding
representatives from OSHA or NIOSH to the SACC.
Number of significant digits
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SACC
SACC COMMENTS:
Tables in the evaluation should consistently use
two significant digits.
EPA has recalculated values with a consistent method for
applying significant figures. Results are presented to at least
2 significant digits, with numbers >10 generally reported to
the nearest whole integer.
Insufficient time to review
49, 57,
43,41
PUBLIC COMMENTS:
Insufficient time was allowed for the public to
review the draft risk evaluation prior to the SACC
meeting.
SACC meetings should be scheduled after the
close of the comment period to enable a more
informed review.
EPA will consider this comment for future risk evaluations.
Comments related to the 2017 proposed ban on MC
SACC
SACC COMMENTS:
The first mention of the new rule on MC in
residential paint strippers in Section 1.4.1 appears
too late in the evaluation. Also, this paragraph has
descriptions of COUs that are not consistent with
the problem formulation.
EPA's regulation prohibiting MC for consumer paint and
coating removal is mentioned in the executive summary and
then Section 1.4.1. EPA maintains that these are reasonable
locations.
The conditions of use the reviewer noted ("metal products not
covered elsewhere, apparel and footwear care products, and
laundry and dishwashing products") are listed because they
were identified in the problem formulation and, after
additional analysis to further understand the COU (e.g., SDS,
literature, industry engagement), EPA found no applicable
consumer products for these uses. EPA has determined that
there is no known, intended, or reasonably foreseen consumer
use of these products. There are only industrial and
commercial uses of methylene chloride for these conditions of
use, and these conditions of use were assessed.
55, 49,
33, 73,
54, 44,
69, 77,
72, 71,
75, 64,
48
PUBLIC COMMENTS:
In 2017, EPA proposed banning the use of MC
chemicals in paint strippers.
Earlier this year, EPA finalized a ban on consumer
sales and uses of MC in paint strippers, but did not
implement a commercial ban, leaving workers and
others at risk.
Regulatory actions to address unreasonable risks are outside
the scope of this risk evaluation.
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EPA has not presented an adequate justification for
excluding commercial paint stripping uses from the
ban. Since 2009, a REACH Restriction entered into
force regarding the use of MC in paint strippers,
effectively prohibiting the use of MC in such
applications.
In the absence of a regulatory backstop from EPA,
there is a concern that industry will fail to make a
meaningful investment in less toxic alternatives to
MC.
Commenters urge EPA to move forward to finalize
a ban on commercial paint stripping uses.
Overall ban of MC in occupational scenarios
69
PUBLIC COMMENTS:
Research on methylene chloride fatalities finds
current policies inadequate to protect workers and
recommends elimination of methylene chloride use
in commercial settings.
The number of fatalities per year did not appear to
be reduced by CPSC's 1987 mandatory labelling
requirement and OHS A's updated standard in
1997.
The most effective next step is to institute an
elimination of methylene chloride in occupational
scenarios to prevent further fatalities.
The Risk Evaluation for methylene chloride describes the
risk to workers for the conditions of use in scope of the risk
evaluation. Regulatory actions to address unreasonable risks
are outside the scope of this risk evaluation.
Need to consider environmental and human health effects mediated by ozone depletion
SACC,
49, 62,
75
SACC COMMENTS:
The impact of MC emissions to the atmosphere on
ozone depletion should be considered in the
evaluation.
PUBLIC COMMENTS:
MC is an ozone-depleting substance. According to
a 2017 study in Nature Communications, rising
MC emissions alone could delay the recovery of
the ozone layer by 5-30 years, undermining the
progress made under the Montreal Protocol.
Assessing ozone depletion is out of scope for this Risk
Evaluation. EPA did not include the emission pathways to
ambient air from commercial and industrial stationary
sources, because stationary source releases of methylene
chloride to ambient air are managed under the jurisdiction of
Section 112 of the Clean Air Act (CAA). Resulting exposure
were out of scope as described in the problem formulation for
MC.
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EPA ignores ozone-depleting effects in its draft
risk evaluation. Ozone depletion presents both
risks to the environment and human health.
EPA cannot claim that MC's ozone-depleting
effects are adequately addressed by the CAA, since
EPA has not regulated MC under Title VI of the
CAA.
More than 2.5 million pounds of MC are emitted to
the air each year. Global emissions of MC are
increasing rapidly.
TSCA should be utilized to assess new concerns
that are unaddressed by the limited regulatory
scope of CAA Title VI.
General issues with TSCA systematic review
73, 49,
58, 69,
71, 75
PUBLIC COMMENTS:
A protocol describing the methods for the
systematic review should be published and peer-
reviewed prior to commencing the review.
A protocol should pre-define search terms, search
strategy, inclusion/exclusion criteria, and
procedures for study selection. The protocol should
address specific questions that are identified in the
problem formulation.
OPPT should consult with the IRIS program on
how to best develop a protocol in consideration of
requirements under TSCA.
EPA should include protocols for all systematic
reviews conducted for a specific risk assessment as
appendixes to the assessment.
Any changes made after the protocol is in place
should be transparent, and the rationale for each
should be stated.
As described in Section 3.4 of the
Keview m ial,A kisk evaluations, TSCA reauirements and the
results of scoping/problem formulation (i.e., conceptual
model(s), analysis plan) framed the specific scientific risk
assessment questions to be addressed in each of the first 10
TSCA risk evaluations. The timeframe for development of the
TSCA Scope documents was very compressed and the first ten
chemical substances were not subject to prioritization, the
process through which EPA expects to collect and screen much
of the relevant information about chemical substances. As a
result, EPA had limited ability to develop a protocol upfront. For
these reasons, the protocol development was staged in phases
while conducting the assessment work (see Section 3.1 of the
Application of Systematic Review in TSCA Risk Evaluations
for more discussion of this step).
EPA published the Strategy for Conducting Literature
Searches for Methylene Chloride in June 2017 along with the
scope document for MC, similar to all 10 first TSCA
chemical risk evaluations. This document outlined the
literature search strategy and title/abstract inclusion/exclusion
criteria used for screening, found in Appendix E.
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Along with publishing the problem formulation for MC in
May 2018, EPA published the inclusion/exclusion criteria
statements used during full text screening for each chemical
in appendices to those documents as well as a separate
document titled Application of Systematic Review in TSCA
Risk Evaluations that described the data quality criteria used
for each discipline and outlined data integration strategies that
will be further developed for the next risk evaluations.
Because the systematic review steps have been published and
are available to the public, EPA did not publish the protocols
in the risk evaluation documents.
EPA has identified within the MC risk evaluation document
where changes were made, such as evaluations of additional
studies that were not part of the original systematic review
process.
EPA consulted extensively with the IRIS program when
developing the systematic review process and has continued
to engage with the IRIS program. EPA plans to publish a
protocol document for the next TSCA chemicals undergoing
risk evaluation. Furthermore, EPA anticipates feedback from
the NASEM TSCA Committee on its systematic review
process and will carefully review their recommendations.
49, 57,
43, 58,
68, 75
PUBLIC COMMENTS:
There are consistent problems in both the design
and implementation of the systematic review
system:
EPA should describe efforts undertaken to
calibrate the reviews of different reviewers both
within and across chemicals, as some
inconsistencies in data quality evaluation remain.
The SACC has previously noted a high fraction of
studies where the initial quality score was later
changed, indicating that the data quality evaluation
Because EPA was developing the systematic review process
while simultaneously implementing the process for ten
chemicals, there were some challenges with maintaining
consistency. However, EPA did implement several steps to
ensure consistency and reduce bias. EPA used calibration
steps among multiple screeners during a pilot phase for both
the data screening and data evaluation processes.
Furthermore, instructions were prepared for various aspects of
the systematic review (e.g., data screening, data evaluation,
and data extraction) to guide the reviewers and provide
consistency across reviews. Finally, most studies received two
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protocol is not clearly defined and possibly
inconsistently implemented by different reviewers.
Other concerns included the need for 'backward
reference searching' or 'targeted supplemental
searches,' suggesting that the initial search did not
find all the relevant references, and that the
automated gray literature search found mostly off-
topic documents and missed other useful
documents.
The draft guidance should be peer reviewed and
revised in accordance with the feedback received.
data quality evaluations with reviewers working together to
resolve conflicts, sometimes with a single arbiter across
similar types of studies. EPA has implemented additional
calibration steps and internal guidance documents for the next
20 chemicals going through the systematic review process
now.
Any single set of data quality criteria, even for a given
category of studies (e.g., animal toxicity studies), cannot
necessarily address all aspects of quality relevant for an
individual study in the category. Thus, EPA allowed
reviewers the ability to adjust the final score based on
professional judgment. This approach has been used in other
established tools, including the ToxRTool (Toxicological data
Reliability Assessment Tool) developed by the European
Commission (https://eurl-ecvam.jrc.ec.europa.eu/about-
ecvam/archive-publications/toxrtool).
EPA implemented a literature search process for the first ten
chemicals that included a comprehensive set of key words to
capture as much of the literature for a given discipline as
possible. However, even with a comprehensive literature
search, some important studies may be missed. For instance,
an abstract may not identify the chemical of interest by name
(e.g., if a genotoxicity test was conducted on many chemicals)
and thus might be screened out from further consideration. In
addition, some targeted searching for topics not anticipated at
the beginning of the risk evaluation process (e.g., generic
inputs needed for an exposure model) might be needed.
Therefore, such backwards searching (or snowballing) and
targeted searching remain important aspects of the systematic
review process.
EPA will publish a protocol document for the next TSCA risk
evaluations. Furthermore, EPA anticipates feedback from the
NASEM TSCA Committee on its systematic review process
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and will carefully review their recommendations for the next
20 chemicals.
58, 69,
71, 75
PUBLIC COMMENTS:
Numerical scores falsely imply a relationship
between scores and effect or association.
This 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 and
environmental risks.
Instead of numeric scoring, EPA should assess risk
of bias and quality of individual studies and then,
separately, determine certainty in the body of
evidence.
As stated in Appendix A of Application of Systematic Review
in TSCA Risk Evaluations, EPA's goal in using the numerical
scoring system is to provide consistency and transparency to
the process of evaluating chemicals risks while
simultaneously meeting the science standards under TSCA
Section 26 (h).
The scores were not designed and should not be interpreted
as implying any association with effect; they are strictly used
to evaluate metrics important to understanding the quality of
the studies and data used in the TSCA risk assessments,
irrespective of the results of a study. The chosen metrics
were informed by previous systematic review frameworks
and professional scientific judgment.
The system is designed to independently score individual
metrics; low scores for the individual metrics would not result
in an overall low score unless a certain number of metrics
receive low scores. However, a study or data source could be
considered unacceptable based on a serious flaw in a single
metric. EPA implemented this option because there are
criteria associated with individual metrics (e.g., lack of a
negative control group) that make a study or data source
unusable. Situations that would result in unacceptable ratings are
identified a priori in Appendices B through H of Application of
Systematic Review in TSCA Risk Evaluations.
EPA is reviewing its data quality criteria and will publish a
protocol document for the next TSCA risk evaluations. In
addition, EPA anticipates feedback from the NASEM TSCA
Committee, who will review EPA's systematic review
process under TSCA. EPA will consider revisions to its
approach based on these activities.
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68
PUBLIC COMMENTS:
EPA should provide a description of the specific
studies that were evaluated or screened out, along
with a rationale behind the decision to include or
exclude.
In June 2017, EPA provided a full bibliography of MC
studies that were included and excluded during the
title/abstract screening process along with a strategy
document describing the literature process and
inclusion/exclusion criteria.
Also, in the draft risk evaluation document, EPA provided
data quality evaluation scores and comments explaining the
scores for individual metrics. This was done for both
acceptable and unacceptable studies. These scores and
comments are provided in multiple supplemental files
published with the draft risk evaluation and will also be
available with the final risk evaluation.
58
PUBLIC COMMENTS:
EPA has not justified removal of the SACC charge
question on systematic review for MC that is in
other risk assessments.
Previously outlined systematic review issues have
not been resolved in this draft risk evaluation.
EPA has received comments on the TSCA risk evaluation
process following SACC review of previous draft risk
evaluations and anticipates feedback from the NASEM
TSCA Committee. EPA determined it was not necessary to
receive feedback for systematic review for each chemical
individually.
Failure to follow the TSCA systematic review guidelines that are in place
49, 58,
69, 68,
71, 75
PUBLIC COMMENTS:
EPA's draft risk evaluation strays from EPA's
systematic review guidance by relying primarily on
"key and supporting" information. This phrase is
subjective and is not adequately defined.
Although it is apparent EPA made the decision to
leverage the literature published in previous
assessments to identify "key and supporting"
information, a justification and rationale for this
decision were not provided.
EPA has revised its searching and screening procedures to
include all studies in the systematic review process
(screening, data evaluation) for the next set of TSCA
chemical risk evaluations.
EPA also added additional justification to the risk evaluation
for MC.
49, 58,
69, 68,
71, 75
PUBLIC COMMENTS:
EPA's "hierarchy of preferences" approach is not
peer-reviewed and is used to exclude "acceptable"
sources of data.
This approach led to the exclusion of almost 100
studies on environmental release and occupational
Different lines of evidence are routinely used in TSCA
chemical assessments because of data availability, sources,
underlying documentation, and quality varies. EPA
preferentially relies on a variety of test and analog data. In the
absence of suitable test data, predictive modeling tools may
be used. For environmental hazards, if the modeling tools
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exposure without adequate justification. There is a
lack of clarity on how EPA chose and evaluated
the 22 remaining key sources that were taken
forward to data extraction and evaluation.
The risk evaluation does not provide transparency
or rationale for how studies are scored or why they
are included or excluded. These methodologies
may result in a biased evidence base used to make
decisions on hazard endpoints, resulting in the
potential for some endpoints (such as
immunotoxicity and reproductive/developmental
toxicity) to be underestimated or excluded.
cannot provide predictions to an endpoint of interest, then
calculations like acute-to-chronic ratios can be used to fill in
For releases and occupational exposures, the hierarchy of
preferences and its use are described in Appendix G of the
Supplemental Information on Releases and Occupational
Exposure Assessment. The determination of the use of data
for each OES are described in Appendix A of the
Supplemental Information on Releases and Occupational
Exposure Assessment, and this determination illustrates the
use of the hierarchy in data decisions for these types of data.
data gaps.
EPA published the title/abstract inclusion/exclusion criteria
for methylene chloride in Appendix E of the Strategy for
Conducting Literature Searches for Methylene Chloride and
inclusion/exclusion criteria statements used during full text
screening in an appendix to the problem formulation
document for methylene chloride. Data quality criteria used
for scoring each discipline are provided in a separate
document titled Application of Systematic Review in T'SCA
Risk Evaluations, which also outlines evidence integration
strategies that will be further developed for the next risk
evaluations.
EPA consulted multiple systematic review frameworks and
the IRIS program when developing the systematic review
process.
EPA is reviewing its data quality criteria and will publish a
protocol document for the next TSCA risk evaluations. In
addition, EPA anticipates feedback from the NASEM TSCA
Committee, who will review EPA's systematic review
process under TSCA. EPA will consider revisions to its
approach based on these activities.
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Use of guideline studies
55, 69
PUBLIC COMMENTS:
According to TSCA systematic review, higher
quality studies are guideline studies or data
collected according to Good Laboratory Practices
(GLP) requirements.
This results in inappropriately favoring industry
studies and can lead to a biased evidence base that
favors no-effect findings.
The TSCA risk evaluation strategies in some cases refer to
study guidelines along with professional judgement as
helpful guidance in determining the adequacy or
appropriateness of certain study designs or analytical
methods. This should not be construed to imply that non-
guideline studies are automatically given lower confidence
ratings than guideline or Good Laboratory Practice (GLP)
studies. EPA considers reasonably available, relevant data
and information that conform to the TSCA science standards
when developing the risk evaluations irrespective of whether
they were conducted in accordance with standardized
methods (e.g., OECD test guidelines or GLP standards).
55
PUBLIC COMMENTS:
Industry-sponsored guideline studies that are
submitted for the purposes of regulatory approval
are not sufficiently sensitive and may
underestimate risks.
Guideline studies focus on major (apical) toxic
effects and are not designed to deal with the issues
of low-dose exposures, endocrine or hormonal
effects, and subtle but significant neurobehavioral
impacts, and therefore may not identify upstream
indicators of potential harm.
EPA considered reasonably available, relevant data and
information that conform to the TSCA science standards
when developing the risk evaluation. Recognizing that each
source of data may have strengths and weaknesses, EPA
considered data quality and relevance and then used
acceptable data in a weight of the scientific evidence
approach.
Furthermore, EPA will consider data and information from
alternative test methods and strategies (or new approach
methodologies or NAMs), as applicable and available, to
support TSCA risk evaluations. This is consistent with
EPA/OPPT's Strategic Plan to Promote the Development and
Implementation of Alternative Test Methods (Draft) to reduce,
refine or replace vertebrate animal testing (U.S. EPA, 2018e).
Since these NAMs may support the analyses for the exposure
and hazard assessments, the data/information quality criteria
may need to be optimized or new criteria may need to be
developed as part of evaluating and integrating NAMs in the
TSCA risk evaluation process.
Other systematic review platforms to be considered
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73, 58,
69, 71,
75, 55
PUBLIC COMMENTS:
While the NAS review is progressing, OCSPP
should adopt one of the recognized systematic
review methodologies endorsed by the NAS and
other peer review bodies. Established systematic
review methods include NTP's Office Health
Assessment and Translation (OHAT) method, the
EPA IRIS method, the Navigation Guide used by
the WHO, and Woodruff and Sutton (2014).
The EPA TSCA program should consider
incorporating scientific approaches from the
systematic evidence-based method recently
published in Nature Reviews Endocrinology.
EPA consulted multiple systematic review frameworks when
developing the systematic review process for the first 10
TSCA risk evaluations. For any future revisions, EPA will
wait to receive feedback from the NASEM TSCA
Committee before adopting other published systematic
review methods.
Data quality criteria: inconsistencies and the impact on epidemiological studies
73, 69,
71, 75
PUBLIC COMMENTS:
EPA has downplayed or dismissed epidemiological
evidence using unsupported or misleading
arguments.
OPPT's updated data quality criteria for
epidemiological studies are flawed and biased and
do not represent best practice.
Certain revisions to these criteria make it more
difficult for epidemiological studies to be scored
overall as high quality. Epidemiological studies are
thus less likely to be considered high quality
overall and as a result may be given more limited
consideration than animal and in vitro studies.
The scheme used to calculate the overall rating for
a particular study is not clearly presented.
OPPT needs to provide explanation or empirical
support for its revisions to the data quality criteria
for epidemiological studies.
EPA should consider other study evaluation tools
that are more appropriate for the consideration of
the quality of observational epidemiologic studies,
such as the Conducting Systematic Reviews and
EPA has comprehensively evaluated the human and animal
studies for MC. Although many epidemiological studies may
have been conducted adequately, there are still inherent
aspects of some of these studies (such as lack of control for
co-exposure to other chemicals that are associated with the
same outcome), which make it difficult to either fully
understand the true relationship between MC and cancer or
use the studies quantitatively in a risk evaluation. However,
EPA clearly identified relevant issues and described the logic
regarding which endpoints and studies would be considered
for dose-response in the weight of scientific evidence section.
EPA/OPPT's quality evaluation method was developed
following identification and review of various published
qualitative and quantitative scoring systems to inform our
own fit-for-purpose tool. The development process involved
reviewing various evaluation tools/frameworks (e.g., OHAT
Risk of Bias tool, CRED, etc.; see Appendix A of the
Application of Systematic Review in TSCA Risk Evaluations
document and references therein), as well as soliciting input
from scientists based on their expert knowledge about
evaluating various data/information sources specifically for
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Meta-Analyses of Observational Studies of
Etiology (COSMOS-E) tool (Dekkers,
Vandenbroucke et al., 2019) and the Navigation
Guide (Woodruff and Sutton, 2014).
risk assessment purposes.
The epidemiologic criteria were later revised to more
stringently distinguish between High, Medium and Low
studies. After additional piloting of the criteria, EPA found
that the initial iteration of the epidemiological data quality
criteria (as published in the Application of Systematic Review
in TSCA Risk Evaluations) was inadvertently skewing quality
scores toward the tail ends of the scoring spectrum (High and
Unacceptable). In order for the criteria to represent a more
accurate depiction of the quality levels of the epi literature,
the criteria were revised using two methods.
The first method was to make the unacceptable metrics less
stringent. This was accomplished by either rewording the
metrics to allow for more professional judgement in the
interpretation of the unacceptable criterion, or in some cases,
completely removing the unacceptable bin from metrics that
EPA determined were not influential enough to completely
disqualify a study from consideration (mostly metrics in the
Analysis and Biomonitoring domain). EPA found that these
criteria changes greatly reduced the type one error in the
Unacceptable scoring. No acceptable studies were
inaccurately classified as Unacceptable.
The second method was to reduce the number of studies that
received an overall High rating. The majority of overall
scores in EPA's initial evaluations during piloting tended to
be High. Therefore, EPA strived to revise the criteria to
provide more degradation in the scoring to more accurately
and objectively distinguish studies of the highest quality
from medium and low-quality studies. To do this, EPA
removed the High criterion from some metrics, particularly
in dichotomous metrics (High/Low or High/Unacceptable)
that were primarily being binned as High by reviewers across
the majority of the studies. These dichotomous metrics were
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MC RESPONSE TO COMMENT
contributing to the overall quality scores being skewed
towards High. To address this, EPA shifted some of the
dichotomous metrics such that the highest metric score
possible (for all studies) is a Medium. The change led to the
dichotomous metrics having less significant impact to the
numerical scoring and the overall quality rating for each
study.
With the aforementioned changes to the criteria, EPA
observed fewer studies with Unacceptable ratings and more
studies shifting from High to Medium, with only the highest
quality studies receiving a High overall rating. Out of the
-200 relevant epidemiologic studies and cohorts evaluated for
data quality for the first 10 TSCA chemicals, the majority
(-80%) still scored as High or Medium. The remaining -20%
of studies scored Low or Unacceptable. EPA is confident that
no studies of acceptable quality were inappropriately assigned
as Unacceptable. EPA is also confident that the revised
criteria bins the quality levels of these epi studies more
appropriately than the previous iteration. Additional
refinements to the epidemiologic data evaluation criteria are
likely to occur as EPA's validation and process improvement
efforts continue.
EPA anticipates feedback from the NASEM TSCA
Committee on its systematic review process, including the
epidemiological data quality criteria, and will carefully
review and implement relevant recommendations.
73
PUBLIC COMMENTS:
With the recent announcement that EPA intends to
move away from using animals for toxicological
testing, EPA should not require evidence from
animal studies where significant epidemiological
evidence exists.
Well-conducted epidemiological studies are more
EPA has used information consistent with the best available
science, as required by TSCA Section 26(h). EPA
comprehensively reviewed epidemiological and animal
studies as well as mechanistic information. EPA used data
from a human experimental studv CPutz et al. 1979) to
evaluate risks for acute exposure scenarios and uses
epidemiological studies to support other endpoints in a weight
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representative of an agent's biological effects on
humans and should therefore be able to provide
sufficient evidence for decision-making.
of the scientific evidence. Also, the existing database for MC
includes numerous animal toxicity studies and hence, it is part
of the "best available" information.
MC has animal evidence that is reasonably available for most
endpoints. EPA used all information reasonably available to
assess the hazards of MC, as specified by TSCA Section 26
(k).
In cases where EPA requests or requires testing for purposes
of TSCA risk evaluations, EPA will comply with the
requirements related to reduction of vertebrate testing in
TSCA section 4(h).
69
PUBLIC COMMENTS:
Concern was expressed regarding the accuracy and
consistency of EPA's evaluation of data quality of
epidemiology studies. An example was provided in
which participant selection was confused with
attrition.
EPA designed evaluation criteria that consider risk of bias and
Bradford Hill criteria when assessing the quality of
epidemiological studies. Refer to Appendices F, G and H of
the Application of Systematic Review in TSCA Risk
Evaluations document for more information.
Furthermore, EPA made changes to the epidemiological
criteria since the Application of Systematic Review in TSCA
Risk Evaluations was published. These changes included
validation and improvement efforts to ensure that the most
relevant studies were included in the TSCA risk evaluations.
The most up-to-date data quality evaluation criteria will be
available for review in the upcoming the Systematic Review
Protocol Supporting the TSCA Risk Evaluations document
(under development).
EPA anticipates feedback from the NASEM TSCA
Committee on its systematic review process, including the
epidemiological data quality criteria and will carefully
review and implement relevant recommendations.
75
PUBLIC COMMENTS:
EPA should consider addressing limitations that
EPA did consider evidence across all epidemiological studies
as well as animal toxicity and mechanistic data (Sections
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are routine in epidemiologic studies (such as small
numbers or co-exposure to other carcinogens) by
using standard statistical adjustments, considering
all the evidence across many studies, and/or
considering supporting evidence from animal
studies and other streams of evidence.
EPA should consider revising its review and
synthesis of the epidemiological evidence to more
fully incorporate the strengths and weaknesses of
the epidemiological studies and integrate these
studies with the available animal and mechanistic
evidence to support conclusions regarding
carcinogenic hazard.
3.3.3 and 3.3.4). EPA will investigate methods, which may
include meta-analyses, for future risk evaluations.
EPA comprehensively reviewed the epidemiological
evidence and considered the merits and limitations of all
studies as described in the weight of scientific evidence
section (Section 3.3.4). EPA has added more discussion of
individual epidemiological studies and the suite of
epidemiological data to the MC risk evaluation (Section
3.3.4).
41, 73
PUBLIC COMMENTS:
EPA should develop formal data quality criteria for
controlled human exposure studies, considering
relevant data quality criteria from available
sources.
EPA evaluated the human controlled experiments
qualitatively drawing upon the types of metrics identified for
both human epidemiological studies and animal studies
published in Application of Systematic Review in TSCA Risk
Evaluations. EPA is also committed to developing criteria
for human exposure studies (e.g., experimental studies such
as the acute inhalation studies of CNS effects). EPA will also
carefully review and implement relevant recommendations of
the NASEM TSCA Committee that may pertain to
developing such criteria.
Data quality evaluation of in vitro and mechanistic studies
41, 56,
68
PUBLIC COMMENTS:
EPA did not re-evaluate genotoxicity studies for
quality but is relying on previous assessments.
EPA does not provide a sufficient justification for
this decision.
EPA should acknowledge that a formal data quality
assessment was not performed on any cited in vitro
studies.
In vitro and mechanistic studies that were used as
supporting evidence in the development of a
proposed MOA should be subject to a formal data
EPA has evaluated the genotoxicity studies for data quality
and added more information to the final risk evaluation
(Section 3.3.3.2, Genotoxicity and Carcinogenicity; Appendix
; Supplemental File on Evaluation of Animal and In Vitro
Studies). Other MOA data were not reviewed.
Thank you for your suggestion regarding tiering in vitro
studies for review. The NASEM TSCA Committee will
review EPA's systematic review process, and EPA will
consider revisions to the process based on their
recommendations.
Page 231 of 246
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quality assessment and the quality should be
discussed in the weight of scientific evidence
section.
In instances where there are numerous studies,
EPA could consider developing a specific tiered
approach for evaluating in vitro data quality in
which a subset of the full data quality domains
deemed critical for each in vitro assay type are
considered first, and those studies that do not meet
these criteria be considered as low quality.
Data availability - Handling of CBI data
73, 49
PUBLIC COMMENTS:
Regarding citations for which EPA does not
possess full study reports, EPA needs to obtain
copies of the full studies and make these available
to the public (e.g., through online portals such as
HERO), allowing better assessment of data quality
and study conclusions.
It is requested that these references be placed in the
docket for the draft risk evaluation and that EPA
provide an opportunity for public comment on
them.
EPA has not provided public access to several
sources that include health and safety information
on which EPA relies in its draft risk evaluation.
These studies cannot receive confidential business
information (CBI) protection under TSCA.
PUBLIC COMMENTS:
Under TSCA Section 14, restrictions on disclosure
of CBI do not apply to "any health and safety study
which is submitted under this Act" for a chemical
substance which "has been offered for commercial
distribution".
Any information, including physical-chemical
properties, fate, human health effects, ecotoxicity,
and exposure assessments, received by EPA on
EPA made the full studies available to peer reviewers and
included a list of the studies and their results in the docket
in accordance with TSCA section 26(j) and 40 CFR
702.51. Data quality evaluations for each study are
available in the appendix and supplemental files.
Conditions of use with CBI or unknown function were
evaluated and considered for the methylene chloride risk
evaluation; however, the non-CBI elements of the
category, subcategory, function and industrial sector were
used in the analysis as these data were higher quality. This
applies to CBI function for petrochemical manufacturing,
paint additives and coating additives not described by
other codes for CBI industrial sector, laboratory chemicals
for CBI industrial sectors, manufacturing of CBI and oil
and gas drilling, extraction, and support activities. For
Processing as a Reactant, Arkema Inc. submitted data
claimed as CBI for a fluorochemicals manufacturing
facility. The CBI data were not included in this
assessment. Higher quality data from HSIA were used
instead.
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MC RESPONSE TO COMMENT
such a chemical is not protected as CBI and must
be disclosed.
Comments related to the methods of evidence/data integration
73,71,
75, 56,
68, 69
PUBLIC COMMENTS:
OPPT has not provided a pre-established
methodology for data/evidence integration and
does not sufficiently describe its approach. Only
general, high-level principles are described,
without specific details.
This may lead to bias and inconsistency in how
EPA conducts WOE integration across risk
evaluations.
EPA should describe its general approach to
evidence integration in a revised systematic review
methodology document and then incorporate that
When synthesizing and integrating evidence for each human
health hazard endpoint, EPA considered quality, consistency,
relevancy, coherence and biological plausibility as specified
in Application of Systematic Review in TSCA Risk
Evaluations. EPA used an informal framework for most
endpoints but did array the immunological evidence within a
more formal framework to respond to a comment by the
SACC (see Appendix A below and Appendix M in the risk
evaluation).
Sections 3.2.3 and 3.3.4 describe EPA's process of weighing
and integrating scientific evidence for hazard endpoints.
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MC RESPONSE TO COMMENT
into specific protocols it develops for each risk
evaluation. This approach should be fit-for-purpose
to meet statutory and regulatory requirements and
should be subject to review and public comment.
It is recommended that EPA conduct separate
evidence synthesis and determinations about the
certainty of the evidence for each stream of
evidence and describe how different streams of
evidence are integrated to reach a conclusion for
each health effect.
EPA should follow the recommendations of the
NASEM.
EPA is developing and implementing more formal and
structured data integration strategies for the next set of TSCA
chemical risk evaluations. In addition, EPA anticipates
feedback from the NASEM TSCA Committee on its
systematic review process and will carefully review and
implement relevant recommendations.
Editorial
SACC,
66
SACC and PUBLIC COMMENTS:
The SACC and public comments provided many
suggestions for editorial comments that EPA will
consider.
EPA considered and revised many of the editorial
suggestions and comments provided by the SACC and the
public.
Appendix A: Immunotoxicity Evidence Integration
Human: Epidemiological Evidence
Endpoint
OR/HR/SMR (95%
CI)
Important study
characteristics
Study
Confidence
Rating
Reference
Mortality from
infectious and
parasitic diseases
SMR all divisions: 0.0
(0.0-0.66)a
SMR roll coat: 0.67
(0.14-1.97)a
MeCl exposure
quantified and duration-
adjusted; MeCl was
primary exposure for all
divs; other chemical
exposures possible (not
controlled) for roll coat;
dissimilar comparison
group for all divs;
High
Heame and Pifer
>9)
Mortality from
influenza and
SMR males: 1.25
(N/A)
MeCl exposure
quantified; Other
Medium
Gib!
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MC RESPONSE TO COMMENT
pneumonia
SMR females: 4.36
(N/A)
chemical exposures not
controlled; dissimilar
comparison group
Mortality from
bronchitis (non-
specific)
HR: 9.21 (1.03-82.69)
MeCl exposure estimated
based on job duties;
Other chemical
exposures identified (~
21 solvents) but not
controlled
Medium
Radican et al. (2008)
Mortality from
non-malignant
respiratory
disease
SMR: 0.97 (0.42-1.90)
MeCl exposure
quantified; methanol and
acetone exposure not
controlled; dissimilar
comparison group
Medium
Lanes et al. (1993)
Sjorgen's
Syndrome
(autoimmune)
OR: 9.28 (2.60-33.0)
3.04 [cum.] (0.50 -
18.3)
MeCl exposure estimated
based on job duties;
Other chemical
exposures not controlled
Medium
Chaigne et al. (2.015)
a SMRs reported in study on different scale: SMR all divs = 0 (0 - 66) and SMR roll coat = 67 (14 - 197)
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Animal Evidence
Species
Exposure
Route
Doses/
Concentration
Duration
NOAELa
Effect
Study
Confidence
Rating
Reference
Rat, SD
Inhalation
0, 5187 ppm
6
hrs/day,
5
days/wk,
28 days
5187
ppm
NoIgM
antibody
response after
sheep RBC
injection;
Decreased
spleen wts
(females)
High
Warbrick et
al. (2003)
Mouse,
CD-I
(female)
Inhalation
0, 52, 95 ppm
3 hrs
52 ppm
Acute: |
mortality
(12.2%; p <
0.01) from S.
zooepidemicus;
J, bactericidal
activity
(12%; p< 0.001)
Medium
iyi et al.
!6)
0, 51 ppm
3 hrs/day
for 5
days
51 ppm
None re:
mortality or
bactericidal
activity
Rat,
F344
Inhalation
0, 1000, 2000,
4000 ppm
6
hrs/day,
5
days/wk,
2 years
1000
ppm
Splenic fibrosis;
no patterns in
inflammatory
cells in
respiratory tract
High
NTP (1986)
Mouse,
B6C3F1
Inhalation
0, 2000, 4000
ppm
6
hrs/day,
5
days/wk,
2 years
2000
ppm
Splenic
follicular
atrophy; no
patterns in
inflammatory
cells in
respiratory tract
High
NTP (1986)
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Rat, SD
Inhalation
0, 50, 200, 500
ppm
6
hrs/day,
5
days/wk,
2 years
500 ppm
No
histopathological
or other changes
in lymph nodes,
thymus or
spleens; no
patterns in
inflammatory
cells in
respiratory tract
High
Nitschke et
8)
Rats,
Inhalation
0, 500, 1500,
6
3500
No
High
Burek et al.
hamsters
3500 ppm
hrs/day,
5
days/wk,
2 years
ppm
histopathological
or other changes
in lymph nodes,
thymus or
spleens; no
patterns in
inflammatory
cells in
respiratory tract
!4)
aEPA-derived as related to immune endpoint
Mechanistic Evidence
System
Effect
Study
Confidence
Rating
Reference
Male were rats treated with
hemin arginate (HAR), which
induces heme oxygenase-1
(HO-1). Hemorrhage was
then induced in the mice. In
part of the experiment, the
mice were then treated with a
heme oxygenase-1 blocker,
and then administered 100
HAR resulted in [ pro-
inflammatory cytokine TNF-alpha
and | anti-inflammatory cytokine
IL-10.
The HO-1 blocker abolished this
effect but then administration of
methylene chloride restored the
anti-inflammatory response.
N/A
Kubulus et al.
(2008)
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MC RESPONSE TO COMMEN
T
mg/kg-bw methylene
chloride.
The authors suggest that the anti-
inflammatory response is partly due
to carbon monoxide release from
administration of methylene
chloride (in addition to the HAR
administration/HO-1 induction)
Evaluation of peripheral
blood mononuclear cells in
carp after exposure to 0.004-
40 mg/kg-bw methylene
chloride by i.p.
t mitochondrial activity and H202 of
peripheral blood mononuclear cells in a
dose-dependent fashion suggesting an
immunomodulary effect related to an
acute pro-inflammatory state. Also, |
apoptosis and generation of other ROS
was observed.
Exact immunomodulary effects are
unclear.
N/A
Uraga-Tovar et al.
(2014)
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Evidence Integration Summary Judgment: Immunotoxicity
Summary of Human, Animal, and Mechanistic Evidence
Inferences across
evidence streams
Evidence from Studies of Exposed Humans
Bacterial resistance
and histopathological
changes in the spleen
are assumed to be
relevant to humans
Some evidence for
decreased resistance
to infection
(bactericidal assay in
rats; increased
mortality in humans
from flu/pneumonia)
but lack of support
from IgM RBC assay
Autoimmunity
evaluated in only one
study
Effects on spleen
common to multiple
studies
Susceptible
populations may
include people with
compromised immune
systems and the
elderly
Other solvents have
been associated with
effects on the immune
system
Studies, outcomes, and
confidence
Factors that increase
strength or certainty
Factors that decrease
strength or certainty
Key findings and
interpretation
Evidence stream summary
Mortality from
infectious disease -
SMRs > and < 1
Autoimmunity - OR > 1
Mortality from non-
specific respiratory
disease - SMR/HR >
and< 1
Hearne and Pifer 1999):
high confidence; all
others: medium
confidence
Lack of quantitative
methylene chloride air
concentration
measurements and use
of dissimilar
comparison groups in
most studies,
Lack of control for
other chemicals, some
of which are solvents
and may also be
associated with
immunotoxicity
Maanitude of effect
Large OR for one of
the autoimmunity
measurements
One large SMR for
morality from
bronchitis (but a
non-specific effect)
SMRs > 1 for study
of mortality from
flu/pneumonia (a
severe outcome)
Inconsistency
Infectious disease:
one SMR > 1 and
another is < 1
Imprecision
Lack of information on
precision for one study
(Gibbs); imprecise
association for cum
exposure odds ratio for
autoimmunity
(Chaigne)
Dose-resDonse
Insufficient
information to judge
gradient
Coherence across tvues
of immunity
Inconsistency within
types of studies and
limited study numbers
make it difficult to
judge coherence
Mortality from
infectious disease:
Possible association
with methylene
chloride but results are
inconsistent and
outcome is severe
(mortality)
Autoimmunity:
Possible strong
association with
methylene chloride but
only one study is
available
Some study designs
may limit ability to
discern effects
associated specifically
with methylene
chloride
Results across human
epidemiological studies suggest
that methylene chloride may be
associated with
immunosuppression and
autoimmunity
Inconsistencies across studies,
severity of outcome (mortality)
and limitations of study design
preclude firm conclusions
Mechanistic evidence: SuDDort
unclear given the limited
database
Evidence from In vivo Animal Studies
Studies, outcomes, and
confidence
Factors that increase
strength or certainty
Factors that decrease
strength or certainty
Key findings and
interpretation
Evidence stream summary
Bacterial resistance
assay - effect observed
Functional immune
(IgM) assay - no effect
observed
Clinical chemistry/
histopathology results
(multiple studies) -
change in
histopathology of spleen
within some studies
Aranyietal. 1986):
Effect
size/precision:
Bacterial resistance
assay showed two
statistically-
significant possibly
related results of
similar magnitude
Consistency
Several studies
showed effects on
Only a single study of
bacterial resistance is
available
Burek didn't identify
histopathological
changes in the spleen
at a concentration
identified with splenic
changes in other
studies
Splenic fibrosis
showed somewhat
One study positive for
bactericidal activity
but limited support
Support from animal
studies only includes
histopathological
changes in the spleen
in some studies.
Limited information based on a
single study of bactericidal
resistance with some changes in
spleens in some studies.
However, lack of support from
IgM RBC assay
Mechanistic evidence: SuDDort is
unclear given the limited
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medium confidence; all
others: high confidence
spleen (decreased
weight, atrophy,
fibrosis)
Dose-resconse
aradient - suleen
effects observed at
higher
concentrations
unclear dose-response
trend (2%, 10%, 20%,
14%at0, 1000,2000
and 4000 ppm)
Two-year studies
didn't identify effects
on immune cells and
organs than the spleen
No increased rates of
infection were
identified in 13-week
and 2-year studies
RBC study to
determine IgM
response was negative.
database
Mechanistic Evidence or Supplemental Information
Biological events or
pathways (or other
information)
Species or model systems
Key findings, limitations, and interpretation
(for each row below)
Evidence stream summary
Pro-inflammatory, but
somewhat non-specific,
changes (one study)
Anti-inflammatory
changes (one study)
Two in vivo studies
Rat and carp
The limited number of studies, differences in
species, types of cells and substances studied as
well as differences in processes evaluated make
it difficult to make any conclusions regarding
these studies.
Little can be concluded from these
two studies that have very different
study protocols. It is not clear
whether the studies suggest
opposite effects or are just two
aspects of a coordinated immune
response.
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Appendix B: Evaluation of Steep Dose-Response Information for Acute Exposure Endpoint
Most case reports of human deaths lack information on exposure conditions; some that do have such information, however, include a
fairly low exposure concentration within that range (100 ppm for 55 minutes and lower). Thus, EPA still considers the possibility that
there could be a steep dose-response from more subtle CNS effects up to death in humans.
Winneke (1974) exposed individuals at 300, 500 or 800 ppm methylene chloride in four separate experiments. A more direct
comparison between these results and the results from Putz et i 9} was attempted by considering them on a scale of increasing
methylene chloride concentrations (See Table below). Overall, EPA did not consider measures among Winne and Putz et al.
(j [[79} to be similar enough to allow a full assessment of the steepness of any dose response. However, considering the magnitude of
responses for the data described by the Winneke (1974) experiments, the results don't provide evidence for a steep dose-response
curve. Specifically, the results of both visual and auditory vigilance tests were the same or greater at 300 ppm compared with 500
ppm; the effect at 800 ppm is approximately 2x the effect at 300 and 500 ppm but is still an 8% change.
Visual and Auditory Effects Compared with Controls (3.8
to 4 Hours)
Cone, (ppm)
Visual
Auditory vigilance
Reference
195
36% dec. hand-eye a
17% dec. peripherala
17% decrease b
Putz et t 9)
300
[tests 2 +3]
~ 0.95 decrement in CFF 0
Omission errors: ~ 4% increase
b
Winneke (br" 5)
500
[tests 1 +3]
~ 0.95 decrement in CFF 0
Omission errors: ~ 3% increase
b
800
[test 2]
-2.5 decrement in CFF 0
Omission errors: ~ 8% increase
b
a Dual task: Eye-hand coordination - participant manipulates a small hand control level to position an oscilloscope beam in the center of a scope face; the participant had to track
the forcing function that moved the beam and force it back to center (hence, the eye-hand coordination). The second part of the task was to monitor peripheral stimuli for
occurrence of a signal. The participant pressed a response switch to respond to the signal.
b Piitz ft al. (1979): Participants listened to a train of white noise pulses. At random intervals (and a probability of 0.20) a slightly less intense or more intense pulse was inserted.
The participant had to press a hand-held button when they heard the less intense signal. The measure reported here is percent of correct detections, not including responses when no
signal was sent out). All tests were automated using a laboratory digital computer. Winneke (1974): A similar test was used, but with slight differences. Probability was 0.03 and
only less intense pulses were used. Response was omission errors, or percent of signals missed per 15 minutes. Although the methods are similar, it is not clear that the outcome
measures are comparable. However, if they are comparable, then the magnitude difference compared with controls was greater at a lower concentration and appears to show an
inverse dose-response. No information on automation.
c - Critical flicker frequency was determined using an electronic flicker device, brightness of flicker light and with the on-off ratio held constant. Descending presentation was
employed, although it is not clear what this means. The result is an average of 8 single descending CFF determinations
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EPA also investigated the presence of a dose-response relationship at 2 hours. EPA compared reaction time information between
Garoberale et al. (1975) and Divincenzo et al. (1972). Although these studies both received low data quality evaluations, reaction time
changes were not observed at concentrations of 100 and 200 ppm (Divincenzo et al... 1972) and up to 750 ppm (Gamberale et al..
1975). but changes were seen at 1000 ppm (Gamberale et al.. 1975). These comparisons do not provide enough information on the
steepness of the dose-response curve because changes were observed only at the highest concentration.
References
Also. S; Take. M; Kasai. T; Senoh. H; IJmeda. Y; Matsumoto. M; Fukushima. S. (2014). Inhalation carcinogenicity of
dichloromethane in rats and mice. Inhal Toxicol 26: 435-451.
https:
id/4238148
Andersen, ME;
JL; Pendse.
Ctewett, HI; Pottenger, LH; Bus. IS; Dodd, DE; Kemp, DC; McMutten, PP.
An do.
(2017). Combining transcriptomics and PBPK modeling indicates a primary role of hypoxia and altered circadian signaling in
dichloromethane carcinogenicity in mouse lung and liver. Toxicol Appl Pharmacol 332: 149-158.
http://dx.doi.oix 10 [0]? 'j.taap.201 / 0--1 002
T; Otsuka. S; Nishiyama. M; Senoo. K; Watanabe. MM; Matsumoto. S. (2003). Toxic Effects of Pichloromethane and
Trichloroethylene on the Growth of Planktonic Green Algae, Chlorella vulgaris NIES227, Selenastrum capricornutum
NIES35, and Volvulina steinii NIES545. 18: 43-46.
WJ; Graham. J A; Miller. FX (1986). The effects of inhalation of organic chemical air contaminants on murine lung
host defenses. Fundam Appl Toxicol 6: 713-720. http://dx.doi.ore/10.1016/0272-0590(86)90184-3
Benignus. VA; Bushnell PI; Boves. WK. (2011). Estimated rate of fatal automobile accidents attributable to acute solvent exposure at
low inhaled concentrations. Risk Anal 31: 1935-1948. http://dx.doi.or^ h>_lj_! l_j_ l_* I _ -6924.201 I
Birge. WJ; Blac Kxiehne. RA. (1980). Effects of Organic Compounds on Amphibian Reproduction. 39 p. (NTIS PB80-147523).
Black. J A; Birge, WJ; McDonnell. WE; Westerman. AG; Ram user, DM. (1982). The aquatic toxicity of organic
compounds to embryo-larval stages of fish and amphibians. (Research Report No. 133). Lexington, KY: University of
Kentucky.
Bomschein. RL; Hastings. L; Manson. JM. (1980). Behavioral toxicity in the offspring of rats following maternal exposure to
dichloromethane. Toxicol Appl Pharmacol 52: 29-37. http://dx.doi.orK t0 10 i- 0041~008X(80)90i 1 S_
Bos. PM; Zeilmaker. MJ; van. Eijkere (2006). Application of physiologically based pharmacokinetic modeling in setting acute
exposure guideline levels for methylene chloride. Toxicol Sci 91: 576-585. http://dx.doi.org 10 1093/toxsci/ktj I "/>>
Burek. JD; Nitschke. KD; Bell. TJ; Wackerle. PL; Chitds. R; Beyer. JE; Ditten Lampy. LW; McKenna. MJ. (1984).
Methylene chloride: A two-year inhalation toxicity and oncogenicity study in rats and hamsters. Fundam Appl Toxicol 4: 30-
47. http://dx.doi.on 93/toxsci/4.1.30
Casanova. M; Cone eck. H. (1996). PNA-protein cross-links (PPX) and cell proliferation in B6C3F1 mice but not Syrian
golden hamsters exposed to dichloromethane: Pharmacokinetics and risk assessment with PPX as dosimeter. Fundam Appl
Toxicol 31: 103-116. http://dx.doi.org/lO t006/faat.l9Q6 0081
Page 242 of 246
-------
MC RESPONSE TO COMMENT
Chaigne. < asfargues v Marie, I; Hlittenb ergot
-------
MC RESPONSE TO COMMENT
Fole> tick, PD; Ton, TV; Frost, M; Kari, F; Anderson, MW; Maronpot RR. (1993). Inhalation exposure to a hepatocarcinogenic
concentration of methylene chloride does not induce sustained replicative DNA synthesis in hepatocytes of female B6C3F1
mice. Carcinogenesis 14: 811-817. http://dx.doi.org 10 hv)3/carcin I ! > S I 1
Foster. JR.; Green. T; Smith. IX; Lewis. RW: Hext. PM; Wyatt I. (1992). Methylene chloridean inhalation study to investigate
pathological and biochemical events occurring in the lungs of mice over an exposure period of 90 days. Fundam Appl Toxicol
18: 376-388. http://dx.doi.org/10 10''3/toxsci I ' o
Gamberalc I. \i in wall G llultengren, M. (1975). Exposure to methylene chloride: II. Psychological functions. Scand J Work
Environ Health 1: 95-103.
General Electric Co. (1990). MORBIDITY STUDY OF OCCUPATIONAL EXPOSURE TO METHYLENE CHLORIDE USING A
COMPUTERIZED SURVEILLANCE SYSTEM (FINAL REPORT) WITH COVER SHEETS AND LETTER DATED
041190. (OTS: OTS0522984; 8EHQNum: NA; DCN: 86-900000421; TSCATS RefID: 406678; CIS: NA).
Gibbs. GW. (1992). SUPPLEMENT: MORTALITY OR WORKERS EMPLOYED AT A CELLULOSE ACETATE &
TRIACETATE FIBERS PLANT IN CUMBERLAND, MD (FINAL REPORT) WITH COVER LETTER DATED 061792.
(OTS: OTS0516635-3; 8EHQNum: 8EHQ-0692-0772; DCN: 89-920000119; TSCATS RefID: 427311; CIS: NA).
Guki < S; Stewart. PA; Milliken. K; Purdue. M; Severson. R; Seixas. N; Blah A Iden. KJ. (1993). Mortality update of cellulose fiber production workers. Scand J Work
Environ Health 19: 426-428.
Lash. AA; Becker. CE; So. Y; Shore. M. (1991). Neurotoxic effects of methylene chloride: Are they long lasting in humans? Occup
Environ Med 48: 418-426.
Nac/Aegl. (2008). Methylene chloride - interim acute exposure guideline levels (AEGLs). Washington, DC: National Advisory
Committee for Acute Exposure Guideline Levels.
Niosh. (1976). A Guide to Industrial Respiratory Protection. (HEW Pub. 76-189). Cincinnati, OH: U.S. Department of Health and
Human Services, National Institute for Occupational Safety and Health.
Nitschke. KD; Buret I? P kin iba. RJ, Rampy. LW; McKenna. Ml. (1988). Methylene chloride: A 2-year inhalation toxicity
and oncogenicity study in rats. Fundam Appl Toxicol 11: 48-59. http://dx.doi.orj 3272-0590(88)90269-2
Page 244 of 246
-------
MC RESPONSE TO COMMENT
NRC. (2009). Science and decisions: Advancing risk assessment. Washington, DC: The National Academies Press.
http://dx.doi.on 226/122.09
NTP. (1986). NTP Toxicology and Carcinogenesis Studies of Dichloromethane (Methylene Chloride) (CAS No. 75-09-2) in F344/N
Rats and B6C3F1 Mice (Inhalation Studies). 306: 1-208.
NTP. (2009). Explanation of levels of evidence for immune system toxicity. Research Triangle Park, NC.
http://ntp.niehs.nih.gov/eo/9399
OSHA. (1997). Final rules: Occupational exposure to methylene chloride. Washington, DC: U.S. Department of Labor, Occupational
Safety and Health Administration.
https://www.osha.gov/pls/oshaweb/owadisp.show document?p tabte=FEDERAL REGISTER&p id=l3600
Putz. VR; Johnson. BL; Setzei (1979). A comparative study of the effects of carbon monoxide and methylene chloride on human
performance. J Environ Pathol Toxicol 2: 97-112.
Radican. L; Blair. A; Stew t₯artenberg. D (2008). Mortality of aircraft maintenance workers exposed to trichloroethylene and
other hydrocarbons and chemicals: Extended follow-up. J Occup Environ Med 50: 1306-1319.
Ruder. AM; Yiin. JH; Waters. MA; Carreon. T; Hein. MI; Butler. MA; Calvert. GM; Davis-King. KE; Schull Mandel. IS;
Morton. M Kedin^ i t< fiosenman. i vxewart. PA; Grp. BCCS. (2013). The Upper Midwest Health Study: gliomas and
occupational exposure to chlorinated solvents. Occup Environ Med 70: 73-80.
Russo. J. (2015). Significance of rat mammary tumors for human risk assessment. Toxicol Pathol 43: 145-170.
Schenk. L; Rauroa. M; Fran s son. MN; Joh an son. G. (2018). Percutaneous absorption of thirty-eight organic solvents in vitro using pig
skin. PLoS ONE 13: e0205458. http://dx.doi.on ournal.pone.0205458
Schwarzenbach. RP; Gschwend. PM; Imboden. DM. (2003). Environmental Organic Chemistry (2 ed.). Hoboken, New Jersey: John
Wiley & Sons.
Serota. DG; Thakut U. I Haul U \ I; Kirschman. JC; Brown. NM; Coots. R.H.; Morgareidge. K. (1986). A two-year drinking-water
study of dichloromethane in rodents: I. Rats. Food Chem Toxicol 24: 951-958. http://dx.doi.om hi \±H < 0278-6915(86)90323-
6
Silver, SR; Pinkerton, LE; Flemin [.es. JH; Altee. S; Luo, L; Bertke, SI. (2014). Retrospective Cohort Study of a
Microelectronics and Business Machine Facility. Am J Ind Med 57: 412-424.
Staples. I \ \\ emei U', I i< »ogheem. TJ. (1985). Assessment of priority pollutant concentrations in the United States using STORET
database. Environ Toxicol Chem 4: 131-142. http://dx.doi.org/ 2/etc.5620040202
Stew sher. TN; Hosko. MI; Peterson. JE; Baretta. ED; Dodd. HC. (1972). Experimental human exposure to methylene
chloride. Arch Environ Occup Health 25: 342-348. http://dx.doi.org/10.1080/00039896.1972.10666184
Ten Berge,1 /art., A; Appelman, LM. (1986). Concentration-time mortality response relationship of irritant and systemically
acting vapours and gases. J Hazard Mater 13: 301-309. http://dx.doi.org/10.1016/0304-3894(86)85003-8
(1987). Household solvent products: A national usage survey. (EPA-OTS 560/5-87-005). Washington, DC: Office of Toxic
Substances, Office of Pesticides and Toxic Substances.
https://ntrl.ntis. gov/NTRL/dashboard/searchResults.xhtml?searchQuerv=PB8 S j 1; 881
Page 245 of 246
-------
MC RESPONSE TO COMMENT
(2011). Toxicological review of dichloromethane (methylene chloride) (CASRN 75-09-2): In support of summary
information on the Integrated Risk Information System (IRIS) [EPA Report], (EPA/635/R-10/003F). Washington, D.C.
https://cfpiib.epa.gov/ncea/iris/iris documents/documents/toxreviews/0070tr. pdf
Uraga-Tovai inguez-Lopez. ML; Madera-Sandoval. RL; Nai era-Martinez. M; Garcia-Latorre. E; Vega-Lopez. A. (2014).
Generation of oxyradicals (02. and H202), mitochondrial activity and induction of apoptosis of PBMC of Cyprinus carpio
carpio treated in vivo with halomethanes and with recombinant HSP60 kDa and with LPS of Klebsiella pneumoniae.
Immunopharmacol Immunotoxicol 36: 329-340. http://dx.doi.org/10.3109/08923973.2014.947034
von Ehrenstein. OS: Aral is. H; Cockbum. M; Ritz. B (2014). In Utero Exposure to Toxic Air Pollutants and Risk of Childhood
Autism. Epidemiology 25: 851-858.
von. Ehrenstein. OS: Ling. C; Cui. X; Cockbum. M; Pai Wu. J: Ritz. B. (2019). Prenatal and infant exposure to ambient
pesticides and autism spectrum disorder in children: population based case-control study. BMJ 364:1962.
http://dx.doi.oo )toi .1962
Warbrick, EV; Kilgour, ID; Dearman, RJ; Kimber, I; Dugard, PH. (2003). Inhalation exposure to methylene chloride does not induce
systemic immunotoxicity in rats. J Toxicol Environ Health A 66: 1207-1219. http://dx.doi.org/10 [080/1 > JS 7390306410
Whittaker. C; Rice. F: McKeman. L; Dankox ic 1' Vtacmahon. K; Kuempel. E: Zumwalde. R; Schulte. P. (2016). Current
Intelligence Bulletin 68: NIOSH Chemical Carcinogen Policy. Whittaker, C; Rice, F; Mckernan, L; Dankovic, D; Lentz, T;
Macmahon, K; Kuempel, E; Zumwalde, R; Schulte, P.
Wilson. JEH. (1998). Developmental Arrest in Grass Shrimp Embryos Exposed to Selected Toxicants. 60-75.
Winneke, G (1974). Behavioral effects of methylene chloride and carbon monoxide as assessed by sensory and psychomotor
performance. In C Xintaras; BL Johnson; IDe Groot (Eds.), Behavioral toxicology: Early detection of occupational hazards
(pp. 130-144). Cincinnati, OH: U.S. Department of Health, Education, and Welfare, National Institute for Occupational Safety
and Health.
Page 246 of 246
------- |