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EPA SCIENTIFIC ADVISORY COMMITTEE ON CHEMICALS
CHARGE TO THE PANEL - METHYLENE CHLORIDE
As amended by the Frank R. Lautenberg Chemical Safety for the 21st Century Act on June 22,
2016, the Toxic Substances Control Act (TSCA), requires the U.S. Environmental Protection
Agency (EPA) to conduct risk evaluations on existing chemicals. In December of 2016, EPA
published a list of the initial ten chemical substances that are the subject of the Agency's chemical
risk evaluation process (81 FR 91927), as required by TSCA. Methylene chloride is one of the first
ten chemical substances and the second of the ten to undergo a peer review by the Scientific
Advisory Committee on Chemicals (SACC). In response to this requirement, EPA has prepared
and published a draft risk evaluation for Methylene Chloride. The EPA has solicited comments
from the public on the draft and will incorporate them as appropriate, along with comments from
peer reviewers, into the final risk evaluation.
Methylene Chloride Scope Document
Methylene Chloride Problem Formulation Document
The documents that are part of this review include:
1.	Draft Risk Evaluation for Methylene Chloride
2.	Draft Methylene Chloride Charge
3.	Draft Systematic Review Supplemental File: Data Quality
Fate and Transport Studies
4.	Draft Systematic Review Supplemental File: Data Quality
Releases and Occupational Exposure Data
5.	Draft Systematic Review Supplemental File: Data Quality
Releases and Occupational Exposure Common Sources
6.	Draft Systematic Review Supplemental File: Data Quality
Consumer and Environmental Exposure
7.	Draft Systematic Review Supplemental File: Data Extraction Tables for Consumer and
Environmental Exposure Studies
8.	Draft Systematic Review Supplemental File: Data Quality
Hazard Studies
9.	Draft Systematic Review Supplemental File: Data Quality
Hazard Studies - Animal Studies
10.	Draft Systematic Review Supplemental File: Data Quality
Hazard Studies - Epidemiological Studies
11.	Draft Systematic Review Supplemental File: Data Quality
Hazard Studies - Human Controlled Experiments
12.	Draft Systematic Review Supplemental File: Updates to the Data Quality Criteria for
Epidemiological Studies
13.	Draft Systematic Review Supplemental File: Data Extraction Tables for Human Health
Hazard Studies
14.	Draft Supplemental Information on Consumer Exposure Assessment
15.	Draft Supplemental Information on Surface Water Exposure Assessment
16.	Draft Supplemental Information on Releases and Occupational Exposure Assessment.
Evaluation of Environmental
Evaluation of Environmental
Evaluation of Environmental
Evaluation on Data Sources on
Evaluation of Environmental
Evaluation of Human Health
Evaluation of Human Health
Evaluation of Human Health
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17.	Draft Supplemental File: Methylene Chloride Benchmark Dose and PBPK Modeling
Report
18.	Draft Risk Evaluation for Methylene Chloride, Supplemental Information Risk Calculator
for Occupational Exposures
19.	Draft Risk Evaluation for Methylene Chloride, Supplemental Information Risk Calculator
for Consumer Inhalation Exposures
20.	Draft Risk Evaluation for Methylene Chloride, Supplemental Information Risk Calculator
for Consumer Dermal Exposures
21.	Draft Supplemental File: Methylene Chloride Consumer Exposure Assessment Model
Input Parameters
22.	Draft Supplemental File: Methylene Chloride Consumer Exposure Model Outputs
23.	Draft Systematic Review Supplemental File: Data Quality Evaluation of Physical-
Chemical Properties Studies
The focus of this meeting is to conduct the peer review of the Agency's draft risk evaluation of
methylene chloride and associated supplemental materials. At the end of the peer review process,
EPA will use the reviewers' comments/recommendations, as well as public comment, to finalize
the risk evaluation.
CHARGE QUESTIONS:
EPA is seeking the SACC advice on the clarity and scientific underpinnings of the overall
methylene chloride risk evaluation. The peer review should consider whether the conclusions
presented in the draft risk evaluation are clearly presented, scientifically supported and based on
the best available scientific information. The SACC should also consider whether the methods
employed to generate the information are reasonable for and consistent with the intended use of the
information. As per TSCA, where unreasonable risks are identified in the final risk evaluation will
be used to support rulemaking to mitigate identified risks.
Throughout the peer review, the SACC should be mindful that TSCA now requires that EPA use
data and/or information in a manner consistent with the "best available science" and that EPA base
decisions on the "weight of the scientific evidence". The EPA's Final Rule, Procedures for
Chemical Risk Evaluation Under the Amended Toxic Substances Control Act (82 FR 33726),
defines "best available science" as science that is reliable and unbiased. This involves the use of
supporting studies conducted in accordance with sound and objective science practices, including,
when available, peer-reviewed science and supporting studies and data collected by accepted
methods or best available methods (if the reliability of the method and the nature of the decision
justifies use of the data). The Final Rule also defines the "weight of the scientific evidence" as a
systematic review method, applied in a manner suited to the nature of the evidence or decision, that
uses a pre-established protocol to comprehensively, objectively, transparently, and consistently
identify and evaluate each stream of evidence, including strengths, limitations, and relevance of
each study and to integrate evidence as necessary and appropriate based upon strengths, limitations,
and relevance." 40 CFR 702.33
Below, are a set of charge questions for each major element of the risk evaluation. The SACC is
expected to consider questions and issues raised during public comment as part of its deliberations.
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1.	Environmental Fate 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.
1.1.	Please comment on EPA's qualitative analysis of pathways based on physical/chemical
and fate properties.
1.2.	Please comment on the data, approaches and/or methods used to characterize exposure to
aquatic receptors.
2.	Environmental Exposure and Releases:
EPA evaluated releases to water and aquatic exposures for conditions of use in industrial and
commercial settings. EPA used Toxics Release Inventory (TRI) and Discharge Monitoring Report
(DMR) data to provide a basis for estimating releases. EPA used these releases and associated
inputs within EFAST 2014 to estimate instream chemical concentrations and days of exceedance.
EPA also evaluated monitored values of methylene chloride in surface water and where possible
compared those values to estimated release concentrations.
2.1.	Please comment on the approaches, models, and data used in the water release assessment
including comparison to monitored data.
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.
3.	Environmental hazard:
EPA evaluated environmental hazards for aquatic species from acute and chronic exposure
scenarios.
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?
4.	Occupational and Consumer Exnosure:
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).
4.1. Please comment on the approaches and estimation methods, models, and data used in the
occupational exposure assessment.
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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.
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.
4.4.	Please comment on the assumptions and uncertainties of this approach.
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.
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?
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?
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.
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5. Human Health Hazard:
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.
5.1.	Please comment on the appropriateness of the approach, including the data quality
evaluation, and the approach's underlying assumptions, strengths and weaknesses.
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.
5.3.	Please provide relevant data or documentation and rationale for including other studies
and endpoints for consideration.
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-hrPODs.
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.
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.
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.
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).
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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.
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.
6. Risk Characterization:
EPA calculated environmental risk using exposure data (e.g. modeling tools and monitored
datasets) and environmental 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.
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.
6.2.	Please provide information on additional uncertainties and assumptions that EPA has not
adequately presented.
6.3.	Please comment on whether the information presented supports the findings outlined in the
draft risk characterization section.
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.
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
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occupational non users (ONUs) or consumers used personal protective equipment in the risk
estimation process.
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.
7. Overall Content and 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.
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.
7.2 Please comment on the overall content, organization, and presentation of the draft risk
evaluation of methylene chloride.
7.3. Please provide suggestions for improving the clarity of the information presented in the
documents.
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