EE|R^% United States
1	Environmental Protection Agency
EPA Document# EPA-740-R1-7020
May 2018
Office of Chemical Safety and
Pollution Prevention
Problem Formulation of the Risk Evaluation for
Carbon Tetrachloride
(Methane, Tetrachloro-)
CASRN: 56-23-5
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May 2018

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TABLE OF CONTENTS
ABBREVIATIONS	7
EXECUTIVE SUMMARY	10
1	INTRODUCTION	12
1.1	Regulatory Hi story	14
1.2	Assessment History	14
1.3	Data and Information Collection	15
1.4	Data Screening During Problem Formulation	17
2	PROBLEM FORMULATION	18
2.1	Physical and Chemical Properties	18
2.2	Conditions of Use	19
2.2.1	Data and Information Sources	19
2.2.2	Identification of Conditions of Use	19
2.2.2.1	Categories and Subcategories Determined Not to be Conditions of Use or Otherwise
Excluded During Problem Formulation	20
2.2.2.2	Categories and Subcategories of Conditions of Use Included in the Scope of the Risk
Evaluation	23
2.2.2.3	Overview of Conditions of Use and Lifecycle Diagram	26
2.3	Exposures	30
2.3.1	Fate and Transport	30
2.3.2	Releases to the Environment	32
2.3.3	Presence in the Environment and Biota	34
2.3.4	Environmental Exposures	35
2.3.5	Human Exposures	36
2.3.5.1	Occupational Exposures 	36
2.3.5.2	Consumer Exposures	37
2.3.5.3	General Population Exposures	37
2.3.5.4	Potentially Exposed or Susceptible Subpopulations	38
2.4	Hazards (Effects)	39
2.4.1	Environmental Hazards	39
2.4.2	Human Health Hazards	41
2.4.2.1	Non-Cancer Hazards	41
2.4.2.2	Genotoxicity and Cancer Hazards	42
2.4.2.3	Potentially Exposed or Susceptible Subpopulations	42
2.5	Conceptual Models	43
2.5.1	Conceptual Model for Industrial and Commercial Activities and Uses: Potential Exposures
and Hazards	44
2.5.2	Conceptual Model for Consumer Activities and Uses: Potential Exposures and Hazards.... 47
2.5.3	Conceptual Model for Environmental Releases and Wastes: Potential Exposures and
Hazards	47
2.5.3.1	Pathways That EPA Expects to Include But Not Further Analyze	47
2.5.3.2	Pathways that EPA Does Not Expect to Include in the Risk Evaluation	48
2.6	Analysis Plan	53
2.6.1 Exposure	53
2.6.1.1 Environmental Releases, Fate and Exposures	53
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2.6.1.2	Occupational Exposures	54
2.6.1.3	Consumer Exposures	56
2.6.1.4	General Population	56
2.6.2	Hazards (Effects)	56
2.6.2.1	Environmental Hazards	56
2.6.2.2	Human Health Hazards	56
2.6.3	Risk Characterization	58
REFERENCES	60
APPENDICES	65
Appendix A REGULATORY HISTORY	65
A.l Federal Laws and Regulations									.....................65
A.2 State Laws and Regulations																		71
A.3	International Laws and Regulations......							.72
Appendix B SECOND SCREENING OF PEER-REVIEWED LITERATURE ON CARBON
TETRACHLORIDE	74
B.l	Scope of the Literature Re-screening													..........74
B. 1.1 Identifying Studies for Title/Abstract Re-screening	74
B.2 Prioritizing References for Re-Screening 																		....75
B.2.1 First Round of Prioritization for Re-screening	75
B. 2.1.1 Keyword S earch Method	75
B.2.1.2 DoCTER Method	76
B.2.1.3 List of Prioritized References for Re-Screening	77
B.2.2 Second Round of Prioritization for Re-screening	77
B. 2.2.1 Keyword S earch Method	77
B.2.2.2 DoCTER Method	77
B.2.2.3	List of Prioritized References for Re-Screening	78
B.3 Re-screening Criteria and Process																	79
B.3.1 Re-screening Process	79
B.3.2	Re-screening Criteria	79
B.4	Results.........														82
Appendix C PROCESS, RELEASE AND OCCUPATIONAL EXPOSURE INFORMATION.... 82
C.l	Process Information								...........82
C.	1.1 Manufacture (Including Import)	82
C.	1.1.1 Domestic Manufacture	82
C.l. 1.2 Import	83
C.1.2 Processing and Distribution	83
C. 1.2.1 Reactant or Intermediate	83
C. 1.2.2 Incorporation into a Formulation, Mixture or Reaction Products	84
C. 1.2.3 Repackaging	84
C. 1.2.4 Recycling	84
C.l.3 Uses	86
C. 1.3.1 Petrochemicals-derived Products Manufacturing	86
C.1.3.2 Agricultural Products Manufacturing	86
C. 1.3.3 Other Basic Organic and Inorganic Chemical Manufacturing	86
C.1.3.4 Laboratory Chemicals	86
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C.1.3.5 Other Uses	86
C.1.3.6 Disposal	86
C.2 Occupational Exposure Data.....																86
Appendix D PROCESS AGENT USES FOR CARBON TETRACHLORIDE	89
Appendix E SURFACE WATER ANALYSIS FOR CARBON TETRACHLORIDE RELEASES
90
Appendix F SUPPORTING TABLE FOR INDUSTRIAL AND COMMERCIAL ACTIVITIES
AND USES CONCEPTUAL MODEL	92
Appendix G SUPPORTING TABLE FOR ENVIRONMENTAL RELEASES AND WASTES
CONCEPTUAL MODEL	104
Appendix H INCLUSION AND EXCLUSION CRITERIA FOR FULL TEXT SCREENING 106
H. 1 Inclusion Criteria for Data Sources Reporting Engineering and Occupational Exposure Data 106
H.2 Inclusion Criteria for Data Sources Reporting Human Health Hazards 					109
Appendix I LIST OF RETRACTED PAPERS	112
LIST OF TABLES
Table 1-1. Assessment History of Carbon Tetrachloride	15
Table 2-1. Physical and Chemical Properties of Carbon Tetrachloride	18
Table 2-2. Categories and Subcategories Determined Not to be Conditions of Use or Otherwise
Excluded During Problem Formulation	21
Table 2-3. Categories and Subcategories of Conditions of Use Included in the Scope of the Risk
Evaluation	23
Table 2-4. Production Volume of Carbon Tetrachloride in Chemical Data Reporting (CDR) Reporting
Period (2012 to 2015) a	27
Table 2-5. Environmental Fate Characteristics of Carbon Tetrachloride	32
Table 2-6. Summary of Carbon Tetrachloride TRI Production-Related Waste Managed in 2015 (lbs).. 33
Table 2-7. Summary of Carbon Tetrachloride Toxics Release Inventory (TRI) Releases to the
Environment in 2015 (lbs)	33
Table 2-8. Ecological Hazard Characterization of Carbon Tetrachloride	40
Table 2-9. Potential Sources of Occupational Exposure Data	54
LIST OF FIGURES
Figure 2-1. Carbon Tetrachloride Life Cycle Diagram	29
Figure 2-2. Carbon Tetrachloride Conceptual Model for Industrial and Commercial Activities and Uses:
Potential Exposures and Hazards	46
Figure 2-3. Carbon Tetrachloride Conceptual Model for Environmental Releases and Wastes: Potential
Exposures and Hazards	52
LIST OF APPENDIX TABLES
Table_Apx A-l. Federal Laws and Regulations	65
Table_Apx A-2. State Laws and Regulations	71
Table_Apx A-3. Regulatory Actions by Other Governments and Tribes	72
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TableApx B-l. Topic Extraction Results for 2,749 On-topic Studies using 10 Clusters and k-means
Algorithm	76
Table Apx B-2. Supervised Clustering Results for 1,566 On-topic Studies Using Ensemble Approach
(k-means and NMF Algorithms x 10, 20, and 30 clusters), 50 Seeds, and 0.9 Recall	78
Table Apx B-3. Overview of Complete (Revised) Tagging Structure for Carbon Tetrachloride	80
Table Apx C-l. Summary of Carbon Tetrachloride Personal Monitoring Air Samples Obtained from
OSHA Inspections Conducted Between 2013 and 2015	88
Table Apx C-2. Summary of Monitoring Data from NIOSH Health Hazard Evaluations Conducted
since 1990	 89
TableApx D-l. List of Uses of Carbon Tetrachloride as Process Agent in MP's Directive: Decision
X/14: Process Agents	89
Table Apx E-l. Modeled Carbon Tetrachloride Surface Water Concentrations	90
Table Apx F-l. Industrial and Commercial Activities and Uses Conceptual Model Supporting Table . 92
Table Apx G-l. Environmental Releases and Wastes Conceptual Model Supporting Table	104
Table Apx H-l. Inclusion Criteria for Data Sources Reporting Engineering and Occupational Exposure
Data	107
Table Apx H-2. Engineering, Environmental Release and Occupational Data Necessary to Develop the
Environmental Release and Occupational Exposure Assessments	108
Table Apx H-3. Inclusion and Exclusion Criteria for Data Sources Reporting Human Health Hazards
Related to Carbon Tetrachloride Exposure a	110
LIST OF APPENDIX FIGURES
FigureApx C-l. General Process Flow Diagram for Solvent Recovery Processes	85
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ACKNOWLEDGMENTS
This report was developed by the United States Environmental Protection Agency (U.S. EPA), Office of
Chemical Safety and Pollution Prevention (OCSPP), Office of Pollution Prevention and Toxics (OPPT).
Acknowledgements
The OPPT Assessment Team gratefully acknowledges participation and/or input from Intra-agency
reviewers that included multiple offices within EPA, Inter-agency reviewers that included multiple
Federal agencies, and assistance from EPA contractors GDIT (Contract No. CIO-SP3,
HHSN316201200013W), ERG (Contract No. EP-W-12-006), Versar (Contract No. EP-W-17-006), ICF
(Contract No. EPC14001) and SRC (Contract No. EP-W-12-003).
Docket
Supporting information can be found in public docket:	T--201.6-0733.
Disclaimer
Reference herein to any specific commercial products, process or service by trade name, trademark,
manufacturer or otherwise does not constitute or imply its endorsement, recommendation or favoring by
the U.S. Government.
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ABBREVIATIONS
c
Degrees Celsius
AAL
Allowable Ambient Levels
atm
Atmosphere(s)
AT SDR
Agency for Toxic Substances and Disease Registries
AWQC
Ambient Water Quality Criteria
BCF
Bioconcentration Factor
BUN
Blood Urea Nitrogen
CAA
Clean Air Act
CASRN
Chemical Abstract Service Registry Number
CBI
Confidential Business Information
CDR
Chemical Data Reporting
CEHD
Chemical Exposure Health Data
CERCLA
Comprehensive Environmental Response, Compensation and Liability Act
CFC
Chi orofluorocarb on
cm3
Cubic Centimeter(s)
CNS
Central Nervous System
coc
Concentration of Concern
CoRAP
Community Rolling Action Plan
CPSC
Consumer Product Safety Commission
CS2
Carbon Disulfide
C SAT AM
Community-Scale Air Toxics Ambient Monitoring
CSCL
Chemical Substances Control Law
CYP450
Cytochrome P450
CWA
Clean Water Act
DNA
Deoxyribonucleic Acid
DT50
Dissipation Time for 50% of the compound to dissipate
EC
European Commission
ECHA
European Chemicals Agency
EDC
Ethylene Dichloride
EPA
Environmental Protection Agency
EPCRA
Emergency Planning and Community Right-to-Know Act
ESD
Emission Scenario Document
EU
European Union
FDA
Food and Drug Administration
FFDCA
Federal Food, Drug and Cosmetic Act
FHSA
Federal Hazardous Substance Act
FIFRA
Federal Insecticide, Fungicide, and Rodenticide Act
g
Gram(s)
HAP
Hazardous Air Pollutant
HCFC
Hydrochlorofluorocarbons
HC1
Hydrochloric Acid
HFC
Hydrofluorocarbon
HFO
Hydrofluoroolefin
IDLH
Immediately Dangerous to Life and Health
IMAP
Inventory Multi-Tiered Assessment and Prioritisation
IRIS
Integrated Risk Information System
ISHA
Industrial Safety and Health Act
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km
Kilometer(s)
L
Liter(s)
lb
Pound
log Koc
Logarithmic Soil Organic Carbon:Water Partitioning Coefficient
log Kow
Logarithmic Octanol:Water Partition Coefficient
m3
Cubic Meter(s)
MACT
Maximum Achievable Control Technology
MCL
Maximum Contaminant Level
MCLG
Maximum Contaminant Level Goal
mg
Milligram(s)
mmHg
Millimeter(s) of Mercury
MP
Montreal Protocol
mPas
Millipascal(s)-Second
NAICS
North American Industrial Classification System
NATA
National Air Toxics Assessment
NATTS
National Air Toxics Trends Stations
NEI
National Emissions Inventory
NESHAP
National Emission Standards
NHANES
National Health and Nutrition Examination Survey
NIOSH
National Institute of Occupational Safety and Health
NPDWR
National Primary Drinking Water Regulations
NTP
National Toxicology Program
NWQMC
National Water Quality Monitoring Council
OCSPP
Office of Chemical Safety and Pollution Prevention
ODS
Ozone Depleting Substance
OECD
Organisation for Economic Co-operation and Development
OELs
Occupational Exposure Limits
ONU
Occupational Non-Users
OPPT
Office of Pollution Prevention and Toxics
OSHA
Occupational Safety and Health Administration
OW
Office of Water
PCE
Perchloroethylene
PEL
Permissible Exposure Level
PESS
Potentially Exposed or Susceptible Subpopulations
POD
Point of Departure
POTW
Publicly Owned Treatment Works
ppm
Part(s) per Million
PDM
Probabilistic Dilution Model
QC
Quality Control
REACH
Registration, Evaluation, Authorisation and Restriction of Chemicals
RCRA
Resource Conservation and Recovery Act
RIE
Reactive Ion Etching
SDS
Safety Data Sheet
SDWA
Safe Drinking Water Act
SIAP
Screening Information Dataset Initial Assessment Profile
SIDS
Screening Information Dataset
STEL
Short-term Exposure Limit
STORET
STORage and RETrieval
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SYR
Six-year Review
TCCR
Transparent, Clear, Consistent and Reasonable
TCLP
Toxicity Characteristic Leaching Procedure
TRI
Toxics Release Inventory
TSCA
Toxic Substances Control Act
TURA
Toxic Use Reduction Act
TWA
Time-Weighted Average
UATMP
Urban Air Toxics Monitoring Program
U.S.
United States
USGS
United States Geological Survey
VOC
Volatile Organic Compounds
WHO
World Health Organisation
WQP
Water Quality Portal
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EXECUTIVE SUMMARY
TSCA  6(b)(4) requires the U.S. Environmental Protection Agency (EPA) to establish a risk evaluation
process. In performing risk evaluations for existing chemicals, EPA is directed to "determine whether a
chemical substance presents an unreasonable risk of injury to health or the environment, without
consideration of costs or other non-risk factors, including an unreasonable risk to a potentially exposed
or susceptible subpopulation identified as relevant to the risk evaluation by the Administrator under the
conditions of use." In December of 2016, EPA published a list of 10 chemical substances that are the
subject of the Agency's initial chemical risk evaluations (	7), as required by TSCA 
6(b)(2)(A). Carbon tetrachloride was one of these chemicals.
TSCA  6(b)(4)(D) requires that EPA publish the scope of the risk evaluation to be conducted, including
the hazards, exposures, conditions of use and potentially exposed or susceptible subpopulations (PESS)
that the Administrator expects to consider. In June 2017, EPA published the Scope of the Risk
Evaluation for carbon tetrachloride. As explained in the scope document, because there was insufficient
time for EPA to provide an opportunity for comment on a draft of the scope, as EPA intends to do for
future scope documents, EPA is now publishing and taking public comment on a problem formulation
document to refine the current scope, as an additional interim step prior to publication of the draft risk
evaluation for carbon tetrachloride. Comments on this problem formulation document will inform the
development of the draft risk evaluation.
This problem formulation document refines the conditions of use, exposures and hazards presented in
the scope of the risk evaluation for carbon tetrachloride and presents refined conceptual models and
analysis plans that describe how EPA expects to evaluate the risk for carbon tetrachloride.
Carbon tetrachloride is a high production volume solvent. The Montreal Protocol and Title VI of the
Clean Air Act (CAA) Amendments of 1990 led to a phase-out of carbon tetrachloride production in the
United States for most non-feedstock domestic uses in 1996 and the Consumer Product Safety
Commission (CPSC) banned the use of carbon tetrachloride in consumer products (excluding
unavoidable residues not exceeding 10 ppm atmospheric concentration) in 1970. Currently, carbon
tetrachloride is used as a feedstock in the production of hydrochlorofluorocarbons (HCFCs),
hydrofluorocarbons (HFCs) and hydrofluoroolefins (HFOs). EPA has identified information on the
regulated use of carbon tetrachloride as a process agent in the manufacturing of petrochemicals-derived
and agricultural products and other chlorinated compounds such as chlorinated paraffins, chlorinated
rubber and others that may be used downstream in the formulation of solvents for degreasing and
cleaning, adhesives, sealants, paints, coatings, rubber, cement and asphalt formulations. The use of
carbon tetrachloride for non-feedstock uses (i.e., process agent, laboratory chemical) is regulated in
accordance with the Montreal Protocol.
Recent data on environmental releases from the Toxics Release Inventory (TRI), indicate that
approximately 153,000 pounds of carbon tetrachloride were released to the environment in 2015. Most
of the reported environmental releases for carbon tetrachloride were air emissions (fugitive and point
source air emissions).
This document presents the potential exposures that may result from the conditions of use of carbon
tetrachloride. Exposure may occur through inhalation and oral and dermal pathways, due to carbon
tetrachloride's widespread presence in a variety of environmental media such as air, drinking water,
groundwater, and surface water. Exposures to the general population may occur from industrial, and/or
commercial uses; industrial releases to air, water or land; and other conditions of use. Workers and
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occupational non-users (ONU) may be exposed to carbon tetrachloride during a variety of conditions of
use, such as manufacturing, processing and industrial and commercial uses, including manufacturing of
refrigerants and other chlorinated compounds. EPA expects that the highest exposures to carbon
tetrachloride generally involve workers in industrial and commercial settings. EPA considers workers
and ONU to be PESS. EPA will evaluate whether groups of individuals may be exposed via pathways
that are distinct due to unique characteristics (e.g., life stage, behaviors, activities, duration) that increase
exposure, and whether groups of individuals have heightened susceptibility, and should therefore be
considered PESS for purposes of the risk evaluation.
Carbon tetrachloride has been the subject of numerous health hazard reviews including EPA's Integrated
Risk Information System (IRIS) Toxicological Review and Agency for Toxic Substances and Disease
Registry's (ATSDR's) Toxicological Profile. EPA plans to evaluate all potential hazards for carbon
tetrachloride, including any found in recent literature. Human health hazards of carbon tetrachloride that
have been identified by EPA previously include liver toxicity, renal toxicity and cancer. Carbon
tetrachloride hazards to fish, aquatic invertebrates, aquatic plants, sediment invertebrates and
amphibians have previously been assessed by EPA or other organizations.
The revised conceptual models presented in this problem formulation identify conditions of use;
exposure pathways (e.g., media); exposure routes (e.g., inhalation, dermal, oral); PESS; and hazards
EPA expects to consider in the risk evaluation. The initial conceptual models provided in the scope
document were revised during problem formulation based on evaluation of reasonably available
information for physical and chemical properties, fate, exposures, hazards, and conditions of use, and
based upon consideration of other statutory and regulatory authorities. In each problem formulation
document for the first 10 chemical substances, EPA also refined the activities, hazards, and exposure
pathways that will be included in and excluded from the risk evaluation.
EPA's overall objectives in the risk evaluation process are to conduct timely, relevant, high-quality, and
scientifically credible risk evaluations within the statutory deadlines, and to evaluate the conditions of
use that raise greatest potential for risk. 82 FR 33726, 33728 (July 20, 2017).
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1 INTRODUCTION
This document presents for comment the problem formulation of the risk evaluation to be conducted for
carbon tetrachloride under the Frank R. Lautenberg Chemical Safety for the 21st Century Act. The
Frank R. Lautenberg Chemical Safety for the 21st Century Act amended the Toxic Substances Control
Act (TSCA), the Nation's primary chemicals management law, on June 22, 2016. The new law includes
statutory requirements and deadlines for actions related to conducting risk evaluations of existing
chemicals.
In December of 2016, EPA published a list of 10 chemical substances that are the subject of the
Agency's initial chemical risk evaluations (81 FR 91927), as required by TSCA  6(b)(2)(A). These 10
chemical substances were drawn from the 2014 update of EPA's TSCA Work Plan for Chemical
Assessments, a list of chemicals that EPA identified in 2012 and updated in 2014 (currently totaling 90
chemicals) for further assessment under TSCA. EPA's designation of the first 10 chemical substances
constituted the initiation of the risk evaluation process for each of these chemical substances, pursuant to
the requirements of TSCA  6(b)(4).
TSCA  6(b)(4)(D) requires that EPA publish the scope of the risk evaluation to be conducted, including
the hazards, exposures, conditions of use and PESS that the Administrator expects to consider, within 6
months after the initiation of a risk evaluation. The scope documents for all first 10 chemical substances
were issued on June 22, 2017. The first 10 problem formulation documents are a refinement of what was
presented in the first 10 scope documents. TSCA  6(b)(4)(D) does not distinguish between scoping and
problem formulation, and requires EPA to issue scope documents that include information about the
chemical substance, including the hazards, exposures, conditions of use, and the PESS that the
Administrator expects to consider in the risk evaluation. In the future, EPA expects scoping and problem
formulation to be completed prior to the issuance of scope documents and intends to issue scope
documents that include problem formulation.
As explained in the scope document, because there was insufficient time for EPA to provide an
opportunity for comment on a draft of the scope, as EPA intends to do for future scope documents, EPA
is publishing and taking public comment on a problem formulation document to refine the current scope,
as an additional interim step prior to publication of the draft risk evaluation for carbon tetrachloride.
Comments received on this problem formulation document will inform development of the draft risk
evaluation.
The Agency defines problem formulation as the analytical phase of the risk assessment in which "the
purpose for the assessment is articulated, the problem is defined, and a plan for analyzing and
characterizing risk is determined" (see Section 2.2 of the Framework for Human Health Risk
Assessment to Inform Decision Making). The outcomes of problem formulation are a conceptual
model(s) and an analysis plan. The conceptual model describes the linkages between stressors and
adverse human health effects, including the stressor(s), exposure pathway(s), exposed life stage(s) and
population(s), and endpoint(s) that will be addressed in the risk evaluation (I; ^ \ IP 2014). The
analysis plan follows the development of the conceptual model(s) and is intended to describe the
approach for conducting the risk evaluation, including its design, methods and key inputs and intended
outputs as described in the EPA Human Health Risk Assessment Framework (U.S. EPA. 2014). The
problem formulation documents refine the initial conceptual models and analysis plans that were
provided in the scope documents.
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First, EPA has removed from the risk evaluation any activities and exposure pathways that EPA has
concluded do not warrant inclusion in the risk evaluation. For example, for some activities that were
listed as "conditions of use" in the scope document, EPA has insufficient information following the
further investigations during problem formulation to find they are circumstances under which the
chemical is actually "intended, known, or reasonably foreseen to be manufactured, processed,
distributed in commerce, used, or disposed of."
Second, EPA also identified certain exposure pathways that are under the jurisdiction of regulatory
programs and associated analytical processes carried out under other EPA-administered environmental
statutes - namely, the Clean Air Act (CAA), the Safe Drinking Water Act (SDWA), the Clean Water
Act (CWA), and the Resource Conservation and Recovery Act (RCRA) - and which EPA does not
expect to include in the risk evaluation.
As a general matter, EPA believes that certain programs under other Federal environmental laws
adequately assess and effectively manage the risks for the covered exposure pathways. To use Agency
resources efficiently under the TSCA program, to avoid duplicating efforts taken pursuant to other
Agency programs, to maximize scientific and analytical efforts, and to meet the three-year statutory
deadline, 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, by excluding, on a case-by-case basis, certain exposure pathways that fall under the
jurisdiction of other EPA-administered statutes.1 EPA does not expect to include any such excluded
pathways as further explained below in the risk evaluation. The provisions of various EPA-administered
environmental statutes and their implementing regulations represent the judgment of Congress and the
Administrator, respectively, as to the degree of health and environmental risk reduction that is sufficient
under the various environmental statutes.
Third, EPA identified any conditions of use, hazards, or exposure pathways which were included in the
scope document and that EPA expects to include in the risk evaluation but which EPA does not expect
to further analyze in the risk evaluation. EPA expects to be able to reach conclusions about particular
conditions of use, hazards or exposure pathways without further analysis and therefore plans to conduct
no further analysis on those conditions of use, hazards or exposure pathways in order to focus the
Agency's resources on more extensive or quantitative analyses. Each risk evaluation will be "fit-for-
purpose," meaning not all conditions of use will warrant the same level of evaluation and the Agency
may be able to reach some conclusions without comprehensive or quantitative risk evaluations. 82 FR
33726, 33734, 33739 (July 20, 2017).
EPA received comments on the published scope document for carbon tetrachloride and has considered
the comments specific to carbon tetrachloride in this problem formulation document. EPA is soliciting
public comment on this problem formulation document and when the draft risk evaluation is issued the
Agency intends to respond to comments that are submitted. In its draft risk evaluation, EPA may revise
the conclusions and approaches contained in this problem formulations, including the conditions of use
and pathways covered and the conceptual models and analysis plans, based on comments received.
1 As explained in the final rule for chemical risk evaluation procedures, "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)]
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1.1	Regulatory History
EPA conducted a search of existing domestic and international laws, regulations and assessments
pertaining to carbon tetrachloride. EPA compiled this summary from data available from federal, state,
international and other government sources, as cited in Appendix A. 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, further analysis might be necessary as part of the
risk evaluation. Consideration of the nexus between these existing regulations and TSCA conditions of
use may additionally be made as detailed/specific conditions of use and exposure scenarios are
developed in conducting the analysis phase of the risk evaluation.
Federal Laws and Regulations
Carbon tetrachloride is subject to federal statutes or regulations, other than TSCA, that are implemented
by other offices within EPA and/or other federal agencies/departments. A summary of federal laws,
regulations and implementing authorities is provided in Appendix A.
State Laws and Regulations
Carbon tetrachloride is subject to state statutes or regulations implemented by state agencies or
departments. A summary of state laws, regulations and implementing authorities is provided in
Appendix A.
Laws and Regulations in Other Countries and International Treaties or Agreements
Carbon tetrachloride is subject to statutes or regulations in countries other than the United States and/or
international treaties and/or agreements. A summary of these laws, regulations, treaties and/or
agreements is provided in Appendix A.
1.2	Assessment History
EPA has identified assessments conducted by other EPA Programs and other organizations (see Table
1-1). Depending on the source, these assessments may include information on conditions of use,
hazards, exposures and PESS. Table 1-1 shows the assessments that have been conducted. EPA found an
additional assessment for carbon tetrachloride by the National Industrial Chemicals Notification and
Assessment Scheme (Australia) during the problem formulation and the assessment history table has
been updated accordingly.
In addition to using this information, EPA intends to conduct a full review of the relevant
data/information collected in the initial comprehensive search (see Carbon tetrachloride (CASRN 56-23-
5) Bibliography: Supplemental File for the TSCA Scope Document, EPA-HQ-OI 1.6-0733)
following the literature search and screening strategies documented in the Strategy for Conducting
Literature Searches for Carbon Tetrachloride: Supplemental File for the TSCA Scope Document, J
HQ-QPPT-2016-0733. This will ensure that EPA considers data/information that has been made
available since these assessments were conducted.
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Table 1-1. Assessment History of Carbon Tetrachloride
Authoring Organization
Assessment
EPA assessments
U.S. EPA, Office of Water (OW)
Update of Human Health Ambient Water Oualitv
Criteria: Carbon Tetrachloride 56-23-5. EPA-HQ-
UW-2014-0135-0182 (_Oi h)
U.S. EPA, Integrated Risk Information System
(IRIS)
lexicological Review of Carbon Tetrachloride In
Support of Summary Information on IRIS (2010)
U.S. EPA, Office of Drinking Water
Carbon Tetrachloride Health. Advisory. Office of
Drinking Water US Environmental Protection
icy (1987)
Other U.S.-based organizations
Agency for Toxic Substances and Disease Registry
(AT SDR)
Toxicologic lie for Carbon Tetrachloride
(2.005)
California Environment Protection Agency, Office
of Environmental Health Hazard Assessment
Public Health Goal for Carbon Tetrachloride
(2000)
International
Health Canada
Guidelines for Canadian Drinking Water Oualitv.
Guideline Technical Document Carbon
Tetrachloride (2010)
Organisation for Economic Co-operation and
Development's Screening Information Dataset
(OECD SIDS), Co-CAM, 10-12
SIDS SIAP for Carbon Tetrachloride (2011)

World Health Organisation (WHO)
Carbon Tetrachloride in Drinking Water.
Background document for development of WHO
Guidelines for Drinking -water Oualitv (2004)
National Industrial Chemicals Notification and
Assessment Scheme (Australia)
Environment Ti ssessment for Methane.
Tetrachloro- (2017. last update)
1.3 Data and Information Collection
EPA/OPPT generally applies a systematic review process and workflow that includes: (1) data
collection; (2) data evaluation; and (3) data integration of the scientific data used in risk evaluations
developed under TSCA. Scientific analysis is often iterative in nature as new knowledge is obtained.
Hence, EPA/OPPT expects that multiple refinements regarding data collection may occur during the
process of risk evaluation.
Data Collection: Data Search
EPA/OPPT conducted chemical-specific searches for data and information on: physical and chemical
properties; environmental fate and transport; conditions of use information; environmental exposures,
human exposures, including potentially exposed or susceptible subpopulations (PESS) identified by
virtue of greater exposure; ecological hazard; and human health hazard, including PESS identified by
virtue of greater susceptibility.
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EPA/OPPT designed its initial data search to be broad enough to capture a comprehensive set of sources
containing data and/or information potentially relevant to the risk evaluation. Generally, the search was
not limited by date and was conducted on a wide range of data sources, including but not limited to:
peer-reviewed literature and gray literature (e.g., publicly-available industry reports, trade association
resources, government reports). When available, EPA/OPPT relied on the search strategies from recent
assessments, such as EPA IRIS assessments and the National Toxicology Program's (NTP) Report on
Carcinogens, to identify relevant references and supplemented these searches to identify relevant
information published after the end date of the previous search to capture more recent literature. The
Strategy for Conducting Literature Searches for Carbon Tetrachloride: Supplemental File for the TSCA
Scope Document, EPA-HQ-OPPT-2Q16-0733 provides details about the data sources and search terms
that were used in the initial search.
Data Collection: Data Screening
Following the data search, references were screened and categorized using selection criteria outlined in
the Strategy for Conducting Literature Searches for Carbon Tetrachloride: Supplemental File for the
TSCA Scope Document, ll'.l V'> -I. iQ-OPPT-2016-0733. Titles and abstracts were screened against the
criteria as a first step with the goal of identifying a smaller subset of the relevant data to move into the
subsequent data extraction and data evaluation steps. Prior to full-text review, EPA/OPPT anticipates
refinements to the search and screening strategies, as informed by an evaluation of the performance of
the initial title/abstract screening and categorization process.
The categorization scheme (or tagging structure) used for data screening varies by scientific discipline
(i.e., physical and chemical properties; environmental fate and transport; use/conditions of use
information; human and environmental exposures, including PESS identified by virtue of greater
exposure; human health hazard, including PESS identified by virtue of greater susceptibility; and
ecological hazard). However, within each data set, there are two broad categories or data tags: (1) on-
topic references or (2) off-topic references. On-topic references are those that may contain data and/or
information relevant to the risk evaluation. Off-topic references are those that do not appear to contain
data or information relevant to the risk evaluation. The Strategy for Conducting Literature Searches for
Carbon Tetrachloride: Supplemental File for the TSCA Scope Document, EPA-HQ-QPPT-2016	0733
discusses the inclusion and exclusion criteria that EPA/OPPT used to categorize references as on-topic
or off-topic.
Additional data screening using sub-categories (or sub-tags) was also performed to facilitate further
sorting of data/information - for example, identifying references by source type (e.g., published peer-
reviewed journal article, government report); data type (e.g., primary data, review article); human health
hazard (e.g., liver toxicity, cancer, reproductive toxicity); or chemical-specific and use-specific data or
information. These sub-categories are described in the supplemental document, Strategy for Conducting
Literature Searches for Carbon Tetrachloride: Supplemental File for the TSCA Scope Document, l;.lP-'\-
H.Q~()PPT~2016-0733 and will be used to organize the different streams of data during the stages of data
evaluation and data integration steps of systematic review.
Results of the initial search and categorization can be found in the Carbon tetrachloride (CASRN 56-23-
5) Bibliography: Supplemental File for the TSCA Scope Document, EPA-HQ-OI 16-0733. This
document provides a comprehensive list (bibliography) of the sources of data identified by the initial
search and the initial categorization for on-topic and off-topic references. Because systematic review is
an iterative process, EPA/OPPT expects that some references may move from the on-topic to the off-
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topic categories, and vice versa. Moreover, targeted supplemental searches may also be conducted to
address specific needs for the analysis phase (e.g., to locate specific data needed for modeling); hence,
additional on-topic references not initially identified in the initial search may be identified as the
systematic review process proceeds.
1.4 Data Screening During Problem Formulation
EPA/OPPT is in the process of completing the full text screening of the on-topic references identified in
the Carbon tetrachloride (CASRN 56-23-5) Bibliography: Supplemental File for the TSCA Scope
Document, EP A-HQ-QPPT-2016-0733. Details about the screening process at the full-text level are
provided in the Application of Systematic Review in TSCA Risk Evaluations document (U.S. EPA.
2018). Appendix H provides the inclusion and exclusion criteria applied at the full text screening. Since
full text screening commenced right after the publication of the TSCA Scope document, the criteria were
set to be broad to capture relevant information that would support the risk evaluation. Thus, the
inclusion and exclusion criteria for full text screening do not reflect the refinements to the conceptual
model and analysis plan resulting from problem formulation. As part of the iterative process, EPA is in
the process of refining the results of the full text screening to incorporate the changes in
information/data needs to support the risk evaluation.
These refinements include changes to the inclusion and exclusion criteria to better support the risk
evaluation and will likely reduce the number of data/information sources that will undergo evaluation.
Following the screening process, the quality of the included studies will be assessed using the evaluation
strategies that are described in the Application of Systematic Review in TSCA Risk Evaluations (U.S.
) EPA/OPPT is in the process of completing the full text screening of the on-topic references
identified in the Carbon tetrachloride (CASRN 56-23-5) Bibliography: Supplemental File for the TSCA
Scope Document, EP A-HQ-OPPT-2016-0733. Details about the screening process and criteria at the
full-text level are provided in the Application of Systematic Review in TSCA Risk Evaluations (U.S.
). Following the screening process, the quality of the included studies will be assessed using
the evaluation strategies that are described in the supplemental document on systematic review.
A review of the on topic human health references after the title and abstract screening revealed a large
number of animal studies that were likely to be of limited use for the following reasons: (1) The aim of
the study was to induce a disease state in an animal (e.g., cirrhosis, fibrosis, organ damage: liver, kidney,
testes and others) rather than evaluate the effects of carbon tetrachloride exposure in animals and/or (2)
Exposure was via injection. In order to refine the search results for full-text screening, the
inclusion/exclusion criteria were revised to remove these studies from the "on topic" pool. Appendix B
describes the process used to re-screen the references identified as "on topic" in the first screening
round, including prioritizing the literature for screening and the re-categorization criteria applied during
the re-screening and tagging.
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2 PROBLEM FORMULATION
As required by TSCA, the scope of the risk evaluation identifies the conditions of use, hazards,
exposures and PESS that the Administrator expects to consider. To communicate and visually convey
the relationships between these components, EPA included in the scope document an initial life cycle
diagram and initial conceptual models that describe the actual or potential relationships between carbon
tetrachloride and human and ecological receptors. During the problem formulation, EPA has revised the
life cycle diagram and conceptual models based on further data gathering and analysis as presented in
this problem formulation document. A revised analysis plan is also included, which identifies, to the
extent feasible, the approaches and methods that EPA may use to assess exposures, effects (hazards) and
risks under the conditions of use of carbon tetrachloride.
2.1 Physical and Chemical Properties
Physical-chemical properties influence the environmental behavior and the toxic properties of a
chemical, thereby informing the potential conditions of use, exposure pathways and routes and hazards
that EPA intends to consider. For scope development, EPA considered the measured or estimated
physical-chemical properties set forth in Table 2-1; EPA found no additional information during
problem formulation that would change these values.
Table 2-1. Physical and Chemical Properties of Carbon Tetrachloride
Properly
Value"
References
Molecular formula
ecu

Molecular weight
153.82

Physical form
Colorless liquid, sweet, aromatic and ethereal
odor resembling chloroform
(Merck. 1996}; (U.S.
Coast Guard. 1985)
Melting point
-23C
(Tide. 1999)
Boiling point
76.8C
(Tide. 1999)
Density
1.46 g/cm3 at 20C
CBoublik et al. 1984)
Vapor pressure
115 mm Hg at 25C
ftide. 1999)
Vapor density
5.32 (relative to air)
CBoublik et al. 1984)
Water solubility
793 mg/L at 25C
fflorvath. 1982)
Octanol:water partition
coefficient (log Kow)
2.83b
(Hansch et al. 1995)
Henry's Law constant
0.0276 atm m3/mole
CLeighton and Calo.
1981)
Flash point
None
(US. Coast Guard. 1985)
Autoflammability
Not readily available

Viscosity
2.03 mPas at -23C
CDaubert and Danner.
1989)
Refractive index
1.4607 at 20C
(Merck. 1996)
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Property
Value"
References
Diaelectric constant
2.24 at 20C
(Norbert and Dean. 196 )
a Measured unless otherwise noted. b Estimated value based on modeling
2.2 Conditions of Use
TSCA  3(4) defines the conditions of use as "the circumstances, as determined by the Administrator,
under which a chemical substance is intended, known, or reasonably foreseen to be manufactured,
processed, distributed in commerce, used, or disposed of."
2.2.1	Data and Information Sources
In the scope documents, EPA identified, based on reasonably available information, the conditions of
use for the subject chemicals. As further described in the document, EPA searched a number of available
data sources (e.g., Use and Market Profile for Carbon Tetrachloride, I P >-1 l'','-v)PPT-2016-0733).
Based on this search, EPA published a preliminary list of information and sources related to chemical
conditions of use (see Preliminary Information on Manufacturing, Processing, Distribution, Use, and
Disposal: Carbon Tetrachloride, . Q-OPPT-2016-0733-0003) prior to a February 2017 public
meeting on scoping efforts for risk evaluations convened to solicit comment and input from the public.
EPA also convened meetings with companies, industry groups, chemical users and other stakeholders to
aid in identifying conditions of use and verifying conditions of use identified by EPA. The information
and input received from the public and stakeholder meetings and public comments has been
incorporated into this problem formulation document to the extent appropriate, as indicated in Table 2-3.
Thus, EPA believes the identified manufacture, processing, distribution, use and disposal activities
constitute the intended, known, and reasonably foreseeable activities associated with the subject
chemical, based on reasonably available information.
2.2.2	Identification of Conditions of Use
To determine the current conditions of use of carbon tetrachloride and inversely, activities that do not
qualify as conditions of use, EPA conducted extensive research and outreach. This included EPA's
review of published literature and online databases including the most recent data available from EPA's
Chemical Data Reporting program (CDR) and Safety Data Sheets (SDSs). EPA also reviewed Montreal
Protocol's (MP) directives and related reports (WCRP. 2016) with information on domestic and
international regulation and monitoring of carbon tetrachloride use and emissions. EPA also received
comments on the Scope of the Risk Evaluation for carbon tetrachloride (U.S. EPA. ^ ) that were
used to determine the conditions of use. In addition, EPA convened meetings with companies, industry
groups, chemical users, states, environmental groups, and other stakeholders to aid in identifying
conditions of use and verifying conditions of use identified by EPA.
EPA has removed from the risk evaluation any activities that EPA has concluded do not constitute
conditions of use - for example, because EPA has insufficient information to find certain activities are
circumstances under which the chemical is actually "intended, known, or reasonably foreseen to be
manufactured processed, distributed in commerce, used, or disposed of." EPA has also identified any
conditions of use that EPA does not expect to include in the risk evaluation. As explained in the final
rule for Procedures for Chemical Risk Evaluation Under the Amended Toxic Substances Control Act,
TSCA section 6(b)(4)(D) requires EPA to identify "the hazards, exposures, conditions of use, and the
PESS that the Administrator expects to consider in a risk evaluation," suggesting that EPA may exclude
certain activities that EPA has determined to be conditions of use on a case-by-case basis. (82 FR 33736,
33729; July 20, 2017). For example, EPA may exclude conditions of use that the Agency has sufficient
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basis to conclude would present only de minimis exposures or otherwise insignificant risks (such as use
in a closed system that effectively precludes exposure or use as an intermediate).
The activities that EPA no longer believes are conditions of use or that were otherwise excluded during
problem formulation are described in Section 2.2.2.1. The conditions of use included in the scope of the
risk evaluation are summarized in Section 2.2.2.2.
2.2.2.1 Categories and Subcategories Determined Not to be Conditions of Use or
Otherwise Excluded During Problem Formulation
For carbon tetrachloride, EPA has conducted public outreach and literature searches to collect
information about carbon tetrachloride's conditions of use and has reviewed reasonably available
information obtained or possessed by EPA concerning activities associated with carbon tetrachloride. As
a result of that analysis, EPA has identified activities not currently associated with carbon tetrachloride
and therefore determined not to be conditions of use. In addition, there are conditions of use for which
EPA has sufficient basis to conclude would present only de minimis exposures or otherwise insignificant
risks and that do not warrant further evaluation. Consequently, EPA will not consider or evaluate these
activities and conditions of use or associated hazards or exposures in the risk evaluation for carbon
tetrachloride. These activities and conditions of use consist of incorporation of carbon tetrachloride into
an article (activity that is not a condition of use), and industrial/commercial/consumer uses of carbon
tetrachloride in commercially available aerosol and non-aerosol adhesives/sealants, paints/coatings, and
cleaning/degreasing solvent products (conditions of use with de minimis exposure).
Domestic production and importation of carbon tetrachloride is currently prohibited under regulations
implementing the Montreal Protocol (MP) and CAA Title VI, except when transformed (used and
entirely consumed, except for trace quantities, in the manufacture of other chemicals for commercial
purposes), destroyed (including destruction after use as a catalyst or stabilizer), or used for essential
laboratory and analytical uses. See 40 CFR Part 82; see also 60 FR 24970, 24971 (May 10, 1995). Based
on information obtained by EPA, there are no approved consumer uses for carbon tetrachloride. There
are current regulatory actions that prohibit the direct use of carbon tetrachloride as reactant or additive in
the formulation of commercially available products for industrial/commercial/consumer uses (including
aerosol and non-aerosol adhesives/sealants, paints/coatings, and cleaning/degreasing solvent products),
besides as a laboratory chemical. The use of carbon tetrachloride (and mixtures containing it) in
household products has also been banned by CPSC since 1970, with the exception of "unavoidable
manufacturing residues of carbon tetrachloride in other chemicals that under reasonably foreseen
conditions of use do not result in an atmospheric concentration of carbon tetrachloride greater than 10
parts per million." 16 CFR 1500.17(a)(2).
The domestic and international use of carbon tetrachloride as a process agent is addressed under the
Montreal Protocol (MP) side agreement, Decision X/14: Process Agents (UNEP/Ozone Secretariat.
1998). This decision lists a limited number of specific manufacturing uses of carbon tetrachloride as a
process agent (non-feedstock use) in which carbon tetrachloride may not be destroyed in the production
process. Based on the process agent applications, carbon tetrachloride is used in the manufacturing of
other chlorinated compounds that may be subsequently added to commercially available products (i.e.,
solvents for cleaning/degreasing, adhesives/sealants, and paints/coatings). Given the high volatility of
carbon tetrachloride and the extent of reaction and efficacy of the separation/purification process for
purifying final products, EPA expects insignificant or unmeasurable concentrations of carbon
tetrachloride in the manufactured chlorinated substances in the commercially available products. In its
regulations on the protection of stratospheric ozone at 40 CFR part 82, EPA excludes from the definition
of controlled substance the inadvertent or coincidental creation of insignificant quantities of a listed
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substance (including carbon tetrachloride) resulting from the substance's use as a process agent (40 CFR
82.3). These expectations and current regulations are consistent with public comments received by EPA,
EPA-HO-OPPT-2016-0733-0005 and EPA-HO-OP	733-0017. stating that carbon
tetrachloride may be present in a limited number of industrial products with chlorinated ingredients at a
concentration of less than 0.003% by weight.
Based on the information identified by EPA, carbon tetrachloride is not a direct reactant or additive in
the formulation of solvents for cleaning and degreasing, adhesives and sealants or paints and coatings.
Because industrial, commercial, and consumer use of such products (solvents for cleaning/degreasing,
adhesives/sealants, and paints/coatings) would present only de minimis exposure or otherwise
insignificant risk, EPA has determined that these conditions of use do not warrant evaluation, and EPA
does not expect to consider or evaluate these conditions of use or associated hazards or exposures in the
risk evaluation for carbon tetrachloride. Based on information obtained by EPA and the household
products ban at 16 CFR 1500.17(a)(2), there are no other approved consumer uses for carbon
tetrachloride. Therefore, as a general matter, EPA does not expect to analyze consumer exposures or
associated hazards in the risk evaluation for carbon tetrachloride, and accordingly the initial conceptual
model for consumer activities and uses presented in the Scope of the Risk Evaluation for Carbon
Tetrachloride (U.S. EPA. ^ ) does not appear in this problem formulation document.
In addition, EPA has determined that there is insufficient information to support the classification of one
activity which was identified as a "condition of use" in the Scope document. TSCA defines a chemical's
"conditions of use" as "the circumstances, as determined by the Administrator, under which a chemical
substance is intended, known, or reasonably foreseen to be manufactured, processed, distributed in
commerce, used, or disposed of." 15 USC 2602(4). As explained in the final rule for Procedures for
Chemical Risk Evaluation under the Amended Toxic Substances Control Act, TSCA grants EPA
discretion to determine the circumstances that are appropriately considered to be "conditions of use." 82
FR at 33729. As noted above, EPA has conducted public outreach and literature searches to collect
information about carbon tetrachloride's conditions of use and has reviewed reasonably available
information obtained or possessed by EPA concerning activities associated with carbon tetrachloride. As
a result of that analysis, EPA has determined there is insufficient information to support a finding that
one activity which was listed as a condition of use in the Scope document for carbon tetrachloride
actually constitutes a circumstance under which carbon tetrachloride "is intended, known, or reasonably
foreseen to be manufactured, processed, distributed in commerce, used, or disposed of." This activity
consists of incorporation into articles. Incorporation into an article refers to processing in which the
chemical becomes an integral component of an article (as defined at 40 CFR 704.3) that is distributed
for industrial, trade or consumer use. EPA has not identified information during problem formulation
indicating that carbon tetrachloride is incorporated into articles (see EP A-HO-OPPT-2016-0733-0003).
Consequently, EPA will not consider or evaluate incorporation into articles, or any associated hazards or
exposures, in the risk evaluation for carbon tetrachloride.
Table 2-2. Categories and Subcategories Determined Not to be Conditions of Use or Otherwise
Excluded During Problem Formulation	
l.il'e (vcle Stage
Cal ego rv 11
Subcategory h
References
Processing
Processing-
Incorporation
into Article
Incorporation
into Article
OJ.S. EPA. 2016b)
* not confirmed as a current use
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Life ( vole Slsio
CsiU'gorv 11
Siihcsilcgorv h
UcforoiKTs
Industrial commercial
consumer use
Sol \ cuts lor
Cleaning and
Degreasing
Machinery
cleaning
I sc document.
Public comment. EPAHO-OPPT-
0" >100II
* de minimis exposure.
Textile cleaning
Use document,
H01ittt)s://www. regulations. gov/document?D=EPA-
HO-OPPT-2016-073 3-0(.
0003
* de minimis exposure
Brake cleaning
Use document,
HOhttDs://www. regulations. gov/document?D=EPA-
HO-OPPT-2016-073 3-0(
0003
* de minimis exposure
Adhesives
and Sealants
Rubber cement
Use document,
H01ittos://www. regulations. gov/document?D=EPA-
HO-OPPT-2016-0733-0003OPP
0003
* de minimis exposure
Arts and crafts
Use document. EPA-HO-OPPT-: '33-0003;
Public comment. EPAHO-OP!
0
* de minimis exposure
Asphalt
Use document,
H01ittos://www. regulations. gov/document?D=EPA-
HO-OPPT-2016-073 3-0(
0003
* de minimis exposure
Industrial
adhesives
Use document. EPA-HO-OPPT-2016-073 3-0003:
Public comments. EPA-
HO-OPPT-2016-073 3-
0011. EPA-HO-OPPT2016-0733 -0012. and
EPA-HO-OPPT-20160733-0015
* de minimis exposure
Paints and
Coatings
Paints and
coatings
Use document,
H01ittt)s://www. regulations. gov/document?D=EPA-
HO-OPPT-2016-0733-0003OPPT-2
0003
* de minimis exposure
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2.2.2.2 Categories and Subcategories of Conditions of Use Included in the Scope of
the Risk Evaluation
Table 2-3 summarizes each life cycle stage and the corresponding categories and subcategories of
conditions of use for carbon tetrachloride that EPA expects to consider in the risk evaluation. Using the
2.016 CDR. EPA identified industrial processing or use activities, industrial function categories and
commercial and consumer use product categories. EPA identified the subcategories by supplementing
CDR data with other published literature and information obtained through stakeholder consultations.
For risk evaluations, EPA intends to consider each life cycle stage (and corresponding use categories
and subcategories) and assess relevant potential sources of release and human exposure associated with
that life cycle stage. Beyond the uses identified in the Scope of the Risk Evaluation for carbon
tetrachloride (	), EPA has received no additional information identifying additional
current conditions of use for carbon tetrachloride from public comment and stakeholder meetings.
Table 2-3. Categories and Subcategories of Conditions of Use Included in the Scope of the Risk
Evaluation
l.il'e Cycle Stage
Category 11
Subcategory h
References
Manufacture
Domestic
Manufacture
Domestic manufacture
(U.S. EPA. 2016b")

Import
Import
(U.S. EPA 2016b")
Processing
Processing as a
Reactant/
Intermediate
Hydrochlorofluorocarbons
(HCFCs), Hydrofluorocarbon
(HFCs) and
Hydrofluoroolefin (HFOs)
Use document,
HG-<
0003; Public comments,
EP A-H0-GPPT-2016-


 , H \ H<2-
OPPI-2016-0733-0008.



EPA-HO-OPPT-2016-
0733-0016 and EPA-
HO-OPPT-;
0064; OJ.S. EPA.
2016b)


Perchloroethylene (PCE)
Use document,
HO-OPPT-;
0003; Public comments.
EPA-HO-OPPT-2016-
0733-0007 and EPA-
HO-OPPT-;
0008.(
2016b)


Reactive ion etching (i.e.,
semiconductor
Use document,
HO-OPPT-;


manufacturing)
0003; Public comment.
EPA-HO-OPPT-2016-
0733-0063
Page 23 of 112

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l.il'o Cycle S(;ic
Category "
Subcategory h
References

Incorporation into
Formulation,
Mixture or Reaction
Products
Petrochemicals-derived
manufacturing; Agricultural
products manufacturing;
Other basic organic and
inorganic chemical
manufacturing.
OJ.S. EPA. 2016b"); Use
document, EPA-HQ-
OPPT-2016-0733-0003;
( );
dJNEP/Ozone
Secretari 8");
Public comment. EPA-
HO-OPPT-2016-073 3-
0064

Processing -
repackaging
Laboratory Chemicals
ru.s. EPA. 2016a")

Recycling
Recycling
(U.S. EPA. 2016b").
rU.S. EPA. 2016a")
Distribution in
commerce
Distribution
Distribution in commerce
riJ.S. EPA. 2016a"); Use
document, EPA-HQ-
OPPT-2016-073 3-0003.
Industrial/commercial
use
Petrochemicals-
derived Products
Manufacturing
Processing aid
Use document,
HO-<
0003;(
2016b"); OJNEP/Ozone
Secretarial


Additive
Use document,
HO-OPPT-;
0003; Public comment,
EP A-HO-OPPT-2016-
0733-0012; OJ.S. EPA.
2.016a"); rUNEP/Ozone
Secretari 8)

Agricultural
Products
Manufacturing
Processing aid
(U.S. EPA. 2016b"). Use
document, EPA-HO-
OPPT-2016-073 3-0003;


Public comments, PP \-
HO-OPPT-2016-073 3-
0007 and EPA-HO-
OPPT-2016-073 3-0008;



rUNEP/Ozone
Secretari 8)
Page 24 of 112

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l.il'o Cycle S(;ic
Category "
Subcategory h
References

Other Basic Organic
and Inorganic
Chemical
Manufacturing
Manufacturing of chlorinated
compounds used in solvents
for cleaning and degreasing
Use document, EPA-
HO-OPPT-;
0003; Public comments,
EP A-HO-OPPT-2016-
'.-001 1. I PA 410-
OPPI-2016-0733 -0012
and EPA-HO-OPPT-
2,m o * oot ,
( Ozone
Secretar 8)
Manufacturing of chlorinated
compounds used in adhesives
and sealants
Use document,
HO-OPPT-:
0003; Public comments,
EP A-HO-OPPT-2016-
073 3-001LEP A-HO-
OPPT-2016-073 3 -0024.
EPA-HO-OPPT-2016-
0733-0012. andEPA-
HO-OPPT-:
. ( )zone
Secretar 8)
Manufacturing of chlorinated
compounds used in paints
and coatings
Use document,
HO-OPPT-:
0003 Public comment,
EP A-HO-OPPT-2016-
0733-0024;
( Ozone
Secretar 8)
Manufacturing of inorganic
chlorinated compounds (i.e.,
elimination of nitrogen
trichloride in the production
of chlorine and caustic)
Public comment, EPA-
HO-OPPT-2016-073 3-
0027; rUNEP/Ozone
Secretar 8)

Manufacturing of chlorinated
compounds used in asphalt
Use document, I 'P \-
HO-OPPT-2016-073 3-
0003.( )zone
Secretar 8)
Manufacturing of
Pharmaceuticals
OJNEP/Ozone
Secretar 8)
Other Uses
Processing aid (i.e., metal
recovery).
Use document,
HO-OPPT-;
0003
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l.il'e Cycle Stage
Category "
Subcategory h
References


Specialty uses (i.e.,
aerospace industry)
Public comment, EPA-
HO-OPPT-2016-0733 -
0063
Laboratory
Chemicals
Laboratory chemical
Use document,
HO-OPPT-2016-073 3-
0003,(
2016M. Public
comments, EPA-HO-
OPPT-2016-073 3-0007;
EPA-HO-OPPT-2016-
0733-0013 andEPA-
HO-OPPT-;
0063
Disposal
Disposal
Industrial pre-treatment
i s nn am a
Industrial wastewater
treatment
i s f r\ mi a
Publicly owned treatment
works (POTW)
^ r w \ 201 <:

Underground injection
10
17d
Municipal landfill
10

Hazardous landfill
10

Other land disposal
:o

Municipal waste incinerator
:o

Hazardous waste incinerator
:o

Off-site waste transfer
:o

11 These categories of conditions of use appear in the Life Cycle Diagram, reflect CDR codes and broadly represent
conditions of use of carbon tetrachloride in industrial and/or commercial settings.
b These subcategories reflect more specific uses of carbon tetrachloride.
2.2.2.3 Overview of Conditions of Use and Lifecycle Diagram
The life cycle diagram provided in Figure 2-1 depicts the conditions of use that are considered within
the scope of the risk evaluation during various life cycle stages including manufacturing, processing, use
(industrial, commercial), distribution and disposal. Additions or changes to conditions of use based on
additional information gathered or analyzed during problem formulation were described in Sections
2.2.2.1 and 2.2.2.2. The activities that EPA determined are out of scope during problem formulation are
not included in the life cycle diagram. The information is grouped according to CDR processing codes
and use categories (including functional use codes for industrial uses and product categories for
industrial, commercial and consumer uses), in combination with other data sources (e.g., published
literature and consultation with stakeholders), to provide an overview of conditions of use. EPA notes
that some subcategories of use may be grouped under multiple CDR categories.
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Use categories include the following: "industrial use" means use at a site at which one or more
chemicals or mixtures are manufactured (including imported) or processed. "Commercial use" means
the use of a chemical or a mixture containing a chemical (including as part of an article) in a commercial
enterprise providing saleable goods or services (U.S. EPA. ) This information has not changed
from that provided in the Scope Document.
To understand conditions of use relative to one another and associated potential exposures under those
conditions of use, the life cycle diagram includes the production volume associated with each stage of
the life cycle, as reported in the 2016 CDR (I _S JJIli	2016b). when the volume was not
claimed confidential business information (CBI). The 2016 CDR reporting data for carbon tetrachloride
are provided in Table 2-4 for carbon tetrachloride from EPA's CDR database (	).
Table 2-4. Production Volume of Carbon Tetrachloride in Chemical Data Reporting (CDR)
Reporting Period (2012 to 2015) a	
Reporting Year
2012
2013
2014
2015
Total Aggregate
Production Volume (lbs)
129,145,698
116,658,281
138,951,153
142,582,067
a (TJ.S. EPA. 2017c). Internal communication. The CDR data for the 2016 rcDortinu period is available via ChemView
(httDs://iava.eDa.uov/chemview) (U.S. EPA. 2016b). Because of anoneoine CBI substantiation process reauired bv
amended TSCA, the CDR data available in the problem formulation is more specific than currently in ChemView.
Due to CBI claims in the 2016 CDR, EPA cannot provide the volumes associated with most life cycle
stages (	1016b). Activities related to distribution (e.g., loading, unloading) will be considered
throughout the carbon tetrachloride life cycle, rather than using a single distribution scenario.
Descriptions of the industrial or commercial use categories identified from the 2016 CDR are
summarized below and included in the life cycle diagram (Figure 2-1). The descriptions provide a brief
overview of the use category and Appendix C contains more detailed descriptions (e.g., process
descriptions, worker activities, process flow diagrams, equipment illustrations) for each manufacture,
processing, use and disposal category. The descriptions provided below are primarily based on the
corresponding industrial function category and/or commercial product category descriptions from the
2016 CDR and can be found in EPA's Instructions for Reporting 2016 TSCA Chemical Data Reporting
(	2016a).
The "Petrochemicals-derived and Agricultural Products Manufacturing" category encompasses
chemical substances used for a variety of purposes at petrochemicals-derived and agricultural products
manufacturing sites. This category includes the use of carbon tetrachloride as a process agent (i.e.,
processing aid for catalyst regeneration) in uses listed in the MP side agreement, Decision X/14: Process
Agents, including manufacture of chlorosulphonated polyolefin, manufacture of styrene butadiene
rubber, manufacture of endosulphan (insecticide), production of tralomethrine (insecticide), manufacture
of 1-1, Bis (4-chlorophenyl) 2,2,2- trichloroethanol (dicofol insecticide) (see Appendix D).
The "Other Basic Organic and Inorganic Chemical Manufacturing" category encompasses chemical
substances used to facilitate the manufacturing or production of a particular chemical. Process agents are
not feedstocks, and may not be destroyed in a production process. Use of carbon tetrachloride as a
process agent is specifically listed under the MP side agreement, Decision X/14: Process Agents. This
category includes the use of carbon tetrachloride in the manufacturing of pharmaceuticals (i.e.,
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ibuprofen) and the manufacturing of chlorinated compounds that are subsequently used in the
formulation of solvents for cleaning and degreasing, adhesives and sealants and paints and coatings. The
process agent applications of carbon tetrachloride as a process agent include manufacturing of
chlorinated paraffins (e.g., plasticizer in rubber, paints, adhesives, sealants, plastics) and chlorinated
rubber (e.g., additive in paints, adhesives). The category also includes the use of carbon tetrachloride in
the manufacturing of inorganic chlorinated compounds, such as the use of carbon tetrachloride in the
production of chlorine and caustic.
Figure 2-1 depicts the life cycle diagram of carbon tetrachloride from manufacture to the point of
disposal. Activities related to distribution (e.g., loading, unloading) will be considered throughout the
life cycle, rather than using a single distribution scenario.
As reflected in the life cycle diagram, intended, known and reasonably foreseen uses of carbon
tetrachloride are primarily associated with industrial and commercial activities. As explained above, the
Montreal Protocol and Title VI of the Clean Air Act (CAA) Amendments of 1990 led to a phase-out of
carbon tetrachloride production in the United States for most non-feedstock domestic uses in 1996 and
the CPSC banned the use of carbon tetrachloride in consumer products (excluding unavoidable residues
not exceeding 10 ppm atmospheric concentration) in 1970.
EPA has identified use as a feedstock (Processing as Reactant/Intermediate) as the main use for carbon
tetrachloride. However, there are other industrial/commercial uses that may still exist including: solvent
for laboratory procedures (i.e., extraction solvent), and process agent in the manufacturing of
petrochemicals-derived and agricultural products, and in the manufacturing of chlorinated compounds to
be used in the formulation of solvents for degreasing and cleaning, in adhesives, sealants, paints,
coatings, rubber cement and asphalt formulations rEPA-HQ-OPPT-2016-0733-0003 (
2017d)].
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MFG/IMPORT	PROCESSING	INDUSTRIAL, COMMERCIAL USESb	RELEASES and WASTE DISPOSAL
See Figure 2-3 for Environ mental Releases
and Wastes
| | Manufacture (includes Import)
~ Processing
~ Industrial/commercial use
Recycling
Repackaging
(Volume not reported)
Manufacture
(includes import) a
(142.6 Million lbs)
Laboratory Chemicals
e.g. extraction solvent
Incorporated into
Formulation, Mixture,
or Reaction Products
(Volume not reported)
Disposalc
Processing as
Rea eta nt/Inter mediate
(Volume CBI)
e.g. Intermediate for
refrigerant manufacture;
other chlorinated
compounds (PCE); reactive
ion etching
Other Basic Organic and Inorganic
Chemical Manufacturing
(Volume CBI or not reported)
e.g. Manufacturing of organicand inorganic
compounds as listed in MP Decision X/14
Directive), some of which can be used in
manufacturing of Solvents for Cleaning and
Degreasing,Adhesives, Sealants, Paints and
Coatings.
Petrochemical-derived and
Agricultural Products
Manufacturing
(Volume CBI or not reported)
(uses listed in Montreal Protocol's (MP)
Decision X/14 Directive).
Other Uses
e.g., metal recovery; specialty uses
Figure 2-1. Carbon Tetrachloride Life Cycle Diagram
The life cycle diagram depicts the conditions of use that are within the scope of the risk evaluation during various life cycle stages including
manufacturing, processing, use (industrial or commercial), distribution and disposal. The production volumes shown are for reporting year
2015 from the 2016 CDR reporting period (U.S. EPA. 2016b). Activities related to distribution (e.g., loading, unloading) will be considered
throughout the carbon tetrachloride life cycle, rather than using a single distribution scenario.
a Due to CBI claims, EPA cannot differentiate between manufacturing and import sites.
b See Table 2-3 for additional uses not mentioned specifically in this diagram.
0 Disposal refers to all of the following activities - Industrial pre-treatment, Industrial wastewater treatment. Publicly owned treatment works (POTW), Underground
injection. Municipal landfill. Hazardous landfill. Other land disposal. Municipal waste incinerator. Hazardous waste incinerator. Off-site waste transfer
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2.3 Exposures
For TSCA exposure assessments, EPA expects to evaluate exposures and releases to the environment
resulting from the conditions of use applicable to carbon tetrachloride. Post-release pathways and routes
will be described to characterize the relationship or connection between the conditions of use for carbon
tetrachloride and the exposure to human receptors, including PESS, and ecological receptors. EPA will
take into account, where relevant, the duration, intensity (concentration), frequency and number of
exposures in characterizing exposures to carbon tetrachloride.
2.3.1 Fate and Transport
Environmental fate includes both transport and transformation processes. Environmental transport is the
movement of the chemical within and between environmental media. Transformation occurs through the
degradation or reaction of the chemical with other species in the environment. Hence, knowledge of the
environmental fate of the chemical informs the determination of the specific exposure pathways and
potential human and environmental receptors EPA expects to consider in the risk evaluation. Table 2-5
provides environmental fate data that EPA identified and considered in developing the scope for carbon
tetrachloride. This information has not changed from that provided in the scope document.
During problem formulation, EPA considered volatilization during wastewater treatment, volatilization
from lakes and rivers followed by upward diffusion in the troposphere, biodegradation rates, and soil
organic carbon:water partition coefficient (log Koc) were used when making changes, as described in
Section 2.5 to the conceptual models. Systematic literature review is currently underway, so model
results and basic principles were used to support the fate data used in problem formulation.
EPI Suite (	i) modules were used to predict volatilization of carbon tetrachloride from
wastewater treatment plants, lakes, and rivers. The EPI Suite module that estimates chemical removal
in sewage treatment plants ("STP" module) was run using default settings to evaluate the potential for
carbon tetrachloride to volatilize to air or adsorb to sludge during wastewater treatment. The STP
module estimates that about 90% of carbon tetrachloride in wastewater will be removed by volatilization
and 2% by adsorption.
The EPI Suite module that estimates volatilization from lakes and rivers ("Volatilization" module)
was run using default settings to evaluate the volatilization half-life of carbon tetrachloride in surface
water. The volatilization module estimates that the half-life of carbon tetrachloride in a model river will
be about 1.3 hours and the half-life in a model lake will be about 5 days.
The EPI Suite module that predicts biodegradation rates ("BIOWIN" module) was run using default
settings to estimate biodegradation rates of carbon tetrachloride under aerobic conditions. Three of the
models built into the BIOWIN module (BIOWIN 1, 2 and 6) estimate that carbon tetrachloride will not
rapidly biodegrade in aerobic environments. These results support the biodegradation data presented in
the scope document for carbon tetrachloride, which demonstrate limited biodegradation under aerobic
conditions. However, BIOWIN 5 shows moderate biodegradation under aerobic conditions. On the other
hand, the model that estimates anaerobic biodegradation (BIOWIN 7) predicts that carbon tetrachloride
will biodegrade moderately under anaerobic conditions. Further, previous assessments of carbon
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tetrachloride found that aerobic biodegradation was very slow and anaerobic biodegradation was
moderate to rapid (EOh \	4 !, U SDR. 2.005; CalEPA. 2.0001
Conversely, previous assessment of carbon tetrachloride by HSDB found rapid biodegradation in
aerobic aquatic conditions (NLM. 2003). This may be largely due to fact that carbon tetrachloride
exhibits toxicity to aquatic microorganisms in concentrations higher than 10 mg/L. In water, under
aerobic conditions, a negative result has been reported for a ready biodegradability test according to
OECD TG 301C MITI (I) (Ministry of International Trade and Industry, Japan) test method, toxicity to
aerobic bacteria may have prevented biodegradation due to the high concentration used in this test
(ECH.A. ).
Based on the available environmental fate data, carbon tetrachloride is likely to biodegrade slowly under
aerobic conditions with pathways that are environment- and microbial population-dependent. Anaerobic
degradation has been observed to be faster than aerobic degradation under some conditions with
acclimated microbial populations. Anaerobic biodegradation is expected to be a significant degradation
mechanism in soil and ground water.
The log Koc reported in the carbon tetrachloride scoping document were measured values in the range
of 1.69 - 2.16, while the estimated value range using EPI Suite is 1.6 - 2.5. These values are
supported by the basic principles of environmental chemistry which states that the Koc is typically
within one order of magnitude (one log unit) of the octanol: water partition coefficient (Kow). Indeed, the
log Kow reported for carbon tetrachloride in Table 2-1 is a measured value of 2.83, which is within the
expected range. Further, the Koc could be approximately one order of magnitude larger than predicted
by EPI Suite before sorption would be expected to significantly impact the mobility of carbon
tetrachloride in groundwater. The log Koc and log Kow reported in previous assessments of carbon
tetrachloride were in the range of 1.69 - 2.16 and 2.64 - 2.83 respectively IYECH.A. 20!_, lID. 2011;
PR. 2005)1. and these values are associated with low sorption to soil and sediment.
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Table 2-5. Environmental Fate Characteristics of Carbon Tetrachloride
Properly or K ml point
Value11
References
1 )ireel pholodeui adalion
Minnies (almospheiic-slialospheiic)
( )
Indirect photodegradation
>330 years (atmospheric)
0 )
Hydrolysis half-life
7000 years at 1 ppm
0 )
Biodegradation
6 to 12 months (soil)b
0 )
ffiCHA. 2012)

7 days to 12 months (aerobic water, based
on multiple studies)
( SDR. 2005")
(NLM. 2.003)

3 days to 4 weeks (anaerobic water, based
on multiple studies)

Bioconcentration factor
(BCF)
30 bluegill sunfish
40 rainbow trout
0 )
Bioaccumulation factor
(BAF)
19 (estimated)
( 2012a")
Soil organic carbon:water
1.69-2.16
ffiCI )
partition coefficient (log Koc)
2.06 (weighted mean of two soils-silt loam
and sandy loam)
0 )
"Measured unless otherwise noted. bThis figure (6 to 12 months) represents a half-life estimate based on the estimated
aqueous aerobic biodegradation half-life of carbon tetrachloride.
Carbon tetrachloride shows minimal susceptibility to indirect photolysis by hydroxyl radicals in the
troposphere, where its estimated tropospheric half-life exceeds 330 years. Ultimately, carbon
tetrachloride diffuses upward into the stratosphere where it is photodegraded to form the trichloromethyl
radical and chlorine atoms ("OECD. 2011). Carbon tetrachloride is efficiently degraded by direct
photolysis under stratospheric conditions and the DTso (Dissipation Time for 50% of the compound to
dissipate) value is in the order of minutes. However, the troposphere to the stratosphere migration of
carbon tetrachloride is very long and this migration time limits the dissipation. The rate of
photodegradation increases at altitudes >20 km and beyond.
Carbon tetrachloride dissolved in water does not photodegrade or oxidize in any measurable amounts,
with a calculated hydrolysis half-life of 7,000 years based on experimental data at a concentration of
1 ppm (OEC	). Removal mechanisms from water could include volatilization due to the Henry's
law constant and anaerobic degradation in subsurface environment.
Estimated and measured BCF and BAF values ranging from 19-40 indicates that carbon tetrachloride
has low bioaccumulation potential in fish (	312a; OECD. 2011).
2.3.2 Releases to the Environment
Releases to the environment from conditions of use (e.g., industrial and commercial processes) are one
component of potential exposure and may be derived from reported data that are obtained through direct
measurement, calculations based on empirical data and/or assumptions and models.
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Under the Emergency Planning and Community Right-to-Know Act (EPCRA) Section 313 rule, carbon
tetrachloride is a Toxics Release Inventory (TRI)-reportable substance effective January 1, 1987 (see
Appendix A.l). EPA expects to consider data reported under the TRI program for evaluating exposure
to carbon tetrachloride.
Table 2-6 provides production-related waste managed data (also referred to as waste managed) for
carbon tetrachloride reported by industrial facilities to the TRI program for 2015 (U.S. EPA. 2017fl.
Table 2-7 provides more detailed information on the quantities released to air or water or disposed of on
land.
Table 2-6. Summary of Carbon Tetrachloride TRI Production-Related Waste Managed in
2015 (lbs)	
Number of
I'acililies
Recycling
Knorgy
Recovery
Treatment
Releases il h
Total Production
Related \Yasto
47
5,954,066
5,638,154
15,196,739
151,690
26,940,648
Data source: 2015 TRI Data (undated March 2017^ fU.S. EPA. 2017:0.
11 Terminology used in these columns may not match the more detailed data element names used in the TRI public data and
analysis access points.
b Does not include releases due to one-time event not associated with production such as remedial actions or earthquakes.
Facilities are required to report if they manufacture (including import) or process more than 25,000
pounds of carbon tetrachloride, or if they otherwise use more than 10,000 pounds of carbon
tetrachloride. In 2015, 47 facilities reported a total of 27 million pounds of carbon tetrachloride waste
managed. Of this total, nearly 6 million pounds were recycled, 5.6 million pounds were recovered for
energy, 15 million pounds were treated, and almost 152 thousand pounds were released into the
environment.
Of these releases, the largest releases of nearly 105 thousand pounds were to air (fugitive and point
source air emissions), a little under 500 pounds were released to water (surface water discharges),
50 thousand pounds were released to land (of which disposal to Resource Conservation and Recovery
Act (RCRA) Subtitle C landfills is the primary disposal method), and under 200 pounds were released in
other forms such as indefinite storage. Carbon tetrachloride migration to groundwater from RCRA
Subtitle C landfills regulated by the state/local jurisdictions will likely be mitigated by landfill design
(double liner, leachate capture) and requirements to adsorb liquids onto solid adsorbant and containerize
prior to disposal.
Table 2-7. Summary of Carbon Tetrachloride Toxics Release Inventory (TRI) Releases to the
Environment in 2015 (lbs)	

Nil in her
ol'
I'iicililk's
Air R
Sisick
Air
Releases
k'.iscs
l-'ugiliu*
Air
Rck'siscs
\\ silcr
Relcsiscs
( Isiss 1
I nder-
limund
Injection
.sind Rolens
RCRA
Subtitle C
Isuidlills
es
All oilier
1.SI 11(1
Dispossil
Oilier
Relesises '
Tolsil
Relesises'
Subtotal

69,897
34,941

19,608
27,300
401


Totals
47
104,838
468
47,309
164
152,780
Data source: 2015 TRI Data (updated March 2017s) (IIS, EPA. 20170
3 Terminology used in these columns may not match the more detailed data element names used in the TRI public data and analysis access points.
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Nil 111 her
ol'
l-'sieililies
Air R
Sisiek
Air
Releases
lesises
l"iiiiili\e
Air
Relesises
\\ silcr
RclcSISCS
(kiss 1
I nder-
limund
Injection
sind Helens
RCRA
Subtitle (
Isuidlills
es
All oilier
1.SI 11(1
Dispossil
Oilier
Relesises '
Tolsil
Relesises'
b Upon further evaluation of these reports of other land disposal releases, it was found that the reports consist of misreported disposal values. The incorrect
code uses or waste identification were used in the reports. Therefore these 401 lbs of released waste do not consist of carbon tetrachloride waste released
by other land disposal.
c These release quantities do include releases due to one-time events not associated with production such as remedial actions or earthquakes.
While production-related waste managed shown in Table 2-6 excludes any quantities reported as
catastrophic or one-time releases (TRI section 8 data), release quantities shown in Table 2-7 include
both production-related and non-routine quantities (TRI section 5 and 6 data). As a result, release
quantities may differ slightly and may further reflect differences in TRI calculation methods for reported
release range estimates (	)16a).
During problem formulation, EPA further analyzed the TRI data and examined the definitions of
elements in the TRI data to determine the level of confidence that a carbon tetrachloride release would
result from other types of land disposal, as reported in Table 2-7, given that carbon tetrachloride waste is
regulated as a hazardous waste under RCRA. In 2015, three facilities reported the disposal of a
combined total of 401 lbs of carbon tetrachloride through other land disposal. Upon further
investigation of these reports, EPA has found that these facilities used an incorrect TRI code during
reporting or that the disposed waste did not actually consist of carbon tetrachloride waste. These
incorrectly reported values cannot be removed from the TRI database until the facilities submit the
corresponding revision reports. However, these uncorrected reports are not considered relevant for the
purposes of this problem formulation.
2.3.3 Presence in the Environment and Biota
Monitoring studies or a collection of relevant and reliable monitoring studies provide(s) information that
can be used in an exposure assessment. Monitoring studies that measure environmental concentrations
or concentrations of chemical substances in biota provide evidence of exposure.
Monitoring and biomonitoring data were identified in EPA's data search for carbon tetrachloride.
Though carbon tetrachloride's use has significantly decreased from a peak in the 1970's, its long half-
life and previous ubiquitous use and disposal has resulted in the continued presence in various
environmental media ("ATSDR. 2005). Carbon tetrachloride is listed as a Hazardous Air Pollutant (HAP)
and is included in several multi-year monitoring programs, with data collected across the nation in both
urban and rural locations (I .S .<.'P.\.20 j_7}}, jJi'26). For example, carbon tetrachloride is included in all
three ambient air monitoring programs, collectively known as the National Monitoring Programs:
National Air Toxics Trends Stations (NATTS) network, Community-Scale Air Toxics Ambient
Monitoring (CSATAM) Program and Urban Air Toxics Monitoring Program (UATMP). NATTS sites
are based on preliminary air toxics programs such as the 1996 National Air Toxics Assessment (NATA).
According to the 2015 National Air Toxics Inventory, ambient air monitoring trends from 2003 to 2013
have shown that of the eight HAP monitored, only carbon tetrachloride average concentrations have
slightly increased in the atmosphere over the 10-year period. This is likely primarily due to its extremely
long half-life in the troposphere (	2015a).
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Carbon tetrachloride is specifically regulated under the Safe Drinking Water Act (SDWA). Therefore,
under the National Primary Drinking Water Regulations, carbon tetrachloride is designated as a volatile
organic compound (VOC) contaminant and is monitored in drinking water (U.S. EPA. 2.009). Nationally
representative drinking water monitoring data are available through EPA's SDWA compliance
monitoring. SDWA requires EPA to review each national primary drinking water regulation at least
once every six years and revise as necessary. As part of the "Six-Year Review (SYR)," EPA evaluates
any newly available data, information and technologies to determine if any regulatory revisions are
needed. Internal analysis for SYR3 (2006-2011) data, not yet published, show that 118 systems of
55,735 systems (0.212%) have mean concentrations greater than the Minimum Reporting Level (MRL)
of 0.5 |ig/L. SYR 2 (1998-2005) data showed 650 systems or 1.289% of 50,446 systems had detects
greater than 0.5 |ig/L. Of those, over 75% of the detections were in groundwater (versus surface water
systems). In addition, only 57 (0.113%) systems had detects of carbon tetrachloride greater than the
Maximum Contaminant Level (MCL) of 5 |ig/L. During SYR 2, EPA's Office of Water (OW)
determined the Estimated Quantitation Level (EQL) to be 0.5 ug/L, which is the threshold for
determining if the occurrence data showed a meaningful opportunity to improve health protection. The
basis for the SYR 2 EQL for carbon tetrachloride is the modal MRL reported for each sample in the
SYR 2 ICR dataset (h ttps://wcms.epa.gov/dwsixvearreview/six-vear-review-3-compliance-momtoring-
data-2006-2011).
The U.S. Geological Survey (USGS) monitors organic compounds in ground water and has detected
carbon tetrachloride in community water systems (USGS. 2007). EPA provides the public with storage
and retrieval (STORET) data that maps monitoring sites and allows for download of sampling data of
surface water monitoring sites. These data are searchable via the Water Quality Portal (WQP), a
cooperative service sponsored by the USGS, the EPA and the National Water Quality Monitoring
Council (NWQMC) (NWQMC. 2017). The portal contains data collected by over 400 state, federal,
tribal and local agencies.
Biomonitoring data on carbon tetrachloride are collected in the National Health and Nutrition
Examination Survey (NHANES) (CDC. 201 /).
2.3.4 Environmental Exposures
The manufacturing, processing, use and disposal of carbon tetrachloride can result in releases to the
environment. In this section, EPA presents exposures to aquatic and terrestrial organisms.
Aquatic Environmental Exposures
During problem formulation, EPA modeled industrial discharges to surface water to estimate surface
water concentration using TRI and EPA NPDES permit Discharge Monitoring Report (DMR) data on
the top 10 highest carbon tetrachloride releasing facilities. EPA used the Probabilistic Dilution Model
(PDM) within E-FAST to estimate annual discharges for the facilities. In order to estimate a range of
conservative surface water concentrations, the 2015 NPDES DMR data reporting carbon tetrachloride
discharges were used as a high-end range of possible release days (i.e., 20 and 250 days/year) allowing
the estimation of conservative carbon tetrachloride surface water concentrations (i.e., conservative
exposure scenarios). Appendix E presents the first-tier estimate of surface water concentrations.
Terrestrial Environmental Exposures
Terrestrial species populations living near industrial and commercial facilities using carbon tetrachloride
may be exposed to the chemical through environmental media. Terrestrial species populations living
near industrial and commercial facilities using carbon tetrachloride may be exposed via multiple routes
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such as ingestion of surface waters and inhalation of outdoor air. As described in Section 2.3.3 carbon
tetrachloride is present and measurable through monitoring in a variety of environmental media
including ambient air, surface water and ground water
2.3.5 Human Exposures
In this section, EPA presents occupational, consumer and general population exposures. Subpopulations,
including PESS, within these exposed groups are also presented.
2.3.5.1 Occupational Exposures
Exposure pathways and exposure routes are listed below for worker activities under the various
conditions of use described in Section 2.2. In addition, exposures to occupational non-users (ONU), who
do not directly handle the chemical but perform work in an area where the chemical is present, are listed.
Engineering controls and/or personal protective equipment may impact the occupational exposure levels.
Workers and ONU may be exposed to carbon tetrachloride when performing activities associated with
the conditions of use described in Section 2.2, including, but not limited to:
	Unloading and transferring carbon tetrachloride to and from storage containers to process
vessels.
	Using carbon tetrachloride in process equipment.
	Cleaning and maintaining equipment.
	Sampling chemical, formulations or products containing carbon tetrachloride for quality control
(QC).
	Repackaging chemical, formulations or products containing carbon tetrachloride.
	Handling, transporting and disposing waste containing carbon tetrachloride.
	Use of carbon tetrachloride in laboratories.
	Performing other work activities in or near areas where carbon tetrachloride is used.
Based on these activities, EPA will analyze inhalation exposure to vapor and mists. Dermal exposure,
including skin contact with liquids and vapors for workers will also be analyzed. ONU would not
intentionally handle liquids containing carbon tetrachloride, therefore, dermal exposure will not be
analyzed further in the risk evaluation for ONU. The risk evaluation will not further analyze potential
worker exposure through mists that deposit in the upper respiratory tract and are swallowed. Due to the
high volatility of carbon tetrachloride which results in a high inhalation absorption of mists, swallowing
of carbon tetrachloride mists is not considered a significant route of exposure.
Key Data
Key data that inform occupational exposure assessment and which EPA plans to evaluate include: the
OSHA Chemical Exposure Health Data (CEHD) and National Institute of Occupational Safety and
Health (NIOSH) Health Hazard Evaluation (HHE) program data. OSHA data are workplace monitoring
data from OSHA inspections. The inspections can be random or targeted, or can be the result of a
worker complaint. OSHA data can be obtained through the OSHA Integrated Management Information
System (IMIS) at https://www.osha.gov/osh.stats/index.html. Appendix C.2 provides a summary of
carbon tetrachloride personal monitoring air samples obtained from OSHA inspections conducted
between 2013 and 2015 and a summary of monitoring data from NIOSH HHEs conducted since 1990.
NIOSH HHEs are conducted at the request of employees, union officials, or employers and help inform
potential hazards at the workplace. HHEs can be downloaded at https://www.cdc.gov/niosh/hhe/. In
public comment, EPA-HQ-OPPT-2016-0733-0064. Halogenated Solvents Industry Alliance
characterized potential exposures groups during manufacturing and use of halogenated solvents such as
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carbon tetrachloride and provided summaries of occupational monitoring data from three different
companies. One of the data summaries includes 330 full-shift samples collected over 11 years. In
addition, the Department of Defense has provided a compilation of carbon tetrachloride use scenarios
with their respective exposure controls and workplace exposure assessment information for some of the
use scenarios from the aerospace industry. During risk evaluation, EPA will review these data and
evaluate the utility of these datasets in the risk evaluation.
Inhalation
EPA anticipates that inhalation to vapor is the most important exposure pathway of carbon tetrachloride
for workers and ONU based on the high volatility of the chemical. ONU are not directly handling carbon
tetrachloride; therefore, inhalation exposure to mists are not expected for ONU.
The United States has several regulatory and non-regulatory exposure limits for carbon tetrachloride:
including an OSHA Permissible Exposure Limit (PEL) of 10 ppm time-weighted average (TWA) and
25 ppm ceiling and a NIOSH Recommended Exposure Limit (REL) of 2 ppm (12.6 mg/m3) 60-minute
Short-term Exposure Limit (STEL). Also, NIOSH indicates that carbon tetrachloride has an immediately
dangerous to life and health (IDLH) value of 200 ppm based on acute inhalation toxicity data in humans,
and provides a notation that carbon tetrachloride is considered a potential occupational carcinogen. The
influence of these exposure limits on occupation exposures will be considered in the occupational
exposure assessment.
During problem formulation, EPA has identified information on the thermal decomposition of carbon
tetrachloride into phosgene, a highly toxic gas. However, thermal decomposition of carbon tetrachloride
is more likely to occur in open environments and less likely in the type of closed systems used during
the manufacturing and processing of carbon tetrachloride. Furthermore, TRI data shows that no single
facility ever reported releases of both carbon tetrachloride and phosgene. EPA does not plan to evaluate
exposure to phosgene during the manufacturing and processing of carbon tetrachloride.
2.3.5.2	Consumer Exposures
Consumer products and/or commercial products containing chlorinated compounds made with carbon
tetrachloride as a process agent are available for public purchase at common retailers fEPA-HQ-OPPT-
2016-0733-0003. sections 3 and 4, (	017d)1. However, these products are not expected to
contain measurable amounts of carbon tetrachloride because carbon tetrachloride is not used in the
manufacturing of the actual products. Trace levels of carbon tetrachloride in the chlorinated substances
used to manufacture the products are expected to volatilize during the product manufacturing process.
Therefore, EPA does not plan to evaluate consumer exposures to carbon tetrachloride due to the use of
products containing chlorinated compounds made with carbon tetrachloride as a process agent (see
Section 2.2.2.1).
2.3.5.3	General Population Exposures
Wastewater/liquid wastes, solid wastes or air emissions of carbon tetrachloride could result in potential
pathways for inhalation, oral or dermal exposure to the general population.
Inhalation
The volatility of carbon tetrachloride makes inhalation exposures a likely exposure pathway when it is
released (via air or as a result of waste disposal) during industrial or commercial uses (see Figure 2-3)
Inhalation of carbon tetrachloride, due to its volatilization, during household use of contaminated water
(e.g., during bathing/showering, dishwashing) could be a source of exposure to the general population.
According to a study from the New Jersey Department of Environmental Protection (NJ DEP), the
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acceptable shower water criteria for carbon tetrachloride is 0.15 ug/L and the associated shower air
concentration of carbon tetrachloride would be acceptable at 1.5 x 10"5ug/m3 (NJDEP. 2002). Vapor
intrusion is an additional source of exposure in indoor environments. VOCs such as carbon tetrachloride
can evaporate rapidly and migrate into air. Therefore, there is a potential for carbon tetrachloride from
TSCA conditions of use (see Table 2-7) to migrate from groundwater to indoor air via vapor intrusion.
Oral
Oral ingestion pathways may include exposure to contaminated drinking water or breast milk. However,
breast milk is not expected to be significantly contaminated with carbon tetrachloride as the chemical
does not bioaccumulate in tissues. EPA conducted a screening level estimate of carbon tetrachloride
concentrations in drinking water using the PDM and the facility discharges in 2015 as reported in the
NPDES Discharge Monitoring Reports. Ninety four percent of the modeled acute exposures were well
below the EPA drinking water Minimum Contaminant Level of 5 ug/L.
Oral ingestion may include incidental ingestion of carbon tetrachloride residue on the hand/body. Based
on the presence of carbon tetrachloride in water used for bathing or recreation, the oral ingestion of
contaminated water could contribute, to a lesser degree, to oral exposures.
Dermal
Dermal exposure via water could occur through contact, such as washing and bathing with household
water contaminated with carbon tetrachloride. The source of the contaminated water could either be
contaminated surface or ground waters. As explained in Section 2.3.3, a first-tier analysis of the carbon
tetrachloride monitored drinking water concentrations (i.e., SYR data) indicates that 94% of the reported
facility discharge levels resulted in drinking water estimates below the EPA Minimum Contaminant
Level of 5 ug/L.
2.3.5.4 Potentially Exposed or Susceptible Subpopulations
TSCA requires that the determination of whether a chemical substance presents an unreasonable risk to
"a potentially exposed or susceptible subpopulation identified as relevant to the risk evaluation" by
EPA. TSCA  3(12) states that "the term 'potentially exposed or susceptible subpopulation' means a
group of individuals within the general population identified by the Administrator who, due to either
greater susceptibility or greater exposure, may be at greater risk than the general population of adverse
health effects from exposure to a chemical substance or mixture, such as infants, children, pregnant
women, workers, or the elderly." General population is "the total of individuals inhabiting an area or
making up a whole group" and refers here to the U.S. general population (	).
As part of the Problem Formulation, EPA identified potentially exposed and susceptible subpopulations
(PESS) for further analysis during the development and refinement of the life cycle, conceptual models,
exposure scenarios, and analysis plan. In this section, EPA addresses the PESS identified as relevant
based on greater exposure. EPA will address the subpopulations identified as relevant based on greater
susceptibility in the hazard section.
EPA identifies the following as PESS due to their greater exposure, that EPA expects to consider in the
risk evaluation:
 Workers and ONU based on inhalation and dermal routes of exposure (See Figure 2-2).
In developing exposure scenarios, EPA will analyze available data to ascertain whether some human
receptor groups may be exposed via exposure pathways that may be distinct to a particular
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subpopulation or lifestage and whether some human receptor groups may have higher exposure via
identified pathways of exposure due to unique characteristics (e.g., activities, duration or location of
exposure) (	006).
In summary, in the risk evaluation for carbon tetrachloride, EPA plans to analyze the following
potentially exposed groups of human receptors: workers and ONU. EPA may also identify additional
PESS that will be considered based on greater exposure.
2.4 Hazards (Effects)
For scoping, EPA conducted comprehensive searches for data on hazards of carbon tetrachloride, as
described in the Strategy for Conducting Literature Searches for Carbon Tetrachloride: Supplemental
File for the TSCA Scope Document (EPA-H.Q-OPP'T-201.6-0733). Based on initial screening, EPA plans
to analyze the hazards of carbon tetrachloride identified in this problem formulation document.
However, when conducting the risk evaluation, the relevance of each hazard within the context of a
specific exposure scenario will be judged for appropriateness. For example, hazards that occur only as a
result of chronic exposures may not be applicable for acute exposure scenarios. This means that it is
unlikely that every identified hazard will be analyzed for every exposure scenario.
Further, as explained in Section 2.3, EPA's focus in the risk evaluation process is on conducting timely,
relevant, high-quality, and scientifically credible risk evaluations 82 FR 33726, 33728 (July 20, 2017).
Each risk evaluation will be "fit-for-purpose," meaning the Agency may be able to reach some
conclusions without extensive or quantitative risk evaluations, and EPA expects to be able to reach
conclusions about particular hazards without extensive evaluation.
2.4.1 Environmental Hazards
For the scope document, EPA consulted the following sources of environmental hazard data for carbon
tetrachloride: ECHA. (ECHA. .iM ), < M CD SIPS Initial Assessment Profile (SI.\U;i *ECD. 2011). and
Australia's National Industrial Chemicals Notification and Assessment Scheme (NICNAS). These
previous assessments included an evaluation of the environmental hazard data quality. Only the on-topic
references listed in the Ecological Hazard Literature Search Results were considered as potentially
relevant data/information sources for the risk evaluation. Inclusion criteria were used to screen the
results of the ECOTOX literature search (as explained in the Strategy for Conducting Literature
Searches for Carbon Tetrachloride: Supplemental File for the TSCA Scope Document, EPA-HQ-OPPT-
201.6-0733. Data from the screened literature are summarized below (Table 2-8) as ranges (min-max).
EPA plans to review these data/information sources during risk evaluation using the data quality review
evaluation metrics and the rating criteria described in the Application of Systematic Review in TSCA Risk
Evaluations (	08).
Toxicity to Sediment and Terrestrial Organisms
During data screening, the limited number of environmental toxicity studies for carbon tetrachloride on
sediment and terrestrial organisms were determined to contain data or information not relevant (off-
topic) for the risk evaluation. The studies were considered off-topic references during the data screening
process (see Section 1.3). No relevant (on-topic) toxicity data were available for carbon tetrachloride to
birds. Hazard studies for sediment and terrestrial organisms are not likely to be conducted because
exposure to carbon tetrachloride by these organisms is not expected due to the fate and transport
properties of the chemical.
Toxicity to Aquatic Organisms
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During problem formulation, EPA identified aquatic (aqueous-only) data reported in literature to assess
the aquatic hazard of carbon tetrachloride. For the aquatic environment, the acute hazard endpoint for
fish (96-h LCso) exposed to carbon tetrachloride ranges from 7.6 - 125 mg/L (Japanese Ministry of
Environment 2015; Dawson. 1977). The acute hazard endpoint for aquatic invertebrates (48-h EC50)
exposed to carbon tetrachloride ranges from 8.1 - 35 mg/L (Japanese Ministry of Environment. 2015;
Leblanc. 1980). The acute hazard endpoint for aquatic plants (72-hr EC50) exposed to carbon
tetrachloride ranges from 0.246 - 23.590 mg/L (Tsai. 2007; Brack. 1994). The chronic hazard endpoint
for fish (23-day LC50) exposed to carbon tetrachloride is 1.97 mg/L (Black. 1982). The chronic hazard
endpoint for aquatic invertebrates (21-day NOEC) exposed to carbon tetrachloride ranges from 0.49 -
3.1 mg/L (Japanese Ministry of Environment. 2015; Thomson et al.. 1997). For aquatic plants, the
chronic hazard endpoint (72-hr EC10/NOEC ) for carbon tetrachloride ranges from 0.0717 - 2.2 mg/L
(Gancet. 2011; Brack. 1994). The acute toxicity of amphibian embryo-larval stages ranged from 0.9 to
22.420 mg/L (Black. 1982; Birge. 1980V
Table 2-8. Ecological Hazard Characterization of Carbon Tetrachloride
Duration
Test
organism
Endpoint
Hazard value*
Units
Effect Endpoint
References

Fish
LC50
7.6- 125
mg/L
Mortality
(Japanese Ministry
of Environment.
2015; Dawson.
1977)
Acute
Aquatic
invertebrates
ECso
8.1-35
mg/L
Immobilization
(Japanese Ministry
of Environment.
2015; Leblanc.
1980)

Algae
ECso
0.246-23.590
mg/L
Biomass/growth
rate
(Tsai, 2007; Brack,
1994)

Amphibians
L/ECso
0.9-22.420
mg/L
Mortality
(Black. 1982; Birse.
1980)

Acute COC
0.062
mg/L



Fish
ChV
1.97
mg/L
Mortality
(Black. 1982)
Chronic
Aquatic
invertebrates
NOEC
0.49-3.1
mg/L
Growth and
reproduction
(Japanese Ministry
of Environment.
2015; Thomson et
al.. 1997)

Algae
EC10/NOEC
0.0717-2.2
mg/L
Biomass/growth
rate
(Gancet. 2011;
Brack, 1994).

Chronic COC
0.007
mg/L

* Values in the tables are presented as reported by the study authors
Concentrations of Concern
The screening-level acute and chronic COCs for carbon tetrachloride were derived based on the lowest
or most toxic ecological toxicity values (e.g., L/EC50). The information below describes how the acute
and chronic COC's were calculated for environmental toxicity of carbon tetrachloride using assessment
factors. The application of assessment factors is based on established EPA/OPPT methods (U.S. EPA.
2013. 2012b) and were used in this hazard assessment to calculate lower bound effect levels (referred to
as the concentration of concern; COC) that would likely encompass more sensitive species not
specifically represented by the available experimental data. Also, assessment factors are included in the
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COC calculation to account for differences in inter- and intra-species variability, as well as laboratory -
to-field variability. It should be noted that these assessment factors are dependent upon the availability
of datasets that can be used to characterize relative sensitivities across multiple species within a given
taxa or species group, but are often standardized in risk assessments conducted under TSCA, due to
limited data availability.
The acute COC is derived by dividing the algal 72-hr ECso of 0.246 mg/L (the lowest acute value in the
dataset) by an assessment factor (AF) of 4:
	Lowest value for the 72-hr fish ECso (0.246 mg/L) / AF of 4 = 0.062 mg/L or 62 |ig/L.
The acute COC of 62 |ig/L, derived from experimental algal endpoint, is used as a conservative hazard
level in this problem formulation for carbon tetrachloride.
The chronic COC is derived by dividing the 72-hr algal ECio of 0.0717 mg/L (the lowest chronic value
in the dataset) by an assessment factor of 10:
	Lowest value for the 72-hr algal chronic value (0.0717 mg/L) / AF of 10 = 0.007 mg/L or 7
Hg/L-
The chronic COC of 7 |ig/L, derived from experimental algal endpoint, is used as the lower bound
hazard level in this problem formulation for carbon tetrachloride.
2.4.2 Human Health Hazards
Carbon tetrachloride has an existing I P \ IRIS \sscssmcnl (	) and an \ I SDR
Toxicological Profile ("ATSDR. 2005); hence, many of the hazards of carbon tetrachloride have been
previously compiled. EPA expects to use these previous analyses as a starting point for identifying key
and supporting studies to inform the human health hazard assessment, including dose-response analysis.
The relevant studies will be evaluated using the data quality criteria in the Application of Systematic
Review in TSCA Risk Evaluations document. EPA also expects to consider other studies (e.g., more
recently published, peer-reviewed alternative test data) that have been published since these reviews, as
identified in the literature search conducted by the Agency for carbon tetrachloride (Carbon
tetrachloride (CASRN 56-23-5) Bibliography: Supplemental File for the TSCA Scope Document, EPA-
HQ-OPPT-^ [33). EPA expects to consider potential human health hazards associated with carbon
tetrachloride. Based on reasonably available information, the following sections describe the potential
hazards associated with carbon tetrachloride. In addition to these hazards, EPA plans to evaluate hazards
(e.g., reproductive toxicity, developmental toxicity) that may be identified during the evaluation of the
key studies from the IRIS Toxicological Review of Carbon Tetrachloride.
2.4.2.1 Non-Cancer Hazards
Acute Toxicity
Following acute exposures, human case reports identify liver as a primary target organ of toxicity and
the kidney as an additional primary target organ of toxicity (	) Neurotoxicity indicated as
central nervous system (CNS) depression is another primary effect of carbon tetrachloride in humans
following acute exposures, with examples of neurotoxic effects including drowsiness, headache,
dizziness, weakness, coma and seizures (U.S. EPA. ). Gastrointestinal symptoms such as nausea
and vomiting, diarrhea and abdominal pain are considered another initial acute effect.
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Liver Toxicity
Liver toxicity has consistently been demonstrated following human and animal exposures to carbon
tetrachloride (U.S. EPA. 2010). Suggestive evidence of an effect of occupational exposure on serum
enzymes indicative of hepatic effects was reported in a cross-sectional epidemiology study. Similar to
humans, data from acute, subchronic and chronic animal studies suggest that the liver is the major target
organ for carbon tetrachloride toxicity (	.010).
Kidney Toxicity
Renal toxicity effects include oliguria, elevated blood urea nitrogen (BUN) and histopathological
changes (e.g., nephrosis, degeneration and interstitial inflammation in fatal cases) were observed in
humans following acute exposures. In animals, renal toxicity was observed in inhalation (but not oral)
studies. In subchronic studies, renal toxicity generally occurred at higher concentrations than those
producing liver damage, whereas changes in renal and liver endpoints were reported at the same
concentration in chronic inhalation toxicity studies in rats and mice (U.S. EPA. 2010).
Irritation/Sensitization
Following dermal exposures, primary irritation was observed in rabbits and guinea pigs (ATSDR. 2005).
Guinea pigs also exhibited degenerative change in epidermal cells and edema (ATSDR. 2005). In the
murine local lymph node assay, carbon tetrachloride showed weak dermal sensitization potential
(OECD. 2011).
2.4.2.2	Genotoxicity and Cancer Hazards
The IRIS Assessment for carbon tetrachloride evaluated data for genotoxicity and cancer hazard. Carbon
tetrachloride has been extensively studied for its genotoxic and mutagenic effects. Overall, results are
largely negative. There is little direct evidence that carbon tetrachloride induces intragenic or point
mutations in mammalian systems. The mutagenicity studies that have been performed using transgenic
mice have yielded negative results, as have the vast majority of the mutagenicity studies that have been
conducted in bacterial systems. The weight of evidence suggests that carbon tetrachloride is more likely
an indirect mutagenic agent (i.e., lipid peroxidation, protein modifications) rather than a direct mutagen
(deoxyribonucleic acid [DNA] modifications) (U.S. EPA. 2010).
In the IRIS carcinogenicity assessment, carbon tetrachloride is considered "likely to be carcinogenic to
humans" by all routes of exposure based on inadequate evidence of carcinogenicity in humans, and
sufficient evidence in animals by oral and inhalation exposure. The animal evidence shows that carbon
tetrachloride is a liver carcinogen in rats, mice and hamsters following oral and inhalation exposure in
eight bioassays. Carbon tetrachloride also induced pheochromocytomas in mice exposed by the oral and
inhalation routes of exposure.
2.4.2.3	Potentially Exposed or Susceptible Subpopulations
TSCA requires that the determination of whether a chemical substance presents an unreasonable risk
include consideration of unreasonable risk to "a potentially exposed or susceptible subpopulation
identified as relevant to the risk evaluation" by EPA. TSCA  3(12) states that "the term 'potentially
exposed or susceptible subpopulation' means a group of individuals within the general population
identified by the Administrator who, due to either greater susceptibility or greater exposure, may be at
greater risk than the general population of adverse health effects from exposure to a chemical substance
or mixture, such as infants, children, pregnant women, workers or the elderly." In developing the hazard
assessment, EPA will analyze available data to ascertain whether some human receptor groups may have
greater susceptibility than the general population to the chemical's hazard(s).
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EPA's IRIS assessment identified the following as factors that might influence susceptibility to carbon
tetrachloride: age (e.g., childhood, senescence), gender, nutritional status, disease status and exposure to
other chemicals (U.S. EPA. 2010. 2006). The IRIS assessment noted that because metabolism of carbon
tetrachloride to reactive metabolites by cytochrome P450 (CYP450) enzymes is hypothesized to be a
key event in the toxicity of this compound, variability in CYP450 levels due to age-related differences
or other factors such as exposure to other chemicals that either induce or inhibit microsomal enzymes
may impact an individual's response to carbon tetrachloride. In addition, variability in nutritional status,
alcohol consumption and/or underlying diseases (e.g., diabetes) may alter metabolism or antioxidant
protection systems and thereby also alter susceptibility to carbon tetrachloride (	,010). EPA
expects to consider these factors, and others that may be identified from more current literature, in the
risk evaluation for carbon tetrachloride.
2.5 Conceptual Models
EPA risk assessment guidance (\,_ S_lj T L_-Pi J, I 98) defines Problem Formulation as the part of the
risk assessment framework that identifies the factors to be considered in the assessment. It draws from
the regulatory, decision-making and policy context of the assessment and informs the assessment's
technical approach.
A conceptual model describes the actual or predicted relationships between the chemical substance and
receptors, either human or environmental. These conceptual models are integrated depictions of the
conditions of use, exposures (pathways and routes), hazards and receptors. The initial conceptual models
describing the scope of the assessment for carbon tetrachloride, have been refined during problem
formulation. The changes to the conceptual models in this problem formulation are described along with
the rationales.
In this section EPA outlines those pathways that will be included and further analyzed in the risk
evaluation; will be included but will not be further analyzed in risk evaluation; and will not be included
in the TSCA risk evaluation; and the underlying rationale for these decisions.
EPA determined as part of problem formulation that it is not necessary to conduct further analysis on
certain exposure pathways that were identified in the carbon tetrachloride scope document and that
remain in the risk evaluation. Each risk evaluation will be "fit-for-purpose," meaning not all conditions
of use will warrant the same level of evaluation and the Agency may be able to reach some conclusions
without extensive or quantitative risk evaluations. 82 FR 33726, 33734, 33739 (July 20, 2017).
As part of this problem formulation, EPA also identified exposure pathways under regulatory programs
of other environmental statutes, administered by EPA, which adequately assess and effectively manage
exposures and for which long-standing regulatory and analytical processes already exist, i.e., the CAA,
the SDWA, the Clean Water Act (CWA) and the RCRA. OPPT worked closely with the offices within
EPA that administer and implement the regulatory programs under these statutes. In some cases, EPA
has determined that chemicals present in various media pathways (i.e., air, water, land) fall under the
jurisdiction of existing regulatory programs and associated analytical processes carried out under other
EPA-administered statutes and have been assessed and effectively managed under those programs. EPA
believes that the TSCA risk evaluation should generally focus on those exposure pathways associated
with TSCA conditions of use that are not adequately assessed and effectively managed under the
regulatory regimes discussed above because these pathways are likely to represent the greatest areas of
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risk concern. As a result, EPA does not expect to include in the risk evaluation certain exposure
pathways identified in the carbon tetrachloride scope document.
2.5.1 Conceptual Model for Industrial and Commercial Activities and Uses: Potential
Exposures and Hazards
The revised conceptual model (Figure 2-2) describes the pathways of exposure from industrial and
commercial activities and uses of carbon tetrachloride that EPA expects to include in the risk evaluation.
EPA plans to evaluate exposures to workers and/or ONU via inhalation routes and to workers via dermal
routes during manufacturing, processing, use and disposal of carbon tetrachloride for all the identified
uses. In addition to the pathways illustrated in the figure, EPA will evaluate activities resulting in
exposures associated with distribution in commerce (e.g., loading, unloading) throughout the various
lifecycle stages and conditions of use (e.g., manufacturing, processing, industrial use, commercial use,
disposal) rather than a single distribution scenario.
Inhalation
Based on the physical-chemical properties (e.g., high vapor pressure), inhalation is expected to be the
main exposure pathway for carbon tetrachloride. Inhalation exposures for workers are regulated by
OSHA's occupational safety and health standards for carbon tetrachloride which include a PEL of 10
ppm TWA, exposure monitoring, control measures and respiratory protection (29 CFR 1910.1000). EPA
expects that for workers and ONU, exposure via inhalation will be the most significant route of exposure
for most exposure scenarios. EPA plans to further analyze inhalation exposures to vapors for workers
and ONU in the risk evaluation.
There are potential worker exposures through mists that deposit in the upper respiratory tract. EPA
initially assumed that mists may be swallowed. However, based on physical chemical properties, mists
of carbon tetrachloride will likely be rapidly absorbed in the respiratory tract or evaporate and contribute
to the amount of carbon tetrachloride vapor in the air. Furthermore, if carbon tetrachloride vapors were
ingested orally the available toxicological data do not suggest significantly different toxicity from
considering vapors as an inhalation exposure. ONU are not directly handling carbon tetrachloride;
therefore, exposure to mists is not expected for ONU. EPA plans no further analysis of this pathway
(swallowing of carbon tetrachloride mists) for workers or ONU in the risk evaluation.
Dermal
There is the potential for dermal exposures to carbon tetrachloride in many worker scenarios. These
dermal exposures would be concurrent with inhalation exposures and the overall contribution of dermal
exposure to the total exposure is expected to be small; however, there may be exceptions for occluded
scenarios. ONU are not directly handling carbon tetrachloride; therefore, skin contact with liquid carbon
tetrachloride is not expected for ONU. EPA does not plan to further analyze this pathway in the risk
evaluation. EPA plans to further analyze dermal exposures for skin contact with liquids and vapors in
occluded situations for workers.
Waste Handling, Treatment and Disposal
Figure 2-2 shows that waste handling, treatment and disposal is expected to lead to the same pathways
as other industrial and commercial activities and uses. The path leading from the "Waste Handling,
Treatment and Disposal" box to the "Hazards Potentially Associated with Acute and/or Chronic
Exposures See Section 2.4.2" box was re-routed to accurately reflect the expected exposure pathways,
routes, and receptors associated with these conditions of use of carbon tetrachloride.
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For each condition of use identified in Table 2-3, a determination was made as to whether or not each
unique combination of exposure pathway, route, and receptor will be analyzed further in the risk
evaluation. The results of that analysis along with the supporting rationale are presented in Appendix F.
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INDUSTRIAL AND COMMERCIAL
ACTIVITIES / USES
EXPOSURE PATHWAY
EXPOSURE ROUTE
RECEPTORS c d
Dermal (occluded)
Occupational
Non-Users
Fugitive
Emissionsa
Inhalation
Vapor/ Mistb
Liquid Contact
OutdoorAir
Recycling
Other Uses
Manufacturing
Laboratory Chemicals
Waste Handling,
Treatment and Disposal
Petrochemical-derived
and Agricultural Products
Manufacturing
Other Basic Organic and
InorganicChemical
Manufacturing
Processing:
	As reactant/
intermediate
	Incorporation into
Formulation, Mixture or
Reaction Products
	Repackaging
Hazards Potentially Associated with
Acute and/orChronic Exposures
See Section 2.4.2
KEY:
~	Pathways that will be further analyzed.
>	Pathwaysthat are in the risk evaluation with no further analysis.
Wastewater, Liquid Wastes
(See Figure 2-3)
Figure 2-2. Carbon Tetrachloride Conceptual Model for Industrial and Commercial Activities and Uses: Potential Exposures and
Hazards
The conceptual model presents the exposure pathways, exposure routes and hazards to human receptors from industrial and commercial
activities and uses of carbon tetrachloride.
a Fugitive air emissions include fugitive equipment leaks from valves, pump seals, flanges, compressors, sampling connections, open-ended lines; evaporative losses from
surface impoundment and spills; and releases from building ventilation systems.
b Includes possible vapor intrusion into industrial or commercial facility from carbon tetrachloride ground water; exposure to mists is not expected for ONU.
0 Receptors include PESS (see Section2.4.2.3).
d When data and information are available to support the analysis, EPA also considers the effect that engineering controls and/or personal protective equipment have on
occupational exposure levels.
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2.5.2	Conceptual Model for Consumer Activities and Uses: Potential Exposures and
Hazards
As explained in Section 2.2.2.1, there are current regulatory actions that prevent the direct use of carbon
tetrachloride in the formulation of commercially available products, besides the use of carbon
tetrachloride as a laboratory chemical. The domestic and international use of carbon tetrachloride as a
process agent is regulated under EPA's stratospheric ozone protection regulations at 40 CFR part 82.
This process agent use is also addressed by the MP side agreement, Decision X/14: Process Agents,
from the tenth meeting of the parties in November 1998 (UNEP/Ozone Secretariat. 1998). This MP
decision lists a limited number of approved uses of carbon tetrachloride as a process agent (i.e., non-
feedstock uses) in which carbon tetrachloride is not expected to be destroyed in the production process
(see Appendix D). Based on the process agent uses, carbon tetrachloride is used to manufacture other
chlorinated compounds (i.e., chlorinated paraffins) that may subsequently be added to commercially
available products (i.e., adhesives). Given the high volatility of carbon tetrachloride and the extent of
reaction and efficacy of the separation/purification process for purifying final products, EPA does not
expect that carbon tetrachloride will be present in the commercially available products. Furthermore, the
use of carbon tetrachloride in consumer products has been banned by the CPSC (16 CFR 1500.17) since
1970. EPA does not expect to evaluate consumer activities and uses for carbon tetrachloride, and has
excluded these conditions of use from the scope of the risk evaluation (see Section 2.2.2.1). Therefore,
there is no conceptual model provided for consumer activities and uses.
2.5.3	Conceptual Model for Environmental Releases and Wastes: Potential Exposures and
Hazards
The revised conceptual model (Figure 2-3) illustrates the expected exposure pathways to human and
ecological receptors from environmental releases and waste streams associated with industrial and
commercial activities for carbon tetrachloride that EPA expects to include in the risk evaluation. The
pathways that EPA expects to include but not further analyze in the risk evaluation are described in
Section 2.5.3.1 and shown in the conceptual model, Figure 2-3. The pathways that EPA does not expect
to include in the risk evaluation are described in Section 2.5.3.2. EPA does not expect to further analyze
any exposure pathways to human or ecological receptors from environmental releases and waste streams
associated with industrial and commercial activities for carbon tetrachloride.
2.5.3.1 Pathways That EPA Expects to Include But Not Further Analyze
EPA does not expect to further analyze carbon tetrachloride exposures to aquatic species from sediments
and suspended solids. Due to its log Koc (1.7 - 2.16) and high solubility of 793 mg/L at 25C, sorption
of carbon tetrachloride to sediments and suspended solids is unlikely.
EPA does not expect to further analyze risk to aquatic species exposed to carbon tetrachloride in surface
water. Wastewater from industrial discharges as reported under TRI for 2015 shows only 468.2 pounds
of carbon tetrachloride were released to surface water nationally and significant levels of carbon
tetrachloride are not expected from disposal of consumer and commercial products.
EPA considered worst-case scenarios to estimate carbon tetrachloride concentrations in surface water
resulting from industrial discharges. Using NPDES Discharge Monitoring Reporting data available for
2015, the largest releases of carbon tetrachloride were modeled for releases over 20 days and 250 days
per year. In these conservative scenarios, surface water concentrations were below the acute COC for
aquatic species (see Appendix E); hence there is not an acute aquatic concern. Although the chronic
COC was exceeded by one facility by a factor of 3.5 (i.e., worst-case scenario) based on predicted
conservative exposure concentrations in surface water, these carbon tetrachloride releases are not
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continuously released over time (i.e., chronic exposure); hence there is not a chronic aquatic
concern. Furthermore, carbon tetrachloride discharges to surface waters are expected to undergo
volatilization and dilution in surface water, processes that were not considered for estimating the
predicted conservative exposure concentrations in surface water. Due to its physical-chemical
properties, carbon tetrachloride is not anticipated to bioaccumulate in fish (BCF 30-40) thus there is no
bioconcentration or bioaccumulation concern. Thus, EPA does not expect to further analyze exposure
pathways to ecological aquatic species in the risk evaluation.
2.5.3.2 Pathways that EPA Does Not Expect to Include in the Risk Evaluation
Exposures to receptors (i.e. general population, terrestrial species) may occur from industrial and/or
commercial uses; industrial releases to air, water or land; and other conditions of use. As described in
Section 2.5, EPA does not expect to include in the risk evaluation pathways under programs of other
environmental statutes, administered by EPA, which adequately assess and effectively manage
exposures and for which long-standing regulatory and analytical processes already exist. These
pathways are described below.
Ambient Air Pathway
The Clean Air Act (CAA) contains a list of HAP and provides EPA with the authority to add to that list
pollutants that present, or may present, a threat of adverse human health effects or adverse
environmental effects. For stationary source categories emitting HAP, the CAA requires issuance of
technology-based standards and, if necessary, additions or revisions to address developments in
practices, processes, and control technologies, and to ensure the standards adequately protect public
health and the environment. The CAA thereby provides EPA with comprehensive authority to regulate
emissions to ambient air of any HAP.
Carbon tetrachloride is a HAP. EPA has issued a number of technology-based standards for source
categories that emit carbon tetrachloride to ambient air and, as appropriate, has reviewed or is in the
process of reviewing remaining risks. Because stationary source releases of carbon tetrachloride to
ambient air are adequately assessed and any risks effectively managed when under the jurisdiction of the
CAA, EPA does not expect to include emission pathways to ambient air from commercial and industrial
stationary sources or associated inhalation exposure of the general population or terrestrial species in
this TSCA evaluation.
Drinking Water Pathway
EPA has regular analytical processes to identify and evaluate drinking water contaminants of potential
regulatory concern for public water systems under the SDWA. Under SDWA, EPA must also review
and revise "as appropriate" existing drinking water regulations every 6 years.
EPA has promulgated National Primary Drinking Water Regulations (NPDWRs) for carbon
tetrachloride under the Safe Drinking Water Act. EPA has set an enforceable MCL as close as feasible
to a health based, non-enforceable Maximum Contaminant Level Goal (MCLG). Feasibility refers to
both the ability to treat water to meet the MCL and the ability to monitor water quality at the MCL,
SDWA Section 1412(b)(4)(D), and public water systems are required to monitor for the regulated
chemical based on a standardized monitoring schedule to ensure compliance with the MCL. The MCL
and MCLG values for carbon tetrachloride are presented in Appendix A. 1.
Hence, because the drinking water exposure pathway for carbon tetrachloride is currently addressed in
the SDWA regulatory analytical process for public water systems, EPA does not expect to include this
pathway in the risk evaluation for carbon tetrachloride under TSCA. EPA's OW and OPPT will continue
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to work together providing understanding and analysis of the SDWA regulatory analytical processes and
to exchange information related to toxicity and occurrence data on chemicals undergoing risk evaluation
under TSCA.
Ambient Water Pathways
EPA develops recommended water quality criteria under section 304(a) of the CWA for pollutants in
surface water that are protective of aquatic life or human health designated uses. EPA develops and
publishes water quality criteria based on priorities of states and others that reflect the latest scientific
knowledge. When states adopt criteria that EPA approves as part of states' regulatory water quality
standards, exposure is considered when state permit writers determine if permit limits are needed and at
what level for a specific discharger of a pollutant to ensure protection of the designated uses of the
receiving water. This is the process used under the CWA to address risk to human health and aquatic life
from exposure to a pollutant in ambient waters.
EPA has identified carbon tetrachloride as a priority pollutant and EPA has developed recommended
water quality criteria for protection of human health for carbon tetrachloride which are available for
adoption into state water quality standards for the protection of human health and are available for use
by NPDES permitting authorities in deriving effluent limits to meet state narrative criteria. As such,
EPA does not expect to include this pathway in the risk evaluation under TSCA. EPA's OW and OPPT
will continue to work together providing understanding and analysis of the CWA water quality criteria
development process and to exchange information related to toxicity of chemicals undergoing risk
evaluation under TSCA. EPA may update its CWA section 304(a) water quality criteria for carbon
tetrachloride in the future under the CWA.
EPA has not developed CWA section 304(a) recommended water quality criteria for the protection of
aquatic life for carbon tetrachloride, so there are no national recommended criteria for this use available
for adoption into state water quality standards and available for use in NPDES permits. As a result, this
pathway will undergo aquatic life risk evaluation under TSCA but as described in Section 2.5.3.1 (i.e.,
conservative estimates of surface water concentrations) this pathway will not be further analyzed. EPA
may publish CWA section 304(a) aquatic life criteria for carbon tetrachloride in the future if it is
identified as a priority under the CWA.
Biosolids Pathways
CWA Section 405(d) requires EPA to 1) promulgate regulations that establish numeric criteria and
management practices that are adequate to protect public health and the environment from any
reasonably anticipated adverse effects of toxic pollutants during the use or disposal of sewage sludge,
and 2) review such regulations at least every two years to identify additional toxic pollutants that occur
in biosolids (i.e., "Biennial Reviews") and regulate those pollutants if sufficient scientific evidence
shows they may be present in sewage sludge in concentrations which may adversely affect public health
or the environment. EPA also periodically conducts surveys to determine what may be present in sewage
sludge. EPA has conducted four sewage sludge surveys and identified compounds that occur in biosolids
in seven Biennial Reviews. EPA has regulated 10 chemicals in biosolids under CWA 405(d).
EPA has identified carbon tetrachloride in biosolids biennial reviews. The purpose of such reviews is to
identify additional toxic pollutants in biosolids. EPA can potentially regulate those pollutants under
CWA 405(d), based on a subsequent assessment of risk. EPA's Office of Water is currently developing
modeling tools in order to conduct risk assessments for chemicals in biosolids. Because the biosolids
pathway for carbon tetrachloride is currently being addressed in the CWA regulatory analytical process,
this pathway will not be further analyzed in the risk evaluation for carbon tetrachloride under TSCA.
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EPA's OW and OPPT will continue to work together to discuss significant data gaps and exchange
information related to exposure and toxicity of this chemical as OW conducts the risk assessment under
the CWA.
Disposal Pathways
Carbon tetrachloride is included on the list of hazardous wastes to RCRA 3001 (40 CFR  261.33) as a
listed waste on the D, K, F and U lists. The general standard in RCRA section 3004(a) for the technical
criteria that govern the management (treatment, storage, and disposal) of hazardous waste are those
"necessary to protect human health and the environment," RCRA 3004(a). The regulatory criteria for
identifying "characteristic" hazardous wastes and for "listing" a waste as hazardous also relate solely to
the potential risks to human health or the environment. 40 C.F.R.  261.11, 261.21-261.24. RCRA
statutory criteria for identifying hazardous wastes require EPA to "tak[e] into account toxicity, persistence,
and degradability in nature, potential for accumulation in tissue, and other related factors such as
flammability, corrosiveness, and other hazardous characteristics." Subtitle C controls cover not only
hazardous wastes that are landfilled, but also hazardous wastes that are incinerated (subject to joint control
under RCRA Subtitle C and the CAA hazardous waste combustion MACT) or injected into UIC Class I
hazardous waste wells (subject to joint control under Subtitle C and the SDWA).
EPA does not expect to 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. CAA section 129 also requires EPA to review and, if necessary, add provisions to
ensure the standards adequately protect public health and the environment. Thus, combustion by-
products from incineration treatment of carbon tetrachloride wastes (over 15 million lbs identified in
Table 2-6) would be subject to the aforementioned regulations, as would carbon tetrachloride burned for
energy recovery (5.6 million lbs).
EPA does not expect to include on-site releases to land that go to underground injection in its risk
evaluation. TRI reporting in 2015 indicated 19,608 pounds released to underground injection to a Class I
well and no releases to underground injection wells of Classes II-VI. Environmental disposal of carbon
tetrachloride injected into Class I well types is managed and prevented from further environmental
release by RCRA and SDWA regulations. Therefore, disposal of carbon tetrachloride via underground
injection is not likely to result in environmental and general population exposures.
EPA does not expect to include on-site releases to land that go to RCRA Subtitle C hazardous waste
landfills in its risk evaluation. Based on 2015 reporting to TRI, the majority of the chemical is disposed
of in Subtitle C landfills (27,300 lbs on-site and 401 lbs other land disposal). Design standards for
Subtitle C landfills require double liner, double leachate collection and removal systems, leak detection
system, run on, runoff, and wind dispersal controls, and a construction quality assurance program. They
are also subject to closure and post-closure care requirements including installing and maintaining a
final cover, continuing operation of the leachate collection and removal system until leachate is no
longer detected, maintaining and monitoring the leak detection and groundwater monitoring system.
Bulk liquids may not be disposed in Subtitle C landfills. Subtitle C landfill operators are required to
implement an analysis and testing program to ensure adequate knowledge of waste being managed, and
to train personnel on routine and emergency operations at the facility. Hazardous waste being disposed
in Subtitle C landfills must also meet RCRA waste treatment standards before disposal. Given these
controls, general population and terrestrial organisms exposure to carbon tetrachloride in groundwater
from Subtitle C landfill leachate is not expected to be a significant pathway.
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EPA does not expect to include on-site releases to land from RCRA Subtitle C hazardous waste landfills
or exposures of the general population (including susceptible subpopulations) or terrestrial species from
such releases in the TSCA evaluation.
Based on 2015 reporting to TRI, 401 lb of carbon tetrachloride wastes were released as other land
disposals (see Table 2-7). Upon evaluation of these reports of other land disposal releases, it was found
that the reports consist of misreported disposal values. The incorrect code uses or waste identification
were used in the reports. Therefore these 401 lbs of released waste do not consist of carbon tetrachloride
waste released by other land disposal. EPA does not expect to include these misreported other land
disposals for carbon tetrachloride in the TSCA evaluation.
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RELEASES AND WASTES FROM
INDUSTRIAL / COMMERCIAL USES
EXPOSURE PATHWAY
---H
Wastewater or
Liquid Wastes a
Industrial Pre-
Treatmentor
Industrial WWT
^ Indirect discharge
Dirc.ct
discharge
*" ~l
t _ .
!	K
Water,
Sediment
POTW
RECEPTORS
HAZARDS
Aquatic *
y Species
I Hazards Potentially Associated with
1 -^l Acute and Chronic Exposures:
I	See Section 2.4.1
KEY:
xt: Uses/activities/receptors that are in the risk evaluation with no further analysis.
 -~ Pathways that are in the risk evaluation with no further analysis.
Figure 2-3. Carbon Tetrachloride Conceptual Model for Environmental Releases and Wastes: Potential Exposures and Hazards
The conceptual model presents the exposure pathways, exposure routes and hazards to environmental receptors from environmental water
releases of carbon tetrachloride.
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2.6 Analysis Plan
The analysis plan in the problem formulation elaborates on the initial analysis plan that was published in
the Scope of the Risk Evaluation for carbon tetrachloride (s ' I T \ .01 ^).
The analysis plan outlined here is based on the conditions of use of carbon tetrachloride, as described in
Section 2.2 of this problem formulation. EPA is implementing systematic review approaches and/or
methods to identify, select, assess, integrate and summarize the findings of studies supporting the TSCA
risk evaluation. The analytical approaches and considerations in the analysis plan are used to frame the
scope of the systematic review activities for this assessment. The supplemental document, Application of
Systematic Review in TSCA Risk Evaluations, provides additional information about the criteria,
approaches and/or methods that have been and will be applied to the first ten chemical risk evaluations.
While EPA has conducted a search for readily available information from public sources as described in
the Scope of the Risk Evaluation for Carbon Tetrachloride (U.S. EPA. 2Q17e). EPA encourages
submission of additional existing data, such as full study reports or workplace monitoring from industry
sources, that may be relevant for refining conditions of use, exposures, hazards and PESS. EPA will
continue to consider new information submitted by the public.
During the risk evaluation, EPA will rely on the comprehensive literature results [Carbon tetrachloride
(CASRN 56-23-5) Bibliography: Supplemental File for the TSCA Scope Document; (!	\ ,i'17a)1
or perform supplemental literature searches to address specific questions. Further, EPA may consider
any relevant CBI information in the risk evaluation in a manner that protects the confidentiality of the
information from public disclosure. The analysis plan is based on EPA's knowledge of carbon
tetrachloride to date which includes partial, but not complete review of identified literature. Should
additional data or approaches become available, EPA may refine its analysis plan based on this
information.
2.6.1 Exposure
Based on physical-chemical properties, expected sources, and transport and transformation within the
outdoor and indoor environment chemical substances are more likely to be present in some media and
less likely to be present in others. Media-specific concentrations will vary based on the chemical
substance of interest. For most chemical substances, level(s) can be characterized through a combination
of available monitoring data and modeling approaches.
2.6.1.1 Environmental Releases, Fate and Exposures
EPA does not plan to further analyze environmental releases to environmental media based on
information described in Section 2.5. For the purposes of developing estimates of occupational
exposure, EPA may use release related data collected under selected data sources such as the Toxics
Release Inventory (TRI) and National Emissions Inventory (NEI) programs. Analyses conducted using
physical and chemical properties, fate information and TRI/DMR show that TSCA-related
environmental releases for carbon tetrachloride do not result in significant exposure to aquatic species
through water and sediment exposure pathways (see Section 2.5.3.1). For the pathways of exposures for
the general population and terrestrial species, EPA has determined that the existing regulatory programs
and associated analytical processes adequately assess and effectively manage the risks of carbon
tetrachloride that may be present in other media pathways. EPA believes that the TSCA risk evaluation
for carbon tetrachloride should focus not on those exposure pathways, but rather on exposure pathways
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associated with TSCA conditions of use that are not subject to those regulatory processes, because the
latter pathways are likely to represent the greatest areas of risk concern.
2.6.1.2 Occupational Exposures
EPA expects to consider and analyze exposures to workers and ONU as follows:
1) Review reasonably available exposure monitoring data for specific condition(s) of use. Exposure
data to be reviewed may include workplace monitoring data collected by government agencies
such as OSHA and NIOSH, data submitted by Halogenated Solvents Industry Alliance and
Department of Defense and monitoring data found in published literature. These workplace
monitoring data include personal exposure monitoring data (direct exposures) and area
monitoring data (indirect exposures). During risk evaluation, EPA will review these data and
evaluate the utility of these datasets in the risk evaluation. Data, information, and studies will be
evaluated using the evaluation strategies laid out in the Application of Systematic Review in
TSCA Risk Evaluations.
EPA has reviewed available monitoring collected by OSHA and NIOSH and matched them to
applicable conditions of use. EPA has also identified data sources that may contain relevant
monitoring data for the various conditions of use. EPA will review these sources. Data gaps will
be identified where no data are found for particular conditions of use. EPA will attempt to
address data gaps identified as described in steps 2 and 3 below. Where possible, job descriptions
may be useful in distinguishing exposures to different subpopulations within a particular
condition of use. EPA has also identified additional data sources that may contain relevant
monitoring data for the various conditions of use. EPA will review these sources, identified in
Table 2-9 and other relevant data sources, and will extract relevant data for consideration and
analysis during risk evaluation.
Table 2-9. Potential Sources of Occupational Exposure Data	
ATSDR Toxicological Profile for Carbon Tetrachloride
U.S. OSHA CEHD program data
U.S. NIOSH Health Hazard Evaluation (HHE) Program reports
Industry workplace exposure monitoring summary data submitted to EPA by Halogenated
Solvents Industry Alliance
Industry workplace exposure information submitted to EPA by the Department of Defense
U.S. EPA Generic Scenarios
OECD Emission Scenario Documents (ESD)
Sector-specific Worker Exposure Descriptions (SWEDs)
2) Review reasonably available exposure data for surrogate chemicals that have uses and chemical
and physical properties similar to carbon tetrachloride. EPA will review literature sources
identified and if surrogate data are found, these data will be matched to applicable conditions of
use for potentially filling data gaps.
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For conditions of use where data are limited or not available, review existing exposure models
that may be applicable in estimating exposure levels. EPA has identified potentially relevant
OECD ESDs and EPA GS corresponding to some conditions of use. EPA will need to critically
review these generic scenarios and ESDs to determine their applicability to the conditions of use
assessed. EPA is working in the identification of exposure scenarios corresponding to several
conditions of use, including manufacture of carbon tetrachloride, use of carbon tetrachloride as
an intermediate, and recycling of carbon tetrachloride. EPA will perform additional targeted
research to understand those conditions of use, which may inform identification of exposure
scenarios. EPA may also need to perform targeted research to identify applicable models that
EPA may use to estimate exposures for certain conditions of use.
Review reasonably available data that may be used in developing, adapting, or applying
exposure models to the particular risk evaluation. This step will be performed after Steps 2 and 3
above. Based on information developed from Step 2 and Step 3, EPA will evaluate relevant data
to determine whether the data can be used to develop, adapt, or apply models for specific
conditions of use (and corresponding exposure scenarios). EPA will consider the effect of
evaporation when evaluating options for dermal exposure assessment. In addition, EPA will
consider the impact of occluded exposure or repeated dermal contacts.
Consider and incorporate applicable engineering controls and/or personal protective equipment
into exposure scenarios. EPA will review potentially relevant data sources on engineering
controls and personal protective equipment as identified in Appendix F and to determine their
applicability and incorporation into exposure scenarios during risk evaluation.
Evaluate the weight of the evidence of occupational exposure data. EPA will rely on the weight
of the scientific evidence when evaluating and integrating occupational exposure data. The data
integration strategy will be designed to be fit-for-purpose in which EPA will use systematic
review methods to assemble the relevant data, evaluate the data for quality and relevance,
including strengths and limitations, followed by synthesis and integration of the evidence.
Map or group each condition of use to occupational exposure assessment scenario(s). EPA has
identified exposure scenarios and mapped them to some conditions of use. EPA grouped similar
conditions of use (based on factors including process equipment and handling, usage rates of
carbon tetrachloride and formulations containing carbon tetrachloride, exposure/release sources)
into scenario groupings but may further refine these groupings as additional information is
identified during risk evaluation.
EPA was not able to identify occupational exposure scenarios corresponding to several
conditions of use due generally to a lack of understanding of those conditions of use. EPA will
perform targeted research to understand those uses which may inform identification of
occupational exposure scenarios.
Evaluate the weight of the evidence of occupational exposure data. EPA will rely on the weight
of the scientific evidence when evaluating and integrating occupational exposure data. The data
integration strategy will be designed to be fit-for-purpose in which EPA will use systematic
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review methods to assemble the relevant data, evaluate the data for quality and relevance,
including strengths and limitations, followed by synthesis and integration of the evidence.
2.6.1.3	Consumer Exposures
EPA does not expect to consider and analyze consumer exposures in the risk evaluation for carbon
tetrachloride. Based on domestic and international regulatory information; Use document, EPA-HQ-
OPPT-2016-0733-0003; and submitted public comments; carbon tetrachloride is expected to be present
in consumer products at trace levels resulting in de minimis exposures or otherwise insignificant risks.
2.6.1.4	General Population
EPA does not expect to include general population exposures in the risk evaluation for carbon
tetrachloride. EPA has determined that the existing regulatory programs and associated analytical
processes adequately assess and effectively manage the risks of carbon tetrachloride that may be present
in various media pathways (e.g., air, water, land) from TSCA conditions of use and subsequent
partitioning and transport processes (i.e., vapor intrusion) for the general population. EPA believes that
the TSCA risk evaluation should focus not on those exposure pathways, but rather on exposure
pathways associated with TSCA conditions of use that are not subject to those regulatory processes,
because the latter pathways are likely to represent the greatest areas of concern to EPA.
2.6.2 Hazards (Effects)
2.6.2.1	Environmental Hazards
Environmental hazards will not be further analyzed because exposure analysis conducted using physical
and chemical properties, fate information and TRI/DMR environmental releases for carbon tetrachloride
show that aquatic species are not significantly exposed to TSCA-related environmental releases of this
chemical. During data screening, the limited number of environmental toxicity studies for carbon
tetrachloride on sediment and terrestrial organisms were determined to contain data or information not
relevant (off-topic) for the risk evaluation. The studies were considered off-topic references during the
data screening process (see Section 1.3). No relevant (on-topic) toxicity data were available for carbon
tetrachloride to birds. Hazard studies for sediment and terrestrial organisms are not likely to be
conducted because exposure to carbon tetrachloride by these organisms is not expected due to the fate
and transport properties of the chemical. Furthermore, EPA does not expect to include exposures to
sediment and terrestrial organisms in the risk evaluation because these are pathways under programs of
other environmental statutes, administered by EPA, which adequately assess and effectively manage
exposures and for which long-standing regulatory and analytical processes already exist (see Section
2.5.3.2).
2.6.2.2	Human Health Hazards
EPA expects to consider and analyze human health hazards as follows:
1) Review reasonably available human health hazard data, including data from alternative test methods
(e.g., computational toxicology and bioinformatics; high-throughput screening methods; data on
categories and read-across; in vitro studies; systems biology).
Human health studies will be evaluated using the evaluation strategies laid out in the Application of
Systematic Review in TSCA Risk Evaluations. Human, animal, and mechanistic data will be
identified and included as described in the inclusion and exclusion criteria in Appendix H. EPA
plans to prioritize the evaluation of mechanistic evidence. Specifically, EPA does not plan to
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evaluate mechanistic studies unless needed to clarify questions about associations between carbon
tetrachloride and health effects and its relevance to humans. Systematic Review Approaches and
Methods Applied to TSCA Risk Evaluations describes how studies will be evaluated using specific
data evaluation criteria and a predetermined systematic approach. Study results will be extracted and
presented in evidence tables by each hazard endpoint. EPA intends to review studies published after
the IRIS assessment (see Carbon tetrachloride (CASRN 56-23-5) Bibliography: Supplemental File
for the TSCA Scope Document, EPA-HQ-OPPT-2016-0733) using the approaches and/or methods
described in the Application of Systematic Review in TSCA Risk Evaluations to ensure that EPA is
considering information that has been made available since these assessments were conducted. EPA
will also evaluate information in the IRIS assessment using OPPT's structured process described in
the document. Application of Systematic Review in TSCA Risk Evaluations (	018. 2.010).
For irritation and sensitization (not addressed in the IRIS assessment), EPA will rely on the ATSDR
Toxicological Profile and 2011 OECD SIDS Initial Assessment Profile as a starting point to
understand data for this chemical (OECD. 2011; ATSDR. 2005). In addition, EPA intends to
conduct a full review of the data collected (see Carbon tetrachloride (CASRN 56-23-5)
Bibliography: Supplemental File for the TSCA Scope Document, EPA-HQ-OPPT-2016-073 3) as
described in Application of Systematic Review in TSCA Risk Evaluations to ensure that EPA is
considering information that has been made available since these assessments were conducted.
2)	In evaluating reasonably available data, determine whether particular human receptor groups may
have greater susceptibility to the chemical's hazard(s) than the general population.
Reasonably available human health hazard data will be evaluated to ascertain whether some human
receptor groups may have greater susceptibility than the general population to carbon tetrachloride
hazard(s). Susceptibility of particular human receptor groups to carbon tetrachloride will be
determined by evaluating information on factors that influence susceptibility.
3)	Conduct hazard identification (the qualitative process of identifying non-cancer and cancer
endpoints) and dose-response assessment (the quantitative relationship between hazard and
exposure) for identified human health hazard endpoints.
Human health hazards from acute and chronic exposures will be identified by evaluating the human
and animal data that meet the data quality criteria described in the Application of Systematic Review
in TSCA Risk Evaluations document. Data quality evaluation will be performed on key studies
identified from the IRIS assessment (U.S. EPA. JO 10) and the ATSDR Toxicological Profile
(ATSDR. 2005). Data quality evaluation will also be performed on studies published after 2009 that
were identified in the comprehensive literature search and that met the inclusion criteria for full-text
screening (see Systematic Review Approaches and Methods Applied to TSCA Risk Evaluations for
more information). Hazards identified by studies meeting data quality criteria will be grouped by
routes of exposure relevant to humans (oral, dermal, inhalation) and by cancer and noncancer
endpoints.
Dose-response assessment will be performed in accordance with methods from EPA technical
documents (\ _ J \[\ i, 2000a. 1994). Dose-response analyses performed for the EPA (2009)
IRIS oral and inhalation reference dose determinations may be used if the data meet data quality
criteria and if additional information on the identified hazard endpoints are not available or would
not alter the analysis.
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The cancer mode of action (MOA) determines how cancer risks can be quantitatively evaluated.
EPA will evaluate information on genotoxicity and the mode of action for all cancer endpoints to
determine the appropriate approach for quantitative cancer assessment in accordance with the U.S.
EPA Guidelines for Carcinogen Risk Assessment ("ATSDR. 2005).
4)	Derive points of departure (PODs) where appropriate; conduct benchmark dose modeling depending
on the available data. Adjust the PODs as appropriate to conform (e.g., adjust for duration of
exposure) to the specific exposure scenarios evaluated.
Hazard data will be evaluated to determine the type of dose-response modeling that is applicable.
Where modeling is feasible, a set of dose-response models that are consistent with a variety of
potentially underlying biological processes will be applied to empirically model the dose-response
relationships in the range of the observed data consistent with the EPA Benchmark Dose Technical
Guidance Document. Where dose-response modeling is not feasible, NOAELs or LOAELs will be
identified.
EPA will evaluate whether the available PBPK and empirical kinetic models are adequate for route-
to-route and interspecies extrapolation of the POD, or for extrapolation of the POD to appropriate
exposure durations for the risk evaluation.
5)	Consider the route(s) of exposure (oral, inhalation, dermal), available route-to-route
extrapolation approaches, available biomonitoring data and available approaches to correlate internal
and external exposures to integrate exposure and hazard assessment.
At this stage of review EPA believes there will be sufficient data to conduct dose-response analysis
and benchmark dose modeling for both inhalation and oral routes of exposure. If sufficient dermal
toxicity studies are not identified in the literature search to assess risks from dermal exposures, then
a route-to-route extrapolation from the inhalation and oral toxicity studies would be needed to assess
systemic risks from dermal exposures. Without an adequate PBPK model, the approaches described
in the EPA guidance document Risk Assessment Guidance for Superfund Volume I: Human Health
Evaluation Manual (PartE, Supplemental Guidance for Dermal Risk Assessment) may be applied.
These approaches may be able to further inform the relative importance of dermal exposures
compared with other routes of exposure.
6)	Evaluate the weight of the evidence of human health hazard data.
EPA will rely on the weight of the scientific evidence when evaluating and integrating human health
hazard data. The data integration strategy will be designed to be fit-for-purpose in which EPA will
use systematic review methods to assemble the relevant data, evaluate the data for quality and
relevance, including strengths and limitations, followed by synthesis and integration of the evidence.
2.6,3 Risk Characterization
Risk characterization is an integral component of the risk assessment process for both ecological and
human health risks. EPA will derive the risk characterization in accordance with EPA's Risk
Characterization Handbook (U.S. EPA... 2000b). As defined in EPA's Risk Characterization Policy, "the
risk characterization integrates information from the preceding components of the risk evaluation and
synthesizes an overall conclusion about risk that is complete, informative and useful for decision
makers." Risk characterization is considered to be a conscious and deliberate process to bring all
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important considerations about risk, not only the likelihood of the risk but also the strengths and
limitations of the assessment, and a description of how others have assessed the risk into an integrated
picture.
Risk characterization at EPA assumes different levels of complexity depending on the nature of the risk
assessment being characterized. The level of information contained in each risk characterization varies
according to the type of assessment for which the characterization is written. Regardless of the level of
complexity or information, the risk characterization for TSCA risk evaluations will be prepared in a
manner that is transparent, clear, consistent and reasonable (TCCR) (U.S. EPA. 2000b). EPA will also
present information in this section consistent with approaches described in the Procedures for Chemical
Risk Evaluation Under the Amended Toxic Substances Control Act (8!	5). EPA will also
present information in this section consistent with approaches described in the Risk Evaluation
Framework Rule. For instance, in the risk characterization summary, EPA will further carry out the
obligations under TSCA section 26; for example, by identifying and assessing uncertainty and
variability in each step of the risk evaluation, discussing considerations of data quality such as the
reliability, relevance and whether the methods utilized were reasonable and consistent, explaining any
assumptions used, and discussing information generated from independent peer review. EPA will also
be guided by EPA's Information Quality Guidelines (U.S. EPA. 2002) as it provides guidance for
presenting risk information. Consistent with those guidelines, in the risk characterization, EPA will also
identify: (1) Each population addressed by an estimate of applicable risk effects; (2) the expected risk or
central estimate of risk for the PESS affected; (3) each appropriate upper-bound or lower-bound estimate
of risk; (4) each significant uncertainty identified in the process of the assessment of risk effects and the
studies that would assist in resolving the uncertainty; and (5) peer reviewed studies known to the
Agency that support, are directly relevant to, or fail to support any estimate of risk effects and the
methodology used to reconcile inconsistencies in the scientific information.
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WHO (World Health Organization). (2004). Carbon tetrachloride in drinking-water. Background
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APPENDICES
Appendix A REGULATORY HISTORY
A.l Federal Laws and Regulations
Table Apx A-l. Federal Laws and Regulations
Statutes/Regulations
Description of Aiilhoritv/Uegulalion
Description of Regulation
KPA Regulations
TSCA - Section 0(b)
UIW is directed to identify and begin
risk evaluations on 10 chemical
substances drawn from the 2014 update
of the TSCA Work Plan for Chemical
Assessments.
Carbon tetrachloride is on the initial
list of chemicals to be evaluated for
unreasonable risk under TSCA (81
FR 91927, December 19, 2016).
TSCA - Section 8(a)
The TSCA section 8(a) CDR Rule
requires manufacturers (including
importers) to give EPA basic exposure-
related information on the types,
quantities and uses of chemical
substances produced domestically and
imported into the United States.
Carbon tetrachloride manufacturing
(including importing), processing
and use information is reported
under the CDR Rule (76 FR 50816,
August 16, 2011).
TSCA - Section 8(b)
EPA must compile, keep current and
publish a list (the TSCA Inventory) of
each chemical substance manufactured,
processed, or imported in the United
States.
Carbon tetrachloride was on the
initial TSCA Inventory and therefore
was not subject to EPA's new
chemicals review process under
TSCA section 5 (60 FR 16309,
March 29, 1995).
TSCA - Section 8(d)
Provides EPA with authority to issue
rules requiring producers, importers and
(if specified) processors of a chemical
substance or mixture to submit lists
and/or copies of health and safety
studies.
Two submissions received (1947-
1994) (U.S. EPA, ChemView.
Accessed April 13, 2017).
TSCA - Section 8(e)
Manufacturers (including imports),
processors and distributors must
immediately notify EPA if they obtain
information that supports the conclusion
that a chemical substance or mixture
presents a substantial risk of injury to
health or the environment.
Three submissions received (1992-
2010) (U.S. EPA, ChemView.
Accessed April 13, 2017).
TSCA - Section 4
Provides EPA with authority to issue
rules and orders requiring manufacturers
(including importers) and processors to
test chemical substances and mixtures.
Seven section 4 notifications
received for carbon tetrachloride:
two acute aquatic toxicity studies,
one bioaccumulation report and four
monitoring reports (1978-1980)
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(U.S. EPA, ChemView. Accessed
April 13, 2017).
EPCRA- Section 313
Requires annual reporting from facilities
in specific industry sectors that employ
10 or more full time equivalent
employees and that manufacture,
process, or otherwise use a TRI-listed
chemical in quantities above threshold
levels.
Carbon tetrachloride is a listed
substance subject to reporting
requirements under 40 CFR 372.65
effective as of January 1, 1987.
Federal Insecticide,
Fungicide, and
Rodenticide Act
(FIFRA) - Sections 3
and 6
FIFRA governs the sale, distribution and
use of pesticides. Section 3 of FIFRA
generally requires that pesticide products
be registered by EPA prior to
distribution or sale. Pesticides may only
be registered if, among other things, they
do not cause "unreasonable adverse
effects on the environment." Section 6 of
FIFRA provides EPA with the authority
to cancel pesticide registrations if either
(1) the pesticide, labeling, or other
material does not comply with FIFRA;
or (2) when used in accordance with
widespread and commonly recognized
practice, the pesticide generally causes
unreasonable adverse effects on the
environment.
Use of carbon tetrachloride as a
grain fumigant was banned under
FIFRA in 1986 (51 FR 41004,
November 12, 1986).
Federal Food, Drug,
and Cosmetic Act
(FFDCA) - Section
408
FFDCA governs the allowable residues
of pesticides in food. Section 408 of the
FFDCA provides EPA with the authority
to set tolerances (rules that establish
maximum allowable residue limits), or
exemptions from the requirement of a
tolerance, for all residues of a pesticide
(including both active and inert
ingredients) that are in or on food. Prior
to issuing a tolerance or exemption from
tolerance, EPA must determine that the
tolerance or exemption is "safe."
Sections 408(b) and (c) of the FFDCA
define "safe" to mean the Agency has a
reasonable certainty that no harm will
result from aggregate exposures to the
pesticide residue, including all dietary
exposure and all other exposure (e.g.,
non-occupational exposures) for which
EPA removed carbon tetrachloride
from its list of pesticide product inert
ingredients used in pesticide
products in 1998 (63 FR 34384, June
24, 1998).
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there is reliable information. Pesticide
tolerances or exemptions from tolerance
that do not meet the FFDCA safety
standard are subject to revocation. In the
absence of a tolerance or an exemption
from tolerance, a food containing a
pesticide residue is considered
adulterated and may not be distributed in
interstate commerce.

CAA - Section 112(b)
This section lists 189 HAPs that must be
addressed by EPA and includes authority
for EPA to add or delete pollutants. EPA
may, by rule, add pollutants that present,
or may present, a threat of adverse
human health effects or adverse
environmental effects.
Lists carbon tetrachloride as a HAP
(70 FR 75047, December 19, 2005).
CAA - Section 112(d)
Directs EPA to establish, by rule.
National Emission Standards
(NESHAPs) for each category or
subcategory of major sources and area
sources of HAPs. The standards must
require the maximum degree of emission
reduction that EPA determines is
achievable by each particular source
category. This is generally referred to as
maximum achievable control technology
(MACT).
There are a number of source-
specific NESHAPs for carbon
tetrachloride, including:
Rubber tire manufacturing (67 FR
45588, July 9, 2002)
Chemical Manufacturing Area
Sources (74 FR 56008, October 29,
2009)
Organic HAP from the Synthetic
Organic Chemical Manufacturing
and Other Processes (59 FR 19402,
April 22,1994),
Halogenated solvent cleaning
operations (59 FR 61801, December
2, 1994)
Wood Furniture Manufacturing
Operations (60 FR 62930, December
7,1995)
Group 1 Polymers and Resins (61
FR 46906, September 5, 1996)
Plywood and Composite Wood
Products (69 FR 45944, July 30,
2004)
CAA - Sections
112(d) and 112(f)
Risk and technology review (RTR) of
section 112(d) MACT standards. Section
112(f)(2) requires EPA to conduct risk
assessments for each source category
subject to section 112(d) MACT
standards, and to determine if additional
EPA has promulgated a number of
RTR NESHAP (e.g., the RTR
NESHAP for Group 1 Polymers and
Resins (76 FR 22566; April 21,
201 1)) and will do so, as required.
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standards are needed to reduce
remaining risks. Section 1 12(d)(6)
requires EPA to review and revise the
MACT standards, as necessary, taking
into account developments in practices,
processes and control technologies.
for the remaining source categories
with NESHAP.
CAA - Section 604
Establishes a mandatory phase-out of
ozone depleting substances.
The production and import of carbon
tetrachloride for non-feedstock
domestic uses was phased out in
1996 (58 FR 65018, December 10,
1993). However, this restriction does
not apply to production and import
of amounts that are transformed or
destroyed. 40 CFR 82.4.
"Transform" is defined as "to use
and entirely consume (except for
trace quantities) a controlled
substance in the manufacture of
other chemicals for commercial
purposes." 40 CFR 82.3.
CWA - Section
304(a)(1)
Requires EPA to develop and publish
ambient water quality criteria (AWQC)
reflecting the latest scientific knowledge
on the effects on human health that may
be expected from the presence of
pollutants in any body of water.
In 2015, EPA published updated
AWQC for carbon tetrachloride,
including recommendations for
"water + organism" and "organism
only" human health criteria for states
and authorized tribes to consider
when adopting criteria into their
water quality standards.
CWA - Sections
301(b), 304(b), 306,
and 307(b)
Requires establishment of Effluent
Limitations Guidelines and Standards for
conventional, toxic, and
non-conventional pollutants. For toxic
and non-conventional pollutants, EPA
identifies the best available technology
that is economically achievable for that
industry after considering statutorily
prescribed factors and sets regulatory
requirements based on the performance
of that technology.

CWA - Section 307(a)
Establishes a list of toxic pollutants or
combination of pollutants under the
CWA. The statute specifies a list of
families of toxic pollutants also listed in
the Code of Federal Regulations at 40
Carbon tetrachloride is designated as
a toxic pollutant under section
307(a)(1) of the CWA and as such is
subject to effluent limitations.
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CFR401.15. The "priority pollutants"
specified by those families are listed in
40 CFR part 423, Appendix A. These are
pollutants for which best available
technology effluent limitations must be
established on either a national basis
through rules, see section 301(b), 304(b),
307(b), 306, or on a case-by-case best
professional judgment basis in NPDES
permits. CWA 402(a)(1)(B).

SDWA- Section 1412
Requires EPA to publish a non-
enforceable maximum contaminant level
goals (MCLGs) for contaminants which
1. may have an adverse effect on the
health of persons; 2. are known to occur
or there is a substantial likelihood that
the contaminant will occur in public
water systems with a frequency and at
levels of public health concern; and 3. in
the sole judgment of the Administrator,
regulation of the contaminant presents a
meaningful opportunity for health risk
reductions for persons served by public
water systems. When EPA publishes an
MCLG, EPA must also promulgate a
National Primary Drinking Water
Regulation (NPDWR) which includes
either an enforceable maximum
contaminant level (MCL), or a required
treatment technique. Public water
systems are required to comply with
NPDWRs.
Carbon tetrachloride is subject to
National Primary Drinking Water
Regulations (NPDWR) under
SDWA and EPA has set a MCLG of
zero and an enforceable MCL of
0.005 mg/L (56 FR 3526 January 30,
1991).
Comprehensive
Environmental
Response,
Compensation and
Liability Act
(CERCLA) - Sections
102(a) and 103
Authorizes EPA to promulgate
regulations designating as hazardous
substances those substances which, when
released into the environment, may
present substantial danger to the public
health or welfare or the environment.
EPA must also promulgate regulations
establishing the quantity of any
hazardous substance the release of which
must be reported under Section 103.
Section 103 requires persons in charge of
vessels or facilities to report to the
National Response Center if they have
Carbon tetrachloride is a hazardous
substance under CERCLA. Releases
of carbon tetrachloride in excess of
10 pounds must be reported (40 CFR
302.4).
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knowledge of a release of a hazardous
substance above the reportable quantity
threshold.

RCRA - Section 3001
Directs EPA to develop and promulgate
criteria for identifying the characteristics
of hazardous waste, and for listing
hazardous waste, taking into account
toxicity, persistence, and degradability in
nature, potential for accumulation in
tissue, and other related factors such as
flammability, corrosiveness, and other
hazardous characteristics.
Carbon tetrachloride is included on
the list of hazardous wastes pursuant
to RCRA 3001. Two categories of
carbon tetrachloride wastes are
considered hazardous: discarded
commercial chemicals (U211) (40
CFR 261.31(a)), and spent
degreasing solvent (F001) (40 CFR
261.33(f)) (45 FR 33084 May 19,
1980).
RCRA solid waste that leaches
0.5 mg/L or more carbon
tetrachloride when tested using the
TCLP leach test is RCRA hazardous
(DO 19) under 40 CFR 261.24 (55 FR
11798 March 29, 1990).
In 2013, EPA modified its hazardous
waste management regulations to
conditionally exclude solvent-
contaminated wipes that have been
cleaned and reused from the
definition of solid waste under
RCRA (40 CFR 261.4(a)(26)) (78
FR 46447, July 31, 2013).
Oilier l-'cricr;il Ucgiihilions
I'cderal Hazardous
Substance Act
(FHSA)
Requires precautionary labeling on the
immediate container of hazardous
household products and allows the
Consumer Product Safety Commission
(CPSC) to ban certain products that are
so dangerous or the nature of the hazard
is such that required labeling is not
adequate to protect consumers.
Use of carbon tetrachloride in
consumer products was banned in
1970 by the CPSC (16 CFR
1500.17).
FFDCA
Provides the U.S. Food and Drug
Administration (FDA) with authority to
oversee the safety of food, drugs and
cosmetics.
The FDA regulates carbon
tetrachloride in bottled water. The
maximum permissible level of
carbon tetrachloride in bottled water
is 0.005 mg/L (21 CFR 165.110).
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Mat iiles/Uegiilal ions
Description of Authority/Regulation
Description of Regulation


All medical devices containing or
manufactured with carbon
tetrachloride must contain a warning
statement that the compound may
destroy ozone in the atmosphere (21
CFR 801.433).
Carbon tetrachloride is also listed as
an "Inactive Ingredient for approved
Drug Products" by FDA (FDA
Inactive Ingredient Database.
Accessed April 13, 2017).
OSHA
Requires employers to provide their
workers with a place of employment free
from recognized hazards to safety and
health, such as exposure to toxic
chemicals, excessive noise levels,
mechanical dangers, heat or cold stress,
or unsanitary conditions.
In 1970, OSHA issued occupational
safety and health standards for
carbon tetrachloride that included a
PEL of 10 ppm TWA, exposure
monitoring, control measures and
respiratory protection (29 CFR
1910.1000).

Under the Act, OSHA can issue
occupational safety and health standards
including such provisions as permissible
exposure limits (PELs), exposure
monitoring, engineering and
administrative control measures, and
respiratory protection.
OSHA prohibits all workplaces from
using portable fire extinguishers
containing carbon tetrachloride (29
CFR 1910.157(c)(3)).
Atomic Energy Act
The Atomic Energy Act authorizes the
Department of Energy to regulate the
health and safety of its contractor
employees.
10 CFR 851.23, Worker Safety and
Health Program, requires the use of
the 2005 ACGIH TLVs if they are
more protective than the OSHA
PEL. The 2005 TLV for carbon
tetrachloride is 5 ppm (8hr Time
Weighted Average) and 10 ppm
Short Term Exposure Limit (STEL).
A.2 State Laws and Regulations
State Actions
Description of Action
State agencies of interest
State permissible exposure limits
California PEL: 12.6 mg/L (Cal Code Regs. Title 8,
section 5155), Hawaii PEL: 2 ppm (Hawaii
Administrative Rules section 12-60-50).
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State Actions
Description of Action
State agencies of interest
State Right-to-Know Acts
Massachusetts (454 Code Mass. Regs, section 21.00),
New Jersey (8:59 N.J. Admin. Code section 9.1),
Pennsylvania (34 Pa. Code section 323).
State air regulations
Allowable Ambient Levels (AAL): Rhode Island (12
R.I. Code R. 031-022), New Hampshire (RSA 125-1:6,
ENV-A Chap. 1400).
State drinking water standards and guidelines
Arizona (14 Ariz. Admin. Register 2978, August 1,
2008), California (Cal Code Regs. Title 26, section 22-
64444), Delaware (Del. Admin. Code Title 16, section
4462), Connecticut (Conn. Agencies Regs, section 19-
13-B102), Florida (Fla. Admin. Code R. Chap. 62-
550), Maine (10 144 Me. CodeR. Chap. 231),
Massachusetts (310 Code Mass. Regs, section 22.00),
Minnesota (Minn R. Chap. 4720), New Jersey (7:10
N.J Admin. Code section 5.2), Pennsylvania (25 Pa.
Code section 109.202), Rhode Island (14 R.I. Code R.
section 180-003), Texas (30 Tex. Admin. Code section
290.104).
Other
In California, carbon tetrachloride was added to the
Proposition 65 list in 1987 (Cal. Code Regs. Title 27,
section 27001).
Carbon tetrachloride is on the MA Toxic Use
Reduction Act (TURA) list of 1989 (301 Code Mass.
Regs, section 41.03).
A.3 International Laws and Regulations
Table Apx A-3. Regulatory Actions by Other Governments and Tribes
Country/Organization
Requirements and Restrictions
Regulatory Actions by other Governments and Tribes
Montreal Protocol
Carbon tetrachloride is considered an ozone depleting substance (ODS) and
its production and use are controlled under the 1987 Montreal Protocol on
Substances That Deplete the Ozone Layer and its amendments (Montreal
Protocol Annex B - Group II).
Canada
Carbon tetrachloride is on the Canadian List of Toxic Substances (CEPA
1999 Schedule 1). Other regulations include:
Federal Halocarbon Regulations, 2003 (SOR/2003-289).
ODS Regulations, 1998 (SOR/99-7).
European Union (EU)
Carbon tetrachloride was evaluated under the 2012 Community rolling
action plan (CoRAP) under regulation (European Commission [EC]) No
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( on ill rv/Orgsi ni/nl ion
Requirements ;iihI Restrictions

1907/2006 - REACH (Registration, Evaluation, Authorisation and
Restriction of Chemicals) ECHA database. Accessed April 18, 2017).

Carbon tetrachloride is restricted by regulation (EC) No 2037/2000 on
substances that deplete the ozone layer.
Australia
Carbon tetrachloride was assessed under Environment Tier II of the
Inventory Multi-Tiered Assessment and Prioritisation (IMAP), and there
have been no reported imports of the chemical as a feedstock in the last
10 years (National Industrial Chemicals Notification and Assessment
Scheme, NICNAS, 2017, Environment Tier II Assessment for Methane,
Tetrachloro-. Accessed April, 18 2017).
Japan
Carbon tetrachloride is regulated in Japan under the following
legislation:
	Industrial Safety and Health Act (ISHA)
	Act on the Evaluation of Chemical Substances and Regulation of
Their Manufacture, etc. (Chemical Substances Control Law
(CSCL))
	Act on Confirmation, etc. of Release Amounts of Specific Chemical
Substances in the Environment and Promotion of Improvements to
the Management Thereof
	Poisonous and Deleterious Substances Control Act
	Act on the Protection of the Ozone Layer through the Control of
Specified Substances and Other Measures
	Air Pollution Control Law
	Water Pollution Control Law
	Soil Contamination Countermeasures Act
(National Institute of Technology and Evaluation (NITE) Chemical
Risk Information Platform (CHIRP). Accessed April 13, 2017).
Australia, Austria,
Belgium, Canada,
Denmark, EU, Finland,
France, Germany, Ireland,
Israel, Japan, Latvia, New
Zealand, People's
Republic of China,
Poland, Singapore, South
Korea, Spain, Sweden,
Switzerland, United
Kingdom
Occupational exposure limits (OELs) for carbon tetrachloride. (GESTIS
International limit values for chemical agents (Occupational exposure
limits, OELs) database. Accessed April 18, 2017).
Basel Convention
Halogenated organic solvents (Y41) are listed as a category of waste under
the Basel Convention-Annex I. Although the United States is not currently
a party to the Basel Convention, this treaty still affects U.S. importers and
exporter.
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( on ill rv/Orgsi ni/nl ion
Requirements nnd Restrictions
OECD Control of
Transboundary
Movements of Wastes
Destined for Recovery
Operations
Halogenated organic solvents (A3150) are listed as a category of waste
subject to The Amber Control Procedure under Council Decision C (2001)
107/Final.
Appendix B SECOND SCREENING OF PEER-REVIEWED
LITERATURE ON CARBON TETRACHLORIDE
This appendix describes the process used to re-screen the references identified as "on topic" in the first
screening round, including prioritizing the literature for screening and the re-categorization criteria
applied during the re-screening and tagging.
B.1 Scope of the Literature Re-screening
The aim of the first literature screening phase was to include all potentially relevant references that met
the screening criteria. A more detailed review of the "on topic" references revealed a large number of
animal studies that were likely to be of limited use for the following reasons:
si The aim of the study was to induce a disease state in an animal (e.g., cirrhosis, fibrosis, organ
damage: liver, kidney, testes and others) rather than evaluate the effects of carbon tetrachloride
exposure in animals
	Exposure was often via injection
In order to refine the search results for full-text screening, the inclusion/exclusion criteria were revised
to remove these studies from the "on topic" pool.
B.l.l Identifying Studies for Title/Abstract Re-screening
References (a total of 2,244) that were tagged to one or more of the categories below were identified for
re-screening. These were studies where carbon tetrachloride-treated animals were used as a model for
disease (e.g., cirrhosis, liver fibrosis) and/or in which the therapeutic or ameliorative properties of
different compounds were evaluated in carbon tetrachloride-treated animals:
i Animal Hazard ID
	Health Effects (in addition to Animal Hazard ID)
Hepatic non-cancer
-	Renal non-cancer
Neurological non-cancer
-	Reproductive/Developmental non-cancer
-	Immunological non-cancer
-	Cardiovascular non-cancer
-	Gastrointestinal non-cancer
Irritation
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Respiratory non-cancer
 Carcinogenicity
Other non-cancer health effect
	ADME
	Susceptibility
i MOA
	Unable to Determine
References tagged to "human hazard ID" were not included for re-screening, since they met the
screening criteria as "on topic". References tagged to "foreign language" were not considered a priority
for re-screening and so were not included for re-screening. Similarly, references included in the IRIS
assessment on carbon tetrachloride were not included in the re-screening since those studies conducted
on carbon tetrachloride were "on topic", as explained in the Literature Search Strategy documents.
B.2 Prioritizing References for Re-Screening
B.2.1 First Round of Prioritization for Re-screening
A keyword search and topic extraction (i.e., a form of unsupervised machine learning) were used to
identify a priority batch of 690 studies from the 2,244 studies eligible for re-screening (see Section
B. 1.1 Identifying Studies for Title/Abstract Re-screening). Topic extraction was conducted in ICF's
Document Classification and Topic Extraction Resource or DoCTER which includes functions for
supervised and unsupervised machine learning.
B.2.1.1 Keyword Search Method
A set of keywords was derived from the titles and abstracts of the on-topic references to be tagged to off-
topic during the second screening. The following references are examples of the types of studies that
EPA identified as off-topic\
i HERO ID 3482047; Preethi, KCK, R. (2009). Hepato and reno protective action of Calendula
officinalis L. flower extract. Indian journal of experimental biology 47: 163-168.
	HERO ID 3481928; Ozturk, FG, M. Ates, B. Ozturk, I. C. Cetin, A. Vardi, N. Otlu, A. Yilmaz, I.
(2009). Protective effect of apricot (Prunus armeniaca L.) on hepatic steatosis and damage induced
by carbon tetrachloride in Wistar rats. The British journal of nutrition 102: 1767-1775.
i HERO ID 3481815; Murugesan, GSS, M. Jayabalan, R. Binupriya, A. R. Swaminathan, K. Yun, S.
E. (2009). Hepatoprotective and curative properties of Kombucha tea against carbon tetrachloride-
induced toxicity. Journal of microbiology and biotechnology 19: 397-402.
	HERO ID 894818; Quan, JP, L. Wang, X. Li, T. Yin, X. (2009). Rossicaside B protects against
carbon tetrachloride-induced hepatotoxicity in mice. Basic & Clinical Pharmacology & Toxicology
Online Pharmacology Online 105: 380-386.
	HERO ID 1454032; Gao, JS, C. R. Yang, J. H. Shi, J. M. Du, Y. G. Zhang, Y. Y. Li, J. H. Wan, H.
T. (2011). Evaluation of the hepatoprotective and antioxidant activities of Rubus parvifolius L.
Journal of Zhejiang University Science B 12: 135-142.
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The keyword search, conducted in EndNote on the 2,244 studies eligible for re-screening (see F-l.l.
Identifying Studies for Title/Abstract Re-screening) returned 587 studies using the following search
strategy:
(hepatoprotective OR hepato protective OR hepatoprotection OR renoprotective OR reno protective OR
renoprotection)
B.2.1.2 DoCTER Method
To identify a priority set of studies for re-screening, we also used DoCTER's topic extraction function.
Unsupervised machine learning or topic extraction does not require a training dataset or seed studies.
DoCTER clusters or groups a list of titles and abstracts using automated text analysis on titles and
abstracts into a user-specified number of clusters. Studies in the same cluster are expected to be more
similar to one another based on automated text analysis of the titles and abstracts. DoCTER also
produces a set of keywords for each cluster that serves as a topic signature and provides insight into the
studies contained within.
Topic extraction was used to cluster all 2,749 on topic studies into 10 topic clusters using the k-means
algorithm and a word grouping length of one word. The terms copyright, publication, and abstract were
added as stop words and not included in the DoCTER analysis. Clusters 3 and 5 were prioritized for re-
screening and were combined with the results of the keyword search described above (TableApx B-l).
The 690 studies identified from the keyword search and topic extraction clusters 3 and 5 were re-
screened.
Table Apx B-l. Topic Extraction Results for 2,749 On-topic Studies using 10 Clusters and k-
means Algorithm	
Cliislcr
Number of
Results
ko words
1
157
factor nf fibrosis expression inflammatory il tnf hepatic anti rats
levels ccl kg oxidative effects treatment serum significantly
aminotransferase injury
2
98
stem marrow bone cells mscs transplantation mesenchymal derived
fibrosis human cell mice strong transplanted bm msc br injured
differentiation cirrhosis
3
200
antioxidant hepatoprotective glutathione activities sod activity gsh ast
superoxide alt mda ccl aminotransferase oxidative dismutase serum
extract injury levels mice
4
96
mir fibrosis expression tgf hscs hsc activation hepatic cells stellate
role factor cell mirnas proliferation growth fibrotic signaling
microrna fibrogenesis
5
266
hepatoprotective extract activity antioxidant rats strong extracts br
damage kg hepatotoxicity leaves effect mg silymarin serum
significant total activities scavenging
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( 'luster
Number ol
Results
ko words
6
370
fibrosis mice cells hepatic stellate expression hscs activation strong
injury cell br chronic hsc type activated role collagen inflammation
wild
7
317
kg rats ccl group mg oxidative antioxidant groups glutathione ml
protective effect damage treated activities serum treatment dose lipid
control
8
110
cirrhosis cirrhotic portal hypertension rats br strong pressure bacterial
intestinal resistance arterial hepatic vascular fibrosis translocation
increased expression gut ascites
9
867
rats injury mice exposure hepatotoxicity acute effect rat effects
fibrosis hepatic metabolism toxicity damage cell role lipid response
dna hepatocytes
10
268
strong br group fibrosis It model rats groups expression control
hepatic 05 significantly weeks methods normal levels 01 results tgf
B.2.1.3 List of Prioritized References for Re-Screening
References identified using both the keyword search and DoCTER's topic extraction were combined
and duplicate references removed to identify a priority batch of 690 studies from the 2,244 studies
eligible for re-screening (see Section B.l.l). Note the batch of studies eligible for re-screening excludes
studies cited in the IRIS assessment or tagged to human hazard identification or foreign-language.
B.2.2 Second Round of Prioritization for Re-screening
B.2.2.1 Keyword Search Method
A second keyword search was conducted in EndNote on the 1,566 remaining studies eligible for re-
screening. The 1,566 studies (2,244 studies eligible for screening (see Section B.l.l) minus 678 studies
screened in the first round of prioritization; note 12 studies, primarily foreign-language, were screened
in the batch of 690 from the first round of screening and were not included in the 2,244 studies eligible
for re-screening.) The following search strategy returned 602 studies:
(((carbon tetrachloride-induced OR ccl4-induced) AND (cirrhosis OR fibrosis OR liver damage OR
steatosis)) OR (oxidative stress OR oxidative damage OR antioxidant*))
B.2.2.2 DoCTER Method
For the second round of prioritization we used supervised clustering with an ensemble approach. With
supervised clustering, DoCTER clusters or groups a list of titles and abstracts plus seed studies using
automated text analysis on titles and abstracts into a user-specified number of clusters exactly as
described above in Section B.2.1. Seed studies may be positive or negative. Positive seeds or known
relevant studies are used to provide a quantitative signal as to which clusters to prioritize. Negative
seeds or known off-topic studies are optional and are used to predict precision for each cluster.
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Supervised clustering using an ensemble approach refers to running topic extraction with seeds using
multiple models. A model refers to an algorithm-cluster size combination (e.g., using k-means
algorithm to group into 10 clusters or KM-10 as a model). The results from each model run are compiled
and each reference is given a score based on how many models predicted it to be relevant. Scores for
each reference range from 0 (i.e., study not predicted relevant by any model) to n where n is the number
of models used and is the maximum score a study can receive.
We ran the 1,566 eligible studies through six models using the k-means and NMF algorithms and 10, 20,
and 30 clusters (i.e., KM-10, KM-20, KM-30, NMF-10, NMF-20, NMF-30) with 50 positive seeds.
Seeds (references) were randomly selected from results of the first round of re-screening i.e., references
that met the exclusion criteria (see Section B.2). A positive seed is a study used to find similar studies
and in this context positive seeds are studies that were excluded or re-tagged as not on topic in the first
round of re-screening. Supervised clustering was used here to identify additional studies that may be
excluded from the on topic pool of carbon tetrachloride studies.
Recall was set to 0.90 in DoCTER, such that for each model clusters were included until at least 90
percent of seeds were captured. Using all six models 98 percent of seeds were actually captured and 493
studies were identified as a priority for re-screening by one or more models (see Table below).
Table Apx B-2. Supervised Clustering Results for 1,566 On-topic Studies Using Ensemble
(>l'OII|)
( liislcr Scoit
Number of Studios
Running 1 oi ;i 1
A
6
7
7
B
5
24
31
C
4
44
75
D
3
80
155
E
2
106
261
F
1
232
493
Total
493
Notes:
Studies with a cluster score of 6 were predicted relevant by all six models
B.2.2.3 List of Prioritized References for Re-Screening
References identified using both the second keyword search (602) and supervised clustering in DoCTER
(493) were combined and duplicate references removed to identify 782 studies from the 1,566 studies
eligible for re-screening (see Section B.l.l). These references were screened in two batches; 493 from
DoCTER and 289 from the key word search method (duplicates removed). Note the batch of studies
eligible for re-screening excludes studies cited in the IRIS assessment or tagged to human hazard
identification or foreign-language.
Following the second round of prioritization, 784 studies remained. These were rescreened against the
criteria below.
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B.3 Re-screening Criteria and Process
This section describes the criteria applied during the second screening of the literature, the new criteria
applied and the process used to conduct the screening.
B.3.1 Re-screening Process
All references were re-screened in Distiller. The same screeners involved in the first round of screening
were involved in re-screening the literature. The screening process proceeded as follows:
i Batches of prioritized literature were imported into Distiller without the original tags from the first
screening round.
	An experienced screener trialed the screening instructions and amended them as needed, prior to
conducting the full screening exercise.
	Screeners were briefed on how to conduct the screening and given a set of instructions prior to
commencing the screening.
i An experienced screener was available to answer any questions and provide feedback to screeners.
	Each study was screened independently by two reviewers. Two other invididuals not involved in the
screening resolved the conflicts.
B.3.2 Re-screening Criteria
Studies were considered off-topic if:
Carbon tetrachloride was used to induce a non-cancer effect (e.g., Liver effects: hepatotoxicity, hepatic
steatosis, cirrhosis, liver injury, liver fibrosis; renal/kidney effects, repro/developmental effects:
testicular injury and others) to evaluate the protective or therapeutic effects of another compound
(e.g., plant extracts, drugs, antioxidants, or medicinal herbs).
Carbon tetrachloride was used as a model to induce a particular disease state in an animal. Often
includes studies where carbon tetrachloride was given to animals via injection to induce cirrhosis,
liver fibrosis or oxidative damage in the testes or brain. Often the study then evaluates either the
MOA or ameliorative effects of a therapeutic compound.
Carbon tetrachloride was used to induce toxicity or organ damage by measuring levels of e.g., serum
liver enzymes, markers of oxidative stress or damage in a particular organ (liver, kidney, testes,
brain), or histological changes, prior to, or after administering another (therapeutic) compound.
Carbon tetrachloride was used to induce fibrosis or cirrhosis and treatment was given after as a way to
treat that effect.
Studies that do not meet the exclusion criteria above were also considered off-topic if:
* Carbon tetrachloride was not specifically mentioned in the title or abstract
i Incorrectly tagged as on-topic during first round screening
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Table Apx B-3. Overview of Complete (Revised) Tagging Structure for Carbon Tetrachloride
"I'iiji Csilcfion
liH'liision/l'Aclusioii Crilerhi
I-Aiimplc keywords
on topic, cinirai. in man ihai.tn tacs
Animal Hazard ID
INCLUDE:
	Studies evaluating animal health effects resulting from controlled
exposure to the chemical in mammals such as primates, rodents, dog,
rabbit, and mink.
	* *Also choose applicable health effect tags in next section "Carbon
Tetrachloride Health Effect Tags"
EXCLUDE:
	Studies where carbon tetrachloride was used to induce a particular disease
state or noncancer effect in an animal to (e.g., Liver effects:
hepatotoxicity, hepatic steatosis, cirrhosis, liver injury, liver fibrosis;
renal/kidney effects; repro/developmental effects: testicular injury, and
others) to:
o evaluate the protective or therapeutic effects of another
compound (e.g., plant extracts, drugs, antioxidants, or medicinal
herbs) or,
	Studies where carbon tetrachloride was used in addition to other
treatments (e.g., 2-AAf, LPS, or partial hepatectomy) in order to cause a
specific effect or response in the liver
	Studies that evaluated carbon tetrachloride-induced toxicity or organ
damage by measuring levels of e.g., serum liver enzymes, markers of
oxidative stress or damage in a particular organ (liver, kidney, testes,
brain), or histological changes, prior to, or after administering another
(therapeutic) compound.
chronic; developmental;
incidence; NOEL/LOEL;
NOAEL/LOAEL; dose;
response
MOA
INCLUDE:
	Studies evaluating the mode of action (MOA) of a chemical (i.e.,
molecular events occurring after exposure that may contribute to the
development of adverse health effects) in animals and humans
	Studies in knockout mice
	Assessment of hormone levels or gland function, immune system
parameters
"Also choose applicable MOA tags in section below under "Carbon
Tetrachloride MOA Tags"
EXCLUDE:
	Studies that evaluated carbon tetrachloride-induced toxicity or organ
damage by measuring levels of e.g., serum liver enzymes, markers of
oxidative stress or damage in a particular organ (liver, kidney, testes,
brain), or histological changes, prior to, or after administering another
(therapeutic) compound.
in vitro models, genomics,
proteomics, genotoxicity,
indirect genotoxicity, changes
in gene expression or mRNA
levels
ON TOPIC. CARBON 11.1 RA( IIIORIDI. (( ( 1.4) III AI I II I I-IT.CT TACS
I Iepalic non-cancer
INCLUDE:
 Studies evaluating hepatic effects in the liver, biliary tract, gall bladder
fatty degeneration, cirrhosis,
fibrosis, necrosis,
hypertrophy, hyperplasia,
proliferation,
increased/decreased liver
enzymes, bile acids,
cholesterol and triglycerides
in serum/blood,
increased/decreased liver
weight, jaundice,
vacuolization
Renal non-cancer
INCLUDE:
 Studies evaluating renal effects in the kidney, bladder, ureter and related
nephropathy, oliguria,
increased/decreased blood
urea nitrogen, nephritis,
nephrosis, hyaline droplet
formation, necrosis and
regeneration of proximal
tubules, markers of kidney
damage e.g. excretion of
proteins/blood in urine, alpha
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I'jili ('silicon
liH'liisioii/I'lxcliisioii Criioriii
I'Aiimpk' keywords


2U globulin
Neurological non-cancer
INCLUDE:
 Studies evaluating effects in the central nervous system (CNS) or
peripheral nervous system, brain, nerves, behavior, neurochemical
alterations, sensory effects, neurodevelopmental effects in exposed infants
and children
changes in brain pathology,
CNS depression (dizziness,
drowsiness, sleepiness, loss of
consciousness/ anesthesia,
hypo activity, ataxia, lethargy,
impaired coordination or
balance, narcosis),
nerve/neuronal injury and/or
degeneration,
neuropsychological outcomes
(e.g. mood/personality
changes), changes in
neurobehavioral tests
(cognitive, motor function)
and neurophysiological effects
(visual and auditory function),
memory
Reproductive/Developmental
non-cancer
INCLUDE:
 Studies examining reproductive outcomes, offspring and/or studies
examining developmental effects
Notes:
Developmental neurotoxicity effects are categorized in the
Reproductive/Developmental non-cancer tag and Neurological non-cancer tag
reduced fertility, effects on
reproductive organs, sperm,
estrous cycle, increased
resorption and post
implantation loss, viability,
fetal death, birth weight,
growth, maturation,
teratogenicity, birth defects,
visceral and/or skeletal
malformations, follicle counts
Immunological non-cancer
INCLUDE:
 Studies examining susceptibility or resistance to infection or disease,
function of innate or adaptive immunity
hypersensitization,
increased/decreased white
blood cells, effects on the
spleen
Cardiovascular non-cancer
INCLUDE:
 Studies examining cardiovascular effects in the heart and vasculature
stroke, hypertension,
tachycardia, cardiac
arrhythmias
Gastrointestinal non-cancer
INCLUDE:
 Studies examining gastrointestinal effects on the mouth, on dentition,
salivary glands, esophagus, stomach, intestines, rectum
nausea, vomiting, abdominal
pain, anorexia
Irritation
INCLUDE:
 Studies examining irritation (primary or secondary) of the skin, eyes,
gastrointestinal tract or respiratory tract
erythema, itching, blisters,
swelling, edema (skin); pain
swelling, lacrimation,
photophobia (eyes); nausea,
vomiting, and abdominal pain
(gastrointestinal tract),
rhinitis, prickling or burning
sensation in the nose and
throat, dry, scratchy throat
(respiratory tract)
Respiratory non-cancer
INCLUDE:
 Studies examining non-cancer respiratory effects in the lungs
chemical pneumonitis,
inflammation,
bronchopneumonia, alveolar
epithelial proliferation,
edema, lung disease,
bronchitis, pulmonary
function tests, FEF, FEV1,
bronchitis, COPD, cough,
chest discomfort, PEFR,
respiratory symptoms,
respiratory infection, dyspnea,
wheeze, lung function, effects
on the nasal cavity (nasal
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I'jili ('silicon
liH'liisi(iii/l'l\cliision Criioriii
I'Aiimpk' keywords


respiratory and olfactory
epithelium), bronchial or
tracheal epithelium
Carcinogenicity
INCLUDE:
 Studies that evaluate any cancer effect
particular cancers include:
breast, liver, kidney, blood,
lymph, adrenal gland
Other non-cancer health effect
INCLUDE:
 Studies in which other non-cancer health effects, not defined by the
cateaories above, were examined
NA
ON TOPIC. CARBON TITRACIIIORIDI (CCI4) MOA TACS
NOT ON TOPIC
Not 011 topic
LNCLIDE:
 Reference is not on topic in the context of any of the outlined categories
(or tags)
NA
B.4	Results
Out of the 2,244 studies eligible for re-screening, 678 studies were identified in the first batch of
prioritized references and screened independently by two individuals. These references were moved to
off-topic since they met the re-screening exclusion criteria. Of the remaining 1,566 studies, the re-
screening resulted in 45 references that met the inclusion criteria and were retained as on-topic
references. The remaining studies, or 1,521, met the criteria for exclusion and were moved to off-topic.
Appendix C PROCESS, RELEASE AND OCCUPATIONAL
EXPOSURE INFORMATION
This appendix provides information and data found in preliminary data gathering for carbon
tetrachloride.
C.l	Process Information
Process-related information potentially relevant to the risk evaluation may include process diagrams,
descriptions and equipment. Such information may inform potential release sources and worker
exposure activities for consideration.
C.l.l Manufacture (Including Import)
C.l.1.1 Domestic Manufacture
Carbon tetrachloride was previously produced solely through the chlorination of carbon disulfide (CS2);
however, in the 1950s chlorination of hydrocarbons became popular (Holbrook. 2000). Currently, most
Carbon tetrachloride is manufactured using one of three methods: chlorination of hydrocarbons or
chlorinated hydrocarbons; oxychlorination of hydrocarbons; or CS2 chlorination (Holbrook. 2000).
 Chlorination of hydrocarbons or chlorinated hydrocarbons - The chlorination of hydrocarbons
involves a simultaneous breakdown of the organics and chlorination of the molecular fragments
at pyrolytic temperatures and is often referred to as chlorinolysis (Holbrook. 2000). A variety of
hydrocarbons and chlorinated hydrocarbon waste streams can be used as feedstocks; however,
methane is the most common (Holbrook. 2000). PCE is formed as a major byproduct of this
Page 82 of 112

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process with small volumes of hexachloroethane, hexachlorobutadiene and hexachlorobenzene
also produced (Holbrook. 2000).
	Oxychlorination of hydrocarbons - The oxychlorination of hydrocarbons involves the reaction
of either chlorine or hydrochloric acid (HC1) and oxygen with a hydrocarbon feedstock in the
presence of a catalyst (Marshall and Pottenger. 2*I *, Holbrook. 2000). This process can be
utilized to convert HC1 produced as a byproduct during the manufacture of chlorinated
hydrocarbons into useful products (Marshall and Pottenger. 2016).
	CS2 Chlorination - The chlorination of CS2 involves the continuous reaction of CS2 with
chlorine in an annular reaction (Holbrook. 2000). The carbon tetrachloride produced is distilled
to have a CS2 content of 0 to 5 ppm. This process produces disulfur dichloride as a byproduct
that is reduced with hydrogen without a catalyst or with a ferric chloride catalyst (Holbrook.
2000).
Based on EPA's knowledge of the chemical industry, worker activities at manufacturing facilities may
involve manually adding raw materials or connecting/disconnecting transfer lines used to unload
containers into storage or reaction vessels, rinsing/cleaning containers and/or process equipment,
collecting and analyzing QC samples, manually loading carbon tetrachloride product or
connecting/disconnecting transfer lines used to load carbon tetrachloride product into containers.
C.l.1.2 Import
EPA has identified activities related to the import of carbon tetrachloride through comments submitted
in public docket EP A-HQ-OPPT -2016-0733. Based on EPA's knowledge of the chemical industry,
imported chemicals are often stored in warehouses prior to distribution for further processing and use. In
some cases, the chemicals may be repackaged into differently sized containers, depending on customer
demand, and QC samples may be taken for analyses.
C.1.2 Processing and Distribution
C.l.2.1 Reactant or Intermediate
Processing as a reactant or intermediate is the use of carbon tetrachloride as a feedstock in the
production of another chemical product via a chemical reaction in which carbon tetrachloride is
consumed to form the product. In the past, carbon tetrachloride was mainly used as feedstock for the
manufacture ch 1 orofluorocarbons (CFCs) (Marshall and Pottenger. 2016). However, due to the
discovery that CFCs contribute to stratospheric ozone depletion, the use of CFCs was phased-out by the
year 2000 to comply with the Montreal Protocol (Holbrook. 2000).
Currently, carbon tetrachloride is used as a feedstock to produce a variety of products including HCFCs,
HFCs, HFOs, vinyl chloride, ethylene dichloride (EDC), PCE, chloroform, hafnium tetrachloride,
thiophosgene and methylene chloride (EPA-HO-OPPT-Ji*I < >733-00030 * I P \	Marshall
and Pottenger. 2016; Weil et at.. 2006; Holbrook. 2003 a. b)) . The specifics of the reaction process (e.g.,
use and types of catalysts, temperature conditions, etc.) will vary depending on the product being
produced; however, a typical reaction process would involve unloading carbon tetrachloride from
containers and feeding into the reaction vessel(s), where carbon tetrachloride would either fully or
partially react with other raw materials to form the final product. Following the reaction, the product
may or may not be purified to remove unreacted carbon tetrachloride (if any exists). Reacted carbon
tetrachloride is assumed to be destroyed and thus not expected to be released or cause potential worker
exposure.
Page 83 of 112

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Carbon tetrachloride is used in reactive ion etching (RIE). RIE involves ion bombardment to achieve
directional etching and a reactive gas, such as carbon tetrachloride, to selectively maintain etched layers
rEPA-HO-OPPT~2.(	)003 (U.S. EPA. 2017d)l.
EPA has not identified specific worker activities related to the processing of carbon tetrachloride as a
reactant or intermediate at this time. However, based on EPA's knowledge of the chemical industry,
worker activities are expected to be similar to that at manufacturing facilities including unloading and
loading activities, rinsing/cleaning activities and collecting and analyzing QC samples.
C. 1.2.2 Incorporation into a Formulation, Mixture or Reaction Products
Incorporation into a formulation, mixture or reaction product refers to the process of mixing or blending
of several raw materials to obtain a single product or preparation. Process descriptions for use of carbon
tetrachloride use as a process agent were not identified at this time. However, the processes are expected
to be similar to those described above and typically involve unloading formulation components from
transport containers, either directly into the mixing equipment or into an intermediate storage vessel,
mixing of components either a batch or continuous system, QC sampling and final packaging of the
formulation in to containers. Depending on the product, formulation products may be filtered prior to
packaging. Transfer from transport containers into storage or mixing vessels may be manual or
automated, through the use of a pumping system. If automated, an automated dispenser may be used to
feed the components into the mixing vessel to ensure that precise amounts are added at the proper time
during the mixing process. Final packaging occurs either through manual dispensing from transfer lines
or through utilization of an automatic system.
There is significant overlap in worker activities across the various formulation processes. The activities
are expected to be similar to manufacturing activities and include unloading and loading activities,
rinsing/cleaning activities and collecting and analyzing QC samples (OECD. 2009a. b).
C. 1.2.3 Repackaging
Typically, repackaging sites receive the chemical in bulk containers and transfer the chemical from the
bulk container into another smaller container in preparation for distribution in commerce. Based on
EPA's knowledge of the chemical industry, worker activities at repackaging sites may involve manually
unloading carbon tetrachloride from bulk containers into the smaller containers for distribution or
connecting/disconnecting transfer lines used to transfer carbon tetrachloride product between containers
and analyzing QC samples. EPA will further investigate the potential use of carbon tetrachloride in this
type of process during the risk evaluation.
C.l.2.4 Recycling
TRI data from 2015 indicate that some sites ship carbon tetrachloride for off-site recycling. A general
description of waste solvent recovery processes was identified. Waste solvents are generated when it
becomes contaminated with suspended and dissolved solids, organics, water or other substance (U.S.
EPA. 1980). Waste solvents can be restored to a condition that permits reuse via solvent
reclamation/recycling (U.S. EPA. 1980). The recovery process involves an initial vapor recovery (e.g.,
condensation, adsorption and absorption) or mechanical separation (e.g., decanting, filtering, draining,
setline and centrifuging) step followed by distillation, purification and final packaging (U.S. EPA.
1980). Worker activities are expected to be unloading of waste solvents and loading of reclaimed
solvents. Figure Apx C-l illustrates a typical solvent recovery process flow diagram (	980).
Page 84 of 112

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Storage
Tank
Vent
Storage
Tank
Vent
Fugitive
Emissions
Fugitive
Emissions
Fugitive
Emissions
Fugitive
Emissions
Solvent
Incinerator Stack
Fugitive Emissions
Storage
and
Handling
Storage
and
Handling
FigureApx C-l. General Process Flow Diagram for Solvent Recovery Processes
Source: (U.S. EPA. 1980)
Page 85 of 112

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C.1.3 Uses
In this document, EPA has grouped uses based on CDR categories and identified examples within these
categories as subcategories of use. Note that some subcategories may be grouped under multiple CDR
categories. The differences between these uses will be further investigated and defined during risk
evaluation.
C.l.3.1 Petrochemicals-derived Products Manufacturing
EPA has identified uses of carbon tetrachloride as a process agent (i.e., processing aid such as catalyst
regeneration or as an additive) at manufacturing facilities of petrochemicals-derived products [EPA-HQ-
QPPT-2016-0733-0003; (\ \ U" \ A) I ,1); (UNEP/Ozone Secretariat. 1998V1. EPA has also identified
a patent which indicates a potential use of carbon tetrachloride as a fuel additive.
C.l.3.2 Agricultural Products Manufacturing
EPA has identified uses of carbon tetrachloride as a process agent in the manufacturing of fertilizers and
other agricultural products fEP A-HQ-OPPT- 733-0003; (U.S. EPA. 2017d); OJNEP/Ozone
Secretariat. 1998).
C.l.3.3 Other Basic Organic and Inorganic Chemical Manufacturing
EPA has identified uses of carbon tetrachloride as a process agent in the manufacturing of inorganic
compounds (i.e., chlorine), pharmaceuticals (i.e., ibuprofen) and chlorinated compounds that are used in
the formulation of solvents for cleaning and degreasing, adhesive and sealants, paints and coatings and
asphalt [H* \ ' lQ-OPPT-20j u-0 '33-0003, (l_ S_rp_\	Therefore, EPA expects carbon
tetrachloride is only present in cleaning, degreasing, paints, coatings, and asphalt formulations as an
impurity rather than serving a specific function. Appendix D presents a list of domestic and
internationally approved uses of carbon tetrachloride as a process agent in MP side agreement: Decision
X/14: Process Agents OJNEP/Ozone Secretariat. 1998).
C.l.3.4 Laboratory Chemicals
Carbon tetrachloride is used in laboratories as a chemical reagent, extraction solvent and a reference
material or solvent in analytical procedures, such as spectroscopic measurements [EPA-HQ-OPPT-
2016-0733-0003; (U.S. EPA.: )].
C.l.3.5 Other Uses
Carbon tetrachloride may also be used in metal recovery and other specialty uses identified by the
aerospace industry, such as the manufacture, operations and maintenance of aerospace products and for
specific cleaning operations (EPA-HQ-OPPT-2016-0733-0063).
C.l.3.6 Disposal
Table 2-6 and Table 2-7 present the production-related waste managed data for carbon tetrachloride
reported to the TRI program for 2015. Waste containing carbon tetrachloride is classified as hazardous
waste (see Table Apx A-l). Facilities generating waste containing carbon tetrachloride must comply
with EPA regulations for treatment, storage, and disposal.
C.2 Occupational Exposure Data
EPA presents below an example of occupational exposure-related information from the preliminary data
gathering. EPA will consider this information and data in combination with other data and methods for
Page 86 of 112

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use in the risk evaluation. TableApx C-l. summarizes OSHA CEHD data by NAICS (North American
Industrial Classification System) code (see Section 2.3.5.1) and Table Apx C-2. summarizes NIOSH HHE data.
Page 87 of 112

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TableApx C-l. Summary of Carbon Tetrachloride Personal Monitoring Air Samples Obtained from OSHA Inspections Conducted
Between 2013 and 2015
i- Sivniiriii
NAICS
NAICS
IK'siripiiiui
N-lir TWA CiiiHi-nlnilinn (ppm)'
S i l l., IViik, in- ( i-iliii!! CiiiHeiilralinn (ppm)
NiiihIkt
til' l);il;i
Points
Minim n
in
M;i\iiiiiiin
Awr;ii-
Number ill'
/.i-m
Values1'
Number
hI' l);il;i
Points
Mini
ill u in
M;i\iniiini
A\erae
Number
III' /l-I'll
Values1'
Unknown-job
title and
company
information did
not indicate
how carbon
tetrachloride
may be used
322121
Paper (except
Newsprint)
Mills
4
0
0
0
4
4
0
0
0
4
Vapor
degreasing or
cold cleaning
331512
Steel
Investment
Foundries
3
0.026
0.027
0.026
0
No Data Available
Vapor
degreasing or
cold cleaning
332439
Other Metal
Container
Manufacturing
2
0.026
0.026
0.026
0
No Data Available
Vapor
degreasing or
cold cleaning
336111
Automobile
Manufacturing
2
0
0
0
2
2
0
0
0
2
Unknown - this
seems to be for
OSHA
inspectors
which could
have been
collected during
site inspections
926150
Regulation,
Licensing, and
Inspection of
Miscellaneous
Commercial
Sectors
1
0
1
1
0
1
a Assumes all TWA data are 8-hr TWA.
b For facilities where all samples are measured as zero, it is unclear if carbon tetrachloride is present at the facility.
Page 88 of 112

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Table Apx ( -2. Summnry of Monitoring Data from NIOSH I
l);il;i Sou i co
Report
Nil in Ikt
Kxposiiiv/Kcleiise
Sccnsirio
l-'sicilil>
Description
N urn her
ol'
|-'.\pOMIIV
Ssimples
Minimum
ol'
|-'.\pOMIIV
\ 'sillies
(ppill)
Msiximum
ol'
l'l\pOMIIV
\ SlIlK'S
(ppill)
( ommenls
NIOSH 1992a
HETA-
1990-
223-
2211
Vapor degreasing
Cathode ray
tube
manufacturing
0
No exposure data for
carbon tetrachloride
provided.

NIOSH, 1992b
HETA-
1991-
188-
2205
General
population
exposures
Elementary
school
6
ND
0.03
1 to 2-hr area
measurements.
NIOSH, 2005
HETA-
2004-
169-
2982
Manufacture of
carbon
tetrachloride
Magnesium
manufacturer
11
PBZ: ND
Area: ND
PBZ: 0.03
Area: ND
8-hr TWA values
ealth Hazard Evaluations Conducted since 1990
Appendix D PROCESS AGENT USES FOR CARBON TETRACHLORIDE
Table Apx D-l. List of Uses of Carbon Tetrachloride as Process Agent in MP side agreement: Decision X/14: Process Agents
i
Elimination of nitrogen trichloride in the production of chlorine and caustic
10
Manufacture of chlorinated paraffin
2
Recovery of chlorine in tail gas from production of chlorine
11
Production of pharmaceuticals - ketotifen, anticol and disulfiram
3
Manufacture of chlorinated rubber
12
Production of tralomethrine (insecticide)
4
Manufacture of endosulphan (insecticide)
13
Bromohexine hydrochloride
5
Manufacture of isobutyl acetophenone (ibuprofen - analgesic)
14
Diclofenac sodium
6
Manufacture of 1-1, Bis (4-chlorophenyl) 2,2,2- trichloroethanol (dicofol insecticide)
15
Cloxacilin
7
Manufacture of chlorosulphonated polyolefm (CSM)
16
Phenyl glycine
8
Manufacture of poly-phenylene-terephtal-amide
17
Isosorbid mononitrate
9
Manufacture of styrene butadiene rubber
18
Omeprazol
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Appendix E SURFACE WATER ANALYSIS FOR CARBON
TETRACHLORIDE RELEASES
During problem formulation, EPA modeled industrial discharges to surface water to estimate surface
water concentration using EPA NPDES permit Discharge Monitoring Report (DMR) data on the top 10
highest carbon tetrachloride releasing facilities. DMR data are submitted by facilities in order to comply
with NPDES permit requirements, including limits to pollutants discharged to receiving waters. EPA
used the Probabilistic Dilution Model (PDM) within E-FAST to estimate annual discharges for the
facilities. In order to estimate a range of conservative surface water concentrations, the 2015 NPDES
DMR data reporting carbon tetrachloride discharges were used in a first-tier analysis, which estimates
conservative carbon tetrachloride surface water concentrations (i.e., conservative exposure scenarios).
The surface water concentrations were estimated using a range of high-end number of release days (i.e.,
20 and 250 days/year) instead of the default 365 days/year. Other conservative assumptions in the first-
tier analysis include the use of zero percent removal of carbon tetrachloride by the wastewater treatment
facility and low hydrological flow.
DMR data confirmed that facility discharges used in this first-tier analysis were discharging at least 20
days per year. EPA did not include a single day release scenario since this was not a likely scenario that
would be allowed under current NPDES permit requirements. The other input parameter important for
determining surface water concentrations is wastewater removal efficiency since the NPDES permits
require industrial wastewater treatment removal. Table Apx E-l presents the first-tier estimate of surface
water concentrations. Public owned treatment works (POTW with SIC 4952) are municipal facilities that
receive industrial discharges containing carbon tetrachloride and reported these concentrations in the
facility DMRs. Since these facilities discharge 365 days per year, the 20-day discharge scenario is not
considered and the 250 day/year discharge is the only modeled scenario. Using these conservative
scenarios, carbon tetrachloride surface water concentrations were mostly below the COCs for aquatic
species (62 [j,g/L and 7 [j,g/L for acute and chronic, respectively). The PDM calculates the probability of
the COC being exceeded using 7Q10 (i.e., 7 consecutive days of 10th percentile low flow) low flow
statistics. Thus, surface water concentrations that slightly exceed the chronic COC are not considered
statistically significant as to present a concern for aquatic organisms.
Table Apx E-l. Modeled Carbon Tetrachloride Surface Water Concentrations
SIC
( Olio
Tool
Pounds
(Ihs/vr) -
2015
l)Mk
Diilii
PI)
1 up
20 dsivs
(k)
SurfjuT \N ;il
(oiHTiilnili
20 dsivs
(uji/l.)
Cl-
ous
250 dsivs
(uji/l.)
Aculo
COC
(uji/l.)
C h ronic
c oc
(uii/L)
4952
134
N/Aa
0.24
N/Aa
24 77b
62
7
2819
110
2.49
0.20
0.13
0.011
62
7
2819
23.7
0.54
0.04
0.002
0.0002
62
7
2869
325
7.37
0.59
0.030
0.002
62
7
2869
20.9
0.12
0.04
28.37
8.98
62
7
2812
13.9
0.31
0.02
0.037
0.003
62
7
7996
13.8
0.31
0.03
0.74
0.06
62
7
2869
12.9
0.29
0.02
20.14
1.6
62
7
Page 90 of 112

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Tot;il
I'DM
Surface Water



Pounds
Inputs
Concent rations



(lhs/vr) -







2015




Acute
Chronic
SIC
l)MK
20 dsivs
250 dsivs
20 daYs
250 daYs
COC
COC
C "ode
Data
(k/d:i>)
(k$>/d:i\)
(UJi/l.)
dig/l.)
(UJi/l.)
(UJi/l.)
2819
9.85
0.22
0.02
0.0009
0.0001
62
7
4953
8.94
0.20
0.02
13.05
1.04
62
7
a Not applicable; the 20-day discharge scenario is not considered because this facility only discharges 365 days per year
B This surface water concentration value above the Chronic COC is based on highly conservative assumptions, including 0%
removal of carbon tetrachloride by the waste water treatment facility. As explained in Section 2.3.1, the EPI Suite STP
module estimates that about 90% of carbon tetrachloride in wastewater will be removed by volatilization and 2% by
adsorption.
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Appendix F SUPPORTING TABLE FOR INDUSTRIAL AND COMMERCIAL
ACTIVITIES AND USES CONCEPTUAL MODEL
During problem formulation, EPA reviewed preliminary data and mapped conditions of use into corresponding exposure scenarios. TableApx F-l
summarizes the scenario mapping. The table also provides rationale on whether EPA will further assess each scenario during risk evaluation.
Table Apx F-l. Industrial and Commercial Activities and Uses Conceptual Model Supporting Table
"Note that rows shaded in gray are not proposed for further analysis) 			
l .ile ( >cle
S(;ie
Csilcfion
SulK'siU'^on
Kok'iiso /
r.\|)(isuiv
Smiiirio
l'l\|)UMIIV
I'iilliNin
r.\|)(isuiv
Koulo
Km'plor /
Population
Proposed
for l-'iirihcr
Risk
l.\;ilu;i(ion
Kiilioiiiilo for l iiidu i-
r.Miliinlion / no l-'urlhcr
ll\;ilu;i(ion
Manufacture
Domestic
Manufacture
Domestic
Manufacture
Manufacture of
carbon
tetrachloride via
chlorination of
hydrocarbons,
oxychlorination
of
hydrocarbons,
chlorination of
carbon
disulfide, and as
a byproduct
Liquid
Contact
Dermal
Workers
Yes
Contact time with skin is
expected to be <2 min due to
rapid volatilization.
However, the number of
workers exposed may be high
per CDR (3 submissions
reporting 100-500 workers
per submission).
Vapor
Inhalation
Workers
Yes
Due to high volatility (VP =
115 mmHg) at room
temperature, inhalation
pathway should be further
analyzed.
Liquid
( OIllJIOl
1 >criii;i 1
<>\l
\o
Domini ONpusiiio iso\poolod
lii ho prini:iril\ id uorkors
diioolK in\i
-------
l .ile ( >cle
S(;ie
Csilcfion
SulK'siU'^on
Kok'iiso /
r.\|)(isuiv
Scciiiii'io
l'l\|)UMIIV
I'illllWil.t
l'l\|)UMIIV
Koulo
Km'plor /
I'upiikilion
Proposed
for I n rllier
Kisk
r.\iilu;ilion
Kiilioiiiilo I'oi" l iiidu i-
l-'\;iln;iliui / no l-'urtlier
l'l\iilu;ilion




Vapor
Inhalation
ONU
Yes
Due to high volatility (VP =
115 mmHg) at room
temperature, inhalation
pathway should be further
analyzed.
\lls|
Dermal
Inhalation
Workers.
()\l
\d
Mm uciicralimi imi c\|xvlcd
diiiiiiu maiiiilacliiriim
Manufacture
Import
Import
Repackaging of
import
containers
Liquid
Contact
Dermal
Workers
Yes
Contact time with skin is
expected to be <2 min due to
rapid volatilization. The
number of import sites is
limited (<6 sites) per CDR.
Exposure will only occur in
the event the imported
material is repackaged.
Vapor
Inhalation
Workers
Yes
Exposure expected only in
the event the imported
material is repackaged into
different sized containers.
Exposure frequency may be
low.
Liquid
( oniacl
Dermal
<>\l
\o
Dermal e\pnsure ise\pecled
lii he primariK lo u orkers
direclk in\i
-------
l .ile ( >cle
S(;ie
Csilcfion
SulK'siU'^on
Kok'iiso /
r.\|)(isuiv
Scciiiirio
l'l\|)UMIIV
I'alhwin
r.\|)(isuiv
Koulo
Km'plor /
Population
Proposed
I'o i* lurdur
Risk
l-'\illllill ifill
Rationale I'oi* l-'urilKT
l-'\;iln;iliui / no I'llrllier
ll\aliia(ion




\lls|
Dermal
Inhalation
Willie is.
()\l
\n
Mm ueueralinu uni e\pecled
diiriiiu impoi'i.
Processing
Processing as a
reactant
Intermediate in
industrial gas
and
semiconductor
manufacturing;
Manufacture of
HCFCs, HFCs,
HFOs, and
PCE; Reactive
ion etching
Liquid
Contact
Dermal
Workers
Yes
Contact time with skin is
expected to be <2 min due to
rapid volatilization.
However, the number of
workers may be high per
CDR (2 submissions
reporting <10 workers, 1
submission reporting 10-25
workers, 1 submission
reporting 25-50 workers, and
2 submissions reporting 100-
500 workers).
Vapor
Inhalation
Workers
Yes
Due to high volatility (VP =
115 mmHg) at room
temperature, inhalation
pathway should be further
analyzed. However, potential
for exposure may be low in
scenarios where carbon
tetrachloride is consumed as
a chemical intermediate.
Liquid
( unlacl
Dermal
()\l
\n
Dermal e\pnsure ise\pecled
lii he primarily in workers
direclk m\iil\ed in worknm
u iili ihe chemical
Page 94 of 112

-------
l .ile ( >cle
S(;ie
Csilcfion
SulK'siU'^on
Kok'iiso /
r.\|)(isuiv
Scciiiirio
r.\|)(isuiv
Piilliw ;i>
r.\|)(isuiv
Koulo
Km'plor /
Population
Proposed
for l-'iirihcr
Risk
l.\alua(ion
Rationale I'oi* l-urtIter
l'l\;ilii;ilion / no I'll rl her
ll\alua(ion




Vapor
Inhalation
ONU
Yes
Due to high volatility (VP =
115 mmHg) at room
temperature, inhalation
pathway should be further
analyzed. However, potential
for exposure may be low in
scenarios where carbon
tetrachloride is consumed as
a chemical intermediate.
\lls|
Dermal
Inhalation
Workers.
()\l
\o
Mm ueueralimi noi c\|xvlcd
durum processiim as an
lllkTIUcdiak'.
Page 95 of 112

-------
l .ile ( >cle
S(;ie
Csilcfion
SulK'siU'^on
Kok'iiso /
r.\|)(isuiv
Smiiirio
l'l\pOMIIV
I'iilliNin
r.\|)(isuiv
Uoule
Km'plor /
Population
Proposed
for l-'urihcr
Risk
l.\alua(ion
Rationale I'oi* l-urtIter
r.\aliialion / no l-~nrllior
ll\alua(ion
Processing
Incorporated
into
formulation,
mixture or
reaction
product
Petrochemical-
derived and
agricultural
products
manufacturing;
Other basic
organic and
inorganic
chemical
manufacturing;
Other uses
Manufacturing
of organic and
inorganic
chlorinated
chemicals,
pharmaceutical
manufacturing,
use in specialty
operations by
aerospace
industry
Liquid
Contact
Dermal
Workers
Yes
Contact time with skin is
expected to be <2 min due to
rapid volatilization.
Vapor
Inhalation
Workers
Yes
Exposure frequency may be
low.
Liquid
( ouiacl
Dermal
OM
\o
Dermal e\pnsurc ise\pecled
lii he primarily lo workers
direclK iu\ol\ed iiiworkiuu
w iih ihe chemical.
Vapor
Inhalation
ONU
Yes
Exposure frequency may be
low.
\lls|
Dermal
Inhalation
Workers.
<)\l
\o
Misi ueucralinii noi e\pecled
Processing
Repackaging
Laboratory
Chemicals
Repackaging
into large and
small containers
Liquid
Contact
Dermal
Workers
Yes
Contact lime w illi skin is
expected to be <2 min due to
rapid volatilization.
Vapor
Inhalation
Workers
Yes
Exposure frequency may be
low.
Liquid
(ouiacl
Dermal
<)\l
\o
Dermal e\pnsurc ise\pecled
lii he primarily lo workers
direclK iu\iil\ed uiwiirkiim
w illi ihe chemical.
Vapor
Inhalation
ONU
Yes
Exposure frequency may be
low.
\lls|
Dermal
Inhalation
Workers.
OM
\o
Misi ueiieralinii nui e\pecled
durum repackauiuu
Page 96 of 112

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l .ile ( >cle
S(;ie
Csilcfion
SulK'siU'^on
Kok'iiso /
r.\|)(isuiv
Scciiiii'io
l'l\|)UMIIV
I'illllWil.t
r.\|)(isuiv
Koulo
Km'plor /
Pnpuhilion
Proposed
lor l-'iirihcr
Risk
l-'\illllill ifill
Kiilioiiiilo I'oi* lui'llur
l-'\;iln;iliui / no I'llrllier
ll\;ilu;i(ion
Processing
Recycling
Recycling
Recycling of
process solvents
containing
carbon
tetrachloride
Liquid
Contact
Dermal
Workers
Yes
Contact time with skin is
expected to be <2 min due to
rapid volatilization.
Vapor
Inhalation
Workers
Yes
Inhalation exposure is
expected at recycling sites.
Due to high volatility (VP =
115 mmHg) at room
temperature, inhalation
pathway should be further
analyzed.
Liquid
( Diiiacl
Dermal
()\l
\o
Dermal c\posuic is especial
lii he primarily lo workers
dueclK iu\ol\cd mi woikinu
u nh ilie chemical
Vapor
Inhalation
ONU
Yes
Inhalation exposure is
expected at recycling sites.
Due to high volatility (VP =
115 mmHg) at room
temperature, inhalation
pathway should be further
analyzed.
\lls|
Dermal
liihalalK
-------
l .ile ( >cle
S(;ie
Csilcfion
SulK'siU'^on
Kok'iiso /
r.\|)(isuiv
Scciiiirio
l'l\pOMIIV
I'iilliNin
l'l\pOMIIV
Uoule
Km'plor /
Population
Proposed
for l ur(lu r
Risk
l.\;ilu;i(ion
Kiilioiiiilo for l urdur
1'\;iIn;i 1 ion / no l-'iirlhcr
ll\;ilii;i(ion
Distribution
in commerce
Distribution
Distribution
Distribution of
bulk shipment
of carbon
tetrachloride;
and distribution
of formulated
products
Liquid
Contact,
Vapor
Dermal/
Inhalation
Workers,
ONU
Yes
EPA will further analyze
activities resulting in
exposures associated with
distribution in commerce
(e.g. loading, unloading)
throughout the various
lifecycle stages and
conditions of use (e.g.
manufacturing, processing,
industrial use) rather than as
a single distribution scenario.
Industrial /
commercial
use
Petrochemical-
derived and
agricultural
products
manufacturing
Petrochemical-
derived and
agricultural
products
manufacturing
Inert solvent,
processing
agent,
processing aid,
and additive
Liquid
Contact
Dermal
Workers
Yes
Contact time with skin is
expected to be <2 min due to
rapid volatilization.
However, EPA will need
additional information to
fully understand the use of
carbon tetrachloride in this
scenario to determine
potential for dermal
exposure.
Vapor
Inhalation
Workers
Yes
Due to high volatility (VP =
115 mmHg) at room
temperature, inhalation
pathway should be further
analyzed. However, EPA will
need additional information
to fully understand the use of
carbon tetrachloride in this
scenario to determine
potential for inhalation
exposure.
Page 98 of 112

-------
l .ile ( >cle
S(;ie
Csilcfion
SulK'siU'^on
Kok'iiso /
r.\|)(isuiv
Smiiirio
l'l\pOMIIV
I'iilliNin
l'l\pOMIIV
Uoule
Km'plor /
Population
Proposed
for l ur(lu r
Risk
l.\;ilu;i(ion
Kiilioiiiilo for l urdur
1'\;iIn;i 1 ion / no l-'urlhcr
ll\;ilii;i(ion




1 .K|llld
(ouiacl
Dermal
DM
\o
Dermal e\pnsnie ise\pecled
Ui he pi'iniai'ils lo workers
direclls in\iil\ed inworkiim
u uh llie eliemieal.
Vapor
Inhalation
ONU
Yes
Due to high volatility (VP =
115 mmHg) at room
temperature, inhalation
pathway should be further
analyzed. However, EPA will
need additional information
to fully understand the use of
carbon tetrachloride in this
scenario to determine
potential for inhalation
exposure.
\lls|
Dermal
Inhalation
Workers.
()\l
\o
Mm ueneralioii noi e\pecled
durum use of industrial
proeessum aueui
Industrial /
commercial
use
Other basic
organic and
inorganic
chemical
manufacturing
Manufacturing
of chlorinated
compounds used
in solvents for
cleaning and
degreasing,
adhesives and
sealants, paints
and coatings,
and asphalts;
Inert solvent,
processing
agent,
processing aid,
and additive
Liquid
Contact
Dermal
Workers
Yes
Contact time with skin is
expected to be <2 min due to
rapid volatilization.
However, EPA will need
additional information to
fully understand the use of
carbon tetrachloride in this
scenario to determine
potential for dermal
exposure.
Page 99 of 112

-------
l .ile ( >cle
S(;ie
Csilcfion
SulK'siU'^on
Kok'iiso /
r.\|)(isuiv
Scciiiirio
r.\|)(isuiv
Piilliw ;i>
r.\|)(isuiv
Koulo
Km'plor /
Population
Proposed
for l-'iirihcr
Risk
l.\;ilua(ion
Rationale for liii'llur
1'\;iIn;i 1 ion / no l-'iirlhcr
ll\aluation


Manufacturing
of inorganic
compounds

Vapor
Inhalation
Workers
Yes
Due to high volatility (VP =
115 mmHg) at room
temperature, inhalation
pathway should be further
analyzed. However, EPA will
need additional information
to fully understand the use of
carbon tetrachloride in this
scenario to determine
potential for inhalation
exposure.
1. K| 111 cl
( ouiacl
Dermal
()\l
\o
Dermal c\posure isc\pecled
lii he primarily to workers
direct l\ iu\ol\ed in uorkiuu
u iili ihe chemical.
Vapor
Inhalation
ONU
Yes
Due lo high \okilihiv (VI'
115 mmHg) at room
temperature, inhalation
pathway should be further
analyzed. However, EPA will
need additional information
to fully understand the use of
carbon tetrachloride in this
scenario to determine
potential for inhalation
exposure.
\lls|
Dermal
Inhalation
Workers.
DM
\o
Misi ucueralioii not c\pecled
durum use of industrial
pmcessum aueut
Page 100 of 112

-------
l .ile ( >cle
S(;ie
Csilcfion
SulK'siU'^on
Kok'iiso /
r.\|)(isuiv
Scciiiirio
l'l\|)UMIIV
I'iilliNin
l'l\|)UMIIV
Koulo
Km'plor /
I'upiikilion
Proposed
for I n rllier
Kisk
l-'\illllill ifill
Kiilioiiiilo for l iiidu i-
l-'\;iln;il iui / no I 'll rl lier
ll\iiliiiilioii
Industrial /
commercial
Other uses
Metal recovery;
specialty uses by
aerospace
industry
Metal recovery;
and uses in
aerospace
industry
Liquid
Contact
Dermal
Workers
Yes
Contact time with skin is
expected to be <2 min due to
rapid volatilization.
Vapor
Inhalation
Workers
Yes
Due to high volatility (VP =
115 mmHg) at room
temperature, inhalation
pathway should be further
analyzed.
Liquid
( Diiiacl
Dermal
<>\l
\o
Dermal exposure is especial
lii he primarily lo workers
direclk iii\ol\ed iiiwiirkinu
u illi ihe chemical.
Vapor
Inhalation
ONU
Yes
Due to high volatility (VP =
115 mmHg) at room
temperature, inhalation
pathway should be further
analyzed.
Mist
Dermal/
Inhalation
Workers,
ONU
Yes
EPA will further evaluate to
determine if mist generation
is applicable to specific
conditions of use in this
scenario.
Industrial /
commercial
use
Laboratory
chemical
Laboratory
chemical
Use as reagent
in laboratories
Liquid
Contact
Dermal
Workers
Yes
Contact time with skin is
expected to be <2 min due to
rapid volatilization. Number
of exposed workers may be
low per CDR (1 submission
reports 10-25 workers).
Page 101 of 112

-------
l .ile ( >cle
S(;ie
Csilcfion
SulK'siU'^on
Kok'iiso /
r.\|)(isuiv
Scciiiirio
r.\|)(isuiv
Piilliw ;i>
r.\|)(isuiv
Uoule
Km'plor /
Population
Proposed
for l ur(lu r
Risk
l.\;ilu;i(ion
Kiilioiiiilo for l urdur
1'\ ;i In ;i I ion / no l-'urlhcr
ll\iilii;ilion




Vapor
Inhalation
Workers
Yes
Inhalation exposure is
expected from laboratory
uses. Due to high volatility
(VP =115 mmHg) at room
temperature, inhalation
pathway should be further
analyzed. However, number
of exposed workers may be
low per CDR (1 submission
reports 10-25 workers).
1. K| 111 cl
( Olllacl
Dermal
()\l
\n
Dermal e\pnsme is especial
lii he priiii;iril\ id workers
direclK iii\ol\cd mi workiim
u iili ihc chemical.
Vapor
Inhalation
ONU
Yes
Inhalation exposure is
expected from laboratory
uses. Due to high volatility
(VP =115 mmHg) at room
temperature, inhalation
pathway should be further
analyzed. However, number
of exposed workers may be
low per CDR (1 submission
reports 10-25 workers).
Mist
Dermal/
Inhalation
Workers.
ONU
No
Mist generation not expected
during laboratory uses.
Page 102 of 112

-------
l .ile ( >cle
S(;ie
Csilcfion
SulK'siU'^on
Kok'iiso /
r.\|)(isuiv
Scciiiii'io
l'l\|)UMIIV
I'illllWil.t
l'l\|)UMIIV
Koulo
Km'plor /
I'upiikilion
Proposed
for I n rllier
Kisk
l.\;ilii;i(ion
Kiilioiiiilo I'oi" l iiidu i-
l-'\;iln;il iui / no I 'll rl lier
ll\iiliiiilioii




Liquid
Contact
Dermal
Workers
Yes
Contact time with skin is
expected to be <2 min due to
rapid volatilization.
Frequency of exposure and
the potential for dermal
immersion needs to be
further analyzed.
Disposal
Waste
Handling,
Treatment and
Disposal
Disposal of
carbon
tetrachloride
wastes
Worker
handling of
wastes
Vapor
Inhalation
Workers
Yes
Due to high volatility (VP =
115 mmHg) at room
temperature, inhalation
pathway should be further
analyzed.



Liquid
( OIllJICl
Domini
()\l
\o
Domini e\pnMire is especial
lo he priiikii'il\ In workers
directl\ Mi\ol\ed mi woikmu
u illi llie chcmic;il




Vapor
Inhalation
ONU
Yes
Due to high volatility (VP =
115 mmHg) at room
temperature, inhalation
pathway should be further
analyzed.
a ONU = occupational non-users
Page 103 of 112

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Appendix G SUPPORTING TABLE FOR ENVIRONMENTAL RELEASES AND
WASTES CONCEPTUAL MODEL
As part of the Problem Formulation, EPA considered if each unique combination of exposure pathway, route, and receptor in the lifecycle of carbon
tetrachloride would be further evaluated. All possible exposure scenarios for each condition of use were identified according to the conditions of use
identified in Table 2-3. EPA used readily available fate, engineering, exposure and/or toxicity information to determine whether to conduct further analysis
on each exposure scenario based on available information. EPA identified exposure scenarios and mapped them to relevant conditions of use in Table Apx
G-l.
Table A
px G-l. Environmental Re
eases and Wasi
tes Conceptual Model Supporting Table
Lite
(vole
St si lie
Use
Category
Category
Release
Kxposure
Pathway
Receptor
In rt Iter
Analysis
Rationale lor l-'iirlher Analysis /
no l-'iirlher Analysis
Disposal
Disposal
Waslew liter
or Liquid
Wastes
Industrial
WWT
operations
Water
Aquatic
Species
No
ConseiAiili\e hiuh-end screening
indicates thi.it iK|iiiilic species
exposures to carbon tetrachloride
in water are orders of nuiuniliide
below hazardous concentrations
Seel im en I
Aquatic
Species
No
IJiised on the physical and
chemical properties of carbon
tetrachloride (lou koc of 1.7-2 l(\
hiuh water solubility and
\olatility) sorption of carbon
tetrachloride to sediments is
unlikely
Page 104 of 112

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Life
Cycle
Stage
I se
Category
Category
Release
Kxposure
Palhwav
Receptor
I'll rl her
Analysis
Rationale lor l-'iirlher Analysis /
110 1' iirlher Analysis



Induslrinl
w aslcw aler
pre ircntmeni
operations,
then transfer
lo POTW
Publicly
ow neil
irealmenl
works
(POTW)
Wilier
Sediment
Wnlcr
Scil i men l
\i|iuilie
Species
\i|iinlic
Species
Ai|iuilic
Species
\i|iinlic
Species
No
No
No
No
Coiiscia nli\e hiuh-enil screeninu
inilicnles llinl ni|iuilic species
exposures lo enrhon tetrachloride
in wnler are orders of mnuniliide
below hn/.nrdous conceninilions
liaseil 011 the ph\ sical nnil
chemiciil properties ofenrbon
lelrnchloriile (lou Koc of 1 7-2 l(\
hiuh wnler solubility nnil
\olmiliiy) sorption ofenrbon
lelrnchloriile lo sediments is
unlikely.
Conser\ nli\ e hiuh-enil screeninu
inilicnles llinl ni|iuilic species
exposures to enrbon tetrachloride
in wnler nre orders of mnunilude
below hn/.nrdous concenirntions
linseil on the physicnl nnil
chemiciil properties of enrbon
lelrnchloriile (lou Koc ol" 1 7-2 l(\
hi uh wnler solubility nnil
\olnlilily) sorption ofenrbon
lelrnchloriile lo sediments is
unlikely
Page 105 of 112

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Appendix H INCLUSION AND EXCLUSION CRITERIA FOR
FULL TEXT SCREENING
This appendix contains the eligibility criteria for various data streams informing the TSCA risk
evaluation: environmental fate; engineering and occupational exposure; exposure to the general
population and consumers; and human health hazard. The criteria are applied to the on-topic references
that were identified following title and abstract screening of the comprehensive search results published
on June 22, 2017.
Systematic reviews typically describe the study eligibility criteria in the form of PECO statements or a
modified framework. PECO stands for Population, Exposure, Comparator and Outcome and the
approach is used to formulate explicit and detailed criteria about those characteristics in the publication
that should be present in order to be eligible for inclusion in the review. EPA/OPPT adopted the PECO
approach to guide the inclusion/exclusion decisions during full text screening.
Inclusion and exclusion criteria were also used during the title and abstract screening, and
documentation about the criteria can be found in the Strategy for Conducting Literature Searches
document published in June 2017 along with each of the TSCA Scope documents. The list of on-topic
references resulting from the title and abstract screening is undergoing full text screening using the
criteria in the PECO statements. The overall objective of the screening process is to select the most
relevant evidence for the TSCA risk evaluation. As a general rule, EPA is excluding non-English
data/information sources and will translate on a case by case basis.
The inclusion and exclusion criteria for ecotoxicological data have been documented in the ECOTOX
SOPs. The criteria can be found at https://cfpub.epa.gov/ecotox/h.elp.cfm.?h.elptabs=tab4) and in the
Strategy for Conducting Literature Searches document published along with each of the TSCA Scope
documents.
Since full text screening commenced right after the publication of the TSCA Scope document, the
criteria were set to be broad to capture relevant information that would support the initial scope. Thus,
the inclusion and exclusion criteria for full text screening do not reflect the refinements to the conceptual
model and analysis plan resulting from problem formulation. As part of the iterative process, EPA is in
the process of refining the results of the full text screening to incorporate the changes in
information/data needs to support the revised scope.
These refinements will include changes to the inclusion and exclusion criteria discussed in this appendix
to better reflect the revised scope of the risk evaluation and will likely reduce the number of
data/information sources that will undergo evaluation.
H.1 Inclusion Criteria for Data Sources Reporting Engineering and
Occupational Exposure Data
EPA/OPPT developed a generic RESO statement to guide the full text screening of engineering and
occupational exposure literature (Table Apx H-l). RESO stands for Receptors, Exposure, Setting or
Scenario, and Outcomes. Subsequent versions of the RESO statement may be produced throughout the
process of screening and evaluating data for the chemicals undergoing TSCA risk evaluation. Studies
that comply with the inclusion criteria specified in the RESO statement will be eligible for inclusion,
Page 106 of 112

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considered for evaluation, and possibly included in the environmental release and occupational exposure
assessments, while those that do not meet these criteria will be excluded.
The RESO statement should be used along with the engineering and occupational exposure data needs
table (TableApx H-2) when screening the literature.
Since full text screening commenced right after the publication of the TSCA Scope document, the
criteria for engineering and occupational exposure data were set to be broad to capture relevant
information that would support the initial scope. Thus, the inclusion and exclusion criteria for full text
screening do not reflect the refinements to the conceptual model and analysis plan resulting from
problem formulation. As part of the iterative process, EPA is in the process of refining the results of the
full text screening to incorporate the changes in information/data needs to support the revised scope.
Table Apx H-l. Inclusion Criteria for Data Sources Reporting Engineering and Occupational
Exposure Data	
KI-'.SO 1. lemon (
l.\ iriiwKT
Receptors
 Humans:
Workers, including occupational non-users (ONU)
Exposure
 Worker exposure to and occupational environmental releases of the chemical substance of
interest
o Any exposure route (list included: dermal, inhalation, oral) as indicated in the
conceptual model
o Any media/pathway [list included: water, land, air, incineration, and other(s)] as
indicated in the conceptual model
Please refer to the conceptual models for more information about the routes and media/pathways
included in the TSCA risk evaluation.
Setting or
Scenario
 Any occupational setting or scenario resulting in worker exposure and environmental releases
(includes all manufacturing, processing, use, disposal indicated in Table A-3 below except
(state none excluded or list excluded uses)
Outcomes
	Quantitative estimates* of worker exposures
	General information and data related and relevant to the occupational estimates*
* Metrics (e.g., mg/kg/day or mg/m3 for worker exposures, kg/site/day for releases) are determined by
toxicologists for worker exposures and by exposure assessors for releases; also, the Engineering Data Needs
(Table Apx H-2) provides a list of related and relevant general information.
TSCA=Toxic Substances Control Act
Page 107 of 112

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TableApx H-2. Engineering, Environmental Release and Occupational Data Necessary to
Develop the Environmental Release and Occupational Exposure Assessments	

Ohjiiiitc
Ik'k'nniiK'd
(lurinii Scoping
Tjpc or l);il;i
General
Engineering
Assessment (may
apply for either
or both
Occupational
Exposures and /
or Environmental
Releases)
1.	Description of the life cycle of the chemical(s) of interest, from manufacture to end-of-life (e.g., each
manufacturing, processing, or use step), and material flow between the industrial and commercial life cycle
stages. [Tags: Life cycle description, Life cycle diagram]3
2.	The total annual U.S. volume (lb/yr or kg/yr) of the chemical(s) of interest manufactured, imported,
processed, and used; and the share of total annual manufacturing and import volume that is processed or
used in each life cycle step. [Tags: Production volume, Import volume, Use volume, Percent PV]11
3.	Description of processes, equipment, unit operations, and material flows and frequencies (lb/site-day or
kg/site-day and days/yr; lb/site-batch and batches/yr) of the chemical(s) of interest during each industrial/
commercial life cycle step. Note: if available, include weight fractions of the chemicals (s) of interest and
material flows of all associated primary chemicals (especially water). [Tags: Process description, Process
material flow rate, Annual operating days, Annual batches, Weight fractions (for each of above,
manufacture, import, processing, use)]a
4.	Basic chemical properties relevant for assessing exposures and releases, e.g., molecular weight, normal
boiling point, melting point, physical forms, and room temperature vapor pressure. [Tags: Molecular
weight, Boiling point, Melting point, Physical form, Vapor pressure, Water solubility]a
5.	Number of sites that manufacture, process, or use the chemical(s) of interest for each industrial/
commercial life cycle step and site locations. [Tags: Numbers of sites (manufacture, import, processing,
use), Site locations]a
Occupational
Exposures
6.	Description of worker activities with exposure potential during the manufacture, processing, or use of the
chemical(s) of interest in each industrial/commercial life cycle stage. [Tags: Worker activities
(manufacture, import, processing, use)]a
7.	Potential routes of exposure (e.g., inhalation, dermal). [Tags: Routes of exposure (manufacture, import,
processing, use)]a
8.	Physical form of the chemical(s) of interest for each exposure route (e.g., liquid, vapor, mist) and activity.
[Tags: Physical form during worker activities (manufacture, import, processing, use)]a
9.	Breathing zone (personal sample) measurements of occupational exposures to the chemical(s) of interest,
measured as time-weighted averages (TWAs), short-term exposures, or peak exposures in each
occupational life cycle stage (or in a workplace scenario similar to an occupational life cycle stage). [Tags:
PBZ measurements (manufacture, import, processing, use)]a
10.	Area or stationary measurements of airborne concentrations of the chemical(s) of interest in each
occupational setting and life cycle stage (or in a workplace scenario similar to the life cycle stage of
interest). [Tags: Area measurements (manufacture, import, processing, use)]a
11.	For solids, bulk and dust particle size characterization data. [Tags: PSD measurements (manufacture,
import, processing, use)]a
12.	Dermal exposure data. [Tags: Dermal measurements (manufacture, import, processing, use)]
13.	Data needs associated with mathematical modeling (will be determined on a case-by-case basis). [Tags:
Worker exposure modeling data needs (manufacture, import, processing, use)]a
14.	Exposure duration (hr/day). [Tags: Worker exposure durations (manufacture, import, processing, use)]a
15.	Exposure frequency (days/yr). [Tags: Worker exposure frequencies (manufacture, import, processing,
use)]a
16.	Number of workers who potentially handle or have exposure to the chemical(s) of interest in each
occupational life cycle stage. [Tags: Numbers of workers exposed (manufacture, import, processing, use)]
a
17.	Personal protective equipment (PPE) types employed by the industries within scope. [Tags: Worker PPE
(manufacture, import, processing, use)]a
Page 108 of 112

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Objec(i\e
Delermineri
(In rin vi Scoping
T\|>e of Dalii

18. Engineering controls employed to reduce occupational exposures in each occupational life cycle stage (or
in a workplace scenario similar to the life cycle stage of interest), and associated data or estimates of
exposure reductions. [Tags: Engineering controls (manufacture, import, processing, use), Engineering
control effectiveness data]a
Environmental
Releases
19.	Description of sources of potential environmental releases, including cleaning of residues from process
equipment and transport containers, involved during the manufacture, processing, or use of the
chemical(s) of interest in each life cycle stage. [Tags: Release sources (manufacture, import, processing,
use)]a
20.	Estimated mass (lb or kg) of the chemical(s) of interest released from industrial and commercial sites to
each environmental medium (air, water, land) and treatment and disposal methods (POTW, incineration,
landfill), including releases per site and aggregated over all sites (annual release rates, daily release rates)
[Tags: Release rates (manufacture, import, processing, use)]"
21.	Release or emission factors. [Tags: Emission factors (manufacture, import, processing, use)]a
22.	Number of release days per year. [Tags: Release frequencies (manufacture, import, processing, use)]a
23.	Data needs associated with mathematical modeling (will be determined on a case-by-case basis). [Tags:
Release modeling data needs (manufacture, import, processing, use)]a
24.	Waste treatment methods and pollution control devices employed by the industries within scope and
associated data on release/emission reductions. [Tags: Treatment/ emission controls (manufacture, import,
processing, use), Treatment/ emission controls removal/ effectiveness data]a
Notes:
a These are the tags included in the full text screening form. The screener makes a selection from these specific tags,
which describe more specific types of data or information.
Abbreviations:
hr=Hour
kg=Kilogram(s)
lb=Pound(s)
yr=Year
PV=Particle volume
PBZ=
POTW=Publicly owned treatment works
PPE=Personal projection equipment
PSD=Particle size distribution
TWA=Time-weighted average
H.2 Inclusion Criteria for Data Sources Reporting Human Health
Hazards
EPA/OPPT developed a carbon tetrachloride-specific PECO statement to guide the full text screening of the
human health hazard literature. Subsequent versions of the PECOs may be produced throughout the process of
screening and evaluating data for the chemicals undergoing TSCA risk evaluation. Studies that comply with the
criteria specified in the PECO statement will be eligible for inclusion, considered for evaluation, and possibly
included in the human health hazard assessment, while those that do not meet these criteria will be excluded
according to the exclusion criteria.
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In general, the PECO statements were based on (1) information accompanying the TSCA Scope document, and
(2) preliminary review of the health effects literature from authoritative sources cited in the TSCA Scope
documents. When applicable, these authoritative sources (e.g., IRIS assessments, EPA/OPPT's Work Plan
Problem Formulations or risk assessments) will serve as starting points to identify PECO-relevant studies.
TableApx H-3. Inclusion and Exclusion Criteria for Data Sources Reporting Human Health Hazards
Related to Carbon Tetrachloride Exposure a
PECO
Element
Evidence
Stream
Papers/Features Included
Papers/Features Excluded
Population
Human
	Any population
	All lifestages
	Study designs:
o Controlled exposure, cohort, case-control, cross-
sectional, case-crossover, case studies, and case series
for all endpoints


Animal
	All non-human whole-organism mammalian species
	All lifestages
 Non-mammalian species

Mechanistic
 All data that may inform mechanisms of genotoxicity
and carcinogenicity *
 Data related to other mechanisms of toxicity
a
Exposure
Human
	Exposure based on administered dose or concentration of
carbon tetrachloride, biomonitoring data (e.g., urine,
blood or other specimens), environmental or
occupational-setting monitoring data (e.g., air, water
levels), job title or residence
	Primary metabolites of interest as identified in
biomonitoring studies
	Exposure identified as or presumed to be from oral,
dermal, inhalation routes
	Any number of exposure groups
	Quantitative, semi-quantitative or qualitative estimates of
exposure
	Exposures to multiple chemicals/mixtures only if carbon
tetrachloride or related metabolites were independently
measured and analyzed
	Route of exposure not by inhalation, oral or
dermal type (e.g., intraperitoneal, injection)
	Multiple chemical/mixture exposures with
no independent measurement of or exposure
to carbon tetrachloride (or related
metabolite)

Animal
	A minimum of 2 quantitative dose or concentration levels
of carbon tetrachloride plus a negative control group "
	Acute, subchronic, chronic exposure from oral, dermal,
inhalation routes
	Exposure to carbon tetrachloride only (no chemical
mixtures)
	Only 1 quantitative dose or concentration
level in addition to the control"
	Route of exposure not by inhalation, oral or
dermal type (e.g., intraperitoneal, injection)
	No duration of exposure stated
	Exposure to carbon tetrachloride in a
chemical mixture

Mechanistic
	Exposure based on concentrations of the neat material of
carbon tetrachloride
	A minimum of 2 dose or concentration levels tested plus a
control group *
	Exposure to carbon tetrachloride in a
chemical mixture
	Only 1 quantitative dose or concentration
level in addition to the control *
Comparator
Human
 A comparison population [not exposed, exposed to
lower levels, exposed below detection] for all endpoints
 No comparison population for all
endpoints

Animal
 Negative controls that are vehicle-only treatment and/or
no treatment
 Negative controls other than vehicle-only
treatment or no treatment
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IM'.CO
r.k-iiK'iii
l.\ iricniT
Siiviim
I'iipors/l-'oiiliiivs Included
Piipers/I-Viilu ivs Included

Mechanistic
	Exposed to vehicle-only treatment and/or no treatment
	For genotoxicity studies only, studies using positive
controls
	Negative controls other than vehicle-only
treatment or no treatment
	For genotoxicity studies only, a lack of
positive controls
Outcome
Human and
Animal
	Endpoints described in the carbon tetrachloride scope
documentb:
o Cancer
o Liver toxicity
o Kidney toxicity
o Neurotoxicity
o Gastrointestinal toxicity
o Irritation
o Sensitization
	Other endpoints (e.g., reproductive toxicity)b,c


Mechanistic
 All data that may inform the mechanism(s) of cancer
and genotoxicity"
 Data related to other mechanisms of toxicity
a
(I'lUTiil ('onsidi-mlimis
P;i |)i-rs/ |-V;i 1 u lis 1 nil udi-d
P;i|K*rs/I'Vii 1 uivs I'Ai'ludi'd

	Written in English 11
	Reports a primary source or meta-analysis *
	Full-text available
	Reports both carbon tetrachloride exposure and a health
outcome (or mechanism of action)
	Not written in English
	Reports a secondary source (e.g., review
papers)a
	No full-text available (e.g., only a study
description/abstract, out-of-print text)
	Reports a carbon tetrachloride-related
exposure or a health outcome, but not both
(e.g. incidence, prevalence report)
a Some of the studies that are excluded based on the PECO statement may be considered later during the systematic review process. For carbon
tetrachloride, EPA will evaluate studies related to susceptibility and may evaluate toxicokinetics and physiologically based pharmacokinetic models after
other data (e.g., human and animal data identifying adverse health outcomes) are reviewed. EPA may need to evaluate mechanistic data in addition to data
on mechanisms of genotoxicity and carcinogenicity depending on the review of health effects data. Finally, EPA may also review other data as needed (e.g.,
animal studies using one concentration, review papers).
b EPA will review key and supporting studies in the IRIS assessment that were considered in the dose-response assessment for non-cancer and cancer
endpoints as well as studies published after the IRIS assessment.
c EPA may screen for hazard effects other than those listed in the scope document if identified in the updated literature search for carbon tetrachloride that
accompanied the scope document.
d EPA may translate studies as needed.
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Appendix I LIST OF RETRACTED PAPERS
The following on-topic articles were retracted by the journal ad are considered off-topic.
Cha, JY; Ahn, HY; Moon, HI; Jeong, YK; Cho, YS. (2012). Effect of fermented Angelicae
gigantis Radix on carbon tetrachloride-induced hepatotoxicity and oxidative stress in rats.
Immunopharmacol Immunotoxicol 34: 265-274.
http://dx.doi.org/10.3109/08923973.2011.60Q76S
El-Sayed, YS; Lebda, MA; Hassinin, M; Neoman, SA. (2015). Chicory (Cichorium intybus L.)
root extract regulates the oxidative status and antioxidant gene transcripts in CC14-induced
hepatotoxicity. PLoS ONE 10: eO 121549. http://dx.doi.ore/	>umal.PGme.0121549
Li, C; Jiang, W; Zhu, H; Hou, J. (2012). Antifibrotic effects of protocatechuic aldehyde on
experimental liver fibrosis. Pharmaceutical Biology 50: 413-419.
http://dx.doi.org/10.3109/13880209.2011.6Q8193
Ping, J; Gao, AM; Qin, HQ; Wei, XN; Bai, J; Liu, L; Li, XH; Li, RW; Ao, Y; Wang, H. (2011).
Indole-3-carbinol enhances the resolution of rat liver fibrosis and stimulates hepatic stellate cell
apoptosis by blocking the inhibitor of kB kinase a/inhibitor of KB-a/nuclear factor-KB pathway. J
Pharmacol Exp Ther 339: 694-703. http://dx.doi.org 10 I ! ^ I tpet. I 11 I /9820
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