EPA Document# EPA-740-R1-7012
May 2018
United States Office of Chemical Safety and
Environmental Protection Agency Pollution Prevention
Problem Formulation of the Risk Evaluation for
1,4-Dioxane
CASRN: 123-91-1
O
May, 2018
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TABLE OF CONTENTS
ACKNOWLEDGEMENTS 5
ABBREVIATIONS 6
EXECUTIVE SUMMARY 8
1 INTRODUCTION 10
1.1 Regul atory Hi story 12
1.2 Assessment History 12
1.3 Data and Information Collection 14
1.4 Data Screening During Problem Formulation 15
2 PROBLEM FORMULATION 16
2.1 Physical and Chemical Properties 16
2.2 Conditions of Use 17
2.2.1 Data and Information Sources 17
2.2.2 Identification of Conditions of Use 17
2.2.2.1 Categories and Subcategories Determined Not to be Conditions of Use During Problem
Formulation 18
2.2.2.2 Categories and Subcategories of Conditions of Use Included in the Scope of the Risk
Evaluation 18
2.2.2.3 Overview of Conditions of Use and Lifecycle Diagram 21
2.3 Exposures 24
2.3.1 Fate and Transport 24
2.3.2 Releases to the Environment 26
2.3.3 Presence in the Environment and Biota 28
2.3.4 Environmental Exposures 28
2.3.5 Human Exposures 30
2.3.5.1 Occupational Exposures 30
2.3.5.2 Consumer Exposures 31
2.3.5.3 General Population Exposures 31
2.3.5.4 Potentially Exposed or Susceptible Subpopulations 32
2.4 Hazards (Effects) 32
2.4.1 Environmental Hazards 32
2.4.2 Human Health Hazards 35
2.4.2.1 Non-Cancer Hazards 35
2.4.2.2 Genotoxicity and Cancer Hazards 36
2.4.2.3 Potentially Exposed or Susceptible Subpopulations 36
2.5 Conceptual Models 36
2.5.1 Conceptual Model for Industrial and Commercial Activities and Uses: Potential Exposures
and Hazards 37
2.5.2 Conceptual Model for Consumer Activities and Uses: Potential Exposures and Hazards.... 41
2.5.3 Conceptual Model for Environmental Releases and Wastes: Potential Exposures and
Hazards 41
2.5.3.1 Pathways That EPA Plans to Include and Further Analyze in the Risk Evaluation 41
2.5.3.2 Pathways that EPA Plans to Include in the Risk Evaluation But Not Further Analyze. 41
2.5.3.3 Pathways That EPA Does Not Plan to Include in the Risk Evaluation 42
2.6 Analysis Plan 47
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2.6.1 Exposure 47
2.6.1.1 Environmental Releases, Fate and Exposures 47
2.6.1.2 Occupational Exposures 48
2.6.1.3 General Population 49
2.6.2 Hazard 50
2.6.2.1 Environmental Hazards 50
2.6.2.2 Human Health Hazards 50
2.6.3 Risk Characterization 52
REFERENCES 53
APPENDICES 59
Appendix A REGULATORY HISTORY 59
A.l Federal Laws and Regulations . 59
A.2 State Laws and Regulations .............65
A.3 International Laws and Regulations 65
Appendix B PROCESS, RELEASE AND OCCUPATIONAL EXPOSURE INFORMATION .. 67
B.l Process Information.. .67
B. 1.1 Manufacture (Including Import) 67
B. 1.2 Processing and Distribution 67
B. 1.2.1 Processing as a Reactant/Intermediate 67
B. 1.2.2 Processing - Non-Incorporative 68
B.1.2.3 Repackaging 68
B. 1.2.4 Recycling 68
B.1.3 Uses 68
B. 1.3.1 Processing Aids, Not Otherwise Listed 68
B. 1.3.1 Functional Fluids (Open and Closed Systems) 68
B.1.3.2 Laboratory Chemicals 68
B. 1.3.3 Adhesives and Sealants 69
B. 1.3.4 Other Uses 69
B.1.4 Disposal 69
B.2 Occupational Exposure Data[[[ ...................69
Appendix C ANALYSIS: ENVIRONMENTAL CONCENTRATION OF CONCERN (COC).. 70
Appendix D SUPPORTING TABLE FOR INDUSTRIAL AND COMMERCIAL ACTIVITIES
AND USES CONCEPTUAL MODEL 71
Appendix E SUPPORTING TABLE FOR ENVIRONMENTAL RELEASES AND WASTES
CONCEPTUAL MODEL 81
Appendix F INCLUSION AND EXCLUSION CRITERIA FOR FULL TEXT SCREENING... 83
F. 1 Inclusion Criteria for the Data Sources Reporting Environmental Fate Data. .......83
F.2 Inclusion Criteria for Data Sources Reporting Engineering and Occupational Exposure Data..84
F.3 Inclusion Criteria for Data Sources Reporting Environmental and General Population
Exposure ..87
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LIST OF TABLES
Table 1-1. Assessment History of 1,4-Dioxane 13
Table 2-1. Physical and Chemical Properties of 1,4-Dioxane 16
Table 2-2. Categories and Subcategories Determined Not to Be Conditions of Use During Problem
Formulation 18
Table 2-3. Categories and Subcategories of Conditions of Use Included in the Scope of the Risk
Evaluation 19
Table 2-4. Production Volume of 1,4-Dioxane in Chemical Data Reporting (CDR) Reporting Period
(2012 to 2015) a 22
Table 2-5. Environmental Fate Characteristics of 1,4-Dioxane 25
Table 2-6. Summary of 1,4-Dioxane TRI Production-Related Waste Managed in 2015 (lbs) 26
Table 2-7. Summary of 1,4-Dioxane TRI Releases to the Environment in 2015 (lbs) 26
Table 2-8. Ecological Hazard Characterization of 1,4-Dioxane 33
Table 2-9. 1,4-Dioxane Conditions of Use that May Produce a Mist 38
Table 2-10. Potential Sources of 1,4-Dioxane Occupational Exposure Data 48
LIST OF FIGURES
Figure 2-1. 1,4-Dioxane Life Cycle Diagram 23
Figure 2-2. 1,4-Dioxane Conceptual Model for Industrial and Commercial Activities and Uses: Potential
Exposures and Hazards 40
Figure 2-3. 1,4-Dioxane Conceptual Model for Environmental Releases and Wastes: Potential
Exposures and Hazards 46
LIST OF APPENDIX TABLES
Table_Apx A-l. Federal Laws and Regulations 59
Table_Apx A-2. State Laws and Regulations 65
Table_Apx A-3. Regulatory Actions by other Governments and Tribes 65
TableApx B-l. Summary of Industry Sectors with 1,4-Dioxane Personal Monitoring Air Samples
Obtained from OSHA Inspections Conducted Between 2002 and 2016 69
Table Apx D-l: Industrial and Commercial Occupational Exposure Scenarios for 1,4-Dioxane 71
Table Apx E-l: Environmental Releases and Wastes Exposure Scenarios for 1,4-Dioxane 81
Table Apx F-l: Inclusion Criteria for Data Sources Reporting Engineering and Occupational Exposure
Data 85
Table Apx F-2: Engineering, Environmental Release and Occupational Data Necessary to Develop the
Environmental Release and Occupational Exposure Assessments 86
Table Apx F-3: Inclusion and Exclusion Criteria for Data Sources Reporting Human Health Hazards
Related to 1,4-Dioxane Exposure21 88
LIST OF APPENDIX FIGURES
Figure Apx B-l: General Process Flow Diagram for 1,4-Dioxane Manufacturing 67
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ACKNOWLEDGEMENTS
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--201.6-0723.
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 United States Government.
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ABBREVIATIONS
°c
Degrees Celsius
AAL
Allowable Ambient Level
ACGIH
American Conference of Government Industrial Hygienists
AEGL
Acute Exposure Guideline Level
AES
Alkyl Ethyl Sulphates
AMA
Ambient Monitoring Archive
AQS
Air Quality System
atm
Atmosphere(s)
AT SDR
Agency for Toxic Substances and Disease Registries
BAF
Bioaccumulation Factor
BCF
Bioconcentration Factor
BSER
Best System of Emission Reduction
CAA
Clean Air Act
CASRN
Chemical Abstracts Service Registry Number
CBI
Confidential Business Information
CCL
Candidate Contaminant List
CDR
Chemical Data Reporting
CERCLA
Comprehensive Environmental Response, Compensation and Liability Act
cm3
Cubic Centimeter(s)
coc
Concentration of Concern
cou
Conditions of Use
CP
Centipoise
CPCat
Chemical and Product Categories
CSCL
Chemical Substances Control Law
EC
European Commission
EPA
Environmental Protection Agency
EPCRA
Emergency Planning and Community Right-to-Know Act
EU
European Union
FDA
Food and Drug Administration
FFDCA
Federal Food, Drug and Cosmetic Act
g
Gram(s)
GACT
Generally Available Control Technology
HAP
Hazardous Air Pollutant
HHE
Health Hazard Evaluation
HPV
High Production Volume
IARC
International Agency for Research on Cancer
IRIS
Integrated Risk Information System
ISHA
Industrial Safety and Health Act
kg
Kilogram(s)
kPa
Kilopascal(s)
L
Liter(s)
lb
Pound
Log Koc
Logarithmic Soil Organic Carbon:Water Partitioning Coefficient
Log Kow
Logarithmic Octanol:Water Partition Coefficient
3
m
Cubic Meter(s)
MACT
Maximum Achievable Control Technology
mg
Milligram(s)
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ng
Microgram(s)
mmHg
Millimeter(s) of Mercury
MSDS
Material Safety Data Sheet
NAC
National Advisory Committee
NAICS
North American Industry Classification System
NATA
National Air Toxics Assessment
NCEA
National Center for Environmental Assessment
NEI
National Emissions Inventory
NESHAP
National Emission Standards for Hazardous Air Pollutants
NICNAS
National Industrial Chemicals Notification and Assessment Scheme
NIH
National Institute of Health
NIOSH
National Institute of Occupational Safety and Health
NOAEL
No-Observed-Adverse-Effect Level
NPRI
National Pollutant Release Inventory
NSPS
New Source Performance Standards
NTP
National Toxicology Program
OCSPP
Office of Chemical Safety and Pollution Prevention
OECD
Organisation for Economic Co-operation and Development
ONU
Occupational Non-User
OPPT
Office of Pollution Prevention and Toxics
OSHA
Occupational Safety and Health Administration
PBPK
Physiologically Based Pharmacokinetic
PEL
Permissible Exposure Limit
PESS
Potentially Exposed or Susceptible Subpopulations
PET
Polyethylene Terephthalate
POD
Point of Departure
POTW
Publicly Owned Treatment Works
ppm
Part(s) per Million
PWS
Public Water System
RCRA
Resource Conservation and Recovery Act
REL
Recommended Exposure Level
SDS
Safety Data Sheet
SDWA
Safe Drinking Water Act
SIDS
Screening Information Data Set
TCA
1,1,1 -Trichloroethane
TCCR
Transparent, Clear, Consistent and Reasonable
TLV
Threshold Limit Value
TRI
Toxics Release Inventory
TSCA
Toxic Substances Control Act
TWA
Time-Weighted Average
UCMR
Unregulated Contaminant Monitoring Rule
U.S.
United States
UV
Ultraviolet
VCCEP
Voluntary Children's Chemical Evaluation Program
VOC
Volatile Organic Compound
WHO
World Health Organisation
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EXECUTIVE SUMMARY
TSCA § 6(b)(4) requires the United States Environmental Protection Agency (U.S. 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 ( ), as
required by TSCA § 6(b)(2)(A). 1,4-Dioxane 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 that the
Administrator expects to consider. In June 2017, EPA published the Scope of the Risk Evaluation for
1,4-Dioxane. 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 1,4-
dioxane. Comments received on this problem formulation document will inform 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 1,4-dioxane and presents refined conceptual models and analysis
plans that describe how EPA expects to evaluate the risk for 1,4-dioxane.
1,4-Dioxane is a clear volatile liquid used primarily as a solvent and is subject to federal and state
regulations and reporting requirements. 1,4-Dioxane has been a reportable Toxics Release Inventory
(TRI) chemical under Section 313 of the Emergency Planning and Community Right-to-Know Act
(EPCRA) since 1987. It is designated a Hazardous Air Pollutant (HAP) under the Clean Air Act (CAA),
and listed as a waste under the Comprehensive Environmental Response, Compensation and Liability
Act (CERCLA). It was listed on the Safe Drinking Water (SDWA) Candidate Contaminant List (CCL)
and identified in the third Unregulated Contaminant Monitoring Rule (UCMR3).
Information on domestic manufacture, processing and use of 1,4-dioxane is available to EPA through its
Chemical Data Reporting (CDR) Rule, issued under TSCA. In 2016, approximately 1 million pounds
per year was reported to be manufactured in the U.S. ( 1116c). 1,4-Dioxane is currently used
in industrial processes and for industrial and commercial uses. Industrial processing uses include use as
a processing aid and in functional fluids in open and closed systems. 1,4-Dioxane has uses as a
laboratory chemical reagent, in adhesives and sealants and several other identified uses. Historically,
90% of 1,4-dioxane produced was used as a stabilizer in chlorinated solvents such as 1,1,1-
trichloroethane (TCA). Use of 1,4-dioxane has decreased since TCA was phased out by the Montreal
Protocol in 1996.
The most recent data on environmental releases, according to the Toxics Release Inventory (TRI),
indicate that approximately 675,000 pounds of 1,4-dioxane were released to the environment in 2015
G . !"-J h.\ /_<')• Releases are reported to all types of environmental media: air, water and land. The
environmental fate of 1,4-dioxane is characterized by partitioning to the atmosphere, surface water and
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groundwater, and degradation by atmospheric oxidation or biodegradation. It is expected to be
moderately persistent in the environment and has a low bioaccumulation potential.
This document presents the potential exposures that may result from the conditions of use of 1,4-
dioxane. Workers and occupational non-users may be exposed to 1,4-dioxane during industrial and
commercial conditions of use such as manufacturing, processing, distribution, use and disposal. EPA
plans to further analyze inhalation exposures to vapors and mists for workers and occupational non-users
and dermal exposures for skin contact with liquids in occluded situations for workers in the risk
evaluation. For environmental release pathways, EPA plans to include surface water exposure to aquatic
vertebrates, invertebrates and aquatic plants, exposure to sediment organisms and exposure to 1,4-
dioxane in land-applied biosolids in the risk evaluation.
1,4-Dioxane has been the subject of numerous human health reviews including EPA's Integrated Risk
Information System (IRIS) Toxicological Review, Agency for Toxic Substances and Disease Registry's
(ATSDR's) Toxicological Profile, Health Canada Screening Assessment, and Interim Acute Exposure
Guideline Levels (AEGL). Many targets of toxicity from exposures to 1,4-dioxane have been identified
in animal and human studies for both oral and inhalation exposures. EPA plans to evaluate all potential
hazards for 1,4-dioxane, including any found in recent literature. Hazard endpoints identified in previous
assessments include acute toxicity, non-cancer effects and cancer. Non-cancer effects include irritation
of the eyes and respiratory tract, liver toxicity and kidney toxicity. Animals exposed to 1,4-dioxane by
inhalation and oral exposure have also developed multiple types of cancer. If additional hazard concerns
are identified during the systematic review of the literature, these will also be considered. These hazards
will be evaluated based on the specific exposure scenarios identified.
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); potentially exposed or
susceptible subpopulations; and hazards EPA expects to further analyze in the risk evaluation. The
initial conceptual models provided in the scope document (U.S. EPA. ) were revised during
problem formulation based on evaluation of reasonably available information for physical and chemical
properties, fate, exposures and hazards to indicate conditions of use, exposure pathways, exposure
routes, and hazards, conditions of use and 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
1,4-dioxane 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 potentially exposed or susceptible subpopulations 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, such as the hazards, exposures,
conditions of use, and the potentially exposed or susceptible subpopulations 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 1,4-dioxane. 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, (\ J I \ 20J-V). The outcome of problem formulation is 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 2014c). 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. 2014c). 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 in the risk evaluation as further explained below. 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 1,4-dioxane and has considered the
comments specific to 1,4-dioxane in this problem formulation document. EPA is soliciting public
comments 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 formulation, 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 1,4-dioxane. EPA compiled this summary from data available from federal, state,
international and other government sources, as cited in Appendix A. As noted in public comments to the
scope document, the NESHAP for Rubber Manufacturing does not apply to 1,4-dioxane and has been
removed from Table Apx A-l. EPA evaluated and considered the impact of existing laws and
regulations 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
uses 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
1,4-Dioxane 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.l.
State Laws and Regulations
1,4-Dioxane 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.2.
Laws and Regulations in Other Countries and International Treaties or Agreements
1,4-Dioxane 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.3.
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 potentially exposed or susceptible subpopulations. Table 1-1 shows the
assessments that have been conducted. EPA found no additional assessments beyond those listed in the
Scope document.
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 1,4-Dioxane (CASRN123-91-1)
Bibliography: Supplemental File for the TSCA Scope Document, EPA-HQ-0 ) 1.6-0723) following
the literature search and screening strategies documented in the Strategy for Conducting Literature
Searches for 1,4-Dioxane: Supplemental File for the TSCA Scope Document, EPA-H.Q-OPPT-:
0723. 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 1,4-Dioxane
Authoring Organization
Assessment
EPA assessments
EPA, Office of Chemical Safety and Pollution
Prevention (OCSPP), Office of Pollution
Prevention and Toxics (OPPT)
TSCA Work Plan Chemical Problem Formulation,
and Initial Assessment: 1.4-Dioxe N
(2015c")
EPA, National Center for Environmental
Assessment (NCEA)
lexicological Review of 1,4-Dioxane (With
Inhalation Uod* (2013c)
EPA, NCEA
lexicological review of 1.4-Dioxane (CAS No.
i'M iu2010}
EPA, Office of Water (OW)
Drinking Water Health. Advisory (2012a)
Other U.S.-based organizations
National Toxicology Program (NTP)
Report on Carcinogens. Fourteenth Edition. 1.4-
Dioxane(2016)
Agency for Toxic Substances and Disease Registry
(AT SDR)
Toxicological Profile for 1.4-Dioxane (2012.)
National Advisory Committee for Acute Exposure
Guideline Levels for Hazardous
Substances (NAC/AEGL Committee)
Interim. Acute Exposure Guideline Level rL)
fc-i 1 4 Dioxane (CAS Reg. No 123-'"> 1-1)
(2005b)
International
International Cooperation on Cosmetics Regulation
Report of the ICCR Working Group:
Considerations on. Acceptable Trace Level o
Dioxane in Cosmetic Products (2017)
International Agency for Research on Cancer
(IARC)
IARC Monographs on the Evaluation of
Carcinogenic Risks to Humans Volut ( 9)
Government of Canada, Environment Canada,
Health Canada
Screening Assessment for the Challenge. 1.4-
Dioxane. CASRN 123- ( )
Research Center for Chemical Risk Management,
National Institute of Advanced Industrial Science
and Technology, Japan
Estimating Health Risk from Exposure to 1.4-
World Health Organisation (WHO)
tane in Drinking-water (2005)
Employment, Social Affairs, and Inclusion,
European Commission (EC)
Recommendation from the Scientific Committee
on Occupational Exposure Limits for 1.4-dioxane
(2004)
European Chemicals Bureau, Institute for Health
and Consumer Protection
European Union Risk Assessment Report. 1.4-
dioxane. No: 204-
661-8. (2002)
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Authoring Organization
Assessment
National Industrial Chemicals Notification and
Assessment Scheme (NICNAS), Australian
Government
1 l-Oioxane "rn n ttv Existing Chemical No. 7.
Full Public Ret) ( 98)
Organisation for Economic Co-operation and
Development (OECD), Screening Information
Data Set (SIDS)
Dioxane. SIDS initial assessment profile
( )
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; ecological hazard,
human health hazard, including potentially exposed or susceptible subpopulations.
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). For human health hazard, EPA/OPPT relied on the search strategies
from recent assessments, such as EPA Integrated Risk Information System (IRIS) assessments and the
NTP Report on Carcinogens, 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
1,4-Dioxane: Supplemental File for the TSCA Scope Document (EPA-HQ-OIT I '¦11 ^ 111" 3) provides
details about the data and information sources and search terms that were used in the literature 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 1,4-Dioxane: Supplemental File for the TSCA Scope
Document (EPA-HQ-QPPT-2016-0723). 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; chemical use/conditions of use
information; environmental exposures, human exposures, including potentially exposed or susceptible
subpopulations identified by virtue of greater exposure; human health hazard, including potentially
exposed or susceptible subpopulations identified by virtue of greater susceptibility; and ecological
Page 14 of 90
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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 supplemental document, Strategy for Conducting
Literature Searches for 1,4-Dioxane: Supplemental File for the TSCA Scope Document (EPA-H.Q-
QPPT-2016-0723) 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 1,4-Dioxane: Supplemental File for the TSCA Scope Document (EPA-H.O-
QPPT-2016-0723) 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 1,4-Dioxane (CASRN123-91-1)
Bibliography: Supplemental File for the TSCA Scope Document (EP A-HQ-QPP'T-2016-0723). 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-
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 1,4-Dioxane (CASRN 123-91-1) Bibliography: Supplemental File for the TSCA Scope Document
(EPA-H.O-QPP'T-21 23). The screening process at the full-text level is described in the Application
of Systematic Review in TSCA Risk Evaluations (U.S. EPA. 2018a). Appendix F provides the inclusion
and exclusion criteria applied at the full text screening. The eligibility criteria are guided by the
analytical considerations in the revised conceptual models and analysis plan, as discussed in the problem
formulation document. Thus, it is expected that the number of data/information sources entering
evaluation is reduced to those that are relevant to address the technical approach and issues described in
the analysis plan of this document. Following the screening process, the quality of the included
data/information sources will be assessed using the evaluation strategies that are described in the
Application of Systematic Review in TSCA Risk Evaluations ( 1018a).
Page 15 of 90
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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 potentially exposed or susceptible subpopulations that the Administrator expects to
consider. To communicate and visually convey the relationships between these components, EPA
included in the scope document a life cycle diagram and conceptual models that describe the actual or
potential relationships between 1,4-dioxane and human and ecological receptors. During the problem
formulation, EPA revised the conceptual models based on further data gathering and analysis as
presented in this Problem Formulation document. An updated 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 1,4-dioxane.
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 and EPA found no additional information during
problem formulation that would change these values.
Table 2-1. Physical and Chemical Properties of 1,4-Dioxane
Property
Value a
References
Molecular formula
C4H8O2
Molecular weight
88.1 g/mole
(Howard. 1990)
Physical form
Clear liquid
(O'Neil et al.„ 2001)
Melting point
11.75°C
(Havmes. 2.014)
Boiling point
101.1°C
(O'Neil et aL 2.006)
Density
1.0329 g/cm3
(O'Neil et aL 2006)
Vapor pressure
40 mm Hg at 25°C
(Lewis. 2.000)
Vapor density
Not readily available
Water solubility
>8.00 x 102 g/L
(Yalkowskv et al. 20 i 0)
Octanol:water partition
-0.27 (estimated)
(Hansch et al.. 1995)
Henry's Law constant
4.8 x 10"6 atm-m3/mole at 25°C
(Sander. 2017); (Howard.
1990); (Atkins. 1986)
Flash point
18.3°C (open cup)
(Lewis.: )
Autoflammability
Not readily available
Viscosity
0.0120 cP at 25°C
(O'Neil. 2013)
Refractive index
1.4224 at 20°C
CHavnes. 2.014)
Dielectric constant
2.209
(Bruno and Svoronos. 2006)
a Measured unless otherwise noted
Page 16 of 90
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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 this document, EPA searched a number of
available data sources (e.g. Use and Market Profile for 1,4-Dioxane, (I V x 1 i1 » 1 il1lT~2QI6 0723).
Based on this search, EPA published a preliminary list of information and sources related to chemical
conditions of use (sqq Preliminary Information on Manufacturing, Processing, Distribution, Use, and
Disposal: 1,4-Dioxane, EPA-HQ-OPPT- 723-0003) 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 has been incorporated into this problem
formulation document to the extent appropriate. 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 1,4-dioxane and inversely, conditions of use that are no
longer ongoing, EPA conducted extensive research and outreach. This included EPA's review of
published literature and online databases including the most recent data available from EPA's Chemical
Data Reporting program (CDR) and Safety Data Sheets (SDSs). EPA also conducted online research by
reviewing company websites of potential manufacturers, importers, distributors, retailers, or other users
of 1,4-dioxane and queried government and commercial trade databases. EPA also received comments
on the Scope of the Risk Evaluation for 1,4-Dioxane (EPA.~H.0~QI 3) that were used to
determine the current conditions of use. In addition, EPA convened meetings with companies, industry
groups, chemical users, states, environmental groups, and other stakeholders to aid in identifying
conditions of use and verifying conditions of use identified by EPA. Those meetings included a
February 14, 2017 public meeting with such entities and a September 15, 2017 meeting with several
representatives from trade associations.
EPA has removed from the risk evaluation activities that EPA 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 plan 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 potentially exposed or
susceptible subpopulations that the Agency expects to consider in a risk evaluation," suggesting that
EPA may exclude certain activities that EPA has determined to be conditions of use on a case-by-case
basis (82 FR 33736, 33729; July 20, 2017). For example, EPA may exclude conditions of use that the
Agency has sufficient basis to conclude would present only de minimis exposures or otherwise
insignificant risks (such as use in a closed system that effectively precludes exposure or as an
intermediate).
Page 17 of 90
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The activities that EPA no longer believes are conditions of use or 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
During Problem Formulation
For 1,4-dioxane, EPA has reviewed reasonably available information about 1,4-dioxane conditions of
use. EPA did not find evidence of any current consumer uses ( 2016c) for 1,4-dioxane and is
excluding consumer uses from the scope of the risk evaluation as explained in the Scope document (
EPA, 2017c). As described in the Scope, contamination of industrial, commercial and consumer
products are not intended conditions of use for 1,4-dioxane and will not be evaluated. For fuels and fuel
additives (Other uses category), EPA contacted several racing authorities that indicated that their
organizations banned the use of dioxane in competitions. The organizations also could not provide
credible information on whether or how often dioxane was used prior to their bans nor whether it is
currently used at all. Based on the lack of information confirming that 1,4-dioxane is currently used as a
fuel or fuel additive and the fact that racing authorities have prohibited this use, use in fuels and fuel
additives is not a condition of use under which EPA will evaluate 1,4-dioxane.
Table 2-2. Categories and Subcategories Determined Not to Be Conditions of Use During Problem
Formulation
l.il'e Cycle Stage
Category
Subcategory
References
Industrial use,
potential commercial
use
Other Uses
Fuels and fuel additives
Use document, EPA-
HO-OPI '23-
0003
2.2.2.2 Categories and Subcategories of Conditions of Use Included in the Scope of
the Risk Evaluation
For 1,4-dioxane, EPA has conducted public outreach and literature searches to collect information about
conditions of use and has reviewed reasonably available information obtained or possessed by EPA
concerning activities associated with 1,4-dioxane.
1,4-Dioxane is currently manufactured, processed, distributed and used in industrial processes and for
industrial and commercial uses. Manufacturing sites produce 1,4-dioxane in liquid form at
concentrations greater or equal to 90% (EPA-HQ-QPPT-2016-0723-0012; BASF (2017). Industrial
processing uses included in the scope include processing as a reactant or intermediate, non-incorporative
processing, repackaging and recycling. Uses include processing aids (not otherwise listed), functional
fluids in open and closed systems, laboratory chemicals, adhesives and sealants, other uses (spray
polyurethane foam, printing and printing compositions) and disposal. Note that during problem
formulation, EPA determined that some subcategories, such as cutting and tapping fluid, may also be
used in open systems and is including these uses. Activities related to distribution (e.g., loading,
unloading) will be considered throughout the 1,4-dioxane life cycle, rather than as a single distribution
scenario. Also included in the scope are 1,4-dioxane use as a laboratory chemical reagent and use in
adhesives and sealants in industrial and/or commercial settings and use in laboratory reference materials
or standards containing 1,4-dioxane. Searches identified two products with greater than 5% of 1,4-
dioxane that are included: a professional film cement and a chemiluminescent laboratory reagent. Other
uses included are spray polyurethane foam; and printing and printing compositions.
Page 18 of 90
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Table 2-3 summarizes each life cycle stage and the corresponding categories and subcategories of
conditions of use for 1,4-dioxane that EPA is including in the scope of the risk evaluation. Using the
2016 CDR (U.S. EPA. 2016c). EPA identified industrial processing or use activities, industrial function
categories and commercial use product categories. EPA identified the subcategories by supplementing
CDR data with other published literature and information obtained through stakeholder consultations.
For this risk evaluation, EPA intends to consider each life cycle stage (and corresponding use categories
and subcategories) and assess certain 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 1,4-Dioxane ( ), EPA
has received no additional information identifying additional current conditions of use for 1,4-dioxane
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 "
Subcategory h
References
Manufacture
Domestic manufacture
Domestic manufacture
Use document 0-
OPPT-2016-0723-0003:
Public Comment, EPA-HO-
OPPT-2016-0723-(
Import
Import
Use document, (V
OPPT-2016-0723 -0003
Processing
Processing as a reactant
Pharmaceutical intermediate
Use document, .0-
OPPT-2016-0723-0003
Polymerization catalyst
Use document. O-
OPPT-2016-0723-0003
Non-incorporative
Pharmaceutical and
medicine manufacturing
(process solvent)
Public Comment, EPA-HO-
OPPT-2016-0723-0012
Basic organic chemical
manufacturing
(process solvent)
Public Comment, EPA-HO-
OPPT-2016-07:
Repackaging
Bulk to packages, then
distribute
Public Comment, EPA-HO-
OPPT-2016-07:
Recycling
Recycling
0 n«\ >0
Distribution in
commerce
Distribution
Distribution
Use document, EPA-HO-
OPPT-2016-0723-0003
Industrial use
Intermediate use
Agricultural chemical
intermediate
Use document, .0-
OPPT-2016-0723-0003
Plasticizer intermediate
Use document, (V
OPPT-2016-0723-0003
Catalysts and reagents for
anhydrous acid reactions,
Use document, .0-
OPPT-2016-0723-0003
Page 19 of 90
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l.il'e ( vole Slsige
Csilegorv 11
Siihe:iU'«or\ h
UeforoiKTs
brominations and
sulfonations
Processing aids, not
otherwise listed
Wood pulping
Use document, Q-
OPPT-2016-0723 -0003
Extraction of animal and
vegetable oils
Use document, ()~
OPPT-2016-0723-0003
Wetting and dispersing
agent in textile processing
Use document, 1 ^ \ S Q-
OPPT-2016-0723-0003
Polymerization catalyst
Use document, EPA-HO-
OPPT -2016-0723-0003
Purification of
pharmaceuticals
Use document. EPA-HO-
OPPT -2016-0723-0003
Etching of fluoropolymers
Public Comment. EPA-HO-
OPPT-2016-0723-(
Functional fluids (open
and closed system); refer
to section 2.5.1 below for
details
Polyalkylene glycol
lubricant
Use document, I 'P \ i 10-
OPPT-2016-0723-0003
Synthetic metalworking
fluid
Use document, ()~
OPPT-2016-0723-0003
Cutting and tapping fluid
Use document, 1 ^ \ S Q-
OPPT-2016-0723-0003
Hydraulic fluid
Use document, O-
OPPT-2016-0723-0003
Industrial use,
potential
commercial use
Laboratory chemicals
Chemical reagent
Use document, ^ O-
OPPT-2016-0723-0003:
Public Comment, EPA-HO-
OPPT-2016-0723-0009
Reference material
Use document, 1 ^ \ S Q-
OPPT-2016-0723-0003
Spectroscopic and
photometric measurement
Use document, O-
OPPT-2016-0723-0003:
Public Comment, EPA-HO-
OPPT-2016-0723-0009
Liquid scintillation counting
medium
Use document, ()~
OPPT-2016-0723-0003
Stable reaction medium
Use document, 1 \ S Q-
OPPT-2016-0723-0003
Cryoscopic solvent for
molecular mass
determinations
Use document, O-
OPPT-2016-0723-0003
Page 20 of 90
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l.il'e Cycle Slagc
Category 11
Subcategory h
References
Preparation of histological
sections for microscopic
examination
I sc document.
OPPT-2016-0723 -0003
Adhesives and sealants
Film cement
Use document. O-
OPPT-2016-0723-0003:
Public Comment, EPA-HO-
OPPT-2016-0723-0021
Other uses
Spray polyurethane foam
Printing and printing
compositions
Use document O-
OPPT-2016-0723-0003:
Public Comment, EPA-HO-
OPPT-2016-072 3 -0012
Disposal
Disposal
Industrial pre-treatment
( 2017d")
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
a These categories of conditions of use appear in the initial life cycle diagram, reflect CDR codes and broadly represent
conditions of use for 1,4-dioxane in industrial and/or commercial settings.
b These subcategories reflect more specific uses of 1,4-dioxane.
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,
distribution, use (industrial, commercial; when distinguishable) and disposal. Additions or changes to
conditions of use based on additional information gathered or analyzed during problem formulation
were described in Section 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 Chemical Data Reporting (CDR) processing codes and use categories (including functional
use codes for industrial uses and product categories for 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 may be grouped under multiple CDR
categories.
Page 21 of 90
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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. ).
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 reporting ( 016c). when the volume was not
claimed confidential business information (CBI).
The 2016 CDR reporting data for 1,4-dioxane are provided in Table 2-4 for 1,4-dioxane from EPA's
CDR database (U.S. EPA. 2016c). This information has not changed from that provided in the scope
document.
Table 2-4. Production Volume of 1,4-Dioxane in Chemical Data Reporting (CDR) Reporting
Period (2012 to 2015) a
Reporting Year
2012
2013
2014
2015
Total Aggregate
Production Volume (lbs)
894,505
1,043,627
474,331
1,059,980
" The CDR data for the 2016 rcportinu period is available via ChemView (httDs://iava.eDa.eov/chemview) (U.S. EPA.
2014a). Because of an onsoins CBI substantiation process reauired bv amended TSCA. the CDR data available in the scope
document is more specific than currently in ChemView.
According to data collected in EPA's JO I * Chemical Data Reporting ' >Rj Rule, over one million
pounds of 1,4-dioxane were produced or imported in the U.S. in 2015 ( :). Data reported
indicate that there was one manufacturer of 1,4-dioxane in the U.S. in 2015. The total volume (in lbs) of
1,4-dioxane manufactured (including imported) in the U.S. from 2012 to 2015 indicates that production
has varied over that time period. Historically, the main use (90%) of 1,4-dioxane was as a stabilizer of
chlorinated solvents such as 1,1,1 trichloroethane (TCA) ( DR. 2012). Use of TCA was phased out
under the 1995 Montreal Protocol and the use of 1,4-dioxane as a solvent stabilizer was terminated
(NTP. 2011; ECJRC. 2002). Lack of recent reports for other previously reported uses (Sapphire Group.
2007) suggest that many other industrial, commercial and consumer uses were also stopped.
Descriptions of the industrial, commercial and consumer use categories identified from the 2016 CDR
(U.S. EPA. 2016a) and included in the life cycle diagram . Descriptions in Appendix B contain detailed
descriptions (e.g., process descriptions, worker activities, process flow diagrams, equipment
illustrations) for each manufacture, processing, distribution, use and disposal category. The descriptions
are primarily based on the corresponding industrial function category and/or commercial and consumer
product category descriptions from the 2016 CDR and can be found in EPA's Instructions for Reporting
2016 TSCA Chemical Data Reporting ( 016b).
Figure 2-1 depicts the life cycle diagram of 1,4-dioxane from manufacture to the point of disposal.
Activities related to distribution (e.g., loading, unloading) will be considered throughout the 1,4-dioxane
life cycle, rather than using a single distribution scenario.
Page 22 of 90
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MFG/IMPORT
PROCESSING
INDUSTRIAL and COMMERCIAL USES3
RELEASES and WASTE DISPOSAL
Manufacture
(Includes Import)
(1 million lbs.)
Processing as a
Reactant/lntermediate
(Not reported in 2016 CDR)
Repackaging
(270,000 lbs.)
Non-lncorporative
Activities
(270,000 lbs.)
Recycling
Processing Aids, Not Otherwise
Listed
(270,000 lbs.)
e.g., wood pulping, pharmaceutical
manufacture, etching of fluoropolymers
Functional Fluids
(Open and Closed Systems)
(<150,000 lbs.)
e.g., hydraulicfluid
Disposal
Laboratory Chemicals
(<150,000 lbs.)
e.g., laboratory reagent
Adhesives and Sealants
e.g., film cement
Other Uses
Spray Polyurethane Foam; Printing and
Printing Compositions
See Figure 2-3 for Environmental
Releases and Wastes
l l Manufacture (Includes Import) I I Processing ~ Industrial uses of 1,4-dioxane.
~ Industrial and/or commercial uses of 1,4-dioxane
Figure 2-1. 1,4-Dioxane Life Cycle Diagram
The life cycle di agram depicts the condi tions of use that are within the scope of the risk evaluation during various life cycle stages including
manufacturing, processing, use (industrial or commercial) and disposal. The production volumes shown are for reporting year 2015 from the
2016 CDR reporting period (U.S. EPA. 2016c). Activities related to distribution (e.g., loading, unloading) will be considered throughout the
1,4-dioxane life cycle, rather than using a single distribution scenario.
a See Table 2-3 for additional uses not mentioned specifically in this diagram.
Page 23 of 90
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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 1,4-dioxane. Post-release pathways and routes will be
described to characterize the relationship between the conditions of use of 1,4-dioxane and the exposure
to human receptors, including potentially exposed or susceptible subpopulations, and ecological
receptors. EPA will take into account, where relevant, the duration, intensity (concentration), frequency
and number of exposures in characterizing exposures to 1,4-dioxane.
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 1,4-
dioxane. This information has not changed from that provided in the scope document.
Fate data including volatilization during wastewater treatment, volatilization from lakes and rivers,
biodegradation rates, and organic carbon:water partition coefficient (log Koc) were used when
considering changes 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™ (U.S. EPA. 2012c) modules were used to predict volatilization of 1,4-dioxane from
wastewater treatment plants, lakes, and rivers and to confirm the data showing slow biodegradation. The
EPI Suite™ module that estimates chemical removal in sewage treatment plants ("STP" module) was
run using default settings to evaluate the potential for 1,4-dioxane to volatilize to air or adsorb to sludge
during wastewater treatment. The STP module estimates that 0.27% of 1,4-dioxane in wastewater will
be removed by volatilization while 1.75% of 1,4-dioxane will be removed 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 1,4-dioxane in surface water. The
volatilization module estimates that the half-life of 1,4-dioxane in a model river will be 4.8 days and the
half-life in a model lake will be 56 days.
The EPI Suite™ module that predicts biodegradation rates ("BIOWIN" module) was run using default
settings to estimate biodegradation rates of 1,4-dioxane in soil and sediment. Three of the models built
into the BIOWIN module (BIOWIN 1, 2, and 5) estimate that 1,4-dioxane will not rapidly biodegrade in
aerobic environments, while a fourth (BIOWIN 6) estimates that 1,4-dioxane will rapidly biodegrade in
aerobic environments. These results support the biodegradation data presented in the 1,4-dioxane scope
document, which demonstrate slow biodegradation under aerobic conditions. The model that estimates
anaerobic biodegradation (BIOWIN 7) predicts that 1,4-dioxane will not rapidly biodegrade under
anaerobic conditions. Further, previous assessments of 1,4-dioxane found that biodegradation was slow
or negligible ( J>K. 2012; NTP. 2011: Health Canada. 2010; ECJRC. 2002; NICNAS. 1998V
The log Koc reported in the 1,4-dioxane scoping document was predicted using EPI Suite™. That value
(0.4) is 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).
Page 24 of 90
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Indeed, the log Kow reported for 1,4-dioxane in the scoping document was -0.27, 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 1,4-dioxane in
groundwater. The log Koc reported in previous assessments of 1,4-dioxane were in the range of 0.4 -
1.23 (U.S. EPA. 2013b: AT SDR. 2012; U.S. EPA. 2010; ECJRC. 2002; NICNAS. 1998) and all values
within that range would be associated with low sorption to soil and sediment (ECJRC. 2002; NICNAS.
1998). and all values within that range would be associated with low sorption to soil and sediment.
Table 2-5. Environmental Fate Characteristics of 1,4-Dioxane
Property or Endpoint
Value a
References
Direct photodegradation
Not expected to undergo direct photolysis
(U.S. EPA. 2015c)
Indirect photodegradation
4.6 hours (estimated for atmospheric degradation)
(U.S. EPA. 2015c)
Hydrolysis half-life
Does not undergo hydrolysis
(U.S. EPA. 2015c)
Biodegradation
<10% in 29 days (aerobic in water, OECD 301F)
<5% in 60 days (aerobic in water, OECD 310)
0% in 120 days, 60% in 300 days (aerobic in soil
microcosm)
(U.S. EPA. 2015c)
Bioconcentration factor
(BCF)
0.2-0.7 (OECD 305C)
(U.S. EPA. 2015c)
Bioaccumulation factor
(BAF)
0.93 (estimated)
(U.S. EPA. 2015c)
Organic carbon:water
partition coefficient (log Koc)
0.4 (estimated)
(U.S. EPA. 2015c)
a Measured unless otherwise noted.
1,4-Dioxane is expected to volatilize from dry surfaces and dry soil due to its vapor pressure of 40 mm
Hg at 25°C (Table 2-1). It reacts with hydroxyl radicals (OH*) in the atmosphere with an estimated
indirect photolysis half-life on the order of hours. 1,4-Dioxane is not expected to be susceptible to direct
photolysis under environmental conditions since this compound lacks functional groups that absorb light
at visible-ultraviolet (UV) light wavelengths.
Due to its water solubility (>800 g/L; Table 2-1) and Henry's Law constant (4.8 x 10"6 atm-m3/mole at
25°C; Table 2-1), 1,4-dioxane is expected to demonstrate limited volatility from water surfaces and
moist soil. Once it enters the environment, 1,4-dioxane is expected to be mobile in soil based on its
organic carbon partition coefficient (estimated log Koc = 0.4) and may therefore migrate to surface
waters and groundwater. 1,4-Dioxane will not hydrolyze in water because it does not have functional
hydrolyzable groups.
In experimental studies, 1,4-dioxane has been demonstrated to be not readily biodegradable but was
subject to biodegradation after acclimation in a soil microcosm. Measured bioconcentration factors for
1,4-dioxane are 0.7 or below and the estimated bioaccumulation factor is 0.93. Therefore, 1,4-dioxane
has low bioaccumulation potential.
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2.3.2 Releases to the Environment
Releases to the environment from conditions of use (e.g., industrial and commercial processes,
commercial or consumer uses resulting in down-the-drain releases) 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.
Under the Emergency Planning and Community Right-to-Know Act (EPCRA) Section 313 rule, 1,4-
dioxane is a TRI-reportable substance effective January 1, 1987. 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 release would result from certain types of disposal to land (i.e. RCRA Subtitle
C hazardous landfill and Class I underground Injection wells) and incineration. EPA also examined how
many facilities recycle 1,4 dioxane, and how it is treated at industrial facilities.
Table 2-6 provides production-related waste managed data (also referred to as waste managed) for 1,4-
dioxane reported by industrial facilities to the TRI program for 2015. 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 1,4-Dioxane TRI Production-Related Waste Managed in 2015 (lbs)
Number of
Facilities
Recycling
Energy
Recovery
Treatment
Releases a'b'c
Total Production
Related Waste
49
4,292
1,591,064
1,923,623
705,691
4,224,670
Data source: 2015 TRI Data (undated March 2017) (U.S. EPA. 2017d).
a 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.
0 Counts all releases including release quantities transferred and release quantities disposed of by a receiving facility
reporting to TRI.
Table 2-7. Summary of 1,4-Dioxane TRI Releases to the Environment in 2015 (
bs)
Air Releases
Number
of
Facilities
Stack Air
Releases
Fugitive
Air
Releases
Water
Releases
Land Disposal
Class I
Under-
ground
Injection
RCRA
Subtitle C
Landfills
All other
Land
Disposala
Other
Releases !
Subtotal
46,219
16,377
563,976
13,376
49
Totals
49
62,596
35,402
577,400
Data source: 2015 TRI Data (updated March 2017) (U.S. EPA. 2017dY
a 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 These release quantities include releases due to one-time events not associated with production such as remedial actions or earthquakes.
0 Counts release quantities once at final disposition, accounting for transfers to other TRI reporting facilities that ultimately dispose of the chemical waste.
Facilities are required to report if they manufacture (including import) or process more than 25,000
pounds of 1,4-dioxane, or if they otherwise use more than 10,000 pounds of 1,4-dioxane. In 2015, 49
facilities reported a total of 4.2 million pounds of 1,4-dioxane waste managed. Of this total, over 4
thousand pounds were recycled, 1.6 million pounds were recovered for energy, 1.9 million pounds were
treated and 700 thousand pounds were released to the environment. No TRI facilities reported recycling
Page 26 of 90
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1,4-dioxane on-site, but one reported transferring it off-site for recycling, specifically for
solvents/organics recovery.
Of the almost 700 thousand pounds of total releases, there were stack and fugitive air releases, water
releases, Class I underground injection, release to Resource Conservation and Recovery Act (RCRA)
Subtitle C landfills and other land disposal (Table 2-7). For stack releases, multiple types of facilities
report on incineration destruction, including hazardous waste facilities, and facilities that perform other
industrial activities and may be privately or publically (i.e., federal, state or municipality) owned or
operated. Approximately 46,000 lbs of 1,4-dioxane releases were reported to TRI as on-site stack
releases, and account for any incineration destruction. Stack releases reported to TRI represent the total
amount of 1,4 dioxane being released to the air at the facility from stacks, confined vents, ducts, pipes or
other confined air streams.
In 2015, 205,725 pounds of 1,4-dioxane were released on-site, and 469,674 pounds were released off-
site. Of the on-site releases, 52% (107,726 pounds) went to land disposal, 30% (62,596 pounds) went to
air, including stack and fugitive releases, and 17% (35,402 pounds) was discharged to water. Of the on-
site land disposal, most went to Class I underground injection wells or RCRA Subtitle C Landfills. Just
47 pounds went to on-site landfills other than RCRA Subtitle C Landfills, and none was disposed of in
on-site Class II-V underground injection wells, on-site land treatment, or on-site surface impoundments.
Of the off-site releases, the vast majority (469,672 lb) went to Class I underground injection wells. Very
small amounts were transferred off-site to RCRA Subtitle C Landfills (0.31 lb), landfills other than
RCRA Subtitle C Landfills (0.1 lb), and other types of land disposal (1.65 lb) and are considered of
negligible concern for exposure.
While most 1, 4-dioxane going to land disposal went to highly regulated land disposal units in 2015, in
past years, the TRI data show 1,4-dioxane going to other types of land disposal as well. From 1989 to
2002 the data show thousands of pounds of 1,4-dioxane disposed of via on-site land treatment. From
2009 to 2011, hundreds of pounds were disposed of in on-site landfills other than RCRA Subtitle C
Landfills. There was also off-site disposal, with thousands of pounds disposed of off-site in landfills
other than RCRA Subtitle C from 2002 to 2005. The volumes then decreased from hundreds, to tens, to
almost no pounds disposed of off-site in landfills other than RCRA Subtitle C from 2006 to 2015.
While the volume of 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
includes both production-related and non-routine quantities (TRI section 5 and 6 data). As a result,
release quantities may differ slightly and may reflect differences in TRI calculation methods for reported
release range estimates (U.S. EPA. 2017d).
EPA's Compilation of Air Pollutant Emission Factors, AP-42 section 6.13 on pharmaceuticals
production provides general process and emissions information and the ultimate disposition of 1,4-
dioxane (air, sewer, incineration, solid waste, product) by pharmaceutical manufacturers. Other sources
of information provide evidence of releases of 1,4-dioxane, including National Emission Standards for
Hazardous Air Pollutants (NESHAPs) promulgated under the Clean Air Act (CAA) or other EPA
standards and regulations that set legal limits on the amount of 1,4-dioxane that can be emitted to a
particular media.
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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 data were
identified in EPA's data search for 1,4-dioxane.
Monitoring data (measured) from EPA's Air Quality System (AQS) and the open literature, as well as
modeled estimates based on the National Air Toxics Assessment (NATA) and TRI emissions data
suggest that 1,4-dioxane is present in ambient air. Monitored and modeled air concentrations from these
sources suggest that many air concentrations may be low (i.e., <1 |ig/m3) and appear to have been higher
in the past, possibly reflecting past uses Q H' \ 2015a. JO I Ui). Recent (2015) air monitoring data).
Recent (2015) air monitoring data were extracted from the Ambient Monitoring Archive (AMA). Of a
total of 1397 collected samples, there were 948 non-detects (68%) and 449 detections (32%), which
ranged from 0.005 to 0.96 ppb. All non-detects and detections for this chemical were sampled in four
states: MI, OH, NC, and IN.
Indoor air monitoring data are available. One recent study reported annual average concentrations of
1,4-dioxane ranging from 0.01 to 0.1 1 [j,g/m3 in several hundred homes in Germany (Wissenbach et at.
2016). Older indoor air monitoring studies are summarized in the U.S. EPA Voluntary Children's
Chemical Evaluation Program (VCCEP) submission and report slightly higher concentrations, possibly
reflecting past uses (Sapphire Group. 2007).
EPA's third Unregulated Contaminant Monitoring Rule (UCMR 3), published in 2012, required
monitoring for 1,4-dioxane, along with 29 other contaminants. Over 28,000 drinking water samples
were collected for chemicals suspected to be present in drinking water that lack health-based standards
under the Safe Drinking Water Act.
Reported levels of 1,4-dioxane in groundwater range from 3 to 31,000 |ig/L (ATSDR. 2012; LISGS.
2002). Such instances of ground water contamination with 1,4-dioxane are documented in the states of
California and Michigan. These data provide a basis for including groundwater in the scope of the
l,4dioxane risk evaluation from manufacturing, processing, distribution and use unless otherwise
regulated or managed.
There are relatively fewer data available on 1,4-dioxane levels in surface water, though some studies of
groundwater contamination also reported levels in nearby surface water. 1,4-Dioxane is released into
surface water and some studies have examined 1,4-dioxane levels in sewage treatment or chemical plant
effluent, combined collection treatments from apartment homes, and in river basin systems (ATSDR.
2012). 1,4-Dioxane has also been detected in landfill leachate (ATSDR. 2012).
1,4-Dioxane has not been measured and is unlikely to be present at elevated levels in sediment, sludge,
soil or dust, based on its physical and chemical properties. Note, 1,4 dioxane is expected to be present in
the water within the biosolids and the porewater within the soil. 1,4-Dioxane has a low bioaccumulation
potential for accumulation in aquatic organisms and is short-lived in humans and few biomonitoring data
are available.
2.3.4 Environmental Exposures
The manufacturing, processing, use and disposal of 1,4-dioxane can result in releases to the
environment. In this section, EPA presents exposures to aquatic and terrestrial organisms.
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Aquatic Environmental Exposures
EPA identified and reviewed national scale monitoring data to support this problem formulation. Based
on national-scale monitoring data from EPA's STOrage and RETreival (STORET) and National Water
Information System (NWIS) for the past ten years, 1,4-dioxoane is detected in surface water. The data
points showed a detection rate of approximately 6% for this media, with detections ranging from 0.568
to 100 |ig/L.
While recent monitoring data on ambient surface water levels indicate relatively low levels, EPA has
used release estimates and measured effluent concentrations from EPA's Toxic Release Inventory (TRI)
and Discharge Monitoring Report (DMR) Pollutant Loading Tool, respectively, to predict surface water
concentrations near such discharging facilities for this problem formulation. To examine whether near-
facility surface water concentrations could approach 1,4-dioxane's concentrations of concern, EPA
employed a conservative approach, using readily-available modeling tools and data, as well as
conservative assumptions. EPA's Exposure and Fate Assessment Screening Tool (U.S. EPA. 2.014b)
was used to estimate site-specific surface water concentrations based on estimated loadings of 1,4-
Dioxane into receiving water bodies or reported on-site releases to surface waters for DMR and TRI
facilities. The estimated loadings for the DMR facilities are calculated by the DMR Tool by combining
the reported effluent concentrations with facility effluent flows. For TRI, the reported releases are based
on monitoring, emission factors, mass balance and/or other engineering calculations. E-FAST 2014
incorporates stream dilution using stream flow information contained within the model. E-FAST also
incorporates wastewater treatment removal efficiencies. Wastewater treatment removal is assumed to be
0% for this exercise, as reported loadings/releases are assumed to account for any treatment. To ensure
this effort was likely to capture high-end surface water concentrations, loading data from the top ten
dischargers from each data source were modeled for the last two years of complete datasets (2014-2015
for TRI sites and 2015-2016 for DMR facilities). Furthermore, as days of release and operation are not
reported in these sources, EPA assumed a range of possible release days (i.e., 1, 20, and 250 days/year
for facilities and 250 days/year for wastewater treatment plants or POTWs). Refer to the E-FAST 2014
Documentation Manual for equations used in the model to estimate surface water concentrations (U.S.
EPA. 2007). Based on availability of site-specific flow data within E-FAST 2014 and scenario results,
refinements were made to clarify or confirm the receiving water body and/or likely days of release.
High-end surface water concentrations (i.e., those obtained assuming low receiving water body stream
flows) from all E-FAST 2014 runs ranged from 0.006 |ig/L to 11,500 |ig/L, with the minimum of 0.006
|ig/L associated with a chronic release scenario (i.e., more than 20 days of release per year assumed) and
the maximum of 11,500 |ig/L associated with an acute release scenario (i.e., fewer than 20 days of
release per year assumed). The maximum acute scenario high-end concentration was 11,500 |ig/L and
the maximum chronic scenario high-end concentration was 5,762 |ig/. Results based on TRI release
estimates were within the same range as those based on DMR annual loading values for the top ten
dischargers and the reporting years covered. For a full table of results, see Appendix E.
Terrestrial Environmental Exposures
Based on its fate properties, 1,4-dioxane is not expected to reside in soil because it will either volatilize
from dry surfaces and dry soil or move through the soil column with pore water.
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2.3.5 Human Exposures
In this section, EPA presents occupational and general population exposures. Subpopulations, including
potentially exposed and susceptible subpopulations, within these exposure categories 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 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 occupational non-users may be exposed to 1,4-dioxane when performing activities
associated with the conditions of use described in Section 2.2, including, but not limited to:
• Unloading and transferring 1,4-dioxane to and from storage containers to process vessels.
• Using 1,4-dioxane in process equipment.
• Cleaning and maintaining equipment.
• Sampling chemical, formulations or products containing 1,4-dioxane for quality control.
• Repackaging chemicals, formulations or products containing 1,4-dioxane.
• Handling, transporting and disposing waste containing 1,4-dioxane.
• Performing other work activities in or near areas where 1,4-dioxane is used.
Key Data
Key data that inform occupational exposure assessment include: the OSHA Chemical Exposure Health
Data (CEHD) and 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/oshstats/index.html. Table Apx B-l in Appendix
B.1.3 provides a summary of industry sectors with 1,4-dioxane personal monitoring air samples obtained
from OSHA inspections conducted between 2002 and 2016. 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/.
Inhalation
Based on these activities, inhalation exposure to vapors and mists are expected for workers and
occupational non-users. There is potential for spray application of some products containing 1,4-dioxane
so exposures to mists are also expected for workers and will be incorporated into the worker inhalation
exposure. See section 2.5.1 for additional details on the pathways EPA expects to analyze for
occupational exposures.
The United States has several regulatory and non-regulatory exposure limits for 1,4-dioxane: An
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (PEL) of 100 ppm
8-hour time-weighted average (TWA) (360 mg/m3) with a skin notation, a National Institute of
Occupational Safety and Health (NIOSH) Recommended Exposure Limit (REL) of 1 ppm (3.6 mg/m3)
as a 30-minute ceiling and an American Conference of Government Industrial Hygienists (ACGIH)
Threshold Limit Value (TLV) of 20 ppm TWA (72 mg/m3) (OSHA. 2005). The influence of these
exposure limits on occupation exposures will be considered in the occupational exposure assessment.
Dermal
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Based on the conditions of use, EPA expects dermal exposure for workers and occupational non-users,
including skin contact with vapors, liquids and mists. Occupational non-users do not handle the
chemical directly, so dermal exposure from liquids containing 1,4-dioxane are not expected.
Oral
Worker exposure via the oral route is not expected. For some uses (described in Section 2.5.1), there are
potential worker exposures through mists that deposit in the upper respiratory tract. Based on physical
chemical properties, mists of 1,4-dioxane will likely be rapidly absorbed in the respiratory tract and will
be considered as an inhalation exposure.
2.3.5.2 Consumer Exposures
As stated in the Scope document (U.S. EPA. 2017c) and Section 2.2.2.1, there are no current consumer
uses for 1,4-dioxane in the U.S.
2.3.5.3 General Population Exposures
Wastewater/liquid wastes, solid wastes or air emissions of 1,4-dioxane could result in potential
pathways for oral, dermal or inhalation exposure to the general population.
Inhalation
The general population may be exposed to 1,4-dioxane through inhalation of ambient air and indoor air.
Ambient air exposures may occur from releases from industrial/commercial sources. Indoor air
exposures may occur from infiltration from ambient air or emissions from tap water during activities
such as showering and bathing. Based on the relatively high water solubility and relatively low Henry's
law constant for 1,4-dioxane, EPA expects that volatilization would be low for many indoor uses.
However, increased water temperature during bathing and showering can increase volatilization. The
Henry's Law constant for 1,4-dioxane is appreciably higher at 40°C (4.9 x 10"4 atm-m3/mole) than 25°C
(4.8 x 10"6 atm-m3/mole). Furthermore, smaller droplets of water created by some indoor uses (e.g.,
showering) have a larger surface area from which 1,4-dioxane may volatize.
Vapor intrusion and volatilization from wastewater treatment are not considered significant sources of
exposure to the general population because the Henry's Law constant (4.8 x 10"6 atm-m3/mole) and high
water solubility of 1,4-dioxane (>800 g/L) indicate that 1,4-dioxane will primarily remain in the aqueous
phase (wastewater or groundwater) and that volatilization from water to air will be limited. Estimated
volatilization from the sewage treatment plant (STP) module in EPI Suite™ found that 0.27% of 1,4-
dioxane in wastewater would be removed by volatilization during wastewater treatment.
Oral
The general population may ingest 1,4-dioxane via contaminated drinking water. Based on reported
uses, down-the-drain sources may contribute to surface water and drinking water levels. Therefore, there
is potential oral exposure to 1,4-dioxane by ingestion of drinking water from surface water and ground
water sources to municipal drinking water.
Dermal
Dermal exposure via water may occur through extended contact with tap water containing 1,4-dioxane
during washing and bathing. The source of the contaminated water may be either contaminated surface
or ground waters used as a source of municipal drinking water.
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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
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 potentially exposed or
susceptible subpopulations 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 potentially exposed or susceptible subpopulations due to their greater
exposure:
• Workers and occupational non-users.
• Other groups of individuals within the general population who may experience greater exposures
due to their proximity to conditions of use identified in Section 2.2 that result in releases to the
environment and subsequent exposures (e.g., individuals who live or work near manufacturing,
processing, distribution, use or disposal sites).
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
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) when compared with the general population (U.S. EPA. 2006).
In summary, in the risk evaluation for 1,4-dioxane, EPA plans to analyze the following potentially
exposed groups of human receptors: workers, occupational non-users and the general population. EPA
may also identify additional potentially exposed or susceptible subpopulations that will be considered
based on greater exposure.
2.4 Hazards (Effects)
For scoping, EPA conducted comprehensive searches for data on hazards of 1,4-dioxane, as described in
Strategy for Conducting Literature Searches for 1,4-Dioxane: Supplemental File for the TSCA Scope
Document (If IP -I iQ-OPPT -2016-0723). Based on initial screening, EPA plans to analyze the hazards of
1,4-dioxane 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.
2.4.1 Environmental Hazards
During problem formulation, EPA analyzed potential environmental health hazards associated with 1,4-
dioxane. EPA identified the following sources of environmental hazard data for 1,4-dioxane: (Health
Page 32 of 90
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Canada. 2010; ECJRC. 2002; OECD. 1999; NICNAS. 1998); and the European Chemicals Agency
(ECHA) Database. Studies published since 2003 were identified in the literature search for 1,4-dioxane
(1,4-Dioxane (CASRN123-91-1) Bibliography: Supplemental File for the TSCA Scope Document, EPA-
HQ-QPPT-2016-0723) and were reviewed as described in Application of Systematic Review in TSCA
Risk Evaluations (U.S. EPA. 2018a) and Strategy for Assessing Data Quality in TSCA Risk Evaluations
(U.S. EPA. 2018b). 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 1-4-Dioxane: Supplemental Document to the TSCA
Scope Document, CASRN: 123-91-1). Data from the screened literature are summarized below (Table
2-8) as ranges (min-max). EPA plans to complete review of 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 (U.S. EPA. 2018a).
Toxicity to Aquatic Organisms
EPA identified 1,4-dioxane environmental hazard data for fish, aquatic invertebrates and aquatic plants
exposed under acute and chronic exposure conditions. Aquatic toxicity studies are summarized in Table
2-8.
Table 2-J
i. Ecological Hazard Characterization of 1,4-Dioxane
Duration
Test organism
Endpoint
Hazard
valuc(s)
Units
Effect(s)
Citation(s)
Aquatic Organisms
Acute
Fish
LCso
>100-
67,000
mg/L
Mortality
(Geieer et al.. 1990)
Aquatic
invertebrates
ECso
>299 -
>1,000
mg/L
Immobilization
(Dow Chemical Comoanv. 1989)
as cited in (ECJRC. 2002)
Algae
ECso
575 - 5600
mg/L
Inhibition
(Brineman and Kulin. 1977)
580
mg/L
Biomass
(ECHA. 2014b)
>1,000
mg/L
Biomass
(ECHA. 2014b)
Acute COC = 60 mg/L
Chronic
Fish
NOECb
565
mg/L
Carcinogenicity
(Johnson et al.. 1993)
MATC°
>145
Development, Hatching,
Survival
(TSCATS. 1989) as cited in
(ECJRC. 2002)
Aquatic
invertebrates
NOEC
1,000
mg/L
Reproduction
(ECHA. 2014a)
Chronic COC = 15 mg/L
Terrestrial Organisms
Chronic
Terrestrial Plant
ECso
1,450
mg/L
Germination/Root
Elongation
(Reynolds. 1989)
aValues in the tables are presented as reported by the study authors.
bNOEC: No Observable Effect Concentration,
°MATC, Maximum Acceptable Toxicant Concentration; Calculated using the geometric mean of LOEC and NOEC values
(as described in (U.S. EPA. 2013a)
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The acute 96-hour LCso values for fish range from >100 mg/L (highest concentration tested) for fathead
minnow {Pimephalespromelas) to 67,000 mg/L for inland silversides (Menidia beryllina). Two studies
on the acute ecotoxicity to aquatic invertebrates (Daphnia magna and Ceridodaphnia dubia) indicate
that the 48-hour EC.mi is >1,000 mg/L (highest concentration tested) (ECJRC. 2002) and >299 mg/L
(highest concentration tested; (Dow Chemical Company. 1989)).
In a chronic study, Medaka (Oryzias latipes) were exposed to measured concentrations of 1,4-dioxane
ranging from 565 to 6,933 mg/L for 28 days under flow-through conditions. There were effects on
growth and survival (Johnson etai. 1993). A no observed effect concentration (NOEC) of 565 mg/L
was reported. In another study, fathead minnows (P. promelas) were exposed to 1,4-dioxane for 32 days
to mean measured concentrations of 27.6, 40.3, 65.3, 99.7 and 145 mg/L to observe the effects on
embroyonic development (i.e., hatching, larval development, and larval survival) under flow-through
conditions. No effects were observed. A NOEC of >103 mg/L based on larval survival and a maximum
acceptable toxicant concentration (MATC) of 145 mg/L was calculated (NOEC=M ATC/V2) (ECJRC.
2002).
In a study on the chronic toxicity of 1,4-dioxane to aquatic invertebrates, water fleas (D. magna) were
exposed to unspecified concentrations of 1,4-dioxane in a 21-day reproduction test. The exposure
conditions were not reported. The highest exposure concentration tested was 1,000 mg/L. No effects on
reproduction, survival, or growth were reported. A 21 -day NOEC of > 1,000 mg/L was reported (ECH.A.
2014a).
Three studies have characterized the toxicity of 1,4-dioxane to aquatic plants. In one study, green algae
(Pseudokirchnerella subcapitata) were exposed to unspecified concentrations of 1,4-dioxane for 72-
hours under static conditions. No effects were observed on growth rate or biomass at 1,000 mg/L, the
highest concentration tested. A 72-hour EC so (growth rate and biomass) of > 1,000 mg/L was reported.
A NOEC (biomass) of 580 mg/L and a NOEC (growth rate) of 1,000 mg/L was reported (ECHA.
2014b). Also, two short-term toxicity studies in Microcystis aeruginosa and Scenedesmus quadricauda
reported EC so cell inhibition of 575 and 5,600 mg/L after eight days of exposure to 1,4-dioxane
(Bringman and Kuhn. 1977).
Toxicity to Sediment and Terrestrial Organisms
In one study, lettuce (Actuca sativa) were exposed to 1,4-dioxane in a germination/root elongation
toxicity test for 3-days. An EC50 of 1,450 mg/L was reported for germination (Reynolds. 1989).
There are no available acute or chronic toxicity studies that characterize the hazard of 1,4-dioxane to
sediment organisms. However, available hazard, fate and exposure characteristics (Sections 2.3.1 and
2.3.3) suggest that sediment organisms are not at risk from 1,4-dioxane exposures.
Concentrations of Concern (COC)
The concentrations of concern (COCs) for aquatic species were calculated based on the summarized
environmental hazard data for 1,4-dioxane. The analysis of the environmental COCs are described in
Appendix C and are based on EPA/OPPT methods (U.S. EPA. 2013a. 2012d). The acute and chronic
COC for 1,4-dioxane are based on the lowest toxicity value in the dataset. For a particular environment
(e.g., aquatic environment), the COC is based on the most sensitive species or the species with the
lowest toxicity value reported in that environment.
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The acute concentration of concern for 1,4-dioxane is based on a 96-hour fish toxicity study where the
LC.mi is >100 mg/L (ECH.A. 2.014a; Geigeretal.. 1990) and the chronic COC is based on a 32-day
MATC fish toxicity value of 145 mg/L (Brooke. 1987). The acute and chronic COCs for 1,4-dioxane are
59,800 ppb and 14,500 ppb, respectively.
2.4,2 Human Health Hazards
1,4-Dioxane has an existing EPA IRIS Assessment ( ), an ATSDR Toxicological
Profile (ATSDR. 2012), a Canadian Screening Assessment (Health Canada. 2010). a European Union
(EU) Risk Assessment Report (ECJRC. 2002) and an Interim AEGL (U.S. EPA. 2005b); hence, many of
the hazards of 1,4-dioxane have been previously compiled and reviewed. 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 (U.S. EPA.
2.018a). EPA also plans to analyze other studies (e.g., more recently published, alternative test data) that
have been published since these reviews, as identified in the literature search conducted by the Agency
for 1,4-dioxane (1,4-Dioxane (CASRN123-91-1) Bibliography: Supplemental File for the TSCA Scope
Document, EPA-HQ-QPPT-2016-0723). Based on reasonably available information, the following
sections describe the potential hazards associated with 1,4-dioxane.
2.4.2.1 Non-Cancer Hazards
Acute Toxicity
Effects following acute exposures were evaluated (U.S. EPA. 2005b). The Interim AEGLs (
2005b) evaluated the data on acute toxicity and irritation and concluded that, in animals, acute toxic
effects of 1,4-dioxane include central nervous system depression, kidney and liver damage and irritation.
Humans acutely exposed to 1,4-dioxane experienced irritation of the eyes, nose and throat, nausea and
vomiting, coma and death. Also, 1,4-dioxane can cause narcosis in animals inhaling very high
concentrations (U.S. EPA. 2005b).
Irritation
Acute inhalation studies in human volunteers noted irritation of the eyes, nose and throat (U.S. EPA.
2005b). In rats, 2 years of inhalation exposure to 1,4-dioxane, resulted in metaplasia, hyperplasia,
atrophy, hydropic change, vacuolic change and preneoplastic cell proliferation in the nasal cavity (U.S.
EPA. 2013c).
Liver Toxicity
In subchronic and chronic repeated exposure studies conducted in rats and mice by the oral (via drinking
water) and inhalation routes, evidence shows that 1,4-dioxane is toxic to the liver ( 013c).
Chronic administration of 1,4-dioxane via the drinking water resulted in hepatocellular degeneration and
preneoplastic changes. Inhalation exposure to 1,4-dioxane resulted in necrosis of the centrilobular region
and preneoplastic changes in the liver.
Kidney Toxicity
In subchronic and chronic repeated exposure studies conducted in rats and mice by the oral (via drinking
water) and inhalation routes, evidence shows that 1,4-dioxane is toxic to the kidney (U.S. EPA. 2013c).
Kidney damage following drinking water exposure to 1,4-dioxane includes degeneration of cortical
tubule cells, necrosis with hemorrhage and glomerulonephritis.
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2.4.2.2 Genotoxicity and Cancer Hazards
;013c) concluded that overall, the available literature indicates that 1,4-dioxane is
nongenotoxic or weakly genotoxic. Per EPA's Cancer Guidelines ( 05a). EPA concluded
"there is insufficient biological support for potential key events and to have reasonable confidence in the
sequence of events and how they relate to the development of nasal tumors following exposure to 1,4-
dioxane". No single mode of action (MO A) accounts for the formation of liver, nasal, peritoneal
(mesotheliomas), and mammary gland tumors seen in laboratory animals exposed to 1,4-dioxane. Some
data support a non-linear MOA for liver tumorigenesis, but currently available data do not support non-
linearity for the remaining tumor types.
EPA evaluated the weight of the evidence for cancer in humans and animals and concluded that
1,4-dioxane is "likely to be carcinogenic to humans" based on evidence of carcinogenicity in several
2-year bioassays (oral and inhalation) conducted in four strains of rats, two strains of mice and in guinea
pigs (U.S. EPA. 2013c). The National Toxicology Program classified 1,4-dioxane as "reasonably
anticipated to be a human carcinogen" (NTP. 2016). and NIOSH has classified it as a "potential
occupational carcinogen" (ATSDR. 2012). Human occupational studies into the association between
1,4-dioxane exposure and increased cancer risk are inconclusive because they are limited by small
cohort size and a small number of reported cancer cases.
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).
2.5 Conceptual Models
EPA risk assessment guidance (( , ?)), 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 1,4-dioxane, 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.
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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 1,4-dioxane 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
comprehensive risk evaluations. 82 FR 33726, 33734, 33739 (July 20, 2017).
As part of this problem formulation, EPA also identified t exposure pathways under 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 Clean Air Act (CAA), the Safe
Drinking Water Act (SDWA), the Clean Water Act (CWA) and the Resource Conservation and
Recovery Act (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 focus on those exposure pathways associated with TSCA uses that are not
subject to the regulatory regimes discuss above because these pathways are likely to represent the
greatest areas of concern to EPA. As a result, EPA does not plan to include in the risk evaluation certain
exposure pathways identified in the 1,4-dioxane 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 1,4-dioxane that EPA plans to include in the risk evaluation. There are
exposures to workers and occupational non-users via dermal and inhalation routes during
manufacturing, processing, use and disposal of 1,4-dioxane for all uses identified in the scope, except
for distribution in commerce. During distribution, 1,4-dioxane is contained in closed systems (e.g.
drums, pails, bottles) so releases and exposures are not expected. Any associated open system loading
and unloading activities into these containers will be analyzed for the condition of use.
The description for uses of 1,4-dioxane as Functional Fluids has been refined to include both open and
closed systems. When the scope of the risk evaluation was determined, the information available to EPA
suggested that 1,4-dioxane was used as Functional Fluids only in closed systems. However, during
problem formulation, EPA determined that some of the subcategories of uses, such as cutting and
tapping fluid, may also include uses in open systems. This change is reflected in the conceptual model (
Figure 2-2).
Inhalation
EPA expects that for workers and occupational non-users, exposure via inhalation will be the most
significant route of exposure for most exposure scenarios. EPA plans to further analyze inhalation
exposures to vapors and mists for workers and occupational non-users in the risk evaluation.
EPA reviewed the potential for occupational exposures associated with subcategories of conditions of
use where a mist may be generated. EPA determined that most subcategories will not produce a mist
during their typical use and, for these, EPA concludes that exposure to 1,4-dioxane would be negligible
and does not plan further analysis. For subcategories of uses where either a spray application or rotary
equipment is likely, EPA determined that these conditions of use may produce a mist that could result in
exposures for workers when the mist is inhaled and subsequently swallowed and EPA plans to analyze
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exposures associated with these uses. EPA will also evaluate subcategories of uses where EPA is
uncertain whether a mist is likely to be produced during use. EPA expects to further evaluate exposure
via a mist for the uses listed in Table 2-9.
Table 2-9.1,4-Dioxane Conditions of Use that May Produce a Mist
Life Cycle S(a«e
Category
Subcategory
Processing
Recycling
Recycling
Industrial use
Processing aids, not otherwise
listed
Wood pulping
Extraction of animal and vegetable
oils
Wetting and dispersing agent in
textile processing
Etching of fluoropolymers
Industrial use
Functional fluids (open and
closed system)
Polyalkylene glycol lubricant
Synthetic metalworking fluid
Cutting and tapping fluid
Hydraulic fluid
Industrial use, potential
commercial use
Other uses
Spray polyurethane foam
Printing and printing compositions
Dermal
There is the potential for dermal exposures to 1,4-dioxane in many worker scenarios. Dermal exposure
from contact with liquids containing 1,4-dioxane are expected primarily for workers, such as operators,
directly involved in working with these liquids. Where workers may be exposed to 1,4-dioxane, the
OSHA standard requires that workers are protected from contact (e.g. gloves) (29 CFR 1910.1052).
Occupational non-users are not directly handling 1,4-dioxane; therefore, skin contact with liquid 1,4-
dioxane is not expected for occupational non-users and will not be further analyzed in the risk
evaluation. EPA plans to further analyze dermal exposures for skin contact with liquids in occluded
situations for workers.
Workers and occupational non-users can have skin contact with 1,4-dioxane vapor concurrently with
inhalation exposures. The parameters determining the absorption of 1,4-dioxane vapor are based on the
concentration of the vapor, the duration of exposure and absorption. The concentration of the vapor and
the duration of exposure are the same for concurrent dermal and inhalation exposures. Therefore, the
differences between dermal and inhalation exposures depend on the absorption. The dermal absorption
can be estimated from the skin permeation coefficient (0.00043 cm/hr from a water solution; (Bronaugh.
1982)) and exposed skin surface area (on the order of 0.2 nr, (U.S. EPA. 201 la)). The absorption of
inhaled vapors can be estimated from the volumetric inhalation rate (approximately 1.25 m3/hr for a
person performing light activity, (U.S. EPA. JO LI 3)) adjusted by a retention factor such as 0.75. Based
on these parameters the absorption of 1,4-dioxane vapor via skin will be orders of magnitude lower than
via inhalation and will not be further analyzed.
Oral
There are potential worker exposures through mists that deposit in the upper respiratory tract. Based on
physical chemical properties, mists of 1,4-dioxane will likely be rapidly absorbed in the respiratory tract
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or evaporate and contribute to the amount of 1,4-dioxane vapor in the air. Furthermore, if 1,4-dioxane
mists were ingested orally the available toxicological data do not suggest significantly different toxicity
from considering the mists as an inhalation exposure.
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 1,4-dioxane.
For each condition of use identified in Table 2-3, a determination was made as to whether each unique
combination of exposure pathway, route, and receptor will be evaluated further in the risk evaluation.
The results of that analysis along with the supporting rationale are presented in Appendix D and
Appendix E.
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INDUSTRIAL AND COMMERCIAL EXPOSURE PATHWAY EXPOSURE ROUTE RECEPTORSd HAZARDS
ACTIVITES / USES a
Manufacture
(Including Import)
Hazards Potentially Associated
with Acute and/or Chronic
Exposures
See Section 2.4.2
Liquid Contact
Dermal
Workerse
Processing:
• Processing as a
reactant/intermediate
• Repackaging
• Non-incorporative
activities
Occupational
Non-Users
Vapor/ Mist
Inhalationc
Fugitive
Emissionsb
Recycling
Processing Aids, Not
Otherwise Listed
Functional Fluids
(Open and Closed Systems)
Laboratory Chemicals
Other Industrial or
Commercial Uses
Waste Handling,
Treatment and
Disposal
KEY:
^ Pathway that will be further analyzed
—^ Pathway that will not be further analyzed
Black txt: In scope; will be further analyzed
Wastewater, Liquid Wastes, Solid Wastes
(See Figure 2-3)
Figure 2-2.1,4-Dioxane 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 1,4-dioxane that EPA plans to analyze.
a Additional uses of 1,4-dioxane are included in Table 2-3.
b Fugitive air emissions are those that are not stack emissions (emissions that occur through stacks, confined vents, ducts, pipes or other confined air streams), and 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.
0 Based on physical chemical properties, 1,4-dioxane in mists that deposit in the upper respiratory tract will likely be rapidly absorbed in the respiratory tract or evaporate
and may be considered an inhalation exposure.
d Receptors include potentially exposed or susceptible subpopulations.
e When data and information are available to support the analysis, EPA also considers the effect that engineering controls and/or personnel 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
The 1,4-dioxane life cycle diagram (Figure 2-1) indicates that no uses of 1,4-dioxane were identified in
consumer products. EPA did not receive data, information or comments that informed a change was
necessary to the scope. Therefore, EPA does not plan to evaluate use of 1,4-dioxane in consumer
products and 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 2-2) illustrates the expected exposure pathways to human and
ecological receptors from environmental releases and waste stream associated with industrial and
commercial activities for 1,4-dioxane. The pathways that EPA plans to include but not analyze further in
risk evaluation are described in Section 2.5.3.2 and shown in the conceptual model. The pathways that
EPA does not plan to include in the risk evaluation are described in Section 2.5.3.2.
2.5.3.1 Pathways That EPA Plans to Include and Further Analyze in the Risk
Evaluation
There are no environmental release and waste pathways for the environment or general populations that
EPA plans to include and further analyze in the risk evaluation (see Figure 2-3).
2.5.3.2 Pathways that EPA Plans to Include in the Risk Evaluation But Not Further
Analyze
The pathways that EPA plans to include in the risk evaluation but not further analyze are ambient water
exposure to aquatic vertebrates, invertebrates and aquatic plants, sediment and land-applied biosolids.
Aquatic Pathways
EPA analyzed risks to aquatic organisms exposed to 1,4-dioxane in surface water based on the relatively
high potential for release, fate properties, and the availability of environmental monitoring data and
hazard data. Based on 2015 TRI reporting, an estimated 35,402 lb of 1,4-dioxane was released to water
from industrial sources. 1,4-Dioxane has high water solubility and slow removal from surface water due
lack of hydrolysis (no hydrolyzable groups) and slow biodegradation (< 10% degradation in 29 days).
Monitored concentrations in surface water from STORET/NWIS are as high as 100 |ig/L and predicted
concentrations in surface water for acute and chronic scenarios are up to 11,500 |ig/L and 5,762 |ig/L,
respectively (Section 2.3.4). Measured and estimated levels of 1,4-dioxane in the environment are
sufficiently below the acute and chronic aquatic COCs of 20,000 |ig/L and 14,500 |ig/L (See
Environmental Hazards, Section 2.4.1 and Analysis of the Environmental Concentrations of Concern,
Appendix C). EPA is including the analysis of risks to aquatic invertebrates and aquatic plants from
exposures to 1,4-dioxane in surface waters in the evaluation, but will not further analyze the data.
Sediment Pathways
EPA does not plan to further analyze 1,4-dioxane pathways to sediment. 1,4-Dioxane is expected to
remain in aqueous phases and not adsorb to sediment due to its water solubility (> 800 g/L) and low
partitioning to organic matter (log KOC = 0.4). Limited sediment monitoring data for 1,4-dioxane that
are available suggest that 1,4-dioxane is present in sediments, but because 1,4-dioxane does not partition
to organic matter (log KOC = 0.4) and biodegrades slowly [<10% biodegradation in 29 days (ECHA,
1996)], 1,4-dioxane concentrations in sediment pore water are expected to be similar to the
concentrations in the overlying water. Thus, the 1,4-dioxane detected in sediments is likely from the
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pore water and not 1,4-dioxane that was sorbed to the sediment solids. While no ecotoxicity studies were
available for sediment organisms, the toxicity of 1,4-dioxane to sediment invertebrates is expected to be
similar to the toxicity to aquatic invertebrates.
Land-Applied Biosolids Pathway
EPA does not plan to further analyze other releases to land during risk evaluation, including biosolids
application to soil. EPA expects releases of 1,4-dioxane to wastewater treatment plants (WWTP),
resulting in biosolids that can be land-applied. Species in the environment including aquatic organisms,
amphibians and terrestrial organisms may come into contact with 1,4-dioxane-contaminated biosolids
and soil pore water when the biosolids are land applied. However, the release of 1,4-dioxane from land-
applied biosolids represents a negligible fraction of its overall environmental release, due to its physical-
chemical properties.
1,4-Dioxane is not expected to adsorb to soil and sediment due to its low partitioning to organic matter
(estimated log Koc = 0.4), so 1,4-dioxane in biosolids is expected to be in the aqueous phase associated
with the biosolids rather than adsorbed to the organic matter. The aqueous phase represents > 95% of
biosolids, or > 70% if the biosolids are dewatered, and at the time of removal the water in the biosolids
will contain the same concentration of 1,4-dioxane as the rest of the wastewater at the activated sludge
stage of treatment. However, the volume of water removed with biosolids represents < 2% of
wastewater treatment plant influent volume ( ), and is < 1% of influent volume when the
sludge is dewatered and the excess water is returned to treatment, a process that is commonly used
(NRC. 1996). Thus, the water released from a treatment plant via biosolids is negligible compared to
that released as effluent. By extension the 1,4-dioxane released from wastewater treatment via biosolids
is expected to be negligible compared to the 1,4-dioxane released with effluents: of the 1,4-dioxane in
influent wastewater, it is expected that approximately 2% will be removed via adsorption to sludge or
volatilization to air, < 2% will be removed with biosolids-associated water, and > 95% will be present in
the effluent (see Section 2.3.1, Fate and Transport). Further, the concentrations of 1,4-dioxane in
biosolids may decrease through volatilization to air during transport, processing (including dewatering
and digestion), handling, and application to soil (which may include spraying). When 1,4-dioxane is
released in the environment, it is expected to be mobile in soil and migrate to surface waters and
groundwater or volatilize to air. 1,4-Dioxane is expected to volatilize readily from dry soil and surfaces
due to its vapor pressure (40 mm Hg). Overall, the exposures to surface water from biosolids will be
negligible compared to the direct release of WWTP effluent to surface water, and therefore exposures of
aquatic organisms from surface water due to land-applied biosolids will not be further analyzed.
2.5.3.3 Pathways That EPA Does Not Plan to Include in the Risk Evaluation
Exposures to receptors (i.e. general population) 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,
pathways under other environmental statutes, administered by EPA, which adequately assess and
effectively manage exposures and for which long-standing regulatory and analytical processes already
exist will not be included in the risk evaluation. These pathways are described below.
Ambient Air Pathway
The Clean Air Act (CAA) contains a list of hazardous air pollutants (HAP), including 1,4-dioxane, 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
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adequately protect public health and the environment. The CAA thereby provides EPA with
comprehensive authority to regulate emissions to ambient air of any HAP.
1,4-Dioxane is a HAP. EPA has issued a number of technology-based standards for source categories
that emit 1,4-dioxane to ambient air and, as appropriate, has reviewed, or is in the process of reviewing
remaining risks. Because stationary source releases of 1,4-dioxane to ambient air are adequately
assessed and any risks effectively managed when under the jurisdiction of the CAA, EPA does not plan
to evaluate 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 Safe Drinking Water Act (SDWA). Under
SDWA, EPA must also review and revise "as appropriate" existing drinking water regulations every 6
years.
The Contaminant Candidate List (CCL) is a list of unregulated contaminants that are known or
anticipated to occur in public water systems and that may require regulation. EPA must publish a CCL
every 5 years and make Regulatory Determinations (RegDet) to regulate (or not) at least five CCL
contaminants every 5 years. To regulate a contaminant EPA must conclude the contaminant may have
adverse health effects, occurs or is substantially likely to occur in public water systems at a level of
concern and that regulation, in the sole judgement of the Administrator, presents a meaningful
opportunity for health risk reduction.
Currently, there is no National Primary Drinking Water regulation for 1,4-Dioxane under SDWA. 1,4-
dioxane released to surface water can contribute to levels of the chemical in drinking water. EPA's
Office of Water has established a Health Advisory level of 35 |ig/L (which corresponds to a 1 in ten
thousand lifetime cancer risk) for 1,4-Dioxane. 1,4-Dioxane is also currently listed on EPA's Fourth
Contaminant Candidate List (CCL 4) and was subject to occurrence monitoring in public water systems
under the third Unregulated Contaminants Monitoring Rule (UMCR 3). Under UMCR 3, water systems
were monitored for 1,4-dioxane during 2013-2015. Of the 4,915 water systems monitored, 1,077
systems had detections of 1,4-dioxane in at least one sample. None of the systems measured levels
greater than the Health Advisory level, however, 341 systems (6.9%) had results at or above 0.35 |ig/L
(which corresponds to a 1 in a million-lifetime cancer risk). In accordance with EPA-OW's process, 1,4-
dioxane is currently being evaluated under the fourth Regulatory Determination process under SDWA.
Hence, because the drinking water exposure pathway for 1,4-dioxane is being addressed under the
regular analytical processes to identify and evaluate drinking water contaminants of potential regulatory
concern for public water systems under SDWA, EPA does not plan to include this pathway in the risk
evaluation for 1,4-dioxane under TSCA. EPA's Office of Water and Office of Pollution Prevention and
Toxics will continue to work together providing understanding and analysis of the SDWA regulatory
analytical processes for public water systems 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. A criterion is a hazard
assessment only; i.e. there is no exposure assessment or risk estimation. When states adopt criteria that
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EPA approves as part of state's 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 not developed CWA section 304(a) recommended water quality criteria for the protection of
aquatic life for 1,4-dioxane, 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. Currently, only one
state (Colorado) includes human health criteria for 1,4-dioxane in their water quality standards and none
include aquatic life criteria for 1,4-dioxane. As a result, this pathway will undergo aquatic life risk
evaluation under TSCA (see Section 2.5.3.2). EPA may publish CWA section 304(a) aquatic life criteria
for 1,4-dioxane in the future if it is identified as a priority under the CWA.
Disposal Pathways
1,4-Dioxane is included on the list of hazardous wastes pursuant to RCRA 3001 (40 CFR §§ 261.33) as
a listed waste on the F and U lists. The general RCRA standard in section 3004(a) for the technical
(regulatory) criteria that govern the management (treatment, storage, and disposal) of hazardous waste
(i.e., Subtitle C) 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 Clean Air Act (CAA) hazardous
waste combustion MACT) or injected into UIC Class I hazardous waste wells (subject to joint control
under Subtitle C and the Safe Drinking Water Act (SDWA)).
Emissions to ambient air from municipal and industrial waste incineration and energy recovery units
will not be included 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 1,4 dioxane wastes (the majority of the 46,000 lbs identified as treated in Table
2-6) would be subject to these regulations, as would 1,4 dioxane burned for energy recovery (1.6 million
lbs).
EPA does not plan to include on-site releases to land that go to underground injection in its risk
evaluation. TRI data ( 1015b) indicate that 94,304 lb of 1,4-dioxane was disposed of on-site to
Class I underground injection wells and no releases to underground injection wells of Classes II-VI.
Environmental disposal of 1,4-dioxane injected into Class I well types are managed and prevented from
further environmental release by RCRA and SDWA regulations. Therefore, disposal of 1,4-dioxane via
underground injection is not likely to result in environmental and general population exposures.
EPA does not plan to include on-site releases to land that go to RCRA Subtitle C hazardous waste
landfills or RCRA Subtitle D municipal solid waste (MSW) landfills in its risk evaluation. TRI data
(U.S. EPA. 2015b) indicate that RCRA Subtitle C Landfills received 13,375 lb of 1,4-dioxane, with a
small amount of 1,4-dioxane (47 lb) reported to on-site landfills other than RCRA Subtitle C Landfills.
Design standards for Subtitle C landfills require double liner, double leachate collection and removal
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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 exposure to 1,4-dioxane in
groundwater from Subtitle C landfill leachate is not expected to be a significant pathway.
EPA does not plan to include on-site releases to land from RCRA Subtitle C hazardous waste landfills or
RCRA Subtitle D municipal solid waste landfills or exposures of the general population (including
susceptible populations) or terrestrial species from such releases in the TSCA evaluation. While
permitted and managed by the individual states, municipal solid waste (MSW) landfills are required by
federal regulations to implement some of the same requirements as Subtitle C landfills. MSW landfills
generally must have a liner system with leachate collection and conduct groundwater monitoring and
corrective action when releases are detected. MSW landfills are also subject to closure and post-closure
care requirements, and must have financial assurance for funding of any needed corrective actions.
MSW landfills have also been designed to allow for the small amounts of hazardous waste generated by
households and very small quantity waste generators (less than 220 lbs per month). Bulk liquids, such as
free solvent, may not be disposed of at MSW landfills.
EPA does not expect to include on-site releases to land from industrial non-hazardous and
construction/demolition waste landfills. Industrial non-hazardous and construction/demolition waste
landfills are primarily regulated under state regulatory programs. States must also implement limited
federal regulatory requirements for siting, groundwater monitoring, and corrective action, and a
prohibition on open dumping and disposal of bulk liquids. States may also establish additional
requirement such as for liners, post-closure and financial assurance, but are not required to do so.
Therefore, EPA does not expect to include this pathway in the risk evaluation.
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RELEASES AND WASTES FROM
INDUSTRIAL / COMMERCIAL USES
EXPOSURE PATHWAY
Direct
Discharge
Water/
Sediment
Indirect
Discharge
Biosolids
POTW
Wastewater or
Liquid Wastes a
Industrial Pre-
Treatment or
Industrial WWT
Land D|sposal
I
Soil
RECEPTORS
HAZARDS
Aquatic
Species
Hazards Potentially Associated with Acute
and/or Chronic Exposures:
See Section 2.4.1
KEY:
Gray text: Receptor that will not be further analyzed
- -k Pathway that will not be further analyzed
Figure 2-3.1,4-Dioxane Conceptual Model for Environmental Releases and Wastes: Potential Exposures and Hazards
The conceptual model presents the exposure pathways, exposure routes and hazards to human and environmental receptors from
environmental releases and wastes of 1,4-dioxane that EPA plans to analyze.
a Industrial wastewater or liquid wastes may be treated on-site and then released to surface water (direct discharge), or pre-treated and released to POTW (indirect
discharge). Drinking water will undergo further treatment in drinking water treatment plants. Ground water may also be a source of drinking water.
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2.6 Analysis Plan
The analysis plan presented in the problem formulation elaborates on the initial analysis plan that was
published in the Scope of the Risk Evaluation for 1,4-Dioxane ( 17c).
The analysis plan is based on the conditions of use of 1,4-dioxane, 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 (U.S. EPA. 2018a), provides additional information about the criteria,
approaches and/or methods that have been and will be applied to the first ten chemical risk evaluations.
This supplemental document will be published in early 2018.
While EPA has conducted a search for reasonably available information as described in the Scope of the
Risk Evaluation for 1,4-Dioxane ( ), 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 potentially exposed or susceptible subpopulations
during the risk evaluation. EPA will continue to consider new information submitted by the public until
the end of the public comment period in 2018.
During the risk evaluation, EPA will rely on the search results [/, 4-Dioxane (CASRN123-91-1)
Bibliography: Supplemental File for the TSCA Scope Document., (U.S. EPA. 2017a) 1 or perform
supplemental 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 1,4-dioxane to date which includes
partial, but not complete review of identified information. Should additional data or approaches become
available, EPA may refine its analysis plan based on this information.
2.6.1 Exposure
For 1,4-dioxane, EPA does not plan to further analyze background levels for ambient air, indoor air,
groundwater, and drinking water.
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 1,4-dioxane do not result in significant exposure to aquatic species through
water and sediment exposure pathways (see Section 2.5.3.3). For the pathways of exposures for the
general population and terrestrial species, EPA has determined that the existing regulatory programs and
associated analytical processes have addressed or are in the process of addressing potential risks of
chemicals that may be present in other media pathways. For these cases, EPA believes that the TSCA
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risk evaluation should focus not on those exposure pathways, but rather on exposure pathways
associated with TSCA uses that are not subject to those regulatory processes.
EPA does not plan to further analyze the environmental fate of 1,4-dioxane based on the conceptual
models described in Section 2.5.2 and Section 2.5.3.
EPA does not plan to further analyze environmental exposures to 1,4-dioxane based on the exposure
assessment presented in Section 2.3.4.
2.6.1.2 Occupational Exposures
EPA expects to evaluate both worker and occupational non-user exposures 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 the NIOSH, and monitoring data found in published literature [e.g.,
personal exposure monitoring data (direct measurements) and area monitoring data (indirect
measurements)]. Studies will be evaluated using the evaluation strategies laid out in the Application
of Systematic Review in TSCA Risk Evaluations ( ,).
EPA will evaluate applicable regulatory and non-regulatory exposure limits. Available data sources
that may contain relevant monitoring data for the various conditions of use are listed in Table 2-10.
Table 2-10. Potential Sources of 1,4-Dioxane Occupational Exposure Data
The 2002 ECJRC Summary Risk Assessment Report: 1,4-Dioxane (ECJRC. 2002)
Health Canada Screening Assessment for the Challenge: 1,4-Dioxane (Health Canada. 2010)
U.S. NIOSH Health Hazard Evaluation (HHE) Program reports (NIOSH H c . 1 82. 1980)
U.S. OSHA Chemical Exposure Health Data (CEHD) program data (OS )
Industry workplace exposure monitoring data submitted to EPA by BASF Corporation and the
American Chemistry Council (ACC) (BASF. 2017: ACC. 2.015)
U.S. EPA Generic Scenarios (https://www.epa.gov/tsca-screening-tools/using-predictive-
methods-assess-exposure-and-fate-under-tsca#fate)
OECD Emission Scenario Documents (OEl II >. ^ > l l)
Buffler, P. A., Wood, S. M., Suarez, L., Kilian, D. J. Mortality follow-up of workers exposed
to 1,4-dioxane. Journal of Occupational and Environmental Medicine. 1978. 20:255-259.
Jezewska, A., Szewczynska, M., Woznica, A. Occupational exposure to airborne chemical
substances in paintings conservators. Medycyna Pracy. 2014. 65:33-41.
Kupczewska-Dobecka, M., Czerczak, S., Jakubowski, M., Maciaszek, P., Janasik, B.
Application of predictive model to estimate concentrations of chemical substances in the work
environment. Medycyna Pracy. 2010. 61:307-314.
2) 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. For example, the GS for Synthetic Fiber Manufacture, the GS on Lubricant Additives, the
ESD on the Use of Metalworking Fluid, and the ESD on the Use of Adhesives are some of the ESDs
and GS's that EPA may use to estimate occupational exposures for conditions of use such as use as a
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wetting and dispersing agent in textile manufacturing, use in hydraulic fluids, and use in film
cement. EPA will need to critically review these generic scenarios and ESDs to determine their
applicability to the conditions of use assessed. EPA was not able to identify ESDs or GS's
corresponding to several conditions of use, including solvent recycling, distribution, wood pulping,
animal and vegetable oil extraction, fluoropolymer etching, and use as a fuel additive. EPA will
perform additional targeted research, such as consulting Kirk-Othmer, in order to better understand
those conditions of use, which may inform the identification of exposure scenarios. EPA may also
need to perform targeted research to identify applicable models that may be used to estimate
exposures for certain conditions of use.
3) Review reasonably available data that may be used in developing, adapting or applying
exposure models to the particular risk evaluation.
If necessary, 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.
4) Consider and incorporate applicable engineering controls and/or personal protective
equipment into exposure scenarios.
EPA will review potential data sources on engineering controls and personal protective equipment as
identified in Table 2-10 to determine their applicability and incorporation into exposure scenarios
during risk evaluation. Studies will be evaluated using the evaluation strategies laid out in the
Application of Systematic Review in TSCA Risk Evaluations (tj S K j> \ 2018a).
5) 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.
6) Map or group each condition of use to occupational exposure assessment scenario(s).
EPA has identified release/occupational exposure scenarios and mapped them to relevant conditions of
use in Appendix D. As presented in the fourth column of the table in this appendix, EPA has grouped
the uses into 23 representative release/exposure scenarios each with 5-6 unique combinations of
exposure pathway, route, and receptor that will be further evaluated. EPA may further refine the
mapping/grouping of occupational exposure scenarios based on factors (e.g., process equipment and
handling, magnitude of production volume used, and exposure/release sources) corresponding to
conditions of use as additional information is identified during risk evaluation. Consumer Exposures
EPA does not expect to consider and analyze consumer exposures in the risk evaluation as described in
the Scope of the Risk Evaluation for 1,4-Dioxane (X \ < i* \ J 1 \ ,).
2.6.1.3 General Population
EPA does not expect to consider and analyze general population exposures in the risk evaluation for 1,4-
dioxane based on Section 2.5.3.3. EPA has determined that the existing regulatory programs and
associated analytical processes have addressed or are in the process of addressing potential risks of 1,4-
dioxane that may be present in various media pathways (e.g., air, water, land) for the general population.
Page 49 of 90
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For these cases, EPA believes that the TSCA risk evaluation should focus not on those exposure
pathways, but rather on exposure pathways associated with TSCA uses that are not subject to those
regulatory processes.
2.6.2 Hazard
2.6.2.1 Environmental Hazards
EPA does not plan to further analyze environmental hazards to 1,4-dioxane based on the hazard
assessment presented in Section 2.4.1.
2.6.2.2 Human Health Hazards
EPA expects to evaluate 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).
For the 1,4 dioxane risk evaluation, EPA will evaluate information in the IRIS assessment and
human health studies using OPPT's structured process described in the document, Application of
Systematic Review in TSCA Risk Evaluations ( 018a). Human, animal and mechanistic
data will be identified and included as described in Appendix F.3. EPA plans to prioritize the
evaluation of mechanistic evidence. Specifically, EPA does not plan to evaluate mechanistic studies
unless needed to clarify questions about associations between 1,4-dioxane and health effects and its
relevance to humans. The protocol 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 hazard endpoint. EPA plans to evaluate key studies used in the
Integrated Risk Information System (IRIS) Toxicological Review of 1,4-Dioxane ( ,013c.
2010). the TSCA Work Plan Problem Formulation and Initial Assessment ( ) and
studies published after 2010 (oral) and 2013 (inhalation) that were captured in the comprehensive
literature search conducted by the Agency for 1,4 Dioxane (/, 4-Dioxane (CASRN123-91-1)
Bibliography: Supplemental File for the TSCA Scope Document, (U.S. EPA. )). EPA intends
to review studies published after the IRIS assessment 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 1,4-dioxane hazard(s).
Susceptibility of particular human receptor groups to 1,4-dioxane 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 all identified human health hazard endpoints.
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Human health hazards from acute and chronic exposures will be identified by evaluating the human
and animal data that meet the systematic review data quality criteria described in the Application of
Systematic Review in TSCA Risk Evaluations document (U.S. EPA. 2.018a). Data quality evaluation
will be performed on key studies identified from the IRIS assessments (U.S. EPA. 2013b. 2010). the
TSCA Work Plan Problem Formulation and Initial Assessment (\_ S f P \ 201 >c) and studies
published after 2010 (oral) and 2013 (inhalation) that were captured in the comprehensive literature
search. 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 EPA guidance (
2011 h, r ^ [). Dose-response analyses performed for the IRIS oral and inhalation reference dose
determinations ( 13c, 2010) 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.
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 tumor types to
determine the appropriate approach for quantitative cancer assessment in accordance with the U.S.
EPA Guidelines for Carcinogen Risk Assessment ( .005a).
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 (U. S. EPA. 2012b). 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 standard
exposure durations (e.g., lifetime continuous exposure). If application of the PBPK model is not
possible, oral PODs may be adjusted by BW3'4 scaling in accordance with (I r \ .011 h), and
inhalation PODs may be adjusted by exposure duration and chemical properties in accordance with
( 4).
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.
EPA believes there are sufficient data to conduct dose-response analysis and/or 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,
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the approaches described in the EPA guidance document Risk Assessment Guidance for Superfund
Volume I: Human Health Evaluation Manual (Part E, Supplemental Guidance for Dermal Risk
Assessment) could 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. 2000). 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
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) ( 2000). 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). 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 potentially
exposed or susceptible subpopulations 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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(AEGLs) 1,4-Dioxane. Washington, DC: NAS/COT Subcommittee for AEGLs.
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environmental exposures to children (pp. 1-145). (EPA/600/R-05/093F). Washington, DC: U.S.
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(E-FAST): Version 2.0, documentation manual [EPA Report],
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No. 123-91-1) in support of summary information on the Integrated Risk Information System
(IRIS) [EPA Report], (EPA-635/R-09-005-F). Washington, DC.
http://www.epa.gov/iri s/toxreviews/0326tr. pdf
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(final). (EPA/600/R-090/052F). Washington, DC: U.S. Environmental Protection Agency, Office
of Research and Development, National Center for Environmental Assessment.
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the default method in derivation of the oral reference dose (pp. 1-50). (EPA/100/R11/0001).
Washington, DC: U.S. Environmental Protection Agency, Risk Assessment Forum, Office of the
Page 56 of 90
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assessment of discrete organic chemicals. Sustainable futures summary assessment [EPA
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(CAS No. 123-91-1) with Inhalation Update. In Integrated Risk Information System (IRIS).
(EPA-635/R-09-005-F). Washington, DC: Environmental Protection Agency.
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inhalation update) (CAS No. 123-91-1) in support of summary information on the Integrated
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Indicators (RSEI) Model-Toxics Release Inventory (TRI) data. Available online at
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Environmental Protection Agency, Office of Chemical Safety and Pollution Prevention.
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chemical data reporting, https://www.epa.eov/chemical-data-report.ine/instaictions-report.ine-
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https://www. epa. gov/ sites/producti on/fil e s/2016-
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reporting (May 2017 release). Washington, DC: US Environmental Protection Agency, Office of
Pollution Prevention and Toxics. Retrieved from https://www.epa.gov/chemical-data-reporting
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Pollution Prevention and Toxics (OPPT), Office of Chemical Safety and Pollution Prevention
(OCSPP). file -JIIC:/Users/2616 l/Saved%20Games/Downloads/EPA-HQ-OPPT-2016-0723 -
0003.pdf
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Agency, Office of Chemical Safety and Pollution Prevention.
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(Water-Resources Investigations Report 01-4221). Indianapolis, Indiana: U.S. Department of the
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APPENDICES
Appendix A REGULATORY HISTORY
A.l Federal Laws and Regulations
Table Apx A-l. Federal Laws and Regulations
Malulcs/Uegulalions
Description of
Authority/Regulation
Description of Regulation
EPA Regulations
TSCA - Section 6(b)
EPA 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.
1,4-Dioxane is on the initial list of
chemicals to be evaluated for 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.
1,4-Dioxane manufacturing (including
importing), processing distribution and
use information is reported under the
CDR rule information about chemicals
in commerce in the United States.
TSCA - Section 8(b)
EPA must compile, keep current
and publish a list (the TSCA
Inventory) of each chemical
substance manufactured or
processed in the United States.
1,4-Dioxane was on the initial TSCA
Inventory and therefore was not
subject to EPA's new chemicals
review process.
TSCA - Section 8(e)
Manufacturers (including
importers), 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.
Ten substantial risk reports from 1989
to 2004 U S ? p (iO 1 1,11 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
1,4-Dioxane is a listed substance
subject to reporting requirements
under 40 CFR 372.65 effective as of
January 01, 1987.
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Stiiliitcs/Ucgiihllions
Description of
Aiilhorily/Ucgiihilion
Description of Requisition
and that manufacture, process or
otherwise use a TRI-listed
chemical in quantities above
threshold levels.
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 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 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.
In 1998, 1,4-dioxane was removed
from the list of pesticide product inert
ingredients because it was no longer
being used in pesticide products. 1,4-
Dioxane is also no longer exempt from
the requirement of a tolerance (the
maximum residue level that can
remain on food or feed commodities
under 40 CFRPart 180, Subpart D).
CAA - Section 111(b)
Requires EPA to establish new
source performance standards
(NSPS) for any category of new
or modified stationary sources
that EPA determines causes, or
1,4-Dioxane is subject to the NSPS for
equipment leaks of volatile organic
compounds (VOCs) in the synthetic
organic chemicals manufacturing
industry for which construction,
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Stiiliitcs/Ucgiihllions
Description of
Aiilhorily/Ucgiihilion
Description of Requisition
contributes significantly to, air
pollution, which may reasonably
be anticipated to endanger public
health or welfare. The standards
are based on the degree of
emission limitation achievable
through the application of the
best system of emission
reduction (BSER) which (taking
into account the cost of achieving
reductions and environmental
impacts and energy
requirements) EPA determines
has been adequately
demonstrated.
reconstruction or modification began
after 1/5/1981 and on or before
11/7/2006 (40 CFR Part 60, Subpart
VV).
CAA - Section 112(b)
Defines the original list of 189
hazardous air pollutants (HAP).
Under 112(c) of the CAA, EPA
must identify and list source
categories that emit HAP and
then set emission standards for
those listed source categories
under CAA section 112(d). CAA
section 112(b)(3)(A) specifies
that any person may petition the
Administrator to modify the list
of HAP by adding or deleting a
substance.
1,4-Dioxane is listed as a HAP under
section 112 (42 U.S.C. § 7412) of the
CAA.
CAA - Section 112(d)
Section 112(d) states that the
EPA must establish (NESHAPs
for each category or subcategory
of major sources and area
sources of HAPs [listed pursuant
to Section 112(c)], The standards
must require the maximum
degree of emission reduction that
the EPA determines to be
achievable by each particular
source category. Different
criteria for maximum achievable
control technology (MACT)
apply for new and existing
sources. Less stringent standards,
known as generally available
There are a number of source-specific
NESHAPs that are applicable to 1,4-
dioxane, including:
Organic Hazardous Air Pollutants
from the Synthetic Organic
Chemical Manufacturing Industry
(40 CFR Part 63, Subpart F),
Organic Hazardous Air Pollutants
from the Synthetic Organic
Chemical Manufacturing Industry
for Process Vents, Storage Vessels,
Transfer Operations, and
Wastewater (40 CFR Part 63,
Subpart G)
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Stiiliitcs/Ucgiihllions
Description of
Aiilhorily/Ucgiihilion
Description of Requisition
control technology (GAC I )
standards, are allowed at the
Administrator's discretion for
area sources.
Off-Site Waste and Reco\ cry
Operations (40 CFRPart 63,
Subpart DD),
Wood Furniture Manufacturing
Operations (40 CFRPart 63,
Subpart JJ),
Pharmaceuticals Production (40 CFR
Part 63, Subpart GGG),
Group IV Polymers and Resins
(thermoplastic product
manufacturing) (40 CFRPart 63,
Subpart JJJ),
Organic Liquids Distribution (Non-
gasoline) (40 CFRPart 63, Subpart
EEEE),
Miscellaneous Organic Chemical
Manufacturing (40 CFR Part 63,
Subpart FFFF),
Site Remediation (40 CFR Part 63,
Subpart GGGGG), and
Miscellaneous Coating
Manufacturing (40 CFR Part 63,
Subpart HHHHH).
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 knowledge of
a release of a hazardous
substance above the reportable
quantity threshold.
1,4-Dioxane is a hazardous substance
under CERCLA. Releases of 1,4-
dioxane in excess of 100 pounds must
be reported (40 CFR 302.4).
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Staliitcs/Ucgulalions
Description of
Aiilhorily/Ucgulalion
Description of Regulation
Safe Drinking Water Act
(SDWA) - Section 1412(b)
Every 5 years, EPA must publish
a list of contaminants that: (1)
are currently unregulated, (2) are
known or anticipated to occur in
public water systems (PWSs) and
(3) may require regulations under
SDWA. EPA must also
determine whether to regulate at
least five contaminants from the
list every 5 years.
1,4-dioxane was identified on both the
Third (2009) and Fourth (2016)
Contaminant Candidate List (CCL) (74
FR 51850, October 8, 2009) (81 FR
81099, November 17, 2016).
SDWA- Section 1445(a)
Every 5 years, EPA must issue a
new list of no more than
30 unregulated contaminants to
be monitored by PWSs. The data
obtained must be entered into the
National Drinking Water
Contaminant Occurrence
Database.
1,4-dioxane was identified in the third
Unregulated Contaminant Monitoring
Rule (UCMR3), issued in 2012 (77 FR
26072, May 2, 2012).
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.
In 1980, 1,4-dioxane became a listed
hazardous waste in 40 CFR 261.33 -
Discarded commercial chemical
products, off-specification species,
container residues, and spill residues
thereof (U108) (45 FR 33084).
Other federal regulations
FFDCA
Provides the U.S. Food and Drug
Administration (FDA) with
authority to oversee the safety of
food, drugs and cosmetics.
FDA established a limit of 10 mg/kg
on the amount of l,4dioxane that can
be present in the food additive
glycerides and polyglycides of
hydrogenated vegetable oils (21 CFR
172.736 and 71 FR 12618, March 13,
2006).
Occupational Safety and
Health Act
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
In 1989, OSHA established a PEL for
1,4-dioxane of 100 ppm or 360 mg/m3
as an 8-hour, TWA (29 CFR
1910.1001).
While OSHA has established a PEL
for 1,4-dioxane, OSHA has recognized
Page 63 of 90
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Stiiliitcs/Ucgiihllions
Description of
Aiilhorily/Ucgiihilion
Description of Requisition
levels, mechanical dangers, heal
or cold stress or unsanitary
conditions.
Under the Act, OSHA can issue
occupational safety and health
standards including such
provisions as PELs, exposure
monitoring, engineering and
administrative control measures
and respiratory protection.
that many of its PN.s are ouldaled and
inadequate for ensuring the protection
of worker health. 1,4-Dioxane appears
in OSHA's annotated PEL tables,
wherein OSHA recommends that
employers follow the California
OSHA limit of 0.28 ppm, the NIOSH
REL of 1 ppm as a 30-minute ceiling
or the ACGIH TLV of 20 ppm (8-hour
TWA).
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.
Federal Hazardous
Materials Transportation
Act
Section 5103 of the Act directs
the Secretary of Transportation
to:
Designate material (including
an explosive, radioactive
material, infectious
substance, flammable or
combustible liquid, solid or
gas, toxic, oxidizing or
corrosive material and
compressed gas) as
hazardous when the Secretary
determines that transporting
the material in commerce
may pose an unreasonable
risk to health and safety or
property.
Issue regulations for the safe
transportation, including
security, of hazardous
material in intrastate,
interstate and foreign
commerce.
The Department of Transportation
(DOT) has designated 1,4-dioxane as a
hazardous material, and there are
special requirements for marking,
labeling and transporting it (49 CFR
Part 171, 40 CFR 173.202 and 40 CFR
173.242).
Page 64 of 90
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A.2 State Laws and Regulations
Table Apx A-2. State Laws and Regulations
State Actions
Description of Action
State PELs
California PEL: 0.28 ppm (Cal Code Regs. Title 8, § 5155).
State Right-to-Know Acts
New Jersey (8:59 N.J. Admin. Code § 9.1), Pennsylvania (34 Pa.
Code § 323).
State air regulations
Allowable Ambient Levels (AAL): New Hampshire (RSA 125-1:6,
ENV-A Chap. 1400), Rhode Island (12 R.I. Code R. 031-022).
State drinking/ground water limits
Massachusetts (310 Code Mass. Regs. § 22.00), Michigan (Mich.
Admin. Code r.299.44 and r.299.49, 2017).
Chemicals of high concern to
children
Several states have adopted reporting laws for chemicals in
children's products that include 1,4-dioxane, such as Oregon
(Toxic-Free Kids Act, Senate Bill 478, 2015) Vermont (Code Vt.
R. § 13-140-077) and Washington State (Wash. Admin. Code §
173-334-130).
Other
In California, 1,4-dioxane was added to the Proposition 65 list in
1988 (Cal. Code Regs, title 27, § 27001).
A.3 International Laws and Regulations
Table Apx A-3. Regulatory Actions by other Governments and Tribes
Country/Organization
Requirements and Restrictions
Canada
1,4-Dioxane is on the Cosmetic Ingredient Hotlist as a substance
prohibited for use in cosmetics. 1,4-Dioxane is also included in
Canada's National Pollutant Release Inventory (NPRI), the publicly-
accessible inventory of pollutants released, disposed of and sent for
recycling bv facilities across the country [Government of Canada
£. 1,4-Dioxane. Accessed April 18, 2017],
Australia
In 1994, 1,4-dioxane was assessed. A workplace product containing
more than 0.1% 1,4-dioxane is classed as a hazardous substance. 1,4-
Dioxane is in Class 3, (Packing Group II) under the Australian
Dangerous Goods Code 0.4-Dioxane. Priority Existing Chemical
No. 7. Full Public Reotn < (i )8Y).
Japan
1,4-dioxane is regulated in Japan under the following legislation:
• 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
Page 65 of 90
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Country/Organization
Requirements and Restrictions
• Industrial Safety and Health Act (ISHA)
• Air Pollution Control Law
• Water Pollution Control Law
(National Institute of Technology and Evaluation (NITE) Chemical
Risk Information Platform (CHIRPHMTE. 2015), Accessed April
18, 2017).
Republic of Korea
The Ministry of the Environment recently adopted a provisional
water quality standard for human health of 50 |ig/L 1,4-dioxane in
drinking water (An et al.. 2.014).
Australia, Austria, Belgium,
Canada, Denmark, European
Union (EU), Finland, France,
Germany, Hungary, Ireland,
Italy, Japan, Latvia, New
Zealand, People's Republic of
China, Poland, Singapore,
South Korea, Spain, Sweden,
Switzerland, The Netherlands,
Turkey, United Kingdom
Occupational exposure limits for 1,4-dioxane (In si tut fur
Asheitsschutz d
-------
Appendix B PROCESS, RELEASE AND OCCUPATIONAL
EXPOSURE INFORMATION
This appendix provides information and data found in preliminary data gathering for 1,4-dioxane.
B.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.
B.l.l Manufacture (Including Import)
The primary method for industrial production of 1,4-dioxane involves an acid-catalyzed conversion of
ethylene glycol (mono-, di-, tri- and polyethylene glycol may be used) by ring closure in a closed
system. The process is carried out at a temperature between 266 and 392°F (130 and 200°C) and a
pressure between 0.25 and 1.1 atm (25 and 110 kPa). The synthesis step is performed in a heated vessel.
The raw 1,4-dioxane product is then moved to a distillation column to start the purification process.
Multiple steps are used to purify the 1,4-dioxane, including separation from water and volatile by-
products by extractive distillation, heating with acids, salting out withNaCl, CaCh orNaOH, and fine
subsequent distillation (ECJRC. 2002). FigureApx B-l (BASF. 2017).
Components
Reaction
~isolation NeuVa Nation
D'stillalcn
F rial PioJuct
Feed
Tank
Disfilltfi en
Colimr
Figure Apx B-l: General Process Flow Diagram for 1,4-Dioxane Manufacturing
Source: EPA-HQ-QPPT-2016-0723-0012 (BASF. 2017).
Two other reactions can be used to make 1,4-dioxane, but they are primarily used to make substituted
dioxanes and not known to be used for industrial 1,4-dioxane production (ECJRC. 2002).
B.1.2 Processing and Distribution
B.l.2.1 Processing as a Reactant/Intermediate
1,4-Dioxane can be used as a chemical reactant in the production of pharmaceuticals, polyethylene
terephthalate (PET) plastics, rubber, insecticides and pesticides, cement, deodorant fumigant, magnetic
Page 67 of 90
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tape and adhesives [EPA-HO-OPPT-lOl / 0723-000 » (I ? U- \ 2017b)1. Exact process operations
involved in the use of 1,4-dioxane as a chemical reactant are dependent on the final product that is being
synthesized. For the use of 1,4-dioxane as a chemical reactant, operations would typically involve
unloading 1,4-dioxane from transport containers and feeding the 1,4-dioxane into a reaction vessel(s),
where the 1,4-dioxane would react either fully or to a lesser extent. Following completion of the
reaction, the produced substance may or may not be purified further, thus removing unreacted 1,4-
dioxane (if any exists). Reacted 1,4-dioxane is assumed to be destroyed and is thus not expected to be
released or cause potential worker exposures.
B.l.2.2 Processing - Non-Incorporative
1,4-Dioxane is used as a process solvent during the manufacturing of cellulose acetate, resins, waxes and
fats [ ; H *-QPPT-201' -0 /23-0003 (U.S. EPA. 2017bn.
B. 1.2.3 Repackaging
Typical repackaging operations involve transferring of chemicals into appropriately sized containers to
meet customer demands/needs.
B.l.2.4 Recycling
1,4-Dioxane is used as a solvent in several applications. In this capacity, 1,4-dioxane can be regenerated
and recycled for reuse.
B.1.3 Uses
B.l.3.1 Processing Aids, Not Otherwise Listed
Processing aids are chemical substances used to improve the processing characteristics or the operation
of process equipment or to alter or buffer the pH of the substance or mixture, when added to a process or
to a substance or mixture to be processed. Processing agents do not become a part of the reaction
product and are not intended to affect the function of a substance or article created (U.S. EPA. 2016c).
1,4-Dioxane is used in a number of industrial processes as a processing aid. These processes include
wood pulping, extraction of animal and vegetable oils, textile processing, polymerization,
pharmaceutical purification and etching of fluoropolymers fEPA-HQ-OPPT~ 723-0003; (U.S.
17b): EPA-HO-QPPT-2016-0723-0012 (BASF. 2017)1. Exact process operations involved in
the use of 1,4-dioxane as a processing aid are dependent on the final product that is being synthesized.
B.l.3.1 Functional Fluids (Open and Closed Systems)
Functional fluids are liquid or gaseous chemical substances used for one or more operational properties
(U.S. EPA. 2016c). 1,4-Dioxane is used in polyalkylene glycol lubricants, synthetic metalworking
fluids, cutting and tapping fluids and hydraulic fluids [EPA-HQ-QPPT-2017-072.3-0003 (
2017b)]. Exact operations involved in the use of 1,4-dioxane as a functional fluid are dependent on the
final product.
B. 1.3.2 Laboratory Chemicals
1,4-Dioxane is used in laboratories as a chemical reagent, reference material, stable reaction medium,
liquid scintillation counting medium, spectroscopic and photometric measurement, cryoscopic solvent
and histological preparation [EPA-HO-OPPT-2Q17-0723-0003 ( )]. Laboratory
procedures are generally done within a fume hood, on a bench with local exhaust ventilation or under
general ventilation.
Page 68 of 90
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B.l.3.3 Adhesives and Sealants
1,4-Dioxane is found in film cement and as a residual contaminant in two-component glues and
adhesives [EPA-HQ-QPPT-2017-0723-0003 ( )]. The application procedure depends on
the type of adhesive and the type of substrate. After the adhesive is received by the user, it may be
diluted or mixed prior to application. The formulation is then loaded into the application reservoir or
apparatus and applied to the substrate via spray, roll, curtain or syringe or bead application. Application
may be manual or automated. After application, the adhesive or sealant is allowed to dry, usually at
ambient temperature, such that the solvent completely evaporates and a bond is formed between the
substrates (OECD. 2015).
B.l.3.4 Other Uses
Other conditions of use where 1,4-dioxane may be formulated into a product or used as part of another
process may include use in fuels and fuel additives [EPA-HQ-OPPT-1 r23~0012 (BASF. 2017)1.
spray polyurethane foam and in printing and printing compositions rEPA-HQ-OPIH'-AM I 0723-0003
(U.S. EPA. 2017b)1.
B.1.4 Disposal
1,4-Dioxane is disposed of to a variety of environmental media: land, water and air. Land disposals
include Class I underground injection, RCRA Subtitle C landfills and to other uncategorized land points.
1,4-Dioxane is sometimes discharged to water. Wastewater treatment may or may not precede these
water releases. Additionally, 1,4-dioxane is also commonly incinerated (U.S. EPA. 2015c).
B.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
use in the risk evaluation.
TableApx B 1 summarizes OSHA CEHD data by North American Industry Classification System
(NAICS) code (OS] ).
Table Apx B-l. Summary of Industry Sectors with 1,4-Dioxane Personal Monitoring Air Samples
Obtained from OSHA Inspections Conducted Between 2002 and 2016
NAICS
NAICS IK'siripliiiii
315225
Men's and Boys' Cut and Sew Work Clothing Manufacturing
325199
All Other Basic Organic Chemical Manufacturing
334418
Printed Circuit Assembly (Electronic Assembly) Manufacturing
336399
All Other Motor Vehicle Parts Manufacturing
926150
Regulation, Licensing, and Inspection of Miscellaneous Commercial Sectors
Page 69 of 90
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Appendix C ANALYSIS: ENVIRONMENTAL CONCENTRATION
OF CONCERN (COC)
The concentrations of concern (COC) for aquatic species were calculated based on the environmental
hazard data for 1,4-dioxane summarized in Section 2.4.1. The methods for calculating the COCs are are
based on published EPA/OPPT methods ( ., 2012d). The acute and chronic COC for 1,4-
dioxane for each endpoint are determined based on the lowest toxicity value in the dataset. For a
particular environment (e.g., aquatic environment), the COC is based and on the most sensitive species
in that environment.
After selecting the lowest toxicity value, an assessment factor (AF) is applied according to EPA/OPPT
methods (U.S. EPA. 2013a. 2012d). The application of AFs provides a lower bound effect level that
would likely encompass more sensitive species not specifically represented by the available
experimental data. AFs are also account for differences in inter- and intra-species variability, as well as
laboratory-to-field variability. 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, since the data
available for most industrial chemicals is limited. The acute COC for the aquatic plant endpoint is
determined based on the lowest value in the dataset divided by an assessment factor (AF) of 4. For fish
and aquatic invertebrates (e.g., daphnia) the acute COC values are divided by an AF of 5. For chronic
COCs, an AF of 10 is used.
Acute COC calculations
The lowest acute toxicity value for aquatic organisms (i.e., most sensitive species) for 1,4-dioxane is
from a 96-hour fish toxicity study where the LC.mi is >100 mg/L (Geiger et at... 1990). The lowest value
was then divided by the assessment factor (AF) of 5 for aquatic invertebrates.
Lowest value for the 96-hour fish toxicity LCso (>100 mg/L) / AF of 5 = 20,000 |ig/L or ppb.
Chronic COC Calculations
For the chronic COC, the lowest chronic toxicity value is from a chronic 32-day MATC fathead minnow
study of > 145 mg/L (Brooke. 1987). This value was divided by an assessment factor of 10 then
multiplied by 1,000 to convert from mg/L to |ig/L or ppb.
Lowest value for 32-day fish MATC = 145 mg/L / 10 = 14.5 x 1000 = 14,500 |ig/L or ppb.
Summary
The acute concentration of concern for 1,4-dioxane is based on the 96-hour toxicity value for fish of
>100 mg/L (Geiger et at.. 1990) and the chronic COC is based on a 32-day MATC fish toxicity value of
145 mg/L (Brooke. 1987). The acute and chronic COCs for 1,4-dioxane are 20,000 ppb and 14,500 ppb,
respectively.
Page 70 of 90
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Appendix D SUPPORTING TABLE FOR INDUSTRIAL AND COMMERCIAL ACTIVITIES
AND USES CONCEPTUAL MODEL
As part of the Problem Formulation, EPA considered if each unique combination of exposure pathway, route, and receptor in the lifecycle of
1,4-dioxane would be further evaluated. All possible exposure scenarios for each condition of use were identified according to the COU in
Table 2-3 and the conceptual model in Figure 2-2 and are presented in Table Apx D-l. EPA used readily available fate, engineering,
exposure and/or toxicity information to determine whether to conduct further analysis on each exposure scenario.
EPA has identified release/occupational exposure scenarios and mapped them to relevant conditions of use in the table below. As presented in
the Release/Exposure Scenario column of this table, representative release/exposure scenarios each with 5-6 unique combinations of exposure
pathway, route, and receptor will be further analyzed. EPA may further refine the mapping/grouping of industrial and commercial
occupational exposure scenarios based on factors (e.g., process equipment and handling, magnitude of production volume used, and
exposure/release sources) corresponding to conditions of use as additional information is identified during risk evaluation.
Table Apx E
>-1: Industrial and Commercial Occupational Exposure Scenarios for 1,4-
Jioxane
l.il'e Cjck'
S(;i»e
Siihciileiion
Kck'sisi'/
l'l\pOMIIV
SiTii.irio
Kxposiir
0
l\i(h\\;i\
l'l\|)OMIIV
Route
Rm-plor
I'm ri her
l.\;ilu;ilion?
Kiilioiiiilo lor l-'iirlhcr 1'\ ;i In ;i I ion / no
lurllur l.\;ilu;ilion
Manufacture
Domestic
Manufacture
or Import
Domestic
Manufacture or
Import
Manufacture of
1,4-dioxane via
acid catalyzed
conversion of
ethylene glycol
by ring closure
Repackaging of
import
containers
Liquid
Contact
Dermal
Workers
Yes
Workers are expected to routinely handle
liquids containing 1,4-dioxane.
Manufacture
Domestic
Manufacture
or Import
Domestic
Manufacture or
Import
Vapor
Dermal
Workers
No
The absorption of 1,4-dioxane vapor via
skin is expected to be orders of
magnitude lower than via inhalation and
will not be further analyzed.
Manufacture
Domestic
Manufacture
or Import
Domestic
Manufacture or
Import
Vapor
Inhalation
Workers
Yes
Due to high volatility (VP = 40 mmHg)
at room temperature, inhalation exposure
from vapor should be further evaluated.
Manufacture
Domestic
Manufacture
or Import
Domestic
Manufacture or
Import
Liquid
( oiiiael
Dermal
<>\l
(()eeiipali
nual \mi-
l sen
\n
Dermal e\pnsure is e\peeled In he
primariK in worker direelh in\nl\edin
haiidliim I lie chemical
Manufacture
Domestic
Manufacture
or Import
Domestic
Manufacture or
Import
Vapor
Dermal
ONU
No
The absnrpunii nf 14-din vine \ apnr \ la
skin is expected to be orders of
magnitude lower than via inhalation and
will not be further analyzed.
Page 71 of 90
-------
Manufacture
Domestic
Manufacture
or Import
Domestic
Manufacture or
Import
Vapor
Inhalation
ONU
Yes
Due to high volatility (VP = 40 mmHg)
at room temperature, inhalation exposure
from vapor should be further evaluated.
Manufacture
Domestic
Manufacture
or Import
Domestic
Manufacture or
Import
\lls|
Dermal In
halation ()
nil
Workers.
()\l
\o
Misi ueneralion is uoi e\pecled
Processing
Processing
as a Reactant
1. iquid
Contact
Dermal
Workers
Yes
Workers are expected to routinely handle
liquids containing 1,4-dioxane.
Processing
Processing
as a Reactant
Vapor
Dermal
Workers
No
The absorption of 1,4-dioxane vapor via
skin is expected to be orders of
magnitude lower than via inhalation and
will not be further analyzed.
Processing
Processing
as a Reactant
Pharmaceutical
Pharmaceutical
Vapor
Inhalation
Workers
Yes
Due to high volatility at room
temperature, inhalation exposure from
vapor should be further evaluated.
However, potential for exposure may be
low in scenarios where 1,4-dioxane is
consumed as a chemical intermediate or
used as a catalyst.
Processing
Processing
as a Reactant
Intermediate
product
manufacture
Liquid
( oniacl
Dermal
<>\l
\o
Dermal e\posure is e\peeled lo he
primariK lo workeis direelK iii\ol\edni
haiidlinu llie chemical.
Processing
Processing
as a Reactant
Polymerization
catalyst
Polymer
manufacture
Vapor
Dermal
ONU
No
The absorption of 1,4-dioxane vapor via
skin is expected to be orders of
magnitude lower than via inhalation and
will not be further analyzed.
Processing
Processing
as a Reactant
Vapor
Inhalation
ONU
Yes
Due to high volatility at room
temperature, inhalation exposure from
vapor should be further evaluated.
However, potential for exposure may be
low in scenarios where 1,4-dioxane is
consumed as a chemical intermediate or
used as a catalvst
Processing
Processing
as a Reactant
\llsl
Dermal In
halation ()
nil
Workers.
<>\l
\o
Misi izeiieralioii is noi e\peeled.
Processing
Liquid
Contact
Dermal
Workers
Yes
Workers are expected to routinely handle
liquids containing 1,4-dioxane.
Processing
Non-
Pharmaceutical
and medicine
Pharmaceutical
product
Vapor
Dermal
Workers
No
The absorption of 1,4-dioxane vapor via
skin is expected to be orders of
Page 72 of 90
-------
incorporativ
e
Repackaging
manufacturing
(process
solvent)
Basic organic
chemical
manufacturing
(process
solvent)
Bulk to
packages, then
distribute
manufacture
Basic organic
chemical
manufacture
Repackaging to
large and small
containers
magnitude lower than via inhalation and
will not be further analyzed.
Processing
Vapor
Inhalation
Workers
Yes
Due to high volatility at room
temperature, inhalation exposure from
vapor should be further evaluated.
Processing
Liquid
( ouiacl
Dermal
<>\l
\o
Dermal e\posure is e\pecled in he
primarily in worker direct l\ uiuil\ediu
haiidliuu 11 ic chemical
Processing
Vapor
Dermal
ONU
No
The absorption of 1,4-dioxane vapor via
skin is expected to be orders of
magnitude lower than via inhalation and
will not be further analyzed.
Processing
Vapor
Inhalation
ONU
Yes
Due to high volatility at room
temperature, inhalation exposure from
vapor should be further evaluated.
Processing
\lls|
Dermal In
halation ()
nil
Workers.
<>\l
No
Misi ueiieralKiu is uoi e\pecled
Processing
Recycling
Recycling
Recycling of
process solvents
containing 1,4-
dioxane
Liquid
Contact
Dermal
Workers
Yes
Workers are expected to routinely handle
liquids containing 1,4-dioxane.
Processing
Recycling
Recycling
Vapor
Dermal
Workers
No
The absorption of 1,4-dioxane vapor via
skin is expected to be orders of
magnitude lower than via inhalation and
will not be further analyzed.
Processing
Recycling
Recycling
Vapor
Inhalation
Workers
Yes
Due to high volatility at room
temperature, inhalation exposure from
vapor should be further evaluated.
Processing
Recycling
Recycling
Liquid
( ouiacl
Dermal
<>\l
\o
Dermal e\posure is e\pecled In he
primarily lo worker direclK iu\ol\cdiii
haudliiiu I lie chemical.
Processing
Recycling
Recycling
Vapor
Dermal
ONU
No
The absorption of 1,4-dioxane vapor via
skin is expected to be orders of
magnitude lower than via inhalation and
will not be further analyzed.
Processing
Recycling
Recycling
Vapor
Inhalation
ONU
Yes
Due to high volatility at room
temperature, inhalation exposure from
vapor should be further evaluated.
Processing
Recycling
Recycling
Mist
Dermal/In
halation/O
ral
Workers,
ONU
Yes
EPA requires additional information on
industry practices for recycling waste
solvents containing 1,4-dioxane to
Page 73 of 90
-------
determine if exposures to mists are
possible.
Distribution
in commerce
Distribution
Distribution
Distribution of
bulk shipment
of 1,4-dioxane
Liquid
Contact,
Vapor,
Mist
Dermal/In
halation/O
ral
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 use
Liquid
Contact
Dermal
Workers
Yes
Workers are expected to routinely handle
liquids containing 1,4-dioxane.
Industrial use
Agricultural
chemical
Agricultural
product
manufacture
Plasticizer
manufacture
Anhydrous acid,
bromination and
sulfonation
reaction
chemical
manufacture
Polymer
Manufacture
Vapor
Dermal
Workers
No
The absorption of 1,4-dioxane vapor via
skin is expected to be orders of
magnitude lower than via inhalation and
will not be further analyzed.
Industrial use
Intermediate
Use
intermediate
Plasticizer
intermediate
Catalysts and
Vapor
Inhalation
Workers
Yes
Due to high volatility at room
temperature, inhalation exposure from
vapor should be further evaluated.
However, potential for exposure may be
low in scenarios where 1,4-dioxane is
consumed as a chemical intermediate or
used as a catalyst.
Industrial use
reagents for
anhydrous acid
reactions,
Liquid
( ouiacl
Dermal
<>\l
\n
Dermal e\pnMiie is e\pecled In he
piiuiaiiK lii workeiN direct l\ uiuil\ediu
haudliim I lie chemical.
Industrial use
Processing
aids, not
otherwise
brominations
and sulfonations
Vapor
Dermal
ONU
No
The absorption of 1,4-dioxane vapor via
skin is expected to be orders of
magnitude lower than via inhalation and
will not be further analyzed.
Industrial use
listed
Polymerization
catalyst
Vapor
Inhalation
ONU
Yes
Due to high volatility at room
temperature, inhalation exposure from
vapor should be further evaluated.
However, potential for exposure may be
low in scenarios where 1,4-dioxane is
consumed as a chemical intermediate or
used as a catalyst.
Page 74 of 90
-------
Industrial use
\lisi
Dermal In
halation ()
nil
Willie is.
()\l
\n
Misi ueiicialinii is urn e\pecled
Industrial use
Processing
aids, not
otherwise
listed
Liquid
Contact
Dermal
Workers
Yes
Workers are expected to routinely handle
liquids containing 1,4-dioxane.
Industrial use
Processing
aids, not
otherwise
listed
Vapor
Dermal
Workers
No
The absorption of 1,4-dioxane vapor via
skin is expected to be orders of
magnitude lower than via inhalation and
will not be further analyzed.
Industrial use
Processing
aids, not
otherwise
listed
Wood pulping
Extraction of
Wood pulping
Vapor
Inhalation
Workers
Yes
Due to high volatility at room
temperature, inhalation exposure from
vapor should be further evaluated.
Industrial use
Processing
aids, not
otherwise
listed
animal and
vegetable oils
Wetting and
Extraction of
animal and
vegetable oils
l.k|iiid
( niilacl
Dermal
<>\l
Yes
Dermal e\pnsiiie is e\pecled In he
piimaiiK lo woikeis direclh in\ i»l\ ed in
handliiiu I lie chemical
Industrial use
Processing
aids, not
otherwise
listed
dispersing agent
in textile
processing
Textile
processing
Vapor
Dermal
ONU
No
The absorption of 1,4-dioxane vapor via
skin is expected to be orders of
magnitude lower than via inhalation and
will not be further analyzed.
Industrial use
Processing
aids, not
otherwise
listed
Vapor
Inhalation
ONU
Yes
Due to high volatility at room
temperature, inhalation exposure from
vapor should be further evaluated.
Industrial use
Processing
aids, not
otherwise
listed
Mist
Dermal/In
halation/O
ral
Workers,
ONU
Yes
Mist generation may occur during these
processes.
Industrial use
Processing
aids, not
otherwise
listed
Liquid
Contact
Dermal
Workers
Yes
Workers are expected to routinely handle
liquids containing 1,4-dioxane.
Industrial use
Processing
aids, not
otherwise
listed
Purification of
pharmaceuticals
Pharmaceutical
product
manufacture
Vapor
Dermal
Workers
No
The absorption of 1,4-dioxane vapor via
skin is expected to be orders of
magnitude lower than via inhalation and
will not be further analyzed.
Industrial use
Processing
aids, not
Vapor
Inhalation
Workers
Yes
Due to high volatility at room
temperature, inhalation exposure from
vapor should be further evaluated.
Page 75 of 90
-------
otherwise
listed
Industrial use
Processing
aids, not
otherwise
listed
l.k|iiid
(nulacl
Dermal
<>\l
\o
Dermal c\pnsiiic is e\peeled in he
pi'imai'iK lo workeiN direelK in\ ol\ ed in
haiidlinu I lie chemical
Industrial use
Processing
aids, not
otherwise
listed
Vapor
Dermal
ONU
No
The absorption of 1,4-dioxane vapor via
skin is expected to be orders of
magnitude lower than via inhalation and
will not be further analyzed.
Industrial use
Processing
aids, not
otherwise
listed
Vapor
Inhalation
ONU
Yes
Due to high volatility at room
temperature, inhalation exposure from
vapor should be further evaluated.
Industrial use
Processing
aids, not
otherwise
listed
\lls|
Dermal In
halation ()
nil
Workers.
<>\l
\n
Misi uciicralinii is imi e\peeled
Industrial use
Processing
aids, not
otherwise
listed
Liquid
Contact
Dermal
Workers
Yes
Workers are expected to routinely handle
liquids containing 1,4-dioxane.
Industrial use
Processing
aids, not
otherwise
listed
Vapor
Dermal
Workers
No
The absorption of 1,4-dioxane vapor via
skin is expected to be orders of
magnitude lower than via inhalation and
will not be further analyzed.
Industrial use
Processing
aids, not
otherwise
listed
Etching of
Etching of
Vapor
Inhalation
Workers
Yes
Due to high volatility at room
temperature, inhalation exposure from
vapor should be further evaluated.
Industrial use
Processing
aids, not
otherwise
listed
fluoropolymers
fluoropolymers
Liquid
(nulacl
Dermal
()\l
\n
Dermal c\pnsiiic is c\pecled In he
pi'imai'iK lo wDikeiN direelK in\ ol\ ed in
handlnm 11 ic chemical.
Industrial use
Processing
aids, not
otherwise
listed
Vapor
Dermal
ONU
No
The absorption of l,4-dio\ane \ apor \ la
skin is expected to be orders of
magnitude lower than via inhalation and
will not be further analyzed.
Industrial use
Processing
aids, not
otherwise
listed
Vapor
Inhalation
ONU
Yes
Due to high volatility at room
temperature, inhalation exposure from
vapor should be further evaluated.
Page 76 of 90
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Industrial use
Processing
aids, not
otherwise
listed
Mist
Dermal/In
halation/O
ral
Workers,
ONU
Yes
Mist generation may occur during these
processes.
Industrial use
Functional
fluids
(closed/open
system)
Polyalkylene
glycol lubricant
Cutting and
Tapping Fluid
Synthetic
metalworking
fluid
Hydraulic fluid
Use of
lubricants
Use of
metalworking
fluids
Servicing
hydraulic
equipment and
charging
hydraulic fluids
in original
equipment
manufacture
Liquid
Contact
Dermal
Workers
Yes
Workers are expected to routinely handle
liquids containing 1,4-dioxane.
Industrial use
Functional
fluids
(closed/open
system)
Vapor
Dermal
Workers
No
The absorption of 1,4-dioxane vapor via
skin is expected to be orders of
magnitude lower than via inhalation and
will not be further analyzed.
Industrial use
Functional
fluids
(closed/open
system)
Vapor
Inhalation
Workers
Yes
Due to high volatility at room
temperature, inhalation exposure from
\ ;i|x>r should be liii'llicr e\ alualed
Industrial use
Functional
fluids
(closed/open
system)
liquid
( niilael
Dermal
<>\l
\n
Dermal e\pi»siire is e\peeled In he
piimai'iK lo woikeis direelh in\ i»l\ ed in
haiidlum I lie chemical
Industrial use
Functional
fluids
(closed/open
system)
Vapor
Dermal
ONU
No
The absorption of 1,4-dioxane vapor via
skin is expected to be orders of
magnitude lower than via inhalation and
will not be further analyzed.
Industrial use
Functional
fluids
(closed/open
system)
Vapor
Inhalation
ONU
Yes
Due to high volatility at room
temperature, inhalation exposure from
vapor should be further evaluated.
Industrial use
Functional
fluids
(closed/open
system)
Mist
Dermal/In
halation/O
ral
Workers,
ONU
Yes
Mist exposure can occur during open
system uses and potentially while
charging and servicing equipment with
hydraulic fluid.
Industrial
use, potential
commercial
use
Laboratory
chemicals
Chemical
reagent
Reference
material
Spectroscopic
and photometric
Laboratory
chemical use
Liquid
Contact
Dermal
Workers
Yes
Workers are expected to routinely handle
liquids containing 1,4-dioxane.
Industrial
use, potential
commercial
use
Laboratory
chemicals
Vapor
Dermal
Workers
No
The absorption of 1,4-dioxane vapor via
skin is expected to be orders of
magnitude lower than via inhalation and
will not be further analyzed.
Page 77 of 90
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Industrial
use, potential
commercial
use
Laboratory
chemicals
measurement
Liquid
scintillation and
Vapor
Inhalation
Workers
Yes
Due to high volatility at room
temperature, inhalation exposure from
vapor should be further evaluated.
Industrial
use, potential
commercial
use
Laboratory
chemicals
counting
medium
Stable reaction
Liquid
( nuiacl
Dermal
()\l
\n
Dermal censure is e\pccleil in he
primarily in woikeiN direelK iu\iil\ediu
hauilliuu 11 ic chemical.
Industrial
use, potential
commercial
use
Laboratory
chemicals
medium
Cryoscopic
solvent for
Vapor
Dermal
ONU
No
The absorption of 1,4-dioxane vapor via
skin is expected to be orders of
magnitude lower than via inhalation and
will not be further analyzed.
Industrial
use, potential
commercial
use
Laboratory
chemicals
molecular mass
determinations
Preparation of
Vapor
Inhalation
ONU
Yes
Due to high volatility at room
temperature, inhalation exposure from
\ apnr should be fuilhei' c\ alualed
Industrial
use, potential
commercial
use
Laboratory
chemicals
histological
sections for
microscopic
examination
\llsl
Dermal In
halalinu ()
nil
Workers.
<>\l
\n
Misi ucucralinii is uni e\peeled
Industrial
use, potential
commercial
use
Liquid
Contact
Dermal
Workers
Yes
Workers are expected to routinely handle
liquids containing 1,4-dioxane.
Industrial
use, potential
commercial
use
Industrial and
commercial
small brush
application
Vapor
Dermal
Workers
No
The absorption of 1,4-dioxane vapor via
skin is expected to be orders of
magnitude lower than via inhalation and
will not be further analyzed.
Industrial
use, potential
commercial
use
Adhesives
and sealants
Other Uses
Film cement
Vapor
Inhalation
Workers
Yes
Due to high volatility at room
temperature, inhalation exposure from
vapor should be further evaluated.
Industrial
use, potential
commercial
use
Liquid
(nuiacl
Dermal
()\l
\n
Dermal e\pnsiii'e is e\pecled In he
primarily in workers direelK iu\ nl\ ed m
haiiilliuu 11 ic chemical.
Industrial
use, potential
commercial
use
Vapor
Dermal
ONU
No
The absorption of 1,4-dioxane vapor via
skin is expected to be orders of
magnitude lower than via inhalation and
will not be further analyzed.
Page 78 of 90
-------
Industrial
use, potential
commercial
use
Vapor
Inhalation
ONU
Yes
Due to high volatility at room
temperature, inhalation exposure from
vapor should be further evaluated.
Industrial
use, potential
commercial
use
\lls|
Dermal In
halation ()
nil
Workers.
<>\l
\n
Misi ueiieralmii is urn e\pecled
Industrial
use, potential
commercial
use
Liquid
Contact
Dermal
Workers
Yes
Workers are expected to routinely handle
liquids containing 1,4-dioxane.
Industrial
use, potential
commercial
use
Vapor
Dermal
Workers
No
The absorption of 1,4-dioxane vapor via
skin is expected to be orders of
magnitude lower than via inhalation and
will not be further analyzed.
Industrial
use, potential
commercial
use
Spray
polyurethane
foam
Printing and
printing
compounds
Application of
spray
Vapor
Inhalation
Workers
Yes
Due to high volatility at room
temperature, inhalation exposure from
vapor should be further evaluated.
Industrial
use, potential
commercial
use
Other Uses
polyurethane
foam through a
nozzle
Liquid
( nulacl
Dermal
()\l
\n
Dermal e\pnsiiie is e\peeled in he
primai'iK in woikeiN direelK in\ ol\ ed in
hamllnm 11 ic chemical.
Industrial
use, potential
commercial
use
Use of Printing
Inks
Vapor
Dermal
ONU
No
The absorption of l,4-dio\ane \ apor \ la
skin is expected to be orders of
magnitude lower than via inhalation and
will not be further analyzed.
Industrial
use, potential
commercial
use
Vapor
Inhalation
ONU
Yes
Due to high volatility at room
temperature, inhalation exposure from
vapor should be further evaluated.
Industrial
use, potential
commercial
use
Mist
Dermal/In
halation/O
ral
Workers,
ONU
Yes
Mist generation may occur during these
processes.
Manufacture,
processing,
use, Disposal
Emissions to
air
Air
Industrial pre-
Worker
Handling of
wastes
Liquid
Contact
Dermal
Workers
Yes
Workers are expected to routinely handle
liquids containing 1,4-dioxane.
Manufacture,
processing,
use, Disposal
Wastewater
treatment
Industrial
Vapor
Dermal
Workers
No
The absorption of 1,4-dioxane vapor via
skin is expected to be orders of
Page 79 of 90
-------
Solid wastes
and liquid
wastes
wastewater
treatment
Publicly owned
treatment works
(POTW)
Underground
Injection
Municipal
landfill
Hazardous
landfill
magnitude lower than via inhalation and
will not be further analyzed.
Manufacture,
processing,
use, Disposal
Vapor
Inhalation
Workers
Yes
Due to high volatility at room
temperature, inhalation exposure from
vapor should be further evaluated.
Manufacture,
processing,
use, Disposal
Liquid
( milacl
Dermal
<>\l
\n
Dermal e\pnMiie is e\peeled In he
primariK lo uoikei's diieelK iiiuil\edni
haiidlniu 11 ic chemical
Manufacture,
processing,
use, Disposal
Vapor
Dermal
ONU
No
The absorption of 1,4-dioxane vapor via
skin is expected to be orders of
magnitude lower than via inhalation and
will not be further analyzed.
Manufacture,
processing,
use, Disposal
Vapor
Inhalation
ONU
Yes
Due to high volatility at room
temperature, inhalation exposure from
vapor should be further evaluated.
Manufacture,
processing,
use, Disposal
\lisi
Dermal In
halation ()
nil
Willie is.
()\l
\n
Misi ueiieialKin is uni c\pecled
Page 80 of 90
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Appendix E SUPPORTING TABLE FOR ENVIRONMENTAL RELEASES AND WASTES
CONCEPTUAL MODEL
All possible exposure scenarios for each condition of use were identified according to the COU in Table 2-3 and the environmental releases
conceptual model in Figure 2-3 and are presented in Table Apx E-l. EPA used readily available fate, exposure and/or toxicity information to
determine whether to conduct further analysis on each exposure scenario.
EPA has identified release/environmental exposure scenarios and mapped them to relevant conditions of use in the table below. EPA may
further refine the mapping/grouping of exposure scenarios based on factors corresponding to conditions of use as additional information is
identified during risk evaluation.
Table Apx E-l: Environmental Releases and Wastes Exposure Scenarios for 1,4-Dioxane
l.ilVock' Si;i»e
I so
Release
l'l\|)OMIIV
Pill h \\ ;¦>
l'l\|)OMIIV
Roule
Reeeplor
l-'urfher
l.\;ilii;i(ion?
R;iliun;ile for I'll rl her r.\;ilu;ilion / no
lull lie i- l.\;ilu;ilion
Manufacturing
and Processing
TBD
Industrial wastewater
treatment operations
Water
N/A
Aquatic
Species
No
Conservative screening indicates low
potential for risk to aquatic organisms.
Manufacturing
and Processing
TBD
Industrial wastewater
treatment operations
Water, Air
N/A
Terrestrial
Species
No
Ingestion of water and inhalation of air are
not expected to be primary exposure routes
for terrestrial organisms (see OPP tool).
Manufacturing
and Processing
TBD
Industrial wastewater
treatment operations
Sediment
N/A
Terrestrial
Species
No
1,4-Dioxane has low sorption to soil, sludge,
and sediment and will instead stay in the
associated aqueous phases.
Manufacturing
and Processing
TBD
Industrial wastewater
treatment operations
Sediment
Aquatic
Species
No
Manufacturing
and Processing
TBD
Industrial wastewater
treatment operations
Biosolids
disposed to
soil,
migration to
groundwater
N/A
Terrestrial
Species
No
1,4 dioxane is not expected to remain in soil
for long periods of time due to migration to
groundwater and volatilization from soil.
Manufacturing
and Processing
TBD
Industrial pre-
treatment, then
transfer to Publicly
Owned Treatment
Works (POTW)
Water
N/A
Aquatic
Species
No
Conservative screening indicates low
potential for risk to aquatic organisms.
Manufacturing
and Processing
TBD
Industrial pre-
treatment, then
transfer to Publicly
Water, Air
N/A
Terrestrial
Species
No
Ingestion of water and inhalation of air are
not expected to be primary exposure routes
for terrestrial organisms (see OPP tool).
Page 81 of 90
-------
Owned Treatment
Works (POTW)
Manufacturing
and Processing
TBD
Industrial pre-
treatment, then
transfer to Publicly
Owned Treatment
Works (POTW)
Sediment
N/A
Terrestrial
Species
No
1,4-Dioxane has low sorption to soil, sludge,
and sediment and will instead stay in the
associated aqueous phases.
Manufacturing
and Processing
TBD
Industrial pre-
treatment, then
transfer to Publicly
Owned Treatment
Works (POTW)
Sediment
Aquatic
Species
No
Manufacturing
and Processing
TBD
Industrial pre-
treatment, then
transfer to Publicly
Owned Treatment
Works (POTW)
Biosolids
disposed to
soil,
migration to
groundwater
N/A
Terrestrial
Species
No
1,4 dioxane is not expected to remain in soil
for long periods of time due to migration to
groundwater and volatilization from soil.
Disposal
TBD
Municipal landfill,
Hazardous Landfill,
and other land
disposal
Soil
N/A
Terrestrial
Species
No
2015 TRI data indicates 3 sites reporting
13,422 lbs to landfill. However, 1,4-dioxane
has low sorption to soil.
Page 82 of 90
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Appendix F INCLUSION AND EXCLUSION CRITERIA FOR
FULL TEXT SCREENING
Appendix F 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.
F.l Inclusion Criteria for the Data Sources Reporting Environmental
Fate Data
EPA/OPPT developed a generic PESO statement to guide the full text screening of environmental fate
data sources. PESO stands for Pathways and Processes, Exposure, Setting or Scenario, and Outcomes.
Subsequent versions of the PESO 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 in the PESO statement are eligible for inclusion, considered for evaluation, and
Page 83 of 90
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possibly included in the environmental fate assessment. On the other hand, data sources are excluded if
they do not meet the criteria in the PESO statement.
During the development of conceptual models and consideration of the nexus between TSCA and other
EPA regulations for 1,4-dioxane it was determined that no pathways for consumer or environmental
exposure requiring environmental fate information would be further analyzed. As described in Section
2.5.2, EPA does not plan to evaluate exposure pathways to human receptors from consumer uses of 1,4-
dioxane. As described in Section 2.5.3, there are no exposure pathways for general population or
ecological receptors from environmental releases and waste streams associated with industrial and
commercial activities for 1,4-dioxane that EPA plans to include and further analyze in the risk
assessment.
For 1,4-dioxane no exposure pathways to human and ecological receptors from consumer products,
environmental releases, or waste streams associated with industrial and commercial activities will be
further analyzed in risk evaluation. In the absence of exposure pathways for further analysis,
environmental fate data will not be evaluated further. Therefore, no PESO statement or fate data needs
and associated processes, media and exposure pathways considered in the development of the
environmental fate assessment for 1,4-dioxane will be presented.
F.2 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 (TableApx F-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,
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 (Table Apx F-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 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.
Page 84 of 90
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TableApx F-l: Inclusion Criteria for Data Sources Reporting Engineering and Occupational
Exposure Data
KI-'.SO l.lemcnl
11 \ iriencc
Receptors
• Humans:
Workers, including occupational non-users
Please refer to the conceptual models for more information about the human
receptors included in the TSCA risk evaluation.
Exposure
• Worker exposure and relevant environmental releases of the chemical
substance of interest
o Dermal and inhalation exposure routes (as indicated in the
conceptual model)
o Surface water (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
relevant environmental releases (includes all manufacturing, processing,
use, disposal indicated in Table Apx F-2 below.
Outcomes
• Quantitative estimates* of worker exposures and of relevant
environmental releases from occupational settings
• 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 F-2) provides a list of related and relevant general information.
TSCA=Toxic Substances Control Act
Page 85 of 90
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TableApx F-2: Engineering, Environmental Release and Occupational Data Necessary to
Develop the Environmental Release and Occupational Exposure Assessments
Ohjiiiitc
Dckriniiiod
(In rin vi Scoping
l \|)o ol' l);K;i
General
Engineering
Assessment (may
apply for either
or both
Occupational
Exposures and /
or Environmental
Releases)
2.
3.
4.
5.
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
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}a
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)}11
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
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.
7.
9.
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
Potential routes of exposure (e.g., inhalation, dermal). {Tags: Routes of exposure (manufacture, import,
processing, use)}a
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
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
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
Page 86 of 90
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Objec(i\e
Delermineri
(Inrinvi Scopiii"
l \|H' of Dala
Environmental
Releases
1Dcbci'ipuon of iclc\ anl s>ouiv.vs> of poleiiual en\ iioimieiiial reload, 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
relevant environmental media (water) and treatment and disposal methods (POTW), including releases per
site and aggregated over all sites (annual release rates, daily release rates) {Tags: Release rates
(manufacture, import, processing, use)}"
21. Relevant 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)}11
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
F.3
Inclusion Criteria for Data Sources Reporting Environmental and
General Population Exposure
EPA/OPPT developed a generic PECO statement to guide the full text screening of environmental and
general population exposure data sources. 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 to be eligible for inclusion in the review. Subsequent versions
of the PECO statement may be produced throughout the process of screening and evaluating data for the
chemicals undergoing TSCA risk evaluation. Exposure pathways to human and ecological receptors
from environmental releases associated with industrial and commercial activities will not be further
analyzed in risk evaluation (see Section 2.5.3.2 and Section 2.5.3.3). In the absence of exposure
pathways for further analysis, data related to environmental and general population exposure will not be
further analyzed.
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F.4 Inclusion Criteria for Data Sources Reporting Human Health
Hazards
TableApx F-3: Inclusion and Exclusion Criteria for Data Sources Reporting Human Health
Hazards Related to 1,4-Dioxane Exposure"
PECO
Element
Evidence
Stream
Papers/Features Included
Papcrs/Fcatu res 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
• Human or animal cells, tissues, or biochemical reactions
(e.g., ligand binding assays) with in vitro exposure
regimens; bioinformatics pathways of disease analysis; or
high throughput screening data.
Exposure
Human
• Exposure based on administered dose or concentration of
1,4-dioxane, 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 (e.g., HTTA) as identified in
biomonitoring studies
• All routes of exposure
• Any number of exposure groups
• Quantitative, semi-quantitative or qualitative estimates of
exposure
• Exposures to multiple chemicals/mixtures only if 1,4-
dioxane or related metabolites were independently measured
and analyzed
• Multiple chemical/mixture exposures with
no independent measurement of or exposure
to 1,4-dioxane (or related metabolite)
Animal
• A minimum of 2 quantitative dose or concentration levels of
1,4-dioxane plus a negative control group a
• Acute, subchronic, chronic exposure from oral, dermal,
inhalation routes
• Exposure to 1,4-dioxane only (no chemical mixtures)
• Only 1 quantitative dose or concentration
level in addition to the controla
• Route of exposure not by inhalation, oral or
dermal type (e.g., intraperitoneal, injection)
• No duration of exposure stated
• Exposure to 1,4-dioxane in a chemical
mixture
Mechanistic
• Exposure based on concentrations of the neat material of
1,4-dioxane
• A minimum of 2 dose or concentration levels tested plus a
control group a
• Only 1 quantitative dose or concentration
level in addition to the controla
• Exposure to 1,4-dioxane in a chemical
mixture
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
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 1,4-dioxane scope documentb:
o Cancer
o Liver toxicity
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PI'.CO
I! lemon 1
l.\ idcncc
Siiviim
P;i|)crs/l"V;ilures Included
Pii|K'rs/l-Vii(uivs l.xcliidcd
o Kidney toxicity
o Neurotoxicity
o Irritation
o Acute Toxicity/Poisoning
• Other endpointsc
Mechanistic
• All mechanistic data that may inform the following health
outcomes:
o Cancer
o Genotoxicity
o Neurological/Behavior
o Renal
o Hepatic
o Irritation
o Acute Toxicity/Poisoning
o ADME/PBPK
• Data related to other mechanisms of toxicity
a
General Considerations
Papers/Features Included
Pa pe rs/Featu res Excluded
• Written in English11
• Reports a primary source or meta-analysis a
• Full-text available
• Reports both 1,4-dioxane exposure and a health outcome
(or mechanism of action)
• Not written in Englishd
• Reports a secondary source (e.g., review
papers)"
• No full-text available (e.g., only a study
description/abstract, out-of-print text)
• Reports a 1,4-dioxane-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 1,4-dioxane, EPA
will evaluate studies related to susceptibility after other data are reviewed. 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 hazards other than those listed in the scope document if they were identified in the updated literature search that accompanied the
scope document.
d EPA may translate studies as needed.
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F.5 List Of Retracted Papers
The following reference was retracted by the journal:
HERO ID: 3538089 (1,4-dioxane; HBCD)
Kreipke, CW; Rafols, JA; Reynolds, CA; Schafer, S; Marinica, A; Bedford, C; Fronczak, M; Kuhn, D;
Armstead, WM. (2011). Clazosentan, a novel endothelin A antagonist, improves cerebral blood flow and
behavior after traumatic brain injury. Neurol Res 33: 208-213.
http://dx.doi.org/10.! 179/016164111X12881719352570
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