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Dossier for Candidate Low-Priority Substance 1,2-Hexanediol
(CASRN 6920-22-5)
For Release at Proposal
August 9, 2019
Office of Pollution Prevention and Toxics
U.S. Environmental Protection Agency
1200 Pennsylvania Avenue
Washington, DC 20460
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Contents
1. Introduction 1
2. Background on 1,2-Hexanediol 3
3. Physical-Chemical Properties 4
3.1 References 6
4. Relevant Assessment History 7
5. Conditions of Use 8
6. Hazard Characterization 10
6.1 Human Health Hazard 13
6.1.1 Absorption, Distribution, Metabolism, Excretion 14
6.1.2 Acute Toxicity 15
6.1.3 Repeated Dose Toxicity 15
6.1.4 Reproductive and Developmental Toxicity 15
6.1.5 Genotoxicity 16
6.1.6 Carcinogenicity 16
6.1.7 Neurotoxicity 17
6.1.8 Skin Sensitization 17
6.1.9 Skin Irritation 17
6.1.10 Eye Irritation 17
6.1.11 Hazards to Potentially Exposed or Susceptible Subpopulations 17
6.2 Environmental Hazard 17
6.2.1 Acute Aquatic Toxicity 18
6.2.2 Chronic Aquatic Toxicity 18
6.3 Persistence and Bioaccumulation Potential 18
6.3.1 Persistence 18
6.3.2 Bioaccumulation Potential 19
7. Exposure Characterization 20
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7.1 Production Volume Information 20
7.2 Exposures to the Environment 20
7.3 Exposures to the General Population 21
7.4 Exposures to Potentially Exposed or Susceptible Subpopulations 21
7.4.1 Exposures to Workers 21
7.4.2 Exposures to Consumers 21
8. Summary of Findings 22
8.1 Hazard and Exposure Potential of the Chemical Substance 22
8.2 Persistence and Bioaccumulation 23
8.3 Potentially Exposed or Susceptible Subpopulations 23
8.4 Storage Near Significant Sources of Drinking Water 24
8.5 Conditions of Use or Significant Changes in Conditions of Use of the Chemical Substance 25
8.6 The Volume or Significant Changes in Volume of the Chemical Substance Manufactured or Processed.... 25
8.7 Other Considerations 26
9. Proposed Designation 27
Appendix A: Conditions of Use Characterization I
A.1 CDR Manufacturers and Production Volume I
A.2 Uses II
A.2.1 Methods for Uses Table II
A.2.2 Uses of 1,2-Hexanediol IV
A.3 References X
Appendix B: Hazard Characterization XIV
B.1 References XXV
Appendix C: Literature Search Outcomes XXVII
C.1 Literature Search and Review XXVII
C.1.1 Search for Analog Data XXVII
C.1.2 Search Terms and Results XXVIII
C.2 Excluded Studies and Rationale XXIX
C.2.1 Human Health Hazard Excluded References XXIX
C.2.2 Environmental Hazard XXXIV
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C.2.3 Fate XXXVII
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Tables 3
Table 1:1,2-Hexanediol at a Glance
Table 2: Physical-Chemical Properties for 1,2-Hexanediol 4
Table 3: Conditions of Use for 1,2-Hexanediol 9
Table 4: Low-Concern Criteria for Human Health and Environmental Fate and Effects 10
Table 5:1,2-Hexanediol and Analog Structures 14
Table A.1:1986-2015 National Production Volume Data for 1,2-Hexanediol (Non-Confidential Production I
Volume in Pounds)
Table A.2: Sources Searched for Uses of 1,2-Hexanediol II
Table A.3: Uses of 1,2-Hexanediol IV
Table B.1: Human Health Hazard XIV
Table B.2: Environmental Hazard XXII
Table B.3: Fate XXIV
Table C.1: Sources Used for Analog Search XXVIII
Table C.2: Search Terms Used in Peer-Reviewed Databases XXVIII
Table C.3: Search Terms Used in Grey Literature and Additional Sources XXIX
Table C.4: Off-Topic References Excluded at Title/Abstract Screening for Human Health Hazard XXXI
Table C.5: Screening Questions and Off-Topic References Excluded at Full-Text Screening for Human XXX
Health Hazard
Table C.6: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for XXXI
Human Health Hazard - Animal
Table C.7: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for XXXIII
Human Health Hazard - In Vitro
Table C.8: Off-Topic References Excluded at Title/Abstract Screening for Environmental Hazard XXXIV
Table C.9: Screening Questions and Off-Topic References Excluded at Full-Text Screening for XXXV
Environmental Hazard
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Table C.10: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for XXXVI
Environmental Hazard
Table C.11: Off-Topic References Excluded at Initial Screening for Fate XXXVII
Table C.12: Screening Questions and Off-Topic References Excluded at Full-Text Screening for Fate XXXVII
Table C.13: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for XXXVII
Fate
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1. Introduction
In the Lautenberg amendments to the Toxic Substances Control Act (TSCA) (section 6(b)(1)(B)) and
implementing regulations (40 CFR 702.3), a low-priority substance is described as a chemical
substance that the Administrator concludes does not meet the statutory criteria for designation as a
high-priority substance, based on information sufficient to establish that conclusion, without
consideration of costs or other non-risk factors. A high-priority substance is defined as a chemical
substance that the Administrator concludes, without consideration of costs or other non-risk factors,
may present an unreasonable risk of injury to health or the environment because of a potential hazard
and a potential route of exposure under the conditions of use, including an unreasonable risk to
potentially exposed or susceptible subpopulations identified as relevant by the Administrator. 1,2-
Hexanediol is one of the 40 chemical substances initiated for prioritization as referenced in a March
21, 2019 notice (84 FR 10491).1
Before determining low or high prioritization status, under EPA's regulations at 40 CFR 702.92 and
pursuant to section 6(b)(1)(A) of the statute, EPA will generally use reasonably available information
to screen the candidate chemical substance under its conditions of use against the following criteria
and considerations:
• the hazard and exposure potential of the chemical substance;
• persistence and bioaccumulation;
• potentially exposed or susceptible subpopulations;
• storage near significant sources of drinking water;
• conditions of use or significant changes in the conditions of use of the chemical substance;
• the chemical substance's production volume or significant changes in production volume; and
• other risk-based criteria that EPA determines to be relevant to the designation of the chemical
substance's priority.
Designation of a low-priority substance indicates that the chemical does not meet the statutory criteria
for a high-priority substance and that a risk evaluation is not warranted at the time.
This risk-based, screening-level review is organized as follows:
• Section 1 (Introduction): This section explains the requirements of the Lautenberg
amendments to the Toxic Substances Control Act (TSCA) and implementing regulations -
including the criteria and considerations ~ pertinent to prioritization and designation of low-
priority substances.
1 https://www.federalregister.gov/docimients/2019/03/21/2019-054Q4/initiation-of-prioritization-under-tlie-toxic-substances-
control-act-tsca
2 Hie prioritization process is explained in the Procedures for Prioritization of Chemicals for Risk Evaluation Under the
Toxic Substances Control Act (82 ER 33753).
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• Section 2 (Background on the Proposed Low-Priority Substance): This section includes
information on attributes of the chemical substance, including its structure, and relates them
to its functionality.
• Section 3 (Physical-Chemical Properties): This section includes a description of the physical-
chemical properties of the chemical substance and explains how these properties lead to the
chemical's fate, transport, and exposure potential.
• Section 4 (Relevant Assessment History): This section includes an overview of the outcomes
of other governing entities" assessments of the chemical substance.
• Section 5 (Conditions of Use): This section presents the chemical substance's known,
intended, and reasonably foreseen conditions of use under TSCA.
• Section 6 (Hazard Characterization): This section summarizes the reasonably available
hazard information and benchmarks the information against low-concern thresholds.
• Section 7 (Exposure Characterization): This section includes a qualitative summary of
potential exposures to the chemical substance.
• Section 8 (Summary of Findings): In this section, EPA presents information pertinent to
prioritization against each of the seven statutory and regulatory criteria and considerations,
and proposes a conclusion based on that evidence.
• Section 9 (Proposed Designation): In this section, EPA presents the proposed designation for
this chemical substance.
• Appendix A (Conditions of Use Characterization): This appendix contains a comprehensive
list of TSCA and non-TSCA uses for the chemical substance from publicly available
databases.
• Appendix B (Hazard Characterization): This appendix contains information on each of the
studies used to support the hazard evaluation of the chemical substance.
• Appendix C (Literature Search Outcomes): This appendix includes literature search outcomes
and rationales for studies that were identified in initial literature screening but were found to
be off-topic or unacceptable for use in the screening-level review.
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2. Background on 1,2-Hexanediol
Table 1 below provides the CAS number, synonyms, and other information on 1,2-hexanediol.
Table 1:1,2-Hexanediol at a Glance
Chemical Name
1,2-Hexanediol
CASRN
6920-22-5
Synonyms
Hexane-1,2-diol; 1,2-Dihydroxyhexane; 5,6-Dihydroxyhexane; DL-hexane-1,2-diol
Trade Name(s)
None found
Molecular Formula
C6H14O2
Representative Structure
H
1,2-Hexanediol is an alcohol in the diol (or glycol) family. It is an organic chemical compound
containing two hydroxyl (-OH) groups on a six-carbon backbone. Because of the adjacent positioning
of the two hydroxyl groups, 1,2-alkanediols contain a stereocenter, leading to two stereoisomers: cis-
1,2-hexanediol and trans-1,2-hcxanediol. Because the hydroxyl groups are located on the first and
second carbons on one end of a six-carbon chain, 1,2-hexanediol is an amphiphilic molecule that acts
as both a cosurfactant and solvent. A cosurfactant increases the effectiveness of surfactants, which are
compounds containing both hydrophilic and hydrophobic moieties that work to lower the surface
tension at an interface (e.g., between two liquids). Surfactants may function as detergents, emulsifiers,
foaming agents, wetting agents, and dispersants in a variety of applications and product sectors. See
Section 5 for 1.2-hexanediol's conditions of use.
In addition, 1,2-hexanediol is hygroscopic and thus acts as a humectant, which means that it absorbs
water and increases hydration in products. Also, straight-chain 1,2-alkanediols, including 1,2-
hexanediol, have broad spectrum antimicrobial properties and are used alone or in combination with
other chemicals, to serve as preservatives and/or preservative boosters. These properties contribute to
the use of 1,2-hexanediol as a multifunctional ingredient in products. Section 5 includes conditions of
use for this chemical.
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3. Physical-Chemical Properties
Table 2 lists the physical-chemical properties for 1,2-hexanediol. A chemical's physical-chemical properties provide a basis for understanding a
chemical's behavior, including in the environment and in living organisms. These endpoints provide information generally needed to assess
potential environmental release, exposure, and partitioning as well as insight into the potential for adverse toxicological effects.
Table 2: Physical-Chemical Properties for 1,2-hexanediol
Source/Model
Data Type
Endpoint
Endpoint value
Notes
ECHA 2017
Experimental
State at room
temperature
Liquid
Substance is a clear, colorless liquid at room temperature
ECHA 2017
Calculated
Molecular weight
118 g/mol
Calculated from molecular formula C6 H14 02
Lyman etal. 1990
Estimated
Molar volume
155cm3/mol
LeBas Molar Volume, calculated according to the volume parameters
reported in Lyman et al., 1990
Johnson 2012
Experimental
Melting point
<25°C
Substance is a liquid at room temperature
ECHA 2017
Experimental
Melting point
2°C
Reported as solidification temperature at 1 atm. ISO 1392.
• Solidification temperature measured as the maximum temperature
resulting from the solidification process as the chemical is cooled.
• It was noted that the temperature rose during cooling as a result of heat
of crystallization.
ECHA 2017
Experimental
Boiling point
228.3 °C
Reported at standard atmospheric pressure. EU Method A.2
Siwoloboff method using photo cell detection.
EPISuite v4.113
Estimated
Boiling point
220°C
ECHA 2017
Experimental
Vapor pressure
0.00432 mm Hg at
25°C (Reported as
0.576 Pa)
Estimated as 9.4x10 3 mm Hg
Johnson 2012
Experimental
Vapor pressure
0.0194 mm Hg
Unpublished data for commercial product Hydrolite-6 (99% 1,2-hexanediol).
EPISuite v4.11
Estimated
Vapor pressure
0.008 mm Hg
ECHA 2017
Experimental
Water solubility
9000 mg/L at 23.5°C
Reported as >9 g/g water at23.5°C and pH 6.91.
• Concluded to be miscible. EU Method A.6, flask method.
• GLP compliant.
EPISuite v4.11
Estimated
Water solubility
6.89x104 mg/L
Experimental input values: MP = 2°C; log Kow = 0.58
ECHA 2017
Experimental
Log Kow
0.58
Reported at 25°C and pH 7.09-7.49.
• EU Method A.8; shake-flask method.
3 Physical properties used for estimation: Water Solubility 26171 mg/L, log Kow 0.69, SMILES: 0CC(0)CCCC
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Table 2: Physical-Chemical Properties for 1,2-hexanediol
Source/Model
Data Type
Endpoint
Endpoint value
Notes
• GLP compliant
Johnson 2012
Experimental
Log Kow
0.25
Unpublished data for commercial product Hydrolite-6 (99% 1,2-hexanediol).
EPISuite v4.11
Estimated
Log Kow
0.69
EPISuitev4.11
Estimated
Henry's Law
Constant
7.5x10"8 atm-m3/mole
Experimental input values: VP = 4.32x10 3 mm Hg; WS = 9x103 mg/L
EPISuitev4.11
Estimated
Sediment/soil
adsorption/
desorption - Koc
2.6
Estimated as Log Koc = 0.42.
EPISuitev4.11
Estimated
Level III fugacity
Air: 1.3%
Assumes equal emissions of 1,000 kg/hour to air, water, and soil (EPISuite
model
Water: 38.2%
Soil: 60.5%
Sediment: 0.1%
default values)
EPISuitev4.11
Estimated
Atmospheric half-
life
6.9 hours
Atmospheric half-life is estimated from a gas-phase rate constant, however,
if any amount of this substance partitions to the atmosphere it is expected to
exist as a solid
Explosivity
No data located
Pyrolysis
No data located
pH
No data located
Johnson 2012
Experimental
pKa
14.22
Unpublished data for commercial product Hydrolite-6 (99% 1,2-hexanediol)
EPISuitev4.11
Estimated
BCF
3.2
EPISuitev4.11
Estimated
BAF
1.1
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EPA's Sustainable Futures/P2 Framework Manual4 was used to interpret the physical-chemical
properties provided in Table 2. Based on its reported physical form and measured melting point, 1,2-
hexanediol is a liquid under ambient conditions. Because of its measured vapor pressure, 1,2-
hexanediol is also expected to be volatile when present as a "neat" or undiluted substance (ECHA,
2017; Johnson, 2012). As a result, exposure to 1,2-hexanediol is possible through direct dermal
contact with the substance and through inhalation of vapors or aerosols if they are generated. Based
on measured data, 1,2-hexanediol is water soluble, indicating the potential for this substance to
dissolve in water and form an aqueous solution (ECHA, 2017). Water soluble substances have an
increased potential for absorption through the lungs; therefore, if inhalation of vapors or aerosols
occurs, absorption through the lungs is likely. Exposure potential changes when 1,2-hexanediol is
present in diluted form. The estimated Henry's Law constant for 1,2-hexanediol indicates
volatilization from water and aqueous solutions (i.e., 1,2-hexanediol when diluted in water) will be
minimal (US EPA, 2019) and therefore exposure through breathing vapor is expected to be minimal.
The fact tat 1,2-hexanediol is water soluble increases the potential for oral exposure via ingestion of
contaminated drinking water, including well water. Oral exposure to this chemical could result in
moderate absorption through the gastrointestinal tract. However, based on its estimated log Kow, 1,2-
hexanediol is unlikely to cross lipid membranes and sequester in fatty tissues, as confirmed by its
estimated bioconcentration factor (BCF) and bioaccumulation factor (BAF) (US EPA, 2019). The
estimated log Koc indicates this substance is unlikely to adsorb to soil or sediment particles (US EPA,
2019). Based on the log Koc and water solubility, 1,2-hexanediol is expected to be highly mobile in
soils increasing its potential for leaching into, and transport in, groundwater, including well water.
1,2-Hexanediol is expected to have very low persistence (US EPA, 2019). Experimental data
demonstrate it is readily biodegradable in aerobic conditions (discussed further in Section 6.3.1), and
analog data indicate it is ultimately degradable anaerobically (discussed further in Section 6.3.1),
meaning that if it were to enter groundwater, it is likely to be broken down into carbon dioxide and
water.
3.1 References
Johnson, W., Bergfeld, W. F., Belsito, D. V., Hill, R. A., Klaassen, C. D., Liebler, D., Marks, J. G.,
Shank, R. C., Slaga, T. J., Snyder, P. W., Andersen, F. A. (2012). Safety Assessment of 1,2-Glycols
as Used in Cosmetics. International Journal of Toxicology, 31, 147S-168S
European Chemicals Agency (ECHA). (2017). DL-hexane-l,2-diol. Retrieved from
https://ccha.curopa.cu/rcgistration-dossicr/-/rcgistcrcd-dossicr/l 1614
Lyman, Warren J., Reehl, W. F., Rosenblatt, D. H. (1990). Handbook of chemical property estimation
methods: environmental behavior of organic compounds. American Chemical Society
US EPA. (2019). Estimation Programs Interface Suite, v 4.11. United States Environmental
Protection Agency, Washington, DC, USA
4 https://www.epa.gov/sites/prodiKtion/files/2015-05/documents/Q5.pdf
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4. Relevant Assessment History
EPA assessed the toxicological profile of 1,2-hexanediol and added the chemical to the Safer Choice
Program's Safer Chemical Ingredients List (SCIL) in January 2016 under the functional class
of solvents. The SCIL5 is a continuously updated list of chemicals that meet low-concern Safer
Choice criteria.6
Internationally, the German Environment Agency (UBA) designated 1,2-hexanediol as "low hazard to
waters" (rating of 1) in March 2019 based on an assessment of ecotoxicity and environmental fate.7
5 https://www.epa.gov/saferchoice/safer-iiigredients
0 https://www.epa.gov/sites/prodiiction/files/2013-12/dociiiiieiits/dfe master criteria safer ingredients v2 l.pdf
7 https://webrigoletto.iiba.de/rigoletto/piiblic/searchDetail.do7kenniininieF4987
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5. Conditions of Use
Per TSCA section 3(4), the term "conditions of use" means 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. EPA assembled information
on all uses of 1,2-hexanediol (Appendix A) to inform which uses would be determined conditions of
use.8 One source of information that EPA used to help determine conditions of use is 2016 Chemical
Data Reporting (CDR). The CDR rule (previously known as the Inventory Update Rule, or IUR),
under TSCA section 8, requires manufacturers (including importers) to report information on the
chemical substances they produce domestically or import into the U.S., generally above a reporting
threshold of 25,000 lb. per site per year. CDR includes information on the manufacturing, processing,
and use of chemical substances with information dating to the mid-1980s. CDR may not provide
information on other life-cycle phases such as the chemical substance's end-of-life after use in
products (i.e., disposal).
Based on CDR reporting, 1,2-hexanediol is manufactured domestically and imported. It is a solvent
used in processing (incorporation into article, and incorporation into formulation, mixture, or product)
in the industrial printing ink manufacturing sector; as well as in ink, toner, and colorant products for
consumer and commercial use (EPA 2017b). Based on the known manufacturing, processing, and
uses of this chemical substance, EPA assumes distribution in commerce. Based on CDR, two
facilities reported that 1,2-hexanediol was not recycled (e.g., not recycled, remanufactured,
reprocessed, or reused). Another facility reported this information as confidential business
information (CBI). No information on disposal is found in CDR or through EPA's Toxics Release
Inventory (TRI) Program9 because 1,2-hexanediol is not a TRI-reportable chemical. Although
reasonably available information did not specify additional types of disposal, for purposes of this
proposed prioritization designation, EPA assumed end-of-life pathways that include releases to air,
wastewater, surface water, and land via liquid wastes based on the conditions of use (e.g.,
incineration, landfill).
To supplement CDR, EPA conducted research through the publicly available databases listed in
Appendix A (Table A.2) and performed additional internet searches to clarify uses or identify
additional occupational1" and consumer uses. This research improved the Agency's understanding of
the conditions of use for 1,2-hexanediol. Although EPA identified uses of 1,2-hexanediol in personal
care products, this screening review covers TSCA conditions of use for the chemical substance and
personal care products are not considered further in EPA's assessment. Exclusions to TSCA's
regulatory scope regarding "chemical substance" can be found at TSCA section 3(2). Table 3 lists the
conditions of use for 1,2-hexanediol considered for chemical substance prioritization, per TSCA
section 3(4). Table 3 reflects the TSCA uses determined as conditions of use listed in Table A.3
(Appendix A).
8 Hie prioritization process, including the definition of conditions of use, is explained in the Procedures for Prioritization of
Chemicals for Risk Evaluation Under the Toxic Substances Control Act (82 FR 33753).
9 https://www.epa.gov/toxics-release-inventorv-tri-program
10 Occupational uses include industrial and/or commercial uses
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Table 3: Conditions of Use for 1,2-Hexanediol
Life Cycle Stage
Category
Subcategory of Use
Source
Manufacturing
Domestic manufacture
Domestic manufacture
EPA (2017b)
Import
Import
Processing
Processing- incorporation into
article
Other use in printing ink manufacturing
EPA (2017b)
Processing- incorporation into
formulation, mixture or product
Solvents (which become part of product formulation
or mixture) in printing ink manufacturing
Recycling
Recycling
EPA (2017b)11
Distribution
Distribution
Distribution
EPA (2017b)
Commercial uses
Ink, toner, and colorant products
EPA (2017b)
Consumer uses
Ink, toner, and colorant products
Printing ink
EPA (2017b)
Industrial/commercial/consumer
uses
Fuel and lubricant additive
Fuel and lubricant additives
Ullmann's (2012)
Disposal
Releases and waste disposal
Releases to air, wastewater, solid and liquid wastes
Though not explicitly identified, releases from
disposal are assumed to be reasonably
foreseen12
11 In the 2016 CDR, two facilities reported that 1,2-hexanediol was not recycled (e.g., not recycled, remanufactured, reprocessed, or reused). One facility reported this information
as CBI (EPA 2017b).
12 See Section 5 for a discussion on why releases are assumed to be reasonably foreseen for purposes of this proposed prioritization designation.
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6. Hazard Characterization
EPA reviewed peer-reviewed literature and other data sources to identify reasonably available
information. This literature review approach13 is tailored to capture the reasonably available
information associated with low-hazard chemicals. EPA also used this process to verify the
reasonably available information for reliability, completeness, and consistency. EPA reviewed the
reasonably available information to identify relevant, quality studies to evaluate the hazard potential
for 1,2-hexanediol against the endpoints listed below. EPA's New Chemicals Program has used these
endpoints for decades to evaluate chemical substances under TSCA14 and EPA toxicologists rely on
these endpoints as key indicators of potential human health and environmental effects. These
endpoints also align with internationally accepted hazard characterization criteria, such as the
Globally Harmonized System of Classification and Labelling of Chemicals15 as noted above in
Section 4 and form the basis of the comparative hazard assessment of chemicals.
Human health endpoints evaluated: Acute mammalian toxicity, repeated dose toxicity,
carcinogenicity, mutagenicity/genotoxicity, reproductive and developmental toxicity, neurotoxicity,
skin sensitization, and eye and skin irritation.
Environmental fate and effects endpoints evaluated: Aquatic toxicity, environmental persistence,
and bioaccumulation and bioconcentration.
The low-concern criteria used to evaluate both human health and environmental fate and effects are
included in Table 4 below.
Table 4: Low-Concern Criteria for Human Health and Environmental Fate and Effects
Human Health
Acute Mammalian
Toxicity16
Very High
High
Moderate
Low
Oral LDso (mg/kg)
<50
>50 - 300
> 300 - 2000
> 2000
Dermal LD50 (mg/kg)
<200
>200- 1000
> 1000- 2000
> 2000
Inhalation LC50
(vapor/gas) (mg/L)
<2
>2-10
>10-20
>20
Inhalation LC50
(dust/mist/fume)
(mg/L)
<0.5
>0.5-1.0
>1.0-5
>5
13 Discussed in the document "Approach Document for Screening Hazard Information for Low-Priority Substances Under
TSCA", and also released at proposal.
14 https://www.epa. gov/sustainable-futures/sustainable-futures-p2 -framework-manual
15 https://www.unece.org/fileadmin/DAM/trans/danger/publi/ghs/ghs rev07/English/ST SG AC10 30 Rev7e.pdf
10 Values derived from GHS criteria (Chapter 3.1: Acute Toxicity'. 2009, United Nations).
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Table 4: Low-Concern Criteria for Human Health and Environmental Fate and Effects
Repeated Dose
Toxicity (90-day
study)17
High
Moderate
Low
Oral (mg/kg-bw/day)
<10
10-100
> 100
Dermal (mg/kg-
bw/day)
<20
20-200
>200
Inhalation
(vapor/gas)
(mg/L/6h/day)
<0.2
0.2-1.0
> 1.0
Inhalation
(dust/mist/fume)
(mg/L/6h/day)
<0.02
0.02-0.2
>0.2
Reproductive
Toxicity18
High
Moderate
Low
Oral (mg/kg/day)
<50
50-250
>250
Dermal (mg/kg/day)
<100
100-500
>500
Inhalation (vapor,
gas, mg/L/day)
< 1
1-2.5
>2.5
Inhalation
(dust/mist/fume,
mg/L/day)
<0.1
0.1-0.5
>0.5
Developmental
Toxicity18
High
Moderate
Low
Oral (mg/kg/day)
<50
50-250
>250
Dermal (mg/kg/day)
<100
100-500
>500
Inhalation (vapor,
gas, mg/L/day)
< 1
1-2.5
>2.5
Inhalation
(dust/mist/fume,
mg/L/day)
<0.1
0.1-0.5
>0.5
Mutagenicity/
Genotoxicity19
Very High
High
Moderate
Low
Germ cell
mutagenicity
GHS Category 1A
or 1B: Substances
known to induce
heritable mutations
or to be regarded
as if they induce
heritable mutations
in the germ cells of
humans.
GHS Category 2:
Substances which
cause concern for
humans owing to the
possibility that they
may induce heritable
mutations in the germ
cells of humans.
Evidence of
mutagenicity support by
positive results in vitro
OR in vivo somatic cells
of humans or animals
Negative for
chromosomal
aberrations and gene
mutations, or no
structural alerts.
17 Values from GHS criteria for Specific Target Organ Toxicity Repeated Exposure (Chapter 3.9: Specific Target Organ
Toxicity' Repeated Exposure. 2009, United Nations).
18 Values derived from the US EPA's Office of Pollution Prevention & Toxics criteria for HPV chemical categorizations
(Methodology> for Risk-Based Prioritization Under ChM tP), and the EU REACH criteria for Annex IV (2007).
19 From GHS criteria (Chapter 3.5: Germ Cells Mutagenicity. 2009, United Nations) and supplemented with considerations
for mutagenicity and genotoxicity in cells other than germs cells.
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Table 4: Low-Concern Criteria for Human Health and Environmental Fate and Effects
Mutagenicity and
genotoxicity in
somatic cells
OR
Evidence of
mutagenicity
supported by positive
results in in vitro AND
in vivo somatic cells
and/or germ cells of
humans or animals.
Carcinogenicity20
Very High
High
Moderate
Low
Known or
presumed human
carcinogen (GHS
Category 1A and
1B)
Suspected human
carcinogen (GHS
Category 2)
Limited or marginal
evidence of
carcinogenicity in
animals (and
inadequate21 evidence
in humans)
Negative studies or
robust mechanism-
based, structure
activity relationship
(SAR)
Neurotoxicity
(90-day study)17
High
Moderate
Low
Oral (mg/kg-bw/day)
<10
10-100
> 100
Dermal (mg/kg-
bw/day)
<20
20-200
>200
Inhalation
(vapor/gas)
(mg/L/6h/day)
<0.2
CD
CM
CD
> 1.0
Inhalation
(dust/mist/fume)
(mg/L/6h/day)
<0.02
0.02-0.2
>0.2
Sensitization22
High
Moderate
Low
Skin sensitization
High frequency of
sensitization in
humans and/or high
potency in animals
(GHS Category 1A)
Low to moderate
frequency of
sensitization in human
and/or low to moderate
potency in animals
(GHS Category 1B)
Adequate data
available and not
GHS Category 1Aor
1B
Respiratory
sensitization
Occurrence in
humans or evidence
of sensitization in
humans based on
animal or other tests
(equivalent to GHS
Category 1A or 1B)
Limited evidence
including the presence
of structural alerts
Adequate data
available indicating
lack of respiratory
sensitization
20 Criteria mirror classification approach used by the IARC (Preamble to the L4RC Monographs: B. Scientific Review and
Evaluation: 6. Evaluation and rationale. 2019J and incorporate GHS classification scheme (Chapter 3.6: Carcinogenicity.
2009, United Nations).
21 EPA's approach to determining the adequacy of information is discussed in the document "Approach Document for
Screening Hazard Information for Low-Priority Substances Under TSCA", also released at proposal.
22 Incorporates GHS criteria (Chapter 3.4: Respiratory or Skin Sensitization. 2009, United Nations).
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Table 4: Low-Concern Criteria for Human Health and Environmental Fate and Effects
Irritation/
Corrosivity23
Very High
High
Moderate
Low
Eye irritation/
corrosivity
Irritation persists
for >21 days or
corrosive
Clearing in 8-21
days, severely
irritating
Clearing in 7 days or
less, moderately
irritating
Clearing in less than
24 hours, mildly
irritating
Skin irritation/
corrosivity
Corrosive
Severe irritation at 72
hours
Moderate irritation at 72
hours
Mild or slight irritation
at 72 hours
Environmental Fate and Effects
Acute Aquatic
Toxicity Value
(L/E/ICso)24
Chronic Aquatic
Toxicity Value
(L/E/ICso)24
Persistence (Measured in terms of level of
biodegradation)25
Bioaccumulation
Potential26
May be low concern
if <10 ppm...
...and <1 ppm...
...and the chemical meets the 10-day window as
measured in a ready biodegradation test...
Low concern if >10
ppm and <100
ppm...
...and >1 ppm and
<10 ppm...
...and the chemical reaches the pass level within
28 days as measured in a ready biodegradation
test
...and BCF/BAF <
1000.
Low concern if >100
ppm...
...and > 10 ppm...
... and the chemical has a half-life < 60 days...
6.1 Human Health Hazard
Below is a summary of the information that EPA included in the hazard evaluation of 1,2-hexanediol.
In many cases, EPA used analogous chemicals to make findings for a given endpoint. Where this is
the case, use of the analog is explained. If the chemical studied is not named, the study is for 1,2-
hexanediol. Appendix B contains more information on each study used to assess hazards.
1,2-Hexanediol is a linear aliphatic diol with a carbon chain length containing six carbons. EPA used
best professional judgement to select analogs for 1,2-hexanediol based on similarity in structure,
molecular weight, and functionality, with the assumption that these chemicals will have similar
physical-chemical properties, environmental transport and persistence characteristics, bioavailability,
and toxicity profiles. As shown in Table 5, all proposed analogs are linear aliphatic 1,2-diols like the
candidate chemical, 1,2-hexanediol, and differ only in their chain lengths. 1,2-butanediol contains
four carbons, pentylene glycol contains five carbons and 1,2-octanediol contains eight carbons.
23 Criteria derived from the Office of Pesticide Programs Acute Toxicity Categories (US EPA. Label Review Manual. 2010).
24 Derived from GHS criteria (Chapter 4.1: Hazards to the Aquatic Environment. 2009, United Nations), EPA OPPT New
Chemicals Program (Pollution Prevention (P2) Framework, 2005) and OPPT's criteria for HPV chemical categorization
(Methodology> for Risk Based Prioritization Under C1l4MP. 2009).
25 Derived from OPPT's New Chemicals Program and DIE Master Criteria and reflects OPPT policy on PBTs (Design for
the Environment Program Master Criteria for Safer Chemicals, 2010).
20 Derived from OPPT's New Chemicals Program and Arnot & Gobas (2006) [Arnote, J.A. and F.A. Gobas, A review of
bioconcentration factor (BCF) and bioaccimndation factor (B*4F) assessments for organic chemicals in aquatic organisms.
Environmental Reviews, 2006. 14: p. 257-297.]
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Table 5:1,2-Hexanediol and Analogs Structures
CASRN
Name
Structure
6920-22-5
1,2-Hexanediol
OH
584-03-2
1,2-Butanediol
OH
5343-92-0
Pentylene glycol
OH
1117-86-8
1,2-Octanediol
OH
6.1.1 Absorption, Distribution, Metabolism, Excretion
Absorption
If 1,2-hexanediol is inhaled as a vapor, dust, or aerosol, absorption through the lungs is likely based
on its water solubility (discussed in Section 3).
The potential for dermal absorption of 1,2-hexanediol is predicted to be moderate through skin based
on its molecular weight, water solubility, and log K0„ (discussed in Section 3).
Further, in the event of oral ingestion, absorption across the GI tract is also predicted to be moderate
based on its molecular weight, water solubility and log Kow (discussed in Section 3).
Distribution
Following absorption through the lungs, skin, or GI tract, hexanediol is expected to be distributed via
blood. Based on the log kow and water solubility (Section 3), 1,2-hexanediol is unlikely to cross lipid
membranes or be sequestered in fatty tissues.
Metabolism
1,2-Hexanediol is predicted to be absorbed and metabolized through oxidation and glucuronide
conjugation metabolic pathways.27 Because quality experimental data13 found through the literature
search on 1,2-hexanediol metabolite formation were limited, the Quantitative Structure-Activity
Relationship (QSAR) toolbox28 was used to run the rat liver S9 metabolism simulator, the skin
metabolism simulator, and the in vivo rat metabolism simulator. The QSAR toolbox was used to
identify putative 1,2-hexanediol metabolites. In vivo metabolites are 2-hydroxyhexanoic acid and 2-
hydroxyhexanal as potential metabolites.
Excretion
Following metabolism, 1,2-hexanediol and metabolites are expected to be excreted via urine. No
accumulation in the body is expected as a result of excretion through efficient metabolic pathways
and the formation of soluble degradation products.
27 Final Report of the Cosmetic Ingredient Review Expert Panel: On the Safety Assessment of 1,2-Glycols as Used in
Cosmetics. June 28, 2011.
28 https://www.oecd.org/chemicalsafetv/risk-assessment/oecd-qsar-toolbox.htm
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6.1.2 Acute Toxicity
EPA assessed the potential for mammalian toxicity from acute exposures to 1,2-hexanediol using the
results of an OECD Guideline 401 study on rats exposed to the chemical by oral gavage. This study
indicated low concern for acute exposures with an LD50 greater than the low-concern criteria
threshold of 2000 mg/kg for both males and females (ECHA. 1981a). EPA also assessed the potential
for toxicity from acute dermal and inhalation exposures using read-across predictions from pentylene
glycol. No adverse effects were observed in rats after a 24-hour dermal exposure to a 2000 mg/kg
dose (ECHA. 1982a). indicating low concern for acute dermal exposure by having an LD50 greater
than the 2000 mg/kg dermal low-concern threshold. Further, no mortality was observed in rats after a
4-hour aerosol inhalation exposure to pentylene glycol, indicating low concern for acute exposures
(ECHA. 1982b). The LD50 was greater than the low-concern criteria threshold of 5 mg/L. These
results indicate low concern for acute exposures to 1,2-hexanediol from oral, inhalation, and dermal
exposure pathways.
6.1.3 Repeated Dose Toxicity
EPA assessed the potential for repeated dose mammalian toxicity based on the results of an OECD
Guideline 411 90-day dermal, repeated dose study on rats for 1,2-hexanediol. This study identified a
repeated dose no observed adverse effect level (NOAEL) of 700 mg/kg-day, with a lowest observed
adverse effect level (LOAEL) of 1000 mg/kg-day based on reduced body weight gain in males and
females and increased total leukocyte count and urinary protein in females (ECHA. 2002a). These
results indicate low concern for repeated dermal exposures to 1,2-hexanediol by exceeding the low-
concern threshold of 200 mg/kg-day for a 90-day exposure.
Oral repeated dose studies were available for the analogs, pentylene glycol and 1,2-octanediol. In a
90-day oral gavage study in rats exposed to pentylene glycol, adverse effects were not observed in
groups dosed up to the highest dose tested at 1000 mg/kg-day (ECHA. 2013). A 28-day study in rats
exposed to 1,2 octanediol via oral gavage reported a NOAEL of 300 mg/kg-day and LOAEL of 1000
mg/kg-day based on slightly reduced locomotor activity and changes in organ weights (ECHA. 2004).
These results from closely-related analogs indicate low concern for repeated oral exposures to 1,2-
hexanediol by exceeding the low concern threshold of 100 mg/kg-day for a 90-exposure (300 mg/kg-
day for a ~30-day exposure).
6.1.4 Reproductive and Developmental Toxicity
The sub-chronic toxicity study discussed in Section 6.1.3 also examined estrous cycle evaluations in
females and sperm parameters (sperm count, motility and morphology) in males. No adverse effects
were noted for the evaluated reproductive parameters, resulting in a NOAEL of 1000 mg/kg-day
(ECHA. 2002a. b). To further assess the reproductive and developmental toxicity potential for 1,2-
hexanediol, EPA evaluated two oral gavage studies for the chemical in pregnant female rats. In the
first study, results from exposure during gestation days 5-19 indicated no adverse maternal or
developmental effects at the highest dose tested, resulting in a NOAEL of 300 mg/kg-day (Johnson et
al.. 2012; ECHA. 2006). In the second study, rats exposed during gestation days 6-19 to higher doses
of 1,2-hexanediol reported no developmental effects at any doses, resulting in a developmental
NOAEL at the highest dose of the study, 750 mg/kg-day. However, the females exposed to 750
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mg/kg-day displayed decreased absolute and relative feed consumption, leading to decreased body
weight. The maternal NOAEL for this study was 500 mg/kg-day and the LOAEL was 750 mg/kg-day
(ECHA. 2003a). These results taken with the low-concern criteria oral threshold of 250 mg/kg-day
indicate low concern for reproductive and developmental toxicity.
6.1.5 Genotoxicity
EPA assessed experimental studies on genotoxicity as a potential indicator of genotoxic
carcinogenicity. Three in vitro gene mutation results on two different bacteria species and a cell line
indicate negative results for gene mutation with and without metabolic activation (ECHA. 2013.
1998b). Chinese hamster ovarian cells exposed to 1,2-hexanediol were negative for chromosomal
aberrations with and without metabolic activation (ECHA. 2000). These negative results indicate low
concern for genotoxicity.
6.1.6 Carcinogenicity
Because quality experimental data on 1-2 hexanediol were limited, EPA relied on publicly available
quantitative structure activity relationship (QSAR) models and structural alerts (SA) to assess the
carcinogenic potential for 1,2-hexanediol, discussed further below.
Structural alerts represent molecular functional groups or substructures that are known to be linked to
the carcinogenic activity of chemicals. The most common structural alerts are those for electrophiles
(either direct acting or following activation). Modulating factors that will impact the carcinogenic
potential of a given electrophile will include its relative hardness or softness, its molecular flexibility
or rigidity, and the balance between its reactivity and stability.29 For this chemical, there is an absence
of the types of reactive structural features that are present in genotoxic carcinogens. 1,2-Hexanediol is
not an electrophile. EPA's analysis of structurally related analogs and metabolites using ISS profile, a
QSAR model,3" supports this expectation. The Virtual models for property Evaluation of chemicals
within a Global Architecture (VEGA) models"31 results indicate 1,2-hexanediol has low potential to
be carcinogenic or mutagenic.
1,2-Hexanediol is an aliphatic diol that is likely to be metabolized through oxidation and glucuronide
conjugation. 1,2-Hexanediol and its metabolites are expected to be excreted from the body. Therefore,
it is anticipated that this chemical will not remain in the body for a long period of time, reducing
concern for carcinogenicity.
Based on 1,2-hexanediors metabolism, a lack of structural alerts and experimental genotoxicity
studies (Section 6.1.5), 1,2-hexanediol is of low concern for carcinogenicity or mutagenicity.
29 "Fundamental and Guiding Principles for (Q)SAR Analysis of Chemical Carcinogens with Mechanistic Considerations:
Series on Testing and Assessment, No. 229." 2015. Environment Directorate, Joint Meeting of the Chemicals Committee
and the Working Party on Chemicals, Pesticides and Biotechnology.
30 Carcinogenicity alerts by ISS 2.4 profiler as encoded in the QSAR Toolbox 4.3 (qsartoolbox.org). A summary of the
results from these models is provided in Appendix B.
31 There are four carcinogenicity models housed within the VEGA 1.1.4 software tool available from
https://www.vegaliub.eu. A summary of the results from these models is provided in Appendix B.
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6.1.7 Neurotoxicity
Experimental studies conducted solely on the potential for 1,2-hexanediol or the closely-related
analogs 1,2-butanediol, pentylene glycol, and 1,2-octanediol to cause neurotoxicity were limited. The
repeated dose oral studies in rats for the analogs pentylene glycol and 1,2-octanediol reported
minimal or no effects on the limited neurological endpoints that were evaluated. No effects on
functional observational battery (FOB) parameters and motor activity measurements at doses of
pentylene glycol up to 1000 mg/kg-day in a 90-day study (highest dose tested) (ECHA. 2013).
Slightly reduced locomotor activity was observed at 1000 mg/kg-day (LOAEL) in a 28-day oral study
of 1,2-octanediol; however, no effects were observed on histopathology of the brain, spinal cord or
sciatic nerve in this study (ECHA. 2004). These data from closely-related analogs indicate there is
low concern for neurotoxicity associated with 1,2-hexanediol. This finding is also supported by the
low-hazard findings for other human health hazard endpoints, including, but not limited to, toxicity
from acute and chronic exposures, reproductive toxicity, and developmental toxicity.
6.1.8 Skin Sensitization
EPA assessed the potential for 1,2-hexanediol to cause skin sensitization using the results of an
OECD Guideline 429 LLNA study on mice (ECHA. 2003b). The negative findings in this study
indicate 1,2-hexanediol is of low concern for skin sensitization.
6.1.9 Skin Irritation
EPA assessed available experimental data on skin irritation. An OECD Guideline 404 study on
rabbits reported negative results (ECHA. 1981b). A study on humans also reported negative results
(Lee et al.. 2011). These results indicate low concern for 1,2-hexanediol to cause skin irritation.
6.1.10 Eye Irritation
EPA identified potential for eye irritation from exposure to 1,2-hexanediol. Rabbits exposed to 1,2-
hexanediol for 24 hours exhibited moderate eye irritation. After the 24-hour exposure, the animals
were observed for reversibility. The effects were reversible in 14 days for corneal irritation, 7 days for
iris irritation, and 10 days for conjunctivae irritation (ECHA. 1998a). These results indicate moderate
to high concern for eye irritation (with reversible effects) by 1,2-hexanediol.
6.1.11 Hazards to Potentially Exposed or Susceptible Subpopulations
The above information supports a low human health hazard finding for 1,2-hexanediol based on low-
concern criteria. This finding includes considerations such as the potential for developmental toxicity,
reproductive toxicity, and acute or repeated-dose toxicity that may impact potentially exposed or
susceptible subpopulations. Based on the hazard information discussed in Section 6, EPA did not
identify populations with greater susceptibility to 1,2-hexanediol.
6.2 Environmental Hazard
EPA assessed environmental hazard for 1,2-hexanediol based on available data on 1,2-hexanediol and
closely-related analogs described above. EPA estimated chronic toxicity values using the Ecological
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Structure Active Relationships (ECOSAR) Predictive Model32 and available experimental data.
Appendix B contains a summary of the reasonably available environmental hazard data.
6.2.1 Acute Aquatic Toxicity
EPA assessed environmental hazard from acute exposures to 1,2-hexanediol based on available
experimental data. Two studies evaluated the effects of acute exposure of 1,2-hexanediol to aquatic
invertebrates. Both studies reported no mortality at the highest dose (100 mg/L), resulting in EC50S
greater than 100 mg/L (Lee et al.. 2017; ECHA. 2012). For algal toxicity, S. siibspicatus acutely
exposed to pentylene glycol (ECHA. 1990) and 1,2-butanediol (ECHA. 1991) indicated very low
concern, with EC50S ranging from 500-9334 mg/L. However, another species of algae, P. subcapitata,
exposed to 1,2-octanediol resulted in an EC50 of 35 mg/L (ECHA. 2007). Aquatic vertebrates acutely
exposed to pentylene glycol indicated low concern with an LC50 greater than 1096 mg/L (ECHA.
1994). A chemical with acute aquatic toxicity values >10 ppm and <100 ppm is considered low
concern for hazard if the chemical reaches a threshold level ofbiodegradation (typically 60%) within
28 days as measured in a ready biodegradation test without degradation products of concern. Given
the low persistence of 1,2-hexanediol (see Section 6.3.1, below), these aquatic toxicity studies
indicate low concern for acute aquatic exposure by exceeding the low-concern threshold of 10 mg/L
and demonstrating greater than 60% biodegradation within 28 days.
6.2.2 Chronic Aquatic Toxicity
EPA assessed environmental hazard from chronic exposures to 1,2-hexanediol based on available
experimental data and estimated values using ECOSAR. Aquatic invertebrates chronically exposed to
1,2-hexanediol showed no mortality at the highest dose (10 mg/L), resulting in a no observed effect
concentration (NOEC) of 10 mg/L (Lee et al.. 2017). Toxicity from chronic exposures were estimated
by ECOSAR using the neutral organics chemical class to occur at 66 mg/L for algae and 120 mg/L
for aquatic vertebrates. These toxicity values indicated that 1,2-hexanediol has low environmental
hazard based on the low-concern criteria chronic aquatic toxicity threshold of 10 mg/L.
6.3 Persistence and Bioaccumulation Potential
6.3.1 Persistence
EPA assessed environmental persistence for 1,2-hexanediol. An experimental OECD Guideline 301B
biodegradation study demonstrated this substance aerobically biodegraded by greater than 60 percent
in 28 days, confirming it is readily biodegradable in a sewage sludge inoculum (ECHA. 1997). No
degradation products of concern were identified for this chemical substance. Given the aquatic
toxicity values for this chemical, the low-concern criteria require that 1,2-hexanediol not produce
degradation products of concern and readily biodegrade within 28 days. The available biodegradation
results meet the low-concern threshold and indicate this chemical will have low persistence.
EPA also assessed the potential for anaerobic biodegradation using read-across predictions from 1,2-
octanediol. An OECD Guideline 311 indicated the analog anaerobically biodegraded by 68% in 60
days, indicating 1,2-hexanediol will biodegrade in anaerobic environments (ECHA. 2008).
32https://www.epa.go v/tsca-screening-tools/ecological-striictin'e-activity-relationships-ecosar-predictive-model
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6.3.2 Bioaccumulation Potential
Based on the estimated bioaccumulation factor (BAF) value of 1.1, using Estimation Programs
Interface (EPI) Suite models,33 1,2-hexanediol has low potential for bioaccumulation in the
environment based on the low-concern threshold of less than 1000.
33 https://www.epa.gov/tsca-screemiig-tools/epi-suitetm-estimation-program-iiiterface
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7. Exposure Characterization
EPA considered reasonably available information on exposure for 1,2-hexanediol. In general, there is
limited information on exposure for low-hazard chemicals. EPA consulted sources of use information
that include CDR database and other databases and public sources. Of these sources, EPA determined
that the CDR database contained the primary source of information on the conditions of use for this
exposure characterization. EPA used these sources (described in Table A.2) only where they
augmented information from the CDR database to inform intended, known, or reasonably foreseen
uses (Section 5).
As shown in Tables 3 and A.3, 1,2-hexanediol is a solvent used in processing (incorporation into an
article and into a formulation, mixture, or product) in the industrial printing ink manufacturing sector;
as well as in ink, toner, and colorant products for consumer and commercial use (EPA 2017b). Non-
TSCA uses are beyond the scope of this assessment because of the exclusions under TSCA section
3(2) (See Table A.3).
Under the conditions of use identified in Table 3, EPA assessed the potential exposure to the
following categories: the environment, the general population, and potentially exposed or susceptible
subpopulations including workers and consumers.
7.1 Production Volume Information
Production volume information for 1,2-hexanediol is based on an analysis of CDR data reported from
1998 to 2016.34 The CDR database indicates that, for reporting year 2015, three companies
manufactured or imported 1,2-hexanediol at three sites. In 1998 and 2002 reporting years, aggregate
production volume for 1,2-hexanediol was between 10,000 and 500,000 lbs., and in 2006 aggregate
production volume was less than 500,000 lbs. The exact amount is available for one year, 2011, in
which 94,095 lbs. of 1,2-hexanediol was produced or imported. Between 2012 and 2015, volume
ranged between 25,000 and 500,000 lbs. Aggregate production volumes for each reporting year are
provided in Table A.l.
7.2 Exposures to the Environment
EPA expects most exposures to the environment to occur during the processing of 1,2-hexanediol,
specifically, the formulation of printing inks and toners. Exposure is also possible from other uses,
such as manufacturing, distribution, consumer and commercial use, and disposal. These activities
could result in releases of 1,2-hexanediol to media including surface water, landfills, and air.
EPA expects high levels of removal of 1,2-hexanediol during wastewater treatment (either directly
from the facility or indirectly via discharge to a municipal treatment facility or Publicly Owned
Treatment Works (POTW)). Further, 1,2-hexanediol has low persistence (aerobic and anaerobic
biodegradation are discussed in Section 6.3.1) and has the potential to break down in the environment
into carbon dioxide and water. Therefore, any release of this chemical is expected to break down,
34 Hie CDR requires manufacturers (including importers) to report information on the chemical substances they produce
domestically or import into the U.S above 25,000 lb. per site per year.
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reducing exposure to aquatic organisms in the water column, benthic organisms, and groundwater
sources of drinking water, including well water.
If disposed of in a landfill, this chemical is expected to degrade under aerobic and anaerobic
conditions (aerobic and anaerobic biodegradation are discussed in Section 6.3.1).
If incineration releases during manufacturing and processing occur, EPA expects significant
degradation of 1,2-hexanediol to the point that it will not be present in air.
7.3 Exposures to the General Population
EPA expects the general population is unlikely to be exposed to 1,2-hexanediol from the potential
environmental releases described above. Air exposure is unlikely from incineration. If 1,2-hexanediol
is present in the air from volatilization, it is expected to be reduced because of its short atmospheric
half-life of 6.9 hours (see Table 2 in Section 3). 1,2-Hexanediol is unlikely to be present in surface
water because of its degradation (aerobic and anaerobic biodegradation are discussed in Section
6.3.1), reducing the potential for the general population to be exposed by oral ingestion or dermal
exposure. Given the low bioaccumulation or bioconcentration potential of 1,2-hexanediol, oral
exposure to 1,2-hexanediol via fish ingestion is unlikely.
7.4 Exposures to Potentially Exposed or Susceptible Subpopulations
EPA identified workers as a potentially exposed or susceptible subpopulation based on greater
exposure to 1,2-hexanediol than the general population during manufacturing, processing,
distribution, use, and disposal. EPA also identified consumers as a population that may experience
greater exposure to 1,2-hexanediol than the general population through use of ink, toner, and colorant
products.
7.4.1 Exposures to Workers
Based on its reported physical form and measured melting point (Table 2), 1,2-hexanediol is a liquid
under ambient conditions. Based on 1,2-hexanediors conditions of use (Table 3), workers may be
exposed to liquids through direct dermal contact with the substance and inhalation of aerosols if they
are generated. Based on its measured vapor pressure (Table 2), 1,2-hexanediol is expected to be
volatile at ambient temperatures, and therefore workers may be exposed through inhalation of vapors.
However, if 1,2-hexanediol is in a dilute form, the estimated Henry's Law constant for 1,2-hexanediol
indicates volatilization from water and aqueous solutions is expected to be minimal. Workers may be
exposed to 1,2-hexanediol in manufacturing, processing, distribution, use, and disposal.
7.4.2 Exposures to Consumers
Consumers could be exposed to 1,2-hexanediol through the use of ink, toner, and colorant products.
Consumer exposure could occur through dermal contact with ink printed on products or in initial
installation of a printer cartridge or toner. If dermal contact does occur, 1,2-hexanediol is expected to
be moderately absorbed through the skin. EPA does not include intentional misuse, such as people
drinking products containing this chemical, as part of the known, intended or reasonably foreseen
conditions of use that could lead to an exposure (82 FR 33726). Thus, oral exposures will be
incidental (meaning inadvertent and low in volume). 1,2-hexanediol is expected to be metabolized
and excreted, further reducing the duration of exposure.
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8. Summary of Findings
EPA has used reasonably available information on the following statutory and regulatory criteria and
considerations to screen 1,2-hexanediol against each of the priority designation considerations in 40
CFR 702.9(a), and discussed individually in this section, under its conditions of use:
• the hazard and exposure potential of the chemical substance (See Sections 6 and 7);
• persistence and bioaccumulation (See Section 6.3);
• potentially exposed or susceptible subpopulations (See Section 7.4);
• storage near significant sources of drinking water (See Section 8.4);
• conditions of use or significant changes in the conditions of use of the chemical substance
(See Section 5);
• the chemical substance's production volume or significant changes in production volume
(See Section 7.1); and
• other risk-based criteria that EPA determines to be relevant to the designation of the chemical
substance's priority.
EPA conducted a risk-based screening-level review based on the criteria and other considerations
above and other relevant information described in 40 CFR 702.9(c) to inform the determination of
whether the substance meets the standard of a high-priority substance. High-priority substance means
a chemical substance that EPA determines, without consideration of costs and other non-risk factors,
may present an unreasonable risk of injury to health or the environment because of a potential hazard
and a potential route of exposure under the conditions of use, including an unreasonable risk to
potentially exposed or susceptible subpopulations identified as relevant by EPA (40 CFR 702.3). This
section explains the basis for the proposed designation and how EPA applied statutory and regulatory
requirements, addressed issues, and reached conclusions.
8.1 Hazard and Exposure Potential of the Chemical Substance
Approach: EPA evaluated the hazard and exposure potential of 1,2-hexanediol. EPA used this
information to inform its proposed determination of whether 1,2-hexanediol would meet the statutory
criteria and considerations for proposed designation as a low-priority substance.
• Hazard potential:
For 1,2-hexanediol's hazard potential, EPA gathered information for a broad set of human health and
environmental endpoints described in detail in Section 6 of this document. EPA benchmarked this
information against low-concern thresholds. EPA found that 1,2-hexanediol is of low concern for
human health and environmental hazard across the range of endpoints in these low-concern criteria
except for eye irritation (see the discussion below).
• Exposure potential:
To understand exposure potential, EPA gathered information on physical-chemical properties,
production volumes, and the types of exposures likely to be faced by workers, the general population,
and consumers (discussed in Sections 3 and 7). EPA also gathered information on environmental
releases. EPA identified workers, the general population, consumers, and the environment as most
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likely to experience exposures. EPA determined that while the general population, consumers and
workers may be exposed to 1,2-hexanediol, exposure by dermal, inhalation and ingestion pathways
are reduced by metabolism and excretion (discussed in Section 6.1.1). If 1,2-hexanediol is released
into the environment, its exposure potential will be reduced through biodegradation under aerobic and
anaerobic conditions.
Rationale: EPA found that 1,2-hexanediol is moderately irritating to eyes. In the case of 1,2-
hexanediol, the moderate effects are reversible, reducing concern for longer-term effects. Workers
could be exposed during processing, manufacturing, distribution, use, and disposal, splashing of
solutions, or hand-to-face and eye contact. Other uses covered under TSCA, especially consumer uses
in products such as ink, toner, and colorant products, would be unlikely to result in more than
incidental eye exposure. Eye irritation resulting from exposure in an occupational and consumer
setting is mitigated by the reversible nature of the effect and addressed by rinsing with water.
Proposed Conclusion: Based on analysis of reasonably available hazard and exposure information,
EPA proposes to conclude that the risk-based, screening-level review under 40 CFR 702.9(a)(1) does
not support a finding that 1,2-hexanediol meets the standard for a high-priority substance. The
reasonably available hazard and exposure information described above provides sufficient
information to support this proposed finding.
8.2 Persistence and Bioaccumulation
Approach: EPA has evaluated both the persistence and bioaccumulation potential of 1,2-hexanediol
based on a set of EPA and internationally accepted measurement tools and thresholds that are
indicators of persistence and bioaccumulation potential (described in Section 6). These endpoints are
key components in evaluating a chemical's persistence and bioaccumulation potential.
Rationale: EPA review of experimental data indicates 1,2-hexanediol is readily biodegradable under
aerobic conditions, with greater than 60 percent biodegradation within 28 days, and is expected to be
biodegradable under anaerobic conditions with 68% biodegradation in 60 days based on a closely-
related analog. EPA's EPI Suite models indicate a low potential for bioaccumulation and
bioconcentration.
Proposed Conclusion: Based on an analysis of reasonably available information on persistence and
bioaccumulation, EPA proposes to conclude that the screening-level review under 40 CFR
702.9(a)(2) does not support a finding that 1,2-hexanediol meets the standard for a high-priority
substance. The reasonably available persistence and bioaccumulation information described above
provides sufficient information to support this proposed finding.
8.3 Potentially Exposed or Susceptible Subpopulations
Approach: TSCA Section 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 a 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, consumers, or the elderly." EPA
identified workers engaged in the manufacturing, processing, distribution, use, and disposal of 1,2-
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hexanediol as a potentially exposed or susceptible subpopulation. Consumers are also a potentially
exposed subpopulation because of their use of products such as ink, toner, and colorant products
(described in more detail in Section 7).
Rationale: EPA expects workers and consumers to have a higher exposure to 1,2-hexanediol than the
general population. Because of the chemical's low-concern hazard properties and reversibility of the
effects, this exposure does not pose a significant increase in risk for consumers or workers.
Proposed Conclusion: Based on the Agency's understanding of the conditions of use and expected
users such as potentially exposed or susceptible subpopulations, EPA proposes to conclude that the
screening-level review under 40 CFR 702.9(a)(3) does not support a finding that 1,2-hexanediol
meets the standard for a high-priority substance. While the conditions of use will result in an increase
in exposures to certain populations, the consistently low-hazard profile of 1,2-hexanediol provides
sufficient evidence to support a finding of low concern. The reasonably available information on
conditions of use, hazard, and exposure described above provides sufficient information to support
this proposed finding.
8.4 Storage Near Significant Sources of Drinking Water
Approach: In Sections 6 and 7, EPA explains its evaluation of the elements of risk relevant to the
storage of 1,2-hexanediol near significant sources of drinking water. For this criterion, EPA focused
primarily on the chemical substance's potential human health hazards, including to potentially
exposed or susceptible subpopulations, and environmental fate properties, and explored a scenario of
a release to a drinking water source. EPA also investigated whether the chemical was monitored for
and detected in a range of environmental media. The requirement to consider storage near significant
sources of drinking water is unique to prioritization under TSCA Section 6(b)(1)(A) and 40 CFR
702.9(a)(4).
Rationale: In terms of health hazards, 1,2-hexanediol is expected to present low concern to the
general population, including susceptible subpopulations, across a spectrum of health endpoints.
In the event of an accidental release into a surface drinking water source, 1,2-hexanediol is expected
to be water soluble (see Section 3) and has low persistence (see Section 6) in the drinking water
supply. In the event of an accidental release to land, the estimated log Koc indicates this substance is
highly mobile in soils, increasing its potential for leaching into groundwater, including well water.
The fate and transport evaluation indicates 1,2-hexanediol is unlikely to partition into sediment,
predicted to biodegrade under aerobic and anaerobic conditions (see Section 3), and unlikely to
bioaccumulate (see Section 6), minimizing the likelihood that the chemical would be present in
sediment or groundwater to pose a longer-term drinking water contamination threat.
A sudden release of large quantities of the chemical near a drinking water source could have
immediate effects on the usability of a surface drinking water source. If such a release were to occur,
two primary factors would operate together to reduce concern. First, the chemical would be expected
to present low concern to the general population, including susceptible subpopulations, across a
spectrum of health endpoints (see Section 6). Second, 1,2-hexanediol would degrade in aerobic and
anaerobic environments (see Section 6). Together, these factors mean that any exposures to this
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chemical through drinking water sources would be short-lived, and that if ingestion were to take
place, concern for adverse health effects would be low..
EPA also explored whether the chemical had been identified as a concern under U.S. environmental
statutes in the past. EPA searched lists of chemicals and confirmed that 1,2-hexanediol does not
appear on these lists. The lists reviewed include EPA's List of Lists
(https://www.epa.gov/sites/production/files/2015-03/documents/list of lists.pdf). EPA also searched
the lists of chemicals included in the National Primary Drinking Water Regulations and the
Unregulated Contaminant Monitoring Rule (UCMR) under the Safe Drinking Water Act (SDWA).
Proposed Conclusion: Based on a qualitative review of a potential release near a significant source
of drinking water, EPA proposes to conclude that the screening-level review under 40 CFR
702.9(a)(4) does not support a finding that 1,2-hexanediol meets the standard for a high-priority
substance. The reasonably available information on storage near significant sources of drinking water
described above provides sufficient information to support these proposed findings.
8.5 Conditions of Use or Significant Changes in Conditions of Use of the
Chemical Substance
Approach: EPA evaluated the conditions of use for 1,2-hexanediol and related potential exposures
and hazards.
Rationale: EPA evaluated the conditions of use of 1,2-hexanediol (see Section 5 and Appendix A)
and found it to have a small range of conditions of use. EPA expects that even if the conditions of
use were to expand beyond activities that are known, intended, or reasonably foreseen, the outcome
of the screening review would likely not change and would not alter the Agency's conclusion of low
concern. EPA bases this expectation on 1,2-hexanediors consistently low-concern hazard
characteristics across the spectrum of hazard endpoints and regardless of a change in the nature or
extent of its use and resultant increased exposures.
Proposed Conclusion: EPA's qualitative evaluation of potential risk does not support a finding that
1,2-hexanediol meets the standard for a high-priority substance based on its low hazard profile under
the current conditions of use. EPA proposes to find that even if conditions of use broaden, resulting in
an increase in the frequency or amount of exposures, the analysis conducted to support screening-
level review under 40 CFR 702.9(a)(5) would not change significantly. In particular, the analysis of
concern for hazard, which forms an important basis for EPA's findings, would not be impacted by a
change in conditions of use. Therefore, such changes would not support a finding that 1,2-hexanediol
meets the standard for a high-priority substance. The reasonably available information on conditions
of use, or significant changes in conditions of use, described above provides sufficient information to
support this proposed finding.
8.6 The Volume or Significant Changes in Volume of the Chemical
Substance Manufactured or Processed
Approach: EPA evaluated the current production volumes of 1,2-hexanediol (Section 7.1) and
related potential exposures (Sections 7.2 through 7.4).
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Rationale: EPA used reasonably available information on production volume (see Appendix A) in
considering potential risk. It is possible that designation of 1,2-hexanediol as a low-priority substance
could result in increased use and higher production volumes. EPA expects, however, that any changes
in 1,2-hexanediors production volume would not alter the Agency's assessment of low concern given
the low hazard profile of the chemical. EPA bases this expectation on 1,2-hexanediors consistently
low-concern hazard characteristics across the spectrum of hazard endpoints. This expectation would
apply, even with a significant change in the volume of the chemical manufactured or processed and
resultant increased exposures.
Proposed Conclusion: Based on the screening criteria under 40 CFR 702.9(a)(6), EPA proposes to
find that even if production volumes increase, resulting in an increase in the frequency or levels of
exposure, 1,2-hexanediol does not meet the standard for a high-priority substance. The reasonably
available information on production volume, or significant changes in production volume, described
above provides sufficient information to support this proposed finding.
8.7 Other Considerations
EPA did not identify other considerations for the screening review to support the proposed
designation of 1,2-hexanediol as a low-priority substance.
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9. Proposed Designation
Based on a risk-based, screening-level review of the chemical substance and, when applicable,
relevant information received from the public and other information as appropriate and consistent
with TSCA section 26(h) and (i), EPA is proposing to designate 1,2-hexanediol as a low-priority
substance as it does not meet the statutory criteria for a high-priority substance.
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Appendix A: Conditions of Use Characterization
EPA gathered information on and related to conditions of use including uses of the chemical,
products in which the chemical is used, types of users, and status (e.g., known, regulated).
A.1 CDR Manufacturers and Production Volume
The Chemical Data Reporting (CDR) rule (previously known as the Inventory Update Rule, or IUR),
under TSCA section 8, requires manufacturers (including importers) to report information on the
chemical substances they produce domestically or import into the U.S., generally above a reporting
threshold of 25,000 lbs. per site per year. According to the 2016 CDR database, three companies
manufactured or imported 1,2-hexanediol for reporting year 2015. Individual production volumes
were withheld by EPA to protect against disclosure of CBI.
Table presents the historic production volume of 1,2-hexanediol from the CDR from 1986-2015. Prior
to 1994, 1,2-hexanediol was not reported in the CDR. This does not mean it was not being produced
or imported, but more likely that no single entity site was producing above the reporting threshold. In
1998 and 2002 reporting years, aggregate production volume for 1,2-hexanediol was between 10,000
and 500,000 lbs., and in 2006 aggregate production volume was less than 500,000 lbs. The exact
amount is available for one year, 2011, in which 94,095 lbs. of 1,2-hexanediol was produced or
imported. Between 2012 and 2015, volume ranged between 5,000 and 500,000 lbs. In general, since
1998, production volume has remained relatively stable without significant increases or decreases.
Table A.1
: 1986-2015 National Production Volume Data for 1,2-Hexanediol (Non-Confidential Production Volume
in Pounds)
1986
1990
1994
1998
2002
2006
2011
2012
2013
2014
2015
NDR
NDR
NDR
10 K —
10 K —
< 500 K
94,095
25K-
100K-
100K-
25K-
500 K
500 K
<100K
<500 K
<500 K
<100K
Note(s):
K = Thousand; M =
Million; NDR = No data reported
Source(s):
EPA ((2018a): (2017b): (2006): (2002))
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A.2 Uses
A.2.1 Methods for Uses Table
Section A.2.2 provides a list of known uses of 1,2-hexanediol, organized by category of use. To
compile the uses, EPA searched publicly available databases listed in Table and conducted additional
internet searches to clarify uses. Search terms differed among databases because of different search
term requirements for each database (i.e., some databases search by CASRN while others search by
chemical name).
Table A.2: Sources Searched for Uses of 1,2-Hexanediol
Title
Author and Year
Search Term(s)
Found Use Information?1
Sources searched for all use reports
California Links to
California Dept of Pesticide
6920-22-5; 1,2-hexanediol
No
Pesticides Data
Regulation (2013)
Canada Chemicals
Management Plan
Government of Canada (2018)
1,2-hexanediol
No
information sheets
Chemical and Product
Categories (CPCat)
CPCat (2019)
6920-22-5
Yes
ChemView2
EPA (2018)
6920-22-5
Yes
Children's Safe Product
Act Reported Data
Washington State Dept. of
Ecology (2018)
6920-22-5
No
Consumer Product
Information Database
DeLima Associates (2018)
6920-22-5
Yes
(CPID)
Danish surveys on
chemicals in consumer
products
Danish EPA (2018)
N/A, There is no search,
but report titles were
checked for possible
Yes
information on the chemical
Datamyne
Descartes Datamyne (2018)
1,2-hexanediol
No
DrugBank
DrugBank (2018)
6920-22-5
Yes
European Chemicals
Agency (ECHA)
EPA (2018)
6920-22-5
Yes
Registration Dossier
eChemPortal2
OECD (2018)
6920-22-5
Yes
Envirofacts2
EPA (2018)
6920-22-5; 1,2-hexanediol
No
Functional Use Database
(FUse)
EPA (2017)
6920-22-5
Yes
Kirk-Othmer Encyclopedia
of Chemical Technology
Kirk-Othmer (2006)
1,2-hexanediol; hexanediol
No
Non-Confidential 2016
Chemical Data Reporting
EPA (2017)
6920-22-5
Yes
(CDR)
PubChem Compound
Kimetal. (2016)
6920-22-5
Yes
Safer Chemical Ingredients
List (SCIL)
EPA (2018)
6920-22-5
Yes
Synapse Information
Resources2
Synapse Information
Resources (n.d.)
1,2-hexanediol
No
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Table A.2: Sources Searched for Uses of 1,2-Hexanediol
Title
Author and Year
Search Term(s)
Found Use Information?1
Resource Conservation
and Recovery Act (RCRA)
EPA (2017)
1,2-hexanediol; hexanediol;
hexane; 1,2
No
Scorecard: The Pollution
Information Site
GoodGuide (2011)
6920-22-5; 1,2-hexanediol;
1,2-hex; DL-hexane
No
Skin Deep Cosmetics
Database
EWG (2018)
6920-22-5
Yes
Toxics Release Inventory
(TRI)
EPA (2018)
6920-22-5
No
TOXNET2
NLM (2018)
6920-22-5
Yes
Ullmann's Encyclopedia of
Industrial Chemistry
Ullmann's (2000)
1,2-hexanediol; hexanediol
Yes
Additional Sources Identified from Reasonably Available
Danish Environmental
Protection Agency (Danish
EPA)
Danish EPA (2015)
Incidentally identified while
researching details of this
chemical's uses and
products.
Yes
Expanscience Laboratories
Expanscience Laboratoires
(2017)
Food-grade antimicrobials
potentiate the antibacterial
activity of 1,2-hexanediol
Yogiaraetal. (2015)
International Fragrance
Association (IFRA)
IFRA (2016)
National Pesticide
Information Retrieval
System (NPIRS)
National Pesticide Information
Retrieval System (2016)
Nature Republic
Nature Republic (2018)
Xerox Corporation
Xerox Corporation (2018a)
Note(s):
1. If use information was found in the resource, it will appear in Table unless otherwise noted.
2. This source is a group of databases; thus the exact resource(s) it led to will be cited instead of the database as whole.
The U.S. Patent and Trademark Office has an online database that shows 3,079 patents referencing
"" 1.2-hexancdiol" (USPTO (2018)). Although patents could be useful in determining reasonably
foreseen uses, it is difficult to confirm whether any of the patented technologies are currently in use.
Uses inferred from patents containing 1,2-hexanediol were not included in Table . Note that the uses
in Table A.2 that are covered under TSCA are included in Section 5, Table 3 of this document.
Ill
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A.2.2 Uses of 1,2-Hexanediol
Table A.3: Uses of 1,2-Hexanediol
Use
Description of Use and References
TSCA Conditions of Use: Ink, Toner, and Colorant Products
According to the 2016 CDR, 1,2-hexanediol is a solvent used in processing (incorporation into article, and incorporation into formulation, mixture, or product) in the industrial
printing ink manufacturing sector; as well as in ink, toner, and colorant products for consumer and commercial use (EPA 2017b).
ECHA (2018)
Ink used in textiles,
leather, and fur
Commercial
The ECHA registration dossier indicates that 1,2-hexanediol has been used in commercial inks, the end use of which is reported as
manufacture of textiles, leather, and fur. No further information about this use could be found and it is unknown whether this is an
ongoing use in the United States.
Expected users are commercial due to ECHA's inclusion as a use by professional workers.
Xerox Corporation (2018a, 2018b); EPA (2017b); Ullmann's (2012)
Printing ink
Consumer,
commercial,
industrial
1,2-Hexanediol was reported to be used in printing ink manufacturing and ink, toner, and colorant products in the 2016 CDR. A few
current SDSs for printer ink containing 1,2-hexanediol were also available online. CDR indicates that the chemical functions as a
solvent in this sector.
CDR identified consumer and commercial use in "ink, toner, and colorant' products, and industrial use in printing ink
manufacturing.
EPA (2017b)
Toner
Consumer,
commercial
1,2-Hexanediol was reported to be used in ink, toner, and colorant products in the 2016 CDR. No examples of toner products
confirmed to contain the chemical could be found. The functional use of the chemical in toners is unknown.
CDR identified consumer and commercial use in "ink, toner, and colorant" products.
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Table A.3: Uses of 1,2-Hexanediol
Use Description of Use and References
Other TSCA Uses
Fuel and lubricant
additive
Consumer,
commercial,
industrial
Ullmann's (2012)
Ullmann's Encyclopedia reports 1,2-hexanediol as being used in fuel and lubricant additives. This use was not reported in the most
recent CDR and no additional information on the chemical's use as a fuel or lubricant additive could be found.
Fuel and lubricant additives are available for consumer, commercial, and industrial use, depending on their application. Due to
limited available information, EPA has not confirmed any of these expected users.
Non-TSCA Uses
Acne treatment
Consumer
EWG (2018)
EWG previously listed an acne treatment product in the Skin Deep database that contained 1,2-hexanediol but the product has
since been removed. It is unknown whether other current acne products contain the chemical.
After shave
Consumer
EWG (2018)
Anti-aging cream
and liquid
Consumer
DeLima Associates (2015c, 2009, 2008); EWG (2018)
EWG's Skin Deep and CPID generally include products for consumer use; therefore, the expected user is a consumer.
Baby lotion
Consumer
EWG (2018)
Baby soap
Consumer
EWG (2018)
Baby wipes
Consumer
EWG (2018)
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Table A.3: Uses of 1,2-Hexanediol
Use
Description of Use and References
Nature Republic (2018); DeLima Associates (2015a, 2015b, 2015c)
Beauty-related eye
product
Consumer
This use category includes eye creams, mascara, depuffers, and anti-aging products. The functional use of 1,2-hexanediol in these
products is unknown.
Blush
Consumer
EWG (2018)
Body soap (liquid)
Consumer
DeLima Associates (2016b); EWG (2018)
Body soap
Consumer
DeLima Associates (2015a); EWG (2018)
EWG (2018)
Bronzer
Consumer
The bronzer product reported by EWG no longer contains 1,2-hexanediol according to the ingredients listed on the company's
website. However, it is possible that other bronzers still contain the chemical.
Concealer
Consumer
EWG (2018)
Conditioner
Consumer
EWG (2018)
ECHA (2018); National Pesticide Information Retrieval System (2016)
Disinfectant
Industrial
The ECHA registration dossier indicates that 1,2-hexanediol has been used in biocidal (e.g., disinfectant; pest control) products.
No further information about this use could be found, and it is unknown whether this is an ongoing use in the United States. The
National Pesticide Information Retrieval system indicates that no federally active pesticide products contain 1,2-hexanediol.
Expected users are industrial due to ECHA's inclusion as a use at industrial sites.
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Table A.3: Uses of 1,2-Hexanediol
Use
Description of Use and References
Exfoliant scrub
Consumer
EWG (2018)
Eye liner
Consumer
EWG (2018)
Eye shadow
Consumer
EWG (2018)
Face mask
Consumer
EWG (2018); DrugBank (2018)
Facial soap
Consumer
CPCat (2019); EWG (2018)
Foundation
Consumer
EWG (2018)
IFRA (2016); Danish EPA (2015)
Fragrance
Unknown
The International Fragrance Association (IFRA) reported the use of 1,2-hexanediol as a fragrance compound in 2015. The list does
not specify the country of use or manufacture. One currently available fragrance product containing the chemical was identified, but
it is unknown whether the function of 1,2-hexanediol in the product is as a fragrance itself, or if it is serving another function.
The expected users are unknown, due to the limited availability of information.
Hair spray
Consumer
DeLima Associates (2016a, 2015d); EWG (2018)
Hair styling gel
Consumer
EWG (2018)
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Table A.3: Uses of 1,2-Hexanediol
Use
Description of Use and References
Lip gloss, lip balm,
and lipstick
Consumer
CPCat (2019); EWG (2018)
Makeup primer
Consumer
EWG (2018)
Makeup remover
Consumer
EWG (2018)
Moisturizer
Consumer
CPCat (2019); EWG (2018)
Nail polish
Consumer
EWG (2018)
Perfume
Consumer
EWG (2018); Expanscience Laboratoires (2017)
EWG's Skin Deep included a perfume spray product containing 1,2-hexanediol. It is unknown whether the chemical is used for its
fragrance or some other functional use within the product.
Expected users are consumer, based on the one identified fragrance product sold to consumers. The product's website indicates
that it can be used for babies.
Pharmaceutical
Consumer,
commercial
ECHA (2018)
The ECHA registration dossier indicates that 1,2-hexanediol has been used in cosmetic and pharmaceutical products. No further
information about this use could be found and it is unknown whether this is an ongoing use in the United States.
Expected users are consumer and commercial due to ECHA's inclusion as a professional use and consumer use.
Shampoo
Consumer
EWG (2018)
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Table A.3: Uses of 1,2-Hexanediol
Use
Description of Use and References
Shaving cream
Consumer
EWG (2018)
Sunscreen
Consumer
EWG (2018)
Tanning oil
Consumer
EWG (2018)
Children's Products
CDR reports did not include any uses in children's products; however, uses in baby lotion, baby wipes, baby soap, and one perfume product intended for babies are found in
this table.
Recycling and Disposal
In the 2016 CDR, two facilities reported that 1,2-hexanediol was not recycled (e.g., not recycled, remanufactured, reprocessed, or reused). One facility reported this
information as CBI (EPA 2017b).
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A.3 References
California Dept of Pesticide Regulation. (2013). DPR Databases. Available online at
https://www.cdpr.ca.gov/dprdatabase .htm
Danish EPA. (2015). Survey of fragrance substances. Available online at
https://www2.mst.dk/Udgiv/publications/2015/05/978-87-93352-25-4.pdf
Danish EPA. (2018). Danish surveys on chemicals in consumer products. Available online at
https://eng.mst.dk/chemicals/chemicals-in-products/consumers-consumer-products/danish-
survevs-on-consumer-products/
DeLima Associates. (2008). Aveeno Active Naturals Positively Ageless Rejuvenating Serum (Cream).
Available online at
https://www.whatsinproducts.com/tvpes/tvpe detail/1/8717/standard/Aveeno%20Active%20Natu
rals%20Positivelv%20Ageless%20Reiuvenating%20Serum/10-001-074
DeLima Associates. (2009). Aveeno Active Naturals Positively Ageless Rejuvenating Serum (Liquid).
Available online at
https://www.whatsinproducts.com/tvpes/tvpe detail/l/9747/standard/Aveeno%20Active%20Natu
rals%20Positivelv%20 Ageless%20Reiuvenating%20 Serum/10-001-130
DeLima Associates. (2015a). Olay Eyes Eye DepufFing Roller For Bags Under Eyes. Available online at
https://www.whatsinproducts.com/tvpes/tvpe detail/l/17743/standard/p%20class=%22pl%22%3
E01av%20Eves%20Eve%20Depuffing%20Roller%20For%20Bags%20Under%20Eves-
02/24/2015/p%3E/16-033-099
DeLima Associates. (2015b). Olay Eyes, Eye Lifting Serum For Sagging Skin. Available online at
https://www.whatsinproducts.com/tvpes/tvpe detail/l/17744/standard/p%20class=%22pl%22%3
E01av%20Eves.%20Eve%20Lifting%20Serum%20For%20Sagging%20Skin-
02/12/2015/p%3E/16-033-100
DeLima Associates. (2015c). Olay Total Effects Anti-Aging Eye Treatment. Available online at
https://www.whatsinproducts.com/tvpes/tvpe detail/l/17799/standard/p%20class=%22pl%22%3
E01av%20Total%20Effects%20Anti-Aging%20Eve%20Treatment-02/13/2015/p%3E/16-033-
156
DeLima Associates. (2015d). Pantene Pro-V Style Series Hairspray, Flexible Hold, Alcohol Free,
Aerosol. Available online at
https://www.whatsinproducts.com/tvpes/tvpe detail/1/17705/standard/p%20class=%22p 1 %22%3
EPantene%20Pro-
V%20Stvle%20Series%20Hairsprav.%20Flexible%20Hold.%20Alcohol%20Free.%20Aerosol-
02/24/2015/p%3E/16-033-061
DeLima Associates. (2016a). Pantene Pro-V Style Series Maximum Hold Hairspray. Available online at
https://www.whatsinproducts.com/tvpes/tvpe detail/1/18693/standard/p%20class=%22pl%22%3
X
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*** Proposal Draft - Do Not Cite, Quote or Release During the Review ***
EPantene%20Pro-V%20Stvle%20Series%20Maximum%20Hold%20Hairsprav-
09/16/2016/p%3E/16-033-510
DeLima Associates. (2016b). Tone Petal Soft Body Wash, Pink Peony and Rose Oil. Available online at
https://www.whatsinproducts.com/tvpes/tvpe detail/1/18506/standard/p%3ETone%20Petal%20S
oft%20Bodv%20Washspan%20class=%22sl%22%3E.%20/span%3EPink%20Peonv%20and%2
0Rose%20Oil-09/29/2016/p%3E/04-002-644
DeLima Associates. (2018). Consumer Product Information Database. Available online at
https ://www.whatsinproducts. com/
Descartes Datamyne. (2018). 1,2-hexanediol exports.
Dionisio, KL; Frame, AM; Goldsmith, M-R; Wambaugh, JF; Liddell, A; Cathey, T; Smith, D; Vail, J;
Ernstoff, AS; Fantke, P; Jolliet, O; Judson, RS. (2015). Exploring consumer exposure pathways
and patterns of use for chemicals in the environment. 2: 228-237. Curated chemical and product
categories data were retrieved from the CPCat Database, U.S. EPA, RTP, NC. World Wide Web
(URL: http://actor.epa.gov/cpcat). [Dec. 2016],
DrugBank. (2018). 1,2-Hexanediol. Available online at https://w ww.driigbank.ca/drugs/DB 14108
EWG. (2018). Skin Deep Cosmetics Database. Available online at
https://www.ewg.org/skindeep/ingredient/700001/l%2C2-HEXANEDIQL/
Expanscience Laboratoires. (2017). Musti Eau de Soin Spray. Available online
European Chemicals Agency (ECHA). (2018). DL-hexane-l,2-diol. Available online at
https://echa.europa.eu/registration-dossier/-/registered-dossier/11614
GoodGuide. (2011). Scorecard: The Pollution Information Site. Available online at
http://scorecard.goodguide.com/chemical-profiles/index.tcl
Government of Canada. (2018). Chemical Substances: Services and Information. Available online at
https://www.canada.ca/en/health-canada/services/chemical-substances.html
Kim, S; Thiessen, PA; Bolton, EE; Chen, J; Fu, G; Gindulyte, A; Han, L; He, J; He, S; Shoemaker, BA;
Wang, J; Yu, B; Zhang, J; Bryant, SH. (2016). PubChem Substance and Compound databases.
44: D1202-D1213. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702940/
Nature Republic. (2018). All in One Dual Stretch Mascara. Available online at
https://www.naturerepublicusa.com/products/all-in-one-dual-stretch-mascara
Organisation for Economic Cooperation and Development (OECD). (2018). eChemPortal: Global Portal
to Information on Chemical Substances. Available online at
https://www.echemportal.org/echemportal/index.action
XI
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*** Proposal Draft - Do Not Cite, Quote or Release During the Review ***
The International Fragrance Association (IFRA). (2016). IFRA Volume of Use Survey 2016:
Transparency List. Available online at http://admin-
ifra.alligence.com/Upload/Docs/Transparencv%201ist.pdf
U.S. Environmental Protection Agency (EPA). (2002). 1986-2002 Historical IUR Data. Available online
at Excel File
U.S. Environmental Protection Agency (EPA). (2006). 2006 IUR Public Database.
https://www.epa.gov/chemical-data-reporting/downloadable-2006-iur-public-database
U.S. Environmental Protection Agency (EPA). (2017b). Non-Confidential 2016 Chemical Data Reporting
(CDR). Available online at https://www.epa.gov/chemical-data-reporting
U.S. Environmental Protection Agency (EPA). (2018a). ChemView. Available online at
https://chemview.epa.gov/chemview
U.S. Environmental Protection Agency (EPA). (2018b). Envirofacts Multisystem Search. Available
online at https://www3.epa.gov/enviro/facts/multisvstem.html
U.S. Environmental Protection Agency (EPA). (2018c). Look up table for BR Waste Code (National
Biennial RCRA Hazardous Waste Report). Available online at
https://iaspub.epa.gov/enviro/brs codes v2.waste lookup
U.S. Environmental Protection Agency (EPA). (2018d). Safer Chemical Ingredients List. Available online
at https://www.epa.gov/saferchoice/safer-ingredients
U.S. Environmental Protection Agency (EPA). (2018e). TRI-Listed Chemicals. Available online at
https://www.epa.gov/toxics-release-inventorv-tri-program/tri-listed-chemicals
U.S. National Library of Medicine (NLM). (2018). TOXNET® (TOXicology DataNETwork). Available
online at https: //toxnet. nlm .nih. gov/
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Available online at http: //patft. uspto. gov/netacgi/nph-
Parser?Sectl=PT02&Sect2=HIT0FF&p=l&u=%2Fnetahtml%2FPT0%2Fsearch-
bool.html&r=0&f=S&l=50&TERMl=%221%2C2-
hexanediol%22&FIELDl=&col=AND&TERM2=&FIELD2=&d=PTXT
Ullmann's. (2012). Encyclopedia of Industrial Chemistry: Alcohols, Polyhyric.
Washington State Dept. of Ecology. (2018). Children's Safe Product Act Reported Data. Available online
at https://fortress.wa.gov/ecv/cspareporting/
Xerox Corporation. (2018a). Safety Data Sheet: High Fusion Ink - Black. Available online at
https://www.xerox.com/download/ehs/msds/F-60028.en-us.pdf
XII
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Xerox Corporation. (2018b). Safety Data Sheet: High Fusion Ink - Magenta. Available online at
https://www.xerox.com/download/ehs/msds/F-60030.en-us.pdf
Yogiara; Hwang, SJ; Park, S; Hwang, JK; Pan, JG. (2015). Food-grade antimicrobials potentiate the
antibacterial activity of 1,2-hexanediol. Letters in applied microbiology 60: 431-439.
XIII
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Appendix B: Hazard Characterization
Table B.1: Human Health Hazard
Acute Mammalian Toxicity
Source
(HERO
ID)
Exposure
Route
Species &
Strain (if
available)
Duration
Doses and Replicate
Number
Effect
Study Details
4729532
Oral (gavage)
Sprague-Dawley
Rats
Single dose, 14
day observation
period
Doses and
respective replicate
information:
• 2043 mg/kg:3M, No
F
• 4408 mg/kg: 5M, 5F
• 5339 mg/kg: 5M, 5F
• 6470 mg/kg: 5M, 5F
• 7338 mg/kg: 5M,
10F
• 9500 mg/kg: 10F,
no M
LDso:
• Males: Between 6166
mg/kg and 7338
mg/kg
• Females: Between
5339 mg/kg and 9500
mg/kg
Methods:
• Test substance reported as CASRN 6920-22-5
• Purity not reported
• OECD Guideline 401 study (Acute oral toxicity)
• GLP compliance not reported
5076436
Inhalation
(aerosol)
Tif: Ralf (SPF)
Rats
4 hours, 14-day
observation
period
Doses: 3.38 mg/L and
7.015 mg/L
Replicates: 10 per
sex per group
LCso > 7.015 mg/L
Methods:
• Test substance reported as CASRN 5343-92-
0
• Purity not reported
• OECD Guideline 403 study (Acute inhalation
toxicity)
• Not GLP compliant
XIV
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Table B.1:
Human Health Hazard
5076431
Dermal
Tif: Ralf (SPF)
Rats
24 hours, 14-day
observation
period
Dose: 2000 mg/kg
Replicates: 5 per sex
LDso > 2000 mg/kg
Methods:
• Test substance reported as CASRN 5343-92-
0
• Purity not reported
• OECD Guideline 402 study (Acute dermal
toxicity)
• Not GLP compliant
Repeated Dose Toxicity
Source
(HERO
ID)
Exposure
Route
Species & Strain (if
available)
Duration
Doses and Replicate
number
Effect
Study Details
4729540
Dermal
Sprague-Dawley Rats
91-93 days
Doses: 0, 350, 700,
1000 mg/kg-day
Replicates: 15 rats
per sex per group
NOAEL: 700 mg/kg-day
LOAEL: 1000 mg/kg-
day based on reduced
body weight gain in
males and females and
increased total
leukocyte count and
urinary protein in
females.
Methods:
• Test substance reported as CASRN 6920-22-5
• Purity not reported
• OECD Guideline
• GLP compliant
5353269
Oral (gavage)
Wister Rats
91-92 days
Doses: 0, 50, 250,
1000 mg/kg-day
Replicates: 10 per
sex per group
NOAEL: 1000 mg/kg-
day
Methods:
• Test substance reported as CASRN 5343-92-
0
• Purity: 99.7%
• OECD Guideline 408
• GLP compliant
5353268
Oral (gavage)
Wister Rats
28 days
Doses: 0, 50, 300,
1000 mg/kg-day
Replicates: 5 per sex
per group
NOAEL: 300 mg/kg-
day;
LOAEL: 1000 mg/kg-
day based on reduced
locomotor activity, and
changes in organ weight
Methods:
• Test substance reported as CAS RN 1117-86-
8
• Purity >98%
• OECD Guideline 407
• GLP compliant
Results:
• Kidney weights in both sexes and liver
weights in males were slightly higher than
controls
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GQ
0>
-Q
f0
1—
Human Health Hazard
Reproductive Toxicity
Source
(HERO
ID)
Exposure
Route
Species & Strain (if
available)
Duration
Doses and Replicate
Number
Effect
4729567
Dermal
Sprague-Dawley Rats
91-93 days
Doses: 0, 350, 700,
or 1000 mg/kg-day
Replicates: 15 per
sex per group
NOAEL: 1000 mg/kg-
day
Methods
• Test Substance reported as CASRN 6920-22-5
• Purity not reported
• OECD Guideline 411
• GLP compliant
Developmental Toxicity
Source
(HERO
ID)
Exposure
Route
Species & Strain (if
available)
Duration
Doses and Replicate
Number
Effect
Study Details
3038919,
4729568
Oral (gavage)
Sprague-Dawley Rat;
CD strain
Gestational
day 5-19
Doses: 0,30,100, &
300 mg/kg-day
Replicates: 24
pregnant rats per
group
NOAEL (maternal and
development): 300
mg/kg-day
Methods:
• Test substance reported as CASRN 6920-22-5
• 99% purity
• OECD Guideline 414 study
• GLP compliant
4729569
Oral (gavage)
Sprague-Dawley Rats
Gestational
day 6-19
Doses: 0,250,500,
750 mg/kg-day
Replicates: 25 per
dose
Maternal
NOAEL: 500 mg/kg-day
LOAEL: 750 mg/kg-day
based on decreased
body weight and
decreased absolute and
relative feed
consumption
Developmental
NOAEL: 750 mg/kg-day
Methods:
• Test substance reported as CASRN 6920-22-5
• Purity not reported
• OECD Guideline 414 study (Prenatal
Developmental Toxicity Study)
• GLP compliant
XVI
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CQ
Q)
-Q
TO
1—
Human Health Hazard
Cancer
Source
Effect
Study Details
Oncologic
8.0
Oncologic currently has no assessment
criteria regarding diols.
Results:
Structure could not be evaluated by Oncologic.
ISS
v2.435
Negative (Estimated)
1,2-Hexanediol is an aliphatic diol
which does not contain any structural
features indicative of electrophilic
potential. It is rapidly metabolized
through oxidation and glucuronidation.
Methods:
Carcinogenicity alerts (genotoxic and non-genotoxic) by ISS profiler as available within the OECD Toolbox v4.3
Results:
No alerts were identified for the parent structure (an aldehyde alert was identified for the initial aldehyde metabolite that
is formed in the first oxidation transformation that occurs during the metabolism of 1,2-hexanediol). This aldehyde will be
rapidly transformed to the corresponding carboxylic acid.
VEGA
1.1.436
1,2-Hexanediol was processed through
all 4 models. IRFMN/ISSCAN-GX 1.0.0
predicted it to be non-carcinogenic with
moderate reliability.37
Methods:
VEGA 1.1.4 contains 4 models for carcinogenicity-CAESAR 2.1.9, ISS 1.0.2, IRFMN/Antares 1.0.0, IRFMN/ISSCAN-
GX 1.0.0
Results:
• CAESAR 2.1.9: Low reliability (1,2-hexanediol lies outside of the applicability domain (AD) of the model)
• ISS 1.0.2: Low reliability (1,2-hexanediol lies outside of the AD)
• IRFMN/Antares 1.0.0: Low reliability (1,2-hexanediol lies outside of the AD)
• IRFMN/ISSCAN-GX 1.0.0: Moderate reliability (1,2-hexanediol could be outside of the AD)
Genotoxicity
Source
(HERO
ID)
Test Type &
Endpoint
Species & Strain (if
available)
Metabolic
Activation
Doses and Controls
Results
Study Details
4729541
Gene
mutation (In
vitro)
E. coli WP2 uvr A
pKM 101
With and
without
Doses: 0, 25, 75, 200,
600, 1800, and 5000
pg/plate
Negative both with and
without metabolic
activation
Methods:
• Test substance reported as CASRN 6920-22-
5
• Purity not reported
• OECD Guideline 471 study (Bacterial
Mutation Assay)
• GLP compliant
35 Carcinogenicity alerts by ISS profiler comprises 55 structural alerts for genotoxic and non-genotoxic carcinogenicity. Hie alerts have been compiled upon existing knowledge of
the mechanism of action of carcinogenic chemicals that have been published elsewhere (Benigni andBossa (2011) Chem Rev 111: 2507-2536 andBenigni R et al. (2013) Chew
Rev. 113:2940-2957).
XVII
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GQ
0>
-Q
ro
1—
Human Health Hazard
4729541
Gene
mutation (In
vitro)
Salmonella
typhimurium TA98,
TA100, TA1535,
TA1537, TA1538
With and
without
Doses: 0, 25, 75, 200,
600, 1800, and 5000
pg/plate
Negative both with and
without metabolic
activation
Methods:
• Test substance reported as CASRN 6920-22-
5
• Purity not reported
• GLP compliance not reported
Results:
• Cytotoxicity observed at 5000 pg/plate.
4729566
Gene
mutation (In
vitro)
Chinese hamster lung
fibroblasts V79
With and
without
Doses: 36.94,73.88,
147.75, 295.5, 591
and 1182 pg/mL
Negative both with and
without metabolic
activation
Methods:
• Test substance reported as CASRN 6920-22-5
• Purity: 99.6%
• OECD Guideline 476 study (In vitro mammalian
cell gene mutation test)
• GLP compliant
Results:
• No cytotoxicity
4729542
Chromosomal
aberrations
(In vitro)
Chinese hamster
ovary cell
With and
without
Doses: 148, 295, 590,
and 1180 ug/mL
Negative both with and
without metabolic
activation
Methods:
• Test substance reported as CASRN 6920-22-
5
• Purity not reported
30 VEGA 1.1.4 contains 4 different models to facilitate an;'w silico assessment of carcinogenicity potential. Hie models are summarized in Golbamaki et al. (2016) J Environ Sci
and Health Part C http://dx.doi.org/10.1080/10590501.2Q16.1166879 as well as in documentation that is downloadable from within the VEGA tool itself
(https://www. vegahub. eu/).
• CAESAR 2.1.9 is a classification model for carcinogenicity based on a neural network.
• ISS 1.0.2 is a classification model based on the ISS ruleset (as described above for the OECD Toolbox).
• IREMN/Antares 1.0.0 and IREMN/ISSCAN-GX 1.0.0 are classification models based on a set of rules built with SARpy software (part of the same suite of VEGA tools
https://www.vegahub.eu/) extracted from the Antares and ISSCAN-CGX datasets respectively.
37 Each model is characterized by an applicability domain (AD) that depends on at least 5 components:
• Similar substances with known experimental values within the underlying training set
• Accuracy of prediction for similar substances
• Concordance for similar substances,
• Fragments similarity check on the basis of atom centered fragments,
• Model descriptors range check.
A global AD index takes into account the other 5 components to provide an overall reliability score - low, moderate or high. EPA has not included low-reliability model results.
XVIII
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GQ
0>
-Q
f0
1—
Human Health Hazard
• OECD Guideline 473 study (In vitro mammalian
chromosome aberration test)
• GLP compliant
Results:
• No cytotoxicity
Neurotoxicity
Source
Exposure
Species
Duration
Doses and
Effect
Study Details
(HERO
Route
& strain
replicate
ID)
(if
available)
number
5353269
Oral (gavage)
Wister
91-92
Doses: 0,
NOAEL: 1000 mg/kg-
Methods:
Rats
days
50, 250,
day
• Test substance reported as CASRN 5343-92-0
and 1000
• Purity: 99.7%
mg/kg-day
Replicates:
• OECD Guideline 408
• GLP compliant
10 per sex
per group
5353268
Oral (gavage)
Wister
28 days
Doses: 0,
NOAEL: 300 mg/kg-
Methods:
Rats
50, 300,
and 1000
day
LOAEL: 1000 mg/kg-
• Test substance reported as CAS RN 1117-86-8
• Purity >98%
mg/kg-day
day based on reduced
• OECD Guideline 407
Replicates:
5 per sex
per group
locomotor activity
• GLP compliant
Results:
• Slight reduction in locomotor activity in 1000 mg/kg group
• No effects on histopathology of the brain, spinal cord or sciatic nerve
Sensitization
Source
(HERO
ID)
Exposure
Route
Species & Strain (if
available)
Duration
Doses and Replicate
Number
Effect
Study Details
4729535
Skin
Female CBA mice
3
Dose: 0.25 pi at
Negative
Methods:
consecutive
concentrations of 10,
• Test substance reported as CASRN 6920-22-5
days
50, and 100%
Replicates: 5 animals
per dose
• Purity not reported
• OECD Guideline 429 study (LLNA), OECD
Guideline 406 principles
• GLP compliant
Results:
XIX
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GQ
0>
-Q
f0
1—
Human Health Hazard
• Stimulation index < 3
Irritation
Source
(HERO
ID)
Exposure
Route
Species & Strain (if
available)
Duration
Doses
Effect
Study Details
4729533
Skin
Russian Albino rabbit
4 hours
Dose: 0.5 mL
Replicates: 3 per sex
Negative
Methods:
• Test substance reported as CASRN 6920-22-5
• Purity >97%
• OECD Guideline 404 study (Acute Dermal
Irritation/Corrosion)
• GLP compliance not reported
4674233
Skin
Human
24 hours
Dose: 20 pL
Replicates: 38
Females, 1 Male
Negative
Methods:
• Test substance reported as CASRN 6920-22-5
• Purity: 98%
• Dose administered on filter paper to the skin
• Patches evaluated at 30 minutes and 24 hours
after patch removal
• Erythema scored 0-4
Results:
• Objective irritation score was <0.2/4
4729534
Eye
New Zealand white
rabbit
24 hours
Dose: 10 pL
Replicates: 1 male, 2
females
Positive
Methods:
• Test substance reported as CASRN 6920-22-5
• Purity not reported
• Standard method for Evaluation of Eye Irritation
in Albino Rabbits, E 1055-85, ASTM, OECD
Guideline 405
• GLP compliant
Results:
• Cornea opacity: scored 2/4, but fully reversible by
14 day
• Iris: scored V2 at 1,24, 48hrs, and 0.67/2 at 72
hours, but fully reversible by 7 days
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Do Not Cite, Quote or
Release During the Review ***
DQ
Q)
-Q
TO
1—
Human Health Hazard
• Conjunctivae: scored 2/3 at 1, 24 and 48hr and
1.3334 at 72 hours, but fully reversible within 10
day
• Chemosis: 2/4 at 1,24, and 48 hours, 1.33/4 at
72 hours, but fully reversible within 10 day
XXI
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*** Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table B.2: Environmental Hazard
Aquatic Toxicity: Experimental
Source (HERO ID)
Species & strain
(if available)
Duration
Doses and
replicate number
Effect
Study Details
5076435
Scenedesmus
subspicatus
72 hours
Doses: 1500,
3000, 6000,
12000, 24000, and
48000 mg/L
(nominal
concentrations)
ECso: 9334.69
mg/L
Methods:
• Test substance reported as CASRN 5343-92-0
• Purity not reported
• Test method: DIN 38412 Part 9
• Not GLP compliant
5076430
Scenedesmus
subspicatus
72 hours
Doses: 0, 31.25,
62.5, 125, 250,
and 500 mg/L
(nominal
concentrations)
ECso > 500
mg/L
Methods:
• Test substance reported as CASRN 584-03-2.
• Purity not reported
• Test method: DIN 38412 part 9
• Not GLP compliant
5076433
Pseudokirchneriella
subcapitata
72 hours
Doses: 2, 5, 10,
20, 50,100, 2and
00 mg/L (nominal
concentrations)
EC50: 35 mg/L
Methods:
• Test substance reported as CASRN 1117-86-6
• Purity not reported
• OECD Guideline 201 study (Freshwater algae and
Cyanobacteria, Growth Inhibition Test)
• GLP compliant.
3605033
Daphnia magna
48 hours
Doses: 0, 6.25,
12.5, 25,50, and
100 mg/L (nominal
concentrations)
ECso >100
mg/L
Methods:
• Test substance reported as CASRN 6920-22-5
• Purity: 98%
• OECD Guideline 202 (Acute immobilization test)
• GLP compliance not reported
XXII
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4729531
Daphnia magna
48 hours
Dose: 110 mg/L
Replicates: 4
replicates
ECso >110
mg/L
Methods:
• Test substance reported as CASRN 6920-22-5
• Purity not reported
• OECD Guideline 202 study (Acute immobilization test)
• GLP complaint
3605033
Daphnia magna
21 days
Doses: 0, 0.1, 0.3,
1.0,3.2, and 10.0
mg/L (nominal
concentrations); 0,
0.09, 0.29, 0.89,
2.96, and 9.05
mg/L (measured
concentrations)
NOEC: 10 mg/L
Methods:
• Test substance reported as CASRN 6920-22-5
• Purity: 98%
• OECD Guideline 211 study (Daphnia magna Reproduction test)
• GLP compliance not specified
5076429
Danio rem
96 hours
Doses: 0, 48,100,
183, 449, 1096
mg/L (measured
concentrations)
LCso > 1096
mg/L
Methods:
• Test substance reported as CASRN 5343-92-0
• Purity: 99%
• OECD Guideline 203 study (Fish, Acute toxicity test)
• GLP compliant
Aquatic Toxicity: Estimated
Model
Chemical Class
Species
Predicted Effect
Level
Notes
ECOSAR v2.0
Neutral organics
Green
algae
96-hour ECso: 330
mg/L
Physical properties used for estimation: WS 26171 mg/L (est), log K0w 0.69 (est);
SMILES: OCC(0)CCCC
ECOSAR v2.0
Neutral organics
Fish
96-hour LC50:1450
mg/L
Physical properties used for estimation: WS 26171 mg/L (est), log Kow 0.69 (est);
SMILES: OCC(0)CCCC
ECOSAR v2.0
Neutral organics
Fish
ChV: 120 mg/L
Physical properties used for estimation: WS 26171 mg/L (est), log K0w 0.69 (est);
SMILES: OCC(0)CCCC
ECSAR v2.0
Neutral organics
green
algae
ChV: 66 mg/L
Physical properties used for estimation: WS 26171 mg/L (est), log K0w 0.69 (est);
SMILES: OCC(0)CCCC
XXIII
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Table B.3: Fate
Environmental Fate: Experimental
Source
(HERO
ID)
Endpoint
Duration
Doses and
number of
replicates
Results
Study Details
4729530
Environmental
persistence
28 days
• Sludge:
Activated,
non-adapted
sludge (2500
mg solids/L)
• Chemical: 10
mg/L (based
on TOC)
• Two test
replicates
• Replicate 1: 82.1%
degradation in 28
days
• Replicate 2: 83.7%
degradation in 28
days
• Test substance
reported to be
readily
biodegradable
Methods:
• Test substance reported as CASRN 6920-22-5
• Purity not reported
• OECD Guideline 301B (CO2 Evolution)
• GLP compliant
5076434
Anaerobic
biodegradation
60 days
• Test
substance
dose: 77.4
mg/L
• Replicates: 8
• Ultimately
anaerobically
biodegradable
Methods:
• Test substance reported as CASRN 1117-86-8
• Purity not reported
• OECD Guideline 311 (Anaerobic Biodegradability of Organic Compounds in
Digested Sludge)
• GLP compliant
• Sludge: Anaerobic digested sludge from a WWTP
Replicate average results:
• 0%/ 0 days; 5.4%/ 7 days; 11.4%/14 days; 16.3%/ 21 days; 41.7%/ 28 days;
59.0%/ 36 days; 63.2%/ 42 days; 65.2%/ 49 days; 67.3%/ 56 days
Experimental Fate: Modelled
Model
Data Type
Endpoint
Predicted
Endpoint
Notes
EPISuite
v4.11
Estimated
BCF
3.2
Experimental input value: log IW 0.58
EPISuite
v4.11
Estimated
BAF
1.1
Experimental input value: log IW 0.58
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B.1 References
ECHA (European Chemicals Agency). (1981a). DL-hexane-l,2-diol: Acute Toxicity: oral.
https://echa.europa.eu/registration-dossier/-/registered-dossier/l 1614/7/3/2
ECHA (European Chemicals Agency). (1981b). DL-hexane-l,2-diol: Skin irritation / corrosion.
https://echa.europa.eu/registration-dossier/-/registered-dossier/l 1614/7/4/2
ECHA (European Chemicals Agency). (1982a). Pentane-l,2-diol: Acute toxicity: dermal.
https://www.echa.europa.eu/web/guest/registration-dossier/-/registered-dossier/2101/7/3/4
ECHA (European Chemicals Agency). (1982b). Pentane-l,2-diol: Acute toxicity: inhalation.
https://www.echa.europa.eu/web/guest/registration-dossier/-/registered-dossier/2101/7/3/3
ECHA (European Chemicals Agency). (1990). Pentane-l,2-diol: Toxicity to aquatic algae and
cyanobacteria: 001 Key | Experimental result, https://www.echa.europa.eu/web/guest/registration-
dossier/-/registered-dossier/2101/6/2/6/?documentUUID=06b35b66-19d5-4db6-b8d4-
57a013cd5430
ECHA (European Chemicals Agency). (1991). Butane-1,2-diol: Toxicity to aquatic algae and
cyanobacteria. https://www.echa.europa.eu/web/guest/registration-dossier/-/registered-
dossier/23 064/6/2/6
ECHA (European Chemicals Agency). (1994). Pentane-1,2-diol: Short-term toxicity to fish: 001 Key |
Experimental result. https://www.echa.europa.eu/web/guest/registration-dossier/-/registered-
dossier/210 l/6/2/2/?documentUUID=4 lc8fe42-e404-4129-bc0f-8efl 6d8f96db
ECHA (European Chemicals Agency). (1997). DL-hexane-1,2-diol: Biodegradation in water: screening
tests. https://echa.europa.eu/registration-dossier/-/registered-dossier/l 1614/5/3/2
ECHA (European Chemicals Agency). (1998a). DL-hexane-1,2-diol: Eye irritation.
https://echa.europa.eu/registration-dossier/-/registered-dossier/l 1614/7/4/3
ECHA (European Chemicals Agency). (1998b). DL-hexane-1,2-diol: Genetic toxicity: in vitro: 001 Key |
Experimental result. https://echa.europa.eu/registration-dossier/-/registered-dossier/l 1614/7/7/2
ECHA (European Chemicals Agency). (2000). DL-hexane-1,2-diol: Genetic toxicity: in vitro: 002 Key |
Experimental result. https://echa.europa.eu/registration-dossier/-/registered-
dossier/11614/7/7/2/?documentUUID=7eafb797-7f09-43el-9355-54c7e564786c
ECHA (European Chemicals Agency). (2002a). DL-hexane-1,2-diol: Repeated dose toxicity: dermal.
https://echa.europa.eu/registration-dossier/-/registered-dossier/l 1614/7/6/4
ECHA (European Chemicals Agency). (2002b). DL-hexane-1,2-diol: Toxicity to reproduction: 002
Weight of evidence | Experimental result. https://echa.europa.eu/registration-dossier/-/registered-
dossier/11614/7/9/2/?documentUUID=34a636c8-6482-4b8c-a7f9-ea9777c87a69
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ECHA (European Chemicals Agency). (2003a). Developmental toxicity / teratogenicity: 002 Supporting |
Experimental result, https://echa.curopa.cu/rcgi stration-dossicr/-/rcgistered-
dossier/1 1614/7/9/3/'.)documcntUUID=S3bO labS-c4c5-4S le-bSf5-0450f9eS5303
ECHA (European Chemicals Agency). (2003b). DL-hexane-l,2-diol: Skin sensitisation.
https://echa.europa.eu/registration-dossier/-/registered-dossier/l 1614/7/5/2
ECHA (European Chemicals Agency). (2004). Octane-1,2-diol: Repeated dose toxicity: oral: 002
Supporting | Experimental result. https://ccha.curopa.cu/dc/rcgistration-dossicr/-/rcgistcrcd-
dossier/14120/7/6/2/?documentUUID=5ff6ec0f-1 d5 9-45 7c-9dcd-4749c25e223 f
ECHA (European Chemicals Agency). (2006). Developmental toxicity / teratogenicity: 001 Key |
Experimental result. https://echa.europa.eu/registration-dossier/-/registered-dossier/l 1614/7/9/3
ECHA (European Chemicals Agency). (2007). Octane-1,2-diol: Toxicity to aquatic algae and
cyanobacteria: 001 Key | Experimental result, https://www.echa.europa.eu/web/guest/registration-
dossier/-/registered-dossier/14120/6/2/6/?documentUUID=5f34041f-a014-4052-af60-
c8c3cbe045fc
ECHA (European Chemicals Agency). (2008). Octane-1,2-diol: Biodegradation in water: screening tests:
003 Key | Experimental result, https://www.echa.europa.eu/web/guest/registration-dossier/-
/registered-dossier/14120/5/3/2/?documentUUID=98dc544b-a3c2-4737-898e-219897cb02a8
ECHA (European Chemicals Agency). (2012). DL-hexane-1,2-diol: Short-term toxicity to aquatic
invertebrates. https://echa.europa.eu/registration-dossier/-/registered-dossier/l 1614/6/2/4
ECHA (European Chemicals Agency). (2013). DL-hexane-1,2-diol: Genetic toxicity: in vitro: 003 Key |
Experimental result. https://echa.europa.eu/registration-dossier/-/registered-
dossier/11614/7/7/2/?documentUUID=509e099e-3all-40el-95e9-3b61fa396ac5
ECHA (European Chemicals Agency). (2013). Pentane-1,2-diol: Repeated dose toxicity: oral: 002 Key |
Experimental result. https://echa.europa.eu/de/registration-dossier/-/registered-
dossier/2101/7/6/2/?documentUUID=6bf051c4-ec56-42f6-99ee-4523307db005
.Johnson. W. Jr; Bergfeld. WF; Belsito. DV: Hill. RA; Klaassen. CD: Liebler. D; Marks. JG. Jr; Shank.
RC: Slaga. TJ: Snyder. PW: Andersen. FA. (2012). Safety Assessment of 1,2-Glycols as Used in
Cosmetics [Review]. Int J Toxicol 31: 147S-168S. http://dx.doi.Org/10.l 177/1091581812460409
Lee. E; An. S: Cho. SA; Yun. Y; Han. J: Hwang. YK; Kim. HK; Lee. TR. (2011). The influence of alkane
chain length on the skin irritation potential of 1,2-alkanediols. Int J Cosmet Sci 33: 421-425.
http://dx.doi.org/10.1111/i. 1468-2494.2011,00646.x
Lee. J: Park. N: Kho. Y; Lee. K; Ji. K. (2017). Phototoxicity and chronic toxicity of methyl paraben and
1,2-hexanediol in Daphnia magna. Ecotoxicology 26: 81-89. http://dx.doi.org/10.1007/slQ646-
016-1743-6
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Appendix C: Literature Search Outcomes
C.1 Literature Search and Review
This section briefly describes the literature search and review process, search terms, and search outcomes
for the hazard and fate screening of 1,2-hexanediol. Search outcomes and reference details are provided
on the candidate's HERO® project page.
EPA created a fit-for-purpose process to transparently document the literature search and review39 of
available hazard and fate information for low-priority substance (LPS) candidates. References from peer-
reviewed primary sources, grey sources,4" and other sources were identified, screened at the title/abstract
and full-text level, and evaluated for data quality based on discipline-specific criteria. An overview of the
literature search and review process is illustrated in Figure C1.
Figure C.l: Overview of the Literature Search and Review Process
CkO
References available at
title/abstract screening
References available at data quality evaluation
References included in LPS screening reviews
References available at full text screening
References excluded at
full text screening
References excluded at
data quality evaluation
References excluded at
title/abstract screening
References available
from grey literature
and other sources
References available
from primary peer-
reviewed sources
C.1.1 Search for Analog Data
To supplement the information on the candidate chemical, 1,2-hexanediol, the following analogs were
identified: 1,2-butanediol (CASRN 584-03-2), pentylene glycol (CASRN 5343-92-0), and 1,2-octanediol
(CASRN 1II17-86-8). For more details and justification on analogs, see section 6.1.1. Analogs were used
to fill data gaps on endpoints for which 1,2-hexanediol lacked quality data, such neurotoxicity, or to add
38 Hie HERO low-priority substance candidate project pages are accessible to the public at https://hero. epa. gov/hero/.
® Discussed in the document "Approach Document for Screening Hazard Information for Low-Priority Substances Under
TSCA", also released at proposal.
40 Grey literature and additional sources are the broad category of studies not found in standard, peer-reviewed literature database
searches. This includes U.S. and international government agency websites, non-government organization (NGO) websites, and
data sources that are difficult to find, or are not included, in the peer-reviewed databases, such as white papers, conference
proceedings, technical reports, reference books, dissertations, and information on various stakeholder websites.
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to the weight of the scientific evidence. EPA collected reasonably available information for these
endpoints by searching specific grey literature and other secondary sources, listed on Table C.l. If
information related to the identified analogs were available in these sources, the references were screened
and evaluated using the same process as references on 1,2-hexanediol described above.39
Table C.1: Sources Used for Analog Search
Resource
URL
ATSDR
http://www.atsdr.cdc.gov/toxprofiies/index.asp
ChemID (EPA - HPVIS via
ChemID)
http://chem.sis.nlm.nih.gov/chemidplus/
CIR
http://www.cir-safety.org/ingredients
ECHA
http://echa.europa.eu/web/guest/information-on-chemicais/registered-substances
ECOTOX
https://cfpub.epa.gov/ecotox/quick_query.htm
EPA - ChemView (incl. TSCATS,
RBP/HC, and HPV/HPVIS)
https://chemview.epa.gov/chemview
European Food Safety Authority
(EFSA)
http://www.efsa.europa.eu/
FDA
https://www.fda.gov/defauit.htm
HERA
http://www.heraproject.com/RiskAssessment.cfm
NICNAS
http://www.nicnas.gov.au/
NITE (J-CHECK)
http://www.safe.nite.go.jp/jchec k/search.action?request_locale=en
NTP
https://ntpsearch.niehs.nih.gov/home
OECD/SIDS
https://hpvchemicals.oecd.org/UI/Search.aspx;
http://webnet.oecd.org/hpv/ui/SponsoredChemicais.aspx
C.1.2 Search Terms and Results
EPA began the literature review process for the hazard screening of 1,2-hexanediol by developing search
terms. To gather publicly available information, specific search terms were applied for each discipline and
across databases and grey literature sources. Table C.2 lists the search terms used in the database search
of peer -reviewed literature for 1,2-hexanediol. For grey literature and other secondary sources, Table C.3
lists the search terms used for 1,2-hexanediol and analogs.
Table C.2: Search Terms Used in Peer-Reviewed Databases
Discipline
Database
Search terms41
Human Health
PubMed
6920-22-5[rn] OR "1,2-Dihydroxyhexane"[tw] OR "1,2-Hexanedioi"[tw] OR "5,6-
Dihydroxyhexane"[tw] OR "DL-1,2-Hexanedioi"[tw] OR "DL-Hexane-1,2-diol"[tw]
OR" 1,2-Hexyleneglycol"[tw] OR "DL-Hexan-1,2-diol"[tw] OR "DL-hexano-1,2-
dioi"[tw]
Toxline
(6920-22-5 [rn] OR "1,2-Hexyleneglycol" OR "DL-Hexan-1,2-dioi" OR "DL-
hexano-1,2-dioi" OR "1 2-dihydroxyhexane" OR "1 2-hexanedioi" OR "5 6-
dihydroxyhexane" OR "dl-1 2-hexanedioi" OR "dl-hexane-1 2-dioi") AND (
ANEUPL [org] OR BIOSIS [org] OR CIS [org] OR DART [org] OR EMIC [org] OR
41 Additional language or syntax such as [tw], [rn], [org], and [nm] were added to search terms. These are unique to individual
databases and must be applied to search terms so that the query can run properly.
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Table C.2: Search Terms Used in Peer-Reviewed Databases
EPIDEM [org] OR HEEP [org] OR HMTC [org] OR IPA [org] OR RISKLINE [org]
OR MTGABS [org] OR NIOSH [org] OR NTIS [org] OR PESTAB [org] OR PPBIB
[org]) AND NOT PubMed [org] AND NOT pubdart [org]
TSCATS1
6920-22-5[rn]
WOS
TS=("1,2-Hexyleneglycol" OR "DL-Hexan-1,2-diol" OR "DL-hexano-1,2-diol" OR
"1,2-Dihydroxyhexane" OR "1,2-Hexanediol" OR "5,6-Dihydroxyhexane" OR "DL-
1,2-Hexanediol" OR "DL-Hexane-1,2-diol")
Environmental
Hazard
WOS
Same as human health strategy synonyms only
Toxline
Same as human health strategy synonyms only
TSCATS1
Same as human health strategy CASRN only
Proquest
"6920-22-5" OR "1,2-dihydroxyhexane" OR "1,2-hexanediol" OR "5,6-
dihydroxyhexane" OR "dl-1,2-hexanediol" OR "dl-hexane-1,2-diol" OR "1,2-
Hexyleneglycol" OR "DL-Hexan-1,2-diol" OR "DL-hexano-1,2-diol"
Fate
WOS
Same as human health strategy synonyms only
Table C.3: Search Terms Used in Grey Literature and Additional Sources
Chemical
Search terms
1,2-Hexanediol
Searched as a string or individually depending on resource: "6920-22-5" OR "1,2-dihydroxyhexane" OR "1,2-
hexanediol" OR "5,6-dihydroxyhexane" OR "dl-1,2-hexanediol" OR "dl-hexane-1,2-diol"
Analogs
searched
pentylene glycol (5343-92-0); 1,2-butanediol (584-03-2); 1,2-octanediol (1117-86-8)
After the search terms were applied, more than 150 references were returned by all search efforts across
peer-reviewed databases and grey literature sources. The total number of references include database
results, additional strategies, and analog searches. All references from the search efforts were screened
and evaluated through the LPS literature search and review process.39 Of these, 18 references were
included for data evaluation and used to support the designation of 1,2-hexanediol as LPS. The included
hazard and fate references are listed in the bibliography of Appendix B.
C.2 Excluded Studies and Rationale
This section lists the excluded references, by HERO ID, found to be off-topic or unacceptable for use in
the hazard screening of 1,2-hexanediol. The excluded references are organized by discipline (human
health hazard, environmental hazard, and fate), presented along with a rationale based on exclusion
criteria. The criteria39 was used to determine off-topic references in the title/abstract or full-text screening
and to determine unacceptable references in the data quality evaluation are provided in the form of
questions.
C.2.1 Human Health Hazard Excluded References
For the screening review of 1,2-hexanediol, EPA excluded a total of 108 references when assessing
human health hazard. Off-topic references (e.g., studies that did not contain information relevant to
human health) were excluded at either title/abstract screening (see Table C.4), or full-text screening (see
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Table C.5). Unacceptable references (e.g., studies that did not meet data quality metrics) were excluded at
full-text screening (see Tables C.6 and C.7). Off-topic and unacceptable references are displayed next to
the corresponding exclusion criteria.
Table C.5: Screening Questions and Off-Topic References Excluded at Full-Text Screening for Human Health Hazard
Question
Off-topic if answer is:
References excluded (HERO ID)
Does the reference contain
No
N/A.
information pertaining to a low-
priority substance candidate?
What type of source is this
Review article or book chapter that
N/A.
reference?
contains only citations to primary
literature sources
What kind of evidence does this
In silico studies that DO NOT
N/A.
reference primarily contain?
contain experimental verification
The following question apply to HUMAN evidence only
Does the reference report an
No
N/A.
exposure route that is or is
presumed to be by an inhalation,
oral, or dermal route?
Does the reference report both test
No
N/A.
substance exposure(s) AND related
health outcome(s)?
If the reference reports an exposure
No
4674226
to a chemical mixture, are
measures of the test substance or
related metabolite(s) reported
independently of other chemicals?
Note: If the paper does not pertain
to mixtures, choose "Not
Applicable".
The following question apply to ANIMAL evidence only
Does the reference report an
No
N/A.
exposure route that is by inhalation,
oral, or dermal route?
Does the reference report both test
No
N/A.
substance-related exposure(s) AND
related health outcome(s)?
Does the reference report the
No
N/A.
duration of exposure?
Does the reference report an
No
N/A.
exposure to the test substance only
(i.e. no mixtures with the exception
of aqueous solutions and
reasonable impurities and
byproducts)?
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Table C.5: Screening Questions and Off-Topic References Excluded at Full-Text Screening for Human Health Hazard
Does the paper report a negative
control that is a vehicle control or
no treatment control?
No42
N/A.
The following questions apply to MECHANISTIC/ALTERNATIVE TEST METHODS evidence only
Does the reference report a
negative control that is a vehicle
control or no treatment control?
No
3037835
4674236
4684041
4684084
Does the reference report an
exposure to the test substance only
(i.e. no mixtures with the exception
of aqueous solutions and
reasonable impurities and
byproducts)?
No
3037835
4674227
4674234
4674236
4683790
4684041
4684084
For genotoxicity studies only: Does
the study use a positive control?
No
N/A.
Table C.4: Off-Topic References Excluded at Title/Abstract Screening for Human Health Hazard
Reference excluded (HERO ID) because the reference did NOT contain information needs43 relevant to human health
hazard
1205485
3039332
4421783
4674224
4674238
4683976
4683986
4684012
4684044
4684079
1612136
3407162
4422636
4674225
4674239
4683977
4683987
4684016
4684045
4684080
1614234
4275027
4428186
4674228
4674889
4683979
4683988
4684019
4684046
4684083
1621555
4399677
4429336
4674229
4683772
4683980
4683993
4684021
4684047
4684086
1962870
4409714
4432999
4674230
4683774
4683981
4684004
4684038
4684048
2044953
4410096
4670341
4674231
4683778
4683982
4684005
4684039
4684049
2046206
4415908
4674220
4674232
4683782
4683983
4684006
4684040
4684061
2960791
4419365
4674222
4674235
4683785
4683984
4684008
4684042
4684065
3037506
4421781
4674223
4674237
4683975
4683985
4684011
4684043
4684067
Reference excluded (HERO ID) because the reference primarily contained in silico data
N/A.
Table C.6: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Human Health
Hazard - Animal
Data Quality Metric
Unacceptable if:
References excluded (HERO ID)
Metric 1:
Test substance identity
• The test substance identity
cannot be determined from
the information provided
(e.g., nomenclature was
unclear and CASRN or
structure were not reported).
OR
• For mixtures, the components
and ratios were not characterized or
N/A.
42 Except for acute mammalian toxicity and skin and eye irritation studies, where the me of a negative control may not be
required (e.g., OECD 403 Acute Inhalation Toxicity Guidelines).
43 Hie information needs for human health hazard includes a list of study characteristics pertaining to the study population/test
organism, types of exposures and routes, me of controls, type and level of effects. A complete list of the information needs is
provided in Table A1 of the "Approach Document for Screening Hazard Information for Low-Priority Substances Under TSCA".
These information needs helped guide the development of questions for title/abstract and full-text screening.
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Table C.6: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Human Health
Hazard - Animal
Data Quality Metric
Unacceptable if:
References excluded (HERO ID)
did not include information that could
result in a reasonable approximation
of components.
Metric 2:
Negative and vehicle controls
A concurrent negative control group
was not included or reported.
OR
The reported negative control group
was not appropriate (e.g.,
age/weight of animals differed
between control and treated
groups).
N/A.
Metric 3:
Positive controls
When applicable, an appropriate
concurrent positive control (i.e.,
inducing a positive response) was
not used.
N/A.
Metric 4:
Reporting of doses/concentrations
Doses/concentrations were not
reported and could not be calculated
using default or reported estimates
of body weight and diet/water intake
(e.g., default intake values are not
available for pregnant animals).
N/A.
Metric 5:
Exposure duration
The duration of exposure was not
reported.
OR
The reported exposure duration was
not suited to the study type and/or
outcome(s) of interest (e.g., <28
days for repeat dose).
N/A.
Metric 6:
Test animal characteristics
The test animal species was not
reported.
OR
The test animal (species, strain, sex,
life-stage, source) was not
appropriate for the evaluation of the
specific outcome(s) of interest (e.g.,
genetically modified animals, strain
was uniquely susceptible or resistant
to one or more outcome of interest).
N/A.
Metric 7:
Number of animals per group
The number of animals per study
group was not reported.
OR
The number of animals per study
group was insufficient to
characterize toxicological effects
(e.g., 1-2 animals in each group).
N/A.
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Table C.6: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Human Health
Hazard - Animal
Data Quality Metric
Unacceptable if:
References excluded (HERO ID)
Metric 8:
Outcome assessment methodology
The outcome assessment
methodology was not sensitive for
the outcome(s) of interest (e.g.,
evaluation of endpoints outside the
critical window of development, a
systemic toxicity study that
evaluated only grossly observable
endpoints, such as clinical signs and
mortality, etc.).
N/A.
Metric 9:
Reporting of data
Data presentation was
inadequate (e.g., the report
does not differentiate among
findings in multiple exposure
groups).
OR
Major inconsistencies were present
in reporting of results.
N/A.
Table C.7: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Human Health
Hazard - In Vitro
Data Quality Metric
Unacceptable if:
References excluded (HERO ID)
Metric 1:
Test substance identity
The test substance identity or
description cannot be determined
from the information provided (e.g.,
nomenclature was unclear and
CASRN or structure were not
reported).
OR
For mixtures, the components and
ratios were not characterized or did
not include information that could
result in a reasonable approximation
of components.
N/A.
Metric 2:
Negative controls
A concurrent negative control group
was not included or reported.
OR
The reported negative control
group was not appropriate (e.g.,
different cell lines used for
controls and test substance
exposure).
N/A.
Metric 3:
Positive controls
A concurrent positive control or
proficiency group was not used.
N/A.
Metric 4:
Assay type
The assay type was not reported.
OR
The assay type was not appropriate
for the study type or outcome of
interest (e.g., in vitro skin corrosion
protocol used for in vitro skin
irritation assay).
N/A.
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Table C.7: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Human Health
Hazard - In Vitro
Data Quality Metric
Unacceptable if:
References excluded (HERO ID)
Metric 5:
Reporting of concentration
The exposure doses/concentrations
or amounts of test substance were
not reported.
N/A.
Metric 6:
Exposure duration
No information on exposure
duration(s) was reported.
OR
The exposure duration was not
appropriate for the study type and/or
outcome of interest (e.g., 24 hours
exposure for bacterial reverse
mutation test).
4674221
Metric 7:
Metabolic activation
No information on the
characterization and use of a
metabolic activation system was
reported.
OR
The exposure duration was
not appropriate for the study
type and/or outcome of
interest (e.g., 24 hours
exposure for bacterial reverse
mutation test).
N/A.
Metric 8:
Test model
The test model was not reported
OR
The test model was not routinely
used for evaluation of the specific
outcome of interest.
N/A.
Metric 9:
Outcome assessment methodology
The outcome assessment
methodology was not reported.
OR
The assessment methodology was
not appropriate for the outcome(s) of
interest (e.g., cells were evaluated
for chromosomal aberrations
immediately after exposure to the
test substance instead of after post-
exposure incubation period).
N/A.
C.2.2 Environmental Hazard
For the screening review of LPS candidate 1,2-hexanediol, EPA excluded a total of 109 references when
assessing environmental hazard. Off-topic environmental hazard references excluded at title/abstract
screening are listed in Table C.8, and those excluded at full-text screening are listed in Table C.9.
References in Table C.10 represent unacceptable studies based on specific data quality metrics for
environmental hazard. Off-topic and unacceptable references are displayed next to the corresponding
exclusion criteria.
Table C.8: Off-Topic References Excluded at Title/Abstract Screening for Environmental Hazard
XXXIV
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Reference excluded (HERO ID) because the reference did NOT contain information needs44 relevant to environmental
hazard
1205485
3039332
4422636
4674231
4683778
4683798
4683975
4683987
4684021
4684049
1612136
3407162
4428186
4674232
4683779
4683799
4683976
4683988
4684038
4684061
1614234
4072237
4429336
4674235
4683782
4683800
4683977
4683993
4684039
4684065
1621555
4275027
4432999
4674238
4683785
4683801
4683979
4684004
4684040
4684067
1962870
4399677
4670341
4674239
4683789
4683803
4683980
4684005
4684042
4684079
2044953
4409714
4674220
4674889
4683791
4683804
4683981
4684006
4684043
4684080
2046206
4410096
4674222
4683769
4683792
4683805
4683982
4684008
4684044
4684083
2283233
4415908
4674224
4683770
4683793
4683807
4683983
4684011
4684045
4684086
2960791
4419365
4674225
4683772
4683794
4683808
4683984
4684012
4684046
2964776
4421781
4674228
4683774
4683795
4683809
4683985
4684016
4684047
3037506
4421783
4674230
4683775
4683796
4683810
4683986
4684019
4684048
Reference excluded (HERO ID) because the reference did NOT present quantitative environmental hazard data
N/A.
Table C.9: Screening Questions and Off-Topic References Excluded at Full-Text Screening for Environmental Hazard
Question
Off-topic if answer is:
References excluded (HERO ID)
Does the reference contain
No
4684031
information pertaining to a low-
priority substance candidate?
What type of source is this
reference?
Review article or book chapter that
contains only citations to primary
literature sources
N/A.
Is quantitative environmental
No
N/A.
hazard data presented?
Is this primarily a
Yes
N/A.
modeling/simulation study?
[Note: select "No" if experimental
verification was included in the
study]
Is environmental hazard data
No
N/A.
presented for standard or non-
standard aquatic or terrestrial
species (fish, invertebrates,
microorganisms, non-mammalian
terrestrial species)?
Is exposure measured for the target
Mixture
N/A.
substance or is the test substance
Formulated Product
N/A.
a mixture (except for reasonable
impurities, byproducts, and
aqueous solutions) or formulated
product?
Does the reference report a
No
N/A.
duration of exposure?
44 Hie information needs for environmental hazard includes a list of study characteristics pertaining to the test organism/species,
type and level of effects, and me of controls. A complete list of the information needs is provided in Table A2 of the "Approach
Document for Screening Hazard Information for Low-Priority Substances Under TSCA". These information needs helped guide
the development of questions for title/abstract and full-text screening.
XXXV
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Table C.9: Screening Questions and Off-Topic References Excluded at Full-Text Screening for Environmental Hazard
Does the reference report a
No
5076432
negative control that is a vehicle
control or no treatment control?
Does the reference include
No
N/A.
endpoints in the information needs?
Table C.10: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for
Environmental Hazard
Question
Unacceptable if:
References excluded (HERO ID)
Metric 1:
The test substance identity or
N/A.
Test substance identity
description cannot be
determined from the information
provided (e.g., nomenclature
was unclear, CASRN or structure
were not reported, substance
name/ description does not
match CASRN).
OR
For mixtures, the components and
ratios were not characterized or did
not include information that could
result in a reasonable approximation
of components.
Metric 2:
A concurrent negative control group
N/A.
Negative controls
was not included or reported.
Metric 3:
The experimental system (e.g.,
N/A.
Experimental System
static, semi-static, or flow-through
regime) was not described.
Metric 4:
Test concentrations were not
N/A.
Reporting of concentrations
reported.
Metric 5:
The duration of exposure was not
N/A.
Exposure duration
reported.
OR
The reported exposure duration was
not suited to the study type and/or
outcome(s) of interest (e.g., study
intended to assess effects on
reproduction did not expose
organisms for an acceptable period
of time prior to mating).
Metric 6:
The test species was not reported.
N/A.
Test organism characteristics
OR
The test species, life stage, or age
was not appropriate for the
outcome(s) of interest.
Metric 7:
The outcome assessment
N/A.
Outcome assessment methodology
methodology was not reported.
Metric 8:
Reporting of data
Data presentation was
inadequate.
OR
Major inconsistencies were present
in reporting of results.
N/A.
XXXVI
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*** Proposal Draft - Do Not Cite, Quote or Release During the Review ***
C.2.3 Fate
For the screening review of LPS candidate 1,2-hexanediol EPA excluded a total of 84 references when
assessing environmental fate. Off-topic fate references excluded at title/abstract screening are listed in
Table C. 11, and those excluded at full-text screening are listed in Table C. 12. References in Table C. 13
represent unacceptable studies based on specific data quality metrics for fate. Off-topic and unacceptable
references are displayed next to the corresponding exclusion criteria.
Table C.11: Off-Topic References Excluded at Initial Screening for Fate
Reference excluded (HERO ID) because the reference did NOT contain information needs45 relevant to environmental
fate
1205485
3407162
4422636
4674228
4683774
4683981
4684004
4684038
4684048
1612136
4275027
4428186
4674230
4683778
4683982
4684005
4684039
4684049
1614234
4399677
4429336
4674231
4683782
4683983
4684006
4684040
4684061
1962870
4409714
4432999
4674232
4683785
4683984
4684008
4684042
4684065
2044953
4410096
4670341
4674235
4683975
4683985
4684011
4684043
4684067
2046206
4415908
4674220
4674238
4683976
4683986
4684012
4684044
4684079
2960791
4419365
4674222
4674239
4683977
4683987
4684016
4684045
4684080
3037506
4421781
4674224
4674889
4683979
4683988
4684019
4684046
4684083
3039332
4421783
4674225
4683772
4683980
4683993
4684021
4684047
4684086
Reference excluded (HERO ID) because the reference did NOT present quantitative environmental fate data
m.
Table C.12: Screening Questions and Off-Topic References Excluded at Full-Text Screening for Fate
Question
Off-topic if answer is:
References excluded (HERO ID)
Does the reference contain
No
3038919
information pertaining to a low-
4731312
priority substance candidate?
4731313
What type of source is this
Review article or book chapter that
N/A.
reference?
contains only citations to primary
literature sources
Is quantitative fate data presented?
No
N/A.
Is this primarily a
Yes
N/A.
modeling/simulation study? [Note:
Select "Yes" only if there is no
experimental verification]
Table C.13: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Fate
Data quality metric Unacceptable if:
References excluded (HERO ID)
45 Hie information needs for fate includes a list of study characteristics pertaining to the associated media and exposure
pathways, associated processes, and use of controls. A complete list of the information needs is provided in Table A3 of the
"Approach Document for Screening Hazard Information for Low-Priority Substances Under TSCA". These information needs
helped guide the development of questions for title/abstract and full-text screening.
XXXVII
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*** Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table C.13: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Fate
Metric 1:
Test substance identity
The test substance identity or
description cannot be determined
from the information provided (e.g.,
nomenclature was unclear and
CASRN or structure were not
reported).
OR
For mixtures, the components and
ratios were not characterized or did
not include information that could
result in a reasonable approximation
of components.
N/A.
Metric 2:
Study controls
The study did not include or report
crucial control groups that
consequently made the study
unusable (e.g., no positive control
for a biodegradation study reporting
0% removal).
OR
The vehicle used in the study was
likely to unduly influence the study
results.
N/A.
Metric 3:
Test substance stability
There were problems with test
substance stability, homogeneity, or
preparation that had an impact on
concentration or dose estimates and
interfered with interpretation of study
results.
N/A.
Metric 4:
Test method suitability
The test method was not reported
or not suitable for the test
substance.
OR
The test concentrations were not
reported.
OR
The reported test concentrations
were not measured, and the nominal
concentrations reported greatly
exceeded the substances water
solubility, which would greatly inhibit
meaningful interpretation of the
outcomes.
N/A.
Metric 5:
Testing conditions
Testing conditions were not
reported, and the omission would
likely have a substantial impact on
study results.
OR
Testing conditions were not
appropriate for the method (e.g., a
biodegradation study at
temperatures that inhibit the
microorganisms).
N/A.
XXXVIII
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Table C.13: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Fate
Metric 6:
System type and design-
partitioning
Equilibrium was not established or
reported, preventing meaningful
interpretation of study results.
OR
The system type and design (e.g.
static, semi-static, and flow-through;
sealed, open) were not capable of
appropriately maintaining substance
concentrations, preventing
meaningful interpretation of study
results.
N/A.
Metric 7: Test organism-
degradation
The test organism, species, or
inoculum source were not reported,
preventing meaningful interpretation
of the study results.
N/A.
Metric 8:
Test organism-partitioning
The test organism information was
not reported.
OR
The test organism is not routinely
used and would likely prevent
meaningful interpretation of the
study results.
N/A.
Metric 9:
Outcome assessment methodology
The assessment methodology did
not address or report the outcome(s)
of interest.
N/A.
Metric 10:
Data reporting
Insufficient data were reported to
evaluate the outcome of interest or
to reasonably infer an outcome of
interest.
OR
The analytical method used was not
suitable for detection or
quantification of the test substance.
OR
Data indicate that disappearance or
transformation of the parent
compound was likely due to some
other process.
N/A.
Metric 11:
Confounding variables
There were sources of variability
and uncertainty in the
measurements and statistical
techniques or between study
groups.
N/A.
Metric 12:
Verification or plausibility of results
Reported value was completely
inconsistent with reference
substance data, related physical
chemical properties, or otherwise
implausible, indicating that a serious
study deficiency exists (identified or
not).
N/A.
XXXIX
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XL
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