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Dossier for Candidate Low-Priority Substance 1-Butanol, 3-
methoxy-, 1-acetate
(CASRN 4435-53-4)
(3-Methoxybutyl Acetate)
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 3-Methoxybutyl Acetate 3
3. Physical-Chemical Properties 4
3.1 References 6
4. Relevant Assessment History 7
5. Conditions of Use 8
6. Hazard Characterization 11
6.1 Human Health Hazard 14
6.1.1 Absorption, Distribution, Metabolism, and Excretion 15
6.1.2 Acute Toxicity 16
6.1.3 Repeated Dose Toxicity 16
6.1.4 Reproductive and Developmental Toxicity 16
6.1.5 Genotoxicity 16
6.1.6 Carcinogenicity 17
6.1.7 Neurotoxicity 17
6.1.8 Skin Sensitization 18
6.1.9 Skin Irritation 18
6.1.10 Eye Irritation 18
6.1.11 Hazards to Potentially Exposed or Susceptible Subpopulations 18
6.2 Environmental Hazard 18
6.2.1 Acute Aquatic Toxicity 18
6.2.2 Chronic Aquatic Toxicity 19
6.3 Persistence and Bioaccumulation Potential 19
6.3.1 Persistence 19
6.3.2 Bioaccumulation Potential 20
7. Exposure Characterization 21
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7.1 Production Volume Information 21
7.2 Exposures to the Environment 21
7.3 Exposures to the General Population 22
7.4 Exposures to Potentially Exposed or Susceptible Subpopulations 22
7.4.1 Exposures to Workers 22
7.4.2 Exposures to Consumers 22
8. Summary of Findings 24
8.1. Hazard and Exposure Potential of the Chemical Substance 24
8.2. Persistence and Bioaccumulation 25
8.3. Potentially Exposed or Susceptible Subpopulations 25
8.4. Storage Near Significant Sources of Drinking Water 26
8.5. Conditions of Use or Significant Changes in Conditions of Use of the Chemical Substance 27
8.6. The Volume or Significant Changes in Volume of the Chemical Substance Manufactured or Processed.... 28
8.7. Other Considerations 28
9. Proposed Designation 29
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 II
A.2.2 Uses of 3-Methoxybutyl Acetate IV
A.3 References XI
Appendix B: Hazard Characterization XIV
References: XXII
Appendix C: Literature Search Outcomes XXIV
C.1 Literature Search and Review XXIV
C.1.1 Search for Analog Data XXIV
C.1.2 Search Terms and Results XXV
C.2 Excluded Studies and Rationale XXVI
C.2.1 Human Health Hazard Excluded References XXVII
C.2.2 Environmental Hazard XXXII
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C.2.3 Fate XXXIV
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Tables
Table 1: 3-Methoxybutyl Acetate at a Glance 3
Table 2: Physical-Chemical Properties for 3-Methoxybutyl Acetate 4
Table 3: Conditions of Use for 3-Methoxybutyl Acetate 9
Table 4: Low-Concern Criteria for Human Health and Environmental Fate and Effects 11
Table 5: 3-Methoxybutyl Acetate and Analog Structures 15
Table A.1:1986-2015 National Production Volume Data for 3-Methoxybutyl Acetate (Non-Confidential ^
Production Volume in Pounds)
Table A.2: Sources Searched for Uses of 3-Methoxybutyl Acetate II
Table A3: Uses of 3-Methoxybutyl Acetate IV
Table B.1: Human Health Hazard XIV
Table B.2: Environmental Hazard XXXX
Table B.3: Fate XX
Table C.1: Sources Used for Analog Search XXV
Table C.2: Search Terms Used in Peer-Reviewed Databases XXV
Table C.3: Search Terms Used in Grey Literature and Additional Sources XXVI
Table C.4: Off-Topic References Excluded at Title/Abstract Screening for Human Health Hazard XXVII
Table C.5: Screening Questions and Off-Topic References Excluded at Full Text Screening for Human
Health Hazard
Table C.6: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for
Human Health Hazard - Animal
Table C.7: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for
Human Health Hazard - In Vitro
Table C.8: Off-Topic References Excluded at Title/Abstract Screening for Environmental Hazard XXXII
Table C.9: Screening Questions and Off-Topic References Excluded at Full Text Screening for
Environmental Hazard XXXIII
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Table C.10: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for
Environmental Hazard
Table C.11: Off-Topic References Excluded at Initial Screening for Fate XXXIV
Table C.12: Screening Questions and Off-Topic References Excluded at Full Text Screening for Fate XXXV
Table C.13: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for
_ , XXXV
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-
Butanol, 3-methoxy-, 1-acetate, referenced as 3-methoxybutyl acetate for the remainder of this
document, 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/documents/2019/03/21/2019-05404/imtiation-of-prioritization-under-tlie-toxic-substances-
control-act-tsca
2 The prioritization process is explained in the Procedures for Prioritization of Chemicals for Risk Evaluation Under the
Toxic Substances Control Act (82 FR 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 (ProposedDesignation): 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 3-Methoxybutyl Acetate
Table 1 below provides the CAS number, synonyms, and other information on 3-methoxybutyl
acetate.
Table 1: 3-Methoxybutyl Acetate at a Glance
Chemical Name
3-Methoxybutyl Acetate
CASRN
4435-53-4
Synonyms
1-Butanol, 3-methoxy-, 1-acetate; 1-Butanol, 3-methoxy-, acetate; 3-Methoxy-1-butanol,
acetate; 3-Methoxy-1-butyl acetate; 3-Methoxybutyl acetate; 3-Methoxybutylester
kyseliny octove; 3-methoxy-n-butylacetat; Acetic acid 3-methoxybutyl; Acetic Acid 3-
Methoxybutyl Ester; Methyl-1,3-butylene glycol acetate; 5-methoxyhexanoate
Trade Name(s)
Butoxyl
Molecular Formula
C7H14O3
Representative Structure
_.o__ y
t^t
3-Methoxybutyl acetate is an organic chemical compound that contains both an ester functional
group, which is a pair of alkyl groups connecting by a carbonyl and a linking oxygen atom (RCOOR),
and an ether functional group, which is an oxygen atom connected two alkyl groups (R-O-R). Shorter
chain ethers and esters typically function as solvents, which are liquids capable of dissolving other
substances. 3-Methoxybutyl acetate is water soluble and miscible with common organic solvents.
These properties make 3-methoxybutyl acetate ideal for use as a solvent in a variety of applications
and product sectors. Section 5 includes conditions of use for this chemical.
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3. Physical-Chemical Properties
Table 2 lists physical-chemical properties for 3-methoxybutyl acetate. 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 3-Methoxybutyl Acetate
Source/
Model
Data Type
Endpoint
Endpoint value
Notes
PubChem2019
Experimental
State at room
temperature
Liquid
EPISuite v.4.113
Experimental
Molecular Weight
146 g/mol
EPISuite v.4.11
Calculated
Molecular Weight
146.19 g/mol
Lyman etal. 1990
Estimation
Molar Volume
187 cm3/mol
EPISuite v.4.11
Experimental
Water Solubility
4600 mg/L
ECHA 2018
Experimental
Water Solubility
60680 - 30000 mg/L
EPISuite v.4.11
Estimated
Water Solubility
10870 mg/L
Kow method
ECHA 2018
Experimental
Water Solubility
4.16x10-1 mo|/L
EPISuite v.4.11
Experimental
Water Solubility
3.15x10-2 mol/L
EPISuite v.4.11
Estimated
Log Kow
1.01
EPISuite v.4.11
Estimated
Log Koa
4.72
EPISuite v.4.11
Estimated
Log Koc
1 (MCI); 1.33 (Kow)
ECHA 2018
Experimental
Vapor Pressure
0.44 mm Hg at25ฐC
Converted from 58 Pa at 25ฐC measured according to OECD 104
EPISuite v.4.11
Estimated
Vapor Pressure
2.77 mm Hg
EPISuite v.4.11
Estimated
Henry's Law
1.40x10"6 atm-
m3/mol
EPISuite v.4.11
Estimated
Volatilization
21 days (river)
23 days (lake)
EPISuite v.4.11
Estimated
Photolysis
(Indirect)
6.81 hours (T1/2)
OH rate constant 1.88E-11 cm3/molecules-second (12 hour day;
1.5E6 OH/cm3)
No ozone reaction estimation
3 Physical Property Inputs - Vapor Pressure = 0.44 mm Hg, Water Solubility = 60680 mg/L) SMILES: 0=C(0CCC(0C)C)C
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EPISuite v.4.11
Estimated
Hydrolysis
2 years at pH 7
78 days at pH 8
Aqueous Base/Acid-Catalyzed Hydrolysis (25 deg C)
EPISuite v.4.11
Estimated
Biodegradation
potential
Ready prediction:
Yes
EPISuite v.4.11
Estimated
BAF
1.29
EPISuite v.4.11
Estimated
BCF
2.15
Based on regression equation
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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 state (PubChem), 3-methoxybutyl
acetate is a liquid at ambient temperature. Liquids have the potential for exposure via direct dermal
contact with the substance, ingestion, or by inhalation of aerosols if they are generated. Based on its
measured vapor pressure (ECHA, 2018), 3-methoxybutyl acetate in its pure form is expected to be
volatile at ambient temperatures. As a result, exposure to 3-methoxybutyl acetate is possible through
inhalation of vapors and aerosols if they are generated. In addition, its estimated Henry's law constant
(EPISuite, 2019) shows that 3-methoxybutyl acetate may also volatilize slowly from water and
aqueous solutions, which can also result in inhalation exposure to the vaporized compound. Based on
measured water solubility (ECHA, 2018), 3-methoxybutyl acetate is considered water soluble. Water
soluble substances have an increased potential absorption through the lungs; therefore, if inhalation of
vapors or aerosols occurs, absorption through the lungs is likely. Based on its water solubility and low
Kow (ECHA, 2018), 3-methoxybutyl acetate has the potential to be moderately absorbed through the
gastrointestinal tract. However, sequestration in fatty tissues is not likely based on its estimated Log
Kow, bioconcentration factor (BCF) and bioaccumulation factor (BAF) (EPISuite, 2019). The
estimated K0c (EPISuite, 2019) indicates 3-methoxybutyl acetate is highly mobile in soil, which
suggests a potential to contaminate groundwater, including well water. Concern for presence in
drinking water is reduced in part by 3-methoxybutyl acetate's biodegradation (discussed in Section
6.3.1). Experimental biodegradation data show that 3-methoxybutyl acetate is readily biodegradable,
meaning that it has the potential to break down in the environment into carbon dioxide and water.
3.1 References
European Chemicals Agency (ECHA). (2019). 3-methoxybutyl acetate. Retrieved from
https://echa.europa.eu/substance-information/-/substanceinfo/100.022.405
Lyman, Warren J., Reehl, W. F., Rosenblatt, D. H. (1990). Handbook of chemical property estimation
methods: environmental behavior of organic compounds. American Chemical Society
U.S. EPA. (2019). Estimation Programs Interface Suite, v 4.11. United States Environmental
Protection Agency, Washington, DC, USA
4 https://www.epa.gOv/sites/production/files/2015-05/documents/05.pdf
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4. Relevant Assessment History
EPA assessed the toxicological profile of 3-methoxybutyl acetate and added the chemical to the Safer
Choice Program's Safer Chemical Ingredients List (SCIL) in September 2016 under the functional
class of solvents. The SCIL5 is a continuously updated list of chemicals that meet low-concern Safer
Choice criteria.6
EPA also reviewed international assessments of 3-methoxybutyl acetate. EPA identified assessments
by Canadian, Finnish, Japanese, German, and New Zealand government agencies.
The Canadian Government, through an assessment of toxicity and exposure as part of its
categorization of the Domestic Substance List, found that 3-methoxybutyl acetate did not meet its
criteria for further attention.7
The Finnish Environment Institute (SYKE)'s data bank of environmental properties of chemicals
identifies 3-methoxybutyl acetate as "confirmed to be readily biodegradable."8
Japan's National Institute of Technology and Evaluation (NITE) categorized 3-methoxybutyl acetate
as hazard class 4 for human health in 2017, the lowest-concern hazard ranking that NITE assigns.9
The German Environment Agency (UBA) designated 3-methoxybutyl acetate as "low hazard to
waters" in August 2017 based on an assessment of ecotoxicity and environmental fate.1"
New Zealand's Environmental Protection Authority lists 3-methoxybutyl acetate in its Chemical
Classification and Information Database (CCID), which includes hazard and physical information
about single chemicals for use in hazard classifications and safety information. It has classification
descriptions: "acutely toxic;" "slightly harmful in the aquatic environment or are otherwise designed
for biocidal action;" rapidly degradable; and not bioaccumulative.11 Sections 6.1.2 and 6.2 of this
dossier contain a summary of the reasonably available hazard information on these endpoints and an
explanation of why EPA has found that acute mammalian toxicity and aquatic toxicity are not a
concern for this chemical.
5 https://www.epa.gov/saferchoice/safer-ingredients
0 https://www.epa.gov/sites/production/files/2013-12/documents/dfe master criteria safer ingredients v2 l.pdf
7 https://canadachemicals.oecd. org/ChemicalDetails.aspx?ChemicalID=614DB9CA-FFD6-46F5-8ADB-DEEFF297FB4A
8 http://wwwp.vmparisto.fi/scripts/Kemrek/Kemrek uk.asp?Method=MAKECHEMdetailsform&txtChemId=2188
9 http://www.safe.nite.go.ip/icheck//direct.action?TYPE=DPAGEl&CAS=4435-53-4&MITI=2-739
10 https://webrigoletto.uba.de/rigoletto/public/searcliDetail.do7kennummeF5020
11 https://www.epa. govt.nz/database-search/chemical-classification-and-information-database-ccid/view/1496
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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 3-methoxybutyl acetate (Appendix A) to inform which uses would be determined
conditions of use.12 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).
According to CDR, 3-methoxybutyl acetate is manufactured domestically and imported. No
processing uses were reported to CDR. Industrial, commercial, and consumer uses include absorbents
and adsorbents, fixing agents, food contact coatings, odor agents, and surface treatments. Additional
consumer uses include anti-freeze and de-icing products; cleaning and washing agents;
dyes/pigments; paints and coatings, among others. Based on the known manufacturing processes and
uses of this chemical substance, EPA assumes distribution in commerce. According to CDR, one
facility withheld recycling information. No other information is available to indicate that recycling is
taking place. No information on disposal is found in CDR or through EPA's Toxics Release
Inventory (TRI) Program13 since 3-methoxybutyl acetate 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 solid and liquid waste 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 conditions of use or
find additional occupational14 and consumer uses. This research improved the Agency's
understanding of the conditions of use for 3-methoxybutyl acetate. Although EPA identified uses of
3-methoxybutyl acetate 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 3-methoxybutyl acetate 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).
12 The 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).
13 https://www.epa.gov/toxics-release-inventorv-tri-program
14 Occupational uses include industrial and/or commercial uses
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Table 3: Conditions of Use for 3-Methoxybutyl Acetate
Life Cycle Stage
Category
Subcategory of Use
Source
Manufacturing
Domestic manufacture
Domestic Manufacture - information on whether manufactured or
import was not reported.
EPA (2017b)
Import
Import- Manufacture - information on whether manufactured or import
was not reported.
Processing
Solvents (which become part
of product formulation or
mixture)
Printing ink manufacturing
SPIN (2018c), SPIN (2018a), SPIN (2018b),
Mimaki Engineering Co., Ltd. (2018)
Other
Chemical product and preparation manufacturing; fabricated metal
product manufacturing; manufacture of furniture; transportation
equipment manufacturing; manufacture, repair, and installation of
machinery and equipment; miscellaneous manufacture.
SPIN (2018b), SPIN (2018a), SPIN(2018c), SPIN
(2018c), Svendsen etal. (2004)
Recycling
Recycling
EPA (2017b)15
Distribution
Distribution
Distribution
EPA (2017b)
Industrial Uses
Solvents (unknown)
SPIN (2018d), Celanese Corporation (2018),
Celanese Corporation (2015)
Process regulator, stabilizer,
inhibitor
SPIN (2018d), (2018c)
Reprographic agent
SPIN (2018d), CPCat (2019)
Other
Construction; wholesale and retail trade and repair of motor vehicles
and motorcycles
SPIN (2018b), SPIN (2018a), SPIN(2018c), SPIN
(2018c)
Industrial/
commercial/
Solvents (which become part
of product formulation or
mixture)
Adhesives and sealants (Two-component glues and adhesives)
SPIN (2018d), ECHA (2018a), Henkel Corporation
(2013), Celanese Corporation (2011)
15 In the 2016 CDR, one facility withheld recycling information (EPA 2017b).
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Table 3: Conditions of Use for 3-Methoxybutyl Acetate
Life Cycle Stage
Category
Subcategory of Use
Source
consumer uses
Other
Absorbents and adsorbents, fixing agents, food contact coatings, odor
agents, surface treatment
SPIN (2018d), Synapse Information Resources
(n.d), CPCat (2019), SPIN (2018b), ECHA (2018a)
Consumer uses
Anti-freeze and de-icing
products
ECHA (2018a)
Cleaning and washing
agents
SPIN (2018d)
Dyes/Pigments
SPIN (2018d), SPIN (2018c), ECHA (2018a)
Fillers
SPIN (2018d); ECHA (2018a)
Paints and Coatings
New Jersey Department of Health (2009), SPIN
(2018d), SPIN (2018c), ECHA (2018a), Synapse
Information Resources (n.d.), Celanese
Corporation (2018)
Other
ECHA (2018a)
Disposal
Releases to air, wastewater,
solid and liquid wastes
Though not explicitly identified, releases from
disposal are assumed to be reasonably foreseen16
10 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 primary literature and other data sources to identify reasonably available information.
This literature review approach17 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 3-methoxybutyl acetate against
the endpoints listed below. EPA's New Chemicals Program has used these endpoints for decades to
evaluate chemical substances under TSCA18 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 Chemicals19 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.
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
Toxicity20
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
17This process is further discussed in the document "Approach Document for Screening Hazard Information for Low-
Priority Substances Under TSCA."
18 https://www.epa. gov/sustainable-futures/sustainable-futures-p2-framework-manual
19 https://www.unece.org/fileadmin/DAM/trans/danger/publi/ghs/ghs rev07/English/ST SG AC10 30 Rev7e.pdf
20 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)21
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
Toxicity22
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
Toxicity22
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/
Genotoxicity23
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
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.
21 Values from GHS criteria for Specific Target Organ Toxicity Repeated Exposure (Chapter 3.9: Specific Target Organ
Toxicity' Repeated Exposure. 2009, United Nations).
22 Values derived from the U.S. 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).
23 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
in the germ cells of
humans.
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.
Carcinogenicity24
Very High
High
Moderate
Low
Known or
presumed human
carcinogen (GHS
Category 1Aand
1B)
Suspected human
carcinogen (GHS
Category 2)
Limited or marginal
evidence of
carcinogenicity in
animals (and
inadequate25 evidence
in humans)
Negative studies or
robust mechanism-
based structure
activity relationship
(SAR)
Neurotoxicity
(90-day study)21
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
Sensitization26
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
Limited evidence
including the presence
of structural alerts
Adequate data
available indicating
lack of respiratory
sensitization
24 Criteria mirror classification approach used by the IARC (Preamble to the L4RC Monographs: B. Scientific Review and
Evaluation: 6. Evaluation and rationale. 2019) and incorporate GHS classification scheme (Chapter 3.6: Carcinogenicity.
2009, United Nations).
25 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.
20 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
(equivalent to GHS
Category 1A or 1B)
Irritation/
Corrosivity27
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)28
Chronic Aquatic
Toxicity Value
(L/E/ICso)28
Persistence (Measured in terms of level of
biodegradation)29
Bioaccumulation
Potential30
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 reasonably available information that EPA included in the hazard
evaluation of 3-methoxybutyl acetate. 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 3-methoxybutyl acetate. Appendix B contains more information
on each study.
EPA used best professional judgement to select an analog for 3-methoxybutyl acetate based on
similarity in structure, physical-chemical properties, and functionality, with the assumption that this
chemical will have similar environmental transport and persistence characteristics, and bioavailability
and toxicity profiles. 3-Methoxybutyl acetate is the acetate ester of 3-methoxybutanol. Therefore, 3-
methoxybutanol is the expected alcohol metabolite of 3-methoxybutyl acetate and the biologically
27 Criteria derived from the Office of Pesticide Programs Acute Toxicity Categories (U.S. EPA. Label Review Manual.
2010).
28 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).
29 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).
30 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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active metabolite in vivo. EPA determined 3-methoxybutanol (Table 5) to be the best analog for 3-
methoxybutyl acetate.
Table 5: 3-Methoxybutyl Acetate and Analog Structures
CASRN
Name
Structure
4435-53-4
3-Methoxybutyl
acetate
0 CI4,
h3c o 0
2517-43-3
3-Methoxybutanol
HO 'J.
ch3
ch3
6.1.1 Absorption, Distribution, Metabolism, and Excretion
Absorption
Based on the chemical's high water solubility (Section 3), there is an increased potential for
absorption through the lungs from inhalation exposure. If oral ingestion occurs, moderate absorption
through the gastrointestinal tract is expected. Due to its log Kow (Section 3), dermal absorption is
expected to be poor to moderate.
Distribution
Because 3-methoxybutyl acetate is considered water soluble (Section 3), it is likely to be distributed
mainly in aqueous compartments in an organism. Based on its low log Kow (Section 3), absorption
and sequestration in fatty tissues is unlikely.
Metabolism
Because quality experimental data31 on 3-methoxybutyl acetate metabolite formation were limited,
the Quantitative Structure-Activity Relationship (QSAR) toolbox32 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 3-methoxybutyl acetate metabolites. The predicted
metabolites included carboxylic acid/ether, aldehyde/ether, alcohol/ether, and C2 carboxylic acid. A
CI aldehyde, ester/ketone, carboxylic acid/alcohol, aldehyde/alcohol, diol, ester/alcohol, and a CI
carboxylic acid were also identified as possible metabolites.
31 This process is further discussed in the document "Approach Document for Screening Hazard Information for Low-
Priority Substances under TSCA."
32 https://www.oecd.org/chemicalsafetv/risk-assessment/oecd-qsar-toolbox.htm
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Excretion
Due to the chemical's low molecular weight and water solubility (Section 3), 3-methoxybutyl acetate
is expected to be mainly excreted via urine. 3-methoxybutyl acetate may also be excreted via feces
and respirable air.
6.1.2 Acute Toxicity
EPA assessed the potential for mammalian toxicity from acute exposures to 3-methoxybutyl acetate
using experimental data and read-across from 3-methoxybutanol. A study on mice exposed to a single
dose of 3-methoxybutyl acetate orally reported no mortalities at the highest tested dose (1000 mg/kg),
resulting in an LD50 greater than 1000 mg/kg (ECHA. 1930). EPA also considered read-across from
an analog because of the limited dose range in acute oral study on 3-methoxybutyl acetate. In an
OECD Guideline 401 study, rats exposed to a single dose of 3-methoxybutanol via oral gavage
demonstrated no adverse effects at that dose (2000 mg/kg), resulting in an LD50 greater than 2000
mg/kg (ECHA. 1991a). Another study on mice exposed to 3-methoxybutanol via oral gavage reported
an LD50 of 3000 mg/kg, with the 95% confidence interval between 2400 and 3700 mg/kg (ECHA.
1966). Note that, as described in section 4 of this report, New Zealand made findings for this
chemical based on a study that identified an LD50 of 4310 mg/kg. All of these studies, including the
study identified by New Zealand, indicate low concern for acute toxicity with LD50S expected to be
greater than the low-concern threshold of 2000 mg/kg.
6.1.3 Repeated Dose Toxicity
EPA assessed the potential for mammalian toxicity from repeated exposures to 3-methoxybutyl
acetate using experimental data. A study on rats exposed to 3-methoxybutyl acetate via oral gavage
for 28 days had a no observed adverse effect level (NOAEL) of 300 mg/kg-day and a lowest observed
adverse effect level (LOAEL) of 1000 mg/kg-day based on abnormal respiration (J-CHECK. 2004).
This study result indicated low concern for toxicity from repeated exposures because the NOAEL and
LOAEL meet the low-concern criteria threshold of 300 mg/kg-day for a ~30-day repeated dose study.
6.1.4 Reproductive and Developmental Toxicity
EPA assessed the potential for mammalian developmental toxicity by 3-methoxybutyl acetate using
an OECD Guideline 414 study in rats exposed via oral gavage during gestation days 7-16 (ECHA.
1997b). No maternal or fetal toxicity was observed at the single dose tested (1000 mg/kg-day),
resulting in a NOAEL of 1000 mg/kg-day. This result, taken with the low-concern criteria oral
threshold of 250 mg/kg-day, indicate low-concern for developmental toxicity. Although reproductive
toxicity data is unavailable, EPA considers concern for this endpoint to be low based on the low-
hazard findings for other mammalian endpoints, including but not limited to acute toxicity, repeated
dose toxicity, and developmental toxicity.
6.1.5 Genotoxicity
EPA assessed the potential for 3-methoxybutyl acetate to cause genotoxicity, a potential indicator of
genotoxic carcinogenicity. A bacteria reverse mutation assay in Salmonella typhimurium strains
exposed to 3-metoxybutyl acetate reported negative results for inducing gene mutations with and
without metabolic activation (ECHA. 1992). A study on Chinese hamster lung fibroblasts exposed to
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3-methoxybutyl acetate reported negative results for chromosomal aberrations with and without
metabolic activation (J-CHECK. 2010). These negative results indicate low concern for genotoxicity.
6.1.6 Carcinogenicity
Because quality experimental data on 3-methoxybutyl acetate were limited, EPA relied on publicly
available quantitative structure activity relationship (QSAR) models and structural alerts (SA) to
assess the carcinogenic potential for 3-methoxybutyl acetate. 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.33 For this chemical and its metabolites, there is an
absence of the types of reactive structural features that are present in genotoxic carcinogens. 3-
Methoxybutyl acetate is not an electrophile. ISS profiler, a QSAR model,34 did not identify any
structural alerts for 3-methoxybutyl acetate. An aldehyde was identified as a potential metabolite
alerts; however, this metabolite is expected to be excreted. Further, the Virtual models for property
Evaluation of chemicals within a Global Architecture (VEGA) models"35 results indicate 3-
methoxybutyl acetate has low potential to be carcinogenic or mutagenic.
3-Methoxybutyl acetate's expected metabolism, lack of structural alerts, and negative genotoxicity
results indicate that this chemical is unlikely to be carcinogenic or mutagenic.
6.1.7 Neurotoxicity
While no traditional neurotoxicity studies were available for 3-methoxybutyl acetate or 3-
methoxybutanol, EPA assessed the potential for neurotoxicity using relevant endpoints measured in a
repeated dose study and searching for predictions by U.S. EPA's ToxCast.36 A repeated dose study in
rats exposed to 3-methoxybutyl acetate by oral gavage reported no effects on the functional
observational battery (FOB) parameters examined at doses up to 1,000 mg/kg-day (highest dose
tested) for 28 days (J-CHECK. 2004). No additional neurotoxicity-related data were available for 3-
methoxybutyl acetate.
Assays related to neurological functions were not identified for 3-methoxybutyl acetate in ToxCast
(U.S. EPA ToxCast, 2019).
33 "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 Bio techno logy.
34 Carcinogenicity alerts by ISS 2.4 profiler as encoded in the QSAR Toolbox 4.3 (qsartoolbox.org) and the 4
carcinogenicity models housed within the VEGA 1.1.4 software tool available from https://www.vegahub.eu. A summary
of the results from these models is provided in Appendix B.
35 There are four carcinogenicity models housed within the VEGA 1.1.4 software tool available from
https://www.vegahub.eu. A summary of the results from these models is provided in Appendix B.
30 https://actor.epa.gov/dashboard/ Chemical specific assay list can be found at
https://actor.epa.gOv/dashboard/#chemical/55934-93-5.
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Based on the functional observation battery results and low-hazard results for other endpoints,
including, but not limited to acute toxicity and developmental toxicity, EPA anticipates low concern
for neurotoxicity.
6.1.8 Skin Sensitization
Though no experimental studies on 3-methoxybutyl acetate or closely-related analogs were available
to assess the potential for 3-methoxybutyl acetate to cause skin sensitization, the OECD QSAR
Toolbox Version 4.2 did not identify any structural alerts for protein binding potential of 3-
methoxybutyl acetate in regard to skin sensitization. These results indicate low concern for skin
sensitization.
6.1.9 Skin Irritation
EPA assessed the potential for skin irritation using read-across from 3-methoxybutanol. In an OECD
Guideline 404 study, rabbits exposed to 3-methoxybutanol dermally displayed slight erythema 1 hour
following exposure, but this effect was fully reversed within 24 hours (ECHA. 1991b). Using read-
across from this study, these results indicate 3-methoxybutyl acetate is low concern for skin
irritation.
6.1.10 Eye Irritation
EPA assessed 3-methoxybutyl acetate's potential to act as an eye irritant using an OECD Guideline
405 study (ECHA. 1997a). Rabbits exposed to 3-methoxybutyl acetate experienced slight
conjunctival redness and chemosis, but these effects were fully reversible in 48 hours. These results
indicate moderate concern for eye irritation by 3-methoxybutyl acetate.
6.1.11 Hazards to Potentially Exposed or Susceptible Subpopulations
The above information supports a low human health hazard finding for 3-methoxybutyl acetate based
on low-concern criteria. This finding includes considerations such as the potential for developmental
toxicity and 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 3-methoxybutyl acetate.
6.2 Environmental Hazard
EPA assessed environmental hazard for 3-methoxybutyl acetate based on available acute
experimental data and estimated chronic toxicity values using the Ecological Structure Active
Relationships (ECOSAR) Predictive Model.37 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 using experimental data and estimated
values from ECOSAR. A study in aquatic invertebrates resulted in an LC50 value of 128 mg/L
37 https://www.epa. gov/tsca-screenmg-tools/ecological-structure-activitv-relationships-ecosar-predictive-model
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(ECHA. 1983). Predictive values from ECOSAR for aquatic vertebrates and algae were 74 mg/L and
86 mg/L, respectively. These aquatic toxicity values indicate moderate concern for acute aquatic
exposure. New Zealand's Environmental Protection Agency classified this chemical as "slightly
harmful in the aquatic environment or are otherwise designed for biocidal action" based on an aquatic
vertebrate LC50 of 7.1 mg/L.38 New Zealand's classification, discussed in Section 4, uses data that
was not of sufficient quality for inclusion in this analysis, based on EPA's literature review.39
Because the toxicity values from this work are the lowest for the chemical, if EPA used them as the
basis of its evaluation, this chemical would still indicate low concern for acute aquatic toxicity. For a
chemical with acute aquatic toxicity values <10 ppm (mg/L) to be considered low concern for
environmental hazard, the chemical must reach 60% degradation within 10 days. Given the low
persistence of 3-methoxybutyl acetate (discussed in Section 6.3.1) in combination with its aquatic
toxicity, studies indicate low concern for acute aquatic toxicity exposure because the aquatic toxicity
data is accompanied by greater than 60% aerobic biodegradation within 10 days.
6.2.2 Chronic Aquatic Toxicity
Chronic toxicity values estimated by ECOSAR for aquatic vertebrates, aquatic invertebrates, and
algae are 6.9 mg/L, 160 mg/L, and 16 mg/L, respectively. These estimations indicate moderate
concern for chronic aquatic toxicity. For a chemical with chronic aquatic toxicity values <10 ppm to
be considered low concern for hazard, the chemical must reach 60% degradation within 28 days as
measured in an aerobic ready biodegradation test without degradation products of concern. Given the
low persistence for 3-methoxybutyl acetate (discussed in 6.3.1), these predictions indicate low
concern for chronic aquatic exposure, because the aquatic toxicity data is accompanied by greater
than 60% aerobic biodegradation within 10 days. Aerobic biodegradation of 3-methoxybutyl acetate
(discussed in Section 6.3.1) is expected to reduce the dissolved concentration in the environment,
reducing the potential for chronic exposures and aquatic toxicity.
6.3 Persistence and Bioaccumulation Potential
6.3.1 Persistence
EPA assessed environmental persistence for 3-methoxybutyl acetate using an experimental study.
Based on an OECD Guideline 30IE study, 95.5% of 3-methoxybutyl acetate degraded within 7 days
under aerobic conditions (ECHA. 1995). Furthermore, microbial inhibition tests in 3-methoxybutanol
indicate that 3-methoxybutyl acetate is non-toxic to microbial populations found in sewage treatment
plants (ECHA. 2009). These results indicate low concern for persistence in aerobic environments by
readily biodegrading in less than 28 days. These results indicate low concern for persistence in
aerobic environments by readily biodegrading in less than 28 days and indicate 3-methoxybutyl
acetate and indicate this chemical will have low persistence.
38 https://www.epa.govt.nz/database-search/chemical-classification-and-information-database-ccid/view/1496
39 A complete list of the information needs is provided in the "Approach Document for Screening Hazard Information for
Low-Priority Substances Under TSCA." This particular study was not included because information written in a foreign
language were not included in EPA's screening review for low-priority substances.
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Anaerobic biodegradation data were not available for 3-methoxybutyl acetate or 3-methoxybutanol.
Though BioWin4" modeling did not predict this chemical to anaerobically biodegrade quickly, this
chemical may still anaerobically biodegrade. No degradation products of concern were identified for
this chemical substance. Given the low-hazard results for mammalian toxicity, and evidence of
aerobic biodegradation, EPA anticipates low concern for this chemical if present in anaerobic
environments.
6.3.2 Bioaccumulation Potential
Based on the estimated BAF value of 7.7, using the Estimation Programs Interface (EPI) Suite
models,41 3-methoxybutyl acetate is expected to have low potential for bioaccumulation in the
environment based on the low-concern threshold of less than 1000.
40 https://envirosim.com/products/biowin
41 https://www.epa.gov/tsca-screening-tools/epi-suitetm-estimation-program-interface
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7. Exposure Characterization
EPA considered reasonably available information on exposure for 3-methoxybutyl acetate. In general,
there is limited information on exposure for low-hazard chemicals. EPA consulted sources of use
information that include CDR and other databases and public sources. 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.
As shown in Tables 3 and A.3, 3-methoxybutyl acetate is a solvent with no processing uses that has a
variety of industrial, consumer, and commercial uses. 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 3-methoxybutyl acetate is based on an analysis of CDR data
reported from 1986 to 2015.42 The CDR database indicates that for reporting year 2015, companies
manufactured or imported 3-methoxybutyl acetate at 16 sites. Prior to 1994, 3-methoxybutyl acetate
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 of generally 25,000 lbs.
In 1994, 1998 and 2002 reporting years, aggregate production volume for 3-methoxybutyl acetate was
between 10,000 and 500,000 lbs., and in 2006 and 2011, aggregate production volume was less than
500, 000 lbs. Since 2012, aggregate production volume has fallen with volumes reported at less than
100,000 lbs. with some years below 25,000 lbs.
7.2 Exposures to the Environment
EPA expects most exposures to the environment to occur during the manufacture, import, and
industrial, commercial, and consumer use of 3-methoxybutyl acetate. Exposure is also possible from
other uses, such as distribution and disposal. These activities could result in releases of 3-
methoxybutyl acetate to media including surface water, landfills, and air.
EPA expects high levels of removal of 3-methoxybutyl acetate during wastewater treatment (either
directly from the facility or indirectly via discharge to a municipal treatment facility or Publicly
Owned Treatment Works (POTW)). Further, 3-methoxybutyl acetate is expected to have low
persistence (aerobic biodegradation is discussed in Section 6.3.1) and has the potential to be broken
down in the environment to carbon dioxide and water. Therefore, any release of this chemical is
expected to break down, reducing exposure to aquatic organisms in the water column and
groundwater sources of drinking water, including well water.
42 The 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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If disposed of in a landfill, this chemical is expected to degrade under aerobic conditions (aerobic
biodegradation is discussed in Section 6.3.1).
If incineration releases during manufacturing occur, EPA expects significant degradation of 3-
methoxybutyl acetate 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 3-methoxybutyl acetate from the
potential environmental releases described above. Air exposure is unlikely from incineration. If 3-
methoxybutyl acetate is present in the air from volatilization, it is expected to be reduced because of
its short atmospheric half-life of 7 hours (see Table 2 in Section 3). 3-methoxybutyl acetate is
unlikely to be present in surface water because it will degrade (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 3-methoxybutyl acetate, oral exposure to 3-
methoxybutyl acetate 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 3-methoxybutyl acetate than the general population during manufacturing, processing,
distribution, use, or disposal. EPA also identified consumers as a population that may experience
greater exposure to 3-methoxybutyl acetate than the general population through use of anti-freeze and
de-icing products; cleaning and washing agents; dyes/pigments; and paints and coatings, for example.
7.4.1 Exposures to Workers
Based on its reported physical form and measured melting point (Table 2), 3-methoxybutyl acetate is
a liquid under ambient conditions. Based on 3-methoxybutyl acetate's 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), 3-methoxybutyl
acetate is expected to be volatile at ambient temperatures and workers may be exposed through
inhalation of vapors. If 3-methoxybutyl acetate is in a dilute form, the estimated Henry's Law
constant for 3-methoxybutyl acetate indicates volatilization from water and aqueous solutions is
likely. Workers may be exposed to 3-methoxybutyl acetate in manufacturing, processing, distribution,
use and disposal.
7.4.2 Exposures to Consumers
Consumers may be exposed to 3-methoxybutyl acetate through the use of anti-freeze and de-icing
products; cleaning and washing agents; dyes/pigments; and paints and coatings, for example. For all
these uses, if dermal contact does occur, 3-methoxybutyl acetate is expected to have poor to moderate
absorption through the skin based on its molecular weight, water solubility and partitioning
coefficients (Section 3). If the chemical is in an aerosol product and inhalation exposure occurs, 3-
methoxybutyl acetate's absorption from the lungs is likely. However, EPA expects exposure to be
low since consumers will, for most uses, avoid direct contact with these types of products. EPA does
not include intentional misuse, such as people drinking products containing this chemical, as part of
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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). 3-
Methoxybutyl acetate 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 3-methoxybutyl acetate 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 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 EPA (40 CFR 702.3). This
section explains the basis for the proposed designation and how EPA applied statutory and regulatory
requirements, addressed rationales, and reached conclusions.
8.1. Hazard and Exposure Potential of the Chemical Substance
Approach: EPA evaluated the hazard and exposure potential of 3-methoxybutyl acetate. EPA used
this information to inform its proposed determination of whether 3-methoxybutyl acetate would meet
the statutory criteria and considerations for proposed designation as a low-priority substance.
Hazard potential:
For 3-methoxybutyl acetate'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 the low-concern thresholds. EPA found that 3-methoxybutyl
acetate is of low concern for human health and environmental hazard across the range of endpoints in
this low-concern criteria.
Exposure potential:
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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,
consumers, and children (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 likely to experience exposures. EPA determined that while the general
populations, consumers, and workers may be exposed to 3-methoxybutyl acetate, exposure by the
dermal pathway is limited by 3-methoxybutyl acetate's physical-chemical properties. If ingestion or
inhalation occurs, 3-methoxybutyl acetate is expected to be metabolized and excreted, reducing the
duration of exposure. If 3-methoxybutyl acetate is released into the environment, its exposure
potential will be reduced through biodegradation under aerobic conditions.
Rationale: Although 3-methoxybutyl acetate may cause moderate eye irritation, the effects are
expected to be relatively low-impact [minimal to moderate] and reversible, thereby reducing concern
for longer-term effects. Workers could be exposed during manufacturing processes, distribution, use,
and disposal through handling and splashing of solutions, or hand-to-face and eye contact. Other uses
covered under TSCA, especially consumer uses in anti-freeze and de-icing products, cleaning and
washing agents, and paints and coatings, would be unlikely to result in more than incidental eye
exposure. Eye irritation resulting from exposure in an occupational and consumer setting is
mitigated primarily by the reversible nature of the effects and addressed by rinsing with water.
Proposed Conclusion: Based on an initial 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 3-methoxybutyl acetate 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 3-methoxybutyl
acetate 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 3-methoxybutyl acetate is biodegradable under
aerobic conditions (discussed in Section 6.3.1). EPA's EPI Suite models indicate a low potential for
bioaccumulation and bioconcentration (Section 6.3.2).
Proposed Conclusion: Based on an initial screen 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 3-methoxybutyl acetate 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
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Administrator who, due to either greater susceptibility or greater exposure, may be at greater risk than
the general population of adverse health effects from exposure to a chemical substance or mixture,
such as infants, children, pregnant women, workers, consumers, or the elderly." EPA identified
workers engaged in the manufacturing processes, distribution, use, and disposal of 3-methoxybutyl
acetate as a potentially exposed or susceptible subpopulation (described in more detail in Section 7).
Consumers are also a potentially exposed or susceptible subpopulation because of their use of
products such as anti-freeze and de-icing products; cleaning and washing agents; dyes/pigments; and
paints and coatings, as shown in Table 3.
Rationale: EPA did not identify hazard effects for this chemical that would make any population
susceptible. EPA expects workers and consumers to have a higher exposure to 3-methoxybutyl
acetate than the general population. Because of the chemical's low-concern hazard properties and
reversibility of the effects, 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 3-methoxybutyl
acetate 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-concern hazard profile and
reversible effects of 3-methoxybutyl acetate provides sufficient evidence to support this proposed
finding. 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 3-methoxybutyl acetate 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).
Rationale: In terms of health hazards, 3-methoxybutyl acetate 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, 3-methoxybutyl acetate is
expected to be water soluble (see Section 3) and not expected to persist (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 3-methoxybutyl acetate is unlikely to partition
into sediment (See Section 3), predicted to biodegrade under aerobic conditions (see Section 6.3), 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.
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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, 3-methoxybutyl acetate would degrade in an
aerobic environment (see Section 6). Together, these factors mean that any exposures to this 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 3-methoxybutyl acetate 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 3-methoxybutyl acetate 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 3-methoxybutyl acetate and related potential
exposures.
Rationale: EPA evaluated the conditions of use of 3-methoxybutyl acetate (see Section 5 and
Appendix A) and found it to have a broad range of conditions of use. EPA expects that even if the
conditions of use were to expand beyond activities that are currently known, intended and 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 3-methoxybutyl acetate's
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
3-methoxybutyl acetate 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 the 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 3-methoxybutyl acetate 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.
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8.6. The Volume or Significant Changes in Volume of the Chemical
Substance Manufactured or Processed
Approach: EPA evaluated the current production volumes of 3-methoxybutyl acetate (Section 7.1)
and related potential exposures (Section 7.2 through 7.4).
Rationale: EPA used reasonably available information on production volume (see Appendix A) in
considering potential risk. It is possible that designation of 3-methoxybutyl acetate as a low-priority
substance could result in increased use and higher production volumes. EPA expects, however, that
any changes in 3-methoxybutyl acetate's production volume would not alter the Agency's assessment
of low concern given the chemical's low-hazard profile. EPA bases this expectation on 3-
methoxybutyl acetate's consistently low-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 this 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 level of
exposures, 3-methoxybutyl acetate 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 3-methoxybutyl acetate 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 3-methoxybutyl acetate 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 lb. per site per year. According to the 2016 CDR database, 1 company
manufactured or imported 3-methoxybutyl acetate at 1 site for reporting year 2015. Individual
production volumes were withheld, but may be available in later releases of the 2016 CDR.
Table A. 1 presents the historic production volume of 3-methoxybutyl acetate from the CDR
(previously known as the Inventory Update Rule, or IUR) from 1986-2015. Prior to 1994, 3-
methoxybutyl acetate 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
1994, 1998 and 2002 reporting years, aggregate production volume for 3-methoxybutyl acetate was
between 10,000 and 500,000 lbs., and in 2006 and 2011 aggregate production volume was less than
500,000 lbs. Since 2012, aggregate production volume has fallen with volumes reported at less than
100,000 lbs. with some years below 25,000 lbs.
Table A.1:1986-2015 National Production Volume Data for 3-Methoxybutyl Acetate (Non-Confidential Production
Volume in Pounds)
1986
1990
1994
1998
2002
2006
2011
2012
2013
2014
2015
NDR
NDR
10 K
500 K
10 K -
500 K
10 K -
500 K
< 500 K
100K-
<500 K
25K - <
100K
<
25K
25K - <
100K
< 25 K
Source(s):
EPA (2018a; 2017b; 2006; 2002)
Note(s):
K = Thousand; M = IV
lillion; NDR
= No data reported
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A.2. Uses
A.2.1 Methods for Uses
Section A.2 provides a list of known uses of 3-methoxybutyl acetate, organized by category of use.
To compile the uses, EPA searched publicly available databases listed in Table A.2 and conducted
additional Google 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 3-Methoxybutyl Acetate
Title
Author and Year
Search Term(s)
Found Use
Information?1
Sources searched for all use reports
California Links to
Pesticides Data
California Dept of Pesticide
Regulation (2013)
4435-53-4
No
Canada Chemicals
Management Plan
information sheets
Government of Canada
(2018)
3-methoxybutyl acetate
No
Chemical and Product
Categories (CPCat)
CPCat (2019)
4435-53-4
Yes
ChemView2
EPA (2018a)
4435-53-4
Yes
Children's Safe Product
Act Reported Data
Washington State Dept. of
Ecology (2018)
4435-53-4
No
Consumer Product
Information Database
(CPID)
DeLima Associates (2018)
4435-53-4
No
Danish surveys on
chemicals in consumer
products
Danish EPA (2018)
N/A, There is no search, but report
titles were checked for possible
information on the chemical
Yes
Datamyne
Descartes Datamyne
(2018)
3-methoxybutyl acetate
No
DrugBank
DrugBank (2018)
3-methoxybutyl acetate
No
European Chemicals
Agency (ECHA)
Registration Dossier
ECHA (2018b)
4435-53-4
Yes
eChemPortal2
OECD (2018)
4435-53-4
No
Envirofacts2
EPA (2018b)
4435-53-4
No
Functional Use Database
(FUse)
EPA (2017a)
4435-53-4
No
Kirk-Othmer Encyclopedia
of Chemical Technology
Kirk-Othmer (2006)
3-methoxybutyl acetate
No
Non-Confidential 2016
Chemical Data Reporting
(CDR)
EPA (2017b)
4435-53-4
Yes
PubChem Compound
Kimetal. (2016)
4435-53-4
Yes
Safer Chemical Ingredients
List (SCIL)
EPA (2018d)
4435-53-4
Yes
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Table A.2: Sources Searched for Uses of 3-Methoxybutyl Acetate
Title
Author and Year
Search Term(s)
Found Use
Information?1
Synapse Information
Resources2
Synapse Information
Resources (2009)
3-methoxybutyl acetate
Yes
Resource Conservation
and Recovery Act (RCRA)
EPA (2018c)
3-methoxybutyl acetate; butoxyl;
acetate
No
Scorecard: The Pollution
Information Site
GoodGuide (2011)
4435-53-4
No
Skin Deep Cosmetics
Database
EWG (2018)
4435-53-4
No
Toxics Release Inventory
(TRI)
EPA (2018e)
4435-53-4
No
TOXNET2
NLM (2018)
4435-53-4
No
Ullmann's Encyclopedia of
Industrial Chemistry
Ullmann's (2000)
3-methoxybutyl acetate
No
Additional sources identified from reasonably available information
Celanese Corporation
Celanese Corporation
(2011)
Incidentally identified while
researching details of this chemical's
uses and products.
Yes
Danish Technological
Institute
Svendsen etal. (2004)
Henkel Corporation
Henkel Corporation (2013)
Mimaki Engineering
Company, Ltd.
Mimaki Engineering Co.
Ltd (2008)
New Jersey Dept. of
Health
New Jersey Department of
Health (2009)
Substances in
Preparations in Nordic
Countries (SPIN)
SPIN (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 1,113 patents referencing
"3-methoxybutyl acetate" (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 3-methoxybutyl acetate were not included in
Table A.3. Note that the uses in Table A.3 that are covered under TSCA are included in Section 5,
Table 3 of this document.
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A.2.2 Uses of 3-Methoxybutyl Acetate
Table A.3: Uses of 3-Methoxybutyl Acetate |
Use or Process
Expected Users
Description of Use and References
TSCA Conditions of Use: Industrial Uses
SPIN (2018a); SPIN (2018b)
Construction
Industrial
SPIN identifies use of 3-methoxybutyl acetate in construction of buildings and specialized construction activities in
Denmark as recently as 2015. 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 industrial due to inclusion in the SPIN Industry National and Industrial (NACE) databases.
SPIN (2018a); ECHA (2018c)
Manufacture of
chemicals and
chemical products
Industrial
SPIN identifies use of 3-methoxybutyl acetate in the manufacture of chemicals and chemical products in Nordic
countries as recently as 2004. The ECHA registration dossier identifies use of 3-methoxybutyl acetate in the
manufacture of bulk, large-scale chemicals and the manufacture of fine chemicals. 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 industrial due to inclusion in the SPIN Industrial (NACE) database and inclusion in ECHA's uses
at industrial sites.
Manufacture of
fabricated metal
product, except
machinery and
equipment
Industrial
SPIN (2018a); SPIN (2018b)
SPIN identifies use of 3-methoxybutyl acetate in the manufacture of fabricated metal products in multiple Nordic
countries as recently as 2016. 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 industrial due to inclusion in the SPIN Industry National and Industrial (NACE) databases.
SPIN (2018a)
Manufacture of
furniture
Industrial
SPIN identifies use of 3-methoxybutyl acetate in the manufacture of furniture in Nordic countries as recently as 2007.
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 industrial due to inclusion in the SPIN Industrial (NACE) database.
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Table A.3: Uses of 3-Methoxybutyl Acetate
Use or Process
Expected Users
Description of Use and References
Manufacture of motor
vehicles, trailers,
semi-trailers, and
other transport
equipment
Industrial
SPIN (2018a)
SPIN identifies use of 3-methoxybutyl acetate in the manufacture of motor vehicles and other transportation
equipment in Nordic countries as recently as 2015. 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 industrial due to inclusion in the SPIN Industrial (NACE) database.
SPIN (2018a)
Manufacture, repair,
and installation of
machinery and
equipment
Industrial
SPIN identifies use of 3-methoxybutyl acetate in the manufacture, repair, and installation of machinery and
equipment in Nordic countries as recently as 2011. 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 industrial due to inclusion in the SPIN Industrial (NACE) database.
SPIN (2018a); SPIN (2018b)
Wholesale and retail
trade and repair of
motor vehicles and
motorcycles
Industrial
SPIN identifies use of 3-methoxybutyl acetate in wholesale and retail trade and repair of motor vehicles and
motorcycles and in automotive painting in multiple Nordic countries as recently as 2016. 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 industrial due to inclusion in the SPIN Industry National and Industrial (NACE) databases.
TSCA Conditions of Use: Personal Care Products
Svendsen etal. (2004)
Toothbrushes
Consumer
A report by the Danish Technological Institute identified use of 3-methoxybutyl acetate in toothbrushes. No further
information about this use could be found and it is unknown whether this is an ongoing use in the United States. No
current products containing 3-methoxybutyl acetate could be found.
This report is a survey of chemical substances found in consumer products; therefore, the expected users are
consumer.
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Table A.3: Uses of 3-Methoxybutyl Acetate |
Use or Process
Expected Users
Description of Use and References
TSCA Conditions of Use: Miscellaneous
SPIN (2018d)
Absorbents and
adsorbents
Industrial, commercial,
consumer uses
SPIN identifies use of 3-methoxybutyl acetate in absorbents and adsorbents in Finland as recently as 2002. 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 assumed to be industrial, commercial, and consumer.
SPIN (2018d); ECHA (2018a); Henkel Corporation (2013); Celanese Corporation (2011)
Adhesives, binding
agents
Consumer, unknown
Celanese Corporation identifies use of 3-methoxybutyl acetate as a solvent in isocyanate and epoxy containing
systems. The Henkel Corporation provides a SDS for an adhesive product that contains 3-methoxybutyl acetate.
SPIN reports use of 3-methoxybutyl acetate in adhesives, binding agents, binding materials, and adhesives based
on organic thinners in multiple Nordic countries as recently as 2015. The ECHA registration dossier also identifies 3-
methoxybutyl acetate as an ingredient in adhesives and sealants in European countries. 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 due to ECHA's inclusion in consumer uses. Other expected users are unknown, due
to the limited availability of information.
ECHA (2018a)
Anti-freeze and de-
icing products
Consumer
The ECHA registration dossier identifies use of 3-methoxybutyl acetate in anti-freeze and de-icing products in
European countries. 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 due to ECHA's inclusion in consumer uses.
SPIN (2018d)
Cleaning/washing
agents
Unknown
SPIN identifies use of 3-methoxybutyl acetate in cleaning/washing agents in multiple Nordic countries as recently as
2015. 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 unknown, due to the limited availability of information.
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Table A.3: Uses of 3-Methoxybutyl Acetate
Use or Process
Expected Users
Description of Use and References
SPIN (2018d); SPIN (2018c); ECHA (2018a)
Coloring agents
Consumer, unknown
SPIN identifies use of 3-methoxybutyl acetate in coloring agents, dyestuff, pigments, and dyeing auxiliaries in
Finland as recently as 2003. The ECHA registration dossier identifies use of 3-methoxybutyl acetate in textile dyes
and finishing and impregnation 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 due to ECHA's inclusion in consumer uses. Other expected users are unknown, due
to the limited availability of information.
SPIN (2018d); ECHA (2018a)
Fillers
Consumer, unknown
SPIN identifies use of 3-methoxybutyl acetate in fillers and insulation materials in multiple Nordic countries as
recently as 2014. The ECHA registration dossier identifies use of 3-methoxybutyl acetate in fillers, putties, plasters
and modeling clay. 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 due to ECHA's inclusion in consumer uses. Other expected users are unknown, due
to the limited availability of information.
SPIN (2018d)
Fixing agents
Industrial, commercial,
consumer uses
SPIN identifies use of 3-methoxybutyl acetate in fixing agents in Finland as recently as 2004. 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 assumed to be industrial, commercial, and consumer.
Synapse Information Resources (2009)
Food-contact coatings
Industrial/
commercial/
consumer uses
Synapse Information Resources reports use of 3-methoxybutyl acetate in food-contact coatings. 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 assumed to be industrial, commercial, and consumer.
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Table A.3: Uses of 3-Methoxybutyl Acetate
Use or Process
Expected Users
Description of Use and References
SPIN (2018d); CPCat (2019)
Odor agents
Industrial/
commercial/
consumer uses
SPIN identifies use of 3-methoxybutyl acetate in odor agents The International Fragrance Association (IFRA) in
Finland as recently as 2012. 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 unknown, due to the limited availability of information.
New Jersey Department of Health (2009); SPIN (2018d); SPIN (2018c); ECHA (2018a); Synapse Information
Resources (2009); Celanese Corporation (2018)
Paints, lacquers,
thinners, and
varnishes
Consumer, unknown
The New Jersey Department of Health identifies use of 3-methoxybutyl acetate as a solvent in the paint and lacquer
industry. Celanese Corporation sells a product, Butoxyl, which is used in brush-applied paints. SPIN identifies use of
3-methoxybutyl acetate in paints, lacquers, primers, diluents, thinners, hardeners, and varnishes in multiple Nordic
countries as recently as 2016. The ECHA registration dossier also identifies 3-methoxybutyl acetate as an ingredient
in coatings and paints, finger paints, thinners, and paint removers. Synapse identifies use of 3-methoxybutyl acetate
in urethane coatings, and acrylic, and nitrocellulose. 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 due to ECHA's inclusion in consumer uses. Other expected users are unknown, due
to the limited availability of information.
ECHA (2018a)
Polishes and wax
blends
Consumer
The ECHA registration dossier identifies use of 3-methoxybutyl acetate in polishes and wax blends in European
countries.
Expected users are consumer due to ECHA's inclusion in consumer uses.
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Table A.3: Uses of 3-Methoxybutyl Acetate
Use or Process
Expected Users
Description of Use and References
SPIN (2018c); SPIN (2018a); SPIN (2018b); Mimaki Engineering Co. Ltd (2008)
Printing inks
Industrial, unknown
Mimaki Engineering identifies use of 3-methoxybutyl acetate as a solvent pigment ink in inks for ink jet printers. SPIN
identifies use of 3-methoxybutyl acetate in printing inks, serigraphy inks, printing and reproduction of recorded media
in multiple Nordic countries as recently as 2010. 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 industrial due to inclusion in the SPIN Industry National and Industrial (NACE) databases. Other
expected users are unknown, due to the limited availability of information.
SPIN (2018d); SPIN (2018c)
Process regulators
Unknown
SPIN identifies use of 3-methoxybutyl acetate in process regulators, stabilizers, and inhibitors in multiple Nordic
countries as recently as 2012. 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 unknown, due to the limited availability of information.
SPIN (2018d); CPCat (2019)
Reprographic agents
Industrial
SPIN identifies use of 3-methoxybutyl acetate in reprographic agents (photographic) in multiple Nordic countries as
recently as 2010. 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 assumed to be industrial.
EPA (2017b); SPIN (2018d); Celanese Corporation (2018); Celanese Corporation (2015)
Solvents
Industrial
CDR reports one domestic producer of 3-methoxybutyl acetate (Celanese Corporation), however, no use information
was reported. Celanese Corporation sells a product in the Americas with a 99.5 percent concentration of 3-
methoxybutyl acetate (Butoxyl), the primary use of which is as a solvent. SPIN identifies use of 3-methoxybutyl
acetate in solvents in multiple Nordic countries as recently as 2015. 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 assumed to be industrial.
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Table A.3: Uses of 3-Methoxybutyl Acetate
Use or Process
Expected Users
Description of Use and References
SPIN (2018d); CPCat (2019); SPIN (2018b); ECHA (2018a); Synapse Information Resources (2009)
Surface treatment
Consumer, industrial
SPIN identifies use of 3-methoxybutyl acetate in surface treatment (fluid property modulators and protection
lacquers) in multiple Nordic countries as recently as 2015. The ECHA registration dossier also identifies use of 3-
methoxybutyl acetate in non-metal surface treatment products. Synapse Information Resources reports use of 3-
methoxybutyl acetate in epoxy and aminoalkyl resins. 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 due to ECHA's inclusion in consumer uses, and industrial due to inclusion in the SPIN
Industry National database.
Children's Products
No uses in products intended for children were identified, however, there is a possible consumer use in toothbrushes, which could be used by children.
Recycling and Disposal
In the 2016 CDR, one facility withheld recycling information (EPA 2017b).
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A.3 References
Amadis Chemical Co. Ltd. (n.d.). 5-methoxyhexanoate. Retrieved from
http://www.amadischem.eom/en/l 88625 .htm
California Dept of Pesticide Regulation. (2013). DPR Databases. Retrieved from
https: //www. cdpr. ca. gov/dprdatabase .htm
Celanese Corporation. (2011). Product Description and Handling Guide Butoxyl. Retrieved from
https://www.celanese.com/-/.../Product%20Descriptions/Product Description and Ha..
Celanese Corporation. (2015). Safety Data Sheet. Retrieved from http s: //www. ce lane se. com/intermediate -
chemistrv/products/Butoxvl/data-sheets.aspx
Celanese Corporation. (2018). Butoxyl. Retrieved from https://www.celanese.com/intermediate-
chemistrv/products/Butoxvl .aspx
Danish EPA. (2018). Danish surveys on chemicals in consumer products. Retrieved from
https://eng.mst.dk/chemicals/chemicals-in-products/consumers-consumer-products/danish-
survevs-on-consumer-products/
DeLima Associates. (2018). Consumer Product Information Database. Retrieved from
https: //www. whatsinproducts. com/
Descartes Datamyne. (2018). Descartes Datamyne. Retrieved from
https://www.descartes.com/datamvne
Dionisio, K. L., Frame, A. M., Goldsmith, M.-R., Wambaugh, J. F., Liddell, A., Cathey, T., . . . Judson,
R. S. (2015). Exploring consumer exposure pathways and patterns of use for chemicals in the
environment. Toxicology! Reports, 2, 228-237. doi:http://dx.doi.org/10.1016/i.toxrep.2014.12.009
DrugBank. (2018). The DrugBank database. Retrieved from https://www.drugbank.ca/
European Chemicals Agency (ECHA). (2018a). Consumer uses. Retrieved from
https://echa.europa.eu/registration-dossier/-/registered-dossier/5167/3/1/6
European Chemicals Agency (ECHA). (2018b). General information. Retrieved from
https://echa.europa.eu/registration-dossier/-/registered-dossier/5167/1
European Chemicals Agency (ECHA). (2018c). Uses at industrial sites. Retrieved from
https://echa.europa.eu/registration-dossier/-/registered-dossier/5167/3/1/4
EWG. (2018). Skin Deep Cosmetics Database. Retrieved from
https: //www. ewg. org/skindeep/#. W 3 7HAs5 KiM9
GoodGuide. (2011). Scorecard: The Pollution Information Site. Retrieved from
http://scorecard.goodguide.com/chemical-profiles/index.tcl
Government of Canada. (2018). Chemical Substances: Services and Information. Retrieved from
https://www.canada.ca/en/health-canada/services/chemical-substances.html
XI
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Henkel Corporation. (2013). Safety Data Sheet. Retrieved from https://www. rshughe s.com/wm/p/wm-
asis/420505a3362f593bc39clfcc73fef9f53dc2a935.pdf?uf=
Kim, S., Thiessen, P. A., Bolton, E. E., Chen, J., Fu, G., Gindulyte, A., . . . Bryant, S. H. (2016).
PubChem Substance and Compound databases. Nucleic Acids Research, -/-/(Database issue),
D 1202-D 1213. doi: 10.1093/nar/gkv951
Kirk-Othmer. (2006). Kirk-Othmer Encyclopedia of Chemical Technology.
Mimaki Engineering Co. Ltd. (2008). Material Safety Data Sheets HS Ink LightMagenta. Retrieved from
https://\\\\\\.midstatclitho.nct/\/vspfilcs/MSDS/MIM AKIHSHS-AlnkLightMagenta.pdf
New Jersey Department of Health. (2009). Right to Know Hazardous Substance Fact Sheet.
Organisation for Economic Cooperation and Development (OECD). (2018). eChemPortal: Global Portal
to Information on Chemical Substances. Retrieved from
https: //www .echemportal. org/cchemportal/index.action
Sherlock, Scott (2019). 3-Methoxybutyl acetate 4435-53-4. Email to Phil Brondsema, Celanese. June 13.
Substances in Preparations in Nordic Countries (SPIN). (2018a). Industrial Use (NACE). Retrieved from
http://www.spin2000.net/spinmvphp/
Substances in Preparations in Nordic Countries (SPIN). (2018b). Industry National. Retrieved from
http://www.spin2000.net/spinmvphp/
Substances in Preparations in Nordic Countries (SPIN). (2018c). Use Category National. Retrieved from
http://www.spin2000.net/spinmyphp/
Substances in Preparations in Nordic Countries (SPIN). (2018d). Use Category UC62. Retrieved from
http://www.spin2000.eu/spinmvphp/
Svendsen et al. (2004). Survey of chemical substances in toothbrushes. Retrieved from:
https://eng.mst.dk/media/mst/69125/42.pdf
Synapse Information Resources. (2009). Specialty Chemicals Source Book. Fourth Edition. Volume 1.
The International Fragrance Association (IFRA). (2016). IFRA Volume of Use Survey 2016:
Transparency List. Retrieved from http://admin-
ifra.alligence.com/Upload/Docs/Transparencv%201ist.pdf
U.S. Environmental Protection Agency (EPA). (2002). 1986-2002 Historical IUR Data. Retrieved from
Excel File
U.S. Environmental Protection Agency (EPA). (2006). 2006 IUR Public Database.
U.S. Environmental Protection Agency (EPA). (2017a). Functional Use Database (FUse). Retrieved
from: https://catalog.data.gov/dataset/functional-use-database-fuse
U.S. Environmental Protection Agency (EPA). (2017b). Non-Confidential 2016 Chemical Data Reporting
(CDR). Retrieved from https://www.epa. gov/chemical-data-reporting
XII
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U.S. Environmental Protection Agency (EPA). (2018a). ChemView. Retrieved from
https: //chemvie w .epa. gov/chemview
U.S. Environmental Protection Agency (EPA). (2018b). Envirofacts Multisystem Search. Retrieved
from 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). Retrieved from
https://iaspub.epa.gov/enviro/brs codes v2.waste lookup
U.S. Environmental Protection Agency (EPA). (2018d). Safer Chemical Ingredients List. Retrieved from
https://www.epa.gov/saferchoice/safer-ingredients
U.S. Environmental Protection Agency (EPA). (2018e). TRI-Listed Chemicals. Retrieved from
https://www.epa.gov/toxics-release-inventorv-tri-program/tri-listed-chemicals
U.S. National Library of Medicine (NLM). (2018). TOXNETฎ (TOXicology DataNETwork). Retrieved
from https://toxnet.nlm.nih.gov/
U.S. Patent and Trademark Office (USPTO). (2018). USPTO Patent Full-Text and Image Database.
Retrieved from http: //patft .uspto. gov/netacgi/nph-
Parser?Sectl=PT02&Sect2=HIT0FF&p=l&u=%2Fnetahtml%2FPT0%2Fsearch-
bool ,html&r=0&f=S&l=5 O&TERM 1=3 -
methoxvbutvl+acetate&FIELD l=&co l=AND&TERM2=&FIELD2=&d=PTXT
Ullmann's. (2000). ULLMANN'S Encyclopedia of Industrial Chemistry.
Washington State Dept. of Ecology. (2018). Children's Safe Product Act Reported Data. Retrieved from
https ://fortress ,wa. gov/ecv/cspareporting/
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Appendix B: Hazard Characterization
Table B.1: Human Health Hazard
Acute Mammalian Toxicity
Source
Exposure Route
Species & strain (if
Duration
Doses and replicate
Effect
Study Details I
available)
number
4839296
Oral
Mice
Single dose
Doses: 100, 500, and
LDso > 1000 mg/kg
Methods: I
1000 mg/kg
Substance
Replicates: 2 per
reported as
dose
CASRN 4435-
53-4
Purity not
reported
Pre-dates GLP
compliant
5093123
Oral (gavage)
Wistar Rats
Single dose, observed
Dose: 2000 mg/kg
LD50 > 2000 mg/kg
Methods: I
for 14 days
Replicates: 5 per sex
Substance
reported as
CASRN 2517-
43-3
Purity: 99.5%
OECD Guideline
401
GLP compliant
5093162
Oral (gavage)
Albino Mice
Single dose, observed
Doses: 1000, 2000,
LD50: 3000 mg/kg, CI
Methods: I
for 6 days
4000 and 8000 mg/kg
Replicates: 3 per
dose
between 2400 and
3700 mg/kg
Substance
reported as
CASRN 2517-
43-3
Purity: 99.8%
Not GLP
compliant
Mortality Results:
1/3 animal in
2000 mg/kg
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2/3 animals in
4000 mg/kg
3/3 animals in
8000 mg/kg
Repeated Dose Toxicity
Source
Exposure Route
Species & strain (if
available)
Duration
Doses and replicate
number
Effect
Study Details
4839287
Oral (gavage)
Crj: CD IGS Rats
28 days
Doses: 0,100, 300,
and 1000 mg/kg-day
Replicates: 5 per sex
per group
NOAEL: 300 mg/kg-
day
LOAEL: 1000 mg/kg-
day; based on
abnormal respiration
Methods:
Substance
reported as
CASRN 4435-
53-4
Purity: 99.8%
OECD Guideline
407
GLP compliant
Results:
LOAEL of 1000
mg/kg-day based
on abnormal
respiration in
males, also
increased and
transient
salivation
observed
Developmental Toxicity
Source
Exposure Route
Species & Strain (if
available)
Duration
Doses and replicate
number
Effect
Study Details
4839284
Oral (gavage)
Wistar Rats
Gestational Days 7-16
Doses: 0 and 1000
mg/kg-day
Replicates: 20
pregnant females per
group
NOAEL: 1000 mg/kg-
day
Methods:
Substance
reported as
CASRN 4435-
53-4
Purity: 99.7%
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OECD Guideline
414
GLP compliant
Results:
No maternal or
fetal toxicity
observed
Cancer
Source
Effect
Study Details
Oncologic v8.0
OncoLogic currently
has no assessment
criteria regarding
methoxy acetates
Structure could not be evaluated by Oncologic
ISS v2.4ซ
Negative (Estimated)
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 aldehyde formed upon hydrolysis)
VEGA 1.1.444
3-Methoxybutyl
acetate was
processed through all
4 models. All of the
models predicted it to
be non-carcinogenic
with low-moderate
reliability.
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: Predicted to be Non-carcinogenic with low reliability (3-Methoxybutyl acetate lies outside of the
applicability domain (AD) of the model)
ISS 1.0.2: Predicted to be Non-carcinogenic with low reliability (3-Methoxybutyl acetate lies outside of the AD)
43 Carcinogenicity alerts by ISS profiler comprises 55 structural alerts for genotoxic and non-genotoxic carcinogenicity. The 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 andBenigniR et al. (2013) Chew
Rev. 113: 2940-2957.
44 VEGA 1.1.4 contains 4 different models to facilitate an in silico assessment of carcinogenicity potential. The models are summarized in Golbamaki et al. (2016) J Environ Sci and Health Part C
http://dx.doi.orq/10.1080/10590501.2016.1166879 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).
IRFMN/Antares 1.0.0 and IRFMN/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.
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Overall, 3-
IRFMN/Antares 1.0.0: Predicted to be Possible Non-carcinogen with low reliability (3-MethoxybutyI acetate lies outside
Methoxybutyl acetate
of the AD)
is expected not to be
IRFMN/ISSCAN-GX 1.0.0: Predicted to be Possible Non-carcinogen with low reliability (3-Methoxybutyl acetate lies
carcinogenic on the
outside of the AD)
basis of the VEGA
predictions.45
Genotoxicity
Source
Test Type &
endpoint
Species & strain (if
available)
Metabolic activation
Doses and controls
Results
Study Details
4839293,
Gene Mutation (in
Salmonella
With and without
Doses: 0, 4, 20,100,
Negative
Methods:
vitro)
typhimurium strains
TA 1535, 1537, 98,
100, and 1538
500, 5,000 and
10,000 pg/plate
Substance
reported as
CASRN 4435-
53-4
Purity: 99.7%
OECD Guideline
471
GLP compliant
4839292
Chromosomal
Chinese Hamster
With and without
Doses: 0,1.25, 2.5,
Negative
Methods:
aberration (in vitro)
Lung Fibroblasts
5, and 10 mM
Substance
reported as
CASRN 4435-
53-4
Purity: 99.8%
GLP compliant
45 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 considers the other 5 components to provide an overall reliability score - low, moderate or high. EPA has not included low-reliability model results.
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Irritation
Source
Exposure Route
Species & Strain (if
Duration
Doses
Effect
Study Details
available)
5094080
Skin
New Zealand White
4 hour exposure,
Dose: 0.5 mL of
Negative
Methods:
Rabbit
observed for 72 hours
undiluted substance
Replicates: 3 rabbits
Substance
reported as
CASRN 2517-
43-3
Purity: 99.5%
OECD Guideline
404
GLP compliant
Results:
Slight erythema
was observed at
1 hour
All effects were
fully reversed
within 1 day
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4839281
Ocular
New Zealand White
24 hour exposure,
Dose: 0.1 mLof
Moderate
Methods:
Rabbit
observed for 72 hours
undiluted substance
Replicates: 3 rabbits
Substance
reported as
CASRN 4435-
53-4
Purity: 99.7%
OECD Guideline
405
GLP compliant
Results:
Conjunctival
Redness score
was 0.6/3 and
was fully
reversed in 2
days
Chemosis score
was 1-3/4 at 1
hour, was fully
reversed in 1 day
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Table B.2: Environmental Hazard
Aquatic Toxicity: Experimental
Source
Species
Duration
Doses and
replicate
number
Effect
Study Details
4839253
Chaetogammarus
marinus
96 hours
Doses: 0,
32,56,100, 180,
320, 560, and
1000 mg/L
LCso: 128 mg/L
Substance reported as CASRN 4435-53-4
Purity not reported
EPA OPPTS 850.1020
GLP compliance not reported
Aquatic Toxicity: Estimated
Model
Chemical Class
Species
Predicted
Effect Level
Notes
EC0SARv2 (Class:
Esters)
Acute
Freshwater
fish
LCso: 74 mg/L
Estimated using the following experimental input value: water solubility= 4.6E+3 mg/L
ECOSAR v2
(Class: Esters)
Acute
Daphnia
magna
LCso: 170 mg/L
Estimated using the following experimental input value: water solubility= 4.6E+3 mg/L
ECOSAR v2
(Class: Esters)
Acute
Green
algae
EC50: 86 mg/L
Estimated using the following experimental input value: water solubility= 4.6E+3 mg/L
ECOSAR v2
(Class: Esters)
Chronic
Freshwater
fish
6.9 mg/L
Estimated using the following experimental input value: water solubility= 4.6E+3 mg/L
ECOSAR v2
(Class: Esters)
Chronic
Daphnia
magna
160 mg/L
Estimated using the following experimental input value: water solubility= 4.6E+3 mg/L
ECOSAR v2
(Class: Esters)
Chronic
Green
algae
16 mg/L
Estimated using the following experimental input value: water solubility= 4.6E+3 mg/L
Table B.3: Fate
Environmental Fate: Experimental
Source
Endpoint
Duration
Doses and number of
replicates
Results
Study Details
4839258
DOC removal
28 hours
Dose: 30 mg/L
95.5% at day 7
Methods:
Substance reported as CASRN 4435-53-4
Purity: 99.6%
OECD Guideline 301E
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GLP compliant
5094143
Toxicity to
microorganisms
3 hours
Doses: 10 to 1000 mg/L
ECso > 1000
mg/L
Methods:
Substance reported as CASRN 2517-43-3
Purity: 98.8%
OECD Guideline 209
GLP compliant
Environmental Fate: Modelled
Model
Data Type
Endpoint
Predicted Endpoint
Notes
EPISuite
v.4.11
Estimated
BAF
1.29
EPISuite
v.4.11
Estimated
BCF
2.15
Regression on eq
EPISuite
v. 4.11
(BIOWIN
7)
Estimated
Anaerobic
biodegradation
Not predicted to biodegrade
quickly under anaerobic
conditions
Predicted probability of 0.3981. Fragment representation is valid.
Fast degradation is defined as predicted probability >0.5.
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References:
EC HA (European Chemicals Agency). (1930). 3-Methoxybutyl acetate: Acute Toxicity: oral: 001 Weight
of evidence | Experimental result. https://echa.europa.eu/registration-dossier/-/registered-
dossier/5167/7/3/2
EC HA (European Chemicals Agency). (1966). 3-Methoxybutan-l-ol: Acute toxicity: oral: 002 supporting
| Experimental result. https://www.echa.europa.eu/web/guest/registration-dossier/-/registered-
dossier/515 5/7/3/2/?documentUUID=f5e 1 ccb4-d94f-4de0-8b 16-57de5056833d
EC HA (European Chemicals Agency). (1983). 3-Methoxybutyl acetate: Short-term toxicity to aquatic
invertebrates: 002 Supporting | Experimental result, https://echa.europa.eu/registration-dossier/-
/registered-dossier/5167/6/2/4/?documentUUID=09ccea20-3a88-4af9-afc3-2ae446b3dcd7
EC HA (European Chemicals Agency). (1991a). 3-Methoxybutan-l-ol: Acute toxicity: oral: 001 Key |
Experimental result. https://www.echa.europa.eu/web/guest/registration-dossier/-/registered-
dossier/5155/7/3/2
EC HA (European Chemicals Agency). (1991b). 3-Methoxybutan-l-ol: Skin irritation/corrosion: 001 key |
Experimental result. https://www.echa.europa.eu/web/guest/registration-dossier/-/registered-
dossier/515 5/7/4/2
EC HA (European Chemicals Agency). (1992). 3-Methoxybutyl acetate: Genetic toxicity: in vitro: 001
Key | Experimental result. https://echa.europa.eu/registration-dossier/-/registered-
dossier/5167/7/7/2
EC HA (European Chemicals Agency). (1995). 3-Methoxybutyl acetate: Biodegradation in water:
screening tests: 001 Key | Experimental result, https://echa.europa.eu/registration-dossier/-
/registered-dossier/5167/5/3/2/?documentUUID=16defc33-07c4-40cc-bc32-b8ec343f4e38
EC HA (European Chemicals Agency). (1997a). 3-Methoxybutyl acetate: Eye irritation: 001 Key |
Experimental result. https://echa.europa.eu/registration-dossier/-/registered-dossier/5167/7/4/3
EC HA (European Chemicals Agency). (1997b). Registration dossier: 3-Methoxybutyl acetate:
Developmental toxicity / teratogenicity: 002 Weight of evidence | Experimental result. Helsinki,
Finland. https://echa.europa.eu/registration-dossier/-/registered-
dossier/5167/7/9/3/?documentUUID=3dc88a4a-l 144-4409-b516-adalaf553312
EC HA (European Chemicals Agency). (2009). 3-Methoxybutan-l-ol: Toxicity to microorganisms: 001
key | Experimental result. https://www.echa.europa.eu/web/guest/registration-dossier/-/registered-
dossier/5155/6/2/8/?documentUUID=823b32f4-c0ea-44b4-bfc0-bl70f483253b
J-CHECK (Japanese CHEmical Collaborative Knowledge database). (2004). #67: Repeated dose toxicity:
oral: subacute [CASRN 4435-53-4], Available online at
http://www.safe.nite.go.jp/icheck/template.action?ano=2669 l&mno=2-0739&cno=4435-53-
4&request locale=en (accessed October 1, 2018).
J-CHECK (Japanese CHEmical Collaborative Knowledge database). (2010). #70: Genetic toxicity in
vitro: chromosome aberration: in vitro mammalian chromosome aberration test [CASRN 4435-
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53-4], Available online at http://www.safe.nite.go.jp/icheck/template.action?ano=26753&mno=2-
0739&cno=4435-53-4&reauest locale=en
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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 3-methoxybutyl acetate. Search outcomes and reference details are
provided on the candidate's HERO46 project page.
EPA created a fit-for-purpose process to transparently document the literature search and review4 7 of
available hazard and fate information for low-priority substance (LPS) candidates. References from peer-
reviewed primary sources, grey sources,48 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 CI.
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, 3-methoxybutyl acetate, the following analog
was used for designation: 3-methoxybutanol (CASRN 2517-43-3). Acetic acid, 2-methoxypropyl ester
(CASRN 70657-70-4) was also considered as an analog but not used for designation. For more details and
The 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.
S Grey literature and additional sources are the broad category of studies not found in standard, peer-reviewed literature database
searches. Hiis 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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justification on the analog, see section 6.1.1. Analogs were used to fill data gaps on endpoints for which
3-methoxybutyl acetate lacked quality data, such as skin irritation, or to add to the weight of scientific
evidence. EPA collected reasonably available information for these endpoints by searching specific grey
literature and other secondary sources, listed on Table C. 1. 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 3-methoxybutyl acetate described above 47
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/jcheck/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 3-methoxybutyl acetate 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 3-methoxybutyl acetate. For grey literature and other
secondary sources, Table C.3 lists the search terms used for 3-methoxybutyl acetate and analogs.
Table C.2: Search Terms Used in Peer-Reviewed Databases
Discipline
Database
Search terms49
Human Health
PubMed
4435-53-4[rn] OR "3-methoxybutyl acetate"[nm] OR "1-Butanol, 3-methoxy-, 1-
acetate"[tw] OR "1-Butanol, 3-methoxy-, acetate"[tw] OR "3-Methoxybutyl
acetate"[tw] OR "Acetic acid, 3-methoxybutyl ester"[tw] OR "Methoxybutyl
acetate, 3-"[tw] OR "Methyl-1,3-butylene glycol acetate"[tw] OR "3-methoxy-1-
butanol, acetate"[tw] OR ("butoxyl"[tw] NOT ("butoxyl radical"[tw] OR "butoxyl
49 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
radicals"[tw] OR "tert-butoxyl radical"[tw] OR "tert-butoxyl radicals"[tw] OR "t-
butoxyl radical"[tw] OR "t-butoxyl radicals"[tw]))
Toxline
(4435-53-4 [rn] OR "1-butanol 3-methoxy-1-acetate" OR "1-butanol 3-methoxy-
acetate" OR "3-methoxybutyl acetate" OR "acetic acid 3-methoxybutyl ester" OR
"methoxybutyl acetate 3-" OR "methyl-1 3-butylene glycol acetate" OR "3-
methoxy-1-butanol acetate" OR ("butoxyl" NOT "butoxyl radical")) AND (
ANEUPL [org] OR BIOSIS [org] OR CIS [org] OR DART [org] OR EMIC [org] OR
EPIDEM [org] OR FEDRIP [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
4435-53-4[rn] AND tscats[org]
WOS
TS=("4435-53-4" OR "1-Butanol, 3-methoxy-, 1-acetate" OR"1-Butanol, 3-
methoxy-, acetate" OR "3-Methoxybutyl acetate" OR "Acetic acid, 3-methoxybutyl
ester" OR "Methoxybutyl acetate, 3-" OR "Methyl-1,3-butylene glycol acetate" OR
"3-methoxy-1-butanol, acetate") OR (TS="butoxyl" NOT TS=("butoxyl radical" OR
"butoxyl radicals"))
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
"4435-53-4" OR "1-Butanol, 3-methoxy-, 1-acetate" OR "1-Butanol, 3-methoxy-,
acetate" OR "3-Methoxybutyl acetate" OR "Acetic acid, 3-methoxybutyl ester" OR
"Methoxybutyl acetate, 3-" OR "Methyl-1,3-butylene glycol acetate" OR "3-
methoxy-1-butanol, acetate" OR "butoxyl"
Fate
WOS
Same as human health strategy synonyms only
Table C.3: Search Terms Used in Grey Literature and Additional Sources
Chemical
Search terms
3-Methoxybutyl
Acetate
Searched as a string or individually depending on source: "4435-53-4" OR "1-Butanol, 3-methoxy-, 1-
acetate" OR "1-Butanol, 3-methoxy-, acetate" OR "3-Methoxybutyl acetate" OR "Acetic acid, 3-
methoxybutyl ester" OR "Butoxyl" OR "Methoxybutyl acetate, 3-" OR "Methyl-1,3-butylene glycol acetate"
Analogs searched
acetic acid, 2-methoxypropyl ester (CASRN 70657-70-4); 3-methoxybutanol (CASRN 2517-43-3)
After the search terms were applied, more than 290 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.47 Of these, 12 references were
included for data evaluation and used to support the designation of 3-methoxybutyl acetate 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 3-methoxybutyl acetate. The excluded references are organized by discipline
XXVI
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(human health hazard, environmental hazard, and fate), presented along with a rationale based on
exclusion criteria. The criteria47 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 3-methoxybutyl acetate, EPA excluded a total of 173 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 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.4: Off-Topic References Excluded at Title/Abstract Screening for Human Health Hazard
1 Reference excluded (HERO ID) because the reference did NOT contain information needs50 relevant to human health 1
hazard
84538
4854457
4376428
4854502
4851240
4854543
2871084
4854477
4851219
4854522
525496
4854458
4770843
4854503
4851255
4854544
2875597
4854478
4851220
4854523
611384
4854459
4834290
4854504
4851272
4854545
2881863
4854479
4851221
4854524
611386
4854460
4851206
4854505
4851281
4854546
2910708
4854480
4851223
4854525
666559
4854461
4851207
4854506
4851287
4854548
3244746
4854481
4851224
4854526
837554
4854462
4851208
4854508
4851315
4854549
3378876
4854482
4851225
4854527
891128
4854463
4851209
4854509
4854454
4854550
3379632
4854483
4851226
4854528
1016309
4854465
4851210
4854510
4854455
4854551
3390578
4854484
4851227
4854529
1182099
4854467
4851211
4854511
4854456
4854553
3407270
4854485
4851228
4854530
1205739
4854468
4851212
4854512
4854532
4854556
3829850
4854486
4851229
4854531
1468551
4854469
4851213
4854514
4854533
4854558
3865611
4854487
4233057
4854590
1613340
4854470
4851214
4854515
4854534
4854559
4071919
4854489
4318601
4854591
2123950
4854471
4851215
4854516
4854535
4854560
4144981
4854490
4348711
4854592
2713362
4854472
4851216
4854517
4854536
4854561
4181676
4854491
4348712
4854595
2807532
4854473
4851217
4854520
4854537
4854562
4182379
4854495
4348713
4854496
2823859
4854475
4851218
4854521
4854539
4854588
4854499
4854501
Reference excluded (HERO ID) because the reference primarily contained in silico data
N/A.
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
information pertaining to a low-
priority substance candidate?
No
2771396
4839288
4839294
4851335
50 The information needs for human health hazard includes a list of study characteristics pertaining to the study population/test
organism, types of exposures and routes, use 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.
XXVII
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4839280
4839285
4839286
What type of source is this
reference?
Review article or book chapter that
contains only citations to primary
literature sources
N/A.
What kind of evidence does this
reference primarily contain?
In silico studies that DO NOT
contain experimental verification
N/A.
The following question apply to HUMAN evidence only
Does the reference report an
exposure route that is or is
presumed to be by an inhalation,
oral, or dermal route?
No
N/A.
Does the reference report both test
substance exposure(s) AND related
health outcome(s)?
No
N/A.
If the reference reports an exposure
to a chemical mixture, are
measures of the test substance or
related metabolite(s) reported
independently of other chemicals?
No
N/A.
Note: If the paper does not pertain
to mixtures, choose "Not
Applicable".
No
N/A.
The following question apply to ANIMAL evidence only
Does the reference report an
exposure route that is by inhalation,
oral, or dermal route?
No
4839290
Does the reference report both test
substance-related exposure(s) AND
related health outcome(s)?
No
4839285
4839290
4839493
Does the reference report the
duration of exposure?
No
5093624
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
4839493
Does the paper report a negative
control that is a vehicle control or
no treatment control?
No51
4839493
4839493
4839290
4839282
4839285
4839282
5093921
51 Except for acute mammalian toxicity and skin and eye irritation studies, where the use of a negative control may not be
required (e.g., OECD 403 Acute Inhalation Toxicity Guidelines).
XXVIII
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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
4839279
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
4839290
For genotoxicity studies only: Does
the study use a positive control?
No
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
did not include information that could
result in a reasonable approximation
of components.
5093729
5093827
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.
5094005
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.
N/A.
XXIX
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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).
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).
5093827
5094005
5093625
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.).
4839289
5093625
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.
5094005
5093625
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
4839280
XXX
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***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
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:
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.
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).
N/A.
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
N/A.
XXXI
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***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
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).
C.2.2 Environmental Hazard
For the screening review of this LPS candidate 3-methoxybutyl acetate, EPA excluded a total of 243
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
Reference excluded (HERO ID) because the reference did NOT contain information needs52 relevant to
environmental hazard
84538
4851305
4851243
4854506
4348713
4854468
2875597
4851331
4851273
4854534
525496
4851307
4851244
4854508
4376428
4854469
2881863
4851332
4851275
4854535
611384
4851309
4851246
4854509
4665318
4854470
2910708
4851333
4851276
4854536
611386
4851310
4851247
4854510
4770843
4854471
3244746
4851334
4851277
4854537
666559
4851311
4851248
4854511
4834290
4854472
3378876
4851335
4851278
4854539
837152
4851312
4851249
4854512
4851206
4854473
3379632
4854450
4851280
4854540
837554
4851313
4851250
4854514
4851207
4854475
3390578
4854451
4851281
4854541
891128
4851314
4851251
4854515
4851208
4854477
3400664
4854454
4851282
4854542
1016309
4851315
4851252
4854516
4851209
4854478
3407270
4854455
4851283
4854543
1036343
4851316
4851253
4854517
4851211
4854479
3829850
4854456
4851284
4854544
1182099
4851317
4851254
4854520
4851212
4854480
3865611
4854457
4851286
4854545
1205739
4851318
4851255
4854521
4851213
4854481
4144981
4854458
4851287
4854546
1468551
4851319
4851256
4854522
4851214
4854482
4181676
4854459
4851289
4854548
1613340
4851320
4851257
4854523
4851215
4854483
4182379
4854460
4851290
4854549
1788641
4851321
4851259
4854524
4851216
4854484
4233057
4854461
4851292
4854550
1940095
4851322
4851262
4854525
4851217
4854485
4318601
4854462
4851294
4854551
2123950
4851323
4851263
4854526
4851218
4854486
4326452
4854463
4851295
4854553
2572747
4851324
4851264
4854527
4851219
4854487
4348711
4854465
4851297
4854556
2713362
4851325
4851265
4854528
4851220
4854489
4348712
4854467
4851302
4854558
2807532
4851326
4851266
4854529
4851223
4854490
2849947
4851329
4851271
4854532
2823859
4851327
4851267
4854530
4851224
4854491
2871084
4851330
4851272
4854533
2836016
4851328
4851270
4854531
4851225
4854495
4851226
4854496
4851228
4854497
4854505
4851229
4851230
4851232
4851234
4854559
4854561
4854588
4854591
4854595
52 The information needs for environmental hazard includes a list of study characteristics pertaining to the test organism/species,
type and level of effects, and use 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.
XXXII
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***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
4854499
4854501
4851231
4851233
4851241
4854560
4854562
4854590
4854592
4854498
4854503
4854502
4854504
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 information
No
N/A.
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 hazard data
No
N/A.
presented?
Is this primarily a modeling/simulation study?
Yes
N/A.
[Note: select "No" if experimental verification
was included in the study]
Is environmental hazard data presented for
No
N/A.
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 a mixture
Formulated Product
N/A.
(except for reasonable impurities,
byproducts, and aqueous solutions) or
formulated product?
Does the reference report a duration of
No
N/A.
exposure?
Does the reference report a negative control
No
4839256
that is a vehicle control or no treatment
4839257
control?
Does the reference include endpoints in the
No
N/A.
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:
Test Substance Identity
The test substance identity or 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.
N/A.
Metric 2:
A concurrent negative control group was not included or reported.
4839257
XXXIII
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***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Negative Controls
Metric 3:
Experimental System
The experimental system (e.g., static, semi-static, or flow-through
regime) was not described.
N/A.
Metric 4:
Reporting of
Concentrations
Test concentrations were not reported.
4839257
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., study intended to assess
effects on reproduction did not expose organisms for an
acceptable period of time prior to mating).
N/A.
Metric 6:
Test Organism
Characteristics
The test species was not reported.
OR
The test species, life stage, or age was not appropriate for the
outcome(s) of interest.
N/A.
Metric 7:
Outcome Assessment
Methodology
The outcome assessment methodology was not reported.
4839252
4839257
Metric 8:
Reporting of Data
Data presentation was inadequate.
OR
Major inconsistencies were present in reporting of results.
N/A.
C.2.3 Fate
For the screening review of this LPS candidate 3-methoxybutyl acetate, EPA excluded a total of 161
references when assessing environmental fate. Off-topic fate references excluded at title/abstract
screening are listed in Table C.l 1, 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 needs53 relevant to environmental
fate
84538
4854468
4851207
4854516
2881863
4854489
4851229
4854536
4854588
84538
525496
4854469
4851208
4854517
2910708
4854490
4851230
4854537
4854590
525496
611384
4854470
4851209
4854520
3244746
4854491
4851231
4854539
4854591
611384
611386
4854471
4851211
4854521
3378876
4854495
4851232
4854540
4854592
611386
666559
4854472
4851212
4854522
3379632
4854496
4851233
4854541
4854595
666559
837554
4854473
4851213
4854523
3390578
4854497
4851234
4854542
4854562
837554
891128
4854475
4851214
4854524
3407270
4854498
4851272
4854543
4854467
891128
53 The information needs for fate includes a list of study characteristics pertaining to the associated media and exposure
pathway s, 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.
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1016309
4854477
4851215
4854525
3829850
4854499
4851281
4854544
4854561
1016309
1182099
4854478
4851216
4854526
3865611
4854501
4851312
4854545
4854465
1182099
1205739
4854479
4851217
4854527
4144981
4854502
4854454
4854546
4854514
1205739
1468551
4854480
4851218
4854528
4181676
4854503
4854455
4854548
4834290
1468551
1613340
4854481
4851219
4854529
4182379
4854504
4854456
4854549
4854560
1613340
2123950
4854482
4851220
4854530
4233057
4854505
4854457
4854550
4854463
2123950
2713362
4854483
4851223
4854531
4318601
4854506
4854458
4854551
4854512
2713362
2807532
4854484
4851224
4854532
4348711
4854508
4854459
4854553
4770843
2807532
2823859
4854485
4851225
4854533
4348712
4854509
4854460
4854556
4854515
2823859
2871084
4854486
4851226
4854534
4348713
4854510
4854461
4854558
4851206
2871084
Reference excluded (HERO ID) because the reference did NOT present quantitative environmental fate data
N/A.
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 information pertaining
to a low- priority substance candidate?
No
N/A.
What type of source is this reference?
Review article or book chapter that contains only
citations to primary literature sources
N/A.
Is quantitative fate data presented?
No
N/A.
Is this primarily a modeling/simulation study? [Note:
Select "Yes" only if there is no experimental
verification]
Yes
N/A.
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)
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
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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.
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.
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.
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Metric 12:
Verification or
Plausibility of Results
Reported value was completely inconsistent with reference substance data,
related physical chemical properties, or otherwise implausible, suggesting that a
serious study deficiency exists (identified or not).
N/A.
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