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Dossier for Candidate Low-Priority Substance Propanol, [2-
(2-butoxymethylethoxy)methylethoxy]-
(CASRN 55934-93-5)
(Tripropylene Glycol n-Butyl Ether)
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 Tripropylene Glycol n-Butyl Ether 3
3. Physical-Chemical Properties 4
3.1 References 6
4. Relevant Assessment History 7
5. Conditions of Use 8
6. Hazard Characterization 12
6.1 Human Health Hazard 15
6.1.1 Absorption, Distribution, Metabolism, and Excretion 17
6.1.2 Acute Toxicity 17
6.1.3 Repeated Dose Toxicity 18
6.1.4 Reproductive and Developmental Toxicity 19
6.1.5 Genotoxicity 19
6.1.6 Carcinogenicity 20
6.1.7 Neurotoxicity 20
6.1.8 Skin Sensitization 21
6.1.9 Skin Irritation 21
6.1.10 Eye Irritation 21
6.1.11 Hazards to Potentially Exposed or Susceptible Subpopulations 22
6.2 Environmental Hazard 22
6.2.1 Acute Aquatic Toxicity 22
6.2.2 Chronic Aquatic Toxicity 22
6.3 Persistence and Bioaccumulation Potential 22
6.3.1 Persistence 22
6.3.2 Bioaccumulation Potential 23
7. Exposure Characterization 12
7.1 Production Volume Information 12
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7.2 Exposures to the Environment 12
7.3 Exposures to the General Population 13
7.4 Exposures to Potentially Exposed or Susceptible Subpopulations 13
7.4.1 Exposures to Workers 13
7.4.2 Exposures to Consumers 14
8. Summary of Findings 15
8.1 Hazard and Exposure Potential of the Chemical Substance 15
8.2 Persistence and Bioaccumulation 16
8.3 Potentially Exposed or Susceptible Subpopulations 17
8.4 Storage Near Significant Sources of Drinking Water 17
8.5 Conditions of Use or Significant Changes in Conditions of Use of the Chemical Substance 18
8.6 The Volume or Significant Changes in Volume of the Chemical Substance Manufactured or Processed.... 19
8.7 Other Considerations 19
9. Proposed Designation 20
Appendix A: Conditions of Use Characterization I
A.1 CDR Manufacturers and Production Volume I
A.2 Uses II
A.2.1 Methods for Uses Table II
A.2.2 Uses of Tripropylene Glycol n-butyl Ether IV
A.3 References XIII
Appendix B: Hazard Characterization XVI
B.1 References XXVII
Appendix C: Literature Search Outcomes XXXI
C. 1 Literature Search and Review XXXI
C.1.1 Search for Analog Data XXXI
C.1.2 Search Terms and Results XXXIII
C.2 Excluded Studies and Rationale XXXVI
C.2.1 Human Health Hazard Excluded References XXXVI
C.2.2 Environmental Hazard XLII
C.2.3 Fate XLV
Appendix D: Summary of Public Comments XLVIII
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Tables
Table 1: Tripropylene Glycol n-Butyl Ether at a Glance 3
Table 2: Physical-Chemical Properties for TPnB 4
Table 3: Conditions of Use for Tripropylene Glycol n-Butyl Ether 9
Table 4: Low-Concern Criteria for Human Health and Environmental Fate and Effects 12
Table 5: Tripropylene Glycol n-Butyl Ether and Analog Structures 16
Table A.1:1986-2015 National Production Volume Data for Tripropylene Glycol n-Butyl Ether (Non- ^
Confidential Production Volume in Pounds)
Table A.2: Sources Searched for Uses of Tripropylene Glycol n-Butyl Ether II
Table A3: Uses of Tripropylene Glycol n-Butyl Ether IV
Table B.1: Human Health Hazard XVI
Table B.2: Environmental Hazard XXIV
Table B.3: Fate XXV
Table C.1: Sources Used for Analog Search XXXIII
Table C.2: Search Terms Used in Peer-Reviewed Databases XXXIII
Table C.3: Search Terms Used in Grey Literature and Additional Sources XXXV
Table C.4: Off-Topic References Excluded at Title/Abstract Screening for Human Health Hazard XXXVI
Table C.5: Screening Questions and Off-Topic References Excluded at Full Text Screening for Human Yyy\/i
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 XLII
Table C.9: Screening Questions and Off-Topic References Excluded at Full Text Screening for
Environmental Hazard XLIII
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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 XLV
Table C.12: Screening Questions and Off-Topic References Excluded at Full Text Screening for Fate XLV
Table C.13: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for
_ , XLV
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, 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. Propanol, [2-(2-butoxymethylethoxy)methylethoxy]-, referenced as tripropylene
glycol n-butyl ether 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 702.9 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.
• 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.
1 https://www.federalregister.gov/documents/2019/03/21/2019-05404/imtiation-of-prioritization-under-tlie-toxic-substances-
control-act-tsca
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Section 4 (Relevant Assessment History): This section includes an overview of the outcomes of
other governing entities" assessments of the chemical substance.
Section 5 (Conditions of Use): This section presents the chemical substance's known, intended,
and reasonably foreseen conditions of use under TSCA.
Section 6 (Hazard Characterization): This section summarizes the reasonably available hazard
information and benchmarks the information against low-concern thresholds.
Section 7 (Exposure Characterization): This section includes a qualitative summary of potential
exposures to the chemical substance.
Section 8 (Summary of Findings): In this section, EPA presents information pertinent to
prioritization against each of the seven statutory and regulatory criteria and considerations, and
proposes a conclusion based on that evidence.
Section 9 (Proposed Designation): In this section, EPA presents the proposed designation for this
chemical substance.
Appendix A (Conditions of Use Characterization): This appendix contains a comprehensive list of
TSCA and non-TSCA uses for the chemical substance from publicly available databases.
Appendix B (Hazard Characterization): This appendix contains information on each of the
studies used to support the hazard evaluation of the chemical substance.
Appendix C (Literature Search Outcomes): This appendix includes literature search outcomes and
rationales for studies that were identified in initial literature screening but were found to be off-
topic or unacceptable for use in the screening-level review.
Appendix D (Summary of Public Comments): This appendix includes sources of information for
the chemical substance that the public recommended to EPA during a 90-day comment period.
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2. Background on Tripropylene Glycol n-Butyl Ether
Table 1 below provides the CAS number, synonyms, and other information on tripropylene glycol n-butyl
ether.
Table 1: Tripropylene Glycol n-Butyl Ether at a Glance
Chemical Name
Tripropylene Glycol n-Butyl Ether
CASRN
55934-93-5
Synonyms
Tripropylene glycol butyl ether; Tripropylene glycol monobutyl ether; (2-(2-
Butoxymethylethoxy)methylethoxy) propanol; ((Butoxymethylethoxy)methylethoxy)propan-1-
ol; 1 -[(2-Butoxy-1 -methylethoxy)-1 -methylethoxy]-2- propanol; PPG-3 butyl ether
Trade Name(s)
DOWANOL TPnB Glycol Ether; TPnB
Molecular Formula
C13H28O4
Representative Structure
ch3
CH3 ch3
Tripropylene glycol n-butyl ether (TPnB) is a P-series glycol ether, meaning that it is made from
propylene oxide. Glycol ethers are organic chemical compounds that contain both an alcohol functional
group (R-OH) and an ether functional group, which is an oxygen atom connected to two alkyl groups (R-
O-R). TPnB is a linear molecule that can be composed of three isomeric propylene oxide groups linked
together through ether groups, terminating in a n-butyl carbon chain on one end and an alcohol on the
other. Shorter chain ethers and esters, such as TPnB, are liquids capable of dissolving other substances
and typically function as solvents. TPnB is a colorless to light yellow hydrophobic liquid with a high
boiling point and low volatility. These properties make TPnB a useful solvent, coalescing agent, and film-
forming agent 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 tripropylene glycol n-butyl ether. 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 TPnB
Source/
Model
Data Type
Endpoint
Endpoint value
Notes
Sigma Aldrich 2019
Experimental
Physical state at
room temp
(based on melting
point)
Liquid (-75°C)
Staples and Davis 2002
Experimental
Molecular weight
248 g/mol
EPISuite v.4.112
Calculated
Molecular weight
248.4 g/mol
Lyman 1990
Calculated
Molar volume
336.4 cm3/mol
Staples and Davies 2002
Experimental
Water solubility
25,000 mg/L
ECHA 2018
Experimental
Water solubility
40,200 mg/L at20°C
atpH 7;
46,000 mg/L (4.6
wt%) at 20°C at pH
7;
25,000 mg/L at 20°C
atpH 7
EPISuite v.4.11
Estimated
Water solubility
8,187 mol/L(from Log
Kow); 95,000 mg/L
(fragment method)
Staples and Davis 2002
Experimental
Water solubility
0.101 mol/L
ECHA 2019
Experimental
Water solubility
0.162 mol/L;
0.185 mol/L;
0.101 mol/L
2 EPI Suite Physical Property Inputs - Melting Point= -75 deg C; Log P = 1.896; Water Solubility = 25000 mg/L; Henry's Law Constant = 4.05E-08 atm-m3/mole; SMILES:
OC(C)COC(C)COC(C)COCCCC
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Table 2: Physical-Chemical Properties for TPnB
Source/
Model
Data Type
Endpoint
Endpoint value
Notes
Staples and Davis 2002
Experimental
Log Kow
1.9
ECHA reports a calculated Log Kow that is identical to the measured value
presented in Staples and Davis 2002
EPISuite v.4.11
Estimated
Log Kow
1.3
EPISuite v.4.11
Estimated
Log Koa
7.68
EPISuite v.4.11
Estimated
Log Koc
1 (MCI); 1.29 (Kow)
Staples and Davis 2002
Experimental
Vapor pressure
3.08x10-3 mm Hg
(0.41 Pa) at 25°C
ECHA 2019
Experimental
Vapor pressure
1.5x10-3 mm Hg (0.2
Pa at 20°C);
2.3x10-3 mm Hg (0.3
Pa at 25°C)
EPISuite v.4.11
Estimated
Vapor pressure
1.08x10-4 mm Hg
EPISuite v.4.11
Estimated
Henry's Law
constant
3E-8 atm-m3/mole
Staples and Davis 2002
Experimental
Henry's Law
constant
4.05E-8 atm-m3/mole
Calculated from experimental vapor pressure and water solubility
EPISuite v.4.11
Estimated
Volatilization
960 days (river)
1.05x104 days (lake)
EPISuite v.4.11
Estimated
Photolysis
(Indirect)
1.80 hours (T1/2)
• OH rate constant 7.15 E-11 cm3/molecules-sec (12 hour day; 1.5E6
OH/cm3)
• No ozone reaction estimation
EPISuite v.4.11
Estimated
Hydrolysis
Rate constants
cannot be estimated
Not hydrolyzable
EPISuite v.4.11
Estimated
Biodegradation
potential
Ready prediction: No
EPISuite v.4.11
Estimated
BAF
6.22
EPISuite v.4.11
Estimated
BCF
8.22
Based on regression equation
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EPA's Sustainable Futures/P2 Framework Manual3 was used to interpret the physical-chemical
properties provided in Table 2. Based on its reported physical form and measured melting point,
tripropylene glycol n-butyl ether is a liquid under ambient conditions. Liquids have the potential for
exposure via direct dermal contact with the substance, ingestion, or by inhalation of aerosols if they
are generated. Exposure through direct dermal contact with this substance is expected to result in poor
to moderate dermal absorption based on its molecular weight, water solubility and log Kow. Based on
its measured vapor pressure (Staples and Davis, 2002), tripropylene glycol n-butyl ether is expected
to volatilize at ambient temperatures. As a result, exposure to tripropylene glycol n-butyl ether is
possible through inhalation of vapors or aerosols if they are generated. Based on measured solubility
data (Staples and Davis, 2002), tripropylene glycol n-butyl ether is considered water soluble,
indicating the potential for this substance to dissolve in water and form an aqueous solution. Water
soluble substances have an increased potential for absorption through the lungs; therefore, if
inhalation of vapors or aerosols occurs, absorption through the lungs is likely. Exposure potential
changes if tripropylene glycol n-butyl ether is present in dilute form. The Henry's Law constant
(Staples and Davis, 2002) for this compound indicates that volatilization from water and aqueous
solutions is expected to be minimal and therefore exposure through breathing vapor from a dilute
form is expected to be minimal. Based on its estimated log K0W(EPI Suite, 2019), tripropylene glycol
n-butyl ether is unlikely to cross lipid membranes. Absorption and sequestration in fatty tissues is
therefore unlikely, as reflected in the estimated bioconcentration factor (BCF) and bioaccumulation
(BAF) values for this compound (EPI Suite, 2019). The estimated log Koc (EPI Suite, 2019) indicates
tripropylene glycol n-butyl ether is highly mobile in soils, increasing its potential for leaching into
and transport in groundwater, including ground water sources of drinking water. If oral exposure
occurs via ingestion of contaminated drinking water, including well water, absorption through the
gastrointestinal tract is expected to be moderated based on the log Kow (EPI Suite, 2019). Concern for
presence in drinking water is reduced in part by tripropylene glycol n-butyl ether's expected low
persistence. Experimental data indicate tripropylene glycol n-butyl ether is readily biodegradable
(ECHA, 1998, 4985135), meaning that it has the potential to break down in the environment.
3.1 References
European Chemicals Agency (ECHA). (2019). [(butoxymethylethoxy)methylethoxy]propan-l-ol.
Retrieved from https://echa.europa.eu/substance-information/-/substanceinfo/100.054.446
Lyman, Warren J., Reehl, W. F., Rosenblatt, D. H. (1990). Handbook of chemical property estimation
methods: environmental behavior of organic compounds. American Chemical Society
Sigma Aldrich (2019). Tri(propylene glycol) butyl ether, mixture of isomers. Retrieved from
https://www.sigmaaldrich.com/catalog/product/aldrich/484229?lang=en®ion=US
Staples, CA; Davis, JW. (2002). An examination of the physical properties, fate, ecotoxicity and
potential environmental risks for a series of propylene glycol ethers. Chemosphere, Oct;49(l):61-73.
U.S. EPA. (2019). Estimation Programs Interface Suite, v 4.11. United States Environmental
Protection Agency, Washington, DC, USA
3 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 tripropylene glycol n-butyl ether and added the chemical to
the Safer Choice Program's Safer Chemical Ingredients List (SCIL) in December 2012 under the
functional class of solvents. The SCIL4 is a continuously updated list of chemicals that meet low-
concern Safer Choice criteria. 5
Internationally, EPA identified one assessment by the German Environmental Agency (UBA), which
designated tripropylene glycol n-butyl ether as "low hazard to waters" in August 2017 based on an
assessment of ecotoxicity and environmental fate.6
4 https://www.epa.gov/saferchoice/safer-ingredients
5 https://www.epa.gov/sites/production/files/2013-12/documents/dfe master criteria safer ingredients v2 l.pdf
0 https://webrigoletto.uba.de/rigoletto/public/searcliDetail.do7kennummeF7169
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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 tripropylene glycol n-butyl ether (Appendix A) to inform which uses would be
determined conditions of use.7 One source of information that EPA used to understand 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. 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, tripropylene glycol n-butyl ether is imported. It is used in processing
(incorporation into formulation, mixture or reaction) for other basic organic chemicals. It has
industrial uses (non-incorporative activities for coatings, construction, mining chemicals, oil and gas
drilling, and wholesale and retail trade). Consumer uses include cleaning and furnishing care
products, air care products, anti-freeze and deicing products, and inks, toners, and colorant products.
Based on the known manufacturing, processing, and uses of this chemical substance, EPA assumes
distribution in commerce. According to CDR, three facilities reported that the chemical was not
recycled, and one facility reported this information as confidential business information (CBI). No
information on disposal is found in CDR or through EPA's Toxics Release Inventory (TRI) Program8
because tripropylene glycol n-butyl ether is not a TRI-reportable chemical. Although reasonably
available information did not specify additional types of disposal, for purposes of this proposed
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
identify additional occupational9 and consumer uses. This research improved the Agency's
understanding of the conditions of use for tripropylene glycol n-butyl ether. Although EPA identified
uses of tripropylene glycol n-butyl ether in personal care products, this screening review covers
TSCA conditions of use for the chemical substance and personal care products are not considered 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 tripropylene glycol n-butyl ether
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).
7 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).
8 https://www.epa.gov/toxics-release-inventorv-tri-program
9 Occupational uses include industrial and/or commercial uses
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Table 3: Conditions of Use for Tripropylene Glycol n-Butyl Ether
Life Cycle Stage
Category
Subcategory of Use
Source
Manufacturing
Import
Import
EPA (2017b)
Processing
Processing- incorporation into
formulation, mixture or reaction
Solvents: all other basic organic chemical
EPA (2017b)
Processing- incorporation into
formulation, mixture or reaction
Coatings, paint manufacturing
ECHA (2018), CPCat (2019)
Recycling
Recycling
EPA (2017b)10
Distribution
Distribution
Distribution
EPA (2017b)
Industrial
Use—non-incorporative activities
Communication equipment manufacturing, electrical manufacturing,
fabricated metal product manufacturing, furniture manufacturing,
wood manufacturing, construction, mining chemicals, oil and gas
drilling, wholesale and retail trade
ECHA (2018), CPCat (2019)
Processing aids, not otherwise listed
EPA (2017b)
Plasticizers- wholesale and retail trade
Commercial uses
Cleaning and furniture care products
Metal cleaner/ polish
CLR Brands (2018d)
Industrial/commercial
Metal working fluids
ECHA (2018)
Commercial/consumer
Cleaning and furniture care products
Bath cleaner, descalers, degreaser, kitchen cleaner, mold and
mildew stain remover
CLR Brands (2018a); CLR Brands
(2018b); CLR Brands (2018f);
CPCat (2019), CLR Brands (2018c),
CLR Brands (2018g)
Consumer
Air care products
Air care products
ECHA (2018)
Cleaning and furniture care products
Hardwood floor finish, multi-surface cleaner
DeLima Associates (2018b), CLR
Brands (2018e), EPA (2017b)
Adhesives and sealants
ECHA (2018)
Anti-freeze and de-icing products
ECHA (2018)
Inks, toners, and colorant products
Inks and toners
10 In the 2016 CDR, three facilities reported that the chemical was not recycled, and one facility reported this information as CBI.
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Table 3: Conditions of Use for Tripropylene Glycol n-Butyl Ether
Life Cycle Stage
Category
Subcategory of Use
Source
Fabric, textile, and leather products not
covered elsewhere
Leather treatment products
Disposal
Releases to air, wastewater, solid and
liquid wastes.
Releases to air, wastewater, solid and liquid wastes.
Though not explicitly identified,
releases from disposal are assumed
to be reasonably foreseen11
11 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 approach12 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 tripropylene glycol n-butyl ether
against the endpoints listed below. EPA's New Chemicals Program has used these endpoints for
decades to evaluate chemical substances under TSCA13 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 Chemicals14 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
Toxicity15
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
12This process is further discussed in the document "Approach Document for Screening Hazard Information for Low-
Priority Substances Under TSCA."
13 https://www.epa. gov/sustainable-futures/sustainable-futures-p2-framework-manual
14 https://www.unece.org/fileadmin/DAM/trans/danger/publi/ghs/ghs rev07/English/ST SG AC10 30 Rev7e.pdf
15 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)16
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
Toxicity17
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
Toxicity17
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/
Genotoxicity18
Very High
High
Moderate
Low
Germ cell
mutagenicity
GHS Category 1A
or 1B: Substances
known to induce
heritable mutations
or to be regarded
as if they induce
heritable mutations
in the germ cells of
humans.
GHS Category 2:
Substances which
cause concern for
humans owing to the
possibility that they
may induce heritable
mutations in the germ
cells of humans.
Evidence of
mutagenicity support by
positive results in vitro
OR in vivo somatic cells
of humans or animals
Negative for
chromosomal
aberrations and gene
mutations, or no
structural alerts.
10 Values from GHS criteria for Specific Target Organ Toxicity Repeated Exposure (Chapter 3.9: Specific Target Organ
Toxicity' Repeated Exposure. 2009, United Nations).
17 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).
18 From GHS criteria (Chapter 3.5: Germ Cells Mutagenicity'. 2009, United Nations) and supplemented with considerations
for mutagenicity and genotoxicity in cells other than germs cells.
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Table 4: Low-Concern Criteria for Human Health and Environmental Fate and Effects
Mutagenicity and
genotoxicity in
somatic cells
OR
Evidence of
mutagenicity
supported by positive
results in in vitro AND
in vivo somatic cells
and/or germ cells of
humans or animals.
Carcinogenicity19
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
inadequate20 evidence
in humans)
Negative studies or
robust mechanism-
based structure
activity relationship
(SAR)
Neurotoxicity
(90-day study)16
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
Sensitization21
High
Moderate
Low
Skin sensitization
High frequency of
sensitization in
humans and/or high
potency in animals
(GHS Category 1A)
Low to moderate
frequency of
sensitization in human
and/or low to moderate
potency in animals
(GHS Category 1B)
Adequate data
available and not
GHS Category 1Aor
1B
Respiratory
sensitization
Occurrence in
humans or evidence
of sensitization in
humans based on
animal or other tests
(equivalent to GHS
Category 1A or 1B)
Limited evidence
including the presence
of structural alerts
Adequate data
available indicating
lack of respiratory
sensitization
19 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).
20 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."
21 Incorporates GHS criteria (Chapter 3.4: Respiratory or Skin Sensitization. 2009, United Nations).
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Table 4: Low-Concern Criteria for Human Health and Environmental Fate and Effects
Irritation/
Corrosivity22
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)23
Chronic Aquatic
Toxicity Value
(L/E/ICso)23
Persistence (Measured in terms of level of
biodegradation)24
Bioaccumulation
Potential25
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 tripropylene glycol n-butyl ether. 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 tripropylene glycol n-butyl ether. Appendix B contains
more information on each study.
Tripropylene glycol n-butyl ether is a propylene glycol ether composed of three 1-methylethoxy
repeating units with an n-butyl ether substitution on one of the terminal alcohols. EPA used best
professional judgement to select analogs based on similarity in structure, physical-chemical
properties, and functionality, with the assumption that these chemicals will have similar
environmental transport and persistence characteristics, and bioavailability and toxicity profiles. All
analogs used to inform EPA's understanding of this chemical are either di- or tri-propylene glycol
ethers or ether acetates that vary by the length of the aliphatic ether chain length (methyl, ethyl or
butyl). All of the glycol ethers are expected to metabolize via similar pathways in vivo. The glycol
ether acetate is expected to rapidly hydrolyze in vivo to the corresponding propylene glycol ether. As
noted in the table, four of the analogs are named as isomeric mixtures that may contain either the 1-
22 Criteria derived from the Office of Pesticide Programs Acute Toxicity Categories (U.S. EPA. Label Review Manual.
2010).
23 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).
24 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).
25 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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methylethyl or 2-methylethyl substitution patterns in each propylene glycol unit. For ethers of
dipropylene glycol and tripropylene glycol, the structural differences among the individual possible
isomers are not expected to result in significant differences in the properties, persistence or hazards of
these chemicals. Based on these factors, the environmental and toxicological effects of these analogs
are expected to be very similar to those of tripropylene glycol n-butyl ether.
Table 5: Tripropylene Glycol n-Butyl Ether and Analog Structures
CASRN
Name
Structure
55934-93-5
Tripropylene glycol n-butyl
ether (isomeric mixture)
30025-38-8
Dipropylene glycol
monoethyl ether (isomeric
mixture)
0 ch3
Representative structure
34590-94-8
Dipropylene glycol, methyl
ether (isomeric mixture)
ch3
-°H
ch3
Representative structure
29911-28-2
Dipropylene glycol
monobutyl ether
H,C
25498-49-1
Tripropylene glycol
monomethyl ether (isomeric
mixture)
ch3
HO' Y '0^^o^V"°^ch3
CKj ch3
Kepresentative structure
88917-22-0
Dipropylene glycol methyl
ether acetate
(isomeric mixture)
O CH;
H3C 0
0^ ,ch3
0
ch3
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Dipropylene glycol, ethyl ether (CASRN 15764-24-6) and tripropylene glycol methyl ether (CASRN
20324-33-8) were also included in analog data searches; relevant, quality studies26 were only
identified for the CASRNs listed in Table 5.
6.1.1 Absorption, Distribution, Metabolism, and Excretion
Absorption
Based on tripropylene glycol n-butyl ether's molecular weight and water solubility (Table 2),
tripropylene glycol n-butyl ether is expected to be absorbed through the gastrointestinal tract and
from the lungs. These properties, along with the log kow (Table 2), indicate poor to moderate skin
absorption is expected.
Distribution
Because tripropylene glycol n-butyl ether is water soluble (Section 3), after absorption it is expected
to be widely distributed throughout the body to various tissues including the liver, kidney and skin.
Metabolism
Because quality experimental data26 on tripropylene glycol n-butyl ether metabolite formation were
limited, the Quantitative Structure-Activity Relationship (QSAR) toolbox27 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 tripropylene glycol n-butyl ether
metabolites. The predicted metabolites from the skin metabolism simulator included propionic acid,
propanal, butanal and 1-butanol. Additional metabolites of tripropylene glycol n-butyl ether identified
by one or more of the metabolism simulators included derivative primary and secondary alcohols,
carboxylic acids, aldehydes, ketones and secondary diols.
Excretion
Based on the molecular weight and water solubility of tripropylene glycol n-butyl ether, after
metabolism tripropylene glycol n-butyl ether is expected to be excreted primarily in urine and exhaled
air.
6.1.2 Acute Toxicity
EPA assessed the mammalian toxicity potential from acute exposure by tripropylene glycol n-butyl
ether using experimental evidence from oral, dermal, and inhalation exposures.
Two OECD Guideline 401 studies exposed rats to a single oral dose of tripropylene glycol n-butyl
ether (ECHA. 1988b. c). In one study there were no mortalities, resulting in an LD50 greater than
2000 mg/kg (ECHA. 1988b). The second study reported a LD50 of 2800 mg/kg (ECHA. 1988c). An
OECD Guideline 423 study exposed rats to a single dose (2000 mg/kg) of tripropylene glycol n-butyl
ether by oral gavage (ECHA. 2001b). There was one mortality (out of three animals), resulting in an
LD50 of greater than 2000 mg/kg. These studies indicate low concern for acute, oral toxicity with
expected LD50S above the low-concern threshold of 2000 mg/kg.
20 This process is further discussed in the document "Approach Document for Screening Hazard Information for Low-
Priority Substances Under TSCA."
27 https://www.oecd.org/chemicalsafetv/risk-assessment/oecd-qsar-toolbox.htm
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Rats exposed to tripropylene glycol n-butyl ether dermally reported no mortalities at the single dose
tested (2000 mg/kg), resulting in an LD50 greater than 2000 mg/kg (ECHA. 1988a). This study
indicates low concern for acute, dermal toxicity with an expected LD50 above the low-concern
threshold of 2000 mg/kg.
EPA also assessed the mammalian toxicity potential from acute exposure to tripropylene glycol n-
butyl ether using an inhalation exposure study from an analog, dipropylene glycol methyl ether
acetate (DPMA). A study on rats exposed via inhalation to 5.7 mg/L (734 ppm) of DPMA vapor for
four hours and observed for two weeks reported no mortalities (OECD. 2003; ECHA. 1982). This
concentration exceeds the expected air saturation concentration of 135 ppm, indicating no effects at
complete air saturation (OECD. 2003). These results indicate low concern for acute, inhalation
toxicity based on no effects at air saturation.
6.1.3 Repeated Dose Toxicity
EPA assessed the potential for toxicity from repeated exposures by tripropylene glycol n-butyl ether
using experimental data and read-across from analogs.
A study on rats exposed to tripropylene glycol n-butyl ether via oral gavage for 28 days resulted in a
no observed adverse effect level (NOAEL) of 100 mg/kg-day and a lowest observed adverse effect
level (LOAEL) of 350 mg/kg-day based on increases in both absolute and relative liver weights,
though quantitative data were not available from the study to determine the biological significance of
these increases (ECHA. 1990c). Another study on rats exposed to tripropylene glycol n-butyl ether
orally for 13 weeks reported a NOAEL of 350 mg/kg-day and a LOAEL of 1000 mg/kg-day based on
increased hepatocyte size, altered cytoplasm staining in the liver, and increases in absolute and
relative liver and kidney weights. EPA considered these effects adaptive and reversible because the
effects were not seen following a 4-week recovery period in a group exposed to 1000 mg/kg-day
(ECHA. 1991). Based on the results of the 13-week study, the experimental results indicate low
concern for toxicity resulting from repeated oral exposures by exceeding the low-concern threshold of
100 mg/kg-day for 90-day studies or 300 mg/kg-day for 30-day studies.
Two 90-day dermal studies in rabbits exposed to dipropylene glycol, methyl ether reported a LOAEL
of 9500 mg/kg-day (Dow Chemical. 2000b; Rowe et al.. 1954) and a NOAEL of 4750 mg/kg-day
(Dow Chemical. 2000a). A dermal study in rats exposed to dipropylene glycol, methyl ether for 28
days reported a NOAEL of 714 mg/kg-day (Fairhurst et al.. 1989). EPA also considered a study on
rabbits dermally exposed to another analog, tripropylene glycol monomethyl ether, for 90 days. The
study reported a NOAEL of 960 mg/kg-day and a LOAEL of 2900 mg/kg-day based on decreased
body weight and increased kidney weight (Dow Chemical. 2000c; Rowe et al.. 1954).These results
indicate low concern for toxicity resulting from sub-chronic and chronic dermal exposures by
exceeding the low-concern threshold of 200 mg/kg-day for 90-day studies or 600 mg/kg-day for 30-
day studies.
A 13-week inhalation study in rats and rabbits exposed to dipropylene glycol, methyl ether reported
no adverse effects at the highest tested concentration (1.212 mg/L), resulting in aNOAEC of 1.212
mg/L (Landry and Yano. 1984). These results indicate low concern for repeated inhalation toxicity by
exceeding the low-concern threshold of 1 mg/L for vapor inhalation exposures.
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6.1.4 Reproductive and Developmental Toxicity
EPA used read across from closely related analogs to evaluate tripropylene glycol n-butyl ether's
potential to induce reproductive and developmental toxicity.
A one-generation reproductive study in rats exposed to dipropylene glycol monobutyl ether by oral
gavage reported a reproductive NOAEL of 1000 mg/kg-day (ECHA. 1994). These results indicate
low concern for reproductive toxicity by exceeding the low-concern oral threshold of 250 mg/kg-day.
A developmental inhalation study in rats exposed to tripropylene glycol methyl ether aerosol from
gestation days (GD) 6-15 reported a no observed adverse effect concentration (NOAEC) of 8.9 mg/L
(Bio-Research Laboratories LTD. 1985a). Another developmental inhalation study in rats exposed to
tripropylene glycol monomethyl ether aerosol from GD 6-15 reported a NOAEC of 1 mg/L-day (129
ppm), which is above tripropylene glycol monomethyl ether's theoretical air saturation vapor
concentration of 7.88 ppm (Bio-Research Laboratories LTD. 1985b). Two studies where rats were
exposed from GD 6-15 and rabbits were exposed from GD 7-19 to dipropylene glycol methyl ether
vapor both reported NOAECs of 0.45 mg/L (53 ppm), which is also above dipropylene glycol methyl
ether's theoretical air saturation vapor concentration of 26 ppm (ECHA. 1990a. b). These results
indicate low concern for developmental toxicity from vapor exposures based on no effects at air
saturation.
6.1.5 Genotoxicity
EPA used experimental studies and read-across from analogs to assess tripropylene glycol-n-butyl
ether's potential for genotoxicity as a potential indicator of genotoxic carcinogenicity.
One in vitro gene mutation study resulted in a negative finding with and without metabolic activation
in Salmonella typhimiirium exposed to tripropylene glycol-n-butyl ether (ECHA. 1989).
EPA used read-across from analogs to assess genotoxicity through other mechanisms. Rat hepatocyte
cells exposed to tripropylene glycol monomethyl ether did not elicit unscheduled DNA synthesis
(Dow Chemical. 1982). Mice injected with dipropylene glycol monobutyl ether were negative for
significant increases in the presence of micronuclei (OECD. 2003). Several studies on chromosomal
aberrations in Chinese hamster ovary cells were available. Rat liver cells and Chinese hamster lung
cells exposed to dipropylene glycol, methyl ether indicated negative results for chromosomal
aberrations (ECHA. 2000b; Shell Chemical. 1983). Chinese hamster ovary cells exposed to
dipropylene glycol monoethyl ether were negative for chromosomal aberrations (ECHA. 1997).
Chinese hamster ovary cells had mixed results for increases in chromosomal aberrations when
exposed to dipropylene glycol monobutyl ether. One study reported negative results for inducing
aberrations with and without activation (OECD. 2003). Two other studies reported dipropylene glycol
monobutyl ether as positive for inducing chromosomal aberrations with and without activation;
however, these results were observed at cytotoxic concentrations (OECD. 2003). Weighing the
negative results in several cell lines with the positive results occurring only at cytotoxic
concentrations, EPA interprets these results to indicate DPMA has low concern for inducing
genotoxicity.
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6.1.6 Carcinogenicity
Because quality experimental data on tripropylene glycol n-butyl ether were limited, EPA relied on
publicly available quantitative structure activity relationship (QSAR) models and structural alerts
(SA) to assess the carcinogenic potential for tripropylene glycol n-butyl ether. 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.28 For this chemical, there is an absence of the
types of reactive structural features that are present in genotoxic carcinogens. Tripropylene glycol n-
butyl ether is not an electrophile. ISS profiler, a QSAR model,29 did not identify any alerts for the
parent structure but did identify an aldehyde metabolite alert for a metabolite. However, this aldehyde
is expected to be short lived and eliminated from the body. Further, the Virtual models for property
Evaluation of chemicals within a Global Architecture (VEGA) models'3" results indicate tripropylene
glycol n-butyl ether has low potential to be carcinogenic or mutagenic.
Tripropylene glycol-n-butyl ether's metabolism, lack of structural alerts, and negative experimental
genotoxicity results indicate that this chemical is unlikely to be carcinogenic or mutagenic.
6.1.7 Neurotoxicity
No guideline neurotoxicity studies on tripropylene glycol n-butyl ether or closely related analogs
were available to assess the potential for tripropylene glycol n-butyl ether to cause neurotoxicity.
However, EPA reviewed supporting evidence from repeated dose studies and ToxCast31 to inform
EPA's assessment of neurotoxicity.
A repeated dose oral gavage study of dipropylene glycol ethyl ether in rats reported minimal effects
on the neurological endpoints that were evaluated (i.e., brain, sciatic nerve and spinal cord
histopathology, field and motor activity measurements and a battery of neurobehavioral functions that
were not described). Decreased hindlimb grip strength (magnitude of effect not reported) was
observed in female rats at 1,000 mg/kg-day of dipropylene glycol ethyl ether in a 90-day oral gavage
study. Hindlimb grip strength was not affected by treatment in males from this study and no effects
were noted in males or females during a 2-week recovery period. Dipropylene glycol ethyl ether did
not produce histopathological lesions in the brain, spinal cord and sciatic nerves or affect field or
motor activity measurements (ECHA. 2000a).
28 "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.
29 Carcinogenicity alerts by ISS 2.4 profiler as encoded in the QSAR Toolbox 4.3 qsartoolbox.org
30 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.
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A 13-week inhalation study of dipropylene glycol methyl ether in rats and rabbits did not report
histopathological effects in the brain, peripheral nerve, or spinal cord in rats and rabbits at a
concentration of 1.212 mg/L-day (Landry and Yano. 1984).
ToxCast32 results for tripropylene glycol n-butyl ether included 8 in vitro high throughout
biochemical- and cell-based assays related to neurological functions.33 Bioactivity was not induced in
any assay by tripropylene glycol n-butyl ether.
Tripropylene glycol n-butyl ether's low-concern findings for other human health hazard endpoints,
including, but not limited to, acute, reproductive and developmental toxicity, and predictions by
ToxCast, indicate low concern for neurotoxicity.
6.1.8 Skin Sensitization
No quality experimental studies34 on tripropylene glycol n-butyl ether or closely related analogs were
available to assess the potential for tripropylene glycol n-butyl ether to cause skin sensitization.
However, no structural alerts were identified for protein binding potential of tripropylene glycol n-
butyl ether in regard to skin sensitization, using the QSAR Toolbox, Version 4.2. These results
indicate tripropylene glycol n-butyl ether is of low concern for skin sensitization.
6.1.9 Skin Irritation
EPA assessed dermal irritation effects using experimental data in rabbits. One study demonstrated
tripropylene glycol n-butyl ether induced slight erythema in all three animals tested and edema in one
of three animals, but these effects were reversible by day 7. Tripropylene glycol n-butyl ether was
considered to be moderately irritating (ECHA. 1987b). Another study reported tripropylene glycol n-
butyl ether slight erythema in three of three animals, but the result was fully reversible in 8 days
(ECHA. 2001a). Due to the low severity and reversibility, these studies indicate tripropylene glycol n-
butyl ether is of moderate concern for skin irritation.
6.1.10 Eye Irritation
To assess potential for eye irritation, EPA used the results of two studies in rabbits. Rabbits exposed
to tripropylene glycol n-butyl ether displayed slight eye irritation at 24 hours in the form of iris
irritation, conjunctivae, and chemosis, but the effects were fully reversible by 14 days (ECHA.
1988d). Another study was negative for inducing eye irritation (ECHA. 2001c). Given the mixed
results, these studies indicate tripropylene glycol n-butyl ether is of moderate concern for eye
irritation.
32 https://actor.epa.gov/dashboard/. Chemical specific assay list can be found at
https://actor.epa.gOv/dashboard/#chemical/55934-93-5
33 Identified by supplemental information in Chushak Y., Shows H., Gearhart J., Pangbum H. 2018. In silico identification
of protein targets for chemical neurotoxins using Toxcast in vitro data and read-across within the QSAR toolbox.
Toxicology Research issue 3. Supplemental files:
https://pubs.rsc.Org/en/content/articlelanding/2018/tx/c7tx00268h#idivAbstract
34 This process is further discussed in the document "Approach Document for Screening Hazard Information for Low-
Priority Substances Under TSCA."
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6.1.11 Hazards to Potentially Exposed or Susceptible Subpopulations
The above information supports a low human health hazard finding for tripropylene glycol n-butyl
ether based on low-concern criteria. This finding includes considerations such as the potential for
developmental toxicity, reproductive toxicity, and acute or repeated dose toxicity that may impact
potentially exposed or susceptible subpopulations. Based on the hazard information discussed in
Section 6, EPA did not identify populations with greater susceptibility to tripropylene glycol n-butyl
ether.
6.2 Environmental Hazard
EPA assessed environmental hazard for tripropylene glycol n-butyl ether based on available acute
toxicity experimental data and estimated chronic toxicity values using the Ecological Structure Active
(ECOSAR) Predictive Model.35. Appendix B contains a summary of the reasonably available
environmental hazard data.
6.2.1 Acute Aquatic Toxicity
EPA assessed environmental hazard from acute exposures to tripropylene glycol n-butyl ether.
Aquatic vertebrates exposed to tripropylene glycol n-butyl ether resulted in an LC50 of 564 mg/L
(ECHA. 1988f. 1987a). Invertebrates exposed to tripropylene glycol n-butyl ether resulted in an EC50
greater than 100 mg/L (ECHA. 2002b. 1988e). Algae exposed to tripropylene glycol n-butyl ether
resulted in EC50S of 351 mg/L for cell volume and 265 mg/L for cell count (ECHA. 2009).These
aquatic toxicity studies indicate low concern for acute aquatic exposure by exceeding the low-concern
threshold of 100 mg/L.
6.2.2 Chronic Aquatic Toxicity
Chronic toxicity values were estimated using ECOSAR. Chronic toxicity is predicted to occur at 72
mg/L for aquatic vertebrates, 35 mg/L for invertebrates, and 56 mg/L for algae. These toxicity values
indicate that tripropylene glycol n-butyl ether is expected to have low environmental hazard based on
the low-concern criteria chronic aquatic toxicity threshold of 10 mg/L.
6.3 Persistence and Bioaccumulation Potential
6.3.1 Persistence
EPA assessed the environmental persistence for tripropylene glycol n-butyl ether using available
experimental data on both ready biodegradation and inherent biodegradation.
Tripropylene glycol n-butyl ether passed two OECD 301-series ready tests and was considered
readily biodegradable, meeting the 10-day window in the OECD 301F test (Dow Chemical. 1998;
ECHA. 1998). but did not meet the 10-day window in the OECD 301A test (ECHA. 2002a). An
inherent biodegradability test OECD 302B (ECHA. 1993) provides additional evidence that
tripropylene glycol n-butyl ether is inherently and ultimately biodegradable. Furthermore, the
35https://www.epa.gov/tsca-screening-tools/ecological-striicture-activity-relationships-ecosar-predictive-model}
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microbial inhibition tests indicate that this substance is non-toxic to microbial populations found in
sewage treatment plants (ECHA. 200Id).
Anaerobic biodegradation data were not available for tripropylene glycol n-butyl ether or closely
related analogs. Though BIOWIN modeling did not predict this chemical to anaerobically biodegrade
quickly, these results do not indicate this chemical would not anaerobically biodegrade. Tripropylene
glycol n-butyl ether's low-hazard results for environmental and mammalian toxicity and evidence of
aerobic biodegradation indicate low concern for this chemical if present in anaerobic environments.
Based on the available information, the experimental data indicate that tripropylene glycol n-butyl
ether is readily biodegradable under aerobic conditions, and complete mineralization of this chemical
has been reported using both standard and non-standard test methods. No degradation products of
concern were identified for this chemical substance. The available biodegradation results meet the
low-concern threshold and indicate this chemical will have low persistence.
6.3.2 Bioaccumulation Potential
Based on the estimated bioaccumulation factor (BAF) value of 6.22 using the Estimation Programs
Interface (EPI) Suite models,36 tripropylene glycol n-butyl ether is expected to have low potential for
bioaccumulation in the environment based on the low-concern threshold of less than 1000.
30 https://www.epa.gov/tsca-screeniiig-tools/epi-suite1m-estimation-program-mterface
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7. Exposure Characterization
EPA considered reasonably available information on exposure for tripropylene glycol n-butyl ether.
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) to inform the Agency's understanding of intended, known, or reasonably
foreseen uses (Section 5).
As shown in Tables 3 and A.3, tripropylene glycol n-butyl ether is a solvent used in processing
(incorporation into an article and into a formulation, mixture, or product), as a plasticizer, and in
cleaning products, as well as in ink, toner, and colorant products (among others) for consumer and
commercial use. It is used in 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 tripropylene glycol n-butyl ether is based on an analysis of the
CDRfrom 1986 to 2015.37 From 1986 to 1994 reporting years, no data was reported for the aggregate
production volume of tripropylene glycol n-butyl ether. 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. For the 1998 reporting year, the aggregate production volume of tripropylene
glycol n-butyl ether was between 500,000 and 1,000,000 lbs. From 2002 to 2015 reporting years, the
aggregate production volume of tripropylene glycol n-butyl ether was between 1,000,000 and
10,000,000 lbs. For the 2011 reporting, aggregate production volume information was withheld. In
general, since 2012, production volume has remained relatively stable without significant increases or
decreases.
7.2 Exposures to the Environment
EPA expects most exposures to the environment to occur during the manufacture, import, processing,
and industrial, commercial, and consumer uses of tripropylene glycol n-butyl ether. Exposure is also
reasonably foreseen from other uses, such as distribution and disposal. These activities could result in
releases of tripropylene glycol n-butyl ether to media including surface water, landfills, and air.
EPA expects high levels of removal of tripropylene glycol n-butyl ether during wastewater treatment
(either directly from the facility or indirectly via discharge to a municipal treatment facility or
Publicly Owned Treatment Works (POTW)). Further, tripropylene glycol n-butyl ether is expected to
have low persistence (aerobic biodegradation is discussed in Section 6.3.1) and has the potential to
37 The CDR requires manufacturers (including importers) to report information on the chemicals they produce domestically
or import into the U.S above 25,000 lb. per site per year.
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break down in the environment into carbon dioxide and water. Therefore, any release of this chemical
to surface water is expected to break down, reducing exposure to aquatic organisms in the water
column and groundwater sources of drinking water, including well water. Based on the estimated log
Koc (Section 3), tripropylene glycol n-butyl ether is expected to have negligible adsorption to
sediment, reducing the potential toxicity to benthic organisms. Tripropylene glycol n-butyl ether's
biodegradability during treatment processes will reduce the exposure potential to aquatic organisms.
If disposed of in a landfill, this chemical is expected to degrade under aerobic and anaerobic
conditions (aerobic and anaerobic biodegradation are discussed in Section 6.3.1).
If incineration releases during manufacturing and processing occur, EPA expects significant
degradation of tripropylene glycol n-butyl ether to the point that it will not be present in air.
7.3 Exposures to the General Population
EPA expects the general population could be exposed to tripropylene glycol n-butyl ether from the
potential environmental releases described above. Air exposure is unlikely from incineration. If
tripropylene glycol n-butyl ether is present in the air from volatilization, it is expected to be reduced
because of its short atmospheric half-life of less than 2 hours (Table 2). With the exception of time
immediately following a release, tripropylene glycol n-butyl ether 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 tripropylene glycol n-butyl ether, oral exposure to tripropylene glycol n-
butyl ether via fish ingestion is unlikely.
7.4 Exposures to Potentially Exposed or Susceptible Subpopulations
EPA identified workers as potentially exposed or susceptible subpopulations based on greater
exposure to tripropylene glycol n-butyl ether than the general population during manufacturing,
processing, distribution, use, and disposal. EPA identified consumers as a population that may
experience greater exposure to tripropylene glycol n-butyl ether than the general population through
use of ink, toner, and colorant products; anti-freeze and de-icing products; and cleaning and
furnishing care products, for example.
7.4.1 Exposures to Workers
Based on its reported physical form and measured melting point (Table 2), tripropylene glycol n-butyl
ether is a liquid under ambient conditions. Based on tripropylene glycol n-butyl ether'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, tripropylene
glycol n-butyl ether is expected to be volatile at ambient temperatures, and therefore workers may be
exposed through inhalation of vapors. However, if tripropylene glycol n-butyl ether is in a dilute
form, the estimated Henry's Law constant for tripropylene glycol n-butyl ether suggests volatilization
from water and aqueous solutions is expected to be minimal. Workers may be exposed to tripropylene
glycol n-butyl ether in manufacturing, processing, distribution, industrial use, and disposal.
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7.4.2 Exposures to Consumers
Consumers could be exposed to tripropylene glycol n-butyl ether through the use of ink, toner, and
colorant products, cleaning and furnishing care products; and anti-freeze and de-icing products,
among others (Table 3). For all these uses, if dermal contact does occur, tripropylene glycol n-butyl
ether 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, tripropylene glycol n-butyl ether's absorption from the lungs is likely.
EPA does not include intentional misuse, such as people drinking products containing this chemical,
as part of the known, intended or likely conditions of use that could lead to an exposure (82 FR
33726). Thus, oral exposures will be incidental (meaning inadvertent and low in volume).
Tripropylene glycol n-butyl ether 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 tripropylene glycol n-butyl ether against each of the priority designation
considerations in 40 CFR 702.9(a), 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 tripropylene glycol n-butyl ether.
EPA used this information to inform its proposed determination of whether tripropylene glycol n-
butyl ether would meet the statutory criteria and considerations for proposed designation as a low-
priority substance.
• Hazard potential:
For tripropylene glycol n-butyl ether'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 tripropylene glycol
n-butyl ether is of low concern for human health and environmental hazard across the range of
endpoints in these 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,
children, and consumers (discussed in Sections 3 and 7). EPA also gathered information on
environmental releases. EPA identified workers, the general population, consumers, and the
environment as most likely to experience exposures. EPA determined that while the general
population, workers and consumers may be exposed to tripropylene glycol n-butyl ether, exposure by
the dermal pathway is limited by tripropylene glycol n-butyl ether's physical-chemical properties. If
ingestion occurs, tripropylene glycol n-butyl ether is expected to be metabolized and excreted,
reducing the duration of exposure. Inhalation of tripropylene glycol n-butyl ether in dilute products is
expected to be minimal; however, workers may be exposed to vapors of this chemical in neat form. If
tripropylene glycol n-butyl ether is released into the environment, its exposure potential will be
reduced through biodegradation.
Rationale: Although tripropylene glycol n-butyl ether may cause moderate eye and skin 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 processing,
manufacturing, distribution, use, and disposal through splashing or hand-to-face and eye contact.
Other uses covered under TSCA, such as consumer uses in cleaning and furnishing care products,
would be unlikely to result in more than incidental skin and eye exposure. Eye and skin irritation
resulting from exposure in an occupational and consumer setting is mitigated 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 tripropylene glycol n-butyl ether 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 tripropylene
glycol n-butyl ether 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 tripropylene glycol n-butyl ether is readily
biodegradable under aerobic conditions, with greater than 60 percent biodegradation expected within
28 days. EPA's EPI Suite models indicate a low potential for bioaccumulation and bioconcentration.
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 tripropylene glycol n-butyl ether 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.
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8.3 Potentially Exposed or Susceptible Subpopulations
Approach: TSCA Section 3(12) states that the "term 'potentially exposed or susceptible
subpopulation' means a group of individuals within the general population identified by the
Administrator who, due to either greater susceptibility or greater exposure, may be at greater risk than
the general population of adverse health effects from exposure to a chemical substance or mixture,
such as infants, children, pregnant women, workers, or the elderly." EPA identified workers engaged
in the manufacturing, processing, distribution, use, and disposal of tripropylene glycol n-butyl ether
as a potentially exposed or susceptible subpopulation (described in more detail in Section 7). EPA
also identified consumers as a potentially exposed subpopulation because of their use of ink, toner,
and colorant products, cleaning and furnishing care products, and other types of products.
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 tripropylene glycol n-
butyl ether than the general population. Because of the chemical's low-concern hazard properties and
reversibility of the effects, this exposure does not pose a significant increase in risk for workers or
consumers.
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 tripropylene glycol
n-butyl ether 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 of
tripropylene glycol n-butyl ether provides sufficient evidence to support a finding of low concern.
The reasonably available information on conditions of use, hazard, and exposure described above
provides sufficient information to support this proposed finding.
8.4 Storage Near Significant Sources of Drinking Water
Approach: In Sections 6 and 7, EPA explains its evaluation of the elements of risk relevant to the
storage of tripropylene glycol n-butyl ether 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, tripropylene glycol n-butyl ether 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, tripropylene glycol n-butyl
ether 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 tripropylene glycol n-butyl ether is
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unlikely to partition into sediment, predicted to biodegrade under aerobic conditions (see Section 3),
and unlikely to bioaccumulate (see Section 6), minimizing the likelihood that the chemical would be
present in sediment or groundwater to pose a longer-term drinking water contamination threat.
A sudden release of large quantities of the chemical near a drinking water source could have
immediate effects on the usability of a surface drinking water source. If such a release were to occur,
two primary factors would operate together to reduce concern. First, the chemical would be expected
to present low concern to the general population, including susceptible subpopulations, across a
spectrum of health endpoints (see Section 6). Second, tripropylene glycol n-butyl ether would degrade
in aerobic environments (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 tripropylene glycol n-butyl
ether 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 tripropylene glycol n-butyl ether 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 tripropylene glycol n-butyl ether and related
potential exposures and hazards.
Rationale: EPA evaluated the conditions of use of tripropylene glycol n-butyl ether (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 known,
intended, or reasonably foreseen, the outcome of the screening-level review would likely not change
and would not alter the Agency's conclusion of low concern. EPA bases this expectation on
tripropylene glycol n-butyl ether'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
tripropylene glycol n-butyl ether 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
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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 tripropylene glycol n-butyl ether meets the standard for a high-priority substance. The
reasonably available information on conditions of use, or significant changes in conditions of use,
described above provides sufficient information to support this proposed finding.
8.6 The Volume or Significant Changes in Volume of the Chemical
Substance Manufactured or Processed
Approach: EPA evaluated the current production volumes of tripropylene glycol n-butyl ether
(Section 7.1) and related potential exposures (Sections 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 tripropylene glycol n-butyl ether as a low-
priority substance could result in increased use and higher production volumes. EPA expects,
however, that any changes in tripropylene glycol n-butyl ether'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 tripropylene glycol n-butyl ether's consistently low-concern hazard characteristics
across the spectrum of hazard endpoints. This expectation would apply, even with a significant
change in the volume of the chemical manufactured or processed and resultant increased exposures.
Proposed conclusion: Based on 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
exposure, tripropylene glycol n-butyl ether 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-level review to support the proposed
designation of tripropylene glycol n-butyl ether 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 tripropylene glycol n-butyl ether 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. According to the 2016 Chemical Data Reporting (CDR) database,
four companies manufactured or imported tripropylene glycol n-butyl ether at four sites for reporting
year 2015.
Table A.l presents the historic production volume of tripropylene glycol n-butyl ether from the CDR
(previously known as the Inventory Update Rule, or IUR) from 1986-2015. From 1986 to 1994
reporting years, no data was reported for the aggregate production volume of tripropylene glycol n-
butyl ether. 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. For the 1998 reporting year, the aggregate
production volume of tripropylene glycol n-butyl ether was between 500,000 and 1,000,000 lbs. From
2002 to 2015 reporting years, the aggregate production volume of tripropylene glycol n-butyl ether
was between 1,000,000 and 10,000,000 lbs. For the 2011 reporting, aggregate production volume
information was withheld. In general, since 2012, production volume has remained relatively stable
without significant increases or decreases.
Table A.1:1986-2015 National Production Volume Data for Tripropylene Glycol n-Butyl Ether (Non-Confidential
Production Volume in Pounds)
1986
1990
1994
1998
2002
2006
2011
2012
2013
2014
2015
NDR
NDR
NDR
500 K-
1M
1 M-
10 M
1 M-
10 M
Withheld
1 M-
10 M
1 M-
10 M
1 M-
10 M
1 M-
10 M
Source(s):
EPA (2002; 2006; 2017b; 2018a)
Note(s):
K = Thousand; M = Million; NDR = No data reported
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A.2 Uses
A.2.1 Methods for Uses Table
Section A.l provides a list of known uses of tripropylene glycol n-butyl ether, 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 Tripropylene Glycol n-Butyl Ether
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)
55934-93-5
No
Canada Chemicals
Management Plan
information sheets
Government of Canada
(2018)
Tripropylene glycol n-
butyl ether
No
Chemical and Product
Categories (CPCat)
CPCat (2019)
55934-93-5
Yes
ChemView2
EPA (2018a)
55934-93-5
Yes
Children's Safe Product Act
Reported Data
Washington State Dept. of
Ecology (2018)
55934-93-5
No
Consumer Product
Information Database
(CPID)
DeLima Associates (2018a)
55934-93-5
Yes
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
No
Datamyne
Descartes Datamyne (2018)
Tripropylene glycol n-
butyl ether
No
DrugBank
DrugBank (2018)
55934-93-5
No
European Chemicals
Agency (ECHA)
Registration Dossier
ECHA (2018)
55934-93-5
Yes
eChemPortal2
OECD (2018)
55934-93-5
No
Envirofacts2
EPA (2018b)
55934-93-5
No
Functional Use Database
(FUse)
EPA (2017a)
55934-93-5
Yes
Kirk-Othmer Encyclopedia
of Chemical Technology
Kirk-Othmer (2006)
Tripropylene glycol n-
butyl ether; Tripropylene
glycol monobutyl ether
No
Non-Confidential 2016
Chemical Data Reporting
(CDR)
EPA (2017b)
55934-93-5
Yes
PubChem Compound
Kim etal. (2016)
55934-93-5
Yes
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Table A.2: Sources Searched for Uses of Tripropylene Glycol n-Butyl Ether
Title
Author and Year
Search Term(s)
Found Use Information?1
Safer Chemical Ingredients
List (SCIL)
EPA (2018d)
55934-93-5
Yes
Synapse Information
Resources2
Synapse Information
Resources (2009)
Tripropylene glycol n-
butyl ether
Yes
Resource Conservation
and Recovery Act
EPA (2018c)
Tripropylene glycol n-
butyl ether; Tripropylene
glycol butyl ether;
No
Scorecard: The Pollution
Information Site
GoodGuide (2011)
55934-93-5
No
Skin Deep Cosmetics
Database
EWG (2018)
55934-93-5
No
Toxics Release Inventory
(TRI)
EPA (2018e)
55934-93-5
No
TOXNET 2
NLM (2018a)
55934-93-5
Yes
Ullmann's Encyclopedia of
Industrial Chemistry
Ullmann's (2000)
Tripropylene glycol n-
butyl ether; Tripropylene
glycol monobutyl ether
No
Additional sources identified from reasonably available information
CLR Brands
CLR Brands (2018a)
Incidentally identified
while researching details
of this chemical's uses
and products.
Yes
Note(s):
1. If use information was found in the resource, it will appear in Table 3-2 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 526 patents referencing
"tripropylene glycol n-butyl ether" (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 tripropylene glycol n-butyl ether 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 Tripropylene Glycol n-butyl Ether
Table A.3: Uses of Tripropylene Glycol n-Butyl Ether
Use
Expected Users
Description of Use and References
TSCA Conditions of Use: Cleaning and Furnishing Care Products
CDR reports use of tripropylene glycol n-butyl ether in consumer cleaning and furnishing care products at concentrations of at least 1 percent but less than 30 percent by
weight (EPA 2017b).
ECHA (2018)
Air care products
Consumer
The ECHA registration dossiers lists the use tripropylene glycol n-butyl ether in air
care products. ECHA does not expand on this use, however this category generally
includes products such as air fresheners, candles, and scented gels. 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 based on inclusion in ECHA's consumer uses.
CLR Brands (2018a)
Bath cleaner
Consumer,
commercial
Tripropylene glycol n-butyl ether is listed as an ingredient in consumer and
commercial bathroom cleaner products, for grout and tile, sinks and toilets.
Expected users are consumer and commercial, as the product is available for
consumer and commercial use.
CLR Brands (2018f); CLR Brands (2018b)
Descalers
Consumer,
commercial
Tripropylene glycol n-butyl ether is listed as an ingredient in a descalers such as
kitchen, lime and rust remover products.
Expected users are consumer and commercial, as the products is available for use
in both consumer and commercial settings.
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Table A.3: Uses of Tripropylene Glycol n-Butyl Ether
Use
Expected Users
Description of Use and References
CPCat (2019); ECHA (2018)
Cleaning/washing agent
Consumer,
commercial, industrial
CPCat lists the use of tripropylene glycol n-butyl ether in cleaning and washing
agents. The ECHA registration dossier indicates the use of tripropylene glycol n-
butyl ether in washing and cleaning products/ agents.
Expected users are consumer, commercial, and industrial based on inclusion in
ECHA's consumer uses, uses by professional workers, and uses at industrial sites.
Degreaser
Consumer,
commercial
CPCat (2019)
CPCat lists the use of tripropylene glycol n-butyl ether in "degreasers (cold
degreasing, de-waxing, de-polishing)."
DeLima Associates (2018b)
Hardwood floor finish
Consumer
CPID generally includes products for consumer use; therefore the expected user is a
consumer.
CLR Brands (2018c)
Kitchen cleaner
Consumer,
commercial
Tripropylene glycol n-butyl ether is listed as an ingredient in consumer and
commercial kitchen cleaner products
Expected users are consumer and commercial, as the product is available for
consumer and commercial use.
CLR Brands (2018d)
Metal cleaner/ polish
Commercial
Tripropylene glycol n-butyl ether is listed as an ingredient in a commercial metal
cleaning product.
Expected users are commercial, as the product is available for commercial use.
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Table A.3: Uses of Tripropylene Glycol n-Butyl Ether
Use
Expected Users
Description of Use and References
CLR Brands (2018g)
Mold and mildew stain remover
Consumer,
commercial
Tripropylene glycol n-butyl ether is listed as an ingredient in mold and mildew stain
remover products.
Expected users are consumer and commercial, as the products is available for use
in both consumer and commercial settings.
CLR Brands (2018e)
Multi-surface cleaner
Consumer
Tripropylene glycol n-butyl ether is listed as an ingredient in a kitchen and multi-
surface cleaner currently available for use.
Expected users are consumer, as the product is available for consumer use.
TSCA Conditions of Use: Industrial Uses
ECHA (2018)
Coatings
Industrial
The ECHA registration dossier lists the use tripropylene glycol n-butyl ether in
coatings used for various industrial processes and products including chemical and
in industrial spraying.
Expected users are industrial based on inclusion in ECHA's uses at industrial sites.
CPCat (2019)
Construction
Industrial
CPCat lists the use of tripropylene glycol n-butyl ether in construction materials and
in the construction of buildings.
Expected users are industrial based on CDR's Industrial Processing and Use report.
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Table A.3: Uses of Tripropylene Glycol n-Butyl Ether
Use
Expected Users
Description of Use and References
ECHA (2018)
Metal working fluids
Commercial,
industrial
The ECHA registration dossiers lists the use tripropylene glycol n-butyl ether in
"metal working fluids/ rolling oils." It is unknown if use is ongoing in the United
States.
Expected users are commercial and industrial based on inclusion in ECHA's uses by
professional workers and uses at industrial sites.
ECHA (2018)
Mining chemicals
Industrial
The ECHA registration dossier lists the use of tripropylene glycol n-butyl ether in
mining chemicals. No further information could be found on this use in the United
States.
Expected users are industrial based on inclusion in ECHA's uses at industrial sites.
ECHA (2018)
Oil and gas drilling
Industrial
The ECHA registration dossier lists the use of tripropylene glycol n-butyl ether in oil
and gas field drilling and production operations. No further information could be
found on this use in the United States.
Expected users are industrial based on inclusion in ECHA's uses at industrial sites.
EPA (2017b)
Wholesale and retail trade
Industrial
CDR reports use of tripropylene glycol n-butyl ether as a plasticizer in wholesale and
retail trade. No further information could be found on this specific use.
Expected users are industrial based on CDR's Industrial Processing and Use report.
VII
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***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table A.3: Uses of Tripropylene Glycol n-Butyl Ether
Use
Expected Users
Description of Use and References
TSCA Conditions of Use: Manufacturing
EPA (2017b); CPCat (2019); ECHA (2018)
Chemical manufacturing
Industrial
CDR reports use of tripropylene glycol n-butyl ether as a solvent and processing aid
in "chemical product and preparation manufacturing" and in "other basic organic
chemical manufacturing" at concentrations of at least percent by weight. CPCat lists
the use of tripropylene glycol n-butyl ether in chemical, chemical products, and basic
organic chemical manufacturing. The ECHA registration dossier lists the use of
tripropylene glycol n-butyl ether as an intermediate in the manufacture of "bulk, large
scale chemical (including petroleum products)" and fine chemicals.
Expected users are industrial based on CDR's Industrial Processing and Use report.
CPCat (2019)
Communication equipment manufacturing
Industrial
CPCat lists the use of tripropylene glycol n-butyl ether in the manufacture of "radio,
television and communication equipment."
Expected users are industrial based on CPCat's user classification.
CPCat (2019)
Electrical manufacturing
Industrial
CPCat lists the use of tripropylene glycol n-butyl ether in the manufacture of
electrical machinery, apparatus and optical equipment.
Expected users are industrial based on CPCat's user classification.
CPCat (2019)
Fabricated metal product manufacturing
Industrial
CPCat lists the use of tripropylene glycol n-butyl ether in the manufacture of
"fabricated metal products, except machinery."
Expected users are industrial based on CPCat's user classification.
VIII
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***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table A.3: Uses of Tripropylene Glycol n-Butyl Ether
Use
Expected Users
Description of Use and References
CPCat (2019)
Furniture manufacturing
Industrial
CPCat lists the use of tripropylene glycol n-butyl ether in the manufacture of
furniture, and in industrial varnishing and acid washing of furniture.
Expected users are industrial based on CPCat's user classification.
CPCat (2019)
Paint manufacturing
Industrial
CPCat lists the use of tripropylene glycol n-butyl ether in the manufacture of "paints,
varnishes, and similar coatings, print."
Expected users are industrial based on CPCat's user classification.
CPCat (2019)
Wood manufacturing
Industrial
CPCat lists the use of tripropylene glycol n-butyl ether in the manufacture of "wood
and products of wood and cork."
Expected users are industrial based on CPCat's user classification.
TSCA Conditions of Use: Pesticides and Agriculture
ECHA (2018)
Agrochemicals
Commercial
The ECHA registration dossiers lists the use tripropylene glycol n-butyl ether in
agrochemicals. It is unknown if use is ongoing in the United States.
Expected users are commercial based on inclusion in ECHA's uses by professional
workers.
CPCat (2019)
Inert ingredient
Unknown
CPCat lists the use of tripropylene glycol n-butyl ether as an inert ingredient in
pesticides.
Expected users are unknown, due to the limited availability of information.
IX
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***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table A.3: Uses of Tripropylene Glycol n-Butyl Ether
Use
Expected Users
Description of Use and References
TSCA Conditions of Use: Miscellaneous
ECHA (2018)
Adhesives and sealants
Consumer
The ECHA registration dossiers lists the use tripropylene glycol n-butyl ether in
adhesives and sealants. It is unknown if use is ongoing in the United States.
Expected users are consumer based on inclusion in ECHA's consumer uses.
ECHA (2018)
Anti-freeze and deicing products
Consumer
The ECHA registration dossiers lists the use tripropylene glycol n-butyl ether in anti-
freeze and de-icing products. It is unknown if use is ongoing in the United States.
Expected users are consumer based on inclusion in ECHA's consumer uses.
ECHA (2018)
Inks and toners
Consumer
The ECHA registration dossiers lists the use tripropylene glycol n-butyl ether in inks
and toners. It is unknown if use is ongoing in the United States.
Expected users are consumer based on inclusion in ECHA's consumer uses.
ECHA (2018)
Leather treatment products
Consumer
The ECHA registration dossiers lists the use tripropylene glycol n-butyl ether in
leather treatment products. It is unknown if use is ongoing in the United States.
Expected users are consumer based on inclusion in ECHA's consumer uses.
ECHA (2018)
Lubricants and greases
Consumer
The ECHA registration dossiers lists the use tripropylene glycol n-butyl ether in
"lubricants, greases, release products." It is unknown if use is ongoing in the United
States.
Expected users are consumer based on inclusion in ECHA's consumer uses.
X
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***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table A.3: Uses of Tripropylene Glycol n-Butyl Ether
Use
Expected Users
Description of Use and References
ECHA (2018)
Non-metal surface treatment products
Consumer
The ECHA registration dossiers lists the use tripropylene glycol n-butyl ether in non-
metal surface treatment products. It is unknown if use is ongoing in the United
States.
Expected users are consumer based on inclusion in ECHA's consumer uses.
CPCat (2019); ECHA (2018)
Paint, lacquers, coatings, varnishes
Consumer,
commercial
CPCat lists the use of tripropylene glycol n-butyl ether in paints, lacquers and
varnishes, including water based, thinners, decorative, and protective exterior. The
ECHA registration dossier lists the use of tripropylene glycol n-butyl ether in coatings
and paints, thinner and painter removes.
Expected users are consumer and commercial based on inclusion in ECHA's
consumer uses and uses by professional workers.
ECHA (2018)
Perfumes and fragrances
Consumer
The ECHA registration dossiers lists the use tripropylene glycol n-butyl ether in
perfumes and fragrances. It is unknown if use is ongoing in the United States.
Expected users are consumer based on inclusion in ECHA's consumer uses.
ECHA (2018)
Polishes and wax blends
Consumer
The ECHA registration dossiers lists the use tripropylene glycol n-butyl ether in
polishes and wax blends. It is unknown if use is ongoing in the United States.
Expected users are consumer based on inclusion in ECHA's consumer uses.
XI
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***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table A.3: Uses of Tripropylene Glycol n-Butyl Ether
Use
Expected Users
Description of Use and References
ECHA (2018)
Textile dyes
Consumer
The ECHA registration dossiers lists the use tripropylene glycol n-butyl ether in
"textile dyes, and impregnating products." It is unknown if use is ongoing in the
United States.
Expected users are consumer based on inclusion in ECHA's consumer uses.
ECHA (2018)
Welding and soldering products
Consumer
The ECHA registration dossiers lists the use tripropylene glycol n-butyl ether in
"welding and soldering products, flux products." It is unknown if use is ongoing in the
United States.
Expected users are consumer based on inclusion in ECHA's consumer uses.
Non-TSCA Uses
ECHA (2018)
Biocides
Consumer
The ECHA registration dossiers lists the use tripropylene glycol n-butyl ether in
biocidal products such disinfectants and for pest control. It is unknown if use is
ongoing in the United States.
Expected users are consumer based on inclusion in ECHA's consumer uses.
ECHA (2018)
Cosmetics, personal care products
Consumer
The ECHA registration dossiers lists the use tripropylene glycol n-butyl ether in
cosmetics, personal care products. More specific uses within this use category were
not listed, therefore it is unknown if this is an ongoing use in the Unity States.
Expected users are consumer based on inclusion in ECHA's consumer uses.
CDR reports did not include any uses in children's products.
Children's Products
Recycling and Disposal
In the 2016 CDR, three facilities reported that the chemical was not recycled, and one facility reported this information as CBI. (EPA 2017b)
XII
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***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
A.3 References
California Dept of Pesticide Regulation. (2013). DPR Databases. Retrieved from
https: //www. cdpr. ca. gov/dprdatabase .htm
CLR Brands. (2018a). CLR PRO® BATH CLEANER. Retrieved from
https://clrbrands.com/PROLINE/Commercial-Products/CLR-PROLINE/CLR-PRQ-Bath-Cleaner
CLR Brands. (2018b). CLR PRO® CALCIUM LIME AND RUST REMOVER. Retrieved from
https: //clrbrands. com/PROLINE/C ommercial-Products/C LR-PROLINE/C LR-PRO-C alcium-
Lime-and-Rust-Remover
CLR Brands. (2018c). CLR PRO® KITCHEN CLEANER.
CLR Brands. (2018d). CLR PRO® METAL CLEANER. Retrieved from
https: //clrbrands. com/PROLINE/C ommercial-Products/C LR-PROLINE/C LR-PRO-Metal-
Cleaner
CLR Brands. (2018e). CLR® BATH & KITCHEN CLEANER.
CLR Brands. (2018f). CLR® CALCIUM, LIME, & RUST REMOVER. Retrieved from
https: //clrbrands. com/Products/C LR-Household/C LR-C alcium-Lime-Rust-Remover
CLR Brands. (2018g). CLR® MOLD & MILDEW STAIN REMOVER. Retrieved from
https: //clrbrands. com/Products/C LR-Household/C LR-Mold-Mildew- Stain-Remover
Danish EPA. (2018). Danish surveys on chemicals in consumer products. Retrieved from
https://cng.mst.dk/chcmicals/chcmicals-in-products/consumcrs-consumcr-products/danish-
survevs-on-consumer-products/
DeLima Associates. (2018a). Consumer Product Information Database. Retrieved from
https: //www. whatsinproducts. com/
DeLima Associates. (2018b). Minwax Ultimate Floor Finish, Professional Formula, Semi-Gloss,
131020000, Professional Use-05/29/2018. Retrieved from
https://www.whatsinproducts.com/tvpes/tvpe detail/1/20814/standard/div%20id=%22cke pasteb
in%22%3EMinwax%20Ultimate%20Floor%20Finish.%20Professional%20Formula.%20Semi-
Gloss.%20131020000.%20Professional%20Use-05/29/2018/div%3E/13-018-166
Descartes Datamyne. (2018). Descartes Datamyne Import-Export Database.
Dionisio, K. L. (CPCat), 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). DrugBank Database. Retrieved from https://www.drugbank.ca/
European Chemicals Agency (ECHA). (2018). [(butoxymethylethoxy)methylethoxy]propan-l-ol.
XIII
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EWG. (2018). BEHENYL ALCOHOL. Retrieved from
https://www.ewg.org/skindeep/ingredient/70Q659/BEHENYL ALCOHOL/# W5bipflKiUk
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
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.
Organisation for Economic Cooperation and Development (OECD). (2018). eChemPortal: Global Portal
to Information on Chemical Substances. Retrieved from
https: //www .echemportal. org/echemportal/index. action
Synapse Information Resources. (2009). Specialty Chemicals Source Book. Fourth Edition. Volume 1.
The Dow Chemical Company. (2015). Product Safety Assessment DOWANOL TPnB Glycol Ether
[Tripropylene Glycol n-Butyl
Ether], Retrieved from
http://msdssearch.dow.com/PublishedLiteratureDOWCQM/dh 096d/0901b8038096dc22.pdf?file
path=productsafetv/pdfs/noreg/23 3 -00469 .pdf&fromPage=GetDoc
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
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
XIV
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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). (2018a). ChemlDplus, a TOXNET Database. Retrieved from
https: //chem .nlm .nih. gov/chemidplus/
U.S. National Library of Medicine (NLM). (2018b). Haz-Map. Retrieved from
https://hazmap.nlm .nih. gov/categorv-details?id=19026&table=copvtblagents
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=50&TERMl=tripropvlene+glvcol+n-
butvl+ether&FIELD 1=&co 1 =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/
XV
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***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Appendix B: Hazard Characterization
Table B.1: Human Health Hazard
Acute Mammalian Toxicity
Source
Exposure
Route
Species &
strain (if
available)
Duration
Doses and
replicate number
Effect
Study Details
5178571
Oral (gavage)
Wistar rats
Single
exposure, 14
day
observation
Doses: 2400, 3200,
and 4200 mg/kg
Replicates: 5 per
sex per dose
LDso: 2800 mg/kg
Methods:
• Test substance reported as CASRN 55934-93-5
• Purity: 99%
• OECD Guideline 401
• GLP compliant
Mortality Results:
• 3/10 in 2400 mg/kg dose
• 6/10 in 3200 mg/kg dose
• 10/10 in 4200 mg/kg dose
5178572
Oral
Fisher 344
rats
Single
exposure, 14
day
observation
Dose: 2000 mg/kg
Replicates: 3
females
LD50 > 2000 mg/kg
Methods:
• Test substance reported as CASRN 55934-93-5
• Purity: 85%
• OECD Guideline 401
• GLP compliance not reported
Mortality Results:
• 1/3 animals
5178576
Oral (gavage)
Wistar rats
Single
exposure
Dose: 2000 mg/kg
Replicates: 6 per
sex
LD50 > 2000 mg/kg
Methods:
• Test substance reported as CASRN 55934-93-5
• Purity not reported
• OECD Guideline 423
• GLP compliant
Mortality Results:
• 1/12 animals
5178577
Dermal
Wistar rats
25 hour
exposure, 14
day
observation
Dose: 2000 mg/kg
Replicates: 5 per
sex
LD50 > 2000 mg/kg
Methods:
• Test substance reported as CASRN 55934-93-5
• Purity: 99%
• OECD Guideline 402
• GLP compliant
XVI
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Table B.1: Human Health Hazard
Mortality Results:
• No mortalities
4956637,
Inhalation
Fischer 344
4 hour
Doses: 0 and 5.7
LCso > 5.7 mg/L
Methods
5015984
rats
exposure, 14
day
observation
mg/L
Replicates: 6 males
per group
• Test substance reported as CAS RN 88917-22-0
• Purity not reported
• Equivalent to OECD Guideline 403
• GLP compliant
Mortality Results:
• No mortalities
Repeated Dose Toxicity
Source
Exposure
Route
Species &
strain (if
available)
Duration
Doses and
replicate number
Effect
Study Details
5178575
Oral (gavage)
Fischer 344
28 days
Doses: 0,100, 350
NOAEL: 100 mg/kg-
Methods:
rats
and 1000 mg/kg-day
Replicates: 5 per
sex per dose
day
LOAEL: 350 mg/kg-
day based on
increased liver weight
and enlarged
hepatocyte
• Test substance reported as CASRN 55934-93-5
• Purity: 80.67%
• OECD Guideline 407
• GLP compliant
5178581
Oral (drinking
Fischer 344
13 weeks
Doses: 0,100, 350
NOAEL: 350 mg/kg-
Methods:
water)
rats
and 1000 mg/kg-day
Replicates (by
dose):
• 0 mg/kg-day:
20 per sex
• 100 mg/kg-day:
10 per sex
• 350 mg/kg-day:
10 per sex
• 1000 mg/kg-
day: 20 per sex
day
LOAEL: 1000 mg/kg-
day based on
increased liver and
kidney weights
• Test substance reported as CASRN 55934-93-5
• Purity: 97.7%
• OECD Guideline 408
• GLP compliant
• 10/20 animals in the 0 mg/kg-day and 1000 mg/kg-
day groups were given a 4-week recovery period
XVII
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***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table B.1: Human Health Hazard
3041622,
Dermal
Rabbits
90 days
Doses: 0, 950,
LOAEL: 9500 mg/kg-
Methods:
4944882
2850, 4750, and
9500 mg/kg-day
Replicates: 5-7
males per group
day (based on
increased mortality)
• Test substance reported as CASRN 34590-94-8
• Purity not reported; test substance was presumably
undiluted
• Doses reported in mL/kg-day; converted to mg/kg-
day based on a density of 0.95 g/mL
• GLP compliance not reported
4146480
Dermal
Porton-
28 days
Doses: 0,100, and
NOAEL1000 mg/kg-
Methods:
Wistar rats
1000 mg/kg-day
Replicates: 8 males
per group
day
• Test substance reported as CASRN 34590-94-8
• Purity not reported
• GLP compliance not reported
5077871
Dermal
Rabbits
90 days
Doses: 0, 2850, and
4750 mg/kg-day
Replicates: 5 males
per group
NOAEL: 4750 mg/kg-
day
Methods:
• Test substance reported as CASRN 34590-94-8
• Purity not reported
• GLP compliance not reported
4956637
Dermal
Wistar rats
13 weeks
Doses: 0, 91, 273,
and 910 mg/kg-day
Replicates: 10 per
sex per group
NOAEL: 91 mg/kg-day
LOAEL: 273 mg/kg-
day based on
decreased body
weights in males and
increased white blood
cell counts in both
sexes
Methods:
• Test substance reported as CAS RN 29911-28-2
• Purity > 95%
• GLP compliant
4944882,
Dermal
Rabbits
90 days
Doses: 0, 960,
NOAEL: 960 mg/kg-
Methods:
5077872,
2900, 4,800, and
day
• Test substance reported as CAS RN 25498-49-1
4956637
9600 mg/kg-day
Replicates: 5-8
males per group
LOAEL: 2900 mg/kg-
day based on
decreased body weight
and increased kidney
weight
• Purity not reported
• GLP compliance not reported
4946620
Inhalation
Fisher 344
13 weeks
Doses: 0, 0.091,
NOAEC: 1.212 mg/L-
Methods:
rats
0.393, and 1.212
mg/L-day
Replicates: 10 per
sex per group
day
• Test substance reported as CASRN 34590-94-8
• Purity: 99%
• GLP compliance not reported
XVIII
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Table B.1: Human Health Hazard
4946620
Inhalation
New
13 weeks
Doses: 0, 0.091,
NOAEC: 1.212 mg/L-
Methods:
Zealand
0.393, and 1.212
day
• Test substance reported as CASRN 34590-94-8
White
mg/L-day
• Purity: 99%
rabbits
Replicates: 10 per
sex per group
• GLP compliance not reported
Reproductive Toxicity
Source
Exposure
Route
Species &
Strain (if
available)
Duration
Doses and
replicate number
Effect
Study Details
5077928
Oral (gavage)
Sprague-
1 generation
Doses: 0, 50, 225,
NOAEL: 1000 mg/kg-
Methods:
Dawley rats
and 1000 mg/kg-day
Replicates:
32 per sex per dose
day
• Test substance reported as CASRN 30025-38-8
• Purity > 90.15%
• OECD Guideline 415
• GLP compliant
Developmental Toxicity
Source
Exposure
Route
Species &
Strain (if
available)
Duration
Doses and
replicate number
Effect
Study Details
4956637
Dermal
Wistar-
GD 6-15
Doses: 0, 273, and
NOAEL: 910 mg/kg-
Methods:
derived
910 mg/kg-day
day
• Test substance reported as CAS RN 29911-28-2
SPF-bred
Replicates: 21-25
• Purity > 95%
albino rats
per dose
• OECD Guideline 414
• GLP compliant
5077931
Inhalation
New
GD 7-19
Doses: 0.076, 0.23,
NOAEC: 0.45 mg/L-
Methods:
Zealand
and 0.45 mg/L for 6
day
• Test substance reported as CASRN 34590-94-8
White
hours per day
• Purity 100%
rabbits
Replicates: 16 per
dose
• EPA OTS 798.4350
• GLP compliant
5077930
Inhalation
Fisher 344
GD 6-15
Doses: 0.076, 0.23,
NOAEC: 0.45 mg/L-
Methods:
rats
and 0.45 mg/L for 6
hours per day
Replicates: 32-37
per dose
day
• Test substance reported as CASRN 34590-94-8
• Purity 100%
• EPA OTS 798.4350
• GLP compliant
XIX
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Table B.1: Human Health Hazard
5077934
Inhalation
Sprague
Dawley rats
GD 6-15
Doses: 0, 0.1, 0.3,
and 1.0 mg/L for 6
hours per day
Replicates: 25 per
dose
NOAEC: 1.0 mg/L-day
Methods:
• Test substance reported as CAS RN 25498-49-1
• Purity 98.5%
• GLP compliance not reported
5077932
Inhalation
Albino rats
GD 6-15
Doses: 0, 0.3, 0.9,
2.7, and 8.9 mg/L for
6 hours per day
Replicates: 7 per
dose
NOAEC: 8.9 mg/L-day
Methods:
• Test substance reported as CAS RN 25498-49-1
• Purity 98.5%
• GLP compliance not reported
Cancer
Source
Exposure
Route
Species &
Strain (if
available)
Duration
Doses and
replicate number
Effect
Study Details
OncoLogic v8.0
OncoLogic currently
has no assessment
criteria regarding
aliphatic ethers.
Structure could not be evaluated by Oncologic.
Genotoxicity
Source
Test Type &
endpoint
Species &
strain (if
available)
Metabolic
activation
Doses and controls
Results
Study Details
5178583
Gene
Salmonella
With and
Doses: 0, 50,158,
Negative
Methods:
mutation (in
typhimurium
without
500, 1580, and 5000
• Test substance reported as CASRN 55934-93-5
vitro)
strains
TA98,
TA100,
TA1535,
andTA1537
pg/plate
• Purity: 96.12%
• OECD Guideline 471
• GLP compliant
5077927
Chromosomal
Rat liver
Without
Doses: 0, 625,
Negative
Methods:
aberrations
RL4 cells
1250, 2500, and
• Test substance reported as CASRN 34590-94-8
(in vitro)
5000 pg/mL
• Purity not reported
• GLP compliance not reported
XX
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Table B.1: Human Health Hazard
5077935
Chromosomal
CHL/IU cells
With and
Doses: 0, 371,741,
Negative
Methods:
aberrations
without
and 1482 pg/mL
• Test substance reported as CASRN 34590-94-8
(in vitro)
• Purity > 99%
• Japan Guidelines for Screening Mutagenicity Testing
of Chemicals
• GLP compliant
5077938
DNA damage
Rat
Without
Doses: 0.1, 0.316,
Negative
Methods:
and repair
hepatocyte
cells
1,3.16, 10,31.6,
and 100 mM
• Test substance reported as CAS RN 25498-49-1
• Purity: 98.7%
• GLP compliance not reported
5077989
Chromosomal
Chinese
With and
Doses: 0,101,203,
Negative
Methods:
aberrations
hamster
without
405, 810, and 1620
• Test substance reported as CASRN 30025-38-8
(in vitro)
ovary cells
Ijg/mL
• Purity not reported
• OECD Guideline 473
• GLP compliant
4956637
Micronuclei
assay (in
vivo)
Mouse
With
Doses: 0, 250, 833,
and 2500 mg/kg
Replicates: 5 per
sex per dose
Negative
Methods:
• Test substance reported as CAS RN 29911-28-2
• Purity: 99.5%
• GLP compliant
4956637
Chromosomal
Chinese
With and
Doses:
Positive at cytotoxic
Methods:
aberrations
(in vitro)
hamster
ovary cells
without
• 0, 333, 1000,
and 3332
|jg/mL with
metabolic
activation;
• 0,1000, 2000,
3000, and 4000
|jg/mL without
activation
concentrations (3332
|jg/mL with activation)
• Test substance reported as CAS RN 29911 -28-2
• Purity > 95%
• GLP compliant
Results:
• Cytotoxicity observed at 1000 and 3332 pg/mL
with metabolic activation and 3000 and 4000
|jg/mL without metabolic activation
XXI
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***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table B.1: Human Health Hazard
4956637
Chromosomal
Chinese
With and
Doses:
Significantly increased
Methods:
aberrations
hamster
without
• 0, 500, 1000,
frequency of
• Test substance reported as CAS RN 29911-28-2
(in vitro)
ovary cells
2000, and 3000
|jg/mL with
metabolic
activation
• 0,1000, 2000,
3500, and 5000
|jg/mL without
activation
aberrations was
observed at 18-h
incubation period for
500,1000 and 3000
|jg/mL with metabolic
activation and 1000
and 5000 pg/mL
without metabolic
activation
• Purity not reported
• GLP compliant
Results:
• Significantly increased frequency of aberrations was
observed at 18-hour incubation period for 500,1000
and 3000 pg/mL with metabolic activation and 1000
and 5000 pg/mL without metabolic activation
• Cytotoxicity observed at 3000 pg/mL with metabolic
activation and 5000 pg/mL without metabolic
activation
4956637
Chromosomal
Chinese
With and
Doses: 0, 500,
Negative
Methods:
aberrations
hamster
without
1667, and 5000
• Test substance reported as CAS RN 29911-28-2
(in vitro)
ovary cells
Ijg/mL
• Purity: 99.5%
• GLP compliant
4956637
Chromosomal
Chinese
With
Doses: 0, 500,
Negative
Methods:
aberrations
hamster
1667, and 5000
• Test substance reported as CAS RN 29911-28-2
(in vitro)
ovary cells
Ijg/mL
• Purity: 99.5%
• GLP compliant
Irritation
Source
Exposure
Route
Species &
Strain (if
available)
Duration
Doses
Effect
Study Details
5178574
Dermal
New
Exposure for
Dose: 0.5 mL
Moderately Irritating
Methods:
Zealand
4 hours,
undiluted test
• Test substance reported as CASRN 55934-93-5
White
observed for
substance
• Purity: 99%
rabbits
7 days
Replicates: 3
rabbits
• OECD Guideline 404
• GLP Compliant
Results:
• Slight erythema in 3/3 animals
• Edema in 1/3 animals
XXII
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Table B.1: Human Health Hazard
5178579
Dermal
New
Exposure for
Dose: 0.5 mL
Moderately Irritating
Methods:
Zealand
24 hours,
undiluted test
• Test substance reported as CASRN 55934-93-5
White
observed for
substance
• Purity not reported
rabbits
8 days
Replicates: 3
rabbits
• OECD Guideline 404
• GLP Compliant
Results:
• Slight erythema in 3/3 animals but fully
reversible in 8 days
5178585
Ocular
New
Single
Dose: 0.1 mL
Irritating
Methods:
Zealand
exposure, 14
Replicates: 3
• Test substance reported as CASRN 55934-93-5
White
day
females
• Purity: 99%
rabbits
observation
• OECD Guideline 405
• GLP compliance not reported
Results:
• Iris score: 0.3/2 at 24 hours but fully reversible
by 48 hours
• Conjunctivae score: 1.7/3 but fully reversible by
14 days
• Chemosis score: 1/4 but fully reversible by 7
days
5178582
Ocular
New
Single
Dose: 0.1 mL of
Negative
Methods:
Zealand
exposure, 72
undiluted test
• Test substance reported as CASRN 55934-93-5
White
hour
substance
• Purity not reported
rabbits
observation
Replicates: 3 total
animals
• OECD Guideline 405
• GLP compliant
Results:
1 hour after exposure:
• Conjunctivae score: 2/3
• Chemosis score: 1.33/4
• Conjunctival discharge occurred in 3/3 animals
Averages for 24,48 and 72 hours after exposure:
• Conjunctivae score: 0.3/3
• All other average scores were 0
• All effects fully reversible by 72 hours
XXIII
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Table B.2: Environmental Hazard
Aquatic Toxicity: Experimental
Source
Species & strain
(if available)
Duration
Doses and
replicate number
Effect
Study Details
4985128, 4985120
Poecilia reticulata
96 hours
Doses: 0, 56,100,
180, 320, 560, and
1000 mg/L
(nominal)
Replicates: 2
replicates, each
with 6 organisms
per dose
LCso: 564 mg/L
(95%
confidence 501
to 691 mg/L)
Methods:
• Test substance reported as CASRN 55934-93-5
• Purity: 99%
• OECD Guideline 203
• GLP compliant
Endpoints:
• Based on behavior (pigmentation, hyperactivity, and inhibition of
swimming ability)
• EC50 > 180 mg/L to < 320 mg/L
• NOEC: 180 mg/L
4985123, 4985119
Daphnia magna
48 hours
Doses: 0,12.5,
25, 50, 100 mg/L
(nominal)
ECso > 100
mg/L
Methods:
• Test substance reported as CASRN 55934-93-5
• Purity not reported
• OECD Guideline 202
• GLP compliant
4985112
Pseudokirchneriella
5 days
Doses: 15.9, 22.3,
EC50: 351 mg/L
Methods:
subcapitata
33.3, 50.7, 84.4,
135.2,217.4,
355.4, 522.9 and
848.1 mg/L
(measured)
(cell volume);
265 mg/L (cell
count)
• Test substance reported as CASRN 55934-93-5
• Purity: 83%
• EPA OPP 122-2 (Algal Toxicity, Tiers I and II)
• GLP compliant
Aquatic Toxicity: Estimated
Model
Endpoint
Species
Predicted Effect
Level
Notes
ECOSAR v2.0
Chronic value
Freshwater
72 mg/L
SMILES Input: OCC(COCCOC(CCCOCC)C)C. I
(Class: Neutral
fish
Organics)
ECOSAR v2.0 (Class:
Chronic value
Daphnia
35 mg/L
I SMILES Input: OCC(COCCOC(CCCOCC)C)C. I
Neutral Organics)
magna
ECOSAR v2.0 (Class:
Chronic value
Green
56 mg/L
I SMILES Input: OCC(COCCOC(CCCOCC)C)C. I
Neutral Organics)
algae
XXIV
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***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table B.3: Fate
Environmental Fate: Experimental
Source
Endpoint
Duration
Doses and number of
replicates
Results
Study Details
4951403,
Biodegradation
28 days
Dose: 90 mg/L
Readily
Methods:
4985135
biodegradable
• Test substance reported as CASRN 55934-93-5
• Purity: 97.7%
• OECD Guideline 301F
• GLP compliant
Results:
• Degradation during test: 10% in 7.3 days; 60% in 10.5 days; 72% at
10-day window; 59% in 28 days by 02 consumption; 58% average
removal by DOC at 28 days and 56% mineralization to C02 after 28
days
4985134
Biodegradation
14 days
Doses: 20 and 32 mg/L
Readily
biodegradable
Methods:
• Test substance reported as CASRN 55934-93-5
• Purity not reported
• OECD Guideline 301A
• GLP compliant
Results:
• Kinetic degradation results: 2% in 1 day, 9% in 3 days, 69% in 5
days, 88% in 7 days, and 96% in 14 days
4985143
Biodegradation
28 days
Doses: 10 and 20 mg/L
Not readily
biodegradable
Methods:
• Test substance reported as CASRN 55934-93-5
• Purity: 98.47%
• OECD Guideline 301B
• GLP compliant
Results:
• 21.5% and 24.3% in 28 days (for 10 and 20 mg/L, respectively),
32% and 31% in 37 days
4985140
Biodegradation
28 days
Doses: 141.7 and 139 mg
DOC/L
Readily
biodegradable
Methods:
• Test substance reported as CASRN 55934-93-5
• Purity > 95%
• OECD Guideline 302B
• GLP compliant
Results:
XXV
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• 86% in 14 days, 92% in 21 days, 93% in 28 days
4985126
Toxicity to
microorganisms
30 minutes
Doses: 1000 mg/L
(nominal)
Negative
Methods:
• Test substance reported as CASRN 55934-93-5
• Purity not reported
• OECD Guideline 209
• GLP compliant
Environmental Fate: Modelled
Model
Data Type
Endpoint
Predicted Endpoint
Notes
EPISuite
v.4.11
Estimated
BAF
6.22
EPI Suite Physical Property Inputs - MP= -75 deg C; Log P = 1.896; WS = 25000 mg/L; HLC =
4.05E-08), SMILES: OC(C)COC(C)COC(C)COCCCC
EPISuite
v.4.11
Estimated
BCF
8.22 (regression on eq)
EPISuite
v.4.11
(BIOWIN
7)
Estimated
Anaerobic
biodegradation
Not predicted to
biodegrade quickly under
anaerobic conditions
Predicted probability of -0.7805. Fragment representation is valid.
Fast degradation is defined as predicted probability >0.5.
XXVI
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B.1 References
Bio-Research Laboratories LTD. (1985a). A range-finding teratological study of inhaled Dowanol TPM
(tripropylene glycol methyl ether) in the albino rat. (OTS0521266).
https://ntrl.ntis.gov/NTRL/dashboard/searchResults/titleDetail/OTSQ521266.xhtml
Bio-Research Laboratories LTD. (1985b). A teratological study of inhaled Dowanol TPM in the albino rat
with attached appendices. (OTS0521267).
https://ntrl.ntis.gov/NTRL/dashboard/searchResults/titleDetail/OTSQ521267.xhtml
Dow Chemical (Dow Chemical Company). (1982). Evaluation of Dowanol TPM in the rat hepatocyte
unscheduled DNA synthesis assay. (OTS0520748).
https://ntrl.ntis.gov/NTRL/dashboard/searchResults/titleDetail/QTS0520748.xhtml
Dow Chemical (Dow Chemical Company). (1998). Evaluation of ready biodegradability of five glycol
ethers using the oecd method 30If: manometric respirometry test, with cover letter dated
9/23/1998 (sanitized). (86980000183S).
Dow Chemical (Dow Chemical Company). (2000a). Chronic skin absorption of dipropylene glycol
methyl ether (50b). (OTS0520738).
https://ntrl.ntis.gov/NTRL/dashboard/searchResults/titleDetail/QTS0520738.xhtml
Dow Chemical (Dow Chemical Company). (2000b). Chronic skin absorption of propylene glycol methyl
ether (33b) and dipropylene glycol methyl ether (50b) in rabbits.
Dow Chemical (Dow Chemical Company). (2000c). Chronic skin absorption of tripropylene glycol
methyl ether (62b) with attachments. (OTS0520746. EPA Doc # 86-890001236.).
https://ntrl.ntis.gov/NTRL/dashboard/searchResults/titleDetail/QTS0520746.xhtml
EC HA (European Chemicals Agency). (1982). A mixture of RR and RS isomers of: (2-(2-methoxy-l-
methyl)ethoxy)-l-methylethyl acetate; (2-(2-methoxy-2-methyl)ethoxy)-l-methylethyl acetate;
(2-(2-methoxy-2-methyl)ethoxy)-2-methylethyl acetate; (2-(2-methoxy-1 -methyl)ethoxy)-2-
methylethyl acetate: acute toxicity: inhalation: 001 key | experimental result.
https://echa.europa.eu/registration-dossier/-/registered-dossier/15979/7/3/3
EC HA (European Chemicals Agency). (1987a). [(butoxymethylethoxy)methylethoxy]propan-l-ol: short-
term toxicity to fish: 001 key | experimental result, https://echa.europa.eu/registration-dossier/-
/registered-dossier/13383/6/2/2/?documentUUID=292bb7bb-fac6-4c46-8616-2cf6bl3e446b#
EC HA (European Chemicals Agency). (1987b). [(butoxymethylethoxy)methylethoxy]propan-l-ol: skin
irritation / corrosion: 002 supporting | experimental result, https://echa.europa.eu/registration-
dossier/-/registered-dossier/13383/7/4/2/?documentUUID=a5949aba-41d5-4415-b642-
55bc39868752
ECHA (European Chemicals Agency). (1988a). [(butoxymethylethoxy)methylethoxy]propan-l-ol: acute
toxicity dermal: 001 key | experimental result, https://echa.europa.eu/registration-dossier/-
/registered-dossier/13383/7/3/4
XXVII
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
EC HA (European Chemicals Agency). (1988b). [(butoxymethylethoxy)methylethoxy]propan-l-ol: acute
toxicity oral: 003 supporting | experimental result, https://ccha.curopa.cu/rcgistration-dossicr/-
/reaistered-dossier/13 3 83/7/3/2/?documentUUID=5 6401192-7944-49d3 -bf2d-9025 7c5 9e97f
EC HA (European Chemicals Agency). (1988c). [(butoxymethylethoxy)methylethoxy]propan-l-ol: acute
toxicity: oral: 001 key | experimental result, https://ccha.curopa.cu/rcgistration-dossicr/-
/registered-dossier/13383/7/3/2
EC HA (European Chemicals Agency). (1988d). [(butoxymethylethoxy)methylethoxy]propan-l-ol: eye
irritation: 002 supporting | experimental result, https://echa.europa.eu/registration-dossier/-
/registered-dossier/13383/7/4/3/?documentUUID=b015fa81-3580-4b76-b393-82201b96720c
EC HA (European Chemicals Agency). (1988e). [(butoxymethylethoxy)methylethoxy]propan-l-ol: short-
term toxicity to aquatic invertebrates: 002 supporting | experimental result.
https://www.echa.europa.eu/web/guest/registration-dossier/-/registered-
dossier/13383/6/2/4/?documentUUID=00c29155-llel-404f-b006-734eada5e6cd
EC HA (European Chemicals Agency). (1988f). [(butoxymethylethoxy)methylethoxy]propan-l-ol: short-
term toxicity to fish: 001 key | experimental result, https://echa.europa.eu/registration-dossier/-
/registered-dossier/13383/6/2/2/?documentUUID=292bb7bb-fac6-4c46-8616-2cf6bl3e446b#
EC HA (European Chemicals Agency). (1989). [(butoxymethylethoxy)methylethoxy]propan-l-ol: genetic
toxicity: in vivo: experimental result. https://echa.europa.eu/registration-dossier/-/registered-
dossier/133 83/7/7/3
EC HA (European Chemicals Agency). (1990a). (2-methoxymethylethoxy)propanol: developmental
toxicity / teratogenicity: 001 key | experimental result.
https://www.echa.europa.eu/web/guest/registration-dossier/-/registered-
dossier/1475 l/7/9/3/?documentUUID=e 8135 7dc-b2 lb-48b5 -968 0-fa0c79cd3 610
EC HA (European Chemicals Agency). (1990b). (2-methoxymethylethoxy)propanol: developmental
toxicity / teratogenicity: 002 key | experimental result.
https://www.echa.europa.eu/web/guest/registration-dossier/-/registered-
dossier/14751/7/9/3/?documentUUID=358e7ca7-9d2b-4569-898d-f2d306664c34
EC HA (European Chemicals Agency). (1990c). [(butoxymethylethoxy)methylethoxy]propan-l-ol:
repeated dose toxicity oral: 002 supporting | experimental result.
https://echa.europa.eu/registration-dossier/-/registered-
dossier/13383/7/6/2/?documentUUID=6e40e7de-ca61-4860-9cd7-0a717bc55c26
EC HA (European Chemicals Agency). (1991). [(butoxymethylethoxy)methylethoxy]propan-l-ol:
repeated dose toxicity: oral: 001 key | experimental result, https://echa.europa.eu/registration-
dossier/-/registered-dossier/13383/7/6/2
ECHA (European Chemicals Agency). (1993). [(butoxymethylethoxy)methylethoxy]propan-l-ol:
Biodegradation in water: Screening tests: 003 Supporting | experimental result.
https://echa.europa.eu/registration-dossier/-/registered-
dossier/13383/5/3/2/?documentUUID=e94b3cla-e9d0-4a24-b980-673492312d8c
ECHA (European Chemicals Agency). (1994). l-(2-ethoxypropoxy)propan-2-ol; l-[(l-ethoxypropan-2-
yl)oxy]propan-2-ol: Toxicity to reproduction: 001 Weight of evidence | Experimental result.
XXVIII
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***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
https://www.echa.europa.eu/web/guest/registration-dossier/-/registered-
dossier/5800/7/9/2/?documentUUID=2ea91d99-9f68-442b-ae87-e84a0ade9051
EC HA (European Chemicals Agency). (1997). l-(2-ethoxypropoxy)propan-2-ol; l-[(l-ethoxypropan-2-
yl)oxy]propan-2-ol: genetic toxicity: in vitro: 003 key | experimental result.
https://\\\v\\ .ccha.curopa.cu/\vcb/gucst/rcgistration-dossicr/-/rcgistcrcd-
dossier/5800/7/7/2/?documentUUID=7483f0e2-bada-420b-bcdd-f6259be2434b
EC HA (European Chemicals Agency). (1998). [(butoxymethylethoxy)methylethoxy]propan-l-ol:
biodegradation in water: screening tests: 001 key | experimental result.
https://echa.europa.eu/registration-dossier/-/registered-
dossier/13383/5/3/2/?documentUUID=fl89898c-7bbb-4b00-8cle-c42269e8b080
EC HA (European Chemicals Agency). (2000a). l-(2-ethoxypropoxy)propan-2-ol; l-[(l-ethoxypropan-2-
yl)oxy]propan-2-ol: Repeated dose toxicity: oral: 001 key | experimental result.
https://www.echa.europa.eu/web/guest/registration-dossier/-/registered-
dossier/5800/7/6/2/?documentUUID=la294915-822a-4587-a7b4-3cl7051a96ac
EC HA (European Chemicals Agency). (2000b). (2-methoxymethylethoxy)propanol: genetic toxicity: in
vitro: 005 key| experimental result, https://www.echa.europa.eu/web/guest/registration-dossier/-
/registered-dossier/1475 l/7/7/2/?documentUUID=f 1 dO 1 db7-8b86-45 93 -a2fc-f8ec 1 cec6de7
EC HA (European Chemicals Agency). (2000c). A mixture of RRand RS isomers of: (2-(2-methoxy-l-
methyl)ethoxy)-l-methylethyl acetate; (2-(2-methoxy-2-methyl)ethoxy)-l-methylethyl acetate;
(2-(2-methoxy-2-methyl)ethoxy)-2-methylethyl acetate; (2-(2-methoxy-1 -methyl)ethoxy)-2-
methylethyl acetate: Toxicity to aquatic algae and cyanobacteria: 001 Key | experimental result.
https://echa.europa.eu/registration-dossier/-/registered-
dossier/15 979/6/2/6/?documentUUID=e73 5 95 64-a5 68-4c2f-ae3 9-e6b 106bd7046
EC HA (European Chemicals Agency). (2001a). l-butoxypropan-2-ol: skin irritation/corrosion: 005
supporting | experimental result. https://echa.curopa.cu/rcgistration-dossicr/-/registered-
dossier/14287/7/4/2/'MocumcntUUID=36a9a5c2-138c-465c-975a-2c34a60el4f4
EC HA (European Chemicals Agency). (2001b). [(butoxymethylethoxy)methylethoxy]propan-l-ol: acute
toxicity: oral: 002 supporting | experimental result, https://echa.europa.eu/registration-dossier/-
/registered-dossier/13383/7/3/2/?documentUUID=000fbal6-7ee2-479a-9b51-31c8cfa9e6f8
EC HA (European Chemicals Agency). (2001c). [(butoxymethylethoxy)methylethoxy]propan-l-ol: eye
irritation: 001 key | experimental result. https://echa.europa.eu/registration-dossier/-/registered-
dossier/133 83/7/4/3
EC HA (European Chemicals Agency). (200 Id). [(butoxymethylethoxy)methylethoxy]propan-l-ol:
toxicity to microorganisms: activated sludge respiration inhibition testing: 001 key | experimental
result. https://echa.europa.eu/registration-dossier/-/registered-
dossier/13383/6/2/8/?documentUUID=f35fbd75-d48e-4655-8646-7c5fe80874fe
EC HA (European Chemicals Agency). (2002a). [(butoxymethylethoxy)methylethoxy]propan-l-ol:
biodegradation in water: screening tests: 002 supporting | experimental result.
https://echa.europa.eu/registration-dossier/-/registered-
dossier/13 3 83/5/3/2/?documentUUID=63 71 f 16d-815 3 -4093 -aef3 -14f8 lb8624df
XXIX
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***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
EC HA (European Chemicals Agency). (2002b). [(butoxymethylethoxy)methylethoxy]propan-l-ol: short-
term toxicity to aquatic invertebrates: 002 supporting | experimental result.
https://echa.europa.eu/registration-dossier/-/registered-
dossier/13383/6/2/4/?documentUUID=61e66b27-6643-4158-bd05-af3d93a893b3
EC HA (European Chemicals Agency). (2009). [(butoxymethylethoxy)methylethoxy]propan-l-ol: toxicity
to aquatic algae and cyanobacteria: 001 key | experimental result.
https://echa.europa.eu/registration-dossier/-/registered-
dossier/13383/6/2/6/?documentUUID=aldfdf28-9366-4429-be98-05dalf409b34
Fairhurst. S; Knight. R; Marrs. TC; Scawin. JW; Spurlock. MS; Swanston. DW. (1989). Percutaneous
toxicity of ethylene glycol monomethyl ether and of dipropylene glycol monomethyl ether in the
rat. Toxicology 57: 209-215. htto://dx.doi.org/10.1016/0300-483X(89)90166-2
Landry. TP; Yano. BL. (1984). Dipropylene glycol monomethyl ether: A 13-week inhalation toxicity
study in rats and rabbits. Fundam Appl Toxicol 4: 612-617. http://dx.doi.org/10.1016/Q272-
0590(84)90051-4
OECD (Organisation for Economic Co-operation and Development). (2003). Propylene glycol ethers:
SIDS initial assessment report for SIAM 17: Arona, Italy, 11-14 November 2003. (SIDS Initial
Assessment Meeting (SIAM) 17). UNEP Publications.
http://www.inchem.org/documents/sids/sids/pges.pdf
Rowe. VK; Mccollister. DP; Spencer. HC: Oven. F; Hollingsworth. RL; Drill. VA. (1954). Toxicology of
mono-, di-, and tri-propylene glycol methyl ethers. AMA Arch Ind Hyg Occup Med 9: 509-525.
Shell Chemical (Shell Chemical Company). (1983). Toxicity studies with Dowanol DPM: Tests for in
vitro genotoxicity with attachments, cover sheets and letter dated 060689. (OTS0520390. EPA
Doc No: 86-890000952).
https://ntrl.ntis.gov/NTRL/dashboard/searchResults/titleDetail/OTS052039Q.xhtml
XXX
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***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
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 tripropylene glycol n-butyl ether. Search outcomes and reference
details are provided on the candidate's HERO38 project page.
EPA created a fit-for-purpose process to transparently document the literature search and review39 of
available hazard and fate information for low-priority substance (LPS) candidates. References from peer-
reviewed primary sources, grey sources,40 and other sources were identified, screened at the title/abstract
and full text-level, and evaluated for data quality based on discipline-specific criteria. An overview of the
literature search and review process is illustrated in Figure C1.
Figure C.l: Overview of the Literature Search and Review Process
GO
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, tripropylene glycol n-butyl ether, the following
analogs were used for designation: dipropylene glycol, monoethyl ether (CASRN 30025-38-8);
dipropylene glycol, methyl ether (CASRN 34590-94-8); dipropylene glycol, monobutyl ether (CASRN
29911-28-2); tripropylene glycol, monomethyl ether (25498-49-1). Dipropylene glycol, ethyl ether
(15764-24-6) and tripropylene glycol, methyl ether (20324-33-8) were also considered. For more details
and justification on analogs, see section 6.1.1. Analogs were used to fill data gaps on endpoints for which
38 The HERO low-priority substance candidate project pages are accessible to the public at https://hero.epa.gov/liero/.
This process is further discussed in the document "Approach Document for Screening Hazard Information for Low-Priority
Substances Under TSCA."
40 Grey literature and additional sources are the broad category of studies not found in standard, peer-reviewed literature database
searches. This includes U.S. and international government agency websites, non-government organization (NGO) websites, and
data sources that are difficult to find, or are not included, in the peer-reviewed databases, such as white papers, conference
proceedings, technical reports, reference books, dissertations, and information on various stakeholder websites.
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tripropylene glycol n-butyl ether lacked quality data, such as developmental toxicity, or to add to the
weight of the scientific evidence. EPA collected reasonably available information for these endpoints by
searching specific grey literature and other secondary sources, listed on Table C.l. If information related
to the identified analogs were available in these sources, the references were screened and evaluated using
the same process as references on tripropylene glycol n-butyl ether described above.26 EPA also used read
across from the LPS candidate, dipropylene glycol methyl ether acetate (CASRN 88917-22-0). The two
LPS chemicals along with the analogs mentioned above fall under the propylene glycol ethers cluster in
HERO.
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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 tripropylene glycol n-butyl ether 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 the propylene glycol ethers cluster including tripropylene glycol n-
butyl ether. For grey literature and other secondary sources, Table C.3 lists the search terms used for the propylene glycol ethers LPS candidates
and analogs.
Table C.2: Search Terms Used in Peer-Reviewed Databases
Discipline
Database
Search terms41
Human Health
PubMed
88917-22-0[rn] OR 55934-93-5[rn] OR "dipropylene glycol monomethyl ether acetate"[nm] OR
"((Butoxymethylethoxy)methylethoxy)propan-1-ol"[tw] OR "Dipropylene glycol monomethyl ether acetate"[tw] OR
41 Additional language or syntax such as [tw], [m], [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
Discipline
Database
Search terms41
"Dowanol TPnB"[tw] OR "PPG-2 methyl ether acetate"[tw] OR "PPG-3 BUTYL ETHER"[tw] OR "Propanol, (2-(2-
butoxymethylethoxy)methylethoxy)-"[tw] OR "Propanol, (2-methoxymethylethoxy)-, acetate"[tw] OR "Propanol, 1(or
2)-(2-methoxymethylethoxy)-, acetate"[tw] OR "Tripropylene glycol butyl ether"[tw] OR "Tripropylene glycol n-butyl
ether"[tw] OR "(2-(2-butoxymethylethoxy)methylethoxy)propanol"[tw] OR "(2-methoxymethylethoxy)propanol
acetate" [tw]
Toxline
(88917-22-0[rn] OR 55934-93-5[rn] OR "Dipropylene glycol monomethyl ether acetate" OR "PPG-2 methyl ether
acetate") 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]
"((Butoxymethylethoxy)methylethoxy)propan-1-ol" OR "Dowanol TPnB" OR "PPG-3 BUTYL ETHER" OR
"Propanol, (2-(2-butoxymethylethoxy)methylethoxy)-" OR "Propanol, (2-methoxymethylethoxy)-, acetate" OR
"Propanol, 1(or 2)-(2-methoxymethylethoxy)-, acetate" OR "Tripropylene glycol butyl ether" OR "Tripropylene
glycol n-butyl ether" OR "(2-(2-butoxymethylethoxy)methylethoxy)propanol" OR "(2-
methoxymethylethoxy)propanol acetate"
TSCATS1
(88917-22-0 [rn] OR 55934-93-5 [rn]) AND (TSCATS [org]) AND NOT PubMed [org] AND NOT pubdart [org]
WOS
TS=("88917-22-0" OR "55934-93-5" OR "((Butoxymethylethoxy)methylethoxy)propan-1-ol" OR "Dipropylene glycol
monomethyl ether acetate" OR "Dowanol TPnB" OR "PPG-2 methyl ether acetate" OR "PPG-3 BUTYL ETHER"
OR "Propanol, (2-(2-butoxymethylethoxy)methylethoxy)-" OR "Propanol, (2-methoxymethylethoxy)-, acetate" OR
"Propanol, 1(or 2)-(2-methoxymethylethoxy)-, acetate" OR "Tripropylene glycol butyl ether" OR "Tripropylene
glycol n-butyl ether" OR "(2-(2-butoxymethylethoxy)methylethoxy)propanol" OR "(2-
methoxymethylethoxy)propanol acetate")
lndexes=SCI-EXPANDED, CPCI-S, CPCI-SSH, BKCI-S, BKCI-SSH, CCR-EXPANDED, IC Timespan=AII years
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
TITLE=("88917-22-0" OR "55934-93-5" OR "Butoxymethylethoxy methylethoxy propan-1-ol" OR "Dipropylene
glycol monomethyl ether acetate" OR "PPG-2 methyl ether acetate" OR "Tripropylene glycol butyl ether" OR
"Tripropylene glycol n-butyl ether")
2 hits manually added (+1 dupe within this query)
SUBJECT=("88917-22-0" OR "55934-93-5" OR "Butoxymethylethoxy methylethoxy propan-1-ol" OR "Dipropylene
glycol monomethyl ether acetate" OR "PPG-2 methyl ether acetate" OR "Tripropylene glycol butyl ether" OR
"Tripropylene glycol n-butyl ether")
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Table C.2: Search Terms Used in Peer-Reviewed Databases
Discipline
Database
Search terms41
3 hits manually added
ABSTRACT=("88917-22-0" OR "55934-93-5" OR "Butoxymethylethoxy methylethoxy propan-1-ol" OR
"Dipropylene glycol monomethyl ether acetate" OR "PPG-2 methyl ether acetate" OR "Tripropylene glycol butyl
ether" OR "Tripropylene glycol n-butyl ether")
"Dowanol TPnB" OR "PPG-3 BUTYL ETHER" OR "Propanol, 2- 2-butoxymethylethoxy methylethoxy -" OR
"Propanol, 2-methoxymethylethoxy -, acetate" OR "2- 2-butoxymethylethoxy methylethoxy propanol" OR "2-
methoxymethylethoxy propanol acetate"
Fate
wos
Same as human health strategy synonyms only
Table C.3: Search terms used in grey literature and additional sources
Chemical
Search terms
Propylene glycol ether cluster
(Tripropylene glycol n-butyl
ether; DPMA)
Query string searched as a string or individually depending on resource: "5131-66-8" OR "107-
98-2" OR "108-65-6" OR "88917-22-0" OR "55934-93-5" OR "1-Butoxy-2-propanol" OR "1-
methoxy 2-propyl acetate" OR "1-methoxy-2-propanol" OR "1-methoxy-2-propyl acetate" OR "1-
Methoxypropan-2-ol" OR "2-acetoxy-1-methoxypropane" OR "2-methoxypropyl acetate" OR "2-
methoxy-1-methylethyl acetate" OR "3-Methoxy-2-propanol" OR "Butoxypropanol" OR
"Dipropylene glycol monomethyl ether acetate" OR "methoxyisopropanol" OR "Methoxyisopropyl
acetate" OR "n-Butoxy-2-propanol" OR "PGMEA" OR "PPG-2 methyl ether acetate" OR
"Propylene glycol methyl ether" OR "Propylene glycol monobutyl ether" OR "Propylene glycol
monomethyl ether" OR "propylene glycol n-butyl ether" OR "1-Butoxypropan-2-ol" OR "1-
methoxy-2-acetoxypropane" OR "propylene glycol 1 -methyl ether" OR "Propyleneglycol
monomethyl ether acetate" OR "Tripropylene glycol butyl ether" OR "Tripropylene glycol n-butyl
ether"
Analogs searched
Dipropylene glycol, ethyl ether (15764-24-6); dipropylene glycol, monoethyl ether (30025-38-8);
dipropylene glycol, methyl ether (34590-94-8); dipropylene glycol, monobutyl ether (29911-28-2);
tripropylene glycol, monomethyl ether (25498-49-1); tripropylene glycol, methyl ether (20324-33-
8)
After the search terms were applied, more than 100 references 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.26 Of these, 48 references were included for data evaluation and
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used to support the designation of tripropylene glycol n-butyl ether 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 tripropylene
glycol n-butyl ether. The excluded references are organized by discipline (human health hazard, environmental hazard, and fate), presented along
with a rationale based on exclusion criteria. The criteria26 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 tripropylene glycol n-butyl ether, EPA excluded a total of 47 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
Reference excluded (HERO ID) because the reference did NOT contain information needs42 relevant to human health hazard
1549118
4742957 2292715 4951403
Reference excluded (HERO ID) because the reference primarily contained in silico data
4946621
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
No
58939
to a low- priority substance candidate?
95230
655409
3114932
5015980
5015981
42 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.
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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)
5015982
5015983
5015985
5015986
5015987
5015988
5015989
5015990
5015992
5015993
5015994
5015996
5015997
5015998
5015999
5016000
5016001
5016002
5016003
5016004
5016005
5016006
5016009
5016011
5016015
5016016
5016020
5015992
5015994
What type of source is this reference?
Review article or book chapter that contains only
4851358
citations to primary literature sources
5015978
What kind of evidence does this reference
In silico studies that DO NOT contain experimental
N/A.
primarily contain?
verification
The following question apply to HUMAN evidence only
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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 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?
Note: If the paper does not pertain to mixtures,
choose "Not Applicable".
No
3114932
The following question apply to ANIMAL evidence only
Does the reference report an exposure route that
is by inhalation, oral, or dermal route?
No
5015178
Does the reference report both test substance-
related exposure(s) AND related health
outcome(s)?
No
N/A.
Does the reference report the duration of
exposure?
No
5015178
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
N/A.
Does the paper report a negative control that is a
vehicle control or no treatment control?
No43
5015178
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
N/A.
43 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).
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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 report an exposure to the test
substance only (i.e. no mixtures with the exception
of aqueous solutions and reasonable impurities
and byproducts)?
No
N/A.
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.
4956637
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).
4956637
Metric 3:
Positive controls
When applicable, an appropriate concurrent positive
control (i.e., inducing a positive response) was not
used.
N/A.
Metric 4:
Reporting of doses/concentrations
Doses/concentrations were not reported and could
not be calculated using default or reported
estimates of body weight and diet/water intake (e.g.,
default intake values are not available for pregnant
animals).
2530089
4956637
5016012
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Table C.6: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Human Health Hazard - Animal
Data Quality Metric
Unacceptable if:
References excluded (HERO ID)
Metric 5:
Exposure duration
The duration of exposure was not reported.
OR
The reported exposure duration was not suited to
the study type and/or outcome(s) of interest (e.g.,
<28 days for repeat dose).
2530089
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).
5015171
2530089
5015991
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).
2530089
4956637
5015171
5015991
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.).
2530089
4956637
5015171
5015991
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.
2530089
4956637
5014494
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Table C.7: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Human Health Hazard - In Vitro
Data Quality Metric
Unacceptable if:
References excluded (HERO ID)
Metric 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.
4956637
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).
4956637
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).
2530089
Metric 7:
Metabolic activation
No information on the characterization and use of a
metabolic activation system was reported.
OR
N/A.
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Table C.7: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Human Health Hazard - In Vitro
Data Quality Metric
Unacceptable if:
References excluded (HERO ID)
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).
Metric 8:
Test model
The test model was not reported
OR
The test model was not routinely used for
evaluation of the specific outcome of interest.
N/A.
Metric 9:
Outcome assessment methodology
The outcome assessment methodology was not
reported.
OR
The assessment methodology was not appropriate
for the outcome(s) of interest (e.g., cells were
evaluated for chromosomal aberrations immediately
after exposure to the test substance instead of after
post-exposure incubation period).
4956637
C.2.2 Environmental Hazard
For the screening review of LPS candidate tripropylene glycol n-butyl ether, EPA excluded a total of 21 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 needs44 relevant to environmental hazard
4742957
2563138
2530089
2292715
1549118
44187
3114932
4951403
4946621
3114932
4946621
4742957
Reference excluded (HERO ID) because the reference did NOT present quantitative environmental hazard data
N/A.
44 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.
XLII
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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 pertaining
No
3827368
to a low- priority substance candidate?
4985113
4985115
4985117
4985121
4985125
4985127
4985130
4985131
4985132
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 substance or
Mixture
N/A.
is the test substance a mixture (except for
Formulated Product
N/A.
reasonable impurities, byproducts, and aqueous
solutions) or formulated product?
Does the reference report a duration of exposure?
No
N/A.
Does the reference report a negative control that is
No
4985113
a vehicle control or no treatment control?
4985116
4985125
4985130
Does the reference include endpoints in the
No
N/A.
information needs?
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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.
4956637
Metric 2:
Negative controls
A concurrent negative control group was not
included or reported.
N/A.
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.
N/A.
Metric 5:
Exposure duration
The duration of exposure was not reported.
OR
The reported exposure duration was not suited to
the study type and/or outcome(s) of interest (e.g.,
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.
N/A.
Metric 8:
Reporting of data
Data presentation was inadequate.
OR
Major inconsistencies were present in reporting of
results.
N/A.
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C.2.3 Fate
For the screening review of LPS candidate tripropylene glycol n-butyl ether, EPA excluded a total of 9 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 needs45 relevant to environmental fate
1549118
2292715
2530089
4946621
4742957
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
4985137
4985138
4985141
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
N/A.
45 The information needs for fate includes a list of study characteristics pertaining to the associated media and exposure pathways, associated processes, and use of controls. A
complete list of the information needs is provided in Table A3 of the "Approach Document for Screening Hazard Information for Low-Priority Substances Under TSCA". These
information needs helped guide the development of questions for title/abstract and full-text screening.
XLV
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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)
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:
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.
4956637
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.
4956637
Metric 4:
Test method suitability
The test method was not reported or not suitable
for the test substance.
OR
The test concentrations were not reported.
OR
The reported test concentrations were not
measured, and the nominal concentrations reported
greatly exceeded the substances water solubility,
which would greatly inhibit meaningful interpretation
of the outcomes.
4956637
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.
N/A.
XLVI
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***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table C.13: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Fate
Data quality metric
Unacceptable if:
References excluded (HERO ID)
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.
Metric 7: Test organism-degradation
The test organism, species, or inoculum source
were not reported, preventing meaningful
interpretation of the study results.
4956637
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.
4956637
Metric 12:
Verification or plausibility of results
Reported value was completely inconsistent with
reference substance data, related physical chemical
properties, or otherwise implausible, indicating that
a serious study deficiency exists (identified or not).
N/A.
XLVII
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***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Appendix D: Summary of Public Comments
On March 21, 2019, EPA initiated the prioritization process for 20 chemical substances as candidates for
designation as Low-Priority Substances. EPA published a document in the Federal Register providing the
identity of the chemical substances being initiated for prioritization and a general explanation of why the
Agency chose these chemical substances. EPA provided a 90-day comment period during which
interested persons could submit relevant information on these chemical substances.46
For tripropylene glycol n-butyl ether, EPA received public comment recommending that the Agency
consider specific publicly available data sources. EPA reviewed all of these sources as part of its
screening review of the chemical. Table 1 below lists these recommended sources, the HERO ID (if
applicable), and notes about each source. EPA used the Health & Environmental Research Online
(HERO) database to search, retrieve, and/or store data sources supporting scientific assessments. For
references with HERO IDs, more information on the references can be found by searching the HERO ID
at https://hero.epa.gov/hero/index.cfm/search/index.
Table D.1: Recommended Sources for Tripropylene Glycol N-Butyl Ether based on Public Comment
Source
HERO ID
Notes
Amended Safety Assessment of Butyl Polyoxyalkylene
Ethers as Used in Cosmetics
2530089
This assessment was part of EPA's literature
review process but was excluded due to data
quality issues.
46 Docket number EPA-HQ-OPPT-2019-0131 includes the list of 20 chemical substances that are candidates for
designation as Low-Priority Substances for risk evaluation
(https://www.federalregister.gOv/documents/2019/03/21/2019-05404/initiation-of-prioritization-
under-the-toxic-substances-control-act-tsca). Individual dockets were established for each of the 20 low-
priority candidates. Docket number EPA-HQ-OPPT-2019-0118 addresses tripropylene glycol n-butyl ether.
XLVIII
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