***Proposal Draft - Do Not Cite, Quote or Release During Review***
Dossier for Candidate Low-Priority Substance propanol, [(1-
methyl-l,2-ethanediyl)bis(oxy)]bis-
(CASRN 24800-44-0)
(Tripropylene Glycol)
For Release at Proposal
August 9, 2019
Office of Pollution Prevention and Toxics
U.S. Environmental Protection Agency
1200 Pennsylvania Avenue
Washington, DC 20460
-------
***Proposal Draft - Do Not Cite, Quote or Release During Review***
Contents
1. Introduction 1
2. Background on Tripropylene Glycol 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 16
6.1.2 Acute Toxicity 17
6.1.3 Repeated Dose Toxicity 18
6.1.4 Reproductive and Developmental Toxicity 18
6.1.5 Genotoxicity 19
6.1.6 Carcinogenicity 19
6.1.7 Neurotoxicity 19
6.1.8 Skin Sensitization 20
6.1.9 Skin Irritation 20
6.1.10 Eye Irritation 20
6.1.11 Hazards to Potentially Exposed or Susceptible Subpopulations 20
6.2 Environmental Hazard 21
6.2.1 Acute Aquatic Toxicity 21
6.2.2 Chronic Aquatic Toxicity 21
6.3 Persistence and Bioaccumulation Potential 21
6.3.1 Persistence 21
6.3.2 Bioaccumulation Potential 22
7. Exposure Characterization 23
-------
***Proposal Draft - Do Not Cite, Quote or Release During Review***
7.1 Production Volume Information 23
7.2 Exposures to the Environment 23
7.3 Exposures to the General Population 24
7.4 Exposures to Potentially Exposed or Susceptible Subpopulations 24
7.4.1 Exposures to Workers 24
7.4.2 Exposures to Consumers 24
8. Summary of Findings 26
8.1. Hazard and Exposure Potential of the Chemical Substance 26
8.2. Persistence and Bioaccumulation 27
8.3. Potentially Exposed or Susceptible Subpopulations 28
8.4. Storage near Significant Sources of Drinking Water 28
8.5. Conditions of Use or Significant Changes in Conditions of Use of the Chemical Substance 29
8.6. The Volume or Significant Changes in Volume of the Chemical Substance Manufactured or Processed.... 30
8.7. Other Considerations 30
9. Proposed Designation 31
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 IV
A.3 References XIII
Appendix B: Hazard Characterization XVI
B.1 References XXXI
Appendix C: Literature Search Outcomes XXXVI
C.1 Literature Search and Review XXXVI
C.1.1 Search for Analog Data XXXVI
C.1.2 Search Terms and Results XXXVII
C.2 Excluded Studies and Rationale XL
C.2.1 Human Health Hazard Excluded References XL
C.2.2 Environmental Hazard XLVIII
C.2.3 Fate Llll
ii
-------
***Proposal Draft - Do Not Cite, Quote or Release During Review***
Appendix D: Summary of Public Comments 58
iii
-------
***Proposal Draft - Do Not Cite, Quote or Release During Review***
Tables
Table 1: Tripropylene Glycol at a Glance 3
Table 2: Physical-Chemical Properties for Tripropylene Glycol 4
Table 3: Conditions of Use for Tripropylene Glycol 10
Table 4: Low-Concern Criteria for Human Health and Environmental Fate and Effects 12
Table 5: Tripropylene Glycol and Analog Structures 16
Table A.1:1986-2015 National Production Volume Data for Tripropylene Glycol (Non-Confidential ^
Production Volume in Pounds)
Table A.2: Sources Searched for Uses of Tripropylene Glycol II
Table A3: Uses of Tripropylene Glycol IV
Table B.1: Human Health Hazard XVI
Table B.2: Environmental Hazard XXVI
Table B.3: Fate XXVII
Table C.1: Search Terms Used in Peer-Reviewed Databases XXXVIII
Table C.2: Search Terms Used in Grey Literature and Additional Sources XXXIX
Table C.3: Off-Topic References Excluded at Title/Abstract Screening for Human Health Hazard XL
Table C.4: Screening Questions and Off-Topic References Excluded at Full-text Screening for Human
Health Hazard
Table C.5: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for
Human Health Hazard - Animal
Table C.6: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for
Human Health Hazard - In Vitro
Table C.7: Off-Topic References Excluded at Title/Abstract Screening for Environmental Hazard XLIX
Table C.8: Screening Questions and Off-Topic References Excluded at Full-text Screening for LI
Environmental Hazard
i
-------
***Proposal Draft - Do Not Cite, Quote or Release During Review***
Table C.9: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for ^
Environmental Hazard
Table C.10: Off-Topic References Excluded at Initial Screening for Fate Llll
Table C.11: Screening Questions and Off-Topic References Excluded at Full-text Screening for Fate LV
Table C.12: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for
Fate
ii
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
1. Introduction
In the Lautenberg amendments to the Toxic Substances Control Act (TSCA) (section 6(b)(1)(B)) and
implementing regulations (40 CFR 702.3), a low-priority substance is described as a chemical
substance that the Administrator concludes does not meet the statutory criteria for designation as a
high-priority substance, based on information sufficient to establish that conclusion, without
consideration of costs or other non-risk factors. A high-priority substance is defined as a chemical
substance that the Administrator concludes, without consideration of costs or other non-risk factors,
may present an unreasonable risk of injury to health or the environment because of a potential hazard
and a potential route of exposure under the conditions of use, including an unreasonable risk to
potentially exposed or susceptible subpopulations identified as relevant by the Administrator.
Propanol, [(1-methyl-l,2-ethanediyl)bis(oxy)]bis-, referenced as tripropylene glycol for the remainder
of this document, is one of the 40 chemical substances initiated for prioritization as referenced in a
March 21, 2019 notice (84 FR 10491)1.
Before determining low or high prioritization status, under EPA's regulations at 40 CFR 702.92 and
pursuant to section 6(b)(1)(A) of the statute, EPA will generally use reasonably available information
to screen the candidate chemical substance under its conditions of use against the following criteria
and considerations:
the hazard and exposure potential of the chemical substance;
persistence and bioaccumulation;
potentially exposed or susceptible subpopulations;
storage near significant sources of drinking water;
conditions of use or significant changes in the conditions of use of the chemical substance;
the chemical substance's production volume or significant changes in production volume; and
other risk-based criteria that EPA determines to be relevant to the designation of the chemical
substance's priority.
Designation of a low-priority substance indicates that the chemical does not meet the statutory criteria
for a high-priority substance and that a risk evaluation is not warranted at the time.
This risk-based, screening-level review is organized as follows:
Section 1 (Introduction): This section explains the requirements of the Lautenberg
amendments to the Toxic Substances Control Act (TSCA) and implementing regulations -
including the criteria and considerations ~ pertinent to prioritization and designation of low-
priority substances.
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.
1 https://www.federalregister.gov/documents/2019/03/21/2019-05404/imtiation-of-prioritization-under-tlie-toxic-substances-
control-act-tsca
2 The prioritization process is explained in the Procedures for Prioritization of Chemicals for Risk Evaluation Under the
Toxic Substances Control Act (82 FR 33753).
1
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Section 3 (Physical-Chemical. Properties) : This section includes a description of the physical-
chemical properties of the chemical substance and explains how these properties lead to the
chemical's fate, transport, and exposure potential.
Section 4 (Relevant Assessment History): This section includes an overview of the outcomes
of other governing entities" assessments of the chemical substance.
Section 5 (Conditions of Use): This section presents the chemical substance's known,
intended, and reasonably foreseen conditions of use under TSCA.
Section 6 (Hazard Characterization): This section summarizes the reasonably available
hazard information and benchmarks the information against low-concern thresholds.
Section 7 (Exposure Characterization): This section includes a qualitative summary of
potential exposures to the chemical substance.
Section 8 (Summary of Findings): In this section, EPA presents information pertinent to
prioritization against each of the seven statutory and regulatory criteria and considerations,
and proposes a conclusion based on that evidence.
Section 9 (ProposedDesignation): In this section, EPA presents the proposed designation for
this chemical substance.
Appendix A (Conditions of Use Characterization): This appendix contains a comprehensive
list of TSCA and non-TSCA uses for the chemical substance from publicly available
databases.
Appendix B (Hazard Characterization): This appendix contains information on each of the
studies used to support the hazard evaluation of the chemical substance.
Appendix C (Literature Search Outcomes): This appendix includes literature search outcomes
and rationales for studies that were identified in initial literature screening but were found to
be off-topic or unacceptable for use in the screening-level review.
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.
2
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
2. Background on Tripropylene Glycol
Table 1 below provides the CAS number, synonyms, and other information on tripropylene glycol.
Table 1: Tripropylene Glycol at a Glance
Chemical Name
Tripropylene Glycol
CASRN
24800-44-0
Synonyms
Propanol, [(1 -methyl-1,2-ethanediyl)bis(oxy)]bis-; ((M ethyl ethyl ene)bis(oxy) )di propanol;
2-(2-(2-Hydroxypropoxy)propoxy)-1-propanol; 2-(2-(2-Hydroxypropoxy)propoxy)propan-
1-ol; Tripropylene glycolmixture of isomers; 1-Propanol, 2-(2-(2-
hydroxypropoxy)propoxy)-; 1,4,7-tri methy I-3,6-dioxaoctane-1,8-diol
Trade Name(s)
TPG
Molecular Formula
C9H20O4
Representative Structure
ch3
ch3 ch3
Source(s):
Kimetal. (2016)
Tripropylene glycol 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 ). In the case
of tripropylene glycol, there are two ether functional groups connected by an iso-propyl group.
Tripropylene glycol is produced as a byproduct of the manufacture of propylene glycol, and is a
mixture of isomeric chemical compounds. Tripropylene glycol is a hygroscopic solvent with a high
boiling point and is completely soluble in water while also maintaining the ability to dissolve oils.
These properties make tripropylene glycol a highly functional solvent used in a variety of applications
and product sectors. Section 5 includes conditions of use for this chemical.
3
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
3. Physical-Chemical Properties
Table 2 lists physical-chemical properties for tripropylene glycol. 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 Tripropylene Glycol
Source/
Model
Data Type
Endpoint
Endpoint value
Notes
Sigma Aldrich 2019
Experimental
Physical state at
room temp
(based on melting
point)
Liquid (-19.99°C at
1013 hPa (760
mmHg))
ECHA, 2008; OECD SIDS,
2001; Kirk-Othmer 2006
Experimental
Molecular weight
192 g/mol
EPISuitev.4.113
Calculated
Molecular weight
192.26 g/mol
Lyman 1990
Experimental
Molar volume
242 cm3/mol
ECHA 2019
Experimental
Water solubility
1000000 mg/L (100%
vol) at 20 °C and pH
7.1-8.4
ECHA value measured according to EU Method A.6, flask method.
OECD SIDS 2001
Experimental
Water solubility
1000000 mg/L
(Freely soluble) at 25
°C
EPISuite v.4.11
Estimated
Water solubility
5.47x105 mg/L
ECHA 2019
Experimental
Water solubility
5.20 mol/L
OECD SIDS 2001
Experimental
Water solubility
5.20 mol/L
ECHA 2019
Experimental
Log Kow
-0.379 at21.5°C and
pH 5.9
ECHA value measured according to EU Method A.8, shake flask.
OECD SIDS 2001
Experimental
Log Kow
0.5-0.6 at 25 °C
EPISuite v.4.11
Estimated
Log Kow
-0.5
EPISuite v.4.11
Estimated
Log Koa
8.14
3 EPI Suite Physical Property Inputs - Boiling Point = 271 deg C, Melting Point = -30 deg C, Vapor Pressure = 0.00195 mm Hg, Water Solubility = 1000000 mg/L, Log P = -0.38,
SMILES: CC(0)COC(C)COC(C)CO
4
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table 2: Physical-Chemical Properties for Tripropylene Glycol
Source/
Model
Data Type
Endpoint
Endpoint value
Notes
EPISuite v.4.11
Estimated
Log Koc
1.0 (MCI); -0.29 (M
ECHA 2019
Experimental
Vapor pressure
0.00195 mm Hg
(0.26 Pa) at 25 °C
ECHA value measured according to EU Method A.4
OECDSIDS 2001
Experimental
Vapor pressure
1.05 mm Hg (140 Pa)
at 25 °C
Kirk-Othmer 2006
Experimental
Vapor Pressure
0.0023 mm Hg
(0.0003 kPa) at 25
°C
EPISuite v.4.11
Estimated
Vapor pressure
4.82x10-3 mm Hg
EPISuite v.4.11
Estimated
Henry's Law
<1E-8 atm-m3/mole
EPISuite v.4.11
Estimated
Volatilization
69000 days (river)
750000 days (lake)
EPISuite v.4.11
Estimated
Photolysis
(Indirect)
2.28 hours (T1/2)
OH rate constant 5.63 E-11 cm3/molecule-second (12 hour day; 1.5E6
OH/cm3)
No ozone prediction
EPISuite v.4.11
Estimated
Hydrolysis
Hydrolysis cannot be
estimated
No hydrolyzable functional groups
EPISuite v.4.11
Estimated
Biodegradation
potential
Ready prediction: No
EPISuite v.4.11
Estimated
BAF
0.9
EPISuite v.4.11
Estimated
BCF
3.16
5
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Based on its reported physical form and measured melting point, tripropylene glycol is a liquid under
ambient conditions (Sigma Aldrich, 2019). Exposure through direct dermal contact with the substance
is possible, but concern is lessened because this chemical is expected to be a slow skin penetrant
(discussed in Section 6.1.1) and likely to be minimally absorbed through skin based on its molecular
weight, water solubility and log Kow. Because of its measured vapor pressure (OECD SIDS, 2001),
tripropylene glycol is expected to be volatile when in neat form at ambient temperatures. As a result,
exposure to tripropylene glycol is possible through inhalation of vapors and aerosols if they are
generated. Based on measured solubility data (OECD SIDS, 2001), tripropylene glycol 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 absorption through the lungs;
therefore, if inhalation of vapors or aerosols occurs, absorption through the lungs is likely. Exposure
potential changes if tripropylene glycol is present in diluted form. The estimated Henry's Law
constant for tripropylene glycol (EPI Suite, 2019) indicates volatilization from water and aqueous
solutions would be minimal; therefore exposure through breathing vapor from a dilute form is
expected to be minimal. Absorption and sequestration in fatty tissues is unlikely, as reflected in the
estimated bioconcentration factor (BCF) and bioaccumulation factor (BAF) values for this compound
(EPI Suite, 2019). The estimated log Koc (EPI Suite, 2019) indicates this substance is highly mobile in
soils, increasing its potential for leaching into groundwater, including well water. If oral exposure
occurs via ingestion of contaminated drinking water, including well water, absorption through the
gastrointestinal tract is likely based on experimental evidence (discussed in Section 6.1.1). Concern
for presence in drinking water is reduced in part by tripropylene glycol's biodegradation (discussed in
Section 6.3.1) and low-hazard findings from toxicological studies of organisms exposed to a closely
related analog in drinking water (discussed in Section 6.1).
3.1 References
Hazardous Substance Database (HSDB). (2016). Tripropylene glycol. Retrieved from
http s: //toxnet .nlm.nih.gov/
European Chemicals Agency (ECHA). (2019). [(methylethylene)bis(oxy)]dipropanol. Retrieved from
https://echa.europa.eu/registration-dossier/-/registered-dossier/14788
Kirk-Othmer. (2006). Kirk-Othmer Encyclopedia of Chemical Technology.
Lyman, Warren J., Reehl, W. F., Rosenblatt, D. H. (1990). Handbook of chemical property estimation
methods: environmental behavior of organic compounds. American Chemical Society
OECD SIDS (2001). Dipropylene glycol (mixed isomers and dominant isomer Cas No: 25265-71-8
and 110-98-5 https://heronet.epa.gov/heronet/index.cfm/reference/download/reference id/4940388
Sigma Aldrich (2019). Tripropylene glycol. Retrieved from
https://www.sigmaaldrich.eom/catalog/product/aldrich/l 87593?lang=en®ion=US
U.S. EPA. (2019). Estimation Programs Interface Suite, v 4.11. United States Environmental
Protection Agency, Washington, DC, USA
6
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
4. Relevant Assessment History
EPA assessed the toxicological profile of tripropylene glycol and added the chemical to the Safer
Choice Program's Safer Chemical Ingredients List (SCIL) in September 2012 under the functional
class of solvents. The SCIL4 is a continuously updated list of chemicals that meet low-concern Safer
Choice criteria.5
EPA also reviewed international assessments of tripropylene glycol. EPA identified assessments by
the Organisation for Economic Co-operation and Development (OECD), and government agencies in
Canada, Australia, and Germany.
The OECD Screening Information Datasets (SIDS) Initial Assessment Meeting (SIAM) discussed the
SIDS Initial Assessment Report (SIAR) on tripropylene glycol in July 1994. The SIAM determined
this chemical to be "low potential risk and low priority for further work/'6
The Canadian Government, through an assessment of toxicity and exposure as part of its
categorization of the Domestic Substance List, found that tripropylene glycol did not meet its criteria
for further attention.7
Japan's National Institute of Technology and Evaluation (NITE) categorized tripropylene glycol as
Class 5 for Exposure in 2016, and "Out of classification for 2017.8
The German Environment Agency (UBA) designated tripropylene glycol as "low hazard to waters" in
August 2017 based on an assessment of ecotoxicity and environmental fate.9
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
6 https://lipvchemicals.oecd.org/ui/handler.axd?id=0904e02a-7bd2-4898-816f-2f26670b6992
7 https://canadacheniicals.oecd. org/CheniicalDetails.aspx?CheniicalID=1355D4A8-AED4-463A-8818-AE290EE9D32B
8 http://www.safe.nite.go.ip/icheck//direct.action?TYPE=DPAGEl&CAS=24800-44-0&MITI=2-430
9 https://webrigoletto.uba.de/rigoletto/public/searcliDetail.do7kennuninieF779
7
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
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 (Appendix A) to inform which uses would be determined conditions
of use.1" One source of information that EPA used to help determine conditions of use is 2016
Chemical Data Reporting (CDR). The CDR rule (previously known as the Inventory Update Rule, or
IUR), under TSCA section 8, requires manufacturers (including importers) to report information on
the chemical substances they produce domestically or import into the U.S., generally above a
reporting threshold of 25,000 lb. per site per year. CDR includes information on the manufacturing,
processing, and use of chemical substances with information dating to the mid-1980s. CDR may not
provide information on other life-cycle phases such as the chemical substance's end-of-life after use
in products (i.e., disposal).
According to CDR, tripropylene glycol is manufactured domestically and imported. It is used in
processing (incorporation into formulation, mixture or reaction for mining (except oil and gas) and
support activities, and incorporation into articles, such as textiles, apparel, leather manufacturing); it
is also used as a reactant in plastic material and resin manufacturing and petrochemical
manufacturing. Industrial, commercial, and consumers uses include cleaning and furniture care
products, lubricants and greases, and water treatment. Based on the known manufacturing,
processing, and uses of this chemical substance, EPA assumes distribution in commerce. According
to CDR, six facilities reported not recycling (e.g., not recycled, remanufactured, reprocessed, or
reused) tripropylene glycol, and one facility reported recycling information as confidential business
information (CBI). No information on disposal is found in CDR or through EPA's Toxics Release
Inventory (TRI) Program11 since tripropylene glycol is not a TRI-reportable chemical. Although
reasonably available information did not specify additional types of disposal, for purposes of this
proposed prioritization designation, EPA assumed end-of-life pathways that include releases to air,
wastewater, surface water, and land via solid and liquid waste based on the conditions of use (e.g.,
incineration, landfill).
To supplement CDR, EPA conducted research through the publicly available databases listed in
Appendix A (Table A.2) and performed additional internet searches to clarify conditions of use or
find additional occupational12 and consumer uses. This research improved the Agency's
understanding of the conditions of use for tripropylene glycol. In the course of this research, EPA
identified uses of tripropylene glycol in laboratory chemicals, cleaning and furnishing care products,
lubricants and greases, water treatments, antifreeze and deicing products, agricultural products,
adhesives, and drilling fluids. Although EPA identified uses of tripropylene glycol in personal care
products, this screening review covers TSCA conditions of use for the chemical substance and
10 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).
11 https://www.epa.gov/toxics-release-inventorv-tri-program
12 Occupational uses include industrial and/or commercial uses
8
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
personal care products are not considered further in EPA's assessment. Exclusions to TSCA's
regulatory scope regarding "chemical substance" can be found at TSCA section 3(2). Table 3 lists the
conditions of use for tripropylene glycol 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).
9
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table 3: Conditions of Use for Tripropylene Glycol
Life Cycle Stage
Category
Subcategory of Use
Source
Manufacturing
Domestic manufacture
Domestic manufacture
EPA (2017b)
Import
Import
Processing
Processing- incorporation into
formulation, mixture or reaction
Intermediates: mining (except oil and gas) and support
activities
EPA (2017b)
Processingincorporation into article
Finishing agents- textiles, apparel, and leather
manufacturing
Processing as a reactant
Intermediates- plastic material and resin manufacturing;
petrochemical manufacturing
Metal manufacturing;
transportation equipment manufacturing;
wood manufacturing
SPIN (2018)
Recycling
Recycling
EPA (2017b)13
Distribution
Distribution
Distribution
EPA (2017b)
Commercial uses
Fabric, textile, and leather products not
covered elsewhere
EPA (2017b); SPIN (2018)
Lubricants and greases
EPA (2017b)
Laboratory chemicals
Sigma Aldrich (2018), ECHA (2018)
industrial/commercial/
consumer uses
Cleaning and furniture care products
Cleaning/washing agents, window/glass cleaner
GoodGuide (2011); Synapse
Information Resources (n.d.); ECHA
(2018)
Lubricants and greases
EPA (2017b); Silver Fern Chemical,
lnc.(2018); Synapse Information
Resources (n.d.); NLM (2018b);
ECHHA (2018); SPIN (2018)
Water treatment
ECHA (2018)
13 In the 2016 CDR, six facilities reported not recycling (e.g., not recycled, remanufactured, reprocessed, or reused) tripropylene glycol, and one facility reported recycling
information as CBI (EPA 2017b).
10
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table 3: Conditions of Use for Tripropylene Glycol
Life Cycle Stage
Category
Subcategory of Use
Source
Commercial/consumer
Anti-freeze and de-icing products
Synapse Information Resources (n.d.)
Unknown
Solvent
Agricultural products (non-pesticidal)14
NLM (2018b); ECHA (2018)
Dry cleaning detergents; adhesives and sealant
chemicals; automotive trade and repair; cooling media;
drilling fluids; emulsion-inhibiting agents; inks; paints
and coatings; process regulators
NLM (2018b), Synapse Information
Resources (n.d.)
SPIN (2018);
Ullmann's (2010); Kirk-Othmer (2004);
Dow (2018); ECHA (2018); Dow
(2016); Ullman's 2011
Surfactants
SPIN (2018)
Disposal
Releases to air, wastewater, solid and
liquid wastes.
Though not explicitly identified,
releases from disposal are assumed to
be reasonably foreseen15
14 Information on the use of tripropylene glycol in agricultural products is not sufficient to determine if the use is a TSCA or non-TSCA use.
15 See Section 5 for a discussion on why releases are assumed to be reasonably foreseen for purposes of this proposed prioritization designation.
11
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
6. Hazard Characterization
EPA reviewed primary literature and other data sources to identify reasonably available information.
This literature review approach16 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 against the
endpoints listed below. EPA's New Chemicals Program has used these endpoints for decades to
evaluate chemical substances under TSCA17 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 Chemicals18 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
Toxicity19
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
1 "Discussed in the document "Approach Document for Screening Hazard Information for Low-Priority Substances Under
TSCA."
17 https://www.epa. gov/sustainable-futures/sustainable-futures-p2-framework-manual
18 https://www.unece.org/fileadmin/DAM/trans/danger/publi/ghs/ghs rev07/English/ST SG AC10 30 Rev7e.pdf
19 Values derived from GHS criteria (Chapter 3.1: Acute Toxicity. 2009, United Nations).
12
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table 4: Low-Concern Criteria for Human Health and Environmental Fate and Effects
Repeated Dose
Toxicity (90-day
study)20
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
Toxicity21
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
Toxicity21
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/
Genotoxicity22
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.
20 Values from GHS criteria for Specific Target Organ Toxicity Repeated Exposure (Chapter 3.9: Specific Target Organ
Toxicity' Repeated Exposure. 2009, United Nations).
21 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).
22 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.
13
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
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.
Carcinogenicity23
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
inadequate24 evidence
in humans)
Negative studies or
robust mechanism-
based structure
activity relationship
(SAR)
Neurotoxicity
(90-day study)20
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
Sensitization25
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
23 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).
24 EPA's approach to determining the adequacy of information is discussed in the document "Approach Document for
Screening Hazard Information for Low-Priority Substances Under TSCA", also released at proposal.
25 From GHS criteria (Chapter 3.4: Respiratory or Skin Sensitization. 2009, United Nations).
14
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table 4: Low-Concern Criteria for Human Health and Environmental Fate and Effects
Irritation/
Corrosivity26
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)27
Chronic Aquatic
Toxicity Value
(L/E/ICso)27
Persistence (Measured in terms of level of
biodegradation)28
Bioaccumulation
Potential29
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. In many cases, EPA used analogous chemicals to make findings for
a given endpoint. Where this is case, use of the analog is explained. If the chemical studied is not
named, the study is for tripropylene glycol. Appendix B contains more information on each study.
Tripropylene glycol is an oligomeric propylene glycol formed by the condensation of three propylene
oxide (methyl oxirane) units. The positions of the methyl groups in the product are unspecified. Both
analogs used to inform EPA's understanding of this chemical are oligomeric propylene glycols like
tripropylene glycol. Dipropylene glycol is a mixture of dipropylene glycol isomers similar to
tripropylene glycol but containing two propylene oxide equivalents instead of three. The analog 1,1'-
dimethyl diethylene glycol is a specific isomer and a component of dipropylene glycol. As shown in
Table 5, EPA used best professional judgement to select analogs for tripropylene glycol 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
20 Criteria derived from the Office of Pesticide Programs Acute Toxicity Categories (U.S. EPA. Label Review Manual.
2010).
27 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 ChAK-fP. 2009).
18 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).
29 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.]
15
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
bioavailability and toxicity profiles. Differences in the methyl group positions in these chemicals are
not expected to significantly affect their chemical and hazard profiles. Based on these factors, the
environmental and toxicological effects of dipropylene glycol and tripropylene glycol are expected to
be very similar to each other.
Table 5: Tripropylene Glycol and Analog Structures
CASRN
Name
Structure
24800-44-0
Tripropylene glycol
(mixture)
CHj
Representative structure
CH,
25265-71-8
Dipropylene glycol
(mixed isomers)
Representative structure
110-98-5
1,1 '-Dimethyldiethylene
glycol
Representative structure
6.1.1 Absorption, Distribution, Metabolism, and Excretion
Absorption
To assess absorption potential, EPA used experimental studies on tripropylene glycol and dipropylene
glycol. Rats exposed to 14C-tripropylene glycol by oral gavage rapidly absorbed the chemical, as
indicated by recovery of 91.4% of the administered dose 24 hours following exposure (OECD. 2001;
ECHA. 1995a).
In vitro studies were used to assess the potential for dermal absorption by dipropylene glycol. Excised
abdominal skin from human cadavers demonstrated dipropylene glycol is a slow penetrant, with
results indicating a permeability coefficient of 3.85 x 10"5 cm/hour (Fasano et al.. 2011; ECHA.
2007b; Fasano. 2007).
16
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Based on its low molecular weight and high water solubility (Section 3), tripropylene glycol is
expected to be absorbed from the lungs if inhaled.
Distribution
Tripropylene glycol is considered water soluble based on its physical-chemical properties (table 2)
and is likely to be distributed mainly in aqueous compartments in an organism. This prediction is
supported by experimental evidence. Rats exposed to tripropylene glycol by oral gavage displayed
radiolabeled tripropylene glycol in the tissues and the carcass 24 hours following exposure.
Specifically, tripropylene glycol was reported in the liver at 0.20%, kidneys at 0.09%, carcass at
0.06%, blood at 0.03%, and skin, brain, muscle, and fat at less than 0.03%. (as percent of the
administered dose per gram of tissue) (OECD. 2001; ECHA. 1995a). These data indicate tissue
distribution of tripropylene glycol was rapid, especially to the liver and kidney, 24 hours after dosing
and provide evidence that tripropylene glycol will be rapidly distributed following oral absorption.
Metabolism
Tripropylene glycol was orally administered in rats and was rapidly metabolized to dipropylene
glycol, then to propylene glycol, which is converted to lactic and pyruvic acids or excreted in the
urine. Lactate and pyruvate may be further metabolized through the citric acid cycle to yield carbon
dioxide and water or may be stored as glycogen (OECD. 2001; ECHA. 1995a). Rats exposed to 14C-
tripropylene glycol by oral gavage excreted approximately 13% as free or conjugated tripropylene
glycol, approximately 8.4% as free and conjugated dipropylene glycol, and approximately 3.9% as
free and conjugated propylene glycol (OECD. 2001; ECHA. 1995a). These data indicate that
tripropylene glycol will be rapidly metabolized.
Excretion
Following the oral administration of tripropylene glycol to rats, 52% was recovered in urine, 21% in
exhaled CO2, and 5% in the feces after 24 hours (OECD. 2001; ECHA. 1995a). These data indicate
that tripropylene glycol will be excreted from the body following exposure.
6.1.2 Acute Toxicity
EPA assessed the mammalian toxicity potential from acute exposure by tripropylene glycol using
results from oral, dermal, and inhalation exposure studies. One study exposed rats to tripropylene
glycol by oral gavage and reported a LD50 of 11,500 mg/kg (ECHA. 1974c). Another study exposed
rats to tripropylene glycol via drinking water and reported no mortality in any dose group, resulting in
a predicted LD50 greater than 2000 mg/kg (JETOC. 1997; ECHA. 1993a). These results indicate low
concern for acute toxicity with expected LD50S above the low-concern threshold of 2000 mg/kg for
oral exposures.
A study on rabbits exposed to tripropylene glycol dermally reported no adverse effects at the single
dose tested (16,320 mg/kg), resulting in an LD50 greater than 16,320 mg/kg (ECHA. 1974a). These
studies indicate low concern for acute toxicity with expected LD50S above the low-concern threshold
of 2000 mg/kg for dermal exposures.
17
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
A study on rats exposed to 0.083 mg/L of tripropylene glycol in saturated vapor for eight hours and
then observed for two weeks reported no mortalities (ECHA. 1974b). Based on tripropylene glycol's
vapor pressure of 0.00195 torr, the expected air saturation concentration is around 0.02 mg/L at room
temperature, which is below the study concentration of 0.083 mg/L, indicating no adverse effects are
likely at complete air saturation. Considering the chemical's physical-chemical properties (discussed
in Section 3) and available experimental data, these results indicate tripropylene glycol is of low
concern for acute toxicity from inhalation exposures based on no adverse effects reported at the
expected air saturation.
6.1.3 Repeated Dose Toxicity
EPA assessed the potential for mammalian toxicity from repeated exposures by tripropylene glycol
using a combined repeated dose, reproductive, and developmental study (OECD. 1994; ECHA.
1993c). Rats were exposed to tripropylene glycol via oral gavage for 49 days, beginning 14 days prior
to mating and through lactation day 3 for females. The no observed adverse effect level (NOAEL)
was 200 mg/kg-day and the lowest observed adverse effect level (LOAEL) was 1000 mg/kg-day
based on changes in organ weight in parents.
For further supporting evidence, EPA also assessed results from mice and rats repeatedly exposed to
dipropylene glycol in drinking water. A study on mice exposed to dipropylene glycol in drinking
water for 13 weeks demonstrated a NOAEL of 2620 mg/kg-day and a LOAEL of 4790 mg/kg-day
based on increased liver weight (ECHA. 2004g; NTP. 2004). A study on rats exposed to dipropylene
glycol in drinking water for 14 weeks demonstrated a NOAEL of 425 mg/kg-day and a LOAEL of
890 mg/kg-day based on relative liver weight (ECHA. 2004f; NTP. 2004). A two year study on mice
exposed to dipropylene glycol in drinking water demonstrated a NOAEL of 1040 mg/kg-day and a
LOAEL of 1950 mg/kg-day based on decreased mean body weight (ECHA. 2004e; NTP. 2004). A
study on rats exposed to dipropylene glycol for two years in drinking water demonstrated a NOAEL
of 115 mg/kg-day and a LOAEL of 470 mg/kg-day based on incidence of nephropathy, focal
histiocytic and focal granulomatous inflammation in male livers (ECHA. 2004b. d; NTP. 2004).
All of these results indicate low concern for toxicity resulting from repeated exposures by exceeding
the oral low-concern threshold of 100 mg/kg-day for a 90-day study.
6.1.4 Reproductive and Developmental Toxicity
EPA assessed the potential for mammalian reproductive and developmental toxicity using the
combined repeated dose, reproductive, and developmental study discussed in Section 6.1.3 (OECD.
1994; ECHA. 1993c). Rats were exposed to tripropylene glycol via gavage for 49 days, beginning 14
days prior to mating and continuing through lactation day 3 for females. The authors reported no
reproductive (mating, fertility and estrus cycle) or developmental effects (external examinations of
the pups and pup body weight gain) at the highest dose tested (1000 mg/kg-day). The NOAEL for this
study was 1000 mg/kg-day. These results indicate low concern for reproductive toxicity by exceeding
the 250 mg/kg-day oral threshold.
EPA further assessed the potential for developmental toxicity using read across from dipropylene
glycol. A study on pregnant rats exposed during gestational day (GD) 6-15 reported a developmental
18
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
NOAEL of 2000 mg/kg-day and a LOAEL of 5000 mg/kg-day based on decreased fetal weight
(QECD. 2001: BUA. 1996; Bates etal.. 1992b; ECHA. 1990b). A study on rabbits exposed to
dipropylene glycol during GD 6-19 reported no adverse effects at the highest dose tested (1200
mg/kg-day), resulting in a NOAEL of 1200 mg/kg-day (QECD. 2001; Bates et al.. 1992a; ECHA.
1990a). These results indicate low concern for developmental toxicity by exceeding the 250 mg/kg-
day threshold.
6.1.5 Genotoxicity
EPA assessed experimental studies on genotoxicity as a potential indicator of genotoxic
carcinogenicity using read across from dipropylene glycol. Three in vitro gene mutation studies
resulted in negative findings from dipropylene glycol exposure with and without metabolic activation
in Salmonella typhimiiriiim (ECHA. 2004c; NTP. 2004; ECHA. 1992a) and mouse lymphoma cells
(ECHA. 1988). Further, a mouse in vivo study indicated negative results for chromosomal aberrations
in the form of micronucleated polychromatic erythrocytes from dipropylene glycol exposure (QECD.
2001; ECHA. 1999). These negative results in dipropylene glycol indicate tripropylene glycol has low
concern for genotoxicity.
6.1.6 Carcinogenicity
EPA assessed the potential for tripropylene glycol to cause carcinogenicity in mice and rats using
read across from dipropylene glycol. A study on rats exposed to dipropylene glycol in drinking water
for two years demonstrated no dose-related effects on cancer incidence or cancer-related effects at the
highest dose tested (3040 mg/kg-day in males, 2330 mg/kg-day in females), resulting in a negative
finding for carcinogenicity (ECHA. 2004a. b; NTP. 2004). Similarly, a study on mice exposed to
dipropylene glycol in drinking water for two years also demonstrated no adverse effects at the highest
dose tested (2390 mg/kg-day in males, 1950 mg/kg-day in females), resulting in a negative finding for
carcinogenicity (ECHA. 2004a; NTP. 2004). Using read-across from this analog, these negative
results indicate low concern for carcinogenicity for tripropylene glycol.
6.1.7 Neurotoxicity
While no traditional neurotoxicity studies were available for tripropylene glycol or closely related
analogs, EPA assessed the potential for neurotoxicity using relevant endpoints measured in repeated
dose studies and using predictions made by U.S. EPA's ToxCast.3"
A repeated dose study on rats exposed to tripropylene glycol by oral gavage reported no effects on the
limited neurological endpoints that were evaluated (i.e., brain histopathology only). Tripropylene
glycol did not produce histopathological lesions in the brain of rats at doses up to 1,000 mg/kg-day
(highest dose tested) in a study when males were exposed for 49 days and females were exposed from
14 days prior to mating until day 3 of lactation (QECD. 1994).
30 https://actor.epa.gov/dashboard/ Chemical specific assay list can be found at
https://actor.epa.gOv/dashboard/#chemical/55934-93-5.
19
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
ToxCast results for tripropylene glycol included 8 in vitro high throughput biochemical- and cell-
based assays related to neurological functions.31 Bioactivity was not induced in any assay by
tripropylene glycol.
These data indicate there is low concern for neurotoxicity associated with tripropylene glycol. This
finding is also supported by the low hazard findings for other human health hazard endpoints,
including, but not limited to, toxicity from acute exposures, reproductive toxicity, and developmental
toxicity.
6.1.8 Skin Sensitization
EPA assessed the potential for tripropylene glycol to cause skin sensitization using available
experimental studies on dipropylene glycol. A study on guinea pigs (ECHA. 1995d) and two human
studies (ECHA. 1995c; Johansen et al.. 1995; Leberco Labs. 1994) reported negative results for
dipropylene glycol, suggesting low concern for tripropylene glycol to induce skin sensitization.
6.1.9 Skin Irritation
EPA assessed dermal irritation effects using experimental results on rabbits and humans. These
results are supported by another study in rabbits that demonstrated tripropylene glycol displayed mild
irritation (ECHA. 1974e). A study on humans exposed to tripropylene glycol in a dermal patch study
displayed mild erythema at 30 minutes, but the effects were fully reversed by 24 hours, resulting in
negative results for skin irritation (ECHA. 1995b). A longer dermal patch study for 14 days also
reported negative results for tripropylene glycol to induce skin irritation in humans (ECHA. 1997).
The results of these studies indicate low concern for skin irritation by tripropylene glycol.
6.1.10 Eye Irritation
To assess potential for eye irritation, EPA used the results of in vivo and in vitro studies. Rabbits
exposed to tripropylene glycol displayed conjunctival redness and a subset displayed chemosis after
one hour, but these results were fully reversible by 24 hours, leading to a negative result for eye
irritation (ECHA. 2010a). These results are supported by another rabbit study with similar reversible
effects and a non-irritating finding (ECHA. 1974d). An in vitro human corneal epithelium model
study also reported tripropylene glycol as negative for inducing ocular irritation (ECHA. 2010b).
These results indicate low concern for eye irritation by tripropylene glycol.
6.1.11 Hazards to Potentially Exposed or Susceptible Subpopulations
The above information supports a low human health hazard finding for tripropylene glycol 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
31
As identified by supplementary information from 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. https://pubs.rsc.org/en/content/articlepdf/2018/tx/c7txQ0268h
Supplementary files: https://pubs.rsc.Org/en/content/articlelanding/2018/tx/c7tx00268h#idivAbstract
20
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
exposed or susceptible subpopulations. Based on the hazard information discussed in Section 6, EPA
did not identify populations with greater susceptibility to tripropylene glycol.
6.2 Environmental Hazard
EPA assessed environmental hazard for tripropylene glycol based on available experimental data and
estimated toxicity values using the Ecological Structure Active (ECOSAR) Predictive Model.32
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. No adverse effects
were observed in aquatic vertebrates, aquatic invertebrates, or algae exposed to tripropylene glycol at
the highest doses tested (1000 mg/L), resulting in effects expected at concentrations greater than 1000
mg/L for all three trophic levels (ECHA. 1994a. b; OECD. 1994). 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
EPA assessed environmental hazard from chronic exposure using available experimental data and
estimated values from ECOSAR. A 21-day exposure to Daphnia magna indicated no adverse effects
at concentrations less than 1000 mg/L. For other trophic levels, toxicity from chronic exposure to
tripropylene glycol was predicted to occur at 1600 mg/L for aquatic vertebrates and 480 mg/L for
algae. These toxicity values indicate that tripropylene glycol 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
Varied results are observed in the experimental ready test data presented in Appendix B. Due to the
differences in the test conditions of the OECD ready test methods, some of this variability is likely a
result of performance under different test designs rather than an inherent limitation of the
biodegradability of the test substance. Given the varied results, EPA relied on studies on tripropylene
glycol and dipropylene glycol to make a weight of the scientific evidence conclusion. An explanation
of ready and inherent biodegradation tests is provided below.
Ready biodegradation tests are stringent test methods in which a high concentration of test substance
is evaluated using a non-adapted inoculum. Passing this type of test indicates that a chemical is likely
to biodegrade rapidly in the environment and has low potential for persistence. However, not passing
the ready criteria is not necessarily an indication that a chemical is recalcitrant or that it will be
persistent in the environment. In contrast, inherent biodegradability tests use more favorable
conditions to promote a high expected capacity for degradation, including the use of prolonged
exposure periods and a low ratio of test substance to inoculum biomass. Passing this type of test
indicates that a substance is inherently biodegradable but does not provide evidence for ready
32https://www.epa.gov/tsca-screening-tools/ecological-striicture-activity-relationships-ecosar-predictive-model
21
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
biodegradation. The reasonably available information included tests for both ready biodegradation
and inherent biodegradation.
Tripropylene glycol was tested in three ready tests (OECD 301C, OECD 301B, and OECD 301D)
that reported < 5% degradation over 28-day incubation periods, indicating that it is not readily
biodegradable (OECD. 1994; ECHA. 1993b. 1991b). However, in another OECD 30ID test,
tripropylene glycol reached 69% O2 consumption after 28 days and just missed the 10-day window
criterion at 59% in 11 days (ECHA. 1991a). In addition, both dipropylene glycol and tripropylene
glycol reached S81% O2 consumption after 28 days in the OECD 301F test, meeting the criteria for
ready biodegradation but did not meet the 10-day window (ECHA. 2007a. c, 1994c). These data
indicate that tripropylene glycol is biodegradable and may be readily biodegradable under the right
conditions. Results from additional aerobic studies, including the inherent biodegradability test
(OECD 302A) and a seawater biodegradability test (OECD 306) on tripropylene glycol provide
further support that tripropylene glycol has the capacity to biodegrade under environmental
conditions (Zgola-Grzcskow iak et al.. 2008; ECHA. 1994c). Furthermore, the microbial inhibition
tests on tripropylene glycol and dipropylene glycol indicate that these substances are non-toxic to
microbial populations found in sewage treatment plants (ECHA. 2010c. 1992b).
Based on the weight of the scientific evidence, the data suggest tripropylene glycol is expected to
biodegrade under aerobic conditions. Although under some test conditions this chemical may not
meet the benchmark for ready biodegradation, both ready and inherent biodegradation of these
substances has been demonstrated using a variety of standard and non-standard test methods. No
quality experimental studies were available to assess anaerobic biodegradation. 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'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.
No degradation products of concern were identified for this chemical substance. The available
biodegradation results meet the low-concern threshold and indicate this chemical has low persistence.
6.3.2 Bioaccumulation Potential
Based on the estimated bioaccumulation factor (BAF) value of 0.9 using the Estimation Programs
Interface (EPI) Suite models,33 tripropylene glycol is expected to have low potential for
bioaccumulation in the environment based on the low-concern threshold of less than 1000.
33 https://www.epa.gov/tsca-screeni11g-tools/epi-suitelm-estimation-program-mterface
22
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
7. Exposure Characterization
EPA considered reasonably available information on exposure for tripropylene glycol. In general,
there is limited information on exposure for low-hazard chemicals. EPA consulted sources of
exposure and use information that include CDR and other databases and public sources. Of these
sources, EPA determined that the CDR database contained the primary source of information on the
conditions of use for this exposure characterization. EPA used these other databases and public
sources (described in Table A.2) only where they augmented information from the CDR database and
to inform intended, known, or reasonably foreseeable uses.
Tripropylene glycol is a solvent used in processing (incorporation into an article and into a
formulation, mixture, or product) and as a reactant in plastic, resin, and petrochemical manufacturing
(EPA 2017b). Tripropylene glycol is also used in a variety of industrial, commercial, and consumer
uses, as shown in Table 3. 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 is based on an analysis of CDR data reported
from 1986 to 2015.34 In reporting years 1986, 1990, 1994, 1998, 2002, 2006 and between 2012 and
2015, aggregate production volume for tripropylene glycol was between 10,000,000 and 500,000,000
lbs. The exact amount is available for one year, 2011, in which 25,531,268 lbs. of tripropylene glycol
was produced or imported. Since 2011, production volume has remained relatively stable.
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. Exposure is also possible from
other uses, such as distribution and disposal. These activities could result in releases of tripropylene
glycol to media including surface water, landfills, and air.
Tripropylene glycol is expected to biodegrade aerobically in the environment (discussed in Section
6.3.1). Any release of this chemical is expected to break down, reducing exposure to aquatic
organisms in the water column and ground water sources of drinking water, including well water.
Based on the estimated log Koc (Section 3), tripropylene glycol is expected to have negligible
adsorption to sediment, reducing the potential toxicity to benthic organisms.
34 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.
23
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
If disposed of in a landfill, this chemical is expected to degrade under aerobic conditions (aerobic
biodegradation is discussed in Section 6.3.1).
If incineration releases during manufacturing and processing occur, EPA expects significant
degradation of tripropylene glycol to the point that it will not be present in air.
7.3 Exposures to the General Population
EPA expects the general population is unlikely to be exposed to tripropylene glycol from the potential
environmental releases described above. Air exposure is unlikely from incineration. If tripropylene
glycol is present in the air from volatilization, it is expected to be reduced because of its short
atmospheric half-life of 5 hours (see Table 2 in Section 3). With the exception of time immediately
following a release, tripropylene glycol 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 and bioconcentration potential
of tripropylene glycol (Table 2 and Section 6.3.2), oral exposure to tripropylene glycol 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 than the general population during manufacturing, processing,
distribution, use, and disposal. EPA also identified consumers as a population that may experience
greater exposure to tripropylene glycol than the general population through use of cleaning and
furniture care products and anti-freeze and de-icing products, for example.
7.4.1 Exposures to Workers
Based on its reported physical form and measured melting point (Table 2), tripropylene glycol is a
liquid under ambient conditions. Based on tripropylene glycol's conditions of use (Table 3), workers
may be exposed to liquids through direct dermal contact with the substance and inhalation of aerosols
if they are generated. Based on its measured vapor pressure (Table 2), tripropylene glycol is expected
to be volatile at ambient temperatures, and therefore workers may be exposed through inhalation of
vapors. If tripropylene glycol is in a dilute form, the estimated Henry's Law constant for tripropylene
glycol suggests volatilization from water and aqueous solutions is expected to be minimal. Workers
may be exposed to tripropylene glycol in manufacturing, processing, distribution, use and disposal.
7.4.2 Exposures to Consumers
In addition to the exposure pathways relevant for the general population described in Section 7.3,
consumers may be exposed to tripropylene glycol through the use of cleaning and furniture care
products, lubricants and greases, and anti-freeze and de-icing products, for example. For all these
uses, if dermal contact does occur, tripropylene glycol is expected to have minimal absorption
through the skin based on experimental data (Section 6.1.1). If the chemical is in an aerosol product
and inhalation exposure occurs, tripropylene glycol's absorption from the lungs is likely. EPA does
24
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
not include intentional misuse, such as people drinking products containing this chemical, as part of
the known, intended, or reasonably foreseen conditions of use that could lead to an exposure (82 FR
33726). Thus, oral exposures will be incidental (meaning inadvertent and low in volume).
Tripropylene glycol is expected to be metabolized and excreted, further reducing the duration of
exposure. Therefore, EPA expects the exposures to tripropylene glycol through use of these products
to be low.
25
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
8. Summary of Findings
EPA has used reasonably available information on the following statutory and regulatory criteria and
considerations to screen tripropylene glycol against each of the priority designation considerations in
40 CFR 702.9(a), listed below and discussed individually in this section, under its conditions of use:
the hazard and exposure potential of the chemical substance (See Sections 6 and 7);
persistence and bioaccumulation (See Section 6.3);
potentially exposed or susceptible subpopulations (See Section 7.4);
storage near significant sources of drinking water (See Section 8.4);
conditions of use or significant changes in the conditions of use of the chemical
substance (See Section 5);
the chemical substance's production volume or significant changes in production
volume (See Section 7.1); and
other risk-based criteria that EPA determines to be relevant to the designation of the
chemical substance's priority.
EPA conducted a risk-based screening-level review based on the 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. EPA used this
information to inform its proposed determination of whether tripropylene glycol would meet the
statutory criteria and considerations for proposed designation as a low-priority substance.
Hazard potential:
For tripropylene glycol'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 is of low concern
for human health and environmental hazard across the range of endpoints in these low-concern
criteria.
26
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Exposure potential:
To understand exposure potential, EPA gathered information on physical-chemical properties,
production volumes, and the types of exposures likely to be faced by workers, the general population,
consumers, and children (discussed in Sections 3 and 7). EPA also gathered information on
environmental releases. EPA identified workers, the general population, consumers, and the
environment as most likely to experience exposures. EPA determined that while the general
population, consumers, and workers may be exposed to tripropylene glycol, exposure by the dermal
pathway is limited by tripropylene glycol's physical-chemical properties. If ingestion occurs,
tripropylene glycol is expected to be quickly metabolized and excreted, reducing the duration of
exposure. Inhalation of tripropylene glycol from dilute products is expected to be minimal; however,
workers may be exposed to vapors of neat tripropylene glycol. If tripropylene glycol is released into
the environment, its exposure potential will be reduced through biodegradation under aerobic
conditions.
Rationale: EPA determined that while workers, consumers, and children could be exposed to
tripropylene glycol during processing, manufacturing, distribution, use, or disposal, these exposures
do not pose a significant risk because of the chemical's low-hazard results across a range of endpoints
(discussed in Section 6). In summary, the concern for exposure is mitigated by the low-hazard profile
of this chemical.
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 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 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 is 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 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.
27
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
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 as a potentially
exposed or susceptible subpopulation (described in more detail in Section 7). Consumers are also a
potentially exposed subpopulation because of their use of products such as cleaning and furniture care
products, lubricants and greases, and anti-freeze and de-icing products, as shown in Table 3.
Rationale: EPA did not identify hazard effects for this chemical that would make any population
susceptible. EPA expects workers and consumers to have a higher exposure to tripropylene glycol
than the general population. Because of the chemical's low-concern hazard properties, this exposure
does not pose a significant increase in risk for consumers or for workers
Proposed Conclusion: Based on the Agency's understanding of the conditions of use and expected
users such as potentially exposed or susceptible subpopulations, EPA proposes to conclude that the
screening-level review under 40 CFR 702.9(a)(3) does not support a finding that tripropylene glycol
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
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 near significant sources of drinking water. EPA focused primarily on
the chemical'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. This 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 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 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 is unlikely to partition into
sediment, predicted to biodegrade under aerobic conditions (see Section 3), and unlikely to
28
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
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. Further, as
explained in section 6.1.3, repeated exposures of mice and rats to a closely related analog,
dipropylene glycol, through the drinking water exposure pathway indicate low concern for exposure
through drinking water to this chemical.
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 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 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 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 and related potential
exposures.
Rationale: EPA evaluated the conditions of use of tripropylene glycol (see Section 5 and Appendix
A) and found it to have a broad range of conditions of use. EPA expects that even if the conditions of
use were to expand beyond activities that are currently known, intended and reasonably foreseen, the
outcome of the screening review would likely not change and would not alter the Agency's
conclusion of low concern. EPA bases this expectation on tripropylene glycol'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 meets the standard for a high-priority substance based on its low-hazard profile
29
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
under the current conditions of use. EPA proposes to find that even if conditions of use broaden,
resulting in an increase in the frequency or amount of exposures, the analysis conducted to support
the screening level review under 40 CFR 702.9(a)(5) would not change significantly. In particular, the
analysis of concern for hazard, which forms an important basis for EPA's findings, would not be
impacted by a change in conditions of use. Therefore, such changes would not support a finding that
tripropylene glycol 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 (Section 7.1) and
related potential exposures (Section 7.2 through 7.4).
Rationale: EPA used reasonably available information on production volume (see Appendix A) in
considering potential risk. It is reasonably foreseeable that designation of tripropylene glycol as a
low-priority substance could result in increased use and higher production volumes. EPA expects,
however, that any changes in tripropylene glycol's production volume would not alter the Agency's
assessment of low concern given the low-hazard profile of the chemical. EPA bases this expectation
on tripropylene glycol's consistently low-hazard characteristics, which, across the spectrum of hazard
endpoints and regardless of a significant change in the volume of the chemical manufactured or
processed and resultant increased exposures, would still be expected to pose a low concern.
Proposed Conclusion: Based on this screening criteria under 40 CFR 702.9(a)(6), EPA proposes to
find that even if production volumes increase, resulting in an increase in the frequency or level of
exposures, tripropylene glycol does not meet the standard for a high-priority substance. The
reasonably available information on production volume, or significant changes in production volume,
described above provides sufficient information to support this proposed finding.
8.7. Other Considerations
EPA did not identify other considerations for the screening review to support the proposed
designation of tripropylene glycol as a low-priority substance.
30
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
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 as a low-priority
substance as it does not meet the statutory criteria for a high-priority substance.
31
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Appendix A: Conditions of Use Characterization
EPA gathered information on and related to conditions of use including uses, products, types of users,
and status (e.g., ongoing, regulated) for the chemical tripropylene glycol (CAS RN 24800-44-0).
A.1. CDR Manufacturers and Production Volume
The Chemical Data Reporting (CDR) rule (previously known as the Inventory Update Rule, or IUR),
under TSCA section 8, requires manufacturers (including importers) to report information on the
chemical substances they produce domestically or import into the U.S., generally above a reporting
threshold of 25,000 lb. per site per year. According to the 2016 Chemical Data Reporting (CDR)
database, five companies manufactured or imported tripropylene glycol at seven sites for reporting
year 2015. Individual production volumes were withheld by EPA to protect against disclosure of CBI.
Table A.l presents the historic production volume of tripropylene glycol from the CDR (previously
known as the Inventory Update Rule, or IUR) from 1986-2015. In reporting years 1986, 1990, 1994,
1998, 2002, 2006 and between 2012 and 2015, aggregate production volume for tripropylene glycol
was between 10,000,000 and 500,000,000 lbs. The exact amount is available for one year, 2011, in
which 25,531,268 lbs. of tripropylene glycol was produced or imported. Since 2011, production
volume has remained relatively stable without significant increases or decreases.
Table A.1:1986-2015 National Production Volume Data for Tripropylene glycol (Non-Confidential Production
Volume in Pounds)
1986
1990
1994
1998
2002
2006
2011
2012
2013
2014
2015
>10M
>10M
>10M -
>10M -
>10M
10 M-
25,531,268
10 M -
10 M -
10 M -
10 M -
-50M
-50M
50 M
50 M
-50M
< 50 M
50 M
50 M
50 M
50 M
Source(
s):
EPA (2018a; 2017b; 2006; 2002)
Note(s):
K = Thousand; M :
= Million; NDR = No data reported
I
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
A.2. Uses
A.2.1 Methods for Uses Table
Section A. 1 provides a list of known uses of tripropylene glycol organized by category of use. To
compile the uses, EPA searched publicly available databases listed in Table 3-1 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
:or Uses of Tripropylene glycol
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)
24800-44-0
No
Canada Chemicals
Management Plan information
sheets
Government of Canada
(2018)
24800-44-0; tripropylene glycol
No
Chemical and Product
Categories (CPCat)
CPCat (2019)
24800-44-0
Yes
ChemView2
EPA (2018a)
24800-44-0
Yes
Children's Safe Product Act
Reported Data
Washington State Dept. of
Ecology (2018)
24800-44-0
No
Consumer Product
Information Database (CPID)
DeLima Associates (2018)
24800-44-0
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
No
DrugBank
DrugBank (2018)
24800-44-0; tripropylene glycol
No
European Chemicals Agency
(ECHA) Registration Dossier
ECHA (2018)
24800-44-0
Yes
eChemPortal2
OECD (2018)
24800-44-0
No
Envirofacts2
EPA (2018b)
24800-44-0
No
Functional Use Database
(FUse)
EPA (2017a)
24800-44-0
Yes
Kirk-Othmer Encyclopedia of
Chemical Technology
Kirk-Othmer (2006)
24800-44-0; tripropylene glycol
Yes
Non-Confidential 2016
Chemical Data Reporting
(CDR)
EPA (2017b)
24800-44-0
Yes
PubChem Compound
Kim etal. (2016)
24800-44-0
Yes
Safer Chemical Ingredients
List (SCIL)
EPA (2018e)
24800-44-0
Yes
II
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table A.2: Sources Searched for Uses of Tripropylene glycol
Title
Author and Year
Search Term(s)
Found Use
Information? 1
Synapse Information
Resources2
Synapse Information
Resources (2009)
Tripropylene glycol
Yes
Resource Conservation and
Recovery Act (RCRA)
EPA (2018d)
Tripropylene glycol; TPG
No
Scorecard: The Pollution
Information Site
GoodGuide (2011)
24800-44-0
Yes
Skin Deep Cosmetics
Database
EWG (2018)
24800-44-0
Yes
Toxics Release Inventory
(TRI)
EPA (2018f)
24800-44-0
No
TOXNET2
NLM (2018c)
24800-44-0
Yes
Ullmann's Encyclopedia of
Industrial Chemistry
Ullmann's (2000)
24800-44-0; tripropylene glycol
Yes
Additional Sources Identified from Reasonably Available Information
Sigma Aldrich
Sigma Aldrich (2018)
Incidentally identified while
researching details of this
chemical's uses and products.
Yes
Silver Fern Chemical Inc.
Silver Fern Chemical Inc.
(2018)
Substances in Preparations in
Nordic Countries (SPIN)
SPIN (2018)
The Dow Chemical Company
(Dow)
Dow (2018)
U.S. EPA's InertFinder
EPA (2018c)
Note(s):
1. If use information was found in the resource, it will appear in Table A.3 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 16,175 patents referencing
"tripropylene glycol" (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 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.
Ill
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
A.2.2 Uses of Tripropylene glycol
Table A.3: Uses of Tripropylene glycol
Use
Expected Users
Description of Use and References
TSCA Conditions of Use: Agriculture and Food Products
NLM (2018b); ECHA (2018)
Agricultural chemicals
Unknown
NLM's HSDB identifies use of tripropylene glycol as a solvent for agricultural chemicals. ECHA
identifies use of tripropylene glycol in agrochemicals in European countries. No further
information about this use could be found and it is unknown whether this is an ongoing use in
the United States.
Expected users are unknown, due to the limited availability of information. ECHA identifies this
use under consumer uses and uses by professional workers.
Silver Fern Chemical Inc. (2018); CPCat (2019); SPIN (2018)
Insecticides
Unknown
Silver Fern Chemical identifies use of tripropylene glycol in insecticides. The California
Department of Pesticide Regulation does not list any pesticides currently used in California
that contain tripropylene glycol. CPCat identifies use of tripropylene glycol as an inert
ingredient in pesticides, however EPA's InertFinder (2018c) does not report and food, non-
food, or fragrance use of pesticides that contain tripropylene glycol as an inert ingredient.
SPIN reports use of tripropylene glycol in biocides in Nordic countries.
Expected users are unknown, due to the limited availability of information.
TSCA Conditions of Use: Cleaning Products
GoodGuide (2011); Synapse Information Resources (2009); ECHA (2018)
Cleaning agents
Consumer, commercial, industrial
Pollution Scorecard identifies use of tripropylene glycol in household hard surface cleaners.
Synapse Information Resources identifies use of tripropylene glycol in disinfectants, varnish
removers, hard surface cleaners, and penetrating oils. ECHA identifies use of tripropylene
glycol in cleaning agents in European countries.
Expected users are consumer based on identification under Pollution Scorecard's consumer
products and ECHA's consumer uses. Expected users are commercial and industrial based on
inclusion in ECHA's uses by professional workers and uses at industrial sites.
IV
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table A.3: Uses of Tripropylene glycol
Use
Expected Users
Description of Use and References
Soaps
Unknown
NLM (2018b); Synapse Information Resources (2009)
NLM's HSDB identifies use of tripropylene glycol in dry-cleaning soaps, and Synapse
Information Resources identifies use in soap.
Expected users are unknown, due to the limited availability of information.
TSCA Conditions of Use: Manufacturing
Builders' carpentry and joinery
manufacturing
Unknown
SPIN (2018)
SPIN reports use of tripropylene glycol in the manufacture of builders' carpentry and joinery in
Nordic countries. No further information about this use could be found and it is unknown
whether this is an ongoing use in the United States.
Expected users are unknown, due to the limited availability of information.
Chemical manufacturing
Unknown
SPIN (2018)
SPIN reports use of tripropylene glycol in the manufacture of chemicals and chemical products
in Nordic countries. No further information about this use could be found and it is unknown
whether this is an ongoing use in the United States.
Expected users are unknown, due to the limited availability of information.
Machinery and equipment
manufacturing
Unknown
SPIN (2018)
SPIN reports use of tripropylene glycol in the manufacture of machinery and equipment in
Nordic countries. No further information about this use could be found and it is unknown
whether this is an ongoing use in the United States.
Expected users are unknown, due to the limited availability of information.
V
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table A.3: Uses of Tripropylene glycol
Use
Expected Users
Description of Use and References
SPIN (2018)
Metal manufacturing
Industrial
SPIN reports use of tripropylene glycol in the manufacture of fabricated metal products, as
well as the treatment and coating of metals, in Nordic countries. No further information about
this use could be found and it is unknown whether this is an ongoing use in the United States.
Expected users are unknown, due to the limited availability of information.
EPA (2017b)
Petrochemical manufacturing
Industrial
CDR reports use of tripropylene glycol as an intermediate in petrochemical manufacturing.
Expected users are industrial based on reporting under CDR's Industrial Processing and Use
Report.
EPA (2017b); NLM (2018b); Synapse Information Resources (2009); ECHA (2018); SPIN
(2018); Ullmann's (2018)
Plastic material and resin
manufacturing
Commercial, industrial
CDR reports use of tripropylene glycol as an intermediate in plastic material and resin
manufacturing. NLM's HSDB identifies use as a plasticizer for 2-hydroxypropyl cellulose resin.
Synapse Information Resources identifies use of tripropylene glycol as a comonomer for alkyd
resins and unsaturated polyester resins, a chain extender for polyurethane, and an initiator for
urethane polyols. Ullmann's states that tripropylene glycol is in an important industrial building
block for polyurethane foams and elastomers. ECHA identifies use of tripropylene glycol in
polymer processing in European countries. SPIN reports use in the manufacture of rubber and
plastic products in Nordic countries.
Expected users are industrial based on reporting under CDR's Industrial Processing and Use
Report and commercial based on inclusion in ECHA's uses by professional workers.
SPIN (2018)
Transportation equipment
manufacturing
Industrial
SPIN reports use of tripropylene glycol in the manufacture of other transportation equipment in
Nordic countries. No further information about this use could be found and it is unknown
whether this is an ongoing use in the United States.
Expected users are unknown, due to the limited availability of information.
VI
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table A.3: Uses of Tripropylene glycol
Use
Expected Users
Description of Use and References
SPIN (2018)
Wood manufacturing
Industrial
SPIN reports use of tripropylene glycol in the manufacture of wood and cork products,
including straw and plaiting materials, in Nordic countries. No further information about this
use could be found and it is unknown whether this is an ongoing use in the United States.
Expected users are unknown, due to the limited availability of information.
TSCA Conditions of Use: Miscellaneous
NLM (2018b); SPIN (2018); Ullmann's (2010)
Adhesives and binding agents
Unknown
NLM's HSDB identifies use of tripropylene glycol as a solvent for gums. Ullmann's identifies
use of tripropylene glycol in ultraviolet/electric beam curing adhesives. SPIN reports use in
adhesives and binding agents in Nordic countries.
Expected users are unknown, due to the limited availability of information
Synapse Information Resources (2009); ECHA (2018)
Anti-freeze and de-icing products
Consumer, commercial
Synapse Information Resources identifies use of tripropylene glycol in lubricant and antifreeze
for carburetor fluids. ECHA identifies use in anti-freeze and de-icing products in European
countries. No further information about this use could be found and it is unknown whether this
is an ongoing use in the United States.
Expected users are consumer and commercial based on inclusion in ECHA's consumer uses
and uses by professional workers.
NLM (2018b); Synapse Information Resources (2009); SPIN (2018)
Automotive trade and repair
Unknown
NLM's HSDB and Synapse Information Resources identify use of tripropylene glycol in brake
and hydraulic fluid components. SPIN reports use in wholesale and retail trade, repair, and
maintenance of motor vehicles and motorcycles in Nordic countries.
Expected users are unknown, due to the limited availability of information.
VII
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table A.3: Uses of Tripropylene glycol
Use
Expected Users
Description of Use and References
Synapse Information Resources (2009)
Cooling media
Unknown
Synapse Information Resources identifies use of tripropylene glycol in cooling media. No
further information about this use could be found and it is unknown whether this is an ongoing
use in the United States.
Expected users are unknown, due to the limited availability of information.
Kirk-Othmer (2004)
Drilling fluids
Unknown
Kirk-Othmer identifies use of tripropylene glycol in water-based drilling fluids for the petroleum
industry. No further information about this use could be found and it is unknown whether this is
an ongoing use in the United States.
Expected users are unknown, due to the limited availability of information.
SPIN (2018)
Emulsion-inhibiting agents
Unknown
SPIN identifies use of tripropylene glycol in emulsion-inhibiting agents, which are often used in
the petroleum industry. No further information about this use could be found and it is unknown
whether this is an ongoing use in the United States.
Expected users are unknown, due to the limited availability of information.
EPA (2017b); SPIN (2018)
Fabric, textile, and leather
Commercial, industrial
CDR reports use of liquid tripropylene glycol in fabric, textile, and leather products not covered
elsewhere at concentrations of at least one percent but less than 30 percent by weight. CDR
also reports use of tripropylene glycol as a finishing agent in textile, apparel, and leather
manufacturing. SPIN identifies use of tripropylene glycol in washing agents for textiles and
textile impregnation materials in Nordic countries.
Expected users are commercial based on CDR's consumer/commercial classification and
reporting under CDR's Industrial Processing and Use Report.
VIII
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table A.3: Uses of Tripropylene glycol
Use
Expected Users
Description of Use and References
ECHA (2018)
Fuels
Consumer
ECHA identifies use of tripropylene glycol in fuels in European countries. No further
information about this use could be found and it is unknown whether this is an ongoing use in
the United States.
Expected users are consumer based on inclusion in ECHA's consumer uses.
NLM (2018b); Dow (2018); Synapse Information Resources (2009); SPIN (2018)
Inks
Unknown
Dow identifies use of tripropylene glycol as a resin solubilizer for common printing ink, and
NLM's HSDB reports use of tripropylene glycol in inks. Synapse Information Resources
identifies use of tripropylene glycol as a solvent and homogenizer for inks and other coloring
materials, including color concentrations. SPIN reports use in coloring agents and in the
manufacture of printing inks and mastics in Nordic countries.
Expected users are unknown, due to the limited availability of information.
Sigma Aldrich (2018); ECHA (2018)
Laboratory chemicals
Commercial, institutional
Sigma Aldrich identifies use of tripropylene glycol in laboratory chemicals. ECHA identifies use
in laboratory reagents in European countries.
Expected users are commercial and industrial based on inclusion in ECHA's uses by
professional workers and uses at industrial sites.
IX
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table A.3: Uses of Tripropylene glycol
Use
Expected Users
Description of Use and References
Lubricants and greases
Consumer, commercial, industrial
EPA (2017b); Silver Fern Chemical Inc. (2018); Synapse Information Resources (2009); NLM
(2018b); ECHA (2018); SPIN (2018)
CDR reports use of liquid tripropylene glycol in commercial lubricants and greases. Silver Fern
Chemical identifies use in mold lubricants, and Synapse Information Resources identifies use
in cutting oils. NLM's HSDB identifies use as a coupling agent in cutting oils and soluble oils.
ECHA identifies use of tripropylene glycol in consumer and commercial lubricants, binders,
release agents, metal working fluids, and rolling oils in European countries, and SPIN reports
use in lubricants and additives in Nordic countries.
Expected users are commercial based on CDR's consumer/commercial classification, and
consumer and industrial based on inclusion in ECHA's consumer uses and uses at industrial
sites.
Mining
Industrial
EPA (2017b)
CDR reports use of tripropylene glycol as an intermediate in non-oil and gas mining and
support activities.
Expected users are industrial based on reporting under CDR's Industrial Processing and Use
Report.
Paints and coatings
Unknown
NLM (2018b); ECHA (2018); SPIN (2018); Dow (2016); Ullmann's (2011)
NLM's HSDB identifies use of tripropylene glycol in some paints. Dow identifies growing use of
tripropylene glycol in the radiation cure industry, and Ullmann's identifies use as a monomer in
radiation-curable acrylate systems. ECHA identifies use in coatings in European countries,
and SPIN identifies use in paints (including the manufacture of paints), lacquers, and
varnishes in Nordic countries.
Expected users are unknown, due to the limited availability of information.
X
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table A.3: Uses of Tripropylene glycol
Use
Expected Users
Description of Use and References
SPIN (2018)
Process regulators
Unknown
SPIN reports use of tripropylene glycol in process regulators in Nordic countries. No further
information about this use could be found and it is unknown whether this is an ongoing use in
the United States.
Expected users are unknown, due to the limited availability of information.
SPIN (2018)
Surfactants
Unknown
SPIN reports use of tripropylene glycol in surface active agents in Nordic countries. No further
information about this use could be found and it is unknown whether this is an ongoing use in
the United States.
Expected users are unknown, due to the limited availability of information.
ECHA (2018)
Water treatment
Consumer, commercial, industrial
ECHA identifies use of tripropylene glycol in water treatment chemicals in European countries.
No further information about this use could be found and it is unknown whether this is an
ongoing use in the United States.
Expected users are based on inclusion in ECHA's consumer uses, uses by professional
workers, and uses at industrial sites.
Non-TSCA Uses
Antiperspirant/ deodorant
Consumer
DeLima Associates (2016); EWG (2018)
CPID and EWG generally list consumer products; therefore the expected users are consumer.
Synapse Information Resources (2009); CPCat (2019) (2015)
Food
Unknown
Synapse Information Resources identifies use of tripropylene glycol in food. CPCat reports
use of tripropylene glycol as a food additive, however tripropylene glycol is not listed in FDA's
Substances Added to Food (2018).
Expected users are unknown, due to the limited availability of information.
XI
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table A.3: Uses of Tripropylene glycol
Use
Expected Users
Description of Use and References
Makeup remover
Consumer
EWG (2018)
EWG generally lists consumer products; therefore the expected users are consumer
Silver Fern Chemical Inc. (2018); NLM (2018b)
Pharmaceuticals
Unknown
Silver Fern Chemical, Inc. identifies use of tripropylene glycol as an intermediate in
pharmaceuticals. NLM's HSDB identifies use as a solvent for essential oils and
pharmaceuticals. DrugBank does not list any current drug-related uses that include
tripropylene glycol.
Expected users are unknown, due to the limited availability of information.
NLM (2018a)
Shampoo
Consumer
NLM's Household Products Database identifies use of tripropylene glycol in shampoos and
shampoo/conditioners. None of these products are currently for retail sale, and this use may
be historical.
The Household Products Database lists household products; therefore, the expected users
are consumer.
CDR reports did not include any uses in children's products.
Children's Products
Recycling and Disposal
In the 2016 CDR, six facilities reported not recycling (e.g., not recycled, remanufactured, reprocessed, or reused) tripropylene glycol, and one facility reported recycling
information as CBI (EPA 2017b).
XII
-------
***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
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. (2016). Speed Stick GEAR DRYCORE Antiperspirant and Deodorant Gel, Fresh
Force-04/19/2016. Retrieved from
https://www.whatsinproducts.com/tvpes/tvpe detail/l/17090/standard/p%20class=%22pl%22%3
ESpeed%20Stick%20GEAR%20DRYCQRE%20Antiperspirant%20and%20Deodorant%20Gel.
%20Fresh%20Force-04/19/2016/p%3E/03-008-273
DeLima Associates. (2018). Consumer Product Information Database. Retrieved from
https: //www. whatsinproducts. com/
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). [(methylethylene)bis(oxy)]dipropanol. Retrieved from
https://echa.europa.eu/registration-dossier/-/registered-dossier/14788
EWG. (2018). TRIPROPYLENE GLYCOL. Retrieved from
https://www.ewg.org/skindeep/ingredient/706712/TRIPROPYLENE GLYCOL/
GoodGuide. (2011). ((1 -METHYL-1,2-ETHANEDIYL)BIS(OXY))BISPROPANOL. Retrieved from
http://scorecard.goodguide.com/chemical-profiles/consumer-
products.tcl?edf substance id=24800-44-0
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. (2004). Drilling Fluids. Retrieved from
httnsy/on1infi1ihrarv.wilev.com/doi/10.1002/0471238961.0418091203120118.a01.pub2
Kirk-Othmer. (2006). Kirk-Othmer Encyclopedia of Chemical Technology.
XIII
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
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
Sigma Aldrich. (2018). Tripropylene Glycol Safety Data Sheet. Retrieved from
https://www.sigmaaldrich.com/MSDS/MSDS/DisplavMSDSPage.do?countrv=US&language=en
&productNumber=187593&brand=ALDRICH&PageToGoToURL=https%3A%2F%2Fwww.sig
maaldrich.com%2Fcatalog%2Fproduct%2Faldrich%2F187593%3Flang%3Den
Silver Fern Chemical Inc. (2018). Tripropylene Glycol. Retrieved from
http://www.silverfernchemical.com/products/tripropylene-glvcol/
Substances in Preparations in Nordic Countries (SPIN). (2018). tripropylenglycol. Retrieved from
http://www.spin2000.net/spinmvphp/
Synapse Information Resources. (2009). Specialty Chemicals Source Book. Fourth Edition. Volume 1.
The Dow Chemical Company. (2016). Technical Data Sheet - Dow Tripropylene Glycol, Acrylate Grade.
Retrieved from
http://msdssearch.dow.com/PublishedLiteratureDOWCQM/dh 0973/090lb80380973ala.pdf?file
path=propyleneglvcol/pdfs/noreg/l 17-22801 .pdf&fromPage=GetDoc
The Dow Chemical Company. (2018). What specific grades of tripropylene glycol does Dow offer?
Retrieved from https://dowservice.custhelp.eom/app/answers/detail/a id/16844
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://chemview.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). InertFinder. Retrieved from
https://iaspub.epa.gov/apex/pesticides/f?p=INERTFINDER:2:: :NO:::
U.S. Environmental Protection Agency (EPA). (2018d). 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). (2018e). Safer Chemical Ingredients List. Retrieved from
https://www.epa.gov/saferchoice/safer-ingredients
XIV
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
U.S. Environmental Protection Agency (EPA). (2018f). TRI-Listed Chemicals. Retrieved from
https://www.epa.gov/toxics-release-inventorv-tri-program/tri-listed-chemicals
U.S. Food and Drug Administration (FDA). (2018). Substances Added to Food. Retrieved from
https://www.accessdata.fda.gov/scripts/fdcc/?set=FoodSubstances&sort=Sortterm&order=ASC&
startrow= 1 &tvpe=basic&search=24800-44-0
U.S. National Library of Medicine (NLM). (2018a). Household Products Database. Retrieved from
https: //hpd .nlm .nih. gov/cgi-bin/household/brands ?tbl=chem&id=3 688
U.S. National Library of Medicine (NLM). (2018b). HSDB: Tripropylene Glycol. Retrieved from
https://toxnet.nlm.nih.gOv/cgi-bin/sis/search2/f7./temp/~6ZXsEH:2
U.S. National Library of Medicine (NLM). (2018c). TOXNET Hazardous Substances Data Bank.
Retrieved from https://toxnet.nlm.nih.gov/cgi-bin/sis/search2
U.S. Patent and Trademark Office (USPTO). (2018). USPTO Patent Full-Text and Image Database.
Retrieved from http: //patft .uspto. gov/netacgi/nph-
Parser?Sectl=PT02&Sect2=HIT0FF&p=l&u=%2Fnetahtml%2FPT0%2Fsearch-
bool .html&r=0&f=S&l=5 O&TERM 1 =tripropylene+glvcol&FIELD 1=&co 1 =AND&TERM2=&F
IELD2=&d=PTXT
Ullmann's. (2000). ULLMANN'S Encyclopedia of Industrial Chemistry.
Ullmann's. (2010). Adhesives, 1. General. Retrieved from
https ://onlinelibrarv. wilev .com/doi/10.1002/143 5 6007 ,a01 221 ,pub3
Ullmann's. (2011). Paints and Coatings, 3. Paint Systems. Retrieved from
https://onlinelibrarv.wilev.com/doi/10.1002/14356007.ol8 o02.pub2
Ullmann's. (2018). Propanediols. Retrieved from
https://onlinelibrarv. wilev .com/doi/10.1002/143 5 6007 ,a22 163 ,pub2
Washington State Dept. of Ecology. (2018). Children's Safe Product Act Reported Data. Retrieved from
https://fortress.wa.gov/ecv/cspareporting/
XV
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Appendix B: Hazard Characterization
Table B.1: Human Health Hazard
ADME
Source
Exposure Route
Species &
strain (if
available)
Duration
Doses and
replicate
number
Effect
Study Details
4940456, 4940388
Oral (gavage)
Fischer 344 rats
Single
exposure, 24
hour
observation
Doses: 48.2
mg/kg
Replicates: 5
male rats
The test material is
rapidly absorbed
and distributed,
and primarily
excreted through
urine. It is also
extensively
metabolized to
dipropylene and
monopropylene
glycol and further
oxidized to C02.
Methods:
Test substance reported as CAS RN
24800-44-0
Purity: 99.8%
GLP compliant
Results:
Absorption: 91.4 ± 2.07 % of the dose
administered was recovered indicating
tripropylene glycol is rapidly absorbed
Distribution: The liver and kidney had the
greatest amounts of tripropylene glycol
Metabolism: Tripropylene glycol is
extensively metabolized. 5.8% of the
dose was recovered as unmetabolized
parent compound. Tripropylene glycol is
metabolized to dipropylene and
monopropylene glycol and further
oxidized to CO2
Excretion: Dipropylene glycol was
excreted primarily in the urine (52.3 ±
3.54%) and in exhaled breath
(20.7±0.59%)
XVI
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table B.1: Human Health Hazard
4940508, 4940301,
Dermal (in vitro)
Human cadaver
24 hours
Dose: 768
The test material
Methods:
3039551
skin
undiluted test
substance
Replicates: 7
samples from 4
cadavers
was considered a
slow penetrant
Test substance reported as CAS RN
25265-71-8
Purity: 99.9%
OECD Guideline 428
GLP compliant
Results:
Steady state penetration was 39.3
|jg/cm2-hour and the permeability
coefficient was 3.85x10 5 cm/hour
Acute Mammalian Toxicity
Source
Exposure Route
Species &
strain (if
available)
Duration
Doses and
replicate
number
Effect
Study Details
2282271,4940516
Oral (in water)
Sprague-Dawley
rats
Single exposure
Doses: 500,
1000, and 2000
mg/kg
Replicates: 5
per sex per
dose
LDso > 2000 mg/kg
Methods:
Test substance reported as CAS RN
24800-44-0
Purity > 98%
OECD Guideline 401
GLP compliant
4940509
Oral (gavage)
Wistar rat
Single
exposure,
observed for 14
days
Doses: 4080,
8160, and
16320 mg/kg
Replicates: 5
males per group
LD50:11500 mg/kg
Methods:
Test substance reported as CAS RN
24800-44-0
Purity not reported
Pre-GLP compliance
Mortalities:
4,080 mg/kg: 0/5
8,160 mg/kg: 0/5
16,320 mg/kg: 5/5
4940517
Inhalation
Rats
8 hour
exposure,
observed for 14
days
Dose: 0.083
mg/L
Replicates: 6
animals
LD50 > 0.083 mg/L
Methods:
Test substance CASRN 24800-44-0
Purity not reported
Pre-GLP compliance
XVII
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table B.1: Human Health Hazard
4940519
Dermal
Albino rabbits
24 hour
Dose: 16320
LDso > 16320
Methods:
exposure,
observed for 14
mg/kg
Replicates: 5
mg/kg
Test substance reported as CAS RN
24800-44-0
days
males
Purity not reported
Pre-GLP compliance
Repeated Dose Toxicity
Source
Exposure Route
Species &
strain (if
available)
Duration
Doses and
replicate
number
Effect
Study Details
4940389, 4940514
Oral (gavage)
Sprague-Dawley
Male: 2 weeks
Doses: 0, 8, 40,
NOAEL: 200
Method:
rats
prior to mating,
200, and 1000
mg/kg-day
Test substance reported as CAS RN
49 days total
mg/kg-day
LOAEL: 1000
24800-44-0
Females: 2
weeks prior to
mating up to
Replicates: 12
per sex per
group
mg/kg-day based
on organ weight
changes in parents
Purity > 98%
OECD Guideline 422
GLP compliant
day 3 of
lactation
4940384, 4940445
Oral (drinking
B6C3F1 mice
2 years
Doses:
NOAEL: 1040
Methods:
water)
Males: 0, 735,
1220, and 2390
mg/kg-day
Females: 0,
575, 1040, 1950
mg/kg-day
Replicates: 50
per sex per
dose
mg/kg-day
LOAEL: 1950
mg/kg-day based
on decreased mean
body weight
Test substance reported as CAS RN
25265-71-8
Purity: 99%
NTP Guideline
GLP compliant
XVIII
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table B.1: Human Health Hazard
4940466, 4940384
Oral (drinking
B6C3F1 mice
13 weeks
Doses:
NOAEL: 2620
Methods:
water)
Males: 0, 715,
mg/kg-day (male)
Test substance reported as CAS RN
1350, 2620,
LOAEL: 4790
25265-71-8
4790 and
mg/kg-day (male),
Purity: 99%
11,000 mg/kg-
based on increased
NTP Guideline
day;
liver weight
GLP compliant
Females: 0,
Endpoints:
1230, 2140,
Morality
4020, 7430 and
o 7,430 mg/kg-day females:
14700 mg/kg-
(1/10) hypothermia
day
o 11,000 mg/kg-day males:
Replicates: 10
(3/10) dehydration
per sex per
o 14,700 mg/kg-day females:
dose
(1/10) dehydration
4940384, 4940465,
Oral (drinking
F344/N rats
2 years
Doses:
NOAEL: 115
Methods:
4940455
water)
Males: 0,115,
mg/kg-day
Test substance: CASRN 25265-71 -8
470, and 3040
LOAEL: 470
Purity: 99%
mg/kg-day;
mg/kg-day based
GLP compliance not reported
females: 0,140,
on increased
530, and 2330
incidence of
mg/kg-day
nephropathy, focal
Replicates: 50
histiocytic, and
per sex per
focal
dose
granulomatous
inflammation in
male livers
XIX
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table B.1: Human Health Hazard
4940384, 4940462
Oral (drinking
F344/N rats
14 weeks (3
Doses:
NOAEL: 425
Methods:
water)
months)
Males 0, 425,
890, 1840,
3890, and
12,800 mg/kg-
day
Females: 0,
460, 920, 1690,
3340, and 8950
mg/kg-day
Replicates: 10
per sex per
dose
mg/kg-day
LOAEL: 890
mg/kg-day based
on relative liver
weight
Test substance reported as CAS RN
25265-71-8
Purity: 99%
GLP compliance not reported
Reproductive Toxicity
Source
Exposure Route
Species &
Strain (if
available)
Duration
Doses and
replicate
number
Effect
Study Details
4940389, 4940514
Oral (gavage)
Sprague-Dawley
Male: 2 weeks
Doses: 0, 8, 40,
NOAEL: 1000
Method:
rats
prior to mating,
49 days total;
Females: 2
weeks prior to
mating up to
day 3 of
lactation
200, and 1000
mg/kg-day
Replicates: 12
per sex per
group
mg/kg-day
Test substance reported as CAS RN
24800-44-0
Purity >98%
OECD Guideline 422
GLP compliant
Developmental Toxicity
Source
Exposure Route
Species &
Strain (if
available)
Duration
Doses and
replicate
number
Effect
Study Details
XX
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table B.1: Human Health Hazard
4940450, 4440869,
4940388, 3041958
Oral (gavage)
Pregnant
Sprague-Dawley
rats
GD6-15
Doses: 0, 800,
2000, and 5000
mg/kg-day
Replicates: 20-
27 per dose
NOAEL: 2000
mg/kg-day
LOAEL: 5000
mg/kg-day based
on decreased fetal
body weight
Methods:
Test substance reported as CAS RN
25265-71-8
Purity >96%
NTP Guideline
GLP compliance
4440871, 4940459,
4940388
Oral (gavage)
New Zealand
White rabbit
GD6-19
Doses: 0, 200,
400, 800, and
1200 mg/kg-day
Replicates: 24
per group
NOAEL: 1200
mg/kg-day
Methods:
Test substance: CASRN 25265-71 -8
Purity > 96%
NTP protocol NTP-90-CTER-126
GLP compliant
Cancer
Source
Exposure Route
Species &
Strain (if
available)
Duration
Doses and
replicate
number
Effect
Study Details
4940448, 4940455,
4940384
Oral (drinking
water)
Fischer 344 rats
2 years
Doses:
Males: 0,115,
470 and 3,040
mg/kg-day
Females: 0,
140, 530 and
2,330 mg/kg-
day
Replicates: 50
per sex per
dose
Negative
Methods:
Test substance reported as CAS RN
25265-71-8
Purity: 99%
NTP Guideline
GLP compliant
XXI
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table B.1: Human Health Hazard
4940384, 4940448
Oral (drinking
water)
B6C3F1 mice
2 years
Doses:
Males: 735,
1220, 2390
mg/kg-day
Females: 575,
1040,1950
mg/kg-day
Replicates: 50
per sex per
dose
Negative
Methods:
Test substance reported as CAS RN
25265-71-8
Purity: 99%
NTP Guideline
GLP compliant
Genotoxicity
Source
Test Type &
endpoint
Species &
strain (if
available)
Metabolic
activation
Doses and
controls
Results
Study Details
4940446, 4940384
Gene mutation (in
vitro)
Salmonella
typhimurium
strains TA 97,
TA98, TA100,
TA 1535, TA
1538
With and
without
Doses: 0,100,
333, 1000, 3333
and 10000
pg/plate
Negative
Methods:
Test substance reported as CAS RN
25265-71-8
Purity >99%
NTP Guideline
GLP compliant
4940463
Gene mutation (in
vitro)
Mouse
Lymphoma
L5178Y cells
With and
without
Doses: 50,100,
300, 500, 700,
1000, 2500 and
5000 [jg/mL
Negative
Methods:
Test substance reported as CAS RN
25265-71-8
Purity not reported
OECD Guideline 476
GLP compliant
4940467
Gene mutation (in
vitro)
Salmonella
typhimurium
strains TA98,
TA100, TA
1535, TA1537,
TA 1538
With and
without
Doses: 0.100,
0.316, 1.00,
3.16, 10.0,31.6
and 100
[jL/plate
Negative
Methods:
Test substance reported as CAS RN
25265-71-8
Purity: 99.9%
OECD Guideline 471
GLP compliant
XXII
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table B.1: Human Health Hazard
4940451, 4940388
Chromosomal
Mouse
N/A
Doses: 0, 500,
Negative
Methods:
aberrations (in
micronuclei
1000, and 2000
Test substance reported as CAS RN
vivo)
mg/kg
Replicates: 6
per group
25265-71-8
Purity: 99.9%
OECD Guideline 474
GLP Compliant
Sensitization
Source
Exposure Route
Species &
Strain (if
available)
Duration
Doses and
replicate
number
Effect
Study Details
4940444, 4946133
Dermal patch
Human
2 day exposure,
observed 7
days
Study 1
Doses: 1%,
2%, 5%, and
10%
Replicates: 34
patients
Study 2
Dose: 10%
Replicates:
503 volunteers
212 Males
291 Females
Equivocal
Methods:
Test substance reported as CAS RN
25265-71-8
Purity >96%
GLP compliance not reported
Results:
1 person had positive reaction (only to
standard grade dipropylene glycol)
488 subjects showed no reaction and 13
subjects showed equivocal reaction to
standard grade substance
480 subjects showed no reaction and 17
subjects showed equivocal reaction to
cosmetic grade substance
Irritation was indicated in 2 analytical
grade and 5 cosmetic grade volunteers
4940460
Dermal
Guinea pigs
6 hour
exposure,
induction
repeated 3
times during 2
weeks
Dose: 0.5 mL
Replicates: 10
animals (7
Males, 3
Females)
Negative
Methods:
Test substance reported as CAS RN
25265-71-8
Purity: 100%
EPA OPP 81-6
GLP compliant
Results:
1 animal displayed slight patchy
erythema 24 hours after
XXIII
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table B.1: Human Health Hazard
3118622
Dermal
patch
Humans
24 hour
exposure,
scored after 48
hours; repeated
for 9
applications
Dose: 0.4 mL
Replicates: 42
volunteers
Negative
Methods:
Test substance reported as CAS RN
25265-71-8
Purity not reported
Modified Draize Method
GLP compliance not reported
Irritation
Source
Exposure Route
Species &
Strain (if
available)
Duration
Doses
Effect
Study Details
4940512
Dermal
Rabbits
24 hours
Dose: 0.01 mL
of undiluted
solution
Replicates: 5
animals
Minimally irritating
Methods
Test substance reported as CAS RN
24800-44-0
Purity not reported
Pre-GLP compliance
Results:
Mean irritation score was 2 out of 10
(with 1 = no irritation). Moderate capillary
injection was observed on 4 rabbits
4940527
Dermal patch
Humans
24 hours
Dose: 0.2 mL of
25% solution
Replicates: 33
volunteers
Negative
Methods
Test substance reported as CAS RN
24800-44-0
Purity not reported
Non-GLP compliant
Results:
2 volunteers had mild erythema at 0.5
hours which resolved by 24 hours
4940526
Dermal patch
Humans
Daily for 14
days
Dose: 0.2mL of
50% solution
Replicates: 26
volunteers
Negative
Methods
Test substance reported as CAS RN
24800-44-0
Purity not reported
Non-GLP compliant
1/26 subjects did not complete the due
to reasons unrelated to exposure
XXIV
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table B.1: Human Health Hazard
4940520
Ocular
Rabbits
Single
exposure,
observed over
24 hours
Dose: 0.5 mL of
undiluted
solution
Replicates: 5
rabbits
Negative
Methods
Test substance reported as CAS RN
24800-44-0
Purity not reported
Predates GLP compliance
Results:
The overall irritation score was 1 (trace or
no injury) and was fully reversible. The
test material was considered non-
irritating
4940518
Ocular
New Zealand
Single
Dose: 0.1 mLof
Negative
Methods
White rabbits
exposure,
observed over
72 hours
undiluted
solution
Replicate: 2
animals
Test substance reported as CAS RN
24800-44-0
Purity: 99.6%
OECD Guideline 405
GLP compliant
Results:
2/2 animals had mild conjunctival
redness, chemosis, and conjunctival
discharge at the 1-hour scoring
All effects were reversible by 24 hours.
4940513
Ocular
SkinEthic
Human Corneal
Epithelium
Model (in vitro)
10 minutes
Dose: 30 pL of
undiluted
solution
Replicates: 3
replicates
Negative
Methods
Test substance reported as CAS RN
24800-44-0
Purity: 99.6%
GLP compliant
Other
Source
Exposure Route
Species &
Strain (if
available)
Duration
Doses
Effect
Study Details
XXV
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table B.1: Human Health Hazard
4088550
Cell viability
Human
NA
Doses: 0.0001-
NOAEL: 0.00745M
Methods:
embryonic stem
0.1 M
for hESCs
Test substance reported as CAS RN
cells (hESCs)
IC50: 0.04 M for
25265-71-8
and human
hESCs and hPF
Purity not reported
adult pulmonary
GLP compliance not reported
fibroblasts (hPF)
Results:
In hESCs the estimated NOAEL was
0.00745M and the IC50 was 0.045M,
only the highest concentration tested was
significantly different from (vehicle)
controls
The IC50 in hPF cells was identical
(0.04M), but a reliable NOAEL could not
be determined
Table B.2: Environmental Hazard
Aquatic Toxicity: Experimental
Source
Species & strain
(if available)
Duration
Doses and
replicate number
Effect
Study Details
4940389, 4940442
Oryzias latipes
96 hours
Doses: 5
concentrations
between 95-1000
mg/L (nominal)
Replicates: 10 per
group
LCso > 1000
mg/L
Methods:
Test substance reported as CASRN 24800-44-0
Purity: 97%
OECD Guideline 203
Not GLP compliant
4940389, 4940433
Daphnia magna
24 hours
Doses: 5
concentrations
between 10-1000
mg/L
Replicates: 4
replicates per
concentration, 5
organisms per
replicates
ECso > 1000
mg/L
Methods:
Test substance reported as CASRN 24800-44-0
Purity: 97%
OECD Guideline 202
Not GLP compliant
XXVI
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table B.2: Environmental Hazard
4940434, 4940389
Daphnia magna
21 days
Doses: 5
concentrations
between 10-1000
mg/L
Replicates: 4
replicates per
concentration, 10
organisms per
replicates
NOEC: 1000
mg/L
Methods:
Test substance reported as CASRN 24800-44-0
Purity: 97%
OECD Guideline 202
Not GLP compliant
Results:
LCso > 1000 mg/L for mortality
EC50 > 1000 mg/L for reproduction rate
4940389
Selenastrum
72 hours
Doses: 5 nominal
ECso > 1000
Methods:
capricornutum
concentrations 95-
1000 mg/L
mg/L
Test substance reported as CASRN 24800-44-0
Purity: 97%
OECD Guideline 201
Not GLP compliant
Aquatic Toxicity: Estimated
Model
Chemical Class
Species
Predicted Effect
Level
Notes
ECOSAR v2.0 (Class:
Neutral Organics)
ChV
Aquatic
vertebrates
1600 mg/L
Physical properties used for estimation Log K0w -0.38; water solubility 1000 mg/L; melting
point-30°C SMILES: CC(0)COC(C)COC(C)CO
ECOSAR v2.0 (Class:
Neutral Organics)
ChV
Green algae
480 mg/L
Physical properties used for estimation Log K0w -0.38; water solubility 1000 mg/L; melting
point-30°C SMILES: CC(0)COC(C)COC(C)CO
Table B.3:
:ate
Environmental Fate: Experimental
Source
Endpoint
Duration
Doses and number of
replicates
Results
Study Details
4940389
BOD
28 days
Dose: 100 mg/L
Not readily
biodegradable
Method:
Test substance reported as CASRN 24800-44-0
Purity not reported
OECD Guideline 301C
GLP compliant
Results:
0% degradation by TOC and 0-3% by GC after 28 days
1 -2% BOD degradation after 28 days
XXVII
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table B.3:
:ate
4940425
CO2 evolution
28 days
NA
Not readily
biodegradable
Method:
Test substance reported as CASRN 24800-44-0
Purity: 95%
OECD Guideline 301B
GLP compliant
Results:
0% degradation by DOC after 28 days
4-5% degradation by CO2 evolution after 28 days
4940426
O2 consumption
28 days
NA
69%
degradation
after 28 days
Method:
Test substance reported as CASRN 24800-44-0
Purity: 99.43%
OECD Guideline 301D
GLP compliant
Results:
59% in 11 days
69% degradation after 28 days
4940432
02
consumption,
C02
consumption,
DOC removal
28 days
Dose: 100 mg/L
Readily
biodegradable
Method:
Test substance reported as CASRN 24800-44-0
Purity: 99.9%
OECD Guideline 301F
GLP compliant
Results:
81.9% O2 consumption, 61% CO2 consumption, 91.7% DOC removal
after 28 days
55.3% biodegradation within 10-day window
4940431
O2 consumption
28 days
NA
Not readily
biodegradable
Method:
Test substance reported as CASRN 24800-44-0
Purity: 99.43%
OECD Guideline 301D
GLP compliant
Results:
0% degradation by O2 consumption after 28day (below detection limit
of <2.5% ThOD)
4940428
Aerobic
seawater
64 days
Dose: 51.2 mg/L
46.1%
DOC
removal
Method:
XXVIII
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table B.3:
:ate
after 64
Test substance reported as CASRN 24800-44-0
days
Purity 99.4%
33.5%
OECD Guideline 306
C02
evolution
GLP compliant
after 62
days
4946320
Sediment/water
20 days
Doses: 5 and 10 mg/L
Inherently
Biodegradable
Method:
Test substance reported as CASRN 24800-44-0
Purity not reported
OECD Guideline 301E
GLP compliant
Endpoint:
<10% after 20 days with 10 mg/L dose
100% biodegradation by day 16 with 5 mg/L
Authors suggest that oxidation products may be toxic to inoculum
and TPG is inherently biodegradable
4940429
DOC removal
using activated
sludge inoculum
6 weeks
Dose: 18.5 mg/L
DOC removal
83.6% after 6
weeks
Methods:
Test substance reported as CASRN 25265-71 -8
Purity > 99.9%
OECD Guideline 301F or OECD Guideline 302A
GLP compliant
Endpoints:
DOC removal 83.6% after 6 weeks
Biodegradation from days 10-42 of 82.5-84.7%
4940437
Toxicity to
3 hours
Doses: 10, 32, 100, 320
NOEC> 1000
Methods:
microorganisms
and 1000 mg/L
mg/L
Test substance reported as CASRN 24800-44-0
Purity: 99.9%
OECD Guideline 209
GLP compliant
Results:
EC50 >1000 mg/L (nominal)
4940441
Toxicity to
18 hours
Doses:
EC10 > 1000
Methods:
microorganisms
Range Finding: 0.1,1,100,
and 1000 mg/L
mg/L
Test substance reported as CASRN 25265-71 -8
Purity: 99.9%
GLP compliant
XXIX
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table B.3:
:ate
Main study: 1.95, 3.91,
7.81, 15.63,31.25, 62.5,
125, 250, 500, and 1000
mg/L
Environmental Fate: Modelled
Model
Data Type
Endpoint
Predicted Endpoint
Notes
EPISuite
v.4.11
Estimated
BAF
0.9
EPISuite
v.4.11
Estimated
BCF
3.16
EPISuite
v.4.11
(BIOWIN
7)
Estimated
Anaerobic
biodegradation
Not predicted to biodegrade
quickly under anaerobic
conditions
Probability of -0.0712. Fragment representation is valid.
Fast degradation is defined as predicted probability >0.5.
EPI Suite
Reference
The measured melting point
and boiling point entered
into EPI Suite were taken
from PhysProp. The
measured vapor pressure
and Log K0w were taken
from ECHA.
EPI Suite (Physical Property Inputs - BP = 271 deg C, MP = -30 deg C, VP = 0.00195 mm
Hg, WS = 1000000 mg/L, Log P = -0.38 SMILES: CC(0)COC(C)COC(C)CO
XXX
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
B.1 References
Bates. HK; Price. CJ; Marr. MC; Myers. CB; Heindel. JJ; Schwetz. BA. (1992a). Final report on the
developmental toxicity of dipropylene glycol (CAS #25265-71-8) in New Zealand white rabbits.
(NTP Study No. TER-90-14). Research Triangle Park, NC: National Toxicology Program.
Bates. HK; Price. CJ; Marr. MC; Myers. CB; Heindel. JJ; Schwetz. BA. (1992b). Final report on the
developmental toxicity of dipropylene glycol (CAS No. 25265-71-8) in Sprague-Dawley (CD
(trade name)) rats. Research Triangle Park, NC: National Toxicology Program.
BUA (GDCh Advisory Committee on Existing Chemicals). (1996). Dipropylene glycol. In GD BUA
(Ed.). Stuttgart, Germany: S. Hirzel.
EC HA (European Chemicals Agency). (1974a). [(methylethylene)bis(oxy)]dipropanol: acute toxicity:
dermal. Helsinki, Finland. https://echa.europa.eu/registration-dossier/-/registered-
dossier/14788/7/3/4
EC HA (European Chemicals Agency). (1974b). [(methylethylene)bis(oxy)]dipropanol: acute toxicity:
inhalation: 001 key | experimental result. Helsinki, Finland, https://echa.europa.eu/registration-
dossier/-/registered-dossier/14788/7/3/3/?documentUUID=b3324441-49d4-432b-b4fc-
72047a3b05d2
EC HA (European Chemicals Agency). (1974c). [(methylethylene)bis(oxy)]dipropanol: acute toxicity:
oral: 002 supporting | experimental result. Helsinki, Finland, https://echa.europa.eu/registration-
dossier/-/registered-dossier/14788/7/3/2/?documentUUID=ca7e2977-01ec-4b31-97da-
eb08a!18b3af
EC HA (European Chemicals Agency). (1974d). [(methylethylene)bis(oxy)]dipropanol: eye irritation: 003
supporting | experimental result. Helsinki, Finland, https://echa.europa.eu/registration-dossier/-
/registered-dossier/14788/7/4/3/?documentUUID=93b85621-2813-4cb3-be0f-c81034a5c6ee
EC HA (European Chemicals Agency). (1974e). [(methylethylene)bis(oxy)]dipropanol: skin
irritation/corrosion. Helsinki, Finland. https://echa.europa.eu/registration-dossier/-/registered-
dossier/14788/7/4/2
EC HA (European Chemicals Agency). (1988). Oxydipropanol: genetic toxicity: in vitro: 002 key |
experimental result. Helsinki, Finland. https://echa.europa.eu/registration-dossier/-/registered-
dossier/16016/7/7/2/?documentUUID=389098d4-4996-4c60-a762-d2b60df89dcc
EC HA (European Chemicals Agency). (1990a). Oxydipropanol: developmental toxicity/teratogencity:
002 key | experimental result. Helsinki, Finland, https://echa.europa.eu/registration-dossier/-
/registered-dossier/16016/7/9/3/?documentUUID=996f3dc0-f578-45ab-9a89-b92637f28c00
EC HA (European Chemicals Agency). (1990b). Oxydipropanol: developmental toxicity/teratogenicity:
001 key | experimental result. Helsinki, Finland, https://echa.europa.eu/registration-dossier/-
/registered-dossier/16016/7/9/3
EC HA (European Chemicals Agency). (1991a). [(methylethylene)bis(oxy)]dipropanol: biodegradation in
water: screening tests: 004 supporting | experimental result, https://echa.europa.eu/registration-
XXXI
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
dossier/-/registered-dossier/14788/5/3/2/?documentUUID=caad96d0-3b36-4255-9bd2-
0e2da25ee91e
EC HA (European Chemicals Agency). (1991b). [(methylethylene)bis(oxy)]dipropanol: biodegradation in
water: screening tests: 005 supporting | experimental result. Helsinki, Finland.
https://ccha.curopa.cu/registration-dossier/-/registered-
dossier/147SS/5/3/2/'MocumcntUUID=00fSfa90-fc45-491c-b4SS-434c429S 1995
EC HA (European Chemicals Agency). (1992a). Oxydipropanol: genetic toxicity: in vitro: 003 supporting
| experimental result. Helsinki, Finland. https://echa.europa.eu/registration-dossier/-/registered-
dossier/16016/7/7/2/?documentUUID=9d24fl2e-lbf0-4481-8ae5-e7640975e049
EC HA (European Chemicals Agency). (1992b). Oxydipropanol: toxicity to microorganisms. Helsinki,
Finland. https://echa.europa.eu/registration-dossier/-/registered-dossier/16016/6/2/8
EC HA (European Chemicals Agency). (1993a). [(methylethylene)bis(oxy)]dipropanol: acute toxicity:
oral: 001 key | experimental result. https://echa.europa.eu/registration-dossier/-/registered-
dossier/14788/7/3/2
EC HA (European Chemicals Agency). (1993b). [(methylethylene)bis(oxy)]dipropanol: biodegradation in
water: screening tests: 003 supporting | experimental result. Helsinki, Finland.
https://echa.europa.eu/registration-dossier/-/registered-
dossier/14788/5/3/2/?documentUUID=10b66ef0-9fbb-4f6e-8371-693280a318dl
EC HA (European Chemicals Agency). (1993c). [(methylethylene)bis(oxy)]dipropanol: repeated dose
toxicity: oral: 002 key | experimental result. Helsinki, Finland, https://echa.europa.eu/registration-
dossier/-/registered-dossier/14788/7/6/2/?documentUUID=814b4a8c-4620-4c5c-bf90-
b3f8622b63f6
EC HA (European Chemicals Agency). (1994a). [(methylethylene)bis(oxy)]dipropanol: short-term
toxicity to aquatic invertebrates: 001 key | experimental result, https://echa.europa.eu/registration-
dossicr/-/rcgiste red-dossier/14788/6/2/4"/'.>documentUU I D=e7896c5 7-46b4-445a-ac8b-
2c4107d544fa
ECHA (European Chemicals Agency). (1994b). [(methylethylene)bis(oxy)]dipropanol: short-term
toxicity to fish: 001 key | experimental result. Helsinki, Finland.
https://echa.europa.eu/registration-dossier/-/registered-
dossier/14788/6/2/2/?documentUUID=dd8cb796-a0f9-4d90-8fb2-57a6fe859ffa
ECHA (European Chemicals Agency). (1994c). Oxydipropanol: biodegradation in water: screening tests:
003 supporting | experimental result. Helsinki, Finland, https://echa.europa.eu/registration-
dossier/-/registered-dossier/16016/5/3/2/?documentUUID=4dl6933c-e52a-4975-8416-
9c9534d5eal9
ECHA (European Chemicals Agency). (1995a). [(methylethylene)bis(oxy)]dipropanol: basic
toxicokinetics: in vivo. Helsinki, Finland. https://echa.europa.eu/registration-dossier/-/registered-
dossier/14788/7/2/2
XXXII
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
EC HA (European Chemicals Agency). (1995b). [(methylethylene)bis(oxy)]dipropanol: exposure related
observations in humans: other data: 001 key | experimental result. Helsinki, Finland.
https://echa.europa.eu/registration-dossier/-/registered-dossier/14788/7/ll/6
EC HA (European Chemicals Agency). (1995c). Oxydipropanol: sensitisation data (human). Helsinki,
Finland. https://echa.europa.eu/registration-dossier/-/registered-dossier/16016/7/11/5
EC HA (European Chemicals Agency). (1995d). Oxydipropanol: skin sensitisation: in vivo (non-LLNA).
https://echa.europa.eu/registration-dossier/-/registered-dossier/16016/7/5/2
EC HA (European Chemicals Agency). (1997). [(methylethylene)bis(oxy)]dipropanol: exposure related
observations in humans: other data: 002 key | experimental result.
https://echa.europa.eu/registration-dossier/-/registered-
dossier/14788/7/1 l/6/?documentUUID=ca6dcade-09d9-479c-b79c-dccdc9d4493 7
EC HA (European Chemicals Agency). (1999). Oxydipropanol: genetic toxicity: in vivo.
https://echa.europa.eu/registration-dossier/-/registered-dossier/16016/7/7/3
EC HA (European Chemicals Agency). (2004a). Oxydipropanol: carcinogenicity: oral. Helsinki, Finland.
https://echa.europa.eu/registration-dossier/-/registered-
dossier/16016/7/8/? documentUUID=22067ce9-4d3f-474a-a0eb-e0466eaa8a37
EC HA (European Chemicals Agency). (2004b). Oxydipropanol: carcinogenicity: oral: 001 key |
experimental result. https://echa.europa.eu/registration-dossier/-/registered-dossier/16016/7/8
EC HA (European Chemicals Agency). (2004c). Oxydipropanol: genetic toxicity: in vitro: 001 key |
experimental result. Helsinki, Finland. https://echa.europa.eu/registration-dossier/-/registered-
dossier/16016/7/7/2/?documentUUID=74e59391-4529-4883-958e-083dla25594e
EC HA (European Chemicals Agency). (2004d). Oxydipropanol: repeated dose toxicity: oral: 001 key |
experimental result. Helsinki, Finland. https://echa.europa.eu/registration-dossier/-/registered-
dossier/16016/7/6/2
EC HA (European Chemicals Agency). (2004e). Oxydipropanol: repeated dose toxicity: oral: 002
supporting | experimental result. Helsinki, Finland, https://echa.europa.eu/registration-dossier/-
/registered-dossier/16016/7/6/2/?documentUUID=9b888e96-d05d-4451-9709-64fabae21fbc
EC HA (European Chemicals Agency). (2004f). Oxydipropanol: repeated dose toxicity: oral: 003
supporting | experimental result. https://echa.europa.eu/registration-dossier/-/registered-
dossier/16016/7/6/2/?documentUUID=9796c071 -d03 9-468a-b2f1 -0493 5 82fdc5 0
EC HA (European Chemicals Agency). (2004g). Oxydipropanol: repeated dose toxicity: oral: 004
supporting | experimental result. https://echa.europa.eu/registration-dossier/-/registered-
dossier/16016/7/6/2/?documentUUID=aeb50875-5f7d-41e6-802b-de9b618599ec
EC HA (European Chemicals Agency). (2007a). [(methylethylene)bis(oxy)]dipropanol: biodegradation in
water: screening tests: 001 key | experimental result. Helsinki, Finland.
https://echa.europa.eu/registration-dossier/-/registered-
dossier/14788/5/3/2/?documentUUID=bf8b2f2f-7880-495b-adle-7a003f2c96c7
EC HA (European Chemicals Agency). (2007b). [(methylethylene)bis(oxy)]dipropanol: dermal absorption
in vitro/ex vivo. https://echa.europa.eu/registration-dossier/-/registered-dossier/14788/7/2/3
XXXIII
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
EC HA (European Chemicals Agency). (2007c). Oxydipropanol: biodegradation in water: screening tests:
001 key | experimental result. Helsinki, Finland, https://echa.europa.eu/registration-dossier/-
/registered-dossier/16016/5/3/2
EC HA (European Chemicals Agency). (2010a). [(methylethylene)bis(oxy)]dipropanol: eye irritation: 001
key | experimental result. Helsinki, Finland, https://echa.europa.eu/registration-dossier/-
/registered-dossier/1478 8/7/4/3
EC HA (European Chemicals Agency). (2010b). [(methylethylene)bis(oxy)]dipropanol: eye irritation: 002
key | experimental result. https://echa.europa.eu/registration-dossier/-/registered-
dossier/14788/7/4/3/?documentUUID=6112967b-d401-4691-92fc-cl090a4e63c5
EC HA (European Chemicals Agency). (2010c). [(methylethylene)bis(oxy)]dipropanol: toxicity to
microorganisms: 001 key | experimental result. Helsinki, Finland.
https://echa.europa.eu/registration-dossier/-/registered-
dossier/14788/6/2/8/?documentUUID=95e7699a-lff8-4acc-a8f6-fba87bb72c52
Fasano. WJ. (2007). Dipropylene glycol: in vitro dermal absorption rate testing [TSCA Submission],
Fasano, WJ. https://chemview.epa.gov/chemview/proxv?filename=2008-l-8EHQ-08-
16930B 8eha 0108 16930b.pdf
Fasano. WJ; ten Berge. W; Banton. MI: Heneweer. M: Moore. NP. (2011). Dermal penetration of
propylene glycols: Measured absorption across human abdominal skin in vitro and comparison
with a QSAR model. Toxicol In Vitro 25: 1664-1670. http://dx.doi.Org/10.1016/i.tiv.2011.07.003
JETOC (Japan Chemical Industry Ecology-Toxicology & Information Center). (1997). Toxicity testing
results of environmental chemicals. JETOC Info Sheet No. 26 (Special Issue No. 2): 1-83.
Johansen. JD: Jemec. GBE: Rastogi. SC. (1995). Contact sensitization to dipropylene glycol in an eczema
population [Abstract]. Contact Derm 33: 211-212. http://dx.doi.org/10.1111/i.1600-
0536.1995 ,tb00560.x
Leberco Labs (Leberco Laboratories). (1994). Letter from [] to usepa submitting irritation toxicity studies
of 2-propanol, l,l'-oxybis- in the rabbit dated 03/24/94 (sanitized). (86940000234S).
NTP (National Toxicology Program). (2004). NTP technical report on the toxicology and carcinogenesis
studies of dipropylene glycol (CAS NO. 25265-71-8) in F344/N rats and B6C3F1 mice (pp. 6-
260). Research Triangle Park, NC: U.S Department of Health and Human Services. Public Health
Service. National Institutes of Health, https://ntp.niehs.nih.gov/ntp/htdocs/lt rpts/tr511 .pdf
OECD (Organisation for Economic Co-operation and Development). (1994). SIDS Initial Assessment
Report for SIAM 2 (Paris, 4-6 July 1994)Tripropylene glycol: CAS No: 24800-440.
https://hpvchemicals.oecd.org/UI/handler.axd?id=00205ec6-f694-448b-bbb2-be4121e9a7fe
OECD (Organisation for Economic Co-operation and Development). (2001). Dipropylene glycol (mixed
isomers and dominant isomer Cas No: 25265-71-8 and 110-98-5).
http://www.inchem.org/documents/sids/sids/25265-71-8.pdf
XXXIV
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Zgola-Grzeskowiak. A; Grzeskowiak. T; Zembrzuska. J; Franska. M; Franski. R; Lukaszewski. Z. (2008).
Bio-oxidation of tripropylene glycol under aerobic conditions. Biodegradation 19: 365-373.
http://dx.doi.org/10.1007/slQ532-007-9142-6
XXXV
-------
***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. Search outcomes and reference details are
provided 011 the candidate's HERO project page.
EPA created a fit-for-purpose process to transparently document the literature search and review36 of
available hazard and fate information for low-priority substance (LPS) candidates. References from peer-
reviewed primary sources, grey sources,37 and other sources were identified, screened at the title/abstract
and full-text level, and evaluated for data quality based on discipline-specific criteria. An overview of the
literature search and review process is illustrated in Figure CI.
Figure C.l: Overview of the Literature Search and Review Process
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, the following LPS
candidates were used as analogs for read-across: 1,T-dimethyldiethylene glycol and dipropylene glycol.
For more details and justification on analogs, see section 6.1.1. Analogs were used to fill data gaps on
endpoints for which tripropylene glycol lacked quality data, such as developmental toxicity, and to add to
The HERO low-priority substance candidate project pages are accessible to the public at https://hero.epa.gov/liero/.
30 Discussed in the document "Approach Document for Screening Hazard Infonnation for Low-Priority Substances Under
TSCA", also released at proposal.
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.
XXXVI
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
the weight of the scientific evidence. Analog references were searched, screened and evaluated using the
same process as references on tripropylene glycol described above.36 Tripropylene glycol and the two
analogs mentioned above fall under the glycol cluster.
C.1.2 Search Terms and Results
EPA began the literature review process for the hazard screening of tripropylene glycol 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. 1 lists the search terms used in the
database search of peer -reviewed literature for the glycol cluster including tripropylene glycol. For grey
literature and other secondary sources, Table C.2 lists the search terms used for the glycol cluster.
XXXVII
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table C.1: Search Terms Used in Peer-Reviewed Databases
Discipline
Database
Search terms
Human Health
PubMed
25265-71-8[rn] OR 110-98-5[rn] OR 24800-44-0[rn] OR "((1-methyl-1,2-ethanediyl)bis(oxy))bispropanol"[tw] OR
"((Methylethylene)bis(oxy))dipropanol"[tw] OR" 1,1'-Dimethyldiethylene glycol"[tw] OR "1,1'-Oxybis(2-propanol)"[tw] OR "1,1'-
Oxybis-2-propanol"[tw] OR "1,1'-Oxydi-2-propanol"[tw] OR "1,1'-Oxydipropan-2-ol"[tw] OR "2,2'-Dihydroxydipropyl ether"[tw]
OR "2-(2-(2-Hydroxypropoxy)propoxy)-1-propanol"[tw] OR "2-Propanol, 1,1'-oxybis-"[tw] OR "2-Propanol, 1,1'-oxydi-"[tw] OR
"4-Oxa-2,6-heptandiol"[tw] OR "4-Oxaheptane-2,6-diol"[tw] OR "ADK DPG-RF"[tw] OR "Bis(2-hydroxypropyl) ether"[tw] OR
"Bis(3-hydroxypropyl)ether"[tw] OR "Diisopropylene glycol"[tw] OR "Dipropylene glycol"[tw] OR "DIPROPYLENEGLYCOL"[tw]
OR "DIPROPYLENGLYKOL"[tw] OR "Dowanol DPG"[tw] OR "DPG-FC"[tw] OR "DPG-RF"[tw] OR "NIAX catalyst D-19"[tw]
OR "oxidipropanol"[tw] OR "Oxybispropanol"[tw] OR "Oxydipropanol"[tw] OR "Propanol, ((1-methyl-1,2-
ethanediyl)bis(oxy))bis-"[tw] OR "Propanol, oxybis-"[tw] OR "Tripropylene glycol"[tw]
Toxline
(25265-71-8[rn] OR 110-98-5[rn] OR 24800-44-0[rn] OR "((1 -methyl-1,2-ethanediyl)bis(oxy))bispropanol" OR
"((Methylethylene)bis(oxy))dipropanol" OR "1,1 '-Dimethyldiethylene glycol" OR "1,1'-Oxybis(2-propanol)" OR "1,1 '-Oxybis-2-
propanol" OR "1,1 '-Oxydi-2-propanol" OR "1,1'-Oxydipropan-2-ol" OR "2,2'-Dihydroxydipropyl ether" OR "2-(2-(2-
Hydroxypropoxy)propoxy)-1-propanol" OR "2-Propanol, 1,1'-oxybis-" OR "2-Propanol, 1,1 -oxydi-" OR "4-Oxa-2,6-heptandiol"
OR "4-Oxaheptane-2,6-diol" OR "ADK DPG-RF" OR "Bis(2-hydroxypropyl) ether" OR "Bis(3-hydroxypropyl)ether" OR
"Diisopropylene glycol" OR "Dipropylene glycol" OR "DIPROPYLENEGLYCOL" OR "DIPROPYLENGLYKOL" OR "Dowanol
DPG" OR "DPG-FC" OR "DPG-RF" OR "NIAX catalyst D-19" OR "oxidipropanol" OR "Oxybispropanol" OR "Oxydipropanol"
OR "Propanol, ((1 -methyl-1,2-ethanediyl)bis(oxy))bis-" OR "Propanol, oxybis-" OR "Tripropylene glycol") AND (ANEUPL [org]
OR BIOSIS [org] OR CIS [org] OR DART [org] OR EMIC [org] OR EPIDEM [org] OR FEDRIP [org] OR HEEP [org] OR HMTC
[org] OR IPA [org] OR RISKLINE [org] OR MTGABS [org] OR NIOSH [org] OR NTIS [org] OR PESTAB [org] OR PPBIB [org]
) AND NOT PubMed [org] AND NOT pubdart [org]
TSCATS1
(25265-71-8 [rn] OR 110-98-5 [rn] OR 24800-44-0 [rn]) AND (TSCATS [org]) AND NOT PubMed [org] AND NOT pubdart
[org]
WOS
TS=("25265-71-8" OR "110-98-5" OR "24800-44-0" OR "((1-methyl-1,2-ethanediyl)bis(oxy))bispropanol" OR
"((Methylethylene)bis(oxy))dipropanol" OR "1,1 '-Dimethyldiethylene glycol" OR "1,1'-Oxybis(2-propanol)" OR "1,1 '-Oxybis-2-
propanol" OR "1,1 '-Oxydi-2-propanol" OR "1,1 '-Oxydipropan-2-ol" OR "2,2'-Dihydroxydipropyl ether" OR "2-(2-(2-
Hydroxypropoxy)propoxy)-1-propanol" OR "2-Propanol, 1,1'-oxybis-" OR "2-Propanol, 1,1-oxydi-" OR "4-Oxa-2,6-heptandiol"
OR "4-Oxaheptane-2,6-diol" OR "ADK DPG-RF" OR "Bis(2-hydroxypropyl) ether" OR "Bis(3-hydroxypropyl)ether" OR
"Diisopropylene glycol" OR "Dipropylene glycol" OR "DIPROPYLENEGLYCOL" OR "DIPROPYLENGLYKOL" OR "Dowanol
DPG" OR "DPG-FC" OR "DPG-RF" OR "NIAX catalyst D-19" OR "oxidipropanol" OR "Oxybispropanol" OR "Oxydipropanol"
OR "Propanol, ((1 -methyl-1,2-ethanediyl)bis(oxy))bis-" OR "Propanol, oxybis-" OR "Tripropylene glycol")
lndexes=SCI-EXPANDED, CPCI-S, CPCI-SSH, BKCI-S, BKCI-SSH, CCR-EXPANDED, IC Timespan=AII years
WOS
Same as human health strategy synonyms only; no other restrictions
XXXVIII
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table C.1: Search Terms Used in Peer-Reviewed Databases
Environmental
Hazard
Toxline
Same as human health strategy synonyms only; no other restrictions
TSCATS1
Same as human health strategy CASRN only; no other restrictions
Proquest
Agricola
TITLE=("25265-71-8" OR "1,1'-Oxybis 2-propanol" OR "1,1 '-Oxybis-2-propanol" OR "1,1 '-Oxydi-2-propanol" OR "1,1'-
Oxydipropan-2-ol" OR "2-Propanol, 1,1-oxybis-" OR "Bis 2-hydroxypropyl ether" OR "Dipropylene glycol" OR
"DIPROPYLENEGLYCOL" OR "Propanol, oxybis-" OR "Tripropylene glycol")
ABSTRACT=("25265-71 -8" OR "1,1'-Oxybis 2-propanol" OR "1,1 '-Oxybis-2-propanol" OR "1,1 '-Oxydi-2-propanol" OR "1,1'-
Oxydipropan-2-ol" OR "2-Propanol, 1,1-oxybis-" OR "Bis 2-hydroxypropyl ether" OR "Dipropylene glycol" OR
"DIPROPYLENEGLYCOL" OR "Propanol, oxybis-" OR "Tripropylene glycol")
SUBJECT=("25265-71 -8" OR "1,1'-Oxybis 2-propanol" OR "1,1 '-Oxybis-2-propanol" OR "1,1 '-Oxydi-2-propanol" OR "1,1'-
Oxydipropan-2-ol" OR "2-Propanol, 1,1'-oxybis-" OR "Bis 2-hydroxypropyl ether" OR "Dipropylene glycol" OR
"DIPROPYLENEGLYCOL" OR "Propanol, oxybis-" OR "Tripropylene glycol")
("110-98-5" OR "24800-44-0" OR" 1 -methyl-1,2-ethanediyl bis oxy bispropanol" OR "Methylethylene bis oxy dipropanol" OR
"1,1 '-Dimethyldiethylene glycol" OR "2,2-Dihydroxydipropyl ether" OR "2- 2- 2-Hydroxypropoxy propoxy -1-propanol" OR "2-
Propanol, 1,1 -oxydi-" OR "4-Oxa-2,6-heptandiol" OR "4-Oxaheptane-2,6-diol" OR "ADK DPG-RF" OR "Bis 3-hydroxypropyl
ether" OR "Diisopropylene glycol" OR "DIPROPYLENGLYKOL" OR "Dowanol DPG" OR "DPG-FC" OR "DPG-RF" OR "NIAX
catalyst D-19" OR "oxidipropanol" OR "Oxybispropanol" OR "Oxydipropanol" OR "Propanol, 1 -methyl-1,2-ethanediyl bis oxy
bis-")
Fate
WOS
Same as human health strategy synonyms only; no other restrictions
Table C.2: Search Terms Used in Grey Literature and Additional Sources
Chemical
Search terms
Glycol cluster
(1,1'-
Dimethyldiethylene
glycol; dipropylene
glycol, tripropylene
glycol)
Searched as a string or individually depending on resource: "25265-71-8" OR "110-98-5" OR "24800-44-0"
OR "Dipropylene glycol" OR "Dipropyleneglycol" OR "Propanol, oxybis-" OR "Tripropylene glycol"
After the search terms were applied, more than 620 references were returned by all search efforts across peer-reviewed databases and grey
literature sources. The total number of references include database results, additional strategies, and analog searches. All references from the
search efforts were screened and evaluated through the LPS literature search and review process.36 Of these, 71 references were included for data
XXXIX
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
evaluation and used to support the designation of tripropylene glycol 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. The excluded references are organized by discipline (human health hazard, environmental hazard, and fate), presented along with a
rationale based on exclusion criteria. The criteria36 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, EPA excluded a total of 539 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.3), or full-text
screening (see Table C.4). Unacceptable references (e.g., studies that did not meet data quality metrics) were excluded at full-text screening (see
Tables C.5 and C.6). Off-topic and unacceptable references are displayed next to the corresponding exclusion criteria.
Table C.3: Off-topic references excluded at Title/Abstract Screening for human health hazard
Reference excluded (HERO ID) because the reference did NOT contain information needs38 relevant to human health hazard
33975
4949055
4948960
4947155
4705492
1201178
4949084
4948984
4948886
4946188
44187
4949056
4948961
4947156
4706833
1204953
4949085
4948985
4948887
4946189
404898
4949058
4948962
4947159
4738360
1249186
4949086
4948986
4948890
4946190
628230
4949060
4948963
4947160
4738993
1254062
4949087
4948988
4948891
4946193
628727
4949061
4948964
4947161
4742957
1314113
4949089
4948989
4948892
4946194
635083
4949063
4948965
4947175
4828940
1316100
4949090
4948990
4948893
4946210
744085
4949064
4948966
4947177
4828943
1321888
4949092
4948991
4948894
4946247
789593
4949065
4948967
4947178
4847997
1458307
4949094
4948992
4948895
4946257
789651
4949066
4948968
4947179
4853443
1496934
4949095
4948993
4948896
4946258
38 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.
XL
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table C.3: Off-topic references excluded at Title/Abstract Screening for human health hazard
926985
4949067
4948969
4947182
4909646
1549118
4949096
4948994
4948898
4946259
992939
4949068
4948970
4947185
4940595
1580047
4949098
4948995
4948899
4946263
1058389
4949070
4948971
4947187
4940694
1611582
4949099
4948996
4948900
4946320
1058433
4949071
4948972
4947189
4940855
1612753
4949100
4948997
4948902
4946322
1112905
4949072
4948974
4947194
4941419
1615034
4949102
4948998
4948904
4946324
1124442
4949074
4948975
4947200
4945941
1689217
4949103
4948999
4948905
4946329
1124901
4949075
4948977
4947201
4946008
1763085
4949104
4949000
4948906
4946359
1142139
4949076
4948978
4947202
4946061
1763087
4949105
4949001
4948909
4946360
1153582
4949078
4948979
4947203
4946132
1763125
4949106
4949002
4948911
4946361
1156301
4949080
4948980
4947204
4946147
1763137
4949108
4949003
4948912
4946374
1167387
4949081
4948981
4947223
4946178
1763157
4949109
4949004
4948913
4946375
1201159
4949082
4948982
4947224
4946179
1781960
4949110
4949005
4948914
4946376
1201176
4949083
4948983
4948885
4946180
1808388
4949111
4949006
4948915
4946380
3036899
4949156
4949040
4948950
4947131
1808755
4949112
4949007
4948916
4946387
3037885
4949157
4949042
4948951
4947132
1865871
4949113
4949009
4948918
4946408
3038973
4949158
4949044
4948952
4947135
1955931
4949116
4949010
4948919
4946410
3039406
4949159
4949045
4948953
4947136
1967450
4949117
4949011
4948920
4946411
3039791
4951048
4949046
4948954
4947137
1970619
4949118
4949012
4948921
4946419
3041527
4951050
4949047
4948955
4947138
2231679
4949119
4949013
4948922
4946423
3041622
4951055
4949049
4948956
4947140
2232056
4949120
4949015
4948923
4946506
3041638
4951170
4949051
4948958
4947141
2232422
4949121
4949016
4948925
4946513
3041935
4951176
4949052
4948959
4947154
2232425
4949122
4949017
4948926
4946538
3047394
4951181
4949053
4339757
4576534
2232427
4949123
4949018
4948927
4946547
3051635
4951206
4949054
4376725
4579583
2232444
4949126
4949020
4948928
4946614
XLI
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table C.3: Off-topic references excluded at Title/Abstract Screening for human health hazard
3051709
4951208
3753956
4388064
4583202
2232562
4949128
4949021
4948930
4946615
3103598
4951228
3823035
4391261
4656492
2273142
4949129
4949022
4948931
4946617
3114932
4428638
3830342
4395587
4660346
2292715
4949130
4949023
4948932
4946619
3115961
4428838
3830898
4398518
4704876
2302957
4949131
4949024
4948933
4946620
3119596
4433785
3846566
4399866
3577212
2530089
4949132
4949026
4948934
4946621
3225794
4436364
3847436
4400649
3577235
2563138
4949134
4949027
4948935
4946623
3374286
4436864
3874693
4404349
3590105
2692340
4949135
4949028
4948936
4947105
3402924
4438060
4146480
4408404
3619406
2745927
4949138
4949029
4948938
4947106
3445046
4438415
4148076
4420372
3625221
2824290
4949140
4949030
4948940
4947107
3476490
4425601
4148079
4420932
4275583
2875983
4949141
4949031
4948942
4947108
3477473
4426820
4168926
4420947
4276472
2883990
4949142
4949032
4948943
4947109
3491334
3559324
4173202
4421954
4423539
2887419
4949149
4949033
4948944
4947110
3539276
3562800
4222683
4948949
4947130
2892020
4949150
4949034
4948946
4947111
3009070
4949153
4949037
4948948
4947115
2978028
4949152
4949035
4948947
4947113
3036268
4949154
4949039
Reference excluded (HERO ID) because the reference primarily contained in silico data
N/A.
Table C.4: 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
1322754
to a low- priority substance candidate?
1629162
1776453
1875316
2301122
2301139
3041082
XLII
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table C.4: 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)
4219489
4862648
4940454
4941418
4946053
4947114
4951209
61412
824457
1744616
1744618
3039593
4441664
4442235
4862648
4940287
4940288
4940320
4940383
4940385
4940387
4940395
4940392
4946053
4948456
4949088
4951173
4951178
What type of source is this reference?
Review article or book chapter that contains only
1004739
citations to primary literature sources
3038211
4940386
4946377
628176
3036785
XLIII
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table C.4: 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)
What kind of evidence does this reference
primarily contain?
In silico studies that DO NOT contain experimental
verification
N/A.
The following question apply to HUMAN evidence only
Does the reference report an exposure route that
is or is presumed to be by an inhalation, oral, or
dermal route?
No
N/A.
Does the reference report both test substance
exposure(s) AND related health outcome(s)?
No
N/A.
If the reference reports an exposure to a chemical
mixture, are measures of the test substance or
related metabolite(s) reported independently of
other chemicals?
Note: If the paper does not pertain to mixtures,
choose "Not Applicable".
No
4951213
The following question apply to ANIMAL evidence only
Does the reference report an exposure route that
is by inhalation, oral, or dermal route?
No
N/A.
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
N/A.
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
4951261
4951218
4951185
1230541
Does the paper report a negative control that is a
vehicle control or no treatment control?
No39
4951261
The following questions apply to MECHANISTIC/ALTERNATIVE TEST METHODS evidence only
39 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).
XLIV
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table C.4: 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 a negative control that is
a vehicle control or no treatment control?
No
3036587
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
3036587
Table C.5: 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.
N/A.
Metric 2:
Negative and vehicle controls
A concurrent negative control group was not
included or reported.
OR
The reported negative control group was not
appropriate (e.g., age/weight of animals differed
between control and treated groups).
N/A.
Metric 3:
Positive controls
When applicable, an appropriate concurrent positive
control (i.e., inducing a positive response) was not
used.
N/A.
Metric 4:
Reporting of doses/concentrations
Doses/concentrations were not reported and could
not be calculated using default or reported
estimates of body weight and diet/water intake (e.g.,
1763148
3041958
4940388
4940524
XLV
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table C.5: 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)
default intake values are not available for pregnant
animals).
4940510
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).
4940388
4940389
4941420
4946133
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).
4941420
1763148
4940389
4940388
3041958
4946133
Metric 7:
Number of animals per group
The number of animals per study group was not
reported.
OR
The number of animals per study group was
insufficient to characterize toxicological effects (e.g.,
1-2 animals in each group).
N/A.
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.).
1763148
2282271
4940388
4940389
4941420
4946133
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
4940388
4940524
4941420
2282271
4442235
XLVI
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table C.5: 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)
results.
4940303
4940394
4946044
4940452
Table C.6: 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.
3039551
Metric 2:
Negative controls
A concurrent negative control group was not
included or reported.
OR
The reported negative control group was not
appropriate (e.g., different cell lines used for
controls and test substance exposure).
N/A.
Metric 3:
Positive controls
A concurrent positive control or proficiency group
was not used.
N/A.
Metric 4:
Assay type
The assay type was not reported.
OR
The assay type was not appropriate for the study
type or outcome of interest (e.g., in vitro skin
corrosion protocol used for in vitro skin irritation
assay).
N/A.
Metric 5:
Reporting of concentration
The exposure doses/concentrations or amounts of
test substance were not reported.
N/A.
Metric 6:
No information on exposure duration(s) was
4940521
XLVII
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table C.6: 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)
Exposure duration
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).
4940522
4940389
2282271
Metric 7:
Metabolic activation
No information on the characterization and use of a
metabolic activation system was reported.
OR
The exposure duration was not appropriate
for the study type and/or outcome of interest
(e.g., 24 hours exposure for bacterial reverse
mutation test).
N/A.
Metric 8:
Test model
The test model was not reported
OR
The test model was not routinely used for
evaluation of the specific outcome of interest.
N/A.
Metric 9:
Outcome assessment methodology
The outcome assessment methodology was not
reported.
OR
The assessment methodology was not appropriate
for the outcome(s) of interest (e.g., cells were
evaluated for chromosomal aberrations immediately
after exposure to the test substance instead of after
post-exposure incubation period).
4940451
4940388
C.2.2 Environmental Hazard
For the screening review of LPS candidate tripropylene glycol, EPA excluded a total of 547 references when assessing environmental hazard. Off-
topic environmental hazard references excluded at title/abstract screening are listed in Table C.7, and those excluded at full-text screening are
listed in Table C.8. References in Table C.9 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.
XLVIII
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table C.7: Off-Topic References Excluded at Title/Abstract Screening for Environmental Hazard
Reference excluded (HERO ID) because the reference did NOT contain information needs40 relevant to environmental hazard
44187
4440871
4949112
4948988
4946374
2892020
4738993
1744618
4949052
4948891
404898
4441664
4949113
4948989
4946375
2978028
4742957
1763125
4949053
4948892
635083
4442235
4949116
4948990
4946376
3009070
4828940
1763137
4949054
4948893
744085
4940392
4949117
4948991
4946377
3036268
4828943
1763148
4949055
4948894
789593
4940395
4949118
4948992
4946380
3036587
4847997
1763157
4949056
4948895
789651
4941420
4949119
4948993
4946387
3036785
4853443
1776453
4949058
4948896
824457
4944882
4949120
4948994
4946408
3036899
4862648
1808755
4949060
4948898
926985
4946008
4949121
4948995
4946419
3037885
4909646
2112816
4949061
4948899
1058389
4946016
4949122
4948996
4946513
3038211
4940595
2301122
4949063
4948900
1058433
4946044
4949123
4948997
4946538
3038973
4940694
2301139
4949064
4948902
1112905
4946053
4949126
4948998
4946547
3039406
4940855
2745927
4949065
4948904
1124442
4946054
4949128
4948999
4946614
3039551
4941418
3041082
4949066
4948905
1124901
4946055
4949129
4949001
4946615
3039791
4941419
3041527
4949067
4948906
1142139
4946135
4949130
4949002
4946617
3041935
4945941
3041622
4949068
4948909
1153582
4946142
4949132
4949003
4946619
3114932
4946061
3041638
4949070
4948911
1156301
4946194
4949134
4949004
4946620
3115961
4946132
3103598
4949071
4948912
1167387
4946244
4949135
4949005
4946623
3225794
4946133
3118622
4949072
4948913
1201159
4946247
4949138
4949006
4947105
3374286
4946147
4222683
4949074
4948914
1201176
4946261
4949140
4949007
4947107
3402924
4946178
4259576
4949075
4948915
1201178
4946314
4949141
4949009
4947108
3445046
4946179
4440869
4949076
4948916
1204953
4946316
4949142
4949010
4947109
3476490
4946180
4948954
4949078
4948918
1249186
4946333
4949149
4949011
4947110
3477473
4946188
4948955
4949080
4948919
1321888
4946334
4949150
4949012
4947111
3491334
4946189
4948956
4949081
4948920
1458307
4946361
4949152
4949013
4947113
3539276
4946190
4948958
4949082
4948921
1496934
4946362
4949153
4949015
4947114
3559324
4946191
4948959
4949083
4948922
40 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.
XLIX
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
1549118
4946363
4949154
4949016
4947115
3562800
4946193
4948960
4949084
4948923
1611582
4946410
4949156
4949017
4947130
3577212
4946210
4948961
4949085
4948925
1612753
4946411
4949157
4949018
4947131
3577235
4946257
4948962
4949086
4948926
1615034
4946412
4949158
4949020
4947132
3590105
4946258
4948963
4949087
4948927
1689217
4946414
4949159
4949021
4947135
3619406
4946259
4948964
4949088
4948928
1781960
4946416
4951181
4949022
4947136
3625221
4946263
4948965
4949089
4948930
1808388
4946420
1763085
4949023
4947137
3753956
4946322
4948966
4949090
4948931
1865871
4946423
1763087
4949024
4947138
3830342
4946324
4948967
4949092
4948932
1875316
4946424
4946320
4949026
4947140
3830898
4946329
4948968
4949094
4948933
1955931
4946506
4949131
4949027
4947141
3846566
4946359
4948969
4949095
4948934
1967450
4946511
992939
4949028
4947155
3847436
4946360
4948970
4949096
4948935
1970619
4946541
3051635
4949029
4947156
3874693
4420932
4948971
4949098
4948936
2231679
4946621
3051709
4949030
4947159
4088550
4420947
4948972
4949099
4948938
2232056
4947224
4951048
4949031
4947160
4146480
4421954
4948974
4949100
4948940
2232422
4948456
2282271
4949032
4947161
4148076
4423539
4948975
4949102
4948942
2232425
4949000
33975
4949033
4947175
4148079
4425601
4948977
4949103
4948943
2232427
4951050
61412
4949034
4947177
4168926
4426820
4948978
4949104
4948944
2232444
4951055
628176
4949035
4947182
4173202
4428638
4948979
4949105
4948946
2232562
4951170
628230
4949037
4947185
4275583
4428838
4948980
4949106
4948947
2273142
4951173
628727
4949039
4947189
4276472
4433785
4948981
4949108
4948948
2292715
4951176
1004739
4949040
4947201
4339757
4436364
4948982
4949109
4948949
2302957
4951185
1230541
4949042
4947202
4376725
4436864
4948983
4949110
4948950
2563138
4951207
1254062
4949044
4947203
4388064
4438060
4948984
4949111
4948951
2692340
4951209
1314113
4949045
4947204
4391261
4438415
4948985
4579583
4948952
2824290
4951213
1316100
4949046
4948885
4395587
4576534
4948986
4583202
4948953
2875983
4951218
1322754
4949047
4948886
4398518
4404349
4705492
4660346
4420372
2883990
4951261
1580047
4949049
4948887
4399866
4408404
4706833
4704876
4400649
2887419
4738360
1629162
4949051
4948890
Reference excluded (HERO ID) because the reference c
id NOT presenl
quantitative environmental hazard data
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
N/A.
Table C.8: 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
to a low- priority substance candidate?
No
1580138
4731313
4851358
4951178
1744616
4940286
4951206
4951228
4940436
4947106
4951208
What type of source is this reference?
Review article or book chapter that contains only
citations to primary literature sources
4219489
Is quantitative environmental hazard data
presented?
No
N/A.
Is this primarily a modeling/simulation study?
[Note: select "No" if experimental verification was
included in the study]
Yes
N/A.
Is environmental hazard data presented for
standard or non-standard aquatic or terrestrial
species (fish, invertebrates, microorganisms, non-
mammalian terrestrial species)?
No
N/A.
Is exposure measured for the target substance or
is the test substance a mixture (except for
reasonable impurities, byproducts, and aqueous
solutions) or formulated product?
Mixture
N/A.
Formulated Product
N/A.
Does the reference report a duration of exposure?
No
N/A.
Does the reference report a negative control that is
a vehicle control or no treatment control?
No
7504
4940435
4940366
4940397
LI
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table C.8: 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 include endpoints in the
information needs?
No
N/A.
Table C.9: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Environmental Hazard
Question
Unacceptable if:
References excluded (HERO ID)
Metric 1:
Test Substance Identity
The test substance identity or description cannot
be determined from the information provided
(e.g., nomenclature was unclear, CASRN or
structure were not reported, substance name/
description does not match CASRN).
OR
For mixtures, the components and ratios were not
characterized or did not include information that
could result in a reasonable approximation of
components.
N/A.
Metric 2:
Negative Controls
A concurrent negative control group was not
included or reported.
4951174
4951208
Metric 3:
Experimental System
The experimental system (e.g., static, semi-static,
or flow-through regime) was not described.
4940436
4940440
4951174
4940388
3041958
Metric 4:
Reporting of Concentrations
Test concentrations were not reported.
4951174
4951208
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).
4951208
4951174
Metric 6:
Test Organism Characteristics
The test species was not reported.
OR
N/A.
Lll
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
The test species, life stage, or age was not
appropriate for the outcome(s) of interest.
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.
4940388
3041958
C.2.3 Fate
For the screening review of LPS candidate tripropylene glycol, EPA excluded a total of 453 references when assessing environmental fate. Off-
topic fate references excluded at title/abstract screening are listed in Table C. 10, and those excluded at full-text screening are listed in Table C. 11.
References in Table C.12 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.10: Off-Topic References Excluded at Initial Screening for Fate
Reference excluded (HERO ID'
) because the reference did NOT contain information needs41 relevant to environmental fate
44187
4949033
4948959
4946621
4146480
2232444
4949089
4949005
4948895
4847997
404898
4949034
4948960
4946623
4148076
2232562
4949090
4949006
4948896
4853443
635083
4949035
4948961
4947105
4148079
2273142
4949092
4949007
4948898
4862648
744085
4949037
4948962
4947107
4168926
2292715
4949094
4949009
4948899
4909646
789593
4949039
4948963
4947108
4173202
2302957
4949095
4949010
4948900
4940595
789651
4949040
4948964
4947109
4275583
2563138
4949096
4949011
4948902
4940694
824457
4949042
4948965
4947110
4276472
2692340
4949098
4949012
4948904
4940855
926985
4949044
4948966
4947111
4339757
2824290
4949099
4949013
4948905
4941418
992939
4949045
4948967
4947113
4376725
2875983
4949100
4949015
4948906
4941419
1058389
4949046
4948968
4947114
4388064
2883990
4949102
4949016
4948909
4941420
1058433
4949047
4948969
4947115
4391261
2887419
4949103
4949017
4948911
4945941
1112905
4949049
4948970
4947130
4395587
2892020
4949104
4949018
4948912
4946061
1124442
4949051
4948971
4947131
4398518
2978028
4949105
4949020
4948913
4946132
41 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.
LIN
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table C.10: Off-Topic References Excluded at Initial Screening for Fate
1124901
4949052
4948972
4947132
4399866
3009070
4949106
4949021
4948914
4946133
1142139
4949053
4948974
4947135
4400649
3036268
4949108
4949022
4948915
4946147
1153582
4949054
4948975
4947136
4404349
3036587
4949109
4949023
4948916
4946178
1156301
4949055
4948977
4947137
4408404
3036785
4949110
4949024
4948918
4946179
1167387
4949056
4948978
4947138
4420372
3036899
4949111
4949026
4948919
4946180
1201159
4949058
4948979
4947140
4420932
3037885
4949112
4949027
4948920
4946188
1201176
4949060
4948980
4947141
4420947
3038211
4949113
4949028
4948921
4946189
1201178
4949061
4948981
4947155
4421954
3038973
4949116
4949029
4948922
4946190
1204953
4949063
4948982
4947156
4423539
3039406
4949117
4949030
4948923
4946191
1249186
4949064
4948983
4947159
4425601
3039551
4949118
4949031
4948925
4946193
1321888
4949065
4948984
4947160
4426820
3039791
4949119
4949032
4948926
4946194
1458307
4949066
4948985
4947161
4428638
3041935
4949120
4946380
4948927
4946210
1496934
4949067
4948986
4947175
4428838
3114932
4949121
4946387
4948928
4946247
1549118
4949068
4948988
4947177
4433785
3115961
4949122
4946408
4948930
4946257
1611582
4949070
4948989
4947182
4436364
3225794
4949123
4946410
4948931
4946258
1612753
4949071
4948990
4947185
4436864
3374286
4949126
4946419
4948932
4946259
1615034
4949072
4948991
4947189
4438060
3402924
4949128
4946506
4948933
4946263
1689217
4949074
4948992
4947201
4438415
3445046
4949129
4946513
4948934
4946322
1781960
4949075
4948993
4947202
4576534
3476490
4949130
4946538
4948935
4946324
1808388
4949076
4948994
4947203
4579583
3477473
4949132
4946547
4948936
4946329
1865871
4949078
4948995
4947204
4583202
3491334
4949134
4946614
4948938
4946359
1875316
4949080
4948996
4947224
4660346
3539276
4949135
4946615
4948940
4946360
1955931
4949081
4948997
4948885
4704876
3559324
4949138
4946617
4948942
4946361
1967450
4949082
4948998
4948886
4705492
3562800
4949140
4946619
4948943
4946374
1970619
4949083
4948999
4948887
4706833
3577212
4949141
4946620
4948944
4946375
2231679
4949084
4949000
4948890
4738360
3577235
4949142
4948952
4948946
4946376
2232056
4949085
4949001
4948891
4738993
3590105
4949149
4948953
4948947
4946377
2232422
4949086
4949002
4948892
4742957
3619406
4949150
4948954
4948948
4949157
2232425
4949087
4949003
4948893
4828940
3625221
4949152
4948955
4948949
4949158
2232427
4949088
4949004
4948894
4828943
3753956
4949153
4948956
4948950
4949159
3830898
4949156
3847436
3874693
4088550
3830342
4949154
4948958
4948951
4951181
3846566
Reference excluded (HERO ID) because the reference did NOT present quantitative environmental fate data
N/A.
LIV
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table C.11: 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
4940397
4940399
4949131
1763087
4940401
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.12: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Fate
Data quality metric
Unacceptable if:
References excluded (HERO ID)
Metric 1:
Test substance identity
The test substance identity or description cannot be
determined from the information provided (e.g.,
nomenclature was unclear and CASRN or structure
were not reported).
OR
For mixtures, the components and ratios were not
characterized or did not include information that
could result in a reasonable approximation of
components.
N/A.
Metric 2:
Study controls
The study did not include or report crucial control
groups that consequently made the study unusable
(e.g., no positive control for a biodegradation study
reporting 0% removal).
OR
The vehicle used in the study was likely to unduly
influence the study results.
4940366
4940402
4940404
Metric 3:
Test substance stability
There were problems with test substance stability,
homogeneity, or preparation that had an impact on
4940404
4940430
LV
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table C.12: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Fate
Data quality metric
Unacceptable if:
References excluded (HERO ID)
concentration or dose estimates and interfered with
interpretation of study results.
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.
4940402
4940404
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).
4940366
4940402
4940404
Metric 6:
System type and design- partitioning
Equilibrium was not established or reported,
preventing meaningful interpretation of study
results.
OR
The system type and design (e.g. static, semi-static,
and flow-through; sealed, open) were not capable of
appropriately maintaining substance concentrations,
preventing meaningful interpretation of study
results.
N/A.
Metric 7: Test organism-degradation
The test organism, species, or inoculum source
were not reported, preventing meaningful
interpretation of the study results.
4940402
4940430
Metric 8:
Test organism-partitioning
The test organism information was not reported.
OR
N/A.
LVI
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table C.12: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Fate
Data quality metric
Unacceptable if:
References excluded (HERO ID)
The test organism is not routinely used and would
likely prevent meaningful interpretation of the study
results.
Metric 9:
Outcome assessment methodology
The assessment methodology did not address or
report the outcome(s) of interest.
1763085
4940402
4940404
4940388
4940389
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.
4940402
4940404
4940430
Metric 12:
Verification or plausibility of results
Reported value was completely inconsistent with
reference substance data, related physical chemical
properties, or otherwise implausible, suggesting that
a serious study deficiency exists (identified or not).
1763085
4940366
4940402
4940404
LVII
-------
***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.42
For tripropylene glycol, 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 based on Public Comment
Source
HERO ID
Notes
The Dow Chemical Company. (2016) Product Safety
Assessment: Tripropylene Glycol
NA
EPA captured this information from other
sources in Section 3: Physical-Chemical
Properties.
Fiume, Monice M. etal. (2012). Safety Assessment of
Propylene Glycol, Tripropylene Glycol, and PPGs as Used
in Cosmetics. International Journal of Toxicology, 31
(Supplement 2),
3036587
This review article was part of EPA's literature
review process but was excluded due to a lack of
sufficient details needed to evaluate the studies
cited.
Fowles, J. R., Banton, M. I., & Pottenger, L. H. (2013). A
toxicological review of propylene glycols. Critical reviews in
toxicology, 43(4), 363-390.
3038211
This is a review article that contains citations to
other literature sources, which EPA consulted.
West, R., Banton, M., Hu, J., & Klapacz, J. (2014). The
Distribution, Fate, and Effects of Propylene Glycol
Substances in the Environment. Reviews of Environmental
Contamination and Toxicology Volume 232. Springer,
Cham, 2014. 107-138.
2537482
This is a review article that contains citations to
other literature sources, which EPA consulted.
EU REACH and ECHA datasets
NA
EPA reviewed and included information in
Section 4: Relevant Assessment History.
Environment Canada
NA
EPA reviewed and included information in
Section 4: Relevant Assessment History.
OECD SIDS Initial Assessment
NA
EPA reviewed and included information in
Section 4: Relevant Assessment History.
EPA's Safer Chemical Ingredients List
NA
EPA reviewed and included information in
Section 4: Relevant Assessment History.
42 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 fhttpsV/www.federalregister. gov/documents/2019/03/21/2019-05404/initiation-of-
prioritization-under-the-toxic-substances-control-act-tsca'l. Individual dockets were established for each of the 20 low-priority
candidates. Docket number EPA-HQ-OPPT-2019-0122 addresses tripropylene glycol.
58
------- |