U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2014

SCREENING-LEVEL HAZARD CHARACTERIZATION

Propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-hydroxy-2,2-dimethylpropyl

ester

(CASRN 1115-20-4)

The High Production Volume (HPV) Challenge Program 1 was conceived as a voluntary
initiative aimed at developing and making publicly available screening-level health and
environmental effects information on chemicals manufactured in or imported into the United
States in quantities greater than one million pounds per year. In the Challenge Program,
producers and importers of HPV chemicals voluntarily sponsored chemicals; sponsorship
entailed the identification and initial assessment of the adequacy of existing toxicity
data/information, conducting new testing if adequate data did not exist, and making both new
and existing data and information available to the public. Each complete data submission
contains data on 18 internationally agreed to "SIDS" (Screening Information Data Setl1'2)
endpoints that are screening-level indicators of potential hazards (toxicity) for humans or the
environment.

The Environmental Protection Agency's Office of Pollution Prevention and Toxics (OPPT) is
evaluating the data submitted in the HPV Challenge Program on approximately 1400 sponsored
chemicals by developing hazard characterizations (HCs). These HCs consist of an evaluation of
the quality and completeness of the data set provided in the Challenge Program submissions.

They are not intended to be definitive statements regarding the possibility of unreasonable risk of
injury to health or the environment.

The evaluation is performed according to established EPA guidance2'3 and is based primarily on
hazard data provided by sponsors; however, in preparing the hazard characterization, EPA
considered its own comments and public comments on the original submission as well as the
sponsor's responses to comments and revisions made to the submission. In order to determine
whether any new hazard information was developed since the time of the HPV submission, a
search of the following databases was made from one year prior to the date of the HPV
Challenge submission to the present: (ChemID to locate available data sources including
Medline/PubMed, Toxline, HSDB, IRIS, NTP, AT SDR, IARC, EXTOXNET, EPA SRS, etc.),
STN/CAS online databases (Registry file for locators, ChemAbs for toxicology data, RTECS,
Merck, etc.), Science Direct and ECHA4. OPPT's focus on these specific sources is based on
their being of high quality, highly relevant to hazard characterization, and publicly available.

OPPT does not develop HCs for those HPV chemicals which have already been assessed
internationally through the HPV program of the Organization for Economic Cooperation and
Development (OECD) and for which Screening Initial Data Set (SIDS) Initial Assessment

1	U.S. EPA. High Production Volume (HPV) Challenge Program; http://www.epa.gov/chemrtk/index.htm.

2	U.S. EPA. HPV Challenge Program - Information Sources; http://www.epa.gov/chemrtk/pubs/general/guidocs.htm.

3	U.S. EPA. Risk Assessment Guidelines; http://cfpub.epa.gov/ncea/raf/rafguid.cfm.

4	European Chemicals Agency, http://echa.europa.eu.


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U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2014

Reports (SIAR) and SIDS Initial Assessment Profiles (SIAP) are available. These documents are
presented in an international forum that involves review and endorsement by governmental
authorities around the world. OPPT is an active participant in these meetings and accepts these
documents as reliable screening-level hazard assessments.

These hazard characterizations are technical documents intended to inform subsequent decisions
and actions by OPPT. Accordingly, the documents are not written with the goal of informing the
general public. However, they do provide a vehicle for public access to a concise assessment of
the raw technical data on HPV chemicals and provide information previously not readily
available to the public.

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Chemical Abstract Service

Registry Number
	(CASRN)	

1115-20-4

Chemical Abstract Index
Name

Propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-hydroxy-2,2-
dimethylpropyl ester

Structural Formula



o

HO

CH,

O

OH

CH,

CH,

'3	'3

SMILES: Q=C(OCC(CO)(C)C)C(CO)(C)C

Summary

Propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-hydroxy-2,2-dimethylpropyl ester is a low melting
solid with moderate vapor pressure and high water solubility. It is expected to have high
mobility in soil. It has been shown to be readily biodegradable in one OECD guideline ready test
and inherently biodegradable in a second OECD test. Volatilization is expected to be low. The
rate of hydrolysis is considered negligible. The rate of atmospheric photooxidation is moderate.
Propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-hydroxy-2,2-dimethylpropyl ester is expected to
have low persistence (PI) and low bioaccumulation potential (Bl).

The acute oral toxicity of propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-hydroxy-2,2-
dimethylpropyl ester in rats is low. The acute inhalation toxicity of propanoic acid, 3-hydroxy-
2,2-dimethyl-, 3-hydroxy-2,2-dimethylpropyl ester in rats was not determined because the
concentration tested was too low. Propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-hydroxy-2,2-
dimethylpropyl ester did not induce gene mutation in bacteria in vitro. Propanoic acid, 3-
hydroxy-2,2-dimethyl-, 3-hydroxy-2,2-dimethylpropyl ester is irritating to rabbit eyes.

For propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-hydroxy-2,2-dimethylpropyl ester, the 96-h LCso
for fish is 3160 mg/L, the 48-h ECso for aquatic invertebrates is > 500 mg/L and the 72-h ECso
for toxicity to aquatic plants is 3170 mg/L and 1600 mg/L for growth rate and biomass,
respectively.

The repeated-dose, reproductive and developmental toxicity, and chromosomal aberrations
endpoints were identified as data gaps under the HPV Challenge Program.	


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U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2014

The sponsor, BASF Corporation, submitted a Test Plan and Robust Summaries to EPA for
propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-hydroxy-2,2-dimethylpropyl ester (CASRN 1115-
20-4) dated November 28, 2006. EPA posted the submission on the ChemRTK HPV Challenge
website on January 19, 2007

(http://www.epa.gov/chemrtk/pubs/summaries/prpacd3h/cl6470tc.htm). Revised robust
summaries were submitted to EPA on December 28, 2006, and posted to the website on April 27,
2009. EPA comments on the original submission were posted to the website on June 4, 2009.
Public comments were also received and posted to the website.

Justification for Supporting Chemicals

The sponsor proposed using data from two supporting chemicals: neopentyl glycol (CASRN
126-30-7), a metabolite of the sponsored substance, and isobutyl isobutyrate (CASRN 97-85-8),
a structural analog of the sponsored substance. The use of data for neopentyl glycol is not
supported because the test plan provides no data to show whether hydrolysis of the sponsored
substance to neopentyl glycol occurs, and whether or not it occurs rapidly. The use of data for
isobutyl isobutyrate is not supported because there are three major structural differences between
isobutyl isobutyrate and the sponsored substance that are not adequately addressed in the test
plan: (1) the presence of quaternary carbon atoms in the sponsored substance but not isobutyl
isobutyrate; (2) a higher degree of steric crowding in the sponsored substance than in isobutyl
isobutyrate; and (3) two hydroxy groups in the sponsored substance but none in isobutyl
isobutyrate. Therefore, data submitted by the sponsor for neopentyl glycol and isobutyl
isobutyrate are not used as supporting chemicals for this hazard characterization.

1. Chemical Identity

1.1	Identification and Purity

Propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-hydroxy-2,2-dimethylpropyl ester is a low melting
solid with moderate vapor pressure and high water solubility. It is used as an intermediate in the
manufacture of binding agents and coatings. It is also used as a monomer in the manufacture of
polymers. Purity is given in the test plan as generally greater or equal to 97.5%.

1.2	Physical-Chemical Properties

The physical-chemical properties of CASRN 1115-20-4 are summarized in Table 1.

Table 1. Physical-Chemical Properties of Propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-

hydroxy-2,2-dimethylpropyl ester 1

Property

Value

CASRN

1115-20-4

Molecular Weight

204.27

Physical State

Solid

Melting Point

48-54.9°C (measured)

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Hazard Characterization Document

September, 2014

Table 1. Physical-Chemical Properties of Propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-

hydroxy-2,2-dimethylpropyl ester 1

Property

Value

Boiling Point

283.2°C (measured)

Vapor Pressure

0.75 mm Hg at 115.17°C (measured);
0.0060 mm Hg at 25°C (estimated)2

Dissociation Constant

Not applicable

Henry's Law Constant

1.7xl0"9atm-m3/mol (estimated)3

Water Solubility

270,000 mg/L at 25°C (measured)

Log Kow

0.858 (measured)

'BASF Corporation. 2009. Test Plan Revision updates for Propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-hydroxy-
2,2-dimethylpropyl ester. Available online at

http://www.epa.gov/chemrtk/pubs/summaries/prpacd3h/cl6470tc.htm as of August 8, 2012.

2N0M05. 1987. PC-Nomograph- Programs to Enhance PC-Gems Estimates of Physical Properties for Organic
Chemicals. Version 2.0. The Mitre Corp.

3U.S. EPA. 2012. Estimation Programs Interface Suite™ for Microsoft® Windows, v4.10. U.S. Environmental
Protection Agency, Washington, DC, USA. Available online at
http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm as of August 8, 2012.

2. General Information on Exposure

2.1	Production Volume and Use Pattern

Propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-hydroxy-2,2-dimethylpropyl ester had an aggregated
production and/or import volume in the United States between 1 and 10 million pounds during
calendar year 2005.

Non-confidential information in the IUR indicated that the industrial processing and uses of the
chemical include resin and synthetic rubber manufacturing as intermediates; and the information
not readily obtainable (NRO). No commercial and consumer uses were reported for the
chemical.

2.2	Environmental Exposure and Fate

Propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-hydroxy-2,2-dimethylpropyl ester is expected to
have high mobility in soil. It was readily biodegradable, degrading 99% after 21 days as
measured by dissolved organic carbon (DOC) removal using activated sludge in a DOC Die
Away test (OECD TG 301 A). It was also shown to be inherently biodegradable using mixed
liquor suspended solids (MLSS) from a waste water treatment facility as inoculum in a Modified
Zahn-Wellens test (OECD TG 302B). However, it only achieved 5% of its theoretical
biochemical oxygen demand (BOD) after 28 days using an activated sludge inoculum in a MITI
test (OECD TG 301C). The rate of volatilization is considered low based on the Henry's Law
constant for this substance. The hydrolysis half-life of propanoic acid, 3-hydroxy-2,2-dimethyl-,
3-hydroxy-2,2-dimethylpropyl ester was estimated as >10 years under environmental conditions.

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The rate of atmospheric photooxidation is moderate. Propanoic acid, 3-hydroxy-2,2-dimethyl-,
3-hydroxy-2,2-dimethylpropyl ester is expected to have low persistence (PI) and low
bioaccumulation potential (Bl).

The environmental fate properties of Propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-hydroxy-2,2-
dimethylpropyl ester are provided in Table 2.

Table 2. Environmental Fate Properties of Propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-

hydroxy-2,2-dimethylpropyl ester 1

Property

Value

CASRN

1115-20-4

Photodegradation Half-life

11.8 hours (estimated)2

Hydrolysis Half-life

11.3 years at pH 8 (estimated)2

Biodegradation

99% after 21 days (readily biodegradable, OECD 301 A);
100% after 28 days (inherently biodegradable, OECD 302B);
5% after 28 days (not readily biodegradable, OECD 301C)3

Bioaccumulation Factor

BAF =1.0 (estimated)2

Log Koc

1.0 (estimated)2

Fugacity

(Level III Model)2

Air (%)
Water (%)
Soil (%)
Sediment (%)

<0.1
30.7
69.2
<0.1

Persistence4

PI (low)

Bi oaccumul ati on4

Bl (low)

'BASF Corporation. 2009. Test Plan Revision updates for Propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-hydroxy-
2,2-dimethylpropyl ester. Available online at

http://www.epa.gov/chemrtk/pubs/summaries/prpacd3h/cl6470tc.htm as of August 8, 2012.

2U.S. EPA. 2012. Estimation Programs Interface Suite™ for Microsoft® Windows, v4.10. U.S. Environmental
Protection Agency, Washington, DC, USA. Available online at
http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm as of August 8, 2012.

3 National Institute of Technology and Evaluation. Chemical Risk Information Platform (CHRIP) database.
Searchable by CASRN online at http://www.safe.nite.go.ip/english/db.html as of August 15, 2012.

4Federal Register. 1999. Category for Persistent, Bioaccumulative, and Toxic New Chemical Substances. Federal
Register 64, Number 213 (November 4, 1999) pp. 60194-60204.

Conclusion: Propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-hydroxy-2,2-dimethylpropyl ester is a
low melting solid with moderate vapor pressure and high water solubility. It is expected to have
high mobility in soil. It has been shown to be readily biodegradable in one OECD guideline
ready test and inherently biodegradable in a second OECD test. Volatilization is expected to be
low. The rate of hydrolysis is considered negligible. The rate of atmospheric photooxidation is
moderate. Propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-hydroxy-2,2-dimethylpropyl ester is
expected to have low persistence (PI) and low bioaccumulation potential (Bl).

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3. Human Health Hazard

A summary of health effects data for SIDS and other endpoints is provided in Table 3.

Acute Oral Toxicity

Sprague-Dawley rats (5/sex/dose) were administered propanoic acid, 3-hydroxy-2,2-dimethyl-,
3-hydroxy-2,2-dimethylpropyl ester (100% purity) via oral gavage at 4640 or 10,000 mg/kg and
observed for 7 days following dosing. One of five female rats died at 4640 mg/kg
and 4/5 females and 3/5 males died at 10,000 mg/kg.

LDso = 8000 mg/kg

Acute Inhalation Toxicity

Twelve Sprague-Dawley rats (both sexes; number per sex not specified) were exposed via
inhalation to a saturated atmosphere of propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-hydroxy-2,2-
dimethylpropyl ester (100% purity) at an estimated concentration of 0.04 mg/L for 8 hours and
were observed for 7 days following exposure. No mortalities were observed.

8-hour LC50 > 0.04 mg/L

Repeated-Dose, Reproductive and Developmental Toxicity

No adequate data were available.

Genetic Toxicity — Gene Mutation
In vitro

Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538 were exposed to
propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-hydroxy-2,2-dimethylpropyl ester at concentrations
of 4, 20, 100, 500 or 2500 |ig/plate with and without metabolic activation. Positive and negative
controls were included, and responded appropriately. No cytotoxicity were noted at any dose
including the highest concentration tested. Propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-hydroxy-
2,2-dimethylpropyl ester did not induce gene mutation with or without activation.

Propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-hydroxy-2,2-dimethylpropyl ester was not
mutagenic in this assay.

Genetic Toxicity — Chromosomal Aberrations

No adequate data were available.

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Additional Information
Eye Irritation

Propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-hydroxy-2,2-dimethylpropyl ester (0.05 mL, 100 %
purity) was instilled into the conjunctival sac of one eye of each of two male rabbits (strain not
specified) and eye reactions were examined for up to 8 days post-instillation. Moderate
reddening, edema and corneal opacity developed > one hour, and persisted throughout the post-
instillation observation period. The eye reactions were not expected to be reversible.

Propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-hydroxy-2,2-dimethylpropyl ester was
irritating to rabbit eyes in this study.

Conclusion: The acute oral toxicity of propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-hydroxy-2,2-
dimethylpropyl ester in rats is low. The acute inhalation toxicity of propanoic acid, 3-hydroxy-
2,2-dimethyl-, 3-hydroxy-2,2-dimethylpropyl ester in rats was not determined because the
concentration tested was too low. Propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-hydroxy-2,2-
dimethylpropyl ester did not induce gene mutation in bacteria in vitro. Propanoic acid, 3-
hydroxy-2,2-dimethyl-, 3-hydroxy-2,2-dimethylpropyl ester is irritating to rabbit eyes.

Table 3. Summary Table of the Screening Information Data Set
as Submitted under the U.S. HPV Challenge Program -
Human Health Data

Endpoints

Propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-
hydroxy-2,2-dimethylpropyl ester
(1115-20-4)

Acute Oral Toxicity
LDso (mg/kg)

8000

Acute Inhalation Toxicity
8-h LC50 (mg/L)

>0.04

Repeated-Dose Toxicity
NOAEL/LOAEL (mg/kg-day)

No Data

Reproductive Toxicity
NOAEL/LOAEL (mg/kg-day)

No Data

Developmental Toxicity
NOAEL/LOAEL (mg/kg-day)

No Data

Genetic Toxicity - Gene Mutation
In vitro

Negative

Genetic Toxicity - Chromosomal

Aberrations

In vivo

No Data

Additional Information

Eye Irritation

Positive

Measured data in bold

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4. Hazard to the Environment

A summary of aquatic toxicity data submitted for SIDS endpoints is provided in Table 4.

Acute Toxicity to Fish

(1)Fathead	minnow (Pimephalespromelas; ten fish per replicate, two replicates per test
concentration) were exposed to propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-hydroxy-2,2-
dimethylpropyl ester for 96 hours under static conditions. Nominal concentrations were 0, 95.0,
171.5, 308.5, 555.5 and 1000.0 mg/L. Corresponding measured concentrations were 97.1, 176.3,
307.8, 586.4 and 1023.9 mg/L for the first series; 99.5, 179.1, 323.5, 546.0 and 1030.9 mg/L for
the second series. Water quality parameters were the following: Hardness and total alkalinity
(both as CaCCb) were 120 mg/L and 92 mg/L, respectively, pH = 7.3 - 8.2 and DO = 7.0 -9.0
mg/L. No mortalities or sub-lethal effects were observed during the study.

96-h LCso > 1024 mg/L

(2)	Golden orfe (Leuciscus idus) were exposed to propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-
hydroxy-2,2-dimethylpropyl ester for 96 hours under conditions according to the German
Industrial Standard DIN 38412, Part 15 and OECD TG 203. Nominal concentrations were 0,
1,000, 2,150, 4,640, 10,000 and 10,000 (neutralized) mg/L. Sub-lethal effects observed were
tumbling at the 2,150 mg/1 treatment group from 24 - 96 hours and narcosis at 1 hour in the
4,460 mg/L treatment group. pH = 5.7 - 7.9, DO = 7.5 - 8.5 mg/L and temp. = 20 °C throughout
the study.

96-h LCso =3160 mg/L

Acute Toxicity to Aquatic Invertebrates

(1)Water	fleas (Daphnia magna) were exposed to propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-
hydroxy-2,2-dimethylpropyl ester (ten organism per treatment; purity at ~ 98.4 %) for 48 hours
under static conditions to nominal concentrations of 0, 95.0, 171.5, 308.5, 555.5 and 1000.0
mg/L. Measured concentrations were 96.0, 175.8, 290.3, 568.5 and 1125.8 mg/L for the first
series; 98.0, 173.3, 342.6, 559.6 and 1048.8 mg/L for the second series. In the first experiment,
1/10 daphnids exposed to 1125.8 mg/L were immobile at 24 hours. 1/10 exposed to 175.8 mg/L
and 1/10 exposed to 1125.8 mg/L were immobile at 48 hours. In the second experiment, 1/10
daphnids exposed to 173.3 mg/L, 1/10 exposed to 342.6 mg/L and 2/10 exposed to 1048.8 mg/L
were immobile at 48 hours. Water quality parameters were the following: hardness and total
alkalinity (both as CaC03) during the study were 120 mg/L and 92 mg/L, respectively. The pH
and dissolved O2 concentration ranged from 8.0 - 8.3 and 8.3 - 9.0 mg/L, respectively.
Temperature remained at 20 ± 2°C throughout the test.

48-h ECso > 560 mg/L

(2)	Water fleas (Daphnia magna; 20 animals per concentration) were exposed to propanoic acid,
3-hydroxy-2,2-dimethyl-, 3-hydroxy-2,2-dimethylpropyl ester for 48 hours under static
conditions to nominal concentrations of 0, 7.81, 15.6, 31.2, 62.5, 125, 250, and 500 mg/L. pH =

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7.61-8.14, DO = 8.3 - 8.7 mg/L, temp. = 19 °C. Immobility was observed in the 15.6 mg/L
treatment group at 24 and 48 hours (1/20), and in the 500 mg/L treatment group at 24 and 48
hours (2/20).

48-h ECso > 500 mg/L

Toxicity to Aquatic Plants

Green algae (Desmodesmus subspicatus; four replicates per test concentrations, 8 replicates per
control) were exposed to propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-hydroxy-2,2-
dimethylpropyl ester for 72 hours under static conditions. Nominal concentrations were 0, 200,
400, 800, 1,600, 3,200, and 6,400 mg/L. Algae were exposed under constant illumination of
10,000 lux and pH = 7.9 - 9.6.

72-h EbCso = 1600 mg/L
72-h ErCso = 3170 mg/L

Conclusion: For propanoic acid, 3-hydroxy-2,2-dimethyl-, 3-hydroxy-2,2-dimethylpropyl ester,
the 96-h LC50 for fish is 3160 mg/L, the 48-h EC50 for aquatic invertebrates is > 500 mg/L and
the 72-h EC50 for toxicity to aquatic plants is 3170 mg/L and 1600 mg/L for growth rate and
biomass, respectively.

Table 4. Summary of the Screening Information Data Set
as Submitted under the U.S. HPV Challenge Program -
Aquatic Toxicity Data

Endpoint

Propanoic Acid, 3-Hydroxy-2,2-Dimethyl-, 3-Hydroxy-
2,2-Dimethylpropyl Ester
(1115-20-4)

Fish

96-h LCso
(mg/L)

3160

Aquatic Invertebrates

48-h ECso

(mg/L)

>560

Aquatic Plants
72-h ECso
growth rate (mg/L)
biomass (mg/L)

3170
1600

Bold = measured data (ie, derived from testing)

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