SCREENING-LEVEL HAZARD CHARACTERIZATION
FOR HIGH PRODUCTION VOLUME CHEMICALS

SPONSORED CHEMICAL

3-(Dodecylthio)propionic Acid, Neopentanetetrayl Ester
(CAS No. 29598-76-3)

CI Name: Propanoic Acid, 3-(dodecylthio)-, 2,2-bis[[3-(dodecylthio)-l-
oxopropoxy]methyl]-l,3-propanediyl ester]

August 2007

Prepared by

High Production Volume Chemicals Branch
Risk Assessment Division
Office of Pollution Prevention and Toxics
Environmental Protection Agency
1200 Pennsylvania Avenue, NW
Washington, DC 20460-0001


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SCREENING-LEVEL HAZARD CHARACTERIZATION
OF HIGH PRODUCTION VOLUME CHEMICALS

The High Production Volume (HPV) Challenge Program1 is 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 sponsor chemicals; sponsorship entails the identification and
initial assessment of the adequacy of existing toxicity data/information, conducting new testing if adequate data do
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 Set1'2) 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. OPPT is using a hazard-
based screening process to prioritize review of the submissions. The hazard-based screening process consists of two
tiers described below briefly and in more detail on the Hazard Characterization website3.

Tier 1 is a computerized sorting process whereby key elements of a submitted data set are compared to established
criteria to "bin" chemicals/categories for OPPT review. This is an automated process performed on the data as
submitted by the sponsor. It does not include evaluation of the quality or completeness of the data.

In Tier 2, a screening-level hazard characterization is developed by EPA that consists of an objective evaluation of
the quality and completeness of the data set provided in the Challenge Program submissions. The evaluation is
performed according to established EPA guidance2'4 and is based primarily on hazard data provided by sponsors.
EPA may also include additional or updated hazard information of which EPA, sponsors or other parties have
become aware. The hazard characterization may also identify data gaps that will become the basis for a subsequent
data needs assessment where deemed necessary. Under the HPV Challenge Program, chemicals that have similar
chemical structures, properties and biological activities may be grouped together and their data shared across the
resulting category. This approach often significantly reduces the need for conducting tests for all endpoints for all
category members. As part of Tier 2, evaluation of chemical category rationale and composition and data
extrapolation(s) among category members is performed in accord with established EPA2 and OECD5 guidance.

The screening-level hazard characterizations that emerge from Tier 2 are important contributors to OPPT's existing
chemicals review process. These hazard characterizations are technical documents intended to support 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. The public, including
sponsors, may offer comments on the hazard characterization documents.

The screening-level hazard characterizations, as the name indicates, do not evaluate the potential risks of a chemical
or a chemical category, but will serve as a starting point for such reviews. In 2007, EPA received data on uses of
and exposures to high-volume TSCA existing chemicals, submitted in accordance with the requirements of the
Inventory Update Reporting (IUR) rule. For the chemicals in the HPV Challenge Program, EPA will review the
IUR data to evaluate exposure potential. The resulting exposure information will then be combined with the
screening-level hazard characterizations to develop screening-level risk characterizations4'6. The screening-level
risk characterizations will inform EPA on the need for further work on individual chemicals or categories. Efforts
are currently underway to consider how best to utilize these screening-level risk characterizations as part of a risk-
based decision-making process on HPV chemicals which applies the results of the successful U.S. High Production
Volume Challenge Program and the IUR to support judgments concerning the need, if any, for further action.

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. HPV Chemicals Hazard Characterization website (http://www.epa.gov/hpvis/abouthc.html).

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

5	OECD. Guidance on the Development and Use of Chemical Categories; http://www.oecd.org/dataoecd/60/47/1947509.pdf.

6	U.S. EPA. Risk Characterization Program; http://www.epa.gov/osa/spc/2riskchr.htm.

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SCREENING-LEVEL HAZARD CHARACTERIZATION
3-(Dodecylthio)propionic Acid, Neopentanetetrayl Ester (CAS No. 29598-76-3)

Introduction

The sponsor, Chemtura Corporation (formerly Crompton Corporation), submitted a Test Plan and Robust
Summaries to EPA for 3-(dodecylthio)propionic acid, neopentanetetrayl ester (CAS No. 29598-76-3; 9th CI name:
propanoic acid, 3-(dodecylthio)-, 2,2-bis[[3-(dodecylthio)-l-oxopropoxy]methyl]-l,3-propanediyl ester) on August
27, 2003. EPA posted the submission on the ChemRTK HPV Challenge Web site on October 2, 2003
(http://www.epa.gov/chemrtk/pubs/summaries/oxopropo/cl4713tc.htm). EPA comments were posted on the
original submission on February 4, 2004. Public comments were also received and posted to the website. The
sponsor submitted revised documents on March 18, 2004, which were posted to the ChemRTK website on June 30,
2004 and on November 10, 2006.

This screening-level hazard characterization is based primarily on the review of the test plan and robust summaries
of studies submitted by the sponsor(s) under the HPV Challenge Program. 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. A summary table of SIDS endpoint data with the
structure(s) of the sponsored chemical(s) is included in the appendix. The screening-level hazard characterization
for environmental and human health toxicity is based largely on SIDS endpoints and is described according to
established EPA or OECD effect level definitions and hazard assessment practices.

Summary-Conclusion

The estimated log Kow value provided for 3-(dodccvlthio)propionic acid, neopentanetetrayl ester is inadequate, but
does indicate the log Kow for this chemical is high (> 4). indicating that its potential to bioaccumulatc is expected to
be high. 3-(Dodccyllhio)propionic acid, neopentanetetrayl ester is readily biodegradable, indicating that it does not
have the potential to persist in the environment.

The potential acute hazard of 3-(dodccvllhio)propionic acid, neopentanetetrayl ester to aquatic organisms is
expected to be low.

3-(Dodccyllhio)propionic acid, neopentanetetrayl ester shows low acute oral toxicity to rats. Repeated exposure to
this chemical via oral gavagc affected the heart (increased weight and histopathological changes), and enzyme levels
(increased AST levels) in rats at all doses (ranging from 100 to 1000 mg/kg-bw/day). There was no reproductive or
developmental toxicity observed in this study: specifically, no treatment-related effects on fertility, weight of pups,
the number and survivability of pups or external abnormalities in live or dead pups. The submitted data indicate that
this chemical docs not induce gene mutations and chromosome mutations.

The potential health hazard of 3-(dodccylthio)propionic acid, neopentanetetrayl ester is moderate based on repeated-
dose toxicity.

No data gaps were identified under the HPV Challenge Program.

1. Physical-Chemical Properties and Environmental Fate

A summary of physical-chemical properties and environmental fate data submitted is provided in the Appendix. For
the purpose of the screening-level hazard characterization, the review and summary of these data was limited to the
octanol-water partition coefficient and biodegradation endpoints as indictors of bioaccumulation and persistence,
respectively.

Octanol-Water Partition Coefficient
Log Kow: 24.8 (estimated)

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The model used to estimate the Kow submitted (KOWWIN v. 1.66) has been demonstrated to be accurate in
predicting log Kows between -4 and 10. The estimate for 3-(dodecylthio)propionic acid, neopentanetetrayl ester is
outside this range, which indicates that the absolute value may not be accurate. Nonethless, it is reasonable to
conclude that this prediction is indicative that the log Kow for this chemical is high (> 4).

Biodegradation

After 29 days, 72.43% of -(dodecylthio)propionic acid, neopentanetetrayl ester degraded in the ready biodegradation
test using domestic sewage as inoculum.

3-(dodecylthio)propionic acid, neopentanetetrayl ester is readily biodegradable.

Conclusion: The estimated log Kow value provided for 3-(dodecylthio)propionic acid, neopentanetetrayl ester is
inadequate, but does indicate the log Kow for this chemical is high (> 4), indicating that its potential to
bioaccumulate is expected to be high. 3-(Dodecylthio)propionic acid, neopentanetetrayl ester is readily
biodegradable, indicating that it does not have the potential to persist in the environment.

2. Environmental Effects - Aquatic Toxicity

No measured data were submitted for aquatic toxicity. EPA did not recommend testing in its test plan comments
because no aquatic toxicity is expected for this chemical at or below water saturation because of the very low
estimated water solubility of the chemical (1.3 xlO"21 mg/L at 25°C; estimated by EPIWIN).

Conclusion: The potential acute hazard of 3-(dodecylthio)propionic acid, neopentanetetrayl ester to aquatic
organisms is expected to be low.

3. Human Health Effects
Acute Toxicity

Acute oral toxicity data show that 3-(dodecylthio)propionic acid, neopentanetetrayl ester has low toxicity to rats.
Only limited details were provided for this study.

LDS0 > 15,000 mg/kg-bw

Repeated-Dose Toxicity

In a combined repeated-dose/reproductive/developmental toxicity screening test, male and female rats were exposed
to 3-(dodecylthio)propionic acid, neopentanetetrayl ester by oral gavage at 0, 100, 400 or 1000 mg/kg-bw/day
(vehicle used is not mentioned in the robust summary). Males were dosed for a minimum of 4 weeks (2 weeks prior
to mating, during mating and about 2 weeks following mating). Females were dosed for 2 weeks prior to mating,
during mating, gestation and until postnatal day 4. Animals in a recovery group were observed for 14 days after
treatment for reversibility, persistence or delayed occurrence of effects. Aspartate aminotransferase (AST) activity
was increased in males at all dose groups and in females at 400 and 1000 mg/kg-bw/day. AST activity from the
recovery group animals was comparable to the control group at the end of 14 day recovery period. Relative heart
weights were increased in males at 400 and 1000 mg/kg-bw/day. Histopathological changes in the heart were
observed in both males and females at all doses. Fibrosis in the hearts of the high-dose recovery group animals was
observed after cessation of exposure; the severity of the fibrosis was less than that in the treatment groups.

NOAEL = Not established

LOAEL = 100 mg/kg-bw/day (based on histopathological changes in the heart in males and females and increased
AST levels in males)

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Reproductive Toxicity

In the combined repeated-dose/reproductive/developmental toxicity screening test in rats described previously, there
were no treatment-related effects on gestation and lactation body weights and food consumption, number and weight
of pups, survivability of pups or fertility indices.

LOAEL > 1000 mg/kg-bw/day
NOAEL = 1000 mg/kg-bw/day

Developmental Toxicity

In the combined repeated-dose/reproductive/developmental toxicity screening test in rats described previously ,
there were no treatment-related effects on pup mortality or observations of external abnormalities of live and dead
pups at any of the treated doses.

LOAEL > 1000 mg/kg-bw/day
NOAEL = 1000 mg/kg-bw/day

Genetic Toxicity - Gene Mutation

In vitro

A bacterial reverse mutation assay was conducted using Salmonella typhimurium strains TA 98, TA 100, TA 1535
and TA 1537 and Escherichia coli WP2 uvrA with and without metabolic activation and test substance
concentrations from 50 to 5000 |ig/plate. The positive controls were included in the assay and gave an appropriate
response. 3-(Dodecylthio)propionic acid, neopentanetetrayl ester did not induce muatagenic activity in the presence
or absence of metabolic activation.

3-(Dodecylthio)propionic acid, neopentanetetrayl ester was not mutagenic in this assay.

Genetic Toxicity - Chromosomal Aberration
In vitro

Cultured Chinese hamster ovary (CHO) cells were treated with 3-(Dodecylthio)propionic acid, neopentanetetrayl
ester up to 5000 ng/mL in the presence and absence of metabolic activation. The positive controls were included in
the test and gave an appropriate response. The test substance did not induce chromosomal aberrations.
3-(Dodecylthio)propionic acid, neopentanetetrayl ester was not mutagenic in this assay.

Conclusion: 3-(Dodecylthio)propionic acid, neopentanetetrayl ester shows low acute oral toxicity to rats. Repeated
exposure to this chemical via oral gavage affected the heart (increased weight and histopathological changes), and
enzyme levels (increased AST levels) in rats at all doses (ranging from 100 to 1000 mg/kg-bw/day). There was no
reproductive or developmental toxicity observed in this study; specifically, no treatment-related effects on fertility,
weight of pups, the number and survivability of pups or external abnormalities in live or dead pups. The submitted
data indicate that this chemical does not induce gene mutations and chromosome mutations.

The potential health hazard of 3-(dodecylthio)propionic acid, neopentanetetrayl ester is moderate based on
observations of systemic effects in a repeated-dose toxicity test in experimental animals.

4. Hazard Characterization

The estimated log Kow value provided for 3-(dodecylthio)propionic acid, neopentanetetrayl ester is inadequate, but
does indicate the log Kow for this chemical is high (> 4), indicating that its potential to bioaccumulate is expected to
be high. 3-(Dodecylthio)propionic acid, neopentanetetrayl ester is readily biodegradable, indicating that it does not
have the potential to persist in the environment.

The potential acute hazard of 3-(dodecylthio)propionic acid, neopentanetetrayl ester to aquatic organisms is
expected to be low.

3-(Dodecylthio)propionic acid, neopentanetetrayl ester shows low acute oral toxicity to rats. Repeated exposure to
this chemical via oral gavage affected the heart (increased weight and histopathological changes), and enzyme levels

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(increased AST levels) in rats at all doses (ranging from 100 to 1000 mg/kg-bw/day). There was no reproductive or
developmental toxicity observed in this study; specifically, no treatment-related effects on fertility, weight of pups,
the number and survivability of pups or external abnormalities in live or dead pups. The submitted data indicate that
this chemical does not induce gene mutations and chromosome mutations.

The potential health hazard of 3-(dodecylthio)propionic acid, neopentanetetrayl ester is moderate based on repeated-
dose toxicity.

5. Data Gaps

No data gaps were identified under the HPV Challenge Program.

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APPENDIX

Summary Tabic of the Screening Information Data Set
as submitted under the U.S. HPV Challenge Program

Endpoints

SPONSORED CHEMICAL
3-(Dodccylthio)propionic acid, ncopcntanctctrayl ester
(29598-76-3)

Structure



O

4

Summary of Physical-Chemical Properties and Environmental Fate Data

Melting Point (°C)

51.2

Boiling Point (°C)

352.2

Vapor Pressure (hPa at 25°C)

9><10"24 (estimated)

Log K„w

24.8 (estimated)

Water Solubility (mg/L at 25°C)

1.3 xlO"21 (estimated)

Direct Photodegradation

—

Indirect (OH )Photodegradation Half-Life

(ti/2)

0.9 h

Stability in Water (Hydrolysis) Half-Life (tV2)

> 1 year at pH 7 (estimated)
59.4 days at pH 8 (estimated)

Biodegradation
% Degradation in 28 days

72.43 (29-days)
Readily biodegradable

Fugacity
(Level III Model)

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

0.031
2.38
28.9
68.7

Summary of Environmental Effects - Aquatic Toxicity Data

No measured data are available for aquatic toxicity and EPA did not recommend any testing in its test plan
comments because no aquatic toxicity is expected for this chemical at or below its water solubility limit based on the
submitted EPIWIN estimate (1.3 xlO"21 mg/L at 25°C).

Fish

96-hr LCS0 (mg/L)

N/A

Aquatic Invertebrates
48-hr EC50 (mg/L)

N/A

Aquatic Plants

72-hr EC50 (mg/L) (growth) (biomass)

N/A

Chronic Toxicity Data

N/A

Summarv of Human Health Data

Acute Oral Toxicity
LDS0 (mg/kg-bw)

> 15,000

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

LOAEL = 100
NOAEL = Not established

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

LOAEL > 1000
NOAEL = 1000

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Su mmary Tabic of the Screening Information Data Set
as submitted under the U.S. HPV Challenge Program

Endpoints

SPONSORED CHEMICAL
3-(Dodccylthio)propionic acid, ncopcntanctctrayl ester
(29598-76-3)

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

LOAEL > 1000
NOAEL = 1000

Genetic Toxicity - Gene Mutation
In vitro

Negative

Genetic Toxicity - Gene Mutation
In vivo



Genetic Toxicity - Chromosomal aberrations
In vitro

Negative

Genetic Toxicity - Chromosomal aberrations
In vivo



Additional Information

—

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