HIGH PRODUCTION VOLUME (HPV)
CHEMICAL CHALLENGE PROGRAM
TEST PLAN
For
Dimethyl 3,3'-thiobispropionate
CAS No. 4131-74-2
Submitted to the US EPA
BY
Crompton Corporation.
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1. General Information
CAS Number: 4 13l-74-2
1.1
Molecular Weight: 206.26
1.2
Structure and formula: C8H1404S
1.3
1.4 Introduction
Dimethyl 3,3'-thiobispropionate is used as an antioxidant in PVC systems.
2. Justification for Use of Read Across Data for Human Health Toxicity Endpoints
Studies have been reported in the literature concerning the metabolism of thiodipropionic acid (TDPA)
and its esters (seerobust summary section 5). These studies show that estersof TDPA are almost
completely absorbed and hydrolysed to TDPA, which itself is largely eliminated in the urine, either as
the free acid or as an acid labile conjugate. Absorption of the various estersof TDPA is not
significantly affected by the water solubility as demonstratedby the high degree of absorption of one
analog, didodecyl3,3'-thiodipropionate (insoluble in water), following oral administration in the rat.
Radiolabeled studies show estersof TDPA will undergo hydrolytic cleavage. This processcan occur
to a significant extent within the gastrointestinal tract. It is therefore likely that any toxicity, or lack of
toxicity, will be as a consequenceof exposure to hydrolytic degradants, particularly the parent acid. It
can be predicted that TDPA will be the most significant degradant following oral ingestion of
dimethyl 3,3'-thiodipropionate, therefore the toxicity of this product has been evaluated indirectly
from toxicity studieswith didodecyl3,3'-thiodipropionate.
3. Review of Existing Data and Development of Test Plan
Crompton Corporation has undertaken a comprehensive evaluation of all relevant data on the SIDS
endpoints of concern for dimethyl 3,3'-thiobispropionate and structural analogs.
The availability of the data on the specific SIDS endpoints is summarized in Table 1. Table 1 also
shows data gaps that will be filled by additional testing.
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Available adequate data and proposed testing on Dimethyl 3,3'-thiobispropionate
Table 1:
CAS No. 10081-67-l
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24
Y/N Y/N Y/N Y/N Y/N Y/N Y/N
* Data available on analogs
Evaluation of Existing Physicochemical Data and Proposed Testing
A.
1. Melting Point
The substance is a liquid at room temperature. The melting point is estimated to be -38.3"C
using MPBPWIN ~1.40.
2. Boiling Point
The boiling point is estimated to be 242癈 using MPBPWIN ~1.40.
3. Vapour Pressure
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The vapour pressure is estimated to be 0.055 hPa at 25癈 using MPBPWIN ~1.40.
4. Water Solubility
The MSDS for dimethyl 3,3'-thiodipropionate states that it is practically insoluble in water.
5. Partition Coefficient
The partition coefficient is estimated as log Kow = 0.98 using KOWWIN ~1.66.
Summary of Physicochemical Properties Testing: Existing data for melting point, boiling point,
vapour pressure, water solubility and partition coefficient are considered to fdl these endpoints
adequately. No additional testing is recommended.
B. Evaluation of Existing Environmental Fate Data and Proposed Testing
1. Biodegradation
The biodegradability of the chemical has been estimated using Biowin ~4.00 and the results
indicate the chemical to be readily biodegradable.
2. Hydrolysis
The half life is estimated to be 1.02 years at pH7 using HYDROWIN ~1.67.
3. Photodegradation
The potential for photodegradation has been estimated using the AOPWIN VI .90, and
indicates atmospheric oxidation via OH radicals reaction with a half-life of 6.2 hours.
Transport and Distribution between Environmental Compartments
4.
An Epiwin Level III Fugacity Model calculation has been conducted for the chemical and
indicates distribution mainly to water and soil for emissions of 1000 kg/hr simultaneously to
air water and soil compartments.
Summary of Environmental Fate Testing: The endpoints for biodegradation, hydrolysis,
photodegradation and transport and distribution between environmental compartments are
filled adequately. No additional testing is recommended.
C. Evaluation of Existing Ecotoxicity Data and Proposed Testing
1. Acute Toxicity to Fish
The LC50 (96 h) is estimated to be 109.7 mg/L, calculated using ECOSAR vO.99g.
2. Acute Toxicity to Algae
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The EC50 (96 h) is estimated to be 8.41 mg/L, calculated using ECOSAR vO.99g.
Acute Toxicity to Daphnia
3.
The EC50 (48 h) is estimated to be 1388.7 mg/L, calculated using ECOSAR vO.99g.
Summary of Ecotoxicity Testing: No further ecotoxicity testing is recommended due to the
extremely low water solubility and high estimated log &, value. The ecotoxicity endpoints are
considered to be adequate.
Evaluation of Existing Human Health Effects Data and Proposed Testing
D.
1. Acute Oral Toxicity
The LDso (rat) has been reported as between >2500 and ~5000 mg/kg b.w. and LD50 (mouse)
as >2000 in studies conducted using the analog didodecyl3,3'-thiodipropionate. In studies
using the parent thiodipropionic acid, LDsO (mouse) of 2000 mg/kg b.w. and LD50 (rat) of
3000 mg/kg b.w. were reported.
Repeat Dose Toxicity
2.
In a repeat dose toxicity study (oral, 13 weeks, rat) using the analog didodecyl3,3'-
thiodipropionate a NOAEL of 350 mg/kg b.w./day was reported.
3. Genotoxicity
An Ames test will be conducted using OECD 47 1.
An in vitro chromosome aberration study will be conducted using OECD Method 473.
Reproductive and Developmental Toxicity
4.
In a study using the analog didodecyl3,3'-thiodipropionate (oral, 13 week, rat) no adverse
effects were seen in the reproductive organs of the test animals up to and including the high
dose of 1000 mgikg b.w./day. This is suggestive of no adverse effects on reproduction.
Developmental toxicity studies have been conducted using the analog didodecyl3,3'-
thiodipropionate (oral, essentially following OECD 414, rat, mouse, rabbit, hamster). In all
these studies, no adverse effects were seen in the parents or the offspring at the highest dose
used.
Summary of Human Health Effects Testing: The potential to cause in vitro chromosomal
aberrations will be determined using OECD Method 473 and an Ames test will be performed
using OECD Method 471. Existing data for the analog substance and parent thiopropionic acid
are considered to fdl the remaining endpoints adequately.
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Evaluation of Data for Quality and Acceptability
3.
The collected data were reviewed for quality and acceptability following the general US EPA
guidance [2] and the systematic approach described by Klimisch et al [3]. These methods include
consideration of the reliability, relevance and adequacy of the data in evaluating their usefulness for
hazard assessment purposes. This scoring system was only applied to ecotoxicology and human
health endpoint studies per EPA recommendation [4]. The codification described by Klimisch
specifies four categories of reliability for describing data adequacy. These are:
Reliable without restriction: Includes studies or data complying with Good Laboratory
(1)
Practice (GLP) procedures, or with valid and/or internationally accepted testing guidelines, or
in which the test parameters are documented and comparable to these guidelines.
Reliable with Restrictions: Includes studies or data in which test parameters are documented
(2)
but vary slightly from testing guidelines.
Not Reliable: Includes studies or data in which there are interferences, or that use non-relevant
(3)
organisms or exposure routes, or which were carried out using unacceptable methods, or
where documentation is insufficient.
Not Assignable: Includes studies or data in which insufficient detail is reported to assign a
(4)
rating, e.g. listed in abstracts or secondary literature.
4. References
PI US EPA, EPI Suite Software, 2000
USEPA (1998). Guidance for Meeting the SIDS Requirements (The SIDS Guide). Guidance
PI
for the HPV Challenge Program. Dated 1 l/2/98.
Klimisch, H.-J., et al (1997). A Systematic Approach for Evaluating the Quality of
[31
Experimental Toxicological and Ecotoxicological Data. Regul. Toxicol. Pharmacol. 25: l-5
USEPA (1999). Determining the Adequacy of Existing Data. Guidance for the HPV
[41
Challenge Program. Draft dated 2/l O/99.
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