2,2-bis(methylthio)propane

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

478-900-1

EC Name:

-

Cas Number:

6156-18-9

Molecular formula:

C5 H12 S2

IUPAC Name:

2,2-bis(methylthio)propane

Details on test material:

- Name of test material (as cited in study report): BMTP
- Synonym: Bismethylthiopropane
- Analytical purity: 97.22%
- Purity test date: 2007-11-19
- Lot/batch No.: 2KS149
- Expiration date of the lot/batch: November 2008
- Storage condition of test material: at room temperature and protected from light

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: approximately 8 weeks old
- Weight at study initiation: 364 ± 11 g for the males and 252 ± 8 g for the females
- Fasting period before study: no
- Housing: GR900 cages with stainless steel lid (405 cm x 355 cm x 230 cm)
- Diet: free access to SsniffR/M-H pelleted diet (SSNIFF Spezialdiäten GmbH, Soest, Germany)
- Water: drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 30 to 70
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12

IN-LIFE DATES: 24 January 2008 - 07 February 2008

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: none

Details on dermal exposure:

The undiluted test item was applied at the dose-level of 2000 mg/kg, taking into consideration that its specific gravity was 0.987 g/mL. The volume of administration was therefore 2.03 mL/kg.
The test item was placed directly on an area of the skin representing approximately 10% of the total body surface of the animals, calculated according to Meeh's formula (1) (i.e. approximately 5 cm x 7 cm for the males and 5 cm x 6 cm for the females). A hydrophilic gauze pad was then applied to the skin.
The test item and the gauze pad were held in contact with the skin for 24 hours by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage. This dressing prevented ingestion of the test item by the animals.
No residual test item was observed on removal of the dressing.

The dose applied to each animal was adjusted according to the body weight determined on the day of treatment.

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

CLINICAL EXAMINATIONS
- Clinical signs and mortality
The animals were observed frequently during the hours following administration of the test item, for detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day until day 15. Type, time of onset and duration of clinical signs were recorded for each animal individually. From day 2, any local cutaneous reaction was recorded.

- Body weight
The animals were weighed individually just before administration of the test item on day 1 and then on days 8 and 15.
The body weight gain of the treated animals was compared to that of CIT control animals with a similar initial body weight.

PATHOLOGY
- Sacrifice
On completion of the observation period, all animals were deeply anesthetized by an intra peritoneal injection of pentobarbital and killed by exsanguination.

- Macroscopic necropsy examination
All study animals were subjected to a macroscopic examination as soon as possible after death.
After opening the thoracic and abdominal cavities, a macroscopic examination of the main organs (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities) was performed.

- Preservation of tissues
No organ samples were taken.

Statistics:

Not appropriate

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 2 000 mg/kg bw

Remarks on result:

other: (No mortality was observed)

Mortality:

No deaths occurred during the study.

Clinical signs:

other: No systemic clinical signs were observed during the study. Crusts were noted in 1/5 males from day 6 until day 14.

Gross pathology:

Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD0 of Bismethylthiopropane was equal to or higher than 2000 mg/kg in rats.

Executive summary:

The acute dermal toxicity of BISMETHYLTHIOPROPANE (BMTP) was evaluated in rats according to OECD guideline 402. BMTP was applied to the skin of one group of ten Sprague-Dawley rats (five males and five females). The application was performed with the undiluted BMTP at the dose-level of 2000 mg/kg, taking into consideration that its specific gravity was 0.987 g/mL. BMTP was then covered by a semi-occlusive dressing for 24 hours. Clinical signs, mortality and body weight gain were checked for a period of 14 days following the single application of the test item. All animals were subjected to necropsy. No deaths and no systemic clinical signs were observed during the study. Crusts were noted in 1/5 males from day 6 until day 14. When compared to laboratory historical control animals, a slightly lower body weight gain was observed in 1/5 females between day 1 and day 8, without any relevant consequence at the end of the observation period. The body weight gain of the other animals was not affected by treatment with BMTP. No apparent abnormalities were observed at necropsy in any animal. The dermal LD₀ of BISMETHYLTHIOPROPANE was equal to or higher than 2000 mg/kg in rats.