Sodium methanethiolate

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:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Sodium methanethiolate

EC Number:

225-969-9

EC Name:

Sodium methanethiolate

Cas Number:

5188-07-8

Molecular formula:

CH4S.Na

IUPAC Name:

sodium methylsulfanide

Details on test material:

Test article name : Sodium methylmercaptide
CAS RN°: 5188-07-8
Origin: Elf Aquitaine, Lacq
Batch: 93-7074

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Iffa Crédo, 69210 L'Arbresle, France
- Age at study initiation: ca. 8 weeks
- Weight at study initiation: 271 +/- 14 g for males and 230 +/- 8 g for females
- Fasting period before study:
- Housing: 4 to 7 in polycarbonate cages
- Diet (ad libitum): UAR A04 C
- Water (e.g. ad libitum): filtered tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 50 +/-20
- Air changes (per hr): 13 cycles/hr of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

Sodium methylmercaptide (21.2% solution in water) was administered by dermal route to a group of 10 Sprague-Dawley rats (5 males and 5 females). As the test substance was anticipated to be corrosive, 2 animals were used in a first assay. The test substance in its original form was applied directly to the skin at a dose of 2000 mg/kg (i.e. 424 mg/kg in raw material), taking into consideration that the specific gravity (SG) of the test substance was 1.12. In a second assay, on 8 animals (4 males and 4 females), the test substance at a dose of 400 mg/kg (i.e. 84.8 mg/kg in raw material) was dissolved in water and applied directly to the skin in a volume of 5 ml/kg.
After 24 hours under a semi-occlusive dressing, no residual test substance was observed on removal of the dressing.

Doses:

2000 and 400 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

The animals given 400 mg/kg were checked for clinical signs, mortality and body weight gain for a period of 14 days following the single application of the test substance.
A necropsy was performed on each animal sacrificed during the study or sacrificed at the end of the study.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 84.8 mg/kg bw

Based on:

act. ingr.

Effect levels 2

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 400 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 21.2% solution in water

Mortality:

At 2000 mg/kg, the 2 treated animals were sacrificed on day 2 for humane reasons.
At 400 mg/kg no deaths were noted.

Clinical signs:

other: At 2000 mg/kg, tissue lesions on the whole depth of the skin (necrosis) were noted after removal of the dressing on day 2.  At 400 mg/kg, no cutaneous reactions was noted. Hypoactivity, tremors  were noted on day 2 in one female. No clinical signs and no 

Gross pathology:

No macroscopic lesions were observed at necropsy.

Applicant's summary and conclusion

Conclusions:

The LD0 of SODIUM METHYLMER-CAPTIDE when administered by dermal route in rats was > 400 mg/kg using the formulated test substance (21.2% in water) or > 84.8 mg/kg using the pure test substance.

Executive summary:

Sodium methanethiolate (21.2% solution in water) was applied directly to the skin of one male and one female rat at 2000 mg/kg body weight (424 mg active ingredient (a.i.) /kg bw) in an OECD TG 402 study. After occlusion for 24 hours, tissue lesions on the whole depth of the skin were noted and these animals were euthanized for humane reasons. Eight additional rats (4/sex) were dosed with 400 mg/kg bw test solution in water (84.8 mg a.i. /kg bw). The dose site was wrapped with a semi-occlusive dressing for 24 hours. Two females exhibited reversible body weight loss and clinical signs that included hypoactivity and tremors between days 1 and 5. No cutaneous reactions or deaths were observed for any of the animals over the 14-day observation period, resulting in LD₅₀of >400 mg/kg bw for the 21.2% water solution and > 84.8 mg/kg bw for the active ingredient.