Sodium methanethiolate

Endpoint summary

Description of key information

In two acute oral toxicity studies conducted according to OECD TG 401, male and female Sprague-Dawley rats were given a single oral dose of formulated Sodium methanethiolate in water and were observed for 14 days. Based on the results and in accordance with OECD guideline 401 in the first and second acute oral toxicity study the oral LD50 was determined to be 116 and 109 mg/kg bw, respectively. Thus, the substance meets the criteria of the CLP Regulation 1272/2008 for being classified as Acute Tox. 3, H301.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted 1981

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- Test article name : Sodium methylmercaptide
- CAS NR: 5188-07-8
- Origin: Atochem, Pilote UDL-AE no. 83562
- Batch: 897016
- Composition: Sodium methylmercaptide: 19.9% solution in water, Na2S: 0.30%, Free NaOH: 1.1%, releasable NaOH: 12.75%

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

All animals were fasted before treatment.

Route of administration:

oral: unspecified

Vehicle:

water

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: In the first assay, the test substance (19.9% solution in water) was administered at a volume of 2.05 mL/kg bw. In the second assay, the test substance in aqueous solution was administered at a volume of 10 mL/kg bw.

Doses:

First assay: 2000 mg/kg bw
Second assay: 400, 620, 950 and 1400 mg/kg bw

No. of animals per sex per dose:

First assay: 5 animals per sex and dose
Second assay: 5 males each for the dose group 1400 and 400 mg/kg bw; 5 animals per sex for the dose group 620 and 950 mg/kg bw

Control animals:

no

Details on study design:

In a first assay, Sodium methylmercaptide (19.9% solution in water), was administered in its original form to a group of 10 Sprague-Dawley rats (5 males and 5 females) at a dose level of 2000 mg/kg bw at a volume of 2.05 mL/kg taking into consideration that the specific gravity (SG) of the test substance was 0.977. In a second assay, the test substance was administered at the dose levels of 400, 620, 950 and 1400 mg/kg bw to 4 groups of 5 males and at the dose levels of 620 and 950 mg/kg bw to 2 groups of 5 females. The mortality, general behaviour and bodyweight gain of the animals were observed for a period of 14 days after the single administration of the test substance. A necropsy was performed on each animal found dead or sacrificed at the end of the study.

Statistics:

The LD50 in males was calculated according to Finney's method.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

116 mg/kg bw

Based on:

test mat.

Remarks on result:

other:

Remarks:

pure test substance

Sex:

male/female

Dose descriptor:

LD50

Effect level:

581 mg/kg bw

Based on:

test mat.

Remarks on result:

other:

Remarks:

formulated test substance: 19.9% in water

Mortality:

The mortality was respectively 20%, 40%, 100%, 100% and 100% at the dose levels of 400, 620, 950, 1400 and 2000 mg/kg bw in the males and 60%, 100% and 80% at the dose levels of 620, 950 and 2000 mg/kg bw in the females. Mortality was recorded within minutes of treatment.

Clinical signs:

A significant decrease in spontaneous activity, dyspnea at the dose levels of 400 and 620 mg/kg bw, tonico-clonic convulsions at the dose levels of 950 and 1400 mg/kg bw before death of the rats, and ataxia and coma at the dose level of 2000 mg/kg bw were the main clinical signs recorded.

Body weight:

The body weight gain of the surviving animals was normal at the dose level of 400 mg/kg bw and slackened off slightly until D5 at 620 and 2000 mg/kg bw.

Gross pathology:

An abnormal red colouration of the stomach was observed during the macroscopic examination of all animals from all dose levels found dead during the study. The necropsy performed on animals sacrificed at the end of the study revealed no macroscopic abnormalities.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Based on the results, the oral LD50 was determined to be 116 mg/kg bw. Thus, the substance meets the criteria of the CLP Regulation 1272/2008 for being classified as Acute Tox. 3, H301.

Executive summary:

In an acute oral toxicity study (OECD 401), Sprague-Dawley rats (5 animals per sex) were given a single oral dose of 2000 mg/kg bw of Sodium methanethiolate (19.9% solution in water) in a first assay. In a second assay, the test substance was administered at the dose levels of 400, 620, 950 and 1400 mg/kg to 4 groups of 5 males and at the dose levels of 620 and 950 mg/kg to 2 groups of 5 females. The animals were observed for 14 days. The mortality was respectively 20%, 40%, 100%, 100% and 100% at the dose levels of 400, 620, 950, 1400 and 2000 mg/kg bw in the males and 60%, 100% and 80 % at the dose levels of 620, 950 and 2000 mg/kg bw in the females. Furthermore, all animals showed signs of toxicity. A significant decrease in spontaneous activity, dyspnea at the dose levels of 400 and 620 mg/kg bw, tonico-clonic convulsions at the dose levels of 950 and 1400 mg/kg bw before death of the rats, and ataxia and coma at the dose level of 2000 mg/kg bwwere the main clinical signs recorded. At necropsy, an abnormal red colouration of the stomach was observed during the macroscopic examination of all animals from all dose levels found dead during the study. However, the necropsy performed on animals sacrificed at the end of the study revealed no macroscopic abnormalities.

Based on the results, the oral LD50 for both sexes using the formulated test substance (19.9% in water) was determined to be 581 mg/kg bw and the oral LD50 after recalculation towards the pure test substance was determined to be 116 mg/kg bw in male and female rats. Thus, the substance meets the criteria of the CLP Regulation 1272/2008 for being classified as Acute Tox. 3, H301.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted 1981

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- Test article name : Sodium methylmercaptide
- CAS NR: 5188-07-8
- Origin: Atochem, Pilote UDL-AE no. 83563
- Batch: 897017
- Composition: Sodium methylmercaptide: 19.6% solution in methanol, Na2S: 1%, Free NaOH: =< 0.1%, releasable NaOH: 12.2%

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: In the 2000 mg/kg bw dose group: 2.18 mL/kg bw, all other dose groups: 10 mL/kg bw

Doses:

The test item (19.6% solution in methanol), undiluted or diluted with water was adminstered to animals at doses of: 300, 420, 580, 820 and 2000 mg/kg bw

No. of animals per sex per dose:

Dose groups 300 and 820 mg/kg bw: 5 males
Dose groups 420, 580 and 2000 mg/kg bw: 5 animals/sex

Control animals:

no

Details on study design:

Sodium methylmercaptide (19.6% solution in methanol), undiluted or diluted with water, was administered by gavage to male and female rats. The mortality, general behaviour and bodyweight gain of the
animals were observed for a period of 14 days after the single administration. A necropsy was performed on each animal found dead during the study or sacrificed at the end of the study.

Statistics:

The LD50 in males was calculated according to Finney's method.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

109 mg/kg bw

Based on:

test mat.

Remarks on result:

other: pure test substance

Sex:

male/female

Dose descriptor:

LD50

Effect level:

559 mg/kg bw

Based on:

test mat.

Remarks on result:

other:

Remarks:

formulated test substance: 19.6% in methanol

Mortality:

See section "any other information on results incl. tables"

Clinical signs:

- decreased spontaneous activity at 300 and 420 mg/kg bw,
- marked decrease in spontaneous activity and tonic-clonic convulsions at 580 and 820 mg/kg bw,
- ataxia accompanied by sedation and lateral recumbency followed by coma at 2000 mg/kg bw.

Gross pathology:

The macroscopic examination of animals found dead during the study revealed an abnormal appearance of the stomach in 2 rats at 800 mg/kg bw and in all rats at 2000 mg/kg bw. The necropsy of the animals found dead during the study or sacrificed at the end of the study revealed no macroscopic abnormalities at 300, 420 and 580 mg/kg bw.

Table 2: Mortality

Dose (mg/kg bw)
19.6 % solution	Calculated pure test material	Mortality (%) Male	Mortality (%) Female
300	59	0
420	82	20	0
580	114	40	40
820	161	100
2000 (undilut.)	392	100	100

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Based on the results, the LD50 value was determined to be 109 mg/kg bw. Thus, the substance meets the criteria of the CLP Regulation 1272/2008 for being classified as Acute Tox. 3, H301.

Executive summary:

In an acute oral toxicity study (OECD 401), Sprague-Dawley rats were given a single oral dose via gavage of 300, 420, 580, 820 or 2000 mg/kg bw of Sodium methanethiolate (19.6% solution in methanol) undiluted or diluted with water. After treatment the animals were observed for 14 days. The mortality was respectively 0 %, 20%, 40%, 100% and 100% at the dose levels of 300, 420, 580, 820 and 2000 mg/kg in the males and 0, 40% and 100% at the dose levels of 420, 580 and 2000 mg/kg in the females. Furthermore, all animals showed signs of toxicity. A significant decrease in spontaneous activity at the dose levels of 300 and 420 mg/kg bw, marked decrease in spontaneous activity and tonico-clonic convulsions at the dose levels of 580 and 820 mg/kg bw, as well as ataxia accompanied by sedation and lateral recumbency followed by coma at 2000 mg/kg bw were the main clinical signs recorded. At necropsy, an abnormal appearance of the stomach in 2 rats at 800 mg/kg bw and in all rats at 2000 mg/kg bw was observed during the macroscopic examination. The necropsy of the animals found dead during the study or sacrificed at the end of the study revealed no macroscopic abnormalities at 300, 420 and 580 mg/kg bw.

Based on the results, the oral LD50 based on the formulated test substance was determined to be 559 mg/kg bw and the oral LD50 recalculated towards the pure test substance was determined to be 109 mg/kg bw. Thus, the substance meets the criteria of the CLP Regulation 1272/2008 for being classified as Acute Tox. 3, H301.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

109 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Additional information

Data from two acute oral and one acute dermal toxicity studies were published in the OECD SIDS dossier for Sodium methanethiolate (SIAM 27, October 2008).

In the first acute oral toxicity study (OECD 401) presented, Sprague-Dawley rats (5 animals per sex) were given a single oral dose of 2000 mg/kg bw of Sodium methanethiolate (19.9% solution in water) in a first assay. In a second assay, the test substance was administered at the dose levels of 400, 620, 950 and 1400 mg/kg to 4 groups of 5 males and at the dose levels of 620 and 950 mg/kg to 2 groups of 5 females. The animals were observed for 14 days. The mortality was respectively 20%, 40%, 100%, 100% and 100% at the dose levels of 400, 620, 950, 1400 and 2000 mg/kg bw in the males and 60%, 100% and 80 % at the dose levels of 620, 950 and 2000 mg/kg bw in the females. Furthermore, all animals showed signs of toxicity. A significant decrease in spontaneous activity, dyspnea at the dose levels of 400 and 620 mg/kg bw, tonico-clonic convulsions at the dose levels of 950 and 1400 mg/kg bw before death of the rats, and ataxia and coma at the dose level of 2000 mg/kg bw were the main clinical signs recorded. At necropsy, an abnormal red colouration of the stomach was observed during the macroscopic examination of all animals from all dose levels found dead during the study. However, the necropsy performed on animals sacrificed at the end of the study revealed no macroscopic abnormalities.

Based on the results, the oral LD50 for both sexes using the formulated test substance (19.9% in water) was determined to be 581 mg/kg bw and the oral LD50 after recalculation towards the pure test substance was determined to be 116 mg/kg bw in male and female rats.

In the second acute oral toxicity study (OECD 401) presented, Sprague-Dawley rats were given a single oral dose via gavage of 300, 420, 580, 820 or 2000 mg/kg bw of Sodium methanethiolate (19.6% solution in methanol) undiluted or diluted with water. After treatment the animals were observed for 14 days. The mortality was respectively 0 %, 20%, 40%, 100% and 100% at the dose levels of 300, 420, 580, 820 and 2000 mg/kg in the males and 0, 40% and 100% at the dose levels of 420, 580 and 2000 mg/kg in the females. Furthermore, all animals showed signs of toxicity. A significant decrease in spontaneous activity at the dose levels of 300 and 420 mg/kg bw, marked decrease in spontaneous activity and tonico-clonic convulsions at the dose levels of 580 and 820 mg/kg bw, as well as ataxia accompanied by sedation and lateral recumbency followed by coma at 2000 mg/kg bw were the main clinical signs recorded. At necropsy, an abnormal appearance of the stomach in 2 rats at 800 mg/kg bw and in all rats at 2000 mg/kg bw was observed during the macroscopic examination. The necropsy of the animals found dead during the study or sacrificed at the end of the study revealed no macroscopic abnormalities at 300, 420 and 580 mg/kg bw.

Based on the results, the oral LD50 of the formulated test substance was determined to be 559 mg/kg bw and the oral LD50 recalculated towards the pure test substance was determined to be 109 mg/kg bw.

By assessing the results in weight-of-evidence approach, the substance meets the criteria of the CLP Regulation 1272/2008 for being classified as Acute Tox. 3, H301.

In addition, data from an acute dermal toxicity study (OECD 402) was published in the OECD SIDS dossier. In this study, Sprague-Dawley rats (1/sex) were applied a single dermal dose of 2000 mg/kg bw of Sodium methanethiolate (21.2% solution in water, equalling 424 mg/kg bw raw material) and eight animals (4/sex) were treated with a single dermal dose of 400 mg/kg (i.e. 84.8 mg/kg bw raw material). After treatment, the animals were observed for 14 days. At 2000 mg/kg bw, tissue lesions on the whole depth of the skin were noted after removal of the dressing on day 2. The two treated animals were sacrificed on day 2 for humane reasons. At 400 mg/kg bw, no cutaneous reactions and no deaths were noted. Hypoactivity, tremors and reversible body weight loss between days 1 and 5 were noted in one female. No clinical signs and no alteration of the general behaviour were noted in the other animals. Based on the results, the dermal LD0 was determined to be > 400 mg/kg bw and after recalculation towards the pure substance, the dermal LD0 can be considered to be > 84.8 mg/kg bw.

Justification for classification or non-classification

Based on the available data, Sodium methanethiolate does warrant classification for acute oral toxicity (Acute Tox. 3, H301).