Sodium 2-mercaptoethanolate

Endpoint summary

Description of key information

Oral LD50 (OECD401): 98 mg/kg bw
Inhalation LC50: ca. 2.6 mg/L
Dermal LD50: 143.36 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Upon their arrival at the laboratory the animals were acclimatized to the experimental environment for at least 5 days before treatment, during which time they were observed daily.
On the day of treatment, the animals were approximately 6 weeks old and had a mean body weight of 175 ± 4 g for the males and 150 ± 5 g for the females. They were identified individually by earmarks or earnotches.
During the acclimatization period and throughout the study, the animals were kept in a conventional air-conditioned animal room. The ambient conditions were as follows : Temperature: 22 ± 3°C, relative humidity: 50 ± 20%, light/dark cycle: 12 hours of light/12 hours of dark.
The air was non-recycled and filtered.
The animals were housed in groups of 4 to 7 animals of the same sex during the acclimatization period and groups of 5 animals of the same sex during the study. They were housed in polycarbonate cages (48. x 27 x 20 cm) covered with a stainless steel lid containing food and a water bottle. Sifted and dusted sawdust was provided as litter. An analysis of the potential residues and major contaminants was performed periodically.
During the study, the animals were fed ad libitum (except during fasting) with a certified pelleted diet. An analysis of the diet for quality and major contaminants (pesticides, heavy metals, mycotoxins, etc.) was performed by the supplier and given for each batch.
During the study, the animals had free access to tap water filtered by a 0.22 micron filter membrane and contained in water bottles. Bacteriological and chemical analyses of the water and detection of major contaminants (pesticides, heavy metals and nitrosamines) are made periodically.

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

The day before treatment, the animals were fasted for a period of approximately 18 hours prior to administration of the test substance. They received food 4 hours after treatment.
As the test substance was supposed to be toxic, the study began by a preliminary -assay performed on a reduced number of animals in order to define the approximate dose levels to be administered for the evaluation of the LD50. The results of this preliminary test (which are not mentioned in this report) enabled to constitute 3 groups of 10 animals (5 males and 5 females in each).
The test substance was administered in a single dose by oral route using a gavage cannula fitted with a stainless steel round-shaped probe fitted to a glass syringe.

Doses:

86, 150 and 250 mg/kg

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

The animals were observed frequently after administration of the test substance and at least once a day for 14 days in order to determine the reversibility or irreversibility of any clinical signs. The appearance or disappearance of any clinical signs was recorded for each animal.
The animals were checked frequently for mortality just after administration of the test substance and at least twice a day during the 14-day observation period. The time of death was recorded individually, in terms of hours or days after administration of the test substance.
The animals were individually weighed just before administration of the test substance and then on days 5, 8 and 15. The body weight gain of the treated animals was compared to a reference curve of control animals with the same initial weight.
A necropsy was performed on the animals that died during the study. On the 15th day, the surviving animals were sacrificed by C02 inhalation in excess and a necropsy was performed. After opening the thoracic and abdominal cavities, a macroscopic examination of the main organs was performed: digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organ with obvious abnormalities.
Due to the absence of macroscopic lesions, no organ samples were taken and no histological examination was performed.

Statistics:

The LD50 was calculated according to Probit's method. Confidence interval calculated by Fieller's method (1944).

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

98 mg/kg bw

Based on:

act. ingr.

95% CL:

32 - 135

Sex:

male

Dose descriptor:

LD50

Effect level:

162 mg/kg bw

Based on:

act. ingr.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

131 mg/kg bw

Based on:

act. ingr.

95% CL:

98 - 168

Mortality:

Deaths were noted between 4 hours and 24 hours post-treatment. The mortality rate was 20%, 50% and 100% in rats at 86, 150 and 250 mg/kg respectively. The test substance was slightly less toxic in males compared to females.

Clinical signs:

A slight to marked decrease in spontaneous activity was observed during the 24 hours post-dosing. Sedation or hypoactivity appeared from 2 hours post-treatment at 86 and 150 mg/kg and from 1 hour post-treatment at 250 mg/kg. The clinical signs had reversed by day 3 at 86 and 150 mg/kg.

Body weight:

The body weight gain of the surviving animals was not affected by the treatment.

Gross pathology:

Macroscopic post-mortem examination of the main organs of the animals found dead during the study or sacrificed at the end of the study revealed no abnormalities .

Interpretation of results:

Category 3 based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

98 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Principles of method if other than guideline:

Estimation of an inhalative LC50 value

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

other: ChR-CD

Sex:

male

Details on test animals or test system and environmental conditions:

- Weight at study initiation: 243 - 304 g

Route of administration:

inhalation: vapour

Type of inhalation exposure:

not specified

Vehicle:

not specified

Details on inhalation exposure:

The test substance was heated in a T-tube to ca. 100-125°C to insure complete vaporization; dry air stream carried the vapour to 8-liter bell jar containing 4 rats

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

4 h

Concentrations:

975, 2030, 4060, 8100 and 16200 mg/m³ (300, 625, 1250, 2500 and 5000 ppm)

No. of animals per sex per dose:

4

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days

Sex:

male

Dose descriptor:

LC50

Effect level:

ca. 2.03 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

4/4 rats died at concentrations ≥ 1250 ppm (died during exposure in high dose groups or found dead 1 d after exposure at 1250 ppm); 2/4 rats died one d after exposure at 625 ppm; all rats survived in the low dose group. LC50 estimated (no calculation given by the authors).

Clinical signs:

other: During exposure of lethal concentrations rats showed red ears, inactivity, hyperpnea followed by dyspnea, pumping respiration, ruffled fur, fluid around the nose, discomfort, incoordination, tremor, convulsions, prolonged extension of body and limbs; afte

Gross pathology:

Rats that died during exposure showed congestion of various organs (vascular collapse). Edema and emphysema of the lungs in rats found dead the day after exposure. At 2500 ppm 2 rats showed yellow staining of liver sinusoids. No lesions in survivors.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Findings indicate effects on central nervous system, respiratory and circulatory systems and possibly on the liver.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

2.6 mg/m³

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Principles of method if other than guideline:

Test method according to Hill, Ass. Food and Drug Off. 18, 1954.
Restrictions: No guideline study, no GLP study, low number of animals, post exposure observation period 7 days, LD50 not calculated

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

- Purity: 88-97%, up to 5% water, up to 2% thiodiglycol

Species:

rabbit

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Weight at study initiation: 2.26 - 2.5 kg

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Application of 0.05, 0.1 or 0.2 ml undiluted TS per kg bw (corresponding to 56, 112, 224 mg/kg bw; density 1.12 g/mL, on the clipped back (area 40-70 cm²); occlusive; animals immobilized; exposure duration 24 h; post exposure observation period 7 d; 3 rabbits per dose; necropsy performed.

Duration of exposure:

24 h

Doses:

56, 112, 224 mg/kg (= 0.05, 0.1, 0.2 ml/kg)

No. of animals per sex per dose:

3

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 7 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Statistics:

none

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 112 - ca. 224 mg/kg bw

Based on:

test mat.

Mortality:

- 0.2 mL/kg (exposed area about 50 cm2): 2/2 (within 8 - 20 h)
- 0.1 mL/kg (exposed area about 48 - 76 cm2): 1/3 (within 8 - 20 h)
- 0.005 mL/kg (exposed area about 42 - 68 cm2): 0/3

Clinical signs:

- 0.2 mL/kg bw: no specific resorptive intoxication symptoms observed; necropsy: one rabbit with moderate congestion of the lung.
- 0.1 mL/kg bw: apathy, local reddening and edema; necropsy of this rabbit: atelectase of the lung, congestion of liver and kidney.
- 0.05 mL/kg bw: apathy, local inflammation; necropsy: no effects.
Slight decrease in bw of all survivors (ca. 100 g decrease).

Gross pathology:

- 0.1 mL/kg: atelectase of the lung, congestion of liver and kidney.
- 0.05 mL/kg bw: no effects.

Mortality:

Dose	Exposed area	Mortality
0.2 ml/kg	ca. 50 cm2	3/3 (within 8 - 20 h)
0.1 ml/kg	ca. 48 - 76 cm2	1/3 (within 8 - 20 h)
0.05 ml/kg	ca. 42 - 68 cm2	0/3

Interpretation of results:

Category 2 based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

143.36 mg/kg bw

Additional information

Acute oral toxicity:

SNEA (1993) reported an OECD guideline 401 study with sodium-2-mercaptoethanolate Male and female rats were given orally doses (gavage) of 86, 150 and 250 mg/kg. The mortality rate was 20% at 86 mg/kg, 50% at 150 mg/kg and 100% at 250 mg/kg. Hypoactivity, sedation, rapid breathing, muscular weakness, tremor, convulsions, cyanosis, and protraction were observed in rats as clinical symptoms of toxicity. Macroscopic post-mortem examination of the main organs of the animals found dead during the study or sacrificed at the end of the study revealed no abnormalities. The LD50 value for male and female rats was found to be 162 and 98 mg/kg bw, respectively.

Read across: 2 -Mercaptoethanol

No studies regarding the acute inhalation and dermal toxicity of sodium 2 -mercaptoethanolate were available. However, in accordance with column 2 of Annex VII of legislation EC1907/2006, these studies do not have to be conducted since the substance is classified as corrosive to the skin. Nonetheless, for classification purposes data on the structural analogue 2 -mercaptoethanol (CAS: 60 -24 -2) have been used.

Acute inhalation toxicity:

DuPont (1992) estimated an inhalative LC50 value of about 2 mg/L/air for 4 hours. Male rats were given vapour concentrations of 975, 2030, 4060, 8100 and 16200 mg/m3. The findings observed indicated effects on central nervous system, respiratory and circulatory systems and possibly on the liver. All rats survived the low concentration group; all rats died at concentrations > 4060 mg/m3.

Acute dermal toxicity:

BASF (1965) reported an acute dermal LD50 value of about 112 - 224 mg/kg bw for male and female rabbits. The undiluted test substance was applicated occlusive in doses of 56, 112 and 224 mg/kg (= 0.05, 0.1, 0.2 ml/kg). All animals (3/3) died in the high dose group with no specific resorptive intoxication symptoms. One animal (1/3) died in the mid dose group showing apathy, local reddening and edema as clinical signs. No animal (0/3) died in the low dose group showing apathy and local inflammation.

Justification for classification or non-classification

Based on the available data, the substance is classified as acute tox 3 for oral and inhalation route (H301, H331) and acute tox 2 for dermal toxicity (H310) according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.