Dimethyl disulphide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

remark : GLP guideline study but the DMDS tested in this study did not correspond to the specifications of DMDS proposed for registration (high level of methyl mercaptan).
RAC concludes that the presence of methyl mercaptan as an impurity at such a low concentration does not affect the acute oral toxicity profile of DMDS ; the study is considered valid.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: EPA 40 CFR 163.81-1

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyl disulphide

EC Number:

210-871-0

EC Name:

Dimethyl disulphide

Cas Number:

624-92-0

Molecular formula:

C2H6S2

IUPAC Name:

(methyldisulfanyl)methane

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ORGANISMS:
- Source: Royalhart Colony, Newhampton, NY 
- Age: no data
- Weight at study initiation: 163-269 g
- Adaptation period: 14 days
- Fasting before treatment: 18 hours
- Adaptation period : 14 days

HOUSING : The animals were housed individually in suspended stailess steel  wire-bottomed cages

FOOD and WATER
- Food: Purina rat chow ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature : 68-72°F
- Relative humidity : no data
- Light/dark cycle : 12h/12h
- Ventilation : no data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 3% CMC (carboxymethyl cellulose)

Details on oral exposure:

- Volume administered: no data

Doses:

125, 188, 250, 375 and 500 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Clinical signs, mortality and body weight gain were checked for a period  of up to 14 days following the single administration of the test item.  All animals were subjected to necropsy.

Statistics:

Litchfield-Wilcoxon method of probit analysis.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

190 mg/kg bw

95% CL:

150 - 240

Remarks on result:

other: Post-exposure clinical signs: sedation, hypotonia, dyspnea, piloerection and coma

Mortality:

Group        Dose                Mortality         Mortality %
  g/kg   Male     Female
1                0.125                0/5        1/5                10
2                0.188                5/5        1/5                60
3                0.250                3/5        4/5                70
4                0.375                5/5        5/5                100
5                0.50                 5/5        5/5                100

Clinical signs:

other: Dose Level 0.125 g/kg: One female died approximately 2-1/2 hours after administration of the test material. The second female did not exhibit any movement on the day of dosing, but appeared to be recovered by the next morning, and did not exhibit any sign

Gross pathology:

Dose Level : 0.125 g/kg - Group 1: The necropsy of the 1 mortality showed evidence of pulmonary hemorrhage and an enlarged spleen. Necropsy of the survivons was unrevealing. All organs and tissues appeared normal.

Dose Level 0.188 g/kg: Necropsy of the mortalities on the day of dosing revealed evidence of pulmonary hemorrhage and one animal exhibited an enlarged spleen. Necropsy of the survivons was unreveallng. All organs and tissues appeared normal.

Dose Level 0.250 g/kg: Necropsy of the mortalities revealed evidence of pulmonary hemorrhage. One male exhibited gastro-intestinal hemorrhage and an enlarged spleen. Necropsy of survivors was unreveallng. All organs and tissues appeared normal.

Dose Level 0.375 g/kg: The necropsy revealed evidence of pulmonary hemorrhage in all but 2 rats. One male  exhibited an enlarged spleen, and 1 female exhibited a gastro-intestinal hemorrhage. One male and 1 female did not exhibit any abnormal organs or tissues.

Dose Level 0.50 g/kg: 5 All animals died approximately 2-1/2 hours after administration of the test material. The necropsy revealed evidence of pulmonary hemorrhage in all animalis. One male and 1 female exhibited enlarged spleens, and 2 females exhibited gastro-intestinal hemorrhages.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Under these experimental conditions, the oral LD50 of DMDS was 190 (150 -240) mg/kg in female and male rats.

Executive summary:

The Acute oral toxicity of DIMETHYL DISULFIDE was evaluated in male and female Wistar rats according to EPA 40 CFR 163.81-1and in compliance with principles of Good Laboratory Practices. Animals were treated with dose levels of 125, 188, 250, 375 and 500 mg/kg and then observed for 14 days for mortality, clinical signs and effect on body weight.

According to the dose levels, mortality was 10, 60, 70, 100 and 100% respectively.

Sedation, hypotonia, dyspnea, piloerection and coma, appeared just after the administration and disappeared after 24 hours. No effect was noted on the body weight gain of the surviving rats. Haemorragic stomachs was observed at the macroscopic examination of the rats dead on the first day (250 and 500 mg/kg)

Under these experimental conditions, the oral LD50 of DMDS was 190 (150 -240) mg/kg in female and male rats.