Disulfiram

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

7 Nov - 19 Dec 1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1977

Report date:

1977

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted in 1987

Deviations:

not specified

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Disulfiram

EC Number:

202-607-8

EC Name:

Disulfiram

Cas Number:

97-77-8

Molecular formula:

C10H20N2S4

IUPAC Name:

disulfiram

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Shizuoka Agricultural Cooperative Association for Experimental Animals, Shizuoka
- Age at study initiation: 7 weeks
- Weight at study initiation: Male 240-270 g, Female 200-220 g
- Housing: 10 animals/ cage
- Diet: CE-2 Type (Nihon Clea Co., Osaka), ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 ± 1°C
- Humidity (%): 60 ± 10%

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

corn oil

Doses:

500, 650, 845, 1000, 1300, 1700, 2200, 2860, 3850 and 5000 mg/kg bw

No. of animals per sex per dose:

10 animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes

Statistics:

No data

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

1 860 mg/kg bw

Based on:

test mat.

95% CL:

1 510 - 2 290

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

2 090 mg/kg bw

Based on:

test mat.

95% CL:

1 960 - 2 480

Mortality:

At 1000 and above: Death was found in 1-7 days post-treatment.

Mortalities were:
- 500 mg/kg bw: 0/10 males, 0/10 females
- 650 mg/kg bw: 0/10 males, 0/10 females
- 845 mg/kg bw: 0/10 males, 0/10 females
- 1000 mg/kg bw: 1/10 males, 1/10 females
- 1300 mg/kg bw: 2/10 males, 1/10 females
- 1700 mg/kg bw: 3/10 males, 2/10 females
- 2200 mg/kg bw: 8/10 males, 4/10 females
- 2860 mg/kg bw: 10/10 males, 10/10 females
- 3850 mg/kg bw: 10/10 males, 10/10 females
- 5000 mg/kg bw: 10/10 males, 10/10 females

Summarized results can be found in Attachment 1 in the attached background material.

Clinical signs:

other: At 500 mg/kg: No toxic symptoms were seen. At 650 and 845 mg/kg: Only slight motor ataxia was observed. At 1000 and above: Decrease of spontaneous motor activity, piloelection, irregular respiration and dyspnea were developed 3-4 hours after administratio

Body weight:

other body weight observations

Remarks:

not examined

Gross pathology:

No remarkable changes were found in any animals of each group.

Any other information on results incl. tables

Sex difference was not seen.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The study was conducted similar to OECD guideline 401. The LD50 for female rats was 2090 mg/kg bw, the LD50 for male rats was 1860 mg/kg bw. Based on the LD50 in males, the substance should be classified for acute oral toxicity category 4 (Acute Tox. 4, H302) according to the Regulation (EC) 1272/2008.