Disulfiram

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study, GLP-compliance, available as unpublished report, no restrictions, adequate for assessment.

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

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

Details on test material:

- Name of test material (as cited in study report): ETHYL THIURAD
- Physical state: off-white powder
- Purity: 98.6%
- Lot/batch No.: 5394

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Sasco, Inc., O’Failon, MO
- Age at study initiation: Young adult (Approximately 8 weeks)
- Weight at study initiation: 230-262 grams (males) and 166-190 grams (females)
- Fasting period before study: fasted overnight
- Housing: one per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least five days

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Doses:

2500, 3606, 5200 and 7500 mg/kg

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical observations: 3 times within the first 8 hours after dosing and twice daily therafter until sacrifice.
Body weights: recorded on days 0, 7 and 14.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

7 074 mg/kg bw

Based on:

test mat.

95% CL:

4 962 - 420 000

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

> 5 200 mg/kg bw

Based on:

test mat.

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

4 573 mg/kg bw

Based on:

test mat.

95% CL:

3 241 - 6 710

Mortality:

Female rats were more susceptible to lethal intoxication by the test material than were male rats. Most of the deaths occurred from the fourth through sixth days after dosing.

Clinical signs:

Most clinical signs of toxicity were observed in more female than male animals.
Notable signs of intoxication included ataxia, tremors, and an abnormal gait.
Other commonly observed clinical abnormalities included lethargy, ptosis and lacrimation.

Body weight:

Body weight loss occurred during the firts week on test in 15 of the 16 male rats that survived for at least seven days after dosing and in 10 of the 12 surviving female animals. The average loss in the 15 male rats was 13% of initial weight. During the study's second week, survivor animals gained weight: For males, the average increase was 24% of the weight at he end of the first week. For females, the average weight gain was 20% of the previous weight.

Gross pathology:

Effects like depletion of adipose tissue, congestion of the brain's vascular system, dark red pituitary, distended/hemorrhaged intestines and dark red lungs occurred sporadically and/or were considered to be secondary results of intoxication.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU