Disulfiram

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

4 Aug - 18 Aug 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

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 402 (Acute Dermal Toxicity)

Version / remarks:

adopted in 2017

Deviations:

yes

Remarks:

1/ Clinical observation: On one day, observations were only recorded once, and on two other days, they were not recorded. 2/ Environmental conditions not reported. Both protocol deviations were not considered to adversely affect study results

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

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:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Isaacs’ Rabbitry, Litchfield, Illinois
- Age at study initiation: Young adult
- Weight at study initiation: 2.27 - 2.64 kg
- Housing: one per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

Administration / exposure

Type of coverage:

occlusive

Vehicle:

physiological saline

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal surface
- % coverage: 10 - 30% of total body surface
- Type of wrap if used: wrap of latex rubber


REMOVAL OF TEST SUBSTANCE
- Washing (if done): the excess material was wiped from the animal
- Time after start of exposure: 24 hours

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

one group of 5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made three times during the first eight hours following test material administration and routinely twice daily (morning and afternoon) thereafter until sacrifice. On one day, observations were only recorded once, and on two other days, they were not recorded. These protocol deviations were not considered to adversely affect study results.
Body weights were recorded on days 0 (day of exposure), 7, and 14.
- Necropsy of survivors performed: yes

Results and discussion

Preliminary study:

None

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 3

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed

Clinical signs:

other: Erythema in the exposed area was observed in one female and two male animals on the day after dosing and in the same female rabbit on the following day. No other clinical abnormalities were observed.

Body weight:

other body weight observations

Remarks:

All animals gained weight as would be expected for this strain and age. Summarized results can be found in Attahcment 1 in the attached background material.

Gross pathology:

At necropsy, one male and two female animals had off-white fibrous tissue in and/or a marbled appearance of all hepatic lobes. Two of these same animals had numerous hard, yellow foci on all lobes of the liver, and one also had an area of green, necrotic hepatic tissue. All three of these animals also had tapeworm cysts in the mesentery. Pale renal coloration was observed in each of two animals, one of which also had kidneys with pitted exteriors. No abnormalities were observed in the remaining five rabbits.

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

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The study was conducted similar to OECD guideline 402 The acute dermal LD50 of the test substance was > 2000 mg/kg bw in male and in female animals.
According to Regulation (EC) No 1272/2008 the test substance does not require classification for dermal toxicity.