Dapsone

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPP 81-2 (Acute Dermal Toxicity)

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Dapsone

EC Number:

201-248-4

EC Name:

Dapsone

Cas Number:

80-08-0

Molecular formula:

C12H12N2O2S

IUPAC Name:

4,4'-sulfonyldianiline

Test material form:

semi-solid (amorphous): gel

Remarks:

migrated information: paste

Details on test material:

1% dapsone gel, formula #05/44-1, lot # 020-97

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Administration / exposure

Type of coverage:

occlusive

Details on dermal exposure:

TEST SITE
- Area of exposure: back of the animal (shaved)
- Type of wrap if used: polyethylene plastic

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2g/kg bw
- Constant volume or concentration used: yes/no no
- For solids, paste formed: yes, 1% in a gel paste

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

Each 5 males and 5 females

Control animals:

not required

Details on study design:

Ten rabbits (5 per gender) were used. The back of each animal was haved. Half the animals received epidermal abrasions on the shaved area. The test article (1% dapsone gel) was applied to the back of each animal at a dose of 2g/kg and covered with polyethylene plastic. The rabbits were fitted with collars and the test article was left in place for 24 hours. The test sites were then wiped clean and the rabbits were monitored for 14 days for signs of illness, mortality,, and dermal reactions (erythema and edema) at the site of application. Body weights were recorded at the time of dosing and after 14 days.

Results and discussion

Preliminary study:

Very slightly (barely perceptible) erythema was observed for the first 7 to 12 days after treatment; this may have been due to shaving, occlusion, taping, etc. No edema was observed. No effects on body weight, survival, clinical signs, or gross necropsy were observed.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Mortality:

None

Clinical signs:

other: Very slightly (barely perceptible) erythema was observed for the first 7 to 12 days after treatment; this may have been due to shaving, occlusion, taping, etc. No edema was observed.

Gross pathology:

No effect

Other findings:

No effects on body weights

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose by dermal route in NZW rabbits (LD50) was > 2000 mg/kg.

Executive summary:

An acute dermal toxicity study is available in the Norman A. See, Pharmacology review (2005). The study was conducted in compliance with gool laboratory practice in 1997. Ten New Zealand white rabbits (5 per gender) were used. The back of each animal was shaved. Half the animals recieved epidermal abrasions on the shaved area. The test article (1% dapsone gel) was applied to back of each animal at a dose of 2g/kg and covered with polyethylene plastic. The rabbits were fitted with collars and the test article left in place for 24 hours. The test sites were then wiped clean and the rabbits were monitored for 14 days for signs of illness, mortality and dermal reactions (erythema and edema) at the site of application. Body weights were recorded at the time of dosing and after 14 days. 

Very slight erythma was observed for the first 7 to 12 days after treatment; this may have been due to shacing, occlusion, taping, etc. No edema was observed. No effects on body weight, survival, clinical signs or gross necropsy were observed. 

Under the conditions of this study, the test article did not appread to induce toxicity.