Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 200 mg/kg bw

Acute toxicity: via dermal route

Link to relevant study records
Reference
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:
other: The study has been performed under GLP and in compliance with guideline
Qualifier:
equivalent or similar to
Guideline:
EPA OPP 81-2 (Acute Dermal Toxicity)
Deviations:
not specified
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
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.
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.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Mortality:
None
Clinical signs:
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.
Body weight:
No effect
Gross pathology:
No effect
Other findings:
none
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 (dermal) > 2000 mg/kg. No clinical signs of toxicity
Executive summary:

The dermal LD50 in the rabbit is > 2000 mg/kg. No clinical signs observed.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Justification for selection of acute toxicity – oral endpoint
Under test conditions in rabbit, LD0 value is 600 mg/kg bw with no toxic effect detectable, and LDLo range is 700 to 910 mg/kg with self-mutilations observed which indicates a low toxicity. Also a variety of acute oral toxicity studies with Dapsone as a pharmaceutical have been conducted in humans and the range of TDlows when the substance is orally applied is 18 - 37.5 mg/kg bw which confirms a low toxicty as well in Human.

Justification for classification or non-classification

The substance is classified for acute oral toxicity (Cat 4) with an LD50 >1000 mg/kg bw. The substance is also classified for Specific Target Organ Toxicity after single exposure Category 2 for effects on blood due to methemoglobin formation. There is no classification required for acute toxicity on the dermal route.