Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985-03-19 to 1985-04-02
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD 402) performed under GLP-like quality controlled conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted on 12 May 1981
Deviations:
no
GLP compliance:
no
Remarks:
Predating compulsory compliance to GLP, QA statement included
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: solid
- Storage condition of test material: room temperature

Test animals

Species:
rat
Strain:
other: Rat, Tif:RAIf(SPF), F3-crosses of RII 1/Tif X RII 2/Tif
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY LTD. Tierfarm, 4334 Sisseln, Switzerland
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 215 - 233 g
- Housing: conventional laboratory conditions. Animals were caged individually in Macrolon cages type 2 with standardized softwood bedding (Societe Parisienne des Sciures, Pantin).
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature: 22+3° C
- Humidity: 55±15%
- Air changes: 15 air changes/h
- Photoperiod: 12 hours light/day

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
other: Distilled water containing 0.5% carboxymethylcellulose and 0.1% polysorbate 80
Details on dermal exposure:
TEST SITE
- Area of exposure: Back of the rat
- % coverage: 10 % of the body surface
- Type of wrap: gauze-lined semiocclusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing: the skin was cleaned with lukewarm water
- Time after start of exposure: After an exposure period of 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight

VEHICLE
- Amount(s) applied (volume or weight with unit): 4 mL/kg bw
- Concentration: 500 mg / mL
- Distilled water containing 0.5% carboxymethylcellulose and 0.1% polysorbate 80 (prepared by Pharmaceuticals Division, Ciba-Geigy Ltd.).

Pretreatment: Approximately 24 hours before treatment, an area on the back of the rat of at least 10% of the body surface was shaved with an electric clipper.
Administration: The required amount of the test substance was evenly dispersed on the skin. It was covered with a gauze-lined semiocclusive dressing, which was fastened around the trunk with an adhesive elastic bandage. After an exposure period of 24 hours the dressing was removed and the skin was cleaned with lukewarm water. Thereafter the reaction of the skin was appraised repeatedly.
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Observation Period: 14 days
Mortality: daily, a.m. and p.m., a.m. on weekends
Signs and Symptoms: daily
Body weight: on days 1, 7, and 14
Necropsies: The animals were submitted to a gross necropsy at the end of the observation period.
Statistics:
From the body weights, the group means and their standard deviations were calculated.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred
Clinical signs:
Dyspnea, ruffled fur, and abnormal body positions were seen, being common symptoms in acute dermal tests. Additionally, diarrhea was observed on
day 1 after application. The animals recovered within 13 days.
Body weight:
All animals gained bodyweight throughout the study.
Gross pathology:
No deviations from normal morphology were found.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Conclusions:
The dermal LD50 in the rat was determined at greater than 2000 mg/kg body weight
Executive summary:

In a dermal acute toxicity study according to OECD guideline 402, five male and five female rats were treated semiocclusively with the test article in distilled water containing 0.5% carboxymethylcellulose and 0.1% polysorbate 80 for 24 hours and observed for 14 days. There were no deaths. Dyspnea, ruffled fur, and abnormal body positions were seen, being common symptoms in acute dermal tests. Additionally, diarrhea was observed on day 1 after application. The animals recovered within 13 days. All gained weight by day 14 of the study. No irritations were noted on any of the test sites. All animals appeared normal at necropsy. Under the conditions of this study, the LD50 is greater than 2000 mg/kg bw in male and female rats when topically applied.