Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From June 05, 2002 to June 19, 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to OECD Guideline 402, EU Method B.3 and EPA OPPTS 870.1200 Method, in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report date:
2002

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Structural Analogue 01
IUPAC Name:
Structural Analogue 01
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Structural Analogue 01

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Gartenstrasse 27, D-33178 Borchen
- Age at study initiation: 6 to 10 weeks
- Weight at study initiation: Males: mean=266.2 g (=100%) (S.D.=±12.7 g); female animals: mean=219.4 g (= 100%) (S.D.=±7.5 g)
- Housing: In transparent macrolon® cages (type III) on soft wood granulate in an air-conditioned room, 1 animal per cage
- Diet: Ssniff® R/M-H (V 1534), ad libitum
- Water: Tap water in plastic bottles, ad libitum
- Acclimation period: At least 5 d
-Animal identification: Cage numbering
-Randomization procedure: Computer generated algorithm (archived with raw data) randomization schemes 2001.0453 and 2001.0455
ENVIRONMENTAL CONDITIONS
- Temperature: 22±3°C (except short lasting deviations due to disturbances of air condition)
- Humidity: 50±20 % (except short lasting deviations due to disturbances of air condition)
- Photoperiod: 12 h light/dark cycle

IN-LIFE DATES: From: To: June 05, 2002 to June 19, 2002

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: sesame oil
Details on dermal exposure:
TEST SITE
Before dermal treatment the fur was mechanically removed from the dorsal skin of the animals over an area of approximately 30 cm². The appropriate amountof the test substance was moistened on a two-ply gauze and an aluminum foil (6 x 8 cm) and distributed as uniformly as possible. Together with the foil the test substance was administered to the shaved and intact dorsal skin. The foil was held in place with an elastic plaster bandage fixed around the animal's body (Fixomull and Elastoplast, 8 cm in width, both manufactured by Beiersdorf Aktiengesellschaft).

REMOVAL OF TEST SUBSTANCE
At the end of the dermal exposure period of 24 h the bandage was removed and the treated skin area washed with warm water in order to remove any unabsorbed remnants of the test substance.

PREPARATION OF THE TEST SUBSTANCE
0.5 g of test substance was moistened with 0.25 mL sesame oil
Duration of exposure:
24 h
Doses:
2,000 mg/kg bw
No. of animals per sex per dose:
Five/sex/dose
Control animals:
not specified
Details on study design:
The observation period after the dermal administration lasted for 14 d.

Symptoms were recorded twice every day (in the morning and in the afternoon), on weekends and public holidays only once. During this time the animals were weighed weekly. At the end of the observation period the animals were killed by carbon dioxide asphyxiation, dissected and examined for macroscopically visible changes.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the whole study
Clinical signs:
No symptoms were observed after administration of test substance. The skin of the animals was discolored by the test substance from 2 d onwards. However, in most animals the discoloration disappeared at 6 d of the study. Only two females showed persistent discoloration up to the study end.
Body weight:
Development of body weight was not impaired.
Gross pathology:
The animals killed at the end of the observation period showed no macroscopically visible changes.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the study conditions, the dermal LD50 of the test substance was found to be >2,000 mg/kg bw in rats
Executive summary:

A study was conducted to assess the acute dermal toxicity of the test substance in Hsd:Sprague Dawley (SD) rats according to OECD Guideline 402, EU Method B.3. and EPA OPPTS 870.1200, in compliance with GLP.

 

Groups of five female and five male rats received a single dermal dose of 2,000 mg/kg bw. 

500 mg of test substance was moistened with 0.25 mL sesame oil and was applied topically under occlusive conditions for 24 h.

 

No mortality occurred, no clinical symptoms were observed and no significant macroscopic abnormalities were seen at necropsy. Body weight was also not impaired. However, the skin of the animals was discolored by the test substance from 2 d onwards. Except in two females, discoloration disappeared in all other treated animals at 6 d of the study.

 

Under the study conditions, the dermal LD50 of the test substance was found to be >2,000 mg/kg bw in rats.