Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08 December 1997 to 23 December 1997
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
and Method B3 of Commission Directive 92/69/EEC
(which constitutes Annex V of Council Directive 67/548/EEC)
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
(R)-1-Acetyl-3-(1-methyl-2-pyrrolidinyl methyl)-5-[2-(phenylsulphonyl)vinyl] -1H-indole
EC Number:
639-693-5
Cas Number:
180637-88-1
Molecular formula:
C24 H26 N2 O3 S
IUPAC Name:
(R)-1-Acetyl-3-(1-methyl-2-pyrrolidinyl methyl)-5-[2-(phenylsulphonyl)vinyl] -1H-indole
Test material form:
solid: bulk
Details on test material:
brown crystalline solid
Specific details on test material used for the study:
Brown Solid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
CD (Crl : CD ® BR)
Sex:
male/female
Details on test animals or test system and environmental conditions:
At the start of the study the males weighed 209 to 224g, and the females 200 to 210g, and were approximately eight to twelve weeks old. After a minimum acclimatisation period of five days the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card. The animals were housed in suspended polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study. Free access to mains drinking water and food (Rat and Mouse Expanded Diet No.1, Special Diets Services Limited, Witham, Essex, UK) was allowed throughout the study.
The animal room was maintained at a temperature of 19 to 22*C and relative humidity of 49 to 60%. The rate of air exchange was approximately fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Remarks:
For the purpose of the study the test material was moistened with distilled water prior to application.
Details on dermal exposure:
The appropriate amount of the test material, was applied uniformly to an area of shorn skin (approximating to 10')/0 of the total body surface area). A piece of surgical gauze was placed over the treatment area and semioccluded with a piece of self-adhesive bandage. The bandage was further secured with a piece of BLENDERM wrapped around each end. The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days. After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material. The animals were returned to group housing for the remainder of the study period.
After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and scored according to the following scale from Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 Female/ 5 Male
Control animals:
no
Details on study design:
On the day before treatment the back and flanks of each animal were clipped free of hair using veterinary clippers. A group of 5 male and 5 females were treated for 24 hours with the test material.

Results and discussion

Preliminary study:
none conducted
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths recorded
Clinical signs:
other: No signs of systemic toxicity were noted during the study
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
No signs of skin irritation were noted during the study

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal median lethal dose (LD 50) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight. No symbol and risk phrase are required according to CLP labelling regulations.