Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16-30 December 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
(adopted 24 February 1987)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
Commission Directive 92/69/EEC
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Test material form:
solid: bulk
Details on test material:
Buff-colored

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Rats were supplied by Charles River (UK) Ltd, Margate, Kent. At the start of the study, males weighed 200 to 230 g and females 200 to 218g and were approximately 8-12 weeks old. After a minimum acclimatisation period of 5 days, the animals were selected at random and given a unique number.

They were housed in suspended PE cages furnished with woodflakes. They were housed individually during the 24h 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 21C and relative humidity of 49 to 60%. The rate of air exchange was approximately 15 changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
On the day before treatment the back and flanks of each animal were clipped free of hair using veterinary clippers. The appropriate amount of test material was applied uniformly to an area of shorn skin (approximating to 10% of the total body surface area). A piece of surgical gauze was placed over treatment area and semi-occluded with a piece of self-adhesive bandage. The bandage was further secured with a piece of BLENDERM wrapped around each end. The animals were caged individually for the 24-hour exposure period. Shortly after dosing, the dressings were examined to ensure that they were securely in place.

After the 24h contact period, the bandage was carefullyu 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.
Duration of exposure:
24h
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.

After removal of the dressings and subsequently once daily for 14 days, the test sites were examined for evidence of primary irritation and scored according to the Draize scale for erythema, eschar and oedema formation. Any other skin reactions, if present, were also recorded.

Individual body weights were recorded prior to application of the test material on Day 0 and on Days 7 and 14. At the end of the study the animals were killed by cervical dislocation and subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths were observed.
Clinical signs:
No signs of systemic toxicity were noted during the study.
Body weight:
All animals showed an expected gain in body weight during the study.
Gross pathology:
No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal medial lethal dose (LD50) of the test material, UK-114,958, in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg body weight. No pictogram and hazard statement are required according to EU labelling regulations.
Executive summary:

A study was performed to assess the acute dermal toxicity of the test material in the Sprague-Dawley CD strain rat. The method used followed that described in the OECD Guidelines for Testing of Chemicals No. 402 "Acute Dermal Toxicity" (adopted 24 February 1987) and Method B3 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC). The results may be used as a basis for classification and labelling.

A group of ten animals (five males and five females) was given a single 24 -hour semi-occluded dermal application to intact skin at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after the day of treatment and were then killed for gross pathological examination.

There were no deaths. No signs of systemic toxicity or skin irritation were noted during the study. All animals showed an expected gain in body weight during the study. No abnormalities were noted at necropsy.

The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg body weight. No pictogram and hazard statement are required according to EU labelling regulations.