Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was performed between 08 April 2008 and 22 April 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not effect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Sponsor's identification: C-Y9
Description: orange powder
Batch number: 071217
Date received: 24 January 2008
Storage conditions: room temperature in the dark over silica gel

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Five male and five female Sprague-Dawley CD (Crl: CD (SD) IGS BR) strain rats were supplied by Charles River (UK) Ltd, Margate, Kent, UK
- Age at study initiation: Eight to twelve weeks of age.
- Weight at study initiation: At least 200 g.
- Fasting period before study: None.
- Housing: The animals were housed in suspended solid-floor 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.
- Diet (e.g. ad libitum): Free access to food (Certified Rate and Mouse Diet) was allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water was allowed throughout the study.
- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Set to achieve limits of 19 to 25°C
- Humidity (%): Set to achieve limits of 30 to 70%.
- Air changes (per hr): At least fifteen changes per hour.
- Photoperiod (hrs dark / hrs light): Lighting was controlled by a time switch to give twelve hours continous light and twelve hours darkness.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
arachis oil
Details on dermal exposure:
On the day before treatment the back and flanks of each animal were clipped free of hair.

The appropriate amount of test material, moistened with arachis oil BP, was applied as evenly as possible to an area of shorn skin (approximately 10% of the total body surface area). A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage. 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 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test material. The animals were returned to group housing for the remainder of the study period.

Duration of exposure:
24 hours.
Doses:
Using available information on the toxicity of the test material, a group of five male and five female rats was treated with the test material at a dose level of 2000 mg/kg.
No. of animals per sex per dose:
Five males and five females.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.

- Frequency of observations and weighing: The 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 fourteen days, the test sites were examined for evidence of primary irritation and scored according to the Draize scale (see below).
Any other skin reactions, if present were also recorded. Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.

- Necropsy of survivors performed: At the end of the study the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. 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
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
There were no signs of systemic toxicity.
Body weight:
All animals showed expected gains in bodyweight over the study period.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
There were no signs of dermal irritation.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
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 bodyweight.
Executive summary:

Introduction.

The study was performed to assess the acute dermal toxicity of the test material in the Sprague-Dawley CD strain rat. The method was designed to meet the requirements of the following:

• GECD Guidelines for the Testing of Chemicals No. 402 "Acute Dermal Toxicity" (adopted 24 February 1987)

• Method B3 Acute Toxicity (Dermal) of Commission Directive 92/69/EEC

Method.

A group of ten animals (five males and five females) was given a single, 24-hour, semi-occluded dermal application of the test material to intact skin at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality.

There were no deaths.

Clinical Observations.

There were no signs of systemic toxicity

Dermal Irritation.

There were no signs of dermal irritation.

Bodyweight.

All animals showed expected gains in bodyweight over the study period.

Necropsy.

No abnormalities were noted at necropsy.

Conclusion.

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 bodyweight.