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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
February 13, 2002 until July 08, 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and guideline study

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. certificate)
Remarks:
testing lab.
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Young adult animals with a comparable weight were used. The acclimatization period was at least one week.
The animals were housed in fully air-conditioned rooms with central air-conditioning in a range of 20 - 24°C for temperature and of 30 - 70% for relative humidity. The day/night rhythm was 12 hours dark and 12 hours light. The animals were singly housed in stainless steel wire mesh cages.
Animal identification was done by cage cards and tail marking. A standardized animal diet and drinking water were available ad libitum.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Single application to the clipped epidermis (dorsal and dorsolateral parts of the trunk); covering of the application site with a semi-occlusive dressing (the bandage consists of 4 layers absorbent gauze, Ph. Eur. Lohmann GmbH & Co. KG and Fixomull stretch (adhesive fleece), Beiersdorf AG) for 24 hours, afterwards removal of the dressing. Rinsing of the application site with warm water.
Clipping of the fur about 24 hours before the beginning of the study.
Application area: about 40 cm2
Duration of exposure:
single application
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Body weight determination: Individual body weights shortly before application (day 0), weekly thereafter and at the end of the study .
Signs and symptoms: Recording of signs and symptoms several times on the day of administration, at least once each workday for the individual animals.
Scoring of skin findings: Individual readings 30 - 60 minutes after removal of the semiocclusive dressing (day 1), as a rule weekly thereafter and at the end of the study (last day of the observation period).
Assessment of skin findings: According to Draize, J .H . (1959): Appraisal of the safety of chemicals in foods, drugs and cosmetics. The association of food and drug officials of the United States Austin, Texas.
Mortality: A check for any dead or moribund animal was made twice each workday and once on Saturdays, Sundays and on public holidays.
Pathology: Necropsy with gross-pathology examination on the last day of the observation period after killing with C02.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
none
Clinical signs:
Male animals:
No signs of systemic toxicity were observed during clinical examination.
Skin effects at the application site comprised well-defined erythema to moderate to severe erythema, erythema extending beyond the area of exposure, slight edema to moderate edema, edema extending beyond the area of exposure, application area distinct yellow discolored, bleeding at the inferior edge of the application area (diameter about 0.5 cm), petechiae, petechiae at the inferior edge of the application area (diameter about 1.5 cm), eczematoid skin change at the inferior edge of the application area (diameter about 1 cm up to 2 cm), due to complete detached crust in the region of eczematoid skin change the skin underneath appeared sleek and were observed on study day 1 and persisted until including study day 14.

Female animals:
No signs of systemic toxicity were observed during clinical examination.
Skin effects at the application site comprised well-defined erythema to moderate to severe erythema, erythema extending beyond the area of exposure, very slight edema to moderate edema, edema extending beyond the area of exposure, application area distinct yellow discolored, brownish discolored parts at the inferior edge of the application area, bleeding, bleeding extending beyond the area of exposure, bleeding at the inferior edge of the application area (diameter about 0 .5 cm), petechiae, eczematoid skin change extending beyond the area of exposure, eczematoid skin change at the inferior edge of the application area (diameter about 2 cm), due to complete detached skin in the region of eczematoid skin change the skin underneath apperared sleek like a scar and reddened and were observed on study day 1 and persisted until including study day 14.

Body weight:
The mean body weights of the animals increased throughout the study period.
Gross pathology:
No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study, except in the skin of the application site, where few skin lesions with incrusted surface were observed (three male and all female animals).

Applicant's summary and conclusion