STI571 F8

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Limit test:

yes

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Details on test material:

Batch number: 022401

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Number of animals and sex: 8 males and 8 females (range-finding and main study). Females were nulliparous and non-pregnant.
Age: Young adult animals, approximately 8 weeks (males) and 12 weeks (females) at the time of administration.
Body weights: For each sex, body weight variation did not exceed ± 20 % of the mean.
Health conditions: A health inspection was performed prior to the commencement of treatment to ensure, that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from any abnormality.

Hygienic status: Optimal hygienic conditions.
Room temperature: Average of 22 °C (continuous control and recording).
Relative humidity: Average of 54 % (continuous control and recording).
Air exchange: 12 per hour.
Light Artificial light: from 6 a.m. to 6 p.m.
Cages: Single caging in Makrolon cages type III (39 cm x 23 cm x 18 cm). Wire mesh lids. Sanitation of cages once a week.
Bedding material: Aspen wood chips, type "ABEDD", (Fa. ABEDD Dominik Mayr KEG,
A-8580 Köflach), autoclaved. Bedding material was changed weekly. Samples of the bedding material are checked periodically for contaminants by the supplier.
Environmental enrichment: Nibbling wood bricks (10 cm x 2 cm x 2 cm) and nesting material,
(same source and material as the bedding material), were offered to the animals once a week.
Feed Altromin 1324 forte, (Producer: Altromin GmbH, D-32791 Lage) gamma irradiated with 25 kGy 60Co, ad libitum. Random samples of the feed are analysed for contaminants by Altromin.
Water: Tap water from an automatic watering system, ad libitum. Random samples of the water are analysed to check, if the water fulfils the requirements for drinking water for humans (exception: the pH).
Identification: Labelling with felt-tipped pen on the tail and on the cage.
Acclimatisation: 5 days under laboratory conditions.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

A cellulose patch with the calculated amount of the test substance on the surface and soaked with deionised water to get optimal contact with the skin, was applied to the test site and held in place by fixing marginally with non irritating tape. Patch and

Details on dermal exposure:

"STI571 F8", was administered once dermally on an area of approximately 6.5 cm x 8 cm on the dorsal thoracal region of 5 male and 5 female Sprague Dawley rats. The dose was 2000 mg per kg body weight.
A cellulose patch with the calculated amount of the test substance on the surface and soaked with deionised water to get optimal contact with the skin, was applied to the test site and held in place by fixing marginally with non irritating tape. Patch and tape were covered with a semi-occlusive dressing The duration of the exposure was 24 hours.

Duration of exposure:

24 h

Doses:

The dose was 2000 mg per kg body weight.

Control animals:

no

Details on study design:

Investigations
• Body weights: before the administration, 7 and 14 days after the administration (p.a.).
• Clinical observations: at least once per day.
• Necropsy: A macroscopic examination was performed after terminal sacrifice
(14 days p.a.).

Observations were performed 0 - 0.5, > 0.5 - 1, > 1 - 2, > 2 - 4 and > 4 - 6 hours after administration of the test substance (p.a.) and then at least once a day for a total of 2 weeks. Observations included but were not limited to changes in skin, fur, eyes, the occurrence of secretions and excretions, autonomic activity, changes in gait, posture and the presence of convulsions.
No skin examination of the administration site was possible during the exposure period, while
it was covered by the patch and wrappings.
All animals were killed by inhalation of 80 % CO2 + 20 % O2 14 days p.a. and subjected to a
necropsy including a gross pathological examination.

Results and discussion

Preliminary study:

In a range finding study three groups of one male and one female each were dosed with 400,
894 or 2000 mg per kg body weight. All animals survived for 7 days p.a. Therefore a limit-test
with one dose of 2000 mg per kg body weight was performed.
Both animals, dosed with 2000 mg/kg in the preliminary test, were included into the main
study.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0

All animals survived until the scheduled termination of the study.

Clinical signs:

other: Signs of toxicity related to dose levels: Three females showed a low weight gain during the first week of study and one of these continued to show a low weight gain during the second week of the study.

Gross pathology:

Effects on organs: No test substance related effects.
General findings: All animals were normal during the entire observation period.
Observations of skin condition: Exposed skin was not found to be altered by the test
substance.
All animals were normal at terminal necropsy.
No noteworthy sex difference in the response to the test substance was derived from clinical
observations or post-mortem findings.

Other findings:

Signs of toxicity (local):
No test substance related effects.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Remarks:

Cat 5 for GHS, Not classified for CLP

Conclusions:

Acute dermal toxicity study in rats, animals were administered 2000 mg/kg of STI571 F8 in a single dermal administration performed by spreading the undiluted test substance on an area of at least 10 % of the estimated body surface. All animals were normal during the entire observation period. Observations of skin condition: Exposed skin was not found to be altered by the test
substance. All animals survived until the scheduled termination of the study.The LD50,dermal of "STI571 F8" is higher than 2000 mg/kg body weight in rats.