2-Propen-1-one, 3-(dimethylamino)-1-(3-pyridinyl)-

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

07 September 1999 - 10 September 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study has been performed according to OECD and EC guidelines and according to GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

STI571 Y5A

IUPAC Name:

STI571 Y5A

Details on test material:

- Name of test material (as cited in study report): STI571 Y5A
- Physical state: Brown solid
- Analytical purity: 98.6%
- Lot/batch No.: 992301
- Expiration date of the lot/batch: 01 July 2001
- Stability under test conditions: Not indicated
- Storage condition of test material: In refrigerator in the dark

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Limited, Margate, Kent, England.
- Age at study initiation: at least 6 weeks old
- Weight at study initiation: less than 3.5 kg.
- Housing: Individually housed in labelled cages with perforated floors (Scanbur, Denmark) and equipped with an automatic drinking system (ITL, Bergen, The Netherlands).
- Diet: Approximately 100 g of standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Germany) per day.
- Water: Free access to tap-water.
- Acclimation period: Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
Air-conditioned room with approximately 15 air changes per hour and the environment controlled with optimal conditions considered as being a temperature of 21°C and a relative humidity of 50%. Fluctuations from these optimal conditions were noted, but were considered not to have affected study integrity. Lighting was 12 hours artificial fluorescent light and 12 hours dark per day.

IN-LIFE DATES: From: 07 September 1999 To: 10 September 1999

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped with electric clippers

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 gram of the moistened test substance

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3 males

Details on study design:

TEST SITE
Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimeters (10x15 cm2). Whenever considered necessary the treated skin areas were reclipped at least 3 hours before the observations, to facilitate scoring. Each animal was treated by dermal application of 0.5 gram of the moistened test
substance to the skin of one flank,.using a Metalline patch (Lohmann GmbH, Neuwied, Germany) of 2x3 cm. The patch was mounted on Micropore tape (3M, St. Paul, Minnesota, U.S.A.), which was wrapped around the abdomen and secured with Coban elastic bandage.
Four hours after the application, the dressing was removed and the skin cleaned
of residual test substance using water.

REMOVAL OF TEST SUBSTANCE
Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using water.

SCORING SYSTEM:
At each observation, the highest scores given was recorded:
ERYTHEMA AND ESCHAR FORMATION
No erythema ....................................................................... 0
Very slight erythema (barely perceptible) ..................... 1
Well defined erythema ....................................................... 2
Moderate to severe erythema .......................................... 3
Severe erythema (beet redness) ...................................... 4

In cases where signs of necrosis or corrosion (injuries in depth) prevent erythema scoring, the maximum grade for erythema (= 4) is given.

OEDEMA FORMATION
No oedema .............................................................................................................................. 0
Very slight oedema (barely perceptible) ............................................................................. 1
Slight oedema (edges of area well defined by definite raising)........................................ 2
Moderate oedema (raised approximately 1 mm) .............................................................. 3
Severe oedema (raised more than 1 mm and extending beyond area of exposure).... 4

Results and discussion

In vivo

Results

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 1h after end of exposure

Score:

>= 1

Max. score:

1

Reversibility:

fully reversible within: 24 h

Irritant / corrosive response data:

There was no evidence of a corrosive effect on the skin.

Other effects:

Yellow staining of the treated skin by the test substance was observed throughout the study period. This staining did not hamper the scoring.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC), STI571 Y5A does not have to be classified and has no obligatory labelling requirement for skin irritation.