2-Butenamide, N-[4-[(3-chloro-4-fluorophenyl)amino]-7-[[(3S)-tetrahydro-3-furanyl]oxy]-6-quinazolinyl]-4-(dimethylamino)-, (2E)-

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

30 January 2003 - 24 February 2003

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

(2E)-N-{4-[(3-chloro-4-fluorophenyl)amino]-7-[(3S)-oxolan-3-yloxy]quinazolin-6-yl}-4-(dimethylamino)but-2-enamide

EC Number:

923-981-5

Cas Number:

850140-72-6

Molecular formula:

C24 H25 Cl F N5 O3

IUPAC Name:

(2E)-N-{4-[(3-chloro-4-fluorophenyl)amino]-7-[(3S)-oxolan-3-yloxy]quinazolin-6-yl}-4-(dimethylamino)but-2-enamide

Test material form:

solid: crystalline

Test animals

Species:

rabbit

Strain:

Himalayan

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: LPT Laboratory of Pharmacology and Toxicology
- Age at study initiation: approx. 5.5 - 6.5 months
- Weight at study initiation:
animal no. 1: 2.7 kg
animal no. 2: 2.5 kg
animal no. 3: 2.4 kg
- Housing: animals were kept singly in cages measuring 425 mm x 600 mm x 380 mm
- Diet (e.g. ad libitum): food was available ad libitum before and after the exposure period
- Water (e.g. ad libitum): drinking water was offered ad libitum before and after the exposure period

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C ± 3°C
- Humidity (%): 55% + 15%
- Photoperiod (hrs dark / hrs light): 12 hr dark / 12 hr light cycle

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

other:

Amount / concentration applied:

500 mg/patch

Duration of treatment / exposure:

4h

Observation period:

60 minutes, 24 hr, 48 hr & 72 hr

Number of animals:

3

Details on study design:

TEST SITE
- Dermal application onto the shaved, intact dorsal skin
- Type of wrap if used: gauze pad

REMOVAL OF TEST SUBSTANCE
- No residual test substance had to be removed, as no test substance was left on the skin after removal of the patch.

OBSERVATION TIME POINTS
Scores were taken 60 minutes, 24, 48 & 72 hours after patch removal.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 1h, 24h, 48h

Score:

1

Max. score:

4

Remarks on result:

other: There were no systemic intolerance reactions.

Results 2

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 72h

Score:

0

Max. score:

4

Remarks on result:

other: There were no systemic intolerance reactions.

Results 3

Irritation parameter:

erythema score

Basis:

animal: #2, #3

Time point:

other: 1h, 24h, 48h & 72h

Score:

0

Max. score:

4

Remarks on result:

other: There were no systemic intolerance reactions.

Results 4

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 1h, 24h, 48h and 72h

Score:

0

Max. score:

4

Remarks on result:

other: There were no sytemic intolerance reactions.

Applicant's summary and conclusion

Interpretation of results:

other: not classified acc. CLP

Conclusions:

Under the present test conditions three rabbits were exposed for 4 hours to 500 mg BIBW2992MA2/BIBW2992BS/patch and animal (semi-occlusive
condition). Animal no. 1 only showed an erythema (grade 1) 1 hour to 48 hours after patch removal.
There were no systemic intolerance reactions.

BIBW2992MA2/BIBW2992BS was non - irritating to skin, hence, no labelling is required (no classification with R-phrases).