Reaction Mass of 6-(1-bromoethyl)-4-chloro-5-fluoropyrimidine and Toluene

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10th to 13th July 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

6-(1-bromoethyl)-4-chloro-5-fluoropyrimidine

Cas Number:

188416-28-6

Molecular formula:

C6H5BrClFN2

IUPAC Name:

6-(1-bromoethyl)-4-chloro-5-fluoropyrimidine

Test material form:

liquid

Details on test material:

Amber Oil

Specific details on test material used for the study:

Identification: UK134,821
Appearance: Clear Yellow Liquid
Batch: 5494/96/1
Purity/Composition: 95.5%
Test item storage: At room temperature in the dark

Test animals

Species:

rabbit

Strain:

New Zealand White

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

Approximately 0,5 mi of the test substance was applied under a 25 nun x 25 mm mum pad to one intact site on each animal

Duration of treatment / exposure:

4 hours

Observation period:

Examination of the treated ski was made on Day I (ie approximately 60 minutes after removal of the dressings) and on Days 2, 3 and 4 (equivalent to 24, 48 and 72 hours after exposure). Additional observations were made for all animals on Day 5 through Day 14.

Number of animals:

3

Details on study design:

Approximately 24 hours prior to application of the test substance, hair was removed with electric clippers from the dorso-lumbar region of each rabbit exposing anarea. of skin approximately 100 mm x 100 rum
Approximately 0,5 mi of the test substance was applied under a 25 nun x 25 mm mum pad to one intact site on each animal.
Each treatment site was covered with "Elastoplast" elastic adhesive dressing I'ôr four hours. The animals were not restrained during the exposure period and were returned to their cages immediately after treatment.
At the end of the exposure period, the semi-occlusive dressing and gauze pad were removed and the treatment site was washed with warm water (37°C) to remove any residual test substance. The treated area was blotted dry with absorbent paper.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

14 d

Score:

ca. 4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

14 d

Score:

4

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

14 d

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

14 d

Score:

2

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

14 d

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

14 d

Score:

1

Max. score:

2

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Results 7

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

14 d

Remarks on result:

not measured/tested

Results 8

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

> 2 - < 4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Results 9

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

> 2 - < 4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Irritant / corrosive response data:

Severe erythema and oedema was seen in all animals. These reactions were accompanied in all rabbits by blanching and necrosis of skin, with subsequent thickening, hardening and cracking of the treated area. Severe erythema with very slight or slight oedema persisted in all animals to study teimination on Day 14.

Other effects:

There were no signs of clinical toxicity or ill health in any rabbit dating the observation period

Applicant's summary and conclusion

Interpretation of results:

Category 1B (corrosive) based on GHS criteria

Conclusions:

A single semi-occlusive application of UK-134,821 to intact rabbit skin for four hours elicited severe dermal irritation.

Executive summary:

A study was performed to assess the skin irritation potential of 1JK-134,821 to the rabbit. The method followed was that described in: EEC Methods for the determination of toxicity, Annex to Directive 92/69/EEC (Official Journal No, 1.,383A, 29,12.92), Part B. Method BA. Acute toxicity (Skin irritation). OECD Guideline for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion", Adopted 17 July 1992. Three rabbits were each administered a single dermal dose of 0.5 ml of the test substance and observed for 14 days. A single semi-occlusive application of UK-134,821 to intact rabbit skin for four hours elicited severe dermal irritation. Based on the results of this study it is indicated that UK-134,821 is corrosive.