CMP

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

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:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

occlusive dressing used

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

occlusive dressing used

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

yes

Remarks:

occlusive dressing used

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

435-030-7

EC Name:

-

Cas Number:

26452-81-3

Molecular formula:

C5H5N2OCl

IUPAC Name:

4-chloro-6-methoxypyrimidine

Test material form:

other: solid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Young adults
- Weight at study initiation: 3056 - 3132 g
- Housing: individually, in cages suitable for this strain and the weight range expected during the course of the study
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): ≥15
- Photoperiod (hrs dark / hrs light): 12 / 12

Test system

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

deionised

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 500 mg in 0.5 mL water

Duration of treatment / exposure:

approx. 4 hours

Observation period:

10 days

Number of animals:

2 males, 1 female

Details on study design:

TEST SITE
- Area of exposure: approx 2.5 x 2.5 cm on the left flank
- Type of wrap if used: 4-ply surgical gauze (2.5 cmx2.5 cm) secured by two strips of surgical tape (approx. size 1x8 cm). This was covered by a piece of impermeable rubber sheeting (approx. size 35x13 cm) wrapped once around the trunk of the animal and secured with adhesive impermeable polyethylene tape.

REMOVAL OF TEST SUBSTANCE
- Washing: cleansed using clean swabs of absorbent cotton wool soaked in clean warm water and then dried gently with clean tissue paper.
- Time after start of exposure: approx. 4 hours.

SCORING SYSTEM: Draize

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Results 2

Irritation parameter:

erythema score

Basis:

animal: #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 10 days

Results 4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 48 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 10 days

Results 5

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 72 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 10 days

Results 6

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: mean 24, 48, and 72 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 10 days

Results 7

Irritation parameter:

edema score

Basis:

animal: #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no edema was observed during the course of the study

Results 8

Irritation parameter:

edema score

Basis:

animal: #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no edema was observed during the course of the study

Results 9

Irritation parameter:

edema score

Basis:

animal: #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no edema was observed during the course of the study

Irritant / corrosive response data:

Very slight erythema was seen in two animals (one male and the female) approximately 1 hour after decontamination only, and was seen in the remaining male animal for 7 days. There were no signs of oedema in any animal. In addition, slight thickening of the skin was seen in one animal from 3 to 7 days after application. All signs of irritation had completely resolved 10 days after application.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance is considered to be slightly irritating to the rabbit skin.

Executive summary:

In a GLP compliant skin irritation study, performed according to OECD guideline 404, an amount of test substance (500 mg) was moistened and applied under occlusion to the skin of three New Zealand White rabbits for 4 hours. After 4 hours, the dressing was removed and the skin was cleansed. After this, observations were made for an additional 10 days. The test substance showed an edema score of 0 during the whole observation period. An erythema score of 1 was observed in two animals (one male and one female) 1 hour after decontamination only, and was seen in the remaining male animal for 7 days. In addition, slight thickening of the skin was seen in one animal from 3 to 7 days after application.No corrosive effects were noted. Under the conditions of this experiment, the test substance was found to be slightly irritating. All observed effects were non-classifiable.