4,4'-methylenebis(2,6-diisopropylaniline)

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October 1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Report date:

1983

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

internal substance code

IUPAC Name:

internal substance code

Test material form:

liquid: viscous

Details on test material:

The test article was a brown viscous liquid supplied in a glass screw-capped bottle labelled P5240. The test article was stored at room temperature in the dark. Information supplied by the study sponsor indicated the test article was stable under normal conditions.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Species, strain and supplier:
Three young adult female New Zealand White rabbits obtained from Morton Commerical Rabbits, Parsonage Road, Stansted, Essex, were used for the study.

Specification:
At the start of the study the rabbits weighed between 2.55 and 2.83 kg and were at least 11 weeks old. They were acclimatised to the laboratory environment for at least 3 days and were examined for signs of ill health or injury shortly before the study commenced. All animals appeared healthy and no animals were rejected.

Husbandry:
The animals were individually housed in grid floor cages in a single air conditioned room at a temperature between 18 and 20°C and a relative humidity between 51 and 62%. The animals were exposed to a constant daily photoperiod of 14 hours artificial light (06.00 - 20.00) and 10 hours darkness. Temperature and humidity were recorded twice daily on weekdays and once daily at week-ends.

Diet and drinking water:
The animals were allowed free access to mains water and food (Standard Rabbit Diet, Special Diets Services Ltd., Stepfield, Witham, Essex) throughout the study.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped the day prior to treatment

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

The test article was melted by warming to approximately 70°C. The test article was allowed to cool to approximately 37°C at
which temperature it was sufficiently liquid to be administered by a 1 ml syringe. The test article concentration applied was 0.5 ml undiluted.

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3 female rabbits

Details on study design:

Treatment procedure:
The back of each animal was clipped free of hair the day prior to treatment using electric veterinary clippers. A portion of test article (0.5 ml) was applied to an area of skin approximately 6 cm2 on each animal and covered with a gauze patch. The patch was occluded and secured using a strip of impermeable adhesive tape. A plastic collar was placed around the neck of each animal to
prevent premature removal of the wrappings and ingestion of the test article. Four hours after application the patches were
removed and the skin wiped with a disposable paper towel moistened with water to remove any test article still remaining.

Evaluation of effects:
One hour after removal of the wrappings the skin reactions were scored using the Draize scale. The evaluation was repeated 24,48 and 72 hours after removal of the patches. No irritation was noted at the 72 hour observation and the study was terminated.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

All treated skin sites appeared normal throughout the study period. A primary irritation index of 0 was obtained. The test item was regarded as non-irritant to rabbit skin. No corrosive effects were noted.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item was classified as a non-irritant to rabbit skin.

Executive summary:

A study was performed to determine the primary skin irritation index and corrosive effects of the test item in the New Zealand White rabbit. The study design was based on OECD Guidelines No. 404. Three female rabbits were tested and 0.5 ml test substance applied undiluted onto the clipped skin area of the animals. A single 4 -hour application produced a primary irritation index of 0. The test item was classified as a non-irritant to rabbit skin. No corrosive effects were noted.