p-phenetidine

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: No data on GLP compliance.

Data source

Reference

Reference Type:

publication

Title:

EVALUATION OF THE CUTANEOUS-IRRITATION POTENTIAL OF 56 COMPOUNDS

Author:

GUILLOT JP, GONNET JF, CLEMENT C, CAILLARD L, TRUHAUT R

Year:

1982

Bibliographic source:

Fd Chem. Toxic. Vol. 20. pp. 563 to 572, 1982

Report date:

1982

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: French authorities for the testing of cosmetics and toiletries (Journal Officiel 21 April 1973, p. 3862; ibid 5 June 1973, p. 3953)

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: AFNOR (Association Francaise de Normalisation, 1982)

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: OECD (Organisation for Economic Co-operation and Development, 1979)

Deviations:

no

Principles of method if other than guideline:

This paper describes the results obtained on 56 substances tested at IFT (Institut François de Toxicologie) in a manner designed to permit a comparison between three of the available methods.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

p-phenetidine

EC Number:

205-855-5

EC Name:

p-phenetidine

Cas Number:

156-43-4

Molecular formula:

C8H11NO

IUPAC Name:

4-ethoxyaniline

Test animals

Species:

rabbit

Strain:

other: New Zealand albino

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Roucher SA, Couhe
- Age at study initiation: adult
- Weight at study initiation: 2-5 kg
- Sex

Test system

Type of coverage:

other: occlusive and semi-occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml

Duration of treatment / exposure:

The pads were removed after 23 hr (for the Cosmetic protocol) or after 4 hr (AFNOR and both OECD procedures).

Observation period:

Macroscopic observations were recorded at 1 and 48 hr after patch removal for the Cosmetic protocol, at 1, 24 and 48 hr for the AFNOR tests and at 1, 24, 48 and 72 hr for both types of OECD test. Further readings at day 7 and day 14 were added to the AFNOR and OECD observations in cases of pronounced irritation, to evaluate the possible reversibility of the lesions.

Number of animals:

Each test material was tested by the three (occlusive) protocols in a single group of six rabbits, so that comparison of the results was not confused by variations in individual reactions.
A fresh group of six rabbits was also used for each substance tested by the semi-occlusive OECD protocol.

Details on study design:

TEST SITE
- Area of exposure: 2 x 2 cm (occlusive tests) and 6 cm2 (semi-occlusive test)
- Type of wrap if used:
four-layered sterile absorbent-gauze square, kept in contact with the skin by a patch and held in place with adhesive tape (occlusive tests) and
four-layered sterile absorbent-gauze square; the pads were held in place with adhesive tape (semi-occlusive test)

SCORING SYSTEM:
Each treated area was scored for erythema and oedema using a numerical system (0-4 in each case according to severity) based on that described by Draize, Woodard & Calvery (1948). For any one of the protocols, the scores obtained for erythema and oedema at both of the treated sites in all six animals at the two or more reading times were totalled. The sum obtained was then divided by the total number of readings to provide a mean score (never greater than 8) termed the primary cutaneous irritation index (PCI). For this purpose, the total numbers of readings (erythema + oedema) for the Cosmetic, AFNOR and OECD protocols were 24, 36 and 48, respectively, corresponding to two application sites on six animals at 1 and 48 hr, at 1, 24 and 48 hr, and at I, 24, 48 and 72 hr, respectively, after removal of the patches.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 23 h

Score:

0.58

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: (test procedure: cosmetic)

Results 2

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 4 h

Score:

0.67

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: (test procedure: AFNOR)

Results 3

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 4 h

Score:

0.04

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: (test procedure: OECD)

Irritant / corrosive response data:

According to the test procedure:
Cosmetic: slightly irritant
AFNOR: slightly irritant
OECD: non-irritant

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

p-Phenetidine was considered as slightly irritant by the Cosmetic and AFNOR protocols and non-irritant by OECD.

Executive summary:

The primary cutaneous irritation of 56 chemicals was tested in the rabbit using three different procedures. The three protocols selected for the tests were the method published by the French authorities for the testing of cosmetics and toiletries (Journal Officiel 21 April 1973, p. 3862;ibid5 June 1973, p. 3953) and the methods proposed for the testing of chemicals by the Association Francaise de Normalisation (AFNOR) and, in 1979, by the Organisation for Economic Cooperation and Development. The results of the three sets of tests were compared and the effects of differences in procedure and numbers of animals were studied, together with the possible relation between irritancy and the pH of the test material. It was concluded that the AFNOR protocol best met the requirements for such tests and that gloves should be worn for the handling of all substances classified as moderately or severely irritant on that scale.

p-Phenetidine was considered as slightly irritant by the Cosmetic and AFNOR protocols and non-irritant by OECD.