N-[2-[(2-chloro-4,6-dinitrophenyl)azo]-5-(diethylamino)-4-methoxyphenyl]acetamide

Endpoint summary

Description of key information

Skin sensitising

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

No studies on "skin sensitisation" are available for the substance in itself. Nevertheless a study has been conducted with an analogue molecule (Similar Substance 03). Further information are reported in the Read Across justification attached to section 13.

The study was performed to assess the skin sensitisation potential of the test sample in the albino guinea pig. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1981) No. 406 "skin Sensitisation" - Magnusson and Kligman Maximisation Test. Twenty test and ten control animals were used for the main study. Following sighting studies, the following concentrations were used in the induction and challenge phases:

Intradermal Induction       5% (w/v) in arachis oil

Topical Induction             50% (w/w) in petroleum jelly

Topical Challenge             50% (w/w) in petroleum jelly; re-challenge at 25% and 10%

 

 

Yellow/green coloured staining of the skin was noted at all test sample sites but did not prevent assessment of the skin responses.

 

Initial Challenge - 50% (w/w)

Positive results were also observed in the negative control group. The sensitisation potential of the test sample could not be evaluated at this concentration. A re-challenge was performed at two lower concentrations.

Re-challenge - 25% and 10% (w/w)

Moderate and diffuse redness (score 2) and scattered mild redness (score 1) were noted at the 25% and 10% test sample re-challenge sites of test animalsat the 24-hour observation and at the 25% test sample re-challenge sites of test animals at the 48-hour observation. Scattered mild redness (score 1) continued to be noted at the 10% test sample re-challenge sites of the test animals at the 48-hour observation. Severe desquamation was noted at a number of 25% test sample re-challenge sites and at one 10% test sample re-challenge site at the 48-hour observation. The 25% and 10% test sample sites of control animals showed no erythema at the 24 or 48-hour observations.

The test sample, therefore, at re-challenge concentrations of 25% and 10%, produced a skin reaction in 85% (17/20) and 80% (16/20) animals, respectively after 24 hours. After 48 hours, a skin reaction was observed in 45% (9/20) and 15% (3/20) atconcentrations of 25% and 10%, respectively.

Bodyweight gains of surviving guinea pigs in the test group, between day 0 and day 24, were comparable to those observed in the control group animals over the same period.

 

The test substance caused positive reactions in more than 30% of animals after 24 hours after removal of the test substance at 10% and 25% test substance contentration. After 48 hours, only the 25% concentration caused skin reddening in more that 30% of test animals.

The test substance is hence considered to be a skin sensitiser at concentrations of 25% and above.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

SKIN SENSITIZATION

Category 1

Substances shall be classified as skin sensitizers in category 1 where data are not sufficient for sub-categorisation in accordance with the following criteria:

(a) if there is evidence in humans that the substance can lead to sensitisation by skin contact in a substantial number of persons; or

(b) if there are positive results from an appropriate animal test.

Specific criteria of animal test:

when an adjuvant type test method for skin sensitisation is used, a response of at least 30 % of the animals is considered as positive.

For a non-adjuvant Guinea pig test method a response of at least 15 % of the animals is considered positive.

Furthermore, stimulation index of three or more is considered a positive response in the local lymph node assay.

Sub-category 1A

Substances showing a high frequency of occurrence in humans and/or a high potency in animals can be presumed to have the potential to produce significant sensitisation in humans. Severity of reaction may also be considered.

Specific criteria:

Local lymph node assay-EC3 value ≤ 2 %

Guinea pig maximisation test-≥ 30 % responding at ≤ 0,1 % intradermal induction dose or ≥ 60 % responding at > 0,1 % to ≤ 1 % intradermal induction dose

Buehler assay - ≥ 15 % responding at ≤ 0,2 % topical induction dose or ≥ 60 % responding at > 0,2 % to ≤ 20 % topical induction dose

Sub-category 1B

Substances showing a low to moderate frequency of occurrence in humans and/or a low to moderate potency in animals can be presumed to have the potential to produce sensitisation in humans. Severity of reaction may also be considered.

Local lymph node assay - EC3 value > 2 %

Guinea pig maximisation test- ≥ 30 % to < 60 % responding at > 0,1 % to ≤ 1 % intradermal induction dose or ≥ 30 % responding at > 1 % intradermal induction dose.

Buehler assay - ≥ 15 % to < 60 % responding at > 0,2 % to ≤ 20 % topical induction dose or ≥ 15 % responding at > 20 % topical induction dose.

 

Based on the results obtained in the in vivo test carried out(Guinea pig maximisation test) and according to the paragraph 3.4. of the CLP Regulation n. 1272/2008, the test substance is classified in Category 1B.