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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

For testing of skin sensitization, the optimization test was used, an intracutaneous sensitization procedure similar to the method recommended in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959), the US Association of Food and Drug Officials (AFDO). A second study is available adressing the skin sensitization potential in the presence of UV light (photosensitization.). A polymer containing the substance was tested in the Human Repeat Insult Patch Test (Ciba-Geigy 1979).

The key study was performed on groups of 10 male and 10 female guinea pigs of the Pirbright white strain. No results of a positive control group are reported, but this test was routinely run at these laboratories and sufficient experimental data is contained in the sponor's archive.

During the induction period the animals received one injection every second day (except weekends) to a total of 10 intracutaneous injections of a freshly prepared 0.1 % dilution in polyethylene glycol (PEG 400) + saline (70 : 30 parts). On the first day, injections of 0.1 ml were administered into the shaven skin of the right flank and the back, while on the following days a single intracutaneous injection was given into the back. During the second and third week of the induction period the test material was incorporated in a mixture of the normal vehicle with complete Bacto Adjuvant. Fourteen days after the last sensitizing injection, a challenge injection of 0.1 ml of a freshly prepared 0.1 % dilution in polyethylene glycol (PEG 400) + saline (70 : 30 parts) was administered into the skin of the left flank. Twenty-four hours after each injection during the first week of the induction period and 24 hours after the challenge injection the reactions were recorded. Ten days after the intracutaneous challenge injection a subirritant dose of the test compound at 5% in vaseline was applied epicutaneously under occlusive dressings which were left in place for 24 hours. Upon intradermal challenge 12/20 test group animals and 1/20 control group animals showed a skin reaction, whereas after epicutaneous exposure, none of the 20 animals showed skin reactions. This shows that the substance needs to be actively injected into the skin in order to elicit a reaction. From the investigations on subacute oral toxicity, it is known that the substance causes an infiltration of macrophages in the gastrointestinal epithelium which evolves into a granulomatous inflammation at higher doses or longer duration. It is likely that a similar effect is observed upon intradermal injection which would yield high local doses.

A modified protocol was applied to investigate the potential of the substance to cause sensitization in the presence of UV light in each 10 male and female guinea pigs (Ciba-Geigy 1980). Guinea pigs were treated by dermal application with the test substance und irradiated with visible light plus UV-A or UV-A and UV-B for a total of 3 weeks. The first and the second challenges were performed after rest periods of 12 days and a further 14 days. The skin reaction were evaluated according to Draize Scoring Scale.

As vehicle, 80% DAE433 (40% Dimethylacetamide, 30% acetone, 30% ethanol) was used and the concentration for induction and challenge was 0.1%. Epicutaneous open exposure was used.

In the control group, one animal showed a weak reaction at the first challenge. In the test group, one animal showed scaling formation at the end of the first induction week. Slight scaling formation was observed in the test group at the end of the second challenge. Erythema was not observed. The intensity of the skin reactions and the incidence does not show a significant difference to the control group.

Migrated from Short description of key information:
The substance caused no skin sensitization in guinea pigs in the Maurer Optimization test with epidermal challange exposure. No indication of photo-sensitization was observed.

Justification for selection of skin sensitisation endpoint:
The other study adresses photo-sensitization.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for skin sensitization under Directive 67/548/EEC, as amended for the 31st time in Directive2009/2/EG.


Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for skin sensitization under Regulation (EC) No. 1272/2008, as amended for the third time in Directive (EC 618/2012).

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