reaction product of: C.I. Leuco Sulfur Black 1 with (3-chloro-2-hydroxypropyl)trimethylammonium chloride

Endpoint summary

Description of key information

Not a skin sensitiser

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitisation potential was evaluated in an experimental study according to the "Buehler Test" (Guinea Pig Sensitisation Testing by the Buehler Topical Closed Patch Technique by Ritz, H.L., and Buehler, E.V., 1979) as specified in the OECD Guideline 406 (1992) and the EU Method B.6 (1992).

An induction screening test was first performed (four female animals were administered 10, 15, 25 and 50 % (w/w) to four different quadrants of the back for 6 hours and were monitored for erythema and oedema 24 and 48 hours after exposure), which established a representative concentration for immune hypersensitivity stimulation of 50 % (w/w) test item in bi-distilled water. In the induction application, 20 female animals were administered 50 % (w/w) test item in bi-distilled water to the left, cranial, posterior quadrant of the back for 6 hours, three times spaced one week apart. Erythema and oedema were assessed after 24 hours.

A challenge screening test was first performed (four female animals were administered 10, 15, 25 and 50 % (w/w) to four different quadrants of the back for 6 hours and were monitored for erythema and oedema 24 and 48 hours after exposure), which established 50 % (w/w) test item as an appropriate challenge test concentration based on the highest non-irritating concentration. On test day 29, the test animals plus an additional group of control animals (10 females) were administered 50 % (w/w) test item in bi-distilled water for 6 hours, one time to the left, caudal, posterior quadrant of the back. Erythema and oedema were assessed 24 and 48 hours after patch removal.

One animal from the test group was found dead on day 14. Post-mortem macroscopic examination demonstrated strong red discolouration in the lungs of this animal. One induction screening animal and one challenge screening animal lost weight during their treatment. No skin reactions were observed among test or control animals after the challenge performed with test item at the highest non-irritating concentration 50 % in bi-distilled water.

Therefore, the substance has no skin sensitising potential.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Skin sensitiser means a substance that will lead to an allergic response following skin contact. Sensitisation includes two phases: the first phase is induction of specialised immunological memory in an individual by exposure to an allergen. The second phase is elicitation, i.e. production of a cell-mediated or antibody-mediated allergic response by exposure of a sensitised individual to an allergen. For respiratory sensitisation, the pattern of induction followed by elicitation phases is shared in common with skin sensitisation. For skin sensitisation, an induction phase is required in which the immune system learns to react; clinical symptoms can then arise when subsequent exposure is sufficient to elicit a visible skin reaction (elicitation phase). As a consequence, predictive tests usually follow this pattern in which there is an induction phase, the response to which is measured by a standardised elicitation phase, typically involving a patch test. Usually, lower levels are necessary for elicitation than are required for induction.

According to the CLP Regulation (EC 1272/2008), substances showing (a) a high frequency of occurrence in humans and/or (b) a high potency in animals can be presumed to have the potential to produce significant sensitisation in humans. Specifically, a substance shall be classified as a Category 1A Skin Sensitiser if 15 % or more of test animals respond to topical induction dose of ≤ 0.2 %, or if 60 % or more of test animals respond to a concentration > 0.2 % to ≤ 20 %, in a Buehler Assay.

Substances showing (a) a low to moderate frequency of occurrence in humans and/or (b) a low to moderate potency in animals can be presumed to have the potential to produce sensitisation in humans. Specifically, a substance shall be classified as a Category 1B Skin Sensitiser if at least 15 % but < 60 % of test animals respond to a topical induction dose of > 0.2 % to ≤ 20 %, or if 15 % or more of test animals respond to a concentration of > 20 %, in a Buehler Assay.

Substances shall be classified as Category 1 Skin Sensitisers 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 numer of persons; or (b) if there are positive results from an appropriate animal test. This may include positive data from patch testing, normally obtained in more than one dermatology clinic, epidemiological studies showing allergic contact dermatitis caused by the substance (situations in which a high proportion of those exposed exhibit characteristic symptoms are to be looked at with special concern, even if the number of cases is small), positive data from appropriate animal studies, positive data from experimental studies in man, and/or well documented episodes of allergic contact dermatitis (normally obtained in more than one dermatology clinic). The severity of the reaction may also be considered.

No test or control animals responded to a dermal application challenge of 50 % test item in the "Buehler Assay" (Guinea Pig Sensitisation Testing by the Buehler Topical Closed Patch Technique, 1979); therefore, the substance cannot be considered a Skin Sensitiser, and therefore no classification is warranted according to the CLP Regulation (EC 1272/2008).