Registration Dossier

Diss Factsheets

Administrative data

Description of key information

OECD 406, GPMT; Not 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 Guinea Pig Maximisation Test (GPMT), comparable to the OECD Guideline 406 (1981). A separate, preliminary study found that the test item was non-irritant to skin, so the following test concentrations were determined as appropriate: 5.0 % (w/v) in distilled water and in adjuvant for induction by intradermal injection; and 25 % (w/v) in distilled water for induction by topical induction and for the challenge applications.

Induction: 10 male and 10 female guinea pigs were administered 3 pairs of 0.1 ml intradermal injections along the side of a 4 x 6 cm area on the clipped shoulder region. The three pairs of injections contained the following: 1. 0.1 ml 5.0 % (w/v) test item in distilled water; 2. 0.1 ml Complete adjuvant (50 % v/v in water); 3. 0.1 ml 5.0 % (w/v) test item emulsified in 50 % (v/v) Complete adjuvant. An additional 5 male and 5 female control guinea pigs were administered three pairs of injections containing: 1. 0.1 ml distilled water; 2. 0.1 ml Complete Adjuvant (50 % (v/v) in water); 3. 0.1 ml Complete Adjuvant (50 % (v/v) in water. One week later, the same region was re-clipped and a 2 x 4 cm patch of Whatman No. 3 filter paper, saturated in 25 % (w/v) test item (test group) or vehicle (control group), was secured using overlapping occlusive tape for 48 hours.

Challenge: Two weeks later, the flanks of test and control animals were clipped (5 x 5 cm area). 2 x 2 cm patch of filter paper saturated with 25 % test item was applied to the left flank, and another saturated with distilled water to the right flank, with overlapping occlusive tape for 24 hours, at which time the dressing was removed. Skin reactions were recorded 24 and 48 hours after the dressing was removed.

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.

The Guinea Pig Maximisation Test (GPMT) is a two-phase, in vivo sensitisation test involving initial intradermal injection of the substance and an adjuvant and subsequent epidermal exposure to evaluate sensitisation potential in guinea pigs which may be applicable to humans. A significant skin sensitising effect following the GPMT is defined as "redness (score ≥ 1) in ≥ 30% of the test animals", according to the CLP Classification Criteria (EC 1272/2008).

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 30 % or more of test animals respond to an intradermal induction concentration of ≤ 0.1 %, or if 60 % or more of test animals respond to a concentration > 0.1 % to ≤ 1 %, in a GPMT.

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 30 % but < 60 % of test animals respond to an intradermal induction concentration of > 0.1 % to ≤ 1 %, or if 30 % or more test animals respond to a concentration of > 1 %, in a GPMT.

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 an intradermal induction concentration of 5.0 % test item followed by a subsequent dermal application challenge of 25 % test item in the Guinea Pig Maximisation Test (GPMT); therefore, the substance cannot be considered a Skin Sensitiser, and therefore no classification is warranted according to the CLP Regulation (EC 1272/2008).

Based on the read across considerations same results apply to the target substance

Categories Display