Registration Dossier

Administrative data

Description of key information

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 in vivo experimental study performed according to the Guinea Pig Maximisation Test (GPMT) outlined in the OECD Guideline 406 (1981), and the EU Method B.6 (1984).

In a preliminary study, the lowest concentration to produce a positive reaction following intradermal injection was 1.0 % test item, therefore this concentration was selected for intradermal injection in the main study. No skin reactions were observed following epidermal exposure, therefore, the highest concentration tested (25 %) was selected for epidermal application.

The main study comprised an induction followed by two challenges with the test item. During the induction, 10 male and 10 female guinea pigs were administered 3 pairs of 0.1 ml intradermal injections along the lateral borders of a 4 x 4 cm area of a clipped, dorsal skin of the scapular region. The three pairs of injections contained the following: 1st: Freunds' complete adjuvant 50:50 with physiological saline; 2nd: 1 % test item in physiological saline; 3rd: 1 % test item in Freunds' complete adjuvant 50:50 with physiological saline. An additional 5 male and 5 female control guinea pigs were administered the same with the omission of the test item. One week later, the scapular region of all animals was re-clipped and a 4 x 4 cm patch of filter paper, saturated in 25 % test item, was secured to the same site (left flank) with aluminium foil, elastic plaster and impervious adhesive tape for 48 hours. The right flank (control) was treated similarly with physiological saline only. Skin was monitored for erythema and oedema 0, 24 and 48 hours after application. Two weeks later, the first challenge was performed: the flanks of both the test and control animals were clipped (5 x 5 cm area). A 2 x 2 cm patch of filter paper saturated with 25 % test item was applied to the left flank, and another saturated with physiological solution to the right flank, with aluminium foil, elastic plaster and impervious adhesive tape for 24 hours, at which time the dressing was removed and skin was monitored for erythema and oedema 0, 24 and 48 hours after application. Two weeks later, the second challenge was performed, however, the left and right flanks was inverted and the controls received treatment of vehicle only.

No mortality, systemic symptoms or adverse changes in body weights were observed during the study period.

The maximum proportion of animals with positive reactions was 5 % (at 24 hours after the first challenge; at 24 and 48 hours after the second challenge).

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) no. 1272/2008.

According to the CLP Regulation (EC 1272/2008), in a GPMT a substance shall be classified as:

- 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 %;

- 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 %.

Based on the observed reults in the GPMT performed (the maximum proportion of animals with positive reactions was 5 %), the substance does not meet the criteria for skin sensitiser according to the CLP Regulation (EC) no. 1272/2008.