Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

In order to assess the cutaneous allergenic potential of Y-15099, the Maximization-Test was performed in 15 (10 test and 5 control) female albino guinea pigs, in accordance with OECD Guideline No. 406 (Arcelin, 2001). The intradermal induction of sensitization in the test group was performed in the nuchal region with the undiluted liquid test item (100%). The epidermal induction of sensitization was conducted for 48 hours under occlusive conditions with the undiluted test item one week after the intradermal induction and following pre-treatment of the test areas with 10% Sodium-Lauryl-Sulfate (SLS) 24 hours prior to application of the test item. The animals of the control group were treated with 10% SLS only. Two weeks after epidermal induction the control and test animals were challenged by epidermal application of the undiluted test item under occlusive dressing. Cutaneous reactions were evaluated at 24 and 48 hours after removal of the dressing.

No toxic symptoms were evident in the guinea pigs of the control or test group. No deaths occurred. Eight (at the 24 -hour reading) and 9 (at the 48 -hour reading) out of 10 test animals showed discrete/patchy to moderate/confluent erythema after the challenge treatment with Y-15099 at 100%. No skin effect was observed in the control group. Thus, the test substance showed a skin sensitising potential under the conditions of this guinea pig maximisation test.

Y-15099 was evaluated as provided to determine its ability to sensitize the skin of normal volunteer subjects using a semi-occlusive standard repeated insult patch study procedure with nine 24 -hour induction applications and one 24 -hour challenge application (Dosik, 2002). Ninety-eight subjects completed the study.

One subject presented evidence of possible sensitization at challenge. Re-challenge was conducted under semi-occlusive conditions 2 weeks later. Reactions of erythema and oedema with papules were present. Two weeks after completing re-challenge, the subject participated in a Provocative Use phase. Product application was stopped by the subject after 6 applications due to "itching and redness". She was observed the following day and presented erythema and papules spreading beyond the open application area. Sensitization was confirmed with re-challenge and provocative use. Under the conditions employed in this study, there was evidence of sensitization to Y-15099.

The sensitization potential of Y-15099 was evaluated in a modified Buehler study according to OECD guideline 406 (Morris, 2001). Test groups of 10 male and 10 female Hartley albino guinea pigs were dosed topically with the undiluted test article weekly for a total of three induction exposures under occlusive conditions. The duration of each exposure was six hours. Two weeks after the last induction exposure, Test Group animals were challenge-dosed for detection of sensitization by topical application of the test article (10% concentration diluted in peanut oil) to previously unexposed areas of skin. The test article concentrations used for induction and challenge dosing were selected from range-finding results of the Primary Irritation Phase. A Naive Control Group of five male and five female guinea pigs was dosed a challenge in the same manner as the Test Group and served as irritation control. Reactions to challenge dosing were evaluated at approximately 24 and 48 hours after completion of exposure. Body weights and clinical observations were recorded a randomization (study day -1) and at study termination (study day 28). Positive control data were not generated as part of this study. The WIL Research Laboratories historical positive control data from a study conducted within six months of this test were used to demonstrate the reliability of the experimental design.

There were no deaths, test article-related clinical findings or remarkable body weigh changes in the main study. The number of animals with positive skin reactions upon challenge treatment was similar between treatment and control groups. Thus under the conditions of this study a clear interpretation of the results was judged to be difficult.


Migrated from Short description of key information:
Y-15099 was found to be sensitising in a guinea pig maximisation test and a human volunteer repeated insult patch test. Ambiguous results were found in a Buehler study.

Justification for classification or non-classification

According to DSD (67/548/EEC) or CLP (1272/2008/EC) classification criteria for sensitisation, Y-15099 has to be classified as skin sensitiser.

DSD: Xi, R43: May cause sensitisation by skin contact.

CLP: Category 1, H317: May cause an allergic skin reaction.