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Administrative data

Description of key information

In a guinea pig maximization test according to OECD TG 406, no adverse skin reactions were observed in any animal after intradermal (5%), epicutaneous (undiluted) induction and epicutaneous (undiluted) challenge treatment with octocrilene.

Key value for chemical safety assessment

Skin sensitisation

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

In the chosen key study for skin sensitization, i.e. a guinea pig maximization test performed according to OECD TG 406 under GLP, 10 Dunkin-Hartley guinea pigs were treated with 5% Octocrilene in paraffin oil with/without Freund`s Adjuvans for intradermal induction and undiluted Octocrilene for occlusive epicutaneous induction on day 7, followed by an occlusive epicutaneous challenge with the undiluted Octocrilene 14 days after the epicutaneous induction (BASF 2001; 30H0495/002167). The intradermal induction caused intense erythema and swelling and the epicutaneous induction caused partially open incrustation, moderate and confluent erythema and swelling in all test group animals. No adverse skin reactions were observed in any animal of the test or control group after challenge treatment. Based on the results of this study it was concluded, that Octocrilene does not have a sensitizing effect on the skin of the guinea pig in the Maximization Test under the test conditions chosen.

In a supporting study, i.e. a guideline compliant guinea pig maximization test under GLP, 20 Dunkin-Hartley guinea pigs were treated intradermally with 50% test substance (Octocrilene, not further specified) in paraffin oil with/without Freund`s Adjuvans and the test substance as such for semiocclusive epicutaneous induction on day 7 (EVIC-CEBA 1991; K 544/3606). Animals were challenged on day 21 with a semiocclusive epicutaneous application of the test substance as such. No cutaneous reaction at the challenge site was observed in treated (and in control) animals. No sensitization potential of the test substance Octocrilene (not further specified) was detected under the conditions of this test.

In a local lymph node assay (LLNA), reported in literature with insufficient documentation, Octocrilene was applied to 3 female CBA/Ca mice per dose group at 1%; 2.5%; 5%; 15%; 30% in acetone/olive oil (4:1 v/v) on the dorsum of the ears daily for three consecutive days (Karlsson et al. 2011). After intravenous injection of [3H]thymidine 5 days after the first treatment, thymidine incorporation was measured by β-scintillation counting in the draining lymph nodes pooled for each treatment group. The resulting SI values were 1.3; 1.63; 2.25; 5.01 and 4.38 for the 1%; 2.5%; 5%; 15%; 30% dose groups, respectively. The EC3 was calculated as 7.7% by interpolation. Thus, Octocrilene was determined to be a moderate skin sensitizer according to the authors.

Several limitations of the LLNA were identified and question the relevance of these findings, that are in contrast to the results of the guideline studies in guinea pigs. The study was not performed under quality assurance according to the OECD Good Laboratory Practice Guideline and in deviation from the current OECD guideline, e.g. a lower animal number (i.e. 3 instead of min. 4 animals) per group were used in this study. No information on variability within the groups is available, since the lymph nodes of the animals in one dose group were pooled. Furthermore, the test concentrations were no evenly spaced 2-fold and it remains unclear due to limited documentation, if precipitation with trichloroacetic acid has been done prior to liquid scintillation counting. The citation does not provide results with positive control substances to demonstrate the reliability of procedures performed.

Possible UV-irradiation of the mice from windows or laboratory lighting was not controlled in the LLNA published by Karlsson and coworkers. In literature, a variety of human patch test data provide evidence for photoallergic reactions due to Octocrilene exposure and a correlation of these effects with photosensitisation to ketoprofen is evident. Karlsson and others have identified a very high concordance of positive photopatch test reactions to ketoprofen and Octocrilene. Since the endpoint photosensitization is beyond the scope of REACh and is not part of the standard information requirements as lined out in the REACh Annex VII-X, this aspect is not further elaborated. However, with regard to discussion of skin sensitising properties of Octocrilene, the LLNA study of Karlsson et al. is limited as the relevant parameter UV irradiation has not been controlled. Therefore, the study does not suffice to demonstrate skin sensitization properties of Octocrilene in the absence of UV light.

In a human repeated insult patch test, Octocrilene has been tested on 205 volunteers in a lotion containing 3 additional UV filter (Dermatology Research, 1992). The test substance contained a combination of Octocrilene (10%), avobenzone (4%), oxybenzone (5%) and octyl salicylate (5%) and has been applied for 24 hours under occlusive patch conditions 3 times per week for 3 consecutive weeks. After a resting period of 14 days, a challenge and rechallenge patch has been applied for 48h using the same test substance formulation. After the first challenge application, 1 individual with a skin grading score 1 (Macular, faint erythema) was observed. After the second challenge application, no skin findings were observed in any of the tested individuals. Thus, it is concluded, that under these exaggerated exposure conditions, no allergic skin reactions were observed, which further supports the absence of a skin sensitization potential of Octocrilene under use conditions.

 

Overall, based on the guideline key and supportive studies in guinea pigs, using a very stringent exposure regimen (i.e. intradermal induction in the presence of Adjuvans and occlusive dermal application of undiluted test substance), Octocrilene is not considered to be a skin sensitizer. 


Respiratory sensitisation

Endpoint conclusion
Additional information:

No data available.

Justification for classification or non-classification

The present data on dermal sensitization do not fulfill the criteria laid down in 67/548/EEC and CLP, and therefore, a non-classification is warranted.