Registration Dossier

Administrative data

Description of key information

not skin sensitising

Key value for chemical safety assessment

Skin sensitisation

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

The following data were obtained for Similar Substance 01. It is expected that the Target Substance will present similar skin sensatisation potential. Justification for the use of a Read Across approach is provided in Section 13 of IUCLID.

The potential of Similar Substance 01 to cause skin sensitisation reactions following topical application to the skin of CBA/JN mice, was assessed using the LLNA:BrdU-ELISA method, according to the OECD Guideline for testing of chemicals No. 442b (2010). Five concentrations [25 (maximum feasible concentration), 10, 5, 2.5 and 1 % w/w in acetone: olive oil 4:1 (v/v)] were tested in the preliminary phase, in order to identify a non toxic and minimally irritant concentration and avoid false positive results. Based on the results observed, in the main assay, Similar Substance 01 was topically administered at the concentrations of 25, 10 and 5 % (w/w), in acetone: olive oil 4:1 (v/v).

No mortality nor clinical signs were recorded in any animal. Changes in bodyweight observed during the study were within the expected range for this strain and age of animals. A slight increase in cell proliferation of draining lymph nodes was observed in the low dose group, with a Stimulation Index of 1.98. The other calculated indices (SI) were 0.95 and 1.28 respectively, in medium and high dose groups. No correlation with the doses nor statistical significance was observed. These results indicate that Similar Substance 01 may elicit a sensitisation response. However, due to the presence of an outlier in the low dose group, the absence of dose-response relationship and statistical significance, the observed reaction is not sufficient to indicate classification.

Similar Substance 02 also tested negative to skin sensitisation potential in the in vivo LLNA assay, according to the EU Method B.42 (2012). In an experimental study on Similar Substance 03, it also tested negative to skin sensitising potential in a different skin sensitisation test, the in vivo Guinea Pig Maximisation Test (GPMT), according to the OECD Guideline 406 (1981) and the EU Method B.6 (1984), whereby 20 Guinea Pigs were administered Similar Substance 03 intradermally and were subsequently challenged topically alongside both negative and positive controls; no animals demonstrated sensitisation after 24 or 48 hours. The presence of consistently negative skin irritation experimental studies across the board supports the use of the read-across approach for estimating the skin sensitising potential of the Target Substance.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

SKIN SENSITISATION

In the CLP Regulation (EC 1272/2008) a skin sensitizer is defined as “a substance that will lead to an allergic response following skin contact”. A substance classified as skin sensitiser (Category 1) may be allocated to one of the two sub-categories 1A or 1B in accordance with the criteria given in Annex I, Part 3, Table 3.4.2.

In case of animal tests, for the reduced LLNA:BrdU-ELISA (OECD TG 442B) the criteria for determining the positive response is different from that of the traditional LLNA (OECD TG 429). Full details are given in the corresponding OECD Test Guidelines. There is no guidance for subcategorisation.

According to the OECD 442B (2010): the decision process regards a result as positive when SI ≥ 1.6. However, the strength of the dose-response relationship, the statistical significance and the consistency of the solvent/vehicle and PC responses may also be used when determining whether a borderline result (i.e. SI value between 1.6 and 1.9) is declared positive. For a borderline positive response between a SI of 1.6 and 1.9, users may want to consider additional information such as dose-response relationship, evidence of systemic toxicity or excessive irritation, and where appropriate, statistical significance together with SI values to confirm that such results are positives. Consideration should also be given to various properties of the test substance, including whether it has a structural relationship to known skin sensitizers, whether it causes excessive skin irritation in the mouse, and the nature of the dose-response observed. These and other considerations are discussed in detail elsewhere.

Based on the results of skin sensitisation of the LLNA: BrdU-ELISA performed on the test substance, there is no dose-response relationship and no statistical significance. Moreover, the SI values obtained in the medium and high dose groups are < 1.6; the only higher SI value obtained in the low dose group is due to an outlier. Considering the aforementioned, no classification for skin sensitization is warranted under the CLP Regulation (EC 1272/2008).