Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

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

Dermal sensitization potential of the test substance (i.e. PC2414) was investigated using the local lymph node assay in accordance with OECD Guideline for Testing of Chemicals 429 and EEC method B42. Groups of 5 female mice (CBA/CaOlaHsd) were dosed at 0% (control), 10%, 25% and 50% solutions of PC2414 in DMSO. Stimulation index (SI) values were 3.54, 3.32 and 3.50 for the 10%, 25% and 50% dose groups, respectively. The EC3 value could not be calculated, due to flat dose response. Based on the SI values, PC2414 was suggested to be a skin sensitizer in this assay.

Positive and vehicle controls were within the range to ensure the validity of the test, such that a positive control SI value of 3.25 was obtained at a dose of 15%. This result was from the latest positive control study performed by the testing laboratories (Harlan Laboratories) on June 2010 using α-Hexylcinnamaldehyde (15%), and was in the low part of range but still within the range of positive control data.

Even though PC2414 was found to be a skin sensitizer based on the SI values, it is emphasized that no dose response was established and statistical significant results only obtained using 10% and 25% PC2414. On the other hand, in the vast majority of assays conventional dose responses are recorded with sensitizing chemicals such that increasing concentrations of the allergen provoke increasingly more vigorous proliferative responses. In some instances, as in this study, the dose response profile was relatively flat suggesting either that saturation kinetics for absorption have been achieved or that maximal immune stimulation has been induced.

 

Based on the SI values obtained in this study, the result is evaluated to be a “borderline result” because no dose response was established and significant results only obtained using 10 and 25% PC2414. Therefore, it is evaluated that the obtained results are a "false positive". In support, an initial qualitative prediction of the possible toxicity of PC2414, based on the chemical structure, was performed using the DEREK software for Windows system (LHASA Limited). A number of toxicological endpoints, including skin sensitization, were investigated by this predictive software and no alerts were trigged by the structure of PC2414 (see attached document below). Further, testing showed that PC2414 was not corrosive and not irritating to skin and eye (see section 7.3.1 and 7.3.2).

Consequently, the result is a “borderline result”, and thus it is evaluated that the positive result obtained in this study is a "false positive" and that PC2414 is not a skin sensitizer.


Migrated from Short description of key information:
PC2414 was found to be a skin sensitiser in the LLNA study using concentrations of 10, 25 and 50%. Based on the SI values obtained in this study, the result is though evaluated to be a “borderline result” because no dose response was established and significant results only obtained using 10 and 25% PC2414. Further, the SI values were all only very slightly above 3.

Overall, because of the result being a “borderline result”, it is evaluated that the positive result obtained in this study is a "false positive" and that PC2414 is not a skin sensitizer.

Justification for classification or non-classification

PC2414 was found to be a skin sensitiser in the LLNA study using concentrations of 10, 25 and 50%. The result is though evaluated to be a “borderline result” because no dose response was established and significant results only obtained using 10 and 25% PC2414. Further, the SI values were all only very slightly above 3. Therefore, it is evaluated that the obtained results are a "false positive". In support, no toxicological alerts including skin sensitization were trigged by the structure of PC2414 using DEREK prediction software.Further, testing showed that PC2414 was not corrosive and not irritating to skin and eye.

Overall, because of the result being a “borderline result”, it is evaluated that the positive result obtained in this study is a "false positive" and that PC2414 is not a skin sensitizer.

Based on these results, it is evaluated that PC2414 is not hazardous and should not be classified according to GHS and DSD-DPD and in accordance with the criteria in Council Directive 67/548/EEC and Regulation (EC) 1272/2008.