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Administrative data

Description of key information

No in vitro skin sensitization studies were conducted because adequate data from an in vivo skin sensitization study were available, and this study was initiated before October 11th 2016.

Based on the results of the Local Lymph Node Assay (LLNA), the test item was not regarded as a skin sensitizer (van San, 2018, OECD 429).

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

No in vitro skin sensitization studies were conducted because adequate data from an in vivo skin sensitization study were available, and this study was initiated before October 11th 2016.

In this study, three experimental groups of five female CBA/J mice were treated with test item concentrations of 0.25, 0.5 or 1% w/w on three consecutive days, by open application on the ears. Five vehicle control animals were similarly treated, but with vehicle alone (Acetone/Olive oil (4:1 v/v)).

Three days after the last exposure, all animals were injected with 3H-methyl thymidine and after five hours the draining (auricular) lymph nodes were excised and pooled for each animal. After precipitating the DNA of the lymph node cells, radioactivity measurements were performed. The activity was expressed as the number of Disintegrations Per Minute (DPM) and a stimulation index (SI) was subsequently calculated for each group.

No erythema of the ears in any of the animals examined, no mortality occurred, and no clinical signs of systemic toxicity were observed in the animals of the main study. All auricular lymph nodes of the animals of the experimental and control groups were considered normal in size. No macroscopic abnormalities of the surrounding area were noted for any of the animals.

Mean DPM/animal values for the experimental groups treated with test item concentrations 0.25, 0.5 and 1% were 1005, 948 and 1282 DPM, respectively. The mean DPM/animal value for the vehicle control group was 634 DPM. The SI values calculated for the test item concentrations 0.25, 0.5 and 1% were 1.6, 1.5 and 2 respectively.

There was no indication that the test item elicits a SI ≥ 3 when tested up to 1%. It was established that the EC3 value (the estimated test item concentration that will give a SI =3) (if any) exceeds 1%. 

Based on these results, T001598 at concentration up to 1% was not regarded as a skin sensitizer according to the recommendations made in the test guidelines.

However, based on the fact the maximum dose tested was based on the systemic toxicity observed at this dose level, based on additional information on structurally similar compounds and based on the predictions obtained in the DEREK Nexus assessment of T001598, the test item is considered to be a skin sensitizer category 1B. A justification document to support this classification based on a weight of evidence approach is attached to this endpoint summary.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

In the LLNA study, 1% was the highest concentration of T001598 tested in the main test. Testing at higher concentrations was not considered due to observed systemic toxicity. Structurally related substances were classified as skin sensitizers (T001596 and T001597 as skin sensitizers category 1B).

The Derek Nexus assessment of T001598 confirms that the substance can be considered to be a moderate sensitizer.

Taking all available information into consideration, the registrant considered self-classification of the test subtsance T001598 as skin sensitizing category 1B in a precautionary approach, according to the criteria laid down n the CPL Regulation 1272/2008.