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:

The skin sensitising potential of the test substance was assessed in a GLP compliant study according to OECD guideline 429 and EU method B.42 (Harlan, 2014). Test substance concentrations selected for the main study were based on the results of a preliminary study. In the main study, three experimental groups of five female CBA/J mice were treated with test substance concentrations of 25, 50 % in propylene glycol (PG), as well as with the undiluted test substance (100 %) on three consecutive days, by open application on the ears. Five vehicle control animals were similarly treated, but with vehicle alone (PG).

Radioactive labeling was used to measure cell proliferations. 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.

The animals did not show any signs of systemic toxicity or local skin irritation during the course of the study and no cases of mortality were observed. Furthermore, no statistically significant increase in ear weights was observed in any of the treatment groups when compared to the vehicle control group. For BALB/c mice, a cut-off value of 1.1 for the ear weight index was reported for a positive response regarding ear skin irritation. None of the indices determined for the test item treated groups reached or exceeded this threshold. Furthermore, the threshold value of 25 % increase in ear weights for excessive local skin irritation mentioned in OECD guideline 429 was not reached or exceeded in any group. In this study SI of 1.40, 1.60 and 2.31 were determined with the test item at concentrations of 25 and 50 % in PG, as well as with the undiluted test item (100 %), respectively.

A statistically significant increase in DPM values but neither in lymph node weight nor –cell count was obtained in all dose groups in comparison to the vehicle control group (p<0.05). Moreover, the cut-off value for a positive response regarding the lymph node cell count index reported for BALB/c mice was not exceeded in any of the test item groups. However this statistically significant increase in DPM values was biologically not relevant, since all SI determined were well below the threshold index of 3 for a positive response concerning skin sensitisation.

Mean DPM/animal values for the experimental groups treated with test substance concentrations 25, 50 and 100 % were 1155.2, 1325.4 and 1912.2 DPM, respectively. The mean DPM/animal value for the vehicle control group was 826.6 DPM. The SI values calculated for the substance concentrations 25, 50 and 100 % were 1.4, 1.6 and 2.31, respectively. The EC3 value could not be calculated, since none of the tested concentrations induced a SI greater than the threshold value of 3.

The test item was not a skin sensitiser under the test conditions of this study.


Migrated from Short description of key information:
LLNA: not sensitising (Harlan, 2014)

Justification for selection of skin sensitisation endpoint:
GLP and guideline compliant study.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available study is considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance does not need to be classified and labelled as skin sensitising under Directive 67/548/EEC, as amended for the 31st time in Directive 2009/2/EC.

 

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance does not need to be classified and labelled as skin sensitising under Regulation (EC) No 1272/2008, as amended for the sixth time in Regulation EC No 605/2014.