N,N'-dibutyl-N,N'-bis(1,2,2,6,6-pentamethylpiperidin-4-yl)-6-(pyrrolidin-1-yl)-1,3,5-triazine-2,4-diamine

Endpoint summary

Description of key information

In this study the test item was assessed for its skin sensitising potential using the Local Lymph Node Assay (LLNA) in mice (OECD 429, GLP). Test item suspension at different concentrations (1. 2. 5%) was prepared in the vehicle 1% (v/v) aqueous Pluronic®. Based on the above-mentioned findings regarding ear skin irritation, an influence of irritation on lymphocyte proliferation cannot be excluded in the mid and high dose. Nevertheless, on the basis of the present data and the high S.I. of 22.5 obtained in the low dose (1%) without accompanying excessive increase in ear weights, the test item has to be classified as a sensitiser. The EC3 value could not be calculated, since all obtained SI´s were considerably above the threshold value of 3. The test item was found to be a skin sensitiser.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

In this study the test item was assessed for its skin sensitising potential using the Local Lymph Node Assay (LLNA) in mice. Test item suspension at different concentrations (1. 2. 5%) was prepared in the vehicle 1% (v/v) aqueous Pluronic®. The highest concentration tested was the highest concentration that could be achieved whilst avoiding systemic toxicity and excessive local skin irritation (as determined by two pre-experiments). The animals did not show any signs of systemic toxicity during the course of the study and no cases of mortality were observed. On days 3 to 5, the animals treated with a test item concentration of 5% showed an erythema of the ear skin (score 1). Animals treated with 1 and 2% test item concentration did not show any signs of local skin irritation (erythema). However, a statistically significant increase in ear weights was observed in the groups treated with test item concentration of 2 and 5% when compared to the vehicle control group. Furthermore, 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. The indices determined for all test item treated groups exceeded this threshold. The threshold value of 25% increase in ear weights for excessive local skin irritation mentioned in OECD guideline 429 was exceeded in the group treated with a test item concentration of 5%, indicating excessive local skin irritation in the high dose group. But as the ear weights in the mid dose group (2%) showed an increase of 24% and thus, nearly reached the threshold mentioned in the OECD 429, the increased ear weights of the mid and high dose group were attributed to the irritant properties of the test item, but not those of the low dose group with a value of 1.12 (increase of 12%). A test item is regarded as a sensitiser in the LLNA if exposure to one or more test item concentration results in a 3-fold or greater increase in incorporation of 3HTdR compared with concurrent controls, as indicated by the Stimulation Index (S.I.). The estimated test item concentration required to produce a S.I. of 3 is referred to as the EC3 value. In this study Stimulation Indices (S.I.) of 22.5, 33.75 and 41.42 were determined with the test item at concentrations of 1, 2 and 5% (w/w) in 1% aqueous Pluronic®, respectively. A clear dose response was observed. A statistically significant and biologically relevant increase in DPM value and also in lymph node weight and cell count was observed in all dose groups in comparison to the vehicle control group, corroborating the presence of a positive response. Furthermore, the cut-off value of 1.55 for a positive response regarding the lymph node cell count index reported for BALB/c mice was exceeded in all three dose groups (indices of 4.97 in the low dose; 5.61 in the mid dose and 6.15 in the high dose).

Based on the above-mentioned findings regarding ear skin irritation, an influence of irritation on lymphocyte proliferation cannot be excluded in the mid and high dose. Nevertheless, on the basis of the present data and the high S.I. of 22.5 obtained in the low dose (1%) without accompanying excessive increase in ear weights, the test item has to be classified as a sensitiser.

The EC3 value could not be calculated, since all obtained SI´s were considerably above the threshold value of 3.

The test item was found to be a skin sensitiser.

Migrated from Short description of key information:
In this study the test item was assessed for its skin sensitising potential using the Local Lymph Node Assay (LLNA, OECD guideline 429, under GLP) in mice. Test item suspension at different concentrations (1, 2 and 5%) was prepared in the vehicle 1% (v/v) aqueous Pluronic®. A statistically significant and biologically relevant increase in DPM value and also in lymph node weight and cell count was observed in all dose groups, corroborating the presence of a positive response. Furthermore, the cut-off value of 1.55 for a positive response regarding the lymph node cell count index reported for BALB/c mice was exceeded in all three dose groups. The EC3 value could not be calculated, since all obtained SI´s were considerably above the threshold value of 3. The test item was found to be a skin sensitiser.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is considered to be classified for skin sensitization under Directive 67/548/EEC.

                               

Classification, Labeling, 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 is considered to be classified for skin sensitization under Regulation (EC) No. 1272/2008.