Reaction mass of N-butylphosphorothioic triamide and N-propylphosphorothioic triamide

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Additional information:

Skin sensitisation:

The skin sensitizing potential of LIMUS-Sambaydestillation was assessed using the radioactive Murine Local Lymph Node Assay according to OECD 429 guideline and GLP (BASF, 2009). The assay simulates the induction phase for skin sensitization in mice. It determines the response of the auricular lymph nodes on repeated application of the test substance to the dorsal skin of the ears. Groups of 5 female CBA/J mice each were treated with 3%, 10% and 50% w/w preparations of the test substance in MEK (methyl ethyl ketone) or with the vehicle alone. The study used 3 test groups and 1 control group. Each test animal was applied with 25 μL per ear of the respective test-substance preparation to the dorsum of both ears for three consecutive days. The control group was treated with 25 μL per ear of the vehicle alone. Three days after the last application the mice were injected intravenously with 20 μCi of 3H-thymidine in 250 μL of sterile saline into a tail vein. About 5 hours after the 3H-thymidine injection, the mice were sacrificed and the auricular lymph nodes were removed. The weights of each animal’s pooled lymph nodes were determined. Thereafter lymph nodes were pooled group wise and further evaluated by measuring their cellular content and 3H-thymidine incorporation into the lymph node cells (indicators of cell proliferation). Moreover, a defined area with a diameter of 0.8 cm was punched out of the apical part of each ear and for each test group the weight of the pooled punches was determined in order to obtain an indication of possible skin irritation.

No signs of systemic toxicity were noticed. When applied as 50% preparation in MEK, the test substance induced a biologically relevant response (increase to 1.5 fold or above of control value = stimulation index (SI) ≥ 1.5) in the auricular lymph node cell counts. In addition there was an increase in lymph node weights. Concomitantly, the increase of 3H-thymidine incorporation into the cells was biologically relevant (increase above the cut off stimulation index of 3) at this concentration.

The 50% test-substance preparation caused minimal increase in ear weights as indication of slight ear skin irritation. No biologically relevant changes in lymph node or ear parameters were observed in the animals treated with 10% and 3% test substance preparations. Thus it is concluded that LIMUS-Sambaydestillation shows a skin sensitizing effect in the Murine Local Lymph Node Assay under the test conditions chosen.

The threshold concentration for sensitization induction was >10% <50 %. The estimated concentration that leads to the SI of 1.5 for cell count (EC 1.5) and the estimated concentration that leads to the SI of 3.0 3H-thymidine incorporation (EC 3) were calculated by linear regression from the results of the 10% and 50 % concentrations to be 26.1 % and 12.8 % respectively.

Migrated from Short description of key information:
LLNA: sensitizing (BASF, 2009)

Justification for classification or non-classification

According to the findings of the available study, the test substance has to be classified R43 (Directive 67/548/EEC) and Skin sensitisation Cat. 1B (CLP).