Registration Dossier

Administrative data

Description of key information

LLNA (OECD 429; GLP): sensitizing (BASF SE; 58V0267/10A539)

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

In the chosen key study according to OECD TG 429 and GLP, the skin sensitizing potential of Tetrahydrolinalool was assessed using the radioactive murine Local Lymph Node Assay (BASF SE;58V0267/10A539). Groups of 5 female CBA/CaOlaHsd mice each were treated with 5%, 10% and 50% w/w preparations of Tetrahydrolinalool in methyl ethyl ketone or with the vehicle alone. Each test animal was treated with 25 µL per ear of the appropriate test-substance preparation, applied to the dorsal surfaces 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 with 3H-thymidine. Lymph node response was evaluated by measuring 3H-thymidine incorporation, cell counts and weights of pooled lymph nodes from each animal. In order to obtain an indication of possible skin irritation, ear samples were punched out and the weight of the pooled punches was determined.

Tetrahydrolinalool, applied as 50% or 10% solution, induced a biologically relevant (increase above the cut off Stimulation Index of 3), statistically significant and concentration dependent increase of 3H-thymidine incorporation into the cells from the auricular lymph nodes. These concentrations induced a biologically relevant and statistically significant response in the auricular lymph node cell counts. Statistically significant increases in lymph node weights were noted at 50%, 10% and 5% concentrations. No relevant increases in ear weights were observed, demonstrating the absence of ear skin irritation. Scaling was observed in all animals applied with the 50% Tetrahydrolinalool on study day 5. No test substance related signs of systemic toxicity was noticed.

The threshold concentration for sensitization induction was >5% <10%. The EC3 for 3H-thymidine incorporation and the EC1.5 for lymph node cell counts was found to be 7.6% and 7.4%, respectively.

Thus, it is concluded that Tetrahydrolinalool exhibits a skin sensitizing potential in the murine Local Lymph Node Assay under the test conditions chosen.

Other animal data reported as short summary from secondary source indicate, that Tetrahydrolinalool might be a weak sensitizer when applied at a concentration of 40% on guinea pigs (skin reactions in 3 of 5 animals; Takasago 1999). Skin reactions in 1/5 animals were observed after application of a 20% tetrahydrolinalool concentration and no reactions at a 10% concentration. However, the predictivity of the study for a sensitising potential of the substance is questionable. Data on pretests to assess the maximum non-irritative concentration are not given.

A human maximization test conducted on 32 healthy volunteers did not show any dermal effects at a concentration of 4 % (2760 µg/cm2) tetrahydrolinalool (Epstein 1976) and a human repeated patch test using concentrations up to 0.5% did not show any skin findings in 46 patients (Takenaka 1986).

Taking together, Tetrahydrolinalool is found to be a skin sensitizer in animal studies.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

No information is available.

Justification for classification or non-classification

Taken together, the present data for Tetrahydrolinalool fulfill the criteria laid down in Regulation (EU) 1272/2008, and therefore, a classification as "Skin sensitisation" (Category 1B) is warranted.