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Diss Factsheets

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Additional information:

In the chosen key study according to OECD TG 429 and GLP, the skin sensitizing potential of Nerolidol was assessed using the radioactive murine Local Lymph Node Assay (BASF SE; 58V0466/09A141). Groups of 5 female CBA/CaOlaHsd mice each were treated with 1%, 5% and 25% w/w preparations of Nerolidol in methyl ethyl ketone or with the vehicle alone. The absence of relevant formation of peroxides in the test substance preparations was confirmed analytically. 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.

When applied as 1%, 5% and 25% preparation in MEK, Nerolidol induced a statistically significant increase of 3H thymidine incorporation into the cells of the auricular lymph nodes, which was above the cut-off value for skin sensitization (increase above the cut off Stimulation Index (SI) of 3) at the 25% concentration. The SI for 3H thymidine incorporation of the 5% test substance preparation was found to be at the border of biological relevance. Concomitantly, the 25% test substance preparation induced a statistically significant and biologically relevant response (increase to 1.5-fold or above of control value = SI ≥ 1.5) in the auricular lymph node cell counts. The increase in cell counts of the 5% test substance preparation was statistically significant as well, but the SI failed the border of biological relevance. All concentrations induced statistically significantly increased lymph node weights.

No Nerolidol related signs of systemic and local toxicity was noticed, and Nerolidol did not cause relevant increases (SI > 1.25) in ear weights demonstrating the absence of relevant ear skin irritation. However, a statistically significant increase in ear weights was noted at the 25% preparation.


In a local lymph node assay with several deviations from the standart protocol (non-radioactive test setup only, divergent data evaluation), the application of the structurally related, natural trans-nerolidol (CAS 40716-66-3) extracted from Cabreuva oil resulted in an EC1.4 of 18.33% or 12.79% (for two different batches tested) on the basis of the lymphocyte counts per lymph node (Robertet 2008). No information on the content of autooxidation products such as peroxides in the tested substance was provided. On the basis of increased ear weights and ear thickness, dermal irritation has been observed after application of undiluted test substance only.

No skin sensitization reactions were observed in studies using guinea pigs. In an Open Epicutaneous Assay, epidermal induction of daily topical open applications (21 applications) of nerolidol over a 3-week period, followed by topical applications as challenge on day 21 and day 35 at the non-irritating concentration (4%) did not result in skin sensitization reactions (Klecak 1985).

In a Draize test, intradermal injection of 2.5% Nerolidol as induction, followed by a 14 day rest period and challenge via intradermal injection in one flank (1%) and topical administration on the other (20 %), did not lead to skin sensitizing reactions (Sharp 1978).

Human data are available from a human maximization test and several patch tests on dermatitis patients. In a human maximization test available as short summary, occlusive dermal application to the same site on the forearms of 25 volunteers for five alternate-day 48 hour periods, followed by a 10-day rest period and an occlusive dermal challenge application using 4 % (2760 µg/cm2) nerolidol in petrolatum did not produce any sensitization reactions (Kligman 1973). Patch testing of a 73 year old female patient with pigmented contact dermatitis using 5% nerolidol did not result in dermal reactions (Hayakawa 1987). Further patch testing on 2 dermatitis patients using propolis products resulted in positive skin reactions whereas patch testing with 5% nerolidol did not result in skin reactions (Kato 1999). However, in two further publications sporadic positive skin reactions to nerolidol were reported for single individuals. Three out of 54 individuals and 3 out of 102 individuals reacted positively to 50% nerolidol in olive oil and 1% nerolidol in petrolatum, respectively (Hjorth 1961, Hausen 2001).

Taking together, Nerolidol is found to be a skin sensitizer.

Justification for classification or non-classification

The present data on dermal sensitization fulfill the criteria laid down regulation (EU) 1272/2008, and therefore, a classification with "Skin sensitisation" (Category 1B) is warranted.