[1α(E),2β]-1-(2,6,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one

Endpoint summary

Description of key information

Skin sensitisation: Skin sensitiser (1A) based on testing in an OECD TG 429.

Delta-damascone is expected not to be a respiratory sensitiser.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

LLNA (key)

In a local lymph node assay, performed comparable to OECD Guideline 429 and GLP, nine groups of 5 CBA/J female mice were treated on the dorsal surface of both ears once per day for 3 days with 0.25, 0.5, 1.0, 2.5, and 5.0% of the test substance, with the vehicle alone (acetone/olive oil in a ratio of 4:1) or with the positive control (isoeugenol) at 0.5, 1, and 5%. The mice were observed daily and no irritation at the dosing site or other signs of toxicity were noted. Three days after the final auricular application, the animals were injected intravenously with 125I- labelled iododeoxyuridine to label proliferating cells. 125I-incorporation was quantified using a gamma counter. The test substance at 1, 2.5, and 5.0% had stimulation indices (SI) > 3. Only for the test substance at 5.0% this was statistically significant (Student's t test). The 5% concentration of isoeugenol resulted in a group SI statistically significantly greater than 3. Since the data indicated that the test article was a skin sensitizer, the EC3 was calculated to be 0.866% and the EC-3 potency value was calculated to be 217 µg/cm2.

LLNA (supporting)

In a local lymph node assay, performed according to OECD Guideline 429 and GLP, five groups of 5 CBA/J female mice were treated on the dorsal surface of both ears once per day for 3 days with 7.5%, 15% or 30% (w/v) of the substance, with the vehicle (diethyl phthalate/ethanol in a ratio of 3:1) or with the positive control (35% hexylcinnamaldehyde).On Day 6 the mice were injected intravenously with 20 μCi of 3H-thymidine in sterile saline. Five hours later, the mice were euthanized and the draining auricular lymph nodes were removed. The lymph node cells were precipitated with 5% trichloroacetic acid (TCA) and the pellets counted in a beta-scintillation counter to determine incorporation of the 3H-thymidine. Exposure to the test substance at 7.5, 15 and 30% (w/v) resulted in stimulation indices of 1.95, 5.70 (p<0.01), and 4.24 (p<0.05), respectively (Statistically significant compared to the vehicle control group). Since the data indicated that the test article was a skin sensitiser, the EC3 was calculated to be 9.6% (w/v).

HRIPT test

The skin sensitising potential of the test substance was evaluated in a repeated insult patch test with 54 human volunteers (Techni-Med Consultants, Inc., 1982). The substance, tested as 1% solution, was applied for 24 hours 4 consecutive weeks for a total of 9 applications. Skin reactions were scored after 24 hours exposure. After 2 weeks rest period, the subjects were rechallenged at a virgin site for 24 hours and the reactions were scored over a period of 3 days. The substance was found to be capable of sensitizing 7 out of the 54 individuals.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Respiratory sensitisation can be assessed using human data such as indicated in R7.3.5.2 of the ECHA guidance (2014) that indicate respiratory reactions e.g. from consumer experience or occupational exposure. In the absence of such data for delta-damascone, the respiratory sensitisation was assessed using the integrated evaluation strategy for respiratory sensitisation data in the ECHA guidance (R7A, Fig. 7.3-2, 2014). Delta-damascone is not expected to be of concern for respiratory sensitisation. According to the REACH guidance on respiratory sensitisation (R.7.3) the substance is not expected to be a respiratory sensitiser because its structure does not contain (di)isocyanate groups which are known for causing such an effect (Scheme of R.7A, Fig. 7.3-2). Delta-damascone also does not contain any structural alerts mentioned in the document on respiratory effects of the EU Scientific committee e.g. iso-thiocyanates, amines, anhydrides, acrylates, diazonium salts, reactive dyes or metals http://ec.europa.eu/health/scientific_committees/reports/index_en.htm, select Annex VI).

Justification for classification or non-classification

Based on the available data, Delta-damascone has to be classified as 1A, H317: May cause an allergic skin reaction in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 and its amendments.

Since Delta-damascone does not have a structural alert for respiratory sensitisation classification and labelling for respiratory sensitisation is not warranted.