Reaction Mass of 2,6-dimethyloct-7-en-2-ol and 2,6-dimethyloct-7-en-2-yl formate

Endpoint summary

Description of key information

Not reactive in DPRA (OECD TG 442C, GLP)

Negative in KeratinoSens (OECD TG 442D, GLP)

Non sensitising up to 25% in LLNA (OECD TG 429, GLP)

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

In vitro: DPRA

An OECD guideline 442C study, Direct Peptide Reactivity Assay (DPRA), following GLP was used to assess the reactivity and sensitizing potential of the test substance. Solutions of the test substance were successfully analyzed by the validated DPRA analytical method in both the Cysteine and Lysine containing synthetic peptides. There was no to minimal reactivity of both peptides in the presence of the test substance. With an overall depletion of peptide of 0.370% (0.74% and -0.0280% for cysteine and lysine, respectively), the reactivity of the test substance is henceforth classified as “no or minimal” therefore the DPRA prediction is negative.

In vitro: KeratinoSens

An in vitro KeratinoSens (ARE-Nrf2 luciferase reporter) assay was performed in accordance with OECD guideline 442D, following GLP, to assess the skin sensitising potential of the test substance. Two independent experiments were performed. Test concentrations ranged from 0.98 to 2000 μM. Cinnamic aldehyde was used as a positive control. The Imax for the test substance was 1.19 in test 1 and 1.15 in test 2. The Imax for both tests was <1.5 fold compared to the DMSO control and therefore the EC1.5 could not be calculated. The IC30 value was 168.73 μM in test 1 and 153.68 μM in test 2 and the IC50 values were 193.79 μM and 183.52 μM in tests 1 and 2, respectively. Graphs showed no overall dose-response for luciferase induction. All acceptance criteria for the positive control, cinnamic aldehyde, were met. It was concluded that the test substance gave a negative response in the KeratinoSens.

Both of the performed in vitro/in chemico tests (DPRA and KeratinoSens) were negative. Based on the negative results in the two tests, the overall conclusion of the in vitro/in chemico tests is that the test substance has no skin sensitizing potential in accordance with Bauch et al., (2012).

Animals

In a local lymph node assay, performed according to OECD Guideline 429 and GLP, four groups of 4 CBA/Ca female mice were treated on the dorsal surface of both ears once per day for 3 days with 0.5, 1, 2.5, 10, or 25% (w/v) of the test substance or the vehicle alone (ethanol/diethylphthalate in a ratio of 1:3). Exposure to the test substance at 0.5, 1, 2.5, 10 and 25% (w/v) resulted in stimulation indices of 0.9, 0.8, 0.8, 0.9, and 1.4. Therefore, the test material is considered to be a non-sensitiser up to 25% under the conditions of the test.

Human

In four studies with human volunteers in which concentrations were tested of 4 to 10%, no sensitising effects were observed.

Overall conclusion

The negative DPRA and KeratinoSENS lead to the conclusion that Dimyrcetol is negative for sensitisation. This is supported with an LLNA up to 25% not showing skin sensitisation, despite not tested up to 100%,

Reference

Bauch, C., Kolle, S.N., Ramirez, T., Eltze, T., Fabian E., Mehling, A., Teubner, W., van Ravenzwaay, B., Landsiedel, R., 2012, Putting the parts together: Combining in vitro methods to test for skin sensitizing potentials, Regul. Toxicol. Pharmacol., 63, 489–504.

Justification for classification or non-classification

The substance is not a skin sensitiser and therefore it does not need to be classified for skin sensitisation according to EU CLP (EC 1272/2008 and its amendments).