Linalool

Endpoint summary

Description of key information

Skin sensitisation

In a human Repeated Insult Patch Test which was conducted with 135 human volunteers according to a usual accepted protocol for this type of study, no increase in skin sensitisation reaction was observed after treatment with 12.7% test substance compared to the concurrent solvent controls. It was concluded that the test substance has no sensitising properties.

 

Dermal absorption

In a toxicokinetic study, one male subject was dermally exposed to massage oil containing 0.5% linalool and 0.6% linalyl acetate. Linalool and linalyl acetate blood levels were detectable 5 minutes after application and were eliminated almost completely after 90 minutes. It was concluded that linalool is absorbed in the blood after dermal application in humans, but is also readily excreted.

Additional information

Skin sensitisation, human, RL1

The senstiziting potential of 12.7% linalool was tested in this human Repeated Insult Patch Test (RIPT). Saline and the vehicle (1:3 EtOH:DEP) were used as control. The skin of 135 human subjects, 45 male and 90 female, was repeatedly exposed (induction, rest, challenge phase) to three patches containing all three substances. During induction, 9 applications of the substance were done in three weeks. Following a rest period of 2 weeks, a challenge was done by application of the same substance on the other side (previously untreated) of the back. Erythema and also edema were assessed and scored after every application period (induction and challenge). In the challenge phase, reactions were scored at 0, 24, 48 and 72 hours after removal of patch with test substance. 119 subjects completed the study (36 male and 83 female). During induction phase 6 reactions were noted for saline, 4 reactions for linalool, and 2 reactions for the vehicle. All reactions were faint, minimal erythema. Linalool only induces slight erythema in one out of 117 and 119 subjects assessed at second and third reading after challenge. 5 reactions after challenge (faint, minimal erythema to erythema) were seen in the saline group. 2 reactions (faint, minimal erythema) were observed in the vehicle group. No difference in effects was observed between application of the test substance and the control substances. When considering the criteria outlined in Annex I of Regulation (EC) No. 1272/2008, linalool will not have to be classified as a sensitiser up to a concentration of 12.7%.

 

Dermal absorption, human, RL2

The dermal absorption of lavender oil (in massage oil) containing linalool was studied in one male human subject. Massage oil was massaged onto the skin for ten minutes. In total 7.23 mg linalool was applied, which corresponds with a dose of 0.12 mg/kg bw. Linalyl acetate dose was 8.64 in total, representing 0.144 mg/kg bw. Subsequently, the concentration of linalool and linalyl acetate in the blood was determined at several time points by GC-FID and GC-MS. The experiment was repeated three times in the same subject for statistical evaluation. Toxicokinetic parameters were estimated with an open two-compartment standard pharmacokinetic model. The results indicate that linalool and linalyl acetate can be detected in the blood after absorption through skin within 5 minutes after application. The mean plasma concentration (100 ng/mL linalool, 121 ng/mL linalyl acetate) is reached after 19 minutes. Within 90 minutes linalool has been eliminated almost completely. Calculated AUC of linalool is 4927.25 (ng/mL)min, for linalyl acetate this was 4174.50 (ng/mL)min, indicating that the concentration of linalool is significantly higher than that of linalyl acetate. Under the conditions of this test, it can be concluded that linalool and linalyl acetate are absorbed in the blood after dermal application in humans, but are also readily excreted.