Investigation of the skin sensitizing activity of linalool.

An increasing range of chemicals appears to be capable of causing skin sensitization as a result of their capacity to undergo air oxidation (autoxidation) with the consequent formation of reactive species such as epoxides and hydroperoxides. In this small investigation, the ability of linalool, a common fragrance ingredient, to cause such effects was quantified using the local lymph node assay before and after careful purification by vacuum distillation. The commercially available grade of linalool (97% purity) was shown to be a weak skin sensitizer. Various impurities, including linalool oxide, dihydrolinalool, epoxylinalool, 3-hexenyl butyrate and 3,7-dimethyl-1,7-octadiene-3,6-diol were identified and were completely removed (except for the dihydrolinalool remaining at 1.4%) and the re-purified linalool retested. Neither linalool or dihydrolinalool are protein-reactive compounds. The sensitization potency of the re-purified linalool sample was considerably reduced, but not entirely eliminated, suggesting either that an allergenic impurity could be very quickly reformed by mechanisms of activation or that certain potent undetectable allergens remained. Both possibilities are consistent with what is understood of the chemistry and composition of commercially available linalool.