Identification of Lilial (R) as a fragrance sensitizer in a perfume by bioassay-guided chemical fractionation and structure-activity relationships

Fragrance materials are among the most common causes of allergic contact de rmatitis. The aim of this study was to identify in a perfume fragrance alle rgens not included in the fragrance mix, by use of bioassay-guided chemical fractionation and chemical analysis/structure-activity relationships (SARs ). The basis for the investigation was a 45-year-old woman allergic to her own perfume. She had a negative patch test to the fragrance mix and agreed to participate in the study. Chemical fractionation of the perfume concentr ate was used for repeated patch testing and/or repeated open application te st on the pre-sensitized patient. The chemical composition of the fractions giving a positive patch-test response and repeated open application test r eactions was obtained by gas chromatography-mass spectrometry. From the com pounds identified, those that contained a "structural alert" in their chemi cal structure, indicating an ability to modify skin proteins and thus behav e as a skin sensitizer, were tested on the patient. The patient reacted pos itively to the synthetic fragrance p-t-butyl-alpha -methylhydrocinnamic ald ehyde (Lilial(R)), a widely used fragrance compound not present in the frag rance mix. The combination of bioassay-guided chemical fractionation and ch emical analysis/structure-activity relationships seems to be a valuable too l for the investigation of contact allergy to fragrance materials.