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

Contact Dermatitis. 2000 Dec;43(6):351-8. doi: 10.1034/j.1600-0536.2000.043006351.x.


Fragrance materials are among the most common causes of allergic contact dermatitis. The aim of this study was to identify in a perfume fragrance allergens 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 concentrate was used for repeated patch testing and/or repeated open application test on the pre-sensitized patient. The chemical composition of the fractions giving a positive patch-test response and repeated open application test reactions was obtained by gas chromatography-mass spectrometry. From the compounds identified, those that contained a "structural alert" in their chemical structure, indicating an ability to modify skin proteins and thus behave as a skin sensitizer, were tested on the patient. The patient reacted positively to the synthetic fragrance p-t-butyl-alpha-methylhydrocinnamic aldehyde (Lilial), a widely used fragrance compound not present in the fragrance mix. The combination of bioassay-guided chemical fractionation and chemical analysis/structure-activity relationships seems to be a valuable tool for the investigation of contact allergy to fragrance materials.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / adverse effects
  • Aldehydes / analysis*
  • Allergens / adverse effects
  • Allergens / analysis*
  • Biological Assay / methods
  • Dermatitis, Allergic Contact / etiology*
  • Female
  • Gas Chromatography-Mass Spectrometry / methods
  • Humans
  • Middle Aged
  • Patch Tests
  • Perfume / adverse effects*
  • Perfume / chemistry*
  • Structure-Activity Relationship


  • Aldehydes
  • Allergens
  • Perfume
  • lilial