Sensitivity to fragrance ingredients is acknowledged as a common and clinically important problem in Europe. At least 1-2% of the general population is allergic (delayed hypersensitivity) to standard indicators of fragrance chemical allergy, which makes contact sensitisation to fragrances the most common cause of contact eczema, next to nickel. At the present time, there is no treatment, other than symptomatic, for fragrance hypersensitivity reactions and the only means available to improve public health in this sector is prevention. The proposed programme aims to increase the safety standard of fragrance compounds by improving primary and secondary prevention. Our objectives are to develop a new risk assessment strategy based on chemical analysis and Quantitative Structure Activity Relationships, to identify new fragrance sensitises, to improve diagnostic means and to assess environmental exposure. This will be achieved through a unique research structure associating university, governmental and industrial research centres, with a trans-European clinical network.
The Fragrance Allergy project respected the whole milestones proposed for the research programme. The different tasks achieved by each workpackage are resumed below.
WP1: A new method has been developed and validated for the identification of sensitizers in complex mixtures using the model of oak moss. The method is based on the combination of bioassay-guided chemical fractionation, gas chromatography-mass spectrometry analysis and structure-activity relationship studies. Atranol and chloroatranol have been identified as major sensitizers in oak moss absolute. A minor sensitizer, methyl-b-orcinol carboxylate, has also been identified.
WP2: The oxidative degradation at air exposure of fragrance terpenes has been studied for limonene, linalool, caryophyllene and myrcene. Different oxidation products have been identified in the oxidised samples e.g. hydroperoxides, alcohols and epoxides. The prevalence of sensitization to these oxidised compounds has been evaluated in the clinical network and showed that there is a risk of contact allergy in the population caused by the oxidised fragrance chemicals studied. It has also been shown that addition of anti-oxidants before air exposure makes these terpenes stable for several months.
WP3: Reliable quantitative structure-activity relationships (QSARs) have been developed for two chemical families of common fragrance allergens: aliphatic aldehydes and a,b-unsaturated aldehydes. Knowledge derived from these QSARs is available to be incorporated into expert toxicity prediction systems.
WP4: Hand exposure to fragrance allergens has been assessed by chemical analysis of domestic and occupational products. Based on this exposure assessment a new diagnostic screening series with 14 compounds has been established and tested on a large number of patients with hand eczema. 10% of the patients gave a positive test to one or more of the allergens in the new series.
WP5: A new diagnostic tool, the Fragrance Mix II (FM-II), has been developed and complements the currently used Fragrance Mix (FM-I). The FM-II is constituted by 6 new fragrance allergens: 4-(4-hydroxy-4-methylpentyl)-3-cyclohexene carboxaldehyde, citral, farnesol, citronellol, a-hexylcinnamic aldehyde and coumarin. Testing within the clinical network confirms that the new FM-II is a valuable tool for identifying subjects with a positive history of adverse reactions to fragrances. 30-50% of these patients would have been missed with the old FM-I.
WP6: The hand immersion technique has been used to assess relations that could exist between hand exposure to fragrance chemicals present in household products and chronic hand eczema. No relation could be evidenced for the 4-(4-hydroxy-4-methylpentyl)-3-cyclohexene carboxaldehyde and hydroxycitronellal models.
WP7: Fragrance allergens giving rise to significant problems in the consumer have been identified. Experimental studies in sensitized patients have shown that these allergens currently are used at unacceptable levels in consumer products causing significant disease in the consumer. This programme has provided data on no-effect levels that, if considered in risk assessment, will lead to safer environment and decreased disease. The results will be submitted to the EU-Commission for taking legislative action.
WP8: Testing within the clinical network with isoeugenol and its derivatives has suggested that isoeugenol ether derivatives may be a safer substitute than ester derivatives in isoeugenol allergic subjects. On another hand, the rate of isoeugenol allergy has not yet shown a consistent decline since the reduction in levels in cosmetic products. The knowledge gained will contribute to EU policy on fragrance allergen substitution.
Funding SchemeCSC - Cost-sharing contracts
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