Fragrance Allergens, Overview with a Focus on Recent Developments and Understanding of Abiotic and Biotic Activation

Abstract

Fragrances and fragranced formulated products are ubiquitous in society. Contact allergies to fragrance chemicals are among the most common findings when patch-testing patients with suspected allergic contact dermatitis, as well as in studies of contact allergy in the general population. The routine test materials for diagnosing fragrance allergy consist mainly of established mixes of fragrance compounds and natural extracts. The situation is more complex as several fragrance compounds have been shown to be transformed by activation inside or outside the skin via abiotic and/or biotic activation, thus increasing the risk of sensitization. For these fragrance chemicals, the parent compound is often non-allergenic or a very weak allergen, but potent sensitizers will be formed which can cause contact allergy. This review shows a series of fragrance chemicals with well-documented abiotic and/or biotic activation that are indicative and illustrative examples of the general problem. Other important aspects include new technologies such as ethosomes which may enhance both sensitization and elicitation, the effect on sensitization by the mixtures of fragrances found in commercial products and the effect of antioxidants. A contact allergy to fragrances may severely affect quality of life and many patients have multiple allergies which further impact their situation. Further experimental and clinical research is needed to increase the safety for the consumer.

Oxidation products and the skin – the effect of hydroperoxides

“…Patch test studies have shown the overall frequencies of contact allergy to different oxidized fragrance compounds to range between 0.1% and 8% of the tested patients . These frequencies are largely comparable to the frequencies of reactions observed for fragrance mix I and fragrance mix II in the established baseline series for the diagnosis of contact allergy .…”

“…The patient's history and concomitant reactions to other markers of fragrance allergy are important to assess. All clinical studies have shown that ∼40% of the patients reacting to oxidized fragrance terpenes also react to fragrance markers in the baseline series . Also, the study by Bennike et al showed a clear association between reactions to the terpene hydroperoxides and reactions to the fragrance markers in the baseline series .…”

“…Furthermore, in the 1980s, hydroperoxides of abietic acid and dehydroabietic acid were shown to be the major haptens in colophonium (rosin) . Since the 1990s, the skin‐sensitizing activity of hydroperoxides from various fragrance monoterpenes has been investigated both experimentally and clinically, and it has been repeatedly established that the hydroperoxides are allergenic (in contrast to hydrogen peroxide, which is non‐sensitizing) . It has also been shown that the hydroperoxides act as specific haptens, and mechanistic studies have shown the formation of specific adducts .…”

“…Thus, it is possible to postulate from the structure of a compound where the most stable hydroperoxides should be formed. Hydroperoxides that are stable enough to accumulate have been detected after air exposure of several fragrance terpenes, and they have been shown to be highly sensitizing . On the basis of this, fragrance terpenes that are able to autoxidize and form sensitizing compounds should be considered as prehaptens in structure–allergy relationship (SAR) analyses.…”

Occupational allergic contact dermatitis in Thai spa therapists

“…Occupational allergic contact dermatitis (ACD) in spa therapists is common, and can result in sick leave, change of occupation, and impaired quality of life . Spa products frequently contain fragrance chemicals that are added to obtain the desired aroma . Although it is recognized that sensitization to fragrance chemicals can occur in aromatherapists, the aim of this study was to determine the prevalence of contact dermatitis in spa therapists and to find common related allergens.…”