Is it possible to assess the allergenicity of mixtures based on in chemico methods? Preliminary results on common fragrance aldehydes

Abstract

Most perfume compositions and cosmetics contain mixtures of fragrance ingredients, synthetic or extracted from natural sources. Many of these are known to be weak or moderate allergens when tested individually. However, fragrances are one of the most common causes of allergic contact dermatitis to consumer products, ranking second after nickel. As consumers are exposed to mixtures of ingredients when using products that contain perfume, it was suggested that mixtures could enhance induction and elicitation of skin allergy to fragrances. Prediction of skin sensitization to chemicals is crucial for the cosmetics industry. Nowadays, methods to assess skin sensitization hazard replacing the use of animals have been developed and validated for the testing of pure substances. However, there is practically no experience with testing of mixtures. Here we evaluated in a very preliminary approach, and from a chemical reactivity perspective, if the validated DPRA, hapten‐peptide reactivity based assay, could be used at a first sight to evaluate the chemical reactivity of mixtures. Two simple binary combinations of fragrance aldehydes were studied, hydroxycitronellal‐citral and citral‐cinnamaldehyde. Their reactivity towards DPRA peptides was compared with that of the single constituents. In general, the chemical described as the most potent sensitizer was driving the reactivity in the mixtures. Therefore, it could be hypothesized that the DPRA would estimate the mixture chemical reactivity similar to that of the stronger sensitizer component. This will be reinforced by conditions described for the DPRA where the tested chemical or mixture of chemicals will be added in large excess to the peptides. Copyright © 2016 John Wiley & Sons, Ltd.

Contact allergy to citral and its constituents geranial and neral, coupled with reactions to the prehapten and prohapten geraniol

“…This could be due to the enhanced effect of mixtures, requiring lower test concentrations to elicit a contact allergic reaction. 29 In the mixture of oxidation products from autoxidized geraniol, strongly sensitizing geraniol hydroperoxides were detected in addition to geranial and neral. The oxidation mixture of geraniol at 10 weeks contained geraniol 59% (wt/wt), geranial 4.6%, neral 1.2%, and geraniol hydroperoxide 3.7%.…”

“…It should be noted that eight of 43 patients reacted only to citral and not to either geranial or neral. This could be due to the enhanced effect of mixtures, requiring lower test concentrations to elicit a contact allergic reaction …”

Chemical Compounds Responsible for Skin Allergy to Complex Mixtures: How to Identify Them?

“…The chemical described as the most potent sensitizer was leading the reactivity in the mixtures. Consequently, it was hypothesized that DPRA would estimate the reactivity of the mixture similar to that of the stronger sensitizer component [9]. KeratinoSens TM was attempted as an in vitro assay for plant extracts [10].…”

In chemico skin sensitization risk assessment of botanical ingredients

“…The in chemico method Direct Peptide Reactivity Assay (DPRA), has been recently tested with binary mixtures (Lang, Giménez‐Arnau, & Lepoittevin, ), but its optimization for the assessment of more complex formulations is still at early developmental stages. Yet, the applicability of chemical methods for predictive screening of mixtures is desirable and certainly needed to provide complementary information to aid the prioritization of more extensive toxicological studies.…”