3. How can fragrance substance become skin allergens?
Allergenic fragrance substances are usually of low molecular weight chemicals that act as ‘haptens’. This means that they provoke an immune reaction in the body only when attached to a carrier protein.
Some substances are allergenic as such, while others must be ‘activated’ before they become allergenic. Here, science distinguishes between prehaptens and prohaptens. A prehapten is a chemical that is itself non- or low-sensitising, but that is transformed into a hapten outside the skin by simple chemical transformation, for example oxidation by air or photo-activation in the presence of UV light. A pro-hapten is a chemical that is itself non- or low-sensitising but that is transformed into a more potent hapten in the skin (‘bioactivation’) usually via enzyme catalysis. It is not always possible to know whether a particular allergen that is not directly reactive acts as a prehapten or as a prohapten, or both. This is because air oxidation and metabolic bio-activation can often give the same product. Many fragrance substances can act as prehaptens or prohaptens, forming allergens which are more potent than the parent substance.
In the case of prehaptens, it is possible to prevent activation outside the body to a certain extent by different measures, for example preventing exposure to air during handling and storage or adding suitable antioxidants. In the case of prohaptens, the possibility to become activated is inherent to the molecule and activation cannot be avoided by extrinsic measures.
Cross- reactivity has been shown for certain alcohols and their corresponding aldehydes, for example between geraniol and geranial (citral) and between cinnamyl alcohol and cinnamal. Cross-reactivity is also expected between ester derivatives and their parent alcohols, as the esters will be hydrolysed by esterases in the skin. Esters of important contact allergens that can be activated by hydrolysis in the skin are isoeugenol acetate, eugenyl acetate and geranyl acetate, all of which are known to be used as fragrance ingredients. More...