Lina Hagvall

Limonene hydroperoxide analogues differ in allergenic activity

Background:  The fragrance terpene R‐limonene is a very weak sensitizer but forms allergenic oxidation products upon contact with air. Oxidized (ox.) limonene is a frequent cause of contact allergy in clinical testing.

Contact allergy to air-exposed geraniol: clinical observations and report of 14 cases

Background. The fragrance terpene geraniol forms sensitizing compounds via autoxidation and skin metabolism. Geranial and neral, the two isomers of citral, are the major haptens formed in both of these activation pathways.

Mechanism of Air Oxidation of the Fragrance Terpene Geraniol

The fragrance terpene geraniol autoxidizes upon air exposure and forms a mixture of oxidation products, some of which are skin sensitizers. Reactions of geraniol with O2 have been studied with DFT (B3LYP) and the computational results compared to experimentally observed product ratios. The oxidation is initiated by hydrogen abstraction, forming an allylic radical which combines with an O2 molecule to yield an intermediate peroxyl radical. In the subsequent step, geraniol differs from previously studied cases, in which the radical chain reaction is propagated through intermolecular hydrogen abstraction. The hydroxy-substituted allylic peroxyl radical prefers an intramolecular rearrangement, producing observable aldehydes and the hydroperoxyl radical, which in turn can propagate the radical reaction. Secondary oxidation products like epoxides and formates were also considered, and plausible reaction pathways for formation are proposed.

Air-oxidized linalool elicits eczema in allergic patients – a repeated open application test study

Linalool is a commonly used fragrance terpene that forms potent sensitizers upon oxidation. In a recent multicentre study, we found that 7% of 2900 patients showed positive patch test reactions to oxidized linalool at 6.0%. No elicitation studies have been performed.

Finding the optimal patch test material and test concentration to detect contact allergy to geraniol.

Background. Geraniol is a commonly used fragrance terpene, and is tested in the baseline series in fragrance mix I. Geraniol is a pro‐hapten and a pre‐hapten, and sensitizers are formed in the autoxidation and skin metabolism of geraniol. Previous patch testing with air‐exposed (oxidized) geraniol has suggested that oxidized geraniol could be a better marker for contact allergy to geraniol than pure geraniol.

Experimental and theoretical investigations of the autoxidation of geranial: a dioxolane hydroperoxide identified as a skin sensitizer.

The autoxidation of geranial with O(2) was studied both experimentally and using density functional theory. Computational results were used to interpret experimentally observed product ratios. Geranial was found to autoxidize, forming 6,7-epoxygeranial as the main oxidation product. Hydroperoxides corresponding to those identified as important skin sensitizers in previous studies of fragrance terpenes could not be detected. Instead, a dioxolan derivative and its corresponding hydroperoxide were identified and detected in high concentrations. The distribution of products in autoxidation generally depends on the stabilities of the intermediate peroxyl radicals. In this study, the formation of a peracyl radical was found to be highly favored. This radical forms peracid which epoxidizes geranial. The epoxide thus produced can react with acyl radical to yield the dioxolan hydroperoxide. The dioxolan derivative is believed to form in an acid catalyzed closed shell reaction between 6,7-epoxygeranial and geranial. The dioxolan hydroperoxide and 6,7-epoxygeranial are strong sensitizers and are considered to be the compounds mainly responsible for the skin sensitization potency of air-exposed geranial.

Occupational contact dermatitis caused by sodium cocoamphopropionate in a liquid soap used in fast-food restaurants.

We report here 2 cases of occupational contact dermatitis aggrevated by contact allergy to sodium cocoamphopropionate, a surfactant present in the disinfectant soap used at the workplace. The patients worked in fast-food restaurants of multinational chains, where hygiene routines require very frequent hand washing. To the best of our knowledge, these are the first cases of contact allergy to sodium cocoamphopropionate.

Characterization of skin sensitizers from autoxidized citronellol – impact of the terpene structure on the autoxidation process

Citronellol is a frequently used fragrance compound in consumer products. It is present in fragrance mix II, which is used for screening of contact allergy to fragrances. Because of its chemical structure, citronellol could be susceptible to autoxidation.

Cross‐reactivity between citral and geraniol – can it be attributed to oxidized geraniol?

The fragrance compound geraniol is susceptible to autoxidation when in contact with air, and to cutaneous metabolism. In both processes, the isomeric aldehydes geranial and neral are formed. Citral consists of geranial and neral. Among patients with positive reactions to citral, we have previously detected concomitant reactions to geraniol in 85% of cases and to oxidized geraniol in 73% of cases.

Air-oxidized linalyl acetate – an emerging fragrance allergen?

Linalyl acetate is a fragrance chemical that is prone to autoxidation. Exposure to linalyl acetate occurs through cosmetic products and essential oils, but is difficult to assess, as linalyl acetate is not labelled in the EU.