Free radicals in antigen formation: reduction of contact allergic response to hydroperoxides by epidermal treatment with antioxidants.

BACKGROUND: For patients with allergic contact dermatitis, the main therapy is anti-inflammatory steroids, a non-specific and symptomatic treatment. In contact allergy, the antigen formation is considered to be the binding of a chemical (hapten) to a biological macromolecule, e.g. a protein. Limonene-2-hydroperoxide (Lim-OOH) is a hapten with a known allergenic effect. It is likely to bind to proteins in the skin via a radical mechanism. It might be possible to inhibit the allergic reaction by epidermal application of substances that can trap free radicals, e.g. antioxidants such as ascorbic acid or alpha-tocopherol, prior to the application of the hapten. OBJECTIVES: To study the influence of antioxidants on the allergenic effect of Lim-OOH in sensitization experiments on guinea pigs. METHODS: Pretreatment with the antioxidants was performed before induction to study the effect on sensitization as well as before challenge testing to study the effect on elicitation. RESULTS: A reduction in the response rate was found both at sensitization and at elicitation. The antioxidants had no effect on cobalt allergy or on the allergenic effect of haptens that form antigens via nucleophilic-electrophilic reactions. No reduction of the effect was seen for irritants. CONCLUSIONS: The protective effect of antioxidants in elicitation could be of practical therapeutic value, as it indicates a possibility for the treatment of patients who have become sensitized to haptens that form full antigens via a radical mechanism.

Contact allergens from surfactants. Atmospheric oxidation of polyoxyethylene alcohols, formation of ethoxylated aldehydes, and their allergenic activity.

Ethoxylated surfactants are susceptible to oxidation upon air exposure. We have previously studied the rate of peroxidation and formaldehyde formation in the chemically well-defined ethoxylated alcohol C12H25(OCH2CH2)5OH. Formaldehyde is a common cause of contact allergy. The aim of the present study was to identify other oxidation products that could be formed upon air exposure of the ethoxylated alcohol and to determine their allergenic activity. It was shown that air oxidation of C12H25(OCH2CH2)5OH gave all the theoretically possible aldehydes of the general formula C12H25(OCH2CH2)nOCH2CHO (n = 0-4) and that the major oxidation product was C12H25(OCH2CH2)4OCH2CHO, dodecyltetraoxyethyleneoxyacetaldehyde. The structure elucidation and synthesis of these aldehydes are here presented for the first time. The major aldehyde was shown to be a contact allergen with the same sensitizing capacity as that of formaldehyde. A dose-response relationship was observed in the sensitization studies. The allergens were formed from the surfactant itself and the skin reactions cannot be explained due to any impurities that may be present in a technical quality of the surfactant. Cases of allergic contact dermatits to ethoxylated surfactants have been reported. To avoid the formation of allergenic oxidation products it is important to control the conditions for storage, handling, and transportation of ethoxylated surfactants.

Percutaneous absorption of organic solvents during intermittent exposure in guinea pigs.

Skin absorption under intermittent exposure of guinea pigs to n-butanol, toluene, 1,1,1-trichloroethane was studied. Groups of guinea pigs were exposed to test organic solvents for 1 min at 30-min intervals during 4 h, in all 8 exposures. Skin absorption of solvent was assessed by following the concentration of solvent in the blood. This intermittent exposure was compared to continuous exposure over 4 h. Absorption of toluene and 1,1,1-trichloroethane was low, but a considerable amount of butanol was absorbed through the skin on intermittent exposure. A typical serrated absorption profile was seen for butanol that was less pronounced for toluene and 1,1,1-trichloroethane. The absorption of butanol was highest at the end of the exposure period. The differences in absorption profiles may be due to the differences in vapour pressure in the solvents in association with the animal method used. The amount absorbed varied inversely with vapour pressure. Hair stubble may act as a trap for solvents with low vapour pressure. Adequate ventilation reduces unoccluded skin absorption of volatile organic solvents.

Maleopimaric acid--a potent sensitizer in modified rosin.

The allergenicity of the maleic-modified rosins and their esters has been studied. The unesterified resins are mainly used in paper size and the esters in printing inks, varnishes and adhesives. The levopimaric-maleic anhydride Diels-Alder adduct (maleopimaric acid) is the main component obtained in the maleic-modified rosins. This compound was synthesized and its structure was determined. Its sensitizing potential was investigated in guinea pigs according to different methods. It was shown that maleopimaric acid is a very potent sensitizer, comparable with the strongest allergen isolated from unmodified gum rosin. The allergen may also be present after esterification unless the process is carried out to completion. The animals sensitized to maleopimaric acid did not react to unmodified rosin, which shows that maleopimaric acid is structurally different from the allergens in rosin.