Ann-Therése Karlberg

Air oxidation of d‐limonene (the citrus solvent) creates potent allergens

Products containing as much as 95% of d‐limonene are used for, e.g., degreasing metal before industrial painting and for cleaning assemblies. Experimental studies on the sensitizing potential of limonene show diverging results. In a previous study, we found that the sensitizing potential of d‐limonene increased with prolonged air exposure. The aim of 1 his study was to make further chemical analyses, to identify compounds formed by air exposure of d‐limonende and to study their allergenic potential. d‐limonene was found lo be a sensitizer after prolonged exposure to air according to 2 Freunds complete adjuvant test (FCAT) experiments and I guinea pig maximization test (GPMT) study. No significant response was obtained to d‐limonene air exposed, even if the animals were sensitized to oxidized d‐limonene. 5 main oxidation products of d‐limoncne were identified. (R)‐(–)‐carvone and a mixture of cis and trans isomers of (+)‐limonene oxide were found to he potent sensitizers, while no significant reactions were obtained m the animals induced with 8 mixture of cis and trans isomers of (–)‐carveol. It can be concluded that air oxidation of d‐limonene is essential for its sensitizing potential, and that potent allergens are created.

The chemistry of contact allergy: why is a molecule allergenic?

This review concentrates on some specific aspects of the chemistry of allergic contact dermatitis. The way low molecular weight chemicals react with skin proteins to form complete antigens will be discussed and the development of molecular modelling techniques to analyse molecular recognition presented. Subsequently, how knowledge of the chemical structure can be used to estimate the allergenic activity of a molecule will be considered. This aspect includes work with qualitative and quantitative structure‐activity relationships (SAR) in the field of contact allergy.

Identification of 15-Hydroperoxyabietic Acid as a Contact Allergen in Portuguese Colophony

Abstract— 15‐Hydroperoxyabietic acid (15‐HPA) has been isolated from Portuguese colophony of the gum rosin type and identified as its methyl ester. The structure of the compound was elucidated using UV, IR, NMR and mass spectrometry. 15‐HPA methyl ester was found to be an elicitor when tested in colophony‐sensitized guinea‐pigs. The sensitizing capacity was verified in the same species and 15‐HPA methyl ester was considered to be a strong allergen. The eliciting potential was also verified in patients with known allergy to colophony. The Portuguese gum rosin investigated contained approximately 1% of 15‐HPA. Based on its allergenicity and the amounts isolated, we conclude that 15‐HPA is a main contact allergen in Portuguese gum rosin.

Contact allergy to dehydroabietic acid derivatives isolated from Portuguese colophony

7‐oxodehydroabietic acid and 15‐hydroxydehydroabietic acid were isolated as their methyl esters from Portuguese colophony of the gum rosin type and identified as contact allergen. Another oxidation product of dehydroabietic acid, 15‐hydroxy‐7‐oxodehydroabietic acid, was synthesized and identified as a component of Portuguese gum rosin. 7‐oxodehydroabietic acid was found to a be a grade III allergen according to the GPMT method. Guinea pigs induced with gum rosin showed only a low response to the isolated compounds, while patients with a known allergy to gum rosin reacted to a greater extent. The result imply that the content of oxidized dehydroabietic acids in gum rosin is too low to give a marked sensitization in the animals. However, the patients might have come in contact with the allergens in technically modified rosins. The compounds showed a pattern of cross‐reactivity in the animal experiments as well as among the patch tested patients.

The Practical Approach

In this chapter, we illustrate how an understanding of chemistry can help solve practical allergy problems: Chemical analysis can identify the actual allergen, which need not be the primary chemical constituent of a product, but may be a contaminant arising in the synthesis or production of the product or one formed during its storage and handling. The physicochemical parameters affect the bioavailability and hence the allergenic properties of a given molecule.

Analysis of contact allergenic compounds in oxidizedd-limonene

SummaryA detailed chemical analysis and quantification of oxygen-containing monoterpenes in auto-oxidizedd-limonene was performed. Some of these, e.g. the cis- and trans-isomers of limonene-2-hydroperoxide, have previously been shown to exhibit strong contact allergenic properties. GC-MS with chemical ionization in negative ion mode was shown to be a successful method for the identification and determination of the molecular weight of chemically unstable limonene hydroperoxides. An HPLC method for isolation of individual compounds in auto-oxidizedd-limonene is presented. Two different stationary phases were used in normal phase mode, cyanopropyl- and diamino-modified silica. The method described can be used for the isolation of individual contact allergens in sensitization experiment vehicles, such as petrolatum and olive oil. This makes it possible to study whether test compounds, such as hydroperoxides, are chemically stable during a sensitization experiment.

Skin symptoms and contact allergy in woodwork teachers

To estimate the occurrence of skin symptoms and the prevalence of contact allergy occupational allergens, 84 mule woodwork teachers were interviewed, clinically examined and patch tested, The tests included a supplemented European standard series and acetone extracts of wood dust of pine spruce, juniper and birch. In addition. 10 colophony‐allergic Volunteer were tested with dilution series of wood dust extracts. Major colophony compounds in the dust extracts were analyzed with gas chromatography. We round a high 1‐year period prevalence of generally mild hand eczema: 19%. Contact allergy was diagnosed to several allergens in the working environment, e.g., benzisothiazolin‐3‐one. Nickel, formaldehyde and colophony. A clear relationship between patch test reactions to colophony and to coniferous woods, especially pine, was found. Exposure to wood dust at work caused dermatitis in a colophony‐sensitized teacher

Experiences with Freund's complete adjuvant test (FCAT) when screening for contact allergens in colophony.

A procedure, using Freunds complete adjuvant test (FCAT), for the determination of the allergenic potential of fractions and components in colophony of the gum rosin type is described and discussed. Gum rosin was shown to be a potent sensitizer in 11 test series (153 animals). FCAT is compared with the guinea pig maximization test (GPMT). Gum rosin was a potent sensitizer according to this method as well. The FCAT method was found to be advantageous over the GPMT method in that it is technically simpler to use and a smaller amount of test substance is needed. However, closed challenge was preferred to the prescribed open challenge. The importance of statistical evaluation of the results obtained in predictive testing is stressed.

Detection of rosin (colophony) components in technical products using an HPLC technique

A method for detection of rosin (colophony) in technical produces has been developed. The technique, using HPLC, is based on the analysis of abietic acid and dehydroabietic acid, major components of rosin. In the procedure described in this paper, the limit of detection was 0.001% for abietic acid and 0.015% for dehydroabietic acid. An average recovery of 88.9% for abietic acid and 88.2% for dehydroabietic acid was obtained. The lowest detectable amount of abietic acid (0.001%) corresponds to a content of 0.003% unmodified rosin in the product, assuming that the resin acid content in rosin is 90%, of which 30–50% is abietic acid. This is an acceptable limit compared to the reactivity in patients with known allergy in rosin. Technical products for analysis were supplied by different Swedish manufacturers, who also gave the approximate content of rosin in the various products. The content of rosin determined in the products was in accordance with the contents, given by the manufacturers.

Maleopimaric acid ― a potent sensitizer in modified rosin

The allergenicity of the maleic‐modified rosins and their esters has been studied. The unesterified resins arc 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 sensitising 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 lion 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.