Analytical methodologies for common skin allergens : Organic thioureas, isothiocyanates and fragrance hydroperoxides in everyday life products

Abstract: This thesis describes analytical methodologies for the determination of important skin-sensitizing chemicals in two types of commercial items: chloroprene rubber and fragrance products which are both well-known to be associated with contact allergy.Chloroprene rubber (neoprene) is widely used in different applications and products, such as bags, gloves, wetsuits, braces, mouse pads et c. Exposure to chloroprene rubber materials has resulted in numerous cases of allergic contact dermatitis. Organic thioureas have been considered the main culprits, even though they at the same time have been classified as weak or non-sensitizers in the murine local lymph node assay (LLNA). Previous findings indicate that a possible reason for sensitization is that organic thioureas are being metabolized in the skin into more reactive electrophiles, such as isothiocyanates and isocyanates, after skin exposure. In this thesis, chemical analyses of a number of chloroprene products from the European open market showed the presence of diethylthiourea in all analyzed items, while other organic thioureas could not be detected. The levels of diethylthiourea varied, with the highest at 158 µg cm-2 in a used back support that had previously caused allergic contact dermatitis in a patient. Furthermore, it was discovered that all the examined items emitted ethyl isothiocyanate. LLNA showed that ethyl isothiocyanate is a strong skin sensitizer, as has been shown earlier for other tested isothiocyanates. Isothiocyanates were shown to be thermally formed from diethyl, diphenyl and dibutylthiourea at a temperature as low as 35 °C, i. e. around skin temperature. Altogether, the results from these experiments, patch tests and chemical analyses revealed that isothiocyanates are important haptens in contact allergy to chloroprene rubber.Fragrances constitute one of the main causes of contact allergy, next to nickel and preservatives. The most widespread fragrances in cosmetics and perfumes on the market are monoterpenes, such as linalool and limonene, which at air exposure easily oxidize to hydroperoxides, which are strongly skin sensitizing compounds and the main haptens. Despite this, there is so far no EU regulation concerning fragrance hydroperoxides in products, which may be due to lack of analytical methods which can reliably measure them in fragrances. Presented in this thesis is a toolbox of different analytical methods, applied on essential oils, shampoo, patch test preparations and different types of perfumes. Furthermore, one of our studies elucidated the first case (to my knowledge) of allergic contact dermatitis as being correlated to a product that contains a fragrance hydroperoxide.Taken together, the thesis shows the importance of developing analytical methods for the identification, measurement and detection of important haptens in contact allergy. 

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