Abstract
. Several fragrances are important contact allergens. Compared to the immense multitude of more than 2,500 fragrances used in cosmetics, the spectrum of single substances and natural extracts used for patch testing appears limited, albeit comprising the supposedly most important contact allergens. The present review summarizes the most important results of the opinion of the Scientific Committee on Consumer Safety on fragrance allergens in cosmetic products from July 2012. Clinical results beyond abovementioned screening allergens, animal results in terms of the LLNA and structure activity considerations point to 100 single substances and extracts, respectively, which, in addition to those 26 already identified, must be considered contact allergens, and the presence of which should be declared in cosmetics. In case of the most commonly used fragrance terpenes limonene and linalool hydroperoxides resulting from autoxidation constitute the major allergens. These have become available as patch test material recently. Altogether 12 single substances have caused a (very) high number of published cases of sensitization. Thus their use concentration should be (further) reduced or, in case of hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC, e.g., Lyral®), use should be abandoned altogether. This is also recommended in case of oak moss and tree moss due to their content of the strong sensitizers atranol and chloroatranol. As generic maximum dose for the remaining 11 single substances 0.8 µg/cm2 are suggested, which corresponds, under conservative assumptions, a maximum concentration of 100 ppm in the finished product.
Highlights
Compared to the immense multitude of more than 2,500 fragrances used in cosmetics, the spectrum of single substances and natural extracts used for patch testing appears limited, albeit comprising the supposedly most important contact allergens
The present review summarizes the most important results of the opinion of the Scientific Committee on Consumer Safety on fragrance allergens in cosmetic products from July 2012
Clinical results beyond abovementioned screening allergens, animal results in terms of the local lymph node assay (LLNA) and structure activity considerations point to 100 single substances and extracts, respectively, which, in addition to those 26 already identified, must be considered contact allergens, and the presence of which should be declared in cosmetics
Summary
A mixture of fragrances, as is used in a perfume or as a perfume component of a cosmetic product, contains several to several hundred single fragrances. There are important differences among European countries, with lower prevalence in the south [9]; in the USA, sensitization to HICC is significantly less frequent [10], which suggests marked differences regarding exposure (use in products, consumer habits) Another mixture that has been used as a screening allergen for years is Balsam of Peru (Myroxylon pereirae, INCI). The oxidation products of terpenes, like limonene, linalool, geraniol, and linalyl acetate, which are frequently used as fragrances, have been identified to be markedly more potential allergens than the nonoxidized raw substances These results concur with clinical trials in which patch tests using oxidized terpenes resulted in a significantly higher prevalence of sensitization than patch tests using nonoxidized material. I.e., for patients, the process of bioactivation is of high importance as it leads to the necessity to take into account the exposure to mother substances that produce the reaction product against which sensitization is present (e.g., isoeugenol acetate results in isoeugenol after scission of the ester bond, and cinnamyl alcohol is metabolized to cinnamal) [15, 16]
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