Compendium of the most significant studies with reference to properties, intake, effects.
Uter W. Contact allergy to fragrances: current clinical and regulatory trends. Allergol Select. 2017 Aug 4;1(2):190-199. doi: 10.5414/ALX01604E.
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.
Nardelli A, Giménez-Arnau E, Bernard G, Lepoittevin JP, Goossens A. Is a low content in atranol/chloroatranol safe in oak moss-sensitized individuals? Contact Dermatitis. 2009 Feb;60(2):91-5. doi: 10.1111/j.1600-0536.2008.01478.x.
Abstract. Background: Chloroatranol and atranol are degradation products of chloroatranorin and atranorin, respectively, and have been identified as important contact allergens in oak moss absolute (Evernia prunastri). Objectives: To investigate whether chemically modified extracts of oak moss produce positive patch test reactions in previously sensitized subjects....Results: The chemically modified sample reacted negatively in six but gave still positive reactions in eight subjects, with the same intensity as the commercially available oak moss patch test materials. Conclusions: Polymer-based treatment of oak moss extract reduces the allergenic elicitation potential in previously sensitized individuals only to a minor extent. The residual concentrations of atranol and chloroatranol being less than 75 p.p.m. and 25 p.p.m., respectively, are unsafe for the consumer.
Johansen JD, Bernard G, Giménez-Arnau E, Lepoittevin JP, Bruze M, Andersen KE. Comparison of elicitation potential of chloroatranol and atranol--2 allergens in oak moss absolute. Contact Dermatitis. 2006 Apr;54(4):192-5. doi: 10.1111/j.0105-1873.2006.00814.x.
Abstract. Chloroatranol and atranol are degradation products of chloroatranorin and atranorin, respectively, and have recently been identified as important contact allergens in the natural fragrance extract, oak moss absolute. Oak moss absolute is widely used in perfumery and is the cause of many cases of fragrance allergic contact dermatitis. Chloroatranol elicits reactions at very low levels of exposure. In oak moss absolute, chloroatranol and atranol are present together and both may contribute to the allergenicity and eliciting capacity of the natural extract. In this study, 10 eczema patients with known sensitization to chloroatranol and oak moss absolute were tested simultaneously to a serial dilution of chloroatranol and atranol in ethanol, in equimolar concentrations (0.0034-1072 microM). Dose-response curves were estimated and analysed by logistic regression. The estimated difference in elicitation potency of chloroatranol relative to atranol based on testing with equimolar concentrations was 217% (95% confidence interval 116-409%). Both substances elicited reactions at very low levels of exposure. It is concluded that the differences in elicitation capacity between the 2 substances are counterbalanced by exposure being greater to atranol than to chloroatranol and that both substances contribute to the clinical problems seen in oak moss absolute-sensitized individuals.
Rastogi SC, Johansen JD, Bossi R. Selected important fragrance sensitizers in perfumes--current exposures. Contact Dermatitis. 2007 Apr;56(4):201-4. doi: 10.1111/j.1600-0536.2007.01067.x.
Abstract. Contact allergy to fragrance ingredients is frequent. Recommendations and regulations of some of the most frequent and potent fragrance allergens have recently been introduced. To investigate current exposures to 4 important fragrance allergens in hydroalcoholic cosmetic products. 25 popular perfume products of Danish as well as international brands were purchased from the Danish retail market. Contents of 4 important fragrance allergens, isoeugenol, hydroxy-iso-hexyl 3-cyclohexene carboxaldehyde (HICC, Lyral), were determined by gas chromatography-mass spectrometry, and atranol and chloro-atranol were determined by liquid chromatography-tandem mass spectrometry. Isoeugenol was found in 56%, HICC in 72%, atranol in 59%, and chloro-atranol in 36% of the 22 eau de toilette/eau de parfum products. The concentrations of isoeugenol were, in all products, below the recommended maximum concentration of 0.02%. HICC reached a maximum of 0.2%, which is 10-fold higher than maximum tolerable concentration considered safe by the EU Scientific Committee. The median concentrations of atranol and chloro-atranol in the investigated products were similar to those found in similar products in 2003. A significant decrease in the frequency of presence of chloro-atranol in the products was observed. There is still a wide-spread exposure to potent fragrance allergens in perfumes.
Rastogi SC, Bossi R, Johansen JD, Menné T, Bernard G, Giménez-Arnau E, Lepoittevin JP. Content of oak moss allergens atranol and chloroatranol in perfumes and similar products. Contact Dermatitis. 2004 Jun;50(6):367-70. doi: 10.1111/j.0105-1873.2004.00379.x.
Abstract. Chloroatranol and atranol have been identified as the main allergens in the fragrance material of botanical origin, oak moss absolute. A previous study has shown that nearly all individuals sensitized to chloroatranol will elicit to 5 microg/ml. in a repeated open application test and that 50% will get a reaction to 0.15 micro g/ml under patch test conditions. Thus, chloroatranol is known as a potent allergen. The aim of the current investigation was to quantify exposure to chloroatranol and the chemically related substance atranol in some popular perfumes, eaux de parfum and eaux de toilette available on the European market. In total, 31 products were analysed by liquid chromatography-electrospray ionization-tandemmass spectrometry (LC-ESI-MS-MS) for their contents of atranol and chloroatranol. The 2 substances were found in 87% (n = 27) of the products. The median concentration of atranol in perfumes was 0.502 micro g/ml and 0.012 micro g/ml in eaux de toilette, and 0.235 micro g/ml and 0.006 micro g/ml for chloroatranol, respectively, in perfumes and eaux de toilette. Chloroatranol was found at a maximum concentration of 53 micro g/ml and atranol at one of 190 micro g/ml. The wide exposure to oak moss allergens, together with significant amounts of these potent allergens in at least half of perfumes and some eaux de toilettes explains the high frequencies of oak moss absolute allergy. It is suggested that regulations should be introduced aimed directly at these substances, and not just at oak moss absolute.
Atranol 
