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.

Paulsen E, Andersen F. Fragrant and sticky allergens from the pinewood: Cohabiting and coreacting. Contact Dermatitis. 2019 Nov;81(5):374-377. doi: 10.1111/cod.13348.

Abstract. Background: Tree moss (Pseudevernia furfuracea [L.] Zopf.), a lichen growing on conifers, is a frequent fragrance sensitizer. Previous studies have shown two subgroups of tree moss-allergic patients: a group sensitized to common allergens of tree and oak moss (Evernia prunastri), and another group sensitized to colophonium-derived allergens, which may contaminate tree moss extract. Objectives: To report the results of including tree moss extract in the baseline series and discuss the clinical implications....Conclusions: The prevalence of positive tree moss reactions is high enough to justify its inclusion in the baseline series. If tree moss is not included, patients with positive colophonium reactions should be informed of possible (false) cross-reactivity to tree moss to avoid this labeled fragrance allergen. © 2019 John Wiley & Sons A/S.

Schnuch A, Uter W, Geier J, Lessmann H, Frosch PJ. Sensitization to 26 fragrances to be labelled according to current European regulation. Results of the IVDK and review of the literature. Contact Dermatitis. 2007 Jul;57(1):1-10. doi: 10.1111/j.1600-0536.2007.01088.x. 

Abstract. To study the frequency of sensitization to 26 fragrances to be labelled according to current European regulation. During 4 periods of 6 months, from 1 January 2003 to 31 December 2004, 26 fragrances were patch tested additionally to the standard series in a total of 21 325 patients; the number of patients tested with each of the fragrances ranged from 1658 to 4238. Hydroxymethylpentylcyclohexene carboxaldehyde (HMPCC) was tested throughout all periods. The following frequencies of sensitization (rates in %, standardized for sex and age) were observed: tree moss (2.4%), HMPCC (2.3), oak moss (2.0), hydroxycitronellal (1.3), isoeugenol (1.1), cinnamic aldehyde (1.0), farnesol (0.9), cinnamic alcohol (0.6), citral (0.6), citronellol (0.5), geraniol (0.4), eugenol (0.4), coumarin (0.4), lilial (0.3), amyl-cinnamic alcohol (0.3), benzyl cinnamate (0.3), benzyl alcohol (0.3), linalool (0.2), methylheptin carbonate (0.2), amyl-cinnamic aldehyde (0.1), hexyl-cinnamic aldehyde (0.1), limonene (0.1), benzyl salicylate (0.1), gamma-methylionon (0.1), benzyl benzoate (0.0), anisyl alcohol (0.0). 1) Substances with higher sensitization frequencies were characterized by a considerable number of '++/+++' reactions. 2) Substances with low sensitization frequencies were characterized by a high number of doubtful/irritant and a low number of stronger (++/+++) reactions. 3) There are obviously fragrances among the 26 which are, with regard to contact allergy, of great, others of minor, and some of no importance at all.

Tanko Z, Shab A, Diepgen TL, Weisshaar E. Polyvalent type IV sensitizations to multiple fragrances and a skin protection cream in a metal worker. J Dtsch Dermatol Ges. 2009 Jun;7(6):541-3. English, German. doi: 10.1111/j.1610-0387.2009.07031.x. 

Abstract. Fragrances are very common in everyday products. A metalworker with chronic hand eczema and previously diagnosed type IV sensitizations to epoxy resin, balsam of Peru, fragrance mix and fragrance mix II was diagnosed with additional type IV sensitizations to geraniol, hydroxycitronellal, lilial, tree moss, oak moss absolute, citral, citronellol, farnesol, Lyral, fragrance mix II and fragrance mix (with sorbitan sesquioleate). In addition, a type IV sensitization to the skin protection cream containing geraniol and citronellol used at the workplace was detected, and deemed occupationally relevant in this case. The patient could have had contact to fragrances through private use of cosmetics and detergents. On the other hand, the fragrance-containing skin protection cream supports occupational exposure. This case report demonstrates that fragrance contact allergy has to be searched for and clarified individually, which requires a thorough history and a detailed analysis of the work place.