Oh

Benzyl cinnamate

Geraniol

Linalool

Anisyl alcohol

Benzyl benzoate

Farnesol

Citronellol

D-Limonene

FIGURE 22.2 Structures of the 16 naturally occurring alleged allergenic substances (part 2). 22.2.4 Recent Data on Sensitization to Fragrances

Benzyl benzoate

Farnesol

Citronellol

D-Limonene

FIGURE 22.2 Structures of the 16 naturally occurring alleged allergenic substances (part 2). 22.2.4 Recent Data on Sensitization to Fragrances

Recently a new study on the sensitization to the 26 fragrance ingredients (24 single substances and two natural extracts) that have to be labeled according to the European Regulation was published by the group of Schnuch et al. (2007). This study was part of the multicenter project Information Network of Departments of Dermatology (IVDK) (Schnuch et al., 1997, 2004). The aim was to study the frequency of sensitization to these 26 alleged allergenic fragrances, in particular the actual frequencies of contact allergy to these 26 fragrances. To test this, the fragrance ingredients were patch tested in consecutive, unselected patients (in total 21,325 patients) by the IVDK network during a 2-year period, consisting of four periods of 6 months. The number of patients tested with each of the fragrance substances ranged from 1658 to 4238.

The frequency of sensitization was expressed by the proportion of patients reacting allergic (% pos.), that is, the number of allergic patients compared to the number of patients tested (n pos./n tested, %) and the frequency of allergic reactions was then standardized for age and sex.

The "allergenic" fragrances were divided into three groups, depending on the frequency of sensitization, based on the 95% confidence interval (CI).

The first group of ingredients with the upper CI > 1.0% could be regarded as important allergens and was called Group I. This group includes the two natural extracts, oakmoss and tree moss, and the substances HMPCC, hydroxycitronellal, isoeugenol, cinnamic acid, and farnesol.

Another group of ingredients with an upper CI between 0.5% and 1.0% was found to be clearly allergenic but less important in terms of sensitization frequency (Group II). This group comprises cinnamic alcohol, citral, citronellol, geraniol, eugenol, coumarin, lilial, amyl-cinnamic alcohol, and benzyl cinnamate.

On the other hand, the third group (Group III) comprises substances that have turned out to be (extremely) rare sensitizers in this study, or which in other instances may even be considered as nonsensitizers, according to the authors. This group with an upper CI of less than 0.5% contains 10 materials: benzyl alcohol, linalool, methylheptin carbonate, a-amyl-cinnamic aldehyde, a-hexyl-cinnamic aldehyde, limonene, benzyl salicylate, g-methylionone, benzyl benzoate, and anisyl alcohol. It was further concluded that sensitization to allergens of the first group is significantly more frequent than sensitization to allergens of the third group.

Regarding Group III it is also worth noting that some molecules are not allergens as such, but only turn into allergens after substantial oxidation, for example, limonene and linalool (Karlberg and Dooms-Goossens, 1992; Karlberg et al., 1992; Hagvall and Karlberg, 2006).

It is interesting to note that there is a difference in the classification of the allergens (reported frequency) according to the opinion of the SCCP (SCCP/0017/98) and the classification in groups by Schnuch et al. For example one substance that is an important allergen according to the study of Schnuch (Group I), farnesol, is according to SCCP "less frequently reported." The same applies to two substances of Group II that are according to SCCP "less frequently reported," namely citro-nellol and benzyl cinnamate. On the other hand, two materials that are according to the study of Schnuch (extremely) rare sensitizers (Group III) are according to SCCP "frequently reported," namely benzyl alcohol and benzyl salicylate. A comparison of the classifications is given in Table 22.3. Differences in classification according to the two sources are highlighted in bold.

It is important to focus in some more depth on the allergenic potential of the natural ingredients, oakmoss and tree moss. In contrast to oakmoss, which is known to be a potent sensitizer since a long time ago, tree moss had not been systematically tested in cosmetic patch test series in the past, and the study by Schnuch et al. (2007) is claimed to be the first study in which tree moss was tested in a larger population. In this study, tree moss was found to be the most frequent allergen. Earlier study reports had already identified atranol and chloroatranol (degradation products of atranorin and chlo-roatranorin) as the most potent allergens (Johansen et al., 2003, 2006). The chemical structures of atranol and chloroatranol are depicted in Figure 22.3.

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Allergic To Everything

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