Patch testing with a new fragrance mix – reactivity to the individual constituents and chemical detection in relevant cosmetic products

Abstract

50 patients (2.9%) showed a positive reaction to 14% FM II and 70 patients (4.1%) to 28% FM II. 24/50 (48%) produced a positive reaction to 1 or more of the individual constituents of 14% FM II and 38/70 (54.3%) to 28% FM II, respectively. If doubtful reactions to individual constituents are included, the break-down testing was positive in 74% and 70%, respectively. Patients with a positive reaction to 14% FM II showed a higher rate of reactions to the individual constituent of the 28% FM II: 36/50 (72%). Positive reactions to individual constituents in patients negative to FM II were exceedingly rare. If doubtful reactions are regarded as negative, the sensitivity, specificity, positive predictive value and negative predictive value for the medium concentration of FM II towards at least 1 individual constituent was 92.3% (exact 95% confidence interval 74.9-99.1%), 98.4% (97.7-99.0%), 48% (33.7-62.6%) and 99.9% (99.6-"100.0%), respectively. For the high concentration, the figures were very similar. The frequency of positive reactions to the individual constituents in descending order was the same for both FM II concentrations: hydroxyisohexyl 3-cyclohexene carboxaldehyde (Lyral) > citral > farnesol > citronellol > alpha-hexyl-cinnamic aldehyde (AHCA). No unequivocally positive reaction to coumarin was observed. Lyral) was the dominant individual constituent, with positive reactions in 36% of patients reacting to 14% FM II and 37.1% to 28% FM II. 5/11 patients developed a positive ROAT after a median of 7 days (range 2-10). The 5 patients with a doubtful or negative reaction to 28% FM II were all ROAT negative except 1. There were 7 patients with a certain fragrance history and a positive reaction to either 28% or 14% FM II but a negative reaction to FM I. Analysis with GC-MS in a total of 24 products obtained from 12 patients showed at least 1-5 individual constituents per product: Lyral (79.2%), citronellol (87.5%), AHCA (58.3%), citral (50%) and coumarin (50%). The patients were patch test positive to Lyral, citral and AHCA. In conclusion, patients with a certain fragrance history and a negative reaction to FM I can be identified by FM II. Testing with individual constituents is positive in about 50% of cases reacting to either 14% or 28% FM II.

Design and Feasibility of an International Study Assessing the Prevalence of Contact Allergy to Fragrances in the General Population: The European Dermato-Epidemiology Network Fragrance Study

“…In fact, to our knowledge, no previous studies have investigated the prevalence of fragrance mix 2 sensitization in the general population. The frequency of contact sensitization to fragrances strictly depends on the number of allergens tested, and patch testing with fragrance mix 2 detects additional patients sensitive to perfumes and missed by fragrance mix 1 testing [7,12,13]; thus, we would expect that the overall prevalence of contact sensitization to fragrances would be higher than prevalence estimates so far. This inclusion could account, at least in part, for the relatively high frequency of contact sensitization to fragrances we found in the pilot investigation.…”

“…Further difficulties in establishing estimates of contact sensitizations to fragrances are related to the variability in the concentrations of allergens in solution (or petrolatum) [12,18]. Moreover, one controversial issue is the reliability of reactions to a fragrance mix [18,19,20].…”

Sensitization Potential of Citronellol

“…However, these studies are by their nature incapable of unambiguously designating citronellol as the cause of the patient's condition. While its inclusion in cosmetic labeling declarations [36] and routine patch testing materials such as 'FM II' [23] may provide further information on its possible causal role in allergic contact dermatitis, the evidence currently available does not indicate that citronellol is a major fragrance allergen. Prospective clinical correlation patch test studies should provide clearer data as to the certainty of this interpretation.…”

“…Subsequent to the review period, a publication has reported studies on a new 'Fragrance Mix II' (FM II) [23] . In this study, 1,701 patients were patch tested to this new mixture, and subsequent patch testing of positively reacting patients to the individual components produced 2 positive (+) and 18 irritant or doubtful (?/IR) reactions to 0.5% citronellol.…”

“…These include a study on 95 patients using 5% citronellol [23] and several other studies using citronellol at 5% [24][25][26][27][28][29][30] .…”