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

• Published in: Contact dermatitis Vol. 52; no. 4; pp. 216 - 225
• Main Authors: Frosch, Peter J., Rastogi, Suresh C., Pirker, Claudia, Brinkmeier, Thomas, Andersen, Klaus E., Bruze, Magnus, Svedman, Cecilia, Goossens, An, White, Ian R., Uter, Wolfgang, Arnau, Elena Giménez, Lepoittevin, Jean-Pierre, Johansen, Jeanne Duus, Menne, Torkil
• Format: Journal Article
• Language: English
• Published: Oxford, UK; Malden, USA Munksgaard International Publishers 01.04.2005; Blackwell
• Subjects: 3-cyclohexene carboxaldehyde; Acrolein - administration & dosage; Acrolein - adverse effects; Acrolein - analogs & derivatives; Adolescent; Adult; Aged; Aged, 80 and over; Aldehydes - administration & dosage; Aldehydes - adverse effects; Allergens - administration & dosage; Allergens - adverse effects; Allergic diseases; alpha-hexyl-cinnamic aldehyde; Biological and medical sciences; citral; Clinical Medicine; Cosmetics - adverse effects; Cosmetics - chemistry; Coumarins - administration & dosage; Coumarins - adverse effects; Cyclohexenes; Dermatitis, Allergic Contact - diagnosis; Dermatitis, Allergic Contact - etiology; Dermatologi och venereologi; Dermatology and Venereal Diseases; Dose-Response Relationship, Drug; farnesol; Farnesol - administration & dosage; Farnesol - adverse effects; Female; fragrance mix; Humans; hydroxyisohexyl; hydroxyisohexyl 3-cyclohexene "carboxaldehyde; Immunopathology; individual constituents; Klinisk medicin; Lyral; Lyral((R)); Male; Maximum Allowable Concentration; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Monoterpenes - administration & dosage; Monoterpenes - adverse effects; new; new fragrance mix; Patch Tests; Perfume - administration & dosage; Perfume - adverse effects; Predictive Value of Tests; product analysis; repeated open application test (ROAT); Sensitivity and Specificity; Skin allergic diseases. Stinging insect allergies; α-hexyl-cinnamic aldehyde; Cosmetic; Human; Terpenoid; Flavoring agent; Toxicity; new fragrance mix; Chemical compound; Perfume; hydroxyisohexyl 3-cyclohexene carboxaldehyde; product analysis; Aldehyde; repeated open application test (ROAT); Mixture; individual constituents; Lyral; farnesol; α-hexyl-cinnamic aldehyde; Detection; Citral; Patch; Skin test
• ISSN: 0105-1873; 1600-0536
• DOI: 10.1111/j.0105-1873.2005.00563.x

A new fragrance mix (FM II), with 6 frequently used chemicals not present in the currently used fragrance mix (FM I), was evaluated in 6 dermatological centres in Europe, as previously reported. In this publication, test results with the individual constituents and after repeated open application test (ROAT) of FM II are described. Furthermore, cosmetic products which had caused a contact dermatitis in patients were analysed for the presence of the individual constituents. In 1701 patients, the individual constituents of the medium (14%) and the highest (28%) concentration of FM II were simultaneously applied with the new mix at 3 concentrations (break‐down testing for the lowest concentration of FM II (2.8%) was performed only if the mix was positive). ROAT was performed with the concentration of the FM II which had produced a positive or doubtful (+ or ?+) patch test reaction. Patients' products were analysed for the 6 target compounds by gas chromatography‐mass spectrometry (GC‐MS). Results: 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 > α‐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.