Objective: To identify the concentration of the fragrance compound hydroxyisohexyl 3-cyclohexene carboxaldehyde (INCI) (HICC) that is sufficiently low not to cause an allergic reaction in patients with proven sensitization.
Methods: Repeated open application testing (ROAT) in 64 subjects with 2 preparations (perfume and cream) in different concentration (0.005-2.5%). Confirmatory patch testing with four preparations in two different concentrations (2.5% and 5%).
Results: The concentrations of HICC being tolerated by 90% of those sensitized to HICC are estimated as <88.2 ppm (cream) and <270 ppm (perfume) equivalent to 1.2 microg/cm(2) (perfume) and 4.9 microg/cm(2) (cream). Patch test preparations differed with regard to sensitivity (88.5-98.1%) and specificity (37.5-87.5%) against the ROAT result as external criterion. ROAT concentrations and the reaction strength in patch testing were inversely correlated (Kendall's tau-b: 0.69), both indicating the existence of different degrees of susceptibility.
Conclusion: To protect 90% (50%) of people sensitized, the use concentration should be in the range of 0.009-0.027% (0.18-0.34%), depending on the product type. Taking into account these results, excessive concentrations should be avoided, as this would continue to sensitize people. Close monitoring is indispensable to prove the efficacy of any recommendations aiming to prevent induction.