title: Feasibility study to support a threshold of sensitization concern  concept in risk assessment based on human data.
abstract: In analogy to the Threshold of Toxicological Concern concept, a Threshold of Sensitization Concern (TSC) concept is proposed for chemicals with respect to their ability to induce an allergic contact dermatitis. Recently, the derivation of a dermal sensitization threshold was suggested based on an evaluation of animal data. In order to establish the concept with human data, we conducted a meta-analysis taking into account No Expected Sensitization Induction Levels for fragrance ingredients from the IFRA/RIFM dataset. Based on a statistical analysis by applying Sensitization Assessment Factors that account for interindividual variability and different exposure conditions, TSC values of 0.91 or 0.30 lg/cm2 can be derived in terms of amount per skin area. TSC values are compared with typical exposure levels of cosmetic products. A substance can be considered to be virtually safe if the quotient of exposure level and TSC is < 1. The findings derived from human data include several conservative assumptions and largely support the dermal sensitization thresholds previously derived from animal data. The TSC concept might in principle be used for any untested chemical and therefore help in some cases to waive animal testing.
authors.affiliation: Corporate Product Safety, Department of Human Safety Assessment, Henkel AG & Co. KGaA, Düsseldorf, Germany.
authors.forename: Detlef
authors.initials: D
authors.lastname: Keller
authors.forename: Matthias
authors.initials: M
authors.lastname: Krauledat
authors.forename: Julia
authors.initials: J
authors.lastname: Scheel
mesh_terms: D000485:Allergens / Q000633:toxicity*; D000818:Animals; D000830:Animals, Laboratory; D003257:Consumer Product Safety; D016208:Databases, Factual; D017449:Dermatitis, Allergic Contact / Q000209:etiology* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005240:Feasibility Studies; D006801:Humans; D007114:Immunization / Q000331:legislation & jurisprudence*; D019055:No-Observed-Adverse-Effect Level; D010476:Perfume / Q000009:adverse effects*; D018570:Risk Assessment; D012882:Skin Tests; D020711:Threshold Limit Values
chemical_list: D000485:Allergens; D010476:Perfume