title: Correlation between experimental human and murine skin sensitization induction thresholds.
abstract: Quantitative risk assessment for skin sensitization is directed towards the determination of levels of exposure to known sensitizing substances that will avoid the induction of contact allergy in humans. A key component of this work is the predictive identification of relative skin sensitizing potency, achieved normally by the measurement of the threshold (the "EC3" value) in the local lymph node assay (LLNA). In an extended series of studies, the accuracy of this murine induction threshold as the predictor of the absence of a sensitizing effect has been verified by conduct of a human repeated insult patch test (HRIPT). Murine and human thresholds for a diverse set of 57 fragrance chemicals spanning approximately four orders of magnitude variation in potency have been compared. The results confirm that there is a useful correlation, with the LLNA EC3 value helping particularly to identify stronger sensitizers. Good correlation (with half an order of magnitude) was seen with three-quarters of the dataset. The analysis also helps to identify potential outlier types of (fragrance) chemistry, exemplified by hexyl and benzyl salicylates (an over-prediction) and trans-2-hexenal (an under-prediction).
authors.affiliation: a Research Institute for Fragrance Materials , Woodcliff Lake , NJ , USA and.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Api
authors.affiliation: b DABMEB Consultancy Ltd , Sharnbrook , Bedfordshire , UK.
authors.forename: David
authors.initials: D
authors.lastname: Basketter
authors.affiliation: a Research Institute for Fragrance Materials , Woodcliff Lake , NJ , USA and.
authors.forename: Jon
authors.initials: J
authors.lastname: Lalko
mesh_terms: D000279:Administration, Cutaneous; D000485:Allergens / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry; D000818:Animals; D017449:Dermatitis, Allergic Contact / Q000175:diagnosis* / Q000209:etiology*; D004056:Differential Threshold; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D023441:Local Lymph Node Assay; D008808:Mice, Inbred CBA; D019055:No-Observed-Adverse-Effect Level; D010328:Patch Tests; D010476:Perfume / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry; D011237:Predictive Value of Tests; D018570:Risk Assessment
chemical_list: D000485:Allergens; D010476:Perfume
keywords: Contact allergy induction; EC3 value; NESIL; fragrance; human repeated insult patch test; local lymph node assay; skin sensitization