title: Quantitative risk assessment for the induction of allergic contact dermatitis: uncertainty factors for mucosal exposures.
abstract: The quantitative risk assessment (QRA) paradigm has been extended to evaluating the risk of induction of allergic contact dermatitis from consumer products. Sensitization QRA compares product-related, topical exposures to a safe benchmark, the sensitization reference dose. The latter is based on an experimentally or clinically determined 'no observable adverse effect level' (NOAEL) and further refined by incorporating 'sensitization uncertainty factors' (SUFs) that address variables not adequately reflected in the data from which the threshold NOAEL was derived. A critical area of uncertainty for the risk assessment of oral care or feminine hygiene products is the extrapolation from skin to mucosal exposures. Most sensitization data are derived from skin contact, but the permeability of vulvovaginal and oral mucosae is greater than that of keratinized skin. Consequently, the QRA for some personal products that are exposed to mucosal tissue may require the use of more conservative SUFs. This article reviews the scientific basis for SUFs applied to topical exposure to vulvovaginal and oral mucosae. We propose a 20-fold range in the default uncertainty factor used in the contact sensitization QRA when extrapolating from data derived from the skin to situations involving exposure to non-keratinized mucosal tissue.
authors.affiliation: The Procter & Gamble Company, Feminine Care Research and Development, Cincinnati, OH 45224, USA. farage.m@pg.com
authors.forename: Miranda A
authors.initials: MA
authors.lastname: Farage
authors.forename: Donald L
authors.initials: DL
authors.lastname: Bjerke
authors.forename: Catherine
authors.initials: C
authors.lastname: Mahony
authors.forename: Karen L
authors.initials: KL
authors.lastname: Blackburn
authors.forename: G Frank
authors.initials: GF
authors.lastname: Gerberick
mesh_terms: D000485:Allergens / Q000633:toxicity*; D019985:Benchmarking; D003627:Data Interpretation, Statistical; D017449:Dermatitis, Allergic Contact / Q000453:epidemiology* / Q000209:etiology*; D005260:Female; D006801:Humans; D009061:Mouth Mucosa / Q000187:drug effects; D009092:Mucous Membrane / Q000187:drug effects*; D019055:No-Observed-Adverse-Effect Level; D018570:Risk Assessment / Q000379:methods*; D035501:Uncertainty; D014844:Vulva / Q000187:drug effects
chemical_list: D000485:Allergens