title: Skin sensitization quantitative risk assessment: A review of underlying assumptions.
abstract: Toxicological risk assessment informs exposure limits, so the potential for adverse effects to human health are minimised or avoided. For skin sensitisers, the situation is complicated by asymptomatic induction of contact allergy, a necessary prerequisite for expression of the disease allergic contact dermatitis (ACD). For fragrance skin sensitisers, the development of quantitative risk assessment (QRA) arose from the need to improve the extent to which contact allergy occurred. However, the perceived impact has been less than anticipated. Accordingly, the science and assumptions upon which QRA was founded have been scrutinised and proposals for refinement have been made. In addition, areas of uncertainty have been made explicit, e.g. inter-individual variability and the impact of concomitant disease, clarifying where numerical safety assessment factors are based on expert judgement. Also, the relatively small contribution of factors eg. age, gender, ethnic origin, vehicle matrix and skin permeability are highlighted by reference to the (now controversial) human experiments carried out in the second half of the last century. Adoption and widespread implementation of the current recommendations for QRA, taken in concert with improved assessment of aggregate exposure from multiple sources, should ensure that the frequency of contact allergy will decrease over the coming years.
authors.affiliation: DABMEB Consultancy Ltd, Sharnbrook, Bedfordshire, UK. Electronic address: dabmebconsultancyltd@me.com.
authors.forename: David
authors.initials: D
authors.lastname: Basketter
authors.affiliation: B-Safe Toxicology Consulting, Rushden, Northamptonshire, UK.
authors.forename: Bob
authors.initials: B
authors.lastname: Safford
mesh_terms: D000818:Animals; D003257:Consumer Product Safety; D017449:Dermatitis, Allergic Contact / Q000209:etiology* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007509:Irritants / Q000009:adverse effects*; D010476:Perfume / Q000009:adverse effects*; D018570:Risk Assessment; D012307:Risk Factors; D012867:Skin / Q000187:drug effects* / Q000276:immunology; D023422:Skin Irritancy Tests / Q000379:methods*; D013045:Species Specificity
chemical_list: D007509:Irritants; D010476:Perfume
keywords: Allergic contact dermatitis; Quantitative risk assessment; Safety factors; Skin sensitization