Skin sensitization quantitative risk assessment: A review of underlying assumptions

• Published in: Regulatory toxicology and pharmacology Vol. 74; pp. 105 - 116
• Main Authors: Basketter, David, Safford, Bob
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.02.2016
• Subjects: Allergic contact dermatitis; Animals; Consumer Product Safety; Dermatitis, Allergic Contact - etiology; Dermatitis, Allergic Contact - immunology; Dose-Response Relationship, Drug; Humans; Irritants - adverse effects; Perfume - adverse effects; Quantitative risk assessment; Risk Assessment; Risk Factors; Safety factors; Skin - drug effects; Skin - immunology; Skin Irritancy Tests - methods; Skin sensitization; Species Specificity; Allergic contact dermatitis; Skin sensitization; Quantitative risk assessment; Safety factors
• ISSN: 0273-2300; 1096-0295; 1096-0295
• DOI: 10.1016/j.yrtph.2015.11.013

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. •Quantitative Risk Assessment (QRA) is central to management of fragrance allergens.•The original QRA has been subject to scrutiny/criticism concerning its efficacy.•Thus, the underlying scientific elements delivering uncertainty have been reviewed.•Recommendations for updating QRA have been proposed.