title: Principles for identification of High Potency Category Chemicals for which the Dermal Sensitisation Threshold (DST) approach should not be applied.
abstract: An essential step in ensuring the toxicological safety of chemicals used in consumer products is the evaluation of their skin sensitising potential. The sensitising potency, coupled with information on exposure levels, can be used in a Quantitative Risk Assessment (QRA) to determine an acceptable level of a given chemical in a given product. Where consumer skin exposure is low, a risk assessment can be conducted using the Dermal Sensitisation Threshold (DST) approach, avoiding the need to determine potency experimentally. Since skin sensitisation involves chemical reaction with skin proteins, the first step in the DST approach is to assess, on the basis of the chemical structure, whether the chemical is expected to be reactive or not. Our accompanying publication describes the probabilistic derivation of a DST of 64 μg/cm(2) for chemicals assessed as reactive. This would protect against 95% of chemicals assessed as reactive, but the remaining 5% would include chemicals with very high potency. Here we discuss the chemical properties and structural features of high potency sensitisers, and derive an approach whereby they can be identified and consequently excluded from application of the DST.
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool L3 3AF, United Kingdom. Electronic address: d.w.roberts@ljmu.ac.uk.
authors.forename: David W
authors.initials: DW
authors.lastname: Roberts
authors.affiliation: Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ 07677, United States. Electronic address: amapi@rifm.org.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Api
authors.affiliation: B-Safe Toxicology Consulting, 31 Hayway, Rushden, Northants NN10 6AG, United Kingdom. Electronic address: bob.safford@bstoxconsult.co.uk.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Safford
authors.affiliation: Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ 07677, United States. Electronic address: jlalko@rifm.org.
authors.forename: Jon F
authors.initials: JF
authors.lastname: Lalko
mesh_terms: D000485:Allergens / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D001681:Biological Assay; D016208:Databases, Factual; D017449:Dermatitis, Allergic Contact / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology; D019055:No-Observed-Adverse-Effect Level; D018570:Risk Assessment / Q000379:methods*; D013329:Structure-Activity Relationship
chemical_list: D000485:Allergens
keywords: Dermal Sensitisation Threshold (DST); High Potency Category Chemicals (HPC); Local Lymph Node Assay (LLNA); Non-animal methods; Sensitisation risk assessment; Skin sensitisation; Structure alerts