title: Alternative Toxicity Testing: Analyses on Skin Sensitization, ToxCast Phases I and II, and Carcinogenicity Provide Indications on How to Model Mechanisms Linked to Adverse Outcome Pathways.
abstract: This article studies alternative toxicological approaches, with new (skin sensitization, ToxCast) and previous (carcinogenicity) analyses. Quantitative modeling of rate-limiting steps in skin sensitization and carcinogenicity predicts the majority of toxicants. Similarly, successful (Quantitative) Structure-Activity Relationships models exploit the quantification of only one, or few rate-limiting steps. High-throughput assays within ToxCast point to promising associations with endocrine disruption, whereas markers for pathways intermediate events have limited correlation with most endpoints. Since the pathways may be very different (often not simple linear chains of events), quantitative analysis is necessary to identify the type of mechanism and build the appropriate model.
authors.affiliation: a Department of Environment and Health , Istituto Superiore di Sanita' , Rome , Italy.
authors.forename: Romualdo
authors.initials: R
authors.lastname: Benigni
authors.affiliation: a Department of Environment and Health , Istituto Superiore di Sanita' , Rome , Italy.
authors.forename: Chiara Laura
authors.initials: CL
authors.lastname: Battistelli
authors.affiliation: a Department of Environment and Health , Istituto Superiore di Sanita' , Rome , Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Bossa
authors.affiliation: a Department of Environment and Health , Istituto Superiore di Sanita' , Rome , Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Giuliani
authors.affiliation: a Department of Environment and Health , Istituto Superiore di Sanita' , Rome , Italy.
authors.forename: Olga
authors.initials: O
authors.lastname: Tcheremenskaia
mesh_terms: D004249:DNA Damage; D008962:Models, Theoretical; D009152:Mutagenicity Tests / Q000379:methods; D021281:Quantitative Structure-Activity Relationship; D012882:Skin Tests / Q000379:methods*; D018675:Toxicity Tests / Q000379:methods*
keywords: ToxCast assays; adverse outcome pathways; carcinogenicity; endocrine disruption; limitations; mechanistic coverage; skin sensitization