The ECVAM international validation study on in vitro tests for acute skin irritation: selection of test chemicals.

摘要: The ECVAM-funded skin irritation validation study (SIVS) was initiated in 2003, with the aim to evaluate whether EpiDerm, EPISKIN and SIFT alternative methods were able reliably identify irritant non-irritant chemicals, could therefore be candidates for replacing rabbit Draize test irritation. primary goal of predictive capacity assays regard EU classification system, which employs risk phrases, "R38", irritants, "no label" non-irritants. A secondary objective retrospective analysis data, assess vitro tests would discriminate between strong irritants (category 2), mild 3) non-irritants (no category), as defined by OECD United Nations proposal a Globally Harmonised System (GHS) labelling dermal irritancy. Chemicals Selection Sub-Committee (CSSC) appointed chemicals used SIVS, existing, high quality vivo data available, correlate measurements. Since from European Centre Ecotoxicology Toxicology (ECETOC) database reference irritation/skin corrosion had been extensively preceding studies, CSSC made use novel sources potential chemicals. first source screened New Database (NCD), is central archive within notification scheme 'new' commercial Data registered NCD originate standard assays, submitted compliance legislation regulates marketing industrial are subject assurance competent authorities Member States. In addition, obtain 'existing' readily available major manufacturing and/or distribution sources, additional databases surveyed, such Toxic Substance Control Act (TSCA) maintained US Environmental Protection Agency (EPA), ECETOC database, exclusion previous optimisation prevalidation phases. total approximately 3500 1600 screened. Pre-determined selection criteria applied, primarily ensure practicability their testing. Overall, number fulfilling found limited, particularly case GHS category 2 However, set 60 selected proposed Management Team SIVS independent coding supply participating laboratories. chemicals: i) represented statistically justified sample sizes distinguishing R38 no-label chemicals; ii) provided balanced representation three categories, allow post hoc evaluation performance that system; iii) acknowledged, certain degree, large prevalence known exist have oedema erythema scores 0. variety molecular structures, functional chemical groups, effect well wide range physico-chemical properties. They challenging relevant current commerce, validate methods.