Potential of concentration-response data to broaden regulatory application of in vitro test guidelines.

Abstract

International chemical regulatory activities are moving towards new approach methodology and away from traditional animal-based models, shifting and expanding from one single in vivo assay towards combined use of different in vitro assays within integrated approaches for testing and assessment and defined approaches to serve hazard identification, classification and selection of points of departure for risk assessment. Whilst many in vitro test guidelines were developed against specific hazard cut-off values, quantitative information is needed in data interpretation procedures for potency assessment purposes or to define points of departure so that assays can fulfill evolving regulatory needs. Utilizing four examples from skin sensitization, phototoxicity, endocrine activity, and non-genotoxic carcinogenicity, we illustrate why a shift in data generation and data interpretation procedures is needed to facilitate the full exploitation of the data that is generated using these assays. This requires the development of a practical approach that uses or expands upon existing guidance. Experience gained with such an approach can then provide a basis for an overarching strategy in test guideline development that should better facilitate combinations of in vitro test guidelines for specific endpoints that will be more transparent, robust, and adaptable for specific regulatory purposes.