title: The use of in vitro data in risk assessment.
abstract: Describing the toxicological profile of a substance is the first step required for risk assessment. Although a wide range of in vitro methods are widely used to characterise toxicological properties including toxicokinetics, regulatory acceptance is mainly confined to in vitro tests which investigate genotoxic end-points. In vitro tests have been proposed for the endpoints acute toxicity, repeated dose toxicity and toxicity to reproduction which encompass the minimum requirements in the OECD SIDS programme. However, until now, limitations of the proposed tests preclude their application in a regulatory framework. Presently, in vitro tests play a major role in obtaining information on mechanism of toxicity with the perspective to be able to identify pathways of toxic responses by applying toxicogenomics techniques. Physiologically based toxicokinetic modelling is using data from in vitro studies to build up the model for a specific compound. Information from both areas is incorporated into the risk assessment to derive compound-specific safety factors, which account for species differences and for the variability among the human population, including possible sensitive subpopulations. Future developments to further enhance the use of in vitro methods in regulatory toxicology include the development of (Q)SAR approaches supplemented by mechanisms of toxicity, which can be addressed by developing methods of molecular toxicology.
authors.affiliation: Federal Institute for Risk Assessment, Thielallee 88-92, D-14195 Berlin, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Bernauer
authors.forename: Axel
authors.initials: A
authors.lastname: Oberemm
authors.forename: Stephan
authors.initials: S
authors.lastname: Madle
authors.forename: Ursula
authors.initials: U
authors.lastname: Gundert-Remy
mesh_terms: D000818:Animals; D002869:Chromosome Aberrations; D005298:Fertility / Q000187:drug effects; D005333:Fetus / Q000187:drug effects; D006801:Humans; D009154:Mutation; D010599:Pharmacokinetics; D021281:Quantitative Structure-Activity Relationship; D018570:Risk Assessment; D014116:Toxicology