title: In vitro testing of basal cytotoxicity: Establishment of an adverse outcome pathway from chemical insult to cell death.
abstract: In this paper, an in vitro basal cytotoxicity testing strategy is described for new chemical entities that lack any pre-existing information on potential toxicity. Special attention is paid to the selection of the cellular system, cytotoxicity assay and exposure conditions. This approach is based on a newly proposed generic adverse outcome pathway from chemical insult to cell death that consists of 3 steps, including initial cell injury, mitochondrial dysfunction and cell demise. The suggested strategy to consider in vitro basal cytotoxicity as a first step in evaluating the toxicity of new chemical entities can be placed in a tiered strategy that could be continued by evaluating more specific types of toxicity.
authors.affiliation: Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium. Electronic address: mvinken@vub.ac.be.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Vinken
authors.affiliation: Institute for Risk Assessment Sciences, Division of Toxicology, Utrecht University, PO Box 80.177, 3508, TD, Utrecht, The Netherlands.
authors.forename: Bas J
authors.initials: BJ
authors.lastname: Blaauboer
mesh_terms: D000818:Animals; D016923:Cell Death; D003603:Cytotoxins / Q000633:toxicity*; D004353:Drug Evaluation, Preclinical; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D018675:Toxicity Tests
chemical_list: D003603:Cytotoxins
keywords: Adverse outcome pathway; Basal cytotoxicity; Chemical; In vitro experimentation