title: Toxicity testing in the 21st century beyond environmental chemicals.
abstract: After the publication of the report titled Toxicity Testing in the 21st Century - A Vision and a Strategy, many initiatives started to foster a major paradigm shift for toxicity testing - from apical endpoints in animal-based tests to mechanistic endpoints through delineation of pathways of toxicity (PoT) in human cell based systems. The US EPA has funded an important project to develop new high throughput technologies based on human cell based in vitro technologies. These methods are currently being incorporated into the chemical risk assessment process. In the pharmaceutical industry, the efficacy and toxicity of new drugs are evaluated during preclinical investigations that include drug metabolism, pharmacokinetics, pharmacodynamics and safety toxicology studies. The results of these studies are analyzed and extrapolated to predict efficacy and potential adverse effects in humans. However, due to the high failure rate of drugs during the clinical phases, a new approach for a more predictive assessment of drugs both in terms of efficacy and adverse effects is getting urgent. The food industry faces the challenge of assessing novel foods and food ingredients for the general population, while using animal safety testing for extrapolation purposes is often of limited relevance. The question is whether the latest paradigm shift proposed by the Tox21c report for chemicals may provide a useful tool to improve the risk assessment approach also for drugs and food ingredients.
authors.affiliation: CAAT-Europe, University of Konstanz, Konstanz, Germany.
authors.forename: Costanza
authors.initials: C
authors.lastname: Rovida
authors.affiliation: Tsukuba Drug Safety, Biopharmaceutical Assessment Core Function Unit, Eisai Co., Ltd., Ibaraki, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Asakura
authors.affiliation: CAAT-Europe, University of Konstanz, Konstanz, Germany.
authors.forename: Mardas
authors.initials: M
authors.lastname: Daneshian
authors.affiliation: Eurofins BioPharma Product Testing Munich GmbH, Planegg, Germany.
authors.forename: Hana
authors.initials: H
authors.lastname: Hofman-Huether
authors.affiliation: CAAT-Europe, University of Konstanz, Konstanz, Germany.
authors.forename: Marcel
authors.initials: M
authors.lastname: Leist
authors.affiliation: Danone Food Safety Center, Utrecht, The Netherlands.
authors.forename: Leo
authors.initials: L
authors.lastname: Meunier
authors.affiliation: Bioinformatics Research Center, Department of Biological Sciences, North Carolina State University, Raleigh, NC, USA.
authors.forename: David
authors.initials: D
authors.lastname: Reif
authors.affiliation: European Food Safety Authority (EFSA), Parma, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Rossi
authors.affiliation: Consultant, Basel, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Schmutz
authors.affiliation: Non-Clinical Development, UCB-Biopharma, Belgium.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Valentin
authors.affiliation: CAAT, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, US.
authors.forename: Joanne
authors.initials: J
authors.lastname: Zurlo
authors.affiliation: CAAT, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, US.|CAAT-Europe, University of Konstanz, Konstanz, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hartung
mesh_terms: D000826:Animal Testing Alternatives / Q000379:methods; D000818:Animals; D017277:Drug Approval; D004341:Drug Evaluation / Q000379:methods*; D004345:Drug Industry; D006801:Humans; D066298:In Vitro Techniques; D018570:Risk Assessment; D012449:Safety / Q000592:standards; D018675:Toxicity Tests / Q000379:methods*; D014481:United States; D014484:United States Environmental Protection Agency
keywords: Tox21c; drugs; food ingredients; safety assessment