The panellists were: Alan Goldberg, Founding Director of the Center for Alternatives to Animal Testing and Professor of Toxicology at the Johns Hopkins Bloomberg School of Public Health; Nicole Kleinstreuer, PhD, a specialist in the field of computational modelling and the extrapolation of in vitro data to in vivo situations; Francois Busquet, PhD, coordinator of the Europe Center of Alternatives to Animal Testing, and Dr. Melvin Andersen from The Hamner Institutes for Health Sciences and co-author of the report “Toxicity in the 21st Century - A Vision and Strategy” (Tox21 for short), which was discussed in the roundtable meeting. The discussion was moderated by James M. McKim, PhD, Editor-in-Chief of the new journal, and among other things, CEO of IONTOX.

Tox21 is about a reorientation in the risk assessment and evaluation of chemicals using human cell models in combination with high-throughput screenings for toxicity tests, about computer models and above all a new perspective on what should ever be included in a toxicological evaluation. No more the end phenomenon sick, healthy, dead etc. should play a role, but relevant and in the focus is the influence of the metabolic pathways and their importance at different levels.

The panellists discussed policy approaches as well as the complexity of implementing the so-called adverse outcome pathways (AOP), a sequence of events from the exposure of an individual (or population) to a chemical to the ultimate toxic effect on an individual or population level.

The discussion also looked back on the report’s origins and the situation at the time of its publication in 2007. The report was written at a time when industry began using cell cultures, as Alan Goldberg reminded. It was considered a milestone that all the participant national government agencies, such as the EPA, the National Toxicology Program, the National Institutes of Environmental Health Sciences, NIH and the FDA signed a memorandum to implement the strategies recommended in the report. Melvin Andersen sees the reports focus as being on in vitro tests that can define “toxicity pathways” (i.e. the metabolic processes influenced by toxic influences). Toxicity pathways are in fact normal cellular metabolic pathways that can nonetheless lead to toxicity in case of sufficiently severe disturbances.

Francois Busquet reported on current developments from an EU perspective. The European Commission and the American EPA are expediting the implementation of the AOP concept (adverse outcome pathways) for regulatory decisions. However, he also pointed out the difficulty of implementation by 28 European regulatory authorities in the Member States. According to Nicole Kleinstreuer, international working groups are currently making great efforts include complex in vitro and high-throughput methods in various areas of AOPs.

The new journal “Applied In Vitro Toxicology” focuses on the application of in vitro tools in risk and safety assessment and is published by Mary Ann Liebert, Inc., publishers.

Click here for the roundtable discussion:
http://online.liebertpub.com/doi/abs/10.1089/aivt.2014.1501?journalCode=aivt