The Precision Toxicology initiative.
The Precision Toxicology initiative. Toxicol Lett. 2023;383:33-42.
Toxicol Lett. 2023;383:33-42.
PrecisionTox is funded by the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No 965406. Additional funding is provided by the Office of the Vice Pres- ident for Research at Indiana University. The project described in this publication is part of ASPIS, which is research cluster of the Horizon 2020 funded projects PrecisionTox, ONTOX, and RISK-HUNT3R that represents Europe’s €60 million recent effort towards a more mecha- nistic approach to regulatory toxicology. The results and conclusions reflect only the authors’ view.
The goal of PrecisionTox is to overcome conceptual barriers to replacing traditional mammalian chemical safety testing by accelerating the discovery of evolutionarily conserved toxicity pathways that are shared by descent among humans and more distantly related animals. An international consortium is systematically testing the toxicological effects of a diverse set of chemicals on a suite of five model species comprising fruit flies, nematodes, water fleas, and embryos of clawed frogs and zebrafish along with human cell lines. Multiple forms of omics and comparative toxicology data are integrated to map the evolutionary origins of biomolecular interactions that are predictive of adverse health effects, to major branches of the animal phylogeny. These conserved elements of adverse outcome pathways (AOPs) and their biomarkers are expected to provide mechanistic insight useful for regulating groups of chemicals based on their shared modes of action. PrecisionTox also aims to quantify risk variation within populations by recognizing susceptibility as a heritable trait that varies with genetic diversity. This initiative incorporates legal experts and collaborates with risk managers to address specific needs within European chemicals legislation, including the uptake of new approach methodologies (NAMs) for setting precise regulatory limits on toxic chemicals.