The Precision Toxicology initiative

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
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specific needs within European chemicals legislation, including the uptake of new approach methodologies
(NAMs) for setting precise regulatory limits on toxic chemicals.