Under the slogan of Toxicology for the 21st Century and spearheaded by EPA, NIH and FDA, chemical and drug safety sciences have embarked to embrace toxicity mechanism. This was very much fueled by the 2007 NRC report “Toxicity Testing in the 21st Century: A Vision and a Strategy”. The concept requires developing quality-assured consensus about toxicity mechanism, in the end more molecular and quantitative than the current OECD efforts of Adverse Outcome Pathways. The Human Toxome project, funded as an NIH Transformative Research grant 2011-2016, is focused on developing the concepts and the means for deducing, validating, and sharing molecular Pathways of Toxicity (PoT). Using the test case of estrogenic endocrine disruption, the responses of MCF-7 human breast cancer cells are being phenotyped by transcriptomics and mass-spectroscopy-based metabolomics. The bioinformatics tools for PoT deduction represent a core deliverable. A key challenge for mapping the Human Toxome is the multi-omics integration. A number of challenges for quality and standardization of cell systems, omics technologies, and bioinformatics are being addressed. In parallel, concepts for annotation, validation, and sharing of PoT information, as well as their link to adverse outcomes, are being developed. A reasonably comprehensive public database of PoT, the Human Toxome Knowledge-base, could become a point of reference for toxicological research and regulatory tests strategies.


Thomas Hartung Professor and Chair for Evidence-based Toxicologyhttp://caat.jhsph.edu

Integrative Ecotoxicology e-session

Photos by : Tyssul Patel