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Mapping the Human Toxome by Systems Toxicology
Author(s) -
Bouhifd Mounir,
Hogberg Helena T.,
Kleensang Andre,
Maertens Alexandra,
Zhao Liang,
Hartung Thomas
Publication year - 2014
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12198
Subject(s) - adverse outcome pathway , prioritization , toxicity , risk assessment , human health , test strategy , risk analysis (engineering) , human cell , computer science , toxicology , computational biology , biology , medicine , business , environmental health , computer security , genetics , process management , software , programming language , cell culture
Abstract Toxicity testing typically involves studying adverse health outcomes in animals subjected to high doses of toxicants with subsequent extrapolation to expected human responses at lower doses. The low‐throughput of current toxicity testing approaches (which are largely the same for industrial chemicals, pesticides and drugs) has led to a backlog of more than 80,000 chemicals to which human beings are potentially exposed whose potential toxicity remains largely unknown. Employing new testing strategies that employ the use of predictive, high‐throughput cell‐based assays (of human origin) to evaluate perturbations in key pathways, referred as pathways of toxicity, and to conduct targeted testing against those pathways, we can begin to greatly accelerate our ability to test the vast ‘storehouses’ of chemical compounds using a rational, risk‐based approach to chemical prioritization and provide test results that are more predictive of human toxicity than current methods. The NIH T ransformative R esearch G rant project M apping the H uman T oxome by S ystems T oxicology aims at developing the tools for pathway mapping, annotation and validation as well as the respective knowledge base to share this information.