title: Review: toxicometabolomics.
abstract: Metabolomics use in toxicology is rapidly increasing, particularly owing to advances in mass spectroscopy, which is widely used in the life sciences for phenotyping disease states. Toxicology has the advantage of having the disease agent, the toxicant, available for experimental induction of metabolomics changes monitored over time and dose. This review summarizes the different technologies employed and gives examples of their use in various areas of toxicology. A prominent use of metabolomics is the identification of signatures of toxicity - patterns of metabolite changes predictive of a hazard manifestation. Increasingly, such signatures indicative of a certain hazard manifestation are identified, suggesting that certain modes of action result in specific derangements of the metabolism. This might enable the deduction of underlying pathways of toxicity, which, in their entirety, form the Human Toxome, a key concept for implementing the vision of Toxicity Testing for the 21st century. This review summarizes the current state of metabolomics technologies and principles, their uses in toxicology and gives a thorough overview on metabolomics bioinformatics, pathway identification and quality assurance. In addition, this review lays out the prospects for further metabolomics application also in a regulatory context.
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Environmental Health Sciences, Chair for Evidence-based Toxicology, Center for Alternatives to Animal Testing, 615 N. Wolfe St., Baltimore, MD, 21205, USA.
authors.forename: Mounir
authors.initials: M
authors.lastname: Bouhifd
authors.forename: Thomas
authors.initials: T
authors.lastname: Hartung
authors.forename: Helena T
authors.initials: HT
authors.lastname: Hogberg
authors.forename: Andre
authors.initials: A
authors.lastname: Kleensang
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
mesh_terms: D000818:Animals; D003627:Data Interpretation, Statistical; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D055432:Metabolomics / Q000379:methods* / Q000706:statistics & numerical data; D012984:Software; D014116:Toxicology / Q000379:methods* / Q000706:statistics & numerical data
keywords: analytical chemistry; bioinformatics; metabolomics; pathways of toxicity; quality assurance; toxicity testing for the 21st century