Systems Biology Approaches in Pharmacology and Toxicology

DALE E. JOHNSON*a,b

aUniversity of Michigan, School of Public Health, Department of Environmental health sciences, Апп arbor, MI 48109-2029, usA; bUniversity of California, Berkeley, Department of nutritional sciences and toxicology, Morgan Hall, Berkeley, CA 94720-3104, UsA *E-mail: This email address is being protected from spam bots, you need Javascript enabled to view it

Introduction

the science and practical field of toxicology has been changing dramatically over the last 15-20 years, transitioning into a more systems biology and network-based approach.1-4 several factors have been involved, including the developing genomics era where the understanding of genetic changes has enhanced the ability to understand diseases and chemically-induced toxic- ities at the molecular level. The genomics era has also ushered in “omics” technologies and approaches such as transcriptomics, metabolomics, proteomics, and epigenomics, which have changed the way we view mechanisms of toxicity and the perturbation of biological systems that lead to adverse outcomes.5 These advances have been coupled with the public availability of large datasets of information and new modeling approaches that have enhanced the ability to understand toxicological events and effects at multiple biological levels.6 since our scientific approaches, inquiries, and visions aimed at understanding toxicological events and outcomes have

Issues in Toxicology No. 31

Computational Systems Pharmacology and Toxicology Edited by Dale E. Johnson and Rudy J. Richardson © The Royal Society of Chemistry 2017 Published by the Royal Society of Chemistry, www.rsc.org been broadened tremendously, this reinforces our need for new and better ways to assess toxicity and risk. The large numbers of uncharacterized chemicals already present in the environment and new chemicals that continue to enter it has required hazard and risk assessments to be made with very few data. these factors have had a major influence on the need to accelerate new approaches and move away from an overdependence on in vivo animal testing and make better use of computational, molecular, and in vitro tools.67 the identification of the majority of toxic events in in vivo animal toxicology studies rely on high-dose exposure to the animals and default linear extrapolation procedures,8 with the incorporation of newer technologies absent in the vast majority of animal studies. this has been considered a shortcoming in risk assessment and several weaknesses in this process include the comparative shape of the dose-response relationship after relevant levels of human exposure, whether biological and/or toxicological thresholds do in fact exist and for what toxicological endpoints, and potential population variability in response.5

 
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