Computational Systems Pharmacology and Toxicology
CHAPTER 4: Linking Environmental Exposure to Toxicity1
Published:01 Mar 2017
Special Collection: 2017 ebook collectionSeries: Issues in Toxicology
Noffisat Oki, Jeremy Leonard, Mark Nelms, Shannon Bell, Yu-Mei Tan, Lyle Burgoon, Stephen Edwards, 2017. "Linking Environmental Exposure to Toxicity1", Computational Systems Pharmacology and Toxicology, Rudy J Richardson, Dale E Johnson
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As the number of chemicals and environmental toxicants in commerce continue to increase, so does the need to understand the links between exposure to these stressors and any potential toxic reactions. Assessing the impact of these stressors on public health as well as our environment requires an understanding of the underlying mechanistic processes connecting their introduction into the environment to the associated adverse outcomes.
Traditional in vivo methods of toxicity testing have become too costly and inefficient. In recent times, in vitro high-throughput toxicity screening methods have been introduced to reduce the burden of in vivo testing and keep pace with the ever increasing number of required tests. The adverse outcome pathway (AOP) concept has been adopted by many in the toxicology community as a framework for linking the biological events that occur from the point of contact with these stressors and the resulting adverse outcome. This provides a mechanistic framework for understanding the potential impacts of perturbations that are measured via in vitro testing strategies. The aggregate exposure pathway (AEP) has been proposed as a companion framework to the AOP. The goal of the AEP is to describe the path the introduction of the stressor into the environment at its source to a target site within an individual that is comparable with the concentrations in the in vitro toxicity tests. Together, these frameworks provide a comprehensive view of the source to adverse outcome continuum.
Standardizing our representation of the mechanistic information in this way allows for increased interoperability for computational models describing different parts of the system. It also aids in translating new research in exposure science and toxicology for risk assessors and decision makers when assessing the impact of specific stressors on endpoints of regulatory significance.