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The fifth edition includes new sections on the use of adverse outcome pathways, how climate change changes how we think about toxicology, and a new chapter on contaminants of emerging concern. Additional information is provided on the derivation of exposure-response curves to describe toxicity and they are compared to the use of hypothesis testing. The text is unified around the theme of describing the entire cause-effect pathway from the importance of chemical structure in determining exposure and interaction with receptors to the use of complex systems and hierarchical patch dynamic theory to describe effects to landscapes.