SPSG #5: Dose-Response Theory

This chapter is a compendium of pharmacology and toxicology theory, and since it doesn’t build on any of the previous chapters, it is essentially a third introductory chapter.  Although does get a bit technical, it is designed to give a sense of what the quantitative issues are without delving into mathematics.  Although it isn’t necessary for most of the later chapters, it is provided as background material for some of the discussions involving theoretical probability in some of the later chapters, especially eight through eleven.  The chapter commences with a survey of basic concepts including biochemical mechanisms underlying the interaction of a toxic chemical with a biological molecule, and toxicokinetic theory that describes what happens before it gets there.  There is also discussion of statistical theories like probit analysis that treat the causal issue as a problem of describing how much the dose required to produce a given effect varies in a population.  There are also hybrid or two-dimensional models that describe the both magnitude of individual effect and population variation as well.  It has long been recognized that there is a temporal component to dose response relationships that can vary between both chemicals and effects; yet the temporal component is often ignored.  All said, biology is complex and dose-response theory is imperfect; there is plenty of room for improvement.  Nonetheless, one thing seems clear; the dose makes the poison.  Effects tend to get bigger as the dose gets bigger, but not necessarily in proportion.