Reference Manual on Scientific Evidence: Fourth Edition (2025)
Chapter: Prologue to the Reference Guide on Exposure Science and Exposure Assessment, the Reference Guide on Epidemiology, and the Reference Guide on Toxicology
Prologue to the Reference Guide on Exposure Science and Exposure Assessment, the Reference Guide on Epidemiology, and the Reference Guide on Toxicology
Courts are sometimes faced with cases that involve toxic substances that cause disease rather than traumatic injury. Those cases often raise difficult questions of factual causation for which scientific evidence is important or essential. The next three reference guides address the disciplines of exposure science and exposure assessment, epidemiology, and toxicology, each of which often plays an important role in such cases.
The discipline of exposure science and exposure assessment focuses on assessing what the dose of a particular substance might have been under a defined set of circumstances. Simply stated, “dose” refers to the amount of a toxic substance that has entered the body. Dose comprises both the magnitude of exposure and the duration of the exposure. Exposure scientists describe the conditions that determine the extent to which a toxic substance enters the body of a person exposed to that substance. For example, if a toxic substance is poorly absorbed through the digestive tract but passes easily into the bloodstream from the lungs, exposure science endeavors to explain the differences between swallowing or inhaling a given quantity of that substance.
The discipline of toxicology focuses on determining the “response” to a dose—that is, both whether an agent causes a specific type of adverse (toxic) effect and how much of a particular substance it takes to cause that effect. Because of the obvious ethical limitations of studying known or suspected toxic substances directly in humans, toxicology relies on a combination of experimental studies using animals (called in vivo studies) and human-derived cells and/or tissues (called in vitro studies). The experimental setting enables toxicologists to carefully control and define dose and exposure. Much of toxicology seeks to understand the mechanism by which a substance causes adverse biological effects.
The discipline of epidemiology is focused (in this context) on evaluating whether the exposure of a population of individuals to a particular substance is associated with a change (usually an increase) in the occurrence of a specific
disease. Epidemiology faces the same ethical constraints against human experimentation as does toxicology. As a result, except for randomized clinical trials of pharmaceutical agents with potential benefits thought to outweigh their potential risks, epidemiologic studies are observational rather than experimental. Observational epidemiologic studies cannot control exposure and dose as toxicological studies can. But epidemiologists, unlike toxicologists, are able to study groups of human beings rather than human tissues or nonhuman animals.
Each of these disciplines may be brought to bear on a particular scientific question concerning a suspected toxic substance, and they interrelate in important ways. Epidemiologists rely heavily on exposure science to help define the dose and duration of exposure to a substance that individuals in a study population received. Toxicologists also rely on careful assessment of dose. Toxicological information about a substance’s mode or mechanism of action helps in assessing whether an observed epidemiologic association reveals a causal relationship between exposure and disease. Conversely, epidemiologic information about a substance’s association with disease in human populations helps in assessing whether toxicological effects seen in animal or in vitro studies may validly be extrapolated to people.
Thus, these three reference guides, while independent, share many common elements. As much as possible, the authors have attempted to use common terms and definitions, although the reader should understand that usage may differ across disciplines. Not surprisingly, there will be some redundancy found among the three reference guides. But such redundancy is perhaps useful to highlight critically important elements that are necessary when assessing the scientific strengths and limitations of causal claims in litigation involving toxic substances and disease. The authors of these three reference guides encourage careful consideration and integration of the key scientific elements highlighted in all three guides: the Reference Guide on Exposure Science and Exposure Assessment, the Reference Guide on Epidemiology, and the Reference Guide on Toxicology.
