The value and utility of these types of information, taken together, to predict risk depends on the type of dietary supplement ingredient that is being considered. Cause for concern with a botanical dietary supplement may be derived from information about risk associated with known chemical constituents, as well as information about risk associated with related toxic plants. Similarly, information about the potential risk of dietary supplements that are pure single chemical compounds may be derived by reviewing a list of known risk-associated chemical compounds and chemical moieties (toxicophores) that raise concern of safety. However, for information about what might occur following ingestion of substances that are normally present in the human body (endogenous substances), it is helpful to understand what the substances do in the body at normal concentrations and to understand their mechanisms of action well enough to shed light on what might occur if the normal concentrations are exceeded. Certainly, for particular dietary supplement ingredients, such information could be more useful than reviewing a list of unrelated toxic chemical structures or substances that are not endogenous. Finally, especially when dietary supplements have undefined chemical composition2 but information about biological activity is available, it may be helpful and it is appropriate to consider whether the exhibited biological activity is the basis for safety concerns of other substances that are considered potentially harmful. Provided below are guiding principles and further descriptions of the different types of “relatedness” information, including discussion of when and why it is appropriate to use this type of information and specific questions that may help in extrapolating the most useful information.
GUIDING PRINCIPLE: Consumption of any botanical ingredient carries a certain degree of inherent risk to at least some segments of the human population, even for those plants used as foods or with a history of use for medicinal purposes. In the absence of comprehensive human trials establishing safety, scientific evidence for risk can be obtained by considering whether the plant constituents are