• If production of a hazardous phytochemical in a botanical appears to be particularly sensitive to environmental and growth conditions, then it may be appropriate to consider its use in dietary supplements as a risk unless quality control or other actions are implemented to assure that toxic levels of compounds are not reached in raw materials or finished products.

• Preparation affects toxicity. Materials that are traditionally consumed in cooked form may not have the same safety profile as in uncooked form, compounds that are concentrated or otherwise altered by the method of preparation will present a hazard that is of greater concern than for unprocessed material, and knowledge about the safety of one plant preparation should not be applied prima facie to different preparations of the same plant.

• Particular concern should arise when nontraditional or excessive levels of plant parts are consumed. There may be a tendency to consume more of the plant material in an encapsulated form than if it were used in its “native” form.

• Extraction of plant material with alcohol or aqueous alcohol, in which low-molecular-weight compounds are generally very soluble, will likely concentrate toxic components several fold. Thus, for botanicals containing toxic compounds, a shift from aqueous to alcoholic extracts should be a cause for concern unless there is credible evidence to mitigate this concern.

The physical–chemical properties and biological effects of a substance are derived from its chemical structure. If the chemical structure of a dietary supplement is known, but additional insight into the biological activity is needed, then it is scientifically appropriate to consider the information about the biological activity of structurally related substances. It is assumed that the biological effects of chemicals, including toxic effects, are implicit