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Dietary Supplements: A Framework for Evaluating Safety
harm, strength of evidence, and dose administered to animals factor into assessing animal data, along with general guidelines for integrating these factors. Animal data that raise a higher level of concern warrant immediate attention to evaluate the potential of the ingredient to cause harm. For data classified as lower to moderate concern, it is important to consider whether other animal data or other types of data (e.g., human data, in vitro data, or data on related substances) add to the level of concern.
POWER AND RELEVANCE OF ANIMAL DATA
Animal testing provides invaluable information about the potential for ingested substances to cause harm in humans. Studies in animals are regularly used as an important step in attempting to predict untoward effects of substances in humans (see, for example, the Food and Drug Administration’s [FDA’s] Redbook [OFAS, 2001, 2003] or guidance documents for new drugs [CDER, 2002]).
Animal studies are powerful because controlled studies can be conducted to predict effects that might not be detected from customary use by humans until they result in overt harmful effects. Animal studies are especially useful in detecting effects of chronic exposures and effects on reproductive and developmental processes because epidemiological methods of studying humans are especially problematic in these areas. The ability to administer agents to animals during their entire lifespan, if necessary, enables scientists to ascertain the potential toxic effects that may arise from long-term (chronic) exposure. Animal studies thus serve as important hypothesis generators and may be sufficient to indicate potentially unreasonable risk to human health, which justifies their use in evaluating the risks dietary supplement ingredients may pose to humans.
In general, adverse effects observed in well-designed and well-conducted animal studies should be treated as if they would occur in at least some members of the human population, assuming humans receive a sufficiently high dose. With some notable and important exceptions, the biological factors affecting the capacity of chemical substances to cause toxicity are broadly similar across mammalian species. Unless there is scientific evidence that raises significant doubt regarding the relevance of specific toxicity findings to humans, it is prudent and scientifically appropriate to consider animal studies relevant in evaluating potential human toxicity, especially in the many cases of dietary supplement ingredients where sufficient human data are not available. Similar positions on the relevance of animal data to human health have been supported by other committees of the National Academies, as well as by other organizations in the United States and internationally (NRC, 1994, 2001; NTP, 2002; WHO, 1999).