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Different categories of animal studies (e.g., acute, subacute/subchronic [often used interchangeably], chronic, carcinogenicity) provide different information relevant to considering the potential toxic properties of a dietary supplement ingredient and can be classified as either traditional toxicology studies or as safety pharmacology studies.

Traditional Toxicology Studies

FDA’s Redbook describes several toxicology studies that are typically conducted in assessing the safety of food additives and other ingested substances (OFAS, 2001, 2003). These studies are applicable to evaluating most ingested substances, including dietary supplement ingredients, irrespective of what is known about their biological activities. It is highly probable that animal data from each type of toxicity study will not be available for every dietary supplement ingredient. However, consideration of the typical study protocols enables the animal data that are available on the dietary supplement ingredient in question to be placed in perspective regarding what type of information and conclusions about safety are appropriate to glean from the different study designs and endpoints. Perspective can also be gained by comparing the information available about a dietary supplement ingredient with the types of data that are often available about other ingested substances before they are considered safe.

In acute (single dose), subacute/subchronic (repeated doses), and chronic toxicity testing, groups of animals are treated with increasing amounts of the test substance to determine the dose that induces overt toxic effects. The resulting toxicities might be within organs (detected by gross examination or by observing behavioral changes), cells (detected by histological examination, such as light or electron microscopic analysis of fixed tissue samples), or subcellular structures (detected in biochemical studies, such as enzyme assays or protein analysis). In chronic toxicity testing (and in subchronic toxicity testing, which is not as lengthy as chronic toxicity testing), the test substance is typically administered to animals on a daily basis for 3 to 24 months (depending on the species) to characterize possible longer-term toxicity.

When conducting animal studies, blood concentrations of the test substance and its active metabolites are often determined. These blood levels are used to provide evidence that the test substance was absorbed, to describe the blood concentration–response curve, and to determine whether the metabolites formed in the test animal are qualitatively and quantitatively similar to those formed in humans. If the metabolites, especially active metabolites formed in the animal species studied, are not the same as

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