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Dietary Supplements: A Framework for Evaluating Safety
any information about likely toxicities associated with these ingredients. Finally, melatonin and chromium picolinate were prepared by collecting only information relevant to the major possible toxicities in evidence from the human data and animal and in vitro toxicity studies. All human data were included in their prototype monographs, but only the animal, in vitro, and related substances data that were likely to reveal any targeted toxicities were included in their prototype monographs.
Given that resources are indeed limited, it is more important to efficiently collect data for integrative evaluations than to produce an exhaustive data collection document. The best approach from the experience with the six prototypes seems to be one between the second and third approaches used. That is, human data that are reasonably available should be collected. Data from animal and in vitro studies that are specifically designed to address safety and toxicity should be collected, as should relevant information about related toxic substances. Data relevant to the concerns raised by this information should then be collected. Finally, abstracts or other summaries of in vitro and animal data that are not from toxicity studies, or validated in vitro studies, per se, should be reviewed and used to judge which full reports need to be considered.
Integrating: Considering Consistency and Plausibility and Evaluating Heterogeneous or Seemingly Inconsistent Data
All data relevant to a particular concern often do not agree or point to the same conclusion. In preparing the prototype monographs, it became clear that articulating how to appropriately weave the different types of information together would be helpful. Thus Chapter 10 provides guidance through the difficult and often imprecise process of “weighing the evidence” to reach a scientifically appropriate conclusion about risk. It describes how biological plausibility and consistency are important, as is discounting “negative” data or studies that would not be expected to detect an effect even if it did occur.
Chaparral provides an illustrative example of how concerns raised by knowledge of the substance NDGA found in chaparral and its chemical structure provides biological plausibility to the human adverse events observed and a possible link to the nephrotoxicity observed in animals. Hypothesizing that lipid-soluble NDGA is the problematic substance is also consistent with the fewer number of adverse effects reported with ingestion of chaparral tea (an aqueous extract) as compared with capsules or tablets. As for reproductive effects of chaparral, there is consistency between the in vitro effects of NDGA on prostanoid synthesis and the animal effects observed. The reproductive effects, if attributable to NDGA, are also consistent with any claimed safe historical use of tea since it seems unlikely they