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due to known genetic polymorphisms (i.e., differences in a gene’s DNA that occur in more than 1 percent of the population) (Hayes, 2001).

In general, it can be said that the human population, because of its extremely diverse genetic, environmental, nutritional, and disease status, is far more variable in response to chemicals than are populations of experimental animals.

Lack of Adverse Effects in Animals

As with any type of scientific study in which an effect is not observed, it is important to remember that a lack of observed or reported detrimental effects in an animal study is not adequate evidence that a particular substance is “safe” to humans.2 The sensitivity of animal experiments in detecting particular effects is of utmost importance when extrapolating from animal studies to humans. Use of animal data to mitigate concerns raised by other data is appropriate only if animal studies are sensitive enough to detect adverse effects if they occur. Sensitivity depends on experimental design factors, such inclusion of positive controls, study power, and whether relevant endpoints were examined in the animals. For example, if an animal study only reported how many animals died or exhibited gross toxicity following short-term administration of an ingredient, it is not acceptable to conclude that this ingredient does not cause cancer following chronic intake by humans. Even if a lack of adverse effects in an appropriate model is reported, it is not scientifically valid to use such information to mitigate other types of information suggesting risk if the study does not have the statistical power necessary, is incompletely reported, does not include positive controls, or is otherwise inadequately designed to detect a risk. In summary, it is only negative data originating from well-designed studies or other credible sources that may mitigate or eliminate a concern raised by other data.

Quality Issues

While all animal experiments may be informative, the nature of the experimental design, the quality of the methodology, and the statistical significance of the results need to be taken into consideration in weighing the evidence of toxicity. As was mentioned earlier in this chapter, recommendations for well-designed safety tests using animals are described in FDA’s Redbook (OFAS, 2001, 2003) while general characteristics of ideal


See also Chapter 10.

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