any extrapolation of animal data to predict human response has to take into account this possibility.
Key issues that are addressed in the data evaluation of human and animal studies are listed in Box 4-1.
The hazard identification step involves the examination of human, animal, and in vitro published evidence addressing the likelihood of a nutrient or food component eliciting an adverse effect in humans. Decisions regarding which observed effects are adverse are based on scientific judgments. Although toxicologists must consider the possibility that many demonstrable structural or functional alterations represent adverse effects with respect to nutrients, some alterations may be considered of little or self-limiting biological importance. As noted earlier, adverse nutrient-nutrient interactions are considered in the definition of an adverse effect.
The identification of a hazard is strengthened by evidence of causality. As explained in Chapter 3, the criteria of Hill (1971) are
BOX 4-1 Development of Tolerable Upper Intake Levels (ULs)
Components of Hazard Identification
Components of Dose-Response Assessment