the risk assessment: to provide an estimate of a level of intake that will protect the health of the healthy population (Mertz et al., 1994).

Although several reports describe the underlying basis for UFs (Dourson and Stara, 1983; Zielhuis and van der Kreek, 1979), the strength of the evidence supporting the use of a specific UF will vary. Because the imprecision of these UFs is a major limitation of risk assessment approaches, considerable leeway must be allowed for the application of scientific judgment in making the final determination. Because the data on nutrient toxicity may not be subject to the same uncertainties as are data on nonessential chemical agents, the UFs for nutrients are typically less than 10. They are lower with higher-quality data and when the adverse effects are extremely mild and reversible.

In general, when determining a UF, the following potential sources of uncertainty are considered:

• Interindividual variation in sensitivity. Small UFs (close to 1) are used if it is judged that little population variability is expected for the adverse effect, and larger factors (close to 10) are used if variability is expected to be great (NRC, 1994).

• Extrapolation from experimental animals to humans. A UF is generally applied to the NOAEL to account for the uncertainty in extrapolating animal data to humans. Larger UFs (close to 10) may be used if it is believed that the animal responses will underpredict average human responses (NRC, 1994).

• LOAEL instead of NOAEL. If a NOAEL is not available, a UF may be applied to account for the uncertainty in deriving a UL from the LOAEL. The size of the UF involves scientific judgment based on the severity and incidence of the observed effect at the LOAEL and the steepness (slope) of the dose response.

• Subchronic NOAEL to predict chronic NOAEL. When data are lacking on chronic exposures, scientific judgment is necessary to determine whether chronic exposure is likely to lead to adverse effects at lower intakes than those producing effects after subchronic exposures (exposures of shorter duration).

The UL is derived by dividing the NOAEL (or LOAEL) by a single UF that incorporates all relevant uncertainties. For infants, ULs were not determined for any of the B vitamins or choline because of the lack of data on adverse effects in this age group and concern regarding infants’ possible lack of ability to handle excess amounts.