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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 to account for the uncertainty in extrapolating animal data to humans is generally applied to the NOAEL when animal data are the primary data set available. While a default UF of 10 is often used to extrapolate animal data to humans for nonessential chemicals, a lower UF may be used because of data showing some similarities between the animal and 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).

Derivation of a UL

The UL is derived by dividing the NOAEL (or LOAEL) by a single UF that incorporates all relevant uncertainties. ULs, expressed as amount per day, are derived for various life stage groups using relevant databases, NOAELs, LOAELs, and UFs. In cases where no data exist with regard to NOAELs or LOAELs for the group under consideration, extrapolations from data in other age groups or animal data are made on the basis of known differences in body size, physiology, metabolism, absorption, and excretion of the nutrient. Generally, any age group adjustments are based solely on differences in body weight, unless there are data demonstrating age-related differences in nutrient pharmacokinetics, metabolism, or mechanism of action.

The derivation of the UL involves the use of scientific judgment to select the appropriate NOAEL (or LOAEL) and UF. The risk assessment requires explicit consideration and discussion of all choices made, regarding both the data used and the uncertainties accounted for. These considerations are discussed in the chapters on nutrients and food components. In this report, because of the lack of data to set a threshold, ULs could not be set for vitamin K, arsenic, chromium, and silicon.



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