no-observed-adverse-effect level (NOAEL) and lowest-observed-adverse-effect level (LOAEL) are determined based on these factors if data are available to do so. Next, an uncertainty factor is applied to the NOAEL or LOAEL. The uncertainty factor is based on expert judgment of the uncertainties of extrapolating from the observed data to the general population. Dividing the NOAEL or LOAEL by the uncertainty factor results in the UL.

The third step is an assessment of the range and distribution of intake or exposure of the nutrient or food component in the general population. If the adverse effect appears to be associated with intake from dietary supplements only, then the UL is for supplements only. It is clearly indicated whether the UL is for total intake, intake from supplements only, or intake from fortified foods and supplements.

The last step is a characterization of the risk. The range of reported intakes of the nutrient is compared with the UL. If a large fraction of the general population is consuming chronic intakes above the UL, this could be a potential at-risk group. The UL does not include policy decisions, but the rationale suggests risk management guidelines for determining the significance of the risk to a population consuming a nutrient at levels above the UL.

REFERENCES

Bergfeld WF, Andersen FA. 2000. The cosmetic ingredient review. In: Estrin NF, Akerson JM, eds. Cosmetic Regulation in a Competitive Environment. New York: Marcel Dekker. Pp. 195–216.


CDER (Center for Drug Evaluation and Research). 2001. Milestone Status of OTC Drug Review Documents as of March 1, 2001. Online. Food and Drug Administration. Available at http://www.fda.gov/cder/otc/milestone/pdf. Accessed March 28, 2002.

CFSAN (Center for Food Safety and Applied Nutrition). 2001. Toxicological Principles for the Safety of Food Ingredients. Redbook 2000. Available at http://www.cfsan.fda.gov/~redbook/red-toca.html. Accessed March 28, 2002.


Degnan FH. 2000. FDA’s Creative Application of the Law. Washington, DC: Food, Drug, and Law Institute. Pp. 19–26.


Hallagan JB, Hall RL. 1995. FEMA GRAS—A GRAS assessment program for flavor ingredients. Flavor and Extract Manufacturers Association. Regul Toxicol Pharmacol 21:422–430.


IOM (Institute of Medicine). 1998. Dietary Reference Intakes. A Risk Assessment Model for Establishing Upper Intake Levels for Nutrients. Washington, DC: National Academy Press.


Woods LA, Doull J. 1991. GRAS evaluation of flavoring substances by the Expert Panel of FEMA. Regul Toxicol Pharmacol 14:48–58.



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement