exposure conditions that are unlikely to cause noncancer health effects, which are typically assumed to have a threshold dose above which deleterious health effects would be expected to occur. The major issues in the calculation of the RfD are identifying the most sensitive effects that are relevant to the human for selecting the no-observed-adverse-effect level (NOAEL) or the lowest-observed-adverse-effect level (LOAEL), the determination of the NOAEL or LOAEL from the most appropriate study, and the magnitudes of the uncertainty factors and the modifying factor used in the process.

ORNL has published a detailed description of the method for deriving the RfD (see Opresko et al. 1998). Briefly, the RfD is calculated by determining the most sensitive and significant NOAEL or LOAEL for noncancer effects and dividing that by the product of a series of uncertainty factors and a modifying factor:

where UFA represents the uncertainty of using experimental animal data for human effects, UFH represents the variable susceptibilities in the human population (e.g., genetic, nutritional, age), UFL represents the expected ratio of the LOAEL to the NOAEL when a LOAEL is used instead of a NOAEL, UFS represents the uncertainty of predicting chronic exposure effects on the basis of subchronic exposure studies, UFD represents the uncertainty assigned to an inadequate data base, and MF is a modifying factor to account for any additional uncertainty not addressed by the standard uncertainty factors.

Typically, uncertainty factors are assigned values ranging from 1 to 10. If information concerning a factor is sparse and uncertainty is high, a default value of 10 generally is used. If information is available, the uncertainty factor might be reduced to 1. For example, UFA would be 1 if the NOAEL or LOAEL is based on human data. A value of less than 1 for the UFA would be used if the NOAEL for the biological end point of concern is more sensitive in animals than in humans. UFH would be less than 10 if the NOAEL or LOAEL is based on a susceptible human subpopulation. UFS would be 1 if adequate chronic exposure studies have been conducted or chronic effects are not expected. UFL would be 1 if a NOAEL is available. UFD would be 1 if an adequate array of human



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