An acceptable daily intake (ADI) can also be determined from a NOAEL. ADI values are used for pesticides and food additives to define the daily intake of chemicals, which appear to be without appreciable risk of harm during an entire lifetime.

In an alternative approach, a specific effect dose or concentration, such as the ED05 (EC05) or ED10 (EC10) (the best estimate of the dose at a 5% or a 10% level of response) is determined for the dose-response curve based on rodent or human epidemiological studies (Crump 1984; Allen et al. 1994 a,b). That dose, which, unlike the NOAEL or LOAEL, does not have to be one of the experimental doses, represents the dose that results in a 5% or 10% response in the study population. The dose is determined from the experimental results by using a dose-response curve fitting program. Studies have confirmed that these levels of response (5-10%) represent the minimal level of effect that can statistically be resolved in a relatively robust bioassay (with the current design for detecting developmental toxicants). The benchmark dose (BMD) is frequently calculated using the lower confidence limit of the dose that results in a 5-10% response and thus represents with 95% confidence the lowest dose giving an increased 5% or 10% response in exposed populations over unexposed populations. Continuous responses from developmental toxicity bioassays include percentage of fetuses malformed, percentage of litters having one or more malformed fetuses, and birth weights (Kavlock et al. 1995).

RfDs and ADI values are derived from NOAELs or BMDs by dividing by uncertainty factors. Uncertainty factors, which are derived from animal and human data, generally involve dividing by a default value of 10 to account for uncertainties (EPA 1991). Uncertainty factors for developmental effects are applied to the NOAEL or BMD to include a 10-fold factor for interspecies extrapolation and a 10-fold factor for intraspecies variation. Additional 10-fold factors might be used to account for insufficiency in the database, extrapolation from subchronic to chronic exposures, and extrapolation from a LOAEL to a NOAEL. In practice, the aggregate product of all the default values is most often a factor of 100 to 1,000 (i.e., the acceptable human exposure concentration is 100- to 1,000-fold lower than the dose in the animal study that had little or no observable developmental effects). Because of increasing concern for susceptibility of children, the Food Quality Protection Act (Public Law 104-170; August 3, 1996) specifies an additional 10-fold default factor be applied under specific conditions. The default values are used unless there are research results that support the use of a different value. The need for uncertainty factors could be reduced with better data on comparative toxicokinetics, susceptible populations, and mechanisms of action. For example, if a NOAEL in a rat developmental toxicity study is used to set a RfD, then, in general, the NOAEL would be divided by 10 to account for extrapolation from animal studies to humans (interspecies extrapolation) and by another 10-fold factor to account for sensitive versus average human responses (intraspecies differences). Modifying factors can be used to change these default

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