Using an RfD or MOE Approach

Once the BMD is identified, the one-sided lower 95th confidence interval on the BMD called the BMDL (benchmark dose lower bound) is used as the POD. Similar to noncancer risk assessment, the POD is then divided by uncertainty factors to account for potential interspecies differences, intraindividual variability, and so on. The current risk assessment paradigm has accepted that, by accounting for uncertainty through use of the BMDL and other uncertainty factors, the resulting dose is either below a toxic threshold or so low as to constitute a virtually safe dose (Bogdanffy et al. 2001). 

Selecting a model to define the POD involves several factors, most importantly the nature of the available data, the desired risk metric, and the size and statistical power of the study. Depending on whether the data is quantal (based on incidence data) or continuous (based on a continuous biological parameter), as well the nature or severity of the adverse outcome, different modeling decisions may be appropriate. For quantal data, excess risk is usually examined, while for continuous data, several other metrics may be more useful (e.g., metrics that measure relative and absolute differences in mean responses, changes in mean relative to the standard deviation of controls, changes above specified value, etc.). Using information on cancer 

Selection of the key endpoint as well as the response level greatly affects the magnitnde of the POD. As shown in Table 26.1, the magnitude of the POD can vary by several orders of magnitude, depending on the selected key endpoint and response level. Eor example, the BMDLi based on cell cytotoxicity is 8500 times Iowct than 

TABLE 26.1. Benchmark Dose Calculation for Various Endpoints from Rat Bladder Cancer Studies at 10% and 1% Response Levels 

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