CONCLUSION

Benchmark doses based on the ED₁₀ and margin-of-exposure characterizations together provide a more realistic treatment of data than the regulatory potency measure (q₁*) based on the linearized multistage model.

The recommendation to use the ED₁₀ to characterize the dose-response relationship and margins of exposure to characterize the risk is consistent with classical assessments of toxicity and safety.

Using the ED₁₀ to characterize the dose-response relationship is consistent with the use of classical measures of toxicity like the no-observed-adverse-effect-level (NOAEL) to reflect dose levels that are likely to be without appreciable risks of deleterious effects.  These classical measures of toxicity are based on the idea of using the observed data to determine a dose level at which there is no detectable increase in the occurrence of adverse health effects (no increase compared to the probability of response at dose zero).

Using margins of exposure to characterize the degree of safety is consistent with use of allowable daily intake by the U.S. Food and Drug Administration, reference dose and reference concentration by the U.S. Environmental Protection Agency, minimum risk level by the U.S. ATSDR, and tolerable intake by the World Health Organization -- where, for example, the U.S. EPA describes the reference dose as ...an estimate (with uncertainty spanning perhaps an order of magnitude) of a daily exposure to the human population (including sensitive subgroups) that is likely to be without appreciable risk of deleterious effects during a lifetime.