risk. EPA should clearly communicate this information as part of its risk characterization.

  • EPA should identify the most important data sets to be used for quantitative risk assessment for each of the four key end points (cancer, immunotoxicity, reproductive effects, and developmental effects). EPA should specify inclusion criteria for the studies (animal and human) used for derivation of the benchmark dose (BMD) for different noncancer effects and potentially for the development of RfD values and discuss the strengths and limitations of those key studies; describe and define (quantitatively to the extent possible) the variability and uncertainty for key assumptions used for each key end-point-specific risk assessment (choices of data set, POD, model, and dose metric); incorporate probabilistic models to the extent possible to represent the range of plausible values; and assess goodness-of-fit of dose-response models for data sets and provide both upper and lower bounds on central estimates for all statistical estimates. When quantitation is not possible, EPA should clearly state it and explain what would be required to achieve quantitation.

  • When selecting a BMD as a POD, EPA should provide justification for selecting a response level (e.g., at the 10%, 5%, or 1% level). The effects of this choice on the final risk assessment values should be illustrated by comparing point estimates and lower bounds derived from selected PODs.

  • EPA should continue to use body burden as the preferred dose metric but should also consider physiologically based pharmacokinetic modeling as a means to adjust for differences in body fat composition and for other differences between rodents and humans.

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