Rfd, and Unaccounted for Contribution of Perchlorate in Food Are Components of The

(FR) notice requesting comments on alternative approaches to analyzing data related to EPA's perchlorate regulatory determination (the Notice; U.S. EPA, 2009b). The Notice says that " these additional comments are sought in an effort to ensure consideration of all the potential options for evaluating whether there is a meaningful opportunity for human health risk reduction of perchlorate through a national primary drinking water rule. " The following four points summarize the response prepared by Intertox on behalf of the Perchlorate Study Group (PSG). 1. Interpretation of physiologically-based pharmacokinetic (PBPK) modeling: The use of scientifically derived PBPK models is the best scientific approach among all alternatives for evaluating the relative sensitivity of different life stages, consistent with the conclusions of EPA's peer reviewers and the National Academy of Sciences National Research Council (NRC). The current EPA PBPK model for perchlorate, however, uses values for some key parameters (e.g., urinary clearance) that are not supported by the scientific evidence. The model also does not account for up-regulation of the sodium iodide symporter (NIS). As a result, the model does not provide the best scientific estimates of iodide uptake inhibition (IUI) that would be associated with a particular perchlorate dose, and likely overestimates IUI from perchlorate exposure for various life stages. Further, input parameters are not selected from consistent points within their distributions, such that it is unclear whether the model output represents low, average, or upper-bound estimates of possible IUI. Nonetheless, the predicted levels of IUI in the Notice are low and would be indistinguishable from fluctuations resulting from differences in diet and feeding styles. No adverse health concern at any life stage would be expected based on exposure to perchlorate at the point of departure dose (7 μg/kg-d). EPA should revise this model to represent science-based accurate information on PBPK parameters and use the results to determine whether regulation is necessary. 2. Derivation of alternative Health Reference Levels (HRLs) based upon body weight and water consumption rates for sensitive life stages: The alternative HRL calculation which relies on life-stage specific body weight and water consumption rates is not scientifically justified. Environmental Health Hazard Assessment (OEHHA)) have conducted rigorous scientific assessments and have determined that the fetus of the hypothyroid pregnant woman is the most sensitive to perchlorate's potential health effects, not the infant as suggested by the alternative HRL calculation. The Notice provides no scientific evidence that shows otherwise and offers …