Impact of updated BMD modeling methods on perchlorate and chlorate assessments of human health hazard.

Several exposure limits for perchlorate have been developed based on an early key event, inhibition of radioactive iodide uptake (RAIU) by the thyroid. These assessments have used a variety of definitions of the point of departure. The current assessment revisited the modeling for inhibition of RAIU, using state of the science methods. Bayesian hierarchical modeling was used to account for the repeated measures on the same individuals in the key dataset, and the underlying Beta distribution used for the modeling correctly reflected the bounding of RAIU between 0 and 1. We defined the BMR as a point value of 8% RAIU (rather than a change in RAIU), based on descriptions in the medical literature that RAIU below this value is considered abnormal. Because a definition of the BMR based on the mean response would correspond to about 50% of the population with a response below the BMR at the benchmark dose, we used a hybrid definition of the BMR. That is, the BMD was defined as the dose at which it was estimated that there would be a 10% extra risk in the population of having RAIU of 8% or lower. The resulting point of departure based on the BMDL was 0.03 mg/kg-day.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This work was supported by Specialised Nutrition Europe (SNE), Brussels, Belgium. The sponsor reviewed a much earlier version of this work, in which the average results from Greer et al. (2002) were modeled using a variety of approaches. However, the sponsor did not see any of the results with the modeling of the individual data from the Greer study prior to submittal of the manuscript. LTH and BCA also have had two recent projects supported by organizations with membership lists that overlap with that of SNE. LTH and BCA received support from Grocery Manufacturers Association, the Institute of Shortening and Edible Oils, the EU Vegetable Oil & Proteinmeal Industry, the Infant Nutrition Council of America, FoodDrink Europe, and the International Technical Caramel Association for a review of benchmark dose modeling methods that was published in 2018. LTH and BCA are also currently receiving support from ILSI NA for an unrelated project.
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