AWWA ACE63226

This presentation outlines a comprehensive research program to improve the current quantitative risk assessment for low dose bromate exposures by developing a much more accurate understanding of the pre-systemic and systemic metabolism of bromate at environmentally relevant doses. The program consists of four stages: developing a comprehensive health research strategy; determining the rate of bromate reduction under simulated human stomach conditions; preliminary studies of bromate decomposition in rat blood; and, determining the relationship between drinking water concentrations and the actual dose to susceptible organs in rats and humans. Preliminary indications are that the dose response will be sub-linear at very low doses, meaning that the current calculated risks at low doses are likely being overestimated. A comprehensive health research strategy was developed in 2005 under a grant from AwwaRF. The report entitled: "Bromate Toxicity including Mechanisms of Cancer Induction", lays out a detailed plan that includes sequential studies of metabolism and pharmacokinetics, a chronic toxicity cancer bioassay in the female rat including in utero exposure, and developmental and neurotoxicity/ototoxicity, if appropriate. Studies of kinetics of bromate reacting under human stomach simulation are completed. They have demonstrated rapid decomposition in low pH hydrochloric acid and hydrogen sulfide and thiols at appropriate concentrations, and slowing at higher pHs and lower concentrations of thiol compounds. There were relatively small slowing effects of concurrent exposure to chlorine and chloramines, and the effects of other oxidizing and reducing agents were also quantified. The relatively small rate effects of chlorine and chloramine on bromate reactions with hydrogen sulfide in HCl indicate that the rate of reduction of bromate in the stomach should not be significantly affected when typical drinking water is consumed. (Miami, 2003-2005) Preliminary studies of the rate of decomposition in rat blood have verified the hypothesis that bromate would be reactive in blood and demonstrated that bromate was rapidly diminished in fresh rat blood and plasma, and also that the IC-ICP/MS analysis technique provides the opportunity to carry out very sensitive analyses of bromate and bromide in biological fluids. (UGa and SNWA, 2005-2006) The proposed final stage is being initiated within the context of the strategy as the result of the favorable preliminary results reported above. Experimental rate studies will be conducted in the rat and a quantitative physiologically-based pharmacokinetic (PBPK) model will be developed for rats and humans. (UGa and SNWA, 2006-2008) The U.S. Environmental Protection Agency's Health Effects Research Laboratory (DeAngelo, Delker, Hatch) is conducting additional studies to carry out parts of the research strategy and complement these projects. The possibility of verifying elements of the model in appropriate human studies is also under consideration.