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This presentation outlines a comprehensive research program to improve the current quantitative risk assessment for low dose bromateexposures by developing a much more accurate understanding of the pre-systemic andsystemic metabolism of bromate at environmentally relevant doses. The program consistsof four stages: developing a comprehensive health research strategy; determiningthe rate of bromate reduction under simulated human stomach conditions; preliminarystudies of bromate decomposition in rat blood; and, determining the relationship betweendrinking water concentrations and the actual dose to susceptible organs in rats andhumans. Preliminary indications are that the dose response will be sub-linear at very lowdoses, meaning that the current calculated risks at low doses are likely beingoverestimated.A comprehensive health research strategy was developed in 2005 under a grantfrom AwwaRF. The report entitled: "Bromate Toxicity including Mechanisms of CancerInduction", lays out a detailed plan that includes sequential studies of metabolism andpharmacokinetics, a chronic toxicity cancer bioassay in the female rat including in uteroexposure, and developmental and neurotoxicity/ototoxicity, if appropriate.Studies of kinetics of bromate reacting under human stomach simulation arecompleted. They have demonstrated rapid decomposition in low pH hydrochloric acidand hydrogen sulfide and thiols at appropriate concentrations, and slowing at higher pHsand lower concentrations of thiol compounds. There were relatively small slowing effectsof concurrent exposure to chlorine and chloramines, and the effects of other oxidizingand reducing agents were also quantified. The relatively small rate effects of chlorine andchloramine on bromate reactions with hydrogen sulfide in HCl indicate that the rate ofreduction of bromate in the stomach should not be significantly affected when typicaldrinking water is consumed. (Miami, 2003-2005)Preliminary studies of the rate of decomposition in rat blood have verified thehypothesis that bromate would be reactive in blood and demonstrated that bromate wasrapidly diminished in fresh rat blood and plasma, and also that the IC-ICP/MS analysistechnique provides the opportunity to carry out very sensitive analyses of bromate andbromide in biological fluids. (UGa and SNWA, 2005-2006)The proposed final stage is being initiated within the context of the strategy as theresult of the favorable preliminary results reported above. Experimental rate studies willbe 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) isconducting additional studies to carry out parts of the research strategy and complementthese projects.The possibility of verifying elements of the model in appropriate human studies isalso under consideration.

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Edition: Vol. - No. Published: 06/01/2006 Number of Pages: 31File Size: 1 file , 360 KB