AWWA WQTC69472

AWWA WQTC69472 Presystemic Metabolism and Detoxification of Bromate after Ingestion: AwwaRF 4042 Progress Report

Conference Proceeding published 11/01/2008 by American Water Works Association

Written By Cotruvo, Joseph; Bull, Richard; Cummings, Brian; Fisher, Jeffrey; Snyder, Shane; Quinones, Oscar; Ong, Choon Nam; Keith, Jason; Gordon, Gilbert; Pacey, Gilbert

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This powerpoint presentation begins by presenting the research strategy that includes the following:develop Physiologically BasedPharmacokinetic (PBPK) Model to quantifyorgan dose from ingestion at low doses; and,mechanism of toxic response at low doses. This leads to areexamination of the basis for health goal, and arevision of risk assessment at low doses. A summary of bromate health risk is presented, along with critical risk assessment issues, pharmacokinetic issues with bromate ingestion, bromate chemistry and kinetics, cellular effects, and metabolism kinetics experiments. Study progress and conclusions indicate the following: developed sampling, storage and analytical proceduresfor bromate in body fluids @ 1ng/ml;rapid reduction by sulfide simulated gastric juice at lowpH and with reducing agents, e.g. ferrous, iodide, nitrite;minor effect of chlorine on reduction rate;liver cells are resistant to bromate toxicity vs kidney;liver is not a target organ for cancer;rapid elimination from blood by iv and ingestion(first pass GI/liver metabolism);half life in minutes vs perchlorate half life ~12 hours;exploring possibility of endogenous formation; and,elucidating, partitioning parameters, organ distribution,bromide effects, PBPK model, risk assessment. Includes tables, figures.

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