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INTERRELATIONSHIPS AMONG EPIGENETIC MECHANISMS FOR RISK ASSESSMENT OF DICHLOROACETIC ACID, A DRINKING WATER BY-PRODUCT OF THE CHLORINE DISINFECTION PROCESS
Citation:
DeAngelo, A B. INTERRELATIONSHIPS AMONG EPIGENETIC MECHANISMS FOR RISK ASSESSMENT OF DICHLOROACETIC ACID, A DRINKING WATER BY-PRODUCT OF THE CHLORINE DISINFECTION PROCESS. Presented at Microbial/Disinfection By-product Health Effects Symposium, Lisle, IL, March 24-26, 2001.
Description:
The reauthorization of The Safe Drinking Water Act of 1996 requires the EPA to develop a priority list of chemicals that are present in drinking water and to conduct research into the modes and mechanisms of action by which they produce adverse effects. The disinfection by-products (DBPs) are included in the list. The haloacetic acids along with the trihalomethanes and haloacetonitriles are the DBPs found at the highest concentrations in finished drinking water following chlorine disinfection of surface waters. Dichloroacetic acid (DCA), one of the most widely detected DBPs following chlorine disinfection of surface waters, occurs in finished drinking water at concentrations greater than 100 ug/L and with median concentrations in the 15 -19 ug/L range.
The carcinogenicity of DCA in the liver of male and female B6C3F1 mouse and the F344/N
male rat has been well demonstrated . More recent data has been generated for
the female B6C3F1 mouse and the C3H and C57BL parental strains of the B6C3F1 mouse (DeAngelo, unpublished observations). When the numbers of hepatocellular carcinomas (multiplicity; HC) per liver were plotted against dose it became apparent that the dose- response curves are biphasic (referred to as hockey stick; Figure 1). There is a gradual increase in the HC multiplicity for male B6C3F1 and C3H mice, strains with a high spontaneous background of liver HC, to 0.5 g/L DCA (p< or = O.O5). The mean daily doses (MDD) were 84 and 120 mg/kg/day respectively. For the female B6C3F1 and male C57BL mice which have a low background of spontaneous liver cancer, no increase in the HC multiplicity was observed at 0.5 g/L DCA ( MDDs of 94 and 66 mg/kg/day repectively). DCA concentrations greater than 0.5 g/L (average MDD of 91 mg/kg/day) resulted in a dose-response curve attaining a steeper slope. At the highest DCA concentrations tested (3.5 g/L, 430-480 mg/kg/day; 5 g/L, 612-746 mg/kg/day) there were no differences in the HC response among all the DCA treated animals.