Studies of the toxic interactions of disinfection by-products.

A large number and variety of compounds are formed in the process of chlorinating drinking water. The classes of compounds formed include trihalomethanes, haloacetic acids, haloacetonitriles, halophenols, and halopropanones. Many of the compounds have been shown to be toxic and are currently being further evaluated by the U.S. Environmental Protection Agency (EPA). One group of the halopropanones found in chlorinated drinking water is the dichloropropanones. The toxicological properties of this group have not been well characterized. In addition, a number of investigators have shown that ketones potentiate the hepatotoxicity of haloalkanes. We conducted a series of studies to explore both the toxicity of the dichloropropanones and their potential interactions with a well-characterized haloalkane, carbon tetrachloride. A variety of toxicological and biochemical endpoints were used to evaluate the toxicity of the dichloropropanones and their interaction with CCl4, including cytochrome P-450 concentration, reduced glutathione levels, pentane generation, serum enzyme activities, and histopathology. Administration of 1,1-dichloropropanone (DCP) resulted in elevated serum enzymes associated with periportal necrosis. Glutathione levels were reduced by the administration of 1,1-DCP; pentane generation was not increased. When 1,1-DCP was given prior to CCl4, the data were consistent with additivity. Administration of 1,3-DCP did not result in elevated serum enzymes, nor was there histopathologic evidence of necrosis. Glutathione levels and pentane generation in the 1,3-DCP-treated groups were the same as those of controls. Inhibition of the toxicologic effects of CCl4 in a dose-related manner was observed when 1,3-DCP was administered prior to CCl4.