Carcinogenicity of by-products of disinfection in mouse and rat liver

Abstract

By-products of disinfection were tested for initiating and/or promoting activity in rat liver by using the rat liver foci bioassay. The assay uses an increased incidence of gamma-glutamyltranspeptidase-positive foci (GGT foci) as an indicator of carcinogenicity. The by-products of disinfection, including chloramine, halogenated humic acids, halogenated ethanes, halogenated acetonitriles, halogenated methanes, halogenated ethylenes, and N-Cl-piperidine, did not initiate GGT foci, which would indicate that they are not capable of initiating carcinogenesis. Chloroform and halogenated benzenes were tested in this assay for their ability to promote the occurrence of GGT foci and tumors initiated by diethylnitrosamine (DENA). Chloroform (1800 ppm in the drinking water) either had no effect or inhibited the occurrence of GGT foci when administered subsequent to a single dose of DENA. However, when the chloroform was administered in drinking water concurrently with weekly doses of DENA, it enhanced the formation of liver tumors. Of 20 halogenated benzenes tested, only 1,2,4,5-tetrachlorobenzene and hexachlorobenzene promoted the occurrence of DENA-initiated GGT foci. Thus in rat liver, the tested by-products of drinking water disinfection did not demonstrate tumor-initiating activity, although a few appeared to possess tumor-promoting activity. Chloroform was also tested for tumor-promoting activity in 15-day-old Swiss mice initiated with ethylnitrosourea (ENU). At weaning they started to receive either 1800 ppm chloroform or 500 ppm sodium phenobarbital (the positive control for tumor promotion) in their drinking water. The mice continued to receive either chloroform or phenobarbital until 51 weeks of age and were sacrificed at 52 weeks of age.(ABSTRACT TRUNCATED AT 250 WORDS)