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THE INDUCTION OF COLORECTAL NEOPLASIA BY A MIXTURE HIGH IN BROMINATED TRIHALOMETHANES (THMS) ADMINISTERED IN THE DRINKING WATER TO MALE F344/N RATS
Citation:
Sistrunk, C. M., M H. George, AND A B. DeAngelo. THE INDUCTION OF COLORECTAL NEOPLASIA BY A MIXTURE HIGH IN BROMINATED TRIHALOMETHANES (THMS) ADMINISTERED IN THE DRINKING WATER TO MALE F344/N RATS. Presented at Society of Toxicology, Nashville, TN, March 17-20,2002.
Description:
THE INDUCTION OF COLORECTAL NEOPLASIA BY A MIXTURE HIGH IN BROMINA TED TRIHALOMETHANES (THMS) ADMINISTERED IN THE DRINKING W A TER TO MALE F344/N RA TS.
Abstract:
The THMs are the most widely distributed and concentrated of the chlorine disinfection by-products (DBPs). Bromodichloromethane (BDCM) and bromoform (TBM) administered in corn oil were found to increase the incidence of colon neoplasia in the rat. BDCM administered in the drinking water to male rats did not induce colon neoplasia. Since THMs occur together in finished drinking water, we initiated a study to evaluate the ability of a mixture high in brominated THMs (Krasner et al., J. Amer. Water Works Assoc., 81: 41-53, 1989) to induce colon neoplasia in male F344/N rats. The animals were exposed to mixtures of THMs at lOx, 100x, 1,000x, and 10,000x ambient concentrations. Water containing 0.25% emulphor (vehicle control), 15 mg azoxymethane/kg ip (positive control) and 477 mg TBM/L (= to the 10,000X mixture) were included. Colon aberrant crypt foci (ACF; putative preneoplastic lesions) or neoplasia were scored at 13, 26 and 52 weeks. At 13 weeks the incidence (% of animals with ACF was 100% (AOM), 63% (TBM) and 88% (IO,OOOX THM). The 26 week incidence of ACF was 12% (0.25% emulphor), IOO% (AOM and TBM), and 63%, 88%, and 88% in the
100X, 1000X, and IO,000X THM groups respectively. At 52 weeks the incidence of ACF declined in all groups from the earlier time points. Pathologic analysis demonstrated an adenomatous polyp and hyperplasia (1/7 rats) in the 477 mg TBM/L and adenocarcinoma (1/7 rats) in the 10,000X mixture freatment group. There are data to support the conclusion that ACF are preneoplastic and colorectal neoplasia is rare in F344/N rats; we consider this finding to be biologically significant. This is the first report of DBPs administered in drinking water to test animals inducing neoplasia in animals at a site concordant with the findings of
epidmiological studies.
This is an abstract of a proposed presentation and does not necessarily reflect the view of the EPA.