Jk. Dunnick et Rl. Melnick, ASSESSMENT OF THE CARCINOGENIC POTENTIAL OF CHLORINATED WATER - EXPERIMENTAL STUDIES OF CHLORINE, CHLORAMINE, AND TRIHALOMETHANES, Journal of the National Cancer Institute, 85(10), 1993, pp. 817-822
Background: Water chlorination has been one of the major disease preve
ntion treatments of this century. While epidemiologic studies suggest
an association between cancer in humans and consumption of chlorinatio
n byproducts in drinking water, these studies have not been adequate t
o draw definite conclusions about the carcinogenic potential of the in
dividual byproducts. Purpose: The purpose of this study was to investi
gate the carcinogenic potential of chlorinated or chloraminated drinki
ng water and of four organic trihalomethane byproducts of chlorination
(chloroform, bromodichloromethane, chlorodibromomethane, and bromofor
m) in rats and mice. Methods: Bromodichloromethane, chlorodibromometha
ne, bromoform, chlorine, or chloramine was administered to both sexes
of F344/N rats and (C57BL/6 X C3H)F1 mice (hereafter called B6C3F1 mic
e). Chloroform was given to both sexes of Osborne-Mendel rats and B6C3
F1 mice. Chlorine or chloramine was administered daily in the drinking
water for 2 years at doses ranging from 0.05 to 0.3 mmol/kg per day.
The trihalomethanes were administered by gavage in corn oil at doses r
anging from 0.15 to 4.0 mmol/kg per day for 2 years, with the exceptio
n of chloroform, which was given for 78 weeks. Results: The trihalomet
hanes were carcinogenic in the liver, kidney, and/or intestine of rode
nts. There was equivocal evidence for carcinogenicity in female rats t
hat received chlorinated or chloraminated drinking water; this evidenc
e was based on a marginal increase in the incidence of mononuclear cel
l leukemia. Rodents were generally exposed to lower doses of chlorine
and chloramine than to the trihalomethanes, but the doses in these stu
dies were the maximum that the animals would consume in the drinking w
ater. The highest doses used in the chlorine and chloramine studies we
re equivalent to a daily gavage dose of bromodichloromethane that indu
ced neoplasms of the large intestine in rats. In contrast to the resul
ts with the trihalomethanes, administration of chlorine or chloramine
did not cause a clear carcinogenic response in rats or mice after long
-term exposure. Conclusion: These results suggest that organic byprodu
cts of chlorination are the chemicals of greatest concern in assessmen
t of the carcinogenic potential of chlorinated drinking water.