Assessment of the carcinogenic potential of chlorinated water: experimental studies of chlorine, chloramine, and trihalomethanes

J Natl Cancer Inst. 1993 May 19;85(10):817-22. doi: 10.1093/jnci/85.10.817.


Background: Water chlorination has been one of the major disease prevention treatments of this century. While epidemiologic studies suggest an association between cancer in humans and consumption of chlorination byproducts in drinking water, these studies have not been adequate to draw definite conclusions about the carcinogenic potential of the individual byproducts.

Purpose: The purpose of this study was to investigate the carcinogenic potential of chlorinated or chloraminated drinking water and of four organic trihalomethane byproducts of chlorination (chloroform, bromodichloromethane, chlorodibromomethane, and bromoform) in rats and mice.

Methods: Bromodichloromethane, chlorodibromomethane, bromoform, chlorine, or chloramine was administered to both sexes of F344/N rats and (C57BL/6 x C3H)F1 mice (hereafter called B6C3F1 mice). Chloroform was given to both sexes of Osborne-Mendel rats and B6C3F1 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 ranging from 0.15 to 4.0 mmol/kg per day for 2 years, with the exception of chloroform, which was given for 78 weeks.

Results: The trihalomethanes were carcinogenic in the liver, kidney, and/or intestine of rodents. There was equivocal evidence for carcinogenicity in female rats that received chlorinated or chloraminated drinking water; this evidence was based on a marginal increase in the incidence of mononuclear cell leukemia. Rodents were generally exposed to lower doses of chlorine and chloramine than to the trihalomethanes, but the doses in these studies were the maximum that the animals would consume in the drinking water. The highest doses used in the chlorine and chloramine studies were equivalent to a daily gavage dose of bromodichloromethane that induced neoplasms of the large intestine in rats. In contrast to the results 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 byproducts of chlorination are the chemicals of greatest concern in assessment of the carcinogenic potential of chlorinated drinking water.

MeSH terms

  • Animals
  • Chloramines / toxicity*
  • Chlorine / toxicity*
  • Chlorofluorocarbons, Methane / toxicity*
  • Dose-Response Relationship, Drug
  • Female
  • Intestinal Neoplasms / chemically induced
  • Kidney Neoplasms / chemically induced
  • Liver / drug effects
  • Liver Neoplasms, Experimental / chemically induced
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Neoplasms, Experimental / chemically induced*
  • Rats
  • Rats, Inbred F344
  • Water Supply / standards*


  • Chloramines
  • Chlorofluorocarbons, Methane
  • Chlorine
  • chloramine