Dunnick J K, Melnick R L
National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, N.C. 27709.
J Natl Cancer Inst. 1993 May 19;85(10):817-22. doi: 10.1093/jnci/85.10.817.
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.
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.
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.
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.
These results suggest that organic byproducts of chlorination are the chemicals of greatest concern in assessment of the carcinogenic potential of chlorinated drinking water.
水氯化处理一直是本世纪主要的疾病预防措施之一。虽然流行病学研究表明人类癌症与饮用水中氯化副产物的摄入之间存在关联，但这些研究尚不足以就单个副产物的致癌潜力得出明确结论。
本研究的目的是调查氯化或氯胺化饮用水以及四种氯化有机三卤甲烷副产物（氯仿、溴二氯甲烷、氯二溴甲烷和溴仿）对大鼠和小鼠的致癌潜力。
将溴二氯甲烷、氯二溴甲烷、溴仿、氯或氯胺分别给予F344/N大鼠和（C57BL/6xC3H）F1小鼠（以下简称B6C3F1小鼠）的雌雄两性。将氯仿给予奥斯本-孟德尔大鼠和B6C3F1小鼠的雌雄两性。氯或氯胺以每天0.05至0.3 mmol/kg的剂量在饮用水中给予2年。三卤甲烷以每天0.15至4.0 mmol/kg的剂量通过玉米油灌胃给予2年，但氯仿给予78周。
三卤甲烷在啮齿动物的肝脏、肾脏和/或肠道中具有致癌性。接受氯化或氯胺化饮用水的雌性大鼠存在致癌性的不确定证据；该证据基于单核细胞白血病发病率的轻微增加。啮齿动物通常接触的氯和氯胺剂量低于三卤甲烷，但这些研究中的剂量是动物在饮用水中会摄入的最大剂量。氯和氯胺研究中使用的最高剂量相当于每天灌胃诱导大鼠大肠肿瘤的溴二氯甲烷剂量。与三卤甲烷的结果相反，长期接触氯或氯胺后，在大鼠或小鼠中未引起明显的致癌反应。
这些结果表明，在评估氯化饮用水的致癌潜力时，氯化有机副产物是最值得关注的化学物质。
