Komulainen Hannu
National Public Health Institute, Division of Environmental Health, Laboratory of Toxicology, P.O. Box 95, FIN-70701 Kuopio, Finland.
Toxicology. 2004 May 20;198(1-3):239-48. doi: 10.1016/j.tox.2004.01.031.
Chlorinated drinking water contains a number of different by-products formed during the chlorination process from organic matter. The carcinogenicity of only a fraction of them have been evaluated in experimental animals. The focus has been on compounds and groups of compounds that are most abundant in chlorinated drinking water or the in vitro toxicity data have suggested genotoxic potential. From trihalomethanes, chloroform causes liver tumors in mice and female rats and renal tumors in male mice and rats. Tumor formation by chloroform is strongly associated with cytotoxicity and regenerative cell proliferation in tissues and that has been considered to be one determinant of its carcinogenicity. From halogenic acetic acids, dichloroacetic acid (DCA) and trichlotoacetic acid (TCA) are hepatocarcinogenic in mice and DCA in male rats. Their genotoxicity is equivocal and nongenotoxic mechanisms, such as peroxisome proliferation and hypomethylation of DNA in the liver, likely contribute to tumor development. From chlorinated furanones (CHFs), 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) is a multisite carcinogen in rats (e.g. in thyroid glands and liver) and it has caused DNA damage in vivo. MX may be a complete carcinogen because it also has promoter properties in vitro. Chlorinated drinking water may also contain brominated by-products providing the raw water contains bromide. At least some of them (bromodichloromethane, bromoform) have been shown to be carcinogenic in laboratory animals. Altogether, although several by-products have been shown to have carcinogenic potential in laboratory animals, it not yet possible to state which compounds or groups of by-products cause the cancer risk in chlorinated drinking water. The cellular mechanisms of their effects and these effects at low concentrations are still poorly understood. The few studies with mixtures of these by-products suggest that the mixture effects may be complex and unpredictable (inhibitory, additive, synergistic).
氯化饮用水含有在氯化过程中由有机物形成的多种不同副产物。其中只有一小部分的致癌性已在实验动物中得到评估。重点一直放在氯化饮用水中含量最丰富的化合物和化合物组上，或者体外毒性数据显示具有遗传毒性潜力的化合物上。在三卤甲烷中，氯仿可导致小鼠和雌性大鼠患肝癌，雄性小鼠和大鼠患肾癌。氯仿导致的肿瘤形成与组织中的细胞毒性和再生细胞增殖密切相关，这被认为是其致癌性的一个决定因素。在卤代乙酸中，二氯乙酸（DCA）和三氯乙酸（TCA）对小鼠具有肝致癌性，DCA对雄性大鼠具有肝致癌性。它们的遗传毒性尚不明确，非遗传毒性机制，如肝脏中的过氧化物酶体增殖和DNA低甲基化，可能有助于肿瘤发展。在氯化呋喃酮（CHFs）中，3-氯-4-（二氯甲基）-5-羟基-2（5H）-呋喃酮（MX）是大鼠的多位点致癌物（如在甲状腺和肝脏中），并且它在体内已导致DNA损伤。MX可能是一种完全致癌物，因为它在体外也具有促癌特性。如果原水含有溴化物，氯化饮用水中可能还含有溴化副产物。其中至少一些（溴二氯甲烷、溴仿）已在实验动物中显示具有致癌性。总之，尽管已证明几种副产物在实验动物中具有致癌潜力，但尚无法确定哪些化合物或副产物组会导致氯化饮用水中的癌症风险。它们作用的细胞机制以及低浓度下的这些作用仍知之甚少。关于这些副产物混合物的少数研究表明，混合物的影响可能很复杂且不可预测（抑制、相加、协同）。
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