Harrington-Brock K, Doerr C L, Moore M M
Environmental Carcinogenesis Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27709, USA.
Mutat Res. 1998 Mar 30;413(3):265-76. doi: 10.1016/s1383-5718(98)00026-6.
The disinfection of water, required to make it safe for human consumption, leads to the presence of halogenated organic compounds. Three of these carcinogenic 'disinfection by-products', dichloroacetic acid (DCA), trichloroacetic acid (TCA) and chloral hydrate (CH) have been widely evaluated for their potential toxicity. The mechanism(s) by which they exert their activity and the steps in the etiology of the cancers that they induce are important pieces of information that are required to develop valid biologically-based quantitative models for risk assessment. Determining whether these chemicals induce tumors by genotoxic or nongenotoxic mechanisms (or a combination of both) is key to this evaluation. We evaluated these three chemicals for their potential to induce micronuclei and aberrations as well as mutations in L5178Y/TK +/- (-)3.7.2C mouse lymphoma cells. TCA was mutagenic (only with S9 activation) and is one of the least potent mutagens that we have evaluated. Likewise, CH was a very weak mutagen. DCA was weakly mutagenic, with a potency (no. of induced mutants/microgram of chemical) similar to (but less than) ethylmethanesulfonate (EMS), a classic mutagen. When our information is combined with that from other studies, it seems reasonable to postulate that mutational events are involved in the etiology of the observed mouse liver tumors induced by DCA at drinking water doses of 0.5 to 3.5 g/l, and perhaps chloral hydrate at a drinking water dose of 1 g/l. The weight-of-evidence for TCA suggest that it is less likely to be a mutagenic carcinogen. However, given the fact that DCA is a weak mutagen in the present and all of the published studies, it seems unlikely that it would be mutagenic (or possibly carcinogenic) at the levels seen in finished drinking water.
为使水可供人类安全饮用而进行的消毒处理会导致卤代有机化合物的存在。其中三种致癌的“消毒副产物”，即二氯乙酸（DCA）、三氯乙酸（TCA）和水合氯醛（CH），已针对其潜在毒性进行了广泛评估。它们发挥活性的机制以及它们诱发癌症的病因学步骤是开发有效的基于生物学的风险评估定量模型所需的重要信息。确定这些化学物质是通过基因毒性还是非基因毒性机制（或两者结合）诱发肿瘤是该评估的关键。我们评估了这三种化学物质在L5178Y/TK +/- (-)3.7.2C小鼠淋巴瘤细胞中诱发微核、畸变以及突变的潜力。TCA具有致突变性（仅在有S9激活时），是我们评估过的效力最低的诱变剂之一。同样，CH是一种非常弱的诱变剂。DCA具有弱致突变性，其效力（每微克化学物质诱导的突变体数量）与经典诱变剂甲磺酸乙酯（EMS）相似（但低于EMS）。当我们的信息与其他研究的信息相结合时，推测突变事件参与了饮用水剂量为0.5至3.5 g/l的DCA以及饮用水剂量为1 g/l的水合氯醛所诱发的小鼠肝肿瘤的病因，这似乎是合理的。关于TCA的证据权重表明它不太可能是诱变致癌物。然而，鉴于DCA在本研究以及所有已发表研究中都是弱诱变剂，在成品饮用水中所见水平下它似乎不太可能具有诱变性（或可能致癌）。
