Chemical, Biological and Environmental Center, SRC, Inc., Syracuse, NY 13212, USA.
Toxicol Appl Pharmacol. 2011 Jul 15;254(2):100-26. doi: 10.1016/j.taap.2011.02.002. Epub 2011 Feb 4.
Reactions between chemicals used to disinfect drinking water and compounds present in source waters produce chemical mixtures containing hundreds of disinfection byproducts (DBPs). Although the results have been somewhat inconsistent, some epidemiological studies suggest associations may exist between DBP exposures and adverse developmental outcomes. The potencies of individual DBPs in rodent and rabbit developmental bioassays suggest that no individual DBP can account for the relative risk estimates reported in the positive epidemiologic studies, leading to the hypothesis that these outcomes could result from the toxicity of DBP mixtures. As a first step in a mixtures risk assessment for DBP developmental effects, this paper identifies developmentally toxic DBPs and examines data relevant to the mode of action (MOA) for DBP developmental toxicity. We identified 24 developmentally toxic DBPs and four adverse developmental outcomes associated with human DBP exposures: spontaneous abortion, cardiovascular defects, neural tube defects, and low birth weight infancy. A plausible MOA, involving hormonal disruption of pregnancy, is delineated for spontaneous abortion, which some epidemiologic studies associate with total trihalomethane and bromodichloromethane exposures. The DBP data for the other three outcomes were inadequate to define key MOA steps.
用于消毒饮用水的化学物质与水源中存在的化合物之间的反应会产生含有数百种消毒副产物 (DBP) 的化学混合物。尽管结果有些不一致，但一些流行病学研究表明，DBP 暴露与不良发育结果之间可能存在关联。在啮齿动物和兔类发育生物测定中，个别 DBP 的效力表明，没有任何一种 DBP 可以解释阳性流行病学研究报告的相对风险估计，这导致了这样一种假设，即这些结果可能是 DBP 混合物的毒性所致。作为 DBP 发育效应混合物风险评估的第一步，本文确定了具有发育毒性的 DBP，并研究了与 DBP 发育毒性作用模式 (MOA) 相关的数据。我们确定了 24 种具有发育毒性的 DBP 和与人类 DBP 暴露相关的四种不良发育结果：自然流产、心血管缺陷、神经管缺陷和低出生体重婴儿。对于自然流产，我们描绘了一个合理的 MOA，涉及妊娠的激素扰乱，一些流行病学研究将其与总三卤甲烷和溴二氯甲烷暴露联系起来。其他三种结果的 DBP 数据不足以确定关键 MOA 步骤。
