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大鼠多代生殖毒性研究中氯化饮用水浓缩物的综合评估。

Comprehensive assessment of a chlorinated drinking water concentrate in a rat multigenerational reproductive toxicity study.

机构信息

National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency , Research Triangle Park, North Carolina 27711, United States.

出版信息

Environ Sci Technol. 2013 Sep 17;47(18):10653-9. doi: 10.1021/es402646c. Epub 2013 Aug 28.

DOI:10.1021/es402646c
PMID:23909560
Abstract

Some epidemiological studies report associations between drinking water disinfection byproducts (DBPs) and adverse reproductive/developmental effects, e.g., low birth weight, spontaneous abortion, stillbirth, and birth defects. Using a multigenerational rat bioassay, we evaluated an environmentally relevant "whole" mixture of DBPs representative of chlorinated drinking water, including unidentified DBPs as well as realistic proportions of known DBPs at low-toxicity concentrations. Source water from a water utility was concentrated 136-fold, chlorinated, and provided as drinking water to Sprague-Dawley rats. Timed-pregnant females (P0 generation) were exposed during gestation and lactation. Weanlings (F1 generation) continued exposures and were bred to produce an F2 generation. Large sample sizes enhanced statistical power, particularly for pup weight and prenatal loss. No adverse effects were observed for pup weight, prenatal loss, pregnancy rate, gestation length, puberty onset in males, growth, estrous cycles, hormone levels, immunological end points, and most neurobehavioral end points. Significant, albeit slight, effects included delayed puberty for F1 females, reduced caput epidydimal sperm counts in F1 adult males, and increased incidences of thyroid follicular cell hypertrophy in adult females. These results highlight areas for future research, while the largely negative findings, particularly for pup weight and prenatal loss, are notable.

摘要

一些流行病学研究报告称,饮用水消毒副产物(DBPs)与不良生殖/发育影响之间存在关联,例如低出生体重、自然流产、死产和出生缺陷。本研究使用多代大鼠生物测定法,评估了一种具有环境相关性的“全”DBPs 混合物,该混合物代表氯化饮用水,包括未识别的 DBPs 以及低毒性浓度下真实比例的已知 DBPs。从一家供水公司获取水源,将其浓缩 136 倍,氯化,并作为饮用水提供给 Sprague-Dawley 大鼠。受孕雌性(P0 代)在妊娠期和哺乳期暴露于该混合物中。断乳幼鼠(F1 代)继续暴露,并繁殖产生 F2 代。大样本量增强了统计能力,尤其是在幼仔体重和产前损失方面。未观察到幼仔体重、产前损失、妊娠率、妊娠期、雄性青春期开始、生长、发情周期、激素水平、免疫终点和大多数神经行为终点的不良影响。虽然作用轻微,但仍存在显著影响,包括 F1 雌性青春期延迟、F1 成年雄性附睾头部精子计数减少以及成年雌性甲状腺滤泡细胞肥大发生率增加。这些结果突出了未来研究的领域,而大量的阴性结果,特别是在幼仔体重和产前损失方面,值得注意。