F344大鼠中消毒副产物的发育毒性：对妊娠维持和眼睛发育的影响
Developmental Toxicity of Disinfection Byproducts in F344 Rats: Effects on Pregnancy Maintenance and Eye Development.
作者信息
Narotsky Michael G, Fuentes Leslie S, Ola Oluwabusola, Willoughby TaCriasha L, Lucas Katherine
机构信息
U.S. Environmental Protection Agency, Office of Research and Development, Center for Public Health and Environmental Assessment, Research Triangle Park, North Carolina, USA.
Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee, USA.
出版信息
Birth Defects Res. 2025 Jan;117(1):e2427. doi: 10.1002/bdr2.2427.
BACKGROUND
Epidemiological studies report associations of drinking water disinfection byproducts (DBPs) with adverse health outcomes, including birth defects. Here, we used a rat model susceptible to pregnancy loss (full-litter resorption; FLR) and eye malformations (anophthalmia, microphthalmia) to test 11 DBPs, including trihalomethanes, haloacetic acids (HAAs), and nitrogen-containing DBPs (N-DBPs).
METHODS
Timed-pregnant F344 rats received gavage doses of chloroform, chlorodibromomethane, iodoform, chloroacetic acid, bromoacetic acid, dibromoacetic acid (DBA), diiodoacetic acid (DIA), trichloroacetic acid (TCA), dibromonitromethane, and iodoacetonitrile on gestation days (GD) 6-10. Bromonitromethane and TCA were administered via drinking water on GD 6-11. Litters were examined on postnatal days 1 and 6.
RESULTS
All trihalomethanes tested caused FLR. The di- and tri-halogenated HAAs, but not the mono-HAAs, caused eye malformations. N-DBPs caused neither effect at the dosages tested. TCA by gavage caused both FLR and eye defects, whereas drinking water exposure only caused eye defects. Potency rankings for causing FLR were chloroform ≥ iodoform > chlorodibromomethane and the rankings for causing eye defects were DIA > TCA = DBA.
CONCLUSION
We confirmed that trihalomethanes caused pregnancy loss and that di- and tri-HAAs were teratogenic. The N-DBPs induced neither effect. Potency rankings were inconsistent with rankings seen in vitro.
背景
流行病学研究报告了饮用水消毒副产物（DBPs）与不良健康后果之间的关联，包括出生缺陷。在此，我们使用一种易发生妊娠丢失（全窝吸收；FLR）和眼部畸形（无眼、小眼）的大鼠模型来测试11种消毒副产物，包括三卤甲烷、卤乙酸（HAAs）和含氮消毒副产物（N-DBPs）。
方法
定时受孕的F344大鼠在妊娠第6至10天经口灌胃给予氯仿、二溴一氯甲烷、碘仿、氯乙酸、溴乙酸、二溴乙酸（DBA）、二碘乙酸（DIA）、三氯乙酸（TCA）、二溴硝基甲烷和碘乙腈。溴硝基甲烷和三氯乙酸在妊娠第6至11天通过饮用水给予。在出生后第1天和第6天检查窝仔。
结果
所有测试的三卤甲烷均导致全窝吸收。二卤代和三卤代卤乙酸导致眼部畸形，而一卤代卤乙酸则不会。在所测试的剂量下，含氮消毒副产物未产生任何一种效应。经口灌胃给予三氯乙酸会导致全窝吸收和眼部缺陷，而通过饮用水接触仅导致眼部缺陷。导致全窝吸收的效力排名为氯仿≥碘仿＞二溴一氯甲烷，导致眼部缺陷的排名为二碘乙酸＞三氯乙酸=二溴乙酸。
结论
我们证实三卤甲烷会导致妊娠丢失，二卤代和三卤代卤乙酸具有致畸性。含氮消毒副产物未产生任何一种效应。效力排名与体外观察到的排名不一致。
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