Developmental Toxicity of Disinfection Byproducts in F344 Rats: Effects on Pregnancy Maintenance and Eye Development

IF 1.6 4区医学 Q4 DEVELOPMENTAL BIOLOGY

Birth Defects Research Pub Date : 2025-01-06 DOI:10.1002/bdr2.2427

Michael G. Narotsky, Leslie S. Fuentes, Oluwabusola Ola, TaCriasha L. Willoughby, Katherine Lucas

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引用次数: 0

Abstract

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.

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消毒副产物对F344大鼠的发育毒性：对妊娠维持和眼睛发育的影响

流行病学研究报告了饮用水消毒副产物（DBPs）与不良健康结局（包括出生缺陷）的关联。在这里，我们使用了一个易感妊娠丢失的大鼠模型(全产仔吸收；FLR)和眼部畸形（无眼症、小眼症）检测11种dbp，包括三卤甲烷、卤乙酸（HAAs）和含氮dbp （n- dbp）。方法妊娠期F344大鼠于妊娠6 ~ 10天（GD）灌胃三氯甲烷、氯二溴甲烷、碘仿、氯乙酸、溴乙酸、二溴乙酸（DBA）、二碘乙酸（DIA）、三氯乙酸（TCA）、二溴甲烷和碘乙腈。在GD 6-11的饮水中给予溴甲烷和TCA。在出生后第1天和第6天对窝仔进行检查。结果三卤甲烷均引起FLR。二卤化和三卤化HAAs引起眼睛畸形，而单卤化HAAs则没有。在测试剂量下，N-DBPs不会产生任何影响。TCA灌胃引起FLR和眼部缺损，而饮水只引起眼部缺损。引起FLR的效价排序为氯仿≥碘仿>；氯二溴甲烷；引起眼缺损的效价排序为DIA >； TCA = DBA。结论三卤甲烷导致妊娠流产，二卤甲烷和三卤甲烷具有致畸作用。N-DBPs没有引起任何影响。效力排名与体外排名不一致。

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来源期刊

Birth Defects Research Medicine-Embryology

CiteScore

3.60

自引率

9.50%

发文量

153

期刊介绍： The journal Birth Defects Research publishes original research and reviews in areas related to the etiology of adverse developmental and reproductive outcome. In particular the journal is devoted to the publication of original scientific research that contributes to the understanding of the biology of embryonic development and the prenatal causative factors and mechanisms leading to adverse pregnancy outcomes, namely structural and functional birth defects, pregnancy loss, postnatal functional defects in the human population, and to the identification of prenatal factors and biological mechanisms that reduce these risks. Adverse reproductive and developmental outcomes may have genetic, environmental, nutritional or epigenetic causes. Accordingly, the journal Birth Defects Research takes an integrated, multidisciplinary approach in its organization and publication strategy. The journal Birth Defects Research contains separate sections for clinical and molecular teratology, developmental and reproductive toxicology, and reviews in developmental biology to acknowledge and accommodate the integrative nature of research in this field. Each section has a dedicated editor who is a leader in his/her field and who has full editorial authority in his/her area.