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环境和剂量暴露于季铵盐消毒剂可导致啮齿类动物神经管缺陷。

Ambient and Dosed Exposure to Quaternary Ammonium Disinfectants Causes Neural Tube Defects in Rodents.

机构信息

E. Via College of Osteopathic Medicine - Virginia Campus, Blacksburg, Virginia.

Department of Biomedical Sciences and Pathobiology, VA-MD College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia.

出版信息

Birth Defects Res. 2017 Aug 15;109(14):1166-1178. doi: 10.1002/bdr2.1064. Epub 2017 Jun 15.

Abstract

BACKGROUND

Quaternary ammonium compounds are a large class of chemicals used for their antimicrobial and antistatic properties. Two common quaternary ammonium compounds, alkyldimethylbenzyl ammonium chloride (ADBAC) and didecyldimethyl ammonium chloride (DDAC), are combined in common cleaners and disinfectants. Introduction of a cleaner containing ADBAC+DDAC in the vivarium caused neural tube defects (NTDs) in mice and rats.

METHODS

To further evaluate this finding, male and female mice were dosed in the feed at 60 or 120 mg/kg/day, or by oral gavage at 7.5, 15, or 30 mg/kg ADBAC+DDAC. Mice also received ambient exposure to ADBAC+DDAC from the disinfectant used in the mouse room. Embryos were evaluated on gestational day 10 for NTDs, and fetuses were evaluated on gestational day 18 for gross and skeletal malformations.

RESULTS

We found increased NTDs with exposure to ADBAC+DDAC in both rats and mice. The NTDs persisted for two generations after cessation of exposure. Notably, male exposure alone was sufficient to cause NTDs. Equally significant, ambient exposure from disinfectant use in the vivarium, influenced the levels of NTDs to a greater extent than oral dosing. No gross or significant axial skeletal malformations were observed in late gestation fetuses. Placental abnormalities and late gestation fetal deaths were increased at 120 mg/kg/day, which might explain the lack of malformations observed in late gestation fetuses.

CONCLUSION

These results demonstrate that ADBAC+DDAC in combination are teratogenic to rodents. Given the increased use of these disinfectants, further evaluation of their safety in humans and their contribution to health and disease is essential. Birth Defects Research 109:1166-1178, 2017. © 2017 The Authors. Birth Defects Research Published by Wiley Periodicals, Inc.

摘要

背景

季铵盐化合物是一类具有抗菌和抗静电性能的化学品。两种常见的季铵盐化合物,烷基二甲基苄基氯化铵(ADBAC)和二癸基二甲基氯化铵(DDAC),在常见的清洁剂和消毒剂中混合使用。在动物饲养室中引入含有 ADBAC+DDAC 的清洁剂,导致小鼠和大鼠出现神经管缺陷(NTD)。

方法

为了进一步评估这一发现,雄性和雌性小鼠分别通过饲料摄入 60 或 120mg/kg/天,或通过口服灌胃 7.5、15 或 30mg/kg ADBAC+DDAC 的方式进行给药。小鼠还通过暴露于动物饲养室中使用的消毒剂来接受 ADBAC+DDAC 的环境暴露。在妊娠第 10 天评估胚胎的 NTD,在妊娠第 18 天评估胎儿的大体和骨骼畸形。

结果

我们发现,接触 ADBAC+DDAC 会导致大鼠和小鼠的 NTD 增加。暴露停止后,NTD 持续了两代。值得注意的是,雄性单独暴露就足以引起 NTD。同样重要的是,来自动物饲养室消毒剂使用的环境暴露,比口服给药更能影响 NTD 的水平。在妊娠晚期胎儿中未观察到大体畸形或明显的轴骨骼畸形。在 120mg/kg/天剂量下,胎盘异常和妊娠晚期胎儿死亡增加,这可能解释了妊娠晚期胎儿未观察到畸形的原因。

结论

这些结果表明,ADBAC+DDAC 联合使用对啮齿动物具有致畸性。鉴于这些消毒剂的使用增加,对其在人类中的安全性及其对健康和疾病的贡献进行进一步评估是必要的。出生缺陷研究 109:1166-1178,2017。©2017 作者。出生缺陷研究由 Wiley 期刊出版公司出版。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc9f/5905424/aec37d2d9cc2/nihms958427f1.jpg

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