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

Ambient and Dosed Exposure to Quaternary Ammonium Disinfectants Causes Neural Tube Defects in Rodents.
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DOI:
10.1002/bdr2.1064
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发表时间:
2017-08-15
影响因子:
2.1
通讯作者:
Hunt PA
Hunt PA
中科院分区:
医学4区
文献类型:
--
作者:
Hrubec TC;Melin VE;Shea CS;Ferguson EE;Garofola C;Repine CM;Chapman TW;Patel HR;Razvi RM;Sugrue JE;Potineni H;Magnin-Bissel G;Hunt PA

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季铵化合物是一类因其抗菌和抗静电性能而被广泛使用的化学物质。两种常见的季铵化合物,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结合使用。在小鼠和大鼠体内引入含有ADBAC+DDAC的清洁剂可引起神经管缺陷(NTDs)。为了进一步评估这一发现,雄性和雌性小鼠在饲料中分别给予60或120 mg/kg/天,或口服7.5、15或30 mg/kg ADBAC+DDAC。小鼠也被暴露于小鼠室使用的消毒剂ADBAC+DDAC的环境中。胚胎在妊娠第10天评估NTDs,胎儿在妊娠第18天评估大体和骨骼畸形。我们发现大鼠和小鼠的NTDs随着ADBAC+DDAC的暴露而增加。ntd在停止接触后持续了两代人。值得注意的是,仅男性接触就足以引起被忽视热带病。同样重要的是,在动物体内使用消毒剂的环境暴露比口服剂量对被忽视热带病水平的影响更大。在妊娠晚期胎儿中未观察到明显或明显的轴向骨骼畸形。胎盘异常和妊娠晚期胎儿死亡在120 mg/kg/天时增加,这可能解释了妊娠晚期胎儿没有观察到畸形的原因。这些结果表明ADBAC+DDAC联合使用对啮齿动物具有致畸作用。鉴于这些消毒剂的使用越来越多,必须进一步评估它们对人体的安全性及其对健康和疾病的影响。
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. 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. 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. 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.
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