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粒径和包衣对小鼠模型中急性摄入的银纳米颗粒的毒理学参数、粪便排泄动力学及组织分布的影响

Effects of particle size and coating on toxicologic parameters, fecal elimination kinetics and tissue distribution of acutely ingested silver nanoparticles in a mouse model.

作者信息

Bergin Ingrid L, Wilding Laura A, Morishita Masako, Walacavage Kim, Ault Andrew P, Axson Jessica L, Stark Diana I, Hashway Sara A, Capracotta Sonja S, Leroueil Pascale R, Maynard Andrew D, Philbert Martin A

机构信息

a Unit for Laboratory Animal Medicine, University of Michigan , Ann Arbor , MI , USA .

b Toxicology Program, Department of Environmental Health Sciences, University of Michigan , Ann Arbor , MI , USA .

出版信息

Nanotoxicology. 2016;10(3):352-60. doi: 10.3109/17435390.2015.1072588. Epub 2015 Aug 24.

Abstract

Consumer exposure to silver nanoparticles (AgNP) via ingestion can occur due to incorporation of AgNP into products such as food containers and dietary supplements. AgNP variations in size and coating may affect toxicity, elimination kinetics or tissue distribution. Here, we directly compared acute administration of AgNP of two differing coatings and sizes to mice, using doses of 0.1, 1 and 10 mg/kg body weight/day administered by oral gavage for 3 days. The maximal dose is equivalent to 2000× the EPA oral reference dose. Silver acetate at the same doses was used as ionic silver control. We found no toxicity and no significant tissue accumulation. Additionally, no toxicity was seen when AgNP were dosed concurrently with a broad-spectrum antibiotic. Between 70.5% and 98.6% of the administered silver dose was recovered in feces and particle size and coating differences did not significantly influence fecal silver. Peak fecal silver was detected between 6- and 9-h post-administration and <0.5% of the administered dose was cumulatively detected in liver, spleen, intestines or urine at 48 h. Although particle size and coating did not affect tissue accumulation, silver was detected in liver, spleen and kidney of mice administered ionic silver at marginally higher levels than those administered AgNP, suggesting that silver ion may be more bioavailable. Our results suggest that, irrespective of particle size and coating, acute oral exposure to AgNP at doses relevant to potential human exposure is associated with predominantly fecal elimination and is not associated with accumulation in tissue or toxicity.

摘要

消费者可能因食用含有银纳米颗粒(AgNP)的产品(如食品容器和膳食补充剂)而通过摄入接触到AgNP。AgNP在尺寸和涂层方面的差异可能会影响其毒性、消除动力学或组织分布。在此,我们将两种不同涂层和尺寸的AgNP以0.1、1和10 mg/kg体重/天的剂量通过口服灌胃给予小鼠3天,直接比较其急性给药情况。最大剂量相当于美国环境保护局(EPA)口服参考剂量的2000倍。以相同剂量的醋酸银作为离子银对照。我们未发现毒性和明显的组织蓄积。此外,当AgNP与广谱抗生素同时给药时也未观察到毒性。给药银剂量的70.5%至98.6%在粪便中回收,且粒径和涂层差异对粪便银含量无显著影响。给药后6至9小时检测到粪便银含量峰值,48小时时在肝脏、脾脏、肠道或尿液中累计检测到的给药剂量不到0.5%。尽管粒径和涂层不影响组织蓄积,但在给予离子银的小鼠的肝脏、脾脏和肾脏中检测到的银含量略高于给予AgNP的小鼠,这表明银离子可能具有更高的生物利用度。我们的结果表明,无论粒径和涂层如何,与潜在人类接触相关剂量的AgNP急性口服暴露主要导致粪便排泄,与组织蓄积或毒性无关。

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