Savery Laura C, Viñas René, Nagy Amber M, Pradeep Prachi, Merrill Stephen J, Hood Alan M, Malghan Subhas G, Goering Peter L, Brown Ronald P
Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.
Department of Mathematics, Statistics, and Computer Science, Marquette University, P.O. Box 1881, Milwaukee, WI 53201, USA.
Regul Toxicol Pharmacol. 2017 Apr;85:108-118. doi: 10.1016/j.yrtph.2017.01.007. Epub 2017 Jan 27.
Silver nanoparticles (AgNP) are incorporated into medical devices for their anti-microbial characteristics. The potential exposure and toxicity of AgNPs is unknown due to varying physicochemical particle properties and lack of toxicological data. The aim of this safety assessment is to derive a provisional tolerable intake (pTI) value for AgNPs released from blood-contacting medical devices. A literature review of in vivo studies investigating critical health effects induced from intravenous (i. v.) exposure to AgNPs was evaluated by the Annapolis Accords principles and Toxicological Data Reliability Assessment Tool (ToxRTool). The point of departure (POD) was based on an i. v. 28-day repeated AgNP (20 nm) dose toxicity study reporting an increase in relative spleen weight in rats with a 5% lower confidence bound of the benchmark dose (BMDL) of 0.14 mg/kg bw/day. The POD was extrapolated to humans by a modifying factor of 1,000 to account for intraspecies variability, interspecies differences and lack of long-term toxicity data. The pTI for long-term i. v. exposure to 20 nm AgNPs released from blood-contacting medical devices was 0.14 μg/kg bw/day. This pTI may not be appropriate for nanoparticles of other physicochemical properties or routes of administration. The methodology is appropriate for deriving pTIs for nanoparticles in general.
银纳米颗粒（AgNP）因其抗菌特性而被纳入医疗设备中。由于其物理化学颗粒性质各异且缺乏毒理学数据，AgNP的潜在暴露量和毒性尚不清楚。本安全性评估的目的是得出从与血液接触的医疗设备中释放的AgNP的暂定可耐受摄入量（pTI）值。通过安纳波利斯协议原则和毒理学数据可靠性评估工具（ToxRTool）对调查静脉内（i.v.）暴露于AgNP引起的关键健康影响的体内研究进行了文献综述。起始点（POD）基于一项静脉内28天重复AgNP（20纳米）剂量毒性研究，该研究报告大鼠相对脾脏重量增加，基准剂量（BMDL）的5%置信下限为0.14毫克/千克体重/天。通过1000的修正因子将POD外推至人类，以考虑种内变异性、种间差异和缺乏长期毒性数据。长期静脉内暴露于从与血液接触的医疗设备中释放出的20纳米AgNP的pTI为0.14微克/千克体重/天。该pTI可能不适用于其他物理化学性质或给药途径的纳米颗粒。该方法一般适用于推导纳米颗粒的pTI。
