Distribution and accumulation of 10 nm silver nanoparticles in maternal tissues and visceral yolk sac of pregnant mice, and a potential effect on embryo growth

Carlye A. Austina, Georgia K. Hinkleyb, Anurag R. Mishrac, Qin Zhangc, Thomas H. Umbreitc, Martha W. Betzc, Bridget E. Wildtc, Brendan J. Caseyc, Sabine Francke-Carrolld, Saber M. Hussaine, Stephen M. Robertsb, Ken M. Browna & Peter L. Goeringc*a Department of Biological Sciences, George Washington University, Washington, DC, USA, b Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL, USA, c Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, MD, USA, d Center for Food Safety and Nutrition, US Food and Drug Administration, College Park, MD, USA, and e Air Force Research Laboratory, Wright-Patterson Air Force Base, Dayton, OH, USACorrespondence: Dr Peter L. Goering, PhD, Center for Devices and Radiological Health, US Food and Drug Administration, White Oak Life Sciences Laboratory, WO64-4064, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA. Tel: +1-301-796-0253. Fax: +1-301-796-9826. E-mail: peter.goering@fda.hhs.govAbstractWe examined the distribution of silver in pregnant mice and embryos/fetuses following intravenous injections of 10 nm silver nanoparticles (AgNPs) or soluble silver nitrate (AgNO3) at dose levels of 0 (citrate buffer control) or 66 µg Ag/mouse to pregnant mice on gestation days (GDs) 7, 8 and 9. Selected maternal tissues and all embryos/fetuses from control, AgNP- and AgNO3-treated groups on GD10 and control and AgNP-treated groups on GD16 were processed for the measurement of silver concentrations, intracellular AgNP localization, histopathology and gross examination of tissue morphology. Inductively-coupled plasma mass spectrometry revealed silver in all examined tissues following either AgNP or AgNO3 treatment, with highest concentrations of silver in maternal liver, spleen and visceral yolk sac (VYS), and lowest concentrations in embryos/fetuses. For VYS, mean silver concentration following AgNO3 treatment (4.87 ng Ag/mg tissue) was approximately two-fold that following AgNP treatment (2.31 ng Ag/mg tissue); for all other tissues examined, mean silver concentrations following either AgNP or AgNO3 treatment were not significantly different from each other (e.g. 2.57 or 2.84 ng Ag/mg tissue in maternal liver and 1.61 or 2.50 ng Ag/mg tissue in maternal spleen following AgNP or AgNO3 treatment, respectively). Hyperspectral imaging revealed AgNP aggregates in maternal liver, kidney, spleen and VYS from AgNP-treated mice, but not AgNO3-treated mice. Additionally, one or more embryos collected on GD10 from eight of ten AgNP-treated mice appeared small for their age (i.e. Theiler stage 13 [GD8.5] or younger). In the control group (N = 11), this effect was seen in embryos from only one mouse. In conclusion, intravenous injection of 10 nm AgNPs to pregnant mice resulted in notable silver accumulation in maternal liver, spleen and VYS, and may have affected embryonic growth. Silver accumulation in embryos/fetuses was negligible.