Distribution, Elimination, and Toxicity of Silver Nanoparticles and Silver Ions in Rats after 28-Day Oral Exposure

Abstract

We report the results of a 28-day oral exposure study in rats, exposed to <20 nm noncoated, or <15 nm PVP-coated silver nanoparticles ([Ag] = 90 mg/kg body weight (bw)), or AgNO(3) ([Ag] = 9 mg/kg bw), or carrier solution only. Dissection was performed at day 29, and after a wash-out period of 1 or 8 weeks. Silver was present in all examined organs with the highest levels in the liver and spleen for all silver treatments. Silver concentrations in the organs were highly correlated to the amount of Ag(+) in the silver nanoparticle suspension, indicating that mainly Ag(+), and to a much lesser extent silver nanoparticles, passed the intestines in the silver nanoparticle exposed rats. In all groups silver was cleared from most organs after 8 weeks postdosing, but remarkably not from the brain and testis. Using single particle inductively coupled plasma mass spectrometry, silver nanoparticles were detected in silver nanoparticle exposed rats, but, remarkably also in AgNO(3) exposed rats, hereby demonstrating the formation of nanoparticles from Ag(+)in vivo that are probably composed of silver salts. Biochemical markers and antibody levels in blood, lymphocyte proliferation and cytokine release, and NK-cell activity did not reveal hepatotoxicity or immunotoxicity of the silver exposure. In conclusion, oral exposure to silver nanoparticles appears to be very similar to exposure to silver salts. However, the consequences of in vivo formation of silver nanoparticles, and of the long retention of silver in brain and testis should be considered in a risk assessment of silver nanoparticles.

Silver nanoparticles induce cytotoxicity, but not cell transformation or genotoxicity on Balb3T3 mouse fibroblasts

“…The comparatively large value reported for NM-300 by Nanoparticle Tracking Analysis System can be related to the limit of detection of the method, which is not reliable for nanoparticles typically below 30-50 nm depending on the NPs optical properties [27][28][29]. Results obtained for NM-300 size distribution by DLS were comparable with those previously observed [30] and indicate a polydispersity of the sample, and therefore an unreliable value of the size measured by DLS [31]. These results were complemented by TEM size distribution analysis and CPS, which indicate both an average diameter of 15-17 nm (see supplementary information).…”

Potential risks and benefits of nanotechnology: perceptions of risk in sunscreens

“…However, both for 20 nm and 100 nm Ag-NP growth retardation was observed during the treatment. A severe increase in liver and spleen size and weight was noted in line with earlier publications (Lankveld et al 2010;Tang et al 2009;Van Der Zande et al 2012;Xue et al 2012). The spleen proliferation was due to an increased cell number.…”

“…Many studies have addressed the fate of Ag-NP after oral administration (Kim 2008;Tang 2009;Jeong 2010;Par 2010;Loeschner 2011;Van der Zande 2012;Hadrup 2012;Lee et al, 2013).…”

“…Several immune parameters were determined in a 28-day repeated dose oral toxicity study of nanosilver (Van Der Zande et al 2012). Blood IgM and IgG levels, and proliferation activity, cytokine production, and natural killer cell activity of isolated spleen cells were not affected, although silver was demonstrated to be present in the spleen.…”

“…A gradual decrease in testicular Ag levels was observed after the five-day repeated administrations and low levels of Ag were still detectable in the testes 12 days after the last IV administration at day 17. Recent evidence from a 28-day oral study in rats with post-exposure follow-up over 1 and 8 weeks suggests that clearance of silver from testis is very slow, regardless of whether silver or nanosilver was applied (Van der Zande et al 2012). Also for mice, Park et al (2010) reported similar or higher organ levels of silver in testes compared to liver following repeated oral exposure to 1 mg/kg bw/d Ag-NPs with a mean size of 22 and 42 nm, while no silver was detectable in testes for 71 and 323 nm sized particles.…”