Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 May 7:11:21.
doi: 10.1186/1743-8977-11-21.

Immunotoxicity of silver nanoparticles in an intravenous 28-day repeated-dose toxicity study in rats

Rob J Vandebriel  1 , Elisa Cm Tonk, Liset J de la Fonteyne-Blankestijn, Eric R Gremmer, Henny W Verharen, Leo T van der Ven, Henk van Loveren, Wim H de Jong
Affiliations

Immunotoxicity of silver nanoparticles in an intravenous 28-day repeated-dose toxicity study in rats

Rob J Vandebriel et al. Part Fibre Toxicol. .

Abstract

Background: Nanosilver is used in a variety of medical and consumer products because of its antibacterial activity. This wide application results in an increased human exposure. Knowledge on the systemic toxicity of nanosilver is, however, relatively scarce. In a previous study, the systemic toxicity of 20 nm silver nanoparticles (Ag-NP) was studied in a 28-day repeated-dose toxicity study in rats. Ag-NP were intravenously administered with a maximum dose of 6 mg/kg body weight (bw)/day. Several immune parameters were affected: reduced thymus weight, increased spleen weight and spleen cell number, a strongly reduced NK cell activity, and reduced IFN-γ production were observed.

Methods: Prompted by these affected immune parameters, we wished to assess exposure effects on the functional immune system. Therefore, in the present study the T-cell dependent antibody response (TDAR) to keyhole limpet hemocyanin (KLH) was measured in a similar 28-day intravenous repeated-dose toxicity study. In addition, a range of immunological parameters was measured. Data obtained using the benchmark dose (BMD) approach were analyzed by fitting dose-response models to the parameters measured.

Results: A reduction in KLH-specific IgG was seen, with a lowest 5% lower confidence bound of the BMD (BMDL) of 0.40 mg/kg bw/day. This suggests that Ag-NP induce suppression of the functional immune system. Other parameters sensitive to Ag-NP exposure were in line with our previous study: a reduced thymus weight with a BMDL of 0.76 mg/kg bw/day, and an increased spleen weight, spleen cell number, and spleen cell subsets, with BMDLs between 0.36 and 1.11 mg/kg bw/day. Because the effects on the spleen are not reflected by increased KLH-specific IgG, they, however, do not suggest immune stimulation.

Conclusions: Intravenous Ag-NP administration in a 28-day repeated-dose toxicity study induces suppression of the functional immune system. This finding underscores the importance to study the TDAR to evaluate immunotoxicity and not to rely solely on measuring immune cell subsets.

PubMed Disclaimer

Figures

Figure 1
Figure 1
BMD with 90% CI. BMR = 5%. Red: increased; Green: decreased. Sorted by BMD.
Figure 2
Figure 2
Experimental design.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Roszek B, De Jong WH, Geertsma RE. Nanotechnology in medical applications: state-of-the-art in materials and devices. http://www.rivm.nl/bibliotheek/rapporten/265001001.html.
    1. Chen X, Schluesener HJ. Nanosilver: a nanoproduct in medical application. Toxicol Lett. 2008;176:1–12. doi: 10.1016/j.toxlet.2007.10.004. - DOI - PubMed
    1. Rai M, Yadav A, Gade A. Silver nanoparticles as a new generation of antimicrobials. Biotechnol Adv. 2009;27:76–83. doi: 10.1016/j.biotechadv.2008.09.002. - DOI - PubMed
    1. Wijnhoven SWP, Peijnenburg WJGM, Herberts CA, Hagens WI, Oomen AG, Heugens EHW, Roszek B, Bisschops J, Gosens I, Van De Meent D, Dekkers S, De Jong WH, Van Zijverden M, Sips AJAM, Geertsma RE. Nano-silver - a review of available data and knowledge gaps in human and environmental risk assessment. Nanotoxicol. 2009;3:109–138. doi: 10.1080/17435390902725914. - DOI
    1. Wijnhoven SWP, Dekkers S, Hagens WI, De Jong WH. Exposure to nanomaterials in consumer products. http://www.rivm.nl/bibliotheek/rapporten/340370001.html.

Publication types

MeSH terms