Nanosilver has become one of the most widely used nanomaterials in consumer products because of its antimicrobial and antiseptic properties. Because of public concern over the potential adverse effects of nanosilver,16
we assessed the toxicity potentials of different concentrations of nanosilver by dermal application because our knowledge of toxicology has been derived only from studies on administration of nanosilver inhalational1
or by mouth.17
In these previous studies, animals exposed to nanosilver showed minimal pulmonary inflammation or cytotoxicity following subacute exposures but longer-term exposures with higher body burdens of nanosilver are needed to ensure that there are no chronic effects and to evaluate possible translocation of nanosilver to other organs.
The present study clearly showed that dermal contact with nanosilver may cause histopathologic abnormalities of the skin, liver, and spleen of animals, which could be magnified by increased concentrations over longer-term exposures. The present study has emphasized also that sub-chronically treated animals exhibit higher dermal, hepatic, and immunological toxicity signs compared with acutely treated animals.
One of the classical toxic responses to the silver is argyria, which was reported for the first time by Blumberg and Carey in a woman who had ingested a total dose of 6.4 g silver nitrate over a 1-year period of time and showed argyria symptoms after the first six months of exposure.18
Rosenman et al reported also respiratory irritation, abdominal pain, and decreased night vision in workers exposed to AgNO3
and silver oxide dusts over one to ten years.4
They later showed that occupational exposure to silver compounds in a group of workers may cause respiratory irritation, decreased night vision, abnormal rise in N-acetyl-B-D glucoseaminidase, and decreased creatinine clearance.19
Discoloration of the conjunctiva and cornea in some workers was reported after inhalational exposure.20
Williams et al, in a case study of a 51-year-old man exposed to silver compounds, showed corneal and conjunctival argyrosis.21
Chang et al recorded a case study of a 59-year-old man who was distressed from dermal and face color change. He had ingested colloidal silver two to three times per year for two years and showed endocrine disruptions such as hyperlipidemia, hypertension, and diabetes as well as blue-grey facial signs.22
Neurologic symptoms are an unusual consequence of silver toxicity which was recently reported in a 75-year-old man who had a history of self-medication with colloidal silver and presented with myoclonic seizures.23
Our study clearly showed that the toxic effects of nanosilver depend on the route of administration. Moreover dose- and time-dependent toxic effects of nanosilver via dermal application in skin, liver, and spleen of male guina pigs were completely different from what has been seen after clinical poisoning with silver salts via inhalational or oral routes of administration.
Some reports have proved that many medical devices loaded with silver could release silver ions (Ag+
) which could be translocated through the blood circulation and accumulate in some organs such as the liver and kidney. It may induce hepatotoxicity or renal toxicity and may lead to death in some cases of extreme exposure to a certain dose of Ag+
We have shown that silver nanoparticles with properties similar to those of Ag+
could be translocated in the body and cause histopathologic changes in the liver and spleen unlike those caused by AgNO3
given by the same route of administration. For example, mononuclear inflammation was noted for AgNO3
-treated animals only, whereas reduced epidermal thickness and thickness of papillary layer were seen after administration of different concentrations of nanosilver in our acute study.
Braydich-Stoll et al25
reported potential cytotoxicity of nanosilver in vitro. They used nanosilver in different concentrations on mammalian stem cells and showed apoptosis and necrosis in cells exposed to ≥10 μg/mL nanosilver. Mitochondrial function and cell viability were reduced by silver nanoparticles at concentrations of 1 to 5 μg/mL.25
We used doses of 10,000, 1000, and 100 μg/mL solutions without recording any sign of mortality. Although the concentrations of nanosilver were high and unrealistic, to our knowledge this is the first study on dermal and systemic toxicity of nanosilver in acute and subchronic treatment. It is necessary to conduct the same study with lower doses and find the NOAEL (no observable adverse effect level) of nanosilver by dermal application.