II.        IS SILVER TOXIC TO HUMAN TISSUE?

There are two well described but often inappropriately interchangeable forms of silver toxicity. One is due to silver itself and the second more severe complication is due to the compounds attached to silver.^(8-10)

(Systemic)

Although absorbed silver interacts with other metals and tissue proteins, these interactions do not appear to be harmful with the exception of the skin discoloration known as Arygria, which is a cosmetic problem.

Argyria is caused by silver granule deposition in skin leading to a permanent blue/gray discoloration.  There is however no tissue injury to skin or other organs yet described. The effect is a cosmetic problem. The most common causes are not from medicinal use of silver but rather the constant exposure to silver either as a chemist, a silver miner or long term exposure from silver cups, plates, etc. Of interest is the fact that the term “blue blood” came from the finding of arygyria in European nobility from the constant use of silver place setting, silverware, and silver cups, leading to a bluish skin color. It would also appear that any form of silver if given in large quantity could be a causative factor in arygyria. (at least 10 grams need to be absorbed).  Silver granules can be found in all organs with use of any silver compound for an extended period or over large surfaces in burns indicating that the silver aggregates, which are produced are not cleared. However, no toxic effect of the silver itself has clearly been defined.

(Local)

Silver itself has been shown to be harmless to normal human tissue. The toxicity results from the salt or complexes which are used to deliver the silver. (Table 2)  Use of a pure silver delivery would be the ideal approach to avoid local toxicity.

Table 2.           Toxicity of Silver Compounds

(Pharmacokinetics of Topical Silver)

Significant absorption of silver ions through burn wounds can occur when patients are treated with topical silver-containing preparations.  The serum and urinary concentrations of silver have been measured in  patients with major burns treated with silver sulfadiazine.  Plasma levels of silver were elevated from the time of treatment initiation until discharge from the hospital.  Urinary excretion of silver was also markedly elevated.  However, there was no evidence of silver toxicity.^(14,15,16)

The effect of exposure of normal human volunteers to silver, following topical application of silver-containing creams, was also determined by measuring silver concentrations in blood, tissues and urine before and after silver sulfadiazine cream was applied to the skin. Results are shown in comparing the levels in volunteers applying silver to a body surface of 25% TBS versus burn patients with average burn size of 25% TBS.

  Exposure to Silver Sulfadiazine   (25% TBS)  

It is clear that silver absorption using a cream is markedly increased if the normal skin barrier is disrupted as is the case in burns.  But despite high tissue levels, no toxicity was noted. The new nanocrystalline silver (Rx Nanocrystal) delivery system has approximately 30 times less silver released despite improved antimicrobial efficacy.  Therefore, a lower silver absorption would be expected.  If in fact there is a systemic toxic effect of silver, nanocrystal silver delivery is less likely to cause any toxicity.