SILVER
Toxic effects of silver have been reported primarily for the cardiovascular and hepatic systems. Olcott (1950)
administered 0.1% silver nitrate in drinking water to rats for 218 days. This exposure (about 89 mg/kg/day) resulted
in a statistically significant increase in the incidence of ventricular hypertrophy. Upon autopsy, advanced
pigmentation was observed in body organs, but the ventricular hypertrophy was not attributed to silver deposition.
Hepatic necrosis and ultrastructural changes of the liver have been induced by silver administration to vitamin E
and/or selenium deficient rats (Wagner et al., 1975; Diplock et al., 1967; Bunyan et al., 1968). Investigators have
hypothesized that this toxicity is related to a silver-induced selenium deficiency that inhibits the synthesis of the
seleno-enzyme glutathione peroxidase. In animals supplemented with selenium and/or vitamin E, exposures of silver
as high as 140 mg/kg/day (100 mg Ag/L drinking water) were well- tolerated (Bunyan et al., 1968).
The critical human study rates a medium confidence. It is an old study (1935) which offers fairly specific information
regarding the total dose of silver injected over a stated period of time. One shortcoming of the study is that only
patients developing argyria are described; no information is presented on patients who received multiple injections
of silver arsphenamine without developing argyria. Therefore, it is difficult to establish a NOAEL. Also, the
individuals in the study were being treated for syphilis and may have been of compromised health.
Confidence in the database is considered to be low because the studies used to support the RfD were not
controlled studies. For clinical case studies of argyria (such as Blumberg and Carey, 1934; East et al., 1980), it is
especially difficult to determine the amount of silver that was ingested
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