Professional Documents
Culture Documents
575–585, 2005
Published by Oxford University Press
doi:10.1093/annhyg/mei019
A critical review of studies examining exposures to the various forms of silver was conducted to
determine if some silver species are more toxic than others. The impetus behind conducting this
review is that several occupational exposure limits and guidelines exist for silver, but the values
for each depend on the form of silver as well as the individual agency making the recommenda-
tions. For instance, the American Conference of Governmental Industrial Hygienists has
575
576 P. L. Drake and K. J. Hazelwood
Table 1. Various uses for silver metal and silver compounds (Catsakis and Sulica, 1978), or accidental puncture
Silver compounds Silver and silver alloys wounds (Rongioletti et al., 1992).
Photography Jewelry Soluble silver compounds are more readily
Batteries Silverware absorbed than metallic or insoluble silver (Rosenman
Bactericide Electronic components
et al., 1979, 1987; HSE, 1998) and thus have the
potential to produce adverse effects on the human
Catalysts Heat sink
body (Weir, 1979). Acute symptoms of overexposure
Medicinals Solders
to silver nitrate are decreased blood pressure,
Lubrication Brazing alloys
diarrhea, stomach irritation and decreased respiration.
Cloud seeding Superconductors Chronic symptoms from prolonged intake of low
Window coatings Bactericide doses of silver salts are fatty degeneration of the liver
Mirrors Dental amalgams and kidneys and changes in blood cells (Venugopal
Flower preservative Bearings and Luckey, 1978). Long-term inhalation or inges-
Electroplating Coinage/medals tion of soluble silver compounds or colloidal
Sanitation of: silver may cause argyria and/or argyrosis (Nordberg
Swimming pools and Gerhardsson, 1988; Fung and Bowen, 1996;
Hot tubs/spas Gulbranson et al., 2000). Soluble silver compounds
Drinking water are also capable of accumulating in small amounts in
Cosmetics the brain and in muscles (Fung and Bowen, 1996).
Silver in any form is not thought to be toxic to the
immune, cardiovascular, nervous, or reproductive
systems (ATSDR, 1990) and is not considered to
Breitstadt, 1995). Localized argyria can also occur by sequestering it in the tissues as harmless silver-
following the application of silver compounds to protein complexes or silver sulfide.
wounds (Buckley, 1963; Fisher et al., 2003).
Generalized argyria is recognized by a widespread Metabolism
pigmentation of the skin, eyes, and nails. Generalized Ingested silver compounds are estimated to be
argyria and argyrosis may result when silver com- absorbed by the body at a level of at most 10%, with
pounds are applied to mucosal surfaces, inhaled, only 2–4% being retained in tissues (Furchner et al.,
ingested, or injected into the body (Hunter, 1969; 1968; Klein, 1978). Silver can be measured in urine,
Rosenblatt and Cymet, 1987). After silver enters blood, and feces. Even though the body eliminates
the body, it is absorbed, carried by the bloodstream silver primarily in feces (Newton and Holmes, 1966;
and deposited in various tissues throughout the body. Furchner et al., 1968; Phalen and Morrow, 1973),
Areas of the body most likely to become pigmented it can be accurately determined in whole blood
include eyes, internal organs, and sun-exposed areas (Armitage et al., 1996) and is, therefore, the biological
such as the face, ears, forearms, hands, and nails medium of choice due to collection convenience.
(Juberg and Hearne, 2001). Generalized argyria was Urinalysis is useful only following a high degree of
most often reported following the ingestion or exposure because little silver is excreted in urine
application of silver-containing medicines, but it (Phalen and Morrow, 1973; Juberg and Hearne, 2001).
has also been reported after occupational exposure Many researchers attribute the pigmentation
among silver nitrate makers (Smith and process associated with generalized argyria solely to
Carson, 1977; Rosenman et al., 1979; Jongerius soluble silver compounds (Hill and Pillsbury, 1939;
and Jongeneelen, 1992). Brooks, 1981; Rosenman et al., 1987; Wobling et al.,
1988; Pifer et al., 1989; ACGIH, 1991; Breitstadt,
Exposure Limit (PEL) of 0.01 mg/m3 for metallic and Medicinal, therapeutic and unintentional exposure
soluble silver compounds (OSHA, 1989; NIOSH, As discussed earlier, silver is very effective at
2003). The National Institute for Occupational Safety eliminating bacterial infections (Hill and Pillsbury,
and Health (NIOSH) established a Recommended 1939; Silver, 2003) and so has been extensively
Exposure Limit (REL) of 0.01 mg/m3 for both soluble used in the past for medicinal purposes. The medical
silver compounds and silver metal dust, which does literature cites numerous cases of argyria appearing
not differ from the OSHA PEL (NIOSH, 1992). after the use of silver-containing preparations. Hill
In 1966, the American Conference of Govern- and Pillsbury (1939) analyzed data from 357 recorded
mental Industrial Hygienists (ACGIH) established a cases of argyria and argyrosis. Of the 357 cases, 317
Threshold Limit Value (TLV) of 0.01 mg/m3 for all followed therapeutic use of colloidal silver and silver
forms of silver (ACGIH, 2001), largely based on Hill compounds and the remaining 40 were due to occu-
and Pillsbury’s (1939) publication. However, in pational exposure to various silver compounds and
response to findings from studies undertaken since metallic silver.
Hill and Pillsbury’s work, in 1980 ACGIH set Colloidal silver protein has been used as an allergy
a new TLV of 0.1 mg/m3 for metallic silver. and cold medication (Jacobs, 1998; Bouts, 1999;
ACGIH recognized the different outcomes from Gulbranson et al., 2000; Tomi et al., 2004), in eye
exposure to soluble and/or insoluble silver, rational- drops to alleviate soreness (Loeffler and Lee, 1987)
izing that ‘the available data on soluble compounds of and for the treatment of various ailments (White
silver demonstrate that silver salts have a greater pro- et al., 2003). The adverse affects from extended
pensity to cause argyria than does the dust or fume of use of colloidal silver protein in these cases were
metallic silver and that the respective exposure levels grossly discolored fingernails, ocular argyrosis, and
of 0.01 mg/m3, for soluble silver, and 0.1 mg/m3, for generalized argyria. The location and degree of
A worker developed a rash on his forearms, face, and and blue–black spots developed in various areas on
neck after exposure to a silver cyanide solution their bodies (Tanita et al., 1985; Sato et al., 1999).
(Heyl, 1979).
Three cases of localized argyria were caused by Occupational exposure to soluble silver
silver earrings (Van den Nieuwenhuijsen et al., compounds
1988; Shall et al., 1990; Sugden et al., 2001). All Thirty workers from an industrial plant involved
three cases were due to the cutaneous implantation with manufacturing silver nitrate and silver oxide
of a silver earring backing, either in the ear lobes or were examined for argyria and ocular argyrosis
directly behind the ear. Discoloration was confined to (Rosenman et al., 1979). This cross-sectional study
the skin around the embedded earring backings. Two revealed that six individuals had generalized argyria
cases of localized argyria occurred after years of acu- and 20 had argyrosis. Personal air sampling conduc-
puncture therapy. In both cases, silver acupuncture ted 4 months prior to the study determined a range
needles had been implanted in the skin for >10 years of silver concentrations from 0.039 to 0.378 mg/m3
580 P. L. Drake and K. J. Hazelwood
for an 8 h TWA, suggesting that better engineering respiratory irritation caused by these compounds
controls were needed to minimize workers’ exposure was inconclusive because silver oxide and nitrate,
to silver. Ten of the 30 workers complained of by nature, are irritants. Kidney function was also
abdominal pain. This symptom was significantly evaluated. Creatinine clearance was significantly
associated with silver in the blood. Decreased vision depressed and urinary N-acetyl-b-D glucosaminidase
at night, of which 10 workers complained, was asso- (NAG) was significantly higher in the exposed group
ciated with duration of employment; however, no compared with unexposed controls. Kidney function
changes in visual function could be attributed to silver appears to be adversely affected but because of
deposits. Although some of these workers were dia- concurrent exposure to known nephrotoxins, such
gnosed with argyria and argyrosis, the authors con- as cadmium and solvents, the authors could not defin-
cluded that the health of these workers was not itively determine if silver was responsible.
adversely affected. However, the permanent discol- Blood silver concentrations in 98 occupationally
oration and the potential effect on night vision exposed workers and 15 controls were assessed
suggest the need to limit exposure to silver. (Armitage et al., 1996). The six factories that
Moss et al. (1979) studied the same group of work- participated in the study were involved in bullion
ers as Rosenman et al. (1979) and also found evidence production, silver chemical manufacturing, jewelry
of argyrosis in these workers. Moss et al. surveyed the manufacturing, silver reclamation, and production
workers and found that 27 of 30 workers had suffered of tableware. The majority of the workers were
burns of the skin from contact with silver nitrate and exposed to both metallic and soluble silver (n = 89).
11 workers had a history of ocular burns. An in-depth Workers classified as melters, refiners, and silver
ophthalmic examination was conducted to determine nitrate producers were found to have the highest
if the workers suffered from any visual deficits from blood-silver levels, with values ranging from 0.1 to
silver were used as a control group. Length of expos- some degree of internal nasal septal pigmentation.
ure ranged from 3 to 20 years, and exposure levels Seven out of 24 workers were found to have ocular
ranged from 0.001 to 0.310 mg/m3 for the soluble silver deposits in the conjunctiva and/or cornea.
group and from 0.003 to 0.540 mg/m3 for the insol- Optometric and contrast sensitivity test results
uble group. In the soluble group, discoloration was revealed no significant deficits in visual performance.
observed in the eyes (argyrosis) of 5 workers, the No abnormalities were revealed during tests of renal
mouth of 2 workers, the nose of 1 worker and the function, pulmonary function, and chest radiographs.
nape of the neck of 1 worker. No symptoms of argyria The researchers concluded there was no evidence
or argyrosis were seen in the insoluble group. supporting the notion that chronic exposure to insol-
Skin biopsies analyzed for silver revealed a range uble silver halides had any detrimental health effects
of 0.03–13.48 p.p.m. for the soluble group (median on exposed workers at the concentration levels meas-
0.115 p.p.m.), 0.03–0.77 p.p.m. for the insoluble ured. They also concluded that silver speciation
group (median 0.085 p.p.m.) and 0.01–0.11 p.p.m. should be considered when assessing the effects of
for the control group (median 0.02 p.p.m.). Silver silver on human health.
concentrations found in skin biopsies and air did An unpublished report obtained from Johnson
not correlate with either ocular deposits or duration Matthey (Linnett and Bradford, 1996) discusses a
of exposure. The authors concluded that the occur- study of 41 workers from the United Kingdom,
rence of argyria and argyrosis is dependent upon who were involved in the recovery and recycling
individual susceptibility. of silver. None of the workers showed signs of argyria
The absorption and excretion of silver was mon- or argyrosis even though past exposure to metallic
itored by measuring blood, urine, fecal, and hair silver exceeded 0.1 mg/m3. Their length of employ-
concentrations from 37 workers occupationally ment ranged from 3 months to 29 years. Median
capacity and carbon monoxide transfer. Since all four allowed to purchase products that are not approved
workers were smokers and the work environment by the FDA and that are potentially toxic. Since
included multiple agents, the role of silver exposure colloidal silver can be freely purchased as a supple-
could not definitively be assessed. ment in health food stores and over the Internet, cases
A study of two men occupationally exposed to sil- of argyria and argyrosis, like the ones described by
ver was conducted by Williams and Gardner (1995). Gulbranson et al. (2000), White et al. (2003) and
The first was a process operator with 3 years experi- Tomi et al. (2004), will most likely continue.
ence exposed primarily to insoluble silver com- The body’s uptake of silver is often much higher
pounds, and the second was a process operator with when taken orally as medication, as opposed to occu-
7 years experience exposed primarily to soluble silver pational exposure, which is predominantly through
compounds. In the case of the first worker, no evid- inhalation. The majority of occupational exposure
ence was seen of argyria or argyrosis or silver depos- reports involve soluble silver compounds, which
ition in the nasal or oral mucosa. Atmospheric seem to cause toxic effects at lower concentrations
concentrations of silver were 0.085 mg/m3 recorded than metallic silver and insoluble silver compounds.
at the incinerator and 1.03–1.36 mg/m3 recorded in For example, silver concentrations in skin biopsies
the pulverizing area, suggesting that the potential for found by Wolbling et al. (1988) and blood-silver
exposure was significantly above the occupational concentrations found by Williams and Gardner
exposure limit. Blood-silver concentration was (1995) and Armitage et al. (1996) were considerably
49 mg/l. The second worker was employed in a silver higher in workers exposed to soluble silver com-
refinery. No evidence of argyria was seen, but argyro- pounds than in workers exposed to metallic silver
sis was evident as a gray pigmentation of the con- or insoluble silver compounds.
junctiva. Atmospheric silver concentrations were Metabolism studies indicate that soluble silver
studies. Additional studies could be undertaken that ACGIH. (2001) Documentation of the threshold limit values
would employ a large enough sample size to deter- and biological exposure indices. Supplement to 6th edn.
mine if certain outcomes are statistically significant. Cincinnati, OH: American Conference of Governmental
Industrial Hygienists.
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confounders, which was a major limitation for most tion of silver in whole blood and its application to biological
of the occupational studies reviewed. monitoring of occupationally exposed groups. Ann Occup
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