Silver Toxicity

Silver Toxicity Experienced in the Use of Silver Preparations for Medical Therapy

Gary B. Clark, MD, MPA and Steven R. Frank

Steven Frank originally founded Klearsen Corp. in 1999 and developed KC-287. The present product, Nature’s Rite Respiratory Relief, is an improved version of the KC-287 referenced in this study.

Over many centuries, silver preparations have been used to treat disease — so much so that some silver treatments have taken on almost a folklore status. In the early 20th century, silver in various forms became particularly popular amongst so-called holistic healers, e.g., naturopaths.

In the latter half of the century, traditionally trained allopathic physicians also became aware of its efficacy in certain cases.

Early silver treatments

In their earliest usage, silver-based remedies were prepared in the form of silver salts, e.g., silver nitrate and silver acetate. Later, non-salt preparations have included silver sulfadiazine and colloidal silver. All of these remedies have been used primarily to treat infectious conditions.

Generally, the silver salt remedies have shown limited effect, usually requiring relatively high doses to achieve any effect. High dosage of such silver salts— especially after regular, long-term use—has produced reportable cases of silver toxicity, known as argyria.

On the other hand, silver colloid preparations are not associated with any reportable toxicity.

Argyria - silver-colored skin

Argyria is characterized as a permanent ashen-gray (bluish) discoloration of the skin, conjunctival sclerae, and internal organs resulting from long-continued use of silver salts—without any otherwise notable adverse effects on general metabolic health.

Today, it is difficult to find any reference to argyria in any standard medical textbook, i.e., internal medicine or pathology. Modern academic medicine seems to have relegated argyria to the status of a medical historical oddity—clinically experienced as infrequently as diphtheria, previously a scourge of the pre-antibiotoic era.

On the other hand, another form of silver combined with an antibiotic has proven itself to be particularly efficacious—i.e., highly therapeutically effective with very low risk of deleterious side effects. Over the last five decades, most authorities have come to consider silver sulfadiazine (e.g., Silvadene) as an agent of first choice for the prevention of infection of burns. This topical drug inhibits the in-vitro growth of nearly all pathogenic bacteria and fungi—including species resistant to sulfonamides. (1)

Silver is slowly released from this compound preparation in concentrations that are toxic to the microorganisms. Very little silver is absorbed, whereas the sulfadiazine is readily absorbed, reaching measurable plasma levels.

Adverse reactions to silver sulfadiazine have been infrequently reported as being relatively minor, e.g., rash and itching. It has not been determined whether these adverse reactions are subsequent to exposure to the silver or the sulfadiazine. It is most likely to be the latter.

Silver bonded to proteins

Parallel to the development of silver sulfadiazine, the use of silver suspended in a protein colloidal solution also became popular over the last century. The naturopaths have been particularly excited about this preparation. However, the efficacy of these protein-colloidal preparations often has been questioned— although the incidence of any reported toxicity has been minimal, so has its effectiveness.

More recently, however, the use of low concentration, i.e., <50 ppm, non- proteinaceous silver colloids, such as Nature’s Rite Sinus Relief, have been found to be tremendously effective against localized cutaneous and upper respiratory infections. The levels of this non-proteinaceous silver colloid required to achieve satisfactory antimicrobial action are 100 times lower than that of the previously used silver salts or protein colloids.

There have been no reported toxicity or adverse events linked to the use of these pure silver non-proteinaceous colloids.

Silver absorption and retention

Silver may be absorbed through the lungs after inhalation, the gastrointestinal tract after ingestion, or directly through the epidermis after contact with liquids, solids, or gases containing silver or its compounds. Absorption rates vary for the various forms of elemental silver and silver compounds.

Silver salts, especially in the form of large particle salt powder, appear to be absorbed relatively readily. Studies evaluating the therapeutic uses in humans and the effects of occupational exposure indicate that silver is significantly less readily absorbed after ingestion or inhalation when in the colloidal form (2, 3, 4).

Absorption through the gastrointestinal tract can vary widely. This is a function of the form of the silver as well as species transit time, which is an inverse function, e.g., the absorption rate is lower with faster transit times. Transit times range from about 8 hours in rats and mice to 24 hours in dogs and primates (5). One could, therefore, expect more uptake from herbivores with their relatively long intestinal tracts and less from carnivores with their proportionally shorter intestines.

In a study by Scott and Hamilton who fed silver to rats through a stomach tube, they recorded that 99% was eliminated through the feces and 0.18% was eliminated through the urine in 4 days; 0.82% was retained. (6)

Other studies have placed retention in larger animals at between 10 and 1% after 2 days.

Whatever the chemical form or method of silver introduction, whatever amount that is absorbed enters the bloodstream from which most is removed by the liver and sent to the bile for excretion. After a period of time has elapsed allowing for distribution, any retained silver is equally distributed through all organs regardless of the route of uptake.

Large particle silver salt powder ingestion seems to be associated with most of the cases of argyria, where large amounts of silver have been retained in humans.

In cases where argyria have occurred, the total body burden has been estimated at between 20 to 90 g. This amount of silver is contained in roughly 1000 liters of KC-287. To achieve such retention, 1000 liters would have to be ingested within one week. More data on absorption (including parenteral) and retention are available on request.

Sample case reports of argyria

Case 1

This report described an experimental study of the toxicity of silver salt. Rats were allowed to drink water with a silver salt for 500 days. The water was 1000 ppm silver salt as this was determined by earlier investigation to not reduce longevity.

Although this researcher chronicled the internal discoloration of organs after this intense ingestion of silver water—thus reporting an animal model of argyria—he did not see fit to determine or estimate the total silver intake. (7)

  • If one were to assume that a human drinks approximately 16 oz. of water per day, the above intake would be equivalent to a human intake of 0.473 g/day or 10 liters of KC-287 per day.

Case 2

This report described a controlled study of the use of an anti-smoking chewing gum containing silver acetate, asking if this treatment risked creating elevated silver concentrations in the serum and tissues and risked causing clinical signs of argyria. (8)

  • The administered amount of silver was estimated at less than 3.2g over a 3- month period. This is equivalent to 100 liters of KC-287 over a 3 month period or roughly 200 times the dose used for M.tb.

  • Although serum silver levels were slightly elevated during the study, they were statistically normal within a few months after study completion. No signs of argyria were noted.

The silver content of KC-287 is 50 ppm or 50 micrograms/ml. A typical treatment for M.tb would consist of less than 500ml, yielding a total dose of less than 25 milligrams of silver.

Case 3

This report described a patient who used an anti-smoking remedy containing silver acetate and experienced argyria. Normally, the total body silver is approximately 0.5 micrograms/gram. This patient was estimated to have had a total body silver content of approximately 6.4 micrograms/gram. This silver content was approximately 8000 times the normal value. (9)

In order to achieve this body burden by using KC-287, one would have to consume 10 liters or 20 times the dose for M.tb. This represents .47g in a 75kg person.

With the estimated normal dietary intake of 50 ug/day, one would expect to have a normal accumulation of 0.22 g by age 70 years.

Case 4

This report described a patient who used topical silver nitrate for 5 years as a treatment for a skin condition. In the course of an unrelated stomach surgery, the surgeon noted the increased pigmentation of the internal organs— evidence of argyria. The report noted that the “minimum oral dosage ingested to yield systemic argyria has been estimated to be 25 to 30 gm over a six-month period.” (10)

  • This is equivalent to more than 500 liters of KC-287 per month.
  • Similarly, it could be considered 1000 times the normal dose of KC-287.

Case 5

This report described a patient with uniformly silver-blue discoloration of all fingernails, with deeper coloring over the lunulae. The nail bed changes resulted from the uncontrolled ingestion of a silver containing granular powder for an undisclosed use. The total silver intake was over 15 g. The only other sign of argyria was a barely perceptible greyish discolouration over the cheeks and the sclerae. (11)

  • In order to match this patient’s intake of 15 g in 3 years one would have to consume more than 1 liter of KC-287 per week.

Case 6

This report described a patient with argyria secondary to the prolonged use of nasal drops containing mild silver protein. This patient used silver- containing nose drops every night for 35 years. The drops were 1% msp and, assuming two drops per nostril per night, and they delivered an estimated total intake of 25.5 g. (12)

  • The drops were 1% msp, which is to say 10,000 ppm. In order to achieve this dose with KC-287, 500 liters or 1000 treatment programs for M.tb would have to be administered.

Much more data on toxicity studies are available on request.

EPA Standards for silver toxicity

According to the EPA, silver is relatively non-toxic. It is not listed in the EPA Primary Standards for water quality. It is listed only in the Secondary Standards, which regulate contaminants that cause offensive taste, odor, color, corrosion, foaming, or staining. The concentration limit is called the secondary maximum contaminant level (SMCL).

Secondary standards are not enforced; they are guidelines for water treatment plant operators and state governments attempting to provide communities with the best quality water possible. The Secondary Maximum Contaminant Level for silver is listed as 0.1 mg/L. This is equivalent to 100 ppb or about 100ug /day for one who consumes 4-8 oz glasses of water per day.

In comparison, the mean content of silver in milk varies between 27 and 54 ug/L in the US. The average person consumes 10 to 90 ug /day in their food.

The EPA critical dose for 160-pound adult, i.e., the amount that should not be exceeded in daily consumption, is 1.09 mg/day or 1,090 ug/day. The EPA allows the ionic form of silver, Ag+, in drinking water at the level of 100 ppb. This is equivalent to .1mg/L. The consumption of 4-8 oz glasses/day is equivalent to 100 ug/day of Ag+.

Likewise, the EPA does not consider silver to be a human carcinogen. In fact, their standards for the allowable levels of silver in drinking water would permit a typical human to consume 50 to 100 micrograms per day. Long-term experiments with rats and rabbits indicate that 2.5ug /kg body weight had no detrimental effects. This would equate to roughly 175 ug/day for a 150-pound human.

Dietary minerals

One can compare other metals and minerals that are consumed intentionally in common vitamin and mineral supplements. Most of these are consumed in far higher doses than would be received by proper use of the Nature’s Rite’s colloidal products.

Element Atomic Weight Daily Amount Per Vitamin Tablet
Magnesium 24.30 100,000 ug/day
Iron 55.85 18,000 ug/day
Zinc 65.38 100,000 ug/day
Copper 63.55 100,000 ug/day
Manganese 54.94 100,000 ug/day
Molybdenum 95.94 100,000 ug/day
Chromium 52.00 100,000 ug/day
Iodine 126.90 100,000 ug/day
Silver used in KC-287 107.87 800 ug/day during treatment period
Tin 118.69 13 ug/day
Nickel 58.70 6.5 ug/day


  1. Goodman and Gilman’s The Pharmacological Basis for Therapeutics. New York: McGraw-Hill, 1996 p 1061.

  2. Hill and Pilsbury, 1939

  3. Newton and Holmes, 1966

  4. Dequidt et al., 1974

  5. Furchner et al., 1968

  6. Scott and Hamilton

  7. Olcott CT. Experimental Argyrosis: Morphologic Changes in the Experimental Animal. Department of Pathology of Cornell University Medical College and the New York Hospital, New York, N.Y. Received for publication July 17, 1947.

  8. Marshall JP, Schneider RP. Systemic Argyria Secondary to Topical Silver Nitrate. Archives of Dermatology, 1977; 113: 1077-1079.

  9. East BW, Boddy K, E.D. Williams, MacIntyre D, McLay ALC. Silver retention, total body silver and tissue silver concentrations in argyria associated with exposure to an anti-smoking remedy containing silver acetate. Clinical and Experimental Dermatology, 1980; 5: 305-311.

  10. Plewig G, Lincke H, Wolff HH. Silver-Blue Nails. The Department of Dermatology, University of Munich, Munich, Germany; Acta Dermatovener (Stockholm), 1997; 57:413-419.

  11. Jensen EJ, Rungby J, Hansen JC, Schmidt E, Pedersen BR, Dahl R. Serum Concentrations and Accumulation of Silver in Skin during three Months Treatment with an Anti-smoking Chewing Gum containing Silver Acetate. Department of Respiratory Medicine, The University Hospital, Aarhus, and Institute of Neurobiology University of Aarhus, and Department of Environmental and Occupational Medicine, University of Aarhus, Denmark. Journal of Toxicology, 1988; 7: 535-540.

  12. Timmins AC, Morgan GAR. Argyria or Cyanosis. Anaesthesia, 1988; 43: 755-756.