Silver (Ag): Exposure Routes and Health Effects

Silver is becoming more pervasive in our food, in dental and medical devices, in implants and even the cloths we wear. Silver forms silver-protein complexes when absorbed into the circulation and these become deposited in key soft tissues, including the skin, liver, kidney, spleen, lungs, and brain and at this stage must be presumed to present a health risk to exposed persons under some circumstances.

Here we show ways we are increasingly exposured to silver and as such help us develop strategies for avoidance and minimisation so as to reduce possible harm.

Having high silver levels in blood or urine is often the result of occupational exposure. However, high silver levels in hair can result from consistent, yet potentially harmful, low level exposure to many of the possible routes outlined in this article.

Cover photo by Hartmut Gunther

Exposure to Silver nanoparticles in consumer products

Silver nanoparticles are currently the largest (∼24%) and fastest growing segment of the commercial market for engineered nanomaterials.

An important feature of nanoparticles is that, on a mass basis, more atoms are available at the particle’s surface to interact with its surroundings. Silver, antiseptic efficacy increases as particle size decreases because of the higher surface area per unit volume and subsequently enhanced surface re-activity. For example a 4-nm particle has 50% of its atoms on the surface, whereas a 30-nm particle has only 5% of its atoms on the surface.

A recent 2018 review entitled A systematic review on silver nanoparticles-induced cytotoxicity: Physicochemical properties and perspectives indicated that the use of silver nanoparticles carries a series of unpredictable concerns regarding their interaction with biological systems. Therefore, the enormous applications of silver nanoparticles raise concerns about human exposure, because they can easily pass through the blood brain barrier (BBB) by transcytosis of capillary endothelial cells or into other critical areas or tissues.

Silver nanoparticles are impregnated in materials such as paints, soaps and laundry detergents, refrigerators, laundry machines, cooking utensils, medical instruments (dressings, catheters, pace-makers) and drug delivery devices, water purifiers, clothing, antibacterial sprays, personal care products (toothpaste, shampoo, cosmetics), electronics, air filters, and humidifiers. Airborne silver nanoparticle generators for disinfection of indoor air have been developed. Considering these uses, high concentrations of airborne Silver nanoparticles could potentially be found indoors (in industrial and household environments) and outdoors (in the vicin- ity of smelters, nanotechnology industries, incinerators, wastewater treatment plants, etc.)

Several silver nanoparticle products are currently available clinically, including silver-impregnated foams (Mepilex™) nanocrystalline nanoparticle films (Acticoat™) and silver-impregnated polymers (Microblock). Additionally, an increasing diversity of oral and nasal colloidal silver nutraceutical products are available, virtually unregulated in form, quality, dosing, and indications.

Many questions remain unanswered regarding silver’s therapeutic and toxicological properties despite massive anecdotal history. This is particularly relevant as clinical trials are ongoing for silver-containing products, and colloidal silver is still widely available for human use in consumer form. Many colloidal silver products are widely marketed as intranasal sprays despite lack of regulatory approval, with limited in vivo studies published on colloidal silver quality control, dosing, or toxicity after intranasal installation.

Small amounts of silver from silver nanoparticles reach the brain following intranasal administration in mice. Yet nasal responses to silver and possible nose-to-brain silver transmission are poorly understood.

Common silver nanoparticles exposures to human tissues include the nasal cavity, gut, ocular surface, and skin. Absorption, tissue processing, and resulting bioavailability of silver nanoparticles after exposure to epithelial barriers have been studied, yet no consensus currently exists regarding dosimetry, exposure, and safety for various silver forms. This ambiguity produces considerable questions and variations in the prevailing literature about mechanism and silver biochemical processing that contribute to confounding published toxicity, safety, therapy, and efficacy claims.

It is clear that silver ion release from silver nanoparticles (as a more biologically active species than silver nanoparticles or colloidal silver) can have significant unwanted side effects when given orally and/or intranasally on the microbiome and other tissues.

In vivo and in vitro studies have now indicated that nanosilver exposure leads possibly to genotoxicity, changes in activity of the immune system and an accumulation of silver in spleen, liver and testes. More data are needed to understand better bacterial response and possible resistance to ionic silver and silver nanoparticle exposure and this represents a serious gap of knowledge considering the increasing use of these silver compounds.

Example consumer products are below.

REF: Comparing ex vivo and in vitro translocation of silver nanoparticles and ions through human nasal epithelium
and Changes in Bacterial Community Structure after Exposure to Silver Nanoparticles in Natural Waters
and Environmental and Human Health Risks of Aerosolized Silver Nanoparticles
and Nanosilver: safety, health and environmental effects and role in antimicrobial resistance

Summary of consumer products claiming to use silver nanotechnology. AgNP = Silver nanoparticles. Table also shows production potential for the Silver nanoparticles to be released into the air.
From Environmental and Human Health Risks of Aerosolized Silver Nanoparticles

Exposure to Silver Compounds

Historically, because of its bactericidal properties, silver was used for surgical prosthesis and splints, fungicides, and coinage. Soluble silver compounds, such as silver salts, have been used in treating mental illness, epilepsy, nicotine addiction, gastroenteritis, and infectious diseases, including syphilis and gonorrhea. Principle routes of human exposure to silver nowadays are through its widespread use as an antimicrobial agent in wound care products and medical devices, including in-dwelling catheters, bone cements, cardiac valves and prostheses, orthopedic pins, and dental devices. Antimicrobial properties of silver are dependent upon release of biologically active silver ion (Ag*) from metallic silver (including nanocrystalline forms), silver nitrate, silver sulfadiazine, and other silver compounds incorporated in the various devices, and its lethal effect on pathogenic organisms.

Rain-making has used silver iodide with the emission of silver iodide crystals during cloud seeding estimated to result in a silver concentration in air of about 0.1 ng/cubic metres.

Cloud seeding has been ongoing in the USA in Utah since 1973. It is estimated that cloud seeding increased runoff by 59.2 billion gallons, during the 2009-2010 season. In 2014, there are four large-scale projects in the Utah state, all of which use ground-based silver iodide generators. The generators use silver iodide-containing pyrotechnic flares which produce trillions of extremely small silver iodide particles. These particles increase the probability of ice crystal formation in a cloud, which then increase in size at the expense of surrounding cloud moisture and eventually fall to the ground as snow.

There have been a number of studies investigating the concentration of silver in snow and groundwater following cloud seeding activities. While most found levels of silver that were higher than the local background level, few if any identified silver concentrations in excess of EPA’s SMCL of 100 ppb. A recent 2013 investigation of sources of metal accumulation in an alpine tarn in a cloud seeding area in the Snowy Mountains of Australia determined that the contribution of cloud seeding to silver levels in lake sediment was negligible Ref: Concerns Regarding Silver Iodide Cloud Seeding.

Anti-smoking tablets, lozenges and gum can contain silver acetate, and the habitual use of silver foil-coated mouth refreshers can build up silver.

Industrial applications, jewelry and silverware, and the photographic industry were the largest consumers of silver in 2003, using 40%, 31% and 22%, respectively with the photographic industry also a big user (photosensitive silver halides). Medically, silver sulfadiazine, is used as a topical antibacterial agent for the treatment of burns.

Liberation during mining and purification from ore. Use in manufacture of silver nitrate for use in mirrors, plating, inks, dyes, and porcelain; and as germicides, antiseptics, caustics, and analytical reagents. Use in manufacture of silver salts as catalysts in oxidation-reduction and polymerization reactions; in chemical synthesis; in glass manufacture, in silver-plating and as lab reagents.

Liberation from manufacture and casting of alloys; during fabrication of silver metal, alloys, and bimetals for electrical uses; and during electroplating operations and fabrication of solders and brazing alloys and during manufacture of silver powder pigments and paints.

Localized argyria can be caused by silver earrings due to the cutaneous implantation of a silver earring backing, either in the ear lobes or directly behind the ear. Discoloration was confined to the skin around the embedded earring backings.

Occupationally, silver exposure occurs in factories involved in bullion production, silver chemical manufacturing, jewelry manufacturing, silver reclamation, and production of tableware and polishing silver cutlery. Workers are exposed to both metallic and soluble silver. Workers classified as melters, refiners, and silver nitrate producers were found to have the highest blood-silver levels, with values ranging from 0.1 to 20 μg/l.

It has been estimated that a person developing six rolls of film could be exposed to up to 16 grams of silver through dermal contact with photographic solutions. However, many people use implements or wear gloves during film developing and therefore this is not expected to result in widespread, high level exposures.

Therefore, principle routes of gastrointestinal absorption of silver include –
(i) contaminated food,
(ii) occupational exposures to metallic silver dust, silver oxide, and silver nitrate aerosols,
(iii) drinking water (including use of silver : copper filters in water purification),
(iv) silver nitrate or colloidal silver therapies in oral hygiene and gastrointestinal infection,
(v) colloidal silver preparations labelled as “food supplements” or “alternative medicines”,
(vi) silver acetate antismoking therapies,
(vii) silver amalgams used in dentistry,
(viii) accidental consumption of silver nitrate or other colourless silver compounds.

REF: Exposure-Related Health Effects of Silver and Silver Compounds: A Review
and
Silver nanoparticles in the environment: Sources, detection and ecotoxicology
and A Pharmacological and Toxicological Profile of Silver as an Antimicrobial Agent in Medical Devices
and SILVER IODIDE

Silver Synonyms and additional exposures

Silver SYNONYMS: Ag | Ag(1+) | Ag+ | Argentum | Silver cation | Silver ion (1+) | Silver metal | Silver(0) | Silver(1+) | Silver(1+) ion | Silver(I) cation

Has been used in Hydraulic Fracturing Operations (Fracking) or Coal Seam Gas (CSG) facilities. Much silver is produced as a by-product of copper, gold, lead, and zinc refining

Silver is widely distributed in the earth’s crust and is found in soil, fresh and sea water, and the air. It is readily absorbed into the human body with food and drink and through inhalation. Silver is not an acknowledged trace element in the human body and fulfills no physiological or biochemical role in any tissue even though it interacts with several essential elements including zinc and calcium. Physiologically, it exists as an ion in the body.

Skin contact occurs from the application of burn creams and from contact with jewelry. Silver can also gain entry into the body through the use of acupuncture needles, catheters, dental amalgams, or accidental puncture wounds.

Silver has been employed in water purification and is currently used to safeguard hospital hot water systems against Legionella infections.

Ref: Toxno Substance Profile – Silver
and Exposure-Related Health Effects of Silver and Silver Compounds: A Review
and SILVER COMPOUNDS

Argentite is the main ore from which silver is extracted by cyanide, zinc reduction, or electrolytic processes. Silver is frequently recovered as a by-product from smelting of nickel ores in Canada, from lead-zinc and porphyry copper ores in the USA, and from platinum and gold deposits in South Africa.

Emissions from smelting operations, manufacture and disposal of certain photographic and electrical supplies, coal combustion, and cloud seeding are other man-made sources of silver in the biosphere. Fallout from cloud seeding with silver iodide (AgI) is not always confined to local precipitation; silver residuals have been detected several hundred kilometres downwind of seeding events.

In 1978 the photographic industry alone accounted for about 47% of all silver discharged into the environment from man-made sources. Silver compounds are used in filters and other equipment to purify swimming pool water and drinking-water and in the processing of foods, drugs, and beverages.

Coal has been reported to contain silver at concentrations of up to 10 ppm. The following silver concentrations
at a bituminous coal-fired electric generating station: coal:0.29 mg/kg and fly-ash:1.6 mg/kg.

Sewage treatment plant influent can contain silver.

In 1984 it was estimated that about 50% of the 214 million people in the United States who used public drinking water supplies had silver present in their water at 0.01-10pg/L and 10-30% could receive water with levels greater than 30pg/L and that 46,000 people in the U.S. receive drinking water with silver concentrations exceeding the current U.S. Safe Drinking Water Act maximum contaminant limit of 50pg/L. Swimming pool water purified with silver – containing systems is another possible source of exposure to silver

Ref: SILVER AND SILVER COMPOUNDS:ENVIRONMENTAL ASPECTS
and
TOXICOLOGICAL PROFILE FOR SILVER

Silver from Food and Water

Note that 1 mg (milligram) = 1000ug (micrograms) and 1ug = 1000ng (nanograms) and 1ng = 1000pg (picograms)

In Food silver also as an E Number: E174 | Food Additives with E Numbers used in Australia, NZ, UK and the EU. Over 400 in total. | Substance has been approved in Australia and NZ, EU and UK and is associated with colours and colouring agents.

The median daily intake of silver from 84 self-selected diets, including drinking-water, was 7.1 μg. Higher figures have been reported in the past, ranging from 20 to 80 μg of silver per day. The relative contribution of drinking-water is usually very low. Where silver salts are used as bacteriostatic agents, however, the daily intake of silver from drinking-water can constitute the major route of oral exposure.

The most important silver compounds from the point of view of drinking-water are silver nitrate (AgNO3, CAS no. 7761-88-8) and silver chloride (AgCl, CAS no. 7783-90-6).

Average silver concentrations in natural waters are 0.2–0.3 μg/litre. Silver levels in drinking- water in the USA that had not been treated with silver for disinfection purposes varied between “non-detectable” and 5 μg/litre. In a survey of Canadian tapwater, only 0.1% of the samples contained more than 1–5 ng of silver per litre. Water treated with silver may have levels of 50 μg/litre or higher; most of the silver will be present as non-dissociated silver chloride.

The 2014 study – Silver: water disinfection and toxicity from the Centre for Research into Environment and Health, found that the efficacy of silver, especially in terms of drinking-water disinfection, is currently a long way from convincing and that the body of evidence seems to suggest that silver (in ionic form or as silver nanoparticles) is toxic to mammalian cells, at least in-vitro and that the sensitivity of mammalian cells varies according to the cell type and the type of silver to which it is exposed and conclude that silver is not an effective drinking-water disinfectant even though it is extensively used.

Also, ambient air concentrations of silver are in the low nanogram per cubic metre range.

TOXICOLOGICAL PROFILE FOR SILVER
Silver in Drinking-water – Background document for development of WHO Guidelines for Drinking-water Quality

Additional Silver Compounds on Toxno with synonym details (in grey) and links to exposure and health information

Some substances are medications. Clicking on link takes you to side effects information