4.2 exposure routes

Silver may enter the body through the digestive tract (ingestion) when eating or drinking substances which contain silver. It may also be absorbed through the skin, epidermis, (dermal) if part of the body is immersed in silver-containing fluids or is in contact with silver-containing powders. Silver and its compounds may also be breathed in (inhalation) and deposited in, or absorbed via, the lungs (Anon. 1990). Intravenous or intraperitoneal injections also introduce silver into the body and silver may be released from silver amalgam dental fillings in unlined cavities (USEPA 1980a).

4.2.1 absorption

The absorption of silver may occur from the lungs after inhalation, from the gastrointestinal tract after ingestion or directly through the epidermis after contact with liquids, solids or gases containing silver or its compounds. Studies evaluating the therapeutic uses of silver in people and the effects of occupational exposure, indicate that silver is readily absorbed after ingestion or inhalation when in the colloidal form (Hill and Pilsbury 1939, Newton and Holmes 1966, Dequidt et al. 1974). Absorption rates are a very low percentage of the applied dose for most silver compounds or for elemental silver.

Absorption is a function of transit time in the gastrointestinal tract; there is a lower absorption rate with faster transit times. Transit times range from about 8 hours in rats and mice to 24 hours in dogs and primates (Furchner et al. 1968). One could therefore expect more uptake from herbivores with their long intestinal tract and less from carnivores with their short intestines. People retain about 21% of an oral dose of silver after 1 week (East et al. 1980, MacIntyre et al. 1978).

Whatever the method of silver introduction, it eventually enters the bloodstream and most is removed by the liver and sent to the bile for excretion. After a reasonable period of time has elapsed to allow mobilization from the site of intake, the remaining silver has the same distribution pattern in other organs regardless of the route of uptake. This distribution is not dependent upon the original exposure route.

4.2.2 oral uptake

4.2.2.1-laboratory animals

Silver is widely distributed in rats following silver nitrate intake in drinking water at 88.9 mg/kg/day silver (Olcott 1948). Silver is found in many tissues: liver, spleen, bone marrow, lymph nodes, skin, kidney, tongue, teeth, salivary glands, thyroid, parathyroid, heart, pancreas, gastrointestinal tract, adrenals and brain. Within these tissues the silver particles are found in the basement membrane of the glomeruli, the walls of blood vessels between the kidney tubules, the portal vein and other parts of the liver, the choroid plexus of the brain and the choroid layer of the eye (Olcott 1948, Moffat and Creasey 1972, Walker 1971).

Death was observed in rats after very high oral doses of colloidal and inorganic silvers. In the drinking water of rats 2.6 g/L is fatal. In mice 95 mg/L of silver in the drinking water for 125 days caused sluggish behaviour, and in rats 1.6 g/L of silver in the drinking water for 37 weeks caused decreased weight gain (Anon. 1990). Experimental rats receiving 222 mg/kg/day of AgNO₃ for long periods, began to die after 23 weeks. Weight loss also began to show up after 23 weeks and surviving animals averaged 50% less weight than controls drinking distilled water (Matuk et al. 1981). Rats receiving AgNO₃ daily for 2 weeks in their drinking water did not die at 181 mg/kg/day but 3 of 12 died at 362 mg/kg/day (Walker 1971). Some rats given 1.7 g/kg/day of colloidal silver for 4 days died (Dequidt et al. 1974).

Liver necrosis in rats is caused by 130 mg/L of silver in the drinking water or food. This toxicity is prevented by 50 µg/L of selenium. Silver causes the same type of hepatic degeneration as selenium deficiency (Green and Bunyan 1969). Ingestion of AgNO₃ and AgCl₂ will also cause deposition of silver granules in the skin and eyes of animals and discolouration of the skin (Matuk et al. 1981, Olcott 1947, Rungby 1986). No loss of fertility was seen in male rats exposed to 89 mg silver/kg/day for two years, as AgNO₃ or AgCl₂ in their drinking water. No silver deposits were seen in the testes and the spermatozoa were normal in appearance (Olcott 1948).

Granular deposits were seen in the brains of 20 female mice exposed to AgNO₃ in their drinking water for four months. The mice were less active than controls and the deposits were primarily in the areas of the brain involved in motor control, red nucleus, deep cerebellar nuclei and motor nuclei of the brain stem. There were lesser amounts in the basal ganglia, anterior olfactory nucleus and general cortex. The test lasted for 125 days and 18 mg/kg/day was administered daily (Rungby and Danscher 1984).

Long-term experiments with rats and rabbits indicated that 2.5 µg silver/kg body weight had no detrimental effects. Conditioned reflexes in the rats and immunological activity in the rabbits were affected at 25 µg/kg. At 25 and 250 µg/kg there were histopathological changes in rabbit vascular, nervous and glial tissues of the encephalon and medulla (Barkov and El'Piner 1968). Rats given drinking water containing silver at 1 g/L had shorter lifespans and increased hypertrophy of the left ventrical. Silver salts in the diet of animals apparently cause vascular hypertension. Experimental rats given 20 mg/L silver in their drinking water had short-term increases in the RNA and DNA of their brains but, after a year, levels dropped and brain dystrophy occurred (MRI 1975).

Adding 130 to 1000 mg/kg to the food or 1500 mg/L to the drinking water of weanling rats on a vitamin E deficient diet caused liver lesions and fatal liver necrosis after 2 weeks. Selenium at 50 to 100 µg/kg prevented necrosis at the 130 mg/kg diet level but not at higher doses (Grasso et al. 1969).

Wistar rats given colloidal silver at 1.7 g/kg for 4 days, or 420 mg/kg for 12 days, absorbed about 2%, and 5% of the dose, respectively (Dequidt et al. 1974). Rats given carrier-free radioactive silver <1 µg by stomach tube, eliminated 99% in the feces and 0.18% in the urine in 4 days (Scott and Hamilton 1950). Radioactively-labelled silver, as silver nitrate, was fed to, and injected intravenously into, rats, beagles and monkeys. Body burden and persistence increased with species size and was greater in the intravenous than the oral route. However, cumulative excretion was between 90 and 99% by the second day. Absorption was low from the gut and proportional to transit time (Furchner et al. 1966, 1968).

4.2.2.2-livestock

Protargol, a silver protein with 8% silver, inhibited the in vitro biosynthesis of prostaglandin in the seminal vescicles of bulls (Deby et al. 1973). Silver acts as an antagonist to copper metabolism in cattle and chickens (MRI 1975). In the absence of copper, the growth of chicks was retarded by 100 mg silver/kg in the diet. Chick mortality on a copper deficient diet was greater when silver was over 50 mg/kg (Hill et al. 1964). Silver is present in animals at the range of 1 to 10 mg/kg in the ash or 1 to 25 µg/kg wet-weight in beef meat (Klein 1978). Analyses of milk samples from 32 cows gave silver concentrations from 37 to 59 µg/L (mean of 47 µg/L). The mean silver content of milk from different cities in the United States varied from 27 to 54 µg/L (Murthy and Rhea 1968).

4.2.2.3-man

Estimates of silver in human diets vary widely. There are estimates of 0.4 µg/day for three Italian populations and 10 to 44 µg/day (with a mean of 27 µg/day) in the UK (USEPA 1980a).

table 4.1

summary table: silver intake
by the average canadian city dweller.

Data in the table are for intake only, absortion and retention may only be 10% to 20% of this figure. Data do not include dental amalgams or cigarette smoke. No breast feeding is assumed since no data are available on silver levels in human breast milk. From Mitchell, M. 1993.

There are many case studies and experiments which indicate that in humans a number of silver compounds, including salts and silver-protein colloids, are absorbed across mucous membranes in the mouth and nasal passages after ingestion. Silver acetate was readily absorbed after an oral dose of 80 µg/kg/day. Some of the silver was radio-active Ag¹¹⁰. About 20% of the dose was retained in the body after 1 week (East et al. 1980, MacIntyre et al. 1978). A woman who repeatedly applied a AgNO₃ solution to her gums developed generalized argyria indicating absorption and translocation of the silver (Marshall and Schneider 1977). A man who used a silver-containing mouthwash for ten years absorbed about 88 gm of silver and had respiratory and kidney problems, proteinuria and elevated macroglobulins. A silver containing compound was used to fill the renal pelvis for an x-ray and resulted in severe gastrointestinal hemorrhaging and death (Zech et al. 1973 and Hill and Pilsbury 1939 in:USEPA 1980a).

4.2.3 inhalation

4.2.3.1-laboratory animals

Acute inhalation of an aerosol containing colloidal silver for two to eight hours led to ultrastructural damage and disruption of the cells of the tracheal epithelium in rabbits (Konradova 1968). A study in dogs gave an estimate of 1 µg/cm²/day absorption rate for metallic silver from the lungs. Six hours after exposure, the silver was found mostly in the lungs (96.9%), but also in the liver (2.4%), and the blood (0.35%). The remaining silver was in the gall bladder and bile (0.14%), intestines (0.10%), kidneys (0.06%), and stomach (0.02%). After 225 days 0.49% of the deposited silver was in the liver and another 0.1% in other organs; the rest of the silver had been excreted. At both times, excluding the deposits in the lungs where it was introduced, 77% of the body burden was in the liver (Phalen and Morrow 1973).

4.2.3.2-man

Silver is taken up primarily by inhalation but also through cuts and injuries. Uptake is primarily by people engaged in occupations where silver is filed, drilled, hammered, turned, engraved, polished, forged, soldered, plated, smelted, mined, purified, cast, alloyed or brazed. Exposure also occurs during the manufacture of silver mirrors, silver nitrate, photographic emulsions, inks, dyes, porcelain, germicidals, antiseptics, caustics, analytical reagents and paints. Film processing, photographic, x-ray and astronomic emulsions, also provide an avenue of exposure.

Radioactive silver metal dust was inhaled during a nuclear reactor accident. Between two and six days after exposure 25% of the detectable silver was found in the liver; some silver was also found in the feces indicating absorption from the lungs (Newton and Holmes 1966). In a AgNO₃ and AgO manufacturing plant, with airborne levels of silver ranging from 0.039 to 0.378 mg/m³, 12 of the 30 workers had blood silver levels over 6 µg/L (Rosenman et al. 1979). Workers in a photographic materials manufacturing plant were exposed to airborne insoluble silver from 0.001 to 0.1 mg/m³. Silver was found in 80% of the blood samples at a mean level of 11 µg/L and in all of the fecal samples at a mean of 15 µg/g. Two urine samples had a mean silver level of 9 ng/L. Control fecal silver levels were at 1.5 µg/g.

4.2.4 dermal application

4.2.4.1-laboratory animals

In guinea pigs, a solution of 41 g/L applied to the skin for 28 days caused reduced weight gain. Although no deaths were reported, guinea pigs stopped gaining weight when 2.0 mL of a 0.239 molar solution of silver nitrate in water was applied to 3.1 cm² of skin for 8 weeks (Wahlburg 1965).

4.2.4.2-man

Although the amount of absorption is low in intact skin, about 1% of the applied dose (Snyder et al. 1975), several silver compounds are absorbed by people. Silver thiosulphate penetrated the skin of a photochemical worker through sweat glands and caused localized argyria within 6 months (Buckley 1963). Silver nitrate (0.5%), and silver sulphadiazine cream are used as topical antibiotics for burned skin and silver is absorbed and distributed throughout the body through such damaged skin (Sano et al. 1982, Bader 1966).

4.2.5 intravenous injection

4.2.5.1-laboratory animals

Acute effects of silver in mammals is usually only associated with intravenous injection; silver has been used to produce pulmonary edema in dogs (Taylor et al. 1980).

4.2.5.2-man

When 10 cc of a 2% solution of silver (20 g/L or 200 mg/10 cc) were administered intravenously the patient died of pulmonary edema in 5 minutes (Hill and Pilsbury 1939).

4.2.6 intraperitoneal injection

4.2.6.1-laboratory animals

In pregnant rats intraperitoneal injection of silver lactate resulted in silver crossing the placenta and being found in fetal liver and brain tissues (Rungby et al. 1983).