Testing Information

Testing Status of Agents at NTP

CAS Registry Number: 7761-88-8 Toxicity Effects

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Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 1

Names (NTP)

  • Silver nitrate
  • NITRIC ACID SILVER(1+)SALT (9CI)

Human Toxicity Excerpts

  • GENERALIZED ARGYRIA ... IS ... RECOGNIZED BY WIDESPREAD PIGMENTATION OF SKIN, AS SEEN IN ... DARK, UNIFORM, SLATE-GREY COLOR OF FACE, FOREARMS & FINGERNAILS OF WORKER IN MFR OF SILVER NITRATE. PIGMENTATION APPEARS EARLY ON FACE, GRADUALLY SPREADING TO EARS & NECK ... & HANDS; IN A LESS SEVERE DEGREE IT APPEARS ON UNCOVERED AREAS OF THE BODY, IN MOST SEVERE CASES THE SKIN BECOMING ALMOST BLACK WITH A METALLIC LUSTRE. [Browning, E. Toxicity of Industrial Metals. 2nd ed. New York: Appleton-Century-Crofts, 1969., p. 299]**PEER REVIEWED**
  • ARGYROSIS OF RESPIRATORY TRACT ... HAS ... BEEN DESCRIBED ... IN TWO MEN EMPLOYED IN MFR OF SILVER NITRATE. ... SYMPTOM WAS MILD CHRONIC BRONCHITIS; THERE WAS NO DISCOLORATION OF SKIN, EYES OR MOUTH BUT NASAL MUCOSA SHOWED BILATERAL SYMMETRICAL IMPREGNATION OF WALLS OF MIDDLE & UPPER REGION. [Browning, E. Toxicity of Industrial Metals. 2nd ed. New York: Appleton-Century-Crofts, 1969., p. 299]**PEER REVIEWED**
  • ... CORNEAL OPACIFICATION & BLEEDING CONJUNCTIVA WITHIN AN HR /REPORTED/ AFTER APPLICATION OF 2 DROPS FROM AN /SRP: ACCIDENTAL USE OF/ SILVER NITRATE STICK INTO THE EYES OF A NEWBORN. OPACIFICATION MAY BE SO SEVERE AS TO CAUSE BLINDNESS. [Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 1887]**PEER REVIEWED**
  • IN PATIENT WITH SEVERE ARGYROSIS RESULTING FROM INDUST EXPOSURE TO SILVER NITRATE: BRONCHIAL MUCOUS MEMBRANE ... SHOWED DEPOSITS IN BASAL MEMBRANE, & THERE WAS SOME SQUAMOUS METAPLASIA, BUT MUCH LESS EVIDENCE OF PHAGOCYTOSIS THAN IN NASAL MUCOSA. [Browning, E. Toxicity of Industrial Metals. 2nd ed. New York: Appleton-Century-Crofts, 1969., p. 300]**PEER REVIEWED**
  • LARGE ORAL DOSES OF SILVER NITRATE CAUSE SEVERE GI IRRITATION DUE TO ITS CAUSTIC ACTION. LESIONS OF KIDNEYS & LUNG & POSSIBILITY OF ARTERIOSCLEROSIS HAVE BEEN ATTRIBUTED TO BOTH INDUSTRIAL & MEDICINAL EXPOSURES. [Doull, J., C.D.Klassen, and M.D. Amdur (eds.). Casarett and Doull's Toxicology. 3rd ed., New York: Macmillan Co., Inc., 1986., p. 625]**PEER REVIEWED**
  • IN FORM OF DUST OR SOLID IT IS DANGEROUS TO EYES, CAUSING BURNS OF CONJUNCTIVA, ARGYRIA, & BLINDNESS. [International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983., p. 2048]**PEER REVIEWED**
  • INGESTION OF CORROSIVE SILVER NITRATE ... HAS BEEN RESPONSIBLE FOR MOST CASES OF ACUTE SILVER POISONING. SYMPTOMS ARE THOSE OF SEVERE GASTROENTERITIS & SHOCK ... VERTIGO, COMA, CONVULSIONS & DEATH. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-145]**PEER REVIEWED**
  • SEVERE & EVEN LETHAL METHEMOGLOBINEMIA HAS RESULTED /FROM USE OF 0.5% SILVER NITRATE TOPICALLY FOR TREATMENT OF BURNS/. SUCH REACTION PRESUMABLY DEPENDS ON BACTERIAL CONTAMINATION OF ESCHAR OR SYSTEMIC INFECTION WITH ORGANISM CAPABLE OF REDUCING NITRATE TO NITRITE. ... [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-145]**PEER REVIEWED**
  • ... Two days after the conjunctival surface of the upper lid of one eye was treated with a solid silver nitrate bead for questionable vernal conjunctivitis, much of the corneal epithelium was missing & the lower 2/3 of the cornea showed wrinkling of Descemet's membrane, fine punctate infiltration of stroma, & a dense gray opacification near the low limbus, but no recognizable color in the cornea. ... Healing was very slow, with wrinkling of the posterior surface & corneal edema gradually becoming less, & the epithelium healing very poorly. Even after 2 months there was reported still to be a defect in the epithelium in the palpebral fissure, & persistent blue discoloration deep in the stroma. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 818]**PEER REVIEWED**
  • ... CASE OF CORNEAL INJURY FROM CAUTERIZATION OF CHALAZION WITH SOLID SILVER NITRATE HAS BEEN REPORTED ... PATIENT HAD DENSE OPACIFICATION & CATARACT, REQUIRING CORNEAL TRANSPLANTATION & LENS EXTRACTION. ... SILVER STILL PRESENT IN THE TISSUE 5 YR AFTER INJURY. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 818]**PEER REVIEWED**
  • ACUTE TOXICITY SYMPTOMS FOLLOWING INGESTION OF CAUSTIC SILVER NITRATE ARE ... FALL IN BLOOD PRESSURE, DECR RESPIRATION, SPASMS, & PARALYSIS LEADING TO DEATH; THE HEART IS LITTLE AFFECTED, WHILE PARALYSIS FIRST AFFECTS THE DIAPHRAGM MUSCLE; THE CNS ALSO IS AFFECTED IN SILVER TOXICITY. [Venugopal, B. and T.D. Luckey. Metal Toxicity in Mammals, 2. New York: Plenum Press, 1978., p. 34]**PEER REVIEWED**
  • ACUTE POISONING: (FROM INGESTION OF SILVER NITRATE) PAIN & BURNING IN MOUTH; BLACKENING OF SKIN & MUCOUS MEMBRANES, THROAT, & ABDOMEN; SALIVATION; VOMITING OF BLACK MATERIAL; DIARRHEA; ANURIA; COLLAPSE; SHOCK; AND DEATH IN CONVULSIONS OR COMA. [Dreisbach, R.H. Handbook of Poisoning. 12th ed. Norwalk, CT: Appleton and Lange, 1987., p. 375]**PEER REVIEWED**
  • NECROTIZING, ULCERATIVE GINGIVITIS HAS BEEN REPORTED TO RESULT FROM APPLICATION OF SILVER NITRATE TO GINGIVA. [Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 1887]**PEER REVIEWED**
  • ... A 46 year old woman ... began using silver nitrate applicators for bleeding gums ... upon the advise of her dentist. ... She had used three applicators per week and continued using them even after the first bluish discoloration appeared about her nose and face. [USEPA; Ambient Water Quality Criteria Doc: Silver p.C-30 (1980) EPA 440/5-80-071]**PEER REVIEWED**
  • Because of the hypotoxicity of the 0.5% silver nitrate dressings and the tendency to precipitate as silver chloride, electrolyte imbalance may occur in a few hours. [USEPA; Ambient Water Quality Criteria Doc: Silver p.C-75 (1980) EPA 440/5-80-071]**PEER REVIEWED**
  • Argyrosis of the cornea in workers who handled silver nitrate may be accompanied by turbidity of the anterior lens capsule and a disturbance of dark adaption. [Browning E; Toxicology of Industrial Metals (1961)]**PEER REVIEWED**
  • ... Solid silver nitrate, known as lunar caustic, can be very injurious to the eye. ... Particles of solid silver nitrate in the conjunctival sac have been known to cause severe inflammation with deep injury to surrounding tissues, scarring, and symblepharon. In a most unusual case of severe injury from solid nitrate ... the cornea became dark brown, and the lens became cataractous. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 817]**PEER REVIEWED**
  • Concn of silver nitrate from 5%-50% applied by mistake or accidentally splashed in the eye have caused severe injury, with permanent corneal opacification in some cases. ... Soln of high concn cause rapid appearance of edema of the conjunctiva & lids, with bloody purulent discharge from the conjunctival sac. Opacification of the cornea may result & may be permanent, but in eyes which have been contaminated with very small amt soln the results have been less disastrous. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 817]**PEER REVIEWED**
  • 2 cc of unknown concn of silver nitrate were administered intravaginally & resulted in death. There was an abortion attempt, therefore death possibly not due to AgNO3. [USEPA; Ambient Water Quality Criteria Doc: Silver Nitrate p.C-69 (1980) EPA 440/5-80-071]**PEER REVIEWED**
  • The ingestion: of 8 g of silver in soln resulted in vomiting. The /vomitus/ contained silver chloride. The patient recovered. [USEPA; Ambient Water Quality Criteria Doc: Silver Nitrate p.C-69 (1980) EPA 440/5-80-071]**PEER REVIEWED**
  • 2-30 g of silver nitrate were administered orally. Survival time was a few hr to a few days. Death usually occurs at doses of 10 g but 30 g has been survived. [USEPA; Ambient Water Quality Criteria Doc: Silver Nitrate p.C-69 (1980) EPA 440/5-80-071]**PEER REVIEWED**
  • In humans taking large doses of silver nitrate orally, the patient suffers violent abdominal pain, abdominal rigidity, vomiting, convulsions, and appears to be in severe shock. [USEPA; Ambient Water Quality Criteria Doc: Silver p.C-68 (1980) EPA 440/5-80-071]**PEER REVIEWED**
  • Argyrosis involves all eye tissues except the optic nerve. Instillation of 0.25% silver nitrate for 3 wks & instillation of 3-5% silver colloid compounds for 5-10 wks have produced argyrosis. [USEPA; Ambient Water Quality Criteria Doc: Silver p.C-73 (1980) EPA 440/5-80-071]**PEER REVIEWED**
  • Two silver nitrate workers afflicted with argyrosis of the lung showed mild chronic bronchitis with silver impregnation in the walls of the middle and upper region of the nasal mucosa. In a more severe case, the bronchial mucous membrane also showed basal membrane deposits and some squamous metaplasia. There was less evidence of phagocytosis than in the nasal mucosa and no hazard of fibrosis. Pigmentation was comparable with that of anthracosis and siderosis. [USEPA; Ambient Water Quality Criteria Doc: Silver p.C-78 (1980) EPA 440/5-80-071]**PEER REVIEWED**
  • SILVER NITRATE IS ... STRONGLY CAUSTIC & CORROSIVE, AS WELL AS POISONOUS. [International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983., p. 2048]**PEER REVIEWED**
  • Silver nitrate is no longer used in 20% of the hospitals in the USA because of the dangers of chemical conjunctivitis. [Shaw EB; Pediat 59: 792 (1977) as cited in USEPA; Ambient Water Quality Criteria Doc: Silver p.C-29 (1980) EPA 440/5-80-071]**PEER REVIEWED**
  • The fatal dose of silver nitrate may be as low as 2 g, although recovery has occurred following ingestion of larger doses. No fatalities have been reported in recent years. ... Silver nitrate causes a local corrosive effect but is not likely to produce systemic effects because silver ion is precipitated by proteins and chloride. [Dreisbach, R.H. Handbook of Poisoning. 12th ed. Norwalk, CT: Appleton and Lange, 1987., p. 373]**PEER REVIEWED**
  • Absorption of the nitrate and reduction to nitrite may cause methemoglobinemia. Reaction with chloride in the body may cause hypochloremia with associated hyponatremia. [Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 941]**PEER REVIEWED**
  • ... DEVELOPMENT /OF ARGYRIA (POISONING BY SILVER OR A SILVER SALT WHICH LEADS TO A PERMANENT ASHEN-GRAY DISCOLORATION OF THE SKIN, CONJUNCTIVA, AND INTERNAL ORGANS)/ FROM INHALATION THROUGH OCCUPATIONAL EXPOSURE APPEARS TO BE VERY SLOW & MAY REQUIRE YEARS. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values, 4th ed., 1980. Cincinnati, Ohio: American Conference of Governmmental Industrial Hygienists, Inc., 1980., p. 367]**PEER REVIEWED**
  • Ingestion of 10 g silver nitrate is usually fatal /for humans/. [USEPA; Ambient Water Quality Criteria Doc: Silver p.C-68 (1980) EPA 440/5-80-071]**PEER REVIEWED**
  • The brain of a 78 yr old woman with argyria was examined at autopsy. Silver nitrate deposition was observed in circumventricular organs & in the paraventricular & supraoptic nuclei of the hypothalamus. These findings parallel animal experiments of other investigators & are the best demonstration so far of regional absence of the blood brain barrier in humans. [Landas S et al; Neurosci Lett 57 (3): 251-6 (1985)]**PEER REVIEWED**
  • The factors relating to the clinical outcome of an industrial aerosol plant explosion are reviewed. Eighteen of 24 workers inside the plant required hospitalization & 5 died. Proximity to the blast was associated with extensive injuries unless workers were shielded by physical barriers or partitions. Burn severity & mortality were increased in those wearing fiber clothing. Facial burns occurred in all unprotected workers. Forearm & hand burns in 11 patients required decompressive escharotomies. Topical treatment with silver sulfadiazine was associated with more significant leukopenia & neutropenia than treatment with silver nitrate. [Hull D et al; J Trauma 25 (4): 303-8 (1985)]**PEER REVIEWED**
  • The inhibitory effects of silver nitrate and silver sulfadiazine on adenosine triphosphate were studied in human kidneys in vitro. Tests utilized ouabain sensitive and ouabain insensitive adenosine triphosphatase, as well as total adenosine triphosphatase. To compare the response of the enzymes to silver nitrate, the metal was applied to preparations in which all sodium and potassium adenosine triphosphatase activity was inhibited. Cysteine was tested for its ability to modify the effects of silver nitrate. In human kidney, the 50 percent molar inhibition of silver nitrate in microsomes and homogenates was 0.0000007 and 0.000003, respectively. A higher concentration of silver was required for inhibition in homogenates than in microsomes. [Nechay BR, Saunders JP; J Environ Pathol Toxicol Oncol 5 (4-5): 119-26 (1984)]**PEER REVIEWED**
  • Two cases of silver nitrate burn occurred after treatment of superior limbic kertatoconjunctivitis with a solid applicator. After medical treatment & several months of observation, visual acuity eventually returned to acceptable levels with minimal corneal scarring. These cases emphasize the fact that silver nitrate should be used very cautiously around the eye & only in a fresh 0.5-1% soln. The use of solid silver nitrate should be prohibited around the eye. [Laughrea PA et al; Cornea 4 (1): 47-50 (1985)]**PEER REVIEWED**
  • ... Fatal methemoglobinemia /was observed/ in a 3 yr old girl suffering from burns involving 82% of the body surface, who was treated with silver nitrate soln. [Marzulli, F.N., H.I. Maibach. Dermatotoxicology 4th ed. New York, NY: Hemisphere Publishing Corp., 1991., p. 866]**PEER REVIEWED**
  • Postmortem exams of patients treated with silver nitrate have revealed that silver has been deposited in internal organs, showing that absorption of silver from topical preparation does occur. ... Excessive use of silver-containing drugs has led to local & systemic argyria ... & to renal damage involving the glomeruli & proteinuria. [Marzulli, F.N., H.I. Maibach. Dermatotoxicology 4th ed. New York, NY: Hemisphere Publishing Corp., 1991., p. 866]**PEER REVIEWED**
  • Workers who inhaled 0.039-0.378 mg/cu m as an 8-hr TWA of silver nitrate/ silver oxide dust for 1-10 yr complained of upper respiratory tract irritation, but no abnormalities were seen on chest radiograms. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1397]**PEER REVIEWED**
  • ... A major photographic industry's use of silver nitrate indicate that cases of generalized argyria were seen when exposures were on the order of 1 mg/cu m of silver. Levels estimated to be on the order of 0.1 mg/cu m of silver resulted in some staining of the mucous membrane of the nose & throat & some eye discoloration. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1397]**PEER REVIEWED**
  • Chronic use of silver-containing nose drops & topical application of silver nitrate to mucous membranes have also caused argyria. Direct ocular or dermal contact with concentrated silver nitrate solutions resulted in chemical burns. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1397]**PEER REVIEWED**
  • Methemoglobinemia is a rare complication in individuals exposed to nitrates or nitrites. Whereas methemoglobinemia is a recognized potential complication in burn patients treated with topical 0.5% silver nitrate solution, no report of methemoglobinemia in burn patients has been present in the literature for more than 15 years. We raise consciousness about this complication with a case report of a 12-month-old child with necrotizing fasciitis resulting from a cutaneous flank infection. The patient developed cyanosis 20 days after initiation of topical treatment with 0.5% silver nitrate solution. Intravenous injection of methylene blue can restore normal blood oxygenation. [Chou TD et al; Burns 25 (6): 549-52 (1999)]**PEER REVIEWED**
  • A case of chyluria is reported in which anuria followed instillation of 3% silver nitrate into the collecting system of both kidneys, with unusual radiographic features. Plain radiographic, ultrasound and computed tomographic findings are discussed. [Gulati MS et al; Australas Radiol 43 (1): 102-3 (1999)]**PEER REVIEWED**
  • ... We formed a complex of silver and cysteine, named silver-cysteine. Healthy human lymphocytes were incubated with silver-nitrate or silver-cysteine. Negligible cell survival was seen at 50 mM silver-nitrate. However, in presence of 1 mM cysteine, the viability remained unaffected up to 1 mM of silver. Further, silver inhibition of isolated Na,K-ATPase was easily reversed by cysteine. Thus, non-toxic silver-cysteine could be used as an anti-viral and cysteine-replenishing agent. [Hussain S et al; Biochem Biophys Res Commun 189 (3): 1444-9 (1992)]**PEER REVIEWED**
  • The primary effect sought with most topical wound therapy is antimicrobial. Topical wound agents are thought to promote normal healing by protecting the wound from infection. In this study, the effect of six commonly used topical wound agents (bacitracin, sodium hypochlorite, silver nitrate, silver sulfadiazine, mafenide acetate, and povidone-iodine) on epithelialization and neovascularization in noninfected wounds /was examined/. For this study, a new wound model was used in which direct visualization and quantification of wound epithelialization and neovascularization were carried out throughout the entire healing process. ... The effect which 500 U per g of bacitracin, 0.25% of sodium hypochlorite, 0.5% silver nitrate, 1% silver sulfadiazine, 8.5% percent mafenide acetate, and 10 percent povodione-iodine had on the rate of wound epithelialization and neovascularization. The agents were applied topically to 99 circular full-thickness wounds (2.25 mm diameter, 0.125 mm depth) created on the dorsum of male hairless mouse ears. This model enabled us to visualize and measure directly wound epithelialization and neovascularization repeatedly throughout healing, using intravital video microscopy and computerized digitized planimetry. ... Control wounds and wounds treated with silver sulfadiazine (n = 18) and mafenide acetate (n = 14) epithelialized in 7.2 + or - 0.7, 7.1 + or - 0.3, and 7.3 + or - 0.3 days, respectively. This was significantly (p < 0.01) faster than the wounds treated with povidone-iodine (n = 10), sodium hypochlorite, (n = 8), and bacitracin (n = 13). Wounds treated with povidone-iodine epithelialized the slowest (11.8 + or - 0.55 days). Wound neovascularization was completed most rapidly in the groups treated with povidone-iodine and silver sulfadiazine (15.0 + or - 0.4 and 15.3 + or - 0.7 days, respectively). This was significantly (p < 0.05) faster than wounds treated with silver nitrate (n = 15), which neovascularized in 18.4 + or - 0.56 days. One-half of the wounds treated with sodium hypochlorite (eight of 16) did not epithelialize or neovascularize. ... The various antimicrobial agents studied in our in vivo model affect wound epithelialization and neovascularization differently. These effects on these two very important aspects of healing should be taken into consideration when indicating a specific agent for treatment of different types of wounds. [Kjolseth D et al; J Am Coll Surg 179 (3): 305-12 (1994)]**PEER REVIEWED**
  • A 69-year-old woman was referred to our hospital for evaluation of pyuria and renal dysfunction. Twenty days earlier, the patient had undergone silver nitrate retrograde instillations for essential renal bleeding. Routine laboratory findings showed renal dysfunction with a serum creatinine concentration of 7.2 mg/dl and blood urea nitrogen concentration of 68 mg/dl. The urine contained numerous red cells and white cells. The plain X-ray film of the abdomen revealed right renal calcification. Computed tomographic scan confirmed the calcifications in the right renal collecting systems and parenchyma. The most likely diagnosis was argyrosis of the upper urinary tract. The patient underwent a right nephrectomy. Histopathological examination of the specimen showed that the renal pelvis was filled with blood clots. Laboratory evaluation including serum creatinine concentration and urinalysis revealed normal parameters postoperatively. We conclude that this patient developed argyrosis of the urinary tract, and review previously published papers concerning complications of silver nitrate instillation. [Kojima Y et al; Hinyokika Kiyo 39 (1): 41-4 (1993)]**PEER REVIEWED**
  • Generalized argyria, the systemic dissemination and tissue deposition of silver-containing particles, is characterized by slate gray discoloration of skin, most pronounced in sun exposed areas. A 33-year-old woman visited our dermatologic clinic complaining of frequent oral ulceration for 10 years and generalized discoloration of her skin for 5 years. She had had her tongue painted with silver nitrate repeatedly 6 years ago for the treatment of oral ulcers. Physical examination showed slate gray discoloration of her skin, most pronounced on the face and neck. The oral mucosa, tongue, sclera, and conjunctiva also had a slightly blue-gray discoloration. Biopsy specimens from the oral mucosa and forearm revealed small brown-black granules scattered in the dermis and basal lamina of eccrine sweat glands, blood vessels, and hair follicles under the light microscope. Tiny black granules were most numerous in the basal laminae of vessels in electron microscopic observation. Energy dispersive X-ray microanalysis (EDXA) confirmed that many of the granules contained silver. [Lee SM, Lee SH; J Dermatol 21 (1): 50-3 (1994)]**PEER REVIEWED**
  • . ... A 42-year-old woman who suffered a corneal injury following the application of a silver nitrate stick to her lid for hemostasis after a chalazion had been incised and drained /is described/. Nine months later there were greenish-yellow deposits in the deep stroma that accounted for a persistent decrease in vision. Physicians should be aware of the potential for ocular injury with the use of silver nitrate applicator sticks. [Stein RM et al; Can J Ophthalmol 22 (5): 279-81 (1987)]**PEER REVIEWED**
  • Generalized argyrosis can produce a number of abnormalities, including skin discoloration, liver and kidney dysfunction. We describe a patient with generalized argyrosis following long-term self-treatment with oral silver intake, in whom skin discoloration, progressive taste and smell disorders, vertigo and hypesthesia were observed. These findings were confirmed by chemosensory tests and electrophysiological investigations. The development of hypogeusia was assessed by subjective tests, while the progression of hyposmia was followed by recording olfactory evoked cortical potentials. Light and electron microscopy of tissue samplings demonstrated electron-dense mineral deposits in basal membranes, in macrophages, in the perineurium of peripheral nerves, along elastic and collagenous fibers, and in necrotic cells of the oral submucosa. Silver and sulfur deposits in affected tissues could be defined by X-ray microanalysis. The quantitative ratio between silver and sulfur in involved tissues was similar to that of an inorganic silver-sulfide (Ag2S) standard. The minute increase in the sulfur content when compared to the inorganic standard suggested a sulfur containing organic matrix of the tissue precipitates. Our findings indicate that the affinity of silver for membrane and neuronal structures and the deposition of silver as an insoluble compound (Ag2S) induce the progression of clinical disease. [Westhofen M, Schafer H; Arch Otorhinolaryngol 243 (4): 260-4 (1986)]**PEER REVIEWED**
  • Abdominal pain has also been reported by workers exposed to silver nitrate and oxide in the workplace ... . The pain was described as "burning in quality and relieved by antacids" and was reported in 10 out of 30 workers examined. Exposure levels were est to be between 0.039 and 0.378 mg silver/m3. [DHHS/ATSDR; Toxicological Profile for Silver p. 13 TP-90-24 (1990)]**PEER REVIEWED**
  • Three infants treated for umbilical granuloma with silver nitrate suffered chemical burns to the periumbilical area which prompted visits to the emergency department. [Chamberlain JM et al; Pediatr Emerg Care 8 (1): 29-30 (1992)]**PEER REVIEWED**

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Non-Human Toxicity Excerpts

  • TOXIC DOSE ... /FROM INGESTION/ FOR THE DOG IS 2-4 G. LARGE DOSES ACT AS IRRITANTS PRODUCING SEVERE GASTROENTERITIS. [Clarke, M. L., D. G. Harvey and D. J. Humphreys. Veterinary Toxicology. 2nd ed. London: Bailliere Tindall, 1981., p. 73]**PEER REVIEWED**
  • In attempts to induce glaucoma in rabbits ... 0.175% silver nitrate soln /was injected/ subconjunctivally, but found that it caused excessive local /injuries/. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 818]**PEER REVIEWED**
  • A LIGHT GRAY CAT ... POISONED BY ADMIN OF 3 G OF SILVER NITRATE BY STOMACH TUBE IS SAID TWO DAYS LATER TO HAVE HAD TRANSIENT BLINDNESS WITH SWELLING OF OPTIC NERVEHEADS & DILATION OF RETINAL VESSELS. PIGMENTATION OF FUNDUS THEN RESEMBLED THAT OF BLACK CAT. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 819]**PEER REVIEWED**
  • 2 MG AG/KG OF SILVER NITRATE INCR METALLOTHIONEIN LEVELS IN LIVER OF RATS BY APPROX 2-FOLD WITHOUT ALTERING KIDNEY METALLOTHIONEIN CONTENT. [MOGILNICKA ET AL, BROMATOL CHEM TOKSYKOL 9 (3): 357 (1976)]**PEER REVIEWED**
  • PACIFIC OYSTERS WERE EXPOSED THROUGHOUT EMBRYOGENESIS TO SILVER NITRATE. SILVER CONCN OF 0.0-18.0 UG/L DECR PERCENT OF NORMAL EMBRYONIC DEVELOPMENT WITH INCR METAL CONCN. SILVER CONCN OF 16.0-18.0 UG/L YIELDED 50% OF NORMAL EMBRYONIC DEVELOPMENT. [COGLIANESE MP, MARTIN M; MAR ENVIRON RES 5 (1): 13 (1981)]**PEER REVIEWED**
  • INTRAUTERINE INJECTION OF 1% SILVER NITRATE BETWEEN DAYS 27 & 43 OF PREGNANCY RESULTED IN VAGINAL BLEEDING IN CYNOMOLGOUS MONKEYS WHICH BEGAN 1 OR 2 DAYS AFTER TREATMENT & LASTED FOR AN AVG OF 5.3 DAYS. IN ALL OF THESE CASES, PREGNANCY WAS TERMINATED. [DUBIN ET AL; FERTIL STERIL 36 (1): 106 (1981)]**PEER REVIEWED**
  • Fundulus heteroclitus (mummichog) exposed to 30 ug/l of silver nitrate for 4 days, showed an in vivo inhibition of 3 liver enzymes. [USEPA; Ambient Water Quality Criteria Doc: Silver p.B-32 (1980) EPA 440/5-80-071]**PEER REVIEWED**
  • Exposure of Nassarius obsoletus to 250 ug/l of silver nitrate for 3 days, /resulted in/ distressed behavior, snail's inability to move; at concentrations of 500 ug/l AgNO3 for 3 days, caused depression in oxygen consumption. [USEPA; Ambient Water Quality Criteria Doc: Silver p.B-31 (1980) EPA 440/5-80-071]**PEER REVIEWED**
  • Oxygen consumption increased significantly when Spisula solidissima (surf clam) larvae & Spisula solidissima adults were exposed to 50 ug/l silver nitrate for 15 days and 4 days, respectively. Oxygen consumption also increased significantly when Spisula solidissima juveniles were exposed to 10 ug/l AgNO3 for 4 days. [Thurberg FP et al; In: Cech JJ et al; Respiration of Marine Organisms p.41 (1975)]**PEER REVIEWED**
  • Oxygen consumption increased significantly in Mytilus edulis (blue mussel) exposed to 100 ug/l of silver nitrate for 4 days. [Thurberg FP et al; In: Vernberg FJ, Vernberg WB (eds); Pollution and Physiology of Marine Organisms p.67 (1974)]**PEER REVIEWED**
  • Twenty one turkey poults, fed a diet containing 0.9% silver as silver nitrate for 4 wks, had significant reductions in body weight gain, hemoglobin, packed cell volume of the blood, & aortic elastin content. An incr in wet heart weight to body weight was observed. Heart enlargement was due to copper deficiency. Six of the poults died (28.6% mortality) during the following 18 wks, during which time they did not receive silver. The factors affected by silver nitrate returned to normal, except for the hearts which were grossly enlarged, blunt at the apex, & exhibited dilation & thinness of the right ventricle. [USEPA; Ambient Water Quality Criteria Doc: Silver p.C-101 (1980) EPA 440/5-80-071]**PEER REVIEWED**
  • The growth regulator ... silver nitrate was applied in weekly or biweekly foliar sprays to watermelon (Citrullus lanatus) plants grown in a greenhouse. ... 500 ppm AgNO3 reduced the number of staminate flowers and promoted hermaphroditic flowering. [Christopher DA, Loy JB; J Am Soc Hortic Sci 107 (3): 401-4 (1982)]**PEER REVIEWED**
  • ... When primary leaves were removed from cuttings of Vigna radiata previously sprayed with silver nitrate, dark-induced abscission of the petioles was inhibited, compared to untreated leafless controls. [Curtis RW; Plant Growth Regul 1 (2): 119-38 (1982)]**PEER REVIEWED**
  • The wilting of cut fronds from maidenhair fern (Adiantum raddianum) after < 2 days in deionized water was associated with a rapid reduction in water potential, loss of water balance, and a sharp decline in the rate of water conduction through the stem. Silver nitrate base solutions maintained water potential, water balance, and turgidity of the fronds for up to two weeks by simultaneously reducing water loss from the pinnae and maintaining water condition of the rachis. [Fujino DW et al; Sci Hortic 19 (3-4): 349-55 (1983)]**PEER REVIEWED**
  • The absorbance maximum (630 nm) of reduced cytochrome d in Escherichia coli membrane particles was diminished by 160 uM silver nitrate ... accompanied by the formation of a ... /cytochrome derivative/ ... with an absorption maximum at 640-645 nm. [Hubbard JA et al; FEBS Lett 164 (2): 241-43 (1983)]**PEER REVIEWED**
  • With increasing concn of silver nitrate (10, 50, & 100 ppm) & duration of the treatment (60 & 90 min), there was a concomitant incr in the % of aberrant cells & a decline in the mitotic indexes in growing onion roots. The various cytologic abnormalities included: mitosis, binucleate cells, breakage & fragmentation of chromosomes, laggard & vagrant chromosomes, telophase bridges, & distributed meta- & anaphases. In recovery experiments in distilled water for 24, 48, & 72 hrs, the dividing cells did not recover from the damage caused by the silver ions in terms of increased mitotic indexes or decline in the % of aberrant cells, indicating that the damage to the genetic system was irreversible. [Suryakumari T et al; Ind Bot Rep 2 (2): 145-6 (1983)]**PEER REVIEWED**
  • Exposure to 500 ug/l of Ag+ as silver nitrate caused a decr in oxygen consumption & depressd activity of liver glucose-6-phosphate dehydrogenase (but not aspartate aminotransferase) in Tautogolabrus adspersus (cunner, a coastal fish). [USEPA; Ambient Water Quality Criteria Doc: Silver p.B-32 (1980) EPA 440/5-80-071]**PEER REVIEWED**
  • ... 10 adult rats and 3 adult rabbits /were given/ drinking water containing 1,500 mg/l silver nitrate for 4 to 20 weeks to study the permeability of medullary vessels of the kidney to protein. Only the rat kidney showed heavy silver deposits ... . Both species had heavy deposits in the inner medulla. [USEPA; Ambient Water Quality Criteria Doc: Silver p.C-51 (1980) EPA 440/5-80-071]**PEER REVIEWED**
  • Treatment of rat eyes with a single 3-drops 0.66% silver nitrate soln caused deposition of silver in the cornea, conjunctiva, subconjunctiva, Bowman's layer, reticular fibers of the corneal stroma, Descemete's membrane and the posterior corneal epithelium. Silver was also found scattered in cells of the outermost part of the anterior corneal epithelium. Silver was not found in the kidneys and liver. These results are discussed in relation to prophylaxis of Crede, ie, use of a 2% AgNO3 soln for the treatment of gonococcal opthalmia neonatorum. [Rungby J; Exp Eye Res 42 (1): 93-4 (1986)]**PEER REVIEWED**
  • Silver nitrate (0.002-0.2 mM) gradually reduced ethylene production. ... Slight browning of apple tissue was observed with 0.1 mM AgNO3. Incubation of the protoplasts with > 0.2 mM AgNO3 caused loss of the viability of all protoplasts. .... [Lis EK et al; Plant Sci Lett 33 (1): 1-6 (1984)]**PEER REVIEWED**
  • Inhibition of ATPase by silver nitrate in vitro was studied in microsomal fractions or tissue homogenates of canine brain & kidney, & human kidney. In microsomal fractions, AgNO3 was an indiscriminate inhibitor of ouabain-sensitive (Na+ + K+ +-ATPase) & ouabain-insensitive (Mg(2+)-ATPase) activities, with 50% inhibition obtained at concentrations on the order of 10-7 to 10-6 M. ... Silver gives a different pattern of Na+ + K+-ATPase inhibition than other metallic inhibitors of the enzyme. [Nechay BR, Saunders JP; J Am Coll Toxicol 3 (1): 37-42 (1984)]**PEER REVIEWED**
  • The primary toxic effects of silver seem to be exerted on the cardiovascular, hepatic, & hematopoietic systems. Cardiac enlargement & ventricular hypertrophy have been reported in turkeys following dietary exposure to 900 mg/kg silver nitrate for 18 wk. ... Deposits of silver granules in the glomeruli & tubules of the kidney, as well as pathological changes in renal tubules were reported ... in rats exposed to 0.2% silver nitrate in drinking water in various groups from 10-50 wk. [Friberg, L., Nordberg, G.F., Kessler, E. and Vouk, V.B. (eds). Handbook of the Toxicology of Metals. 2nd ed. Vols I, II.: Amsterdam: Elsevier Science Publishers B.V., 1986., p. V2 527]**PEER REVIEWED**
  • In rabbits, a 6% soln of silver nitrate causes extensive scarring & a 12% soln of the drug causes blindness. [American Hospital Formulary Service-Drug Information 88. Bethesda, MD: American Society of Hospital Pharmacists, 1988 (Plus supplements)., p. 1529]**PEER REVIEWED**
  • The induction of back mutations from streptomycin dependence to nondependence in Escherichia coli were studied. The bacteria were incubated with six different effective concns of silver nitrate (5 x 10-6 M to 10-5 M) for 3-25 hr. The mutation rate was greater for controls than for treated plates at every concn except the lowest. Therefore, silver nitrate was considered nonmutagenic. [USEPA, Office of Drinking Water; Criteria Document (Draft): Silver p.V-10-1 (1985)]**PEER REVIEWED**
  • Twenty Swiss male mice were given 2 doses/wk of 10% silver nitrate in distilled water for 43 wks starting one wk after topical application of 1.5% 7,12-dimethylbenz(a)anthracene in mineral oil through hair free skin. Croton oil was substituted for the first silver nitrate treatment. At the duration of 44 wks, 6 mice developed 14 tumors (1 was a carcinoma) - avg latent period was 21 wks. Nineteen mice survived 10 wks & 15 mice survived 20 wks. Fifty female mice given only a similar initiating treatment lived 20-140 wks without developing tumors. Among control groups from the same colony, one of 240 females observed for their lifespan developed a papilloma that regressed, & of 240 males, there developed one skin papilloma & a carcinoma of skin appendages. Other control groups totalling 400 mice of both sexes did not develop any tumor within 100 wks. [USEPA; Ambient Water Quality Criteria Doc: Silver p.C-107 (1980) EPA 440/5-80-071]**PEER REVIEWED**
  • Thirty Swiss inbred male mice were given a dose twice/wk of 10% silver nitrate in distilled water topically through the top of the ears for fifty days. The only untoward effect was the presence of 17 +/- 27 (sd) inflammatory cells after 10 days in a standard area of ear epidermis, compared with 3 +/- 2 (sd) in the controls while the tumor promoter 5% croton oil caused 176 +/- 142 (sd) inflammatory cells. There were 25 surviving mice. [USEPA; Ambient Water Quality Criteria Doc: Silver p.C-107 (1980) EPA 440/5-80-071]**PEER REVIEWED**
  • Numerous studies have been cited wherein silver nitrate was administered in the drinking water of rats to study glomerular basement membrane formation. Drinking water containing 2,500 mg/l silver nitrate was given for 12 weeks to hooded female rats, killing pairs of animals at 1 to 12 weeks to study the tissues by light and electrom microscopy. Other pairs of animals were killed at 1 to 10 months after silver intake. Four of each strain were also killed for study at 16 months after the cessation of silver intake. ... The silver content in the liver was similar in both strains, but varied by strain and individuals of the same strain in the kidney. Abnormalities in glomerular epithelial and endothelial cells were not progressive or consistent. [USEPA; Ambient Water Quality Criteria Doc: Silver p.C-49 (1980) EPA 440/5-80-071]**PEER REVIEWED**
  • The treatment of silver nitrate induced peritonitis in rats with lithium hydroxybutyrate led to a 2 fold decr in the amt of peritoneal fluid & to a decr in the number of mesenteric mast cells. In another series of experiments the acute inflammation induced by histamine, serotonin, & PGE2 was prevented by treatment with lithium hydroxybutyrate. Thus, prophylactic application of lithium hydroxybutyrate inhibits acute inflammation by altering the permeability of blood vessels & decreasing the degranulation of mast cells. [Aleksandrov PN, Speranskaya TV; Byull Eskp Biol Med 103 (2): 188-90 (1987)]**PEER REVIEWED**
  • ICR male mice aged 5 wks were injected sc with CdCl2, silver nitrate, copper, a combination of cadmium & silver cmpds, or a combination of copper & silver cmpds. These injections were carried out 3 times. 24 hrs after the last injection, they were sacrificed. Cadmium injection significantly stimulated serum ceruloplasmin activity & copper concn, accompanied by an incr in hepatic copper. In contrast, silver injection markedly decreased both ceruloplasmin activity & copper concn in the serum. Hepatic copper increased slightly after silver injection. Using a combination of cadmium & silver, only the silver effect on the ceruloplasmin activity was noted. With a copper & silver combination, the effect of silver on ceruloplasmin was lost, with a concomitant disappearance of silver from the ceruloplasmin fraction in the serum. [Sugawara N, Sugawara C; Arch Toxicol 59 (6): 432-36 (1987)]**PEER REVIEWED**
  • The inhibitory effects of silver nitrate & silver sulfadiazine on adenosine triphosphate were studied in dog brains & kidneys in vitro. Tests utilized ouabain sensitive & ouabain insensitive adenosine triphosphates, as well as total adenosine triphosphatase. To compare the response of the enzymes to silver nitrate, the metal was applied to preparations in which all sodium & potassium adenosine triphosphatase activity was inhibited. Cysteine was tested for its ability to modify the effects of silver nitrate. In dog tissue, total microsomal adenosine triphosphatase was 50% inhibited by silver nitrate molar concns of 0.0000005-0.0000008. Inhibition was related inversely to the protein content of microsomal aliquots. It appeared that in preparations with predominantly ouabain sensitive adenosine triphosphatase activity, the inhibition of silver in sodium & potassium adenosine triphosphatase was similar to that for total adenosine triphosphatase. In the dog kidney cortex microsomes, the 50% inhibition of silver for ouabain insensitive adenosine triphosphatase was about 3 times higher than for total adenosine triphosphatase activity at the same protein content. [Nechay BR, Saunders JP; J Environ Pathol Toxicol Oncol 5 (4-5): 119-26 (1984)]**PEER REVIEWED**
  • The antagonism of silver and selenium is exerted through an effect on the biosynthesis of the selenium containing enzyme glutathione perioxidase. To test the effect of selenium intake on silver toxicity, two levels of silver, 76 and 751 mg/l /as silver nitrate/, and a control (no silver) were administered in drinking water for 52 days. All experimental groups consisted of ten, 21 day old Holtzman rats, fed a vitamin E deficient diet. A similar regimen was administered to vitamin E deficient rats which had selenium added to their diet. Silver, at 751 mg/l severely depressed the growth of rats on the low selenium diet. Selenium addition overcame this deficit completely in the 76 mg/l silver group but not in the 751 mg/l group. Activity of liver glutathione perioxidase in the selenium supplemented group was reduced to 30% of control at 76 mg/l silver in drinking water and to 40% of control at 751 mg/l. [USEPA, Office of Drinking Water; Criteria Document (Draft): Silver p.V-8 (1985)]**PEER REVIEWED**
  • Incubation with silver nitrate soln of 0.000005 - 0.0001% for 3 to 25 hr resulted in 4.3 to 84% survival of Escherichia coli with 2.1 to 8.2 mutants per 1 x 10+8 bacteria after incubation. In control plates, 2.3 to 8.6 mutants per 1 x 10+8 bacteria were noted. [Demerec J et al; AM Nat 85: 119 (1951)]**PEER REVIEWED**
  • An 18 month study to evaluate the effects of silver nitrate on survival & growth of rainbow trout was conducted. The exposure was initiated with eyed embryos which hatched after 26 days. Premature hatching occurred in silver concns of 0.69, 0.34, & 0.17 mg/l. After a 2 month exposure, the length of fish in the high concn was significantly (p=0.05) less than the length of control fish. At the termination of the exposure, survival of fish exposed to 0.09 ug/l was similar to the 79.9% survival of control fish. Mortality of fish exposed to 0.17 & 0.34 ug/l was 17.2 & 36.6% greater, respectively, than mortality of control fish. The acute-chronic ratio is 54 for silver in rainbow trout. [USEPA; Ambient Water Quality Criteria Doc: Silver p.B-7 (1980) EPA 440/5-80-071]**PEER REVIEWED**
  • DIGESTION WAS NOT INHIBITED IN RABBITS AND GOATS FOLLOWING THE INGESTION OF DIETS CONTAINING 4.2 AND 1 PPM SILVER AS SILVER IODIDE, OR 10 AND 100 PPM SILVER AS SILVER NITRATE. [BAILEY JA ET AL; US NAT TECH INFORM SERV, PB REP; ISS NO 226062/8GA, 1973, 39 PP]**PEER REVIEWED**
  • Topical application of 2 ml of a 0.24 molar soln of silver nitrate to 3.1 sq cm of intact guinea pig skin produced reductions in body weight gain; approx 1% of the applied dose was absorbed into the systemic circulation. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1396]**PEER REVIEWED**
  • Rats given 222 mg silver/kg/day as silver nitrate for up to 37 wk in their drinking water experienced reducions in body weight gain, ocular argyria, & elevated mortality beginning 23 wks after their initial exposure. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1396]**PEER REVIEWED**
  • In a mice study (strain and number unreported), silver nitrate was added to the drinking water at a concentration equivalent to 65 mg/kg/day for 12 days to 14 weeks. No toxicity was observed but silver deposits were observed in the basement membrane of the kidneys at necropsy. [USEPA; Reregistration Eligibility Decision Document - Silver. Washington, DC: USEPA, Off Pest Prog. USEPA 738-R-94-021, p.8 Sept 1992. Available from the Database Query page at http://www.epa.gov/REDs/ as of Feb 24, 2002.]**PEER REVIEWED**
  • In the first study, rats were given silver nitrate in their drinking water at a concentration equivalent to 63.5 mg/kg/day for 218 days ... . No toxic effects were observed, but intense silver pigmentation of many tissues was observed at necropsy, including the basement membrane of the kidneys' tubules, the portal vein and other parts of the liver, the choroid plexus of the brain, the choroid layer of the eyes, and the thyroid gland. [USEPA; Reregistration Eligibility Decision Document - Silver. Washington, DC: USEPA, Off Pest Prog. USEPA 738-R-94-021, p.8 Sept 1992. Available from the Database Query page at http://www.epa.gov/REDs/ as of Feb 24, 2002.]**PEER REVIEWED**
  • ... 139 albino rats were given silver nitrate in their drinking water at a concentration equivalent to 63.5 mg/kg/day for up to 553 days ... . Examination of their eyes at various time points showed the color changing from normal to slightly gray after 218 days (stage 1), to more gray than pink (stage 2) after 373 days, to dark/translucent (stage 3) after 447 days, and to opaque (stage 4) after 553 days. The total cumulative amount of silver consumed at these respective stages were 3.2 g, 5.7 g, 6.8 g, and 9.4 g. Histological observation of the membrane of Bruch showed a few silver granules after 218 days and complete blackening by silver deposits after 553 days. The study did not state whether silver deposition in the eye was by any vision impairment. [USEPA; Reregistration Eligibility Decision Document - Silver. Washington, DC: USEPA, Off Pest Prog. USEPA 738-R-94-021, p.9 Sept 1992. Available from the Database Query page at http://www.epa.gov/REDs/ as of Feb 24, 2002.]**PEER REVIEWED**
  • Older rats (> 9-months old) were given silver nitrate in their drinking water at a concentration equivalent to 63.5 mg/kg/day for an unstated duration ... . The treated rats showed an increase in the relative (to body) weight of the left ventricle (left ventricular hypertrophy rate = 29% in treated rats and 12% in control rats). The total number of rats autopsied was 233. Although blood pressure was not measured, it was postulated that the cardiac effect observed was caused by hypertension, which was brought about by a thickening of the basement membrane of the kidney glomeruli caused by deposits of silver. [USEPA; Reregistration Eligibility Decision Document - Silver. Washington, DC: USEPA, Off Pest Prog. USEPA 738-R-94-021, p.10 Sept 1992. Available from the Database Query page at http://www.epa.gov/REDs/ as of Feb 24, 2002.]**PEER REVIEWED**
  • Rainbow trout embryos were chronically exposed to silver (as AgNO3) in moderately hard water (120 mg CaCO3/L, 0.70 mM Cl-, 1.3 mg/L dissolved organic matter. 12.3 + or -0.1 degrees C) at nominal concentrations of 0.1, 1, and 10 ug/L (measured = 0.117 + or -0.008, 1.22 + or -0.16, and 13.51 + or -1.58 ug/L, respectively) to investigate the effects on mortality, ionoregulation, and silver uptake and distribution of the embryo. Mortalities in the low concentrations (0.1 and 1.2 microg/L) were not significantly different from controls throughout embryonic development (days 1-32 postfertilization). Mortalities of embryos in the 13.5-ug/L treatment reached 56% by day 32 postfertilization (33% when accounting for control mortality), by which time more than 50% of surviving embryos had hatched. Accumulation of silver in whole embryos of 1.2- and 13.5-ug/L treatments reached the highest concentrations of 0.13 and 0.24 ug/g total silver, respectively, by day 32, but whole embryo silver burden was not correlated with mortality. Silver concentrations in different compartments of the whole embryo (chorion, dissected embryo, and yolk) were greatest just before hatch and were higher in the chorion for all experimental treatments. Up to 85% of total whole embryo silver content was bound to the chorion, which acts as a protective barrier during silver exposure. Whole embryo Na+ concentration in the 13.5-ug/L treatment was significantly reduced relative to controls from days 23 to 32 postfertilization, and levels in the embryo were reduced by 40% at day 32 postfertilization, indicating that silver toxicity in the whole embryo is associated with an ion regulatory disturbance that is similar to the acute effect of AgNO3 in juvenile and adult trout. [Guadagnolo CM et al; Environ Toxicol Chem 20 (3): 553-60 (2001)]**PEER REVIEWED**
  • Incisional wounds 15 mm long were induced surgically in the back skin of young adult Wistar rats. They were sutured and used as an experimental model in the therapeutic evaluation of daily applications of 0.5 mL of silver nitrate (SN) at 0.01, 0.1 or 1.0% w/v aqueous solution, or 0.5 g silver sulphadiazine (SSD) over a 10-day period. Control wounds received deionized water only. The silver preparations were not toxic but SN did stain the hair and superficial layers of the stratum corneum. The wounds remained microbiologically clean. Wounds exposed to SN (0.1 or 1.0%) or SSD healed more rapidly than controls. From about the fourth day of treatment, we noted a more rapid exteriorization of sutures, improved wound closure and an earlier loss of scabs and wound debris. Silver treatment appeared to reduce the inflammatory and granulation tissue phases of healing and enhance epidermal repair. Silver from SN was deposited as silver sulphide in extrafollicular hair shafts and superficial aspects of the skin and wound debris but not at deeper levels. Silver uptake was four-fold higher in damaged skin than in intact tissue. SSD was absorbed by intact and wounded skin but the silver did not precipitate as silver sulphide and its localization in the tissue is not known. Uptake of silver from SN or SSD was associated with changes in the concentrations of zinc and calcium in the skin. Zinc levels were depressed during the inflammatory and proliferative phases of healing and then increased. Zinc concentrations had normalized by 10 days when wound healing was achieved. Calcium levels remained higher than normal throughout the observation period. The mechanism of action of silver in advancing wound healing in the rat is unclear. Its ability to reduce the inflammatory and granulation phases of healing, and to invoke metallothionein production and influence metal ion binding are possibly important. [Lansdown AB et al; Br J Dermatol 137 (5): 728-35 (1997)]**PEER REVIEWED**
  • Adult rainbow trout (Oncorhynchus mykiss) were exposed in ion-poor water ( approximately 50 uM Ca) to silver added as AgNO(3) or to AgNO(3) plus either thiosulphate (Na(2)S(2)O(3)) or dissolved organic matter (DOM). The effects of these exposures were assessed through repetitive blood sampling over 4 days. Trout exposed to 0.1 uM AgNO(3) alone accumulated large amounts of Ag on their gills and in their plasma, showed progressive losses of plasma Na and Cl, and had elevated concentrations of plasma glucose. In one set of exposures trout exposed to AgNO(3) alone also had increased cough rates, slightly higher ventilation rates, somewhat lower arterial oxygen tensions, and increased blood lactate concentrations. In contrast, trout exposed to 0.1 uM AgNO(3) plus 5 uM thiosulphate or 35 mg C l(-1) DOM accumulated less Ag on their gills and in their plasma, and showed no adverse ionoregulatory or respiratory effects due to Ag. These results demonstrate ionoregulatory and sometimes respiratory effects in fish exposed to ionic Ag(+) in ion-poor water, depending on water chemistry, and demonstrate the protective effects of synthetic and natural complexing agents through a reduction in the amount of ionic Ag(+) available to bind at the gills. [Rose-Janes NG, Playle RC; Aquat Toxicol 51 (1): 1-18 (2000)]**PEER REVIEWED**
  • Following Crede's prophylaxis with silver-nitrate, the cornea of a newborn presented greyish-brown, lime-like plaques on the nasal part of the right eye. A paracentral ulcerating stromal opacification undermined these appositions, when the patient was admitted to the eye-clinic at Aachen. In the material taken in a lamellar keratectomy scanning electron microscopical examination was able to prove the existence of granules, previously described in light-microscopy. These granules measured 100 to 300 nm in diameter and were placed up to 110 microns deep into the corneal stroma of the specimen. An earlier chemical analysis of necrotic material showed no silver specific reaction. By means of EDX-Analysis these granules could be identified as silver-containing. This was once reassured by a newly developed modification of van-Kossa's-staining-method. The fact that the granular deposits contained mainly silver proves that the onset of a sodium-chloride-irrigation did not promote an intended therapeutic silver-chloride-precipitation and therefore had no effects on the silver-nitrate's penetration abilities. Injuries by silver-nitrate-solutions used for Crede's prophylaxis are seldom but still reported. The mechanism of injury in this case of a child, born by section remains unknown. Neither the use of an unusual silver nitrate solution, that was taken from a disposable ampoule (Mova-Nitrate) was reported, nor any corneal injury during section mentioned. [Schirner G et al; Klin Monatsbl Augenheilkd 199 (4): 283-91 (1991)]**PEER REVIEWED**
  • However, one study has found that 20 female mice exposed to silver nitrate in drinking water for 4 mo, and observed to have such deposits in the CNS, were less active (hypoactive) than unexposed controls ... . Activity was measured using a blind assay. The highest concn of granular deposits occurred in certain areas involved in motor control (i.e., red nucleus, deep cerebellar nuclei, and motor nuclei of the brainstem), with lesser amt observed in the basal ganglia, the anterior olfactory nucleus, and in the cortex in general. [DHHS/ATSDR; Toxicological Profile for Silver p. 20 TP-90-24 (1990)]**PEER REVIEWED**
  • This study evaluated the physiological effects of waterborne silver (added as AgNO(3)) on seawater fish, using acute (48-72 h) high level exposures (250-650 microg/l Ag) on tidepool sculpins (Oligocottus maculosus), and chronic (up to 21 day) low level exposures (1.5-50 microg/l Ag) on tidepool sculpins, plainfin midshipmen (Porichthys notatus), and rainbow trout (Oncorhynchus mykiss). Sculpins were tested at different salinities. Acclimation to lower salinity (18 vs 30 ppt) led to altered physiology, with higher ammonia excretion (J(Amm)), lower oxygen consumption, and lower branchial and intestinal Na(+)/K(+)-ATPase activities, but no difference in drinking rate. Short-term exposure to high silver levels tended to stimulate M(O(2)), J(Amm), and drinking rate. However, long-term exposure to low levels of silver depressed both J(Amm) and M(O(2)), and also led to decreased drinking rates. Both inhibition and stimulation of Na(+)/K(+)-ATPase activity occurred, dependent upon length and concentration of exposure, salinity (18 vs 30 ppt), tissue (gill vs intestine), and fish species (sculpin vs midshipmen vs rainbow trout). While the effects were variable, due to differing balances between inhibitory and compensatory responses, chronic silver exposure significantly altered Na(+)/K(+)-ATPase activity levels in almost all tests. In total, these findings reinforce the view that intestinal osmoregulatory function (drinking, Na(+)/K(+)-ATPase activity) is an important site of toxic impact for waterborne silver, that gill Na(+)/K(+)-ATPase activity is also a site of impact, and that chronic exposures at silver concentrations (1.5, 14.5 microg/l Ag) close to current or proposed water quality guidelines (albeit much higher than normal environmental levels), exert a variety of sublethal effects on marine teleosts. [Webb NA et al; Aquat Toxicol 54 (3-4): 161-78 (2001)]**PEER REVIEWED**
  • Addition of silver nitrate or silver lactate to freshly isolated hepatocytes caused dose-dependent loss of cell viability, measured by trypan blue exclusion, at concentrations within 30-70 uM. Silver cytotoxicity was accompanied by a decrease in hepatic thiol concentration and an increase in lipid peroxidation. Treatment of hepatocytes with the reduced glutathione (GSH)-depleting agent diethylmaleate markedly increased their vulnerability to silver toxicity whereas protective effects were produced by the thiol-reducing agent, dithiothreitol. Both alpha-tocopherol, which protected from the onset of silver-associated lipid peroxidation, and the iron chelator agent, deferoxamine failed to prevent loss of cell viability. These data suggest that perturbation of intracellular thiol homeostasis may play a critical role in the mechanism underlying silver-induced lethal damage to isolated rat hepatocytes. [Baldi C et al; Toxicol Lett 41 (3): 261-8 (1988)]**PEER REVIEWED**
  • Ag+ alters cell growth, neurite extension, cardiomyocyte beating, and fertilized egg constriction. The Russian Space Agency uses electrochemically generated silver ions (Ag+) to purify drinking water for their space station, Mir, and their portion of the International Space Station. U.S. EPA guidelines allow 10.6 micromol x L(-1) Ag+ in human drinking water for up to 10 d. Studies correlate Ag+ exposure with tissue dysfunction in humans, rats, and mice, and with altered ion transport, skeletal muscle contraction, and embryonic cell constriction in other animal cells. Ag+ effects on cell shape change-related functions have not been assessed. Immortalized embryonic human intestinal epithelial cells, freshly explanted embryonic avian nerve cells and cardiomyocytes, and marine fertilized eggs were grown in vitro in medium containing AgNO3. Intestinal cells detach from the substratum and viable cell number decreases by 5-6 d at 5 micromol x L(-1) AgNO3, and faster at higher concentrations. Microtubules appear unaltered in adherent cells. Detached cells are nonviable. Neurite outgrowth and glial cell migration from dorsal root ganglia are inhibited by 3 d at 15 micromol x L(-1) AgNO3 or greater. Contractions stop temporarily in most cardiomyocytes by 5 min at 5 micromol x L(-1) AgNO3 or more, but some cardiomyocytes beat 3 times faster than normal at 7.5-20 micromol x L(-1) AgNO3. Picomolar Ag+ increases marine egg polar lobe constriction within an hour, even in the absence of microtubules. CONCLUSION: Ag+ alters animal cell growth and shape changes by a MT-independent mechanism. This is the first report of Ag+ effects on vertebrate neurite outgrowth, glial cell migration, or cardiomyocyte beat rate. [Corad AH et al; Aviat Space Environ Med 70 (11): 1096-105 (1999)]**PEER REVIEWED**
  • EDTA and EGTA when used in conjunction with AgNO3 enhanced the antibacterial action of the latter significantly, so that strains of Klebsiella pneumoniae and Staphylococcus aureus resistant to 70 ug/ml of AgNO3 were observed to became sensitive to 10 ug/ml of this compound. The synergistic effect of EDTA appears to be due to a mechanism other than the removal of lipopolysaccharide from outer membrane, as its effect could be observed in even non-LPS containing gram positive S. aureus cells. Penicillamine, another potent chelator had an opposite effect so that it decreased the toxicity of silver ions. [Kaur P, Vadehra DV; J Hyg Epidemiol Microbiol Immunol 32 (3): 299-306 (1988)]**PEER REVIEWED**

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • LD50 chick eggs 0.10 mg [Shepard, T.H. Catalog of Teratogenic Agents. 5th ed. Baltimore, MD: The Johns Hopkins University Press, 1986., p. 519]**PEER REVIEWED**
  • LD50 Swiss albino mice (male) ip 13.9 mg/kg [Bienvenu P et al; Compt Rend 256: 1043 (1963) as cited in USEPA; Ambient Water Quality Criteria Doc: Silver p.C-81 (1980) EPA 440/5-80-071]**PEER REVIEWED**
  • LD50 Mouse ip 23,783 ug/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2934]**PEER REVIEWED**
  • LD50 Mouse oral 50 mg/kg [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1396]**PEER REVIEWED**

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Absorption, Distribution and Excretion

  • SILVER, AS AG NITRATE, IS ABSORBED FROM THE RESP & GI TRACTS ... ABSORPTION OF SILVER NITRATE THROUGH THE INTACT SKIN IS OF NO PHYSIOLOGICAL SIGNIFICANCE, HOWEVER, SOME ABSORPTION THROUGH MUCOUS MEMBRANES OF THE NOSE & THROAT PROBABLY OCCURS. ABSORBED SILVER IS TENACIOUSLY RETAINED ... IN ELASTIC TISSUES THROUGHOUT THE BODY. [Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 1889]**PEER REVIEWED**
  • ... Silver in brain and spinal cord sections from rats treated with ... silver nitrate was visualized by physical appearance. The silver penetrated the blood brain barrier and accumulated in the neurons and glia. The distribution of silver in the central nervous system was heterogeneous. Even with low doses and short survival periods, silver accumulated in large motorneurons in the brain stem and spinal cord and in the neurons in the cerebellar nuclei. Silver was only found in the diecenphalic and telecenphalic structures after extensive exposure. Silver distribution following oral ... AgNO3 treatment ... resulted in a relatively high content of silver in the glia. ... Electron microscopic studies /revealed/ ... silver ... intracellularly in the lysosomes and extracellularly in basement membranes and elastic fibers of the vessels. [Rungby J, Danscher G; Acta Neuropathol 60 (1-2): 92-8 (1983)]**PEER REVIEWED**
  • All forms of silver are cumulative once they enter body tissues, and very little is excreted. [Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 1985., p. 789]**PEER REVIEWED**
  • In argyric rats given 0.5 percent silver nitrate in their drinking water for nine months, silver was especially found in lysosomes of the liver's Kupffer cells, at the basal membrane of the capillaries, and the connective tissue cells of the pancreas. [USEPA; Ambient Water Quality Criteria Doc: Silver p.C-49 (1980) EPA 440/5-80-071]**PEER REVIEWED**
  • Ten adult rats and 3 adult rabbits were administered drinking water containing 1,500 mg/l silver nitrate for 4 to 20 weeks to study the permeability of medullary vessels of the kidney to protein. Only the rat kidney showed heavy silver deposits in the glomeruli and outer medulla basement membranes. Both species had heavy deposits in the inner medulla, but the distribution differed markedly. In the rat, most of the silver was in the basement membrane of the vessels and loops of Henle, but the distribution in each vessel or loop was asymetrical. Most of the silver was deposited on the side adjacent to the collecting duct. In the silver dosed rats, the occurence of degenerating kidney cells was more common than in normal rats. [Moffat DB, Creasey M; Acta Anat 83: 346 (1972) as cited in USEPA; Ambient Water Quality Criteria Doc: Silver p.C-51 (1980) EPA 440/5-80-071]**PEER REVIEWED**
  • Significant silver excretion in the urine were found after several ip injections of different forms of silver medicinals. Wistar rats given 12.6 mg/kg silver ip as the nitrate daily for 5 wks (apparently a 4-day work wk) eliminated 10-20 ug/rat/day in the urine. At 5 mg/kg/day silver as silver nitrate for 24 injections within 6 wks the urinary silver excretion was 31 mg/rat/day. [USEPA; Ambient Water Quality Criteria Doc: Silver p.C-57 (1980) EPA 440/5-80-071]**PEER REVIEWED**
  • Silver nitrate was administered in the drinking water of rats to study glomerular basement membrane formation. Drinking water containing 2,500 mg/l silver nitrate was given for 12 weeks to albino and hooded female rats, killing pairs of animals at 1 to 12 weeks to study the tissue by light and electron microscopy. Other pairs of animals were killed for study 16 months after the cessation of silver intake. Sixteen months after removal of silver from drinking water; 0.8-4.1 mg/kg silver in liver of hooded rat; 2.7-4.1 mg/kg silver in kidney of hooded rat; 0.7-1.6 mg/kg silver in liver of albino rat; 3.0-6.0 mg/kg silver in kidney of albino rat. Three months intake of silver at 2,500 mg AgNO3/l in drinking water; 6.1, 7.0 mg/kg silver in liver of hooded rat, 6.1, 9.8 mg/kg silver in kidney of hooded rat; 6.3, 7.0 mg/kg silver in liver of albino rat, 3.7, 7.1 mg/kg silver in kidney of albino rat. Ten months after removal of silver from drinking water; 1.4, 2.8 mg/kg silver in liver of hooded rat; 3.7, 4.3 mg/kg silver in kidney of hooded rat; 2.2, 2.5 mg/kg silver in liver of albino rat; 1.8,3.4 mg/kg silver in kidney of albino rat. [Hall KN, Tange JD; Aust J Exp Biol Med Sci 50: 423 (1972) as cited in USEPA; Ambient Water Quality Criteria Doc: Silver p.C-50 (1980) EPA 440/5-80-071]**PEER REVIEWED**
  • Regardless of route and chemical form administered, fecal excretions of silver always predominate over urinary excretion. Most absorbed silver is excreted into the intestine by the liver via the bile. /Silver/ [USEPA; Ambient Water Quality Criteria Doc: Silver p.C-56 (1980) EPA 440/5-80-071]**PEER REVIEWED**
  • Silver was detected in the urine, blood, and body tissues of humans with seriously burned skin following treatment with topical preparations containing 0.5% silver nitrate to prevent bacterial infection ... . The levels of silver found in the individuals studied ... were 0.038 and 0.12 ppm for urine and blood, respectively, and ranged from below detection in lung and brain to 1250 ppm in skin. [DHHS/ATSDR; Toxicological Profile for Silver p. 25 TP-90-24 (1990)]**PEER REVIEWED**
  • Absorption of silver nitrate across intact skin has been demonstrated in guinea pigs and is similar to that of intact human skin ... . The amt absorbed was est to be approx 1% of the applied dose within 5 hr of exposure. [DHHS/ATSDR; Toxicological Profile for Silver p. 25 TP-90-24 (1990)]**PEER REVIEWED**
  • Silver distributed widely in the rat following ingestion of silver chloride (in the presence of sodium thiosulfate) and silver nitrate in drinking water (at 88.9 mg silver/kg/day for silver nitrate) ... . The amt of silver in the various tissues was not measured, although qualitative descriptions of the degree of pigmentation were made. High concn were observed in the tissues of the reticuloendothelial system in the liver, spleen, bone marrow, lymph nodes, skin, and kidney. Silver was also distributed to other tissues incl the tongue, teeth, salivary glands, thyroid, parathyroid, heart, pancreas, GI tract, adrenal glands, and brain. Within these tissues advanced accumulation of silver particles was 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, the choroid layer of the eye, and in the thyroid gland ... . [DHHS/ATSDR; Toxicological Profile for Silver p. 27 TP-90-24 (1990)]**PEER REVIEWED**
  • Following topical application of silver nitrate for the treatment of burns in two humans, silver was distributed to the muscles (0.03-2.3 ppm), liver (0.44 ppm), spleen (0.23 ppm), kidney (0.14 ppm), heart (0.032-0.04 ppm), and bones (0.025 ppm) ... . [DHHS/ATSDR; Toxicological Profile for Silver p. 28 TP-90-24 (1990)]**PEER REVIEWED**
  • In rats, silver was unevenly distributed in organs and tissues following iv or im injection of radiolabeled metallic silver and/or silver nitrate, respectively. The highest concn were found, in decr order, in the GI tract, liver, blood, kidney, muscle, bone, and skin following im injection ... . Following iv injection the highest concn were found, in decr order, in the liver, pancreas, spleen, and plasma ... . ... the proportion of the dose distributed to the tissues is positively correlated with the dose admin ... . [DHHS/ATSDR; Toxicological Profile for Silver p. 28 TP-90-24 (1990)]**PEER REVIEWED**
  • Whole body retention studies in mice, rats, monkeys, and dogs following iv injection of radiolabeled silver nitrate indicate that silver excretion in these species follows a triexponential profile ... . For mice and monkeys, this differs from the biexponential profile seen following oral exposure. Whole body clearance following iv exposure was slower than clearance following oral exposure in each of the four species observed. In addition, the difference in clearance rate between species was more dramatic. clearance at 2 days post-exposure ranged from 15% in the dog to 82% in the mouse ... . [DHHS/ATSDR; Toxicological Profile for Silver p. 31 TP-90-24 (1990)]**PEER REVIEWED**
  • ORAL DOSES OF SILVER AS SILVER IODIDE HAD NO EFFECT ON THE MICROORGANISMS OF THE RABBIT CECUM OR GOAT RUMEN. RABBITS ELIMINATED 99% OF ORAL DOSE WITHIN 3 DAYS AND 100% IN 6.3 DAYS. 8-26% ENTERED CECUM, WHERE IT DID NOT ACCUM & WAS NOT ABSORBED. DIGESTION WAS NOT INHIBITED IN RABBITS AND GOATS FOLLOWING THE INGESTION OF DIETS CONTAINING 4.2 AND 1 PPM SILVER AS SILVER IODIDE, OR 10 AND 100 PPM SILVER AS SILVER NITRATE. THUS, AG PROBABLY WILL NOT ADVERSELY AFFECT THE DIGESTIVE MICROFLORA OF LIVESTOCK OR WILDLIFE. [BAILEY JA ET AL; US NAT TECH INFORM SERV, PB REP; ISS NO 226062/8GA, 1973, 39 PP]**PEER REVIEWED**
  • The cardiovascular system is currently considered a target for particulate matter, especially for ultrafine particles. In addition to autonomic or cytokine mediated effects, the direct interaction of inhaled materials with the target tissue must be examined to understand the underlying mechanisms. In the first approach, pulmonary and systemic distribution of inhaled ultrafine elemental silver (EAg) particles was investigated on the basis of morphology and inductively coupled plasma mass spectrometry (ICP-MS) analysis. Rats were exposed for 6 hr at a concentration of 133 microg EAg m(3) (3 x 10(6) cm(3), 15 nm modal diameter) and were sacrificed on days 0, 1, 4, and 7. ICP-MS analysis showed that 1.7 microg Ag was found in the lungs immediately after the end of exposure. Amounts of Ag in the lungs decreased rapidly with time, and by day 7 only 4% of the initial burden remained. In the blood, significant amounts of Ag were detected on day 0 and thereafter decreased rapidly. In the liver, kidney, spleen, brain, and heart, low concentrations of Ag were observed. Nasal cavities, especially the posterior portion, and lung-associated lymph nodes showed relatively high concentrations of Ag. For comparison, rats received by intratracheal instillation either 150 microL aqueous solution of 7 microg silver nitrate (AgNO(3) (4.4 microg Ag) or 150 microL aqueous suspension of 50 microg agglomerated ultrafine EAg particles. A portion of the agglomerates remained undissolved in the alveolar macrophages and in the septum for at least 7 days. In contrast, rapid clearance of instilled water-soluble AgNO(3) from the lung was observed. These findings show that although instilled agglomerates of ultrafine EAg particles were retained in the lung, Ag was rapidly cleared from the lung after inhalation of ultrafine EAg particles, as well as after instillation of AgNO(3), and entered systemic pathways. [Takenaka S et al; Environ Health Perspect 109 Suppl 4: 547-51 (2001)]**PEER REVIEWED**
  • Silver is absorbed after topical application, ingestion, or inhalation. GI uptake ranges from <1% of the admin dose in rats, mice, & monkeys to as much as 10% in dogs. Following intratracheal admin of 0.5 um metallic silver particles, 97% of the dose remained in dog lung at 6 hr after treatment; the rate of systemic absorption was calculated as 1 ug/sq cm/day. Of the absorbed silver, 77% of the dose was found in dog liver at 225 days after admin. Pulmonary clearance was triphasic with half-times of 1.7, 8.4, & 40 days. Parenteral injection of metallic silver or silver nitrate demonstrated that rat, dog, & rabbit liver & gut retained the highest silver concns. Silver was eliminated primarily in the bile. /Silver and compounds/ [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1397]**PEER REVIEWED**

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Metabolism/Metabolites

  • The investigators: reported that rats injected iv with radioactive silver nitrate excreted silver in the bile mainly bound to a low molecular-wt complex which appeared to be glutathione. [Friberg, L., Nordberg, G.F., Kessler, E. and Vouk, V.B. (eds). Handbook of the Toxicology of Metals. 2nd ed. Vols I, II.: Amsterdam: Elsevier Science Publishers B.V., 1986., p. V2 525]**PEER REVIEWED**
  • A marked variation in biliary excretion was observed in different species administered silver as silver nitrate in a single iv injection at 0.1 mg/kg of silver over a 2 hour period ... . Thirty minutes after treatment, male Sprague Dawley rats excreted silver into the bile at a rate of 0.25 ug/min/kg, New Zealand White male rabbits excreted 0.05 ug/min/kg, and mongrel male dogs excreted 0.005 ug/min/kg. The concentration of silver in the plasma was markedly lower in the dog than in the rat or rabbit, indicating a larger volume of distribution in the dog. This variation appears to be attributable to differences in the transfer of silver from liver to bile. The species with the lowest biliary excretion rate (dog) had the highest liver concentration of silver (rat 1.24, rabbit = 2.13 and dog = 2.9 ug silver/g liver). In all species, the concentration of silver in the bile was greater than that in plasma with no observable dose gradient, thereby indicating an active transport process and a saturable mechanism. [USEPA; Reregistration Eligibility Decision Document - Silver. Washington, DC: USEPA, Off Pest Prog. USEPA 738-R-94-021, p.12 Sept 1992. Available from the Database Query page at http://www.epa.gov/REDs/ as of Feb 24, 2002.]**PEER REVIEWED**

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TSCA Test Submissions

  • None found

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Footnotes

1 Source: the National Library of Medicine's Hazardous Substance Database, 10/28/2007.

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Web page last updated on May 14, 2008