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10/2/13 COPPER( II) SULFATE - Nati onal Li brary of Medi ci ne HSDB Database toxnet.nlm.nih.gov /cgi-bin/si s/sear ch/a?dbs+hsdb:@term+@DOCNO+916 1/31 SIS Home  About Us  Site Map & Search  Contact Us HSDB  Env. Health & Toxicology  TOXNET HSDB COPPE R(II) SULFATE CASRN: 7758-98-7 This record contains information specific to the title compound. Users with an interest in this substance are strongly encouraged also to retrieve the record named COPPER COMPOUNDS, which has additional information relevant to the toxicity and environmental fate of copper ions and copper compounds. For information on the metal itself, refer to the COPPER, ELEMENTAL record. For more information, search the NLM HSDB database. Human Health Effects: Toxicity Summary: For healthy, non- occupationall y- expos ed humans the major route of expos ure to copp er is oral. T he mean daily di etary intake of copper in adults rang es betw een 0.9 and 2.2 mg. .. . I n some case s, dri nking wate r may make a substantial additional contribution to the total daily intake of copper, particularly in hous eholds whe re corrosive w aters ha ve stoo d in copper pipes. .. . A ll other intakes o f c opp er (i nhalation and dermal ) are insignif ic ant in comparison to the oral route. Inhalation add s 0.3- 2.0 ug/day from dusts and smoke. Women using coppe r IUDs are e xpose d to o nly 80ug or l ess of copper per da y f rom this source. The homeostas is of coppe r involves the dual essentiali ty and toxic ity of the element. I ts essentiality arises from its sp ecif ic incorporation into a large number of proteins for catalytic and structural purpos es. The cel lul ar pathw ays of uptake, incorporation into protein and e xport of c opper are conserved in mamm als a nd modulated by the metal itself . Coppe r is mai nly absorbe d through the g astrointestinal tract. From 20 to 60% of the d ietary c opp er is abso rbed, with the rest be ing excr eted through the feces. Once the metal passe s through the b aso lateral m embrane it is transported to the li ver bound to se rum albumin. The liver is the critical organ for copper homeostatis. The copper is partitioned for excretion through the bile or incorporation into intra- and extracellular proteins. The primary route of excretion is through the bil e. T he transport of copper to the peripheral tissues is accomplished through the plasma attached to serum albumin, ceruloplasmin or low-molecular weight complexes. .. . T he biochemical toxicity of copper, whe n it exceeds homeosta tic control, is derived from its effects o n the structur e a nd functi on of biomolecules, such as DNA, membranes and proteins directly or through oxygen-radical mechanisms. The toxic ity of a s ingl e o ral dose of copper varies w idely betwee n spe cies. ... T he major soluble sa lts (copper(II) sulfate, copper(II) chloride) are generally more toxic than the less soluble salts (copper(II) hydroxide, copper (II) oxide). Death is preceded by gastric hemorrhage, tachycardia, hypotension, hemolytic cri sis, convulsions and pa ralysis. .. . Long-te rm exposure in rat s and mice sho we d no o vert si gns of toxicity other than a dose-related reduction in growth after ingestion ... The effe cts included infla mmation of the liver and degeneration of kidney tubule epithelium. ... Some testi cul ar dege neration and reduced neon atal body and orga n we ights were s een in rats . .. and fetotoxic ef fect s a nd malf ormations  were see n at high do se levels. . .. Neurochemic al changes have be en reported after oral administration .. . A lim ited n umber of immunotoxicity stud ies s how ed humoral an d ce ll-mediated immune function impairment in mice after oral intakes in drinking-water ... Copper is an essential element and adverse hea lth eff ects /in humans/ are related to defi ci ency as well as excess . Coppe r defic iency i s associated with anemia, neutropenia and bone abnormalities but clinically evident defic iency is relatively inf requent in humans. .. Ex cept for occasional acute inci dents of coppe r poisoning, few effects a re note d in normal /human/ pop ulati ons . Eff ects o f single expo sure foll ow ing suici dal or acci denta l oral expos ure ha ve bee n repo rted as metalli c taste, epigas tri c pain, hea dache, naus ea, dizziness , v omi ting and d iarr hea, tachycardia, resp iratory diff icul ty, hemolytic anemi a, hematuria, mas sive ga strointestina l bleed ing, l iver and ki dney fail ure, and de ath. Gastrointestinal effect s ha ve also resulted from single and repea ted ingestion o f drinki ng-wate r containi ng high copper concentrations, and li ver fai lure has been reported follow ing chroni c ingestion of coppe r. Derm al expos ure has no t bee n associated with syste mic toxic ity but copper may induce allergic responses in sensitive individuals. Metal fume fever from inhalation of high concentrati ons in the air in occ upational se ttings have b een reported .. . A number of groups a re des cr ibed whe re appa rent disorders in copper homeos tasis resu lt i n greate r sensitivity to coppe r defi ci t or excess

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SIS Home   About Us   Site Map & Search   Contact UsHSDB   Env. Health & Toxicology  TOXNET HSDB

COPPER(II) SULFATE

CASRN: 7758-98-7

This record contains information specific to the title compound. Users with an interest in this substance are strongly encouraged also

to retrieve the record named COPPER COMPOUNDS, which has additional information relevant to the toxicity and environmental fate of

copper ions and copper compounds. For information on the metal itself, refer to the COPPER, ELEMENTAL record.

For more information, search the NLM HSDB database. 

Human Health Effects:

Toxicity Summary: For healthy, non-occupationally-exposed humans the major route of exposure to copper is oral. The meandaily dietary intake of copper in adults ranges between 0.9 and 2.2 mg. ... In some cases, drinking watermay make a substantial additional contribution to the total daily intake of copper, particularly inhouseholds where corrosive waters have stood in copper pipes. ... All other intakes of copper (inhalationand dermal) are insignificant in comparison to the oral route. Inhalation adds 0.3-2.0 ug/day from dustsand smoke. Women using copper IUDs are exposed to only 80ug or less of copper per day from thissource. The homeostas is of copper involves the dual essentiality and toxicity of the element. Its

essentiality arises from its specific incorporation into a large number of proteins for catalytic and structuralpurposes. The cellular pathways of uptake, incorporation into protein and export of copper are conservedin mammals and modulated by the metal itself. Copper is mainly absorbed through the gastrointestinaltract. From 20 to 60% of the dietary copper is absorbed, with the rest be ing excreted through the feces.Once the metal passes through the baso lateral membrane it is transported to the liver bound to serumalbumin. The liver is the critical organ for copper homeostatis. The copper is partitioned for excretionthrough the bile or incorporation into intra- and extracellular proteins. The primary route of excretion isthrough the bile. The transport of copper to the peripheral tissues is accomplished through the plasmaattached to serum albumin, ceruloplasmin or low-molecular weight complexes. ... The biochemical toxicityof copper, when it exceeds homeostatic control, is derived from its effects on the structure and function of biomolecules, such as DNA, membranes and proteins directly or through oxygen-radical mechanisms. Thetoxicity of a single oral dose of copper varies widely between species. ... The major soluble sa lts(copper(II) sulfate, copper(II) chloride) are generally more toxic than the less soluble salts (copper(II)

hydroxide, copper (II) oxide). Death is preceded by gastric hemorrhage, tachycardia, hypotension,hemolytic crisis, convulsions and paralysis. ... Long-term exposure in rats and mice showed no overt signsof toxicity other than a dose-related reduction in growth after ingestion ... The effects includedinflammation of the liver and degeneration of kidney tubule epithelium. ... Some testicular degenerationand reduced neonatal body and organ weights were seen in rats ... and fetotoxic ef fects andmalf ormations were seen at high dose levels. ... Neurochemical changes have been reported after oraladministration ... A limited number of immunotoxicity studies showed humoral and cell-mediated immunefunction impairment in mice after oral intakes in drinking-water ... Copper is an essential element andadverse health effects /in humans/ are related to de ficiency as well as excess. Copper deficiency isassociated w ith anemia, neutropenia and bone abnormalities but clinically evident deficiency is relativelyinfrequent in humans. .. Except for occasional acute incidents of copper poisoning, few effects are noted innormal /human/ populations. Effects of single exposure following suicidal or accidenta l oral exposure havebeen reported as metallic taste, epigastric pain, headache, nausea, dizziness , vomiting and diarrhea,

tachycardia, respiratory difficulty, hemolytic anemia, hematuria, massive gastrointestinal bleeding, liverand kidney failure, and death. Gastrointestinal effects have also resulted from single and repeatedingestion of drinking-water containing high copper concentrations, and liver failure has been reportedfollowing chronic ingestion of copper. Dermal exposure has not been associated with systemic toxicity butcopper may induce allergic responses in sensitive individuals. Metal fume fever from inhalation of highconcentrations in the air in occupational settings have been reported ... A number of groups are describedwhere apparent disorders in copper homeostasis result in greater sensitivity to copper deficit or excess

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than the general population. Some disorders have a well-defined genetic basis. These include Menkesdisease, a generally fatal manifestation of copper deficiency; Wilson disease (hepatolenticulardegeneration), a condition leading to progressive accumulation of copper; and hereditaryaceruloplasminemia, with clinical symptoms of copper overload. Indian childhood cirrhosis and idiopathiccopper toxicosis are conditions related to excess copper which may be associated with genetically basedcopper sensitivity ... These are fatal conditions in early childhood where copper accumulates in the liver. ...Other groups potentially sensitive to copper excess are hemodialysis patients and subjects with chronicliver disease. Groups at risk of copper deficiency include infants (particularly low birth weight/pretermbabies, children recovering from malnutrition, and babies fed exclusively with cow's milk), people withmaladsorption syndrome (e.g., celiac disease, sprue, cystic fibrosis), and patients on tota l parenteral

nutrition. Copper deficiency has been implicated in the pathogenesis of cardiovascular disease. Theadverse effects of copper must be balanced against its essentiality. Copper is an essential element for allbiota ... At least 12 major proteins require copper as an integral part of their structure. It is essential forthe utilization of iron in the formation of hemoglobin, and most crustaceans and molluscs possess thecopper-containing hemocyanin as their main oxygen-carrying blood protein. ... A critical factor in assessingthe hazard of copper is its bioavailablity. Adsorption of copper to particles and complexation by organicmatter can greatly limit the degree to which copper will be accumulated ... At many sites, physiochemicalfactors limiting bioavailability will warrant higher copper limits. ...[Environmental Health Criteria 200: Copper pp. 1-11 (1998) by the International Programme on Chemical Safety (IPCS) under the joint

sponsorship of the United Nations Environment Programme, the International Labour Organisation and the World Health Organization.]

**PEER REVIEWED**

Human Toxicity Excerpts: 

A ... NUMBER OF CASES OF ACUTE POISONING IN MAN FROM INGESTING COPPER SULFATE, SOME OF THEMFATAL, HAVE BEEN REPORTED ... FROM NEW DELHI ... . THE REPORT CONCERNS 48 HOSPITALIZEDPATIENTS & 5 AUTOPSY CASES, 2/3 MALE, MOSTLY BETWEEN THE AGES OF 16 & 25 YR. DOSAGE ESTIMATESRANGED FROM 1 TO 12 G ... SWALLOWED IN WATER. SYMPTOMS ... WERE ... METALLIC TASTE, BURNING INEPIGASTRIUM, & REPEATED VOMITING. IN MORE SEVERE CASES, DIARRHEA (14 PATIENTS) APPEARED ONTHE FIRST OR SECOND DAY & LASTED 24 HR; 20 ... SHOWED BLOOD IN GI TRACT FROM INJURY TO GASTRICMUCOSA, LEADING TO ULCERATION IN SEVERE CASES. SUPPRESSION OF URINE FOLLOWED JAUNDICE ... .LIVER BIOPSY SHOWED CENTRILOBULAR NECROSIS & BILIARY STASIS. HYPERTENSION LEADING TO SHOCK... CONSIDERED BAD PROGNOSTIC SIGN: 3 OF 4 DIED. COMA DEVELOPED IN 4, PRESUMABLY DUE TOUREMIA FROM RENAL INJURY, & DEATHS OCCURRED IN 7 (14.6%).[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. 1624] **PEER REVIEWED**

CONTACT OF SKIN WITH COPPER SULFATE CAN RESULT IN ITCHING ECZEMA ... CONTACT OF EYE WILLRESULT IN CONJUNCTIVITIS, EDEMA OF EYELIDS, & ULCERATION & TURBIDITY OF CORNEA.[Patty, F. (ed.). Industrial Hygiene and Toxicology: Volume II: Toxicology. 2nd ed. New York: Interscience Publishers, 1963., p. 1035]

**PEER REVIEWED**

A report of 11 patients who had ingested an estimated 1 to 50 g of copper sulfate; they suffered nausea& vomiting, with epigastric pain in 5, diarrhea in 5, hypotension in 2, hematemesis or melena in 10, pallorin 10, jaundice in 8, delirium in 3, & coma in 2. All had intravascular hemolysis & developed oliguria oranuria. Five patients died despite gastric lavage, intravenous fluids, mannitol, diuretics, and dialysis.[Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 931]

**PEER REVIEWED**

... Toxic blood levels can be seen after oral ingestion of as little as 1 g of copper sulfate in an adult. ... Apatient ... ingested 250 gm of copper sulfate, developed transient hepatic dysfunction, and recovered

after the prompt administration of chelation therapy.[Jantsch W et al; J Toxicol Clin Toxicol 22 (6): 585-8 (1984)] **PEER REVIEWED** PubMed Abstract 

The application of copper sulfate crystals to granulations of burns on 7 occasions during 9 wk induced jaundice, hemolytic anemia, & oliguria in a five and a half yr old girl.[Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 931]

**PEER REVIEWED**

May be corrosive to eyes, mucous membranes, skin ... . /Cupric sulfate pentahydrate/[Farm Chemicals Handbook 87. Willoughby, Ohio: Meister Publishing Co., 1987., p. C-69] **PEER REVIEWED**

THERE HAVE BEEN REPORTS ... OF SUICIDE WITH GRAM QUANTITIES OF CUPRIC SULFATE.[National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 252] **PEER REVIEWED**

Copper sulfate is caustic. Acute toxicity is largely due to this property.[Booth, N.H., L.E. McDonald (eds.). Veterinary Pharmacology and Therapeutics. 5th ed. Ames, Iowa: Iowa State University Press, 1982.,

p. 948] **PEER REVIEWED**

Human erythrocytes /incubated/ for 4 hr in a 1 mM copper sulfate solution. Approx 5-10% of theerythrocytes underwent hemolysis, and significant incr in osmotic fragility were observed to occur within 3hr.

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[USEPA; Drinking Water Criteria Document for Copper (Final Draft) p.V-13 (1985) EPA-600/X-84-190-1] **PEER REVIEWED**

Excess ive copper has been demonstrated to reduce the activity of the hexose monophosphate shunt, of which glucose-6-phosphate dehydrogenase apparently plays a role. This has been demonstrated inWilson's disease patients in in vitro incubations with human erythrocytes and in copper sulfate acutepoisoning cases in humans. The concn of copper in the in vitro experiments are much higher than thoseencountered in vivo.[USEPA; Drinking Water Criteria Document for Copper (Final Draft) p.VI-14 (1985) EPA-600/X-84-190-1] **PEER REVIEWED**

A case where a patient died after she was treated w ith an emetic dose of copper sulfate /was reported/.

A 44 yr old female ingested both alcohol and diazepam and was given 20 ml of a 10% soln of coppersulfate (508 mg copper). The patient failed to vomit and stomach contents were removed by lavage.Respiratory collapse, hemolytic anemia, hemoglobinuria, hepatic failure, renal failure, and massivegastrointestinal bleeding were observed, and the patient died. Rapid intestinal absorption of copperundoubtly occurred, as she had a three quarter gastrectomy. On autopsy, acute renal tubular necrosisand a liver copper level of 7.46 mg/100 g were observed.[USEPA; Drinking Water Criteria Document for Copper (Final Draft) p.VI-7 (1985) EPA-600/X-84-190-1] **PEER REVIEWED**

A case of acute copper intoxication in an 18 month o ld boy /was reported/. After drinking a soln estimatedto contain 3 g cupric sulfate (0.76 g copper), the boy began to vomit and was admitted to a hospital. Highcopper levels were observed in serum (1.65 mg/100 ml) and urine (50 ug/100 ml) upon admittance, atwhich time reduced glucose-6-phosphate dehydrogenase activity, hematuria, glycosuria, and proteinuriawere also noted.[USEPA; Drinking Water Criteria Document for Copper (Final Draft) p.VI-6 (1985) EPA-600/X-84-190-1] **PEER REVIEWED**

In humans, a metallic taste, nausea, vomiting, and epigastric pain are the first symptoms reported innearly all cases of acute poisoning with copper sulfate. ... Ingestion of as little as 5.3 mg of copper hasbeen reported to emesis.[USEPA; Drinking Water Criteria Document for Copper (Final Draft) p.V-14 (1985) EPA-600/X-84-190-1] **PEER REVIEWED**

An outbreak of gastroenteritis in 18/50 workmen following ingestion of tea made from copper sulfatecontaminated water was reported. Symptoms ranged from dizziness, headache, diarrhea, vomiting, andabdominal pain to complete collapse. Water from a corroded geyser (heater) was later observed tocontain greater than or equal to 44 ppm total copper. Assuming each 70 kg man drank one cup (0.23 l),the estimated dose was 0.143 mg copper/kg. A similar outbreak of toxicity from contaminated tea infactory workmen /was reported/. Twenty workmen felt sick after ingesting morning tea made in a coppercontaminated geyser. It was not stated how many men were exposed to the tea. Diarrhea occurred in

9/20, vomiting in 6/20, and nausea in 9/20. A sample of tea taken later contained 30 ppm copper. It wasstated that the copper concn was probably higher. Assuming each man (70 kg) drank one cup (0.23 l), theestimated dose was greater than or equal to 0.1 mg/kg.[USEPA; Drinking Water Criteria Document for Copper (Final Draft) p.VI-3 (1985) EPA-600/X-84-190-1] **PEER REVIEWED**

A 27 yr old man who ingested at least 50 g of copper sulfate (20 g copper) was reported to be cyanotic,oliguric, and anemic. The patient also showed signs of severe intravascular hemolysis andmethemolglobinemia and died 16 hr after poisoning.[USEPA; Health Issue Assessment: Copper p.52 (1987) EPA/600/8-87/001] **PEER REVIEWED**

The clinical data from 53 cases of acute copper sulfate poisonings /are reported/. Ingestion of up to 12 gcopper resulted in immediate metallic taste, nausea, vomiting, epigastric pain, diarrhea, jaundice,hemogloblinuria, and/or hematuria, anuria, oliguria, hypotension, and coma. Autopsy of 5 patientsrevealed ulceration of the gastric mucousa, hepatic centrilobular necroses, biliary stasis, and renal tubular

cell necrosis.[USEPA; Health Issue Assessment: Copper p.52 (1987) EPA/600/8-87/001] **PEER REVIEWED**

The case of a suicidal 42 year old male who ingested 250 grams of copper sulfate is reported. Within 10minutes, severe epigastric pain and vomiting occurred. He was taken to the emergency room 90 minutesafter the ingestion. Blood pressure was 130/100 millimeters mercury, pulse was 100 beats per minute,respiration was 28 breaths per minute, and temperature was 37 deg C. The abdomen showed diffuseepigastric tenderness but no sign of peritoneal inflammation. There was no neurologic deficit. Bloodalcohol was 222 milligrams per deciliter, white blood count as 12,200 with a normal differential, hematocritwas 56.1 percent, and blood pH was 7.29. Electrocardiogram revealed sinus tachycardia. Urine showedmicroscopic hematuria without renal tubular cells or casts. The patient was treated with a single injectionof 4 milligrams per kilogram dimercaprol. Vomiting subsided within 10 hours of ingestion. Beginning at thatpoint, activated charcoal, magnes ium sulfate, and 250 milligrams d-penicillamine were given orally every 6

hours. Within 24 hours after initiation of treatment, urinary copper excretion was 8,160 micrograms perdeciliter, compared to a normal value of 15 to 50 micrograms per deciliter. Within 3 days of ingestion,serum bilirubin rose to 6.5 milligrams per deciliter, and hepatic enzymes increased 100 fold. Theseabnormalities subsided w ithin a week. There was no hemolysis or oliguria. The patient's recovery wasprobably due to a brisk emetic response and prompt chelation therapy.[Jantsch W et al; Clin Toxicol 22 (6): 585-88 (1984)] **PEER REVIEWED**

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A case of poisoning in a 23 year old patient who had taken cupric sulfate, 15 g, was reported. Therapyconsisted of gastric lavage, activated charcoal, cathartics, dimercaprol, and penicillamine. Blood levels of copper did not rise, and large amounts of copper were excreted. The patient was discharged 13 days laterwith persistent hemolytic anemia and gastric ulceration.[Takahashi H et al; Gekkan Yakuji 29 (Mar): 653-56 (1987)] **PEER REVIEWED**

Massive ingestion of copper led to a fatality with a hepatic copper content of 1160 micrograms/g. A 47-year old man ingested 20 to 30 mL of copper sulfate solution in 2 1/2 days after profound vomiting,abdominal pain, diarrhea, & jaundice. The hepatic liver copper concn was 61 micrograms/g unit weight.

 /Copper/[Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning.

2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 1555] **PEER REVIEWED**

Overdosage of copper salts is common in developing countries because of its wide use in varioustraditional preparations. Poisoning is due to the ingestion of "spiritual water" following distribution tomembers of spiritual churches. The amount of copper sulfate ingested is about 10 to 20 g, a lethal dose.Within a few hours of ingestion, greenish vomiting & abdominal pain are seen. Anuria may supervenewithin 24 hr. Flapping tremor, toxic psychosis, hemolytic anemia, & jaundice may follow within a few days.Hepatic & renal failure precede death w ithin 7 days. Patients appear to die within a few days of hemodialysis. Analysis of water has revealed copper sulfate concn of 100 to 150 g/L. Similar cases haveoccurred in the United States. /Copper/[Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning.

2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 1555] **PEER REVIEWED**

Removal of copper by dialysis may be useful in the early stages of poisoning when the metal is stillpresent in the circulation as free copper. the copper-chelating drug tetrathimolybdate used in Wilson'sdisease has been assoc with pancytopenia. Its use has not been reported in copper poisoning. Ingestionof 10 to 20 g o f copper sulfate is usually lethal. Hemodialysis has not prevented death in such cases.

 /Copper/[Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning.

2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 1556] **PEER REVIEWED**

When airborne the dusts of inorganic copper sa lts have low toxicity. Vineyard sprayer's lung disease hasbeen assoc with airborne copper sulfate. This is a histiocytic granulomatous lung & liver disease occurringin individuals exposed to copper sulfate spray for 2 to 15 years. A syndrome of intravenous copperintoxication due to copper released from copper tubing during hemodialysis includes symptoms of nausea,vomiting, abdominal pain, diarrhea, anxiety, & depression. /Copper/[Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning.

2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 1555] **PEER REVIEWED**

 /Kidney damage/ Copper causes a focal necrosis of the proximal tubule. The Fanconi syndrome-tubularproteinuria, generalized amino aciduria, phosphaturia, uricosuria, & hypercalciuria may result from thedirect toxic effect of copper or the assoc hemolysis. Hemoglobinemia has been observed after ingestion ...of copper sulfate. /Copper/[Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning.

2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 1555] **PEER REVIEWED**

Skin, Eye and Respiratory Irritations: A STRONG IRRITANT[The Merck Index. 10th ed. Rahway, New Jersey: Merck Co., Inc., 1983., p. 379] **PEER REVIEWED**

Drug Warnings: ... Its routine use as an emetic is not recommended, because of the potential toxicity of improperlyprepared soln and the hazards attending the use of large, corrosive doses.[Osol, A. (ed.). Remington's Pharmaceutical Sciences. 16th ed. Easton, Pennsylvania: Mack Publishing Co., 1980., p. 748] **PEER

REVIEWED**

Overdose may be poisonous (enteritis, hepatitis, nephritis).[Rossoff, I.S. Handbook of Veterinary Drugs. New York: Springer Publishing Company, 1974., p. 136] **PEER REVIEWED**

MAY CAUSE DRAMATIC INCR IN MORTALITY OF TURKEYS GIVEN BLACKHEAD CONTROL DRUGS CONTAININGARSENIC & EXPOSED TO BLACKHEAD.[Rossoff, I.S. Handbook of Veterinary Drugs. New York: Springer Publishing Company, 1974., p. 136] **PEER REVIEWED**

CUPRIC ... SULFATE /AS EMETIC/ OFTEN IS EFFECTIVE, BUT POTENTIAL HEMOLYTIC & RENAL TOXICITY ISTOO GREAT TO RECOMMEND USE.[American Medical Association, AMA Department of Drugs. AMA Drug Evaluations. 4th ed. Chicago: American Medical Association, 1980., p.

1436] **PEER REVIEWED**

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Body Burden: The milk of female vineyard workers, who were exposed to copper sulfate and a variety of otherpesticides, contained 6.2 times as much copper as the milk of milkmaids who did equally hard work but notexposed to pesticides.[Hayes, Wayland J., Jr. Pesticides Studied in Man. Baltimore/London: Williams and Wilkins, 1982., p. 6] **PEER REVIEWED**

Emergency Medical Treatment:

Emergency Medical Treatment: 

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The information contained in the Truven Health Analytics Inc. products isintended as an educational aid only. All treatments or procedures are intendedto serve as an information resource for physicians or other competenthealthcare professionals performing the consultation or evaluation of patientsand must be interpreted in view of all attendant circumstances, indications andcontraindications. The use of the Truven Health Analytics Inc. products is atyour sole risk. These products are provided "as is" and "as available" for use,without warranties of any kind, either express or implied. Truven Health

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The following Overview, *** COPPER SULFATE ***, is relevant for this HSDBrecord chemical.

Life Support:o This overview assumes that basic life support measures

have been instituted.

Clinical Effects:0.2.1 SUMMARY OF EXPOSURE

A) WITH POISONING/EXPOSURE

1) TOPICAL

a) Copper sulfate is a strong irritant to skin and mucous

membranes, including nose, throat, and eyes.

2) INHALATION

a) Burning copper sulfate may produce irritating or

poisonous gases, which may be irritating to the

respiratory tract and lungs.

3) INGESTION

a) Symptoms generally occur within 15 minutes to 1 hour

after ingestion. Initial presenting signs and symptoms

include abdominal pain, nausea and vomiting, diarrhea,

salivation, and metallic taste. Stools, vomitus,

saliva, and mucous membranes are often stained green

or blue. Extensive corrosion and necrosis of the

gastrointestinal tract, with possible perforation, mayoccur due to the corrosive nature of copper sulfate.

b) Severe poisonings may progress to hematemesis, melena,

jaundice, hypotension, gastrointestinal bleeding, and

hemolysis. Refractory shock and hepatic and renal

failure with coma may develop after several days.

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4) PARENTERAL

a) Suicide attempts with intravenous and subcutaneous

copper sulfate resulted in acute renal failure,

gastrointestinal bleeding, coagulopathy, metabolic

acidosis, hemolysis, hepatic injury, and death.

Initial symptoms of vomiting, abdominal pain,

hematemesis, and diarrhea began within 15 minutes of

the injections.

0.2.3 VITAL SIGNS

A) WITH POISONING/EXPOSURE1) Increased temperature may be noted in some cases.

2) Hypotension may occur following ingestions.

3) Tachycardia was reported in a child following an acute

ingestion.

0.2.4 HEENT

A) WITH POISONING/EXPOSURE

1) Eye exposure may result in severe irritation.

0.2.5 CARDIOVASCULAR

A) WITH POISONING/EXPOSURE

1) Hypotension has been reported following ingestions.

0.2.7 NEUROLOGIC

A) WITH POISONING/EXPOSURE

1) Central nervous depression, with coma in severe cases,

may occur.

0.2.8 GASTROINTESTINAL

A) WITH POISONING/EXPOSURE

1) Vomiting usually occurs within 15 minutes of copper

sulfate ingestion. Vomitus is characteristically

greenish-blue. Hemorrhagic gastroenteritis associated

with mucosal erosions, a metallic taste, burning

epigastric sensation, and diarrhea may occur.

0.2.9 HEPATIC

A) WITH POISONING/EXPOSURE1) Hepatomegaly, liver tenderness, and jaundice may occur

on the second or third day postingestion.

0.2.10 GENITOURINARY

A) WITH POISONING/EXPOSURE

1) Oliguria followed by anuria may occur 24 to 48 hours

postingestion. Hemoglobinuria and hematuria may occur.

Necrosis of renal tubular cells has been reported in

fatal cases.

0.2.13 HEMATOLOGIC

A) WITH POISONING/EXPOSURE

1) Hemolysis has been reported. Methemoglobinemia has

occurred but is rare.

0.2.14 DERMATOLOGIC

A) WITH POISONING/EXPOSURE

1) Skin exposure may result in severe irritation.

0.2.21 CARCINOGENICITY

A) At the time of this review, no studies were found on the

possible carcinogenic activity of copper sulfate in

humans.

Laboratory:A) Obtain whole blood copper levels in symptomatic patients.

B) Obtain baseline liver function tests, renal functiontests and CBC.

C) Monitor methemoglobin levels in cyanotic patients.

Treatment Overview:0.4.2 ORAL/PARENTERAL EXPOSURE

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A) Consider insertion of a small, flexible nasogastric tube

to aspirate gastric contents after large, recent

ingestion of copper sulfate. The risk of worsening

mucosal injury (including perforation) must be weighed

against the potential benefit.

B) DILUTION: Immediately dilute with 4 to 8 ounces (120 to

240 mL) of water or milk (not to exceed 4 ounces/120 mL

in a child).

C) Emesis is rapid and spontaneous in most patients

following ingestion of copper sulfate. Inducing emesisis NOT recommended to due to the risk of esophageal or

gastric perforation.

D) Activated charcoal may obscure endoscopy findings but

may also adsorb a clinically significant amount of

copper sulfate. Its use should be considered after

significant ingestions.

E) Keep patient NPO following mucosal decontamination until

after endoscopy consultation.

F) ENDOSCOPY: Early endoscopy allows patients without

gastrointestinal injury to be medically cleared, and

provides important prognostic information in patients

who do have varying degrees of gastrointestinal burns.

In addition, it facilitates the safe placement of

enteral feeding tubes thereby shortening the period of

time that patients with burns are without enteral

nutritional support. Endoscopy should be performed

within the first 24 hours post-ingestion, and should be

avoided from 2 days to 2 weeks post-ingestion since

wound tensile strength is lowest and the risk of

perforation highest during this time. Endoscopy is

indicated for all adults with deliberate ingestion or

any signs or symptoms attributable to ingestion, and for

children with stridor, vomiting, or drooling. Considerendoscopy in children with dysphagia, refusal to

swallow, significant oral burns, or abdominal pain. If

second or third degree burns are found, follow 10 to 20

days later with barium swallow or esophagram.

G) PHARMACOLOGIC TREATMENT: The use of corticosteroids is

controversial. Some authors have advocated the use of

corticosteroids for second degree burns within 48 hours

of ingestion in patients without gastrointestinal

bleeding or evidence of perforation. However, two

prospective trials of corticosteroids for esophageal

injury after caustic ingestion indicated no benefit in

any grade injury, and a recent meta-analysis found no

benefit of corticosteroids in grade II burns and

evidence of harm in grade III burns, so they are not

routinely recommended. Antibiotics are indicated for

suspected perforation or infection and in patients

receiving corticosteroids

H) SURGICAL OPTIONS: Initially, if severe esophageal burns

are found a string may be placed in the stomach to

facilitate later dilation. Insertion of a specialized

nasogastric tube after confirmation of a circumferential

burn may prevent strictures. Dilation is indicated after

2 to 4 weeks if strictures are confirmed; ifunsuccessful, either colonic intraposition or gastric

tube placement may be performed. Consider early

laparotomy in patients with severe esophageal and/or

gastric burns.

I) HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid. If

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hypotension persists, administer dopamine (5 to 20

mcg/kg/min) or norepinephrine (ADULT: begin infusion at

0.5 to 1 mcg/min; CHILD: begin infusion at 0.1

mcg/kg/min); titrate to desired response.

J) RHABDOMYOLYSIS: Administer sufficient 0.9% saline to

maintain urine output of 2 to 3 mL/kg/hr. Monitor input

and output, serum electrolytes, CK, and renal function.

Diuretics may be necessary to maintain urine output.

Urinary alkalinization is NOT routinely recommended.

K) METHEMOGLOBINEMIA: Administer 1 to 2 mg/kg of 1%methylene blue slowly IV in symptomatic patients.

Additional doses may be required.

L) CHELATION - There is little clinical experience in the

use of chelators in the setting of acute copper sulfate

intoxication. Data on efficacy is derived from patients

with chronic copper intoxication (Wilson's disease,

Indian childhood cirrhosis) and animal studies. BAL,

penicillamine, DMPS and EDTA have been used.

D-penicillamine is considered the drug of choice for

Wilson's disease, a condition of chronic copper

overload.

1) D-PENICILLAMINE: Use only if less toxic agents not

available or not tolerated. USUAL DOSE: ADULT: 1000 to

1500 mg/day divided every 6 to 12 hours. CHILD: 10

mg/kg/day initially, gradually increase to 30 mg/kg/day

divided in two or three doses as tolerated. Avoid if

penicillin allergic. Monitor for proteinuria,

hematuria, rash, leukopenia, thrombocytopenia.

2) Administer BAL (Dimercaprol) 3 to 5 mg/kg/dose IM every

4 hours for 2 days; then every 4 to 6 hours for an

additional 2 days; then every 4 to 12 hours for up to 7

additional days.

0.4.4 EYE EXPOSUREA) HOME IRRIGATION - Exposed eyes should be irrigated with

copious amounts of water for at least 30 minutes. An

examination should always be performed. Ophthalmologic

consultation should be obtained.

B) MEDICAL FACILITY: Immediately irrigate each affected eye

with 2 liters of sterile 0.9% saline over about 15 to 20

minutes. After this initial period of irrigation the

corneal pH may be checked with litmus paper and a brief

external eye exam performed. Continue direct copious

irrigation with sterile 0.9% saline until the

conjunctival fornices are free of particulate matter and

returned to pH neutrality (pH 7.4). Once irrigation is

complete a full eye exam should be performed with

careful attention to the possibility of perforation.

C) EYE ASSESSMENT: The extent of eye injury (degree of

corneal opacification and perilimbal whitening) may not

be apparent for 48 to 72 hours after the burn.

0.4.6 PARENTERAL EXPOSURE

A) Parenteral injections, including intravenous and

subcutaneous, have been reported in suicidal poisonings.

Signs and symptoms are similar to those resulting from

ingestions. Refer to the Oral Exposures treatment

section.

Range of Toxicity:A) Ingestion of 250 milligrams of copper sulfate may result

in toxicity.

B) Severe intoxication is associated with serum copper

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levels greater than 500 micrograms/deciliter.

C) Fatalities have occurred following ingestion and

intravenous injection of 1 gram of copper sulfate.

D) Survival has been reported following ingestion of as much

as 30 grams.

[Rumack BH POISINDEX(R) Information System Micromedex, Inc., Englewood, CO, 2013; CCIS Volume 158, edition expires Nov, 2013. Hall AH

& Rumack BH (Eds): TOMES(R) Information System Micromedex, Inc., Englewood, CO, 2013; CCIS Volume 158, edition expires Nov, 2013.]

**PEER REVIEWED**

Antidote and Emergency Treatment: Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratoryinsufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15L/min. Monitor for shock and treat if necessary ... . For eye contamination, flush eyes immediately withwater. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. Foringestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow,has a strong gag reflex, and does not drool. Administer activated charcoal ... . /Copper and relatedcompounds/[Bronstein, A.C., P.L. Currance; Emergency Care for Hazardous Materials Exposure. 2nd ed. St. Louis, MO. Mosby Lifeline. 1994., p.

350] **PEER REVIEWED**

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient

who is unconscious. Start an IV with lactated Ringer's /SRP: "To keep open", minimal flow rate/. Watch forsigns of fluid overload. For hypotension with signs o f hypovolemia, administer fluid cautiously. Considervasopressors if hypotensive with a normal fluid volume. Watch for signs of fluid overload ... . Useproparacaine, hydrochloride to ass ist eye irrigation ... . /Copper and related compounds/[Bronstein, A.C., P.L. Currance; Emergency Care for Hazardous Materials Exposure. 2nd ed. St. Louis, MO. Mosby Lifeline. 1994., p.

351] **PEER REVIEWED**

Animal Toxicity Studies:

Toxicity Summary: For healthy, non-occupationally-exposed humans the major route of exposure to copper is oral. The mean

daily dietary intake of copper in adults ranges between 0.9 and 2.2 mg. ... In some cases, drinking watermay make a substantial additional contribution to the total daily intake of copper, particularly inhouseholds where corrosive waters have stood in copper pipes. ... All other intakes of copper (inhalationand dermal) are insignificant in comparison to the oral route. Inhalation adds 0.3-2.0 ug/day from dustsand smoke. Women using copper IUDs are exposed to only 80ug or less of copper per day from thissource. The homeostas is of copper involves the dual essentiality and toxicity of the element. Itsessentiality arises from its specific incorporation into a large number of proteins for catalytic and structuralpurposes. The cellular pathways of uptake, incorporation into protein and export of copper are conservedin mammals and modulated by the metal itself. Copper is mainly absorbed through the gastrointestinaltract. From 20 to 60% of the dietary copper is absorbed, with the rest be ing excreted through the feces.Once the metal passes through the baso lateral membrane it is transported to the liver bound to serumalbumin. The liver is the critical organ for copper homeostatis. The copper is partitioned for excretionthrough the bile or incorporation into intra- and extracellular proteins. The primary route of excretion is

through the bile. The transport of copper to the peripheral tissues is accomplished through the plasmaattached to serum albumin, ceruloplasmin or low-molecular weight complexes. ... The biochemical toxicityof copper, when it exceeds homeostatic control, is derived from its effects on the structure and function of biomolecules, such as DNA, membranes and proteins directly or through oxygen-radical mechanisms. Thetoxicity of a single oral dose of copper varies widely between species. ... The major soluble sa lts(copper(II) sulfate, copper(II) chloride) are generally more toxic than the less soluble salts (copper(II)hydroxide, copper (II) oxide). Death is preceded by gastric hemorrhage, tachycardia, hypotension,hemolytic crisis, convulsions and paralysis. ... Long-term exposure in rats and mice showed no overt signsof toxicity other than a dose-related reduction in grow th after ingestion ... The effects includedinflammation of the liver and degeneration of kidney tubule epithelium. ... Some testicular degenerationand reduced neonata l body and organ weights were seen in rats ... and fetotoxic effects andmalformations were seen at high dose levels. ... Neurochemical changes have been reported after oraladministration ... A limited number of immunotoxicity studies showed humoral and cell-mediated immunefunction impairment in mice after oral intakes in drinking-water ... Copper is an essential element and

adverse health effects /in humans/ are related to de ficiency as well as excess. Copper deficiency isassociated w ith anemia, neutropenia and bone abnormalities but clinically evident deficiency is relativelyinfrequent in humans. .. Except for occasional acute incidents of copper poisoning, few effects are noted innormal /human/ populations. Effects of single exposure following suicidal or accidenta l oral exposure havebeen reported as metallic taste, epigastric pain, headache, nausea, dizziness , vomiting and diarrhea,tachycardia, respiratory difficulty, hemolytic anemia, hematuria, massive gastrointestinal bleeding, liver

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and kidney failure, and death. Gastrointestinal effects have also resulted from single and repeatedingestion of drinking-water containing high copper concentrations, and liver failure has been reportedfollowing chronic ingestion of copper. Dermal exposure has not been associated with systemic toxicity butcopper may induce allergic responses in sensitive individuals. Metal fume fever from inhalation of highconcentrations in the air in occupational settings have been reported ... A number of groups are describedwhere apparent disorders in copper homeostasis result in greater sensitivity to copper deficit or excessthan the general population. Some disorders have a well-defined genetic basis. These include Menkesdisease, a generally fatal manifestation of copper deficiency; Wilson disease (hepatolenticulardegeneration), a condition leading to progressive accumulation of copper; and hereditaryaceruloplasminemia, with clinical symptoms of copper overload. Indian childhood cirrhosis and idiopathic

copper toxicosis are conditions related to excess copper which may be associated with genetically basedcopper sensitivity ... These are fatal conditions in early childhood where copper accumulates in the liver. ...Other groups potentially sensitive to copper excess are hemodialysis patients and subjects with chronicliver disease. Groups at risk of copper deficiency include infants (particularly low birth weight/pretermbabies, children recovering from malnutrition, and babies fed exclusively with cow's milk), people withmaladsorption syndrome (e.g., celiac disease, sprue, cystic fibrosis), and patients on tota l parenteralnutrition. Copper deficiency has been implicated in the pathogenesis of cardiovascular disease. Theadverse effects of copper must be balanced against its essentiality. Copper is an essential element for allbiota ... At least 12 major proteins require copper as an integral part of their structure. It is essential forthe utilization of iron in the formation of hemoglobin, and most crustaceans and molluscs possess thecopper-containing hemocyanin as their main oxygen-carrying blood protein. ... A critical factor in assessingthe hazard of copper is its bioavailablity. Adsorption of copper to particles and complexation by organicmatter can greatly limit the degree to which copper will be accumulated ... At many sites, physiochemical

factors limiting bioavailability will warrant higher copper limits. ...[Environmental Health Criteria 200: Copper pp. 1-11 (1998) by the International Programme on Chemical Safety (IPCS) under the joint

sponsorship of the United Nations Environment Programme, the International Labour Organisation and the World Health Organization.]

**PEER REVIEWED**

Non-Human Toxicity Excerpts: IN ANIMALS INGESTION OF 3 OZ OF 1% SOLN OF CUPRIC SULFATE WILL PRODUCE INTENSEINFLAMMATION OF GASTROINTESTINAL TRACT, WITH SYMPTOMS OF ABDOMINAL PAIN, VOMITING, & DIARRHEA.[Browning, E. Toxicity of Industrial Metals. 2nd ed. New York: Appleton-Century-Crofts, 1969., p. 147] **PEER REVIEWED**

Daily oral doses of 20 mg of copper sulfate per kg body weight given to sheep resulted in hemolysis afternine weeks. ... Hemolysis also caused acute tubular renal damage in the sheep.[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. 245] **PEER REVIEWED**

COPPER SALTS ADMIN IV TO HAMSTERS ON DAY 8 OF GESTATION CAUSED EMBRYONIC RESORPTIONS ANDDEVELOPMENTAL MALFORMATIONS IN SURVIVING OFFSPRING. HEART DEFECTS OCCURRED. COPPER INCHELATED FORM (COPPER CITRATE) WAS EMBRYOCIDAL BUT MUCH MORE EMBRYOPATHIC THAN INUNCOMPLEXED FORM (COPPER SULFATE).[FERM VH, HANLON DP; BIOL REPROD 11 (1): 97 (1974)] **PEER REVIEWED** PubMed Abstract 

DAILY SC INJECTIONS OF 0.26 MG OF COPPER AS COPPER SULFATE FOR 60 DAYS TO RATS. ... THE EXPOSEDRATS SHOWED REDN IN HEMOGLOBIN CONTENT, RED CELL COUNTS & HEMATOCRITS. MEAN SURVIVAL TIME... WAS 67 DAYS. HISTOLOGICALLY, SIGNS OF ACUTE TOXICITY, BOTH HEPATIC & RENAL, WERE SEEN.[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 244] **PEER REVIEWED**

COPPER SULFATE FED AD LIBITUM IN DIET OF RATS @ LEVEL OF 500 PPM CAUSED RETARDED GROWTH;4000 PPM CAUSED STARVATION & DEATH. ... ACCESS BY SHEEP TO SALT LICKS CONTAINING 5-9% COPPERSULFATE CAUSED ... ANOREXIA, HEMOLYTIC ANEMIA, ICTERUS, & HEMOGLOBINURIA FOLLOWED BY DEATHIN A DAY OR 2. ... AT NECROPSY, LIVER, KIDNEYS, & SPLEEN SHOWED ... DEGENERATIVE CHANGES.[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. 1624] **PEER REVIEWED**

GUINEA PIGS WERE EXPOSED FOR 1 HR TO AEROSOLS OF SULFATE SALTS. WITH THE EXCEPTION OFSODIUM SULFATE, ALL THE SULFATES CAUSED SLIGHT INCREASE IN PULMONARY FLOW RESISTANCE & SLIGHT DECREASE IN PULMONARY COMPLIANCE. COPPER SULFATE WAS LEAST IRRITANT AMONGAMMONIUM SULFATE & AMMONIUM BISULFATE AEROSOLS.[AMDUR MO ET AL; ENVIRON RES 16 (1-3): 1-8 (1978)] **PEER REVIEWED** PubMed Abstract 

EFFECTS OF INTRATRACHEALLY ADMIN AIR POLLUTANT CHEMICALS ON SUSCEPTIBILITY OF MICE TOINFECTION BY AEROSOLIZED BACTERIA WERE COMPARED WITH EFFECTS FROM INHALATION EXPOSURES.THREE (CADMIUM SULFATE, COPPER SULFATE, & ZINC SULFATE) OF THE TWENTY TWO CMPD STUDIED BYINHALATION WHICH CAUSED INCR MORTALITY IN MICE BECAUSE OF INFECTION AFTER 3 HR EXPOSURE TO1-2 MG/CU M, SHOWED LARGE (GREATER THAN 40% OVER SHAM INJECTED) MORTALITY INCREASES WHENADMIN BY INTRATRACHEAL INJECTION AT LUNG CONCN EQUIVALENT TO INHALATION EXPOSURES.

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[HATCH GE ET AL; AM REV RESPIR DIS 124 (2): 167-73 (1981)] **PEER REVIEWED** PubMed Abstract 

CUPRIC SULFATE WAS LETHAL TO FRESH WATER PALAEMONID PRAWN (MACROBRACHIUM KISTNENSIS) AT2.25 PPM. AFTER 24 HR EXPOSURE, OXYGEN CONSUMPTION INCR.[NAGABHUSHANAM R, KULKARNI GK; PROC INDIAN NATL SCI ACAD, PART B; 47 (3): 380-6 (1981)] **PEER REVIEWED**

10 PPM CUPRIC SULFATE INCREASED THE BLOOD GLUCOSE, LACTATE DEHYDROGENASE, GLUTAMIC ACIDOXALACETIC ACID TRANSAMINASE, & GLUTAMIC ACID PYRUVIC ACID TRANSAMINASE LEVELS IN THREESPECIES OF FISH. IN INCREASING ORDER SILVER CARP, CARP & EUROPEAN WELS.[NEMCSOK J, BOROSS L; ACTA BIOL ACAD SCI HUNG 33 (1): 23-7 (1982)] **PEER REVIEWED** PubMed Abstract 

METHOD FOR ASSESSING CHRONIC EFFECT OF COPPER /SRP: AS CUPRIC SULFATE/ ON MIDGE LARVA(PARATANYTARSUS PARTHENOGENETICUS) IS PRESENTED. GROWTH & REPRODUCTION WERE RELATED TOCOPPER CONCN GREATER THAN 0.08 MG/L; 50% REPRODUCTIVE IMPAIRMENT @ 0.37 MG/L. GROWTH & FOOD INTAKE WERE INVERSELY RELATED TO CONCN.[HATAKEYAMA W, YASUNO M; ARCH CONTAM TOXICOL 10 (6): 705-13 (1981)] **PEER REVIEWED**

Decrease in hemolymph glucose in Viviparus bengalensis exposed to cupric sulfate (0.001%) less than orequal to 24 hr was directly proportional to the time of exposure. At the end of 24 hr there was a markeddecrease in the glucose level. In the foot muscle and hepatopancreas of the snail, cupric sulfatedecreased the glycogen reserve. Protein levels in these tissues were increased whereas the lipid contentwas decreased.[Kulkarni AB, Utical VN; J Envir Biol 4 (4): 215-20 (1983)] **PEER REVIEWED**

Hamsters were exposed for 4 hr to cupric sulfate (4.8 mg/cu m). ... Macrophage endocytosis wassignificantly reduced 1 hr after exposure compared with that to unexposed control animals ... . Hamsters

 /exposed to 4.8 mg/cu m/ cupric sulfate for 48 hr showed significant increases in phagocytosis.[Skornik WA, Brain JD; Am Rev Respir Dis 128 (2 Part 1): 297-303 (1983)] **PEER REVIEWED** PubMed Abstract 

Exposure to sublethal concn of cupric sulfate (0.1-5.0 ppm) induced a significant elevation in the rate of whole body oxygen consumption of Onchidium verruculatum up to 4-72 hr of the exposure period.Thereafter, there was a decline in the oxygen consumption up to 96 hr of the exposure period.[Nagabhushanam R, Deshpande UD; J Envir Biol 3 (4): 151-4 (1982)] **PEER REVIEWED**

... Marked dose dependent testicular atrophy was noticed in ... copper sulfate ... fed birds. Mild to severespermatogenic arrest concomitant with testicular atrophy was observed. Histochemically, the interstitial(Leydig) cells and seminiferous tubules showed intense accumulation of cholesterol positive lipids ... .[Shivanandappa T et al; Poult Sci 62 (2): 405-8 (1983)] **PEER REVIEWED** PubMed Abstract 

The results of preliminary investigations on the toxicity of /copper sulfate/ ... for 15, 30, and 45 day oldsheatfish and to the encysted stages of Icthyophthirius multifiliis (ich) showed that an interruption of theparasite life cycle in this stage, w ithout harming the fish, seems to be possible. A concn of 15 ppm coppersulfate /was/ suitable for the elimination of the encysted parasites in the presence of 15 day old and oldersheatfish ... .[Antychowicz J et al; Bull Vet Inst Pulawy 25 (4): 20-3 (1982)] **PEER REVIEWED**

... The motility of /rat/ cauda epididymal spermatozoa in vitro in the presence of different concn of cupricsulfate was investigated. In vitro decrease in motility was more rapid with increasing concn of cupricsulfate soln.[Chinoy NJ, Sanjeevan AG; Int J Androl 3 (6): 719-7 (1980)] **PEER REVIEWED** PubMed Abstract 

Adult male blue crabs (Callinectes sapidus) ... were exposed for 48 hr to river water containing hydratedcopper sulfate reagent at concn of 0, 50, 100, and 1000 ug/l. ... Exposure to 1000 ug/l copper sulfatecaused changes affecting both the integrity and disposition of the dendrites within the aesthetases.Changes included condensation of the dendrites and flocculent extracelluar material into a bandlikeregion, ... loss of the large dendrite profiles, and occurrence of electron dense filamentous structures notpresent in control preparations. Changes in chemoreceptor structures following 100 ug/l copper sulfatewere similar to those /at/ 1000 ug/l, but less pronounced. Exposure to 50 ug/l copper sulfate had little ...effect on morphology of blue crab chemoreceptors. /Hydrated copper sulfate reagent/[Bodammer J; Preliminary Observation on the Cytopathological Effects of Copper Sulfate on the Chemoreceptors of Calinectes sapidus in

Marine Pollution: Functional Responses. Vernberg, WB et al eds p.223-37 (1979)] **PEER REVIEWED**

... Submicron aerosols of /cupric sulfate/ in concn of 4.1-8.8 mg/cu m, administered for 4 hr to anesthetizeddogs, did not affect mechanics of breathing, hemodynamics, or arterial blood gases. In conscious sheep,tracheal mucous velocity was not altered by exposure to the submicron aerosols of the sulfate cmpd.

Cupric sulfate /in 100 mg/ injections produced pulmonary hypertension, a fall in cardiac output, hypoxemia,respiratory acidos is and a decrease of specific total conductance.[Sackner MA et al; J Toxicol Environ Health 7 (6): 951-72 (1981)] **PEER REVIEWED** PubMed Abstract 

No change was observed in whole animal respiration in snails exposed to 2 ppm copper sulfate for 6 hr.[Babu GR, Rao PV; Bull Environ Contam Toxicol 34 (3): 396-402 (1985)] **PEER REVIEWED** PubMed Abstract 

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The effects of copper sulfate (0.0004 and 105 ug copper/l) on growth, reproduction, survival, andhemoglobin content of Daphnia magna were studied in hard reconstituted water and compared to theresponse in diluted water without the addition of copper. The 48 hr EC50 (immobilization) for unfedneonates was 6.5 ug copper/l and the 48 hr and 21 day LC50s (median lethal concn) for fed neonateswere 18.5 and 1.4 ug copper/l, respectively.[Dave G; Comp Biochem Physiol, C: Comp Pharmacol Toxicol 78C (2): 439-43 (1984)] **PEER REVIEWED**

Copper sulfate was toxic as detected by sewage sludge bacterial respiration, nitrification, and growthassays; with biological oxygen demand assay being more suitable for rivers.[King EF; Drug Chem Toxicol 1 (Toxic Screening Proced Using Bact Syst): 175-94 (1984)] **PEER REVIEWED**

CARBOHYDRATE METABOLITES LIKE HEMOLYMPH GLUCOSE & MIDGUT GLAND GLYCOGEN SHOWED INVERSERELATION IN THEIR CHANGES AFTER LESS THAN 72 HR EXPOSURE TO 1.0 PPM CUPRIC SULFATE BUT BOTHMETABOLITES DECREASED GREATLY AFTER PROLONGED (120 HR) EXPOSURE OF FRESHWATER PRAWN(MACROBRACHIUM KISTNENSIS).[NAGABHUSHANAM R, KULKARNI GK; PROC INDIAN NATL SCI ACAD, PART B 47 (3): 380-6 (1981)] **PEER REVIEWED**

Groups of eight pigs /were maintained/ on a corn-soy diet supplemented w ith 250 (3.2 mgcopper(2+)/kg/day) or 500 (5.5 mg copper(2+)/kg/day) ppm copper sulfate for 61 days. In a secondexperiment, groups of 12 pigs were fed a corn-soy diet supplemented w ith 0, 150 (1.8 mgcopper(2+)/kg/day), 200 (2.5 mg copper(2+)/kg/day), or 250 (2.9 mg copper(2+)/kg/day) ppm coppersulfate for 88 days. The control group was normal and had normal blood parameters. Pigs fed 150-250ppm copper sulfate (1.8-3.2 mg copper(2+)/kg/day) all had accelerated weight gain but also had increasesin liver copper that indicated a significant (p< 0.05) linear correlation w ith dose. Reduced grow th and

hemoglobin levels and increased liver copper were observed in the 500 ppm treatment group.[USEPA; Drinking Water Criteria Document for Copper (Final Draft) p.V-10 (1985) EPA-600/X-84-190-1] **PEER REVIEWED**

In a subchronic study, the liver and kidneys of rats treated with 2,000 ppm copper (as copper sulfate) inthe diet for 15 weeks experienced a triphasic response during the exposure period. The first stage wascharacterized by the accumulation of copper with some signs of cellular disruption followed by a secondstage of severe hepatic and renal necrosis. The final phase was marked by decreas ing copper content andregeneration of damaged tissue as the animals appeared to develop tolerence against the effects of copper.[USEPA; Health Issue Assessment: Copper p.33 (1987) EPA/600/8-87/001] **PEER REVIEWED**

 /Researchers/ reported the development of massive hemolysis with high levels of copper in the liver,kidney, and plasma in sheep treated orally with 20 mg copper sulfate pentahydrate/kg body wt/day within

7 weeks. The excess copper caused an incr in the concn of iron in the plasma and spleen, possibly byinterfering with iron metabolism and binding. Hepatic damage was observed in three histopathologicalstudies of sheep chronically exposed to copper. /Copper sulfate, pentahydrate/[USEPA; Health Issue Assessment: Copper p.26 (1987) EPA/600/8-87/001] **PEER REVIEWED**

Liver and kidney necrosis /occurred/ in rats given copper sulfate by gavage for 20 days. Groups of 10 malealbino rats, (Rattus rattus albino) 90 days of age were given 0 or 100 mg copper sulfate/kg body wt/dayby gavage (vehicle not reported) for 20 days. Based on the molecular weight of copper/copper sulfate, theamount of copper given each day was 0 or 25.4 mg/kg. Body weights and tail lengths (a measure of skeletal growth) were recorded each day. On day 20, blood samples were drawn for evaluation of redblood cell count, white blood cell count, hemoglobin level, and hematocrit percentage. All animals werethen killed, and their livers and kidneys were removed for wet weight measurement and routinehistological examination. Several changes in treated rats, absent in control rats, were observed upongross examination. The paws of treated rats had changed from pink to white. Significant decreases in the

tail length, body weight gain, hemoglobin concn, hematocrit percentage, and red blood count of treatedrats were observed as compared with controls. Upon histological examination, the livers and kidneys of control rats appeared normal. In treated rats, however, copper-induced damage to these organs wasobserved. The livers of treated rats showed centrilobular necrosis, perilobular sclerosis, and heavydeposition o f copper in centrilobular parenchyma. Necrosis, tubular engorgement, and copper retentionwere observed in the kidneys of treated rats.[USEPA; Drinking Water Criteria Document for Copper (Final Draft) p.V-6 (1985) EPA-600/X-84-190-1] **PEER REVIEWED**

Pigs appear to be more sensitive to the acute toxicity of copper. Adverse effects /were reported/ in pigsgiven copper supplements in doses as low as 6.4 mg copper(+2) kg/day for 48 days and 2.6 mgcopper(+2) kg/day for 79 days. Beneficial effects of copper (as copper sulfate) supplementation inHampshire and Yorkshire pigs (approximately 24 kg) at doses of 1.8-3.2 mg for 61-88 days /were alsoreported/. Administration of 5.5 mg copper(+2) kg/day for 61 days caused adverse effects (eg, growth

reduction, reduced hemoglobin and increased hepatic copper.[USEPA; Health Issue Assessment: Copper p.49 (1987) EPA/600/8-87/001] **PEER REVIEWED**

The observation of teratogenic effects in two strains of mice fed diets supplemented w ith copper sulfatebefore mating /are reported/. Various numbers of C57BL and DBA mice were maintained for 1 month ondiets supplemented with 0, 500, 1,000, 1,500, 2,000, 3,000, 4,000 ppm copper sulfate. Theseconcentrations are equivalent to 0, 199, 398, 597, 796, 1,195, and 1,593 ppm copper, respectively.