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COPPER(II) SULFATE - National Library of Medicine HSDB Database

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COPPER(II) SULFATE
CASRN: 7758-98-7

T h i sr e c o r dc o n t a i n si n f o r m a t i o ns p e c i f i ct ot h et i t l ec o m p o u n d .U s e r sw i t ha ni n t e r e s ti nt h i ss u b s t a n c ea r es t r o n g l ye n c o u r a g e da l s o t or e t r i e v et h er e c o r dn a m e dC O P P E RC O M P O U N D S ,w h i c hh a sa d d i t i o n a li n f o r m a t i o nr e l e v a n tt ot h et o x i c i t ya n de n v i r o n m e n t a lf a t eo f c o p p e ri o n sa n dc o p p e rc o m p o u n d s .F o ri n f o r m a t i o no nt h em e t a li t s e l f ,r e f e rt ot h eC O P P E R ,E L E M E N T A Lr e c o r d .

For m ore inform ation, 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 mean daily dietary intake of copper in adults ranges between 0.9 and 2.2 mg. ... In some cases, drinking water may make a substantial additional contribution to the total daily intake of copper, particularly in households where corrosive waters have stood in copper pipes. ... All other intakes of copper (inhalation and dermal) are insignificant in comparison to the oral route. Inhalation adds 0.3-2.0 ug/day from dusts and smoke. Women using copper IUDs are exposed to only 80ug or less of copper per day from this source. The homeostasis 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 structural purposes. The cellular pathways of uptake, incorporation into protein and export of copper are conserved in mammals and modulated by the metal itself. Copper is mainly absorbed through the gastrointestinal tract. From 20 to 60% of the dietary copper is absorbed, with the rest being excreted through the feces. Once the metal passes through the basolateral membrane it is transported to the liver bound to serum 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 bile. The transport of copper to the peripheral tissues is accomplished through the plasma attached to serum albumin, ceruloplasmin or low-molecular weight complexes. ... The biochemical toxicity of 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. The toxicity of a single oral dose of copper varies widely between species. ... The major soluble salts (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 signs of toxicity other than a dose-related reduction in growth after ingestion ... The effects included inflammation of the liver and degeneration of kidney tubule epithelium. ... Some testicular degeneration and reduced neonatal body and organ weights were seen in rats ... and fetotoxic effects and malformations were seen at high dose levels. ... Neurochemical changes have been reported after oral administration ... A limited number of immunotoxicity studies showed humoral and cell-mediated immune function impairment in mice after oral intakes in drinking-water ... Copper is an essential element and adverse health effects /in humans/ are related to deficiency as well as excess. Copper deficiency is associated with anemia, neutropenia and bone abnormalities but clinically evident deficiency is relatively infrequent in humans. .. Except for occasional acute incidents of copper poisoning, few effects are noted in normal /human/ populations. Effects of single exposure following suicidal or accidental oral exposure have been reported as metallic taste, epigastric pain, headache, nausea, dizziness, vomiting and diarrhea, tachycardia, respiratory difficulty, hemolytic anemia, hematuria, massive gastrointestinal bleeding, liver and kidney failure, and death. Gastrointestinal effects have also resulted from single and repeated ingestion of drinking-water containing high copper concentrations, and liver failure has been reported following chronic ingestion of copper. Dermal exposure has not been associated with systemic toxicity but copper may induce allergic responses in sensitive individuals. Metal fume fever from inhalation of high concentrations in the air in occupational settings have been reported ... A number of groups are described where 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 Menkes disease, a generally fatal manifestation of copper deficiency; Wilson disease (hepatolenticular degeneration), a condition leading to progressive accumulation of copper; and hereditary aceruloplasminemia, 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 based copper 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 chronic liver disease. Groups at risk of copper deficiency include infants (particularly low birth weight/preterm babies, children recovering from malnutrition, and babies fed exclusively with cow's milk), people with maladsorption syndrome (e.g., celiac disease, sprue, cystic fibrosis), and patients on total parenteral nutrition. Copper deficiency has been implicated in the pathogenesis of cardiovascular disease. The adverse effects of copper must be balanced against its essentiality. Copper is an essential element for all biota ... At least 12 major proteins require copper as an integral part of their structure. It is essential for the utilization of iron in the formation of hemoglobin, and most crustaceans and molluscs possess the copper-containing hemocyanin as their main oxygen-carrying blood protein. ... A critical factor in assessing the hazard of copper is its bioavailablity. Adsorption of copper to particles and complexation by organic matter can greatly limit the degree to which copper will be accumulated ... At many sites, physiochemical factors limiting bioavailability will warrant higher copper limits. ...
[ E n v i r o n m e n t a lH e a l t hC r i t e r i a2 0 0 :C o p p e rp p .1 1 1( 1 9 9 8 )b yt h eI n t e r n a t i o n a lP r o g r a m m eo nC h e m i c a lS a f e t y( I P C S )u n d e rt h ej o i n t s p o n s o r s h i po ft h eU n i t e dN a t i o n sE n v i r o n m e n tP r o g r a m m e ,t h eI n t e r n a t i o n a lL a b o u rO r g a n i s a t i o na n dt h eW o r l dH e a l t hO r g a n i z a t i o n . ] * * P E E RR E V I E W E D * *

Human Toxicity Excerpts: A ... NUMBER OF CASES OF ACUTE POISONING IN MAN FROM INGESTING COPPER SULFATE, SOME OF THEM FATAL, HAVE BEEN REPORTED ... FROM NEW DELHI ... . THE REPORT CONCERNS 48 HOSPITALIZED PATIENTS & 5 AUTOPSY CASES, 2/3 MALE, MOSTLY BETWEEN THE AGES OF 16 & 25 YR. DOSAGE ESTIMATES RANGED FROM 1 TO 12 G ... SWALLOWED IN WATER. SYMPTOMS ... WERE ... METALLIC TASTE, BURNING IN EPIGASTRIUM, & REPEATED VOMITING. IN MORE SEVERE CASES, DIARRHEA (14 PATIENTS) APPEARED ON THE FIRST OR SECOND DAY & LASTED 24 HR; 20 ... SHOWED BLOOD IN GI TRACT FROM INJURY TO GASTRIC MUCOSA, 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 TO UREMIA FROM RENAL INJURY, & DEATHS OCCURRED IN 7 (14.6%).
[ C l a y t o n ,G .D .a n dF .E .C l a y t o n( e d s . ) .P a t t y ' sI n d u s t r i a lH y g i e n ea n dT o x i c o l o g y :V o l u m e2 A ,2 B ,2 C :T o x i c o l o g y .3 r de d .N e wY o r k : J o h nW i l e yS o n s ,1 9 8 1 1 9 8 2 . ,p .1 6 2 4 ]* * P E E RR E V I E W E D * *

CONTACT OF SKIN WITH COPPER SULFATE CAN RESULT IN ITCHING ECZEMA ... CONTACT OF EYE WILL RESULT IN CONJUNCTIVITIS, EDEMA OF EYELIDS, & ULCERATION & TURBIDITY OF CORNEA.
[ P a t t y ,F .( e d . ) .I n d u s t r i a lH y g i e n ea n dT o x i c o l o g y :V o l u m eI I :T o x i c o l o g y .2 n de d .N e wY o r k :I n t e r s c i e n c eP u b l i s h e r s ,1 9 6 3 . ,p .1 0 3 5 ] * * P E E RR E V I E W E D * *

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, pallor in 10, jaundice in 8, delirium in 3, & coma in 2. All had intravascular hemolysis & developed oliguria or anuria. Five patients died despite gastric lavage, intravenous fluids, mannitol, diuretics, and dialysis.
[ R e y n o l d s ,J . E . F . ,P r a s a d ,A . B .( e d s . )M a r t i n d a l e T h eE x t r aP h a r m a c o p o e i a .2 8 t he d .L o n d o n :T h eP h a r m a c e u t i c a lP r e s s ,1 9 8 2 . ,p .9 3 1 ] * * P E E RR E V I E W E D * *

... Toxic blood levels can be seen after oral ingestion of as little as 1 g of copper sulfate in an adult. ... A patient ... ingested 250 gm of copper sulfate, developed transient hepatic dysfunction, and recovered after the prompt administration of chelation therapy.
[ J a n t s c hWe ta l ;JT o x i c o lC l i nT o x i c o l2 2( 6 ) :5 8 5 8( 1 9 8 4 ) ]* * P E E RR E V I E W E D * *P u b M e dA b s t r a c t

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.
[ R e y n o l d s ,J . E . F . ,P r a s a d ,A . B .( e d s . )M a r t i n d a l e T h eE x t r aP h a r m a c o p o e i a .2 8 t he d .L o n d o n :T h eP h a r m a c e u t i c a lP r e s s ,1 9 8 2 . ,p .9 3 1 ] * * P E E RR E V I E W E D * *

May be corrosive to eyes, mucous membranes, skin ... . /Cupric sulfate pentahydrate/
[ F a r mC h e m i c a l sH a n d b o o k8 7 .W i l l o u g h b y ,O h i o :M e i s t e rP u b l i s h i n gC o . ,1 9 8 7 . ,p .C 6 9 ]* * P E E RR E V I E W E D * *

THERE HAVE BEEN REPORTS ... OF SUICIDE WITH GRAM QUANTITIES OF CUPRIC SULFATE.
[ N a t i o n a lR e s e a r c hC o u n c i l .D r i n k i n gW a t e r&H e a l t hV o l u m e1 .W a s h i n g t o n ,D C :N a t i o n a lA c a d e m yP r e s s ,1 9 7 7 . ,p .2 5 2 ]* * P E E RR E V I E W E D * *

Copper sulfate is caustic. Acute toxicity is largely due to this property.

[ B o o t h ,N . H . ,L . E .M c D o n a l d( e d s . ) .V e t e r i n a r yP h a r m a c o l o g ya n dT h e r a p e u t i c s .5 t he d .A m e s ,I o w a :I o w aS t a t eU n i v e r s i t yP r e s s ,1 9 8 2 . , p .9 4 8 ]* * P E E RR E V I E W E D * *

Human erythrocytes /incubated/ for 4 hr in a 1 mM copper sulfate solution. Approx 5-10% of the erythrocytes underwent hemolysis, and significant incr in osmotic fragility were observed to occur within 3 hr.
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[ U S E P A ;D r i n k i n gW a t e rC r i t e r i aD o c u m e n tf o rC o p p e r( F i n a lD r a f t )p . V 1 3( 1 9 8 5 )E P A 6 0 0 / X 8 4 1 9 0 1 ]* * P E E RR E V I E W E D * *

Excessive 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 in Wilson's disease patients in in vitro incubations with human erythrocytes and in copper sulfate acute poisoning cases in humans. The concn of copper in the in vitro experiments are much higher than those encountered in vivo.
[ U S E P A ;D r i n k i n gW a t e rC r i t e r i aD o c u m e n tf o rC o p p e r( F i n a lD r a f t )p . V I 1 4( 1 9 8 5 )E P A 6 0 0 / X 8 4 1 9 0 1 ]* * P E E RR E V I E W E D * *

A case where a patient died after she was treated with 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 copper sulfate (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 massive gastrointestinal bleeding were observed, and the patient died. Rapid intestinal absorption of copper undoubtly occurred, as she had a three quarter gastrectomy. On autopsy, acute renal tubular necrosis and a liver copper level of 7.46 mg/100 g were observed.
[ U S E P A ;D r i n k i n gW a t e rC r i t e r i aD o c u m e n tf o rC o p p e r( F i n a lD r a f t )p . V I 7( 1 9 8 5 )E P A 6 0 0 / X 8 4 1 9 0 1 ]* * P E E RR E V I E W E D * *

A case of acute copper intoxication in an 18 month old boy /was reported/. After drinking a soln estimated to contain 3 g cupric sulfate (0.76 g copper), the boy began to vomit and was admitted to a hospital. High copper levels were observed in serum (1.65 mg/100 ml) and urine (50 ug/100 ml) upon admittance, at which time reduced glucose-6-phosphate dehydrogenase activity, hematuria, glycosuria, and proteinuria were also noted.
[ U S E P A ;D r i n k i n gW a t e rC r i t e r i aD o c u m e n tf o rC o p p e r( F i n a lD r a f t )p . V I 6( 1 9 8 5 )E P A 6 0 0 / X 8 4 1 9 0 1 ]* * P E E RR E V I E W E D * *

In humans, a metallic taste, nausea, vomiting, and epigastric pain are the first symptoms reported in nearly all cases of acute poisoning with copper sulfate. ... Ingestion of as little as 5.3 mg of copper has been reported to emesis.
[ U S E P A ;D r i n k i n gW a t e rC r i t e r i aD o c u m e n tf o rC o p p e r( F i n a lD r a f t )p . V 1 4( 1 9 8 5 )E P A 6 0 0 / X 8 4 1 9 0 1 ]* * P E E RR E V I E W E D * *

An outbreak of gastroenteritis in 18/50 workmen following ingestion of tea made from copper sulfate contaminated water was reported. Symptoms ranged from dizziness, headache, diarrhea, vomiting, and abdominal pain to complete collapse. Water from a corroded geyser (heater) was later observed to contain 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 in factory workmen /was reported/. Twenty workmen felt sick after ingesting morning tea made in a copper contaminated 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 was stated that the copper concn was probably higher. Assuming each man (70 kg) drank one cup (0.23 l), the estimated dose was greater than or equal to 0.1 mg/kg.
[ U S E P A ;D r i n k i n gW a t e rC r i t e r i aD o c u m e n tf o rC o p p e r( F i n a lD r a f t )p . V I 3( 1 9 8 5 )E P A 6 0 0 / X 8 4 1 9 0 1 ]* * P E E RR E V I E W E D * *

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 and methemolglobinemia and died 16 hr after poisoning.
[ U S E P A ;H e a l t hI s s u eA s s e s s m e n t :C o p p e rp . 5 2( 1 9 8 7 )E P A / 6 0 0 / 8 8 7 / 0 0 1 ]* * P E E RR E V I E W E D * *

The clinical data from 53 cases of acute copper sulfate poisonings /are reported/. Ingestion of up to 12 g copper resulted in immediate metallic taste, nausea, vomiting, epigastric pain, diarrhea, jaundice, hemogloblinuria, and/or hematuria, anuria, oliguria, hypotension, and coma. Autopsy of 5 patients revealed ulceration of the gastric mucousa, hepatic centrilobular necroses, biliary stasis, and renal tubular cell necrosis.
[ U S E P A ;H e a l t hI s s u eA s s e s s m e n t :C o p p e rp . 5 2( 1 9 8 7 )E P A / 6 0 0 / 8 8 7 / 0 0 1 ]* * P E E RR E V I E W E D * *

The case of a suicidal 42 year old male who ingested 250 grams of copper sulfate is reported. Within 10 minutes, severe epigastric pain and vomiting occurred. He was taken to the emergency room 90 minutes after 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 diffuse epigastric tenderness but no sign of peritoneal inflammation. There was no neurologic deficit. Blood alcohol was 222 milligrams per deciliter, white blood count as 12,200 with a normal differential, hematocrit was 56.1 percent, and blood pH was 7.29. Electrocardiogram revealed sinus tachycardia. Urine showed microscopic hematuria without renal tubular cells or casts. The patient was treated with a single injection of 4 milligrams per kilogram dimercaprol. Vomiting subsided within 10 hours of ingestion. Beginning at that point, activated charcoal, magnesium 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 per deciliter, 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. These abnormalities subsided within a week. There was no hemolysis or oliguria. The patient's recovery was probably due to a brisk emetic response and prompt chelation therapy.
[ J a n t s c hWe ta l ;C l i nT o x i c o l2 2( 6 ) :5 8 5 8 8( 1 9 8 4 ) ]* * P E E RR E V I E W E D * *

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A case of poisoning in a 23 year old patient who had taken cupric sulfate, 15 g, was reported. Therapy consisted 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 later with persistent hemolytic anemia and gastric ulceration.
[ T a k a h a s h iHe ta l ;G e k k a nY a k u j i2 9( M a r ) :6 5 3 5 6( 1 9 8 7 ) ]* * P E E RR E V I E W E D * *

Massive ingestion of copper led to a fatality with a hepatic copper content of 1160 micrograms/g. A 47year 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/
[ E l l e n h o r n ,M . J . ,S .S c h o n w a l d ,G .O r d o g ,J .W a s s e r b e r g e r .E l l e n h o r n ' sM e d i c a lT o x i c o l o g y :D i a g n o s i sa n dT r e a t m e n to fH u m a nP o i s o n i n g . 2 n de d .B a l t i m o r e ,M D :W i l l i a m sa n dW i l k i n s ,1 9 9 7 . ,p .1 5 5 5 ]* * P E E RR E V I E W E D * *

Overdosage of copper salts is common in developing countries because of its wide use in various traditional preparations. Poisoning is due to the ingestion of "spiritual water" following distribution to members 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 supervene within 24 hr. Flapping tremor, toxic psychosis, hemolytic anemia, & jaundice may follow within a few days. Hepatic & renal failure precede death within 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 have occurred in the United States. /Copper/
[ E l l e n h o r n ,M . J . ,S .S c h o n w a l d ,G .O r d o g ,J .W a s s e r b e r g e r .E l l e n h o r n ' sM e d i c a lT o x i c o l o g y :D i a g n o s i sa n dT r e a t m e n to fH u m a nP o i s o n i n g . 2 n de d .B a l t i m o r e ,M D :W i l l i a m sa n dW i l k i n s ,1 9 9 7 . ,p .1 5 5 5 ]* * P E E RR E V I E W E D * *

Removal of copper by dialysis may be useful in the early stages of poisoning when the metal is still present in the circulation as free copper. the copper-chelating drug tetrathimolybdate used in Wilson's disease has been assoc with pancytopenia. Its use has not been reported in copper poisoning. Ingestion of 10 to 20 g of copper sulfate is usually lethal. Hemodialysis has not prevented death in such cases. /Copper/
[ E l l e n h o r n ,M . J . ,S .S c h o n w a l d ,G .O r d o g ,J .W a s s e r b e r g e r .E l l e n h o r n ' sM e d i c a lT o x i c o l o g y :D i a g n o s i sa n dT r e a t m e n to fH u m a nP o i s o n i n g . 2 n de d .B a l t i m o r e ,M D :W i l l i a m sa n dW i l k i n s ,1 9 9 7 . ,p .1 5 5 6 ]* * P E E RR E V I E W E D * *

When airborne the dusts of inorganic copper salts have low toxicity. Vineyard sprayer's lung disease has been assoc with airborne copper sulfate. This is a histiocytic granulomatous lung & liver disease occurring in individuals exposed to copper sulfate spray for 2 to 15 years. A syndrome of intravenous copper intoxication due to copper released from copper tubing during hemodialysis includes symptoms of nausea, vomiting, abdominal pain, diarrhea, anxiety, & depression. /Copper/
[ E l l e n h o r n ,M . J . ,S .S c h o n w a l d ,G .O r d o g ,J .W a s s e r b e r g e r .E l l e n h o r n ' sM e d i c a lT o x i c o l o g y :D i a g n o s i sa n dT r e a t m e n to fH u m a nP o i s o n i n g . 2 n de d .B a l t i m o r e ,M D :W i l l i a m sa n dW i l k i n s ,1 9 9 7 . ,p .1 5 5 5 ]* * P E E RR E V I E W E D * *

/Kidney damage/ Copper causes a focal necrosis of the proximal tubule. The Fanconi syndrome-tubular proteinuria, generalized amino aciduria, phosphaturia, uricosuria, & hypercalciuria may result from the direct toxic effect of copper or the assoc hemolysis. Hemoglobinemia has been observed after ingestion ... of copper sulfate. /Copper/
[ E l l e n h o r n ,M . J . ,S .S c h o n w a l d ,G .O r d o g ,J .W a s s e r b e r g e r .E l l e n h o r n ' sM e d i c a lT o x i c o l o g y :D i a g n o s i sa n dT r e a t m e n to fH u m a nP o i s o n i n g . 2 n de d .B a l t i m o r e ,M D :W i l l i a m sa n dW i l k i n s ,1 9 9 7 . ,p .1 5 5 5 ]* * P E E RR E V I E W E D * *

Skin, Eye and Respiratory Irritations: A STRONG IRRITANT

[ T h eM e r c kI n d e x .1 0 t he d .R a h w a y ,N e wJ e r s e y :M e r c kC o . ,I n c . ,1 9 8 3 . ,p .3 7 9 ]* * P E E RR E V I E W E D * *

Drug Warnings: ... Its routine use as an emetic is not recommended, because of the potential toxicity of improperly prepared soln and the hazards attending the use of large, corrosive doses.
[ O s o l ,A .( e d . ) .R e m i n g t o n ' sP h a r m a c e u t i c a lS c i e n c e s .1 6 t he d .E a s t o n ,P e n n s y l v a n i a :M a c kP u b l i s h i n gC o . ,1 9 8 0 . ,p .7 4 8 ]* * P E E R R E V I E W E D * *

Overdose may be poisonous (enteritis, hepatitis, nephritis).

[ R o s s o f f ,I . S .H a n d b o o ko fV e t e r i n a r yD r u g s .N e wY o r k :S p r i n g e rP u b l i s h i n gC o m p a n y ,1 9 7 4 . ,p .1 3 6 ]* * P E E RR E V I E W E D * *

MAY CAUSE DRAMATIC INCR IN MORTALITY OF TURKEYS GIVEN BLACKHEAD CONTROL DRUGS CONTAINING ARSENIC & EXPOSED TO BLACKHEAD.
[ R o s s o f f ,I . S .H a n d b o o ko fV e t e r i n a r yD r u g s .N e wY o r k :S p r i n g e rP u b l i s h i n gC o m p a n y ,1 9 7 4 . ,p .1 3 6 ]* * P E E RR E V I E W E D * *

CUPRIC ... SULFATE /AS EMETIC/ OFTEN IS EFFECTIVE, BUT POTENTIAL HEMOLYTIC & RENAL TOXICITY IS TOO GREAT TO RECOMMEND USE.
[ A m e r i c a nM e d i c a lA s s o c i a t i o n ,A M AD e p a r t m e n to fD r u g s .A M AD r u gE v a l u a t i o n s .4 t he d .C h i c a g o :A m e r i c a nM e d i c a lA s s o c i a t i o n ,1 9 8 0 . ,p . 1 4 3 6 ]* * P E E RR E V I E W E D * *

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Body Burden: The milk of female vineyard workers, who were exposed to copper sulfate and a variety of other pesticides, contained 6.2 times as much copper as the milk of milkmaids who did equally hard work but not exposed to pesticides.
[ H a y e s ,W a y l a n dJ . ,J r .P e s t i c i d e sS t u d i e di nM a n .B a l t i m o r e / L o n d o n :W i l l i a m sa n dW i l k i n s ,1 9 8 2 . ,p .6 ]* * P E E RR E V I E W E D * *

Emergency Medical Treatment:

Emergency Medical Treatment:

EMT Copyright Disclaimer: The information contained in the Truven Health Analytics Inc. products is intended as an educational aid only. All treatments or procedures are intended to serve as an information resource for physicians or other competent healthcare professionals performing the consultation or evaluation of patients and must be interpreted in view of all attendant circumstances, indications and contraindications. The use of the Truven Health Analytics Inc. products is at your sole risk. These products are provided "as is" and "as available" for use, without warranties of any kind, either express or implied. Truven Health Analytics Inc. makes no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the productsAdditionally, Truven Health ANALYTICS INC. makes no representation or warranties as to the opinions or other service or data you may access, download or use as a result of use of the Truven Health ANALYTICS INC. products. All implied warranties of merchantability and fitness for a particular purpose or use are hereby excluded. Truven Health Analytics Inc. does not assume any responsibility or risk for your use of the Truven Health Analytics Inc. products. The following Overview, *** COPPER SULFATE ***, is relevant for this HSDB record chemical. Life Support:
o T h i so v e r v i e wa s s u m e st h a tb a s i cl i f es u p p o r tm e a s u r e s h a v eb e e ni n s t i t u t e d .

Clinical Effects:
0 . 2 . 1S U M M A R YO FE X P O S U R E A ) W I T HP O I S O N I N G / E X P O S U R E 1 ) T O P I C A L a ) C o p p e rs u l f a t ei sas t r o n gi r r i t a n tt os k i na n dm u c o u s m e m b r a n e s ,i n c l u d i n gn o s e ,t h r o a t ,a n de y e s . 2 ) I N H A L A T I O N a ) B u r n i n gc o p p e rs u l f a t em a yp r o d u c ei r r i t a t i n go r p o i s o n o u sg a s e s ,w h i c hm a yb ei r r i t a t i n gt ot h e r e s p i r a t o r yt r a c ta n dl u n g s . 3 ) I N G E S T I O N a ) S y m p t o m sg e n e r a l l yo c c u rw i t h i n1 5m i n u t e st o1h o u r a f t e ri n g e s t i o n .I n i t i a lp r e s e n t i n gs i g n sa n ds y m p t o m s i n c l u d ea b d o m i n a lp a i n ,n a u s e aa n dv o m i t i n g ,d i a r r h e a , s a l i v a t i o n ,a n dm e t a l l i ct a s t e .S t o o l s ,v o m i t u s , s a l i v a ,a n dm u c o u sm e m b r a n e sa r eo f t e ns t a i n e dg r e e n o rb l u e .E x t e n s i v ec o r r o s i o na n dn e c r o s i so ft h e g a s t r o i n t e s t i n a lt r a c t ,w i t hp o s s i b l ep e r f o r a t i o n ,m a y o c c u rd u et ot h ec o r r o s i v en a t u r eo fc o p p e rs u l f a t e . b ) S e v e r ep o i s o n i n g sm a yp r o g r e s st oh e m a t e m e s i s ,m e l e n a , j a u n d i c e ,h y p o t e n s i o n ,g a s t r o i n t e s t i n a lb l e e d i n g ,a n d h e m o l y s i s .R e f r a c t o r ys h o c ka n dh e p a t i ca n dr e n a l f a i l u r ew i t hc o m am a yd e v e l o pa f t e rs e v e r a ld a y s .
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4 ) P A R E N T E R A L a ) S u i c i d ea t t e m p t sw i t hi n t r a v e n o u sa n ds u b c u t a n e o u s c o p p e rs u l f a t er e s u l t e di na c u t er e n a lf a i l u r e , g a s t r o i n t e s t i n a lb l e e d i n g ,c o a g u l o p a t h y ,m e t a b o l i c a c i d o s i s ,h e m o l y s i s ,h e p a t i ci n j u r y ,a n dd e a t h . I n i t i a ls y m p t o m so fv o m i t i n g ,a b d o m i n a lp a i n , h e m a t e m e s i s ,a n dd i a r r h e ab e g a nw i t h i n1 5m i n u t e so f t h ei n j e c t i o n s . 0 . 2 . 3V I T A LS I G N S A ) W I T HP O I S O N I N G / E X P O S U R E 1 ) I n c r e a s e dt e m p e r a t u r em a yb en o t e di ns o m ec a s e s . 2 ) H y p o t e n s i o nm a yo c c u rf o l l o w i n gi n g e s t i o n s . 3 ) T a c h y c a r d i aw a sr e p o r t e di nac h i l df o l l o w i n ga na c u t e i n g e s t i o n . 0 . 2 . 4H E E N T A ) W I T HP O I S O N I N G / E X P O S U R E 1 ) E y ee x p o s u r em a yr e s u l ti ns e v e r ei r r i t a t i o n . 0 . 2 . 5C A R D I O V A S C U L A R A ) W I T HP O I S O N I N G / E X P O S U R E 1 ) H y p o t e n s i o nh a sb e e nr e p o r t e df o l l o w i n gi n g e s t i o n s . 0 . 2 . 7N E U R O L O G I C A ) W I T HP O I S O N I N G / E X P O S U R E 1 ) C e n t r a ln e r v o u sd e p r e s s i o n ,w i t hc o m ai ns e v e r ec a s e s , m a yo c c u r . 0 . 2 . 8G A S T R O I N T E S T I N A L A ) W I T HP O I S O N I N G / E X P O S U R E 1 ) V o m i t i n gu s u a l l yo c c u r sw i t h i n1 5m i n u t e so fc o p p e r s u l f a t ei n g e s t i o n .V o m i t u si sc h a r a c t e r i s t i c a l l y g r e e n i s h b l u e .H e m o r r h a g i cg a s t r o e n t e r i t i sa s s o c i a t e d w i t hm u c o s a le r o s i o n s ,am e t a l l i ct a s t e ,b u r n i n g e p i g a s t r i cs e n s a t i o n ,a n dd i a r r h e am a yo c c u r . 0 . 2 . 9H E P A T I C A ) W I T HP O I S O N I N G / E X P O S U R E 1 ) H e p a t o m e g a l y ,l i v e rt e n d e r n e s s ,a n dj a u n d i c em a yo c c u r o nt h es e c o n do rt h i r dd a yp o s t i n g e s t i o n . 0 . 2 . 1 0G E N I T O U R I N A R Y A ) W I T HP O I S O N I N G / E X P O S U R E 1 ) O l i g u r i af o l l o w e db ya n u r i am a yo c c u r2 4t o4 8h o u r s p o s t i n g e s t i o n .H e m o g l o b i n u r i aa n dh e m a t u r i am a yo c c u r . N e c r o s i so fr e n a lt u b u l a rc e l l sh a sb e e nr e p o r t e di n f a t a lc a s e s . 0 . 2 . 1 3H E M A T O L O G I C A ) W I T HP O I S O N I N G / E X P O S U R E 1 ) H e m o l y s i sh a sb e e nr e p o r t e d .M e t h e m o g l o b i n e m i ah a s o c c u r r e db u ti sr a r e . 0 . 2 . 1 4D E R M A T O L O G I C A ) W I T HP O I S O N I N G / E X P O S U R E 1 ) S k i ne x p o s u r em a yr e s u l ti ns e v e r ei r r i t a t i o n . 0 . 2 . 2 1C A R C I N O G E N I C I T Y A ) A tt h et i m eo ft h i sr e v i e w ,n os t u d i e sw e r ef o u n do nt h e p o s s i b l ec a r c i n o g e n i ca c t i v i t yo fc o p p e rs u l f a t ei n h u m a n s .

Laboratory:
A ) O b t a i nw h o l eb l o o dc o p p e rl e v e l si ns y m p t o m a t i cp a t i e n t s . B ) O b t a i nb a s e l i n el i v e rf u n c t i o nt e s t s ,r e n a lf u n c t i o n t e s t sa n dC B C . C ) M o n i t o rm e t h e m o g l o b i nl e v e l si nc y a n o t i cp a t i e n t s .

Treatment Overview:
0 . 4 . 2O R A L / P A R E N T E R A LE X P O S U R E
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A ) C o n s i d e ri n s e r t i o no fas m a l l ,f l e x i b l en a s o g a s t r i ct u b e t oa s p i r a t eg a s t r i cc o n t e n t sa f t e rl a r g e ,r e c e n t i n g e s t i o no fc o p p e rs u l f a t e .T h er i s ko fw o r s e n i n g m u c o s a li n j u r y( i n c l u d i n gp e r f o r a t i o n )m u s tb ew e i g h e d a g a i n s tt h ep o t e n t i a lb e n e f i t . B ) D I L U T I O N :I m m e d i a t e l yd i l u t ew i t h4t o8o u n c e s( 1 2 0t o 2 4 0m L )o fw a t e ro rm i l k( n o tt oe x c e e d4o u n c e s / 1 2 0m L i nac h i l d ) . C ) E m e s i si sr a p i da n ds p o n t a n e o u si nm o s tp a t i e n t s f o l l o w i n gi n g e s t i o no fc o p p e rs u l f a t e .I n d u c i n ge m e s i s i sN O Tr e c o m m e n d e dt od u et ot h er i s ko fe s o p h a g e a lo r g a s t r i cp e r f o r a t i o n . D ) A c t i v a t e dc h a r c o a lm a yo b s c u r ee n d o s c o p yf i n d i n g sb u t m a ya l s oa d s o r bac l i n i c a l l ys i g n i f i c a n ta m o u n to f c o p p e rs u l f a t e .I t su s es h o u l db ec o n s i d e r e da f t e r s i g n i f i c a n ti n g e s t i o n s . E ) K e e pp a t i e n tN P Of o l l o w i n gm u c o s a ld e c o n t a m i n a t i o nu n t i l a f t e re n d o s c o p yc o n s u l t a t i o n . F ) E N D O S C O P Y :E a r l ye n d o s c o p ya l l o w sp a t i e n t sw i t h o u t g a s t r o i n t e s t i n a li n j u r yt ob em e d i c a l l yc l e a r e d ,a n d p r o v i d e si m p o r t a n tp r o g n o s t i ci n f o r m a t i o ni np a t i e n t s w h od oh a v ev a r y i n gd e g r e e so fg a s t r o i n t e s t i n a lb u r n s . I na d d i t i o n ,i tf a c i l i t a t e st h es a f ep l a c e m e n to f e n t e r a lf e e d i n gt u b e st h e r e b ys h o r t e n i n gt h ep e r i o do f t i m et h a tp a t i e n t sw i t hb u r n sa r ew i t h o u te n t e r a l n u t r i t i o n a ls u p p o r t .E n d o s c o p ys h o u l db ep e r f o r m e d w i t h i nt h ef i r s t2 4h o u r sp o s t i n g e s t i o n ,a n ds h o u l db e a v o i d e df r o m2d a y st o2w e e k sp o s t i n g e s t i o ns i n c e w o u n dt e n s i l es t r e n g t hi sl o w e s ta n dt h er i s ko f p e r f o r a t i o nh i g h e s td u r i n gt h i st i m e .E n d o s c o p yi s i n d i c a t e df o ra l la d u l t sw i t hd e l i b e r a t ei n g e s t i o no r a n ys i g n so rs y m p t o m sa t t r i b u t a b l et oi n g e s t i o n ,a n df o r c h i l d r e nw i t hs t r i d o r ,v o m i t i n g ,o rd r o o l i n g .C o n s i d e r e n d o s c o p yi nc h i l d r e nw i t hd y s p h a g i a ,r e f u s a lt o s w a l l o w ,s i g n i f i c a n to r a lb u r n s ,o ra b d o m i n a lp a i n .I f s e c o n do rt h i r dd e g r e eb u r n sa r ef o u n d ,f o l l o w1 0t o2 0 d a y sl a t e rw i t hb a r i u ms w a l l o wo re s o p h a g r a m . G ) P H A R M A C O L O G I CT R E A T M E N T :T h eu s eo fc o r t i c o s t e r o i d si s c o n t r o v e r s i a l .S o m ea u t h o r sh a v ea d v o c a t e dt h eu s eo f c o r t i c o s t e r o i d sf o rs e c o n dd e g r e eb u r n sw i t h i n4 8h o u r s o fi n g e s t i o ni np a t i e n t sw i t h o u tg a s t r o i n t e s t i n a l b l e e d i n go re v i d e n c eo fp e r f o r a t i o n .H o w e v e r ,t w o p r o s p e c t i v et r i a l so fc o r t i c o s t e r o i d sf o re s o p h a g e a l i n j u r ya f t e rc a u s t i ci n g e s t i o ni n d i c a t e dn ob e n e f i ti n a n yg r a d ei n j u r y ,a n dar e c e n tm e t a a n a l y s i sf o u n dn o b e n e f i to fc o r t i c o s t e r o i d si ng r a d eI Ib u r n sa n d e v i d e n c eo fh a r mi ng r a d eI I Ib u r n s ,s ot h e ya r en o t r o u t i n e l yr e c o m m e n d e d .A n t i b i o t i c sa r ei n d i c a t e df o r s u s p e c t e dp e r f o r a t i o no ri n f e c t i o na n di np a t i e n t s r e c e i v i n gc o r t i c o s t e r o i d s H ) S U R G I C A LO P T I O N S :I n i t i a l l y ,i fs e v e r ee s o p h a g e a lb u r n s a r ef o u n das t r i n gm a yb ep l a c e di nt h es t o m a c ht o f a c i l i t a t el a t e rd i l a t i o n .I n s e r t i o no fas p e c i a l i z e d n a s o g a s t r i ct u b ea f t e rc o n f i r m a t i o no fac i r c u m f e r e n t i a l b u r nm a yp r e v e n ts t r i c t u r e s .D i l a t i o ni si n d i c a t e da f t e r 2t o4w e e k si fs t r i c t u r e sa r ec o n f i r m e d ;i f u n s u c c e s s f u l ,e i t h e rc o l o n i ci n t r a p o s i t i o no rg a s t r i c t u b ep l a c e m e n tm a yb ep e r f o r m e d .C o n s i d e re a r l y l a p a r o t o m yi np a t i e n t sw i t hs e v e r ee s o p h a g e a la n d / o r g a s t r i cb u r n s . I ) H Y P O T E N S I O N :I n f u s e1 0t o2 0m L / k gi s o t o n i cf l u i d .I f
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h y p o t e n s i o np e r s i s t s ,a d m i n i s t e rd o p a m i n e( 5t o2 0 m c g / k g / m i n )o rn o r e p i n e p h r i n e( A D U L T :b e g i ni n f u s i o na t 0 . 5t o1m c g / m i n ;C H I L D :b e g i ni n f u s i o na t0 . 1 m c g / k g / m i n ) ;t i t r a t et od e s i r e dr e s p o n s e . J ) R H A B D O M Y O L Y S I S :A d m i n i s t e rs u f f i c i e n t0 . 9 %s a l i n et o m a i n t a i nu r i n eo u t p u to f2t o3m L / k g / h r .M o n i t o ri n p u t a n do u t p u t ,s e r u me l e c t r o l y t e s ,C K ,a n dr e n a lf u n c t i o n . D i u r e t i c sm a yb en e c e s s a r yt om a i n t a i nu r i n eo u t p u t . U r i n a r ya l k a l i n i z a t i o ni sN O Tr o u t i n e l yr e c o m m e n d e d . K ) M E T H E M O G L O B I N E M I A :A d m i n i s t e r1t o2m g / k go f1 % m e t h y l e n eb l u es l o w l yI Vi ns y m p t o m a t i cp a t i e n t s . A d d i t i o n a ld o s e sm a yb er e q u i r e d . L ) C H E L A T I O N-T h e r ei sl i t t l ec l i n i c a le x p e r i e n c ei nt h e u s eo fc h e l a t o r si nt h es e t t i n go fa c u t ec o p p e rs u l f a t e i n t o x i c a t i o n .D a t ao ne f f i c a c yi sd e r i v e df r o mp a t i e n t s w i t hc h r o n i cc o p p e ri n t o x i c a t i o n( W i l s o n ' sd i s e a s e , I n d i a nc h i l d h o o dc i r r h o s i s )a n da n i m a ls t u d i e s .B A L , p e n i c i l l a m i n e ,D M P Sa n dE D T Ah a v eb e e nu s e d . D p e n i c i l l a m i n ei sc o n s i d e r e dt h ed r u go fc h o i c ef o r W i l s o n ' sd i s e a s e ,ac o n d i t i o no fc h r o n i cc o p p e r o v e r l o a d . 1 ) D P E N I C I L L A M I N E :U s eo n l yi fl e s st o x i ca g e n t sn o t a v a i l a b l eo rn o tt o l e r a t e d .U S U A LD O S E :A D U L T :1 0 0 0t o 1 5 0 0m g / d a yd i v i d e de v e r y6t o1 2h o u r s .C H I L D :1 0 m g / k g / d a yi n i t i a l l y ,g r a d u a l l yi n c r e a s et o3 0m g / k g / d a y d i v i d e di nt w oo rt h r e ed o s e sa st o l e r a t e d .A v o i di f p e n i c i l l i na l l e r g i c .M o n i t o rf o rp r o t e i n u r i a , h e m a t u r i a ,r a s h ,l e u k o p e n i a ,t h r o m b o c y t o p e n i a . 2 ) A d m i n i s t e rB A L( D i m e r c a p r o l )3t o5m g / k g / d o s eI Me v e r y 4h o u r sf o r2d a y s ;t h e ne v e r y4t o6h o u r sf o ra n a d d i t i o n a l2d a y s ;t h e ne v e r y4t o1 2h o u r sf o ru pt o7 a d d i t i o n a ld a y s . 0 . 4 . 4E Y EE X P O S U R E A ) H O M EI R R I G A T I O N-E x p o s e de y e ss h o u l db ei r r i g a t e dw i t h c o p i o u sa m o u n t so fw a t e rf o ra tl e a s t3 0m i n u t e s .A n e x a m i n a t i o ns h o u l da l w a y sb ep e r f o r m e d .O p h t h a l m o l o g i c c o n s u l t a t i o ns h o u l db eo b t a i n e d . B ) M E D I C A LF A C I L I T Y :I m m e d i a t e l yi r r i g a t ee a c ha f f e c t e de y e w i t h2l i t e r so fs t e r i l e0 . 9 %s a l i n eo v e ra b o u t1 5t o2 0 m i n u t e s .A f t e rt h i si n i t i a lp e r i o do fi r r i g a t i o nt h e c o r n e a lp Hm a yb ec h e c k e dw i t hl i t m u sp a p e ra n dab r i e f e x t e r n a le y ee x a mp e r f o r m e d .C o n t i n u ed i r e c tc o p i o u s i r r i g a t i o nw i t hs t e r i l e0 . 9 %s a l i n eu n t i lt h e c o n j u n c t i v a lf o r n i c e sa r ef r e eo fp a r t i c u l a t em a t t e ra n d r e t u r n e dt op Hn e u t r a l i t y( p H7 . 4 ) .O n c ei r r i g a t i o ni s c o m p l e t eaf u l le y ee x a ms h o u l db ep e r f o r m e dw i t h c a r e f u la t t e n t i o nt ot h ep o s s i b i l i t yo fp e r f o r a t i o n . C ) E Y EA S S E S S M E N T :T h ee x t e n to fe y ei n j u r y( d e g r e eo f c o r n e a lo p a c i f i c a t i o na n dp e r i l i m b a lw h i t e n i n g )m a yn o t b ea p p a r e n tf o r4 8t o7 2h o u r sa f t e rt h eb u r n . 0 . 4 . 6P A R E N T E R A LE X P O S U R E A ) P a r e n t e r a li n j e c t i o n s ,i n c l u d i n gi n t r a v e n o u sa n d s u b c u t a n e o u s ,h a v eb e e nr e p o r t e di ns u i c i d a lp o i s o n i n g s . S i g n sa n ds y m p t o m sa r es i m i l a rt ot h o s er e s u l t i n gf r o m i n g e s t i o n s .R e f e rt ot h eO r a lE x p o s u r e st r e a t m e n t s e c t i o n .

Range of Toxicity:
A ) I n g e s t i o no f2 5 0m i l l i g r a m so fc o p p e rs u l f a t em a yr e s u l t i nt o x i c i t y . B ) S e v e r ei n t o x i c a t i o ni sa s s o c i a t e dw i t hs e r u mc o p p e r
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l e v e l sg r e a t e rt h a n5 0 0m i c r o g r a m s / d e c i l i t e r . C ) F a t a l i t i e sh a v eo c c u r r e df o l l o w i n gi n g e s t i o na n d i n t r a v e n o u si n j e c t i o no f1g r a mo fc o p p e rs u l f a t e . D ) S u r v i v a lh a sb e e nr e p o r t e df o l l o w i n gi n g e s t i o no fa sm u c h a s3 0g r a m s .
[ R u m a c kB HP O I S I N D E X ( R )I n f o r m a t i o nS y s t e mM i c r o m e d e x ,I n c . ,E n g l e w o o d ,C O ,2 0 1 3 ;C C I SV o l u m e1 5 8 ,e d i t i o ne x p i r e sN o v ,2 0 1 3 .H a l lA H &R u m a c kB H( E d s ) :T O M E S ( R )I n f o r m a t i o nS y s t e mM i c r o m e d e x ,I n c . ,E n g l e w o o d ,C O ,2 0 1 3 ;C C I SV o l u m e1 5 8 ,e d i t i o ne x p i r e sN o v ,2 0 1 3 . ] * * P E E RR E V I E W E D * *

Antidote and Emergency Treatment: Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for shock and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, 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 related compounds/
[ B r o n s t e i n ,A . C . ,P . L .C u r r a n c e ;E m e r g e n c yC a r ef o rH a z a r d o u sM a t e r i a l sE x p o s u r e .2 n de d .S t .L o u i s ,M O .M o s b yL i f e l i n e .1 9 9 4 . ,p . 3 5 0 ]* * P E E RR E V I E W E D * *

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 for signs of fluid overload. For hypotension with signs of hypovolemia, administer fluid cautiously. Consider vasopressors if hypotensive with a normal fluid volume. Watch for signs of fluid overload ... . Use proparacaine, hydrochloride to assist eye irrigation ... . /Copper and related compounds/
[ B r o n s t e i n ,A . C . ,P . L .C u r r a n c e ;E m e r g e n c yC a r ef o rH a z a r d o u sM a t e r i a l sE x p o s u r e .2 n de d .S t .L o u i s ,M O .M o s b yL i f e l i n e .1 9 9 4 . ,p . 3 5 1 ]* * P E E RR E V I E W E D * *

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 water may make a substantial additional contribution to the total daily intake of copper, particularly in households where corrosive waters have stood in copper pipes. ... All other intakes of copper (inhalation and dermal) are insignificant in comparison to the oral route. Inhalation adds 0.3-2.0 ug/day from dusts and smoke. Women using copper IUDs are exposed to only 80ug or less of copper per day from this source. The homeostasis 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 structural purposes. The cellular pathways of uptake, incorporation into protein and export of copper are conserved in mammals and modulated by the metal itself. Copper is mainly absorbed through the gastrointestinal tract. From 20 to 60% of the dietary copper is absorbed, with the rest being excreted through the feces. Once the metal passes through the basolateral membrane it is transported to the liver bound to serum 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 bile. The transport of copper to the peripheral tissues is accomplished through the plasma attached to serum albumin, ceruloplasmin or low-molecular weight complexes. ... The biochemical toxicity of 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. The toxicity of a single oral dose of copper varies widely between species. ... The major soluble salts (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 signs of toxicity other than a dose-related reduction in growth after ingestion ... The effects included inflammation of the liver and degeneration of kidney tubule epithelium. ... Some testicular degeneration and reduced neonatal body and organ weights were seen in rats ... and fetotoxic effects and malformations were seen at high dose levels. ... Neurochemical changes have been reported after oral administration ... A limited number of immunotoxicity studies showed humoral and cell-mediated immune function impairment in mice after oral intakes in drinking-water ... Copper is an essential element and adverse health effects /in humans/ are related to deficiency as well as excess. Copper deficiency is associated with anemia, neutropenia and bone abnormalities but clinically evident deficiency is relatively infrequent in humans. .. Except for occasional acute incidents of copper poisoning, few effects are noted in normal /human/ populations. Effects of single exposure following suicidal or accidental oral exposure have been 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 repeated ingestion of drinking-water containing high copper concentrations, and liver failure has been reported following chronic ingestion of copper. Dermal exposure has not been associated with systemic toxicity but copper may induce allergic responses in sensitive individuals. Metal fume fever from inhalation of high concentrations in the air in occupational settings have been reported ... A number of groups are described where apparent disorders in copper homeostasis result in greater sensitivity to copper deficit or excess than the general population. Some disorders have a well-defined genetic basis. These include Menkes disease, a generally fatal manifestation of copper deficiency; Wilson disease (hepatolenticular degeneration), a condition leading to progressive accumulation of copper; and hereditary aceruloplasminemia, 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 based copper 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 chronic liver disease. Groups at risk of copper deficiency include infants (particularly low birth weight/preterm babies, children recovering from malnutrition, and babies fed exclusively with cow's milk), people with maladsorption syndrome (e.g., celiac disease, sprue, cystic fibrosis), and patients on total parenteral nutrition. Copper deficiency has been implicated in the pathogenesis of cardiovascular disease. The adverse effects of copper must be balanced against its essentiality. Copper is an essential element for all biota ... At least 12 major proteins require copper as an integral part of their structure. It is essential for the utilization of iron in the formation of hemoglobin, and most crustaceans and molluscs possess the copper-containing hemocyanin as their main oxygen-carrying blood protein. ... A critical factor in assessing the hazard of copper is its bioavailablity. Adsorption of copper to particles and complexation by organic matter can greatly limit the degree to which copper will be accumulated ... At many sites, physiochemical factors limiting bioavailability will warrant higher copper limits. ...
[ E n v i r o n m e n t a lH e a l t hC r i t e r i a2 0 0 :C o p p e rp p .1 1 1( 1 9 9 8 )b yt h eI n t e r n a t i o n a lP r o g r a m m eo nC h e m i c a lS a f e t y( I P C S )u n d e rt h ej o i n t s p o n s o r s h i po ft h eU n i t e dN a t i o n sE n v i r o n m e n tP r o g r a m m e ,t h eI n t e r n a t i o n a lL a b o u rO r g a n i s a t i o na n dt h eW o r l dH e a l t hO r g a n i z a t i o n . ] * * P E E RR E V I E W E D * *

Non-Human Toxicity Excerpts: IN ANIMALS INGESTION OF 3 OZ OF 1% SOLN OF CUPRIC SULFATE WILL PRODUCE INTENSE INFLAMMATION OF GASTROINTESTINAL TRACT, WITH SYMPTOMS OF ABDOMINAL PAIN, VOMITING, & DIARRHEA.
[ B r o w n i n g ,E .T o x i c i t yo fI n d u s t r i a lM e t a l s .2 n de d .N e wY o r k :A p p l e t o n C e n t u r y C r o f t s ,1 9 6 9 . ,p .1 4 7 ]* * P E E RR E V I E W E D * *

Daily oral doses of 20 mg of copper sulfate per kg body weight given to sheep resulted in hemolysis after nine weeks. ... Hemolysis also caused acute tubular renal damage in the sheep.
[ F r i b e r g ,L . ,N o r d b e r g ,G . F . ,K e s s l e r ,E .a n dV o u k ,V . B .( e d s ) .H a n d b o o ko ft h eT o x i c o l o g yo fM e t a l s .2 n de d .V o l sI ,I I . :A m s t e r d a m : E l s e v i e rS c i e n c eP u b l i s h e r sB . V . ,1 9 8 6 . ,p .2 4 5 ]* * P E E RR E V I E W E D * *

COPPER SALTS ADMIN IV TO HAMSTERS ON DAY 8 OF GESTATION CAUSED EMBRYONIC RESORPTIONS AND DEVELOPMENTAL MALFORMATIONS IN SURVIVING OFFSPRING. HEART DEFECTS OCCURRED. COPPER IN CHELATED FORM (COPPER CITRATE) WAS EMBRYOCIDAL BUT MUCH MORE EMBRYOPATHIC THAN IN UNCOMPLEXED FORM (COPPER SULFATE).
[ F E R MV H ,H A N L O ND P ;B I O LR E P R O D1 1( 1 ) :9 7( 1 9 7 4 ) ]* * P E E RR E V I E W E D * *P u b M e dA b s t r a c t

DAILY SC INJECTIONS OF 0.26 MG OF COPPER AS COPPER SULFATE FOR 60 DAYS TO RATS. ... THE EXPOSED RATS 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.
[ F r i b e r g ,L . ,N o r d b e r g ,G . F . ,K e s s l e r ,E .a n dV o u k ,V . B .( e d s ) .H a n d b o o ko ft h eT o x i c o l o g yo fM e t a l s .2 n de d .V o l sI ,I I . :A m s t e r d a m : E l s e v i e rS c i e n c eP u b l i s h e r sB . V . ,1 9 8 6 . ,p .V 22 4 4 ]* * P E E RR E V I E W E D * *

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% COPPER SULFATE CAUSED ... ANOREXIA, HEMOLYTIC ANEMIA, ICTERUS, & HEMOGLOBINURIA FOLLOWED BY DEATH IN A DAY OR 2. ... AT NECROPSY, LIVER, KIDNEYS, & SPLEEN SHOWED ... DEGENERATIVE CHANGES.
[ C l a y t o n ,G .D .a n dF .E .C l a y t o n( e d s . ) .P a t t y ' sI n d u s t r i a lH y g i e n ea n dT o x i c o l o g y :V o l u m e2 A ,2 B ,2 C :T o x i c o l o g y .3 r de d .N e wY o r k : J o h nW i l e yS o n s ,1 9 8 1 1 9 8 2 . ,p .1 6 2 4 ]* * P E E RR E V I E W E D * *

GUINEA PIGS WERE EXPOSED FOR 1 HR TO AEROSOLS OF SULFATE SALTS. WITH THE EXCEPTION OF SODIUM SULFATE, ALL THE SULFATES CAUSED SLIGHT INCREASE IN PULMONARY FLOW RESISTANCE & SLIGHT DECREASE IN PULMONARY COMPLIANCE. COPPER SULFATE WAS LEAST IRRITANT AMONG AMMONIUM SULFATE & AMMONIUM BISULFATE AEROSOLS.
[ A M D U RM OE TA L ;E N V I R O NR E S1 6( 1 3 ) :1 8( 1 9 7 8 ) ]* * P E E RR E V I E W E D * *P u b M e dA b s t r a c t

EFFECTS OF INTRATRACHEALLY ADMIN AIR POLLUTANT CHEMICALS ON SUSCEPTIBILITY OF MICE TO INFECTION BY AEROSOLIZED BACTERIA WERE COMPARED WITH EFFECTS FROM INHALATION EXPOSURES. THREE (CADMIUM SULFATE, COPPER SULFATE, & ZINC SULFATE) OF THE TWENTY TWO CMPD STUDIED BY INHALATION WHICH CAUSED INCR MORTALITY IN MICE BECAUSE OF INFECTION AFTER 3 HR EXPOSURE TO 1-2 MG/CU M, SHOWED LARGE (GREATER THAN 40% OVER SHAM INJECTED) MORTALITY INCREASES WHEN ADMIN BY INTRATRACHEAL INJECTION AT LUNG CONCN EQUIVALENT TO INHALATION EXPOSURES.
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[ H A T C HG EE TA L ;A MR E VR E S P I RD I S1 2 4( 2 ) :1 6 7 7 3( 1 9 8 1 ) ]* * P E E RR E V I E W E D * *P u b M e dA b s t r a c t

CUPRIC SULFATE WAS LETHAL TO FRESH WATER PALAEMONID PRAWN (MACROBRACHIUM KISTNENSIS) AT 2.25 PPM. AFTER 24 HR EXPOSURE, OXYGEN CONSUMPTION INCR.
[ N A G A B H U S H A N A MR ,K U L K A R N IG K ;P R O CI N D I A NN A T LS C IA C A D ,P A R TB ;4 7( 3 ) :3 8 0 6( 1 9 8 1 ) ]* * P E E RR E V I E W E D * *

10 PPM CUPRIC SULFATE INCREASED THE BLOOD GLUCOSE, LACTATE DEHYDROGENASE, GLUTAMIC ACID OXALACETIC ACID TRANSAMINASE, & GLUTAMIC ACID PYRUVIC ACID TRANSAMINASE LEVELS IN THREE SPECIES OF FISH. IN INCREASING ORDER SILVER CARP, CARP & EUROPEAN WELS.
[ N E M C S O KJ ,B O R O S SL ;A C T AB I O LA C A DS C IH U N G3 3( 1 ) :2 3 7( 1 9 8 2 ) ]* * P E E RR E V I E W E D * *P u b M e dA b s t r a c t

METHOD FOR ASSESSING CHRONIC EFFECT OF COPPER /SRP: AS CUPRIC SULFATE/ ON MIDGE LARVA (PARATANYTARSUS PARTHENOGENETICUS) IS PRESENTED. GROWTH & REPRODUCTION WERE RELATED TO COPPER CONCN GREATER THAN 0.08 MG/L; 50% REPRODUCTIVE IMPAIRMENT @ 0.37 MG/L. GROWTH & FOOD INTAKE WERE INVERSELY RELATED TO CONCN.
[ H A T A K E Y A M AW ,Y A S U N OM ;A R C HC O N T A MT O X I C O L1 0( 6 ) :7 0 5 1 3( 1 9 8 1 ) ]* * P E E RR E V I E W E D * *

Decrease in hemolymph glucose in Viviparus bengalensis exposed to cupric sulfate (0.001%) less than or equal to 24 hr was directly proportional to the time of exposure. At the end of 24 hr there was a marked decrease in the glucose level. In the foot muscle and hepatopancreas of the snail, cupric sulfate decreased the glycogen reserve. Protein levels in these tissues were increased whereas the lipid content was decreased.
[ K u l k a r n iA B ,U t i c a lV N ;JE n v i rB i o l4( 4 ) :2 1 5 2 0( 1 9 8 3 ) ]* * P E E RR E V I E W E D * *

Hamsters were exposed for 4 hr to cupric sulfate (4.8 mg/cu m). ... Macrophage endocytosis was significantly 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.
[ S k o r n i kW A ,B r a i nJ D ;A mR e vR e s p i rD i s1 2 8( 2P a r t1 ) :2 9 7 3 0 3( 1 9 8 3 ) ]* * P E E RR E V I E W E D * *P u b M e dA b s t r a c t

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.
[ N a g a b h u s h a n a mR ,D e s h p a n d eU D ;JE n v i rB i o l3( 4 ) :1 5 1 4( 1 9 8 2 ) ]* * P E E RR E V I E W E D * *

... Marked dose dependent testicular atrophy was noticed in ... copper sulfate ... fed birds. Mild to severe spermatogenic arrest concomitant with testicular atrophy was observed. Histochemically, the interstitial (Leydig) cells and seminiferous tubules showed intense accumulation of cholesterol positive lipids ... .
[ S h i v a n a n d a p p aTe ta l ;P o u l tS c i6 2( 2 ) :4 0 5 8( 1 9 8 3 ) ]* * P E E RR E V I E W E D * *P u b M e dA b s t r a c t

The results of preliminary investigations on the toxicity of /copper sulfate/ ... for 15, 30, and 45 day old sheatfish and to the encysted stages of Icthyophthirius multifiliis (ich) showed that an interruption of the parasite life cycle in this stage, without harming the fish, seems to be possible. A concn of 15 ppm copper sulfate /was/ suitable for the elimination of the encysted parasites in the presence of 15 day old and older sheatfish ... .
[ A n t y c h o w i c zJe ta l ;B u l lV e tI n s tP u l a w y2 5( 4 ) :2 0 3( 1 9 8 2 ) ]* * P E E RR E V I E W E D * *

... The motility of /rat/ cauda epididymal spermatozoa in vitro in the presence of different concn of cupric sulfate was investigated. In vitro decrease in motility was more rapid with increasing concn of cupric sulfate soln.
[ C h i n o yN J ,S a n j e e v a nA G ;I n tJA n d r o l3( 6 ) :7 1 9 7( 1 9 8 0 ) ]* * P E E RR E V I E W E D * *P u b M e dA b s t r a c t

Adult male blue crabs (Callinectes sapidus) ... were exposed for 48 hr to river water containing hydrated copper sulfate reagent at concn of 0, 50, 100, and 1000 ug/l. ... Exposure to 1000 ug/l copper sulfate caused 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 bandlike region, ... loss of the large dendrite profiles, and occurrence of electron dense filamentous structures not present in control preparations. Changes in chemoreceptor structures following 100 ug/l copper sulfate were 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/
[ B o d a m m e rJ ;P r e l i m i n a r yO b s e r v a t i o no nt h eC y t o p a t h o l o g i c a lE f f e c t so fC o p p e rS u l f a t eo nt h eC h e m o r e c e p t o r so fC a l i n e c t e ss a p i d u si n M a r i n eP o l l u t i o n :F u n c t i o n a lR e s p o n s e s .V e r n b e r g ,W Be ta le d sp . 2 2 3 3 7( 1 9 7 9 ) ]* * P E E RR E V I E W E D * *

... Submicron aerosols of /cupric sulfate/ in concn of 4.1-8.8 mg/cu m, administered for 4 hr to anesthetized dogs, 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 acidosis and a decrease of specific total conductance.
[ S a c k n e rM Ae ta l ;JT o x i c o lE n v i r o nH e a l t h7( 6 ) :9 5 1 7 2( 1 9 8 1 ) ]* * P E E RR E V I E W E D * *P u b M e dA b s t r a c t

No change was observed in whole animal respiration in snails exposed to 2 ppm copper sulfate for 6 hr.
[ B a b uG R ,R a oP V ;B u l lE n v i r o nC o n t a mT o x i c o l3 4( 3 ) :3 9 6 4 0 2( 1 9 8 5 ) ]* * P E E RR E V I E W E D * *P u b M e dA b s t r a c t

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The effects of copper sulfate (0.0004 and 105 ug copper/l) on growth, reproduction, survival, and hemoglobin content of Daphnia magna were studied in hard reconstituted water and compared to the response in diluted water without the addition of copper. The 48 hr EC50 (immobilization) for unfed neonates was 6.5 ug copper/l and the 48 hr and 21 day LC50s (median lethal concn) for fed neonates were 18.5 and 1.4 ug copper/l, respectively.
[ D a v eG ;C o m pB i o c h e mP h y s i o l ,C :C o m pP h a r m a c o lT o x i c o l7 8 C( 2 ) :4 3 9 4 3( 1 9 8 4 ) ]* * P E E RR E V I E W E D * *

Copper sulfate was toxic as detected by sewage sludge bacterial respiration, nitrification, and growth assays; with biological oxygen demand assay being more suitable for rivers.
[ K i n gE F ;D r u gC h e mT o x i c o l1( T o x i cS c r e e n i n gP r o c e dU s i n gB a c tS y s t ) :1 7 5 9 4( 1 9 8 4 ) ]* * P E E RR E V I E W E D * *

CARBOHYDRATE METABOLITES LIKE HEMOLYMPH GLUCOSE & MIDGUT GLAND GLYCOGEN SHOWED INVERSE RELATION IN THEIR CHANGES AFTER LESS THAN 72 HR EXPOSURE TO 1.0 PPM CUPRIC SULFATE BUT BOTH METABOLITES DECREASED GREATLY AFTER PROLONGED (120 HR) EXPOSURE OF FRESHWATER PRAWN (MACROBRACHIUM KISTNENSIS).
[ N A G A B H U S H A N A MR ,K U L K A R N IG K ;P R O CI N D I A NN A T LS C IA C A D ,P A R TB4 7( 3 ) :3 8 0 6( 1 9 8 1 ) ]* * P E E RR E V I E W E D * *

Groups of eight pigs /were maintained/ on a corn-soy diet supplemented with 250 (3.2 mg copper(2+)/kg/day) or 500 (5.5 mg copper(2+)/kg/day) ppm copper sulfate for 61 days. In a second experiment, groups of 12 pigs were fed a corn-soy diet supplemented with 0, 150 (1.8 mg copper(2+)/kg/day), 200 (2.5 mg copper(2+)/kg/day), or 250 (2.9 mg copper(2+)/kg/day) ppm copper sulfate for 88 days. The control group was normal and had normal blood parameters. Pigs fed 150-250 ppm copper sulfate (1.8-3.2 mg copper(2+)/kg/day) all had accelerated weight gain but also had increases in liver copper that indicated a significant (p< 0.05) linear correlation with dose. Reduced growth and hemoglobin levels and increased liver copper were observed in the 500 ppm treatment group.
[ U S E P A ;D r i n k i n gW a t e rC r i t e r i aD o c u m e n tf o rC o p p e r( F i n a lD r a f t )p . V 1 0( 1 9 8 5 )E P A 6 0 0 / X 8 4 1 9 0 1 ]* * P E E RR E V I E W E D * *

In a subchronic study, the liver and kidneys of rats treated with 2,000 ppm copper (as copper sulfate) in the diet for 15 weeks experienced a triphasic response during the exposure period. The first stage was characterized by the accumulation of copper with some signs of cellular disruption followed by a second stage of severe hepatic and renal necrosis. The final phase was marked by decreasing copper content and regeneration of damaged tissue as the animals appeared to develop tolerence against the effects of copper.
[ U S E P A ;H e a l t hI s s u eA s s e s s m e n t :C o p p e rp . 3 3( 1 9 8 7 )E P A / 6 0 0 / 8 8 7 / 0 0 1 ]* * P E E RR E V I E W E D * *

/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 by interfering with iron metabolism and binding. Hepatic damage was observed in three histopathological studies of sheep chronically exposed to copper. /Copper sulfate, pentahydrate/
[ U S E P A ;H e a l t hI s s u eA s s e s s m e n t :C o p p e rp . 2 6( 1 9 8 7 )E P A / 6 0 0 / 8 8 7 / 0 0 1 ]* * P E E RR E V I E W E D * *

Liver and kidney necrosis /occurred/ in rats given copper sulfate by gavage for 20 days. Groups of 10 male albino rats, (Rattus rattus albino) 90 days of age were given 0 or 100 mg copper sulfate/kg body wt/day by gavage (vehicle not reported) for 20 days. Based on the molecular weight of copper/copper sulfate, the amount 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 red blood cell count, white blood cell count, hemoglobin level, and hematocrit percentage. All animals were then killed, and their livers and kidneys were removed for wet weight measurement and routine histological examination. Several changes in treated rats, absent in control rats, were observed upon gross 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 treated rats 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 was observed. The livers of treated rats showed centrilobular necrosis, perilobular sclerosis, and heavy deposition of copper in centrilobular parenchyma. Necrosis, tubular engorgement, and copper retention were observed in the kidneys of treated rats.
[ U S E P A ;D r i n k i n gW a t e rC r i t e r i aD o c u m e n tf o rC o p p e r( F i n a lD r a f t )p . V 6( 1 9 8 5 )E P A 6 0 0 / X 8 4 1 9 0 1 ]* * P E E RR E V I E W E D * *

Pigs appear to be more sensitive to the acute toxicity of copper. Adverse effects /were reported/ in pigs given copper supplements in doses as low as 6.4 mg copper(+2) kg/day for 48 days and 2.6 mg copper(+2) kg/day for 79 days. Beneficial effects of copper (as copper sulfate) supplementation in Hampshire and Yorkshire pigs (approximately 24 kg) at doses of 1.8-3.2 mg for 61-88 days /were also reported/. Administration of 5.5 mg copper(+2) kg/day for 61 days caused adverse effects (eg, growth reduction, reduced hemoglobin and increased hepatic copper.
[ U S E P A ;H e a l t hI s s u eA s s e s s m e n t :C o p p e rp . 4 9( 1 9 8 7 )E P A / 6 0 0 / 8 8 7 / 0 0 1 ]* * P E E RR E V I E W E D * *

The observation of teratogenic effects in two strains of mice fed diets supplemented with copper sulfate before mating /are reported/. Various numbers of C57BL and DBA mice were maintained for 1 month on diets supplemented with 0, 500, 1,000, 1,500, 2,000, 3,000, 4,000 ppm copper sulfate. These concentrations are equivalent to 0, 199, 398, 597, 796, 1,195, and 1,593 ppm copper, respectively.
toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+916 12/31