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Acute ingestion of copper sulphate: A review on its clinical manifestations and management



Ingestion of copper sulphate is an uncommon mode of poisoning in the Indian subcontinent. Cases are mainly suicidal in nature. The clinical course of the copper sulphate intoxicated patient is often complex involving intravascular hemolysis, jaundice and renal failure. The treatment is mainly supportive. In severe cases methemoglobinemia needs treatment. Mortality is quite high in severe cases. A comprehensive review of the clinical presentation and management of copper sulphate poisoning is done.
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Review Article
Acute ingestion of copper sulphate: A review on its
clinical manifestations and management
Kavitha Saravu, Jimmy Jose*, Mahadeva N. Bhat**, Beena Jimmy*, B. A. Shastry
Ingestion of copper sulphate is an uncommon mode of poisoning in the Indian subcontinent. Cases are mainly sui-
cidal in nature. The clinical course of the copper sulphate intoxicated patient is often complex involving intravascular
hemolysis, jaundice and renal failure. The treatment is mainly supportive. In severe cases methemoglobinemia needs
treatment. Mortality is quite high in severe cases. A comprehensive review of the clinical presentation and manage-
ment of copper sulphate poisoning is done.
Key words: Acute ingestion, copper sulphate, poisoning
Department of Medicine, Kasturba Medical College, Manipal, *Department
of Clinical Pharmacy, 4th Floor Shirdi Sai Baba Cancer Hospital, Kasturba
Hospital, Manipal, **Canara Health Centre, First Floor, Sheikh Hina Complex,
Anjuman Road, Udupi, India
For correspondence:
Dr. Kavitha Saravu, Department of Medicine, Kasturba Medical College,
Manipal University, Manipal - 576 104, India.
Copper sulphate forms bright blue crystals containing
Þ ve molecules of water [CuSO4. 5H2O]. It is commonly
known as “Blue Vitriol” or “Blue Stone”. It is used chieß y
for agricultural purposes as a pesticide and in leather
industry. It was also being used as a precipitator in
heavy metal poisoning and was used to treat gastric and
topical exposure to phosphorous. It has a nauseous and
metallic taste. Solutions are acid to litmus, freely soluble
in water.[1,2] It is consumed mainly with suicidal intentions.
Accidental poisonings have been reported from children
as well.[3-7]
The incidence of copper sulphate poisoning varies at
different geographical areas depending on the local use
of copper sulphate and the availability of other suicidal
poisons. Its incidence is reported to be 34% and 65%
of the total poisoning cases in two studies from Agra
and New Delhi in 1960’s. The mortality rates vary from
14-18.8%.[8,9] In another study from Aligarh in 1970’s, it
was the commonest mode of poisonings at that center
accounting to 118 cases over four and a half years.[10]
However, the incidence of copper sulphate poisoning is
declining in certain parts of India. Chugh et al., reported
a decrease in the number of cases of acute renal failure
attributed to intentional copper sulphate ingestion among
patients admitted to a renal unit in northern India over a
period of three decades from Þ ve per cent in the 1960s
to one per cent in the 1980s.[11] In another autopsy
series from north India, copper sulphate ingestion was
responsible for 22% of deaths due to poisoning from
1972 to 1977.[12,13] However, it declined to 3.85 and
3.33% between 1977-1982 and 1982-1987 respectively.
Pediatric cases of copper sulphate ingestion are rare, with
only few case reports available in literature.[4-7]
As some of the clinicians are faced with unfamiliarity
when challenged to manage the cases of copper sulphate
poisoning, we have attempted a comprehensive review
on the clinical manifestations and management of copper
sulphate poisoning.
Kinetics of Copper
The total body content of copper is 150 mg.[14]
Approximately 30% is absorbed from the gastrointestinal
tract.[15] In blood, copper is initially albumin-bound and
transported via the hepatic portal circulation to the liver
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where it is incorporated into ceruloplasmin (an alpha
globulin synthesized in hepatic microsomes). Copper is
present in serum in two forms; 93% is tightly bound to
ceruloplasmin and 7% is loosely bound to albumin.[14]
The copper-albumin complex represents the toxicological
active portion of the serum copper.[1] Systemic transport
of copper from liver is primarily as ceruloplasmin, which
appears to donate copper to tissues. Copper is distributed
to all tissues with the highest concentrations in liver,
heart, brain, kidneys and muscle. Intracellular copper is
predominantly bound to metallothionein. Copper is found
extensively in red blood cells as erythrocuprein and other
proteins. Fecal and biliary excretion accounts for 80
percent of excreted copper. Approximately four percent
is excreted in the urine.[15] The average half-life of copper
in a healthy individual is estimated to be 26 days.[16]
The kinetics of copper during over dose differs from
that during the normal. The gastrointestinal absorption
varies with the copper intake and it can be as low as
12% in patients with high copper intake. However, in the
presence of damaged mucosa following acute overdose,
the fractional absorption is likely to be higher.[17] In acute
poisoning, albumin, rather than ceruloplasmin, binds the
excess copper. The liver is the major site of deposition of
copper following large ingestion, with most of the copper
bound to metallothionein. The copper content in normal
adult liver ranges from 18-45 mg/g dry weight. When
the concentration of hepatic copper is greater than 50
mg/g dry weight, liver cell necrosis occurs with release
of large amount of copper into the serum. This released
copper is rapidly taken up by erythrocytes and results in
oxidative damage and may result in hemolysis of RBCs.[1]
This may account for the delayed secondary episode of
hemolysis that occurs in some copper sulphate poisoning
Mechanism of Toxicity
Copper sulphate is a powerful oxidizing agent, which is
corrosive to mucous membranes. Concentrated solutions
are acidic with pH 4. Cellular damage and cell death may
result from excess copper accumulation. It is proposed
that free reduced copper in the cell binds to sulfhydryl
groups and inactivates enzymes such as glucose-6-
phosphate dehydrogenase and glutathione reductase.[18]
In addition copper may interact with oxygen species (e.g.,
superoxide anions and hydrogen peroxide) and catalyze
the production of reactive toxic hydroxyl radicals. Lethal
dose is about 10-20 g.[14]
Pathology of Copper Sulphate Poisoning
Main brunt of copper toxicity is borne in the order
by the erythrocytes, the liver and then the kidneys.[19]
Intravascular hemolysis appears 12-24h following
ingestion of copper sulphate. Hemolytic anemia, is
caused either by direct red cell membrane damage
or indirectly as a result of the inactivation of enzymes
(including glutathione reductase) which protect against
oxidative stress.[2,20] Copper ions can oxidize hem iron
to form methaemoglobin. This blood loses its oxygen
carrying capacity. Clinically cyanosis and chocolate
brown blood may be seen.[21] Patients with cyanosis show
at least 1/3rd of the blood to be methemoglobin.
Jaundice in copper sulphate poisoning is partly hepatic
in origin in addition to hemolysis.[19] Jaundice appears on
the second or third day following ingestion. Liver damage
has been attributed to liver mitochondrial dysfunction
due to oxidized state.[22] Nature of liver damage is both
cell necrosis as well as obstruction. Obstructive factor
is seen predominantly as opposed to toxic hepatitis.[19]
Level of bilirubin is directly proportional to the severity of
the poisoning. Elevated levels of liver enzymes are seen
in all except mild cases of poisoning.[10,19,23] Liver biopsy
reveals centrilobular necrosis, mononuclear inÞ ltration
and biliary stasis.[9,24]
Intravascular hemolysis plays a major role in the
pathogenesis of renal failure.[18,25] The hem pigment
released due to hemolysis and direct toxic effect of copper
released from lysed red cells contribute to tubular epithelial
damage of the kidney. Severe vomiting, diarrhoea, lack of
replacement of ß uid and gastrointestinal bleed, leading
to hypotension could also contribute to renal failure.[25]
Renal complications are usually seen on the third or
the fourth day and onwards after the poisoning.[26] In
a report of acute renal failure manifestations following
copper sulphate poisoning, histology of kidney revealed
features of acute tubular necrosis in seven out of eight
kidney biopsies and tubules contained hemoglobin
casts. A single case of interstitial granuloma was also
Copper sulphate being a corrosive acid, results in
caustic burns of the esophagus, superÞ cial and deep
ulcers in the stomach and the small intestine.[25] Changes
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of acute gastritis, hemorrhages in the intestinal mucosa,
necrosis of the intestinal mucosa and perforation have
been reported.[5,27,28]
Clinical Features
Gastrointestinal: The immediate symptoms following
ingestion of copper sulphate universally is gastrointestinal
in the form of nausea, vomiting and crampy abdominal
pain.[25] Vomiting usually occurs within 15 minutes of
ingestion. Vomitus is characteristically greenish-blue.
Hemorrhagic gastroenteritis associated with mucosal
erosions, a metallic taste, burning epigastric sensation
and diarrhea may occur.[9] In severe cases hemetenesis
and malena occur. In a case series including 19 patients
requiring hemodialysis after copper sulphate ingestion,
7(37%) developed gastrointestinal bleeding and in
5(26%) this was severe enough to cause signiÞ cant
Cardiovascular: In cases with severe poisoning
cardiovascular collapse, hypotension and tachycardia can
occur early within a few hours of poisoning and may be
responsible for early fatalities or can occur late with other
complications.[9] Vomiting, diarrhea and GI blood loss are
the factors usually responsible for hypovolemia.[17] Severe
methemoglobinemia can result in cardiac dysryhtmia
and hypoxia which could contribute significantly to
cardiovascular collapse.[30] Other factors implicated are
direct effect of copper on vascular and cardiac cells and
sepsis due to transmucosal invasion.[7,17] In a series of
seven autopsies, Þ ve deaths occurred within an hour of
admission due to shock.[27] Four percent of patients in a
series of 50 cases by Wahal et al had early cardiovascular
collapse and succumbed within 10 hours of consumption
of the poison.[9]
Hematological: Intravascular hemolysis occurs12-
24h after ingestion. The discovery of significant
methemoglobinemia occurs early in the patient’s
clinical course and is rapidly followed by hemolysis.
Coagulopathy can occur due to liver injury or direct effect
of free copper ions on the coagulation cascade.[17] The
incidence of methemoglobinemia ranged from 3.4% to
42% and intravascular hemolysis ranged from 47-65%
in two case series.[25,29]
Hepatic: Jaundice appears after 24-48h in more severe
poisonings, which may be hemolytic or hepatocellular. It
may be associated with tender hepatomegaly. Jaundice
was seen in 11(58%) patients and 1(5%) patient died of
hepatic encephalopathy in one series.[29]
Renal: Renal complications are observed usually after
48h.[26] Acute renal failure developed in 20-40% of patients
with acute copper sulphate poisoning.[18,25] Urinary
abnormalities detected are oliguria, anuria, albuminuria,
hemoglobinuria and hematuria.[18,25,26]
Central nervous system: Central nervous system
depression ranging from lethargy to coma or seizure
are likely epiphenomenon related to other organ
Muscular: Rhabdomyolysis with high creatine phospho
kinase (CPK)>3000IU have been reported.[31,32] In one
case myoglobinuria was detected on the second day and
peak CPK level was observed on the sixth day.[27]
Clinical features in paediatric patients
From the limited case reports available in paediatric
patients, the clinical features in paediatric group
resembles that of adults with early gastrointestinal feature
and hemolysis usually occurring after 24h. Hepatic and
renal toxicities develop one to two days after ingestion
as in adults.[4]
Cardiac abnormalities was reported with multiple
ventricular extrasystloes, tachycardia and occasional
unifocal bigeminy in a two-year-old boy who ingested 30
ml of a super-saturated copper sulphate solution (10 gm
of copper sulphate).[7]
Baseline hemoglobin, liver function, renal function and
electrolyte levels should be obtained and monitored as
clinically indicated until symptoms abate. Hemoglobin
should be monitored as clinically indicated to guide the
need for blood transfusion. Monitoring renal functions
and electrolytes is required to assess the ß uid status and
extent of renal failure and the renal toxicity of chelating
agents like penicillamine. In patients with hepatitis and
bleeding manifestations, coagulation parameters have
to be monitored. Methemoglobin level is to be monitored
in cyanotic patients to assess the need for methylene
blue.[33] In one series where biochemical changes in blood
were studied in copper sulphate poisoning, the authors
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suggested a prognostic signiÞ cance for estimation of
levels of serum transaminases along with blood urea
estimations with higher levels seen in more seriously ill
patients.[19] However the signiÞ cance of this observation
was not statistically tested. Urine examination is required
for evidence of hemoglobinuria and hematuria.
For diagnostic purpose, if the history is not clear,
serum and whole blood copper estimation on a sample
collected early in the course may be of help.[17,19] Serum
copper concentrations normally range from 10.5 to
23 micromoles/liter.[16] However it is not mandatory
if the diagnosis is obvious by history and clinical
No correlation was found between plasma copper
concentrations and prognosis in a study by Wahal et al.[23]
In a study by Singh, an increase in serum copper was
found within three hours of ingestion of copper sulphate
and after reaching peak values within 48h it showed
a gradual fall and attained normal levels within 17h to
7 days. The fall in blood copper levels was attributed
to an increase in concentration of copper in tissues
especially liver and the kidneys.[19] Although serum
ceruloplasmin levels rise in patients with acute copper
poisoning, because of increased hepatic synthesis, the
ceruloplasmin cannot be used to deÞ ne the patients’
A) Decreasing absorption
After acute ingestion of copper sulphate, in the
prehospital setup, immediate dilution with water or
milk is advisable. The same action is extrapolated
from recommendations for management of corrosive
ingestions.[35-37] In corrosive ingestion one should avoid
emesis and should begin early dilutional therapy. Water
may be used initially to dislodge adherent solid particles,
as well as to dilute the caustic ingestion. It is important
not to be excessively aggressive with dilution, as this may
cause nausea, vomiting and possible aspiration.
Emesis should be avoided to prevent reexposure of the
esophagus to the corrosive agent.[37] In copper sulphate
poisoning vomiting is likely to occur spontaneously
and hence patient may require antiemetic therapy.[17] In
corrosive acid ingestion, there is a risk of perforation if
blind gastric lavage is attempted, however in patients with
large intentional ingestion of acid who presents within 30
min, consideration can be given to cautious placement
of a narrow nasogastric tube suction to remove the
remaining acid in the gut.[37]
Activated charcoal administration should be considered
after a potentially dangerous ingestion.[38] A dose of
oral activated charcoal, while of unproved beneÞ t, is
unlikely to be harmful and may have potential adsorptive
capacity for copper.[17] Usual dose is 25 to 100 gm in
adults and adolescents and 25 to 50 gm in children aged
1 to 12 years (or 0.5 to 1 gram/kilogram body weight).
Administer charcoal as aqueous slurry; most effective
when administered within one hour of ingestion. Use a
minimum of 240 ml of water per 30 gm charcoal.[39]
B) Supportive measures
1) Management of corrosive burns:
If corrosive oesophageal or gastric damage is
suspected upper GI endoscopy should be carried out,
ideally within 12-24h, to gauge the severity of injury.[40-43]
This recommendation is extrapolated from experience
with ingestion of acids and /or alkaline corrosives.
Endoscopic procedures done during the early period
after corrosive ingestion has shown to be relatively
safe without any complications. In a series of 94
patients with corrosive ingestion, GI endoscopy was
performed in 81 patients within 24h and in 12 patients
within 48h. The procedure was not associated with any
complications.[42] Similarly, in another series of 16 patients
with corrosive acid ingestion, Þ breoptic endoscopy was
done in 13 patients within 24h. The authors concluded
that endoscopy did not give rise to any complications
and it helped in grading the injury caused by corrosive
acids, planning the management of patients and also in
predicting the prognosis.[43]
The period of wound softening starts on the second
or third day post-injury and last for roughly two weeks
during which time there is an increased risk of perforation
if endoscopy is performed.[37] An early surgical opinion
should be sought if there is any suspicion of pending
gastrointestinal perforation or where endoscopy reveals
evidence of grade III burns.
Sucralfate may help to relieve the symptoms of mucosal
injury.[44] Adequate human data regarding role of steroid
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in caustic burn is yet to be generated. The most suitable
group to receive corticosteroid (with antibiotic) is probably
the patients with grade IIb injuries (submucosal lesions,
ulcerations and exudates with near circumferential
injuries). In patients with grade III ulcers (deep ulcers and
necrosis into periesophageal tissues) stricture formation
occurs, irrespective of steroid administration. Moreover,
steroids may mask or worsen the complications of
corrosives in grade III patients and hence steroids are
Considering the experience with the use of steroid in
copper sulphate poisoning, in a study of copper sulphate
poisoning by Gupta et al., the mortality was lower in a
group of 26 patients treated with steroids as compared
to those without steroids.[2] However, this was not a
randomized-controlled study. The role of steroid has not
been tested in any other controlled studies to strongly
recommend this therapeutic intervention.
2) Methemoglobinemia:
Patients with symptomatic methemoglobinemia should
be treated with methylene blue. This usually occurs
at methemoglobin levels above 20 to 30 percent, but
may occur at lower methemoglobin levels in patients
with anemia or underlying pulmonary or cardiovascular
disorders. Administer oxygen while preparing for
methylene blue therapy.
Methylene blue enhances the conversion of
methemoglobin to hemoglobin by increasing the activity of
the enzyme methemoglobin reductase. Initial dose is 1-2
mg/kg/dose (0.1 to 0.2 ml/kg of 1% solution) intravenously
over 5 minutes. The dose may be repeated if cyanosis
does not disappear within one hour.[45] At high levels of
methemoglobin (>70%), methylene blue reduces the half
life from an average of 15-20 hours to 40-90 min. Hence,
improvement from methylene blue therapy should be
observed within one hour of administration.
Failure of methylene blue therapy suggests inadequate
dose of methylene blue, inadequate decontamination,
G-6-PD deÞ ciency, NADPH dependent methemoglobin
reductase deÞ ciency.[45] Further, methylene blue action
requires intact erythrocytes and hence if hemolysis
is severe, it may be ineffective in copper sulphate
poisoning.[17] Large doses of methylene blue itself may
cause methemoglobinemia or hemolysis and the same
needs to be considered while administering this agent.[33]
It is contraindicated in G-6-PD deÞ cient patients in whom
it may cause hemolysis. Exchange transfusion and/or
the transfusion of packed red blood cells may be useful
for methylene blue failures or for patients with G6PD or
NADPH methaemoglobin reductase deÞ ciency. (Nitrates,
Nitrites and methaemoglobinemia.[45] Hyperbaric oxygen
may be beneÞ cial if methylene blue is ineffective.[34]
Hyperbaric oxygen increases the dissolved oxygen
which can protect the patient while the body reduces
methaemoglobin.[34] Another alternative to methylene
blue is the reducing agent ascorbic acid which can be
administered 100-500 mg twice daily either orally or
intravenously. But, this agent probably has a minor effect
on increasing methemoglobin reduction and the clinical
experience with the use of this agent is limited.[45]
3) Hypotensive episode:
Hypotensive episode should be treated with ß uids,
dopamine and noradrenaline
4) Rhabdomyolysis:
Early judicious ß uid replacement of 4-6L/day with careful
monitoring for ß uid overload, mannitol (100 mg/day) and
urine alkalinization are suggested early in the course,
but deÞ nite evidence for the efÞ cacy of these measures
is lacking.[46]
C) Chelation therapy
There is little clinical experience with the use of
chelators for acute copper sulphate intoxication. Data
on efÞ cacy is derived from patients with chronic copper
intoxication (Wilson’s disease, Indian childhood cirrhosis)
and experimental animal studies. British anti Lewisite
(BAL), D-penicillamine, 2, 3-dimercapto-1-propane
sulfonate, Na+ (DMPS) and ethylene diamine tetra
acetate (EDTA) have been used. In severely poisoned
patients the presence of acute renal failure often limits
the potential for antidotes.
1) Penicillamine:
D-penicillamine has been used to treat acute
copper intoxication, but data regarding efficacy are
Adult dose: 1000 to 1500 mg/day divided every six to
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12h, before meals.
Pediatric dose: Initially 10 mg/kg/day, gradually
increase to 30 mg/kg/day divided in two or three doses
as tolerated. Doses up to 100 mg/kg/day in four divided
doses; maximum one gram/day may be used depending
on the severity of poisoning and adverse effects.[49]
Avoid in patients with penicillin allergy. Proteinuria,
hematuria, renal failure, bone marrow suppression and
hepatotoxicity are the common adverse effects.
2) Dimercaprol / BAL:
Intramuscular BAL is probably appropriate in patients in
whom vomiting and gastrointestinal injury prevents oral
D-penicillamine administration. BAL- copper complex
primarily undergoes biliary elimination and hence it is
useful in patients with renal failure. However, BAL may
be less effective than D-penicillamine and hence, when
tolerated, D-penicillamine therapy should be started
simultaneously or shortly after the initiation of therapy
with BAL.[17]
Dose: 3 to 5 mg/kg/dose deep intramuscularly every
four hours for two days, every four to six hours for an
additional two days, then every four to 12h for up to seven
additional days.[6,31,47,50] Adverse reactions are urticaria
and persistent hyperpyrexia.
3) Edetate calcium disodium
The dose of this agent is 75 mg/kg/day deep
intramuscularly or slow intravenous infusion given in
three to six divided doses for up to Þ ve days; may be
repeated for a second course after a minimum of two
days; each course should not exceed a total of 500 mg/kg.
Complications include renal tubular necrosis.[6]
D) Enhanced elimination
Hemodialysis to remove copper is ineffective, but may
be indicated in patients with renal failure secondary to
copper poisoning.[33,51]
Peritoneal dialysis with salt-poor albumin resulted in
extraction of more copper than dialysate without albumin.
However, the amount of copper removed by peritoneal
dialysis was very small.[7] There is insufÞ cient evidence
regarding any role of hemoperfusion and hemodiaÞ ltration
for copper elimination.[31]
Copper sulphate poisoning, which is mostly suicidal,
is associated with high mortality in severe cases due
to methemoglobinemea, hepatotoxicity and renal
failure. Mainstay of treatment is supportive, including
careful fluid therapy and methylene in symptomatic
methemoglobinemia. Chelation therapy though tried
in many cases, their beneÞ ts are not established in
controlled trials. The role of dialysis is limited to the
management of associated renal failure.
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Source of Support: Nil, Con ict of Interest: None declared
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... There is a lack of detailed literature on acute oral fungicide self-poisoning. Review of the literature for cases of acute oral toxicity with fungicides reveals mass casualty events attributed to fungicide contamination of grain [17,18] and a small number of self-poisoning cases lacking clinical details [19][20][21][22][23][24][25][26][27][28][29][30][31][32] (Table 1). Most of the literature focuses on just two fungicides: the OP fungicide edifenphos [19,24,[29][30][31][32] and copper sulfate [27,28,[33][34][35]. ...
... Review of the literature for cases of acute oral toxicity with fungicides reveals mass casualty events attributed to fungicide contamination of grain [17,18] and a small number of self-poisoning cases lacking clinical details [19][20][21][22][23][24][25][26][27][28][29][30][31][32] (Table 1). Most of the literature focuses on just two fungicides: the OP fungicide edifenphos [19,24,[29][30][31][32] and copper sulfate [27,28,[33][34][35]. Edifenphos inhibits phosphatidylcholine biosynthesis in fungi but cholinesterases in mammals (similar to OP insecticides). ...
... Its rat oral LD50 is 150 mg/ kg; it has been classified as WHO hazard class Ib to be consistent with the Globally Harmonized System of Classification and Labelling of Chemicals (GHS)'s system of classification (Toxicity Hazard Category 3) [13]. Copper sulphate inhibits spore germination in fungi but is hemolytic in mammals causing anemia, as well as corrosion in the GI tract, renal and liver failure [27,28,33]. The WHO reports a rat oral LD50 of 300 mg/kg for copper sulphate, resulting in WHO hazard class 2 and GHS toxicity hazard category 3 classifications [13]. ...
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Background: Pesticide self-poisoning is a global clinical and public health problem. While self-poisoning with insecticides and herbicides has been extensively studied, there is minimal literature on acute fungicide self-poisoning. We aimed to study the clinical course and outcome of fungicide self-poisoned patients recruited to a prospective cohort in Sri Lanka. Methods: We conducted a prospective study of patients presenting with fungicide self-poisoning to nine hospitals in Sri Lanka between 2002 and 2020. Patients were enrolled by clinical research assistants, with clinical outcomes being recorded at regular review for each patient. Results: We identified 337 cases of self-poisoning with fungicides (alcohol as only co-ingestant), including 28 different fungicides across 5 different fungicide classes. Median time from ingestion to examination was 3.1 (1.8-5.7) h. Nearly all presented to hospital fully conscious (GCS 15, 15-15)- only 27 patients (8.0%) presented with reduced GCS (<15) and only 2 (0.6%) had GCS 3/15. Most patients (333/337, 98.8%) made a full recovery, of whom only eight (2.37%) required intubation and ventilation. Four patients died (case fatality rate: 1.2%; 95% CI 0.0-23.4) after ingestion of edifenphos (n = 2), propamocarb and pyraclostrobin. Conclusion: Fungicide self-poisoning appears to be less hazardous than insecticide or herbicide self-poisoning, with a substantially lower case fatality in the same cohort. Edifenphos is an exception to this 'less toxic' rule; as a WHO Class Ib highly hazardous pesticide, we recommend its withdrawal from, and replacement in, global agricultural practice. Propamocarb should be listed in the WHO hazard classification as propamocarb hydrochloride to reflect the higher toxicity of the common agricultural formulation. Pyraclostrobin currently has no WHO classification; one is urgently required now that its ingestion has now been linked the death of a patient. Additional prospective clinical data on fungicide self-poisoning is required to expand knowledge on the effects of these diverse compounds.
... Determination of Organochlorinated Pesticides and Close findings were observed in a North Carolina research Polychlorinated Biphenyls: The determination of the with children from women with reduced polychlorinated concentration of OCPs and PCBs in the samples were biphenyl exposure levels. Also, in an Oswego, New York performed using an Agilent 6890 gas chromatography examination of children from women with very high coupled with mass spectroscopy (GC/MS) that is consumption of polychlorinated biphenyls from fish equipped with a micro cell electron capture detector obtained from Lake Ontario revealed similar result [15][16][17][18]. ...
... In this study, rats treated with in agreement with work of Saravu et al.andSarkar et al. Okposi and Uburu salt lake water and salt sample showed [16,17] who observed reduction in the weight of the significant elevation in the level of formation of accessory sex organs of animal given NaAsO . Yu et al. ...
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Organochlorinated pesticidespolychlorinated biphenyls composition of Okposi and Uburu salt lakes and the possible effect of its consumption to some reproductive parameters were determined. The organochlorinated pesticides compound and polychlorinated biphenyls composition were determined using gas chromatography coupled with mass spectroscopic equipments. 200 adult male Sprague-Dawley rats were grouped into eighteen groups of A to Q. Group A to D were given 0.5ml, 1.0ml, 2.0mls and 4.0mls of water from Uburu salt Lake. Group E to H were administered 50, 100, 200 and 400mg/kg of salt respectively, fromUburu salt Lake. Group I to L were given 0.5, 1.0, 2.0 and 4.0mls of water from Okposi salt Lake and group M to P were administered 50, 100, 200 and 400mg/kg of salt from Okposi salt Lake while group Q received deionised water to serve as the control. The experiment lasted for 90 days. At the end of 90 days, the animals were sacrificed. Testes, epididymis and prostate gland were immediately removed and dissected out, cleared from the adhering tissues, blotted dried and weighed individually.Tissues homogenateswere prepared and were used to measure the extent of lipid peroxidation in the reproductive tissues. There was a significant decrease in the testicular weight, epididymal weight and prostate weight in all the treated groups. Rats treated with Okposi and Uburu salt lake water and salt sample showed significant elevation in the level of formation of thiobarbituric acid reactive substances concentration. Reduced glutathione concentration and the activities of catalase and superoxide dismutase in the testes were all significantly reduced in the Okposi and Uburu salt lake sample treated male albino rats in this study. Chemical analysis of the Lakes showed a significant level of some of the organochlorinated pesticides. No polychlorinated biphenyls were found to be present in both lakes.Result shows that consumption of Okposi and Uburu salt lake unprocessed water and salt samples could be dangerous to health and might lead to reproductive function impairment.
... Acute proximal renal tubular dysfunction may lead to aminoaciduria, hypercalciuria, phosphaturia, proteinuria, uricosuria and haematuria. Serum hepatic aminotransferase levels peak within 3 days of ingestion and usually resolve in 1 week [5,6] . ...
... Suicidal behaviour is a global cause of death and disability. Patient management should include not only treatment of the poisoning but also mental health support and follow-up [5][6][7] . ...
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Acute copper toxicity is uncommon in Western countries and is often the result of accidental consumption or a suicide attempt. We report the case of a 65-year-old man presenting to the accident and emergency department after a suicide attempt with ingestion of Bordeaux mixture, ibuprofen, acetaminophen and bleach. Primary evaluation showed caustic oesophagitis, toxic hepatitis and acute renal injury, which were treated with supportive care. During admission, he developed a non-immune haemolytic anaemia associated with high levels of copper in urine and blood. Chelation treatment with penicillamine was started and evolution was favourable after 1 month of treatment. Copper poisoning can be lethal. Prompt diagnosis and treatment are key for a favourable prognosis. Learning points: Acute copper intoxication is rare and early clinical suspicion and diagnosis are essential to reduce mortality.The diagnosis of copper poisoning should be based on clinical presentation and measurement of urine and blood copper levels in addition to serum ceruloplasmin levels.Treatment includes reduction of absorption, supportive measures, management of complications and chelation therapy.
... It is also known as "Blue Vitriol" or "Blue Stone". It was also used as a precipitant in heavy metal poisoning and to treat gastric and topical phosphorous exposure (Saravu et al., 2007). Also, copper sulfate is used as a fungicide, algaecide, and herbicide in both agricultural and non-agricultural settings. ...
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This study was conducted in the laboratories of the Departments of Plant Protection and Animal Production at the College of Agriculture and Forestry / University of Mosul, and the Pharmacognosy laboratory of the College of Pharmacy / University of Mosul for the period from 3/9/2020 to 4/5/2022.The aims at identifying fungi contaminating local maize samples in grain stores (Al-Hawija, Al- Hamdaniya and Tikrit) and the morphological diagnosis of these fungi, including A. flavus. It confirms the diagnosis of the fungus using primers specific to Polymerase chain reaction (PCR) technology. It also determines the susceptibility of isolates of A. flavus in the production of aflatoxin B1(AFB1) and the identification of the most productive isolate of the toxin using High-performance liquid chromatography (HPLC).The growth and sporulation of A. flavus' were examined in vitro using C1, C2 furanocoumarins, Lactobacillus plantarum, a toxin-binding preparation (Anpro), and CuSO4. In maize grains contaminated with A. flavus under storage conditions, the effectiveness of C1, C2 compounds, L. plantarum, Anpro, and CuSO4 on inhibition of growth and sporulation as well as AFB1 production was evaluated. In vivo, quail birds that were fed with a food contaminated with AFB1 were given the aforementioned treatments, and the effects on several blood and biochemical parameters of the birds were examined.
... Cellular damage and cell death may result from excessive copper accumulation through which free reduced copper in the cell binds to sulfhydryl groups and inactivates enzymes such as glucose-6-phosphate dehydrogenase and glutathione reductase (12). ...
The study was conducted on 60 albino rats, approximately one month old, of the same weight (200-220gms), and they were divided equally into 4 groups as follows: the first group was drenched by stomach tube 40 mg/kg BW CuSo4 for two months. The second group was gavage by stomach tube 40 mg/kg BW CuSo4 and injected with alpha-lipoic acid (ALA) (100 mg/kg BW intraperitoneally once daily) for two months. The third group was injected with alpha lipoic acid (100 mg/kg BW intraperitoneally once daily) for two months and the fourth group as the control group received only I/P 0.2 ml of normal saline once daily for two months. After two months all animals were sacrificed after the collection of blood for biochemical tests and livers and kidneys were taken for histopathological examination. In the biochemical study, the results showed that 1 st group showed a significant increase (P ≤ 0.05) in the levels of the liver enzymes (ALT, AST, and ALP) in comparison with the control group, whereas 2 nd group showed a non-significant increase (P > 0.05) in comparison with the control group and a significant decrease (P ≤ 0.05) as compared with 1 st group (CuSo4 group). The microscopic examination of the histopathological sections of livers and kidneys of 1 st group animals showed high severe changes or lesions in both livers and kidneys due to the pathotoxic effect of CuSO4 on these organs, whereas these microscopic changes showed marked decreased or mild severity in the 2 nd group (CuSo4 + ALA) due to the protective and ameliorative effect of ALA against the toxicity of CuSo4.
... Copper is also one of the few heavy metals that inhibits cholinesterase activity in a non-competitive manner (38,39). The prior effects were not isolated from the oxidative stress generated by various concentrations of copper sulfate, where the concentration of malondialdehyde increased significantly and was linked to a drop in serum glutathione levels. ...
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The aim is to investigate the sub-acute neurotoxic effects of copper sulfate in chicks on motor and neurobehavioral activity and its relation to oxidative stress and histopathological changes in chick brain tissue. Thirty chicks were employed in this experiment, randomly separated into 5 groups of 6 chicks. They were given the following concentration 2.5, 5, 10, and 15% of LD50. Each of the chicks is put through the following behavioral tests response to tonic immobility test, righting reflex, testing the motor activity of the chicks inside the open field box. Orally LD50 was 772 mg/kg, Recording an inhibition in the animal's movement in the open field and an increase in the chicks' dormancy duration. The effects are directly proportional to the increase in the chicks' dose. Copper sulfate in 2.5, 5, 10, and 15% of the LD50 showed a significant increase in malondialdehyde concentration, while 15% of LD50 recorded a significant decrease in glutathione and cholinesterase activity. All doses substantially decreased total antioxidant capacity in brain and liver tissue. Chick brain of copper sulfate 15% of LD50 shows in the cortex of cerebrum severe gliosis, satellitosis, perivascular and periaxonal edema, necrosis (karyorrhexis) of neuron, and apoptosis. The rest of the concentrations had histopathological alterations proportionate to the rise in the given dose. We concluded from this work that high concentrations of copper sulfate in the brain generated oxidative stress and histopathological alterations, which influenced chicks' neurobehavior and motor activity in the open environment.
This study was designed to investigate the effect of sodium molybdate and sodium sulfate alone and in combination overloaded intake on copper outcome in mature albino male rats. Twenty eight adult male rats weighed (316-350 g) were randomly housed and divided into four equal groups (seven rat/group) and treated orally through gastric gavage as follows for 60 days: control administered distal water, T1 sodium molybdate 50 mg/kg B.W, T2 500 mg/kg B.W of sodium sulfate. Animals in the T3 group were given sodium molybdate plus sodium sulfate in combination at half dose that administered to T1 and T2. Blood samples were collected by cardiac puncture technique at different periods 0, 30 and day 60 of the experiment for measuring serum concentrations of copper, serum glutathione, blood urea nitrogen, creatinine, total serum bilirubin, red blood cell count, hemoglobin, packed cell volume, clinical signs and body weight change. The results revealed that oral intubation of sodium molybdate and sodium sulphate alone or in combination caused state of copper deficiency indicating by a decrease in serum copper level, a decrease in glutathione level, anemia and significant loss of body weight but in generally at different extent, the disturbances that occurred were higher in sodium molybdate treated group T1 followed by sodium sulfate treated group T2 then combination treated group T3 which have a slighter effect. These functional changes were accompanied by structural changes in the hepatic and renal tissues. Histopathological changes following sodium molybdate (50 mg/kg B.W) exposure were manifested by extensive areas of necrosis, hemorrhage, and hyperplasia of bile ductules. Besides focal area of necrosis and suppurative granuloma observed in liver of rats received 500 mg/kg B.W of sodium sulfate, mild infiltrate of mononuclear cell within the hepatic parenchyma, suppurative granuloma and proliferation of kupffer’s cells with hyperplasia of bile ductules and severe dilatation of hepatic artery contains inflammatory cell and serum protein in their lumena cells seen in liver of rats received combination of them at half dose. While sections in kidneys of sodium molybdenum-treated rats showed marked fibrous thickening of the capsule, severe cortical hemosiderosis with infiltrate of plasma cell and neutrophils. Sections in rat's kidney received sodium sulfate showed atrophy of glomerular tuft, focal interstitial mononuclear cells infiltration, vacuolization of renal tubules, cystic dilatation of cortical renal tubules with deposition of hyaline cast. The histological changes revealed that renal damage was also observed in rat received combination of sodium molybdenum and sodium sulfate but at a little degree. Depending on the result of this study it can be concluded that molybdate and sulfate alone and in combination succeeded to induce copper deficiency with severe changes in parameters related to oxidative stress and hematological disorder in rats.
Copper sulfate occurs as large blue crystals in nature, commonly known as "blue vitriol" or "blue stone." It is a potentially lethal poison with significant mortality. Copper sulfate is a powerful oxidizing agent and causes corrosive injury to the mucous membrane. The clinical course involves intravascular hemolysis resulting in anemia, jaundice, and renal failure. Laboratory diagnosis of the condition is not an issue; the difficulty is suspecting it, promptly initiating chelation therapy, and other supportive symptomatic treatment. We present a case of copper sulfate poisoning in a young female with suicidal intent resulting in severe acute toxicity, which was successfully managed by copper chelator (d-Penicillamine) and other supportive measures.
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For many decades, acute pancreatitis has occupied third place in the structure of emergency surgical abdominal conditions, second to acute calculous cholecystitis and acute appendicitis. Simultaneously, acute pancreatitis ranks first in mortality among other acute surgical conditions. Often acute pancreatitis occurs under the mask of gastroenterological problems. Complex electrolyte and trace element disorders are often formed in the early stages of developing pancreatitis. The concepts of diagnosis and therapeutic and surgical treatment of acute pancreatitis are formulated and reflected in numerous domestic and international monographs and recommendations, which emphasize the important role of water-electrolyte disorders, microbiota, systemic inflammatory response, and cytokine storm as etiological factors in inflammatory development and maintenance and destructive pancreatic and parapancreatic cellular processes. Sepsis, septic shock, and multiple organ failure are the leading causes of mortality in patients with infected pancreatic necrosis. Problems of the interrelation and role of individual trace elements and metalloenzymes as etiological factors in acute pancreatitis formation, prognostic biochemical markers of the severity of patients condition, and prognostic criteria of mortality and recovery are actively studied.
Copper is an essential trace element found in all organs and cells. The redox chemistry of this element makes copper highly suitable as a catalytic cofactor in oxidative enzymes. Copper is involved in numerous biological processes, primarily as an integral part of enzymes, such as those involved in cellular respiration (cytochrome c oxidase), antioxidant defense (superoxide dismutase), connective tissue formation (lysyl oxidase and related proteins), neurotransmitter biosynthesis (dopamine beta-hydroxylase), peptide hormone maturation (peptidyl-glycine alpha-amidating monooxygenase), pigmentation (tyrosinase), keratinization (sulfhydryl oxidase), and iron homeostasis (ceruloplasmin and hephaestin). Copper in our body is absorbed from the diet. The absorption is dependent on the amount ingested, its chemical form, and the composition of other dietary components such as zinc. Drinking water may contribute significantly to the daily copper intake due to the widespread use of copper piping in water supplies. Because copper is a highly reactive metal and thus harmful to cells if present as free ions, intracellular copper levels are strictly controlled by a substantial number of integral transmembrane transporters, including copper-transporting ATPases (ATP7A and ATP7B, respectively), and metallochaperones. ATP7B transports copper into the hepatocyte secretory pathway for incorporation into ceruloplasmin and excretion into the bile. ATP7A transports copper across the gastrointestinal tract, blood–brain barrier, and placenta. ATP7A is also responsible for the copper loading of a large number of the other copper-requiring enzymes. Wilson disease and Menkes disease are inherited disorders of copper transport, caused by mutations in the ATP7B and ATP7A genes, respectively. The clinical features of patients with Wilson disease can be attributed to impaired biliary copper excretion, whereas Menkes disease arises from an altered distribution of copper in the body, with some tissues showing a deficiency and others showing excess accumulation. Ingestion of a large amount of copper salts causes gastrointestinal disturbances. The first symptom to occur is nausea, with increased reporting starting at about 4 mg/L copper in drinking water. In severe cases, systemic effects, especially hemolysis, liver and kidney damage, can also occur. In contrast to data obtained after ingestion, comparatively little is known about health effects related to the inhalation of copper and copper fumes. Copper may cause irritation of the respiratory tract and metal fume fever. For reviews on copper, see Linder and Hazegh-Azam (1996), WHO (1998), Barceloux (1999), Gaetke and Chow (2003), Harris (2003), Tapiero et al. (2003), Stern et al. (2007), Romaňa et al. (2011), Nevitt et al. (2012), Skjørringe et al. (2012), Scheiber et al. (2014), Kaplan and Maryon (2016), Lenartowicz et al. (2016), and Michniewicz et al. (2021).
Copper is an essential trace element, which is an important catalyst for heme synthesis and iron absorption. Following zinc and iron, copper is the third most abundant trace element in the body. Copper is a noble metal, like silver and gold. Useful industrial properties include high thermal and electrical conductivity, low corrosion, alloying ability, and malleability. Most of the metallic copper appears in electrical applications. Copper is a constituent of intrauterine contraceptive devices and the release of copper is necessary for their contraceptive effects. The average daily intake of copper in the US is about 1 mg Cu with the primary source being the diet. The bioavailability of copper from the diet is about 65–70% depending on a variety of factors including chemical form, interaction with other metals, and dietary components. The biological half-life of copper from the diet is 13–33 days with bilary excretion being the major route of elimination. Copper sulfate is a gastric irritant that produces erosion of the lining of the gastrointestinal tract. Chronic copper toxicity is rare and primarily affects the liver. Wilson's disease and Indian childhood cirrhosis are examples of severe chronic liver disease that results from the genetic predisposition to the hepatic accumulation of copper. The serum copper concentration ranges up to approximately 1.5 mg/L in healthy persons. Gastrointestinal symptoms occur at whole blood concentrations near 3 mg Cu/L. Chelating agents (CaNa2EDTA, BAL) are recommended in severe poisoning, but there are little pharmacokinetic data to evaluate the effectiveness of these agents.
In the emergency department, any patient who is suspected of having sustained a caustic ingestion must be handled in a serious manner. All patients should be initially stabilized with regard to airway and circulatory status. Initial questioning concerning the type and quantity of agent ingested will be most helpful. Signs and symptoms of shock, impending perforation, or airway distress take precedence over any further work-up. Patients who have a known history of ingestion require admission to the hospital. Complete physical examination should be carried out, bearing in mind that the lack of oropharyngeal involvement or other symptoms does not rule out the possibility of esophageal burns. One should avoid emesis and should begin early dilutional therapy. Water may be used initially to dislodge adherent solid particles, as well as to dilute the caustic ingestion. It is important not to be excessively aggressive with dilution, as this may cause nausea, vomiting, and possible aspiration. Early otolaryngologic evaluation will be most helpful. The role of early esophagoscopy has been demonstrated to aid greatly in determining the further management. This diagnostic procedure should be carried out within 48 hours after ingestion. Based on the information obtained with esophagoscopy, patients who have had moderate esophageal burns should receive 20 mg methylprednisone intravenously every eight hours if under the age of two and 40 mg intravenously every eight hours if over the age of two. When oral preparations can be used, 2 mg per kg of prednisone should be continued for three to four weeks. Antibiotic coverage should be reserved until the first sign of infection occurs.
• The ingestion of a caustic substance can lead to severe damage to the esophagus. Currently, esophagoscopy is recommended for all patients with a history of caustic substance ingestion because clinical criteria have not proved to be reliable predictors of esophageal injury. The records of 79 consecutive patients younger than 20 years who were first seen with a history of corrosive ingestion were reviewed. The presence or absence of three serious signs and symptoms—vomiting, drooling, and stridor—as well as the presence and location of oropharyngeal burns were compared with the findings on subsequent esophagoscopy. Fifty percent (7/14) of the patients with two or more of these serious signs and symptoms (vomiting, drooling, and stridor) had serious esophageal injury as compared with no positive endoscopic results in the group with none or only one of these clinical findings. The presence of oropharnygeal burns did not identify patients with serious esophageal injury. These results suggest that the presence of two or more signs or symptoms in patients with a history of caustic substance ingestion may be a reliable predictor of esophageal injury. (AJDC 1984;138:863-865)
• We report a case of cupric sulfate intoxication in a child who had a serum copper level of 1,650 μg/100 ml. His course was accompanied by hemolytic anemia and renal tubular damage. We review the pathophysiology of copper metabolism and intoxication. We also review modes of therapy, with specific reference to the initial approach, using dimercaprol (BAL) and edetic acid rather than penicillamine. (Am J Dis Child 131:149-151, 1977)
A 25-year autopsy study (1972-1997) of acute poisoning deaths from a tertiary care hospital in northern India (Postgraduate Institute of Medical Education and Research, Chandigarh) revealed a steep increase in the incidence of acute poisoning since 1987. The majority (68%) of subjects were between the ages of 14 and 30 years, and there was a male preponderance (69%). The main victims were students and unemployed youths, followed by agricultural workers and domestic workers. The proportion of urban victims increased from 45% in the period from 1972 to 1977 to 72% in the period from 1992 to 1997. The proportion of suicidal deaths increased from 34% in the period from 1972 to 1977 to 77% in the period from 1992 to 1997, whereas accidental deaths decreased from 63% to 17% in the same period. Barbiturates (37%) and copper sulfate (22%) were the most common poisons causing mortality between 1972 and 1977; organophosphates (46%) became the most common between 1977 and 1982. Since 1982, aluminum phosphide (65%) has been the most common poison.
To determine whether acid-induced injury to the esophagus is decreased by early dilutional therapy with water or milk. A controlled in-vitro animal model for acid injury to the esophagus was carried out using esophagi harvested from 70 Sprague-Dawley rats of both sexes and weighing 250-350 g. One control and six experimental groups each containing ten esophagi were instilled with 1 mL of 0.5 normal solution of hydrogen chloride (N HCl). Dilution with water or milk was performed at 0, 5, or 30 minutes postinjury in the experimental groups. No dilution was performed with the control group. Specimens were maintained in an oxygenated saline bath for a 60-minute experimental period and then fixed in 10% formalin for histologic evaluation. Injury severity was rated by blinded histopathologic examination using scores of 0 (no injury), 1 (minor), 2 (moderate), and 3 (severe) for the histopathologic categories: cornified epithelial cells (CEs), granular cells (GCs), granular cell nuclei (GNs), and basal cells (BCs). Red blood cells were scored as positive or negative for lysis. The controls showed the most severe outcomes. Significant differences in injury occurred for all time periods and histopathologic categories, except for the GN/water and BC/milk histopathologic category/treatment groups. However, a linear trend analysis was significant for all histopathologic categories except BC. These analyses support decreased injury in the earlier treated groups. Injury severity was highest in the most superficial cell layer (CE). Emergency therapy with water or milk reduces acute acid injury to the esophagus. Earlier treatment is associated with decreased injury severity. This research supports the use of dilutional therapy with water or milk for acute acid injury to the esophagus.
We report the presentation and management of a 25-month-old with copper sulfate ingestion. The child suffered a gastric mucosal burn, but had no evidence of systemic copper toxicity and experienced full recovery with conservative medical management. A literature review of copper sulfate poisoning is provided.