Arsenic poisoning

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Arsenic poisoning
Classification and external resources
Arsenic contamination areas.jpg
Arsenic poisoning is a global problem arising from naturally occurring arsenic in ground water.
ICD-10 T57.0
ICD-9 985.1
eMedicine emerg/42
MeSH D020261

Arsenic poisoning is a medical condition caused by elevated levels of arsenic in the body. The dominant basis of arsenic poisoning is from ground water that naturally contains high concentrations of arsenic. A 2007 study found that over 137 million people in more than 70 countries are probably affected by arsenic poisoning from drinking water.[1]

Signs and symptoms[edit]

Symptoms of arsenic poisoning begin with headaches, confusion, severe diarrhea, and drowsiness. As the poisoning develops, convulsions and changes in fingernail pigmentation called leukonychia striata may occur. When the poisoning becomes acute, symptoms may include diarrhea, vomiting, blood in the urine, cramping muscles, hair loss, stomach pain, and more convulsions. The organs of the body that are usually affected by arsenic poisoning are the lungs, skin, kidneys, and liver.[2] The final result of arsenic poisoning is coma and death.[citation needed]

Arsenic is related to heart disease[3] (hypertension related cardiovascular), cancer,[4] stroke[5] (cerebrovascular diseases), chronic lower respiratory diseases,[6] and diabetes.[7][8]

Night blindness[edit]

Chronic exposure to arsenic is related to vitamin A deficiency which is related to heart disease and night blindness.[9]

Inorganic arsenites (arsenic(III)) in drinking water have a much higher acute toxicity than organic arsenates (arsenic(V)).[10] The acute minimal lethal dose of arsenic in adults is estimated to be 70 to 200 mg or 1 mg/kg/day.[11]

Exposure modalities[edit]

Drinking water[edit]

Chronic arsenic poisoning results from drinking contaminated well water over a long period of time. Many aquifers contain high concentration of arsenic salts.[12] The World Health Organization recommends a limit of 0.01 mg/L (10ppb) of arsenic in drinking water. This recommendation was established based on the limit of detection of available testing equipment at the time of publication of the WHO water quality guidelines.

More recent findings show that consumption of water with levels as low as 0.00017 mg/L (0.17ppb) over long periods of time can lead to arsenicosis. From a 1988 study in China, the US protection agency quantified the lifetime exposure of arsenic in drinking water at concentrations of 0.0017 mg/L, 0.00017 mg/L, and 0.000017 mg/L are associated with a lifetime skin cancer risk of 1 in 10,000, 1 in 100,000, and 1 in 1,000,000 respectively. The World Health Organization asserts that a level of 0.01 mg/L poses a risk of 6 in 10000 chance of lifetime skin cancer risk and contends that this level of risk is acceptable.[13]

One of the worst incidents of arsenic poisoning via well water occurred in Bangladesh, which the World Health Organization called the "largest mass poisoning of a population in history."[14]

Mining techniques such as hydraulic fracturing may mobilize arsenic in groundwater and aquifers due to enhanced methane transport and resulting changes in redox conditions,[15] and inject fluid containing additional arsenic.[16]

Occupational exposures[edit]

Because of its high toxicity, arsenic is little used in the Western world, although in Asia is still a popular pesticide. Arsenic is mainly encountered occupationally in the smelting of zinc and copper ores.

Food[edit]

It has been found that rice is particularly susceptible to accumulation of arsenic from soil.[17] Rice grown in US has an average 260 ppb of arsenic according to a study, but U.S. arsenic intake remains far below WHO recommended limits.[18] China has set a standard for arsenic limits in food (150 ppb),[19] as levels in rice exceed those in water.[20]

In the United States, levels of arsenic that are above natural levels, but still well below danger levels set in federal safety standards, have been detected in commercially grown chickens.[21] The source of the arsenic appears to be the feed additives roxarsone and nitarsone, which are used to increase weight and skin coloring of the poultry.[22]

History[edit]

In addition to its presence as a poison, for centuries arsenic was used medicinally. It has been used for over 2,400 years as a part of traditional Chinese medicine.[23] In the western world, arsenic compounds, such as salvarsan, were used extensively to treat syphilis before penicillin was introduced. It was eventually replaced as a therapeutic agent by sulfa drugs and then by other antibiotics. Arsenic was also an ingredient in many tonics (or "patent medicines").

In addition, during the Elizabethan era, some women used a mixture of vinegar, chalk, and arsenic applied topically to whiten their skin. This use of arsenic was intended to prevent aging and creasing of the skin, but some arsenic was inevitably absorbed into the blood stream.[citation needed]

Some pigments, most notably the popular Emerald Green (known also under several other names), were based on arsenic compounds. Overexposure to these pigments was a frequent cause of accidental poisoning of artists and craftsmen.

Arsenic became a favored method for murder of the Middle Ages and Renaissance, particularly among ruling classes in Italy allegedly. Because the symptoms are similar to those of cholera, which was common at the time, arsenic poisoning often went undetected.[24]:63 By the 19th century, it had acquired the nickname "inheritance powder," perhaps because impatient heirs were known or suspected to use it to ensure or accelerate their inheritances.[24]:21

In ancient Korea, and particularly in Joseon Dynasty, arsenic-sulfur compounds have been used as a major ingredient of sayak (사약; 賜藥), which was a poison cocktail used in capital punishment of high-profile political figures and members of the royal family.[25]  Due to social and political prominence of the condemned, many of these events were well-documented, often in the Annals of Joseon Dynasty; they are sometimes portrayed in historical television miniseries because of their dramatic nature.[26][dead link]

Notable cases[edit]

Arsenic poisoning, accidental or deliberate, has been implicated in the illness and death of a number of prominent people throughout history.

Francesco I de' Medici, Grand Duke of Tuscany[edit]

Recent forensic evidence uncovered by Italian scientists suggests that Francesco (1541-1587) and his wife were poisoned, possibly by his brother and successor Ferdinando.[27]

George III of Great Britain[edit]

George III's (1738–1820) personal health was a concern throughout his long reign. He suffered from periodic episodes of physical and mental illness, five of them disabling enough to require the King to withdraw from his duties. In 1969, researchers asserted that the episodes of madness and other physical symptoms were characteristic of the disease porphyria, which was also identified in members of his immediate and extended family. In addition, a 2004 study of samples of the King's hair[28] revealed extremely high levels of arsenic, which is a possible trigger of disease symptoms. A 2005 article in the medical journal The Lancet[29] suggested the source of the arsenic could be the antimony used as a consistent element of the King's medical treatment. The two minerals are often found in the same ground, and mineral extraction at the time was not precise enough to eliminate arsenic from compounds containing antimony.

Theodor Ursinus[edit]

Theodor Gottlieb Ursinus (1749–1800),[30] a high-ranking Prussian civil servant and justice official, was poisoned by his wife Charlotte Ursinus (1760–1836). At the time, his death was ruled a stroke, but soon after the widow was found to have poisoned, between 1797 and 1801, not only her husband, but also her aunt and her lover, as well as to have attempted to poison her servant in 1803. Her sensational trial led to the first reliable method of identifying arsenic poisoning.[31]

Napoleon Bonaparte[edit]

It has been suggested that Napoleon Bonaparte (1769–1821) suffered and died from arsenic poisoning during his imprisonment on the island of Saint Helena. Forensic samples of his hair did show high levels, 13 times the normal amount, of the element. This, however, does not prove deliberate poisoning by Napoleon's enemies: copper arsenite has been used as a pigment in some wallpapers, and microbiological liberation of the arsenic into the immediate environment would be possible. The case is equivocal in the absence of clearly authenticated samples of the wallpaper. Samples of hair taken during Napoleon's lifetime also show levels of arsenic, so that arsenic from the soil could not have polluted the post-mortem sample. Even without contaminated wallpaper or soil, commercial use of arsenic at the time provided many other routes by which Napoleon could have consumed enough arsenic to leave this forensic trace.[24]:226–228

Simón Bolívar[edit]

South American independence leader Simón Bolívar (1783–1830), according to Dr. Paul Auwaerter from the Division of Infectious Diseases in the Department of Medicine at the Johns Hopkins University School of Medicine, may have died due to chronic arsenic poisoning further complicated by bronchiectasis and lung cancer.[32][33] Dr. Auwaerter has considered murder and acute arsenic poisoning unlikely, arguing that gradual "environmental contact with arsenic would have been entirely possible" as a result of drinking contaminated water in Peru or through the medicinal use of arsenic -which was common at the time- as Bolívar had reportedly resorted to it during the treatment for some of his illnesses.[32]

Charles Francis Hall[edit]

American explorer Charles Francis Hall (1821–1871) died unexpectedly during his third Arctic expedition aboard the ship Polaris. After returning to the ship from a sledging expedition Hall drank a cup of coffee and fell violently ill.[34] He collapsed in what was described as a fit. He suffered from vomiting and delirium for the next week, then seemed to improve for a few days. He accused several of the ship's company, including ship's physician Dr. Emil Bessels with whom he had longstanding disagreements, of having poisoned him.[34] Shortly thereafter, Hall again began suffering the same symptoms, died, and was taken ashore for burial. Following the expedition's return a US Navy investigation ruled that Hall had died from apoplexy.[35]

In 1968, however, Hall's biographer Chauncey C. Loomis, a professor at Dartmouth College, traveled to Greenland to exhume Hall's body. Due to the permafrost, Hall's body, flag shroud, clothing and coffin were remarkably well preserved. Tissue samples of bone, fingernails and hair showed that Hall died of poisoning from large doses of arsenic in the last two weeks of his life,[36] consistent with the symptoms party members reported. It is possible that Hall dosed himself with quack medicines which included the poison, but it is possible that he was murdered by Dr. Bessels or one of the other members of the expedition.[37]

Clare Boothe Luce[edit]

Clare Boothe Luce, (1903–1987) the American ambassador to Italy 1953–1956, did not die from arsenic poisoning, but suffered an increasing variety of physical and psychological symptoms until arsenic was implicated. Its source was traced to the flaking arsenic-laden paint on the ceiling of her bedroom. She may also have eaten food contaminated by arsenic in flaking ceiling paint in the embassy dining room.[24]:356

Emperor Guangxu[edit]

In 2008, testing in the People's Republic of China confirmed that China's second-to-last emperor was poisoned with a massive dose of arsenic; suspects include his dying aunt, the Empress Dowager Cixi, and her strongman, Yuan Shikai.[38]

Phar Lap[edit]

The famous and largely successful Australian racehorse Phar Lap died suddenly in 1932. Poisoning was considered as a cause of death and several forensic examinations were completed at the time of death. In a recent examination, 75 years after his death, forensic scientists determined that the horse had ingested a massive dose of arsenic shortly before his death.[39]

King Faisal I of Iraq[edit]

According to his British nurse, Lady Badget, King Faisal I of Iraq suffered from symptoms similar to those of arsenic poisoning during his last visit to Switzerland for treatment in 1933, at the age of 48.His Swiss doctors found him in a very healthy situation a day before.[40][dead link]

Pathophysiology[edit]

Arsenic interferes with cellular longevity by allosteric inhibition of an essential metabolic enzyme pyruvate dehydrogenase (PDH) complex, which catalyzes the oxidation of pyruvate to acetyl-CoA by NAD+. With the enzyme inhibited, the energy system of the cell is disrupted resulting in a cellular apoptosis episode. Biochemically, arsenic prevents use of thiamine resulting in a clinical picture resembling thiamine deficiency. Poisoning with arsenic can raise lactate levels and lead to lactic acidosis. Low potassium levels in the cells increases the risk of experiencing a life-threatening heart rhythm problem from arsenic trioxide.[citation needed] Arsenic in cells clearly stimulates the production of hydrogen peroxide (H2O2). When the H2O2 reacts with certain metals such as iron or manganese it produces a highly reactive hydroxyl radical. Inorganic arsenic trioxide found in ground water particularly affects voltage-gated potassium channels,[41] disrupting cellular electrolytic function resulting in neurological disturbances, cardiovascular episodes such as prolonged QT interval, neutropenia, high blood pressure,[42] central nervous system dysfunction, anemia, and death. Arsenic is a ubiquitous element present in American drinking water.[43]

Arsenic exposure plays a key role in the pathogenesis of vascular endothelial dysfunction as it inactivates endothelial nitric oxide synthase, leading to reduction in the generation and bioavailability of nitric oxide. In addition, the chronic arsenic exposure induces high oxidative stress, which may affect the structure and function of cardiovascular system. Further, the arsenic exposure has been noted to induce atherosclerosis by increasing the platelet aggregation and reducing fibrinolysis. Moreover, arsenic exposure may cause arrhythmia by increasing the QT interval and accelerating the cellular calcium overload. The chronic exposure to arsenic upregulates the expression of tumor necrosis factor-α, interleukin-1, vascular cell adhesion molecule and vascular endothelial growth factor to induce cardiovascular pathogenesis.

—Pitchai Balakumar1 and Jagdeep Kaur, "Arsenic Exposure and Cardiovascular Disorders: An Overview", Cardiovascular Toxicology, December 2009[44]

Tissue culture studies have shown that arsenic compounds block both IKr and Iks channels and, at the same time, activates IK-ATP channels. Arsenic compounds also disrupt ATP production through several mechanisms. At the level of the citric acid cycle, arsenic inhibits pyruvate dehydrogenase and by competing with phosphate it uncouples oxidative phosphorylation, thus inhibiting energy-linked reduction of NAD+, mitochondrial respiration, and ATP synthesis. Hydrogen peroxide production is also increased, which might form reactive oxygen species and oxidative stress. These metabolic interferences lead to death from multi-system organ failure, probably from necrotic cell death, not apoptosis. A post mortem reveals brick red colored mucosa, due to severe hemorrhage. Although arsenic causes toxicity, it can also play a protective role.[45]

Diagnosis[edit]

Arsenic may be measured in blood or urine to monitor excessive environmental or occupational exposure, confirm a diagnosis of poisoning in hospitalized victims or to assist in the forensic investigation in a case of fatal over dosage. Some analytical techniques are capable of distinguishing organic from inorganic forms of the element. Organic arsenic compounds tend to be eliminated in the urine in unchanged form, while inorganic forms are largely converted to organic arsenic compounds in the body prior to urinary excretion. The current biological exposure index for U.S. workers of 35 µg/L total urinary arsenic may easily be exceeded by a healthy person eating a seafood meal.[46]

Tests are available to diagnose poisoning by measuring arsenic in blood, urine, hair, and fingernails. The urine test is the most reliable test for arsenic exposure within the last few days. Urine testing needs to be done within 24–48 hours for an accurate analysis of an acute exposure. Tests on hair and fingernails can measure exposure to high levels of arsenic over the past 6–12 months. These tests can determine if one has been exposed to above-average levels of arsenic. They cannot predict, however, whether the arsenic levels in the body will affect health.[47] Chronic arsenic exposure can remain in the body systems for a longer period of time than a shorter term or more isolated exposure and can be detected in a longer time frame after the introduction of the arsenic, important in trying to determine the source of the exposure.

Hair is a potential bioindicator for arsenic exposure due to its ability to store trace elements from blood. Incorporated elements maintain their position during growth of hair. Thus for a temporal estimation of exposure, an assay of hair composition needs to be carried out with a single hair which is not possible with older techniques requiring homogenization and dissolution of several strands of hair. This type of biomonitoring has been achieved with newer microanalytical techniques like Synchroton radiation based X ray fluorescence (SXRF) spectroscopy and Microparticle induced X ray emission (PIXE).The highly focused and intense beams study small spots on biological samples allowing analysis to micro level along with the chemical speciation. In a study, this method has been used to follow arsenic level before, during and after treatment with Arsenious oxide in patients with Acute Promyelocytic Leukemia.[48]

Treatment and Methods For removal of Arsenic Contaminants[edit]

Chelation[edit]

Chemical and synthetic methods are used to treat arsenic poisoning. Dimercaprol and dimercaptosuccinic acid are chelating agents that sequester the arsenic away from blood proteins and are used in treating acute arsenic poisoning. The most important side effect is hypertension. Dimercaprol is considerably more toxic than succimer.[citation needed][49] DMSA monoesters e.g. MiADMSA are promising antidotes for arsenic poisoning.[50]

Mineral supplements[edit]

Supplemental potassium decreases the risk of experiencing a life-threatening heart rhythm problem from arsenic trioxide.[51]

Nutritional intervention[edit]

Rats daily dosed with arsenic in their water, in levels equivalent to those found in groundwater in Bangladesh and West Bengal were found to respond to garlic extracts, with 40 percent less arsenic in their blood and liver, and passed 45 percent more arsenic in their urine. The conclusion is that sulfur-containing substances in garlic scavenge arsenic from tissues and blood. The presentation concludes that people in areas at risk of arsenic contamination in the water supply should eat one to three cloves of garlic per day as a preventative.[52][53][54]

Removal Methods[edit]

Various techniques have been evolved for Arsenic removal, most frequently using absorbents such as activated carbon, aluminum oxide, co-operative with iron oxide to form sludge’s, sorption onto iron-oxide-coated polymeric materials, Electrocoagulation, by nanoparticle . To remove the stress of heavy and toxic metals, environment friendly approach must be applied and use of naturally occurring microbe must be emphasized . Bacteria, yeast, fungi, algae all of them can be used for remediation processes and it is always recommended that microbe used for bioremediation must have natural decontamination process and the method should be cost-effective. [55]

See also[edit]

References[edit]

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Further reading[edit]

External links[edit]