Arsenic Part 2 and its History as Medicine and Poison.

Contamination of groundwater, either from anthropogenic or natural sources with several social impacts, has now turned to be a major environmental concern in different parts of the world. Millions of people in several countries are exposed to high levels of as via intake of As-rich groundwater. Elevated level of As in groundwater has been well documented in Chile, Mexico, China, Argentina, USA, and Hungary as well as in the Indian State of West Bengal, Bangladesh, and Vietnam. About 150 million people around the world are estimated to be affected globally with an increasing prospect as new affected areas are continuously discovered. Arsenic, a well-known carcinogen, is considered as one of the world’s most hazardous chemicals. Excessive and long-term (such as 5–10 years) human intake of toxic inorganic As from drinking water and food may result in arsenicosis, a common name generally used for As related health problems including skin disorders, skin cancers, internal cancers (bladder, kidney, and lung), diseases of the blood vessels of the legs and feet, possibly diabetes, increased blood pressure, and reproductive disorders.

 

In terrestrial environment, the inorganic forms of as (such as trivalent arsenate and pentavalent arsenate are more prevalent and toxic than the organic forms in general. As exerts detrimental effects on general protein metabolism with high toxicity by reacting with sulfhydryl groups existing in cysteine residues.

 

Arsenic sis causes dire consequences for the livelihood, family life, and earning capability when individuals fall victim. Deterioration in physical appearance makes women socially excluded. At larger perspectives elevated as contamination of a region may result in societal stress, disability in individuals, poverty, and decreased market value of potentially contaminated agricultural products leading to low income to the affected farmers. Absence of taste, odour, colour, and exposure make as impossible for a layman to detect and avoid. Applying the WHO provisional guideline for drinking water of 10–50?ppb of As, a population of more than 100 million people worldwide is at risk, and of these more than 45 million people mainly in developing countries from Asia are at risk of being exposed to more than 50?ppb of As, which is the maximum concentration limit in drinking water in most of the countries in Asia.

 

At present, as is estimated to affect more than 150 million people worldwide with its increasingly elevated concentrations in drinking water. The major arsenicosis affected areas have been reported in large deltas and/or along major river basins across the world such as in Paraiba do Sul delta, Brazil, Ganga delta, Mekong delta, Cambodia, Danube river basin, Hungry, Hetao river basin, Mongolia, Duero Cenozoic Basin, Spain, Zenne river basin, Belgium, and Tulare Lake, USA. The transfer of as to the food chain will ultimately remain as long-term risks to human and ecological systems. Since water is the principal route through which as enters into the human body, the understanding of the processes of as contamination in groundwater, associated health risks, and mitigation of as problem is required.

Toxicity of Arsenic

Several review articles have documented arsenic toxicity in humans and animals. Arsenic is a potent carcinogen, leading to skin, bladder, liver, and lung cancers. Arsenic induces epidemiological toxicity. It results in the formation of excess ROS thereby damaging organisms. Arsenic is also known to cause cytotoxicity and genotoxicity. In addition, it is well-established fact that chronic exposure to arsenic can lead to arsenicosis, including skin lesions, blackfoot disease, peripheral vascular disease, and cancers. However, several studies have reported arsenicosis due to elevated level of as.

Key facts

• Arsenic is naturally present at high levels in the groundwater of a number of countries.
• Arsenic is highly toxic in its inorganic form.
• Contaminated water used for drinking, food preparation and irrigation of food crops poses the greatest threat to public health from arsenic.
• Long-term exposure to arsenic from drinking-water and food can cause cancer and skin lesions. It has also been associated with developmental effects, cardiovascular disease, neurotoxicity and diabetes.
• The most important action in affected communities is the prevention of further exposure to arsenic by provision of a safe water supply.

Sources of exposure

Arsenic is a natural component of the earth’s crust and is widely distributed throughout the environment in the air, water and land. It is highly toxic in its inorganic form.

People are exposed to elevated levels of inorganic arsenic through drinking contaminated water, using contaminated water in food preparation and irrigation of food crops, industrial processes, eating contaminated food and smoking tobacco.

Long-term exposure to inorganic arsenic, mainly through drinking of contaminated water, eating of food prepared with this water and eating food irrigated with arsenic-rich water, can lead to chronic arsenic poisoning. Skin lesions and skin cancer are the most characteristic effects.

Drinking-water and food

The greatest threat to public health from arsenic originates from contaminated groundwater. Inorganic arsenic is naturally present at high levels in the groundwater of a number of countries, including Argentina, Bangladesh, Chile, China, India, Mexico, and the United States of America. Drinking-water, crops irrigated with contaminated water and food prepared with contaminated water are the sources of exposure.

Fish, shellfish, meat, poultry, dairy products and cereals can also be dietary sources of arsenic, although exposure from these foods is generally much lower compared to exposure through contaminated groundwater. In seafood, arsenic is mainly found in its less toxic organic form.

Industrial processes

Arsenic is used industrially as an alloying agent, as well as in the processing of glass, pigments, textiles, paper, metal adhesives, wood preservatives and ammunition. Arsenic is also used in the hide tanning process and, to a limited extent, in pesticides, feed additives and pharmaceuticals.

Tobacco

People who smoke tobacco can also be exposed to the natural inorganic arsenic content of tobacco because tobacco plants essentially take up arsenic naturally present in the soil. Also, in the past, the potential for elevated arsenic exposure was much greater when tobacco plants used to be treated with lead arsenate insecticide.

Health effects

Arsenic occurs in inorganic and organic forms. Inorganic arsenic compounds (such as those found in water) are highly toxic while organic arsenic compounds (such as those found in seafood) are less harmful to health.

Acute effects

The immediate symptoms of acute arsenic poisoning include vomiting, abdominal pain and diarrhoea. These are followed by numbness and tingling of the extremities, muscle cramping and death, in extreme cases.

Long-term effects

The first symptoms of long-term exposure to high levels of inorganic arsenic (e.g. through drinking-water and food) are usually observed in the skin, and include pigmentation changes, skin lesions and hard patches on the palms and soles of the feet (hyperkeratosis). These occur after a minimum exposure of approximately five years and may be a precursor to skin cancer.

In addition to skin cancer, long-term exposure to arsenic may also cause cancers of the bladder and lungs. The International Agency for Research on Cancer (IARC) has classified arsenic and arsenic compounds as carcinogenic to humans, and has also stated that arsenic in drinking-water is carcinogenic to humans.

Other adverse health effects that may be associated with long-term ingestion of inorganic arsenic include developmental effects, neurotoxicity, diabetes and cardiovascular disease. In China (Province of Taiwan), arsenic exposure has been linked to “Blackfoot disease”, which is a severe disease of blood vessels leading to gangrene. However, this disease has not been observed in other parts of the world, and it is possible that malnutrition contributes to its development.

Magnitude of the problem

Arsenic contamination of groundwater is widespread and there are a number of regions where arsenic contamination of drinking-water is significant.

Arsenic in Bangladesh has attracted much attention since recognition in the 1990s of its wide occurrence in well-water in that country. Since this time, significant progress has since been made and the number of people exposed to arsenic exceeding the Bangladesh drinking-water quality standard has decreased by approximately 40%. Despite these efforts, it is estimated that about 20 million and 45 million people in Bangladesh are at risk of being exposed to arsenic concentrations that are greater than the national standard of 50 μg/litre and the WHO guideline value of 10 μg/litre respectively.

The symptoms and signs caused by long-term elevated exposure to inorganic arsenic differ between individuals, population groups and geographical areas. Thus, there is no universal definition of the disease caused by arsenic. This complicates the assessment of the burden on health of arsenic.

Similarly, there is no method to distinguish cases of cancer caused by arsenic from cancers induced by other factors. As a result, there is no reliable estimate of the magnitude of the problem worldwide.

In 2010, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) re-evaluated the effects of arsenic on human health, taking new data into account. JECFA concluded that for certain regions of the world where concentrations of inorganic arsenic in drinking-water exceed 50–100 μg/litre, there is some evidence of adverse effects. In other areas, where arsenic concentrations in water are elevated (10–50 μg/litre), JECFA concluded that while there is a possibility of adverse effects, these would be at a low incidence that would be difficult to detect in epidemiological studies.

Prevention and control

The most important action in affected communities is the prevention of further exposure to arsenic by the provision of a safe water supply for drinking, food preparation and irrigation of food crops. There are a number of options to reduce levels of arsenic in drinking-water.

• Substitute high-arsenic sources such as groundwater, with low-arsenic, microbiologically safe sources such as rain water and treated surface water. Low-arsenic water can be used for drinking, cooking and irrigation purposes, whereas arsenic-rich water can be used for other purposes such as bathing and washing clothes.
• Discriminate between high-arsenic and low-arsenic sources. For example, test water for arsenic levels and paint tube wells or hand pumps different colours. This can be an effective and low-cost means to rapidly reduce exposure to arsenic when accompanied by effective education.
• Blend low-arsenic water with higher-arsenic water to achieve an acceptable arsenic concentration level.
• Install arsenic removal systems – either centralized or domestic – and ensure the appropriate disposal of the removed arsenic. Technologies for arsenic removal include oxidation, coagulation–precipitation, absorption, ion exchange and membrane techniques. There is an increasing number of effective and low-cost options for removing arsenic from small or household supplies.

Long-term actions are also required to reduce occupational exposure from industrial processes.

Education and community engagement are key factors for ensuring successful interventions. There is a need for community members to understand the risks of high arsenic exposure and the sources of arsenic exposure, including the intake of arsenic by crops (e.g. rice) from irrigation water and the intake of arsenic into food from cooking water.

High-risk populations should also be monitored for early signs of arsenic poisoning – usually skin problems.

WHO response

Arsenic is one of WHO’s 10 chemicals of major public health concern. WHO’s work to reduce arsenic exposure includes setting guideline values, reviewing evidence and providing risk management recommendations. WHO publishes a guideline value for arsenic in its Guidelines for drinking-water quality. The Guidelines are intended for use as the basis for regulation and standard setting worldwide. The current recommended limit of arsenic in drinking-water is 10 μg/litre, although this guideline value is designated as provisional because of measurement difficulties and the practical difficulties in removing arsenic from drinking-water. Where it is difficult to achieve the guideline value, Member States may set higher values as standards taking into account local circumstances, resources and risks from low arsenic sources that are contaminated microbiologically.

Arsenic contamination of groundwater in different parts of the world is an outcome of natural and/or anthropogenic sources, leading to adverse effects on human health and ecosystem. Millions of people from different countries are heavily dependent on groundwater containing elevated level of As for drinking purposes. As contamination of groundwater, poses a serious risk to human health. Excessive and prolonged exposure of inorganic As with drinking water is causing arsenicosis, a deteriorating and disabling disease characterized by skin lesions and pigmentation of the skin, patches on palm of the hands and soles of the feet. Arsenic poisoning culminates into potentially fatal diseases like skin and internal cancers. This paper reviews sources, speciation, and mobility of As and global overview of groundwater As contamination. The paper also critically reviews the As led human health risks, its uptake, metabolism, and toxicity mechanisms. The paper provides an overview of the state-of-the-art knowledge on the alternative as free drinking water and various technologies (oxidation, coagulation flocculation, adsorption, and microbial) for mitigation of the problem of As contamination of groundwater.

Detection of Poisons in Food. Signs and symptoms.

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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.

Signs and symptoms

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, Mees' lines, or Aldrich-Mees' lines 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. The final result of arsenic poisoning is coma and death.

Arsenic is related to heart disease (hypertension-related cardiovascular disease), cancer,stroke (cerebrovascular diseases), chronic lower respiratory diseases, and diabetes.

Night blindness

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

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

Causes

Drinking water:

Chronic arsenic poisoning results from drinking contaminated well water over a long period of time. Many aquifers contain high concentration of arsenic salts. The World Health Organization recommends a limit of 0.01 mg/L (10 parts per billion) of arsenic in drinking water. This recommendation was established based on the limit of detection for most laboratories' 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 (0.17 parts per billion) 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.

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."

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

Occupational exposure:

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

Food

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

Arsenic is a ubiquitous element present in American drinking water. 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. The source of the arsenic appears to be the feed additives roxarsone and nitarsone, which are used to control the parasitic infection coccidiosis as well as to increase weight and skin coloring of the poultry.

High levels of inorganic arsenic were reportedly found in 83 California wines in 2015.

History

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. 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. 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.

In ancient Korea, and particularly in Joseon Dynasty, arsenic-sulfur compounds have been used as a major ingredient of sayak (??; 賜藥), which was a poison cocktail used in capital punishment of high-profile political figures and members of the royal family. 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.

Notable cases

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

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

George III of Great Britain

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 revealed extremely high levels of arsenic, which is a possible trigger of disease symptoms. A 2005 article in the medical journal The Lancet 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

Theodor Gottlieb Ursinus (1749–1800) 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.

Napoleon Bonaparte

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.

Simón Bolívar

South American independence leader Simón Bolívar (1783–1830), according to 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. 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.

Charles Francis Hall

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. 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 Emil Bessels with whom he had longstanding disagreements, of having poisoned him. 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.

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,[53] 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 Bessels or one of the other members of the expedition.

Clare Boothe Luce

Clare Boothe Luce (1903–1987), the American ambassador to Italy from 1953 to 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.

Emperor Guangxu

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.

Phar Lap

The famous and largely successful New Zealand-bred 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.

King Faisal I of Iraq

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.

Anderson Mazoka

The popular opposition leader in Zambia, Anderson Mazoka, whose health deteriorated after the 2001 presidential elections, repeatedly accused government agents of poisoning him. His daughter, Mutinta, confirmed after his death on 24 May 2006 that arsenic was found in his body after he died from kidney complications.

Munir Said Thalib

A human rights activist from Indonesia named Munir Said Thalib was poisoned with arsenic on a flight from Jakarta to Amsterdam on September 7, 2004. He was travelling on state-owned airline Garuda Indonesia. It was concluded from Munir's autopsy and eyewitnesses during the trial that he had died two hours before arrival in Schiphol, Amsterdam. He took the arsenic during his flight transit in Singapore, or sometime near that time.