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In addition to its use as a poison, arsenic was used medicinally for centuries and was used extensively to treat [[syphilis]] before [[penicillin]] was introduced. Arsenic was replaced as a therapeutic agent by [[Sulfonamide (medicine)|sulfa drugs]] and then by [[antibiotic]]s. Arsenic was also an ingredient in many tonics (or "[[patent medicine]]s"). In addition, during the [[Victorian era]], some [[women]] used a mixture of [[vinegar]], [[chalk]], and arsenic applied topically to whiten their skin. The use of arsenic was intended to prevent aging and creasing of the skin, but some arsenic was inevitably absorbed into the blood stream.
In addition to its use as a poison, arsenic was used medicinally for centuries and was used extensively to treat [[syphilis]] before [[penicillin]] was introduced. Arsenic was replaced as a therapeutic agent by [[Sulfonamide (medicine)|sulfa drugs]] and then by [[antibiotic]]s. Arsenic was also an ingredient in many tonics (or "[[patent medicine]]s"). In addition, during the [[Victorian era]], some [[women]] used a mixture of [[vinegar]], [[chalk]], and arsenic applied topically to whiten their skin. The use of arsenic was intended to prevent aging and creasing of the skin, but some arsenic was inevitably absorbed into the blood stream.


Some pigments, most notably the popular [[Paris Green|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.
Some pigments, most notably the popular [[Paris Green|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. One of the biggest unintentional cases of arsenic poisoning is in Bangladesh and called by the World Health Organization as the “largest mass poisoning of a population in history.”<ref>{{cite web|url= http://healthmad.com/health/poisons-in-the-well-exposure-health-effects-and-remediation-of-arsenic-and-manganese-in-bangladesh |title=Poisons in The Well: Exposure, Health Effects and Remediation of Arsenic and Manganese in Bangladesh |accessdate=2009-11-01|publisher=Ebey Soman and HealthMad}}</ref>


===Occupational Exposures===
===Occupational Exposures===

Revision as of 14:53, 1 November 2009

Arsenic poisoning
SpecialtyEmergency medicine Edit this on Wikidata

Arsenic poisoning kills by allosteric inhibition of essential metabolic enzymes, leading to death from multi-system organ failure. It primarily inhibits enzymes that require lipoic acid as a cofactor, such as pyruvate and alpha-ketoglutarate dehydrogenase. Because of this, substrates before the dehydrogenase steps accumulate, such as pyruvate (and lactate). It particularly affects the brain, causing neurological disturbances and death.

Toxicity

The toxicity of arsenic and its compounds is highly variable.[1](citation does not accurately reflect information in previous statement). Organic forms appear to have a lower toxicity than inorganic forms of arsenic. Research has shown that arsenites (trivalent forms) have a higher acute toxicity than arsenates (pentavalent forms).[2] The acute minimal lethal dose of arsenic in adults is estimated to be 70 to 200 mg or 1 mg/kg/day.[3] Most reported arsenic poisonings are not caused by elemental arsenic, but by one of arsenics compounds, especially arsenic trioxide, which is approximately 500 times more toxic than pure arsenic.[citation needed] Symptoms include violent stomach pains in the region of the bowels; tenderness and pressure; retching; excessive saliva production; vomiting; sense of dryness and tightness in the throat; thirst; hoarseness and difficulty of speech; the matter vomited, greenish or yellowish, sometimes streaked with blood; diarrhea; tenesmus; sometimes excoriation of the anus; urinary organs occasionally affected with violent burning pains and suppression; convulsions and cramps; clammy sweats; lividity of the extremities; countenance collapsed; eyes red and sparkling; delirium; death. Some of these symptoms may be absent where the poisoning results from inhalation, as of arseniuretted hydrogen.

Symptoms of arsenic poisoning start with mild headaches and can progress to lightheadedness and usually, if untreated, will result in death.

Arsenic poisoning can lead to a variety of problems, from skin cancer to keratoses of the feet.

Chronic exposure to inorganic arsenic may lead to cutaneous hyperpigmentation.[4]: 859 

Pathophysiology

Main article: Arsenic toxicity

Arsenic disrupts 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.[5]

Diagnosis

There are tests 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.[6]

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 singe 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.[7].

Treatment

Chemical and synthetic methods are now used to treat arsenic poisoning. Dimercaprol and dimercaptosuccinic acid are chelating agents which 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.[8]

In the journal Food and Chemical Toxicology, Keya Chaudhuri of the Indian Institute of Chemical Biology in Kolkata, and her colleagues reported giving rats daily doses of arsenic in their water, in levels equivalent to those found in groundwater in Bangladesh and West Bengal. Those rats which were also fed garlic extracts had 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. [9][10][11]

Unintentional poisoning

In addition to its use as a poison, arsenic was used medicinally for centuries and was used extensively to treat syphilis before penicillin was introduced. Arsenic was replaced as a therapeutic agent by sulfa drugs and then by antibiotics. Arsenic was also an ingredient in many tonics (or "patent medicines"). In addition, during the Victorian era, some women used a mixture of vinegar, chalk, and arsenic applied topically to whiten their skin. The use of arsenic was intended to prevent aging and creasing of the skin, but some arsenic was inevitably absorbed into the blood stream.

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. One of the biggest unintentional cases of arsenic poisoning is in Bangladesh and called by the World Health Organization as the “largest mass poisoning of a population in history.”[12]

Occupational Exposures

Industries that use inorganic arsenic and its compounds include wood preservation, glass production, nonferrous metal alloys, and electronic semiconductor manufacturing. Inorganic arsenic is also found in coke oven emissions associated with the smelter industry.[13]

Occupational exposure to arsenic may occur with copper or lead smelting and wood treatment, among workers involved in the production or application of pesticides containing organic arsenicals. Humans are exposed to arsenic through air, drinking water, and food (meat, fish, and poultry); this food is usually the largest source of arsenic. Arsenic was also found in wine if arsenic pesticides are used in the vineyard. Arsenic is well absorbed by oral and inhalation routes, widely distributed and excreted in urine; most of a single, low-level dose is excreted within a few days after consuming any form of inorganic arsenic. Remains of arsenic in nails and hair can be detected years after the exposure.

Arsenicosis: chronic arsenic poisoning from drinking water

Main article: Arsenic contamination of groundwater

Chronic arsenic poisoning results from drinking water with high levels of arsenic over a long period of time. This may occur due to arsenic contamination of groundwater.[14] 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.[citation needed]

Intentional poisoning

Arsenic became a favorite murder weapon of the Middle Ages and Renaissance, particularly among ruling classes in Italy, notably the Borgias. Because the symptoms are similar to those of cholera, which was common at the time, arsenic poisoning often went undetected. By the 19th C., 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 (사약; 賜藥), which was a poison cocktail used in capital punishment of high-profile political figures and members of the royal family.[15]  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.[16]

On April 27, 2003, sixteen members of the Gustaf Adolph Lutheran Church in New Sweden, Maine, became ill following the church coffee hour; one died a short time later. Investigation revealed that the coffee had been heavily laced with arsenic. As of the 2005 publication of Christine Ellen Young's A Bitter Brew, no one had been formally charged with the crime. However, the Discovery Health channel (date?) reported that Daniel Bondeson, who was found with bullet wounds to his chest at a farm, wrote a note saying that he was responsible for the poisoning. He succumbed to the injuries while undergoing surgery.

Murder mystery stories often feature arsenic poisoning, although they commonly omit the more disagreeable symptoms.

Famous victims (known and alleged)

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 and his wife were poisoned possibly by his brother and successor Fernando.[17]

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[18] revealed extremely high levels of arsenic, which is a possible trigger of disease symptoms. A 2005 article in the medical journal The Lancet[19] 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.

Napoleon Bonaparte

It has been theorized 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. As Napoleon's body lay for nearly 20 years in a grave on the island, before being moved to its present resting place in Paris, arsenic from the soil could not have polluted the sample as the arsenic was found within his hair, which can only be possible when the arsenic was already in the body. 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.

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.[20] 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.[20] 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.[21]

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,[22] consistent with the symptoms party members reported. It is possible that Hall dosed himself with quack medicines which included the poison, but it is more likely that he was murdered by Dr. Bessels or one of the other members of the expedition.[23]

Huo Yuan Jia

Huo Yuan Jia made his name as a Chinese martial artist. There was rumour that he was poisoned in 1910 during his fight with the Japanese, who accused China and the Chinese of being the "sick man of Asia". His death was not due to the fight but of his chronic illness.

Clare Boothe Luce

A later case of arsenic poisoning is that of Clare Boothe Luce, (1903 – 1987) the American ambassador to Italy 1953–1956. Although she did not die from her poisoning, she suffered an increasing variety of physical and psychological symptoms until arsenic poisoning was diagnosed, and its source traced to the old, arsenic-laden flaking paint on the ceiling of her bedroom. Another source (see below) explains her poisoning as resulting from eating food contaminated by flaking of the ceiling of the embassy dining room.

Impressionist painters

Emerald Green, a pigment frequently used by Impressionist painters, is based on arsenic. Cezanne developed severe diabetes, which is a symptom of chronic arsenic poisoning. Monet's blindness and Van Gogh's neurological disorders could have been partially due to their use of Emerald Green. Poisoning by other commonly used substances, including liquor and absinthe, lead pigments, mercury-based Vermilion, and solvents such as turpentine, could also be a factor in these cases.

Phar Lap

75 years after his death in 1932, forensic scientists determined the famous and largely successful Australian racehorse Phar Lap died after ingesting a massive dose of arsenic.[24]

See also

Footnotes

  1. ^ Mathieu D, Mathieu-Nolf M, Germain-Alonso M, Neviere R, Furon D, Wattel F (1992). "Massive arsenic poisoning--effect of hemodialysis and dimercaprol on arsenic kinetics". Intensive Care Med. 18 (1): 47–50. doi:10.1007/BF01706427. PMID 1578049.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ Kingston RL, Hall S, Sioris L (1993). "Clinical observations and medical outcome in 149 cases of arsenate ant killer ingestion". J. Toxicol. Clin. Toxicol. 31 (4): 581–91. PMID 8254700.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  3. ^ Dart, RC (2004). Medical toxicology. Philadelphia: Williams & Wilkins. pp. 1393–1401. ISBN 0-7817-2845-2.
  4. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0721629210.
  5. ^ Klaassen, Curtis (2003). Casarett and Doull's Essentials of Toxicology. McGraw-Hill. p. 512. ISBN 978-0071389143. {{cite book}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  6. ^ "ToxFAQs for Arsenic". Agency for Toxic Substances and Disease Registry. Retrieved 2009-01-06.
  7. ^ *Nicolis, I (2009), "Arsenite medicinal use, metabolism, pharmacokinetics and monitoring in human hair", Biochimie., vol. [Epub ahead of print], no. Jun 13}
  8. ^ Dimercaprol Drug Information, Professional
  9. ^ "Food and Chemical Toxicology - Elsevier". Retrieved 2009-03-05.
  10. ^ "Garlic combats arsenic poisoning - health - 14 January 2008 - New Scientist". Retrieved 2009-03-05.
  11. ^ "ScienceDirect - Food and Chemical Toxicology : In vitro and in vivo reduction of sodium arsenite induced toxicity by aqueous garlic extract". Retrieved 2009-03-05.
  12. ^ "Poisons in The Well: Exposure, Health Effects and Remediation of Arsenic and Manganese in Bangladesh". Ebey Soman and HealthMad. Retrieved 2009-11-01.
  13. ^ "OSHA Arsenic". United States Occupational Safety and Health Administration. Retrieved 2007-10-08.
  14. ^ WHO Water-related diseases
  15. ^ 공포의 '비소' 목재
  16. ^ 구혜선, '왕과 나' 폐비윤씨 사약받는 장면 열연 화제
  17. ^ Mari F, Polettini A, Lippi D, Bertol E (2006). "The mysterious death of Francesco I de' Medici and Bianca Cappello: an arsenic murder?". BMJ. 333 (7582): 1299–301. doi:10.1136/bmj.38996.682234.AE. PMC 1761188. PMID 17185715. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  18. ^ BBC NEWS | Health | King George III: Mad or misunderstood?
  19. ^ Madness of King George Linked to Arsenic - AOL News
  20. ^ a b Mowat Farley. 'The Polar Passion: The Quest for the North Pole'. Toronto: McClelland and Stewart Limited, 1967, p. 124
  21. ^ Parry, Richard. 'Trial By Ice: The True Story of Murder and Survival on the 1871 Polaris Expedition'. New York: Ballantine Books, 2001, p. 293
  22. ^ Fleming, Fergus. 'Ninety Degrees North: The Quest for the North Pole'. New York: Grove Press, 2001, p. 142
  23. ^ Chauncey Loomis. "Charles Francis Hall 1821–1871" (PDF).
  24. ^ "Phar Lap 'died from arsenic poisoning'". The Age. 19 June 2008. Retrieved 2008-01-09. {{cite web}}: Check date values in: |date= (help)
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