Arsenic poisoning

Infobox_Disease
Name = Arsenic poisoning


Caption =
DiseasesDB =
ICD10 = ICD10|T|57|0|t|51
ICD9 = ICD9|985.1
ICDO =
OMIM =
MedlinePlus =
eMedicineSubj = emerg
eMedicineTopic = 42
MeshID = D020261

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.

ymptoms

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.

Treatment and testing

It is extremely important to seek medical advice immediately if arsenic poisoning is suspected. One way to test for arsenic poisoning is by checking hair follicles. If arsenic is in the bloodstream, it will enter hair and [http://www.newsobserver.com/content/news/crime_safety/arsenic/story_graphics/20040928_arsenic.pdf remain there] for many years.

Chemical and synthetic methods are now used to treat arsenic poisoning. Dimercaprol and Succimer 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. [ [http://www.drugs.com/MMX/Dimercaprol.html Dimercaprol Drug Information, Professional ] ]

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 per cent less arsenic in their blood and liver, and passed 45 per cent 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. [http://www.elsevier.com/wps/find/journaldescription.cws_home/237/description#description Journal of Food and Chemical Toxicology, DOI see: 10.1016/j.fct.2007.09.108] [http://www.newscientist.com/article/mg19726385.100-garlic-combats-arsenic-poisoning.html] [http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T6P-4PT0Y7V-2&_user=961305&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000049425&_version=1&_urlVersion=0&_userid=961305&md5=b0917537375df1e9de7fe4f4f897af03]

Potency

The LD₅₀ for pure arsenic is 763 mg/kg (by ingestion) and 13 mg/kg (by intraperitoneal injection). For a 70 kg (~155 lb) human, this works out to about 53 grams (less than 2 ounces). However, compounds containing arsenic can be significantly more toxic. [http://www.chemistry.org/portal/a/c/s/1/feature_tea.html?id=c373e90097f810dd8f6a17245d830100]

Nearly all reported arsenic poisonings were not caused by pure arsenic, but by arsenic-oxygen compounds, especially arsenic trioxide, which is approximately 500 times more toxic than pure arsenic, and by arsine.

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.

Arsenicosis: chronic arsenic poisoning from drinking water

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. [ [http://who.int/water_sanitation_health/diseases/arsenicosis/en/ WHO Water-related diseases] ]

Effects include changes in skin color, formation of hard patches on the skin, skin cancer, lung cancer, cancer of the kidney and bladder, and can lead to gangrene. 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 0.00017mg/L (0.17ppb) over long periods of time can lead to arsenicosis.

Non-carcinogenic chronic effects include liver injury—jaundice and cirrhosis;—peripheral vascular disease involving blueness of the extremities; Raynaud's syndrome; blackfoot disease (a type of gangrene); anemia, resulting from impaired heme biosynthesis; and hyperkeratosis of the skin.

There are also multiple lines of evidence for the carcinogenic effects of arsenic.

Arsenic has been known to cause many problems in Third World countries where groundwater supplies have been contaminated by arsenic derived from geologically recent fluvial deposits containing arseno-pyrites. This is a particular problem in Bangladesh where tube wells installed since the 1970s have intercepted ground waters flowing in the fluvial deposits. Concentrations in these wells can exceed 1 part per thousand whereas the WHO maximum level is 10 parts per billion. "See Arsenic contamination of groundwater".

Roger Smith, Professor of Pharmacology and Toxicology Emeritus, Dartmouth Medical School [http://dartmed.dartmouth.edu/fall06/html/disc_arsenic.php] , [http://www.dartmouth.edu/~toxmetal/TXSHas.shtml] , has confirmed that natural arsenic contamination of drinking water has also been a problem in wells in New Hampshire. Chronic low-level arsenic poisoning, or arsenicosis, as is seen in Bangladesh, can potentially cause cancer.

Intentional poisoning

In the 8th century A.D, an Arab alchemist named Jabir became the first to prepare arsenic trioxide, a white, tasteless, odorless powder. Jabir's preparation seemed the ideal poison as it left no traceable (at the time) elements in the body.

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. Elizabeth Báthory is also suspected of having used arsenic to poison male lovers so that they could never leave her, probably as a result of her first husband having an affair.

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. [ [http://imnews.imbc.com/replay/nwdesk/article/2084429_2687.html 공포의 '비소' 목재] ] 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. [ [http://spn.chosun.com/site/data/html_dir/2008/02/18/2008021800711.html 구혜선, '왕과 나' 폐비윤씨 사약받는 장면 열연 화제] ]

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. [cite web |url=http://www.bmj.com/cgi/content/full/333/7582/1299 |title=The mysterious death of Francesco I de' Medici and Bianca Cappello: an arsenic murder? -- Mari et al. 333 (7582): 1299 -- BMJ |accessdate=2007-08-04 |format= |work=]

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 [ [http://news.bbc.co.uk/1/hi/health/3889903.stm BBC NEWS | Health | King George III: Mad or misunderstood? ] ] revealed extremely high levels of arsenic, which is a possible trigger of disease symptoms. A 2005 article in the medical journal The Lancet [ [http://aolsvc.news.aol.com/news/article.adp?id=20050722092109990013 Madness of King George Linked to Arsenic - AOL News ] ] 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

There is a theory 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 also have polluted the 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.

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 Dr. 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, 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.

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. [ [http://sports.yahoo.com/rah/news?slug=ap-australia-pharlap&prov=ap&type=lgns Phar Lap died of arsenic poisoning - Horse Racing - Yahoo! Sports ] ]

ee also

* 2007 Peruvian meteorite event - a meteorite impact that is believed to have caused arsenic poisoning.

Footnotes

References

*Harvey, Richard A. "Biochemistry, 3rd Edition." Lippincott's Illustrated Reviews, 2005.
* Kind, Stuart and Overman, Michael. "Science Against Crime". Doubleday and Company, Inc., New York, 1972. ISBN 0-385-09249-0.
*cite journal |author=Saha KC |title=Diagnosis of arsenicosis |journal=Journal of environmental science and health. Part A, Toxic/hazardous substances & environmental engineering |volume=38 |issue=1 |pages=255–72 |year=2003 |pmid=12635831 |doi=
*Powell, Michael "101 People You Won't Meet In Heaven" First Lyons Press edition 2007 ISBN 978-1-59921-105-3

External links

* [http://www.atsdr.cdc.gov/csem/arsenic/treatment_management.html#chelation ATSDR - Arsenic Chelation Therapy]
* [http://www.atsdr.cdc.gov/csem/arsenic/ ATSDR - Case Studies in Environmental Medicine: Arsenic Toxicity]
* [http://www-cie.iarc.fr/htdocs/monographs/vol23/arsenic.html Evaluation of the carcinogenicity of arsenic and arsenic compounds] by the IARC
* [http://www.npi.gov.au/database/substance-info/profiles/11.html National Pollutant Inventory - Arsenic]
* [http://www.dartmouth.edu/~toxmetal/TXSHas.shtml Luce case/Dartmouth]