Arsenic poisoning

Arsenic Poisoning

Arsenic poisoning is a global problem arising from naturally occurring arsenic in ground water.
Classification and external resources
Specialty Toxicology
ICD-10 T57.0
ICD-9-CM 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 groundwater 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

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.[2] When the poisoning becomes acute, symptoms may include diarrhea, vomiting,vomiting blood, 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.[3] The final result of arsenic poisoning is coma and death.[4]

Arsenic is related to heart disease[5] (hypertension-related cardiovascular disease), cancer,[6] stroke[7] (cerebrovascular diseases), chronic lower respiratory diseases,[8] and diabetes.[9][10]

Chronic exposure to arsenic is related to vitamin A deficiency, which is related to heart disease and night blindness.[11]

Inorganic arsenites (arsenic(III)) in drinking water have a much higher acute toxicity than organic arsenates (arsenic(V)).[12] The acute minimal lethal dose of arsenic in adults is estimated to be 70 to 200 mg or 1 mg/kg/day.[13]

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.[14] The World Health Organization (WHO) 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.[15][16]

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. WHO 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.[17]

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."[18]

Mining techniques such as hydraulic fracturing may mobilize arsenic in groundwater and aquifers due to enhanced methane transport and resulting changes in redox conditions,[19] and inject fluid containing additional arsenic.[20]

Occupational exposures

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.[21] Rice grown in the U.S. has an average 260 ppb of arsenic, according to a study; but U.S. arsenic intake remains far below World Health Organization-recommended limits.[22] China has set a standard for arsenic limits in food (150 ppb),[23] as levels in rice exceed those in water.[24]

Arsenic is a ubiquitous element present in American drinking water.[25] 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.[26] 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.[27]

High levels of inorganic arsenic were reportedly found in 83 California wines in 2015.[28]

Pathophysiology

Main article: Arsenic toxicity

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. 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,[29] disrupting cellular electrolytic function resulting in neurological disturbances, cardiovascular episodes such as prolonged QT interval, neutropenia, high blood pressure,[30] central nervous system dysfunction, anemia, and death.

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[31]

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.[32]

Diagnosis

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.[33]

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.[34] 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 Synchrotron 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.[35]

Treatment

Chelation

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.[36] DMSA monoesters, e.g. MiADMSA, are promising antidotes for arsenic poisoning.[37] Calcium sodium edetate is also used.

Nutrition

Supplemental potassium decreases the risk of experiencing a life-threatening heart rhythm problem from arsenic trioxide.[38]

Removal

Various techniques have been evolved for arsenic removal, most frequently using absorbents such as activated carbon, aluminium oxide, co-operative with iron oxide to form sludges, adsorption onto iron-oxide-coated polymeric materials, and electrocoagulation by nanoparticle. Bacteria, yeast, fungi, and algae can also be used for remediation processes.[39]

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.[40] 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.

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.[41]: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.[41]: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.[42]  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.[43]

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.[44]

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[45] revealed extremely high levels of arsenic, which is a possible trigger of disease symptoms. A 2005 article in the medical journal The Lancet[46] 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),[47] 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.[48]

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.[41]:226–228

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.[49][50] 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.[49]

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.[51] 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.[51] 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.[52]

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 he was murdered by Bessels or one of the other members of the expedition.[54]

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.[41]:356

Guangxu Emperor

In 2008, testing in the People's Republic of China confirmed that the Guangxu Emperor (1871–1908) was poisoned with a massive dose of arsenic; suspects include his dying aunt, Empress Dowager Cixi, and her strongman, Yuan Shikai.[55]

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.[56]

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.[57]

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.[58]

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.

Thomas Chatterton

The creator of the 'Rowley Poems', elaborately crafted antique verse, who died from an accidental overdose of arsenic and opium on 24 August 1770. He became a figure of Romantic myth for William Wordsworth, Samuel Taylor Coleridge and Robert Southey. John Keats dedicated his Endymion 'to the memory of Thomas Chatterton'.

See also

References

  1. ↑ See:
  2. ↑ Yalçın Tüzün (2009). "Leukonychia" (PDF).
  3. ↑ "Test ID: ASU. Arsenic, 24 Hour, Urine, Clinical Information". Mayo Medical Laboratories Catalog. Mayo Clinic. Retrieved 2012-09-25.
  4. ↑ "Arsenic Poisoning". IHC World. Retrieved 2 May 2014.
  5. ↑ Tseng CH, Chong CK, Tseng CP; et al. (January 2003). "Long-term arsenic exposure and ischemic heart disease in arseniasis-hyperendemic villages in Taiwan". Toxicol. Lett. 137 (1–2): 15–21. doi:10.1016/S0378-4274(02)00377-6. PMID 12505429.
  6. ↑ Smith AH, Hopenhayn-Rich C, Bates MN; et al. (July 1992). "Cancer risks from arsenic in drinking water". Environ. Health Perspect. 97: 259–67. doi:10.2307/3431362. PMC 1519547. PMID 1396465.
  7. ↑ Chiou HY, Huang WI, Su CL, Chang SF, Hsu YH, Chen CJ (September 1997). "Dose-response relationship between prevalence of cerebrovascular disease and ingested inorganic arsenic". Stroke 28 (9): 1717–23. doi:10.1161/01.STR.28.9.1717. PMID 9303014.
  8. ↑ Hendryx M (January 2009). "Mortality from heart, respiratory, and kidney disease in coal mining areas of Appalachia". Int Arch Occup Environ Health 82 (2): 243–9. doi:10.1007/s00420-008-0328-y. PMID 18461350.
  9. ↑ Navas-Acien A, Silbergeld EK, Pastor-Barriuso R, Guallar E (August 2008). "Arsenic exposure and prevalence of type 2 diabetes in US adults". JAMA 300 (7): 814–22. doi:10.1001/jama.300.7.814. PMID 18714061.
  10. ↑ Kile ML, Christiani DC (August 2008). "Environmental arsenic exposure and diabetes". JAMA 300 (7): 845–6. doi:10.1001/jama.300.7.845. PMID 18714068.
  11. ↑ Hsueh YM, Wu WL, Huang YL, Chiou HY, Tseng CH, Chen CJ (December 1998). "Low serum carotene level and increased risk of ischemic heart disease related to long-term arsenic exposure". Atherosclerosis 141 (2): 249–57. doi:10.1016/S0021-9150(98)00178-6. PMID 9862173.
  12. ↑ 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. doi:10.3109/15563659309025763. PMID 8254700.
  13. ↑ Dart, RC (2004). Medical toxicology. Philadelphia: Williams & Wilkins. pp. 1393–1401. ISBN 0-7817-2845-2.
  14. ↑ WHO Water-related diseases
  15. ↑ (August 10, 2011) Concentration of selected toxic metals in groundwater and some cereals grown in Shibganj area of Chapai Nawabganj, Rajshahi, Bangladesh (Page 429) Current Science Journal, retrieved August 29, 2014
  16. ↑ ( April–June, 2012)Rwanda Bureau of Standards Newsletter (Page 35), Rwanda Bureau of Standards, retrieved August 29, 2014
  17. ↑ "Towards an assessment of the socioeconomic impact of arsenic poisoning in Bangladesh: Health effects of arsenic in drinking water (Page 5)" (PDF). Drinking Water Quality. WHO. Retrieved 2014-08-29.
  18. ↑ "Contamination of drinking-water by arsenic in Bangladesh: a public health emergency" (PDF). World Health Organisation. Retrieved 2013-08-27.
  19. ↑ Brown, R.A. and Katrina E. Patterson, K.E., Mitchell D. Zimmerman, M.D., & Ririe, G. T. (May, 2010). Attenuation of Naturally Occurring Arsenic at Petroleum Hydrocarbon–Impacted Sites. Seventh International Conference on Remediation of Chlorinated and Recalcitrant Compounds. ISBN 978-0-9819730-2-9, Battelle Memorial Institute, Columbus, OH, www.battelle.org/chlorcon.
  20. ↑ Murcott, S. (2012). Arsenic contamination in the world. London: IWA Publishing.
  21. ↑ Deborah Kotz (December 8, 2011). "Do you need to worry about arsenic in rice?". Boston Globe. Retrieved December 8, 2011.
  22. ↑ "Surprisingly high concentrations of toxic arsenic species found in U.S. rice".
  23. ↑ "Rice as a source of arsenic exposure".
  24. ↑ "China: Inorganic Arsenic in Rice - An Underestimated Health Threat?".
  25. ↑ http://water.usgs.gov/nawqa/trace/arsenic/
  26. ↑ "Study Finds an Increase in Arsenic Levels in Chicken". New York Times. May 11, 2013.
  27. ↑ "FDA: Pfizer will voluntarily suspend sale of animal drug 3-Nitro".
  28. ↑ "Dangerous arsenic levels found in California wine from 28 producers, suit claims". New York Daily News. March 21, 2015.
  29. ↑ Zhou J, Wang W, Wei QF, Feng TM, Tan LJ, Yang BF (July 2007). "Effects of arsenic trioxide on voltage-dependent potassium channels and on cell proliferation of human multiple myeloma cells". Chin. Med. J. 120 (14): 1266–9. PMID 17697580.
  30. ↑ Konduri GG, Bakhutashvili, I, Eis A, Gauthier KM (2009). "Impaired Voltage Gated Potassium Channel Responses in a Fetal Lamb Model of Persistent Pulmonary Hypertension of the Newborn". Pediatric Research 66 (3): 289–294. doi:10.1203/PDR.0b013e3181b1bc89. PMC 3749926. PMID 19542906.
  31. ↑ Balakumar, Pitchai; Kaur, Jagdeep (December 2009). "Arsenic Exposure and Cardiovascular Disorders: An Overview". Cardiovascular Toxicology 9 (4): 169–76. doi:10.1007/s12012-009-9050-6. PMID 19787300.
  32. ↑ Klaassen, Curtis; Watkins, John (2003). Casarett and Doull's Essentials of Toxicology. McGraw-Hill. p. 512. ISBN 978-0-07-138914-3.
  33. ↑ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 106-110.
  34. ↑ "ToxFAQs for Arsenic". Agency for Toxic Substances and Disease Registry. Archived from the original on 15 January 2009. Retrieved 2009-01-06.
  35. ↑ Nicolis I, Curis E, Deschamps P, Bénazeth S (October 2009). "Arsenite medicinal use, metabolism, pharmacokinetics and monitoring in human hair". Biochimie 91 (10): 1260–7. doi:10.1016/j.biochi.2009.06.003. PMID 19527769.
  36. ↑ Dimercaprol Drug Information, Professional
  37. ↑ [Kreppel H, Reichl FX, Kleine A, Szinicz L, Singh PK, Jones MM. Antidotal efficacy of newly synthesized dimercaptosuccinic acid (DMSA) monoesters in experimental arsenic poisoning in mice. Fundam. Appl. Toxicol. 26(2), 239–245 (1995).]
  38. ↑ Arsenic Trioxide (Trisenox®). The Abramson Cancer Center of the University of Pennsylvania. Last Modified: December 25, 2005
  39. ↑ Roy, Debarshi; Gaur, Priya; Verma, Neeraj; Pathireddy, Monika; Singh, Krishna P. (2013). "Bioremediation of Arsenic (III) from Water Using Baker Yeast Saccharomyces cerevisiae". International Journal of Environmental Bioremediation & Biodegradation 1: 14–19. doi:10.12691/ijebb-1-1-3.
  40. ↑ "Application of arsenic trioxide for the treatment of lupus nephritis". Chinese Medical Association.
  41. 1 2 3 4 James G. Whorton (2011). The Arsenic Century. Oxford University Press. ISBN 978-0-19-960599-6.
  42. ↑ 공포의 '비소' 목재
  43. ↑ 구혜선, '왕과 나' 폐비윤씨 사약받는 장면 열연 화제 Archived April 23, 2008, at the Wayback Machine.
  44. ↑ Mari F, Polettini A, Lippi D, Bertol E (December 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.
  45. ↑ "King George III: Mad or misunderstood?". BBC News. 2004-07-13. Retrieved 2010-04-25.
  46. ↑ Madness of King George Linked to Arsenic - AOL News
  47. ↑ Straubel, Rolf (2009). Biographisches Handbuch der Preußischen Verwaltungs- und Justizbeamten 1740-1806/15. Munich: De Gruyter Saur. pp. 1040–1041. ISBN 978-3-598-23229-9.
  48. ↑ Griffiths, Arthur. The history and romance of crime from the earliest time to the present day 8. London: The Grolier Society. pp. 82–93.
  49. 1 2 "Doctors Reconsider Health and Death of 'El Libertador,' General Who Freed South America". Science Daily. April 29, 2010. Archived from the original on 8 June 2010. Retrieved July 17, 2010.
  50. ↑ Simon Bolivar died of arsenic poisoning 7 May 2010. Nick Allen, The Telegraph. Retrieved on 17 July 2010.
  51. 1 2 Mowat Farley. 'The Polar Passion: The Quest for the North Pole'. Toronto: McClelland and Stewart Limited, 1967, p. 124
  52. ↑ Parry, Richard (2001). Trial By Ice: The True Story of Murder and Survival on the 1871 Polaris Expedition. New York: Ballantine Books. p. 293.
  53. ↑ Fleming, Fergus. 'Ninety Degrees North: The Quest for the North Pole'. New York: Grove Press, 2001, p. 142
  54. ↑ Chauncey Loomis. "Charles Francis Hall 1821–1871" (PDF).
  55. ↑ See:
  56. ↑ "Phar Lap 'died from arsenic poisoning'". The Age. 19 June 2008. Retrieved 2008-01-09.
  57. ↑ Mohammed Al Janabi, 78 years after the murder of King Faisal the first, Iraq Law Network. http://www.qanon302.net/news/news.php?action=view&id=7230 Archived May 18, 2013, at the Wayback Machine.
  58. ↑ gazette.ucoz.com/blog/mutinta_mazoka_mmembe_young_focused_foward_thinking/2013-08-16-9 "g" Check |url= value (help). Commerce gazette.

Further reading

External links

This article is issued from Wikipedia - version of the Friday, April 29, 2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.