Arsenic trioxide

Last updated

Arsenic trioxide
Arsenic trioxide.jpg
As4O6-molecule-from-arsenolite-xtal-3D-balls.png
Arsenic trioxide   As   O
Clinical data
PronunciationAR se nik tri OKS id
Trade names Trisenox, others
Other namesArsenic(III) oxide,
Arsenic sesquioxide,
Arseneous oxide,
Ratsbane,
Arseneous anhydride,
White arsenic,
Aqua Tofani [1]
AHFS/Drugs.com Monograph
MedlinePlus a608017
License data
Pregnancy
category
  • AU:X (High risk)
Routes of
administration 		Intravenous
Drug class Antineoplastic agent
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding 75%
Excretion Urine
Identifiers
  • Diarsenic trioxide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.014.075 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula As2O3
Molar mass 197.840 g·mol−1
3D model (JSmol)
Density 3.74 g/cm3
Melting point 312.2 °C (594.0 °F)
Boiling point 465 °C (869 °F)
Solubility in water 20 g/L (25 °C)
(see text)
  • O1[As]3O[As]2O[As](O3)O[As]1O2
  • InChI=1S/As2O3/c3-1-4-2(3)5-1
     Yes check.svgY
  • Key:GOLCXWYRSKYTSP-UHFFFAOYSA-N
Arsenic trioxide
Identifiers
ECHA InfoCard 100.014.075 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 215-481-4
Hazards
GHS labelling: [4]
GHS-pictogram-acid.svg GHS-pictogram-skull.svg GHS-pictogram-silhouette.svg GHS-pictogram-pollu.svg
Danger
H300, H314, H350, H410
P201, P202, P260, P264, P270, P273, P280, P301+P330+P331, P303+P361+P353, P304+P340+P310, P305+P351+P338+P310, P308+P313, P363, P391, P405, P501
Safety data sheet (SDS) american elements SDS
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Arsenic trioxide is an inorganic compound with the formula As
2O
3. [5] As an industrial chemical, its major uses include the manufacture of wood preservatives, pesticides, and glass. [6] It is sold under the brand name Trisenox among others [2] [3] when used as a medication to treat a type of cancer known as acute promyelocytic leukemia. [7] For this use it is given by injection into a vein. [7]

Contents

Common side effects include vomiting, diarrhea, swelling, shortness of breath, and headaches. [7] Severe side effects may include APL differentiation syndrome and heart problems. [7] Use during pregnancy or breastfeeding may harm the baby. [8] [9] Its mechanism in treating cancer is not entirely clear. [7]

Arsenic trioxide was approved for medical use in the United States in 2000. [7] It is on the World Health Organization's List of Essential Medicines. [10] Approximately 50,000 tonnes are produced a year. [11] Due to its toxicity, a number of countries have regulations around its manufacture and sale. [12]

Uses

Medical

Arsenic trioxide is indicated in combination with tretinoin for treatment of adults with newly-diagnosed low-risk acute promyelocytic leukemia whose acute promyelocytic leukemia is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression; and for induction of remission and consolidation in patients with acute promyelocytic leukemia who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose acute promyelocytic leukemia is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression. [2] [3] [13]

Arsenic trioxide is used to treat a type of cancer known as acute promyelocytic leukemia (APL). [7] It may be used both in cases that are unresponsive to other agents, such as all-trans retinoic acid (ATRA) or as part of the initial treatment of newly diagnosed cases. [7] This initial treatment may include combination therapy of arsenic trioxide with all-trans retinoic acid (ATRA). [14]

Effectiveness appears similar to Realgar/Indigo naturalis, which can be taken by mouth and is less expensive but is less available. [15] It works by encouraging the proteosome breakdown of retinoic acid receptor alpha, by moving the protein on to the nuclear matrix and increasing ubiquitination. [16]

In the 1970s, Chinese researcher Zhang Tingdong and colleagues discovered this use. [17] It was approved for leukemia treatment in the United States in 2000. [18] University of Hong Kong developed a liquid form of arsenic trioxide that can be given by mouth. [19] Organoarsenic compounds, such as feed additives (roxarsone) and medication (neosalvarsan), are derived from arsenic trioxide.[ citation needed ]

Manufacturing

Industrial uses include usage as a precursor to forestry products, in colorless glass production, and in electronics. [11] Being the main compound of arsenic, the trioxide is the precursor to elemental arsenic, arsenic alloys, and arsenide semiconductors. Bulk arsenic-based compounds sodium arsenite and sodium cacodylate are derived from the trioxide.[ citation needed ]

A variety of applications exploit arsenic's toxicity, including the use of the oxide as a wood preservative. Copper arsenates, which are derived from arsenic trioxide, are used on a large scale as a wood preservative in the U.S. and Malaysia, but such materials are banned in many parts of the world. This practice remains controversial. [11] In combination with copper(II) acetate, arsenic trioxide gives the vibrant pigment known as Paris green used in paints and as a rodenticide. This application has been discontinued.[ citation needed ]

Alternative medicine

Despite the well known toxicity of arsenic, arsenic trioxide was used in traditional Chinese medicine, where it is known as pi-shuang (Chinese :砒霜; pinyin :pīshuāng; lit.'arsenic frost'). In homeopathy, it is called arsenicum album. Some discredited patent medicines, e.g., Fowler's solution, contained derivatives of arsenic oxide. [20]

Toxicology

As with other inorganic arsenic compounds, arsenic trioxide is toxic to living organisms. Arsenic trioxide is readily absorbed by the digestive system. Ingestion of as little as 0.1 grams can be fatal. [11]

Chronic arsenic poisoning is known as arsenicosis. This disorder affects workers in smelters, in populations whose drinking water contains high levels of arsenic (0.3–0.4 ppm), and in patients treated for long periods with arsenic-based pharmaceuticals. Long-term ingestion of arsenic trioxide either in drinking water or as a medical treatment can lead to skin cancer. Reproductive problems (high incidences of miscarriage, low birth weight, congenital deformations) have also been indicated in one study of women exposed to arsenic trioxide dust as employees or neighbours of a copper foundry.

In the U.S., the OSHA 1910.1018 occupational permissible exposure limit for inorganic arsenic compounds in breathing zone air is 0.010 mg/m3.

Production and occurrence

Historic arsenic mine Sankt Blasen, Austria St.BlasenArsenikstollen5.jpg
Historic arsenic mine Sankt Blasen, Austria

Arsenic trioxide can be generated via routine processing of arsenic compounds including the oxidation (combustion) of arsenic and arsenic-containing minerals in air. Illustrative is the roasting of orpiment, a typical arsenic sulfide ore.

2 As
2S
3 + 9 O
2 → 2 As
2O
3 + 6 SO
2

Most arsenic oxide is, however, obtained as a volatile by-product of the processing of other ores. For example, arsenopyrite, a common impurity in gold- and copper-containing ores, liberates arsenic trioxide upon heating in air. The processing of such minerals has led to numerous cases of poisonings, [21] and after the mine is closed, the leftover trioxide waste will present environmental hazard (as was the case with the Giant Mine, for example). Only in China are arsenic ores intentionally mined. [11]

In the laboratory, it is prepared by hydrolysis of arsenic trichloride: [22]

2 AsCl3 + 3 H2O → As2O3 + 6 HCl

As
2O
3 occurs naturally as two minerals, arsenolite (cubic) and claudetite (monoclinic). Both are relatively rare secondary minerals found in oxidation zones of As-rich ore deposits.

Properties and reactions

Arsenic trioxide is an amphoteric oxide, and its aqueous solutions are weakly acidic. Thus, it dissolves readily in alkaline solutions to give arsenites. It is less soluble in acids, although it will dissolve in hydrochloric acid. [23]

With anhydrous HF and HCl, it gives AsF3 and the trichloride: [22]

As2O3 + 6 HX → 2 AsX3 + 3 H2O (X = F, Cl)

Only with strong oxidizing agents such as ozone, hydrogen peroxide, and nitric acid does it yield arsenic pentoxide, As
2O
5 or its corresponding acid: [22]

2 HNO3 + As2O3 + 2 H2O → 2 H3AsO4 + N2O3

In terms of its resistance to oxidation, arsenic trioxide differs from phosphorus trioxide, which readily combusts to phosphorus pentoxide.

Reduction gives elemental arsenic or arsine (AsH
3) depending on conditions: [22]

As2O3 + 6 Zn + 12 HNO3 → 2 AsH3 + 6 Zn(NO3)2 + 3 H2O

This reaction is used in the Marsh test.

Structure

In the liquid and gas phase below 800 °C, arsenic trioxide has the formula As
4O
6 and is isostructural with P
4O
6 . Above 800 °C As
4O
6 significantly dissociates into molecular As
2O
3, which adopts the same structure as N
2O
3 . Three forms (polymorphs) are known in the solid state: a high temperature ( > 110 °C) cubic As
4O
6, containing molecular As
4O
6, and two related polymeric forms. [24] The polymers, which both crystallize as monoclinic crystals, feature sheets of pyramidal AsO
3 units that share O atoms. [25]

Arsenolite-xtal-3D-balls-D.png Claudetite-I-layer-3D-balls.png Claudetite-II-layer-3D-balls.png
arsenolite
(cubic)
claudetite I
(monoclinic)
claudetite II
(monoclinic)

Society and culture

Environmental effects

Smelting and related ore processing often generate arsenic trioxide, which poses a risk to the environment. For example, the Giant Mine in Canada processed substantial amounts of arsenopyrite-contaminated gold ores.

Arsenic poisoning in literature and society

The poisonous properties of arsenic are the subject of an extensive literature. [26] [27] [28]

In Austria, there lived the so-called "arsenic eaters of Styria", who ingested doses far beyond the lethal dose of arsenic trioxide without any apparent harm. Arsenic is thought to enable strenuous work at high altitudes, e.g. in the Alps. [29] [30] [31] [32]

Related Research Articles

<span class="mw-page-title-main">Arsenic</span> Chemical element with atomic number 33 (As)

Arsenic is a chemical element with the symbol As and the atomic number 33. It is a metalloid and one of the pnictogens, and therefore shares many properties with its group 15 neighbors phosphorus and antimony. Arsenic is a notoriously toxic heavy metal. It occurs naturally in many minerals, usually in combination with sulfur and metals, but also as a pure elemental crystal. It has various allotropes, but only the grey form, which has a metallic appearance, is important to industry.

<span class="mw-page-title-main">Antimony</span> Chemical element with atomic number 51 (Sb)

Antimony is a chemical element; it has symbol Sb (from Latin stibium) and atomic number 51. A lustrous grey metal or metalloid, it is found in nature mainly as the sulfide mineral stibnite (Sb2S3). Antimony compounds have been known since ancient times and were powdered for use as medicine and cosmetics, often known by the Arabic name kohl. The earliest known description of this metalloid in the West was written in 1540 by Vannoccio Biringuccio.

Fowler's solution is a solution containing 1% potassium arsenite (KAsO2) which was first described and published as a treatment for malaria and syphilis in the late 1700s and was once prescribed as a remedy or a tonic. Thomas Fowler (1736–1801) of Stafford, England, proposed the solution in 1786 as a substitute for a patent medicine, "tasteless ague drop". From 1865, Fowler's solution was a leukemia treatment.

<span class="mw-page-title-main">Tretinoin</span> Medication

Tretinoin, also known as all-trans retinoic acid (ATRA), is a medication used for the treatment of acne and acute promyelocytic leukemia. For acne, it is applied to the skin as a cream, gel or ointment. For acute promyelocytic leukemia, it is effective only when the RARA-PML fusion mutation is present and is taken by mouth for up to three months. Topical tretinoin is also the most extensively investigated retinoid therapy for photoaging.

<span class="mw-page-title-main">Arsenic trisulfide</span> Chemical compound

Arsenic trisulfide is the inorganic compound with the formula As2S3. It is a dark yellow solid that is insoluble in water. It also occurs as the mineral orpiment, which has been used as a pigment called King's yellow. It is produced in the analysis of arsenic compounds. It is a group V/VI, intrinsic p-type semiconductor and exhibits photo-induced phase-change properties.

<span class="mw-page-title-main">Acute promyelocytic leukemia</span> Subtype of acute myeloid leukaemia characterised by accumulation of promyelocytes

Acute promyelocytic leukemia is a subtype of acute myeloid leukemia (AML), a cancer of the white blood cells. In APL, there is an abnormal accumulation of immature granulocytes called promyelocytes. The disease is characterized by a chromosomal translocation involving the retinoic acid receptor alpha (RARA) gene and is distinguished from other forms of AML by its responsiveness to all-trans retinoic acid therapy. Acute promyelocytic leukemia was first characterized in 1957 by French and Norwegian physicians as a hyperacute fatal illness, with a median survival time of less than a week. Today, prognoses have drastically improved; 10-year survival rates are estimated to be approximately 80-90% according to one study.

<span class="mw-page-title-main">Chromium trioxide</span> Chemical compound

Chromium trioxide is an inorganic compound with the formula CrO3. It is the acidic anhydride of chromic acid, and is sometimes marketed under the same name. This compound is a dark-purple solid under anhydrous conditions and bright orange when wet. The substance dissolves in water accompanied by hydrolysis. Millions of kilograms are produced annually, mainly for electroplating. Chromium trioxide is a powerful oxidiser, a mutagen, and a carcinogen.

<span class="mw-page-title-main">Vanadium(V) oxide</span> Precursor to vanadium alloys and industrial catalyst

Vanadium(V) oxide (vanadia) is the inorganic compound with the formula V2O5. Commonly known as vanadium pentoxide, it is a dark yellow solid, although when freshly precipitated from aqueous solution, its colour is deep orange. Because of its high oxidation state, it is both an amphoteric oxide and an oxidizing agent. From the industrial perspective, it is the most important compound of vanadium, being the principal precursor to alloys of vanadium and is a widely used industrial catalyst.

<span class="mw-page-title-main">Arsenic acid</span> Chemical compound

Arsenic acid or arsoric acid is the chemical compound with the formula H3AsO4. More descriptively written as AsO(OH)3, this colorless acid is the arsenic analogue of phosphoric acid. Arsenate and phosphate salts behave very similarly. Arsenic acid as such has not been isolated, but is only found in solution, where it is largely ionized. Its hemihydrate form (2H3AsO4·H2O) does form stable crystals. Crystalline samples dehydrate with condensation at 100 °C.

<span class="mw-page-title-main">Arsenous acid</span> Chemical compound

Arsenous acid (or arsenious acid) is the inorganic compound with the formula H3AsO3. It is known to occur in aqueous solutions, but it has not been isolated as a pure material, although this fact does not detract from the significance of As(OH)3.

<span class="mw-page-title-main">Cacodylic acid</span> Chemical compound

Cacodylic acid is an organoarsenic compound with the formula (CH3)2AsO2H. With the formula R2As(O)OH, it is the simplest of the arsinic acids. It is a colorless solid that is soluble in water.

In chemistry, an arsenite is a chemical compound containing an arsenic oxyanion where arsenic has oxidation state +3. Note that in fields that commonly deal with groundwater chemistry, arsenite is used generically to identify soluble AsIII anions. IUPAC have recommended that arsenite compounds are to be named as arsenate(III), for example ortho-arsenite is called trioxidoarsenate(III). Ortho-arsenite contrasts to the corresponding anions of the lighter members of group 15, phosphite which has the structure HPO2−3 and nitrite, NO−2 which is bent.

Retinoic acid syndrome (RAS) is a potentially life-threatening complication observed in people with acute promyelocytic leukemia (APML) and first thought to be specifically associated with all-trans retinoic acid (ATRA) treatment. Subsequently, so-called RAS was recognized in APML patients who had been treated with another highly efficacious drug, arsenic trioxide, and yet did not appear in patients treated with tretinoin for other disorders. These facts and others support the notion that RAS depends on the presence of the malignant promyelocytes. This has led to the growing deprecation of the term 'retinoic acid syndrome' and to an increasing use of the term differentiation syndrome to signify this APML treatment complication.

<span class="mw-page-title-main">Arsenic pentoxide</span> Chemical compound

Arsenic pentoxide is the inorganic compound with the formula As2O5. This glassy, white, deliquescent solid is relatively unstable, consistent with the rarity of the As(V) oxidation state. More common, and far more important commercially, is arsenic(III) oxide (As2O3). All inorganic arsenic compounds are highly toxic and thus find only limited commercial applications.

<span class="mw-page-title-main">Arsenic trichloride</span> Chemical compound

Arsenic trichloride is an inorganic compound with the formula AsCl3, also known as arsenous chloride or butter of arsenic. This poisonous oil is colourless, although impure samples may appear yellow. It is an intermediate in the manufacture of organoarsenic compounds.

Potassium arsenite (KAsO2) is an inorganic compound that exists in two forms, potassium meta-arsenite (KAsO2) and potassium ortho-arsenite (K3AsO3). It is composed of arsenite ions (AsO33− or AsO2−) with arsenic always existing in the +3 oxidation state. Like many other arsenic containing compounds, potassium arsenite is highly toxic and carcinogenic to humans. Potassium arsenite forms the basis of Fowler’s solution, which was historically used as a medicinal tonic, but due to its toxic nature its use was discontinued. Potassium arsenite is still, however, used as a rodenticide.

Arsenic biochemistry refers to biochemical processes that can use arsenic or its compounds, such as arsenate. Arsenic is a moderately abundant element in Earth's crust, and although many arsenic compounds are often considered highly toxic to most life, a wide variety of organoarsenic compounds are produced biologically and various organic and inorganic arsenic compounds are metabolized by numerous organisms. This pattern is general for other related elements, including selenium, which can exhibit both beneficial and deleterious effects. Arsenic biochemistry has become topical since many toxic arsenic compounds are found in some aquifers, potentially affecting many millions of people via biochemical processes.

Zhang Tingdong is a Chinese medical scientist, pharmaceutical chemist, and educator at Harbin Medical University, 1st affiliated Hospital, and is best known for discovering of using arsenic trioxide to treat leukemia, which is regarded as a significant breakthrough of anti-leukemia medicine in the 20th Century and improvement in the lives of people with leukemia.

Realgar/Indigo naturalis (RIF), also known as Compound Huangdai (复方黄黛), is a medication used to treat acute promyelocytic leukemia. Effectiveness appears similar to arsenic trioxide. It is generally used together with all-trans-retinoic acid (ATRA). It is taken by mouth.

<span class="mw-page-title-main">Medical use of arsenic trioxide</span> Use of arsenic trioxide in the treatment of acute promyelocytic leukemia

Medical use of arsenic trioxide refers to the use of arsenic trioxide as an chemotherapeutic agent in the treatment of acute promyelocytic leukemia. Arsenic trioxide has orphan drug status and is available as the pharmaceutical preparation Trisenox. When in contact with water, it forms arsenous acid, which is believed to be the biologically active substance.

References

  1. ↑ Shakhashiri BZ. "Chemical of the Week: Arsenic". University of Wisconsin-Madison Chemistry Dept. Archived from the original on 2 August 2008. Retrieved 3 August 2008.
  2. 1 2 3 "Trisenox- arsenic trioxide injection, solution". DailyMed. 30 June 2022. Archived from the original on 3 February 2024. Retrieved 3 February 2024.
  3. 1 2 3 "Trisenox EPAR". European Medicines Agency. 10 August 2010. Archived from the original on 16 August 2023. Retrieved 3 February 2024.
  4. ↑ "Safety Data Sheet". American Elements. 2021. Archived from the original on 4 January 2022. Retrieved 4 January 2022.
  5. ↑ Sun H (2010). Biological Chemistry of Arsenic, Antimony and Bismuth. John Wiley & Sons. p. 295. ISBN   9780470976227. Archived from the original on 14 April 2023. Retrieved 18 March 2023.
  6. ↑ Landner L (2012). Chemicals in the Aquatic Environment: Advanced Hazard Assessment. Springer Science & Business Media. p. 259. ISBN   9783642613340. Archived from the original on 14 April 2023. Retrieved 18 March 2023.
  7. 1 2 3 4 5 6 7 8 "Arsenic Trioxide Monograph for Professionals". Drugs.com. Archived from the original on 15 November 2019. Retrieved 15 November 2019.
  8. ↑ British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 907. ISBN   9780857113382.
  9. ↑ "Arsenic trioxide (Trisenox) Use During Pregnancy". Drugs.com. Archived from the original on 15 November 2019. Retrieved 16 November 2019.
  10. ↑ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl: 10665/371090 . WHO/MHP/HPS/EML/2023.02.
  11. 1 2 3 4 5 Grund SC, Hanusch K, Wolf HU. "Arsenic and Arsenic Compounds". Ullmann's Encyclopedia of Industrial Chemistry . Weinheim: Wiley-VCH. doi:10.1002/14356007.a03_113.pub2. ISBN   978-3527306732.
  12. ↑ Consolidated List of Products Whose Consumption And/or Sale Have Been Banned, Withdrawn, Severely Restricted Or Not Approved by Governments: Chemicals (PDF). United Nations Publications. 2009. p. 24. ISBN   9789211302196.
  13. ↑ "Drug Approval Package: Trisenox (Arsenic Trioxide) NDA #21-248". U.S. Food and Drug Administration (FDA). 12 July 2001. Archived from the original on 3 February 2024. Retrieved 3 February 2024.
  14. ↑ Zhu J, Chen Z, Lallemand-Breitenbach V, de Thé H (September 2002). "How acute promyelocytic leukaemia revived arsenic". Nature Reviews. Cancer. 2 (9): 705–713. doi:10.1038/nrc887. PMID   12209159. S2CID   2815389.
  15. ↑ Howard SC. "Proposal for the inclusion of arsenic therapies in the WHO Model List of Essential Medicines for the treatment of acute promyelocytic leukemia" (PDF). WHO. Archived from the original (PDF) on 9 March 2022. Retrieved 15 November 2019.
  16. ↑ Zhu J, Koken MH, Quignon F, Chelbi-Alix MK, Degos L, Wang ZY, et al. (April 1997). "Arsenic-induced PML targeting onto nuclear bodies: implications for the treatment of acute promyelocytic leukemia". Proceedings of the National Academy of Sciences of the United States of America. 94 (8): 3978–3983. Bibcode:1997PNAS...94.3978Z. doi: 10.1073/pnas.94.8.3978 . PMC   20553 . PMID   9108090.
  17. ↑ Rao Y, Li R, Zhang D (June 2013). "A drug from poison: how the therapeutic effect of arsenic trioxide on acute promyelocytic leukemia was discovered". Science China Life Sciences. 56 (6): 495–502. doi: 10.1007/s11427-013-4487-z . PMID   23645104.
  18. ↑ Bian Z, Chen S, Cheng C, Wang J, Xiao H, Qin H (2012). "Developing new drugs from annals of Chinese medicine". Acta Pharmaceutica Sinica B. 2: 1–7. doi: 10.1016/j.apsb.2011.12.007 .
  19. ↑ Au WY, Kumana CR, Kou M, Mak R, Chan GC, Lam CW, et al. (July 2003). "Oral arsenic trioxide in the treatment of relapsed acute promyelocytic leukemia". Blood. 102 (1): 407–408. doi: 10.1182/blood-2003-01-0298 . PMID   12814916.
  20. ↑ Gibaud S, Jaouen G (2010). "Arsenic-Based Drugs: From Fowler's Solution to Modern Anticancer Chemotherapy". Medicinal Organometallic Chemistry. Topics in Organometallic Chemistry. Vol. 32. pp. 1–20. Bibcode:2010moc..book....1G. doi:10.1007/978-3-642-13185-1_1. ISBN   978-3-642-13184-4.
  21. ↑ "Giant Mine – Northwest Territories Region – Indian and Northern Affairs Canada". Archived from the original on 27 June 2006. Retrieved 28 August 2007.
  22. 1 2 3 4 Handbook of Preparative Inorganic Chemistry, 2nd Ed. Edited by G. Brauer, Academic Press, 1963, NY.
  23. ↑ Greenwood, N. N.; & Earnshaw, A. (1997). Chemistry of the Elements (2nd Edn.), Oxford:Butterworth-Heinemann. ISBN   0-7506-3365-4.
  24. ↑ Wells A.F. Structural Inorganic Chemistry. 5th. London, England: Oxford University Press, 1984. Print. ISBN   0-19-855370-6
  25. ↑ Holleman AF, Wiberg E (2001). Inorganic Chemistry. San Diego: Academic Press. ISBN   0-12-352651-5.
  26. ↑ "Stanton v Benzler 9716830". U.S. 9th Circuit Court of Appeals. 17 June 1998. Archived from the original on 21 October 2012. Retrieved 9 June 2008. (...) convicted by a jury of first degree murder for poisoning her ex-husband. Her ex-husband's body was found with traces of arsenic trioxide in it.
  27. ↑ Emsley J (2006). "Arsenic". The Elements of Murder: A History of Poison. Oxford University Press. pp. 93–197. ISBN   978-0-19-280600-0.
  28. ↑ Flaubert G (1856). Madame Bovary .
  29. ↑ "Arsenic Eaters". The New York Times . 26 July 1885. Archived from the original on 27 July 2018. Retrieved 27 July 2018.
  30. ↑ Allesch RM (1959). Arsenik. Seine Geschichte in Österreich. Archiv für vaterländische Geschichte und Topographie. Vol. 54. Klagenfurt: Kleinmayr.
  31. ↑ Przygoda G, Feldmann J, Cullen WR (2001). "The arsenic eaters of Styria: a different picture of people who were chronically exposed to arsenic". Applied Organometallic Chemistry. 15 (6): 457–462. doi:10.1002/aoc.126.
  32. ↑ Whorton JC (2010). The Arsenic Century . Oxford University Press. pp.  270–273. ISBN   978-0-19-960599-6.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.