Arsenic trioxide
Encyclopedia
Arsenic trioxide is the inorganic compound
Inorganic compound
Inorganic compounds have traditionally been considered to be of inanimate, non-biological origin. In contrast, organic compounds have an explicit biological origin. However, over the past century, the classification of inorganic vs organic compounds has become less important to scientists,...

 with the formula
Chemical formula
A chemical formula or molecular formula is a way of expressing information about the atoms that constitute a particular chemical compound....

 As2O3. This commercially important oxide
Oxide
An oxide is a chemical compound that contains at least one oxygen atom in its chemical formula. Metal oxides typically contain an anion of oxygen in the oxidation state of −2....

 of arsenic
Arsenic
Arsenic is a chemical element with the symbol As, atomic number 33 and relative atomic mass 74.92. Arsenic occurs in many minerals, usually in conjunction with sulfur and metals, and also as a pure elemental crystal. It was first documented by Albertus Magnus in 1250.Arsenic is a metalloid...

 is the main precursor to other arsenic compounds, including organoarsenic compound
Organoarsenic compound
Organoarsenic chemistry is the chemistry of compounds containing a chemical bond between arsenic and carbon. A few organoarsenic compounds, also called "organoarsenicals," are produced industrially with uses as insecticides, herbicides, and fungicides. In general these applications are declining in...

s. Approximately 50,000 tonne
Tonne
The tonne, known as the metric ton in the US , often put pleonastically as "metric tonne" to avoid confusion with ton, is a metric system unit of mass equal to 1000 kilograms. The tonne is not an International System of Units unit, but is accepted for use with the SI...

s are produced annually. Many applications are controversial given the high toxicity of arsenic compounds.

Preparation and properties

Arsenic trioxide can be generated via many routine processing of arsenic compounds including the oxidation (combustion) of arsenic and arsenic-containing minerals in air. Illustrative is the roasting of orpiment
Orpiment
Orpiment, As2S3, is a common monoclinic arsenic sulfide mineral. It has a Mohs hardness of 1.5 to 2 and a specific gravity of 3.46. It melts at 300 °C to 325 °C...

, a typical arsenic sulfide ore.
2 As2S3 + 9 O2 → 2 As2O3 + 6 SO2

Most arsenic oxide is, however, obtained as a volatile by-product of the processing of other ores. For example, arsenopyrite
Arsenopyrite
Arsenopyrite is an iron arsenic sulfide . It is a hard metallic, opaque, steel grey to silver white mineral with a relatively high specific gravity of 6.1. When dissolved in nitric acid, it releases elemental sulfur. When arsenopyrite is heated, it becomes magnetic and gives off toxic fumes...

, 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. Only in China are arsenic ores intentionally mined.

Arsenic trioxide is an amphoteric oxide, and its aqueous solutions are weakly acidic
Acidic oxide
An acidic oxide is an oxide that either*reacts with water to form an acid; or*reacts with a base to form a salt.Examples include:...

. Thus, it dissolves readily in alkaline solutions to give arsenite
Arsenite
In chemistry an arsenite is a chemical compound containing an arsenic oxoanion where arsenic has oxidation state +3.The different forms of the anion are the next ones:* ortho-arsenite: AsO33-* meta-arsenite: AsO2-...

s. It is less soluble in acids, although it will dissolve in hydrochloric acid
Hydrochloric acid
Hydrochloric acid is a solution of hydrogen chloride in water, that is a highly corrosive, strong mineral acid with many industrial uses. It is found naturally in gastric acid....

, giving chloro compounds, ultimately arsenic trichloride
Arsenic trichloride
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.-Structure:AsCl3 is a...

 with concentrated acid. Only with strong oxidizing agent
Oxidizing agent
An oxidizing agent can be defined as a substance that removes electrons from another reactant in a redox chemical reaction...

s such as ozone
Ozone
Ozone , or trioxygen, is a triatomic molecule, consisting of three oxygen atoms. It is an allotrope of oxygen that is much less stable than the diatomic allotrope...

, hydrogen peroxide
Hydrogen peroxide
Hydrogen peroxide is the simplest peroxide and an oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. In dilute solution, it appears colorless. With its oxidizing properties, hydrogen peroxide is often used as a bleach or cleaning agent...

, and nitric acid
Nitric acid
Nitric acid , also known as aqua fortis and spirit of nitre, is a highly corrosive and toxic strong acid.Colorless when pure, older samples tend to acquire a yellow cast due to the accumulation of oxides of nitrogen. If the solution contains more than 86% nitric acid, it is referred to as fuming...

 does it give arsenic pentoxide
Arsenic pentoxide
Arsenic pentoxide is the inorganic compound with the formula As2O5. This glassy, white solid is relatively unstable, consistent with the rarity of the As oxidation state. More common, and far more important commercially, is arsenic oxide ....

, As2O5. Reduction gives elemental arsenic or arsine
Arsine
Arsine is the chemical compound with the formula AsH3. This flammable, pyrophoric, and highly toxic gas is one of the simplest compounds of arsenic...

 (AsH3) depending on conditions. In this regard, arsenic trioxide differs from phosphorus trioxide which readily combusts to phosphorus pentoxide
Phosphorus pentoxide
Phosphorus pentoxide is a chemical compound with molecular formula P4O10 . This white crystalline solid is the anhydride of phosphoric acid. It is a powerful desiccant.-Structure:...

.

Structure

In the liquid and in the gas phase below 800 °C, arsenic trioxide has the formula As4O6 and is isostructural with P4O6
Phosphorus trioxide
Phosphorus trioxide is the chemical compound with the molecular formula P4O6. This compound was discovered by Neil G. Mehta . Although it should properly be named tetraphosphorus hexoxide, the name phosphorus trioxide preceded the knowledge of the compound's molecular structure, and its usage...

. Above 800 °C As4O6 significantly dissociated into molecular As2O3, which adopts the same structure as N2O3
Dinitrogen trioxide
Dinitrogen trioxide is the chemical compound with the formula N2O3. This deep blue liquid is one of binary nitrogen oxides. It forms upon mixing equal parts of nitric oxide and nitrogen dioxide and cooling the mixture below −21 °C :Dinitrogen trioxide is only isolable at low...

. Three forms (polymorph
Polymorphism (materials science)
Polymorphism in materials science is the ability of a solid material to exist in more than one form or crystal structure. Polymorphism can potentially be found in any crystalline material including polymers, minerals, and metals, and is related to allotropy, which refers to chemical elements...

s) are known in the solid state: cubic As4O6, containing molecular As4O6, and two related polymeric forms. The polymers, which both crystallized as monoclinic crystals, feature sheets of pyramidal AsO3 units that share O atoms.
arsenolite
(cubic)
claudetite I
(monoclinic)
claudetite II
(monoclinic)

Uses

Large scale applications include its use as a precursor to forestry products, in colorless glass production, and in electronics. Being the main compound of arsenic, the trioxide is the precursor to elemental arsenic, arsenic alloys, and arsenide
Arsenide
Arsenide is an arsenic anion with the charge −3. The trianion is formed by the reduction of arsenic by three electrons. For example heating arsenic powder with excess sodium gives sodium arsenide . The anions have no existence in solution since they are extremely basic...

 semiconductors. Organoarsenic compound
Organoarsenic compound
Organoarsenic chemistry is the chemistry of compounds containing a chemical bond between arsenic and carbon. A few organoarsenic compounds, also called "organoarsenicals," are produced industrially with uses as insecticides, herbicides, and fungicides. In general these applications are declining in...

s, e.g. feed additives (Roxarsone) and pharmaceuticals (Neosalvarsan
Neosalvarsan
Neosalvarsan is a synthetic chemotherapeutic that is an organoarsenic compound. It became available in 1912 and superseded the more toxic and less water-soluble salvarsan as an effective treatment for syphilis...

), are derived from arsenic trioxide. Bulk arsenic-based compounds sodium arsenite
Sodium arsenite
Sodium arsenite is a compound with formula NaAsO2. It is the sodium salt of arsenous acid. It is a crystalline solid consisting of sodium cations, Na+, and catena-arsenite anions, [AsO2], which are infinite -O-As- chains, similar in structure to selenium dioxide, SeO2.It is a pesticide....

 and sodium cacodylate are derived from the trioxide.

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 US and Malaysia, but such materials are banned in many parts of the world. This practice remains controversial. In combination with copper(II) acetate
Copper(II) acetate
Copper acetate, also referred to as cupric acetate, is the chemical compound with the formula Cu2 where OAc- is acetate . The hydrated derivative, which contains one molecule of water for each Cu atom, is available commercially. Anhydrous Cu2 is a dark green crystalline solid, whereas Cu22 is...

 arsenic trioxide gives the vibrant pigment known as paris green
Paris Green
Paris Green is an inorganic compound more precisely known as copper acetoarsenite. It is a highly toxic emerald-green crystalline powder that has been used as a rodenticide and insecticide, and also as a pigment, despite its toxicity. It is also used as a blue colorant for fireworks...

 used both in paints and as a rodenticide. This application has been discontinued.

Medical applications

Despite the well known toxicity of arsenic, arsenic trioxide has long been of biomedical interest, dating to traditional Chinese medicine
Traditional Chinese medicine
Traditional Chinese Medicine refers to a broad range of medicine practices sharing common theoretical concepts which have been developed in China and are based on a tradition of more than 2,000 years, including various forms of herbal medicine, acupuncture, massage , exercise , and dietary therapy...

, where it is known as Pi Shuang and is still used to treat cancer and other conditions, and to homeopathy
Homeopathy
Homeopathy is a form of alternative medicine in which practitioners claim to treat patients using highly diluted preparations that are believed to cause healthy people to exhibit symptoms that are similar to those exhibited by the patient...

, where it is called arsenicum album
Arsenicum album
Arsenicum album is a frequently-used homeopathic substance consisting of arsenic trioxide. It is used by homeopaths to treat a range of symptoms that include digestive disorders , insomnia, allergies, anxiety, depression, and obsessive–compulsive disorder, and it has been studied as a possible...

. Some discredited patent medicines
Patent medicine
Patent medicine refers to medical compounds of questionable effectiveness sold under a variety of names and labels. The term "patent medicine" is somewhat of a misnomer because, in most cases, although many of the products were trademarked, they were never patented...

, e.g., Fowler's solution
Fowler's solution
Fowler's solution is a solution containing potassium arsenite that once was prescribed as a remedy or a tonic. A Dr. Fowler of Stafford, England proposed its use in 1786 as a substitute for a patent medicine, "tasteless ague drop." It was prescribed in the United States until the late 1950s for a...

, contained derivatives of arsenic oxide. Arsenic trioxide under the trade name Trisenox (manufacturer: Cephalon) is a chemotheraputic agent of idiopathic
Idiopathic
Idiopathic is an adjective used primarily in medicine meaning arising spontaneously or from an obscure or unknown cause. From Greek ἴδιος, idios + πάθος, pathos , it means approximately "a disease of its own kind". It is technically a term from nosology, the classification of disease...

 function used to treat leukemia
Leukemia
Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...

 that is unresponsive to "first line" agents. It is suspected that arsenic trioxide induces cancer cells to undergo apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

. Due to the toxic nature of arsenic, this drug carries significant risks. Use as a cytostatic in the treatment of refractory promyelocytic (M3) subtype of acute myeloid leukemia
Leukemia
Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...

. The combination therapy of arsenic trioxide and all-trans retinoic acid (ATRA) has been approved by the U.S. Food and Drug Administration (FDA) for treatment of certain leukemias. University of Hong Kong developed a liquid form of arsenic trioxide that can be administered orally.

Arsenic trioxide also appears to be a promising therapeutic agent for autoimmune diseases.

The enzyme thioredoxin reductase
Thioredoxin reductase
Thioredoxin Reductases are the only known enzymes to reduce thioredoxin . Two classes of thioredoxin reductase have been identified: one class in bacteria and some eukaryotes and one in animals. Both classes are flavoproteins which function as homodimers...

 has recently been identified as a target for arsenic trioxide.

Arsenic trioxide in combination with ascorbic acid and buthionine sulfoxide decrease intracellular glutathione to a greater extent, and render malignant cells more sensitive to apoptosis. Arsenic trioxide induced apoptosis was not enhanced by ascorbic acid in normal cells, suggesting that this combination may be selectively toxic to some malignant cells. http://bloodjournal.hematologylibrary.org/cgi/content/abstract/93/1/268

Natural occurrence

Two minerals are known to possess the As2O3 chemical formula: arsenolite
Arsenolite
Arsenolite is an arsenic mineral, chemical formula As2O3. It is formed as an oxidation product of arsenic sulfides. Commonly found as small octahedra it is white, but impurities of realgar or orpiment may give it a pink or yellow hue...

(regular) and claudetite
Claudetite
Claudetite is an arsenic mineral chemical formula As2O3.It is named for the french chemist, F. Claudet. Claudetite is formed as an oxidation product of arsenic sulfides and is colorless or white. It can be associated with arsenolite as well as realgar, orpiment and sulfur....

 (monoclinic). Both are relatively rare secondary minerals found in oxidation zones of As-rich ore deposits (these are often Co-, Ni-, Ag- and U-bearing, too).

Toxicology

Arsenic trioxide is readily absorbed by the digestive system: toxic effects are also well known upon inhalation or upon skin contact. Elimination is rapid at first (half-life of 1–2 days), by methylation to monomethylarsonic acid and dimethylarsonic acid, and excretion in the urine, but a certain amount (30–40% in the case of repeated exposure) is incorporated into the bones, muscles, skin, hair and nails (all tissues rich in keratin
Keratin
Keratin refers to a family of fibrous structural proteins. Keratin is the key of structural material making up the outer layer of human skin. It is also the key structural component of hair and nails...

) and eliminated over a period of weeks or months.

The first symptoms of acute arsenic poisoning
Arsenic poisoning
Arsenic poisoning is a medical condition caused by increased levels of the element arsenic in the body. Arsenic interferes with cellular longevity by allosteric inhibition of an essential metabolic enzyme...

 by ingestion are digestive problems: vomiting, abdominal pains, diarrhea often accompanied by bleeding. Sub-lethal doses can lead to convulsions, cardiovascular problems, inflammation of the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

 and kidneys and abnormalities in the coagulation of the blood. These are followed by the appearance of characteristic white lines (Mees stripes) on the nails and by hair loss. Lower doses lead to liver and kidney problems and to changes in the pigmentation of the skin. Even dilute solutions of arsenic trioxide are dangerous on contact with the eyes.

The poisonous properties are legendary and the subject of an extensive literature.

Chronic arsenic poisoning is known as arsenicosis. This disorder affects workers in smelters, in populations whose drinking water
Drinking water
Drinking water or potable water is water pure enough to be consumed or used with low risk of immediate or long term harm. In most developed countries, the water supplied to households, commerce and industry is all of drinking water standard, even though only a very small proportion is actually...

 contains high levels of arsenic (0.3–0.4 ppm), and in patients treated for long periods with arsenic-based pharmaceuticals. Similarly, studies on workers exposed in copper
Copper
Copper is a chemical element with the symbol Cu and atomic number 29. It is a ductile metal with very high thermal and electrical conductivity. Pure copper is soft and malleable; an exposed surface has a reddish-orange tarnish...

 foundries in the U.S.,
Japan and Sweden indicate a risk of lung cancer 6–10 times higher for the most exposed workers compared with the
general population. Long-term ingestion of arsenic trioxide either in drinking water or as a medical treatment can lead
to skin cancer. Reproductive problems (high incidence 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 Austria
Austria
Austria , officially the Republic of Austria , is a landlocked country of roughly 8.4 million people in Central Europe. It is bordered by the Czech Republic and Germany to the north, Slovakia and Hungary to the east, Slovenia and Italy to the south, and Switzerland and Liechtenstein to the...

 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.

The current OSHA
Occupational Safety and Health Administration
The United States Occupational Safety and Health Administration is an agency of the United States Department of Labor. It was created by Congress of the United States under the Occupational Safety and Health Act, signed by President Richard M. Nixon, on December 29, 1970...

 1910.1018 occupational permissible exposure limit
Permissible Exposure Limit
The permissible exposure limit is a legal limit in the United States for exposure of an employee to a chemical substance or physical agent. For chemicals, the chemical regulation is usually expressed in parts per million , or sometimes in milligrams per cubic metre . Units of measure for physical...

 for inorganic arsenic compounds in breathing zone air is 0.010 mg/m3.

External links

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