PRODUCTS

ARSENIC TRIOXIDE

Arsenic Trioxide

Arsenic Trioxide = Trisenox

CAS Number = 1327-53-3
EC Number = 215-481-4

Chemical and Physical Properties
Property Name   Property Value
Molecular Weight   197.841
Hydrogen Bond Donor Count   0
Hydrogen Bond Acceptor Count   3
Rotatable Bond Count   0
Exact Mass   197.82793
Monoisotopic Mass   197.82793
Topological Polar Surface Area   3 Å²
Heavy Atom Count   5
Formal Charge   0
Complexity   0
Isotope Atom Count   0
Defined Atom Stereocenter Count   0
Undefined Atom Stereocenter Count   0
Defined Bond Stereocenter Count   0
Undefined Bond Stereocenter Count   0
Covalently-Bonded Unit Count   5
Compound Is Canonicalized   Yes

Formula   As2O3
Molar mass   197.840 g·mol−1
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)

Arsenic trioxide is a chemotherapeutic agent used in the treatment of refractory or relapsed acute promyelocytic leukemia in patients with prior retinoid and anthracycline chemotherapy.

Arsenic trioxide is a chemotherapeutic agent of idiopathic function used to treat leukemia that is unresponsive to first line agents.
It is suspected that arsenic trisulfide induces cancer cells to undergo apoptosis.
In general, arsenic is known to be a naturally toxic substance capable of eliciting a variety of dangerous adverse effects.
The enzyme thioredoxin reductase has recently been identified as a target for arsenic trioxide.

Trade Name(s): Trisenox
Arsenic trioxide is the generic name for the trade name drug Trisenox.
In some cases, health care professionals may use the trade name Trisenox when referring to the generic drug name Arsenic Trioxide.

Arsenic trioxide is used to treat a cancer of the blood and bone marrow called acute promyelocytic (pro-MYE-loe-SIT-ik) leukemia, or APL.

Arsenic trioxide is sometimes given in combination with another medicine called tretinoin.

Arsenic trioxide belongs to the group of cytostatics.
The active ingredient leads to a fragmentation of the DNA and therefore to apoptosis.
It is used for the treatment of acute promyelocytic leukemia (APL), a subtype of blood cancer.

Arsenic trioxide is a form of the naturally occurring compound arsenic.
It has been used by health practitioners (particularly in Asia) for hundreds of years.
It is safe when given in small doses by experienced healthcare professionals.
It seems to work against cancer by causing cancer cells to self-destruct; this is also known as apoptosis.

All forms of arsenic are toxic to some degree, but arsenic trioxide is especially scary because its arsenic is bioavailable and it doesn’t take much to be effective.
Arsenic trioxide, also known as “the poison of kings and the king of poisons” and “inheritance powder” is a white powder with no taste or odor that dissolves readily in warm food or drink.
According to the book The Arsenic Century: How Victorian Britain was Poisoned at Home, Work, & Play” by James C.
Whorton, it was used to poison people for centuries until a reliable method of detecting arsenic in tissues was developed in the mid 1800’s.
Not all arsenic trioxide makes a good poison though – no one is likely to mistake the gray/black arsenic trioxide waste material (ATWM) generated during gold mining operations for something that belongs in food.

Arsenic Trioxide is an inorganic compound.
It is the main originator for organoarsenic compounds (compounds containing arsenic-carbon chemical bond) and numerous other arsenic compounds.
Many applications of As2O3 are controversial because of the toxic nature of arsenic.
The trade name for this compound is Trisenox.

Indications and Usage
Arsenic trioxide is FDA approved:

For induction of remission and consolidation in patients with acute promyelocytic leukemia (APL) who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose APL is characterized by the presence of the t(15;17) translocation or PML/RARA gene expression.
In combination with tretinoin for the treatment of adults with newly-diagnosed low-risk acute promyelocytic leukemia (APL) whose APL is characterized by the presence of the t translocation or the PML/RARA gene expression.

Arsenic compounds exist in a number of inorganic and organic forms.
This Medical Management Guideline focuses on arsenic trioxide (As2O3), one of the most toxic and prevalent forms.
Other inorganic arsenic compounds may vary somewhat in relative toxicity, and organic arsenic compounds appear to be essentially nontoxic.
Physical and chemical properties vary among the various arsenic compounds of toxicological concern.
The physical and chemical properties of arsenic trioxide are presented in this Medical Management Guideline; the guidelines for decontamination and medical treatment are applicable for exposure to arsenic and inorganic arsenic compounds, including arsenic trioxide.

Arsenic trioxide is a white or transparent solid in the form of glassy, shapeless lumps or a crystalline powder that resembles sugar.
It has no odor or taste.
It forms readily when elemental metallic arsenic is heated to high temperatures or burned.
When arsenic trioxide is burned, it releases toxic fumes and arsine gas (see arsine Medical Management Guideline), which is highly toxic

Arsenic trioxide may also be used for other purposes not listed in this medication guide.

Arsenic trioxide is used to treat a cancer of the blood and bone marrow called acute promyelocytic (pro-MYE-loe-SIT-ik) leukemia, or APL.
Arsenic trioxide is sometimes given in combination with another medicine called tretinoin.
Arsenic trioxide may also be used for other purposes not listed in this medication guide.

Arsenic Trioxide is a small-molecule arsenic compound with antineoplastic activity.
The mechanism of action of arsenic trioxide is not completely understood.
This agent causes damage to or degradation of the promyelocytic leukemia protein/retinoic acid receptor-alpha (PML/RARa) fusion protein; induces apoptosis in acute promyelocytic leukemia (APL) cells and in many other tumor cell types; promotes cell differentiation and suppresses cell proliferation in many different tumor cell types; and is pro-angiogenic.

Arsenic trioxide appears as white or transparent, glassy amorphous lumps or crystalline powder.
Slightly soluble in water, but dissolves very slowly; more soluble in hot water.
Noncombustible.
Corrosive to metals in the presence of moisture.
Toxic by ingestion.

An inorganic compound with the chemical formula As2O3 that is used for the treatment of ACUTE PROMYELOCYTIC LEUKEMIA in patients who have relapsed from, or are resistant to, conventional drug therapy.

Arsenic trioxide, sold under the brand name Trisenox among others, is an inorganic compound and medication.
As an industrial chemical, whose major uses include in the manufacture of wood preservatives, pesticides, and glass.
As a medication, it is used to treat a type of cancer known as acute promyelocytic leukemia.
For this use it is given by injection into a vein.

Common side effects include vomiting, diarrhea, swelling, shortness of breath, and headaches.
Severe side effects may include APL differentiation syndrome and heart problems.
Use during pregnancy or breastfeeding may harm the baby.
Arsenic trioxide has the formula As2O3.
Its mechanism in treating cancer is not entirely clear.

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

Arsenic Trioxide structure
Arsenic Trioxide has the formula As4O6 in its liquid and gas phase (below 800 °C).
In these phases it is isostructural with Phosphorus Trioxide (P4O6).
But above 800°C, As4O6 breaks down into molecular As2O3.
In this phase, As2O3 is isostructural with Dinitrogen Trioxide (N2O3).
In its solid state, this compound shows polymorphic capability (the ability to exist in two or more forms of crystal structure).

Arsenic Trioxide Properties
Some of the main properties of Arsenic Trioxide are as follows:

The solutions of Arsenic Trioxide form weak acids with water.
This is due to the fact that the compound is an amphoteric oxide.
It is soluble in alkaline solutions and gives Arsenites.
Arsenic Trioxide has high solubility in Hydrochloric Acid (HCl) and finally gives Arsenic Trichloride and concentrated acid.
It gives Arsenic Pentoxide (As2O5) in the presence of strong oxidizing agents like Hydrogen Peroxide, Ozone and Nitric Acid.
It is almost insoluble in organic solvents.
It appears as a white solid in its normal physical state.
It has a melting point of 312.2°C and a boiling point of 465°C.
The density of this substance is 4.15 g/cm3.

Uses
Medical
Arsenic trioxide is used to treat a type of cancer known as acute promyelocytic leukemia (APL).
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.
This initial treatment may include combination therapy of arsenic trioxide with all-trans retinoic acid (ATRA).

Effectiveness appears similar to Realgar/Indigo naturalis, which can be taken by mouth and is less expensive but is less available.

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

Usage:
Arsenic trioxide is highly distributed throughout the liver, heart, kidneys and lungs.
The treatment is mostly used in treatment of leukemia and is only administered intravenously.1

Mechanism:
The mechanism of action of the drug is not fully understood, but caspase (programmed enzymes) found in arsenic trioxide induce apoptosis (cell death), which inhibits the process of angiogenesis and related cancerous cell production.

Sources/Uses
Arsenic occurs naturally in soil and many kinds of rock (especially minerals and ores that contain copper and lead) as inorganic arsenic.
Arsenic trioxide is produced during the smelting of ores that contain arsenic.
Arsenic trioxide has been used to produce the wood preservative CCA (copper chromated arsenic); however, this treatment process has been phased out in the United States.
Inorganic arsenic compounds have been used as pesticides, but can no longer be used in agriculture.
Some organic arsenic compounds may be used as pesticides or as additives in animal feed.
Small quantities of arsenic metal are used in alloys in products such as lead-acid batteries.
Some arsenic compounds may also be found in semiconductors and light-emitting diodes

Arsenic Trioxide Preparation
There are many ways to prepare As2O3 from arsenic compounds.
One way to produce this chemical compound is from Orpiment, an arsenic sulfide ore.
It is done by the roasting of the orpiment.
The chemical reaction happens in the following way:

2 As2S3 + 9 O2 → 2 As2O3 + 6 SO2

Most arsenic oxides can be obtained as the by-product of the processing of other arsenic ores.
Arsenopyrite is a common impurity in gold and copper and it releases Arsenic Trioxide if heated in the presence of air.
This can cause serious arsenic poisoning.

Arsenic ores are not intentionally mined, except in China.

Manufacturing
Industrial uses include usage as a precursor to forestry products, in colorless glass production, and in electronics.[9] 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.

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.
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.

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.

Arsenic trioxide—also known as ATO, or trisenox—is an anticancer treatment for a subtype of acute myeloid leukemia known as acute promyelocytic leukemia, or APL.
This leukemia subtype is also called “the M3 subtype” of acute myeloid leukemia.

Results using ATO in the treatment of newly diagnosed patients with low-to-intermediate risk APL have been very favorable.
These successes have also spurred scientific research investigating the potential use of ATO in many cancers other than APL, including non-leukemia malignancies such as metastatic colon cancer and the brain tumor, glioblastoma multiforme.

ATO is often combined with all-trans retinoic acid (ATRA), a retinoid agent used in the treatment of acute promyelocytic leukemia.
Retinoid compounds can bind receptors on cells to have important actions on cellular life cycles.
The combination of ATRA plus ATO has been shown to be superior to ATRA plus chemotherapy in the treatment of standard-risk patients with newly diagnosed acute promyelocytic leukemia (APL).

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) and eliminated over a period of weeks or months.

The first symptoms of acute arsenic poisoning 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 and kidneys and abnormalities in the coagulation of the blood.
These are followed by the appearance of characteristic white lines (Mees' lines) 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 well known 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 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 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 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 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.

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.

Physical Properties
Description: Arsenic is a usually a steel grey metal-like material with no characteristic taste or smell.
Arsenic trioxide is a white or transparent solid in the form of glassy, shapeless lumps or a crystalline powder that resembles sugar.
Other arsenic compounds vary in color (ATSDR 2005; HSDB 2007).

Warning properties: Inadequate; odorless and tasteless.
Airborne arsenic trioxide may produce a burning sensation to the nose, mouth, and eyes and cause coughing, shortness of breath, headache, sore throat, and dizziness

Incompatibilities
Arsenic is flammable in the form of dust when exposed to heat or flame or by chemical reaction with powerful oxidizers.
Arsenic is slightly explosive in the form of dust when exposed to flame.
When heated or on contact with acid or acid fumes, arsenic emits highly toxic fumes, including arsine gas.
Arsenic can react vigorously on contact with oxidizing materials.
Arsenicals can react violently with strong oxidizing materials and active metals.
Hydrogen gas can react with inorganic arsenic to form the highly toxic gas, arsine

Production and occurrence

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 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, 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.

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

2 AsCl3 + 3 H2O → As2O3 + 6 HClAs2O3
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.
Sheets of As2O3 stand for part of structures of the recently discovered minerals lucabindiite, (K,NH4)As4O6(Cl,Br), and its sodium-analogue torrecillasite.

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.

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

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, As2O5 or its corresponding acid:

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 (AsH3) depending on conditions:

As2O3 + 6 Zn + 12 HNO3 → 2 AsH3 + 6 Zn(NO3)2 + 3 H2O
This reaction is used in the Marsh test.

How Arsenic Trioxide Works:
Arsenic is a naturally occurring element widely distributed in the earth's crust.
In the environment, arsenic is combined with oxygen, chlorine, and sulfur to form inorganic arsenic compounds.
Arsenic in animals and plants combines with carbon and hydrogen to form organic arsenic compounds.
Inorganic arsenic compounds are mainly used to preserve wood.
Organic arsenic compounds are used as pesticides, primarily on cotton plants.

Arsenic cannot be destroyed in the environment; it can only change its form.
Arsenic in the air will settle to the ground or is washed out of the air by rain.
Many arsenic compounds can dissolve in water.
Fish and shellfish can accumulate arsenic, but this arsenic is mostly in a form that is not harmful.

Exposure to arsenic can occur from eating food, drinking water, or breathing air containing arsenic.
Breathing sawdust from wood treated with arsenic or breathing smoke from burning wood treated with arsenic is another way to be exposed to arsenic.
Some areas of the world have high levels of arsenic in rock that can increase exposure to those living nearby.

Breathing high levels of inorganic arsenic can give you a sore throat or irritated lungs.
Ingesting (swallowing) high levels of inorganic arsenic can result in death.
Lower levels of arsenic can cause nausea and vomiting, decreased red and white blood cells, abnormal heart rhythm, and numbness and tingling in the hands and feet.
Organic arsenic compounds are less toxic than inorganic arsenic.
Exposure to high levels of organic arsenic may cause similar effects as inorganic arsenic.

Arsenic-containing preparations have been in medical use for more than 2000 years.
Arsenic-based therapy was used in the United States and Europe more than 100 years ago to treat leukemia and infections, but modern chemotherapy and antibiotics replaced these treatments.
More recently, interest in arsenic-based therapy was revived by reports of the anti-leukemic activity of some traditional Chinese preparations.
Chinese scientists subsequently found out that the active ingredient was arsenic trioxide.

Structure
In the liquid and gas phase below 800 °C, arsenic trioxide has the formula As4O6 and is isostructural with P4O6.
Above 800 °C As4O6 significantly dissociates into molecular As2O3, which adopts the same structure as N2O3.
Three forms (polymorphs) are known in the solid state: a high temperature ( > 110 °C) cubic As4O6, containing molecular As4O6, and two related polymeric forms.
The polymers, which both crystallize as monoclinic crystals, feature sheets of pyramidal AsO3 units that share O atoms.

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.

Synonyms

arsenic oxide (As2O3)
arsenic oxide (As4O6)
arsenic trioxide
arsenic(III) oxide
arsenolite
arsenous anhydride
As2O3
As4O6
diarsenic trioxide
naonobin
Tetra Arsenic Hexaoxide
Tetra Arsenic Oxide
tetra-arsenic hexaoxide
tetra-arsenic oxide
tetraarsenic hexaoxide
tetraarsenic oxide
Trisenox
Trixenox
arsenic trioxide
arsenic(3+);oxygen(2-)
Arsenic oxidearsenous trioxide
Arsenous oxide [ISO]
Arsenox
Arsenious Acid Anhydride
Oxyde Arsenieux
Caswell No.
059
Rcra waste number P012
RCRA waste no.
P012
Trixonex
CCRIS 5455
HSDB 419
EINECS 215-481-4
UN1561
EPA Pesticide Chemical Code 007001
UN 1561
AI3-01163
UNII-S7V92P67HO
Arsenic trioxide [USAN:JAN]
S7V92P67HO
DTXSID0020103
NSC 92859
NSC 759274
Arsenic trioxide [UN1561] [Poison]
Z3621
EC 215-481-4
SR-01000944371
SR-01000944371-1