Description
Arsenic trioxide, often denoted as As
2O
3 butmore correctly stated as As
4O
6, is an inorganic compound mainly
used as the precursor for organoarsenic compounds. It can be obtained by the oxidation of arsenic-containing
minerals in the air, such as roasting of orpiment.
2As
2S
3 + 9O
2 → As
4O
6 + 6SO
2
Chemical Properties
Arsenic trioxide is a noncombustible, odorless,
white powder or colorless crystalline solid.
Chemical Properties
Arsenic trioxide is an amphoteric oxide that shows a marked preponderance for its acidic
properties. It dissolves readily in alkaline solutions to give arsenites. It is the starting
point for the manufacture of arsenic-based pesticides (sodium arsenite, sodium arsenate,
sodium cacodylate); a starting point for the manufacture of certain arsenic-based
pharmaceuticals (Neosalvarsan) and veterinary products. Arsenic trioxide has several
applications: (i) a decolorizing agent for glasses and enamels; (ii) a preservative for wood,
in animal hides; (iii) in hydrogen recombination poison for metallurgical studies, as a
termite poison; (iv) as a starting material for the preparation of elemental arsenic, arsenic
alloys, and to enhance electrical junctions in semiconductors; (v) as a cytostatic in the
treatment of refractory promyelocytic (M3), a subtype of acute myeloid leukemia; (vi)
arsenic trioxide is also used to treat leukemia in patients who have not responded to other
medications; (vii) arsenic trioxide was mixed with copper II acetate to form the extremely
toxic but exceedingly vibrant pigment, known as Paris green, for use as a rodenticide in
the Paris subways; and (viii) in cases of suicide and murder. Humans can be exposed to
arsenicin several ways, such as ingesting small amounts present in food and water or
breathing air containing arsenic, breathing sawdust or burning smoke from wood treated
with arsenic, living in areas with unusually high natural levels of arsenic in rock, working
in a job that involves arsenic production or use, such as copper or lead smelting, wood
treating, or pesticide application.
Chemical Properties
WHITE POWDER AND FINE CHUNKS
Physical properties
This compound, also known as arsenious acid, is the
hydrolyzed form of As2O3 and has the formula As(OH)3.
As(OH)3 occurs in aqueous solutions and has not been
isolated as a pure material, although this fact does not
detract from the significance of As(OH)3. This
compound is essentially the “hydroxide” of the arsenic
ion but is not basic in character. The molecular weight
of arsenous acid is 125.94 g/mol. As(OH)3 is a pyramidal
molecule consisting of three hydroxyl groups connected
by single bonds to arsenic. In contrast, the nominally
related phosphorous species H3PO3 mainly adopts the
structure HPO(OH)2 in which P(OH)3 is a very minor
equilibrium component of such solutions (if it exists at
all). The differing behaviors of the As and P compounds
reflect a trend whereby high oxidation states are more stable for lighter members of main group elements
than their heavier congeners like As where the +3 valance
state dominates.
Arsenous acid [13464-58-9], AsH3O3, is known to
exist only in solution. It is a weak acid with a dissociation
constant of 8×10
-16 at 25°C. The free acid apparently
has three OH groups attached directly to the arsenic
atom and hence is not analogous to phosphorous acid.
A number of complex arsenites are known, among
which are copper acetate arsenite [12002-03-8],
Cu2(C2H3O2)(AsO3), Paris green, and cupric hydrogen
arsenite [10290-12-7], CuHAsO3, Scheele’s green. These
have been used mainly as insecticides in the past.
As(OH)3 is a weak acid with a Pka of 9.2. The preparation
of As(OH)3 involves a slow hydrolysis of hydolysis
of arsenic trioxide in water. Addition of a base such
as one of the alkali cations converts arsenous acid to the
arsenite ions [AsO(OH)2]
-, [AsO2(OH)]
2-, and
[AsO3]
3-. In other words, arsenous acid is “amphoteric”
and easily forms anions in the presence of more
cationic species like the alkali metals. Note that these
anions are analogous to the mono, di and tri-basic
anions of phosphate. Reactions attributed to aqueous
arsenic trioxide are due to arsenous acid and its conjugate
bases.
Uses
Arsenic trioxide is used as a precursor to forestry products, in colorless glass production, and in electronics. And it is also used as pigments, and preservatives for hides and wood, in the semiconductor industry to create light emitting diodes.
Uses
Starting material for various arsenic compounds. Decolorizer and fining agent in manufacture of glass. In wood preservatives, weed killers, rodenticides.
Uses
It is a reductometric standard.
Definition
A
salt of the hypothetical arsenic(III) acid,
formed by reacting arsenic(III) oxide with
alkalis. Arsenate(III) salts contain the ion
AsO
33-. Copper arsenate(III) is used as an
insecticide.
Definition
arsenolite: A mineral form of arsenic(III) oxide, As
4O
6.
Definition
Claudetite: a mineral form of arsenic(III) oxide, As
4O
6.
Preparation
Arsenic trioxide is obtained by roasting the mineral arsenopyrite, FeAsS, in air at 650 to 700°C. It is also obtained as a by-product during the smelting ofcopper and lead concentrates during the extraction of these metals from their ores that contain arsenic. The latter readily oxidizes to arsenic trioxide which is volatilized. The vapors are then condensed and collected. High purity-grade oxide can be obtained by resublimation of the crude trioxide or by pressure leaching and recrystallization. Arsenic trioxide may also be prepared by hydrolysis of arsenic trichloride, -tribromide or -trifluoride.
Definition
A colorless crystalline solid that is very poisonous (0.1 g would be a lethal dose). Analysis of the solid and vapor states suggests a dimerized structure of As
4O
6. An amphoteric oxide, arsenic(III) oxide is sparingly soluble in water, producing an acidic solution. It is formed when arsenic is burned in air or oxygen.
Reactions
In the processing of As2O3 the oxide is normally reduced withcarbon:
2As2O3+3C?→As4+3CO2
The reaction is endothermic and is carried out at 500–800℃.The elemental arsenic sublimes and is condensed out of the reaction gas by cooling.
brand name
Trisenox (Cephalon).
General Description
Arsenic trioxide is available in 10-mL vials for IV administrationas second-line therapy in the treatment of acutepromyelocytic leukemia (APL). The mechanism of theagent has not been well characterized; however, work hasindicated that the agent may cause the degradation of a proteinthat blocks myeloid differentiation. Acute lymphocyticleukemia is associated with a translocation in which thepromyelocytic leukemia (PML) gene is fused with theretinoic acid receptor gene (RAR), and the protein that resultsfrom this genetic rearrangement prevents myeloid differentiation.Arsenic trioxide is capable of degrading thisprotein and allowing the cells to differentiate. Additional effectshave included stimulation of apoptosis by decreasingBcl-2 activity and stimulation of caspase enzymes and p53.Angiogenesis is inhibited by the inhibition of VEGF at theprotein level.The agent is widely distributed after IV administration;however, the pharmacokinetics of the agenthave not been well characterized. Metabolism studies haveshown that the agent undergoes reduction to trivalent arsenicfollowed by methylation to give monomethylarsonicand dimethylarsinic acids, which are eliminated in theurine. Unlike most other antineoplastic agents, myelosuppressiondoes not occur in fact many patients (50%–60%)experience leukocytosis in which white blood cell count increases.APL differentiation syndrome is seen in many patients(30%) and presents as fever, shortness of breath,weight gain, pulmonary infiltrates, and pleural or pericardialeffusions. This may be fatal and is commonly treatedwith high-dose dexamethasone upon initial suspicion. Thepresentation of APL differentiation syndrome are identicalfor arsenic trioxide and retinoic acid. Additional adverse effectsinclude fatigue, a prolonged QT interval, dizziness,mild hyperglycemia, and mild nausea and vomiting.
General Description
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.
Air & Water Reactions
Slightly soluble in water, but dissolves very slowly; more soluble in hot water [Merck].
Reactivity Profile
Arsenic(III) oxide reacts vigorously with fluorine at ordinary temperatures [Mellor 9:34 1946-47]. Dissolves in aqueous acids. Incompatible with tannic acid, infusions of cinchona and other vegetable astringent infusions and decoctions, and with iron in solution [Merck].
Hazard
A confirmed carcinogen.
Health Hazard
Arsenic trioxide is readily absorbed by the digestive system. The toxic effects are also well
known after inhalation of the dust or fumes and after skin contact. Initially, elimination
is rapid (half-life of 1–2 days) by methylation to cacodylic 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 fi rst symptoms of acute arsenic poisoning by ingestion are digestive problems:
vomiting, abdominal pains, and diarrhea often accompanied by bleeding. Sub-lethal
doses can lead to convulsions, cardiovascular problems, infl ammation of the liver 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. Cases of acute arsenic poisoning after inhalation and after skin contact with arsenic
trioxide are many. The fi rst signs are severe irritation, either of the respiratory tract or
of the exposed skin, followed by longer-term neurological problems. Even dilute solutions
of arsenic trioxide are dangerous on contact with the eyes. Ingesting or breathing
low levels of inorganic arsenic for a long time can cause a darkening of the skin and the
appearance of small “corns” or “warts” on the palms, soles, and torso. Skin contact with
inorganic arsenic may cause redness and swelling. In brief, acute human exposures to
arsenic in well water (typically containing more than 1200 μg/L) is known to cause many
health effects, including abdominal pain, vomiting, diarrhea, muscular weakness and
cramping, pain in arms and legs, skin changes or rashes, swelling of the eyelids, feet, and
hands, and in serious poisoning, death.
Health Hazard
Material is considered super toxic; probable oral lethal dose (human) is less than 5 mg/kg, i.e., a taste (less than 7 drops) for a 70kg (150 lb.) person. Material causes acute gastrointestinal and central nervous system symptoms. Renal and hepatic damage have also been observed. Chronic exposure to material has led to nasal septum perforation, dermatological symptoms (lesions, necrosis, etc.) and an increase in the incidence of lung and lymphatic cancers. Appreciable exposure to respiratory irritant promoters such as metal oxide fumes elicits a carcinogenic response from Arsenic(III) oxide .
Fire Hazard
Toxic fumes of Arsenic(III) oxide and arsine may be formed in fire situations. Contact with halide acids will form toxic volatile halides. Reduction in acid solutions will form arsine. Arsenic(III) oxide and excess zinc filings will explode on heating. Avoid sodium chlorate; fluorine; chlorine trifluoride; chromic oxide; aluminum chloride; phosphorus pentoxide; hydrogen fluoride; oxygen difluoride, tannic acid; infusion cinchona and other vegetable astringent infusions and decoctions; iron in solution. Arsenic(III) oxide is stable in air but slowly oxidizes in acid media.
Flammability and Explosibility
Not classified
Clinical Use
Antineoplastic agent:
Acute promyelocytic leukaemia (APL)
Safety Profile
Confirmed human
carcinogen with experimental neoplastigenic
and tumorigenic data. Poison by ingestion,
subcutaneous, and intravenous routes.
Human systemic effects by ingestion: sleep
changes, muscle weakness, hypermotiltty,
darrhea, cardiac arrhythmias, coma, fatty
degeneration of the liver, depressed renal
function tests. An experimental teratogen.
Other experimental reproductive effects.
Mutation data reported. Reacts vigorously
with Rb2C2, CIF3, F2, Hg, OF2, NaClO3. See
also ARSENIC COMPOUNDS.
Potential Exposure
Arsenic trioxide, a primary raw material
for other arsenic compounds, is used in manufacture of
pesticides, glass, industrial chemicals, and drugs. It is an
intermediate for insecticides, herbicides and fungicides.
The material is used as a wood and tanning preservative
and a decoloring and refining agent in glass manufacture. It
is also used in pharmaceuticals and in the purification of
synthetic gas.
Drug interactions
Potentially hazardous interactions with other drugs
Use with care in combination with other drugs
known to cause QT interval prolongation.
Anti-arrhythmics: increased risk of ventricular
arrhythmias with amiodarone and disopyramide.
Antibacterials: increased risk of ventricular
arrhythmias with delamanid, erythromycin,
levofloxacin and moxifloxacin.
Antidepressants: increased risk of ventricular
arrhythmias with amitriptyline or clomipramine.
Antifungals: increased risk of ventricular
arrhythmias with amphotericin.
Antimalarials: increased risk of ventricular
arrhythmias with piperaquine with artenimol -
avoid.
Antipsychotics: increased risk of ventricular
arrhythmias with antipsychotics that prolong the
QT interval and haloperidol; avoid with clozapine,
increased risk of agranulocytosis.
Beta-blockers: increased risk of ventricular
arrhythmias with sotalol.
Cytotoxics: increased risk of ventricular arrhythmias
with vandetanib - avoid.
Diuretics: increased risk of ventricular arrhythmias
if hypokalaemia occurs due to acetazolamide, loop
diuretics or thiazide diuretics.
Lithium: increased risk of ventricular arrhythmias.
First aid
If this chemical gets into the eyes, remove anycontact lenses at once and irrigate immediately for at least30 min, occasionally lifting upper and lower lids. Seek medical attention immediately. If this chemical contacts theskin, remove contaminated clothing and wash immediatelywith large amounts of soap and water. Seek medical attention immediately. If this chemical has been inhaled, removefrom exposure, begin rescue breathing (using universal precautions, including resuscitation mask) if breathing hasstopped and CPR if heart action has stopped. Transferpromptly to a medical facility. When this chemical has beenswallowed, get medical attention.Note to physician: For severe poisoning, BAL [British AntiLewisite, Dimercaprol, dithiopropanol (C3H8OS2)] has beenused to treat toxic symptoms of certain heavy metals poisoning including arsenic. Although BAL is reported to have alarge margin of safety, caution must be exercised, becausetoxic effects may be caused by excessive dosage. Most canbe prevented by premedication with 1-ephedrine sulfate(CAS: 134-72-5). For milder poisoning penicillamine (notpenicillin) has been used, both with mixed success. Sideeffects occur with such treatment and it is never a substitutefor controlling exposure. It can only be done under strictmedical care.
Metabolism
When placed into solution, arsenic trioxide immediately
forms the hydrolysis product arsenious acid (AsIII), which
is the pharmacologically active species of arsenic trioxide.
The metabolism of arsenic trioxide involves oxidation of
AsIII to arsenic acid (AsV), as well as oxidative methylation
to monomethylarsonic acid (MMAV) and dimethylarsinic
acid (DMAV) by methyltransferases, primarily in the liver.
Approximately 15% of the administered arsenic trioxide
dose is excreted in the urine as unchanged AsIII. The
methylated metabolites of AsIII (MMAV, DMAV) are
primarily excreted in the urine.
storage
Color Code—Blue: Health Hazard/Poison: Store ina secure poison location. Prior to working with this chemicalyou should be trained on its proper handling and storage.Store in tightly closed containers in a cool, dry well-ventilated area away from contact with incompatible materials. Aregulated, marked area should be established where thischemical is handled, used, or stored in compliance withOSHA Standard 1910.1045.
Shipping
UN1561 Arsenic trioxide, Hazard Class: 6.1;
Labels: 6.1-Poisonous materials
Purification Methods
It crystallises in an octahedral form (common form) from H2O or from dilute HCl (1:2), and is then washed, dried and sublimed (193o/760mm). Analytical reagent grade material is suitable for use as an analytical standard after it has been dried at 105o for 1-2hours or has been left in a desiccator for several hours over conc H2SO4. Alternatively: As2O3 (15g) is dissolved by heating in a mixture of H2O (60mL) and HCl (90g, s.g. 1.1), and crystallisation occurs on cooling, accompanied by brilliant flashes of light [Bandrowski Z Phys Chem 17 234 1895]. The amorphous form is a colourless transparent glass (m 200o) which is obtained when the vapour is slowly condensed below the vaporization temperature, and should be kept in a sealed tube because it changes to the octahedral form (m 275o) in the presence of moisture. [Rushton & Daniels J Am Chem Soc 48 384 1926.] A third monoclinic form, is obtained by heating the oxide in a sealed tube at 400o (the vitreous, amorphous form remains at the bottom of the tube) with the monoclinic form subliming onto the intermediate part of the tube at 200o (m 312o), and the octahedral form deposits at the top of the tube. The transition temperature between the last two forms is ~250o. POISONOUS (particularly the vapour, handle in a ventilated fume cupboard). [Schenk in Handbook of Preparative Inorganic Chemistry (Ed. Brauer) Academic Press Vol I p 600 1963.]
Incompatibilities
Sodium chlorate; sodium hydroxide, sulfuric
acid; fluorine; chlorine trifluoride; chromic oxide; aluminum
chloride; phosphorus pentoxide; hydrogen fluoride;
oxygen difluoride; tannic acid; infusion cinchona and other
vegetable astringent infusions and decoctions; iron in solution.
Contact with acids or acid mists releases deadly arsine
gas.
Waste Disposal
Consult with environmental
regulatory agencies for guidance on acceptable disposal
practices. Generators of waste containing this contaminant
(≥100 kg/mo) must conform with EPA regulations governing
storage, transportation, treatment, and waste disposal.
Dissolve in a minimum of concentrated hydrochloric acid.
Dilute with water until white precipitate forms. Add HCl to
dissolve. Saturate with H2S; filter and wash precipitate and
return to supplier. Alternatively, precipitate with heavy
metals, such as lime or ferric hydroxide in lieu of H2S.
If needed, seek professional environmental engineering
assistance from the United States Environmental Protection
Agency Environmental Response Team at (908) 548-8730
(24-hour response line).
