arsine#Toxicology

In its standard state arsine is a colorless, denser-than-air gas that is slightly soluble in water (2% at 20 °C) and in many organic solvents as well.{{Citation needed|date=February 2009}} Arsine itself is odorless,{{cite book|last1=Greaves|first1=Ian|last2=Hunt|first2=Paul|chapter=Ch. 5 Chemical Agents|year=2010|pages=233–344|title=Responding to Terrorism. A Medical Handbook|isbn=978-0-08-045043-8|publisher=Elsevier|doi=10.1016/B978-0-08-045043-8.00005-2|quote=While arsine itself is odourless, its oxidation by air may produce a slight, garlic-like scent. However, it is lethal in concentrations far lower than those required to produce this smell.}} but it oxidizes in air and this creates a slight garlic or fish-like scent when the compound is present above 0.5{{nbsp}}ppm.{{cite web|url=http://www.atsdr.cdc.gov/MMG/MMG.asp?id=1199&tid=278 |archive-url=https://web.archive.org/web/20120124020653/http://www.atsdr.cdc.gov/MMG/MMG.asp?id=1199&tid=278 |url-status=dead |archive-date=January 24, 2012 |title=Medical Management Guidelines for Arsine (AsH₃) |publisher=Agency for Toxic Substances & Disease Registry}} This compound is kinetically stable: at room temperature it decomposes only slowly. At temperatures of ca. 230 °C, decomposition to arsenic and hydrogen is sufficiently rapid to be the basis of the Marsh test for arsenic presence. Similar to stibine, the decomposition of arsine is autocatalytic, as the arsenic freed during the reaction acts as a catalyst for the same reaction.{{cite book|last=Hartman|first=Robert James|title=Colloid Chemistry|publisher=Houghton Mifflin Company|year=1947|editor-last=Briscoe|editor-first=Herman Thompson|edition=2|pages=124}} Several other factors, such as humidity, presence of light and certain catalysts (namely alumina) facilitate the rate of decomposition.{{cite report |author= Institut National de Recherche et de Sécurité |title= Fiche toxicologique nº 53: Trihydrure d'arsenic |date= 2000 |url= http://www.inrs.fr/inrs-pub/inrs01.nsf/IntranetObject-accesParReference/FT%2053/$File/ft53.pdf |access-date= 2006-09-06 |archive-url= https://web.archive.org/web/20061126045357/http://www.inrs.fr/inrs-pub/inrs01.nsf/IntranetObject-accesParReference/FT%2053/$FILE/ft53.pdf |archive-date= 2006-11-26 |url-status = dead |language=fr}}

AsH₃ is a trigonal pyramidal molecule with H–As–H angles of 91.8° and three equivalent As–H bonds, each of 1.519 Å length.{{cite journal

| journal= The Journal of Chemical Physics

| issue= 12

| volume= 20

| date= 1952

| pages= 1955–1956

| doi= 10.1063/1.1700347

| title= The Molecular Structure of Arsine

| last= Nielsen |first=H. H.

| bibcode= 1952JChPh..20.1955N

}}

AsH₃ is generally prepared by the reaction of As³⁺ sources with H⁻ equivalents.{{cite journal|last1=Bellama |first1=J. M. |last2=MacDiarmid |first2=A. G. |title=Synthesis of the Hydrides of Germanium, Phosphorus, Arsenic, and Antimony by the Solid-Phase Reaction of the Corresponding Oxide with Lithium Aluminum Hydride|journal=Inorganic Chemistry|date=1968|volume= 7 |pages= 2070–2|doi=10.1021/ic50068a024|issue=10}}

::4 AsCl₃ + 3 NaBH₄ → 4 AsH₃ + 3 NaCl + 3 BCl₃

As reported in 1775, Carl Scheele reduced arsenic(III) oxide with zinc in the presence of acid.Scheele, Carl Wilhelm (1775) [http://babel.hathitrust.org/cgi/pt?id=mdp.39015039452928;view=1up;seq=293 "Om Arsenik och dess syra"] {{Webarchive|url=https://web.archive.org/web/20160105084518/http://babel.hathitrust.org/cgi/pt?id=mdp.39015039452928;view=1up;seq=293 |date=2016-01-05 }} (On arsenic and its acid), Kongliga Vetenskaps Academiens Handlingar (Proceedings of the Royal Scientific Academy [of Sweden]), 36: 263-294. From p. 290: "Med Zinck. 30. (a) Denna år den endaste af alla så hela som halfva Metaller, som i digestion met Arsenik-syra effervescerar." (With zinc. 30. (a) This is the only [metal] of all whole- as well as semi-metals that effervesces on digestion with arsenic acid.) Scheele collected the arsine and put a mixture of arsine and air into a cylinder. From p. 291: "3:0, Då et tåndt ljus kom når o̊pningen, tåndes luften i kolfven med en småll, lågan for mot handen, denna blef o̊fvedragen med brun fårg, ... " (3:0, Then as [the] lit candle came near the opening [of the cylinder], the gases in [the] cylinder ignited with a bang; [the] flame [rushed] towards my hand, which became coated with [a] brown color, ... ) This reaction is a prelude to the Marsh test.

Alternatively, sources of As³⁻ react with protonic reagents to also produce this gas. Zinc arsenide and sodium arsenide are suitable precursors:"Arsine" in Handbook of Preparative Inorganic Chemistry, 2nd ed., G. Brauer (ed.), Academic Press, 1963, NY, Vol. 1. p. 493.

::Zn₃As₂ + 6 H⁺ → 2 AsH₃ + 3 Zn²⁺

::Na₃As + 3 HBr → AsH₃ + 3 NaBr

The understanding of the chemical properties of AsH₃ is well developed and can be anticipated based on an average of the behavior of pnictogen counterparts, such as PH₃ and SbH₃.

Typical for a heavy hydride (e.g., stibine, {{chem2|H2Te}}, {{chem2|SnH4}}), {{chem2|AsH3}} is unstable with respect to its elements. In other words, it is stable kinetically but not thermodynamically.

::{{chem2|2AsH3 -> 3H2 + 2As}}

This decomposition reaction is the basis of the Marsh test, which detects elemental As.

Continuing the analogy to SbH₃, AsH₃ is readily oxidized by concentrated O₂ or the dilute O₂ concentration in air:

::2 AsH₃ + 3 O₂ → As₂O₃ + 3 H₂O

Arsine will react violently in presence of strong oxidizing agents, such as potassium permanganate, sodium hypochlorite, or nitric acid.

AsH₃ is used as a precursor to metal complexes of "naked" (or "nearly naked") arsenic. An example is the dimanganese species [(C₅H₅)Mn(CO)₂]₂AsH, wherein the Mn₂AsH core is planar.{{cite journal|last1=Herrmann |first1=W. A. |last2=Koumbouris |first2=B. |last3=Schaefer |first3=A. |last4=Zahn |first4=T. |last5=Ziegler |first5=M. L. |title=Generation and Complex Stabilization of Arsinidene and Diarsine Fragments by Metal-Induced Degradation of Monoarsine|journal=Chemische Berichte|date=1985|volume= 118 |pages= 2472–88|doi=10.1002/cber.19851180624|issue=6}}

A characteristic test for arsenic involves the reaction of AsH₃ with Ag⁺, called the Gutzeit test for arsenic.King, E. J. (1959) Qualitative Analysis and Electrolytic Solutions Harcourt, Brace, and World; New York Although this test has become obsolete in analytical chemistry, the underlying reactions further illustrate the affinity of AsH₃ for "soft" metal cations. In the Gutzeit test, AsH₃ is generated by reduction of aqueous arsenic compounds, typically arsenites, with Zn in the presence of H₂SO₄. The evolved gaseous AsH₃ is then exposed to AgNO₃ either as powder or as a solution. With solid AgNO₃, AsH₃ reacts to produce yellow Ag₄AsNO₃, whereas AsH₃ reacts with a solution of AgNO₃ to give black Ag₃As.

The acidic properties of the As–H bond are often exploited. Thus, AsH₃ can be deprotonated:

::AsH₃ + NaNH₂ → NaAsH₂ + NH₃

Upon reaction with the aluminium trialkyls, AsH₃ gives the trimeric [R₂AlAsH₂]₃, where R = (CH₃)₃C.{{cite journal|author1=Atwood, D. A. |author2=Cowley, A. H. |author3=Harris, P. R. |author4=Jones, R. A. |author5=Koschmieder, S. U. |author6=Nunn, C. M. |author7=Atwood, J. L. |author8=Bott, S. G. |title=Cyclic Trimeric Hydroxy, Amido, Phosphido, and Arsenido Derivatives of aluminum and gallium. X-ray Structures of [tert-Bu₂Ga(m-OH)]₃ and [tert-Bu₂Ga(m-NH₂)]₃|journal=Organometallics|date=1993|volume=12 |pages= 24–29|doi=10.1021/om00025a010}} This reaction is relevant to the mechanism by which GaAs forms from AsH₃ (see below).

AsH₃ is generally considered non-basic, but it can be protonated by superacids to give isolable salts of the tetrahedral species [AsH₄]⁺.{{cite journal|author1=R. Minkwitz, R. |author2=Kornath, A. |author3=Sawodny, W. |author4=Härtner, H. |title=Über die Darstellung der Pnikogenoniumsalze AsH₄⁺SbF₆⁻, AsH₄⁺AsF₆⁻, SbH₄⁺SbF₆⁻|journal=Zeitschrift für Anorganische und Allgemeine Chemie|volume= 620 |pages= 753–756|doi=10.1002/zaac.19946200429|date=1994|issue=4|language=de}}

Reactions of arsine with the halogens (fluorine and chlorine) or some of their compounds, such as nitrogen trichloride, are extremely dangerous and can result in explosions.

In contrast to the behavior of PH₃, AsH₃ does not form stable chains, although diarsine (or diarsane) H₂As–AsH₂, and even triarsane H₂As–As(H)–AsH₂ have been detected. The diarsine is unstable above −100 °C.

AsH₃ is used in the synthesis of semiconducting materials related to microelectronics and solid-state lasers. Related to phosphorus, arsenic is an n-dopant for silicon and germanium. More importantly, AsH₃ is used to make the semiconductor GaAs by chemical vapor deposition (CVD) at 700–900 °C:

::Ga(CH₃)₃ + AsH₃ → GaAs + 3 CH₄

For microelectronic applications, arsine can be provided by a sub-atmospheric gas source (a source that supplies less than atmospheric pressure). In this type of gas package, the arsine is adsorbed on a solid microporous adsorbent inside a gas cylinder. This method allows the gas to be stored without pressure, significantly reducing the risk of an arsine gas leak from the cylinder. With this apparatus, arsine is obtained by applying vacuum to the gas cylinder valve outlet. For semiconductor manufacturing, this method is feasible, as processes such as ion implantation operate under high vacuum.

Since before WWII AsH₃ was proposed as a possible chemical warfare weapon. The gas is colorless, almost odorless, and 2.5 times denser than air, as required for a blanketing effect sought in chemical warfare. It is also lethal in concentrations far lower than those required to smell its garlic-like scent. In spite of these characteristics, arsine was never officially used as a weapon, because of its high flammability and its lower efficacy when compared to the non-flammable alternative phosgene. On the other hand, several organic compounds based on arsine, such as lewisite (β-chlorovinyldichloroarsine), adamsite (diphenylaminechloroarsine), Clark 1 (diphenylchloroarsine) and Clark 2 (diphenylcyanoarsine) have been effectively developed for use in chemical warfare.{{cite journal |last= Suchard |first= Jeffrey R. |title= CBRNE — Arsenicals, Arsine |journal= EMedicine |date= March 2006 |url= http://www.emedicine.com/EMERG/topic920.htm |access-date= 2006-09-05 |archive-date= 2006-06-23 |archive-url= https://web.archive.org/web/20060623182153/http://emedicine.com/emerg/topic920.htm |url-status= live }}

{{main|Marsh test}}

AsH₃ is well known in forensic science because it is a chemical intermediate in the detection of arsenic poisoning. The old (but extremely sensitive) Marsh test generates AsH₃ in the presence of arsenic.Holleman, A. F.; Wiberg, E. (2001) Inorganic Chemistry Academic Press: San Diego, {{ISBN|0-12-352651-5}}. This procedure, published in 1836 by James Marsh,{{cite journal

|last= Marsh |first=James

|title= Account of a method of separating small quantities of arsenic from substances with which it may be mixed

|journal= Edinburgh New Philosophical Journal

|volume= 21

|date= 1836

|pages= 229–236

|url= https://archive.org/stream/edinburghnewphil21edin#page/228/mode/2up

}} is based upon treating an As-containing sample of a victim's body (typically the stomach contents) with As-free zinc and dilute sulfuric acid: if the sample contains arsenic, gaseous arsine will form. The gas is swept into a glass tube and decomposed by means of heating around 250–300 °C. The presence of As is indicated by formation of a deposit in the heated part of the equipment. On the other hand, the appearance of a black mirror deposit in the cool part of the equipment indicates the presence of antimony (the highly unstable SbH₃ decomposes even at low temperatures).

The Marsh test was widely used by the end of the 19th century and the start of the 20th; nowadays more sophisticated techniques such as atomic spectroscopy, inductively coupled plasma, and x-ray fluorescence analysis are employed in the forensic field. Though neutron activation analysis was used to detect trace levels of arsenic in the mid 20th century, it has since fallen out of use in modern forensics.

{{for|the toxicology of other arsenic compounds|Arsenic|Arsenic trioxide|Arsenic poisoning}}

The toxicity of arsine is distinct from that of other arsenic compounds. The main route of exposure is by inhalation, although poisoning after skin contact has also been described. Arsine attacks hemoglobin in the red blood cells, causing them to be destroyed by the body.{{cite journal

| journal= New England Journal of Medicine

| volume= 300

| date= 1974

| pages= 1171–1174

| title= Arsine poisoning

|author1=Fowler B. A. |author2=Weissberg J. B. |doi= 10.1056/NEJM197411282912207

| pmid= 4608634

| issue= 22}}{{cite journal

| journal= Journal of Toxicology and Environmental Health Part A

| issue= 2

| volume= 47

| date= 1996

| pages= 145–157

| doi= 10.1080/009841096161852

| pmid= 8598571

| title= Reactions of Arsine with Hemoglobine

| author= Hatlelid K. M.

| bibcode= 1996JTEHA..47..145H

}}

The first signs of exposure, which can take several hours to become apparent, are headaches, vertigo, and nausea, followed by the symptoms of haemolytic anaemia (high levels of unconjugated bilirubin), haemoglobinuria and nephropathy. In severe cases, the damage to the kidneys can be long-lasting.

Exposure to arsine concentrations of 250 ppm is rapidly fatal: concentrations of 25–30 ppm are fatal for 30 min exposure, and concentrations of 10 ppm can be fatal at longer exposure times.{{IDLH|7784421|Arsine}} Symptoms of poisoning appear after exposure to concentrations of 0.5 ppm. There is little information on the chronic toxicity of arsine, although it is reasonable to assume that, in common with other arsenic compounds, a long-term exposure could lead to arsenicosis.{{Citation needed|date=February 2009}}

Arsine can cause pneumonia in two different ways either the "extensive edema of the acute stage may become diffusely infiltrated with polymorphonuclear leucocytes, and the edema may change to ringed with leucocytes, their epithelium degenerated, their walls infiltrated, and each bronchiole the center of a small focus or nodule of pneumonic consolidation", and In the second Case "the areas involved are practically always the anterior tips of the middle and upper lobes, while the posterior portions of these lobes and the whole of the lower lobes present an air-containing and emphysematous condition, sometimes with slight congestion, sometimes with none." which can result in death.{{cite web |title=Collected Studies on the Pathology of War Gas Poisoning, from the Department of Bacteriology and Pathology, Medical Science Section, Chemical Warfare Service, under the direction of M. C. Winternitz, major, M. C., U. S. A. Yale University Press |url=https://books.google.com/books?id=4xU9AAAAYAAJ&dq=The+Chemical+Warfare+Service&pg=PR9 |access-date=28 September 2022 |website=books.google.com | year=1920 |publisher=Yale University press}}

File:Pneumonia forming around bronchioles.png

It is classified as an extremely hazardous substance in the United States as defined in Section 302 of the U.S. Emergency Planning and Community Right-to-Know Act (42 U.S.C. 11002), and is subject to strict reporting requirements by facilities which produce, store, or use it in significant quantities.{{cite report |publisher= Government Printing Office |title= 40 C.F.R.: Appendix A to Part 355—The List of Extremely Hazardous Substances and Their Threshold Planning Quantities |url= http://edocket.access.gpo.gov/cfr_2008/julqtr/pdf/40cfr355AppA.pdf |edition= July 1, 2008 |access-date= October 29, 2011 |archive-url= https://web.archive.org/web/20120225051612/http://edocket.access.gpo.gov/cfr_2008/julqtr/pdf/40cfr355AppA.pdf |archive-date= February 25, 2012 |url-status= dead }}

• Cacodylic acid
• Cacodyl oxide
• Devarda's alloy, also used to produce arsine in the lab
• List of highly toxic gases
• Scheele's Green, a pigment popularly used in the early 19th century

{{Reflist}}

• [http://www.inchem.org/documents/icsc/icsc/eics0222.htm International Chemical Safety Card 0222]
• [https://web.archive.org/web/20051012215141/http://www-cie.iarc.fr/htdocs/monographs/suppl7/arsenic.html IARC Monograph "Arsenic and Arsenic Compounds"]
• [https://www.cdc.gov/niosh/npg/npgd0040.html NIOSH Pocket Guide to Chemical Hazards]
• {{INRS|title=Trihydrure d'arsenic|number=53|year=2000}}
• [https://web.archive.org/web/20070329210220/http://www.us.airliquide.com/en/business/products/gases/gasdata/index.asp?GasID=4 Data on arsine from Air Liquide]

{{Arsenic compounds}}

{{Arsenides}}

{{Hydrides by group}}

{{Chemical agents}}

{{Authority control}}

Category:Arsenic(−III) compounds

Category:IARC Group 1 carcinogens

Category:Industrial gases

Category:Hydrides

Category:Blood agents

Category:Pyrophoric materials