Editing Acetonitrile (section)

==Safety==

===Toxicity===
Acetonitrile has only modest toxicity in small doses.<ref name="encyc-toxic" /><ref name="inrs">{{Citation | last = Institut national de recherche et de sécurité (INRS) | author-link = Institut national de recherche et de sécurité | title = Fiche toxicologique no.&nbsp;104&nbsp;: Acétonitrile | year = 2004 | place = Paris | publisher = [[Institut national de recherche et de sécurité|INRS]] | url = http://www.inrs.fr/inrs-pub/inrs01.nsf/IntranetObject-accesParReference/FT%20104/$File/ft104.pdf | isbn = 2-7389-1278-8 | access-date = 2008-08-19 | archive-url = https://web.archive.org/web/20110728102249/http://www.inrs.fr/inrs-pub/inrs01.nsf/IntranetObject-accesParReference/FT%20104/$File/ft104.pdf | archive-date = 2011-07-28 | url-status = dead }}</ref> It can be [[Metabolism|metabolised]] to produce [[hydrogen cyanide]], which is the source of the observed toxic effects.<ref name="ecb">{{Citation|last=Spanish Ministry of Health |author-link=Ministry of Health (Spain) |title=Acetonitrile. Summary Risk Assessment Report |year=2002 |place=[[Ispra|Ispra (VA), Italy]] |publisher=[[European Chemicals Bureau]] |url=http://ecb.jrc.it/DOCUMENTS/Existing-Chemicals/RISK_ASSESSMENT/SUMMARY/acetonitrilesum006.pdf |id=Special Publication I.01.65 |url-status=dead |archive-url=https://web.archive.org/web/20081217020910/http://ecb.jrc.it/DOCUMENTS/Existing-Chemicals/RISK_ASSESSMENT/SUMMARY/acetonitrilesum006.pdf |archive-date=2008-12-17 }}</ref><ref name="who">{{Citation | last = International Programme on Chemical Safety | author-link = International Programme on Chemical Safety | title = Environmental Health Criteria 154. Acetonitrile | year = 1993 | place = Geneva | publisher = [[World Health Organization]] | url = http://www.inchem.org/documents/ehc/ehc/ehc154.htm}}</ref><ref name="epa">{{Citation | first = Mark | last = Greenberg | title = Toxicological Review of Acetonitrile | year = 1999 | place = Washington, DC | publisher = [[United States Environmental Protection Agency|U.S. Environmental Protection Agency]] | url = http://www.epa.gov/iris/toxreviews/0205tr.pdf }}</ref> Generally the onset of toxic effects is delayed, due to the time required for the body to metabolize acetonitrile to cyanide (generally about 2–12 hours).<ref name="encyc-toxic" />

Cases of acetonitrile poisoning in humans (or, to be more specific, of cyanide poisoning after exposure to acetonitrile) are rare but not unknown, by inhalation, ingestion and (possibly) by skin absorption.<ref name="who" /> The symptoms, which do not usually appear for several hours after the exposure, include breathing difficulties, slow [[pulse rate]], [[nausea]], and vomiting. [[Convulsion]]s and [[coma]] can occur in serious cases, followed by death from [[respiratory failure]]. The treatment is as for [[cyanide poisoning]], with [[oxygen]], [[sodium nitrite]], and [[sodium thiosulfate]] among the most commonly used emergency treatments.<ref name="who" />

It has been used in formulations for [[nail polish remover]], despite its toxicity. At least two cases have been reported of accidental poisoning of young children by acetonitrile-based nail polish remover, one of which was fatal.<ref>{{Cite journal | last1 = Caravati | first1 = E. M. |last2= Litovitz |first2= T. | title = Pediatric cyanide intoxication and death from an acetonitrile-containing cosmetic | year = 1988 | journal = [[Journal of the American Medical Association|J. Am. Med. Assoc.]] | volume = 260 | issue = 23 | pages = 3470–73 | pmid = 3062198 | doi = 10.1001/jama.260.23.3470}}</ref> [[Acetone]] and [[ethyl acetate]] are often preferred as safer for domestic use, and acetonitrile has been banned in cosmetic products in the [[European Economic Area]] since March 2000.<ref>{{cite journal|url=http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2000:065:0022:0025:EN:PDF|title=Twenty-Fifth Commission Directive 2000/11/EC of 10 March 2000 adapting to technical progress Annex II to Council Directive 76/768/EEC on the approximation of laws of the Member States relating to cosmetic products|journal=[[Official Journal of the European Communities]]|volume=L65|date=2000-03-14|pages=22–25}}</ref>

====Metabolism and excretion====
{| class="wikitable" width=30%
|-
! Compound
! Cyanide, concentration in brain (μg/kg)
! Oral {{LD50}} (mg/kg)
|-
| [[Potassium cyanide]]
| align="center" | 700&nbsp;±&nbsp;200
| align="right" | 10
|-
| [[Propionitrile]]
| align="center" | 510&nbsp;±&nbsp;80
| align="right" | 40
|-
| [[Butyronitrile]]
| align="center" | 400&nbsp;±&nbsp;100
| align="right" | 50
|-
| [[Malononitrile]]
| align="center" | 600&nbsp;±&nbsp;200
| align="right" | 60
|-
| [[Acrylonitrile]]
| align="center" | 400&nbsp;±&nbsp;100
| align="right" | 90
|-
| '''Acetonitrile'''
| align="center" | 28&nbsp;±&nbsp;5
| align="right" | 2460
|-
| '''Table salt (NaCl)'''
| align="center" {{n/a}}
| align="right" | 3000
|-
| colspan=3 | <small>Ionic cyanide concentrations measured in the brains of Sprague-Dawley rats one hour after oral administration of an {{LD50}} of various nitriles.</small><ref name="ratdata">{{Citation | last1 = Ahmed | first1 = A.&nbsp;E. |last2= Farooqui |first2=M.&nbsp;Y.&nbsp;H. | title = Comparative toxicities of aliphatic nitriles | journal = Toxicol. Lett. | year = 1982 | volume = 12 | pages = 157–64 | doi = 10.1016/0378-4274(82)90179-5 | issue = 2–3 | pmid=6287676}}</ref>
|-
|}
In common with other [[nitrile]]s, acetonitrile can be [[Metabolism|metabolised]] in [[microsome]]s, especially in the liver, to produce [[hydrogen cyanide]], as was first shown by Pozzani ''et al.'' in 1959.<ref>{{Citation | last1 = Pozzani | first1 = U.&nbsp;C. |last2= Carpenter |first2=C.&nbsp;P.|last3= Palm |first3= P.&nbsp;E.|last4= Weil|first4= C.&nbsp;S.|last5= Nair |first5=J.&nbsp;H. | title = An investigation of the mammalian toxicity of acetonitrile | journal = J. Occup. Med. | year = 1959 | volume = 1 | pages = 634–642 | doi = 10.1097/00043764-195912000-00003 | pmid = 14434606 | issue = 12}}</ref> The first step in this pathway is the oxidation of acetonitrile to [[glycolonitrile]] by an [[NADPH]]-dependent [[cytochrome P450]] [[monooxygenase]]. The glycolonitrile then undergoes a spontaneous decomposition to give hydrogen cyanide and [[formaldehyde]].<ref name="inrs" /><ref name="who" /> Formaldehyde, a toxin and a carcinogen on its own, is further oxidized to [[formic acid]], which is another source of toxicity.

The metabolism of acetonitrile is much slower than that of other nitriles, which accounts for its relatively low toxicity. Hence, one hour after administration of a potentially lethal dose, the concentration of cyanide in the rat brain was {{frac|20}} that for a [[propionitrile]] dose 60 times lower (see table).<ref name="ratdata" />

The relatively slow metabolism of acetonitrile to hydrogen cyanide allows more of the cyanide produced to be detoxified within the body to [[thiocyanate]] (the [[rhodanese]] pathway). It also allows more of the acetonitrile to be excreted unchanged before it is metabolised. The main pathways of excretion are by exhalation and in the urine.<ref name="inrs" /><ref name="who" /><ref name="epa" />