Toxicity Acetonitrile has only modest toxicity in small doses. It can be metabolised to produce
hydrogen cyanide, which is the source of the observed toxic effects. 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).
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.
Metabolism and excretion In common with other
nitriles, acetonitrile can be
metabolised in
microsomes, especially in the liver, to produce
hydrogen cyanide, as was first shown by Pozzani
et al. in 1959. 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. 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 that for a
propionitrile dose 60 times lower (see table). 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 acetonitrile to be excreted unchanged before it is metabolised. The main pathways of excretion are by exhalation and in the urine. ==See also==