Cytochrome-P450 enzyme). This is the most important enzyme for the oxidative metabolism, but also other cytochrome P-450 enzymes may be involved. The oxidative reaction by Cytochrome-P450 enzymes will lead to the formation of an epoxide intermediate, which shows reactivity. This epoxide intermediate is highly unstable and could lead to the formation of cyanide via different transformations. For example, via epoxide hydratase (EH) or via interactions with a sulfhydryl compound, which leads to the formation of a cyanohydrin that could rearrange to an aldehyde and thereby can possibly result in cyanide release. The epoxide can also be conjugated with GSH. It has been shown that treatment of mice with carbon tetrachloride, which acts on the mixed function oxygenase system, results in much lower cyanide concentrations than controls and greatly reduced toxicity of MeAN, indicating that cyanide production is indeed the main pathway of toxicity, unlike AN, which is more carcinogenic. More information about toxicity of cyanide see: cyanide poisoning. Toxicity in humans Human toxicity has not been well analyzed. Minimum threshold values for odor detections are reported to be at 7 ppm, with the majority of subjects detecting it at higher concentrations of 14 or 24 ppm. At concentrations of 24 ppm incidence of throat, eye and nose irritation occur. No deaths caused by methacrylonitrile poisoning have been reported. Effects on animals Inhalation, and oral and dermal administration, of methacrylonitrile can cause acute deaths in animals, often preceded by convulsions and loss of consciousness. Signs of the toxic effects of methacrylonitrile in rats after oral absorption are ataxia, trembling, convulsions, mild diarrhea and irregular breathing. The main cause of toxic effects at lethal (and threshold) levels of MeAN is damage to the central nervous system. This, along with the signs of toxic effects displayed by all tested animals, is consistent with cyanide poisoning. Methacrylonitrile differs herein from acrylonitrile, which does not show cyanide related signs of toxicity. Cyanide production after exposure to MeAN has been tested, and intravenous injection of MeAN in rabbits results in production of significant levels of cyanide in the blood. In Wistar rats too, toxicity is related to the in vivo liberation of cyanide after exposure to MeAN. The acute toxicity of MeAN can also be antagonized with cyanide antidotes. A difference in resistance to the lethal effects of MeAN can be noted between species. For inhalation, a 4-hour exposure period gives a LC50 of 328-700 ppm