Species differences in acrylonitrile metabolism and toxicity between experimental animals and humans based on observations in human accidental poisonings.
The high acute toxicity of acrylonitrile may be a result of its intrinsic biological reactivity or of its metabolite cyanide. Intravenous N-acetylcysteine has been recommended for treatment of accidental intoxications in acrylonitrile workers, but such recommendations vary internationally. Acrylonitrile is metabolized in humans and experimental animals via two competing pathways; the glutathione-dependent pathway is considered to represent an avenue of detoxication whilst the oxidative pathway leads to a genotoxic epoxide, cyanoethylene oxide, and to elimination of cyanide. Cases of acute acrylonitrile overexposure or intoxication have occurred within persons having industrial contact with acrylonitrile; the route of exposure was by inhalation and/or by skin contact. The combined observations lead to the conclusion of a much higher impact of the oxidative metabolism of acrylonitrile in humans than in rodents. This is confirmed by differences in the clinical picture of acute life-threatening intoxications in both species, as well as by differential efficacies of antidotes. A combination of N-acetylcysteine with sodium thiosulfate seems an appropriate measure for antidote therapy of acute acrylonitrile intoxications. Clinical observations also highlight the practical importance of human individual susceptibility differences. Furthermore, differential adduct monitoring, assessing protein adducts with different rates of decay, enables the development of more elaborated biological monitoring strategies for the surveillance of workers with potential acrylonitrile contact.
Thier
R
R
Institut für Arbeitsphysiologie an der Universität Dortmund, Germany. thier@arb-phys.uni-dortmund.de
Lewalter
J
J
Bolt
H M
HM
D000181:Acrylonitrile / Q000378:metabolism* / Q000506:poisoning / Q000633:toxicity*; D000328:Adult; D000818:Animals; D002273:Carcinogens / Q000009:adverse effects / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure; D013045:Species Specificity
D002273:Carcinogens; D000181:Acrylonitrile