Species differences in acrylonitrile metabolism and toxicity between experimental animals and humans based on observations in human accidental poisonings

Thier, Ricarda, Lewalter, Jürgen, & Bolt, Hermann M. (2000) Species differences in acrylonitrile metabolism and toxicity between experimental animals and humans based on observations in human accidental poisonings. Archives of Toxicology, 74(4-5), pp. 184-189.

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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.

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ID Code: 77486
Item Type: Journal Article
Refereed: Yes
Keywords: Acrylonitrile, Antidote therapy, Cyanide, Intoxication, N-Cyanoethyl-asparaginic acid, N-Cyanoethyl-valine, Protein adducts, acetylcysteine, epoxide, industrial chemical, sodium thiosulfate, adult, biological monitoring, clinical article, clinical feature, cyanide poisoning, detoxification, genotoxicity, glutathione metabolism, human, inhalation, male, nonhuman, occupational exposure, occupational hazard, priority journal, review, skin, species difference, Animals, Carcinogens, Humans, Middle Aged, Species Specificity
DOI: 10.1007/s002040000109
ISSN: 0340-5761
Divisions: Current > Schools > School of Clinical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Copyright Owner: Copyright 2000 Springer-Verlag
Deposited On: 16 Oct 2014 01:29
Last Modified: 16 Oct 2014 01:29

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