Abstract:
:Female wistar rats, conventional albino mice, and Chinese hamsters were given a single dose of acrylonitrile, 0.5 or 0.75 mM/kg body weight. The elimination in the urine of thiocyanate, which is the main metabolite of acrylonitrile, indicated a decreasing proportion of biotransformation after oral (over 20%), intraperitoneal, or subcutaneous (2 to 5%), and intravenous (1%) administration in rats. Oral administration of acrylonitrile in hamsters and mice was also followed by higher biotransformation than intraperitoneal administration. Pretreatment of rats with phenobarbital, SKF 525 A, cysteine, or dimercaprol did not significantly influence elimination of thiocyanate in the urine after the administration of acrylonitrile, but simultaneous administration of thiosulfate significantly increased the metabolized portion of acrylonitrile given intraperitoneally in rats (almost twice) and mice (more than three times). Acrylonitrile was found to be strongly bound in blood. The study confirmed the marked effect of distribution (first-pass metabolic phenomenon) on the metabolic fate of foreign compounds. The strong acrylonitrile binding and cyanoethylation are apparently responsible for the unusually high influence of the different routes of administration on the metabolic fate of acrylonitrile. Acrylonitrile was more effectively metabolized to thiocyanate in mice than in rats after oral, intraperitoneal, and intravenous administration. A greater response of acrylonitrile to thiocyanate metabolism and a larger decrease in its acute toxicity after thiosulfate in mice than in rats indicate possible differences in the mechanism of acrylonitrile toxicity in these animals. Cyanide apparently plays a minor role in the acrylonitrile toxicity in rats, but may play quite an important one in mice.
journal_name
Arch Toxicoljournal_title
Archives of toxicologyauthors
Gut I,Nerudová J,Kopecký J,Holecek Vdoi
10.1007/BF00353240keywords:
subject
Has Abstractpub_date
1975-02-14 00:00:00pages
151-61issue
2eissn
0340-5761issn
1432-0738journal_volume
33pub_type
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