Rodent tissue distribution of 2-cyanoethylene oxide, the epoxide metabolite of acrylonitrile.
The direct acting mutagen 2-cyanoethylene oxide (CEO), formed in the liver by oxidation of acrylonitrile (ACN), is thought to mediate the extrahepatic carcinogenic effects of ACN in rats. This study determined the tissue distribution of CEO (3 mg/kg p.o.) in F-344 rats and B6C3F1 mice. Radioactivity from [2,3-14C]CEO was widely distributed in the major organs of rodents by 2 h and decreased by 71% to 90% within 24 h, demonstrating that there was no preferential tissue uptake or retention of CEO. CEO was detected in rodent blood and brain 5-10 min after an oral dose of ACN (10 mg/kg), demonstrating that this mutagenic epoxide metabolite circulates to extrahepatic target organs following ACN administration.
Kedderis
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GL
Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709.
Batra
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Held
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SD
Loos
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MA
Teo
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SK
D000181:Acrylonitrile / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000818:Animals; D001923:Brain Chemistry; D002273:Carcinogens / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005027:Ethylene Oxide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity; D014018:Tissue Distribution
D002273:Carcinogens; C033154:2-cyanoethylene oxide; D005027:Ethylene Oxide; D000181:Acrylonitrile