Comparative toxicokinetics of 2,3-14C- and 1-14C-acrylonitrile in the rat

✍ Scribed by Ahmed E. Ahmed; Mohammed Y. H. Farooqui; Raj K. Upreti; Osama El-Shabrawy

• Publisher: John Wiley and Sons
• Year: 1983
• Tongue: English
• Weight: 838 KB
• Volume: 3
• Category: Article
• ISSN: 0260-437X
• DOI: 10.1002/jat.2550030109

✦ Synopsis

Abstract

The tissue distribution, elimination and covalent binding of 2,3‐^14^C‐ and 1‐^14^C‐acrylonitrile (VCN) were studied in male Sprague—Dawley rats given an oral dose of 46.5 mg kg^−1^. Exhalation of unchanged VCN, ^14^CO~2~ and H^14^CN was monitored at selected intervals. Only 5% of the total dose administered was recovered as unchanged VCN. Rats given 2,3‐^14^C‐VCN exhaled only 2% of ^14^C activity as ^14^CO~2~ and none was recovered as H^14^CN, whereas rats given 1‐^14^C‐VCN exhaled about 12% of ^14^C activity as ^14^CO~2~ and 0.5% as H^14^CN. In the initial 24 h, 40% of radioactivity from 1‐^14^C‐VCN appeared in urine, while 60% was recovered in the urine of rats given 2,3‐^14^C‐VCN. The red blood cells retained significant amounts of radioactivity from both the compounds for more than 10 days after administration, whereas the ^14^C activity in plasma declined sharply. The highest level of radioactivity from both compounds was recovered in the gastrointestinal tract. In liver, kidney, brain, spleen, adrenal, lung and heart tissues the unbound percent radioactivity decreased, while irreversible percent covalent binding to macromolecules in relation to total increased concomitantly. Subcellular fractionation of the tissues showed that most of the covalently bound radioactivity was distributed in non‐cytosolic fractions. As compared to 1‐^14^C‐VCN administered animals, the percentage of covalent binding of 2,3‐^14^C‐VCN was significantly higher even 72 h after dosing. The relationship between covalent binding and acrylonitrile toxicity is discussed.