Metabolism of organonitriles to cyanide by rat nasal tissue enzymes.
1. A method for determination of cyanide release during microsomal metabolism of organonitriles was developed. 2. Vmax values for cyanide release from acetonitrile, propionitrile, butyronitrile, isobutyronitrile, acrylonitrile, benzyl cyanide and succinonitrile were determined for rat nasal and liver microsomal metabolism. 3. Km and Vmax values were determined for nasal and liver microsomal metabolism of benzyl cyanide to cyanide. 4. Vmax values were all greater in nasal microsomes than in liver microsomes. Except for acrylonitrile, butyronitrile and isobutyronitrile metabolism, the ethmoturbinate microsomes had higher activities than the maxilloturbinate microsomes. 5. Two methods for determining Vmax values indicate that rat liver, but not the nose, contains at least two cytochrome P-450 isozymes involved in metabolism of benzyl cyanide to cyanide. 6. These results, and previously reported nasal rhodanese activity data, indicate that inhaled organonitriles are substantially detoxicated in the nasal cavity.
Dahl
A R
AR
Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM 87185.
Waruszewski
B A
BA
D000818:Animals; D003486:Cyanides / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008861:Microsomes / Q000201:enzymology; D008862:Microsomes, Liver / Q000201:enzymology; D009296:Nasal Cavity / Q000201:enzymology*; D009570:Nitriles / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D003486:Cyanides; D009570:Nitriles