Metabolism of 2,6-dichlorobenzonitrile, 2,6-dichlorothiobenzamide in rodents and goats.
1. Twelve 14C-labelled metabolites were isolated from either urine or bile from either rats (11 metabolites) or goats (7 metabolites) given single oral doses of 2,6-dichlorobenzo[14C]nitrile (DCBN). Five of these metabolites were also excreted in urine from rats dosed orally with 2,6-dichlorothiobenz[14C]-amide (DCTBA). 2. All metabolites from either DCBN or DCTBA were benzonitriles with the following ring substituents: Cl2, OH (three isomers); Cl2, (OH)2; Cl, (OH)2; Cl, OH, SH; Cl, OH, SCH3; SCH3, SOCH3, OH; Cl2, S-(N-acetyl)cysteine; Cl, S-(N-acetyl)cysteine; Cl, OH, S-(N-acetyl)cysteine. 3. The thiobenzamide moiety of DCTBA was converted to the nitrile in all the excreted urinary metabolites. No hydrolysis of the nitrile in DCBN to either an amide or an acid was detected. 4. Urine was the major route for excretion; however, enterohepatic circulation occurred. 5. Whole-body autoradiography of 14C-DCBN and 14C-DCTBA in mice showed the presence of bound residues in the mucosa of the nasal cavity, trachea, tongue, oesophagus, the kidney, liver and the intestinal contents.
Bakke
J E
JE
Metabolism and Radiation Research Laboratory, U.S. Department of Agriculture, Fargo, ND 58105.
Larsen
G L
GL
Struble
C
C
Feil
V J
VJ
Brandt
I
I
Brittebo
E B
EB
D000577:Amides / Q000493:pharmacokinetics*; D000818:Animals; D001345:Autoradiography; D001646:Bile / Q000378:metabolism; D002250:Carbon Radioisotopes; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006041:Goats / Q000378:metabolism*; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D009570:Nitriles / Q000378:metabolism / Q000493:pharmacokinetics*; D011865:Radioisotope Dilution Technique; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013854:Thioamides / Q000378:metabolism / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D000577:Amides; D002250:Carbon Radioisotopes; D009570:Nitriles; D013854:Thioamides; C058670:2,6-dichlorothiobenzamide; C055869:dichlobanil