Metabolism of 2-(4-methylsulphonyl-2-nitrobenzoyl)-1,3-cyclohexanedione (mesotrione) in rat and mouse.
1. The metabolic fate of [14C]-2-(4-methylsulphonyl-2-nitrobenzoyl)-1,3-cyclohexanedione (mesotrione) has been determined in the male and female rat and mouse following a single oral dose of either 1 or 100 mg kg(-1), in rat given 14 consecutive oral doses of 1 mg kg(-1), and in the surgically prepared, bile duct-cannulated rat following a single oral dose of 50 mg kg(-1). The excretion of a single i.v,. dose of 1 mg kg(-1) in the male and female rat was also investigated. 2. Mesotrione was extensively absorbed and rapidly excreted via urine in both rat and mouse. The absorbed dose was not well metabolized in either species. Unabsorbed material was subject to metabolic action by the gut microflora. 3. The major metabolic pathway was hydroxylation of the aromatic ring. There was evidence for cleavage of the dione and aromatic rings followed by reduction of the nitro group in the gastrointestinal tract. 4. There were no species differences in the metabolism and excretion of mesotrione, which could explain the species differences in toxicity reported for this class of compounds.
Gledhill
A J
AJ
Zeneca Central Toxicology Laboratory, Macclesfield, Cheshire, UK.
Jones
B K
BK
Laird
W J
WJ
D000818:Animals; D001646:Bile / Q000378:metabolism; D001711:Biotransformation; D002853:Chromatography, Liquid; D003512:Cyclohexanones / Q000493:pharmacokinetics* / Q000652:urine; D005243:Feces / Q000737:chemistry; D005260:Female; D006540:Herbicides / Q000493:pharmacokinetics* / Q000652:urine; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D021241:Spectrometry, Mass, Electrospray Ionization
D003512:Cyclohexanones; D006540:Herbicides; C432907:mesotrione