IMIDOCARB RESIDUES IN EDIBLE BOVINE-TISSUES AND IN-VITRO ASSESSMENT OF IMIDOCARB METABOLISM AND CYTOTOXICITY

Imidocarb residues in liver and muscle were measured by HPLC after a s ingle therapeutic dose to cattle (3 mg imidocarb dipropionate kg(-1)). Imidocarb and 7-ethoxycoumarin metabolism were compared in three diff erent in vitro systems prepared from bovine liver: cultures of hepatoc yte monolayers, precision-cut liver slices, and microsomes, The potent ial hepatotoxicity of imidocarb residues was tested on hepatocyte mono layers and assessed using the neutral red and lactate dehydrogenase le akage assays, The concentration of imidocarb (mean +/- SD) decreased b etween days 14 and 224 after treatment from 5.40 +/- 0.61 to 0.12 +/- 0.01 and from 1.05 +/- 0.31 to 0.06 +/- 0.02 mu g g(-1) in liver and m uscle, respectively. The depletion kinetics of imidocarb fitted a two- compartment model with alpha- and beta-phase half-lives of 31.7 and 48 .5 days in liver and 34.9 and 120.7 days in muscle, respectively Imido carb metabolites were not detected in any in vitro system. 7-Ethoxycou marin metabolism was found in all in vitro systems; the predominant me tabolite produced by hepatocyte and liver slice cultures was umbellife rone glucuronide. Cytotoxicity of imidocarb (100 mu M) to hepatocyte m onolayers was maximal after 72 hr treatment and dose-dependent above 1 0 mu M imidocarb. It is most likely that the hepatotoxicity of imidoca rb is caused by the parent compound, because no evidence for imidocarb metabolism was found.