Subject(s)
Azepines/metabolism , Herbicides/metabolism , Animals , Feces/analysis , Female , Herbicides/administration & dosage , Herbicides/urine , Male , Rats , Sex Factors , Thiocarbamates , Tissue DistributionSubject(s)
Azepines/urine , Herbicides/urine , Animals , Azepines/metabolism , Chromatography, Thin Layer , Female , Herbicides/metabolism , Male , Mass Spectrometry , RatsABSTRACT
Rat metabolism studies were conducted with three organophosphorus ester insecticides: [phenyl- or ethoxy-14C]Dyfonate, O-ethyl S-phenyl ethylphosphonodithioate; [phenyl-14C]Trithion, S-[(4-chlorophenylthio)methyl]O,O-diethylphosphorodithioate; and [phenyl-14C]R-14805, 4-[O,0-diethyl phosphorothioyl)]-acetophenoneoxime-N'-methylcarbamate. Compounds were administered orally to rats at 2 to 8 mg/kg, and biotransformation pathways were established from identified metabolites. Metabolites were isolated from O-96 hr urine and identified by using one or more methods including thin-layer chromatography, radio-gas-liquid chromatography, mass spectrometry, and nuclear magnetic resonance. Each of these model insecticides displayed a distinct bioactivation and detoxification pathway. Conversion to potent acetylcholinesterase inhibitors resulted from desulfuration of Dyfonate, desulfuration and thioether oxidation of Trithion, and desulfuration and a variety of modifications of the leaving group of R-14805. The compounds were deactivated primarily via cleavage of an organophosphorus ester group. All three compounds and their metabolites were rapidly excreted primarily in urine without any bioaccumulation in tissues.
Subject(s)
Insecticides/metabolism , Organothiophosphorus Compounds , Animals , Biotransformation , Cholinesterase Inhibitors , Plants/metabolism , Rats , Structure-Activity RelationshipABSTRACT
Carbophenothion sulfoxide, an oxidative metabolite of carbophenothion, is reduced to carbophenothion in the living rat and by an in vitro system containing rat liver enzyme, reduced nicotinamide adenine dinucleotide phosphate, and flavin adenine dinu cleotide phosphate. Reduction of sulfoxides, formed metabolicially from certain commercial organophosphorus insecticides, may be important in ameliorating the toxicity of these compounds.
Subject(s)
Insecticides/metabolism , Organophosphorus Compounds , Sulfoxides/metabolism , Animals , Cholinesterase Inhibitors/metabolism , Liver/enzymology , Liver/metabolism , Rats , Thiones/metabolismSubject(s)
Insecticides/metabolism , Organothiophosphorus Compounds , Animals , Biotransformation , Chemical Phenomena , Chemistry , Feces/analysis , Male , Rats , Time FactorsSubject(s)
Captan/metabolism , Animals , Carbon Radioisotopes , Carboxylic Acids/metabolism , Chromatography, Gas , Chromatography, Thin Layer , Cystine/metabolism , Digestive System/metabolism , Electrophoresis , Feces/analysis , Female , Glutathione/metabolism , Male , Mass Spectrometry , Phosgene/metabolism , Rats , Spectrophotometry, Infrared , Spectrophotometry, Ultraviolet , Sulfhydryl Compounds/metabolism , Sulfites/metabolism , Sulfur Radioisotopes , Thiazoles/metabolism , Time FactorsSubject(s)
Fluorenes/pharmacology , Liver Neoplasms/chemically induced , Liver/metabolism , Neoplasms, Experimental/chemically induced , Protein Binding/drug effects , Transferases/pharmacology , Animals , Cricetinae , Female , Guinea Pigs , Hydrocarbons/metabolism , Hydrocarbons/pharmacology , Liver/enzymology , Liver Neoplasms/metabolism , Male , Mice , Neoplasms, Experimental/metabolism , Rabbits , Rats , SulfatesABSTRACT
Injections of sulfate ion in rats given the carcinogen N-hydroxy-2-acetylaminofluorene increased (i) the formation of 1-and 3-(methion-S-yl)-2-acetylaminofluorene bound to protein in the liver, (ii) the formation of fluorenyl derivatives bound to total protein, ribosomal RNA, and DNA in the liver, and (iii) the toxicity of the carcinogen. These data provide evidence that the highly reactive ester 2-acetylaminofluorene-N-sulfate, previously suggested as an ultimate reactive and carcinogenic metabolite of N-hydroxy-2-acetylaminofluorene, is formed in the rat liver in vivo.
