Differential metabolism of fenvalerate and granuloma formation. I. Identification of a cholesterol ester derived from a specific chiral isomer of fenvalerate.
On a single po administration of the four chiral isomers of fenvalerate ([RS]-alpha-cyano-3-phenoxybenzyl [RS]-2-(4-cholorophenyl)isovalerate) to rats and mice at 2.5 mg/kg, the [2R, alpha S]-isomer showed relatively higher residues in all analyzed tissues as compared with the other three isomers. Similarly, this isomer showed higher tissue concentrations than other isomers when mice were fed a diet containing 500 ppm of the [2S, alpha S]-, and [2R, alpha R]-isomers for 2 weeks. The [2R, alpha S]-isomer produced a lipophilic metabolite in all the examined tissues on the basis of thin-layer chromatography analysis, but not for the other isomers. The amounts of lipophilic metabolite differed among tissues, being higher in adrenal, liver, and mesenteric lymph nodes following feeding to mice at 500 ppm of the [2R, alpha S]-isomer for 2 weeks. However, the amount did not increase proportionally with time and apparently reached a plateau within a rather short time. This metabolite was identified as cholesteryl [2R]-2-(4-chlorophenyl)isovalerate ([2R]-CPIA-cholesterol ester) on the basis of spectroanalysis and chromatographic behavior after purification on silica gel, Florisil, thin-layer, and high-pressure liquid chromatography. The presence of the same metabolite also was indicated in rat tissues. The CPIA-cholesterol ester was rapidly formed and found in all the analyzed tissues of mice 1 hr after a single po administration of the [2R, alpha S]-isomer.
D000818:Animals; D002250:Carbon Radioisotopes; D002788:Cholesterol Esters / Q000378:metabolism*; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D006099:Granuloma / Q000139:chemically induced* / Q000503:physiopathology; D007306:Insecticides / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009570:Nitriles; D011722:Pyrethrins / Q000378:metabolism* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D002788:Cholesterol Esters; D007306:Insecticides; D009570:Nitriles; D011722:Pyrethrins; C017690:fenvalerate