title: Tissue time course and bioavailability of the pyrethroid insecticide bifenthrin in the Long-Evans rat.
abstract: 1. Pyrethroids are neurotoxic and parent pyrethroid appears to be toxic entity. This study evaluated the oral disposition and bioavailability of bifenthrin in the adult male Long-Evans rat. 2. In the disposition study, rats were administered bifenthrin (0.3 or 3 mg/kg) by oral gavage and serially sacrificed (0.25 h to 21 days). Blood, liver, brain and adipose tissue were removed. In the bioavailability study, blood was collected serially from jugular vein cannulated rats (0.25 to 24 h) following oral (0.3 or 3 mg/kg) or intravenous (0.3 mg/kg) administration of bifenthrin. Tissues were extracted and analyzed for bifenthrin by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). 3. Bifenthrin concentration in blood and liver peaked 1-2-h postoral administration and were approximately 90 ng/ml (or g) and 1000 ng/ml (or g) for both tissues at 0.3 and 3 mg/kg, respectively. Bifenthrin was rapidly cleared from both blood and liver. Brain concentrations peaked at 4-6 h and were lower than in blood at both doses (12 and 143 ng/g). Bifenthrin in adipose tissue peaked at the collected time points of 8 (157 ng/g) and 24 (1145 ng/g) h for the 0.3 and 3 mg/kg doses, respectively and was retained 21 days postoral administration. Following intravenous administration, the blood bifenthrin concentration decreased bi-exponentially, with a distribution half-life of 0.2 h and an elimination half-life of 8 h. Bifenthrin bioavailability was approximately 30%. These disposition and kinetic bifenthrin data may decrease uncertainties in the risk assessment for this pyrethroid insecticide.
authors.affiliation: a U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Research Triangle Park , NC , USA .
authors.forename: Michael F
authors.initials: MF
authors.lastname: Hughes
authors.affiliation: a U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Research Triangle Park , NC , USA .
authors.forename: David G
authors.initials: DG
authors.lastname: Ross
authors.affiliation: a U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Research Triangle Park , NC , USA .
authors.forename: Brenda C
authors.initials: BC
authors.lastname: Edwards
authors.affiliation: b National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park , NC , USA , and.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: DeVito
authors.affiliation: c U.S. Environmental Protection Agency, Office of Research and Development, National Exposure Research Laboratory, Research Triangle Park , NC , USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Starr
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects; D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D001769:Blood / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D007306:Insecticides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008099:Liver / Q000187:drug effects; D008297:Male; D011722:Pyrethrins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D020318:Rats, Long-Evans; D018570:Risk Assessment; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D007306:Insecticides; D011722:Pyrethrins; C099952:bifenthrin
keywords: Bifenthrin; disposition; pharmacokinetics; pyrethroids