title: The pharmacokinetic properties of bifenthrin in the rat following multiple routes of exposure.
abstract: BACKGROUND
  Pyrethroids generally have relatively low oral toxicity but variable inhalation toxicity. The pharmacokinetics of bifenthrin in the rat after oral, inhalation and intravenous administration is described. Pyrethroid acute toxicity via oral and inhalation routes is also presented.
  
  
  RESULTS
  Groups of male rats were dosed by oral gavage at 3.1 mg kg(-1) in 1 mL kg(-1) of corn oil (the critical, acute, oral benchmark dose lower limit, BMDL) and at an equivalent dose by inhalation (0.018 mg L(-1)) for 4 h.  At 2, 4, 6, 8 and 12 h after dosing initiation, blood plasma and brain bifenthrin concentrations were measured. The maximum concentrations of bifenthrin in plasma were 361 ng mL(-1) or 0.853 μM (oral) and 232 ng mL(-1) or 0.548 μM (inhalation), and in brain they were 83 and 73 ng g(-1). The area under the concentration versus time curve (AUC) values were 1969 h ng mL(-1) (plasma) and 763 h ng mL(-1) (brain) following oral gavage dosing, and 1584 h ng mL(-1) (plasma) and 619 h ng mL(-1) (brain) after inhalation. Intravenous dosing resulted in apparent terminal half-life (t1/2 ) values of 13.4 h (plasma) and 11.1 h (brain) and in AUC0-∞ values of 454 and 1566 h ng mL(-1) for plasma and brain. Clearance from plasma was 37 mL min(-1) kg(-1).
  
  
  CONCLUSIONS
  Peak plasma nd brain concentrations were generally a little higher after oral dosing (by ca 14%). Inhalation administration of bifenthrin did not cause increases in exposure in plasma or brain by avoiding first-pass effects in the liver. The elimination t1/2 was comparable with other pyrethroids and indicated little bioaccumulation potential. These pharmokinetics data allow risks following inhalation exposure to be modeled using oral toxicity data.
authors.affiliation: FMC Corporation, Agricultural Solutions, Ewing, NJ, USA.
authors.forename: Derek
authors.initials: D
authors.lastname: Gammon
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Liu
authors.forename: Appavu
authors.initials: A
authors.lastname: Chandrasekaran
authors.forename: Shaaban
authors.initials: S
authors.lastname: ElNaggar
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000378:metabolism; D006207:Half-Life; D019570:Inhalation Exposure; D007306:Insecticides / Q000378:metabolism; D008297:Male; D011722:Pyrethrins / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics*; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D007306:Insecticides; D011722:Pyrethrins; C099952:bifenthrin
keywords: bifenthrin; intravenous; oral inhalation exposure; pharmacokinetics; pyrethroids; toxicity