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 3.1mgkg-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 (0.018mgL-1) for 4h. At 2, 4, 6, 8 and 12h after dosing initiation, blood plasma and brain bifenthrin concentrations were measured. The maximum concentrations of bifenthrin in plasma were 361ng mL-1 or 0.853 μM (oral) and 232ng mL-1 or 0.548 μM (inhalation), and in brain they were 83 and 73ngg-1. The area under the concentration versus time curve (AUC) values were 1969hng mL-1 (plasma) and 763hng mL-1 (brain) following oral gavage dosing, and 1584hng mL-1 (plasma) and 619hng mL-1 (brain) after inhalation. Intravenous dosing resulted in apparent terminal half-life (t1/2) values of 13.4h (plasma) and 11.1h (brain) and in AUC0-∞ values of 454 and 1566hng mL-1 for plasma and brain. Clearance from plasma was 37 mL min-1kg-1. CONCLUSION: Peak plasma and 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.