Toxicokinetics of deltamethrin: Dosage dependency, vehicle effects, and low-dose age-equivalent dosimetry in rats

Abstract

There is increasing concern that infants and children may be at increased risk of neurological effects of pyrethroids, the most widely used class of insecticide. The objectives of this investigation were to (1) characterize the dose-dependent toxicokinetics (TK) of deltamethrin (DLM) for exposures ranging from environmentally relevant to acutely toxic; (2) determine the influence of an aqueous versus oil vehicle on oral absorption and bioavailability; and (3) determine whether DLM exhibits low-dose, age-equivalent internal dosimetry. Serial arterial plasma samples were obtained for 72h from adult, male Sprague Dawley rats given 0.05-5.0mg DLM/kg as an oral bolus in corn oil (CO). DLM exhibited linear, absorption rate-limited TK. Increases in maximumplasma concentration (Cmax) and AUC∞ were directly proportional to the dose. Oral bioavailability was quite limited. The vehicle and its volume had modest effect on the rate and extent of systemic absorption in adult rats. Postnatal day (PND) 15, 21, and 90 (adult) rats received 0.10, 0.25, or 0.50mg DLM/kg orally in CO and were sacrificed periodically for plasma, brain, and liver collection. Age-dependent differences between PND 15 and 90 plasma Cmax and AUC24 8 values progressively diminished as the dose decreased, but there was a lack of low dose age equivalence in these brain and liver dosimeters. Other maturational factors may account for the lack of the low-dose age equivalence in brain and liver. This investigation provides support for the premise that the relatively lowmetabolic capacity of immature subjectsmay be adequate to effectively eliminate trace amounts of DLM and other pyrethroids fromthe plasma.