Relationship Between the Dose Administered, Target Tissue Dose, and Toxicity Level After Acute Oral Exposure to Bifenthrin and Tefluthrin in Young Adult Rats

Abstract

Most pyrethroid insecticides (PYRs) share a similar primary target site in mammals. However, the potency estimates of the lethal and sublethal effects of these compounds differ up to 103-fold. The aim of this study was to evaluate the relationship between the dose administered, the target tissue dose, and the effect of 2 highly toxic PYRs, tefluthrin (TEF; 0.1–9 mg/kg) and bifenthrin (BIF; 0.5–12 mg/kg), by using the oral route, a corn oil vehicle (1 ml/kg) and subcutaneous temperature (Tsc) monitoring assays in adult rats. The Tsc was determined at 30-min intervals for 5 h (TEF) or 4.5 h (BIF) after dosing. Rats were sacrificed at 6 h after dosing, and BIF and TEF concentrations were determined in blood (Bd), liver (Lv), and cerebellum (Cb) by using a GC-ECD system. The minimal effective dose of BIF (3 mg/kg) affecting Tsc was similar to that found in prior studies using other testing paradigms. Regarding TEF, a very steep relationship between the dose administered and toxicity was observed, with a near-threshold to low-effective range for Tsc at 0.1–6 mg/kg, and a near lethal syndrome at ≥ 7.5 mg/kg. At 6–7.5 mg/kg TEF, the Cb/Bd and Cb/Lv concentration ratios were both > 1. Conversely, for BIF, the Cb concentration was barely over the Bd concentration and the Cb/Lv concentration ratio remained < 1. Our results and previous findings call for more comprehensive consideration to establish the relevance of the distribution into target tissues and the tissue dosimetry for health risks through the exposure to PYRs in humans.

Relationship between exposure, body burden and target tissue concentration after oral administration of a low-dose mixture of pyrethroid insecticides in young adult rats

“…We sought to combine low doses of the individual compounds well below threshold levels for PYR-specific signs of neurotoxicity such as salivation, whole body tremors and choreoathetosis based on previous neurobehavioral studies in adult rats (Mosquera-Ortega et al, 2013;Pato et al, 2011;Scollon et al, 2011;Wolansky et al, 2009Wolansky et al, , 2007aWolansky et al, , 2007bWolansky et al, , 2006. Moreover, we performed preliminary single-compound dose-response assays using identical dosing solution preparation protocol, vehicle and dosing procedures, and transponder-based technology to estimate low-effective benchmark dose (BMD) levels (i.e., BMD30s) for body temperature monitoring by BMDS modeling (Pato et al, 2011;Mosquera Ortega et al, in preparation).…”