Relationship between administered dose, body burden and thermoregulatory response after acute oral exposure to multiple pyrethroid insecticides in rats

MOSQUERA ORTEGA, ME; PATO, A.M; ROMERO, D.M; SOSA- HOLT, C.S; ALVAREZ, G.; RIDOLFI, A.; VILLAAMIL LEPORI, E.; WOLANSKY, M.J.

San Francisco

Congreso; Society for Risk Analysis Annual Meeting; 2012

Society for Risk Analysis

Pyrethroids (PYRs) are synthetic insecticides increasingly used in agricultural and household pest control. Little is known on how the toxicity of highly effective bolus doses of single compounds compares to more realistic scenarios of low-level exposure to PYR mixtures. In this study, we examined a quaternary mixture of two noncyano (tefluthrin, TEF; bifenthrin, BIF) and two cyano (α-cypermethrin, α-CPM; deltamethrin, DTM) PYRs in young adult rats. These compounds are mostly composed of PYR isomers ranking top ten in acute lethality in rats. Concurrently, we administered near-threshold levels of the four PYRs dissolved in corn oil by oral route. Six hours later blood was collected and the liver and cerebellum were dissected out to determine PYR concentrations in these tissues using Gas Chromatography with Electron Capture Detector (GC-ECD). The mixture caused mild- to-moderate changes in non-locomotor behaviors and subcutaneous body temperature (up to +1.2?1.5 °C in- crease at 2?4 h after dosing, respectively, compared to pre-dosing records). The most toxic PYRs BIF and TEF reached higher concentrations in the cerebellum than the cyano-compounds α-CPM and DTM. In addition, PYR concentrations in the cerebellum were correlated to single compound proportions in the dosing solution and changes in body temperature. Our results suggest that aggregate exposures resulting in a target tissue burden of ∼10−1 nmoles PYR/g may be toxicologically relevant, expanding the evidence on exposure-dose-effect re- lationships for PYRs, and serving to design convenient pharmacokinetic models for environmentally relevant exposures to PYR mixtures.