Dose-Response Relationship of an Environmental Mixture of Pyrethroids Following an Acute Oral Administration in the Rat.

M.F. HUGHES; D.G. ROSS, J.M. STARR, E.J. SCOLLON; M.J. WOLANSKY; K.M. CROFTON; M.J. DEVITO

San Antonio, Texas

Congreso; Annual Meeting - Society of Toxicology; 2013

Society of Toxicology (USA)

Human exposure to multiple pyrethroid insecticides may occur because of their wide use on crops and for residential pest control. To address the potential risk from exposure to pyrethroids it is important to understand their toxicity and disposition in target organs such as the brain and surrogates such as the blood. The objective of this study was to compare motor activity with pyrethroid concentrations in blood and brain of rats after oral administration of a pyrethroid mixture. Male Long-Evans rats were dosed with a mixture of cyfluthrin (12.9% of dose), cypermethrin (28.8%), deltamethrin (3.4%), esfenvalerate (2.7%) and cis- (20.9%) and trans-permethrin (31.3%) in corn oil at one of seven dose levels (maximum total pyrethroid dose ? 27.4 mg/kg). From 2 to 3 h post-administration, gross motor activity was assessed. At 3.5 h, blood and brain were collected. These tissues were extracted and analyzed for parent pyrethroid using HPLC-tandem mass spectrometry. There was a linear dose-related increase in concentrations of the pyrethroids in blood and brain. Cypermethrin (56-62%) and cis-permethrin (57-70%) were the predominant pyrethroids detected in blood and brain, respectively, at all dose levels. The pyrethroids with the lowest percentage in tissue were trans-permethrin (0.6-2.7%) and β-cyfluthrin (0.4-1.2%) in blood, and deltamethrin (1.1-3.5%) and esfenvalerate (2.4-4.7%) in brain. The approximate EC30 for decrease in motor activity was 300 ng/ml and 200 ng/g of total pyrethroid in blood and brain, respectively. More research is needed to understand the dosimetry of pyrethroids in blood and brain of rat and how this relates to neurotoxic effect.