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Dose-response relationship of an environmental mixture of pyrethroids following an acute oral administration in the rat
Citation:
Hughes, M., D. Ross, J. Starr, E. Scollon, M. Wolansky, K. Crofton, AND M. DeVito. Dose-response relationship of an environmental mixture of pyrethroids following an acute oral administration in the rat. Presented at Society of Toxicology, March 10 - 14, 2013.
Impact/Purpose:
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 ED30 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. (This abstract does not represent U.S. EPA or NIEHS/NTP policy).
Description:
Dose-response relationship of an environmental mixture of pyrethroids following an acute oral administration in the rat M.F. Hughes1, D.G. Ross1, J.M. Starr1, E.J. Scollon1,2, M.J. Wolansky1,3, K.M. Crofton1, M.J. DeVito1,4 1U.S. EPA, ORD, Research Triangle Park, NC, 2U.S. EPA, OPP, Washington, DC, 3 Universidad de Buenos Aires, Buenos Aires, Argentina, 4NlEHS, NTP, Research Triangle Park, NC 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 ED30 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. (This abstract does not represent U.S. EPA or NIEHS/NTP policy).