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DEVELOPMENT OF A PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL FOR DELTAMETHRIN IN THE ADULT MALE SPRAGUE-DAWLEY RAT
MIRFAZAELIAN, A., K. KIM, S. S. ANAND, H. J. KIM, R. TORNERO-VELEZ, J. V. BRUCKNER, AND J. W. FISHER. DEVELOPMENT OF A PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL FOR DELTAMETHRIN IN THE ADULT MALE SPRAGUE-DAWLEY RAT. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 93(2):432-442, (2006).
The Food Quality Protection Act (FQPA) of 1996 requires the USEPA to consider the cumulative effect to human health that can result from exposure to pesticides and other substances that have a common mechanism of toxicity. Through a coordinated multi-disciplinary effort which includes several laboratories at EPA's Office of Research and Development (ORD) and scientists from EPA's Office of Pesticide Programs (OPP), this project will elaborate the general principles for considering cumulative exposure and for developming cumulative dosimetry models. As there will invariably be gaps in exposure information and in pharmacokinetic data, this project will have greatest impact in how best to leverage the value of existing data and how best to coordinate efforts in NERL and NHEERL. The development of cumulative PBPK models of pyrethroids for humans will allow the Agency to conduct a cumulative assessment with state-of-art models.
Deltamethrin (DLT) is a Type II pyrethroid insecticide widely used in agriculture and public health. DLT is a potent neurotoxin that is primarily cleared from the body by metabolism. To better understand the dosimetry of DLT in the central nervous system, a physiologically based pharmacokinetic (PBPK) model for DLT was constructed for the adult, male Sprague-Dawley (SD) rat that employed both flow-limited (brain, GI tract, liver and rapid-perfused tissues) and diffusion limited (fat, blood/plasma and slowly-perfused tissues) rate equations.