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Main Title Construction of a Physiologically Based Pharmacokinetic/Pharmacodynamic (PBPK/PD) Model for Carbofuran Using the Exposure Related Dose Estimating Model (ERDEM).
Author Zhang, X. ; Tsang, A. M. ; Okino, M. S. ; Power, F. W. ; Knaak, J. B. ;
CORP Author Environmental Protection Agency, Research Triangle Park, NC. National Exposure Research Lab.
Publisher Oct 2006
Year Published 2006
Report Number EPA/600/R-06/135; GS-35F-4357D; NERL-RTP-HEASD-06-155;
Stock Number PB2007-100680
Additional Subjects Carbofuran ; Health risks ; Human exposure ; Pesticides ; Literature review ; Risk assessment ; Uncertainty analysis ; Monte Carlo method ; Physiologically Based Pharmacokinetic/Pharmacodynamic model ; Exposure Related Dose Estimating Model ; ADME(Absorption distribution metabolism elimination)
Library Call Number Additional Info Location Last
NTIS  PB2007-100680 Some EPA libraries have a fiche copy filed under the call number shown. 07/26/2022
Collation 234p
Carbofuran, known as 2, 3-dihydro-2, 2-dimethyl-7-benzofuranyl- N-methylcarbamate, is a broad spectrum N-methyl carbamate pesticide. Carbofuran and its metabolite, 3-hydroxycarbofuran, exert their toxicity by reversibly inhibiting acetylcholinesterase (AChE). Carbofuran is widely used in agriculture for pest control. Agricultural workers and the general population may beexposed to it by dermal contact, inhalation, or ingestion as a result ofits application or by food intake. To better characterize the human health risk caused by carbofuran exposure, a physiologically-based pharmacokinetic/ pharmacodynamic (PBPK/PD) model was developed in the Exposure Related Dose Estimating Model (ERDEM) system in order to facilitate an understanding of carbofuran's absorption, distribution, metabolism, elimination (ADME) processes, and AChE inhibition effects for the rat. To obtain relevant experimental measurements and the estimates of physiological, biochemical, and physicochemical parameters for the model, literature reviews were conducted. The focus was placed on oral exposure and modeling carbofuran metabolism in the liver to 16 known metabolites, the enterohepatic circulation of glucuronide conjugates, and the excretion to urine and feces. Cholinesterase inhibition by carbofuran and 3-hydroxycarbofuran is modeled in the bloodand brain.