Eine Plattform für die Wissenschaft: Bauingenieurwesen, Architektur und Urbanistik
Eine Plattform für die Wissenschaft: Bauingenieurwesen, Architektur und Urbanistik
A physiologically based pharmacokinetic model for endosulfan in the male Sprague‐Dawley rats
10.1002/tox.20209.abs
Endosulfan, an organochlorine (OC) insecticide belonging to the cyclodiene group, is one of the most commonly used pesticides to control pests in vegetables, cotton, and fruits. To date, no physiologically based pharmacokinetic (PBPK) model has been located for endosulfan in animal species and humans. The estimation by a mathematical model is essential since information on humans can scarcely be obtained experimentally. The PBPK model was constructed based on the pharmacokinetic data of our experiment following single oral administration of 14C‐Endosulfan to male Sprague‐Dawley rats. The model was parameterized by using reference physiological parameter values and partition coefficients that were determined in the experiment and optimized by manual adjustment until the best visual fit of the simulations with the experimental data were observed. The model was verified by simulating the disposition of 14C‐Endosulfan in vivo after single and multiple oral dosages and comparing simulated results with experimental results. The model was further verified by using experimental data retrieved from the literature. The present model could reasonably predict target tissue dosimetries in rats. Simulation with three‐time repeated administration of 14C‐Endosulfan and experimental data retrieved from the literature by the constructed model fitted fairly well with the experimental results; thus suggesting that the newly developed PBPK model was developed. Sensitivity analyses were used to determine those input parameters with the greatest influence on endosulfan tissue concentrations. © 2006 Wiley Periodicals, Inc. Environ Toxicol 21: 464–478, 2006.
A physiologically based pharmacokinetic model for endosulfan in the male Sprague‐Dawley rats
10.1002/tox.20209.abs
Endosulfan, an organochlorine (OC) insecticide belonging to the cyclodiene group, is one of the most commonly used pesticides to control pests in vegetables, cotton, and fruits. To date, no physiologically based pharmacokinetic (PBPK) model has been located for endosulfan in animal species and humans. The estimation by a mathematical model is essential since information on humans can scarcely be obtained experimentally. The PBPK model was constructed based on the pharmacokinetic data of our experiment following single oral administration of 14C‐Endosulfan to male Sprague‐Dawley rats. The model was parameterized by using reference physiological parameter values and partition coefficients that were determined in the experiment and optimized by manual adjustment until the best visual fit of the simulations with the experimental data were observed. The model was verified by simulating the disposition of 14C‐Endosulfan in vivo after single and multiple oral dosages and comparing simulated results with experimental results. The model was further verified by using experimental data retrieved from the literature. The present model could reasonably predict target tissue dosimetries in rats. Simulation with three‐time repeated administration of 14C‐Endosulfan and experimental data retrieved from the literature by the constructed model fitted fairly well with the experimental results; thus suggesting that the newly developed PBPK model was developed. Sensitivity analyses were used to determine those input parameters with the greatest influence on endosulfan tissue concentrations. © 2006 Wiley Periodicals, Inc. Environ Toxicol 21: 464–478, 2006.
A physiologically based pharmacokinetic model for endosulfan in the male Sprague‐Dawley rats
Chan, Melissa P. L. (Autor:in) / Morisawa, Shinsuke (Autor:in) / Nakayama, Aki (Autor:in) / Kawamoto, Yuko (Autor:in) / Sugimoto, Miki (Autor:in) / Yoneda, Minoru (Autor:in)
Environmental Toxicology ; 21 ; 464-478
01.10.2006
15 pages
Aufsatz (Zeitschrift)
Elektronische Ressource
Englisch
Development of Osteoporosis in Ovariectomized Sprague-Dawley Rats
| British Library Conference Proceedings | 1988