title: Physiologically based pharmacokinetic modeling for 1-bromopropane in F344 rats using gas uptake inhalation experiments.
abstract: 1-Bromopropane (1-BP) was introduced into the workplace as an alternative to ozone-depleting solvents and increasingly used in manufacturing industry. The potential exposure to 1-BP and the current reports of adverse effects associated with occupational exposure to high levels of 1-BP have increased the need to understand the mechanism of 1-BP toxicity in animal models as a mean of understanding risk in workers. Physiologically based pharmacokinetic (PBPK) model for 1-BP has been developed to examine 2 metabolic pathway assumptions for gas-uptake inhalation study. Based on previous gas-uptake experiments in the Fischer 344 rat, the PBPK model was developed by simulating the 1-BP concentration in a closed chamber. In the model, we tested the hypothesis that metabolism responsibilities were shared by the p450 CYP2E1 and glutathione (GSH) conjugation. The results showed that 2 metabolic pathways adequately simulated 1-BP closed chamber concentration. Furthermore, the above model was tested by simulating the gas-uptake data of the female rats pretreated with 1-aminobenzotrizole, a general P450 suicide inhibitor, or d,l-buthionine (S,R)-sulfoximine, an inhibitor of GSH synthesis, prior to exposure to 800 ppm 1-BP. The comparative investigation on the metabolic pathway of 1-BP through the PBPK modeling in both sexes provides critical information for understanding the role of p450 and GSH in the metabolism of 1-BP and eventually helps to quantitatively extrapolate current animal studies to human.
authors: *Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108 and Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, Georgia 30602.
authors: C Edwin
authors: CE
authors: Garner
authors: *Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108 and Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, Georgia 30602.
authors: Shenxuan
authors: S
authors: Liang
authors: *Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108 and Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, Georgia 30602.
authors: Lei
authors: L
authors: Yin
authors: *Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108 and Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, Georgia 30602 yuxz@uga.edu.
authors: Xiaozhong
authors: X
authors: Yu
mesh_terms: D000818:Animals; D005260:Female; D005740:Gases; D006842:Hydrocarbons, Brominated / Q000008:administration & dosage / Q000493:pharmacokinetics; D019570:Inhalation Exposure; D008297:Male; D008954:Models, Biological; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D005740:Gases; D006842:Hydrocarbons, Brominated; C118559:1-bromopropane
keywords: 1-bromopropane; F344 rats; gas uptake inhalation; physiologically based pharmacokinetic modeling
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