Physiologically based pharmacokinetic modeling for 1-bromopropane in rat using gas uptake inhalation studies

Details

• Personal Author:
  Garner E ; Liang S ; Yin L ; Yu X
• Description:
  1-Bromopropane (1-BP) was introduced into the workplace as an ozone depleting alternative solvent (ODA). The potential for human exposure to 1-BP and the reports of adverse effects associated with occupational exposure to high levels of 1-BP have increased the need to understand the mechanism of these adverse effects in animal models as a means of understanding human risk in workers. The objectives of the current studies were to develop a physiologically based pharmacokinetic (PBPK) model for 1-BP. The development of the PBPK model for the 1-BP was accomplished by simulating the closed chamber concentration data from the gas-uptake experiments in F-344 rats. We tested different metabolic hypotheses, including two-pathway hypothesis in which metabolism responsibilities are shared by the p450 CYP2E1 and glutathione transferase pathways (GST). The results show that two metabolic pathways hypotheses generated the best predicted values for the actual chamber concentrations. Furthermore, the above model was tested by simulating the gas-uptake data of rats with pre-treated with 1-aminobenzotrizole (ABT), a potent general P450 suicide inhibitor, or DL-buthionine (S,R)-sulfoximine (BSO), an inhibitor of glutathione (GSH) synthesis, prior to exposure to 800 ppm 1-BP. The comparative investigation on metabolic pathway of 1-BP through the PBPK modeling in both gender provided critical information in understanding the role of p450 and GST pathways and eventually help to quantitatively extrapolate these animal studies to human. [Description provided by NIOSH]
• Subjects:
  Occupational Health Safety Solvents Toxicology
• Keywords:
  Brominated Propanes Chemical Kinetics Pharmacodynamics
• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; Georgia ; New Mexico ; OSHA Region 4 ; OSHA Region 6 ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  144
• Issue:
  1
• NIOSHTIC Number:
  nn:20046033
• Citation:
  Toxicologist 2015 Mar; 144(1):161
• CAS Registry Number:
  1-Bromopropane (CAS RN 106-94-5)
• Federal Fiscal Year:
  2015
• Performing Organization:
  University of Georgia, Athens
• Peer Reviewed:
  False
• Start Date:
  20130901
• Source Full Name:
  The Toxicologist. Society of Toxicology 54th Annual Meeting and ToxExpo, March 22-26, 2015, San Diego, California
• End Date:
  20160831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:4e75ad245a18481a3c9e9a7a9dbf3d45c54450dd5276ca8f1b2994696372521ed162b96c27e972c25edb68e8e4b8e8d5ebc12cec59561f23eab32a0dda79d949
• Download URL:
  https://stacks.cdc.gov/view/cdc/201222/cdc_201222_DS1.pdf
• File Type:
  [PDF - 1.07 MB ]