PMID: 8451462Feb 1, 1993Paper

Pharmacokinetic modeling of trichloroethylene and trichloroacetic acid in humans

Risk Analysis : an Official Publication of the Society for Risk Analysis
B C Allen, J W Fisher

Abstract

The development and application of appropriate physiologically based pharmacokinetic (PBPK) models of chemical contaminants will provide a rational basis for risk assessment extrapolation. Trichloroethylene (TCE) is a widespread contaminant found in soil, groundwater, and the atmosphere. Exposures to TCE and its metabolites have been found to be carcinogenic in rodents. In this study, a PBPK model for TCE and its major metabolite, trichloroacetic acid (TCA), is developed for humans. The model parameters, estimated from the relevant published literature on human exposures to TCE and its metabolites, are described. Key parameters describing the metabolism of TCE and the kinetics of TCA were estimated by optimization. The optimization was accomplished by simultaneously matching model predictions to observations of TCE concentrations in blood and exhaled breath, TCA plasma concentrations, and urinary TCA excretion from five published studies. The optimized human PBPK model provides an excellent description of TCE and TCA kinetics. The predictions were especially good for TCA plasma concentrations following repeated TCE inhalation, an exposure scenario similar to that occurring in the workplace. The human PBPK model can be used to e...Continue Reading

References

Jan 15, 1979·International Archives of Occupational and Environmental Health·A C MonsterW C Duba
Jan 15, 1979·International Archives of Occupational and Environmental Health·A C MonsterH Steenweg
Feb 1, 1977·British Journal of Industrial Medicine·J G FernándezJ R Caperos
Dec 15, 1976·International Archives of Occupational and Environmental Health·A C MonsterW C Duba
Dec 1, 1976·Scandinavian Journal of Work, Environment & Health·I Astrand, P Ovrum
Mar 15, 1989·Toxicology and Applied Pharmacology·M L GargasM E Andersen
Dec 1, 1988·Regulatory Toxicology and Pharmacology : RTP·K T Bogen
Jan 1, 1985·Archives of Toxicology. Supplement. = Archiv Für Toxikologie. Supplement·C R Elcombe
Jul 1, 1985·Toxicology and Applied Pharmacology·T Green, M S Prout
Jul 1, 1985·Toxicology and Applied Pharmacology·M S ProutT Green
Jan 1, 1974·Archives of Toxicology·G MüllerD Henschler
Jul 6, 1971·Annals of the New York Academy of Sciences·E M Sellers, J Koch-Weser
Jan 1, 1970·Archives of Environmental Health·R D StewartD S Erley
Aug 1, 1984·Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology·R J NolanJ H Saunders
Dec 1, 1984·Biochemical Pharmacology·A A Elfarra, M W Anders
Jan 1, 1960·British Journal of Industrial Medicine·B SOUCEK, D VLACHOVA

❮ Previous
Next ❯

Citations

Sep 13, 2006·Environmental Health Perspectives·Weihsueh A ChiuMarina V Evans
Aug 29, 1998·Environmental Health Perspectives·J D PleilA B Lindstrom
Feb 1, 1993·Risk Analysis : an Official Publication of the Society for Risk Analysis·J W Fisher, B C Allen
Apr 1, 2008·Pharmacology & Therapeutics·John C Lipscomb, Torka S Poet
Dec 4, 2003·Risk Analysis : an Official Publication of the Society for Risk Analysis·John C LipscombGregory L Kedderis
Jul 13, 2006·Risk Analysis : an Official Publication of the Society for Risk Analysis·Weihsueh A Chiu, Paul White
Jan 15, 2005·Regulatory Toxicology and Pharmacology : RTP·T A Lewandowski, L R Rhomberg
Nov 18, 2004·Regulatory Toxicology and Pharmacology : RTP·Michael Pelekis, Kannan Krishnan
Aug 8, 2006·Regulatory Toxicology and Pharmacology : RTP·C Eric HackHarvey J Clewell
Dec 16, 1998·Toxicology and Applied Pharmacology·J C LipscombJ Z Byczkowski
Jul 1, 1997·Toxicology and Industrial Health·R P BrownR P Beliles
May 12, 2000·Environmental Health Perspectives·L H LashJ C Parker
Jan 24, 2003·Toxicology and Industrial Health·G L Kedderis, J C Lipscomb
Oct 23, 2019·Expert Opinion on Pharmacotherapy·Oliviero BruniRaffaele Ferri
Feb 1, 1997·Regulatory Toxicology and Pharmacology : RTP·K T Bogen, L S Gold

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.