A physiologically-based algorithm for predicting internal dose of inhaled toluene: Applications for high dose to low dose and rodent to human extrapolations

Sastry S. Isukapalli, Karine Price, Panos G. Georgopoulos, Kannan Krishnan

Research output: Chapter in Book/Report/Conference proceedingConference contribution

1 Scopus citations

Abstract

The objective of this study was to develop a physiologically-based algorithm for predicting the steady-state internal dose of inhaled volatile organic chemicals (VOCs) in rats and humans at various exposure concentrations, using toluene as the model chemical. This was accomplished by the systematic development of the solution to the set of equations constituting pulmonary uptake and metabolic clearance, including the consideration of dose-dependent change in the free concentration of chemical at the metabolizing site (liver). The resulting algorithm, based on critical determinants of the internal dose during chronic exposure to VOCs (i.e., alveolar ventilation rate, blood flow rate to liver, blood: air partition coefficient, maximal velocity of metabolism, Michaelis affinity constant and free concentration of chemical at the metabolizing site) provides predictions of dose metrics (i.e., arterial blood concentration and rate of amount metabolized) identical to those of the full-fledged PBPK models. The algorithm was then applied to conduct high dose to low dose and rodent to human extrapolations of internal dose of inhaled toluene. The physiologically-based algorithm, developed in this study, for the first time facilitates the direct computation of steady-state internal dose for a variety of exposure concentrations of toluene, by consistently accounting for the non-linear processes.

Original languageEnglish (US)
Title of host publicationProceedings of the 2008 Spring Simulation Multiconference, SpringSim'08
Pages583-588
Number of pages6
DOIs
StatePublished - 2008
Event2008 Spring Simulation Multiconference, SpringSim'08 - Ottawa, ON, Canada
Duration: Apr 14 2008Apr 17 2008

Publication series

NameProceedings of the 2008 Spring Simulation Multiconference, SpringSim'08

Other

Other2008 Spring Simulation Multiconference, SpringSim'08
Country/TerritoryCanada
CityOttawa, ON
Period4/14/084/17/08

ASJC Scopus subject areas

  • Computational Theory and Mathematics
  • Computer Networks and Communications
  • Software

Keywords

  • Inhalation
  • PBPK modeling
  • Pharmacometries
  • Toluene

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