2000
DOI: 10.1006/taap.2000.8991
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Validation of a Physiological Modeling Framework for Simulating the Toxicokinetics of Chemicals in Mixtures

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Cited by 71 publications
(54 citation statements)
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“…The validation of the PBPK modeling approach outlined above has been accomplished in a limited number of studies using mixtures of VOCs (12)(13)(14)(15)(16). The overall approach in these studies involved the characterization of the kinetics of chemicals present individually or in binary mixtures for identifying the occurrence and magnitude of binary interactions (e.g., competitive inhibition) as well as for determining the quantitative nature of the interaction mechanism (e.g., Ki).…”
Section: D-a D-b D-c) By Doing This the Modulatory Effect Of D Onmentioning
confidence: 99%
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“…The validation of the PBPK modeling approach outlined above has been accomplished in a limited number of studies using mixtures of VOCs (12)(13)(14)(15)(16). The overall approach in these studies involved the characterization of the kinetics of chemicals present individually or in binary mixtures for identifying the occurrence and magnitude of binary interactions (e.g., competitive inhibition) as well as for determining the quantitative nature of the interaction mechanism (e.g., Ki).…”
Section: D-a D-b D-c) By Doing This the Modulatory Effect Of D Onmentioning
confidence: 99%
“…To obtain the simulations presented in Figure 7, a) the inhibition terms and constants for the two binary interactions EBZ-TOL and EBZ-XYL and b) the PBPK model for EBZ were added to the existing TOL-XYL model (13,14). For simulating the kinetics of EBZ, TOL, and XYL in the presence of other chemicals such as DCM and BEN, one had simply to estimate the binarylevel interaction constants (Table 1) for the additional pairs (DCM-BEN, DCM-TOL, DCM-XYL, DCM-EBZ, BEN-TOL, BEN-XYL, and BEN-EBZ) and obtain the PBPK models for DCM and BEN for incorporation within the existing TOL-EBZ-XYL PBPK model (14)(15)(16). The resulting model simulates the kinetics of TOL, EBZ, XYL, DCM, or BEN in mixtures of varying complexities and compositions, solely on the basis of interconnected information on binary-level interactions (Figures 8, 9).…”
Section: D-a D-b D-c) By Doing This the Modulatory Effect Of D Onmentioning
confidence: 99%
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“…Several models have been developed that simulate the kinetics of inhaled ethylbenzene in animals and humans (Dennison et al 2003;Haddad et al 1999Haddad et al , 2000Haddad et al , 2001Jang et al 2001;Nong et al 2007;Tardif et al 1997). The Dennison et al (2003) and Tardif et al (1997) inhalation models have been incorporated into models of gasoline component mixture models (Dennison et al 2004(Dennison et al , 2005Haddad et al 2001).…”
Section: Physiologically Based Pharmacokinetic (Pbpk)/pharmacodynamicmentioning
confidence: 99%
“…Subsequent enhancements of the Tardif et al (1997) model included simulation of kinetics of an inhaled quaternary mixture that included benzene, ethylbenzene, toluene, and xylene (Haddad et al 1999) or mixtures of the latter quaternary mixture with dichloromethane (Haddad et al 2000(Haddad et al , 2001. In the development of the quaternary mixture model, values for V max and K m for ethylbenzene were re-estimated by fitting data on kinetics of ethylbenzene in venous blood following 4-hour exposures to ethylbenzene (50, 100, or 200 ppm; Haddad et al 1999;Tardif et al 1997).…”
Section: In H a Le D C H E M Ic A L E X H A Le D C H E M Ic A L G I Tmentioning
confidence: 99%