Toxicokinetic models for volatile industrial chemicals and reactive metabolites.
Two approaches of compartmental toxicokinetic modeling of gaseous compounds are presented which are suitable for kinetic analysis of concentration-time data measured in the air of closed exposure systems. The first approach is based on a two-compartment model with physiological gas uptake, the second on a physiologically-based toxicokinetic model. Both models can be used for the description of inhalation, accumulation, exhalation and metabolism of gaseous compounds together with the toxicokinetics of metabolites. Interspecies extrapolation is based on physicochemical, physiological and biochemical parameters. The advantage of the two-compartment model is its limited number of variables and its experimentally easy applicability. Its disadvantage is the impossibility to predict tissue specific concentrations. The advantage of the physiologically-based model is its usability for predictions and for the description of tissue specific concentrations. However, it entails great effort, since a series of parameters has to be determined before meaningful model calculations can be carried out.
Filser
J G
JG
GSF-Forschungszentrum für Umwelt und Gesundheit, Institut für Toxikologie, Oberschleissheim, Germany.
Csanády
G A
GA
Kreuzer
P E
PE
Kessler
W
W
D000818:Animals; D006801:Humans; D008954:Models, Biological; D010599:Pharmacokinetics; D014835:Volatilization