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Z. Wang and J. Chen
(2) parameters that characterize the environmental media and the behavior of the
chemical in certain environmental process. The principles and application of
fugacity models have been described in specialized textbooks [31], and fugacity models have been widely employed for predicting environmental fates of
concerning chemicals [32, 33]. Furthermore, geographical information systems
may improve the fugacity model upon its spatial resolution and visualization
[34, 35].
2.3.2 Physiologically-Based Toxicokinetics Models
Exposure can be further divided into external exposure and internal exposure, depending on whether a chemical is located outside or inside of an organism [36]. Concentrations in environmental compartments predicted by fugacity models only quantify
the external exposure. The response of different target sites inside the body to the
same chemical would be distinct. For example, liver of mammals could metabolize
xenobiotics, but fat tissue would typically store hydrophobic chemicals. Therefore,
the internal distribution of chemicals actually provides useful information for interpreting mechanisms of toxic effects [36].
Analogous to fugacity models, if the situational objects make an individual organism with a negligible counter-influence of the queried chemical object, then the
simulation model would more or less resemble a physiologically based toxicokinetics (PBTK) model [37], which shares similar schemes of parameters and equations
with those of the fugacity model. In brief, a PBTK model employs in silico objects
representing brain, lung, liver, kidney, fat tissues, venous blood, arterial blood or
generally poorly perfused and richly perfused tissues or organs, typically termed
as boxes/compartments [38]. According to the flow of chemicals along the blood
vessels, ordinary differential equations can be developed to solve the concentrations
as a function of time in various boxes [37]. The concentrations in urine or blood
can be reversely extrapolated to total intake doses [39], enabling a direct comparison
between data from biomonitoring and exposure scenarios derived from ESDs and
fugacity models.
Fugacity models or PBTK models have structures that are straightforward to
understand and parameters that can be tuned in the simulation, which permit speculation on the mechanism of associated macroscale systems. With the neglected
counter-influence of the queried chemical objects on the situational objects, simulations of fugacity models or PBTK models are generally fast and always have
deterministic results. Furthermore, with techniques such as Monte Carlo simulation, diagnosis on the sensitivity, and uncertainties are also available making the
macroscale empirical equations-based models more robust [32].
Traditionally, exposure of chemicals is viewed as a linear model from sources of
emission to targets. However, exposure and effects are not mutually independent.
For example, long-term exposure of toxic chemicals would definitely change the
parameters of physiological tissues or organs, which is a topic of toxicodynamics.
Z. Wang and J. Chen
(2) parameters that characterize the environmental media and the behavior of the
chemical in certain environmental process. The principles and application of
fugacity models have been described in specialized textbooks [31], and fugacity models have been widely employed for predicting environmental fates of
concerning chemicals [32, 33]. Furthermore, geographical information systems
may improve the fugacity model upon its spatial resolution and visualization
[34, 35].
2.3.2 Physiologically-Based Toxicokinetics Models
Exposure can be further divided into external exposure and internal exposure, depending on whether a chemical is located outside or inside of an organism [36]. Concentrations in environmental compartments predicted by fugacity models only quantify
the external exposure. The response of different target sites inside the body to the
same chemical would be distinct. For example, liver of mammals could metabolize
xenobiotics, but fat tissue would typically store hydrophobic chemicals. Therefore,
the internal distribution of chemicals actually provides useful information for interpreting mechanisms of toxic effects [36].
Analogous to fugacity models, if the situational objects make an individual organism with a negligible counter-influence of the queried chemical object, then the
simulation model would more or less resemble a physiologically based toxicokinetics (PBTK) model [37], which shares similar schemes of parameters and equations
with those of the fugacity model. In brief, a PBTK model employs in silico objects
representing brain, lung, liver, kidney, fat tissues, venous blood, arterial blood or
generally poorly perfused and richly perfused tissues or organs, typically termed
as boxes/compartments [38]. According to the flow of chemicals along the blood
vessels, ordinary differential equations can be developed to solve the concentrations
as a function of time in various boxes [37]. The concentrations in urine or blood
can be reversely extrapolated to total intake doses [39], enabling a direct comparison
between data from biomonitoring and exposure scenarios derived from ESDs and
fugacity models.
Fugacity models or PBTK models have structures that are straightforward to
understand and parameters that can be tuned in the simulation, which permit speculation on the mechanism of associated macroscale systems. With the neglected
counter-influence of the queried chemical objects on the situational objects, simulations of fugacity models or PBTK models are generally fast and always have
deterministic results. Furthermore, with techniques such as Monte Carlo simulation, diagnosis on the sensitivity, and uncertainties are also available making the
macroscale empirical equations-based models more robust [32].
Traditionally, exposure of chemicals is viewed as a linear model from sources of
emission to targets. However, exposure and effects are not mutually independent.
For example, long-term exposure of toxic chemicals would definitely change the
parameters of physiological tissues or organs, which is a topic of toxicodynamics.