Predicting nonlinear relationships between external and internal concentrations with physiologically based pharmacokinetic modeling
Although external concentrations are more readily quantified and often used as the metric for regulating and mitigating exposures to environmental chemicals, the toxicological response to an environmental chemical is more directly related to its internal concentrations than the external concentration. The processes of absorption, distribution, metabolism, and excretion (ADME) determine the quantitative relationship between the external and internal concentrations. ADME are often susceptible to saturation at high external concentration, which can lead to nonlinear changes in internal concentrations that deviate from proportionality. Using generic physiologically-based pharmacokinetic (PBPK) models, we explored how saturable ADME processes influence the shape of the internal to external concentration (IEC) relationship.
HOER Daniel;
BARTON Hugh;
PAINI Alicia;
BARTELS Michael;
INGLE Brandall;
DOMORADZKI Jeanne;
FISHER Jeffrey;
EMBRY Michelle;
VILLANUEVA Philip;
MILLER David;
NGUYEN James;
ZHANG Qiang;
EDWARDS Stephen;
TAN Cecilia;
2022-03-02
ACADEMIC PRESS INC ELSEVIER SCIENCE
JRC127090
0041-008X (online),
https://publications.jrc.ec.europa.eu/repository/handle/JRC127090,
10.1016/j.taap.2022.115922 (online),
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