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Risk Assessment for Occupational Neurotoxicants
Published in Lucio G. Costa, Luigi Manzo, Occupatinal Neurotoxicology, 2020
The research approach consists of the following three steps: gathering information from all available endpoints or disciplines and using it to generate a neurotoxicity profilecorrelating structural, neurochemical and neurophysiological data with overt behavioral manifestations of neurotoxicitydeveloping a pharmacokinetic/metabolic basis to aid in data interpretation and for interspecies extrapolation. Future strategies for neurotoxicity assessments may include additional disciplines and approaches such as molecular biology and psychology (Figure 2). To allow for successful interspecies extrapolation, physiologically-based pharmacokinetic modeling (PBPk) may be used to predict target tissue exposure to an agent in several species including humans.5
Clinical Pharmacology of Parenteral Dosage Forms
Published in Sandeep Nema, John D. Ludwig, Parenteral Medications, 2019
Another extension of the more empirical classical PK modeling is physiologically based PK (PBPK) modeling, which is mechanistic in nature. Instead of lumping all the tissues into central and peripheral compartments, various tissues are represented by their own compartments (Figure 7.9). Each of the compartments represents the amount or concentration of drug present in the tissue incorporating the physiological parameters such as known tissue/organ volumes and respective blood flow rates. Also, well-mixed tissues with similar blood perfusion rates are lumped together to reduce complexity. Since PBPK models incorporate known physiological parameters, they lend themselves well to extrapolation of PK among species or prediction of tissue concentrations when the route of administration, dose, regimen, or demographics are changed. Additionally, PBPK modeling is particularly useful when the estimation of drug exposures in a particular tissue is of interest from the toxicity or efficacy perspective.
Estimating Human Health Risks for Trichloroethylene, a Water Contaminant, Using Physiological Models
Published in Rhoda G.M. Wang, Water Contamination and Health, 2020
PBPK modeling provides a framework for attempting to “make sense” of multiple bioassay data sets for different routes of exposure. It also allows the use of an internal measure of dose (e.g., amount of TCE metabolized) rather than an external measure of dose (e.g., atmospheric concentration of TCE) in the calculation of cancer risks. In this study, the cancer risks calculated by the U.S. EPA for human exposure to TCE were refined by using PBPK models to estimate the metabolized dose. PBPK models offer promise as a useful tool in the chemical risk assessment process and may provide insight into mechanisms of toxicological action for chemicals.
A critical review on the bioaccumulation, transportation, and elimination of per- and polyfluoroalkyl substances in human beings
Published in Critical Reviews in Environmental Science and Technology, 2023
Yao Lu, Ruining Guan, Nali Zhu, Jinghua Hao, Hanyong Peng, Anen He, Chunyan Zhao, Yawei Wang, Guibin Jiang
Physiologically based pharmacokinetic (PBPK) model is a useful tool to reveal the accumulation, transportation, and elimination of chemicals in organisms and to conduct the risk assessment of chemicals. PBPK models based on PFAS in human can provide a systematic view of the behaviors and mechanisms of PFAS in human beings. Additionally, the established models combined with other data (e.g., genomic data) can be used to assess the health risks of PFAS.