Chapter 2. Quantitative Structure-Activity Relationship (QSAR) Models, Physiologically Based Pharmacokinetic (PBPK) Models, Biologically Based Dose Response (BBDR) and Toxicity Pathways: Computational Tools for Public Health
Chapter 2. Quantitative Structure-Activity Relationship (QSAR) Models, Physiologically Based Pharmacokinetic (PBPK) Models, Biologically Based Dose Response (BBDR) and Toxicity Pathways: Computational Tools for Public Health
Human health risk assessment is “the process to estimate the nature and probability of adverse health effects in humans who may be exposed to chemicals in contaminated environmental media, now or in the future.” Currently, most data required for human risk assessment are derived from toxicological studies conducted in laboratory animals. The “Toxicology in the 21st Century” initiative expands the toxicity testing tools to include the development of alternative toxicity testing methods that examine pathways of toxicity (on a large scale) and the employment of dose-response and extrapolation modeling tools. While the latter methodology is in its infancy, several methodologies for dose-response and extrapolation modeling are more mature. Over the last decade, physiologically based pharmacokinetic (PBPK) modeling has gained acceptance as a computational tool for use in public health assessments. In this chapter, we present examples of quantitative structure-activity relationship (QSAR) models, physiologically based pharmacokinetic (PBPK) models, and biologically based dose response (BBDR) models that have been developed for use in public health assessments and advancing knowledge gained through in silico examinations of biological systems.
Chapter 2. Quantitative Structure-Activity Relationship (QSAR) Models, Physiologically Based Pharmacokinetic (PBPK) Models, Biologically Based Dose Response (BBDR) and Toxicity Pathways: Computational Tools for Public Health
Chapter 2. Quantitative Structure-Activity Relationship (QSAR) Models, Physiologically Based Pharmacokinetic (PBPK) Models, Biologically Based Dose Response (BBDR) and Toxicity Pathways: Computational Tools for Public Health
Human health risk assessment is “the process to estimate the nature and probability of adverse health effects in humans who may be exposed to chemicals in contaminated environmental media, now or in the future.” Currently, most data required for human risk assessment are derived from toxicological studies conducted in laboratory animals. The “Toxicology in the 21st Century” initiative expands the toxicity testing tools to include the development of alternative toxicity testing methods that examine pathways of toxicity (on a large scale) and the employment of dose-response and extrapolation modeling tools. While the latter methodology is in its infancy, several methodologies for dose-response and extrapolation modeling are more mature. Over the last decade, physiologically based pharmacokinetic (PBPK) modeling has gained acceptance as a computational tool for use in public health assessments. In this chapter, we present examples of quantitative structure-activity relationship (QSAR) models, physiologically based pharmacokinetic (PBPK) models, and biologically based dose response (BBDR) models that have been developed for use in public health assessments and advancing knowledge gained through in silico examinations of biological systems.
The concept of effective stress and the effective stress equation is fundamental for establishing the theory of strength and the relationship of stress and strain in soil mechanics and poromechanics. However, up till now, the physical meaning of effective stress has not been explained clearly, and the theoretical basis of the effective stress equation has not been proposed. Researchers have not yet reached a common understanding of the feasibility of the concept of effective stress and effective stress equation for unsaturated soils. Effective Stress and Equilibrium Equation for Soil Mechanics discusses the definition of the soil skeleton at first and clarifies that the soil skeleton should include a fraction of pore water. When a free body of soil skeleton is taken to conduct internal force analysis, the stress on the surface of the free body has two parts: one is induced by pore fluid pressure that only includes normal stress; the other is produced by all the other external forces excluding pore fluid pressure. If the effective stress is defined as the soil skeleton stress due to all the external forces excluding pore fluid pressure, the effective stress equation can be easily obtained by the internal force equilibrium analysis. This equation reflects the relationship between the effective stress, total stress and pore fluid pressure, which does not change with the soil property. The effective stress equation of saturated soils and unsaturated soils is unified, i.e., o ̃=o ̃t –Seuw–(1–Se)ua. For multiphase porous medium, o ̃=o ̃t –u*,u*=Seiui(i=1,2,...,M). In this book, a theoretical formula of the coefficient of permeability for unsaturated soils is derived. The formula of the seepage force is modified based on the equilibrium differential equation of the pore water. The relationship between the effective stress and the shear strength and deformation of unsaturated soils is preliminarily verified. Finally, some possibly controversial problems are discussed to provide a better understanding of the role of the equilibrium equation and the concept of effective stress.
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