Physiologically-based risk assessment

Rao, H.V., and D.R. Brown. 1993. A physiologically based pharmacokinetic assessment of tetrachloroethylene in groundwater for a bathing and showering determination. Risk Anal. 13(l) 37-49. 

Physiologically based toxicokinetic models are nowadays used increasingly for toxicological risk assessment. These models are based on human physiology, and thus take into consideration the actual toxicokinetic processes more accurately than the one- or two-compartment models. In these models, all of the relevant information regarding absorption, distribution, biotransformarion, and elimination of a compound is utilized. The principles of physiologically based pharmaco/ toxicokinetic models are depicted in Fig. 5.41a and h. The... 

Andersen ME, Clewell HJ 3rd, Gargas ME, et al. 1987. Physiologically based pharmacokinetics and the risk assessment process for methylene chloride. Toxicol Appl Pharmacol 87 185-205. 

Notice Approaches for the Application of Physiologically-Based Pharmacokinetic (PBPK) Models and Supporting Data in Risk Assessment E-Docket ID No. ORD-2005-0022. Fed Reg July 28, 2005 70 (144) 43692-43693. 

Clewell HJ 3rd, Gentry PR, Covington TR, Gearhart JM. Development of a physiologically based pharmacokinetic model of trichloroethylene and its metabolites for use in risk assessment. Environ Health Perspect 2000 May 108 Suppl 2 283-305. 

Cronin WJ, Oswald EJ, Shelley ML, et al. 1995. A trichloroethylene risk assessment using a Monte Carlo analysis of parameter uncertainty in conjunction with physiologically-based pharmacokinetic modeling. Risk Anal 15 555-565. 

A large number of research and review papers have been published in recent years on the integration of data on physicochemical properties, in vitro derived toxicity data, and physiologically based kinetics and dynamics as a modeling tool in hazard and risk assessment [72-85]. 

Absorbed lead is distributed in various tissue compartments. Several models of lead pharmacokinetics have been proposed to characterize such parameters as intercompartmental lead exchange rates, retention of lead in various pools, and relative rates of distribution among the tissue groups. See Section 2.3.5 for a discussion of the classical compartmental models and physiologically based pharmacokinetic models (PBPK) developed for lead risk assessments. 

FUN tool is a new integrated software based on a multimedia model, physiologically based pharmacokinetic (PBPK) models and associated databases. The tool is a dynamic integrated model and is capable of assessing the human exposure to chemical substances via multiple exposure pathways and the potential health risks (Fig. 9) [70]. 2-FUN tool has been developed in the framework of the European project called 2-FUN (Full-chain and UNcertainty Approaches for Assessing Health Risks in FUture ENvironmental Scenarios www.2-fun.org). 

Other major early contributions of biochemical engineering have been in the development of the artificial kidney and physiologically based pharmacokinetic models. The artificial kidney has been literally a lifesaver. Pharmacokinetic models divide the body of an animal or human into various compartments that act as bioreactors. These mathematical models have been used very successfully in developing therapeutic strategies for the optimal delivery of chemotherapeutic drugs and in assessing risk from exposure to toxins. 

Andersen ME (1995) Development of physiologically based pharmacokinetic and physiologically based pharmacodynamic models for applications in toxicology and risk assessment. Toxicol Lett 79 35-44... 

Second, there is a procedure for scaling doses between animals and humans, to take account of differences in body size and rates of various physiological processes. Interestingly, as the EPA and other regulators practice risk assessment, animal-to-human extrapolation for carcinogens is based on the use of such scaling factors, rather than... 

Clewell HJ III, Andersen ME. 1985. Risk assessment extrapolations using physiologically-based pharmacokinetic modeling. Toxicol Ind Health 1 111-131. 

Leung, W.W. and D.J. Paustenbach. 1995. Physiologically based pharmacokinetic and pharmacodynamic modeling in health risk assessment and characterization of hazardous substances. Toxicol. Lett. 79 55-65. 

Yang, R.S., H.A. El-Masri, R.S. Thomas, A.A. Constan, and J.D. Tessari. 1995. The apphcation of physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling for exploring risk assessment approaches for chemical mixtures. Toxicol. Lett. 79 193-200. 

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