Physiologically based pharmacokinetic and pharmacodynamic modeling in health risk assessment and characterization of hazardous substances.

Recent advances in physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) modeling have introduced novel approaches for evaluating toxicological problems. Because PBPK models are amenable to extrapolation of tissue dosimetry, they are increasingly being applied to chemical risk assessment. A comprehensive listing of PBPK/PD models for environmental chemicals developed to date is referenced. Salient applications of PBPK/PD modeling to health risk assessments and characterization of hazardous substances are illustrated with examples.

[1]  L S Birnbaum,et al.  A physiological model for simulation of benzene metabolism by rats and mice. , 1989, Toxicology and applied pharmacology.

[2]  J. Kissel,et al.  Assessing the elimination of 2,3,7,8-TCDD from humans with a physiologically based pharmacokinetic model , 1988 .

[3]  F Y Bois,et al.  Precision and sensitivity of pharmacokinetic models for cancer risk assessment: tetrachloroethylene in mice, rats, and humans. , 1990, Toxicology and applied pharmacology.

[4]  D. Paustenbach,et al.  Application of pharmacokinetics to derive biological exposure indexes from threshold limit values. , 1988, American Industrial Hygiene Association journal.

[5]  B C Allen,et al.  Evaluating the risk of liver cancer in humans exposed to trichloroethylene using physiological models. , 1993, Risk analysis : an official publication of the Society for Risk Analysis.

[6]  D Hattis,et al.  Uncertainties in pharmacokinetic modeling for perchloroethylene. I. Comparison of model structure, parameters, and predictions for low-dose metabolism rates for models derived by different authors. , 1990, Risk analysis : an official publication of the Society for Risk Analysis.

[7]  D Hattis,et al.  Uncertainties in pharmacokinetic modeling for perchloroethylene: II. Comparison of model predictions with data for a variety of different parameters. , 1993, Risk analysis : an official publication of the Society for Risk Analysis.

[8]  S. Tsuda,et al.  Pharmacokinetic analysis of protection by an organophosphorus insecticide, chlorfenvinphos, against the toxicity of its succeeding dosage in rats. , 1992, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[9]  A. Koizumi.  Potential of physiologically based pharmacokinetics to amalgamate kinetic data of trichloroethylene and tetrachloroethylene obtained in rats and man. , 1989, British journal of industrial medicine.

[10]  Melvin E. Andersen,et al.  Gas Uptake Inhalation Techniques and the Rates of Metabolism of Chloromethanes, Chloroethanes, and Chloroethylenes in the Rat , 1990 .

[11]  G. Johanson,et al.  A simulation study of physiological factors affecting pharmacokinetic behaviour of organic solvent vapours. , 1991, British journal of industrial medicine.

[12]  H J Clewell,et al.  Physiologically based pharmacokinetic modeling with dichloromethane, its metabolite, carbon monoxide, and blood carboxyhemoglobin in rats and humans. , 1991, Toxicology and applied pharmacology.

[13]  D J Paustenbach,et al.  A physiologically based pharmacokinetic model for 2,3,7,8-tetrachlorodibenzo-p-dioxin in C57BL/6J and DBA/2J mice. , 1988, Toxicology letters.

[14]  E J O'Flaherty,et al.  Physiologically based models for bone-seeking elements. IV. Kinetics of lead disposition in humans. , 1993, Toxicology and applied pharmacology.

[15]  A Vinegar,et al.  Action by the lungs on circulating xenobiotic agents, with a case study of physiologically based pharmacokinetic modeling of benzo(a)pyrene disposition. , 1990, Pharmacology & therapeutics.

[16]  R B Conolly,et al.  Pharmacokinetics of 2-methoxyethanol and 2-methoxyacetic acid in the pregnant mouse: a physiologically based mathematical model. , 1993, Toxicology and applied pharmacology.

[17]  P O Droz,et al.  Variability in biological monitoring of solvent exposure. I. Development of a population physiological model. , 1989, British journal of industrial medicine.

[18]  M. Andersen,et al.  A physiologically-based pharmacokinetic model for 2,3,7,8-tetrachlorodibenzo-p-dioxin , 1989 .

[19]  H J Clewell,et al.  Physiologically based pharmacokinetic modeling of the pregnant rat: a multiroute exposure model for trichloroethylene and its metabolite, trichloroacetic acid. , 1989, Toxicology and applied pharmacology.

[20]  R C Spear,et al.  Modeling benzene pharmacokinetics across three sets of animal data: parametric sensitivity and risk implications. , 1991, Risk analysis : an official publication of the Society for Risk Analysis.

[21]  Lester G. Sultatos.  A Physiologically Based Pharmacokinetic Model of Parathion Based on Chemical-Specific Parameters Determined In Vitro , 1990 .

[22]  M E Andersen,et al.  A physiologically based description of the inhalation pharmacokinetics of styrene in rats and humans. , 1984, Toxicology and applied pharmacology.

[23]  P. Mozzo,et al.  Physiologicomathematical model for studying human exposure to organic solvents: kinetics of blood/tissue n-hexane concentrations and of 2,5-hexanedione in urine. , 1986, British journal of industrial medicine.

[24]  J. Gallo,et al.  Physiological pharmacokinetic modeling of inhaled trichloroethylene in rats. , 1991, Toxicology and applied pharmacology.

[25]  R H Reitz,et al.  In vitro metabolism of methylene chloride in human and animal tissues: use in physiologically based pharmacokinetic models. , 1989, Toxicology and applied pharmacology.

[26]  R C Spear,et al.  Comparison of three physiologically based pharmacokinetic models of benzene disposition. , 1991, Toxicology and applied pharmacology.

[27]  M L Gargas,et al.  Kinetic analysis of furan biotransformation by F-344 rats in vivo and in vitro. , 1993, Toxicology and applied pharmacology.

[28]  M. Andersen,et al.  Risk Assessment Extrapolations and Physiological Modeling , 1985, Toxicology and industrial health.

[29]  R Tardif,et al.  Physiologically based modeling of the toxicokinetic interaction between toluene and m-xylene in the rat. , 1993, Toxicology and applied pharmacology.

[30]  R. Lutz,et al.  Comparison of the pharmacokinetics of several polychlorinated biphenyls in mouse, rat, dog, and monkey by means of a physiological pharmacokinetic model. , 1984, Drug metabolism and disposition: the biological fate of chemicals.

[31]  J. Morris,et al.  A physiologically based pharmacokinetic model for nasal uptake and metabolism of nonreactive vapors. , 1993, Toxicology and applied pharmacology.

[32]  M E Andersen,et al.  Incorporation of in vitro enzyme data into the physiologically-based pharmacokinetic (PB-PK) model for methylene chloride: implications for risk assessment. , 1988, Toxicology letters.

[33]  Andrew J. McMichael,et al.  Complex mixtures and cancer risk. , 1990, IARC scientific publications.

[34]  L S Birnbaum,et al.  Physiological model for the pharmacokinetics of 2,3,7,8-tetrachlorodibenzofuran in several species. , 1983, Toxicology and applied pharmacology.

[35]  A. Khalique,et al.  Physiological pharmacokinetic and pharmacodynamic model of physostigmine in the rat. , 1991, Drug metabolism and disposition: the biological fate of chemicals.

[36]  C. Portier,et al.  Biologically based models for risk assessment. , 1990, IARC scientific publications.

[37]  R C Spear,et al.  Mechanisms of benzene carcinogenesis: application of a physiological model of benzene pharmacokinetics and metabolism. , 1991, Toxicology letters.

[38]  P. Allen,et al.  Physiological model for the pharmacokinetics of methyl mercury in the growing rat. , 1993, Toxicology and applied pharmacology.

[39]  B. Allen,et al.  Evaluation of uncertainty in input parameters to pharmacokinetic models and the resulting uncertainty in output. , 1989, Toxicology letters.

[40]  H W Leung,et al.  Development and utilization of physiologically based pharmacokinetic models for toxicological applications. , 1991, Journal of toxicology and environmental health.

[41]  D B Menzel,et al.  ES Series: Cancer Risk Assessment. 2. Physiological pharmacokinetic modeling. , 1987, Environmental science & technology.

[42]  M E Andersen,et al.  Physiological model for tissue glutathione depletion and increased resynthesis after ethylene dichloride exposure. , 1988, The Journal of pharmacology and experimental therapeutics.

[43]  Marilyn F. Hallock,et al.  Assessment of Task and Peak Exposures to Solvents in the Microelectronics Fabrication Industry , 1993 .

[44]  M. Andersen,et al.  Physiologically based pharmacokinetic model for vinylidene chloride. , 1988, Toxicology and applied pharmacology.

[45]  H J Clewell,et al.  Variability of physiologically based pharmacokinetic (PBPK) model parameters and their effects on PBPK model predictions in a risk assessment for perchloroethylene (PCE). , 1993, Toxicology letters.

[46]  K T Bogen,et al.  Pharmacokinetics for regulatory risk analysis: the case of trichloroethylene. , 1988, Regulatory toxicology and pharmacology : RTP.

[47]  M E Andersen,et al.  Modeling receptor-mediated processes with dioxin: implications for pharmacokinetics and risk assessment. , 1993, Risk analysis : an official publication of the Society for Risk Analysis.

[48]  D J Paustenbach,et al.  Adjusting exposure limits for long and short exposure periods using a physiological pharmacokinetic model. , 1987, American Industrial Hygiene Association journal.

[49]  Melvin E. Andersen,et al.  Use of a Physiologically Based Pharmacokinetic Model and Computer Simulation for Retrospective Assessment of Exposure to Volatile Toxicants , 1990 .

[50]  D. M. Hetrick,et al.  Pharmacokinetics of tetrachloroethylene. , 1988, Toxicology and applied pharmacology.

[51]  G. Johanson,et al.  Physiologically based pharmacokinetic modeling of inhaled 2-butoxyethanol in man. , 1986, Toxicology letters.

[52]  M E Andersen,et al.  A physiologically based pharmacokinetic model for nicotine disposition in the Sprague-Dawley rat. , 1992, Toxicology and applied pharmacology.

[53]  D J Paustenbach,et al.  A physiologically based pharmacokinetic model for inhaled carbon tetrachloride. , 1988, Toxicology and applied pharmacology.

[54]  R A Freeman,et al.  A physiologically based model for gastrointestinal absorption and excretion of chemicals carried by lipids. , 1993, Risk analysis : an official publication of the Society for Risk Analysis.

[55]  C. Travis,et al.  Interspecies extrapolation of pharmacokinetics. , 1990, Journal of theoretical biology.

[56]  M. Higuchi,et al.  Physiologically based pharmacokinetic model for methanol in rats, monkeys, and humans. , 1992, Toxicology and applied pharmacology.

[57]  F. A. Smith,et al.  Physiologically based pharmacokinetics and the risk assessment process for methylene chloride. , 1987, Toxicology and applied pharmacology.

[58]  E J O'Flaherty,et al.  A physiologically based kinetic model of rat and mouse gestation: disposition of a weak acid. , 1992, Toxicology and applied pharmacology.

[59]  H. Matthews,et al.  Distribution and excretion of 2,2',4,4',5,5'-hexabromobiphenyl in rats and man: pharmacokinetic model predictions. , 1980, Toxicology and applied pharmacology.

[60]  C. P. Vlahacos,et al.  A pharmacodynamic model for soman in the rat. , 1988, Toxicology letters.

[61]  M E Andersen,et al.  In vivo metabolic interactions of benzene and toluene. , 1990, Toxicology letters.

[62]  M E Andersen,et al.  Development of a physiologically based pharmacokinetic model for chloroform. , 1990, Toxicology and applied pharmacology.

[63]  D. H. Taylor,et al.  Physiologically based pharmacokinetic modeling of the lactating rat and nursing pup: a multiroute exposure model for trichloroethylene and its metabolite, trichloroacetic acid. , 1990, Toxicology and applied pharmacology.

[64]  A Vinegar,et al.  A Physiologically Based Pharmacokinetic Model for Chloropentafluorobenzene in Primates To Be Used in the Evaluation of Protective Equipment Against Toxic GASES , 1992, Toxicology and industrial health.

[65]  G. Clark,et al.  A mechanistic model of effects of dioxin on gene expression in the rat liver. , 1993, Toxicology and applied pharmacology.

[66]  T. R. Anton,et al.  A physiologically based mathematical model for the human inhalation pharmacokinetics of 1,1,2-trichloro-1,2,2-trifluoroethane , 1991, International archives of occupational and environmental health.

[67]  D J Paustenbach,et al.  A physiological pharmacokinetic description of the tissue distribution and enzyme-inducing properties of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the rat. , 1990, Toxicology and applied pharmacology.

[68]  P. S. McCroskey,et al.  Development of a physiologically based pharmacokinetic model for risk assessment with 1,4-dioxane. , 1990, Toxicology and applied pharmacology.

[69]  M E Andersen,et al.  Estimating the risk of liver cancer associated with human exposures to chloroform using physiologically based pharmacokinetic modeling. , 1990, Toxicology and applied pharmacology.

[70]  H J Clewell,et al.  Quantitative evaluation of the metabolic interactions between trichloroethylene and 1,1-dichloroethylene in vivo using gas uptake methods. , 1987, Toxicology and applied pharmacology.

[71]  R. Melnick,et al.  Species differences in the production and clearance of 1,3-butadiene metabolites: a mechanistic model indicates predominantly physiological, not biochemical, control. , 1993, Carcinogenesis.

[72]  Christopher J. Portier,et al.  Variability of safe dose estimates when using complicated models of the carcinogenic process. A case study: methylene chloride. , 1989 .

[73]  H J Clewell,et al.  Dermal absorption of organic chemical vapors in rats and humans. , 1990, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[74]  D J Paustenbach,et al.  Pharmacokinetics of [125I]-2-iodo-3,7,8-trichlorodibenzo-p-dioxin in mice: analysis with a physiological modeling approach. , 1990, Toxicology and applied pharmacology.

[75]  R W D'Souza,et al.  Physiological Pharmacokinetic Models: Some Aspects of Theory, Practice and Potential , 1988, Toxicology and industrial health.

[76]  M E Andersen,et al.  A physiologically based pharmacokinetic model for 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD) in the rat: tissue distribution and CYP1A induction. , 1993, Toxicology and applied pharmacology.

[77]  G. Johanson,et al.  Dose-dependent kinetics of inhaled methylethylketone in man. , 1990, Toxicology letters.

[78]  B C Allen,et al.  Pharmacokinetic modeling of trichloroethylene and trichloroacetic acid in humans. , 1993, Risk analysis : an official publication of the Society for Risk Analysis.

[79]  P. Mozzo,et al.  "Dynamic" biological exposure indexes for n-hexane and 2,5-hexanedione, suggested by a physiologically based pharmacokinetic model. , 1990, American Industrial Hygiene Association journal.

[80]  Timothy C. Marrs,et al.  General and Applied Toxicology , 1995 .

[81]  H J Clewell,et al.  Biologically motivated models for chemical risk assessment. , 1989, Health physics.

[82]  Melvin E. Andersen,et al.  Physiologically based pharmacokinetic and pharmacodynamic model for the inhibition of acetylcholinesterase by diisopropyfluorophosphate , 1990 .

[83]  H J Clewell,et al.  A physiological pharmacokinetic model for dermal absorption of vapors in the rat. , 1986, Toxicology and applied pharmacology.

[84]  G. Johanson,et al.  Effects of consumption of ethanol on the biological monitoring of exposure to organic solvent vapours: a simulation study with trichloroethylene. , 1991, British journal of industrial medicine.

[85]  D B Menzel,et al.  Planning and using PB-PK models: an integrated inhalation and distribution model for nickel. , 1988, Toxicology letters.

[86]  C T Hung,et al.  A physiological pharmacokinetic model describing the disposition of lead in the absence and presence of L-ascorbic acid in rats. , 1990, Toxicology letters.

[87]  J. Gallo,et al.  The uptake and elimination of 1,1,1-trichloroethane during and following inhalation exposures in rats. , 1989, Toxicology and applied pharmacology.

[88]  C C Travis,et al.  Pharmacokinetics of benzene. , 1990, Toxicology and applied pharmacology.

[89]  M E Andersen,et al.  A Physiologically Based Description of Ethylene Oxide Dosimetry in the Rat , 1992, Toxicology and industrial health.

[90]  D J Paustenbach,et al.  Cancer risk assessment for dioxane based upon a physiologically-based pharmacokinetic approach. , 1990, Toxicology letters.

[91]  J. Fisher,et al.  Gastrointestinal absorption of xenobiotics in physiologically based pharmacokinetic models. A two-compartment description. , 1991, Drug metabolism and disposition: the biological fate of chemicals.

[92]  J. Gillett,et al.  Distribution of HEOD (dieldrin) in mammals: I. Preliminary model , 1974, Archives of environmental contamination and toxicology.

[93]  D W Potter,et al.  A physiologically based pharmacokinetic and pharmacodynamic model to describe the oral dosing of rats with ethyl acrylate and its implications for risk assessment. , 1992, Toxicology and applied pharmacology.

[94]  B. Stahl,et al.  A pharmacodynamic model of triglyceride transport and deposition during feed deprivation or following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the rat. , 1993, Toxicology and applied pharmacology.

[95]  F Y Bois,et al.  An analysis of exposure rate effects for benzene using a physiologically based pharmacokinetic model. , 1992, Regulatory toxicology and pharmacology : RTP.

[96]  L Edler,et al.  Ligand/receptor binding for 2,3,7,8-TCDD: implications for risk assessment. , 1993, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[97]  H. Leung,et al.  Use of physiologically based pharmacokinetic models to establish biological exposure indexes. , 1992, American Industrial Hygiene Association journal.

[98]  R H Reitz,et al.  Physiologically based pharmacokinetic modeling with methylchloroform: implications for interspecies, high dose/low dose, and dose route extrapolations. , 1988, Toxicology and applied pharmacology.

[99]  R L Chinery,et al.  A compartmental model for the prediction of breath concentration and absorbed dose of chloroform after exposure while showering. , 1993, Risk analysis : an official publication of the Society for Risk Analysis.

[100]  H V Rao,et al.  A physiologically based pharmacokinetic assessment of tetrachloroethylene in groundwater for a bathing and showering determination. , 1993, Risk analysis : an official publication of the Society for Risk Analysis.

[101]  H J Clewell,et al.  Risk assessment of chemical mixtures: biologic and toxicologic issues. , 1993, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[102]  L S Birnbaum,et al.  Measurement of steady-state blood concentrations in B6C3F1 mice exposed by inhalation to vinylidene fluoride. , 1990, Toxicology.