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

Leung, Hon-Wing; Paustenbach, Dennis J.

doi:10.1016/0378-4274(95)03357-q

Cited by 37 publications

(13 citation statements)

References 98 publications

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“…PBPK models have been developed for use in toxicity risk assessment for a variety of chemicals and some chemical mixtures (Leung & Paustenbach, 1995;Simmons, 1996). Models that yield simulations consistent with experimental data in one species can be used to extrapolate to other species, dose regimens, or routes of administration (Clewell & Andersen, 1985;Dallas et al, 1995).…”

mentioning

confidence: 99%

Organ Weights and Fat Volume in Rats as a Function of Strain and Age

Schoeffner

Warren²,

Muralidara³

et al. 1999

Journal of Toxicology and Environmental Health, Part A

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The Fischer 344 (F344) rat and the Sprague-Dawley (SD) rat are used commonly to evaluate potential adverse health effects resulting from environmental exposure to chemicals. They are also the most common rat strain/stock used in physiologically based pharmacokinetic (PBPK) modeling. Accurate characterization of model input parameters will improve the usefulness of PBPK model predictions. Thus, organ (i.e., liver, kidneys, spleen, stomach, small intestine, large intestine, heart, lungs, brain) weights and body fat were measured in male SD rats of different ages (4 to 40 wk) and in young (9 to 10 wk) and old (22 to 23 mo) male F344 rats. Comparison of age-matched (9 to 10 wk) F344 and SD rats revealed that the SD rats weighed significantly more and had significantly higher absolute organ weights. These significant differences usually disappeared when organ weights were expressed as a percentage of body weight (relative organ weight). Percent body fat was significantly lower in the age-matched SD rats (6.48%) than in their F344 counterparts (8.67%). As expected, both body weight and absolute organ weights were significantly higher in old than in young F344 rats. However, these differences were largely reversed when relative organ weights were considered, with most relative organ weights significantly lower in the old F344 rats. Body fat as a percentage of body weight was 14.02% in the old F344 rats. When SD rats of various ages were examined, relative organ weights declined between the ages of 4 and 14 wk. In contrast, significant differences in percent body fat were not detected among the SD rats of different ages and weights examined in this study (4 to 40 wk, approximately 75 to approximately 450 g). In summary, values for physiological input parameters are provided that should prove useful in development and implementation of more accurate PBPK models.

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mentioning

confidence: 99%

Organ Weights and Fat Volume in Rats as a Function of Strain and Age

Schoeffner

Warren²,

Muralidara³

et al. 1999

Journal of Toxicology and Environmental Health, Part A

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show abstract

“…Today, the risk assessment community uses PBPK models as an important tool for improving the accuracy of human health risk assessments for hazardous substances (Clewell, 1995;Leung and Paustenbach, 1995;Wilson et al, 2002). The ultimate aim of using PBPK modeling in risk assessment is to provide a measure of dose which better represents the biologically eVective dose-that is, the dose which causally relates to the toxic outcome.…”

Section: Use Of Pbpk Modeling In Chemical Risk Assessmentmentioning

confidence: 98%

Risk assessment of chemicals and pharmaceuticals in the pediatric population: A workshop report

Pohl

Engelen

Wilson

et al. 2005

Regulatory Toxicology and Pharmacology

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“…To enable extrapolation, physiologically based pharmacokinetic (PBPK) models have emerged as an important tool that has seen broad applications in toxicology and more specifically in human health risk assessment (Andersen, 1995;Clewell and Andersen, 1996;Krishnan and Andersen, 2001;Leung and Paustenbach, 1995;Mason and Wilson, 1999). Their potential utility as a modeling tool for biological monitoring has only recently been explored (Garabrant et al, 2008;Tan et al, 2007).…”

Section: Compartmental Pharmacokinetic Modelsmentioning

confidence: 99%

“…PBPK models have been developed to describe target tissue dosimetry for a broad range of environmental contaminants, such as solvents, heavy metals, and pesticides, including organophosphate and carbamate insecticides (Andersen et al, 1987;Corley et al, 1990;Gearhart et al, 1990;Nong et al, 2008;Poet et al, 2004;Sultatos, 1990;Timchalk et al, 2002). A number of reviews have been published on the development, validation, application, and limitations of PBPK models in human health risk assessment (Andersen, 1995(Andersen, , 2003Clewell, 1995;Clewell and Andersen, 1996;Frederick, 1995;Krishnan and Andersen, 2001;Leung and Paustenbach, 1995;Mason and Wilson, 1999).…”

Section: Physiologically Based Pharmacokinetic Modelsmentioning

confidence: 99%

Biomonitoring of Pesticides: Pharmacokinetics of Organophosphorus and Carbamate Insecticides

Timchalk

2011

Anticholinesterase Pesticides

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

Cited by 37 publications

References 98 publications

Organ Weights and Fat Volume in Rats as a Function of Strain and Age

Organ Weights and Fat Volume in Rats as a Function of Strain and Age

Risk assessment of chemicals and pharmaceuticals in the pediatric population: A workshop report

Biomonitoring of Pesticides: Pharmacokinetics of Organophosphorus and Carbamate Insecticides

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