Toxicokinetic modeling and its applications in chemical risk assessment

Andersen, Melvin E.

doi:10.1016/s0378-4274(02)00375-2

Cited by 158 publications

(89 citation statements)

References 71 publications

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“…and (5) adjust parameter values if needed, validate, and re-formulate the model applying plausible biological mechanisms. Among the applications, Leung (2009) listed were (1) dose modeling for human health risk (e.g., Andersen, 2003); (2) dose selection for laboratory animal experiments; (3) drug discovery; (4) mixture analyses; (5) pre-and post-natal toxicological assessments; (6) occupational exposure limits; and (7) evaluation of personal protective equipment. According to Leung (2009), the first application to an environmental chemical, dieldrin, was published by Lindstrom, Gillet, and Rodecap (1974).…”

Section: What Are Pbpk Models?mentioning

confidence: 99%

The evolution of inhaled particle dose modeling: A review

Phalen

Raabe

2016

Journal of Aerosol Science

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a b s t r a c tInhaled aerosol dose models play critical roles in medicine, the regulation of air pollutants and basic research. The models fall into several categories: traditional, computational fluid dynamical (CFD), physiologically based pharmacokinetic (PBPK), empirical, semi-empirical, and "reference". Each type of model has its strengths and weaknesses, so multiple models are commonly used for practical applications. Aerosol dose models combine information on aerosol behavior and the anatomy and physiology of exposed human and laboratory animal subjects. Similar models are used for in-vitro studies. Several notable advances have been made in aerosol dose modeling in the past 80 years. The pioneers include Walter Findeisen, who in 1935 published the first traditional model and established the structure of modern models. His model combined aerosol behavior with simplified respiratory tract structures. Ewald Weibel established morphometric techniques for the lung in 1963 that are still used to develop data for modeling today. Advances in scanning techniques have similarly contributed to the knowledge of respiratory tract structure and its use in aerosol dose modeling. Several scientists and research groups have developed and advanced traditional, CFD, and PBPK models. Current issues under study include understanding individual and species differences; examining localized particle deposition; modeling non-ideal aerosols and nanoparticle behavior; linking the regions of the respiratory tract airways from nasal-oral to alveolar; and developing sophisticated supporting software. Although a complete history of inhaled aerosol dose modeling is far too extensive to cover here, selected highlights are described in this paper.

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Section: What Are Pbpk Models?mentioning

confidence: 99%

The evolution of inhaled particle dose modeling: A review

Phalen

Raabe

2016

Journal of Aerosol Science

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“…In environmental health risk assessment, the internal concentrations of active compounds at their target organs need to be related to the dose to which an animal or human subject has been exposed to [1,2,3,4]. Reason being that, both beneficial and adverse effects produced by a chemical substance, in an animal or human subject, are related to the free concentration of the active chemical agent at the target tissue and not the amount of chemical substance at the site of exposure or absorption.…”

Section: Introductionmentioning

confidence: 99%

“…Reason being that, both beneficial and adverse effects produced by a chemical substance, in an animal or human subject, are related to the free concentration of the active chemical agent at the target tissue and not the amount of chemical substance at the site of exposure or absorption. Physiologically-based biokinetic models are quite useful tools, in assessing the internal dose at target organs, for a wide variety of exposure scenarios [5,1,6,7]. Humans are constantly being exposed to a host of toxic environmental chemicals.…”

Section: Introductionmentioning

confidence: 99%

Development of a Human PBBK Model for Mixtures: Trio Mixture of Mercury, Lead, and Selenium

Maza¹,

Ojo²

2017

IOSR JESTFT

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0.03, 0.21, 0.89, 0.75, and 0.75, respectively. On the other hand, with the combined dose of mercury and lead categorized as high and selenium dose categorized as low, the concentration of mercury and lead in these tissues were modulated by factors of 1.51, 0.68, 1.28, 1.45, and 1.45, respectively, while that of selenium were modified by factors of 0. 05, 0.30, 0.45, 0.60, and 0.60, respectively 0.82, 2.89, 0.96, 0.64, and 0.64, respectively.

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“…Physiologically based pharmacokinetic (PBPK) models have been widely applied in risk assessment of human exposure to air and water contaminants (Andersen 2003). PBPK models describe the relationship between external exposures and internal concentrations of the biologically effective dose, e.g.…”

Section: Introductionmentioning

confidence: 99%

“…tissue-blood partition coefficients). PBPK-models are particularly well-suited to calculate tissue doses of chemicals and their metabolites over a wide range of exposure conditions and can be scaled from one animal species to another (Andersen 2003). However, they are often chemical specific and empirically calibrated, and two major concerns have been the model-complexity and the large amount of biological data that is required to parameterize them (Chiu and White 2006).…”

Section: Introductionmentioning

confidence: 99%

Bioaccumulation potential of air contaminants: Combining biological allometry, chemical equilibrium and mass-balances to predict accumulation of air pollutants in various mammals

Veltman

McKone

Huijbregts

et al. 2009

Toxicology and Applied Pharmacology

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In the present study we develop and test a uniform model intended for single compartment analysis in the context of human and environmental risk assessment of airborne contaminants. The new aspects of the model are the integration of biological allometry with fugacity-based mass-balance theory to describe exchange of contaminants with air. The developed model is applicable to various mammalian species and a range of chemicals, while requiring few and typically well-known input parameters, such as the adult mass and composition of the species, and the octanol-water and air-water partition coefficient of the chemical.Accumulation of organic chemicals is typically considered to be a function of the chemical affinity for lipid components in tissues. Here, we use a generic description of chemical affinity for neutral and polar lipids and proteins to estimate blood-air partition coefficients (K ba ) and tissue-air partition coefficients (K ta ) for various mammals. This provides a more accurate prediction of blood-air partition coefficients, as proteins make up a large fraction of total blood components.The results show that 75% of the modeled inhalation and exhalation rate constants are within a factor of 2 from independent empirical values for humans, rats and mice, and 87% of the predicted blood-air partition coefficients are within a factor of 5 from empirical data. At steady-state, the bioaccumulation potential of air pollutants is shown to be mainly a function of the tissue-air partition coefficient and the biotransformation capacity of the species and depends weakly on the ventilation rate and the cardiac output of mammals.

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Toxicokinetic modeling and its applications in chemical risk assessment

Cited by 158 publications

References 71 publications

The evolution of inhaled particle dose modeling: A review

The evolution of inhaled particle dose modeling: A review

Development of a Human PBBK Model for Mixtures: Trio Mixture of Mercury, Lead, and Selenium

Bioaccumulation potential of air contaminants: Combining biological allometry, chemical equilibrium and mass-balances to predict accumulation of air pollutants in various mammals

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