Development of PK- and PBPK-based modeling tools for derivation of biomonitoring guidance values

Bartels, Michael; Rick, David L.; Lowe, Ezra R.; Loizou, George; Price, Paul S.; Spendiff, Martin; Arnold, Scott M.; Cocker, John; Ball, Nicholas

doi:10.1016/j.cmpb.2012.04.014

Cited by 15 publications

(10 citation statements)

References 39 publications

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“…These parameters were used in a generic PBTK model to relate blood or serum concentrations to corresponding steady-state external dose rates using commercially available software. Bartels et al [ 44 ] presented initial results of a comprehensive effort to develop a generic PBTK model structure that accommodates varying levels of chemical-specific information and allows prediction of biomarker concentrations (both urinary and blood) associated with a specified exposure guidance value. On the toxicity assessment front, Louisse et al [ 45 ] demonstrated the integration of in vitro toxicity data with toxicokinetic models to assess glycol ethers.…”

Section: Using Risk Assessment Methods To Interpret Human Biomonitmentioning

confidence: 99%

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Development of Screening Tools for the Interpretation of Chemical Biomonitoring Data

Becker

Hays

Robison

et al. 2012

Journal of Toxicology

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Evaluation of a larger number of chemicals in commerce from the perspective of potential human health risk has become a focus of attention in North America and Europe. Screening-level chemical risk assessment evaluations consider both exposure and hazard. Exposures are increasingly being evaluated through biomonitoring studies in humans. Interpreting human biomonitoring results requires comparison to toxicity guidance values. However, conventional chemical-specific risk assessments result in identification of toxicity-based exposure guidance values such as tolerable daily intakes (TDIs) as applied doses that cannot directly be used to evaluate exposure information provided by biomonitoring data in a health risk context. This paper describes a variety of approaches for development of screening-level exposure guidance values with translation from an external dose to a biomarker concentration framework for interpreting biomonitoring data in a risk context. Applications of tools and concepts including biomonitoring equivalents (BEs), the threshold of toxicologic concern (TTC), and generic toxicokinetic and physiologically based toxicokinetic models are described. These approaches employ varying levels of existing chemical-specific data, chemical class-specific assessments, and generic modeling tools in response to varying levels of available data in order to allow assessment and prioritization of chemical exposures for refined assessment in a risk management context.

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Section: Using Risk Assessment Methods To Interpret Human Biomonitmentioning

confidence: 99%

“…Similarly, the TTC approach could be applied to a chemical to estimate a conservative level of tolerable external exposure, and a generic PBTK model such as that developed by Bartels et al [ 44 ] could be used to estimate a corresponding biomarker concentration for use as a screening value.…”

Section: Using Risk Assessment Methods To Interpret Human Biomonitmentioning

confidence: 99%

Development of Screening Tools for the Interpretation of Chemical Biomonitoring Data

Becker

Hays

Robison

et al. 2012

Journal of Toxicology

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“…As consequence, a pivotal challenge in IL research is the development of dependable models to relate the physicochemical and structural properties of ILs with their biological effects. These models include predictive quantitative structure–activity relationship (QSAR) models, molecular docking, structure–activity relationship (SAR) systems, read‐across models, physiology‐based pharmacokinetic models, and quantitative toxicity–toxicity relationship (QTTR) models . In addition to toxicity predictions, these models have been successful in forecasting various physicochemical properties of ILs, such as melting points, surface tensions, infinite dilution activity coefficients, viscosities, conductivities, solubilities, glass transition temperatures, and decomposition temperatures …”

Section: Computational Prediction Of the Toxicity Of Ionic Liquidsmentioning

confidence: 99%

An Overview on the Toxicological Properties of Ionic Liquids toward Microorganisms

Sivapragasam

Moniruzzaman

Goto

2020

Biotechnology Journal

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Ionic liquids (ILs), a class of materials with unique physicochemical properties, have been used extensively in the fields of chemical engineering, biotechnology, material sciences, pharmaceutics, and many others. Because ILs are very polar by nature, they can migrate into the environment with the possibility of inclusion in the food chain and bioaccumulation in living organisms. However, the chemical natures of ILs are not quintessentially biocompatible. Therefore, the practical uses of ILs must be preceded by suitable toxicological assessments. Among different methods, the use of microorganisms to evaluate IL toxicity provides many advantages including short generation time, rapid growth, and environmental and industrial relevance. This article reviews the recent research progress on the toxicological properties of ILs toward microorganisms and highlights the computational prediction of various toxicity models.

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“…Finally, it has been argued that Bayesian methods for PB-TK modelling have emerged as the best suited approaches, given the large amount of prior information they require (Bernillon and Bois, 2000). A number of applications of posterior Bayesian PB-TK modelling have been published on chloroform (Lyons et al, 2008), dichloromethane (David et al, 2006), methylmercury (Allen et al, 2007), nanoparticles (Péry et al, 2009), tetrachloroethylene (Chiu and Bois, 2006;Covington et al, 2007) and cadmium (Amzal et al, 2009;EFSA, 2009c (Bartels et al, 2012). PB-PK models have been shown to be of great help for a quantitative interpretation of human biomonitoring data to relate exposure to blood concentrations as exemplified with the NHANES biomonitoring data for cadmium (Clewell et al, 2008;Ruiz et al, 2010).…”

Section: Human Variabilitymentioning

confidence: 99%

Modern methodologies and tools for human hazard assessment of chemicals

2014

EFS2

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This scientific report provides a review of modern methodologies and tools to depict toxicokinetic and toxicodynamic processes and their application for the human hazard assessment of chemicals. The application of these methods is illustrated with examples drawn from the literature and international efforts in the field. First, the concepts of mode of action/adverse outcome pathway are discussed together with their associated terminology and recent international developments dealing with human hazard assessment of chemicals. Then modern methodologies and tools are presented including in vitro systems, physiologically-based models, in silico tools and OMICs technologies at the level of DNA/RNA (transcriptomics), proteins (proteomics) and the whole metabolome (metabolomics). Future perspectives for the potential applications of these modern methodologies and tools in the context of prioritisation of chemicals, integrated test strategies and the future of risk assessment are discussed. The report concludes with recommendations for future work and research formulated from consultations of EFSA staff, expert Panels and other international organisations.

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Development of PK- and PBPK-based modeling tools for derivation of biomonitoring guidance values

Cited by 15 publications

References 39 publications

Development of Screening Tools for the Interpretation of Chemical Biomonitoring Data

Development of Screening Tools for the Interpretation of Chemical Biomonitoring Data

An Overview on the Toxicological Properties of Ionic Liquids toward Microorganisms

Modern methodologies and tools for human hazard assessment of chemicals

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