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A generic PBTK mode...
A generic PBTK model implemented in the MCRA platform : Predictive performance and uses in risk assessment of chemicals
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- Tebby, Cleo (author)
- French National Institute for Industrial Environment and Risks
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- van der Voet, Hilko (author)
- Wageningen University
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- de Sousa, Georges (author)
- TOXALIM Research Centre in Food Toxicology
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- Rorije, Emiel (author)
- National Institute for Public Health and the Environment (RIVM)
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- Kumar, Vikas (author)
- Rovira i Virgili University (URV)
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- de Boer, Waldo (author)
- Wageningen University
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- Kruisselbrink, Johannes W. (author)
- Wageningen University
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- Bois, Frédéric Y. (author)
- French National Institute for Industrial Environment and Risks
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- Faniband, Moosa (author)
- Lund University,Lunds universitet,Tillämpad masspektrometri inom miljömedicin,Forskargrupper vid Lunds universitet,Applied Mass Spectrometry in Environmental Medicine,Lund University Research Groups
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- Moretto, Angelo (author)
- University of Milan
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- Brochot, Céline (author)
- French National Institute for Industrial Environment and Risks
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(creator_code:org_t)
- Elsevier BV, 2020
- 2020
- English.
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In: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915. ; 142
- Related links:
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http://dx.doi.org/10...
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https://www.scienced...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Physiologically-based toxicokinetic (PBTK) models are important tools for in vitro to in vivo or inter-species extrapolations in health risk assessment of foodborne and non-foodborne chemicals. Here we present a generic PBTK model implemented in the EuroMix toolbox, MCRA 9 and predict internal kinetics of nine chemicals (three endocrine disrupters, three liver steatosis inducers, and three developmental toxicants), in data-rich and data-poor conditions, when increasingly complex levels of parametrization are applied. At the first stage, only QSAR models were used to determine substance-specific parameters, then some parameter values were refined by estimates from substance-specific or high-throughput in vitro experiments. At the last stage, elimination or absorption parameters were calibrated based on available in vivo kinetic data. The results illustrate that parametrization plays a capital role in the output of the PBTK model, as it can change how chemicals are prioritized based on internal concentration factors. In data-poor situations, estimates can be far from observed values. In many cases of chronic exposure, the PBTK model can be summarized by an external to internal dose factor, and interspecies concentration factors can be used to perform interspecies extrapolation. We finally discuss the implementation and use of the model in the MCRA risk assessment platform.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Arbetsmedicin och miljömedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Occupational Health and Environmental Health (hsv//eng)
Keyword
- Mixtures
- Physiologically-based ToxicoKinetic (PBTK) model
- Probabilistic model
- Risk assessment
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Tebby, Cleo
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van der Voet, Hi ...
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de Sousa, George ...
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Rorije, Emiel
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Kumar, Vikas
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de Boer, Waldo
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Kruisselbrink, J ...
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Bois, Frédéric Y ...
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Faniband, Moosa
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Moretto, Angelo
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Brochot, Céline
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Pharmacology and ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Health Sciences
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and Occupational Hea ...
- Articles in the publication
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Food and Chemica ...
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Lund University