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Development of a Web-Based Toolbox to Support Quantitative In-Vitro-to-In-Vivo Extrapolations (QIVIVE) within Nonanimal Testing Strategies
- Source :
- Chemical Research in Toxicology, Chemical Research in Toxicology 34 (2021) 2, Chemical Research in Toxicology, 34(2), 460-472
- Publication Year :
- 2021
-
Abstract
- The goal of the present study was to develop an online web-based toolbox that contains generic physiologically based kinetic (PBK) models for rats and humans, including underlying calculation tools to predict plasma protein binding and tissue:plasma distribution, to be used for quantitative in-vitro-to-in-vivo extrapolations (QIVIVE). The PBK models within the toolbox allow first estimations of internal plasma and tissue concentrations of chemicals to be made, based on the logP and pKa of the chemicals and values for intestinal uptake and intrinsic hepatic clearance. As a case study, the toolbox was used to predict oral equivalent doses of in vitro ToxCast bioactivity data for the food additives methylparaben, propyl gallate, octyl gallate, and dodecyl gallate. These oral equivalent doses were subsequently compared with human exposure estimates, as a low tier assessment allowing prioritization for further assessment. The results revealed that daily intake levels of especially propyl gallate can lead to internal plasma concentrations that are close to in vitro biological effect concentrations, particularly with respect to the inhibition of human thyroid peroxidase (TPO). Estrogenic effects were not considered likely to be induced by the food additives, as daily exposure levels of the different compounds remained 2 orders of magnitude below the oral equivalent doses for in vitro estrogen receptor activation. Overall, the results of the study show how the toolbox, which is freely accessible through www.qivivetools.wur.nl, can be used to obtain initial internal dose estimates of chemicals and to prioritize chemicals for further assessment, based on the comparison of oral equivalent doses of in vitro biological activity data with human exposure levels.
- Subjects :
- Team Toxicology
010501 environmental sciences
Pharmacology
Toxicology
01 natural sciences
Article
03 medical and health sciences
chemistry.chemical_compound
In vivo
Toxicity Tests
Distribution (pharmacology)
Life Science
Animals
Humans
Propyl gallate
030304 developmental biology
0105 earth and related environmental sciences
0303 health sciences
Internet
Methylparaben
Biological activity
Dodecyl gallate
General Medicine
Orders of magnitude (mass)
High-Throughput Screening Assays
Kinetics
chemistry
Food Additives
Octyl gallate
Subjects
Details
- Language :
- English
- ISSN :
- 0893228X
- Volume :
- 34
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Chemical Research in Toxicology
- Accession number :
- edsair.doi.dedup.....98b1a552feffcd95be13faae35216cf1