Evaluation of three physiologically based pharmacokinetic (PBPK) modeling tools for emergency risk assessment after acute dichloromethane exposure
Boerleider, R. Z.; Olie, J. D N; van Eijkeren, J. C H; Bos, P. M J; Hof, B. G H; de Vries, I.; Bessems, J. G M; Meulenbelt, J.; Hunault, C. C.
(2015) Toxicology Letters, volume 232, issue 1, pp. 21 - 27
(Article)
Abstract
Introduction: Physiologically based pharmacokinetic (PBPK) models may be useful in emergency risk assessment, after acute exposure to chemicals, such as dichloromethane (DCM). We evaluated the applicability of three PBPK models for human risk assessment following a single exposure to DCM: one model is specifically developed for DCM (Bos) and the
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two others are semi-generic ones (Mumtaz and Jongeneelen). Materials and methods: We assessed the accuracy of the models' predictions by simulating exposure data from a previous healthy volunteer study, in which six subjects had been exposed to DCM for 1. h. The time-course of both the blood DCM concentration and percentage of carboxyhemoglobin (HbCO) were simulated. Results: With all models, the shape of the simulated time course resembled the shape of the experimental data. For the end of the exposure, the predicted DCM blood concentration ranged between 1.52-4.19. mg/L with the Bos model, 1.42-4.04. mg/L with the Mumtaz model, and 1.81-4.31. mg/L with the Jongeneelen model compared to 0.27-5.44. mg/L in the experimental data. % HbCO could be predicted only with the Bos model. The maximum predicted % HbCO ranged between 3.1 and 4.2% compared to 0.4-2.3% in the experimental data. The % HbCO predictions were more in line with the experimental data after adjustment of the Bos model for the endogenous HbCO levels. Conclusions: The Bos Mumtaz and Jongeneelen PBPK models were able to simulate experimental DCM blood concentrations reasonably well. The Bos model appears to be useful for calculating HbCO concentrations in emergency risk assessment.
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Keywords: Biomarkers, Biotransformation, Carboxyhemoglobin, Computer Simulation, Environmental Monitoring, Healthy Volunteers, Humans, Inhalation Exposure, Methylene Chloride, Models, Biological, Risk Assessment, Risk Factors, Solvents, Tissue Distribution, Young Adult, Comparative Study, Evaluation Studies, Journal Article, Toxicology
ISSN: 0378-4274
Publisher: Elsevier BV
Note: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
(Peer reviewed)