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Advancing Chemical Risk Assessment through Human Physiology-Based Biochemical Process Modeling

1
HERACLES Research Center on the Exposome and Health, Center for Interdisciplinary Research and Innovation, Balkan Center, Bldg. B, 10th km Thessaloniki-Thermi Road, 57001 Thermi, Greece
2
Environmental Engineering Laboratory, Department of Chemical Engineering, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece
3
Environmental Health Engineering, Department of Science, Technology and Society, University School for Advanced Study (IUSS), Piazza della Vittoria 15, 27100 Pavia, Italy
*
Author to whom correspondence should be addressed.
Received: 30 September 2018 / Revised: 22 December 2018 / Accepted: 27 December 2018 / Published: 4 January 2019
(This article belongs to the Special Issue Experimental and Numerical Studies in Biomedical Engineering)
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Abstract

Physiology-Based BioKinetic (PBBK) models are of increasing interest in modern risk assessment, providing quantitative information regarding the absorption, metabolism, distribution, and excretion (ADME). They focus on the estimation of the effective dose at target sites, aiming at the identification of xenobiotic levels that are able to result in perturbations to the biological pathway that are potentially associated with adverse outcomes. The current study aims at the development of a lifetime PBBK model that covers a large chemical space, coupled with a framework for human biomonitoring (HBM) data assimilation. The methodology developed herein was demonstrated in the case of bisphenol A (BPA), where exposure analysis was based on European HBM data. Based on our calculations, it was found that current exposure levels in Europe are below the temporary Tolerable Daily Intake (t-TDI) of 4 μg/kg_bw/day proposed by the European Food Safety Authority (EFSA). Taking into account age-dependent bioavailability differences, internal exposure was estimated and compared with the biologically effective dose (BED) resulting from translating the EFSA temporary total daily intake (t-TDI) into equivalent internal dose and an alternative internal exposure reference value, namely biological pathway altering dose (BPAD); the use of such a refined exposure metric, showed that environmentally relevant exposure levels are below the concentrations associated with the activation of biological pathways relevant to toxicity based on High Throughput Screening (HTS) in vitro studies. View Full-Text
Keywords: biochemical processes; biokinetics; human biomonitoring; bisphenol A; exposure reconstruction; risk assessment biochemical processes; biokinetics; human biomonitoring; bisphenol A; exposure reconstruction; risk assessment
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Sarigiannis, D.; Karakitsios, S. Advancing Chemical Risk Assessment through Human Physiology-Based Biochemical Process Modeling. Fluids 2019, 4, 4.

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