Development of a generic lifelong physiologically based biokinetic model for exposome studies

Dimosthenis Α Sarigiannis; Spyros P Karakitsios; Evangelos Handakas; Alberto Gotti

doi:10.1016/j.envres.2020.109307

Development of a generic lifelong physiologically based biokinetic model for exposome studies

Environ Res. 2020 Jun:185:109307. doi: 10.1016/j.envres.2020.109307. Epub 2020 Feb 28.

Authors

Dimosthenis Α Sarigiannis¹, Spyros P Karakitsios², Evangelos Handakas³, Alberto Gotti⁴

Affiliations

¹ Aristotle University of Thessaloniki, Department of Chemical Engineering, Environmental Engineering Laboratory, University Campus, Thessaloniki, 54124, Greece; HERACLES Research Center on the Exposome and Health, Center for Interdisciplinary Research and Innovation, Balkan Center, Bldg. B, 10th km Thessaloniki-Thermi Road, 57001, Greece; School for Advanced Study (IUSS), Science, Technology and Society Department, Environmental Health Engineering, Piazza Della Vittoria 15, Pavia, 27100, Italy. Electronic address: denis@eng.auth.gr.
² Aristotle University of Thessaloniki, Department of Chemical Engineering, Environmental Engineering Laboratory, University Campus, Thessaloniki, 54124, Greece; HERACLES Research Center on the Exposome and Health, Center for Interdisciplinary Research and Innovation, Balkan Center, Bldg. B, 10th km Thessaloniki-Thermi Road, 57001, Greece.
³ Aristotle University of Thessaloniki, Department of Chemical Engineering, Environmental Engineering Laboratory, University Campus, Thessaloniki, 54124, Greece.
⁴ EUCENTRE, Via Adolfo Ferrata, 1, Pavia, 27100, Italy.

PMID: 32229354
DOI: 10.1016/j.envres.2020.109307

Abstract

The current study within the frame of the HEALS project aims at the development of a lifelong physiologically based biokinetic (PBBK) model for exposome studies. The aim was to deliver a comprehensive modelling framework for addressing a large chemical space. Towards this aim, the delivered model can easily adapt parameters from existing ad-hoc models or complete the missing compound specific parameters using advanced quantitative structure activity relationship (QSAR). All major human organs are included, as well as arterial, venous, and portal blood compartments. Xenobiotics and their metabolites are linked through the metabolizing tissues. This is mainly the liver, but also other sites of metabolism might be considered (intestine, brain, skin, placenta) based on the presence or not of the enzymes involved in the metabolism of the compound of interest. Each tissue is described by three mass balance equations for (a) red blood cells, (b) plasma and interstitial tissue and (c) cells respectively. The anthropometric parameters of the models are time dependent, so as to provide a lifetime internal dose assessment, as well as to describe the continuously changing physiology of the mother and the developing fetus. An additional component of flexibility is that the biokinetic processes that relate to metabolism are related with either Michaelis-Menten kinetics, as well as intrinsic clearance kinetics. The capability of the model is demonstrated in the assessment of internal exposure and the prediction of expected biomonitored levels in urine for three major compounds within the HEALS project, namely bisphenol A (BPA), Bis(2-ethylhexyl) phthalate (DEHP) and cadmium (Cd). The results indicated that the predicted urinary levels fit very well with the ones from human biomonitoring (HBM) studies; internal exposure to plasticizers is very low (in the range of ng/L), while internal exposure to Cd is in the range of μg/L.

Keywords: Lifelong generic PBBK; Physiology based biokinetic model; QSARs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Exposome*
Female
Humans
Kinetics
Plasticizers*
Pregnancy
Quantitative Structure-Activity Relationship
Xenobiotics

Substances

Plasticizers
Xenobiotics