Linking fate model in freshwater and PBPK model to assess human internal dosimetry of B(a)P associated with drinking water

Abstract

In the present study, we demonstrate an integrated modeling approach for predicting internal tissue concentrations of chemicals by coupling a multimedia environmental model and a generic physiologically based pharmacokinetic (PBPK) model. A case study was designed for a region situated on the Seine river watershed, downstream of the Paris megacity, and for benzo(a)pyrene emitted from industrial zones in the region. In this case study, these two models are linked only by water intake from riverine system for the multimedia model into human body for the PBPK model. The limited monitoring data sets of B(a)P concentrations in bottom sediment and in raw river water, obtained at the downstream of Paris, were used to re-construct long-term daily concentrations of B(a)P in river water. The re-construction of long-term series of B(a)P level played a key role for the intermediate model calibration (conducted in multimedia model) and thus for improving model input to PBPK model. In order to take into account the parametric uncertainty in the model inputs, some input parameters relevant for the multimedia model were given by probability density functions (PDFs); some generic PDFs were updated with site-specific measurements by a Bayesian approach. The results of this study showed that the multimedia model fits well with actual annual measurements in sediments over one decade. No accumulation of B(a)P in the organs was observed. In conclusion, this case study demonstrated the feasibility of a full-chain assessment combining multimedia environmental predictions and PBPK modeling, including uncertainty and sensitivity analyses.

Preliminary physiologically based pharmacokinetic models for benzo[a]pyrene and dibenzo[def,p]chrysene in rodents

“…parameter values) or the basis for its inclusion. Additional PBPK models for B[a]P in humans have been reported more recently (Chiang and Liao, 2006; Ciffroy et al , 2011), and while their structures and parameterization are better described, neither has been evaluated against pharmacokinetic data.…”

“…No PBPK models exist in the literature for DBC, despite its potency and potential transplacental carcinogenicity. The only published PBPK model for B[a]P in rodents is rudimentary (Roth and Vinegar, 1990), while those described for humans have not been evaluated against any pharmacokinetic data (Chiang and Liao, 2006; Ciffroy et al , 2011). …”

Interpreting PCB levels in breast milk using a physiologically based pharmacokinetic model to reconstruct the dynamic exposure of Italian women

“…Our modeling approach might then be improved by modeling other environmental media (such as soil, plants and animals) and their interactions to lead to a reduced uncertainty in the derived intake. 52 …”

The Use of a Physiologically Based Pharmacokinetic Modelling in a “Full-Chain” Exposure Assessment Framework: A Case Study on Urban and Industrial Pollution in Northern Italy

“…Among these, MERLIN-Expo software (https://merlin-expo.eu/, [2][3][4]) is a free tool developed within the 4FUN Project (funded by the EU 7th Framework Programme) created for Environmental Exposure Assessment (EEA) and Human Exposure Assessment (HEA). It models complex environmental phenomena and pollution pathways from the sources to their deposition and accumulation in human organs and tissues [5].…”