Modelling ecological and human exposure to POPs in Venice lagoon - Part II: Quantitative uncertainty and sensitivity analysis in coupled exposure models.

The study is focused on applying uncertainty and sensitivity analysis to support the application and evaluation of large exposure models where a significant number of parameters and complex exposure scenarios might be involved. The recently developed MERLIN-Expo exposure modelling tool was applied to probabilistically assess the ecological and human exposure to PCB 126 and 2,3,7,8-TCDD in the Venice lagoon (Italy). The 'Phytoplankton', 'Aquatic Invertebrate', 'Fish', 'Human intake' and PBPK models available in MERLIN-Expo library were integrated to create a specific food web to dynamically simulate bioaccumulation in various aquatic species and in the human body over individual lifetimes from 1932 until 1998. MERLIN-Expo is a high tier exposure modelling tool allowing propagation of uncertainty on the model predictions through Monte Carlo simulation. Uncertainty in model output can be further apportioned between parameters by applying built-in sensitivity analysis tools. In this study, uncertainty has been extensively addressed in the distribution functions to describe the data input and the effect on model results by applying sensitivity analysis techniques (screening Morris method, regression analysis, and variance-based method EFAST). In the exposure scenario developed for the Lagoon of Venice, the concentrations of 2,3,7,8-TCDD and PCB 126 in human blood turned out to be mainly influenced by a combination of parameters (half-lives of the chemicals, body weight variability, lipid fraction, food assimilation efficiency), physiological processes (uptake/elimination rates), environmental exposure concentrations (sediment, water, food) and eating behaviours (amount of food eaten). In conclusion, this case study demonstrated feasibility of MERLIN-Expo to be successfully employed in integrated, high tier exposure assessment.

[1]  Thomas J. Smith,et al.  Development of a physiologically based toxicokinetic model for butadiene and four major metabolites in humans: global sensitivity analysis for experimental design issues. , 2007, Chemico-biological interactions.

[2]  M. Jamei,et al.  PBPK modelling of inter-individual variability in the pharmacokinetics of environmental chemicals. , 2010, Toxicology.

[3]  Jon A Arnot,et al.  A quantitative structure‐activity relationship for predicting metabolic biotransformation rates for organic chemicals in fish , 2009, Environmental toxicology and chemistry.

[4]  Frank A. P. C. Gobas,et al.  Bioconcentration of hydrophobic chemicals in fish: Relationship with membrane permeation , 1986 .

[5]  A Opperhuizen,et al.  Bioconcentration of Hydrophobic Chemicals in Fish , 1986 .

[6]  Irina Olenina,et al.  Biovolumes and size-classes of phytoplankton in the Baltic Sea , 2006 .

[7]  R. Dawson,et al.  Sensitivity Analysis for Hydraulic Models , 2009 .

[8]  Thomas F Parkerton,et al.  Multimedia modeling of human exposure to chemical substances: The roles of food web biomagnification and biotransformation , 2010, Environmental toxicology and chemistry.

[9]  Christian Micheletti,et al.  Spatially distributed ecological risk for fish of a coastal food web exposed to dioxins , 2008, Environmental toxicology and chemistry.

[10]  Albert A Koelmans,et al.  Including sorption to black carbon in modeling bioaccumulation of polycyclic aromatic hydrocarbons: uncertainty analysis and comparison to field data. , 2007, Environmental science & technology.

[11]  Max D. Morris,et al.  Factorial sampling plans for preliminary computational experiments , 1991 .

[12]  Shuichi Hirono,et al.  A possible role of multidrug resistance-associated protein 2 (Mrp2) in hepatic excretion of PCB126, an environmental contaminant: PBPK/PD modeling. , 2008, Toxicological sciences : an official journal of the Society of Toxicology.

[13]  Rémy Beaudouin,et al.  A stochastic whole-body physiologically based pharmacokinetic model to assess the impact of inter-individual variability on tissue dosimetry over the human lifespan. , 2010, Regulatory toxicology and pharmacology : RTP.

[14]  Robert Spence,et al.  The Use of Sensitivity Analysis , 1997 .

[15]  J. Dearden,et al.  Predicting Fate-Related Physicochemical Properties , 2007 .

[16]  W. Meylan,et al.  Atom/fragment contribution method for estimating octanol-water partition coefficients. , 1995, Journal of pharmaceutical sciences.

[17]  Paola Gramatica,et al.  Metabolic biotransformation half-lives in fish: QSAR modeling and consensus analysis. , 2014, The Science of the total environment.

[18]  Sven Björkman,et al.  Comparative physiological pharmacokinetics of fentanyl and alfentanil in rats and humans based on parametric single-tissue models , 1994, Journal of Pharmacokinetics and Biopharmaceutics.

[19]  N Roth,et al.  Perspectives for integrating human and environmental exposure assessments. , 2016, The Science of the total environment.

[20]  H Harashima,et al.  Comparative tissue concentration profiles of fentanyl and alfentanil in humans predicted from tissue/blood partition data obtained in rats. , 1990, Anesthesiology.

[21]  Aaron T. Fisk,et al.  Dietary accumulation and depuration of hydrophobic organochlorines: Bioaccumulation parameters and their relationship with the octanol/water partition coefficient , 1998 .

[22]  M E Andersen,et al.  A physiologically based pharmacokinetic model for nicotine disposition in the Sprague-Dawley rat. , 1992, Toxicology and applied pharmacology.

[23]  Rajesh Seth,et al.  Estimating the Organic Carbon Partition Coefficient and Its Variability for Hydrophobic Chemicals , 1999 .

[24]  H Christopher Frey,et al.  Characterizing Variability and Uncertainty in Exposure Assessments Improves Links to Environmental Decision-Making. , 2008, EM.

[25]  Stefano Tarantola,et al.  Global Uncertainty and Sensitivity Analysis and Neighbourhoods. , 2004 .

[26]  A. Saltelli,et al.  The role of sensitivity analysis in ecological modelling , 2007 .

[27]  J. Middelburg,et al.  Uncertainties in ecological, chemical and physiological parameters of a bioaccumulation model: implications for internal concentrations and tissue based risk quotients. , 2010, Ecotoxicology and environmental safety.

[28]  Cian O'Mahony,et al.  Assessing and reporting uncertainties in dietary exposure analysis: Mapping of uncertainties in a tiered approach. , 2015, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[29]  Frank A. P. C. Gobas,et al.  A Generic QSAR for Assessing the Bioaccumulation Potential of Organic Chemicals in Aquatic Food Webs , 2003 .

[30]  Andrea Saltelli,et al.  An effective screening design for sensitivity analysis of large models , 2007, Environ. Model. Softw..

[31]  L L Aylward,et al.  Application of pharmacokinetic modelling for 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure assessment£ , 2014, SAR and QSAR in environmental research.

[32]  Gemma Manache,et al.  Identification of reliable regression- and correlation-based sensitivity measures for importance ranking of water-quality model parameters , 2008, Environ. Model. Softw..

[33]  Frank A. P. C. Gobas,et al.  A review of bioconcentration factor (BCF) and bioaccumulation factor (BAF) assessments for organic chemicals in aquatic organisms , 2006 .

[34]  Antonio Marcomini,et al.  Modelling ecological and human exposure to POPs in Venice lagoon. Part I - Application of MERLIN-Expo tool for integrated exposure assessment. , 2016, The Science of the total environment.

[35]  Ralf Wieland,et al.  Analysing the parameter sensitivity of the agro-ecosystem model MONICA for different crops , 2015 .

[36]  Sang Hyun Lee,et al.  Octanol/water partition coefficients of ionic liquids , 2009 .

[37]  Ad M J Ragas,et al.  Parameter uncertainty in modeling bioaccumulation factors of fish , 2011, Environmental toxicology and chemistry.

[38]  J. Filser,et al.  Distribution and unspecific protein binding of the xenoestrogens bisphenol A and daidzein , 2002, Archives of Toxicology.

[39]  A. J. Hendriks,et al.  Allometric scaling of rate, age and density parameters in ecological models , 1999 .

[40]  S. Yalkowsky,et al.  Correlation and prediction of mass transport across membranes. I. Influence of alkyl chain length on flux-determining properties of barrier and diffusant. , 1972, Journal of pharmaceutical sciences.

[41]  A. Hendriks,et al.  The power of size. 1. Rate constants and equilibrium ratios for accumulation of organic substances related to octanol‐water partition ratio and species weight , 2001, Environmental toxicology and chemistry.

[42]  Andy Hart,et al.  Bayesian Modeling of Measurement Errors and Pesticide Concentration in Dietary Risk Assessments , 2009, Risk analysis : an official publication of the Society for Risk Analysis.

[43]  Stefano Tarantola,et al.  Sensitivity Analysis in Practice: A Guide to Assessing Scientific Models , 2004 .

[44]  C. Ciric,et al.  Use of sensitivity analysis to identify influential and non-influential parameters within an aquatic ecosystem model , 2012 .

[45]  Jürgen B. Bulitta,et al.  Physiologically Based Pharmacokinetics of Zearalenone , 2009, Journal of toxicology and environmental health. Part A.

[46]  H J Clewell,et al.  Variability of physiologically based pharmacokinetic (PBPK) model parameters and their effects on PBPK model predictions in a risk assessment for perchloroethylene (PCE). , 1993, Toxicology letters.

[47]  S. Björkman,et al.  Determination of the steady state tissue distribution of midazolam in the rat. , 1996, Journal of pharmaceutical sciences.

[48]  Marco Ratto,et al.  Global uncertainty and sensitivity analysis of a food‐web bioaccumulation model , 2009, Environmental toxicology and chemistry.

[49]  Ian T Cousins,et al.  Modelling PCB bioaccumulation in a Baltic food web. , 2007, Environmental pollution.

[50]  L S Birnbaum,et al.  Subchronic Exposure of [3H]- 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in female B6C3F1 mice: relationship of steady-state levels to disposition and metabolism. , 2001, Toxicological sciences : an official journal of the Society of Toxicology.

[51]  A. Hendriks,et al.  The power of size: A meta-analysis reveals consistency of allometric regressions , 2007 .

[52]  Jon A Arnot,et al.  Estimating metabolic biotransformation rates in fish from laboratory data , 2008, Environmental toxicology and chemistry.

[53]  Emi Nakashima,et al.  Analysis of Fasting Effect on Biperiden Distribution Kinetics in Rats. , 1991 .

[54]  A Critto,et al.  Assessment of ecological risk from bioaccumulation of PCDD/Fs and dioxin-like PCBs in a coastal lagoon. , 2007, Environment international.

[55]  Igor Linkov,et al.  Importance of Uncertainty and Variability to Predicted Risks from Trophic Transfer of PCBs in Dredged Sediments , 2002, Risk analysis : an official publication of the Society for Risk Analysis.

[56]  Zhipeng Bai,et al.  Human Exposure Assessment for Air Pollution. , 2017, Advances in experimental medicine and biology.

[57]  Igor Linkov,et al.  Model Uncertainty and Choices Made by Modelers: Lessons Learned from the International Atomic Energy Agency Model Intercomparisons † , 2003, Risk analysis : an official publication of the Society for Risk Analysis.

[58]  A. Saltelli,et al.  A quantitative model-independent method for global sensitivity analysis of model output , 1999 .