56 research outputs found

    Application of an integrated approach to evaluate health risks for toxic chemicals by linking multimedia environmental and PBPK models

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    The paradigm of health risk assessment may consist of two main pillars, i.e., the exposure and dose-response assessments. Human exposure to chemicals via multiple pathways can be estimated by environmental multimedia models, which calculate the distribution of chemicals in the component media, i.e., air, water, soil, plants, and animal media. Combined with the information about human behaviors such as dietary habits, time spent outside, and etc, the multimedia models can provide an estimation of the daily chemical intake by inhalation or ingestion by humans. Physiologically based pharmacokinetic (PBPK) models are used to estimate the body burden of toxic chemicals throughout the entire human lifespan, integrating the evolution of the physiology and anatomy from childhood to advanced aged. The use of such PBPK models overcomes the limitations that dose-response modelling holds, e.g., it simply determines the relationship between the dose and the probability of an effect. The European project 2-FUN (Full-chain and UNcertainty Approaches for Assessing Health Risks in FUture ENvironmental Scenarios) aims at improving the approaches currently used in exposure and dose-response assessments. According to the aim of that project, an environmental multimedia model and a generic PBPK model are coupled as an integrated tool (2-FUN tool) and built up on a platform system, Ecolego. This study presents here the first application of the integrated tool to perform the full-chain risk assessment of a chemical for human health, considering multiple exposure pathways of chemical via inhalation of out-door air, and ingestion of water and foods. For this application of the tool, a case study was designed based on the information available in a region situated on the Seine river watershed, downstream of the Paris megacity and Benzo(a)pyrene (B(a)P) was selected as a target chemical substance. This study focuses especially on the propagation of uncertainty and inter-individual variability along the modelling chain. A probabilistic simulation was then performed to identify the input parameters and exposure pathways sensitive to model outputs (e.g., internal effective concentrations in organs)

    Perspectives for integrating human and environmental risk assessment and synergies with socio-economic analysis

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    International audienceFor more than a decade, the integration of human and environmental risk assessment (RA) has become an attractive vision. At the same time, existing European regulations of chemical substances such as REACH (EC Regulation No. 1907/2006), the Plant Protection Products Regulation (EC regulation 1107/2009) and Biocide Regulation (EC Regulation 528/2012) continue to ask for sector-specific RAs, each of which have their individual information requirements regarding exposure and hazard data, and also use different methodologies for the ultimate risk quantification. In response to this difference between the vision for integration and the current scientific and regulatory practice, the present paper outlines five medium-term opportunities for integrating human and environmental RA, followed by detailed discussions of the associated major components and their state of the art. Current hazard assessment approaches are analyzed in terms of data availability and quality, and covering non-test tools, the integrated testing strategy (ITS) approach, the adverse outcome pathway (AOP) concept, methods for assessing uncertainty, and the issue of explicitly treating mixture toxicity. With respect to exposure, opportunities for integrating exposure assessment are discussed, taking into account the uncertainty, standardization and validation of exposure modeling as well as the availability of exposure data. A further focus is on ways to complement RA by a socio-economic assessment (SEA) in order to better inform about risk management options. In this way, the present analysis, developed as part of the EU FP7 project HEROIC, may contribute to paving the way for integrating, where useful and possible, human and environmental RA in a manner suitable for its coupling with SEA

    Perspectives for integrating human and environmental exposure assessments

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    Integrated Risk Assessment (IRA) has been defined by the EU FP7 HEROIC Coordination action as “the mutual exploitation of Environmental Risk Assessment for Human Health Risk Assessment and vice versa in order to coherently and more efficiently characterize an overall risk to humans and the environment for better informing the risk analysis process” (Wilks et al., 2015). Since exposure assessment and hazard characterization are the pillars of risk assessment, integrating Environmental Exposure assessment (EEA) and Human Exposure assessment (HEA) is a major component of an IRA framework. EEA and HEA typically pursue different targets, protection goals and timeframe. However, human and wildlife species also share the same environment and they similarly inhale air and ingest water and food through often similar overlapping pathways of exposure. Fate models used in EEA and HEA to predict the chemicals distribution among physical and biological media are essentially based on common properties of chemicals, and internal concentration estimations are largely based on inter-species (i.e. biota-to-human) extrapolations. Also, both EEA and HEA are challenged by increasing scientific complexity and resources constraints. Altogether, these points create the need for a better exploitation of all currently existing data, experimental approaches and modeling tools and it is assumed that a more integrated approach of both EEA and HEA may be part of the solution. Based on the outcome of an Expert Workshop on Extrapolations in Integrated Exposure Assessment organized by the HEROIC project in January 2014, this paper identifies perspectives and recommendations to better harmonize and extrapolate exposure assessment data, models and methods between Human Health and Environmental Risk Assessments to support the further development and promotion of the concept of IRA. Ultimately, these recommendations may feed into guidance showing when and how to apply IRA in the regulatory decision-making process for chemicals

    Acute-to-chronic species sensitivity distribution extrapolation

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    International audienceSeeking to make greater use of available data for risk assessment of substances, we constructed, for the situation in which chronic data are limited or even nonexistent but acute data are relatively large, an acute to chronic transformation (ACT) methodology based on the concept of species sensitivity distributions (SSDs). This ACT methodology uses a comparison of acute and chronic SSDs, separately for vertebrate data (with 22 substances) and for invertebrate data (with 15 substances). Rather than comparing an acute toxicity value with a chronic value, as when calculating an acute to chronic ratio (ACR), samples of acute and chronic data corresponding to the same category of species were compared. Starting from a sample of acute data, the ACT methodology showed relationships that enable the creation of a sample of predicted chronic values. This sample can then be used to calculate a predicted chronic hazardous concentration potentially affecting 5% of species (HC5%), just as with a sample of real chronic toxicity values. This ACT approach was tested on I I substances. For each substance, the real chronic HC5% and the predicted chronic HC5% were calculated and compared. The ratio between chronic HC5% and ACT HC5% was, on average, 1.6 and did not exceed 4.4 for the I I substances studied

    Effects of data manipulation and statistical methods on species sensitivity distributions

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    International audienceSpecies sensitivity distribution (SSD) methodology currently is used in environmental risk assessment to determine the predicted no-effect concentration (PNEC) of a substance in cases where a sufficient number of chronic ecotoxicological tests have been carried out on the substance, covering, for the aquatic environment with which we are concerned, three taxonomic groups: algae, invertebrates, and vertebrates. In particular, SSD methodology enables calculation of a hazardous concentration that is assumed to protect 95% of species (HC5). This approach is based on the hypothesis that the species for which results of ecotoxicological tests are known are representative, in terms of sensitivity, of the totality of the species in the environment, which raises a number of questions, both theoretical and practical. In this study, we compared various methods of constructing a species sensitivity-weighted distribution (SSWD). Each method is characterized by a different way of taking into account intraspecies variation and proportions of taxonomic groups (vertebrates, invertebrates, and algae), as well as by the statistical method of calculation of the HC5 and its confidence interval. Those methods are tested on 15 substances by using chronic no-observed-effect concentration data available in the literature. The choice of data (intraspecies variation and proportions between taxonomic groups) was found to have more effect on the value of the HC5 than the statistical method used to construct the distribution. The weight of each taxonomic group is the most important parameter for the result of the SSWD and letting literature references decide which proportions of data are used to construct it is not satisfactory

    Utilisation d'un échantillonneur passif (DGT) pour l'évaluation de la remobilisation des métaux dans les sédiments (expérimentation et modélisation)

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    Les enjeux écologiques, réglementaires et économiques imposent que des méthodologies robustes d évaluation des risques environnementaux des sédiments contaminés soient proposées aux gestionnaires et autres parties prenantes. Dans ce travail, nous avons développé une nouvelle démarche permettant d évaluer le transport et la mobilité des métaux dans les sédiments.La DGT (Diffusion Gradient in Thin films) est un échantillonneur passif capable de prélever le métal labile en solution et le métal remobilisable par la phase particulaire. Dans cette étude, un modèle original permettant l interprétation des cinétiques expérimentales de la DGT dans les sédiments appelé PRObabilistic multi-compartmental model for Finting DGT kinetics in Sediments (DGT-PROF) a été développé. Il considère la présence de deux pools de métal labile correspondants aux métaux labiles fortement et faiblement adsorbés sur la phase solide. La pertinence de l approche DGT-PROFS a été évaluée sur un panel de 34 sédiments artificiels constitués en laboratoire qui diffèrent par : la présence ou pas d hydroxydes de fer (goethite ou ferrihydrite), la présence ou pas d acides humiques, le type de contaminant (Cd ou Cu) et l âge de la contamination (8, 65 et 190 jours). Cette démarche permet aussi d évaluer l effet de ces paramètres sur la remobilisation des métaux dans les sédiments.Les résultats montrent que la capacité du sédiment à relarguer le métal dépend inversement du pH et de l âge de la contamination. La présence des hydroxydes de fer augmente significativement la capacité de la phase solide du sédiment à fixer le métal. Cependant, la présence des AH augmente la labilité des métaux vis-vis la DGT via la formation de complexes humiques mobiles.La complémentarité des ces deux outils (DGT et DGT-PROFS) a ensuite été confrontée à des mesures DGT effectuées sur des sédiments naturels provenant de différentes régions de France, et possédant des seuils de contamination en Cd, Ni, Pb et Mn très contrastés.Evaluation of the mobility and bioavailability of metals associated to sediments have an important economic issue for the management of contaminated sites. Therefore, environmental, economic and regulation issues require to have access to a robust methodologies for environmental risk assessment of contaminated sediments. In this work, we developed a new approach for assessing the transport and mobility of metals in sediments. Diffusive gradients in thin-films (DGT) is a dynamic in-situ measuring technique that assesses the kinetics of metal resupply from the solid phase to the pore water. In this study, an original model for the interpretation of DGT experimental kinetics in sediments called DGT-PROFS model was developed. It allow to quantify metal partitioning between two particulate pools, describing weak and strong interactions with metals. The relevance of the DGT / DGT-PROFS approach was evaluated in a variety of formulated sediments that differed in the presence or not of humic acids (HA) and/or iron hydroxides (i.e., goethite and ferrihydrite). The impact of the time after contamination of the solid phase (aging effect) was also evaluated. Also, this approach allows to evaluate the effect of these parameters on the remobilization of metals in sediments. The results showed that sediments capacity to release metals depends strongly on the pH, HA and the age of the contamination. Results interpretation by DGT-PROFS model show that in the presence of HA and absence of iron hydroxides, Cd is mainly associated with weak sites, while Cu is bound to strong sites. Similarly, in the presence of both iron hydroxides and HA, Cu appeared to be more heavily associated with the strong sites than did Cd. When the incubation time increased from 8 to 190 days, a proportion of Cd initially adsorbed onto weak sites transferred to the strong sites, suggesting that the adsorption of Cd on sediments is partially controlled by slow kinetic processes. The complementarity of these tools (DGT device and DGT-PROFS model) was then evaluated on natural sediments from different regions of France, and having contamination levels of Cd, Ni, Pb and Mn very contrasting.AIX-MARSEILLE3-Bib. élec. (130559903) / SudocSudocFranceF

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

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    International audienceIn 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
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