Péritox UMR-I-01
INERIS, MIV/TEAM
Parc ALATA, BP 2
5, rue Taffanel
60550 Verneuil en Halatte, France
Tel: +33 (0)344556596
Development of PBPK models to describe the fate of PFOS and PFOA within humans in order (i) to predict the internal dose of the active compound in targeted tissues and (ii) to estimate population exposures from biomonitoring data.
Today, there are no ready-to-use convenient tools in ecotoxicology to diagnose and predict the accumulation and effects of chemical substances on living organisms, accounting for exposure situations that are known to be complex (routes of exposure, metabolization processes, cocktail effects, etc.). Regarding plant protection products in marketing authorization applications, regulation No 283/2013 (EU) defines the data requirements for active substances with a bioaccumulation test on fish according to OECD Test guideline 305. This research presents new perspectives on the estimation of the bioaccumulation factors via an innovative ready-to-use web tool providing these factors, associated with their uncertainty to facilitate the daily work of regulators, but also of any user, by benefiting of a freely available and user-friendly on-line interface avoiding to invest into underlying mathematical and statistical technicalities. This tool, MOSAICbioacc, is available at https://mosaic.univ-lyon1.fr/bioacc, and can be used by any environmental scientists, ecotoxicologists or managers when accumulation-depuration data are collected and need to be easily and quickly analysed.
Development of the MOSAICbioacc web application (https://mosaic.univ-lyon1.fr/bioacc) and the associated R package rbioacc (co-worker)
The presence of chemicals in the aquatic environment raises the question of their toxicity to organisms. In environmental risk assessment, the effects of a contamination on organisms are evaluated in two steps. Firstly, the toxicokinetics (TK) of the compound of interest are studied, that is to establish the link between the exposure concentration and the bioaccumulated concentration by the organism. Secondly, a toxicodynamic (TD) study is carried out to establish the link between the concentration of the contaminant bioaccumulated in the body and its toxicity.
Bioaccumulation is a variable phenomenon, which depends on the physico-chemical properties of chemicals, the species considered and the environmental conditions. Mathematical tools, such as TK models, have been developed to explain this variability and seem to overcome this difficulty. Nevertheless, implementing such models entailed to unlock several limitations, such as estimating biotransformation rates and metabolites’ fate. Another current limitation of TK models lies in the assessment of uncertainty related to TK parameters.
This thesis has developed a generic model and inference framework for describing and simulating the bioaccumulation of persistent chemicals (hexachlorobiphenyl, hexabromocyclododecane, pentabromodiphenyl-ether, pyrene) by various freshwater benthic invertebrate species (an insect, Chironomus riparius, an amphipod, Gammarus fossarum, and a gastropod mollusk, Radix auricularia).
This thesis was based on a series of laboratory experiments, which provided bioaccumulation data suitable for model calibration, as well as for testing various hypotheses on exposure pathways. Model TK parameters are estimated through Bayesian inference, which simultaneously estimates all the parameters from all the available data, in order to obtain precisely the uncertainty around their value and the predictions of the model.
Each hypothesis tested on the basis of experimental data corresponds to a model, allowing then to compare the performance. These models provided an accurate estimate of the model parameters and their uncertainty. Overall, these models fit well the experimental data, except for HBCD. A biotransformation function was also successfully implemented on the basis of data from the literature (phytopharmaceuticals, drugs, PAH). In that case, Bayesian inference applied to the generic model yielded reduced uncertainty around the biotransformation rate compared to the original models which used classical inference.
This generic modelling and inference framework can be adapted to various species-contaminant pairs, and appears as an effective tool for describing contaminant kinetics, as well as for assessing the uncertainty related to model parameter estimation, or for predictions.
September 2021
November 2022
Postdoctoral fellow - Toxicokinetic modelling
Supervisor: Dr. Céline Brochot
INERIS - Predictive Modelling and Ecotoxicology Team
Verneuil-en-Halatte, France
PBPK modelling and statistical inference (Bayesian inference)
MCSim programming
Predictive toxicology
March 2020
August 2021
Postdoctoral fellow -Developing a calculation tool of bioaccumulation indicators within a regulatory framework - MOSAICbioacc
Supervisor: Prof. Sandrine Charles
CNRS UMR 5558, Biostatistics and Modelling for Health and Environment Department (LBBE) - Predictive Modelling and Ecotoxicology Team, Claude Bernard Lyon 1 University,
Villeurbanne, France
Modelling and statistical inference (Bayesian inference)
R programming (development of a Shiny application and an R package)
Predictive ecotoxicology knowledge
December 2016 December 2020
Ph.D. candidate - Toxicokinetic modelling of the bioaccumulation of persistent organic compounds in benthic freshwater invertebrates.
Supervisor: Dr. Olivier Geffard
French national research institute for agriculture, food and environment (INRAE) - RiverLy, Ecotoxicology laboratory
Villeurbanne, France
Development of a Bayesian approach applied to toxicokinetic (TK) models
Ecotoxicological bioassays on aquatic invertebrates
Chemical analyses (LC-MS/MS, GC-MS, GC-ECD)
November 2016 March 2015
Internship followed by project manager - Biomonitoring of the industrial port area of Fos-sur-Mer by lichens.
Eco-citizen Institute for Knowledge of Pollution (IECP)
Fos-sur-Mer, France
Monitoring and continuity of an environmental study
Biodiversity surveys, ICP-MS, HPLC-UV and GC-MS analyses
Statistical analyses
Publications and communications to citizens
April 2014
July 2014
Internship - Analysis of the degradation products of a pharmaceutical compound: furosemide
Ecole Polytechnique - Laboratory of molecular chemistry (LCM)
Palaiseau, France
Photochemistry experiments
Development of UPLC-MS methods for the analysis of furosemide and its degradation products
Determination of the structures of the degradation products of furosemide
Biological toxicity tests on furosemide and its degradation products Palaiseau, France
2016-2019
Ph.D in ecotoxicology - Toxicokinetic modelling of the bioaccumulation of persistent organic compounds in benthic freshwater invertebrates
Director: O. Geffard Co-directors: C. Lopes and M. Babut
Evolution, Ecosystems, Microbiology, Modeling (E2M2) school
University of Lyon, Claude Bernard Lyon 1 (Villeurbanne, France)
2013-2015
Master degree in chemical pollution and environmental management (PCGE)
Paris-Sud XI - Paris Saclay University (Orsay, France)
2010-2013
Bachelor’s degree in biology and chemistry. Option: chemistry
Paris-Sud XI - Paris Saclay University (Orsay, France)
French: mother tongue
English: professional
Italian: academic
Software: LaTex, MCSim, R, Shiny, Inkscape, ArcGis
Ratier, A., Casas, M., Grazuleviciene, R., Slama, R., Småstuen Haug, L., Thomsen, C., Vafeiadi, M., Wright, J., Zeman, F., Vrijheid, M., Brochot, C. Estimating the dynamic early life exposure to PFOA and PFOS of the HELIX children: Emerging profiles via prenatal exposure, breastfeeding, and diet, Environment International, 108621 (2024). https://doi.org/10.1016/j.envint.2024.108621
Ratier, A., Lopes, C., and Charles, S. (2022). Improvements in Estimating Bioaccumulation Metrics in the Light of Toxicokinetic Models and Bayesian Inference. Archives of Environmental Contamination and Toxicology. https://doi.org/10.1007/s00244-022-00947-2
Ratier, A., Baudrot, V., Kaag, M., Siberchicot, A., Lopes, C., Charles, S. (2022). rbioacc: An R-package to analyze toxicokinetic data. Ecotoxicology and Environmental Safety, 242. https://doi.org/10.1016/j.ecoenv.2022.113875
Astuto, M.C., Di Nicola, M.R., Tarazona, J.V., Devos, Y., Liem, A.K.D., Kass, G.E.N., Bastaki, M., Schoonjans, R., Maggiore, A., Charles, S., Ratier, A., Lopes, C., Gestin, O., Roncaglioni, A., Robinson, T., Carnesecchi, E., Dorne J.L.C.M. (2022). In Silico Methods for Environmental Risk Assessment: Principles, Tiered Approaches, Applications, and Future Perspectives. Chapter 23. Methods in Molecular Biology, 2425: 589-636. https://doi.org/10.1007/978-1-0716-1960-5_23
Ratier, A. and Charles, S. (2022). Accumulation-depuration data collection in support of toxicokinetic modelling. Scientific Data, 9, 130. https://doi.org/10.1038/s41597-022-01248-y
Charles, S., Ratier, A., Lopes, C. (2021). Generic solving of one-compartment toxicokinetic models. Journal of Exploratory Research in Pharmacology (accepted). Preprint: https://doi.org/10.1101/2021.05.06.442956
Charles, S, Ratier, A., Siberchicot, A., Baudrot, V., Lopes, C. (2021). Taking full advantage of modelling to better assess environmental risk due to xenobiotics-the all-in-one facility MOSAIC. Environmental Science and Pollution Research. https://doi.org/10.1007/s11356-021-15042-7
Ratier, A., Lopes, C., Multari, G., Mazerolles, V., Carpentier, P., Charles, S. (2021). New perspectives on the calculation of bioaccumulation metrics for active substances in living organisms. Integrated Environmental Assessment and Management. https://doi.org/10.1002/ieam.4439
Dron, J., Ratier, A., Austruy, A., Revenko, G., Chaspoul, F., Wafo, E. (2021). Effects of meteorological conditions and topography on PAHs and metal elements bioaccumulation variations in native lichens (Xanthoria parietina). Journal of Environmental Sciences 109:193-205. https://doi.org/10.1016/j.jes.2021.03.045
Ratier, A., Lopes, C., Geffard, O., Babut, M. (2021). The added value of Bayesian inference for estimating biotransformation rates of organic contaminants in aquatic invertebrates. Aquatic Toxicology 234:105811. https://doi.org/10.1016/j.aquatox.2021.105811
Ratier, A., Lopes, C., Charles, S. (2020). MOSAIC - Analyse de données d'écotoxicité en ligne: quoi de neuf ? Fiche thématique N°30 INRAE. https://www6.inrae.fr/ecotox/Productions/Fiches-thematiques/Fiche-thematique-N-30-decembre-2020
Ratier A. (2019). Modélisation toxico-cinétique de la bioaccumulation de composés organismes persistants par des invertébrés benthiques d'eau douce. Université de Lyon, France. Thesis. https://tel.archives-ouvertes.fr/tel-02612792/file/TH2019RatierAude.pdf
Ratier, A., Lopes, C., Labadie, P., Budzinski, H., Delorme, N., Quéau, H., Peluhet, L., Geffard, O., Babut, M. (2019). A Bayesian framework for estimating parameters of a generic toxicokinetic model for the bioaccumulation of organic chemicals by benthic invertebrates: proof of concept with PCB 153 and two freshwater species. Ecotoxicology and Environmental Safety 180:33-42. https://doi.org/10.1016/j.ecoenv.2019.04.080
Ratier, A., Dron, J., Revenko, G., Austruy, A., Dauphin, C.E., Chaspoul, F., Wafo, E. (2018). Characterization of atmospheric emission sources in lichen from metal and organic contaminant patterns. Environmental Science and Pollution Research 25:8364-8376. https://doi.org/10.1007/s11356-017-1173-x
Dron, J., Austruy, A., Agnan, Y., Ratier, A., Chamaret, P. (2016). Utilisation de la biosurveillance lichénique sur la zone industrialo-portuaire de Fos-sur-Mer : retour sur trois ans de suivi à l'échelle d'un territoire intercommunal. Pollution atmosphérique N°228. http://lodel.irevues.inist.fr/pollution-atmospherique/index.php?id=5392