Aude RATIER

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Research interests

Development of a PBPK model for PFOS and PFOA in mother, foetus and child

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.

Toxicokinetic modelling for Environmental Risk Assessment

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)

Ph.D project: Toxicokinetic modelling of the bioaccumulation of persistent organic compounds in benthic freshwater invertebrates.

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.

Work experiences

Education and training

Language skills and Software

• French: mother tongue

• English: professional

• Italian: academic

• Software: LaTex, MCSim, R, Shiny, Inkscape, ArcGis

Recent publications

• 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