Biology subjects

Ratier, A.

Publications and source records attributed to Ratier, A..

5 recordsLinked to original sources

bioRxiv2022

Improvements in estimating bioaccumulation metrics in the light of toxicokinetics models and Bayesian inference

The surveillance of chemical substances in the scope of Environmental Risk Assessment (ERA) is classically performed through bio-assays from which data are collected and then analysed and/or modelled. Some analysis are based on the fitting of toxicokinetic (TK) models to assess the bioaccumulation capacity of chemical substances via the estimation of bioaccumulation metrics as required by regulatory documents. Given that bio-assays are particularly expensive and time consuming, it is of crucial importance to deeply benefit from all information contained in the data. By revisiting the calculation of bioaccumulation metrics under a Bayesian framework, this paper suggests changes in the way of characterising the bioaccumulation capacity of chemical substances. For this purpose, a meta-analysis of a data-rich TK database was performed, considering uncertainties around bioaccumulation metrics. Our results were statistically robust enough to suggest an additional criterion to the single median estimate of bioaccumulation metrics to assign a chemical substance to a given bioaccumulation capacity. Our proposal is to use the 75th percentile of the uncertainty interval of the bioaccumulation metrics, which revealed an appropriate complement for the classification of chemical substances (e.g., PBT (persistent, bioaccumulative and toxic) and vPvB (very persistent and very bioaccumulative) under the EU chemicals legislation). The 75% quantile proved its efficiency, similarly classifying 90% of the chemical substances as the conventional method.

pharmacology and toxicology↗

bioRxiv2021

rbioacc: an R-package to analyse toxicokinetic data

O_LI rbioacc is an R-package dedicated to the analysis of experimental data collected from bioaccumulation tests during which organisms are exposed to a chemical (exposure phase) and then put into a clean media (depuration phase). Internal concentrations are regularly measured over time all along the experiment. C_LIO_LI rbioacc provides ready-to-use functions to visualize and fully analyze such data. Under a Bayesian framework, this package fits a generic one-compartment toxicokinetic (TK) model automatically built from the data. It provides TK parameter estimates (appropriate uptake and elimination rates) and bioaccumulation metrics (e.g., BCF, BSAF, BMF). All parameter estimates, bioaccumulation metrics as well as predictions of internal concentrations into organisms are delivered with their uncertainty. C_LIO_LIBioaccumulation metrics are primarily provided in support of environmental risk assessment, in full compliance with regulatory requirements required to approve marketing applications of chemical substances. C_LIO_LIThis paper gives brief worked examples of the use of rbioacc from data collected through standard bioaccumulation tests, and publicly available within the scientific literature. These examples constitute step-by-step user-guides to analyze any new data set, uploaded in the right format. C_LI

ecology↗

bioRxiv2021

Generic solving of one-compartment toxicokinetic models

This paper gives the full analytical solution of the generic set of ordinary differential equations that define one-compartment toxicokinetic models. These models describe uptake and elimination processes taking place within living organisms when exposed to chemical substances. The models solved in this paper consider living organisms as a unique compartment, into which a parent compound enters via several possible exposure routes and from which it is eliminated as well as its potential metabolites. Benefiting from generic solutions of one-compartment toxicokinetic models is particularly useful when fitting them to experimental data, facilitating the writing of the inference algorithms leading to parameter estimates. Additionally, these models are of crucial interest in environmental risk assessment for the calculation of bioaccumulation metrics as required by regulators in support of decision making when they evaluate dossiers for marketing authorisation of active substances. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=129 SRC="FIGDIR/small/442956v2_ufig1.gif" ALT="Figure 1"> View larger version (18K): org.highwire.dtl.DTLVardef@1e8381org.highwire.dtl.DTLVardef@14b957forg.highwire.dtl.DTLVardef@143dc14org.highwire.dtl.DTLVardef@25c478_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO C_FIG

pharmacology and toxicology↗

bioRxiv2021

Accumulation-depuration data collection in support of toxicokinetic modelling

Regulatory bodies requires evaluation of bioaccumulation of chemicals within organisms with the objective to better assess risks linked to the toxicity of active substances. To this end, toxicokinetic (TK) data are particularly useful to relate the chemical exposure concentration to the accumulation and depuration processes happening within organisms. The bioaccumulative property of substances is quantified by bioaccumulation metrics obtained by fitting TK models to data collected from bioaccumulation tests. The internal concentrations of the studied substances are measured within organisms at regular time points during both accumulation and depuration phases, and their time course is captured by TK models thus providing bioaccumulation metrics. Still today, raw TK data remain difficult to access, as most of the time provided within papers in plots only. To increase accessibility to TK data, we present in this paper a wide collection of raw data sets extracted from the scientific literature in support of TK modelling to be performed with the MOSAICbioacc web application (https://mosaic.univ-lyon1.fr/bioacc/).

ecology↗

bioRxiv2021

Taking full advantage of modelling to better assess environmental risk due to xenobiotics

In the European Union, more than 100,000 man-made chemical substances are awaiting an environmental risk assessment (ERA). Simultaneously, ERA of chemicals has now entered a new era. Indeed, recent recommendations from regulatory bodies underline a crucial need for the use of mechanistic effect models, allowing assessments that are not only ecologically relevant, but also more integrative, consistent and efficient. At the individual level, toxicokinetic-toxicodynamic (TKTD) models are particularly encouraged for the regulatory assessment of pesticide-related risks on aquatic organisms. In this paper, we first propose a brief review of classical dose-response models to put into light the on-line MOSAIC tool offering all necessary services in a turnkey web platform whatever the type of data to analyze. Then, we focus on the necessity to account for the time-dimension of the exposure by illustrating how MOSAIC can support a robust calculation of bioaccumulation factors. At last, we show how MOSAIC can be of valuable help to fully complete the EFSA workflow regarding the use of TKTD models, especially with GUTS models, providing a user-friendly interface for calibrating, validating and predicting survival over time under any time-variable exposure scenario of interest. Our conclusion proposes a few lines of thought for an even easier use of modelling in ERA. Graphical art O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=82 SRC="FIGDIR/small/436474v3_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@d98a72org.highwire.dtl.DTLVardef@1066b4org.highwire.dtl.DTLVardef@c6eef3org.highwire.dtl.DTLVardef@71c528_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗