The use of new approach methodologies for the environmental risk assessment of food and feed chemicals.

New Approach Methodologies (NAMs) provide tools for supporting both human and environmental risk assessment (HRA and ERA). This short review provides recent insights regarding the use of NAMs in ERA of food and feed chemicals. We highlight the usefulness of tiered methods supporting weight-of-evidence approaches in relation to problem formulation (i.e., data availability, time, and resource availability). In silico models, including quantitative structure activity relationship models, support filling data gaps when no chemical property or ecotoxicological data are available, and biologically-based models (e.g., toxicokinetic-toxicodynamic models, dynamic energy models, physiologically-based models and species sensitivity distributions) are applicable in more data rich situations, including landscape-based modelling approaches. Particular attention is given to provide practical examples to apply the approaches described in real-world settings. We conclude with future perspectives, with regards to the need for addressing complex challenges such as chemical mixtures and multiple stressors in a wide range of organisms and ecosystems.

Influence of the exposure concentration of dissolved cadmium on its organotropism, toxicokinetic and fate in Gammarus fossarum.

Information on the relationship between the exposure concentrations of metals and their biodistribution among organs remained scarce in invertebrates. The objective of this study was to investigate the effects of Cd concentration on the organotropism, toxico-kinetic and fate of this metal in different organs of gammarids exposed to dissolved radioisotope 109Cd. Gammarids male were exposed for 7 days to three environmental Cd concentrations (i.e. 4, 52 and 350 ng.L-1) before being placed in depuration conditions (i.e. uncontaminated water). At several sampling times, Cd concentrations were determined by 109Cd γ-counting in water, caeca, cephalon, gills, intestine and remaining tissues. Bioconcentration Factors (BCF) and Cd relative proportions in organs were calculated to assess the exposure concentration effect on the bioaccumulation capacities. The dependance of the organ-specific kinetic parameters to Cd water concentrations were estimated by fitting nested one-compartment toxico-kinetic (TK) models to both the accumulation and depuration data, by Bayesian inference. Then, for each Cd concentrations, the metal exchanges among organs over time were formalized by a multi-compartments TK model fitted to all organ data simultaneously. Our results highlighted that, at the end of the exposure phase, BCF and Cd relative proportions, in each organ, were not significantly modulated by water concentrations. Kinetically, Cd accumulation rates in all organs (except intestines) were depended on the exposure concentration, but not the elimination rates. The in vivo management of Cd (i.e. metal exchanges among organs) remained qualitatively unchanged according to exposure concentration. All these results also highlighted key role of that organs in the management of Cd: bioconcentration by caeca, storage by gills and main entry pathway by intestine. This study shows the interest of implementing TK approaches to test the effect of environmental factors on bioaccumulation, inter-organ exchanges and fate of contaminants in invertebrate body to enhance the understanding of the toxicity risk.

Organ-specific accumulation of cadmium and zinc in Gammarus fossarum exposed to environmentally relevant metal concentrations.

One of the best approaches for improving the assessment of metal toxicity in aquatic organisms is to study their organotropism (i.e., the distribution of metals among organs) through a dynamical approach (i.e., via kinetic experiments of metal bioaccumulation), to identify the tissues/organs that play a key role in metal regulation (e.g., storage or excretion). This study aims at comparing the organ-specific metal accumulation of a non-essential (Cd) and an essential metal (Zn), at their environmentally relevant exposure concentrations, in the gammarid Gammarus fossarum. Gammarids were exposed for 7 days to 109Cd- or 65Zn-radiolabeled water at a concentration of 52.1 and 416 ng.L-1 (stable equivalent), respectively, and then placed in clean water for 21 days. At different time intervals, the target organs (i.e., caeca, cephalons, intestines, gills, and remaining tissues) were collected and 109Cd or 65Zn contents were quantified by gamma-spectrometry. A one-compartment toxicokinetic (TK) model was fitted by Bayesian inference to each organ/metal dataset in order to establish TK parameters. Our results indicate: i) a contrasting distribution pattern of concentrations at the end of the accumulation phase (7th day): gills > caeca ≈ intestines > cephalons > remaining tissues for Cd and intestines > caeca > gills > cephalons > remaining tissues for Zn; ii) a slower elimination of Cd than of Zn by all organs, especially in the gills in which the Cd concentration remained constant during the 21-day depuration phase, whereas Zn concentrations decreased sharply in all organs after 24 h in the depuration phase; iii) a major role of intestines in the uptake of waterborne Cd and Zn at environmentally relevant concentrations.

In Silico Methods for Environmental Risk Assessment: Principles, Tiered Approaches, Applications, and Future Perspectives.

This chapter aims to introduce the reader to the basic principles of environmental risk assessment of chemicals and highlights the usefulness of tiered approaches within weight of evidence approaches in relation to problem formulation i.e., data availability, time and resource availability. In silico models are then introduced and include quantitative structure-activity relationship (QSAR) models, which support filling data gaps when no chemical property or ecotoxicological data are available. In addition, biologically-based models can be applied in more data rich situations and these include generic or species-specific models such as toxicokinetic-toxicodynamic models, dynamic energy budget models, physiologically based models, and models for ecosystem hazard assessment i.e. species sensitivity distributions and ultimately for landscape assessment i.e. landscape-based modeling approaches. Throughout this chapter, particular attention is given to provide practical examples supporting the application of such in silico models in real-world settings. Future perspectives are discussed to address environmental risk assessment in a more holistic manner particularly for relevant complex questions, such as the risk assessment of multiple stressors and the development of harmonized approaches to ultimately quantify the relative contribution and impact of single chemicals, multiple chemicals and multiple stressors on living organisms.

One and multi-compartments toxico-kinetic modeling to understand metals' organotropism and fate in Gammarus fossarum.

The use of freshwater invertebrates for biomonitoring has been increasing for several decades, but little is known about relations between external exposure concentration of metals and their biodistribution among different tissues. One and multi-compartments toxicokinetic (TK) models are powerful tools to formalize and predict how a contaminant is bioaccumulated. The aim of this study is to develop modeling approaches to improve knowledge on dynamic of accumulation and fate of Cd and Hg in gammarid's organs. Gammarids were exposed to dissolved metals (11.1 ± 1.2 µg.L-1 of Cd or 0.27 ± 0.13 µg.L-1 of Hg) before a depuration phase. At each sampling days, their organs (caeca, cephalon, intestine and remaining tissues) were separated by dissection before analyses. Results allowed us to determine that i) G.fossarum takes up Cd as efficiently as the mussel M.galloprovincialis, but eliminates it more rapidly, ii) organs which accumulate and depurate the most, in terms of concentrations, are caeca and intestine for both metals; iii) the one-compartment TK models is the most relevant for Hg, while the multi-compartments TK model allows a better fit to Cd data, demonstrating dynamic transfer of Cd among organs.