Couplage d’approches expérimentales et modélisatrices pour l'étude des mécanismes d'effet de perturbateurs endocriniens chez la limnée des étangs, Lymnaea stagnalis.

Plant protection products and biocides may contain chemicals that interfere with the endocrine system and consequently induce adverse effects on wildlife. Such chemicals are known as endocrine disruptors (EDs). To ensure a satisfactory protection level for aquatic molluscs a comprehensive understanding of endocrine disruption is needed. The Organisation for Economic Co-operation and Development supports the standardisation of toxicity tests guideline on mollusc reproductive toxicity, which is intended for environmental risk assessments purposes. This PhD thesis aimed at improving toxicity test protocols and data analysis tools to evaluate effects of chemicals on the great pond snail Lymnaea stagnalis. A suite of toxicity tests was conducted in which snails were exposed to putative androgens (tributyltin, triphenyltin, methyltestosterone), putative oestrogens (alkylphenols and ethynyloestradiol), and solvents. Resulting effects were evaluated using standard statistical approachesand/or a toxicokinetic-toxicodynamic (TKTD) model. Snails were sensitive to tributyltin and triphenyltin, while none of the oestrogenic chemicals and methyltestosterone significantly impacted animals at environmentally relevant concentrations. Triethylene glycol and acetone were the least harmful solvents. Further, the analysis of data from the tributyltin test with the TKTD model suggested a generic mechanism of action of the compound (i.e., not specific for EDs). The demonstration of endocrine disruption in L. stagnalis remained elusive and deserves further research. Finally, the thesis highlightLes produits phytosanitaires contiennent des molécules qui peuvent interférer avec le système endocrinien et induire des effets délétères sur les êtres vivants. Ce sont des perturbateurs endocriniens. Afin d’assurer un niveau de protection satisfaisant pour les mollusques aquatiques, une bonne compréhension des perturbations du système endocrinien est nécessaire. L’organisation pour le développement et la coopération économique s’est exprimée en faveur de la mise en place de protocoles standards d’écotoxicité chez les mollusques, notamment sur la reproduction, dans le cadre des processus d’évaluation du risque écologique et des autorisations de mise sur le marché de nouvelles molécules. Cette thèse vise à proposer des tests standards et des outils d’analyse afin d’évaluer les effets de substances chimiques chez un escargot d’eau douce, Lymnaea stagnalis. Une série de tests de toxicité a été conduite dans laquelle les limnées ont été exposées à des androgènes, des oestrogènes et dessolvants. Les effets observés ont été évalués à l’aide d’approches statistiques standards et d’un modèle de toxicokinétique-toxicodynamique (TKTD). Les limnées ont montré une sensibilité uniquement au tributyltin et triphényltin à des concentrations réalistes d’un point de vue environnemental. Le triéthylène glycol et l’acétone étaient les solvants les moins nocifs. De plus, le modèle TKTD suggère un mécanisme généraliste dans l’action du composé. La manifestation des perturbations endocriniennes chez L. Stagnalis restent évasives et nécessitent d’autres recherches. Enfin, la thèse a montré qu

Predictive models in ecotoxicology: Bridging the gap between scientific progress and regulatory applicability—Remarks and research needs

This paper concludes a special series of 7 articles (4 on toxicokinetic–toxicodynamic [TK–TD] models and 3 on quantitative structure-activity relationship [QSAR] models) published in previous issues of Integrated Environmental Assessment and Management (IEAM). The present paper summarizes the special series articles and highlights their contribution to the topic of increasing the regulatory applicability of effect models. For both TK–TD and QSAR approaches, we then describe the main research needs. The use of TK–TD models for describing sublethal effects must be better developed, particularly through the improvement of the dynamic energy budget (DEBtox) approach. The potential of TK–TD models for moving from lower (molecular) to higher (population) hierarchical levels is highlighted as a promising research line. Some relevant issues to improve the acceptance of QSAR models at the regulatory level are also described, such as increased transparency of the performance assessment and of the modeling algorithms, model documentation, relevance of the chosen target for regulatory needs, and improved mechanistic interpretability. Integr Environ Assess Manag 2019;00:000–000.</p

Predictive models in ecotoxicology : Bridging the gap between scientific progress and regulatory applicability

This special series is the outcome of the session "Predictive models in ecotoxicology: Bridging the gap between scientific progress and regulatory applicability," held at the 27th SETAC Europe annual meeting (Brussels, May 2017). In this foreword the rationale behind the special series, the reasons for proposing it, and its objectives are described briefly

Reproductive impacts of tributyltin (TBT) and triphenyltin (TPT) in the hermaphroditic freshwater gastropod Lymnaea stagnalis

Tributyltin (TBT) and triphenyltin (TPT) are emblematic endocrine disruptors, which have been mostly studied in gonochoric prosobranchs. Although both compounds can simultaneously occur in the environment, they have mainly been tested separately for their effects on snail reproduction. Because large discrepancies in experimental conditions occurred in these tests, the present study aimed at comparing the relative toxicity of TBT and TPT under similar laboratory conditions in the 0–600 ng Sn/L range. Tests were performed on the simultaneous hermaphrodite Lymnaea stagnalis, a freshwater snail in which effects of TPT were unknown. Survival, shell length and reproduction were monitored in a 21d semi-static test. Frequency of abnormal eggs was assessed as an additional endpoint. TPT hampered survival while TBT did not. Major effects on shell solidity and reproduction were observed for both compounds, reproductive outputs being more severely hampered by TBT than by TPT. Considering the frequency of abnormal eggs allowed increasing test sensitivity, since snail responses to TBT could be detected at concentrations as low as 19 ng Sn/L. However, the putative mode of action of the two compounds could not be deduced from the structure of the molecules or from the response of apical endpoints. Sensitivity of L. stagnalis to TBT and TPT was compared to the sensitivity of prosobranch molluscs with different habitats and different reproductive strategies

Investigating apical adverse effects of four endocrine active substances in the freshwater gastropod Lymnaea stagnalis

The hermaphroditic gastropod Lymnaea stagnalis is proposed as a candidate species for the development of OECD guidelines for testing of the reprotoxicity of chemicals, including endocrine active substances (EASs). Up to now, only a few putative EASs have been tested for their reproductive toxicity in this species. In this study, we investigate the effects of four EASs with different affinities to the vertebrate estrogen and androgen receptors (chlordecone as an estrogen; cyproterone acetate, fenitrothion and vinclozolin as anti-androgens) on the reproduction of L stagnalis in a 21-day semi-static test. Testosterone and 17 alpha-ethinylestradiol (EE2) were used as the reference compounds. The tested EASs had no significant effect on growth and survival at the tested concentration ranges (ng to mu g/L. Classical reproduction endpoints (i.e., oviposition and fecundity) were not responsive to the tested chemicals, except for chlordecone and 17 alpha-ethinylestradiol, which hampered reproduction from 19.6 mu g/L and 17.6 mu g/L, respectively. The frequency of polyembryonic eggs, used as an additional endpoint, demonstrated the effects of all compounds except EE2. The molecular pathways, which are involved in such reproduction impairments, remain unknown. Our results suggest that egg quality is a more sensitive endpoint as compared to other reproductive endpoints commonly assessed in mollusk toxicity tests. (C) 2014 Elsevier B.V. All rights reserved

Dynamic energy budgets in population ecotoxicology : applications and outlook

Most of the experimental testing in ecotoxicology takes place at the individual level, but the protection goals for environmental risk assessment are at the population level (or higher). Population modelling can fill this gap, but only models on a mechanistic basis allow for extrapolation beyond the conditions in the experimental tests. The life-history traits of individuals form the basis of population dynamics, and population modelling thus requires a proper understanding of the individual's behaviour. The dynamic energy budget (DEB) theory offers a flexible platform for the development of models at the individual level. Linking DEB models to population models can thus provide a mechanistic basis for extrapolation. Here, we provide a conceptual overview of DEB theory, with emphasis on its applications in ecotoxicology. Furthermore, we briefly review the applications in which a DEB-based individual model has been linked to structured population dynamics. Finally, we discuss some of the most important areas for further research in this context. © 2013 Elsevier B.V