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SETAC Barcelona Session Summaries
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Exposure and Effect Modeling and
Predictive Toxicology (Environment and Human) Session Summaries from SETAC Barcelona

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  • Rational Design of Chemicals and Pharmaceuticals and Other Input Prevention Measures Towards Sustainable Technological Development
    • Ester Papa (University of Insubria and Paris Diderot University), Joana Pereira (University of Aveiro), Klaus Kümmerer (University of Leuphana) and Sonia Ventura (University of Aveiro)
    • The aim of this session was to stimulate the interest of scientists working in industry, academia and regulatory fields toward the sustainable design and use of chemicals. It provided a multidisciplinary forum to exchange experiences gained within the application of the rational design of chemicals by in silico and experimental approaches, and it highlighted the importance of a better exchange among environmental scientists and organic green chemists to support environmentally sustainable technological development.

      The rational design of chemicals is a challenge for the scientific and regulatory community. It is useful to prevent hazardous substances from being developed and entering into the environment, as well as to build safer alternatives to existing hazardous chemicals. Additionally, the application of the rational design of chemicals can result in considerable budget savings in the chemical development processes, because only the solutions combining low potential for environmental hazard with specific beneficial properties would progress to further development and final regulatory assessment.

      Overall, the topics addressed in this session reflected experiences from academia and industry and proposed new and emerging approaches for rational design and re-design of chemicals, such as task-specific structures that need to comply with current environmental safety demands, and mixtures. Studies were performed on different groups of substances including ionic liquids, pharmaceuticals, fragrances, nanoparticles and biofuels.

      The presentations addressed the in silico prediction of different endpoints of toxicity, biodegradability as the criteria to design new “benign by design” chemicals, and safer alternatives to known emerging contaminants. Additionally, several posters addressed the experimental rational design of chemicals using different endpoints and species, and focused on nanomaterials, phenylureas and emerging contaminants.

      A session-specific poster corner was dedicated to ionic liquids, which have a wide range of applicability but have been recently highlighted for their potential ecotoxicity. Despite some successful applications of QSAR modeling, evidence also shows that the structural versatility of these chemicals is associated to the high variability in the related toxicological response (e.g., dependent on the biological system used), which makes modeling and experimental approaches a challenging task (as well as read across procedures likely unsuitable). The session was well attended (~100 persons) with the viewing of the posters and the poster corner also well supported by the conference attendees.

      Results presented at this session clearly indicated that new methods and approaches are currently being developed and applied to generate more sustainable chemicals and eco-friendly alternatives on the basis of in silico and experimental approaches. Additionally, comments from the audience highlighted the need to further promote the use of sustainable and green technologies into currently applied legislation for chemical management and assessment at an international level. Some comments also indicated the triggering of the industries’ interest in these alternative approaches to develop eco-friendlier chemicals.

      Authors’ contact information:,, and

  • Adverse Outcome Pathway Concept in Research and Risk Assessment: Exposure and Effect Modeling and Predictive Toxicology
    • Ksenia Groh (EAWAG), Tilman Gocht (University of Tübingen) and Knut Erik Tollefsen (NIVA)

      This session focused on the use of the adverse outcome pathway (AOP) concept in basic toxicological and ecotoxicological research, and on the application of AOPs in support of hazard and risk assessment. The presentations in this session had reemphasized and expanded on the three major themes particularly crucial for further research progress in the AOP field.

      AOPs provide a framework to collect and organize the knowledge on the progression of toxicity across different levels of biological organization, leading to adverse outcomes of regulatory relevance and on the predictive relationships between the events occurring at different levels.

      Two presentations discussed the practical tools and conceptual approaches that support AOP development. In particular, Steven Enoch described a chemoinformatics approach for chemical category formation based on structural alerts for mitochondrial toxicity. Such in silico methods promise to be of great use in defining the chemicals able to trigger a particular molecular initiating event. Geoffrey Hodges presented the outcomes from a recent workshop that discussed the roles of “-omics” data for enhancement of species sensitivity predictions and for supporting the extrapolation from molecular initiating events to population-relevant endpoints.

      AOPs provide a tool to critically assess the available knowledge and identify data gaps to guide further research.

      Mathieu Vinken presented an illustrative example, an AOP linking the inhibition of bile salt export pump to cholestatic injury and the experimental steps taken to validate this AOP. Gene expression analysis linked to an AOP allowed identification of potential additional key events that in turn themselves may lead the research towards the establishment of novel biomarkers for detection of cholestasis.

      Dries Knapen presented the usefulness of AOP framework for basic research. The AOP concept was applied to elucidate the mechanism of narcosis through defining specific types of membranes that can be targeted in this pathway. It was suggested that interpretation of non-specific mechanisms should be carried out within a specific and well-delineated biological context. This will likely improve the ability to develop the individual steps of the AOP continuum and assist in improving the accuracy of predictions made relying on AOP knowledge.

      Predictive relationships defined by AOPs provide the foundation for the use of alternative testing methods for hazard assessment. Currently, several groups are working on developing quantitative AOPs as these are intuitively the most useful for application in predictive toxicology. However, the maturation process from a qualitative to a quantitative AOP is commonly associated with various challenges.

      Luigi Margiotta-Casaluci provided an example of synthetic glucocorticoid effects in fish. The insight into the approaches for obtaining experimental data necessary for development of quantitative AOPs was enlightening. He demonstrated that chemicals with similar in vitro profiles can sometimes lead to largely different effects in vivo, emphasizing that it is important to consider both chemical-specific toxicokinetic profiles as well as potential polypharmacology (i.e., different AOPs triggered by the same chemical).

      Daniel Villeneuve provided another example of AOP application in predictive ecotoxicology. He described the development of a quantitative AOP linking aromatase inhibition to impaired reproduction in fish. Using a case study, the paper addressed the question “How close are we to making quantitative predictions of in vivo adverse outcomes based purely on in vitro data?” A computational model was built, and its predictions of reproductive output, made using in vitro data from ToxCast assays for aromatase inhibition, were compared to experimental measurements of fecundity in fathead minnows. Although overall this approach appeared promising, several limitations were identified especially for quantitative predictions at low effect concentrations. While currently this computational model is being further optimized, it can be concluded that model results are strongly influenced by a number of variables including the type of input data used for estimating toxicity equivalents, the model parameters and model construct itself. Furthermore, the models should be tested against a variety of exposure scenarios, and chemical-specific toxicokinetics should be accounted for when used for quantitative predictions.

      When developing quantitative AOPs, careful consideration should be given to prioritize the activities that provide the greatest return of value since these research and development costs can be high. However, not all AOPs would need to be fully quantitative. As has been demonstrated in this session, simple qualitative AOPs are often able to support hazard evaluation and risk assessment efforts.

      Authors’ contact information:, and

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