Drafting Molecular Ecotoxicology and Omics Perspectives: Session Highlights from SETAC Europe 2025

Ksenia Groh, Eawag; Sebastian Eilebrecht, Fraunhofer IME; Denina Simmons, Ontario Tech University; Pedro A. Inostroza, RWTH Aachen University

Held during the SETAC Europe 35th Annual Meeting, the session “Molecular Ecotoxicology and Omics Perspectives: Advancing Mechanistic Understanding for Environmental Risk Assessment” drew strong interest with two well-attended morning sessions, an afternoon poster corner and more than 40 posters on display.

Molecular tools and omics technologies, coupled with advances in bioinformatics, data science and systems biology, hold immense potential to provide major contributions to ecotoxicology and chemical risk assessment fields.

Understanding Gene Expression Regulation From Algae to Worm to Fish

Tim Godec, National Institute of Biology in Slovenia, worked with a library of approximately 11,000 gene knockout mutants of green alga Chlamydomonas reinhardtii to identify genes involved in mediation of growth-related outcomes upon exposure to 15 chemicals. Although challenged by the high batch-to-batch variability, this study was able to demonstrate that chemicals with shared modes of action caused similar molecular responses. While several genes were identified that could play an important role in tolerance and susceptibility to chemical exposure, the limited functional annotation available for plants precluded the identification of precise mechanisms of toxicity.

Siyeol Ahn, University of Seoul, shared the outcomes of an RNA interference (RNAi)-based study used to screen the activity of 384 transcription factors in Caenorhabditis elegans exposed to tetrabromobisphenol A (TBBPA). While 19% of screened transcription factors were found to be potentially involved in effects on locomotion, the authors identified nuclear receptor (NR) transcription pathway(s) and retinoic acid signaling as being potentially involved in TBBPA’s mechanism of toxicity.

A poster spotlight by Sven Mosimann, Eawag, drew attention to a combination of RNA- and RIBOseq experiments carried out to explore the mechanisms behind the reduced cell proliferation in a permanent cell line derived from rainbow trout gills, RTgill-W1. Upon exposure to six different chemicals, several genes were identified as regulated differently at the level of transcription and translation. Ongoing analyses explore the underlying molecular mechanisms and the points of pathway convergence leading to cell cycle arrest.

Transcriptomics, Metabolomics and Lipidomics Analyses Across Trophic Levels

A study presented by Vera Slaveykova, University of Geneva, showed how data on algae physiology, metabolite analysis, sub-cellular distribution and intracellular speciation of mercury can be integrated to reveal species-specific responses and gain new insights into metabolic reprogramming in mercury-exposed phytoplankton.

Emily Rose DeTemple, Indiana University, presented a study that combined life history, transcriptomics and metabolomics analyses to explore the individual and interactive effects of nutritional status and arsenic toxicity in Daphnia pulex.

Mathieu Lutier, University of Oslo, presented his work on identifying the tipping points in the lipidome of Arctic zooplankton under ocean acidification, using a method developed to assess over 500 lipid compounds. Approaching the tipping points, an increase in variability was observed with decreasing stability of the ecosystem.

Joao Eduardo Aleixo Rodrigues, University of Aveiro, also identified lipidomics as an important endpoint to be addressed in the future studies, but during the current session, he presented metabolomics analyses which revealed gender-specific responses of Gammarus locusta to simvastatin. That is, females were found to transfer metabolic adaptations to unexposed generation (F3), while males showed effects only upon direct exposure.

Corey Green, Eastern New Mexico University, used metabolomics to study molecular mechanisms underlying eye tremor phenotypes arising in zebrafish exposed to Aroclor 1254, linking to changes in the levels of neurotransmitter-related metabolites. A concomitant transcriptomic analysis identified dysregulation of genes involved in visual function, which could be used as novel biomarkers of polychlorinated biphenyls (PCBs) exposure in fish early life stages.

Gaetan Yannick Tucoo, University of Southern Denmark, highlighted a sensitive and selective detection method developed to explore the presence of vertebrate-like thyroid and steroid hormones in the snail Lymnaea stagnalis and indeed was able to detect some candidate compounds for further study.

Also on the topic related to endocrine disruption, Eunhye Kim, Seoul National University, studied the effects of chemicals released from biodegradable plastics, such as polybutylene adipate terephthalate (PBAT) and polylactic acid (PLA). Extracts from these plastics were found to cause differential expression of genes linked to sex hormone disruption in both the adult zebrafish and in vitro human cells model. While requiring further confirmation, these findings nonetheless underscore the need to subject biodegradable plastics to a similar scrutiny as conventional plastics with regard to their chemical safety.

Alexandra Loll from Fraunhofer IME, presented a project that aims to gather ecotoxicogenomic data of common artificial sweeteners for model organisms representing three different trophic levels. Interestingly, exposure to sucralose was found to significantly alter gene expression in the aquatic plant Lemna minor, even at low, environmentally relevant concentrations.

Focus on Transcriptomics as Versatile Technology for Use in Risk Assessment

Matthias Teigeler, Fraunhofer IME, provided a 101 introduction to using the transcriptomic Point of Departure (tPOD) as a method to derive quantitative threshold values from RNAseq data. In the example of tamoxifen effects in zebrafish, the tPOD derived with zebrafish embryos was found to be in the same order or magnitude but slightly more sensitive than the NOEC derived from a two-generation study. Thus, embryo-derived tPOD provided a conservative estimation of chronic toxicity, paving the way for a broader use of this alternative method to replace animal testing, in line with the 3R principles.

Along the same lines, Nil Basu, McGill University, presented a study that compared tPODs estimated in rainbow trout alevins using a high-throughput test method with the acute and chronic toxicity values derived from conventional fish toxicity tests. In all cases tested so far, and in agreement with results presented by Matthias Teigeler, tPOD values were found to be equally or more conservative than the values from chronic tests.

Two further presentations focused on the use of transcriptomics in diverse risk assessment applications. Steve Uwa Ayobahan, Fraunhofer IME, demonstrated transcriptomic fingerprinting of two pesticides in zebrafish embryos and daphnia, and discussed implications for species sensitivity and risk assessment. Fatma Marghany, Fraunhofer IME, showed how transcriptomics data can be used to anticipate and differentiate modes of actions of fungicides in non-target organisms such as fish.

Computational Approaches to Support Biological Interpretation of Omics Data

Ellis Franklin, Universite de Lorraine, presented a semi-automated tool called Cluefish (CLUstering, Enrichment and FISHing), developed to support exploration of transcriptomic data. The application of this tool was demonstrated on the example of dibutyl phthalate (DBP), where Cluefish provided superior results compared to other methods with regard to the proportion of interpreted data and identification of potentially overlooked disruption pathways.

Fotini Nikiforou, Aristotle University of Thessaloniki, put forward an integrative approach for development of adverse outcome pathways based on multiomics data collected in vitro, demonstrated for a case study of mapping metabolic syndrome genes in tributyltin-exposed adipocytes.

Lastly, Elise Billoir, Universite de Lorraine, CNRS, argued for the need to adopt dose-response (DR) design and modelling for omics data as this could improve mechanistic understanding of (multi)omic data and risk assessment. Applications she presented are implemented in a freely available R package called DRomics.

Proteomics Insights Into Effects of Radioactivity on Tree Frogs and of Antimicrobial Compounds on Fish

While most of the studies presented as part of this session used either transcriptomics or metabolomics, we were excited to hear the presentation by Sandrine Frelon, French Institute of Radiation Protection and Nuclear Safety, who shared the results of a large study that carried out proteomic analyses of the leg muscles from tree frogs collected from the Chernobyl Exclusion Zone. Despite the challenges of working with non-model species, the study was able to identify several disrupted pathways and showed that proteomics data can be used to determine benchmark dose. Some effects were observed below doses supposed to be safe based on laboratory assessments.

In addition, Raina Mackenzie Kerr Hubley, Ontario Tech University, presented a project applying proteomics analysis to mucus, plasma and tissues collected from fathead minnow exposed to a common quaternary ammonium-based disinfectant. The study identified dose-dependent dysregulation of proteins involved in, e.g., digestive system or nervous system disease pathways, and gill proteins were observed to show more sensitive responses than plasma proteins. The results obtained in the laboratory will be later compared to analyses performed in field-exposed fish, collected in the frame of a multi-year, whole-lake exposure study performed by the International Institute of Sustainable Development Experimental Lakes Area (IISD-ELA).

After SETAC Is Before SETAC

To keep the momentum, everyone is warmly invited to join the discussions in the SETAC Omics Interest Group, co-led by Sebastian Eilebrecht and David Beale. We also hope to see you next year at the SETAC Europe 36th Annual Meeting, which will be held from 17–21 May in Maastricht, the Netherlands.

Contact: [email protected]