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Comparing Transcriptomic Points of Departure to Apical Effect Concentrations For Larval Fathead Minnow Exposed to Chemicals with Four Different Modes Of Action

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Abstract

It is postulated that below a transcriptomic-based point of departure, adverse effects are unlikely to occur, thereby providing a chemical concentration to use in screening level hazard assessment. The present study extends previous work describing a high-throughput fathead minnow assay that can provide full transcriptomic data after exposure to a test chemical. One-day post-hatch fathead minnows were exposed to ten concentrations of three representatives of four chemical modes of action: organophosphates, ecdysone receptor agonists, plant photosystem II inhibitors, and estrogen receptor agonists for 24 h. Concentration response modeling was performed on whole body gene expression data from each exposure, using measured chemical concentrations when available. Transcriptomic points of departure in larval fathead minnow were lower than apical effect concentrations across fish species but not always lower than toxic effect concentrations in other aquatic taxa like crustaceans and insects. The point of departure was highly dependent on measured chemical concentration which were often lower than the nominal concentration. Differentially expressed genes between chemicals within modes of action were compared and often showed statistically significant overlap. In addition, reproducibility between identical exposures using a positive control chemical (CuSO4) and variability associated with the transcriptomic point of departure using in silico sampling were considered. Results extend a transcriptomic-compatible fathead minnow high-throughput assay for possible use in ecological hazard screening.

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Data Availability

All sequence data reported in this manuscript are accessible via the Gene Expression Omnibus (BioProject PRJNA104613).

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Acknowledgements

The authors thank M. Tapper and J. Harrill for comments on an earlier version of this manuscript, K. Jensen, J. Cavallin, L. Everett, L. Wehmas, and K. Vitense for technical discussions, and P. Schumann for assistance with uploading data to the Sequence Read Archive. This work is part of an Accelerating the Pace of Chemical Risk Assessment (APCRA) case study: “Transcriptomics-based points of departure for ecotoxicology—investigating the applicability of high-throughput transcriptomics data to inform quantitative hazard assessments for ecological species.” We thank our APCRA partners including C. Inglis, J. Prindiville, A. Nong, J. O’Brien, and F. Page-Lariviere.

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The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Great Lakes Toxicology and Ecology Division, US Environmental Protection Agency, US EPA GLTED, 6201 Congdon Blvd, Duluth, MN, 55804, USA

    Kevin Flynn, Emma Stacy & Daniel L. Villeneuve

  2. Oak Ridge Institute for Science and Education (ORISE) Research Participant, Great Lakes Toxicology and Ecology Division, US Environmental Protection Agency, Duluth, MN, 55804, USA

    Michelle Le, Monique Hazemi, Kendra Bush, John X. Hoang, Mackenzie Morshead & Kelvin Santana Rodriguez

  3. Great Lakes Toxicology and Ecology Division, US Environmental Protection Agency, Cincinnati, OH, 45220, USA

    Adam Biales, David C. Bencic, Robert Flick & John Martinson

  4. Biochemistry and Biotechnology Group, Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM, 87545, USA

    Brett R. Blackwell

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Contributions

Kevin Flynn contributed to Conceptualization, Methodology, Formal analysis, Investigation, Writing—Original Draft, Visualization, and Supervision. Michelle Le contributed to Methodology, Validation, Investigation, and Writing—Review & Editing. Monique Hazemi contributed to Methodology, Software, Formal analysis, Data Curation, and Writing—Review & Editing. Adam Biales contributed to Conceptualization, Resources, Writing—Review & Editing, and Supervision. David C. Bencic contributed to Methodology, Investigation, Resources, and Writing—Review & Editing. Brett R. Blackwell contributed to Methodology, Validation, Writing—Review & Editing, and Supervision. Kendra Bush contributed to Methodology, Validation, Investigation, and Writing—Review & Editing. Robert Flick contributed to Methodology, Investigation, Resources, and Writing—Review & Editing. John X. Hoang contributed to Investigation. John Martinson contributed to Software and Data Curation. Mackenzie Morshead contributed to Investigation. Kelvin Santana Rodriguez contributed to Investigation. Emma Stacy contributed to Methodology, Validation, Investigation, and Writing—Review & Editing. Daniel L. Villeneuve contributed to Conceptualization, Methodology, Formal analysis, Investigation, Writing—Original Draft, Visualization, and Supervision.

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Correspondence to Kevin Flynn.

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Flynn, K., Le, M., Hazemi, M. et al. Comparing Transcriptomic Points of Departure to Apical Effect Concentrations For Larval Fathead Minnow Exposed to Chemicals with Four Different Modes Of Action. Arch Environ Contam Toxicol (2024). https://doi.org/10.1007/s00244-024-01064-y

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