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Comparison of Apical Points of Departure to Transcriptomic Points of Departure in Fathead Minnow Exposures
Citation:
Le, M., K. Bush, K. Santana Rodriguez, M. Hazemi, Dan Villeneuve, AND K. Flynn. Comparison of Apical Points of Departure to Transcriptomic Points of Departure in Fathead Minnow Exposures. SETAC North America 42nd Annual Meeting, Portland, OR, November 14 - 18, 2021. https://doi.org/10.23645/epacomptox.17102648
Impact/Purpose:
Poster presented to the SETAC North America 42nd Annual Meeting November 2021. There is a need for short-term and cost effective high-throughput assays that can be used to evaluate chemical toxicity. Over the past decade, a number of mammalian studies have indicated short-term transcriptomics-based points of departure (PODs) are predictive of overt toxicity, often within a factor of 10 of the toxic concentrations from much longer tests. The present study generated transcriptomics-based points of departure (tPODs) for ten chemicals in fathead minnows (FHM) that were compared against available apical effect data from the ECOTOX knowledgebase, focusing on impacts on survival and growth. On-going research is extending these comparisons to additional chemicals and additional species to evaluate the hypothesis that high-throughput transcriptomics assays with aquatic organisms may be a viable alternative to traditional aquatic toxicity tests for ecological safety evaluations.
Description:
Each year, as the sheer amount of chemicals readily available to the market increases, so does the need for short-term and cost effective high-throughput assays that can be used to evaluate chemical potency and infer potential hazards to human health and/or ecosystems. Over the past decade, a number of mammalian studies have indicated short-term transcriptomics-based points of departure (PODs) are predictive of apical potency, often providing a POD that is within a factor of 10 of those derived from much longer-term tests. The present study generated transcriptomics-based points of departure (tPODs) for ten chemicals in fathead minnows (FHM). Larval FHM (6 days post-fertilization) were exposed to 12 concentrations per chemical, in a ½ log dilution series, for 24h in a 96 well plate format. Whole body RNA was extracted and then sequenced to evaluate whole transcriptome gene expression. Transcripts that exhibited a concentration-dependent response were subsequently fit to concentration-response models using BMDExpress2 software to determine benchmark doses. A tPOD was then calculated based on the 10th centile of the distribution of benchmark doses. Transcriptomics-based PODs for three metals, three selective serotonin reuptake inhibitors, and four neonicotinoid(like) insecticides were compared against available apical effect data from the ECOTOX knowledgebase, focusing on impacts on survival, growth, and reproduction. FHM tPODs were uniformly lower than in vivo effect concentrations reported for fish, with tPODs being up to 2 orders of magnitude lower (i.e., health protective). In contrast, FHM tPODs were not always lower than apical effect concentrations reported for invertebrates, suggesting the need to include additional taxa in a high-throughput transcriptomics-based screening program. On-going research is extending these comparisons to additional chemicals and additional species to evaluate the hypothesis that high-throughput transcriptomics assays with aquatic organisms may be a viable alternative to traditional aquatic toxicity tests for ecological safety evaluations. The contents of this abstract neither constitute, nor necessarily reflect, official US EPA policy.
URLs/Downloads:
DOI: Comparison of Apical Points of Departure to Transcriptomic Points of Departure in Fathead Minnow Exposures
[LE, MICHELLE] 2021 SETAC POSTER V3.PDF (PDF, NA pp, 500.394 KB, about PDF)