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Comparison of zebrafish toxicity between different developmental windows of exposure to three environmentally relevant PFAS compounds
Citation:
Shankar, P., J. Cavallin, M. Ellman, S. Lasee, B. Blackwell, S. Vliet, C. LaLone, AND Dan Villeneuve. Comparison of zebrafish toxicity between different developmental windows of exposure to three environmentally relevant PFAS compounds. SETAC North America, Pittsburgh, PA, November 13 - 17, 2022. https://doi.org/10.23645/epacomptox.21554892
Impact/Purpose:
Poster presented to the Society of Environmental Toxicology and Chemistry (SETAC) annual meeting November 2022. Per and polyfluorinated alkyl substances (PFAS) are a class of chemicals of high concern with respect to potential effects on human health and/or ecosystems. Rapid, small scale, assays employing global gene expression measurements are being evaluated as a higher throughput method for providing toxicity information on PFAS, including potency and potential mode(s) of action. However, it is not clear how much differences in experimental design, such as the developmental stage, or time-period over which the test organisms are exposed may influence the results and the overall uncertainty in the information derived. The present study explores this question by exposing zebrafish to three well-studied PFAS over different developmental windows. Overt toxicity, effects on morphology and behavior, as well as effects on global gene expression are being examined. Results will provide EPA’s program offices and Regions with a better understanding of how data from ecological high throughput transcriptomics assays can best be employed in a tiered approach to assessing the hazards of PFAS or other contaminants of immediate and emerging concern.
Description:
The per- and polyfluoroalkyl substances (PFAS) are of significant global concern due to their highly ubiquitous and persistent nature, bioaccumulation in organisms, and potential toxicity. While studies have identified harmful effects of PFAS, little is known about how varying exposure length impacts chemical hazard. Zebrafish have emerged as a sensitive and high-throughput model for measuring toxicity associated with chemicals, including PFAS, in a relatively short span of time. The current study’s objective is to leverage zebrafish to explore effects of exposure to PFOS, PFOA, and PFHxS for 14 exposure lengths between 6 and 144 hours post fertilization (hpf). Zebrafish were exposed to eight concentrations of each PFAS chemical (0-100 uM), chlorpyrifos (positive control for behavior), and 0.33% DMSO (vehicle control) for varying lengths of time starting at 6, 24, 48, or 96 hpf, and ending at 24, 48, 96, 120, or 144 hpf. Morphology was assessed daily, zebrafish neurobehavioral responses to alternating dark and light cycles were measured at 120 hpf for windows ending at 120 or 144 hpf, and RNA was collected at the end of each window to investigate whole-animal transcriptomics. Daily 50% chemical renewal was conducted, and media was analyzed by liquid chromatography-mass spectrometry at each window’s beginning and end to validate exposure concentrations. Exposures ending at 24, 48 or 96 hpf did not lead to overt toxicity for any of the PFAS tested. When zebrafish were exposed to 100 uM PFOS, except for 96-120 hpf, significant mortality was observed at all exposure windows ending at 120 hpf. For windows 6-144 and 24-144 hpf, significant mortality at 144 hpf was identified at the two highest PFOS concentrations (100 and 35.16 uM). No significant mortality was observed following exposure to PFOA, PFHxS, or any other PFOS concentration. Currently, we are analyzing zebrafish morphology (hatching, growth, and swim bladder inflation) and behavior responses, and evaluating transcriptomic points of departure (tPOD) from whole-animal RNA. Results of this study will provide information on 1) the hazard to zebrafish associated with varying exposure lengths to select PFAS chemicals, and 2) the temporal variability associated with tPODs estimated under various exposure scenarios, specifically different exposure durations and at different zebrafish developmental stages. Contents of this abstract neither constitute, nor necessarily reflect, official USEPA policy.
URLs/Downloads:
DOI: Comparison of zebrafish toxicity between different developmental windows of exposure to three environmentally relevant PFAS compounds
SETAC2022_SHANKAR,PRARTHANA_ZFPFAS POSTER_2022OCT18.PDF (PDF, NA pp, 3078.934 KB, about PDF)