Review of the zebrafish as a model to investigate per- and polyfluoroalkyl substance toxicity

The existence of thousands of per- and polyfluoroalkyl substances (PFAS) and evidence that some cause adverse health effects has created immense need to better understand PFAS toxicity and to move beyond one-chemical-at-a-time approaches to hazard assessment for this chemical class. The zebrafish model enables rapid assessment of large libraries of PFAS, powerful comparison of compounds in a single in vivo system, and evaluation across life stages and generations, and has led to significant advances in PFAS research in recent years. The focus of this review is to assess contemporary findings regarding PFAS toxicokinetics, toxicity and apical adverse health outcomes, and potential modes of action using the zebrafish model. Much of the peer-reviewed literature has focused on a small subset of PFAS structural subclasses, such as the perfluoroalkyl sulfonic acids and perfluoroalkyl carboxylic acids. However, recent data on more diverse PFAS structures are enabling prioritization of compounds of concern. Structure-activity comparisons and the utilization of modeling and 'omics technologies in zebrafish have greatly contributed to our understanding of the hazard potential for a growing number of PFAS and will surely inform our understanding and predictive capabilities for many more PFAS in the future.

Automated summary

The existence of thousands of PFAS with evidence of adverse health effects has raised the need for better understanding of PFAS toxicity beyond one-chemical-at-a-time approaches. The zebrafish model has enabled rapid assessment and comparison of PFAS compounds, leading to significant advances in PFAS research. This review focuses on assessing the toxicity and potential modes of action of PFAS using the zebrafish model, and recent data on diverse PFAS structures are enabling prioritization of compounds of concern.