Perfluorononanoate and Perfluorobutane Sulfonate Induce Cardiotoxic Effects in Zebrafish

Globally, per- and polyfluoroalkyl substances are common artificial ingredients in industrial and consumer products. Recently, they have been shown to be an emerging human health risk. Perfluorononanoic acid (PFNA)/perfluorononanoate and perfluorobutane sulfonic acid (PFBS)/perfluorobutane sulfonate cause reproductive toxicity and hepatotoxicity, disrupt thyroid functions, and damage embryonic development in zebrafish. However, the cardiotoxic effects of PFNA and PFBS have not been fully established. We found that PFNA and PFBS exposures repress hatchability while increasing malformation and mortality in zebrafish embryos. Hematoxylin and eosin staining as well as assessment of the transgenic zebrafish line Tg(myl7:nDsRed) revealed that exposure of embryos to PFNA increases the occurrence of severe cardiac malformations relative to exposure to PFBS. Moreover, we evaluated the differential expressions of cardiac development-associated genes in response to PFNA and PFBS, which validated the potential cardiotoxic effects, consistent with cardiac dysfunctions. Overall, our findings reveal novel cardiotoxic effects of PFNA and PFBS in zebrafish, implying that they may exert some cardiotoxic effect in humans. To the best of our knowledge, ours is the first study to show that PFNA exerts more severe cardiotoxic effects in zebrafish when compared with PFBS. Based on these findings, studies should evaluate the mechanisms of their cardiotoxic effects. Environ Toxicol Chem 2022;41:2527-2536. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.