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6356901 
Journal Article 
Evaluation of developmental toxicity, developmental neurotoxicity, and tissue dose in zebrafish exposed to GenX and other PFAS 
Gaballah, S; Swank, A; Sobus, JR; Howey, XM; Schmid, J; Catron, T; Mccord, J; Hines, E; Strynar, M; Tal, T 
2020 
Yes 
Environmental Health Perspectives
ISSN: 0091-6765
EISSN: 1552-9924 
128 
47005 
English 
BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are a diverse class of industrial chemicals with widespread environmental occurrence. Exposure to long-chain PFAS is associated with developmental toxicity, prompting their replacement with short-chain and fluoroether compounds. There is growing public concern over the safety of replacement PFAS.

OBJECTIVE: We aimed to group PFAS based on shared toxicity phenotypes.

METHODS: Zebrafish were developmentally exposed to 4,8-dioxa-3H-perfluorononanoate (ADONA), perfluoro-2-propoxypropanoic acid (GenX Free Acid), perfluoro-3,6-dioxa-4-methyl-7-octene-1-sulfonic acid (PFESA1), perfluorohexanesulfonic acid (PFHxS), perfluorohexanoic acid (PFHxA), perfluoro-n-octanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), or 0.4% dimethyl sulfoxide (DMSO) daily from 0-5 d post fertilization (dpf). At 6 dpf, developmental toxicity and developmental neurotoxicity assays were performed, and targeted analytical chemistry was used to measure media and tissue doses. To test whether aliphatic sulfonic acid PFAS cause the same toxicity phenotypes, perfluorobutanesulfonic acid (PFBS; 4-carbon), perfluoropentanesulfonic acid (PFPeS; 5-carbon), PFHxS (6-carbon), perfluoroheptanesulfonic acid (PFHpS; 7-carbon), and PFOS (8-carbon) were evaluated.

RESULTS: PFHxS or PFOS exposure caused failed swim bladder inflation, abnormal ventroflexion of the tail, and hyperactivity at nonteratogenic concentrations. Exposure to PFHxA resulted in a unique hyperactivity signature. ADONA, PFESA1, or PFOA exposure resulted in detectable levels of parent compound in larval tissue but yielded negative toxicity results. GenX was unstable in DMSO, but stable and negative for toxicity when diluted in deionized water. Exposure to PFPeS, PFHxS, PFHpS, or PFOS resulted in a shared toxicity phenotype characterized by body axis and swim bladder defects and hyperactivity.

CONCLUSIONS: All emerging fluoroether PFAS tested were negative for evaluated outcomes. Two unique toxicity signatures were identified arising from structurally dissimilar PFAS. Among sulfonic acid aliphatic PFAS, chemical potencies were correlated with increasing carbon chain length for developmental neurotoxicity, but not developmental toxicity. This study identified relationships between chemical structures and in vivo phenotypes that may arise from shared mechanisms of PFAS toxicity. These data suggest that developmental neurotoxicity is an important end point to consider for this class of widely occurring environmental chemicals. https://doi.org/10.1289/EHP5843. 
Index Medicus 
PFAS
• PFBS
     LitSearch: May 2019 - May 2020
          PubMed
• PFHxA
     LitSearch: May 2019 - May 2020
          PubMed
• PFHxS
     LitSearch: May 2019 - May 2020
          PubMed
• PFNA
     LitSearch: May 2019 - May 2020
          PubMed
• PFOA (335-67-1) and PFOS (1763-23-1)
     LitSearch: Feb 2019 - May 2020
          PubMed
     Literature Search Update (Apr 2019 - Sep 2020)
          PubMed
          WOS