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3859704 
Journal Article 
Mixture-specific gene expression in zebrafish (Danio rerio) embryos exposed to perfluorooctane sulfonic acid (PFOS), perfluorohexanoic acid (PFHxA) and 3,3',4,4',5-pentachlorobiphenyl (PCB126) 
Blanc, M; Kärrman, A; Kukucka, P; Scherbak, N; Keiter, S 
2017 
Yes 
Science of the Total Environment
ISSN: 0048-9697
EISSN: 1879-1026 
590-591 
249-257 
English 
Perfluorooctane sulfonic acid (PFOS) and 3,3',4,4',5-pentachlorobiphenyl (PCB126) are persistent organic pollutants of high concern because of their environmental persistence, bioaccumulation and toxic properties. Besides, the amphiphilic properties of fluorinated compounds such as PFOS and perfluorohexanoic acid (PFHxA) suggest a role in increasing cell membrane permeability and solubilizing chemicals. The present study aimed at investigating whether PFOS and PFHxA are capable of modifying the activation of PCB126 toxicity-related pathways. For this purpose, zebrafish embryos were exposed in semi-static conditions to 7.5μg/L of PCB126 alone, in the presence of 25mg/L of PFOS, 15.7mg/L of PFHxA or in the presence of both PFOS and PFHxA. Quantitative PCR was performed on embryos aged from 24h post fertilization (hpf) to 96 hpf to investigate expression changes of genes involved in metabolism of xenobiotics (ahr2, cyp1a), oxidative stress (gpx1a, tp53), lipids metabolism (acaa2, osbpl1a), and epigenetic mechanisms (dnmt1, dnmt3ba). Cyp1a and ahr2 expression were significantly induced by the presence of PCB126. However, after 72 and 78h of exposure, induction of cyp1a expression was significantly lower when embryos were co-exposed to PCB126+PFOS+PFHxA when compared to PCB126-exposed embryos. Significant upregulation of gpx1a occurred after exposure to PCB126+PFHxA and to PCB126+PFOS+PFHxA at 30 and 48 hpf. Besides, embryos appeared more sensitive to PCB126+PFOS+PFHxA at 78 hpf: acaa2 and osbpl1a were significantly downregulated; dnmt1 was significantly upregulated. While presented as environmentally safe, PFHxA demonstrated that it could affect gene expression patterns in zebrafish embryos when combined to PFOS and PCB126, suggesting that such mixture may increase PCB126 toxicity. This is of particular relevance since PFHxA is persistent and still being ejected into the environment. Moreover, it provides additional information as to the importance to integrate mixture effects of chemicals in risk assessment and biomonitoring frameworks. 
Mixture toxicity; Molecular pathway; Zebrafish 
IRIS
• PCBs
     Litsearches
          LitSearch: August 2016-August 2017
               PubMed
               Toxline
               WoS
PFAS
• ^Per- and Polyfluoroalkyl Substances (PFAS)
     PFOA (335-67-1) and PFOS (1763-23-1)
          Literature Search – Adverse outcome pathway (2015-present)
               Pubmed
               WOS
     PFHxA (307-24-4)
          Literature Search
               Pubmed
               WOS
• PFBA
     Protocol References
• PFNA
     Literature Search
          Pubmed
          Toxline
     PFNA May 2019 Update
          Toxnet
• PFOA (335-67-1) and PFOS (1763-23-1)
     Literature Search – Adverse outcome pathway (2015-present)
          Pubmed
          WOS
     Screening Results
          Excluded/Not on Topic
     Literature Search Update (2013-2019)
          PubMed
          WOS