Comparative in vitro toxicity assessment of perfluorinated carboxylic acids

Cecon T. Mahapatra, Nur P. Damayanti, Samuel C. Guffey, Jennifer S. Serafin, Joseph Maria Kumar Irudayaraj, Maria S. Sepúlveda

Research output: Contribution to journalArticle

Abstract

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are synthetic fluorinated compounds that are highly bioaccumulative and persistent organic pollutants. Perfluorooctanoic acid (PFOA), an eight-carbon chain perfluorinated carboxylic acid, was used heavily for the production of fluoropolymers, but concerns have led to its replacement by shorter carbon chain homologues such as perfluorohexanoic acid (PFHxA) and perfluorobutanoic acid (PFBA). However, limited toxicity data exist for these substitutes. We evaluated the toxicity of PFOA, PFHxA and PFBA on a zebrafish liver cell line and investigated the effects of exposure on cell metabolism. Gross toxicity after 96 h of exposure was highest for PFOA and PFO, while PFHxA and PFBA exhibited lower toxicity. Although the structural similarity of these compounds to fatty acids suggests the possibility of interference with the transport and metabolism of lipids, we could not detect any differential expression of peroxisome proliferator-activated receptor (ppar-α, -β and -γ), fabp3 and crot genes after 96 h exposure to up to 10 ppm of the test compounds. However, we observed localized lipid droplet accumulation only in PFBA-exposed cells. To study the effects of these compounds on cell metabolism, we conducted fluorescence lifetime imaging microscopy using naturally fluorescent biomarkers, NADH and FAD. The fluorescence lifetimes of NADH and FAD and the bound/free ratio of each of these coenzymes decreased in a dose- and carbon length-dependent manner, suggesting disruption of cell metabolism. In sum, our study revealed that PFASs with shorter carbon chains are less toxic than PFOA, and that exposure to sublethal dosage of PFOA, PFHxA or PFBA affects cell metabolism.

Original languageEnglish (US)
Pages (from-to)699-708
Number of pages10
JournalJournal of Applied Toxicology
Volume37
Issue number6
DOIs
StatePublished - Jun 2017
Externally publishedYes

Fingerprint

perfluorooctanoic acid
Carboxylic Acids
Metabolism
Toxicity
Carbon
Flavin-Adenine Dinucleotide
NAD
Fluorescence
Lipids
Fluorine containing polymers
Peroxisome Proliferator-Activated Receptors
Organic pollutants
Poisons
Optical Imaging
Coenzymes
Biomarkers
Zebrafish
Lipid Metabolism
Liver
Microscopy

Keywords

  • Fluorescence Lifetime Imaging Microscopy
  • Liver
  • Perfluoroalkyl substances
  • Perfluorobutanoic acid
  • Perfluorohexanoic acid
  • Zebrafish

ASJC Scopus subject areas

  • Toxicology

Cite this

Mahapatra, C. T., Damayanti, N. P., Guffey, S. C., Serafin, J. S., Irudayaraj, J. M. K., & Sepúlveda, M. S. (2017). Comparative in vitro toxicity assessment of perfluorinated carboxylic acids. Journal of Applied Toxicology, 37(6), 699-708. https://doi.org/10.1002/jat.3418

Comparative in vitro toxicity assessment of perfluorinated carboxylic acids. / Mahapatra, Cecon T.; Damayanti, Nur P.; Guffey, Samuel C.; Serafin, Jennifer S.; Irudayaraj, Joseph Maria Kumar; Sepúlveda, Maria S.

In: Journal of Applied Toxicology, Vol. 37, No. 6, 06.2017, p. 699-708.

Research output: Contribution to journalArticle

Mahapatra, CT, Damayanti, NP, Guffey, SC, Serafin, JS, Irudayaraj, JMK & Sepúlveda, MS 2017, 'Comparative in vitro toxicity assessment of perfluorinated carboxylic acids', Journal of Applied Toxicology, vol. 37, no. 6, pp. 699-708. https://doi.org/10.1002/jat.3418
Mahapatra, Cecon T. ; Damayanti, Nur P. ; Guffey, Samuel C. ; Serafin, Jennifer S. ; Irudayaraj, Joseph Maria Kumar ; Sepúlveda, Maria S. / Comparative in vitro toxicity assessment of perfluorinated carboxylic acids. In: Journal of Applied Toxicology. 2017 ; Vol. 37, No. 6. pp. 699-708.
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AB - Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are synthetic fluorinated compounds that are highly bioaccumulative and persistent organic pollutants. Perfluorooctanoic acid (PFOA), an eight-carbon chain perfluorinated carboxylic acid, was used heavily for the production of fluoropolymers, but concerns have led to its replacement by shorter carbon chain homologues such as perfluorohexanoic acid (PFHxA) and perfluorobutanoic acid (PFBA). However, limited toxicity data exist for these substitutes. We evaluated the toxicity of PFOA, PFHxA and PFBA on a zebrafish liver cell line and investigated the effects of exposure on cell metabolism. Gross toxicity after 96 h of exposure was highest for PFOA and PFO–, while PFHxA and PFBA exhibited lower toxicity. Although the structural similarity of these compounds to fatty acids suggests the possibility of interference with the transport and metabolism of lipids, we could not detect any differential expression of peroxisome proliferator-activated receptor (ppar-α, -β and -γ), fabp3 and crot genes after 96 h exposure to up to 10 ppm of the test compounds. However, we observed localized lipid droplet accumulation only in PFBA-exposed cells. To study the effects of these compounds on cell metabolism, we conducted fluorescence lifetime imaging microscopy using naturally fluorescent biomarkers, NADH and FAD. The fluorescence lifetimes of NADH and FAD and the bound/free ratio of each of these coenzymes decreased in a dose- and carbon length-dependent manner, suggesting disruption of cell metabolism. In sum, our study revealed that PFASs with shorter carbon chains are less toxic than PFOA, and that exposure to sublethal dosage of PFOA, PFHxA or PFBA affects cell metabolism.

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