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Cellular toxicity associated with exposure to perfluorinated carboxylates (PFCAs) and their metabolic precursors.

Publication ,  Journal Article
Rand, AA; Rooney, JP; Butt, CM; Meyer, JN; Mabury, SA
Published in: Chemical research in toxicology
January 2014

The biotransformation of fluorotelomer based compounds yields saturated and unsaturated fluorotelomer aldehydes (FTALs and FTUALs, respectively) and carboxylic acids (FTCAs and FTUCAs, respectively) as intermediate metabolites that subsequently transform to perfluorinated carboxylic acids (PFCAs). Previous studies have demonstrated that the FTCAs and FTUCAs are 1 to 5 orders of magnitude more toxic than PFCAs after exposure to aquatic organisms. Additionally, FTUALs have demonstrated reactivity with proteins, which may be associated with toxicity through the inhibition of protein function. The purpose of this study was to carry out a comprehensive assessment of the relative toxicity between PFCAs and their intermediate precursor metabolites: the FTALs, FTUALs, FTCAs, and FTUCAs. Analytes were separately incubated with human liver epithelial (THLE-2) cells to assess how varying the functional group and the fluorinated chain length affects cell viability. For each analyte, dose-response EC50 values were calculated. The EC50 values for FTUCAs and FTCAs were similar, with values ranging from 22 ± 9 and 24 ± 9 μM for the 10:2 congeners to 1004 ± 20 and 1004 ± 24 μM for the 4:2 congeners, respectively. The EC50 values for the PFCAs ranged from 65 ± 41 (PFDA) to 1361 ± 146 (PFBA) μM. The range of toxicity between PFCAs and their acid precursors were similar. However, the comparative toxicity between the 6:2 and 8:2 congeners and their corresponding PFCA had toxicity thresholds that varied depending on the functional headgroup, where FTUALs ≥ FTALs > FTUCAs ≥ FTCAs > PFCAs. For all PFCAs and acid precursors, toxicity depended on the length of the fluorinated chain, where the longer chain lengths yielded greater bioaccumulation and enhanced toxicity, results which agreed with those previously reported. By contrast, FTALs and FTUALs were the most toxic of all the analytes examined, where toxicity was enhanced at shorter chain lengths, with EC50 values of 7 ± 1 μM (6:2 FTUAL) and 8.6 ± 0.8 μM (6:2 FTAL). DNA adducts were not detectable for the aldehyde precursors, using a quantitative long-range PCR method. Our data provide the first evidence that aldehyde intermediates have demonstrated toxicity in cellular systems that is more significant than PFCAs and their corresponding acid intermediates.

Duke Scholars

Published In

Chemical research in toxicology

DOI

EISSN

1520-5010

ISSN

0893-228X

Publication Date

January 2014

Volume

27

Issue

1

Start / End Page

42 / 50

Related Subject Headings

  • Toxicology
  • Structure-Activity Relationship
  • Molecular Structure
  • Hydrocarbons, Fluorinated
  • Humans
  • Dose-Response Relationship, Drug
  • Cytotoxins
  • Cells, Cultured
  • Cell Survival
  • Aldehydes
 

Citation

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Rand, A. A., Rooney, J. P., Butt, C. M., Meyer, J. N., & Mabury, S. A. (2014). Cellular toxicity associated with exposure to perfluorinated carboxylates (PFCAs) and their metabolic precursors. Chemical Research in Toxicology, 27(1), 42–50. https://doi.org/10.1021/tx400317p
Rand, Amy A., John P. Rooney, Craig M. Butt, Joel N. Meyer, and Scott A. Mabury. “Cellular toxicity associated with exposure to perfluorinated carboxylates (PFCAs) and their metabolic precursors.Chemical Research in Toxicology 27, no. 1 (January 2014): 42–50. https://doi.org/10.1021/tx400317p.
Rand AA, Rooney JP, Butt CM, Meyer JN, Mabury SA. Cellular toxicity associated with exposure to perfluorinated carboxylates (PFCAs) and their metabolic precursors. Chemical research in toxicology. 2014 Jan;27(1):42–50.
Rand, Amy A., et al. “Cellular toxicity associated with exposure to perfluorinated carboxylates (PFCAs) and their metabolic precursors.Chemical Research in Toxicology, vol. 27, no. 1, Jan. 2014, pp. 42–50. Epmc, doi:10.1021/tx400317p.
Rand AA, Rooney JP, Butt CM, Meyer JN, Mabury SA. Cellular toxicity associated with exposure to perfluorinated carboxylates (PFCAs) and their metabolic precursors. Chemical research in toxicology. 2014 Jan;27(1):42–50.
Journal cover image

Published In

Chemical research in toxicology

DOI

EISSN

1520-5010

ISSN

0893-228X

Publication Date

January 2014

Volume

27

Issue

1

Start / End Page

42 / 50

Related Subject Headings

  • Toxicology
  • Structure-Activity Relationship
  • Molecular Structure
  • Hydrocarbons, Fluorinated
  • Humans
  • Dose-Response Relationship, Drug
  • Cytotoxins
  • Cells, Cultured
  • Cell Survival
  • Aldehydes