Comparative cytotoxicity induced by parabens and their halogenated byproducts in human and fish cell lines

Abstract

Parabens are a group of para-hydroxybenzoic acid (p-HBA) esters widely used in pharmaceutical industries. Their safety is well documented in mammalian models, but little is known about their toxicity in non-mammal species. In addition, chlorinated and brominated parabens resulting from wastewater treatment have been identified in effluents. In the present study, we explored the cytotoxic effects (EC₅₀) of five parabens: methylparaben (MP), ethylparaben (EP), propylparaben (PP), butylparaben (BuP), and benzylparaben (BeP); the primary metabolite, 4-hydroxybenzoic acid (4-HBA), and three of the wastewater chlorinated/brominated byproducts on fish and human cell lines. In general, higher cytotoxicity was observed with increased paraben chain length. The tested compounds induced toxicity in the order of 4-HBA < MP < EP < PP < BuP < BeP. The halogenated byproducts led to higher toxicity with the addition of second chlorine. The longer chain-parabens (BuP and BeP) caused a concentration-dependent decrease in cell viability in fish cell lines. Intriguingly, the main paraben metabolite, 4-HBA, proved to be more toxic to fish hepatocytes than human hepatocytes by 100-fold. Our study demonstrated that the cytotoxicity of some of these compounds appears to be tissue-dependent. These observations provide valuable information for early cellular responses in human and non-mammalian models upon exposure to paraben congeners.

Keywords:

• Parabens
• halogenated byproducts
• cytotoxicity
• in vitro
• fish cell lines

Acknowledgements

The authors gratefully acknowledge Dr. Matteo Minghetti from Oklahoma State University for kindly providing the RTL-W1 cell line and Professor Niels C. Bols from the University of Waterloo for kindly allowing the use of this cell line in the present study. The authors appreciate the technical assistance of the Baylor University undergraduate students Sanjanaa Senthilkumar and Otoniel Zelaya as well as Grace V. Aquino from the Graduate Writing Center at Baylor University.

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

This research was funded by the C. Gus Glasscock, Jr. Fund of Excellence in Environmental Sciences at Baylor University.