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Assessment of hepatotoxicity and dermal toxicity of butyl paraben and methyl paraben using HepG2 and HDFn in vitro models

Lookup NU author(s): Arathi Kizhedath, Dr Simon Wilkinson, Professor Jarka Glassey



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


© 2018 Elsevier Ltd Parabens, esters of parahydroxybenzoic acid, are widely used in cosmetic, food and pharmaceutical industries mainly for their antibacterial and fungicidal properties. Methyl paraben has shown very low toxicity in a wide range of in vitro and animal tests. However, butyl paraben and derivatives, such as isobutyl parabens, are classified as allergens and have been shown to induce toxic effects. In the present study the effects of exposure to methyl or butyl paraben (5-1000 μM) on cytotoxicity, oxidative stress, mitochondrial dysfunction and genotoxicity were measured in a hepatocarcinoma cell line (HepG2) and human dermal fibroblasts neonatal (HDFn). Butyl paraben caused a concentration dependent decrease (above 400 μM) in cell viability for both cell lines. Toxicity of butyl paraben observed appeared to be mediated via ATP depletion as seen from luminescence assays. Depletion of glutathione was also observed for higher concentrations of butyl paraben, which may indicate the involvement of oxidative stress. Methyl paraben, however, did not show any significant decrease in cell viability, reduction in ATP or glutathione levels in HepG2 and HDFn cell lines at the concentrations tested. In vitro studies based on human cell lines can provide information in the early stages of multitier paraben toxicity studies and can be combined with in vivo and ex vivo studies to build more comprehensive, scientifically sound strategies for paraben safety testing. The results obtained in this study could supplement existing in vivo toxicity data for defining more robust limits for human exposure.

Publication metadata

Author(s): Kizhedath A, Wilkinson S, Glassey J

Publication type: Article

Publication status: Published

Journal: Toxicology in Vitro

Year: 2019

Volume: 55

Pages: 108-115

Print publication date: 01/03/2019

Online publication date: 17/12/2018

Acceptance date: 12/12/2018

Date deposited: 13/12/2018

ISSN (print): 0887-2333

ISSN (electronic): 1879-3177

Publisher: Elsevier Ltd


DOI: 10.1016/j.tiv.2018.12.007


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643056European Commission