Comparison of Methods Used for Evaluation of Mutagenicity/Genotoxicity of Model Chemicals - Parabens

Jan Chrz, Barbora Hošíková, Lada Svobodová, Danuše Očadlíková, Hana Kolářová, Markéta Dvořaková, Kristina Kejlová, Lukáš Malina, Gabriela Jírova, Alena Vlková, Marika Mannerström

    Research output: Contribution to journalArticleScientificpeer-review

    Abstract

    Growing worldwide efforts to replace (reduce) animal testing and to improve alternative in vitro tests which may be more efficient in terms of both time, cost and scientific validity include also genotoxicity/mutagenicity endpoints. The aim of the review article was to summarize currently available in vitro testing approaches in this field, their regulatory acceptance and recommended combinations for classification of chemicals. A study using the combination of Comet Assay performed on two cell lines and the Chromosomal Aberration test on human peripheral lymphocytes was performed with the aim to predict the genotoxic potential of selected paraben esters, serving as a model chemical group. Parabens are widely used in consumer products as preservatives and have been reported to exhibit inconclusive results in numerous genotoxicity studies. The Comet Assay identified Ethylparaben and Benzylparaben as potentially genotoxic. The Chromosomal Aberration test revealed weak genotoxic potential in case of Ethylparaben and positive genotoxicity in case of Butylparaben, Propylparaben and Isopropylparaben. The main reasons for variability seem to be limited water solubility of parabens, determining their bioavailability at the cellular level, and absence of metabolic activation in the Comet Assay. The results confirmed that the Comet Assay should serve as a screening test and should not be used as a stand-alone method for classification of genotoxicity. The weight of evidence approach in risk assessment should be supported with data generated with the use of human relevant in vitro methods based on cells / tissues of human origin.

    Original languageEnglish
    Pages (from-to)S661-S679
    JournalPHYSIOLOGICAL RESEARCH
    Volume69
    DOIs
    Publication statusPublished - 2020
    Publication typeA1 Journal article-refereed

    Keywords

    • Alternative Toxicological Testing
    • Genotoxicity
    • in vitro Methods
    • Mutagenicity
    • Parabens
    • Test Batteries

    Publication forum classification

    • Publication forum level 1

    ASJC Scopus subject areas

    • Physiology

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