Comparison of methods used for evaluation of mutagenicity/genotoxicity of model chemicals - parabens

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.

Comparative Analysis of Transcriptional Responses to Genotoxic and Non-Genotoxic Agents in the Blood Cell Model TK6 and the Liver Model HepaRG

“…The determination of the possible genotoxic potential of a chemical compound is an essential part of a toxicological evaluation. Currently, genotoxicity testing is performed using a battery of in vitro or in vivo tests [ 1 , 32 , 33 , 34 , 35 , 36 ]. The need for a test battery for genotoxicity arises from the limitations of individual test systems, as no single test is capable of detecting all genotoxic mechanisms.…”

Systems for Genetic Assessment of the Impact of Environmental Factors

“…The second approach [111,112,126] is based on the use of such test systems as: 1) Bacterial Reverse Mutation Test (TG471); 2) In vivo test for detection of mammalian erythrocyte micronuclei (TG473); 3) Unscheduled DNA Synthesis (UDS) Test (TG486) or In Vivo Mammalian Alkaline Comet Assay (TG489). The most common methods for assessing genotoxic potential include Bacterial Reverse Mutation Test (TG471), In Vitro Mammalian Cell Micronucleus Test (TG487) and In Vitro Mammalian Chromosomal Aberration Test (TG473) [68].…”

“…To date, the main obstacle to solving this problem is the lack of free access to information on more than 50,000 chemicals, as such information is considered confidential [67]. In addition, for a large number of chemicals, experimental toxicological data are limited [36,68], making it impossible to use classical in vitro approaches to assess the genotoxicity of these chemicals [68]. In everyday life, the human hereditary apparatus is exposed to a large number of external DNA-damaging chemical agents [16,41,59].…”

Exposure Profile and Characteristics of Parabens and Alkylphenols in Plasma among Rural Adults in Central China

“…Although parabens have a long history of use and are generally considered safe and low in toxicity, their effects on the health of organisms are gradually being reported [11]. Several recent in vivo studies have shown that parabens have the ability to accelerate ovarian aging, impede embryo implantation in mice, and interfere with epigenetic regulation in humans and rodents, and may cause reproductive toxicity and genotoxicity [12][13][14][15]. Further epidemiological investigations have found that parabens have weak estrogenic activity and can disrupt sex hormone levels in the body [16], even affecting prenatal fetal and child development and increasing the risk of breast cancer in women [17][18][19].…”