title: In vitro genotoxicity testing of carvacrol and thymol using the micronucleus and mouse lymphoma assays.
abstract: Currently, antimicrobial additives derived from essential oils (Eos) extracted from plants or spices, such as Origanum vulgare, are used in food packaging. Thymol and carvacrol, the major EO compounds of O. vulgare, have demonstrated their potential use as active additives. These new applications use high concentrations, thereby increasing the concern regarding their toxicological profile and especially their genotoxic risk. The aim of this work was to investigate the potential in vitro genotoxicity of thymol (0-250 μM) and carvacrol (0-2500 μM) at equivalent doses to those used in food packaging. The micronucleus (MN) test and the mouse lymphoma (MLA) assay on L5178Y/Tk(±) mouse lymphoma cells were used. The negative results for thymol with the MN with and without the S9 fraction and also with the MLA assay reinforce the view that this compound is not genotoxic in mammalian cells. However, carvacrol presented slight genotoxic effects, but only in the MN test at the highest concentration assayed (700 μM) and in the absence of metabolic activation. The lack of genotoxic response in the MLA assay after 4 and 24h of exposure indicates a low genotoxic potential for carvacrol. Alternatively, the general negative findings observed in both assays suggest that the MN results of carvacrol are marginal data without biological relevance. These results can be useful to identify the appropriate concentrations of these substances to be used as additives in food packaging.
authors.affiliation: Area of Toxicology, Faculty of Pharmacy, University of Sevilla, 41012 Sevilla, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Maisanaba
authors.affiliation: Area of Toxicology, Faculty of Pharmacy, University of Sevilla, 41012 Sevilla, Spain.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Prieto
authors.affiliation: Area of Toxicology, Faculty of Pharmacy, University of Sevilla, 41012 Sevilla, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Puerto
authors.affiliation: Area of Toxicology, Faculty of Pharmacy, University of Sevilla, 41012 Sevilla, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gutiérrez-Praena
authors.affiliation: Department of Biology, Faculty of Sciences, Akdeniz University, 07030-Campus, Antalya, Turkey.
authors.forename: Eşref
authors.initials: E
authors.lastname: Demir
authors.affiliation: Group of Mutagenesis, Department of Genetics and Microbiology, University Autonoma of Barcelona, Cerdanyola del Vallès, Barcelona, Spain; CIBER Epidemiology and Public Health, Instituto de Salud Carlos III, Spain.
authors.forename: Ricard
authors.initials: R
authors.lastname: Marcos
authors.affiliation: Area of Toxicology, Faculty of Pharmacy, University of Sevilla, 41012 Sevilla, Spain. Electronic address: saramh@us.es.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Cameán
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D000081007:Cymenes; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005503:Food Additives / Q000633:toxicity*; D066298:In Vitro Techniques; D007940:Leukemia L5178; D051379:Mice; D015162:Micronucleus Tests; D039821:Monoterpenes / Q000633:toxicity*; D013943:Thymol / Q000633:toxicity*
chemical_list: D000081007:Cymenes; D004273:DNA, Neoplasm; D005503:Food Additives; D039821:Monoterpenes; D013943:Thymol; C073316:carvacrol
keywords: Carvacrol; Food packaging; Micronucleus test; Mouse lymphoma assay; Thymol