Genotoxicity evaluation of carvacrol in rats using a combined micronucleus and comet assay

11 páginas.-- 6 figuras.-- 1 tabla.-- referenciasGenotoxic data of substances which could be incorporated into food packaging are required by the European Food Safety Authority. Due to its antioxidant and antibacterial properties carvacrol is one of these compounds. This work aims to study for the first time the in vivo genotoxic effects produced in rats orally exposed to 81, 256 or 810 mg cavacrol/kg body weight (bw) at 0, 24 and 45 h. A combination of the micronucleus assay (OECD 474) in bone marrow and the standard (OECD 489) and enzyme-modified comet assay was used to determine the genotoxicity on cells isolated from stomach and liver of exposed animals. In addition, a histopathological study was performed on the assayed tissues, and also in the lungs due to the volatility of carvacrol. Direct analytical pyrolysis was used to search for carvacrol in viscera and to ensure that the compound reaches stomach and liver cells. Results from MN-comet assay revealed that carvacrol (81-810 mg/kg bw) did not induce in vivo genotoxicity or oxidative DNA damage in any of the tissues investigated. Moreover, no histopathological changes were observed. Altogether, these results suggest lack of genotoxicity of carvacrol and therefore its good profile for its potential application as food preservative.The authors wish to thank the Spanish Ministry of Science and Innovation (AGL2012-38357-C02-01) co-financed by FEDER funds and Junta de Andalucía (AGR-7252) for the financial support for this study, the Microscopy Service of CITIUS and the animal housing from the Faculty of Pharmacy in the Universidad de Sevilla. María Llana-Ruiz-Cabello also gratefully acknowledges Junta de Andalucía for her predoctoral grant associated to the AGR7252 project.Peer Reviewe