Genotoxicity evaluation of carvacrol in rats using a combined micronucleus and comet assay.
Genotoxic 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.
Area of Toxicology, Faculty of Pharmacy, Universidad de Sevilla, Profesor García González n°2, 41012 Sevilla, Spain. Electronic address: mllana@us.es.
María
M
Llana-Ruiz-Cabello
Area of Toxicology, Faculty of Pharmacy, Universidad de Sevilla, Profesor García González n°2, 41012 Sevilla, Spain.
Sara
S
Maisanaba
Area of Toxicology, Faculty of Pharmacy, Universidad de Sevilla, Profesor García González n°2, 41012 Sevilla, Spain.
María
M
Puerto
Area of Toxicology, Faculty of Pharmacy, Universidad de Sevilla, Profesor García González n°2, 41012 Sevilla, Spain.
Ana I
AI
Prieto
Area of Toxicology, Faculty of Pharmacy, Universidad de Sevilla, Profesor García González n°2, 41012 Sevilla, Spain.
Silvia
S
Pichardo
Department of Pharmacology, Toxicology and Legal and Forensic Medicine, Faculty of Veterinary Medicine, University of Córdoba, Campus de Rabanales, Córdoba, Spain.
Rosario
R
Moyano
IRNAS-CSIC, Av. Reina Mercedes, 10, 41012, Seville, Spain.
José A
JA
González-Pérez
Area of Toxicology, Faculty of Pharmacy, Universidad de Sevilla, Profesor García González n°2, 41012 Sevilla, Spain.
Ana M
AM
Cameán
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D020552:Comet Assay / Q000379:methods*; D000081007:Cymenes; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008099:Liver / Q000187:drug effects; D008297:Male; D015162:Micronucleus Tests / Q000379:methods*; D039821:Monoterpenes / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects
D000081007:Cymenes; D039821:Monoterpenes; C073316:carvacrol
Analytical pyrolysis; Carvacrol; Comet assay; Genotoxicity; Micronucleus; Oxidative DNA damage; Rats