Estudo de toxicidade reprodutiva e genotoxicidade do óleo essencial de Origanum majorana

Origanum majorana L. , a plant rich in essential oils, presents antifungal activity in vitro against Malassezia pachydermatis, Candida spp and Trichosporon asahii, among other activities. However, exposure to chemicals, including herbal medicines, can cause mutagenicity, infertility, maternal toxicity, embryotoxic effects on offspring. Therefore, this study investigated in vivo reproductive toxicity of the Origanum majorana essential oil (Omeo) and major compounds on rats Wistar, effects on the fetal development and behavioral parameters of the offspring, and in vitro mutagenic activity. The in vivo tested doses were 33mg/kg, 100mg/kg or 300mg/kg Omeo, 77mg/kg γ-terpinene or 52mg/kg terpinen-4-ol, established according to previous studies. Male parents were treated for 70 days and females for 14 days prior to mating, during pregnancy and lactation. To identify alterations in reproductive system of males were evaluated organs relative weight, histology, sperm number and morphology of spermatozoa. Reproductive index, body weight gain, intake water and food, and toxicity signs were evaluated. Signs of maternal toxicity, maternal behavior, offspring reproductive parameters, open field behavior and sexual behavior were observed. To evaluated the teratogenic potential, female rats Wistar were treated only during pregnancy and males were not treated. At 21th was performed cesarean, fetuses were diaphanized, stained and evaluated individually for the presence of skeletal alterations. The exposure induced dosedependent way reduction in reproductive index, reduction in sperm number, reduction in daily sperm production, increase in sperm defects to males treated with Omeo and Terpinen-4-ol, reduction in testis and epididymis relative weight to 300mg/kg Omeo, and no pregnancy at this dose and terpinen-4-ol. Maternal toxicity was not observed. The maternal behavior related to the nest was reduced with 100 mg/kg Omeo, but the maternal responsiveness was maintained by the nursing behavior. This dose induced reduction in the number of offspring per parent, increase in the time of pregnancy and changes in the development of males characterized by delayed preputial separation. Other reproductive and behavioral parameters of the male offspring were not affected. However, it was observed skeletal development delay in all treated groups and skeletal malformation at the highest doses of Omeo and terpinen-4-ol. Mutagenicity in vitro was evaluated by the Salmonella/microsome test using the preincubation procedure on TA98, TA97a, TA100, TA102 and TA1535 Salmonella typhimurium strains, with or without metabolic activation. No gene mutation increase was observed. For the in vitro mammalian cell micronucleus test, it was used V79 Chinese hamster lung fibroblasts and Omeo was not able to induce chromosome mutation. In conclusion, Omeo is not able to induce in vitro gene and chromosome mutations, however, the continuous treatment with high doses Omeo and major compounds affect male fertility, induce changes in reproductive rates, cause malformation and adverse effects on the developing offspring, and should not be used during pregnancy and lactation.