title: Repeated-doses and reproductive toxicity studies of the monoterpene 1,8-cineole (eucalyptol) in Wistar rats.
abstract: 1,8-cineole (eucalyptol) is widely used as an excipient in the pharmaceutical industry and as a food flavoring agent, thus providing significant potential for human exposure to the compound. We investigated the preclinical toxicity and reproductive toxicity of 1,8-cineole (CIN). In the repeated-doses toxicity study for 50 days, CIN (100, 500 or 1000 mg/kg) did not produce any signs of toxicity or deaths, but affected body weight gain during the first week of treatment. The hematological and biochemical profiles did not show significant differences except for increase in the MCV, platelet and urea levels or reduction in MCHC, MPV and alkaline phosphatase. Histopathological analysis showed weak changes in the lungs, liver, kidneys and uterus. In the reproductive toxicity, CIN (250, 500 or 1000 mg/kg) produced a reduction in body weight in pregnant rats treated during the pre-implantation or organogenesis periods. The highest doses induced a reduction in the mass of fetuses (pre-implantation) and dead fetuses (both periods) of pregnant rats. The results indicate that the treatment by repeated-doses showed occasional alterations in rats of both sexes. However, provide evidence that possibly 1,8-cineole presents maternal and fetal toxicity. This requires more detailed investigation to better characterize the toxic effects of this compound.
authors.affiliation: Department of Pharmaceutical Sciences, Federal University of Pernambuco, 50740-521, Recife, PE, Brazil.
authors.forename: Germana Freire Rocha
authors.initials: GF
authors.lastname: Caldas
authors.affiliation: Department of Physiology and Pharmacology, Federal University of Pernambuco, 50670-901, Recife, PE, Brazil.
authors.forename: Mayara Marília Ferreira
authors.initials: MM
authors.lastname: Limeira
authors.affiliation: Department of Public Health, Federal University of Pernambuco, Vitória de Santo Antão, 55608-680, Recife, PE, Brazil.
authors.forename: Alice Valença
authors.initials: AV
authors.lastname: Araújo
authors.affiliation: Department of Histology and Embryology, Federal University of Pernambuco, 50670-901, Recife, PE, Brazil.
authors.forename: Giwellington Silva
authors.initials: GS
authors.lastname: Albuquerque
authors.affiliation: Department of Histology and Embryology, Federal University of Pernambuco, 50670-901, Recife, PE, Brazil.
authors.forename: Jacinto da Costa
authors.initials: JD
authors.lastname: Silva-Neto
authors.affiliation: Department of Antibiotics, Federal University of Pernambuco, 50670-901, Recife, PE, Brazil.
authors.forename: Teresinha Gonçalves da
authors.initials: TG
authors.lastname: Silva
authors.affiliation: Department of Physical Education and Sport Sciences, Federal University of Pernambuco, Vitória de Santo Antão, 55608-680, Recife, PE, Brazil.
authors.forename: João Henrique
authors.initials: JH
authors.lastname: Costa-Silva
authors.affiliation: Department of Biological Chemistry, Regional University of Cariri, 63105-000, Crato, CE, Brazil.
authors.forename: Irwin Rose Alencar de
authors.initials: IR
authors.lastname: Menezes
authors.affiliation: Department of Biological Chemistry, Regional University of Cariri, 63105-000, Crato, CE, Brazil.
authors.forename: José Galberto Martins da
authors.initials: JG
authors.lastname: Costa
authors.affiliation: Department of Pharmaceutical Sciences, Federal University of Pernambuco, 50740-521, Recife, PE, Brazil; Department of Physiology and Pharmacology, Federal University of Pernambuco, 50670-901, Recife, PE, Brazil. Electronic address: almir.wanderley@ufpe.br.
authors.forename: Almir Gonçalves
authors.initials: AG
authors.lastname: Wanderley
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D003511:Cyclohexanols / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D000077591:Eucalyptol; D005260:Female; D005333:Fetus / Q000187:drug effects*; D006801:Humans; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D039821:Monoterpenes / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012098:Reproduction / Q000187:drug effects*; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D000890:Anti-Infective Agents; D003511:Cyclohexanols; D039821:Monoterpenes; D000077591:Eucalyptol
keywords: 1,8-Cineole; Monoterpene; Repeated dose toxicity; Reproductive toxicity