title: Long-term exposure of rabbits to imidaclorpid as quantified in blood induces genotoxic effect.
abstract: The present in-vivo study focuses on the genotoxic effect of the neonicotinoid pesticide imidacloprid (IMI) in rabbits. The purpose of the study was to establish a possible relationship between exposure to the pesticide (dose and duration) and genotoxicity. Furthermore, an analytical method for the simultaneous determination of IMI and its major metabolite 6-chloronicotinic acid (6-ClNA) in blood was developed and validated. The isolation of the two analytes from blood was performed by liquid-liquid extraction with dichloromethane. Analysis was performed by Liquid Chromatography - Atmospheric Pressure Chemical Ionization - Mass Spectrometry (LC-APCI-MS). The method was applied on the determination of IMI and 6-ClNA in serum samples obtained from rabbits fed with the insecticide at two low doses. Furthermore, parameters of genotoxicity and cytotoxicity were evaluated by measuring binucleated cells with micronuclei (BNMN), micronuclei (MN) and the Cytokinesis Block Proliferation Index (CBPI), in lymphocytes of exposed rabbits. The results revealed a genotoxic effect of IMI for both exposed groups. There were statistically significant differences in the frequencies of BNMN and MN between control and exposed groups but there was no dose-dependence, neither time-dependence of the genotoxic effect for the administered doses. This is the first time that long term exposure to IMI in rabbits was studied for the determination of its genotoxic effect. The genotoxic effect of IMI as it is depicted by the current study is in accordance with previous studies.
authors: Center of Toxicology Science & Research, Division of Morphology, Medical School, University of Crete, Voutes Campus, Heraklion, 71003, Crete, Greece.
authors: Polychronis D
authors: PD
authors: Stivaktakis
authors: Center of Toxicology Science & Research, Division of Morphology, Medical School, University of Crete, Voutes Campus, Heraklion, 71003, Crete, Greece.
authors: Matthaios P
authors: MP
authors: Kavvalakis
authors: Center of Toxicology Science & Research, Division of Morphology, Medical School, University of Crete, Voutes Campus, Heraklion, 71003, Crete, Greece.
authors: Manolis N
authors: MN
authors: Tzatzarakis
authors: Center of Toxicology Science & Research, Division of Morphology, Medical School, University of Crete, Voutes Campus, Heraklion, 71003, Crete, Greece.
authors: Athanasios K
authors: AK
authors: Alegakis
authors: Center of Toxicology Science & Research, Division of Morphology, Medical School, University of Crete, Voutes Campus, Heraklion, 71003, Crete, Greece.
authors: Michael N
authors: MN
authors: Panagiotakis
authors: Center of Toxicology Science & Research, Division of Morphology, Medical School, University of Crete, Voutes Campus, Heraklion, 71003, Crete, Greece.
authors: Persefoni
authors: P
authors: Fragkiadaki
authors: Center of Toxicology Science & Research, Division of Morphology, Medical School, University of Crete, Voutes Campus, Heraklion, 71003, Crete, Greece.
authors: Elena
authors: E
authors: Vakonaki
authors: Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, 34116, Beyazit, Istanbul, Turkey.
authors: Eren
authors: E
authors: Ozcagli
authors: Harvard School of Public Health, Harvard University, Boston, USA.
authors: Wallace A
authors: WA
authors: Hayes
authors: Federal Scientific Center of Hygiene Named After F.F. Erisman, Department of Pesticides Toxicology and Chemical Safety, Mytishch, Russian Federation.
authors: Valerii N
authors: VN
authors: Rakitskii
authors: Center of Toxicology Science & Research, Division of Morphology, Medical School, University of Crete, Voutes Campus, Heraklion, 71003, Crete, Greece. Electronic address: aris@med.uoc.gr.
authors: Aristidis M
authors: AM
authors: Tsatsakis
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D048749:Cytokinesis; D004249:DNA Damage; D007093:Imidazoles / Q000097:blood / Q000633:toxicity*; D007306:Insecticides / Q000097:blood / Q000378:metabolism / Q000633:toxicity*; D059625:Liquid-Liquid Extraction; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D013058:Mass Spectrometry; D048629:Micronuclei, Chromosome-Defective; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*; D000073943:Neonicotinoids; D009539:Nicotinic Acids; D009574:Nitro Compounds / Q000097:blood / Q000633:toxicity*; D011817:Rabbits
chemical_list: D007093:Imidazoles; D007306:Insecticides; D009153:Mutagens; D000073943:Neonicotinoids; D009539:Nicotinic Acids; D009574:Nitro Compounds; C082359:imidacloprid; C035953:6-chloronicotinic acid
keywords: Blood; Genotoxicity; Imidacloprid; LC-MS; Micronucleus assay