Long-term exposure to cypermethrin and piperonyl butoxide cause liver and kidney inflammation and induce genotoxicity in New Zealand white male rabbits |
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| Affiliation: | 1. Laboratory of Toxicology, Medical School, University of Crete, Voutes, 71409 Heraklion, Crete, Greece;2. Department of Pathology, Medical School Voutes-Stavrakia, Heraklion, Crete, Greece;3. Laboratory of Anatomy, Medical School, University of Crete, Voutes, 71110 Heraklion, Crete, Greece;4. General Chemical State Laboratory of Greece, Department of Hazardous Substances, Mixtures and Articles, 16 An. Tsocha Str, 1152 Athens, Greece;5. Federal Scientific Center of Hygiene, F.F. Erisman, Moscow, Russian Federation;6. UCIBIO-REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal;1. U. S. Environmental Protection Agency, National Exposure Research Laboratory, 944 E. Harmon Ave, Las Vegas, NV 89119, USA;2. School of Life Sciences, University of Nevada, Las Vegas, 4505 S. Maryland Parkway, Las Vegas, NV 89154, USA;1. Fatemeh Zahra Infertility Research Center, Babol University of Medical Sciences, Babol, Iran;2. Department of Immunology, Babol University of Medical Sciences, Babol, Iran;3. Department of Immunology, Qazvin University of Medical Sciences, Qazvin, Iran;4. Department of Pharmacology and Physiology, Babol University of Medical Sciences, Babol, Iran;5. Medical School, Babol University of Medical Sciences, Babol, Iran;1. Department of Biosciences, Integral University, Lucknow 226026, India;2. Developmental Toxicology Division, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow 226001, India;3. In vitro Toxicology Laboratory, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow 226001, India;4. Department of Bioengineering, Integral University, Lucknow 226026, India;1. Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, 1-1-20 Daikou-minami, Higashi-ku, Nagoya, 461-8673, Japan;2. Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan;1. Department of Animals Sciences, College of Animal Sciences, Jilin University, Changchun, China;2. Department of Reproductive Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China;1. Department of Biochemistry and Biophysics, Arrhenius Laboratories for the Natural Sciences, Stockholm University, SE-106 91 Stockholm, Sweden;2. Experimental Cancer Medicine, Clinical Research Center, Novum, Karolinska University Hospital, Huddinge, 141 86 Stockholm, Sweden;3. ImmunoBioTox (IBT) AB, 16954 Solna, Sweden |
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| Abstract: | Cypermethrin (CY) is a frequently used class II pyrethroid pesticide, while piperonyl butoxide (PBO) plays a major role in the pesticide formulation of synthetic pyrethroids. Synthetic pyrethroids are metabolized in mammals via oxidation and ester hydrolysis. PBO can prevent the metabolism of CY and enhances its pesticide effect. While this potentiation effect reduces the amount of pesticide required to eliminate insects, it is not clear how this mixture affects mammals. In our in vivo experiment, New Zealand white male rabbits were exposed to low and high doses of CY, PBO, and their combinations, for 4 months. Genotoxicity and cytotoxicity were monitored by measuring binucleated cells with micronuclei (BNMN), micronuclei (MN) and the cytokinesis block proliferation index (CBPI) in lymphocytes. After two months of exposure, a statistically significant increase in the frequency of BNMN was observed for all exposed animals (p < 0.001) in a dose-dependent way. MN were significantly elevated compared to controls (p < 0.001), with high dose groups reaching a 442% increase when co-exposed. BNMN and MN continued to increase after four months. Histopathological examination of lesions showed damage involving inflammation, attaining lymphoplasmatocytic infiltration in the high dose groups. Both CY and PBO cause liver and kidney inflammation and induce genotoxicity. |
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| Keywords: | Cypermethrin Piperonyl butoxide Potentiation Genotoxicity Micronuclei Cytotoxicity Histology CY" },{" #name" :" keyword" ," $" :{" id" :" kwrd0050" }," $$" :[{" #name" :" text" ," _" :" Cypermethrin CON" },{" #name" :" keyword" ," $" :{" id" :" kwrd0060" }," $$" :[{" #name" :" text" ," _" :" Control CY LD" },{" #name" :" keyword" ," $" :{" id" :" kwrd0070" }," $$" :[{" #name" :" text" ," _" :" Cypermethrin low dose CY HD" },{" #name" :" keyword" ," $" :{" id" :" kwrd0080" }," $$" :[{" #name" :" text" ," _" :" Cypermethrin high dose PBO" },{" #name" :" keyword" ," $" :{" id" :" kwrd0090" }," $$" :[{" #name" :" text" ," _" :" Piperonyl Butoxide PBO LD" },{" #name" :" keyword" ," $" :{" id" :" kwrd0100" }," $$" :[{" #name" :" text" ," _" :" Piperonyl Butoxide low dose PBO HD" },{" #name" :" keyword" ," $" :{" id" :" kwrd0110" }," $$" :[{" #name" :" text" ," _" :" Piperonyl Butoxide high dose MDP" },{" #name" :" keyword" ," $" :{" id" :" kwrd0120" }," $$" :[{" #name" :" text" ," _" :" methylenedioxyphenyl BD" },{" #name" :" keyword" ," $" :{" id" :" kwrd0130" }," $$" :[{" #name" :" text" ," _" :" benzodioxole CBMN" },{" #name" :" keyword" ," $" :{" id" :" kwrd0140" }," $$" :[{" #name" :" text" ," _" :" Cytokinesis Block Micronucleus Assay BNMN" },{" #name" :" keyword" ," $" :{" id" :" kwrd0150" }," $$" :[{" #name" :" text" ," _" :" Binucleated cells with micronucleus CBPI" },{" #name" :" keyword" ," $" :{" id" :" kwrd0160" }," $$" :[{" #name" :" text" ," _" :" Cytokinesis Block Proliferation Index MN" },{" #name" :" keyword" ," $" :{" id" :" kwrd0170" }," $$" :[{" #name" :" text" ," _" :" Micronuclei WHO" },{" #name" :" keyword" ," $" :{" id" :" kwrd0180" }," $$" :[{" #name" :" text" ," _" :" World Health Organization OECD" },{" #name" :" keyword" ," $" :{" id" :" kwrd0190" }," $$" :[{" #name" :" text" ," _" :" Organization for Economic Co-operation and Development H&E stain" },{" #name" :" keyword" ," $" :{" id" :" kwrd0200" }," $$" :[{" #name" :" text" ," _" :" Hematoxylin and Eosin USEPA" },{" #name" :" keyword" ," $" :{" id" :" kwrd0210" }," $$" :[{" #name" :" text" ," _" :" United States Environmental Protection Agency CLP regulation" },{" #name" :" keyword" ," $" :{" id" :" kwrd0220" }," $$" :[{" #name" :" text" ," _" :" classification, labeling, and packaging IGHRC" },{" #name" :" keyword" ," $" :{" id" :" kwrd0230" }," $$" :[{" #name" :" text" ," _" :" The intergovernmental group on health risks from chemicals |
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