Toxicology International (Formerly Indian Journal of Toxicology)

Open Access Open Access  Restricted Access Subscription Access
Open Access Open Access Open Access  Restricted Access Restricted Access Subscription Access

Cyto- and Genotoxic Potentials of Carbamates in Human Lymphocytes


Affiliations
1 Department of Pharmaceutical Toxicology, Istanbul University, Beyazit, Istanbul, Turkey
     

   Subscribe/Renew Journal


Carbamate pesticides are extensively used in agricultural areas due to their broad spectrum and low bioaccumulation. Although it is well-known that their toxicity occurs in the nervous system with reversible acetylcholine esterase inhibition and acetylcholine accumulation in synapses, knowledge regarding their adverse effects on nontarget systems is still limited, especially regarding their DNA-damaging properties. The toxic potential of the commonly used carbamates (aldicarb, carbaryl, methiocarb, and propoxur) have been investigated in freshly isolated human peripheral lymphocytes at the exposure concentrations of 0.5-25.0 μM. The carbamates were found to disturb the membrane permeability but were not harmful to the mitochondrial and lysosomal functions. Besides, they induced DNA damage. Except methiocarb, the DNA-damage for all carbamates was dose-dependent. The cyto- and geno-toxic effects of carbamates should raise concern about the safety associated with their applications in consumer products.

Keywords

Aldicarb, Carbaryl, Cytotoxicity, Genotoxicity, Human Lymphocytes, Methiocarb, Propoxur.
User
Subscription Login to verify subscription
Notifications
Font Size

  • De Sousa G, Fontaine F, Pralavorio M, Botta-Fridlund D, Letreut Y, Rahmani R. Insecticide cytotoxicity and CYP1A1/ 2 induction in primary human and rat hepatocyte cultures. Toxicol in Vitro. 1997; 11:451–7.

  • Bolognesi C. Genotoxicity of pesticides: A review of human biomonitoring studies. Mutat Res. 2003; 543:251–72.

  • Mitra A, Chatterjee C, Mandal FB. Synthetic chemical pesticides and their effects on birds. Res J Environ Toxicol. 2011; 5:81–96.

  • Fernandez M, Pico Y, Manes J. Determination of carbamate residues in fruits and vegetables by matrix solid-phase dispersion and liquid chromatography-mass spectrometry. J Chromatogr A. 2000; 871:43–56.

  • Gupta RC, Milatovic D. Toxicity of organophosphates and carbamates. Marrs TC, editor. Mammalian Toxicology of Insecticides. Cambridge, United Kingdom: Royal Society of Chemistry Publication; 2011. p. 104–36.

  • Maran E, Fernández-Franzón M, Font G, Ruiz MJ. Effects of aldicarb and propoxur on cytotoxicity and lipid peroxidation in CHO-K1 cells. Food Chem Toxicol. 2010; 48:1592–6.

  • Klotz DM, Arnold SF, McLachlan JA. Inhibition of 17 beta-estradiol and progesterone activity in human breast and endometrial cancer cells by carbamate insecticides. Life Sci. 1997; 60:1467–75.

  • Samir AMZ, Eman GEH, Talaat EIA, Somaia ZAR. Carbamate toxicity and protective effect of vit. A and vit. E on some biochemical aspects of male albino rats. Egypt J Hosp Med. 2000; 1:60–77.

  • US EPA (U.S. Environmental Protection Agency), 1997. Reregistration Eligibility Decision (RED). EPA 738-R-97-009. US EPA, Washington, DC, USA. Available from: http://cfpub.epa.gov/ncea/iris/index.cfm?fuseaction=iris.showRedDocs

  • Martinez-Haro M, Mateo R, Guitart R, Soler-Rodriguez F, Perez-Lopez M, Maria-Mojica P, et al. Relationship of the toxicity of pesticide formulations and their commercial restrictions with the frequency of animal poisonings. Ecotoxicol Environ Saf. 2008; 69:396–402.

  • JMPR (The Joint FAO/WHO Meeting on Pesticide Residues). Evaluations of Pesticide Residues in Food-1989 (Part II, Toxicology). FAO Plant Production and Protection Paper 100/2, FAO, Rome; 1989.

  • JMPR (The Joint FAO/WHO Meeting on Pesticide Residues). Pesticide Residues in Food 2006, Aldicarb. Available from: http://www.fao.org/fileadmin/templates/agphome/documents/Pests_Pesticides/JMPR/JMPRrepor2006.pdf

  • JMPR (The Joint FAO/WHO Meeting on Pesticide Residues). Pesticide Residues in Food 2006, Methiocarb; 2006. Available from: http://www.fao.org/fileadmin/templates/agphome/documents/Pests_Pesticides/JMPR/JMPR05report.pdf

  • Alley MC, Scudiero DA, Monks A, Hursey ML, Czerwinski MJ, Fine DL, et al. Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay. Cancer Res. 1988; 48:589–601.

  • Van Meerloo J, Kaspers GJ, Cloos J. Cell sensitivity assays: THe MTT assay. Methods Mol Biol. 2011; 731:237–45.

  • Repetto G, del Peso A, Zurita JL. Neutral red uptake assay for the estimation of cell viability/cytotoxicity. Nat Protoc. 2008; 3:1125–31.

  • Fotakis G, Timbrell JA. In vitro cytotoxicity assays: Comparison of LDH, neutral red, MTT and protein assay in hepatoma cell lines following exposure to cadmium chloride. Toxicol Lett. 2006; 160:171–7.

  • Collins AR. The comet assay for DNA damage and repair: Principles, applications, and limitations. Mol Biotechnol. 2004; 26:249–61.

  • Speit G, Hartmann A. The comet assay: A sensitive genotoxicity test for the detection of DNA damage and repair. Methods Mol Biol. 2006; 314:275–86.

  • Abdollahi M, Ranjbar A, Shadnia S, Nikfar S, Rezaie A. Pesticides and oxidative stress: A review. Med Sci Monit. 2004; 10:RA141–7.

  • Seth V, Banerjee BD, Bhattacharya A, Chakravorty AK. Lipid peroxidation, antioxidant enzymes, and glutathione redox system in blood of human poisoning with propoxur. Clin Biochem. 2000; 33:683–5.

  • Schmuck G, Mihail F. Effects of the carbamates fenoxycarb, propamocarb and propoxur on energy supply, glucose utilization and SH-groups in neurons. Arch Toxicol. 2004; 78:330–7.

  • Wang TC, Chiou CM, Chang YL. Genetic toxicity of N-methylcarbamate insecticides and their N-nitroso derivatives. Mutagenesis. 1998; 13:405–8.

  • Delescluse C, Ledirac N, de Sousa G, Pralavorio M, Lesca P, Rahmani R. Cytotoxic effects and induction of cytochromes P450 1A1/2 by insecticides, in hepatic or epidermal cells: Binding capability to the Ah receptor. Toxicol Lett. 1998; 96-97:33–9.

  • Ruiz MJ, Festila LE, Fernández M. Comparison of basal cytotoxicity of seven carbamates in CHO-K1 cells. Toxicol Environ Chem. 2007; 88:345–54.

  • Kornuta N, Bagley E, Nedopitanskaya N. Genotoxic effects of pesticides. J Environ Pathol Toxicol Oncol. 1996; 15:75–8.

  • Waters MD, Sandhu SS, Simmon VF, Mortelmans KE, Mitchell AD, Jorgenson TA, et al. Study of pesticide genotoxicity. Basic Life Sci. 1982; 21:275–326.

  • Bolognesi C, Landini E, Perrone E, Roggieri P. Cytogenetic biomonitoring of a floriculturist population in Italy: Micronucleus analysis by Fluorescence In Situ Hybridization (FISH) with an all-chromosome centromeric probe. Mutat Res. 2004; 557:109–17.

  • Dulout FN, Pastori MC, Olivero OA, González Cid M, Loria D, Matos E, et al. Sister-chromatid exchanges and chromosomal aberrations in a population exposed to pesticides. Mutat Res. 1985; 143:237–44.

  • Dunkel VC, Zeiger E, Brusick D, McCoy E, McGregor D, Mortelmans K, et al. Reproducibility or microbial mutagenicity assays: II. Testing or carcinogens and noncarcinogens in Salmonella typhimurium and Escherichia coli. Environ Mol Mutagen. 1985; 7:1–51.

  • Cid MG, Matos E. Induction of sister-chromatid exchanges in cultured human lymphocytes by aldicarb, a carbamate pesticide. Mutat Res. 1984; 138:175–9.

  • Cid MG, Matos E. Chromosomal aberrations in cultured human lymphocytes treated with aldicarb, a carbamate pesticide. Mutat Res. 1987; 191:99–103.

  • Zeiger E, Anderson B, Haworth S, Lawlor T, Mortelmans K. Salmonella mutagenicity tests: IV. Results from the testing of 300 chemicals. Environ Mol Mutagen. 1988; 11 Suppl 12:1–157.

  • Onfelt A, Klasterska I. Sister-chromatid exchanges and thioguanine resistance in V79 Chinese hamster cells after treatment with the aneuploidy-inducing agent carbaryl +/- S9 mix. Mutat Res. 1984; 125:269–74.

  • Dzwonkowska A, Hübner H. Induction of chromosomal aberrations in the Syrian hamster by insecticides tested in vivo. Arch Toxicol. 1986; 58:152–6.

  • Gomez-Arroyo S, Diaz-Sanchez Y, Meneses-Perez MA, Villalobos-Pietrini R, De Leon-Rodriguez J. Cytogenetic biomonitoring in a Mexican floriculture worker group exposed to pesticides. Mutat Res. 2000; 466:117–24.

  • Murli H. Mutagenicity test on H 321 in an in vitro cytogenetic assay measuring chromosomal aberration frequencies in Chinese Hamster Ovary (CHO) Cells with a confirmatory assay. Unpublished report no. R 4980 from Hazleton Laboratories America, Inc., Kensingtonb Maryland, USA, 8 March 1990. Submitted to WHO by Bayer AG, Leverkusen, Germany, 1990 [BA; Sub: 11792, Vol. 11].

  • Carbonell E, Valbuena A, Xamena N, Creus A, Marcos R. Temporary variations in chromosomal aberrations in a group of agricultural workers exposed to pesticides. Mutat Res. 1995; 344:127–34.

  • Cid MG, Loria D, Matos E. Genotoxicity of the pesticide propoxur and its nitroso derivative, NO-propoxur, on human lymphocytes in vitro. Mutat Res. 1990; 232:45–8.

  • Vasudev V, Krishnamurthy NB. In vivo cytogenetic analyses of the carbamate pesticides Dithane M-45 and Baygon in mice. Mutat Res. 1994; 323:133–5.

  • Undeger U, Basaran N. Effects of pesticides on human peripheral lymphocytes in vitro: Induction of DNA damage. Arch Toxicol. 2005; 79:169–76.

  • Pandey MR, Guo H. Evaluation of cytotoxicity, genotoxicity and embryotoxicity of insecticide propoxur using Flounder Gill (FG) cells and zebrafish embryos. Toxicol In Vitro. 2014; 28:340–53.

  • Gul A, Benli AC, Ayhan A, Memmi BK, Selvi M, Sepici-Dincel A, et al. Sublethal propoxur toxicity to juvenile common carp (Cyprinus carpio L 1758): Biochemical, hematological, histopathological, and genotoxicity effects. Environ Toxicol Chem. 2012; 31:2085–92.


Abstract Views: 510

PDF Views: 1




  • Cyto- and Genotoxic Potentials of Carbamates in Human Lymphocytes

Abstract Views: 510  |  PDF Views: 1

Authors

Ezgi Oztas
Department of Pharmaceutical Toxicology, Istanbul University, Beyazit, Istanbul, Turkey
Gul Ozhan
Department of Pharmaceutical Toxicology, Istanbul University, Beyazit, Istanbul, Turkey

Abstract


Carbamate pesticides are extensively used in agricultural areas due to their broad spectrum and low bioaccumulation. Although it is well-known that their toxicity occurs in the nervous system with reversible acetylcholine esterase inhibition and acetylcholine accumulation in synapses, knowledge regarding their adverse effects on nontarget systems is still limited, especially regarding their DNA-damaging properties. The toxic potential of the commonly used carbamates (aldicarb, carbaryl, methiocarb, and propoxur) have been investigated in freshly isolated human peripheral lymphocytes at the exposure concentrations of 0.5-25.0 μM. The carbamates were found to disturb the membrane permeability but were not harmful to the mitochondrial and lysosomal functions. Besides, they induced DNA damage. Except methiocarb, the DNA-damage for all carbamates was dose-dependent. The cyto- and geno-toxic effects of carbamates should raise concern about the safety associated with their applications in consumer products.

Keywords


Aldicarb, Carbaryl, Cytotoxicity, Genotoxicity, Human Lymphocytes, Methiocarb, Propoxur.

References





DOI: https://doi.org/10.22506/ti%2F2015%2Fv22%2Fi3%2F137633