Biomonitoring and biomarkers of organophosphate pesticides exposure – state of the art
More details
Hide details
Independent Laboratory of Molecular Biology, Institute of Rural Health, Lublin, Poland
Department of Public Health, University of Information Technology and Management, Rzeszów, Poland
Second Department of Gynecology, Medical University of Lublin, Poland
Centre for Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Warsaw, Poland
Corresponding author
Lucyna Kapka-Skrzypczak   

Independent Laboratory of Molecular Biology, Institute of Rural Health, Lublin, Poland
Ann Agric Environ Med. 2011;18(2):294-303
Human biomonitoring provides an efficient and cost-effective way to identify and quantify exposure to chemical substances, including those having deleterious effects on human organisms. Once the risk of hazardous exposure has been identified and the mechanism of toxic effects has been elucidated, an ultimate decision about how to reduce exposure can be made. A particularly high risk of exposure to hazardous chemicals is associated with the use of pesticides in agriculture, especially the use of organophosphorous pesticides (OP), which are the most widely and commonly used insecticides worldwide. There is some strong evidence that chronic exposure to these compounds may have adverse effects on health. Exposure to pesticides has been associated with an increase in the incidence of non-Hodgkin’s lymphoma, multiple myeloma, soft tissue sarcoma, lung sarcoma, and cancer of the pancreas, stomach, liver, bladder and gall bladder, Parkinson disease, Alzheimer disease, and reproductive outcomes. In view of these findings, the detection of populations at risk constitutes a very important topic. The biomonitoring studies on individuals exposed to pesticides have shown an elevated level of indicators of DNA damage, such as chromosomal aberrations (CA), sister chromatid exchanges (SCE), micronuclei (MN), and recently, single cell gel electrophoresis (SCGE). The cytogenetic markers of DNA damage have become very popular and useful in providing an analytical data for risk assessment, such as internal exposure doses and early biological effects of both occupational and environmental exposure to pesticides. The article describes the usefulness and the limitations of these biomarkers in biomonitoring studies of populations exposed to pesticides, with regard to the main routes of uptake and different matrices, which can be used to monitor risk assessment in occupational settings. The article also summarizes the latest reports about biomarkers of susceptibility, and mentions other biomarkers widely used in biomonitoring studies, such as pesticide or its metabolites level.
Budnik LT, Baur X. Th e Assessment of Environmental and Occupational Exposure to Hazardous Substances by Biomonitoring. Dtsch Arztebl Int 2009;106: 91-7.
Angerer J, Ewers U, Wilhelm M. Human biomonitoring: state of the art. Int J Hyg Environ Health 2007;210: 201-28.
Barr DB, Th omas K, Curwin B, Landsittel D, Raymer J, Lu C, Donnelly KC, Acquavella J. Biomonitoring of exposure in farmworker studies. Environ Health Perspect 2006;114:936-42.
Ngo MA, O’Malley M, Maibach HI. Percutaneous absorption and exposure assessment of pesticides. J Appl Toxicol 2010;30:91-114.
Gerkowicz M, Wróblewska E, Turski W. Th e use of the radioisotope method in studies of pesticide penetration into the eyeball. Ann Agric Environ Med 2002;9: 29-31.
Das PP, Shaik AP, Jamil K. Genotoxicity induced by pesticide mixtures: in-vitro studies on human peripheral blood lymphocyte. Toxicol Ind Health 2007;23:449-58.
Bolognesi C. Genotoxicity of pesticides: a review of human biomonitoring studies. Mutat Res 2003;543:251-72.
Albertini R, Bird M, Doerrer N, Needham L, Robison S, Sheldon L, Zenick H. Th e use of biomonitoring data in exposure and human health risk assessments. Environ Health Perspect 2006;114:1755-62.
Barr DB, Wang RY, Needham LL. Biological monitoring of exposure to environmental chemicals throughout the life stages: requirements and issues for consideration for the National Children’s Study. Environ Health Perspect 2005;113:1083-91.
Timchalk C, Poet TS, Kousba AA, Campbell JA, Lin Y. Noninvasive biomonitoring approaches to determine dosimetry and risk following acute chemical exposure: analysis of lead or organophosphate insecticide in saliva. J Toxicol Environ Health A 2004;67:635-50.
Hanke W, Jurewicz J, Sobala W, Ligocka D. Dermal Exposure to Pesticides Among Women Working in Polish Greenhouses Aft er the Restricted-Entry Intervals Expired. Epidemiology 2008;19:246-247.
Luty S, Latuszyńska J, Halliop J, Tochman A, Obuchowska D, Przylepa E, Korczak E. Toxicity of dermally applied alpha-cypermethrin in rats. Ann Agric Environ Med 1998;5:109-16.
Śpiewak R. Pesticides as a cause of occupational skin diseases in farmers. Ann Agric Environ Med 2001;8:1-5.
Jurewicz J, Hanke W, Sobala W, Ligocka D. Assessment of the dermal exposure to azoxystrobin among women tending cucumbers in selected Polish greenhouses aft er restricted entry intervals expired--the role of the protective gloves. Int J Occup Med Environ Health 2009;22:261-7.
Jurewicz J, Hanke W, Ligocka D. Exposure to Pesticides Among Women in Reproductive Age Working in Polish Greenhouses. Epidemiology 2006;17:460.
Luty S, Latuszyńska J, Halliop J, Tochman A, Obuchowska D, Korczak E, Przylepa E, Bychawski E. Dermal toxicity of paraquat. Ann Agric Environ Med 1997;4,:217–227.
Poet TS, McDougal JN. Skin absorption and human risk assessment. Chem Biol Interact 2002;140:19-34.
Salvatore AL, Bradman A, Castorina R, Camacho J, López J, Barr DB, Snyder J, Jewell NP, Eskenazi B. Occupational behaviors and farmworkers’ pesticide exposure: fi ndings from a study in Monterey County, California. Am J Ind Med 2008;51:782-94.
Arcury TA, Grzywacz JG, Isom S, Whalley LE, Vallejos QM, Chen H, et al. Seasonal variation in the measurement of urinary pesticide metabolites among Latino farmworkers in eastern North Carolina. Int J Occup Environ Health 2009;15:339-50.
Kissel JC, Curl CL, Kedan G, Lu C, Griffi th W, Barr DB. Comparison of organophosphorus pesticide metabolite levels in single and multiple daily urine samples collected from preschool children in Washington State. J Expo Anal Environ Epidemiol 2005;15:164–171.
Aprea C, Colosio C, Mammone T, Minoia C, Maroni M. Biological monitoring of pesticide exposure: a review of analytical methods. J Chromatogr B Analyt Technol Biomed Life Sci 2002;769:191-219.
Kimata A, Kondo T, Ueyama J, Yamamoto K, Mochizuki A, Asai K, et al. Relationship between urinary pesticide metabolites and pest control operation among occupational pesticide sprayers. J Occup Health 2009;51:100-5.
Barr DB, Angerer J. Potential uses of biomonitoring data: a case study using the organophosphorus pesticides chlorpyrifos and malathion. Environ Health Perspect 2006;114:1763-9.
Barr DB, Panuwet P, Nguyen JV, Udunka S, Needham LL. Assessing Exposure to Atrazine and Its Metabolites Using Biomonitoring. Environ Health Perspect 2007; 115:1474-8.
LaKind JS, Barraj L, Tran N, Aylward LL. Environmental Chemicals in People: Challenges in Interpreting Biomonitoring Information. J Environ Health 2008;70:61-4.
Muniz JF, McCauley L, Scherer J, Lasarev M, Koshy M, Kow YW, et al. Biomarkers of oxidative stress and DNA damage in agricultural workers: a pilot study. Toxicol Appl Pharmacol 2008;227:97-107.
Ross JH, Driver JH, Cochran RC, Th ongsinthusak T, Krieger RI. Could pesticide toxicology studies be more relevant to occupational risk assessment? Ann Occup Hyg 2001;45:5-17.
Rosenberg NM, Queen RM, Stamper JH. Sweat-patch test for monitoring pesticide absorption by airblast applicators. Bull Environ Contam Toxicol 1985;35:68-72.
Brunet BR, Barnes AJ, Choo RE, Mura P, Jones HE, Huestis MA. Monitoring Pregnant Women’s Illicit Opiate and Cocaine Use With Sweat Testing. Th er Drug Monit 2010;32:40-9.
Bush DM. Th e U.S. Mandatory Guidelines for Federal Workplace Drug Testing Programs: current status and future considerations. Forensic Sci Int 2008;174:111-9.
Gralewicz S, Swiercz R, Lutz P, Wiaderna D, Wasowicz W. Eff ects of stress pretreatment on the dynamics of blood cholinesterase activity aft er exposure to an organophosphorus pesticide in the rat. Ann Agric Environ Med 2010;17(1):65-71.
De Silva HJ, Samarawickrema NA, Wickremasinghe AR. Toxicity due to organophosphorus compounds: what about chronic exposure? Trans R Soc Trop Med Hyg 2006;100:803-6.
Debord J, Laubarie C, Dantoine T. Microcalorimetric study of the inhibition of butyrylcholinesterase by carbamates. Anal Biochem 2008;373:247-52.
Hofmann JN, Keifer MC, Furlong CE, De Roos AJ, Farin FM, Fenske RA, et al. Serum cholinesterase inhibition in relation to paraoxonase-1 (PON1) status among organophosphate-exposed agricultural pesticide handlers. Environ Health Perspect 2009;117:1402-8.
Stefanidou M, Athanaselis S, Spiliopoulou H. Butyrylcholinesterase: biomarker for exposure to organophosphorus insecticides. Intern Med J 2009;39:57-60.
Timchalk C, Campbell JA, Liu G, Lin Y, Kousba AA. Development of a non-invasive biomonitoring approach to determine exposure to the organophosphorus insecticide chlorpyrifos in rat saliva. Toxicol Appl Pharmacol 2007;219:217-25.
Ng V, Koh D, Wee A, Chia SE. Salivary acetylcholinesterase as a biomarker for organophosphate exposure. Occup Med (Lond) 2009;59:120-2.
Lee DH, Jacobs DR Jr. Serum gamma-glutamyltransferase: new insights about an old enzyme. J Epidemiol Community Health 2009;63:884-6.
Hreljac I, Zajc I, Lah T, Filipic M. Eff ects of Model Organophosphorous Pesticides on DNA Damage and Proliferation of HepG2 Cells. Environ Mol Mutagen 2008;49:360-7.
Lane DP. On the expression of the p53 protein in human cancer. Mol Biol Rep 1994;19:23-9.
Bumroongkit K, Rannala B, Traisathit P, Srikummool M, Wongchai Y, Kangwanpong D. TP53 gene mutations of lung cancer patients in upper northern Th ailand and environmental risk factors. Cancer Genet Cytogenet 2008;185:20-7.
Hagmar L, Strömberg U, Tinnerberg H, Mikoczy Z. Th e usefulness of cytogenetic biomarkers as intermediate endpoints in carcinogenesis. Int J Hyg Environ Health 2001;204:43-7.
Murgia E, Ballardin M, Bonassi S, Rossi AM, Barale R. Validation of micronuclei frequency in peripheral blood lymphocytes as early cancer risk biomarker in a nested case–control study. Mutat Res 2008;639:27-34.
Hagmar L, Bonassi S, Strömberg U, Brøgger A, Knudsen LE, Norppa H, Reuterwall C. Chromosomal Aberrations in Lymphocytes Predict Human Cancer: A Report from the European Study Group on Cytogenetic Biomarkers and Health. Cancer Res 1998;58:4117-21.
Zeljezic D, Garaj-Vrhovac V. Chromosomal aberration and single cell gel electrophoresis (Comet assay) in the longitudinal risk assessment of occupational exposure to pesticide. Mutagenesis 2001;16:359-63.
Chiu BC, Blair A. Pesticides, Chromosomal Aberrations, and Non-Hodgkin’s Lymphoma. J Agromedicine 2009;14:250-5.
Bonassi S, Au WW. Biomarkers in molecular epidemiology studies for health risk prediction. Mutat Res 2002; 511:73-86.
Bayani J, Squire JA. Sister Chromatid Exchange. Curr Protoc Cell Biol 2005;Chapter 22:Unit 22.7.
Martínez-Valenzuela C, Gómez-Arroyo S, Villalobos-Pietrini R, Waliszewski S, Calderón-Segura ME, Félix-Gastélum R, Alvarez-Torres A. Genotoxic biomonitoring of agricultural workers exposed to pesticides in the north of Sinaloa State, Mexico. Environ Int 2009;35:1155-9.
Shaham J, Kaufman Z, Gurvich R, Levi Z. Frequency of sister-chromatid exchange among greenhouse farmers exposed to pesticides. Mutat Res 2001;491: 71-80.
Collins AR, Oscoz AA, Brunborg G, Gaivão I, Giovannelli L, Kruszewski M, Smith CC, Stetina R. Th e comet assay: topical issues. Mutagenesis 2008;23:143-51.
Thierens H, Vral A. The micronucleus assay in radiation accidents. Ann Ist Super Sanita 2009;45:260-4.
Celik A, Mazmanci B, Camlica Y, Askin A, Cömelekoglu U. Induction of micronuclei by lambda-cyhalothrin in Wistar rat bone marrow and gut epithelial cells. Mutagenesis 2005;20:125-9.
Dimitrov BD, Gadeva PG, Benova DK, Bineva MV. Comparative genotoxicity of the herbicides Roundup, Stomp and Reglone in plant and mammalian test systems. Mutagenesis 2006;21:375-82.
Cammerer Z, Elhajouji A, Kirsch-Volders M, Suter W. Comparison of the peripheral blood micronucleus test using fl ow cytometry in rat and mouse exposed to aneugens aft er single-dose applications. Mutagenesis 2007;22:129-3.
Pastor S, Creus A, Parrón T, Cebulska-Wasilewska A, Siff el C, Piperakis S, Marcos R. Biomonitoring of four European populations occupationally exposed to pesticides: use of micronuclei as biomarkers. Mutagenesis 2003;18:249-58.
Valverde M, Rojas E. Environmental and occupational biomonitoring using the Comet assay. Mutat Res 2009;681:93-109.
Brozovic G, Orsolic N, Rozgaj R, Kasuba V, Knezevic F, Knezevic AH, Benkovic V, Lisicic D, Borojevic N, Dikic D. DNA damage and repair aft er exposure to sevofl urane in vivo, evaluated in Swiss albino mice by the alkaline comet assay and micronucleus test. J Appl Genet 2010;51:79-86.
Olewińska E, Kasperczyk A, Kapka L, Kozłowska A, Pawlas N, Dobrakowski M, Birkner E, Kasperczyk S. Level of DNA damage in lead-exposed workers. Ann Agric Environ Med 2010;17(2):231-6.
Sestili P, Martinelli C, Stocchi V. Th e fast halo assay: An improved method to quantify genomic DNA strand breakage at the single-cell level. Mutat Res 2006;607:205-14.
Tucker JD, Moore DH 2nd, Ramsey MJ, Kato P, Langlois RG, Burroughs B, Long L, Garry VF. Multi-endpoint biological monitoring of phosphine workers. Mutat Res 2003;536:7-14.
Windham GC, Titenko-Holland N, Osorio AM, Gettner S, Reinisch F, Haas R, Smith M. Genetic Monitoring of Malathion-Exposed Agricultural Workers. Am J Ind Med 1998;33:164-74.
Costa C, Teixeira JP, Silva S, Roma-Torres J, Coelho P, Gaspar J, et al. Cytogenetic and molecular biomonitoring of a Portuguese population exposed to pesticides. Mutagenesis 2006;21:343-50.
Bull S, Fletcher K, Boobis AR, Battershill JM. Evidence for genotoxicity of pesticides in pesticide applicators: a review. Mutagenesis 2006;21:93-103.
Au WW. Usefulness of biomarkers in population studies: From exposure to susceptibility and to prediction of cancer. Int J Hyg Environ Health 2007;210:239-46.
Au WW, Giri AK, Ruchirawat M. Challenge assay: A functional biomarker for exposure-induced DNA repair defi ciency and for risk of cancer. Int J Hyg Environ Health 2010;213:32-9.
Pastor S, Gutiérrez S, Creus A, Cebulska-Wasilewska A, Marcos R. Micronuclei in peripheral blood lymphocytes and buccal epithelial cells of Polish farmers exposed to pesticides. Mutat Res 2001;495:147-56.
Ergene S, Celik A, Cavaş T, Kaya F. Genotoxic biomonitoring study of population residing in pesticide contaminated regions in Göksu Delta: Micronucleus, chromosomal aberrations and sister chromatid exchanges. Environ Int 2007;33:877-85.
Joksić G, Vidaković A, Spasojević-Tisma V. Cytogenetic Monitoring of Pesticide Sprayers. Environ Res 1997;75:113-8.
Scarpato R, Migliore L, Angotzi G, Fedi A, Miligi L, Loprieno N. Cytogenetic monitoring of a group of Italian fl oriculturists: no evidence of DNA damage related to pesticide exposure. Mutat Res 1996;367:73-82.
Bortoli GM, Azevedo MB, Silva LB. Cytogenetic biomonitoring of Brazilian workers exposed to pesticides: Micronucleus analysis in buccal epithelial cells of soybean growers. Mutat Res 2009;675:1-4.
Au WW, Sierra-Torres CH, Cajas-Salazar N, Shipp BK, Legator MS. Cytogenetic Eff ects from Exposure to Mixed Pesticides and the Infl uence from Genetic Susceptibility. Environ Health Perspect 1999;107:501-5.
Barr DB, Bravo R, Weerasekera G, Caltabiano LM, Whitehead RD Jr, Olsson AO, et al. Concentrations of dialkyl phosphate metabolites of organophosphorus pesticides in the U.S. population. Environ Health Perspect 2004;112:186-200.
Kang SY, Lee KG, Lee W, Shim JY, Ji SI, Chung KW, et al. Polymorphisms in the DNA repair gene XRCC1 associated with basal cell carcinoma and squamous cell carcinoma of the skin in a Korean population. Cancer Sci 2007;98:716-20.
Wong RH, Chang SY, Ho SW, Huang PL, Liu YJ, Chen YC, Yeh YH, Lee HS. Polymorphisms in metabolic GSTP1 and DNA-repair XRCC1 genes with an increased risk of DNA damage in pesticide-exposed fruit growers. Mutat Res 2008;654:168-75.
Cohen M. Environmental toxins and health – the health impact of pesticide. Aust Fam Physician 2007;36:1002-4.
Povey AC. Gene–environmental interactions and organophosphate toxicity. Toxicology 2010;278(3):294-304. Epub 2010 Feb 13.
Wessels D, Barr DB, Mendola P. Use of Biomarkers to Indicate Exposure of Children to Organophosphate Pesticides: Implications for a Longitudinal Study of Children’s Environmental Health. Environ Health Perspect 2003;111:1939-46.
Journals System - logo
Scroll to top