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Objective: The persistence of high prevalence of thyroid pathology (goiter, nodules) in Romanian population, despite the correction of iodine deficiency, determined us to evaluate the impact of factors different than iodine intake on the thyroid gland as environmental endocrine disruptors. We studied the potential correlation between pesticide exposure and parameters of the function, autoimmunity and morphology of the thyroid in a group of greenhouse workers (GHWs) exposed to multiple uncontrolled pesticides across agricultural seasons.
Materials and methods: A group of 108 GHWs, 18–78 year olds, with normal iodine intake, from a plain village, exposed to multiple pesticides was enrolled voluntary in this study. Thyroid echography, thyroid parameters [thyroid stimulating hormone (TSH), free T4 (FT4), and antibody to thyroid peroxidase (ATPO)], some of the used pesticides (chlorpyrifos, trichloropyridinol (TCP), carbofurane, cypermethrin, dimethoate) and cholinesterase activity were determined in biological samples (urine, blood) collected across two agricul-tural seasons.
Results: The median urinary iodine concentration in children from this village was 135.20 µg/L, while median TSH and median FT4 was 1.72 μUI/mL and 16.68 pmol/L, respectively. Hypothyroidism (TSH > 4.2 μUI/mL) was present in 12.4% of patients, median TSH value was 7.26 μUI/mL. In four of them post-thyroidectomy hypothyroidism was present. Elevated titres of anti-TPO antibodies were found in 22 (20.37%). Echographic pattern of thyroiditis was present in 16.49% of the patients, and thyroid nodules were detected by ultrasonography in 38.13%. There were two subjects with Graves’ disease.
The detectable level of TCP was bigger in the first season (range 120–190 μg/L) than in the second (range 0.7–1.7 μg/L). The range of seasonal concentration of urinary carbofurane was 0.004–0.25 μg/mL. Cypermethrin was detected in a small number of subjects (range: 12.5–13.3 μg/g creatinine). Dimethoate was undetectable.
Conclusions: The distribution of thyroid disorders in study group living in an area with normal iodine intake did not differ from known epidemiological studies. The most frequently encountered pesticide was chlorpyri-fos. Some samples presented several pesticides simultaneously.
Endocrine disrupter, pesticides exposure, thyroid autoimmunity, thyroid function
[1] Ankley, G.T., Johnson, R.D., Toth, G., Folmar, L.C., Defenbeck, N.E. & Bradbury, S.P., Development of a research strategy for assessing the ecological risk of endocrine disruptors. Reviews in Toxicology Series B: Environmental Toxicology, 1, pp. 71–106, 1997.
[2] Safe, S.H., Endocrine disruptors and human health–Is there a problem? An update. Environ-mental Health Perspectives, 108, pp. 487–493, 2000.
[3] Langer, P., Polychlorinated biphenyls and thyroid gland minireview. Endocrine Regulations, 32, pp. 193–203, 1998.
[4] Simescu, M., Dumitriu, L., Sava, M., Ciovernache, D., Colda, A., Balmes, E., Ursu, H., Bistriceanu, M., Zosin, I., Duncea, I., Balasz, J., Kun, I., Dragatoiu, G., Hazi, G., Coamesu, I., Harsan, T., Stamoran, L., Florescu, E., Vitiuc, M., Varciu, M., Budura, I., Fugaciu, A., Hutanu, T., Lepadatu, D., Sulac, H. & Sirbu, A., Urinary iodine levels in schoolchildren and pregnant women after the legislative changes in the salt iodization. Acta Endocrinologica, 2, pp. 33–44, 2006.
[5] Simescu, M., IDD Situation in Romania. ICCIDD Meeting - 34th Annual Meeting of the Euro-pean Thyroid Association, Lisbon, 2009.
[6] Simescu, M., IDD Situation in Romania. ICCIDD Meeting - 35th Annual Meeting of the Euro-pean Thyroid Association, Krakow, 2011.
[7] Delange, F., Iodine deficiency in Europe anno 2002. Thyroid International, 5, pp. 1–18, Merck KGaA, Darmstadt, Germany, Edited by Hennemann, G., Krenning, E.P., 2002.
[8] Simescu, M., Elimination of nitrates and organochlorine pesticides in subjects with normal and borderline iodine intake and assessment of their effects on thyroid parameters. The Thyroid and Environment: Merck European Thyroid Symposium, Budapest, 2000.
[9] Simescu, M., Environmental pollution and human health risks – endocrine disrupters. CEEX, Module III Development of Romanian participation in European research programs on the effect of the endocrine disruptors on the thyroid physiopathology - Workshop, Cluj-Napoca, Romania, 2008.
[10] Endocrine disruptor screening program – Federal Register Notice of Environmental Protection Agency, 74(202), 2009.
[11] Aringer, L., Lof, A. & Elinder, G.G., The applicability of the measurement of urinary thioethers. International Archives of Occupational and Environmental Health, 63(5), pp. 341–346, 1991. doi: http://dx.doi.org/10.1007/BF00381585
[12] Croitoru, C., Popa, D., Danulescu, E., Gradinariu, F., Danulescu, R., Borza, V., Ghitescu, M., Chiriac, C. & Mafteri, A., Impactul expunerii profesionale la un cumul de noxe chimice asupra starii de sanatate a muncitorilor. Journal of Preventive Medicine (Iasi), 8(2), pp. 164–165, 2000.
[13] El Gazzar, R.M., Abdel Hamid, H. & Shamy M.Y., Biological monitoring of occupational exposure to electrophilic compounds. The Journal of Environmental Pathology Toxicology and Oncology, 13(1), pp. 19–23, 1994.
[14] Cotrau, M., Popa, L., Stan, T., Preda, N. & Kiricses-Ayatay, M., Toxicologie, ed. Didac, si Pedagogica, Bucuresti, 1991.
[15] Hofmann, J.N., Corden, A., Fenske, R.A., Ruark, H.E. & Keifer, M.C., Evaluation of a clin-ic-based cholinesterase test-kit for the Washington State Cholinesterase Monitoring Pro-gram. American Journal of Industrial Medicine, 51, pp. 532–538, 2008. doi: http://dx.doi. org/10.1002/ajim.20588
[16] Lessinger, J.E., Fifteen years of experience in cholinesterase monitoring of insecticide ap-plicators. Journal of Agromedicine, 10, pp. 49–56, 2005. doi: http://dx.doi.org/10.1300/ J096v10n03_06
[17] Lessinger, J.E. & Reese, B.E., Rational use of cholinesterase activity testing in pesticide poisoning. American Board of Family Products, 12, pp. 307–314, 1999. doi: http://dx.doi. org/10.3122/jabfm.12.4.307
[18] Gamlin, J., Diaz Romo, P. & Hesketh, T., Exposure of young children working on Mexican tobacco plantations to organophosphorus and carbamic pesticides, indicated by cholinesterase depression. Child: Care, Health and Development, 33, pp. 246–248, 2007. doi: http://dx.doi. org/10.1111/j.1365-2214.2006.00702.x
[19] Quandt, S.A., Chen, H., Grzywacz, J.G., Vallejos, Q.M., Galvan, L. & Arcury, T.A., Cholinesterase depression and its association with pesticide exposure across the agricultural season among Latino Farmworkers in North Carolina. Environmental Health Perspectives, 118(5), pp. 635–639, 2010. doi: http://dx.doi.org/10.1289/ehp.0901492
[20] Ion, A.C., Ion, I., Culetu, A., Gherase, D., Moldovan, C.A., Iosub, R. & Dinescu, A., Acetylcholinesterase voltammetric biosensors based on carbon nanostructure-chitosan com-posite material for organophosphate pesticides. Materials Science and Engineering: C, 30, pp. 817–821, 2010. doi: http://dx.doi.org/10.1016/j.msec.2010.03.017
[21] Burns, C.J., Chlorpyrifos exposure and biological monitoring among manufacturing work-ers. Occupational and Environmental Medicine, 63, pp. 218–220, 2006. doi: http://dx.doi. org/10.1136/oem.2005.021139
[22] Barr, D.B., Potential uses of biomonitoring data: a case study using the organophosphorus pesti-cides chlorpyrifos and malathion. Environmental Health Perspectives, 114(11), pp. 1763–1769, 2006.
[23] Farahat, F.M., Fenske, R.A., Olson, J.R., Galvin, K., Bonner, M.R., Rohlman, D.S., Farahat, T.M., Lein, P.J. & Anger, W.K., Chlorpyrifos exposures in Egyptian cotton field workers. Neu-roToxicology, 31, pp. 297–304, 2010. doi: http://dx.doi.org/10.1016/j.neuro.2010.02.005
[24] Fenske, R.A., Children’s exposure to chlorpyrifos and parathion in an agricultural community in Central Washington State. Environmental Health Perspectives, 110(5), pp. 549–553, 2002. doi: http://dx.doi.org/10.1289/ehp.02110549
[25] Hung, J., Ding, M., Zhang, S., Zhang, J., Zhang, J.M. & Shi, S., Diagnostic criteria of acute carbamate insecticides poisoning. Chinese Journal of Industrial Medicine, 2, pp. 1–4, 1989.
[26] Tamarakar, U., Pillai, A. & Gupta, V., A simple colorimetric method for the determination of carbofuran in environmental and biological samples. Journal of the Brazilian Chemical Society, 18(2), pp. 337–341, 2007. doi: http://dx.doi.org/10.1590/S0103-50532007000200014
[27] Heudorf, U. & Angerer, J., Metabolites of pyrethroid insecticides in urine specimens: cur-rent exposure in an urban population in Germany. Environmental Health Perspectives, 109, pp. 213–216, 2001. doi: http://dx.doi.org/10.1289/ehp.01109213
[28] Angerer, J. & Ritter, A., Determination of metabolites of pyrethroids in human urine using solid-phase extraction and gas chromatography-mass-spectrometry. Journal of Chromatogra-phy, 695, pp. 217–226, 1997. doi: http://dx.doi.org/10.1016/S0378-4347(97)00174-6
[29] Janghel, E.K., Rai, J.K., Rai, M.K. & Gupta, V.K., A new sensitive spectrophotometric determination of cypermethrin insecticide in environmental and biological samples. Journal of the Brazilian Chemical Society, 18(3), pp. 590–594, 2007. doi: http://dx.doi.org/10.1590/ S0103-50532007000300015
[30] Niazi, A., Goodarzi, M. & Yazdanipour, A., A comparative study between least-squares sup-port vector machines and partial least squares in simultaneous spectrophotometric determina-tion of cypermethrin, permethrin and tetramethrin. Journal of the Brazilian Chemical Society, 19(3), pp. 11–23, 2008. doi: http://dx.doi.org/10.1590/S0103-50532008000300023
[31] Lopez, F.J., Pitarch E., Egea, S., Beltran, J. & Hernandez-Gas, F., Gas chromatographic de-termination of organochlorine and organophosphorus pesticides in human fluids using solid phase microextraction. Analytica Clinica Acta, 433(2), pp. 217–226, 2001. doi: http://dx.doi. org/10.1016/S0003-2670(01)00793-0
[32] Vanderpump, M.P.J., Epidemiology of thyroid dysfunction – hypothyroidism and hyperthy-roidism. Thyroid international, 2, pp. 3–12, 2009.
[33] He, F., Biological monitoring of occupational pesticides exposure. International Archives of Oc-cupational and Environmental Health, 65, pp. 869–876, 1993. doi: http://dx.doi.org/10.1007/ BF00381310
[34] MacIntosh, D.L., Needham, L.L., Hammerstrom, K.A. & Ryan, P.B., A longitudinal investiga-tion of selected pesticide metabolites in urine. Journal of Exposure Analysis and Environmen-tal Epidemiology, 9(5), pp. 494–501, 1999. doi: http://dx.doi.org/10.1038/sj.jea.7500045
[35] Catana, H.C., Carranza, E., Huamani, D. & Hernandes, A., Plasma cholinesterase levels and health symptoms in Peruvian farmworkers exposed to organophosphate pesticides. Archives of Environmental Contamination and Toxicology, 55(1), pp. 153–159, 2008. doi: http://dx.doi. org/10.1007/s00244-007-9095-0
[36] Adgate, J.L., Barr, D.B., Clayton, C.A., Eberly, L.E., Freeman, N.C., Lioy, P.J., Needham, L.L., Pellizzari, E.D., Quackenboss, J.J., Roy, A. & Sexton, K., Measurement of children’s expo-sure to pesticides: analysis of urinary metabolite levels in a probability-based sample. En-vironmental Health Perspectives, 109(6), pp. 583–590, 2001. doi: http://dx.doi.org/10.1289/ ehp.01109583
[37] Arcury, T.A., Grzywacz, J.G., Talton, J.W., Chen, H., Vallejos, Q.M., Galvan, L., Barr, D.B. & Quandt, S.A., Repeated pesticide exposure among North Carolina migrant and seasonal farm-workers. American Journal of Industrial Medicine, 53(8), pp. 802–813, 2010.
[38] Kissel, J.C., Curl, C.L., Kedan, G., Lu, C., Griffith, W., Barr, D.B., Needham L.L. & Fenske, R.A., Comparison of organophosphorus pesticide metabolite levels in single and multiple daily urine samples collected from preschool children in Washington State. Journal of Exposure Analy-sis and Environmental Epidemiology, 15, pp. 164–171, 2005. doi: http://dx.doi.org/10.1038/ sj.jea.7500384
[39] Schmutzler, C., Gotthardt, I., Hofmann, P.J., Radovic, B., Kovacs, G., Stemmler, L., Nobis, I., Bacinski, A., Mentrup, B., Ambrugger, P., Grüters, A., Malendowicz, L.K., Christoffel, J., Jarry, H., Seidlova-Wuttke, D., Wuttke, W. & Köhrle, J., Endocrine disruptors and the thyroid gland—a combined in Vitro and in Vivo analysis of potential new biomarkers. Environmental Health Perspectives, 115(S-1), pp. 77–83, 2007. doi: http://dx.doi.org/10.1289/ehp.9369
[40] Schmutzler, C., Hamann, I., Hofmann, P.J., Kovacs, G., Stemmler, L., Mentrup, B., Schomburg, L., Ambrugger, P., Grüters, A., Seidlova-Wuttke, D., Jarry, H., Wuttke, W. & Köhrle, J., Endocrine active compounds affect thyrotropin and thyroid hormone levels in serum as well as endpoints of thyroid hormone action in liver, heart and kidney. Toxicology, 105(1–2), pp. 95–102, 2004. doi: http://dx.doi.org/10.1016/j.tox.2004.06.041
[41] Radikova, Z., Tajtakova, M., Kocan, A., Trnovec, T., Sebokova, E., Klimes, I. & Langer, P., Possible effects of environmental nitrates and toxic organochlorines on human thyroid in higly polluted areas in Slovakia. Thyroid, 18(3), pp. 353–362, 2008. doi: http://dx.doi.org/10.1089/ thy.2007.0182
[42] Santini, F., Mantovani, A., Cristaudo, A., Rago, T., Marsili, A., Buselli, R., Mignani, A., Ceccarini, G., Bastillo, R., Taddei, D., Ricco, I., Vitti, P. & Pinchera, A., Thyroid function and exposure to styrene. Thyroid, 18(10), pp. 1065–1069, 2008. doi: http://dx.doi.org/10.1089/ thy.2008.0003
[43] Tassinari, R. & Tait, S., The insecticide chlorpyrifos: a new endocrine disruptor. Food and Vet-erinary Toxicology Unit, Veterinary Public Health and Food Safety Dept. www.iss.it
[44] De Angelis, S. & Tassinari, R., Developmental exposure to chlorpyrifos induces alterations in thyroid and thyroid hormone levels without other toxicity signs in Cd1 mice. Toxicological Sciences, 108(2), pp. 311–319, 2009. doi: http://dx.doi.org/10.1093/toxsci/kfp017
[45] Jeong, S.H., Kim, B.Y., Kang, H.G., Ku, H.O. & Cho, J.H., Effect of chlorphyrifos-methyl on steroid and thyroid hormones in rat F0 and F1 generations. Toxicology, 220(2–3), pp. 189–202, 2006. doi: http://dx.doi.org/10.1016/j.tox.2006.01.005
[46] Boeniger, M.F., Lowey, L.K. & Rosenerg, J., Interpretation of urine results used to as-sess chemical exposure with emphasis on creatinine adjustments: a review. American In-dustrial Hygiene Association Journal, 54(10), pp. 615–627, 1993. doi: http://dx.doi.org/ 10.1080/15298669391355134
[47] Fukuro, T.R., Mechanism of action of organophosphorus and carbamate insecticides. En-viorenmental Health Perspectives, 87, pp. 245–254, 1990. doi: http://dx.doi.org/10.1289/ ehp.9087245