Abstract
In glyphosate (G)-based herbicides (GBHs), the declared active principle G is mixed with several adjuvants that help it to penetrate the plants’ cell membranes and its stabilization and liposolubility. Its utilization is growing with genetically modified organisms engineered to tolerate GBH. Millions of farmers suffer poisoning and death in developing countries, and occupational exposures and suicide make GBH toxicity a worldwide concern. As GBH is found in human plasma, widespread hospital facilities for measuring it should be encouraged. Plasma determination is an essential prerequisite for risk assessment in GBH intoxication. Only when standard ECGs were performed, at least one abnormal ECG was detected in the large majority of cases after intoxication. QTc prolongation and arrhythmias along with first-degree atrioventricular block were observed after GBH intoxication. Thus, life-threatening arrhythmias might be the cause of death in GBH intoxication. Cardiac cellular effects of GBH were reviewed along with few case reports in men and scanty larger studies. We observed in two mammalian species (rats and rabbits) direct cardiac electrophysiological changes, conduction blocks and arrhythmias among GBH-mediated effects. Plasmatic (and urine) level determinations of G and electrocardiographic Holter monitoring seem warranted to ascertain whether cardiovascular risk among agro-alimentary workers might be defined.
Similar content being viewed by others
References
Baynes, R. E., & Riviere, J. E. (1998). Influence of inert ingredients in pesticide formulations on dermal absorption of carbaryl. American Journal of Veterinary Research, 59(2), 168–175.
Marutani, M., & Edirveerasingam, V. (2006). Influence of irrigation methods and an adjuvant on the persistence of carbaryl on pakchoi. Journal of Environmental Quality, 35(6), 1994–1998. doi:10.2134/jeq2005.0484.
Konstantin Popov, H. R. (2002). Critical evaluation of stability constants of phosphonic acids (IUPAC Technical Report). Pure and Applied Chemistry, 74(11), 2227. doi:10.1351/pac200274112227.
Androutsopoulos, V. P., Hernandez, A. F., Liesivuori, J., & Tsatsakis, A. M. (2013). A mechanistic overview of health associated effects of low levels of organochlorine and organophosphorous pesticides. Toxicology, 307, 89–94. doi:10.1016/j.tox.2012.09.011.
Colborn, T., vom Saal, F. S., & Soto A. M. (1993). Developmental effects of endocrine-disrupting chemicals in wildlife and humans. Environmental Health Perspectives, 101(5), 378–384.
Mrema, E. J., Rubino, F. M., Brambilla, G., Moretto, A., Tsatsakis, A. M., & Colosio, C. (2013). Persistent organochlorinated pesticides and mechanisms of their toxicity. Toxicology, 307, 74–88. doi:10.1016/j.tox.2012.11.015.
James, C. (s.d.). Global Status of Commercialized Biotech/GM Crops: 2012. Chair, ISAAA Brief 44.
Bhat, R., & Gomez-Lopez, V. M. (2014). Practical food safety: Contemporary issues and future directions. Chichester, UK: John Wiley & Sons Ltd.
Mesnage, R., Moesch, C., Le Grand, R., Lauthier, G., Spiroux de Vendomois, J., Gress, S., et al. (2012). Glyphosate exposure in a farmer’s family. Journal of Environmental Protection, 03(09), 1001–1003. doi:10.4236/jep.2012.39115.
Acquavella, J. F., Alexander, B. H., Mandel, J. S., Gustin, C., Baker, B., Chapman, P., et al. (2004). Glyphosate biomonitoring for farmers and their families: Results from the Farm Family Exposure Study. Environmental Health Perspectives, 112(3), 321–326.
Curwin, B. D., Hein, M. J., Sanderson, W. T., Striley, C., Heederik, D., Kromhout, H., et al. (2007). Urinary pesticide concentrations among children, mothers and fathers living in farm and non-farm households in iowa. The Annals of Occupational Hygiene, 51(1), 53–65. doi:10.1093/annhyg/mel062.
Curwin, B. D., Hein, M. J., Sanderson, W. T., Nishioka, M. G., Reynolds, S. J., Ward, E. M., et al. (2005). Pesticide contamination inside farm and nonfarm homes. Journal of Occupational and Environmental Hygiene, 2(7), 357–367. doi:10.1080/15459620591001606.
Aris, A., & Leblanc, S. (2011). Maternal and fetal exposure to pesticides associated to genetically modified foods in Eastern Townships of Quebec, Canada. Reproductive Toxicology (Elmsford, N.Y.), 31(4), 528–533. doi:10.1016/j.reprotox.2011.02.004.
Bradberry, S. M., Proudfoot, A. T., & Vale, J. A. (2004). Glyphosate poisoning. Toxicological Reviews, 23(3), 159–167.
Potrebić, O., Jović-Stosić, J., Vucinić, S., Tadić, J., & Radulac, M. (2009). Acute glyphosate-surfactant poisoning with neurological sequels and fatal outcome. Vojnosanitetski pregled, 66(9), 758–762.
Roberts, D. M., Buckley, N. A., Mohamed, F., Eddleston, M., Goldstein, D. A., Mehrsheikh, A., et al. (2010). A prospective observational study of the clinical toxicology of glyphosate-containing herbicides in adults with acute self-poisoning. Clinical Toxicology (Philadelphia, Pa.), 48(2), 129–136. doi:10.3109/15563650903476491.
Faria, N. M. X., da Rosa, J. A. R., & Facchini, L. A. (2009). Poisoning by pesticides among family fruit farmers, Bento Gonçalves, Southern Brazil. Revista de saúde pública, 43(2), 335–344.
Adam, A., Marzuki, A., Abdul Rahman, H., & Abdul Aziz, M. (1997). The oral and intratracheal toxicities of ROUNDUP and its components to rats. Veterinary and Human Toxicology, 39(3), 147–151.
Mesnage, R., Bernay, B., & Séralini, G.-E. (2013). Ethoxylated adjuvants of glyphosate-based herbicides are active principles of human cell toxicity. Toxicology, 313(2–3), 122–128. doi:10.1016/j.tox.2012.09.006.
Peixoto, F. (2005). Comparative effects of the Roundup and glyphosate on mitochondrial oxidative phosphorylation. Chemosphere, 61(8), 1115–1122. doi:10.1016/j.chemosphere.2005.03.044.
Eddleston, M., Street, J. M., Self, I., Thompson, A., King, T., Williams, N., et al. (2012). A role for solvents in the toxicity of agricultural organophosphorus pesticides. Toxicology, 294(2–3), 94–103. doi:10.1016/j.tox.2012.02.005.
Krogh, K. A., Vejrup, K. V., Mogensen, B. B., & Halling-Sørensen, B. (2002). Liquid chromatography-mass spectrometry method to determine alcohol ethoxylates and alkylamine ethoxylates in soil interstitial water, ground water and surface water samples. Journal of Chromatography A, 957(1), 45–57.
Séralini, G.-E., Mesnage, R., Defarge, N., Gress, S., Hennequin, D., Clair, E., et al. (2013). Answers to critics: Why there is a long term toxicity due to a Roundup-tolerant genetically modified maize and to a Roundup herbicide. Food and Chemical Toxicology, 53, 476–483. doi:10.1016/j.fct.2012.11.007.
Jeyaratnam, J. (1985). Health problems of pesticide usage in the Third World. British Journal of Industrial Medicine, 42(8), 505–506.
Lee, H. L., Chen, K. W., Chi, C. H., Huang, J. J., & Tsai, L. M. (2000). Clinical presentations and prognostic factors of a glyphosate-surfactant herbicide intoxication: a review of 131 cases. Academic Emergency Medicine, 7(8), 906–910.
Jeyaratnam, J. (1985). 1984 and occupational health in developing countries. Scandinavian Journal of Work, Environment & Health, 11(3 Spec No), 229–234.
Jeyaratnam, J. (1990). Acute pesticide poisoning: a major global health problem. World Health Statistics Quarterly, 43(3), 139–144.
Zouaoui, K., Dulaurent, S., Gaulier, J. M., Moesch, C., & Lachâtre, G. (2013). Determination of glyphosate and AMPA in blood and urine from humans: about 13 cases of acute intoxication. Forensic Science International, 226(1–3), e20–e25. doi:10.1016/j.forsciint.2012.12.010.
Kwiatkowska, M., Paweł, J., & Bukowska, B. (2013). Glyphosate and its formulations–toxicity, occupational and environmental exposure. Medycyna Pracy, 64(5), 717–729.
Song, H.-Y., Kim, Y.-H., Seok, S.-J., Gil, H.-W., & Hong, S.-Y. (2012). In vitro cytotoxic effect of glyphosate mixture containing surfactants. Journal of Korean Medical Science, 27(7), 711–715. doi:10.3346/jkms.2012.27.7.711.
Kim, Y., Hong, J., Gil, H., Song, H., & Hong, S. (2013). Mixtures of glyphosate and surfactant TN20 accelerate cell death via mitochondrial damage-induced apoptosis and necrosis. Toxicology in Vitro, 27(1), 191–197. doi:10.1016/j.tiv.2012.09.021.
Seok, S.-J., Park, J.-S., Hong, J.-R., Gil, H.-W., Yang, J.-O., Lee, E.-Y., et al. (2011). Surfactant volume is an essential element in human toxicity in acute glyphosate herbicide intoxication. Clinical Toxicology (Philadelphia, Pa.), 49(10), 892–899. doi:10.3109/15563650.2011.626422.
Chan, Y.-C., Chang, S.-C., Hsuan, S.-L., Chien, M.-S., Lee, W.-C., Kang, J.-J., et al. (2007). Cardiovascular effects of herbicides and formulated adjuvants on isolated rat aorta and heart. Toxicology in Vitro, 21(4), 595–603. doi:10.1016/j.tiv.2006.12.007.
Koyama, K., Goto, K., & Yamashita, M. (1994). Circulatory failure caused by a fungicide containing iminoctadine and a surfactant: A pharmacological analysis in rats. Toxicology and Applied Pharmacology, 126(2), 197–201. doi:10.1006/taap.1994.1108.
Daruich, J., Zirulnik, F., & Gimenez, M. S. (2001). Effect of the herbicide glyphosate on enzymatic activity in pregnant rats and their fetuses. Environmental Research, 85(3), 226–231. doi:10.1006/enrs.2000.4229.
Chan, P., & Mahler, J. (1992). NTP technical report on the toxicity studies of Glyphosate (CAS No. 1071-83-6) Administered In Dosed Feed To F344/N Rats And B6C3F1 Mice. Toxicity Report Series, 16, 1–D3.
Marrs, T. C. (1993). Organophosphate poisoning. Pharmacology & Therapeutics, 58(1), 51–66.
Ludomirsky, A., Klein, H. O., Sarelli, P., Becker, B., Hoffman, S., Taitelman, U., et al. (1982). Q-T prolongation and polymorphous (« torsade de pointes ») ventricular arrhythmias associated with organophosphorus insecticide poisoning. The American Journal of Cardiology, 49(7), 1654–1658.
Carrington da Costa, R. B., Pimentel, J., Rebelo, A., Souto Gonçalves, J., & Janeiro da Costa, J. (1988). Acute poisoning with organophosphorus compounds. Acta médica portuguesa, 1(4–6), 291–295.
Singer, A. W., Jaax, N. K., Graham, J. S., & McLeod, C. G, Jr. (1987). Cardiomyopathy in Soman and Sarin intoxicated rats. Toxicology Letters, 36(3), 243–249.
Sorensen, F. W., & Gregersen, M. (1999). Rapid lethal intoxication caused by the herbicide glyphosate-trimesium (touchdown). Human and Experimental Toxicology, 18(12), 735–737.
Talbot, A. R., Shiaw, M. H., Huang, J. S., Yang, S. F., Goo, T. S., Wang, S. H., et al. (1991). Acute poisoning with a glyphosate-surfactant herbicide (’Roundup’): a review of 93 cases. Human and Experimental Toxicology, 10(1), 1–8.
Loffredo, C. A., Silbergeld, E. K., Ferencz, C., & Zhang, J. (2001). Association of transposition of the great arteries in infants with maternal exposures to herbicides and rodenticides. American Journal of Epidemiology, 153(6), 529–536.
Kimmel, G. L., Kimmel, C. A., Williams, A. L., & DeSesso, J. M. (2013). Evaluation of developmental toxicity studies of glyphosate with attention to cardiovascular development. Critical Reviews in Toxicology, 43(2), 79–95. doi:10.3109/10408444.2012.749834.
Kim, Y. H., Lee, J. H., Hong, C. K., Cho, K. W., Park, Y. H., Kim, Y. W., et al. (2014). Heart rate-corrected QT interval predicts mortality in glyphosate-surfactant herbicide-poisoned patients. The American Journal of Emergency Medicine, 32, 203–207. doi:10.1016/j.ajem.2013.09.025.
Kim, J., Shin, D.-H., & Lee, W. J. (2014). Suicidal ideation and occupational pesticide exposure among male farmers. Environmental Research, 128, 52–56. doi:10.1016/j.envres.2013.10.007.
Boocock, M. R., & Coggins, J. R. (1983). Kinetics of 5-enolpyruvylshikimate-3-phosphate synthase inhibition by glyphosate. FEBS Letters, 154(1), 127–133.
Smith, E. A., & Oehme, F. W. (1992). The biological activity of glyphosate to plants and animals: A literature review. Veterinary and Human Toxicology, 34(6), 531–543.
Rueppel, M. L., Brightwell, B. B., Schaefer, J., & Marvel, J. T. (1977). Metabolism and degradation of glyphosphate in soil and water. Journal of Agricultural and Food Chemistry, 25(3), 517–528.
Brewster, D. W., Warren, J., & Hopkins, W. E. (1991). Metabolism of glyphosate in Sprague-Dawley rats: tissue distribution, identification, and quantitation of glyphosate-derived materials following a single oral dose. Fundamental and Applied Toxicology, 17(1), 43–51.
Müller, M. M., Rosenberg, C., Siltanen, H., & Wartiovaara, T. (1981). Fate of glyphosate and its influence on nitrogen-cycling in two Finnish agriculture soils. Bulletin of Environmental Contamination and Toxicology, 27(5), 724–730.
Roberts, D. M., & Buckley, N. A. (2007). Pharmacokinetic considerations in clinical toxicology: Clinical applications. Clinical Pharmacokinetics, 46(11), 897–939. doi:10.2165/00003088-200746110-00001.
Wang, Y., Wu, B., Lian, H., & Shi, C. (2012). [Determination of glyphosate in heart blood of corpse by ion chromatography]. Se pu =. Chinese Journal of Chromatography, 30(4), 419–422.
Tomita, M., Okuyama, T., Watanabe, S., Uno, B., & Kawai, S. (1991). High-performance liquid chromatographic determination of glyphosate and (aminomethyl)phosphonic acid in human serum after conversion into p-toluenesulphonyl derivatives. Journal of Chromatography, 566(1), 239–243.
De Liz Oliveira Cavalli, V. L., Cattani, D., Heinz Rieg, C. E., Pierozan, P., Zanatta, L., Benedetti Parisotto, E., et al. (2013). Roundup disrupts male reproductive functions by triggering calcium-mediated cell death in rat testis and Sertoli cells. Free Radical Biology & Medicine, 65, 335–346. doi:10.1016/j.freeradbiomed.2013.06.043.
Olorunsogo, O. O. (1990). Modification of the transport of protons and Ca2 + ions across mitochondrial coupling membrane by N-(phosphonomethyl)glycine. Toxicology, 61(2), 205–209.
Bechem, M., & Hoffmann, H. (1993). The molecular mode of action of the Ca agonist (-) BAY K 8644 on the cardiac Ca channel. Pflügers Archiv, 424(3–4), 343–353.
Pasdois, P., Quinlan, C. L., Rissa, A., Tariosse, L., Vinassa, B., Costa, A. D. T., et al. (2007). Ouabain protects rat hearts against ischemia-reperfusion injury via pathway involving src kinase, mitoKATP, and ROS. American Journal of Physiology. Heart and Circulatory Physiology, 292(3), H1470–H1478. doi:10.1152/ajpheart.00877.2006.
Puddu, P. E., Jouve, R., Torresani, J., & Jouve, A. (1981). QT interval and primary ventricular fibrillation in acute myocardial infarction. American Heart Journal, 101, 118–120.
Puddu, P. E., Bourassa, M. G., Lespérance, J., Hélias, J., Danchin, N., & Goulet, C. (1983). Can the mode of death be predicted in patients with angiographically documented coronary artery disease? Clinical Cardiology, 6(8), 384–395.
Puddu, P. E., & Bourassa, M. G. (1986). Prediction of sudden death from QTc interval prolongation in patients with chronic ischemic heart disease. Journal of Electrocardiology, 19(3), 203–211.
Hondeghem, L. M. (1978). Validity of Vmax as a measure of the sodium current in cardiac and nervous tissues. Biophysical Journal, 23(1), 147–152. doi:10.1016/S0006-3495(78)85439-3.
Osadchii, O. E. (2013). Procainamide and lidocaine produce dissimilar changes in ventricular repolarization and arrhythmogenicity in guinea-pig. Fundamental & Clinical Pharmacology,. doi:10.1111/fcp.12046.
Mink, P. J., Mandel, J. S., Sceurman, B. K., & Lundin, J. I. (2012). Epidemiologic studies of glyphosate and cancer: a review. Regulatory Toxicology and Pharmacology: RTP, 63(3), 440–452. doi:10.1016/j.yrtph.2012.05.012.
Conflict of interest
None of the Authors has any conflict to disclose. We thank CRIIGEN, in particular, for its financial and structural support to S.G.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Gress, S., Lemoine, S., Séralini, GE. et al. Glyphosate-Based Herbicides Potently Affect Cardiovascular System in Mammals: Review of the Literature. Cardiovasc Toxicol 15, 117–126 (2015). https://doi.org/10.1007/s12012-014-9282-y
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12012-014-9282-y