Glyphosate: Its Effects on Humans

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Glyphosate: Its Effects on Humans Article in Alternative therapies in health and medicine · May 2014 Source: PubMed

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EDITORIAL

Glyphosate: Its Effects on Humans

T

here is quite a bit of debate surrounding the herbicide glyphosate, also known as Roundup, and its degradation byproduct known as aminomethylphosphonic acid (AMPA). Recent studies highlight the potential adverse effects of exposure to this agricultural chemical. First, it is necessary to examine the facts about glyphosate and its mechanism of action. Glyphosate is the most widely used herbicide in the world.1 It was originally patented by Stauffer Chemical Company as a chelating agent, wetting agent, and biologically active compound used principally as a descaling agent to clean out mineral deposits in plumbing pipes, boilers, and heaters in commercial and residential hot-water heaters.2 Glyphosate was later acquired by the Monsanto Company, patented as an herbicide, and eventually marketed under the name Roundup starting in the 1970s. It is a broad-spectrum systemic herbicide, meaning that it spreads throughout the plant, from the leaves to the roots or from soil into the leaves. It does not affect germinating seeds. Glyphosate is used to kill weeds that compete with commercial crops throughout the world. In 2007 in the United States, glyphosate was the most widely used herbicide in agriculture with 85 000 tons used; 3600 tons were used in the home and garden market, and commerce, industry, and government used another 6800 tons.3 The use of glyphosate continues to rise annually worldwide. It was praised at the turn of the century as the most significant chemical in modern agriculture.4 Genetically engineered (GE) crops, known as Roundup Ready and also produced by the Monsanto Company, are resistant to glyphosate, which enables farmers to kill weeds without killing their crops. Glyphosate can be sprayed on these crops several times during the growth season to eradicate weeds without affecting the crops. Soy was the first crop with Roundup Ready. The herbicide-resistant GE crops absorb glyphosate through direct application and from the soil and, therefore, it cannot be washed off.5 The mechanism of action of glyphosate is inhibiting an enzyme in the biosynthesis of tryptophan, phenylalanine, and tyrosine, present in plants, fungi, and bacteria but not in animals or humans. It has excellent water solubility and was thought to be readily degraded to a nontoxic degradation product. Therefore, it was considered the best herbicide to Campbell—Glyphosate

have ever been discovered. The half-life of glyphosate is between 2 and 197 days in soil and between a few days to 91 days in water, according to the National Pesticide Information Center Technical fact sheet on glyphosate.6 It was included neither in testing by the Food and Drug Administration’s Pesticide Residue Monitoring Program nor in the United States Department of Agriculture’s Pesticide Data Program. Field tests on lettuce, carrots, and barley showed glyphosate residue 1 year after treatment of the soil with 3.71 pounds per acre applied with glyphosate.6 Recent studies have demonstrated various toxic aspects of glyphosate. A study published in the Archives of Toxicology by Koller et al7 showed increases in nuclear aberrations indicating DNA damage after 20 minutes of exposure to 10 to 20 mg/L of glyphosate. They also found that Roundup was, under all conditions, more active than glyphosate and that there were genotoxic effects after short exposures to a concentration of a 450 dilution of spraying used in agriculture. In conclusion, inhalation could cause DNA damage in exposed agricultural workers.7 Another study looked at why some agricultural workers who use glyphosate have pregnancy problems and showed that it is toxic to human placental JEG-3 cells within 18 hours of exposure in concentrations lower than those in agricultural use—and that this effect increases with concentration and time with Roundup adjuvants. The authors also tested the effects of glyphosate and Roundup at nontoxic concentrations on aromatase, the enzyme responsible for estrogen synthesis. They found that glyphosate disrupts aromatase and mRNA levels and concluded that Roundup, not just glyphosate, has endocrine and toxic effects.8 In the Farm Family Exposure Study, urinary glyphosate was measured in 48 farmers, their spouses, and their 79 children ages 4 to 18 years on the day before, the day of, and for 3 days after the application of glyphosate. Thirty farmers had detectable levels of glyphosate in their urine, as did 4% of their spouses and 12% of their children, on the day of application. All but 1 child with detectable concentrations had either been present during mixing, loading, or application of glyphosate.9 Residues of glyphosate are found in key foods of the Western diet, mainly in sugar, corn, soy, canola, alfalfa, wheat, and others. These residues inhibit cytochrome P450 (CYP) enzymes, which play a crucial role in helping to ALTERNATIVE THERAPIES, MAY/JUNE 2014 VOL. 20, 3

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detoxify xenobiotics. A recent review shows how this negative effect on the body is insidious and slowly manifests itself over time with inflammatory damages to the cellular systems throughout the body. The hindrance of CYP enzymes acts synergistically by disrupting the biosynthesis on aromatic amino acids by gut bacteria and impairing the transport of serum sulfate. The authors explain that the consequences are the ones associated with the Western diet, which include gastrointestinal disorders, obesity, diabetes, heart disease, depression, autism, infertility, cancer, and Alzheimer’s disease. They demonstrate how glyphosate disrupt homeostasis.10 The United States Geological Survey published a study this year titled “Pesticides in Mississippi Air and Rain: A Comparison Between 1995 and 2007,” which showed that glyphosate and AMPA were found in over 75% of the air and rain samples tested in 2007 in the Mississippi Delta agricultural area. Glyphosate was not measured in 1995 but was now the predominant new herbicide detected in both air and rain, at 86% and 77% respectively, with 2 million kg of glyphosate applied statewide in 2007, or 55% of the total of all herbicides used that year.11 Some of our readers may have been aware from reading in the medical news media of a mysterious illness known as chronic kidney disease of unknown etiology (CKDu) affecting young male farmworkers in the Central American countries of Nicaragua, El Salvador, and Costa Rica; in the Andhra Pradesh region of southwestern India; and in Sri Lanka starting in the early 1990s. Significantly, there was no CKDu prior to the 1990s. An interesting fact of CKDu is that it is not associated with glomerulonephritis, diabetes, or hypertension, as in chronic renal disease. In CKDu, the disease progresses slowly and patients are asymptomatic for most of the course of the disease. Many patients with CKDu do not have symptoms until the end stage when the only treatment is peritoneal and hemodialysis—and eventually kidney transplantation. Its characteristics are tubular proteinuria, either α-1 and β-2 microglobinuria, and elevated urine neutrophil gelatinase–associated lipocalin levels, with >300 ng/mg of creatinine.12,13 Many factors were examined to determine the etiology, including chronic exposure to arsenic, cadmium, and pesticides.14,15 Other etiological factors include exposure to high temperatures resulting in dehydration, low water intake, and consumption of hard water. A new study published this year in the International Journal of Environmental Research and Public Health points out that at glyphosate, in combination with water hardness and nephrotoxic metals, is the cause of this toxic nephropathy.16 Hard water is mainly because of the presence of calcium, magnesium, strontium, iron, carbonate, bicarbonate, sulphate, and chloride anions.17 People who lived in areas endemic to CKDu and drank water from either natural springs or treated municipal water did not have the disease. Titled “Glyphosate, Hard Water and Nephrotoxic Metals: Are They the Culprits Behind the 10

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Epidemic of Chronic Kidney Disease of Unknown Etiology in Sri Lanka?”, the researchers found arsenic in urine, hair, and nail samples in CKDu patients and healthy individuals living in the CKDu endemic area. Arsenic, mainly from chemical fertilizers and pesticides or naturally present in the soil, combined with calcium and/or magnesium in groundwater, can cause nephrotoxicity. CKDu is now present in approximately 400 000 young farmers in Sri Lanka with a death toll of 20 000.16 The mechanism for this toxicity lies in the fact that glyphosate and AMPA can easily leach into the groundwater and chelate to calcium, magnesium, and strontium already present in the groundwater. After all, glyphosate started out as a chelator. The farmers use hard water to dissolve glyphosate to prepare it for spraying and then spray it manually under hot climatic conditions, making glyphosate easily absorbed transdermally. The farmers usually do not have or use personal protective equipment, so absorption via respiration is also most likely.18 No one should be surprised that this chemical compound, the world’s number one herbicide, glyphosate, can be toxic. We regularly add chemicals to our ecosystem only to find out years or decades later that we should have been more diligent in making sure all the effects of these chemicals had been studied. This is the time for all of us to read again Rachel Carson’s The Silent Spring.19

Andrew W. Campbell, MD Editor in Chief

REFERENCES

1. Baylis AD. Why glyphosate is a global herbicide: Strengths, weakness and prospects. Pest Manag Sci. 2000;56(4):299-308. 2. Dock Fon TA, Uhing EH, inventors. Aminomethylenephosphinic acids, salts thereof, and process for their production. US patent 3160632A. December 8, 1964. 3. US Environmental Protection Agency. 2006-2007 Pesticide Market Estimates: Usage. http://www.epa.gov/opp00001/pestsales/07pestsales/usage2007.htm. Updated July 19, 2013. Accessed March 12, 2014. 4. Székács A, Darvas B. Forty years with glyphosate. In: El-Ghany Hasaneen MNA, ed. Agricultural and Biological Sciences. Rijeka, Croatia: InTech; 2012:247-284. 5. Swanson NL. Genetically modified organisms and the deterioration of health in the United States. Sustainable Pulse Web site. http://sustainablepulse.com/wpcontent/uploads/GMO-health.pdf. Published April 24, 2013. Accessed March 12, 2014. 6. National Pesticide Information Center. Glyphosate technical fact sheet. http:// npic.orst.edu/factsheets/glyphotech.pdf. Accessed March 12, 2014. 7. Koller VJ, Fürhacker M, Nersesyan A, Mišík M, Eisenbauer M, Knasmueller S. Cytotoxic and DNA-damaging properties of glyphosate and Roundup in humanderived buccal epithelial cells. Arch Toxicol. 2012; 86(5):805-813. 8. Richard S, Moslemi S, Sipahutar H, Benachour N, Seralini GE. Differential effects of glyphosate and Roundup on human placental cells and aromatase. Environ Health Perspect. 2005;113(6):716-720. 9. Acquavella J, Alexander B, Mandel J, et al. Glyphosate biomonitoring for farmers and their families: results from the Farm Family Exposure Study. Environ Health Perspect. 2004;112(3):321-326. 10. Samsel A, Seneff S. Glyphosate’s suppression of cytochrome P450 enzymes and amino acid biosynthesis by the gut microbiome: Pathways to modern diseases. Entropy. 2013;15(4):1416-1463.

Campbell—Glyphosate


11. Majewski M, Coupe R, Foreman W, Capel P. Pesticides in Mississippi air and rain: A comparison between 1995 and 2007. Environ Toxicol Chem. February 19, 2014. doi:10.1002/etc.2550. [Epub ahead of print] 12. Athuraliya N, Abeysekera T, Amerasinghe P, et al. Uncertain etiologies of proteinuric chronic kidney disease in rural Sri Lanka. Kidney Int. 2011;80(11):12121221. 13. Jayasumana M. Sri Lankan agricultural nephropathy. In: Proceedings from the International Workshop on Chronic Kidney Disease of Nontraditional Causes; November 25-27, 2012; San Salvador, El Salvador. 14. Wanigasuriya K, Peiris-John R, Wickremasinghe R. Chronic kidney disease of unknown aetiology in Sri Lanka: Is cadmium a likely cause? BMC Nephrol. July 2011;12:12-32. 15. Peiris-John RJ, Wanigasuriya JK, Wickremasinghe AR, Dissanayake WP, Hittarage A. Exposure to acetylcholinesterase-inhibiting pesticides and chronic renal failure. Ceylon Med J. 2006;51(1):42-43. 16. Jayasumana C, Gunatilake S, Senanayake P. Glyphosate, hard water and nephrotoxic Metals: are they the culprits behind the epidemic of chronic kidney disease of unknown etiology in Sri Lanka? Int J Environ Res Public Health. 2014; 11(2):2125-2147. 17. World Health Organization. Hardness in drinking water. http://www.who.int/water_sanitation_health/ dwq/chemicals/hardness.pdf. Published 2011. 18. Bradberry S, Proudfoot A, Vale A. Glyphosate poisoning. Toxic Rev. 2004;23(3):159-167. 19. Carson R. The Silent Spring. Boston, MA: Houghton Mifflin; 1962.

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