Should glyphosate be banned without scientific evidence?

Chronic Kidney Disease of Multi-Factorial Origin (CKD-mfo)



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By Prof. Sunil J. Wimalawansa,


MD, PhD, MBA, DSc


We are concerned by the Sri Lankan government’s apparent contemplation of banning the broad-spectrum herbicide glyphosate, commonly known as Roundup, on the presumption that it is causing chronic kidney disease of uncertain aetiology (CKDue/uo). [http://www.colombopage.com/archive_14A/Mar12_1394634963CH.php]. It appears that this consideration has been prompted by a conjecture presented in the form of a hypothesis propounded by Dr. Jayasumana of the Department of Pharmacology, in the article "Glyphosate, hard water and nephrotoxic metals: Are they the culprits behind the epidemic of chronic kidney disease of unknown etiology in Sri Lanka," which was published in the February 2014 issue of the Int. J. Environmental Research & Public Health.


The article hypothesizes that glyphosate forms chemical bonds with heavy metals, forming compounds that persist in drinking water until they break down in people’s kidneys; the article stresses that the "glyphosate metal complexes" in the water are the cause of CKDu. The title of the article says it is a "hypothesis." A hypothesis is a mere suggestion. If backed up by some data or an acceptable and credible rationale, the hypothesis may become a theory, which then is tested by experimental means. This is not the case here. Unless data gathered from different sources support and prove the theory, it is rejected. Right now, the idea put forth in the article is nothing more than a guess. The authors of the article in question also report that analysis of glyphosate complexes is difficult. However, glyphosate levels (as well as measuring its complexes) in water have been available for many years from various countries. The maximum permissible levels of glyphosate in water in the European Union and United States are 0.2 and 0.7 ppm, respectively; such levels are measured regularly.


Worldwide, glyphosate (N-(phosphonomethyl)glycine) is the most commonly used herbicide (a weed killer). To date, no scientific data from any country indicate that this chemical causes renal disease in humans when used as prescribed by the manufacturers. Glyphosate may have other toxic effects, but compared with most other commonly used agrochemicals, it is a relatively safe herbicide. No agrochemical is totally safe. In this regard, the wise words of the father of pharmacology, Professor Bombastus Paracelsus, come to mind: "all substances are poisons, there is none which is not a poison; it is the dosage that differentiates a poison from a remedy." Pharmacologists especially should remember this.


CKD causes and confusions:


A number of agents and toxins have been postulated as causes of CKD of multi-factorial origin (CKD-mfo, also known as CKDu, CKDuo, and CKDue/a). Such agents include heavy metals (cadmium, arsenic), fluoride, algal toxins, agrochemicals, hard water, and ionicity (solutes in the water), leptospirosis, Ayurvedic drugs, tobacco and illicit liquor, paracetamol, inadequate water intake, and many more (see http://www.anandacollege.net/document/14011809Olcott%20Oration%20Book.pdf). Nevertheless, evidence supporting any one of these as the cause of this deadly disease is inadequate. Moreover, the World Health Organization CKD-Group’s 2013 final report is non-conclusive.


Although the hypothesis states that glyphosate metal complexes in hard water are the cause of CKDu (for which there are no data), these complexes are mostly insoluble, making less available and thus less toxic. To date, there is no scientific basis to conclude that glyphosate causes CKD-mfo. If glyphosate causes kidney failure in humans, many American farmers would have died of kidney failure [similar to that we currently see in the North Central Province (NCP)] by now. However, this is not the case.


In addition, the period in which glyphosate use was introduced in Central America and other regions of the world with a high incidence of CKD-mfo/CKDuo disease, does not coincide with this epidemic on those areas. This makes it highly unlikely that glyphosate (or the hard water) is the cause of the kidney failure epidemic currently occurring in these countries or in the NCP.


Glyphosate-metal complexes are less toxic:


The formation of glyphosate metal complexes has been known for many years; this has been reported earlier by scientists worldwide. In previous communications in The Island, at least three independent scientists (and in many others in different forums) have refuted the conjecture that these metal complexes are causing CKD-mfo based on the simple chemistry principle that these chelates are insoluble or markedly less soluble in water. Consequently, the propensity for their absorption by living organisms such as humans and plants is "less" in hard water (see http://www.island.lk/index.php?page_cat=article-details&page=article-details&code_title=98864 and http://www.island.lk/index.php?page_cat=article-details&page=article-details&code_title=99203). In soil, these large glyphosate-ion complexes increased the half-life of glyphosate by a few weeks (but inactive form), while markedly decreasing the availability of soluble free glyphosate; thus, in the presence of hard water, glyphosate becomes less toxic than in soft water further indicating the invalidity of this conjecture.


In addition, in Jaffna, Puttalam, Monaragala, and several other areas in Sri Lanka, water hardness is higher than it is in the NCP. Although farmers in these areas use similar quantities of agrochemicals, including glyphosate, little or no incidence of CKD-mfo has been reported in these areas. Moreover, the distribution of hard water in Sri Lanka does not directly coincide with the distribution of the numbers of patients with CKD-mfo. Considering all available scientific evidence to date, a glyphosate-CKD connection seems unlikely.


Glyphosate use:


Modern agriculture is dependent on agrochemicals to meet the world’s food demands, despite the potential negative effects of such chemicals on the environment. Glyphosate has been in use worldwide for nearly four decades (see http://en.wikipedia.org/wiki/Glyphosate). It is one of the most extensively used, relatively safe, herbicides in the world. It has been used across Sri Lanka since the 1980s, including in areas with hard water, with no demonstrable human kidney failure. In addition to its use in agricultural fields, in the United States and European Union, glyphosate has been approved for use on grass pastures, in forestry, and in sensitive habitats. It is approved for clearing railway lines and for use in river and lake surroundings in some countries. Thus, glyphosate is used almost anywhere, whether in the countryside or in towns and cities.


In Sri Lanka, glyphosate is used more intensively in plantation crops, especially tea, where it is sprayed three or four times a year, than in paddy cultivation in the NCP, where it is sprayed approximately twice a year (once every cultivation season). The high cost of manual weeding and acute labour shortages have made the tea industry in particular dependent on glyphosate for weed management. Apart from it being a cheaper and practical method of weed management, its important role in soil erosion mitigation is substantial. In the past, before herbicides came into use in tea plantations, weeds were controlled manually by scraping weeds with mammoties or with scrapers, sorandiya, which loosen the soil, causing significant erosion.


If glyphosate is banned, there are no equally effective and less toxic herbicides to replace it. One should be cautious that any chemical substitution of glyphosate is likely to be worse. There is no question that the judicious use of all synthetic agrochemicals is necessary to prevent health hazards to humans and animals.


How glyphosate works:


Glyphosate is a simple compound that inhibits aromatic amino acid synthesis in plants. Consequently, weeds die of protein starvation because of their inability to synthesize essential aromatic amino acids and thus plant proteins. This particular enzyme pathway and mechanism of action is not present in animals or humans, making glyphosate relatively safe.


Glyphosate molecules avidly bind to widespread cations in the soil (not to metal), such as calcium, magnesium, zinc, and ferric ions, especially to clay particles, rapidly neutralising its weedicide activity and making them relatively insoluble, large inactive complexes that neither leach into water or are available to plants. Because glyphosate binds to these abundant ions with much higher affinity than that for arsenic and cadmium, the amount of complexes made with the latter two heavy ions is miniscule. The same principle is applicable in the intestine, making the proposed hypothesis even more unlikely. After binding to soil particles, glyphosate complexes are broken down into three benign components by microbes, making them harmless to the environment. The reported median half-life of glyphosate in the soil is approximately 47 days. In water, it varies from a few days to three months, depending on the environmental conditions. Because it rapidly binds to cations such as calcium, the half-life of free glyphosate in hard water is much less, making it even less available to living beings.


Does glyphosate cause CKD-mfo?


Because glyphosate is a phosphonic compound, oral absorption is remarkably poor in humans. If a human ingests a small quantity of glyphosate, even under the best absorptive conditions, the gastrointestinal absorption is estimated to be less than 1.0% of the oral dose. Both glyphosate and its key breakdown product, aminomethylphosphonic acid (AMPA), avidly bind to divalent and trivalent cations in food. Unlike free glyphosate, these complexes have minimum or no gastrointestinal absorption.


Even if small quantities get absorbed, as with many other toxins, glyphosate will get detoxified in the liver through its first pass, via the hepatic CYP450 enzyme system. There is no known physiological way that glyphosate or its complexes can "bypass" the liver and directly damage kidneys. Thus, the idea that large glyphosate-metal complexes can "go to the kidney and cause damage" is another flawed assumption. Under these physiological conditions, it is unlikely that the minuscule amount of glyphosate that may enter the human body via the gut, skin, or inhalation could cause kidney failure. It is concerning that the author of the article in question recommends the public not eat certain locally grown vegetables and rice, ’assuming they are contaminated,’ but no data exist to support this recommendation (http://lankacnews.com/sinhala/news/112221/). These irresponsible statements are likely to harm farming communities and consumers and will not have any effect on reducing the incidence of CKD-mfo.


The need for a national science and technology advisory body:


We believe that the Government should not make a hasty decision about a matter of national interest based only on a mere hypothesis or opinions. Instead, the Government should appoint a team of unbiased (preferably retired) senior scientists to investigate these aspects thoroughly, based on the available scientific evidence, and make a firm recommendation for the benefit of the country and it populace. This suggestion is applicable for all nationally important issues, not just to the speculation regarding glyphosate. Meanwhile, the tea industry in particular should make contact the President seeking a decision on this matter that is based on sound "scientific evidence."


Proposed ban on glyphosate:


By definition, no synthetic agrochemicals are 100% safe [http://www.island.lk/index.php?page_cat=article-details&page=article-details&code_title=98247 ]. Therefore, these chemicals must be used judiciously in appropriate amounts recommended by the manufacturers and the Department of Agriculture based on soil conditions. Currently, no evidence exists that glyphosate causes kidney failure in humans. Banning glyphosate would badly affect agriculture, increasing the cost of agricultural production and decreasing agricultural output, which would mean less income for farming families, causing more hardships to them. In addition, a ban would increase the costs of food for consumers. Most importantly, such a ban will not have the intended effect of reducing the incidence of CKD-mfo in the NCP.


Recommendations:


Because no single ministry or department is taking responsibility for hazardous materials (pollutants and toxins) in the country, it would be prudent to create a new department or an authority of "Toxic Substance Control" for Sri Lanka that would fully focus on all local and imported toxic compounds, including routine and spot testing of relevant material. The primary function of such an agency should be to take proactive steps to identify and eliminate health risks associated with all toxic substances.


The Registrar of Pesticides and agricultural research institutions should voice their scientific views. We urge that the government assemble a forum of reputable, unbiased technocrats to advise on technical and economic matters of major national interest, much like the National Planning Commission of India.


 
 
 
 
 
 
 
 
 
 
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