There is no Scientific Evidence that Herbicide Glyphosate Causing Chronic Kidney Disease of Multi-Factorial Origin (CKD-mfo) in Sri Lanka
Posted on July 6th, 2014
In spite of the pressure to ban glyphosate from Sri Lanka, the Government firmly rejected it at the recommendation of the Pesticide Technical Advisory Committee. There is an assumption that this broad-spectrum herbicide glyphosate, (used to known as Roundup, but now sold under a variety of trade names) may cause chronic kidney disease of uncertain aetiology (CKDue/uo). http://www.colombopage.com/archive_14A/Mar12_1394634963CH.php
However, this consideration was promoted on a hypothesis written in an article, which lacks any evidence for such claims. There are major criticisms of both, supporters and opponents of glyphosate story; being non-scientific and biased. The author takes neither side and the comments below are based on scientific data available to-date.
It has been known for several years that glyphosate forms heavy metal-complexes, making it insoluble. Similarly, the measurement of free glyphosate and its complexes in water has been performed in several countries for many years. The maximum permissible levels of glyphosate in water within the European Union and United States are 0.2 and 0.7 ppm, respectively.
The article in question hypothesizes that glyphosate forms chemical bonds with heavy metals, forming compounds that persist in drinking water until they are broken down in the kidneys and that the “glyphosate metal complexes” in the water are the cause of CKDu. However, authors have not provided any evidence or data to support it. There is, hitherto, no published analytical data on the levels of glyphosate in water anywhere in Sri Lanka. Therefore, until at least such data is available and some evidence that it is linked to renal failure in humans, this hypothesis must remain rejected.
What is glyphosate?
Worldwide, glyphosate (N-(phosphonomethyl)glycine is the most commonly used herbicide (a weed killer). To date, no scientific data from any country indicates that, when used as prescribed by the manufacturers, it causes renal failure in human. Glyphosate may have other toxic effects, but compared to many other commonly used pesticides and herbicides, it is a relatively safe compound. There is no doubt that 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 and the exposure that differentiates a remedy form a poison.”
Glyphosate, has been used successfully as a weed control agent worldwide, for the past several decades (please see: http://en.wikipedia.org/wiki/Glyphosate). Globally, it is perhaps the most extensively used herbicide. It has been used in Sri Lanka since the 1980s, but in the North Central Province (NCP) only since early 2,000. However, patients with Chronic Kidney Disease of multi-factorial origin (CKD-mfo) have been reported several years before the introduction of glyphosate to the region. Despite the concerns of the potential adverse effects of agrochemicals on the environment, modern agriculture continues to dependent on these to meet the world’s increasing food demand.
In addition to its use in agricultural fields, glyphosate has been approved for the use on grass pastures, in forestry and in sensitive habitats in many countries including the United States and the European Union. It is even approved for clearing railway tracks and for use in surroundings areas of rivers and lakes in some countries. Thus, glyphosate is used almost every.
In Sri Lanka, glyphosate is used most intensively in plantation crops (not necessarily in the paddy fields in NCP), especially in tea fields, where it is sprayed three or four times a year. This is in comparison to the paddy cultivations, 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 a practical way of managing weed, its role in mitigating soil erosion is substantial. In the past, before herbicides came into use in tea plantations, weeding was done manually by scraping weeds with mammoties or with scrapers (sorandiya), which loosened the soil causing significant erosion and loss of fertile top soil. If for some reason glyphosate is banned, there are no equally effective and less toxic herbicides to replace it. Moreover, any chemical substitution of glyphosate is likely to be worse. Nevertheless, there is no question that the proper amount and correct use of all synthetic agrochemicals must be propagated and are essential to mitigate environmental pollution and health hazards.
Mechanism of action of glyphosate:
Glyphosate 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 (i.e., this effect is plant specific), making glyphosate relatively safe for other living beings.
Glyphosate molecules avidly bind to most cations in the soil such as calcium, magnesium, zinc, and ferric ions, and to clay particles. Once bound, there glyphosate loses the “weedicidal” activity or toxicity. The generated relatively large insoluble matrices containing inactive glyphosate complexes neither leach into the water nor are available for plants. Glyphosate binds to these abundant soil cations like calcium with higher affinity than with arsenic and cadmium (heavy metals), making very little amounts of complexes with the latter two heavy ions.
After binding to soil particles, glyphosate complexes are broken down into three harmless components by microbes, making them nontoxic 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 water hardness and other environmental conditions. Because it rapidly binds to cations such as calcium, and the half-life of free glyphosate in hard water is low, its availability to living beings is minimal.
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, to safeguard farmers, the environment, and the public, and for cost-effective usage, only the necessary amounts of fertiliser should be released to farmers as recommended by the manufacturers and the agricultural research and extension institutions based on local soil testing data.
Banning glyphosate would badly affect agriculture, increase the cost of agricultural production, and decrease agricultural output and returns for the farmer, and a higher food costs for the consumer. Most importantly, such a ban will not reduce the incidence of CKD-mfo in the country.
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, etc.). The use of the term, CKD-mfo is appropriate, as multiple factors and toxins seem to come together to precipitate this deadly disease. Identifying it with one component or for that matter even with agrochemicals (without scientific, causative data) may mislead and divert the attention and research from “true cause(s)” (open mindedness) of this deadly disease.
The proposed causative agents include heavy metals (cadmium, arsenic), fluoride, algal toxins, agrochemicals, hard water, and ionicity (solutes in the water), leptospirosis, some Ayurvedic drugs, locally grown tobacco and illicit liquor, paracetamol, non-steroidal anti-inflammatory drugs (pain killers), inadequate water intake (chronic dehydration), and others (for detail, please visit; http://www.anandacollege.net/document/14011809Olcott%20Oration%20Book.pdf ). Nevertheless, evidence supporting any one of these agents as the cause of this CKD-epidemic is inadequate, as even the World Health Organization CKD-Group’s 2013, final report is non-conclusive.
Although the said article’s hypothesis states that glyphosate metal complexes in hard water are the cause of CKDu (for which there is no scientific data), these complexes are mostly insoluble, which makes them less available and less toxic to living beings. Even after extensive use of this chemical worldwide for over four decades, there is no medical or scientific evidence that glyphosate causes CKD-mfo. If glyphosate causes kidney failure in humans, many American and European farmers should have been affected by this kidney disease. This is not the case.
In addition, the period in which glyphosate use was introduced in Central America, Southern Europe and other regions of the world from where CKD-mfo/CKDuo patients are reported, does not coincide with this epidemic in those areas: i.e., the CKDu epidemic has been present, even before the introduction of glyphosate, just as in the NCP in Sri Lanka. This point alone makes it highly unlikely that glyphosate (or hard water for that matter, which has been present in the NCP area for centuries) is the cause of the current kidney failure epidemic occurring in dry zonal regions in certain equatorial countries, one of which is the CKD-mfo epidemic in NCP in Sri Lanka.
Glyphosate-metal complexes are less toxic and unlikely to cause kidney failure:
Scientists worldwide have reported the formation of glyphosate metal complexes for many years (this is not new information). Several Sri Lankan scientists have written to The Island, disproving the conjecture that these metal complexes could cause CKD-mfo based on the simple chemistry principle that these heavy metal-chelates are insoluble or markedly less water-soluble. Consequently, the absorption via the gastrointestinal track or the skin is “minimal,” especially in the presence of hard water (please 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).
Because of nature of these large glyphosate-ion complexes, it increases the half-life of glyphosate by a few weeks in farm soils. However, simultaneously, it inactivates glyphosate activity and decrease the likelihood of soluble (free) glyphosate contaminating water sources. Therefore, in the presence of hard water, glyphosate becomes less available for contaminating water and less toxic than in soft water. Ironically, the manufacturers of glyphosate are now using surfactants to keep this molecule in soluble (i.e., to prevent the formation of cations/ metal complexes) to increase its herbicidal activity.
No evidence to suggest glyphosate causing 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 total oral dose. Both glyphosate and its key breakdown product, aminomethylphosphonic acid (AMPA), avidly bind to divalent and trivalent cations in food. These complexes have minimum or no gastrointestinal absorption.
Even if small quantity of glyphosate is absorbed, as happens with many other environmental toxins (i.e., xenobiotics), it will get detoxified during the first pass through the liver, via a evolutionary liver enzyme system (CYP450). There is no known physiological way that glyphosate or its complexes can “bypass” the liver and directly damage the kidneys. Thus, the idea that large glyphosate-metal complexes (need to get absorb first) bypass the liver and “go direct to the kidneys and cause damage” as proposed in the hypothesis is flawed. On the contrary, under these protective physiological conditions, it is unlikely that the minuscule amount of glyphosate that may enter the human body via the gut, skin, or inhalation, would reach kidneys in sufficient amounts to cause kidney damage.
Hard water is not the cause for CKD-mfo:
The distribution pattern of patients and deaths attributed to CKD-mfo correlate with the rainfall and within certain geographical regions. In fact, no patient with CKD-mfo has been documented from the wet zone in Sri Lanka including NuwaraEliya region where farmers use even high quantities of fertiliser.
Moreover, farmers continue to use glyphosate in regions where the water hardness is much higher than that in the most areas within the NCP, such as in Jaffna, Puttalam, Monaragala, and other areas. Yet, the prevalence of CKD-mfo is far less in these areas. The distribution of (natural, ground) hard water in Sri Lanka does not coincide with the distribution of the numbers of patients (or clusters of patients) with CKD-mfo (see the attached figure). Considering all available data to date, the proposed glyphosate-CKD (and hard water) connection is unlikely.
The need for a national science and technology advisory body:
We believe that the Government should not make a hasty decision about matters of national interest based on a mere hypotheses or opinions. Rather than appointing biased scientists and politicians, the Government should consider appointing a team of reputed unbiased, senior scientists with expertise in these filed(s) scientifically investigate this hypothesis and other claims, and propose evidence-based firm decision and directions on this nationally important matter.
The tea industry in particular and the department of agriculture and the Pesticide Technical Advisory Committee should provide balanced scientific evidence to the above-committee for consideration. Meanwhile the relevant scientific institutions and ministries, as well as the government have a fiduciary duty to protect the environment and educate the public based on the available scientific evidence, how to prevent this deadly disease, rather than be non-committal.
What is Needed:
Sri Lanka has the Central Environmental Authority and the Pesticide Technical Advisory Committee. However, it may be time to think whether it would be proper either to (A) strengthen the responsibility, authority and the accountability of these two organisations, or (B) to created a new Authority to control all “Toxic Substances,” in Sri Lanka. Such a department should focus on not only keeping records, creating right policies, and working as an advisory capacity, but primarily focus on testing all imported and locally produced toxic compounds, agrochemicals, and other hazardous material before these are released to the public, and to monitor their usage and distribution channels. Accountability and the transparency should include, reporting the summary of findings and actions the new Authority has taken to the parliament on quarterly basis and releasing these data to the public. The primary function of such an agency should be to proactively protect the public, just like the Food and Drug Administration (FDA) does in the United States and in Europe.
A National Crisis that Requires Presidential Intervention:
It is critical that the Government establishes a “CKD-Alleviation Authority,” rather than relying on conflicting recommendations from various advisory bodies and avoid inherent conflicts of interests. The country needs a firm actions to prevent and eradicate this deadly disease that kills farmers in significant numbers: http://www.wudpeckerresearchjournals.org/WJAR/pdf/2014/May/Wimalawansa%20and%20Wimalawansa.pdf
This action plan should includes but not limited to, (A) preventing environmental pollution, (B) large-scale public education on this disease and practical ways and means on preventing pollution, (C) encouraging organic farming, and (D) provision of clean water to everyone in all affected regions at the earliest possible.
In the absence or delaying of such program, that must cover the entire NCP and other affected areas, the deaths due to CKD-mfo and the miseries of the affected families will continue.