{"id":57762,"date":"2016-08-19T14:08:40","date_gmt":"2016-08-19T20:08:40","guid":{"rendered":"http:\/\/www.lankaweb.com\/news\/items\/?p=57762"},"modified":"2016-08-18T14:24:49","modified_gmt":"2016-08-18T21:24:49","slug":"the-new-zealand-governmet-clear-the-wedicide-glyphosate-as-perfectly-safe-for-use","status":"publish","type":"post","link":"https:\/\/www.lankaweb.com\/news\/items\/2016\/08\/19\/the-new-zealand-governmet-clear-the-wedicide-glyphosate-as-perfectly-safe-for-use\/","title":{"rendered":"The New Zealand governmet clear the wedicide Glyphosate as perfectly safe for use."},"content":{"rendered":"

Chandre Dharmawardana<\/em><\/span><\/h2>\n

The New Zealand government, after an long review of the weedicide Glyphosate (Roundup), has now given it the ALL CLEAR signal, confirming that it is VERY SAFE for use.<\/p>\n

Here is the report:<\/p>\n

http:\/\/www.epa.govt.nz\/Publications\/EPA_glyphosate_review.pdf<\/a><\/p>\n

BACKGROUND TO THE STORY:<\/strong><\/p>\n

Sometime ago there were sensational claims that Glyphosate,\u00a0 the popular weedicide,\u00a0 causes kidney diseases, Cancer etc., and that it should be banned.<\/p>\n

Fools rush in where angels fear to tread.<\/em><\/p>\n

Sri Lanka was the first country to ban the herbicide; this was politically lead by Ven. Ratana and the Minsiter Champika Ranawaka who claimed to rid the country of “Toxins”.\u00a0 It was preceded by a campaign (during the previous government) by Ven Ratana, and by a number of\u00a0 highly politicized\u00a0 Kelaniya University academics who claimed that God Natha had revealed that the Rajarata water has arsenic. This was further elaborated\u00a0 by them and a Sri Lankan Californian doctor to claim that Arsenic combines with glyphosate and hard water to bring the toxin into the human body! This was presented as a “hypothesis” and not a proven fact in a “journal”<\/em>, but it has been presented as a proven fact when broadcasting\u00a0 it to the public!<\/strong><\/p>\n

The arsenic is supposed to be found in imported\u00a0 fertilizers.<\/p>\n

So, according to them, agrochemicals- fertilizers and herbicides<\/em>–\u00a0 are to blame. Even if they are not to blame, some of the “eco-activists”\u00a0 advocated banning them as a “precautionary principle<\/em>“.<\/p>\n

Once imported fertilizers are banned, people have to use “organic fertilizers”, i.e., make the fertilizer themselves by composting leaves, and other plant material “like in the olden days”.<\/p>\n

Or buy the highly polluted\u00a0 “organic fertilizer” imported\u00a0 from India at great cost.<\/p>\n

To get the effect of one kilo of inorganic fertilizer, you need to use something like\u00a0 one TON of organic fertilizer. Such compost is polluted because plants accumulate metal toxins found in trace amounts in the soil.<\/p>\n

Remember, this is a country where “Kassipu” and “Kudu” are freely available. All pharmacies sell “viagra” or cortisone drugs without a prescription. Motor vehicles belch out toxins and diesel fumes all over the country. There are mounds of garbage in every street corner. The general pollution levels are high. But the “eco-activists” and “environmental heroes”\u00a0 (mostly from the affluent strata of Colombo society) are worried about “glyphosate” and arsenic. But their\u00a0 presence in the water or soil in significant amounts have not been confirmed even though searched for by\u00a0 several different teams of scientists who carried out chemical analysis. Even the Kelaniya scientists have failed to find significant amounts of them in the soil or water or food consumed by the people.<\/p>\n

New Zealand and many other countries use even ten times the agrochemicals used by<\/p>\n

Sri Lanka or, say,\u00a0 Nicaragua. The countries that use agrochemicals\u00a0 do not have chronic kidney disease nor do they have a high incidence\u00a0 of diseases. It is the countries like Sri Lanka, Nicaragua, who do\u00a0 NOT use agrochemicals, and who fail to provide a nutritious diet, clean water and a healthy life to their citizens who have chronic diseases. Chronic diseases and agrochemicals ANT-CORRELATE with each other, where as they should correlate if agrochemicals were significantly responsible for chronic disease.<\/p>\n

The New Zealand government, responding to the agitation by eco- extremists in that country and the resulting public fear,\u00a0 initiated a review of all the available facts. After many months of review of the weedicide Glyphosate (Roundup),\u00a0 the NZ govt has\u00a0 given it the ALL CLEAR signal.<\/p>\n

I attach here the report of the NZ government’s\u00a0 review.<\/p>\n

Today, in Sri Lanka, a country with an acute shortage of labour, many of the tea estates are struggling to survive. Chicken and other livestock growers have no animal feed because the\u00a0 Corn (“Bada Iringu”) growers who produced animal feed have given up. Other farming sectors are also in trouble.<\/p>\n

Chandre Dharmawardana<\/p>\n

————————————————————————————————–<\/p>\n

REPORT<\/p>\n

(please go to http:\/\/www.epa.govt.nz\/Publications\/EPA_glyphosate_review.pdf<\/a>\u00a0to read it properly).<\/p>\n

————————————————————————————————–<\/p>\n

Review of the Evidence Relating to
\nGlyphosate and Carcinogenicity
\nPrepared for the Environmental Protection Authority
\n<\/strong>
\nPublished August 2016
\n1
\nIntroduction<\/strong>
\nGlyphosate (N-phosphonomethyl glycine; CAS registry #1071-83-6) is the primary active
\ningredient in many generic herbicides. Glyphosate is formulated primarily as an
\nisopropylamine, ammonium, or sodium salt in water soluble concentrates and water soluble
\ngranules. The relevant impurities in glyphosate technical concentrates are formaldehyde, N-
\nnitrosoglyphosate and N-nitroso-N-phosphonomethylglycine. Surfactants and sulfuric and
\nphosphoric acids may be added to formulations of glyphosate, with type and concentration
\ndiffering by formulation. The United States (US) Environmental Protection Agency (EPA) and
\nother regulatory agencies around the world have registered this chemical as a broad-
\nspectrum herbicide for use on multiple food and non-food use crops. Glyphosate-based
\nherbicides, which have been sold in the US since 1974, are now registered in over 130
\ncountries.
\nGlyphosate is widely considered by regulatory authorities and scientific bodies to have no
\ncarcinogenic potential. The US EPA (1993) has classified glyphosate as a Group E
\ncarcinogen, which is defined as having \u2018\u2018evidence of non-carcinogenicity for humans\u2019\u2019. This
\nclassification was based on \u2018\u2018a lack of convincing evidence of carcinogenicity in adequate
\nstudies with two animal species, rat and mouse\u2019\u2019. Negative results were observed in
\ngenotoxicity studies that were conducted under good laboratory practice conditions and compliant with contemporary regulatory test guidelines.
\nHowever since that time, results of further studies have come to light, and the International
\nAgency for Research on Cancer (IARC) Monograph 112 on glyphosate (released on 29 July
\n2015) came to the conclusion that glyphosate should now be classified as a carcinogenic
\nsubstance in Group 2A (probably carcinogenic to humans). This classification was based on
\nlimited evidence\u201d from human data (regarding non-Hodgkin lymphoma (NHL)) but sufficient
\nevidence\u201d in animal-experiments. The rationale identifies that the IARC working group (IWG)
\nalso notes mechanistic and other relevant data in support of the conclusion; in particular the
\nIWG cites strong evidence\u201d that glyphosate can operate by two key characteristics of known
\nhuman carcinogens, namely genotoxicity and oxidative stress.
\nThis classification was initially published in a short report by Blair et al, (2015) in the Lancet
\nOncology\u201d on 20 March 2015.
\nThis report discusses the relevant data on glyphosate, especially the more recent studies,
\nand reviews the basis on which the IWG classified it as a probable human carcinogen
\n(Group 2A). This involves review of the quality of evidence for carcinogenicity in humans and experimental animals and the mechanistic arguments.
\nCancer in humans<\/strong>
\nThe IWG found there was limited evidence in humans for the carcinogenicity of glyphosate.
\nSome case-control studies of occupational exposure in the USA, Canada, and Sweden
\nreported increased risks for NHL that persisted after adjustment for other pesticide
\nexposures. However the Agricultural Health Study (AHS) cohort did not show a significantly
\nincreased risk of NHL. These studies are discussed below.<\/p>\n

Case-control studies in the Midwest USA<\/strong>
\nThree case-control studies were conducted by the U.S National Cancer Institute in Iowa and
\nMinnesota in the1980s using the same control series, but each investigating a different
\nlymphohaematopoietic cancer. Brown et al, (1990) found a near null association between
\n2
\nglyphosate exposure and leukaemia among white males residing in the area (OR = 0.9; 95%
\nCI 0.5\u20131.6). Among Iowa farmers reporting ever handling glyphosate, there was a slight non-
\nstatistically significant odds ratio for multiple myeloma (OR = 1.7; 95% CI 0.8\u20133.6) (Brown et
\nal, 1993). Cantor et al, (1992) found an approximately null association between glyphosate
\nexposure and NHL among males (OR 1.1; 95% CI 0.7\u20131.9).
\nThe IWG reviewed a later study by De Roos et al, (2003) who used pooled data from three
\ncase-control studies of NHL conducted in the 1980s in Nebraska (Zahm et al, 1990), Iowa
\nand Minnesota (Cantor et al, 1992), and Kansas (Hoar et al, 1986). Reported use of
\nglyphosate as well as several other individual pesticides was associated with an increased
\nrisk of NHL. A total of 650 cases and 1,933 controls were included for the analysis of 47
\npesticides. Reporting glyphosate exposure were 36 cases and 61 controls. After adjusting
\nfor other pesticide use, age, and study area, by two regression techniques, odds ratios of 2.1
\n(1.1\u20134.0) using logistic regression and 1.6 (0.9\u20132.8) using hierarchical regression were
\nfound.
\nIn that regard, a later study by De Roos et al, (2005) where they reviewed the AHS cohort
\ndata is significant. They found no association between glyphosate and NHL. The authors
\nnoted that the aforementioned Midwest USA case control studies were retrospective in
\ndesign and therefore potentially susceptible to recall bias as regards exposure reporting.
\nThe cross-Canada case \u2013 control study<\/strong>
\nThe IWG reviewed a report by McDuffie et al, (2001) who studied the association between
\nNHL and exposure to specific pesticides in a multicentre population-based study with 517
\ncases and 1,506 controls among men of six Canadian provinces. The authors reported a
\nslight, non-statistically significant increased risk for NHL from claimed glyphosate exposure,
\nthe OR being 1.26 (95% CI 0.87\u20131.80) for analysis adjusted for age and province, and 1.20
\n(95% CI 0.83\u20131.74) for analysis adjusted for age, province and high-risk exposures. The
\nstudy also assessed the significance of different exposure durations. When stratified by
\ngreater than or less than two days of glyphosate exposure\/year (< 2d\/year), the values were
\n2.12 (95% CI 1.20\u20133.73) for >2d\/year relative to those with < 2d\/year (assigned OR of 1.0).
\nThe authors commented that although there was not a statistically significant finding for
\nexposure to glyphosate per se, there was a dose-response relationship.
\nCase-control studies in Sweden<\/strong>
\nThe IWG reviewed a study by Eriksson et al, (2008) who reported the results of a population-
\nbased case-control study of exposure to pesticides as a risk factor for NHL. Men and women
\naged 18\u201374 years living in Sweden were included from 1 December 1999 to 30 April 2002.
\nIn total, 910 (91%) cases and 1,016 (92%) controls participated. The authors found NHL
\nassociations with exposure to glyphosate. This exposure was reported by 29 cases and 18
\ncontrols, giving a reported odds ratio of 2.02 (95% CI 1.10\u20133.71) in a multivariate analysis.
\nWhen restricted to a >10 year latency period the OR became 2.26 (95% CI 1.16\u20134.40).
\nOdds ratios were also reported for lymphoma subtypes. For only two of the eight subtypes
\nwere odds ratios statistically significant; likely related to the small numbers. The IWG
\nconsidered that this was a large study; that there was possible confounding from the use of
\nother pesticides including MCPA, but this was controlled for in the analysis. Given the
\nnumber of cases studied for glyphosate (29 cases and 18 controls) this study could hardly
\nbe considered as large. Twelve subjects were in a less than 10 days exposure group and 17
\nin a more than 10 days group. Therefore this study had limited power to detect an effect.
\n3
\nOther findings<\/strong>
\nIn 2014 Schinasi and Leon reported their study of the association between NHL and
\noccupational exposure to various agricultural pesticide chemical groups. Some findings on
\nglyphosate were presented; for example the results from the studies by McDuffie et al,
\n(2001), De Roos et al, (2005) and Eriksson et al, (2008) were given. This review included a
\nseries of meta-analyses, which they asserted showed consistent evidence of positive
\nassociations between NHL and carbamate insecticides, organophosphorus insecticides,
\nlindane, and MCPA. As regards glyphosate (an organophosphorus herbicide\u201d), in a handful
\nof papers\u201d, associations between pesticides and NHL subtypes were reported; B cell
\nlymphoma was positively associated with phenoxy herbicides and glyphosate.
\nThe Agricultural Health Study (AHS) cohort studies<\/strong>
\nThese studies in Ohio and North Carolina involve a large cohort of private and commercial
\npesticide applicators (57,311 as at 2004\u20135). Several studies have been conducted using this
\ncohort.
\nAlavanja et al, (2003) evaluated associations between specific pesticides and prostate
\ncancer in the AHS. Glyphosate was listed as one of the pesticides with sufficient exposure
\ndata for analysis, but the findings for it were not listed, so that it has been assumed that no
\nsignificant positive association was found with prostate cancer.
\nFlower et al, (2004) evaluated associations between pesticide application by parents and
\ncancer among children born to Iowa participants in the AHS. There was no positive
\nassociation between either maternal or paternal use of glyphosate and risk of childhood
\ncancer.
\nDe Roos et al, (2005) evaluated associations between glyphosate exposure and all
\ncancers\u201d or any cancer site using the AHS cohort. This study did not show a significantly
\nincreased risk of NHL. In the group reportedly exposed to glyphosate, small, non-statistically
\nsignificant relative risks of 1.2 (95% CI 0.7\u20131.9) adjusted for age (only) and 1.1 (95% CI 0.7\u2013
\n1.9) adjusted for age, demographic and lifestyle factors and other pesticide exposure were
\nfound for NHL, (De Roos 2005). There was no dose (exposure) response relationship.
\nDe Roos et al, (2005) also found a non-statistically significant association between
\nglyphosate exposure and multiple myeloma, with rate ratios (RR values) of 1.1 (95% CI 0.5\u2013
\n2.4) adjusted for age only, and 2.6 (95% CI 0.7\u20139.4) adjusted for age, demographic and
\nlifestyle factors and other pesticides exposures. Such a finding had not previously been
\nreported.
\nComparisons were made between ever-exposed versus never-exposed groups, and
\nbetween three equal sized groups (tertiles), formed by subdivision either on the basis of total
\ndays of exposure or intensity-weighted exposure days. In the intensity-weighted analysis of
\nglyphosate and lung cancer, the relative risk for the highest tertile was only 0.6 (95% CI 0.3\u2013
\n1.0), for pancreatic cancer the RR for the highest tertile was 0.5, while for multiple myeloma
\nthe RR was 2.1, but the confidence interval was wide (0.6\u20137.0). None of these findings
\nreached statistical significance at 95%. Regarding the whole group (ie ever used
\nglyphosate), the RR for multiple myeloma was 1.1 (95% CI 0.5\u20132.4) adjusted for age only,
\nand 2.6 (95% CI 0.7\u20139.4) adjusted for age, demographic and lifestyle factors and other
\npesticide exposures. Unremarkable, non-statistically significant results were found for the
\nother cancer sites assessed.
\n4
\nThus as regards this study, there was no evidence of a statistically significant positive
\nassociation for any of the cancers for which data were reported (Mink et al, 2012).
\nFurthermore De Roos et al, (2005) acknowledged in their paper that over 13,000 subjects
\nwere excluded from multivariate analyses because of missing data. In analyses of ever\u201d
\nversus never\u201d exposed to glyphosate, the age-adjusted relative risk of multiple myeloma
\nwas 1.1. Lash (2007) assessed the study design and concluded that adjustment for
\nconfounders, which resulted in limiting the data set by 25% because of missing data on the
\nadjustment variables, likely introduced selection bias, which was likely to have been in the
\ndirection away from the null (ie exaggerating any possible risk).
\nIt is also known that multiple myeloma is often preceded by monoclonal gammopathy of
\nundetermined significance (MGUS), a pre-malignant plasma cell disorder (Morgan et al,
\n2002). It is of interest to note that a decreased risk (albeit not statistically significant) of
\nMGUS was observed in glyphosate applicators in the AHS.
\nEngel et al, (2005) evaluated breast cancer risk among wives of farmers in the AHS. No
\nstatistically significant association was found.
\nIn an analysis of colorectal cancer and pesticide use, Lee et al, (2007) found no statistically
\nsignificant association between glyphosate use and cancer of the colon or rectum.
\nAndreotti et al, (2009) reported no significant association of ever\u201d use (versus never use\u201d)
\nof glyphosate with pancreatic cancer among the combined group of AHS applicators and
\nspouses (OR 1.1; 95% CI 0.6\u20131.07), nor was there evidence for a dose-response
\nrelationship.
\nDennis et al, (2010) evaluated associations of 50 pesticides with cutaneous melanoma in the
\nAHS cohort. Glyphosate was listed as one of the 22 pesticides on the enrolment
\nquestionnaire. The authors commented that none of these 22 pesticides was associated with
\nmelanoma.
\nNone of the AHS cohort study analyses reported statistically significant positive findings for
\nglyphosate exposure and total cancer or any site-specific cancer, in adults or children. In
\nparticular, the prospective AHS studies did not corroborate the positive association with NHL
\nreported by the Swedish case-control studies. Analyses of increasing category of glyphosate
\nexposure days and incidence of NHL produced rate ratios that were below the null value of
\n1.0 (De Roos et al, 2005 and Mink et al, 2012).
\nDiscussion of review of epidemiological findings
\nIn a review of glyphosate in 2006, the WHO observed that:
\nwidely used pesticides, like glyphosate, have recently become a focus of epidemiological
\nresearch. In the past few years several epidemiological studies have been published that
\nreported weak associations of glyphosate with lymphopoietic cancers, self-reported adverse
\nreproductive outcomes and self-reported attention deficit hyperactivity disorder in children.
\nHowever, the results of these studies do not meet generally accepted criteria from the
\nepidemiology literature for determining causal relationships. Generally, the associations
\nwere rather weak and rarely statistically significant. Controlling for potential confounding
\nfactors, including other pesticides exposure, was not possible owing to limited available
\ninformation and small numbers of subjects\u201d.
\nWhether or not there was any internal exposure or the extent of such exposure was not
\nmeasured and, accordingly, a possible dose\u2013response relationship could not be evaluated.
\n5
\nThis seems a fair assessment of several of the studies regarding glyphosate and its
\nformulations. De Roos et al, (2005) noted that the Midwest USA case control studies were
\nretrospective in design and therefore potentially susceptible to recall bias as regards
\nexposure reporting. Certainly a large prospective cohort study (such as that by De Roos et
\nal, 2005) is much preferable to smaller case-control studies, the latter of which have much
\nless statistical power to identify causal associations and are subject to more biases,
\nincluding those regarding exposure assessment. Therefore much more weight should be
\ngiven to the De Roos et al, (2005) cohort study than the much smaller De Roos et al, (2003)
\ncase-control study. In that regard, it is important to note that the cohort study found no
\nassociation between glyphosate and NHL. There was, however, a small (non-statistically
\nsignificant) increased risk of multiple myeloma in the 2005 study, but the point estimates of
\nthis risk may have been exaggerated. (Lash 2007.)
\nA re-analysis of some data from the De Roos et al, (2005) study has recently been
\nundertaken, with a focus on multiple myeloma (Sorahan, 2015). Assessing the same data,
\nSorahan found no significant trends of multiple myeloma risk with reported cumulative days
\nof glyphosate use, and unexceptional point estimates of risk for ever-use of glyphosate. This
\nwas irrespective of whether the analysis had made adjustment for a few basic variables (age
\nand gender) or made adjustment for many other lifestyle factors or pesticide exposures; as
\nlong as data on all available pesticide applicators was used.
\nSorahan (2015) argued that the elevated rate ratios (or relative risks) for multiple myeloma
\nreported previously by Roos et al, (2005) arose from use of restricted data sets that,
\nprobably by chance, turned out to be unrepresentative. These restrictions were considered
\nto be unnecessary and undesirable, as potentially informative data on the exposure or
\noutcome under investigation were discarded. For example, it was asserted that there were a
\nnumber of lost cases of multiple myeloma in the group of applicators who had never used
\nglyphosate, because they were excluded by Roos et al, (2005) due to their not having data
\non for example use of alcohol, or smoking. These lost cases in the baseline category gave a
\nfalse impression of elevated rates in ever-users. As a result Sorahan gave more weight to
\nthe point estimate of 1.1 as the RR (adjusted for age only) as opposed to the estimate of 2.6
\nas the RR for ever-use of glyphosate (adjusted for age, demographic and lifestyle factors,
\nand other pesticides).
\nMink et al, (2012) reviewed the epidemiological literature (and relevant methodological and
\nbiomonitoring studies) to evaluate whether exposure to glyphosate is associated causally
\nwith cancer risk in humans. Seven cohort studies and fourteen case-control studies
\nexamining a potential association between glyphosate and one or more cancer outcomes
\nwere subjected to a qualitative analysis.
\nThe cohort studies were all based on analyses of participants or family members of the AHS
\ncohort. Mink et al (2012), observed that none of the AHS cohort study analyses reported
\nstatistically significant positive findings for glyphosate exposure and total cancer or any site-
\nspecific cancer in adults or children. They found no consistent pattern of positive
\nassociations to suggest a causal relationship between human exposure to glyphosate and
\nany cancer.
\nOverall, this 2012 review found no consistent pattern of positive associations between total
\ncancer (in adults or children) or any site-specific cancer, and exposure to glyphosate. They
\nsuggested a cautious interpretation of the few positive associations reported, and concluded
\nthat the epidemiological data, when considered together, did not support a causal
\nassociation between glyphosate exposure and cancer.
\n6
\nSimilarly, the latest report of BfR (2015) to the European Food Safety Authority (EFSA)1
\nbased on the evaluation of over 30 epidemiological studies came to the overall assessment
\nthat there is no validated or significant relationship between exposure to glyphosate and an
\nincreased risk of NHL or other types of cancer.
\nA recent peer review by EFSA2 (2015) essentially confirmed the conclusions in their re-
\nevaluation of glyphosate. They noted that 10 cohort studies (which included the AHS, the
\nlargest series of prospective studies to date), found that glyphosate did not cause different
\ntypes of cancer and did not increase risk of all cancers combined. (As noted earlier, the
\nfindings for NHL were negative in the AHS cohort.) Similarly nine case-control studies did
\nnot indicate an increased risk of carcinogenicity, or did not have sufficient power to assess
\nthis. With regard to NHL, the case-control studies exhibited poor consistency in their results
\nand small numbers of cases limiting the statistical significance of findings in some studies.
\nAs noted above, case-control studies have less power, are more subject to various biases,
\nand are less effective at assessing actual exposure levels than are cohort studies. EFSA
\nconcluded that there is very limited evidence for an association between glyphosate
\nexposure and the occurrence of NHL.
\nCancer in experimental animals<\/strong>
\nMice studies<\/em>
\nGlyphosate was tested in female and male mice by dietary administration in two studies.<\/p>\n

A
\nskin application in one initiation-promotion study was conducted with male mice.
\nThe IWG found that in male CD-1 mice, glyphosate induced a positive trend in the incidence
\nof a rare tumour, renal tubule carcinoma. A second study reported a positive trend for
\nhemangiosarcoma in male mice. A glyphosate formulation promoted skin tumours in an initiation-promotion study in mice.
\nThe IWG noted there was a positive trend in the incidence of renal tubule carcinoma and of
\nrenal tubule adenoma or carcinoma (combined) in male CD-1 mice in a glyphosate feeding
\nstudy (0, 1,000, 5,000, or 30,000 ppm glyphosate ad libitum for 24 months). (This study was
\nconducted prior to the institution of GLP.) The study was submitted to the US EPA which
\nrequested that a pathology working group (PWG) be convened to evaluate the renal
\ntumours. In this second evaluation, the PWG found that the incidence of adenoma was not
\nstatistically significant but the incidence of carcinoma and the incidence of adenoma and
\ncarcinoma (combined) were significant. The IWG considered that this second evaluation
\nindicated a significant increase in the incidence of rare tumours, with a dose-related trend,
\nwhich could be attributed to glyphosate.
\nHowever, this finding is at variance with the US EPA (1993) which reported in their
\nglyphosate review that the occurrence of these adenomas was spontaneous rather than
\ncompound-induced because the incidence of renal tubular adenomas in males was not
\nstatistically significantly different when compared with the concurrent controls. An
\nindependent group of pathologists and biometricians also conducted extensive evaluations
\nof these adenomas and reached the same conclusion. The US EPA concluded glyphosate
\nwas not considered to be carcinogenic in this study.
\n1
\nThe BfR (2015) report addressing the carcinogenicity of glyphosate is a report of Germany
\nspecifically, as Germany was the lead member state for the EFSA review of glyphosate.
\n2
\nEFSA accepted the conclusion relating to glyphosate and cancer (including NHL), with one
\ndissenting member state.
\n7
\nThe IWG reviewed a second feeding study reported to the FAO\/WHO Joint Meeting on
\nPesticide Residues (JMPR), and found there was a significant positive trend in the incidence
\nof hemangiosarcoma in male CD-1 mice. Groups of 50 female and male mice were fed diets
\ncontaining glyphosate at a concentration that was adjusted weekly for the first 13 weeks and
\nevery four weeks thereafter to give doses of 0, 100, 300, or 1,000 mg\/kg body weight, ad
\nlibitum for 104 weeks.
\nIn contrast JMPR (WHO 2006) found that owing to the lack of a dose-response relationship,
\nthe lack of statistical significance and the fact that the incidences recorded in this study fell
\nwithin the historical ranges for controls, these changes were not considered to be caused by
\nadministration of glyphosate. They concluded administration of glyphosate to CD-1 mice for 104 weeks produced no signs of carcinogenic potential at any dose.<\/em><\/p>\n

 <\/p>\n

Initiation-promotion<\/strong><\/p>\n

 <\/p>\n

The IWG found that in a study involving 20 male Swiss mice which had a glyphosate based
\nformulation applied to their skin, it appeared to be a tumour promoter, but they concluded
\nthat this was an inadequate study because its design was poor, with short duration of
\ntreatment, no solvent controls, small numbers of animals, and a lack of histopathological
\nexamination.
\nHowever the BfR (2015) considered that generally testing of formulations should not be used
\nfor the toxicological evaluation of active substances because co-formulants may extensively
\nalter the outcome. The BfR deemed that this IWG finding was not considered by the
\ninstitutions in the EU to be evidence for the carcinogenic properties of glyphosate per se.
\nReview articles \u2013 mice studies<\/strong>
\nThe IWG noted that Griem et al, (2015) had published a review article which included
\ndiscussion of five long-term glyphosate feeding studies in mice. Two of the studies were
\ndiscussed in the IARC monograph. The working group summarised the other three studies
\nbut claimed that it was unable to fully evaluate the other three studies because of the limited
\nexperimental data provided in the review article and supplemental information.
\nGriem et al, (2015) noted that the five mouse studies that they reviewed were submitted to
\nsupport glyphosate renewal in the EU. They considered that all but the oldest study were
\nreliable without restriction and were performed under conditions of GLP and OECD
\nprotocols.
\nDuring the EFSA peer-review process for the renewal of the approval of glyphosate, EFSA
\nalso received a complementary mandate from the EU to consider the findings by IARC
\nregarding the potential carcinogenicity of glyphosate (EFSA 2015).
\nThe EFSA peer review (2015) also evaluated the five mice studies. Only one of these
\nsuggested a potential carcinogenic effect, as evidenced by a statistically significant
\nincreased evidence of malignant lymphomas at the top dose level of 1,460 mg\/kg\/day.
\nHowever the validity of the study was questioned, due to the occurrence of viral infection
\nwhich could have influenced survival rates and the incidence of lymphomas. No carcinogenic
\neffects were observed at the highest dose levels in any of the other studies. The IWG
\nevaluated two of these studies and asserted positive trends in males for renal tubular
\ncarcinomas in one study and for hemangiosarcoma in the other. However EFSA took a
\nweight-of-evidence approach; with considerations including the statistical significance being
\nonly found in trend analysis but not in pairwise comparison, lack of consistency in multiple
\n8
\nanimal studies, the fact that the slightly increased incidences only occurred at doses higher
\nthan those recommended for the oral route in carcinogenicity studies, incidences in test
\nanimals generally being within the historical range for control groups, and the lack of pre-neoplastic lesions.
\nRat studies<\/strong>
\nFive feeding studies in rats and two drinking water studies with glyphosate were reviewed by the IWG.
\nDrinking water<\/strong>
\nOne study in Sprague-Dawley rats was considered by the IWG to be inadequate for
\nevaluation because of its short exposure duration.
\nA glyphosate containing drinking water study with Wistar rats did not show any significant increase in tumour incidence.
\nDietary administration<\/strong>
\nTwo studies in Sprague-Dawley rats showed a significant increase in the incidence of
\npancreatic islet cell adenoma in male rats. One of these studies also showed a significant
\npositive trend in the incidence of hepatocellular adenoma in males and of the thyroid C-cell
\nadenoma in females. However two studies (one in Sprague-Dawley and one in Wistar rats)
\nfound no significant increase in tumour incidence at any site.
\nThe IWG reviewed a chronic feeding study (provided by the US EPA) in which groups of 60
\nfemale and male Sprague Dawley rats were given diets containing glyphosate at a
\nconcentration of 0, 2,000, 8,000 or 20,000 ppm ad libitum for 24 months. In males at the
\nlowest dose, there was a statistically significant increase in the incidence of pancreatic islet
\ncell adenoma compared with controls. Additional analyses by the US EPA revealed a
\nstatistically significant higher incidence of pancreatic islet cell carcinoma in males at the
\nlowest and highest doses compared with controls: lowest dose, 8\/45 (18%); intermediate
\ndose, 5\/49 (10%); highest dose, 7\/48 (15%) versus controls, 1\/43 (2%). The range for
\nhistorical controls for pancreatic cancer islet cell carcinoma reported in males at this
\nlaboratory was 1.8\u20138.5%. The IWG concluded that this study demonstrated a significant
\nincrease in the incidence of pancreatic islet cell adenoma in male rats.
\nHowever the US EPA (1993) had concluded that:
\nthese adenomas were not treatment-related and glyphosate was not considered to be
\ncarcinogenic in this study. With respect to pancreatic islet cells adenomas, there was no
\nstatistically significant positive dose-related trend in their occurrence; there was no
\nprogression to carcinomas; and the incidence of pancreatic hyperplasia (non-neoplastic
\nlesion) was not dose-related. With respect to hepatocellular adenomas, the increased
\nincidence of these neoplasms was not statistically significant in comparison with the controls;
\nthe incidence was within the historical control range; there was no progression to
\ncarcinomas; and the incidence of hyperplasia was not compound-related. With respect to
\nthyroid C-cell adenomas, there was no statistically significant dose-related trend in their
\noccurrence; the increased incidence was not statistically significant; there was no
\nprogression to carcinomas; and there was no significant dose-related increase in severity or
\nincidence of hyperplasia in either sex\u201d.
\n9
\nAlso, in the JMPR (WHO 2006) review of this study they reported:
\nThe historical-control range for this tumour at the testing laboratory was 1.8\u20138.5%, but a
\npartial review of studies reported recently in the literature revealed a prevalence of 0\u201317% in
\ncontrol males with several values being \u00b3 8%. More importantly, the incidences of islet cell
\nadenomas clearly did not follow a dose-related trend in the treated groups of males. There
\nwas no evidence of dose-related pancreatic damage or pre-neoplastic lesions. The only
\npancreatic islet cell carcinoma found in this study occurred in a male in the control group,
\nthus indicating a lack of treatment-induced neoplastic progression. Taken together, the data
\nsupport the conclusion that the occurrence of pancreatic islet cell adenomas in male rats
\nwas spontaneous in origin and unrelated to administration of glyphosate\u201d.
\nReview articles \u2013 rat studies<\/strong>
\nThe IWG noted that Griem et al, (2015) had published a review article containing
\nassessments of nine long-term glyphosate feeding studies in rats. Five of these studies were
\nreviewed by the IWG. The remaining four studies were not evaluated by the IWG which
\nstated that there was limited experimental data provided in the review article. These four
\nstudies had been submitted to various organisations for registration purposes. There was no
\nevidence of a carcinogenic effect related to glyphosate treatment.
\nIts long-term toxicity and carcinogenicity was assessed in nine rat studies. The EFSA peer
\nreview concluded that no significant increase in tumour incidence was apparent. Three of
\nthese studies were not evaluated by the IARC panel. In two studies, increased incidences of
\npancreatic islet cell adenomas were found but were not dose-related. EFSA also noted that
\nthe significance of these findings depended on the statistical analysis: using a pairwise
\ncomparison (as planned for in the study protocol) no significant effect is observed, whereas
\na trend analysis performed by the IWG identified significant changes. EFSA noted that
\ndeviations from the statistical analysis used by the study authors should be limited and
\nproperly justified.
\nOther relevant data<\/strong>
\nThe IWG group noted that soil microbes degrade glyphosate to aminomethylphosphonic acid
\n(AMPA). Blood AMPA detection after glyphosate poisoning incidents suggests intestinal
\nmicrobial metabolism in humans.
\nGlyphosate has been detected in the blood and urine of agricultural workers, indicating
\nabsorption. Neimann et al, (2015) published a critical review and comparison of data
\nobtained in a total of seven studies from Europe and the US. They concluded that no health
\nconcern was revealed because the resulting exposure estimates were several magnitudes
\nlower than the acceptable daily intake (ADI) or the acceptable operator exposure level
\n(AOEL).
\nThe measured internal exposure was clearly below the worst-case predictions made in the
\nevaluation of glyphosate as performed for the renewal of its approval within the European Union.
\nThis is consistent with the risk-based approach that regulatory agencies use when
\nconsidering realistic dosages and real-life conditions. Those studies show that farmers and
\nfarm families are exposed to significantly lower doses of the herbicide than some model
\nestimates would suggest.
\nIt is also in keeping with an earlier review (Williams et al, 2000) of the animal data, in which
\ndose levels from animal toxicity tests were compared to conservative, upper-limit estimates
\n10
\nof human exposure to glyphosate, to give a margin of exposure (MOE) value. MOE analyses
\ncompare the lowest NOAELs determined from animal studies to worst-case levels of human
\nexposure; with MOEs of greater than 100 indicating confidence that no adverse health
\neffects would occur. These authors found in their review that the MOEs for worst-case
\nchronic exposure to glyphosate ranged from 3,370 to 5,420, and concluded that under
\npresent and expected conditions of use, Roundup herbicide does not pose a health risk to humans\u201d.
\nGenotoxicity<\/strong>
\nThe IWG claimed that there is strong evidence that glyphosate is genotoxic. They tabulated
\nnumerous reports of tests relating to the genotoxicity of glyphosate and its formulations, with
\nsome showing a positive association, and some a negative association.
\nThe evaluation of the large volume of genotoxicity data available requires consideration of
\nassay system validation, test system species used, relevance of the endpoint to heritable
\nmutation, reproducibility and consistency of effects and dose-response, and relationship of
\neffects to toxicity. The guidelines for genetic toxicology tests developed for the OECD are a
\npre-eminent source of internationally agreed guidelines.
\nThere were often inconsistent results reported (both positive and negative) from the same
\ntest systems in different laboratories. The relevance of many of the assays in test system
\nspecies (fish, oysters, insects, snails, worms and caimans) which have never been validated
\nfor the assessment of genotoxicity in humans for regulatory purposes, is questionable.
\nAdditionally the intraperitoneal route of exposure for many of the mammalian in vivo studies
\nis not appropriate since it does not reflect normal human exposure, with doses exceeding
\noccupational exposure by orders of magnitude.
\nKier and Kirkland (2013) published a review of the genotoxicity of glyphosate and
\nglyphosate-based formulations. This review concluded that there was a strong weight of
\nevidence that glyphosate and its formulations are predominantly negative in well-conducted,
\ncore bacterial reversion and in vivo mammalian micronucleus and chromosomal aberration
\nassays. Although some positive results for glyphosate and glyphosate-based formulations
\nwere reported in DNA damage assays, and for the micronucleus endpoint for formulations in
\nnon-mammalian studies, the positive results were associated with high dose levels and\/or
\novert toxic effects. The preponderance of negative results in core assays supports the
\nconclusion that reports of DNA damage or non-mammalian micronucleus effects are likely to
\nbe secondary to cytotoxicity rather than indicative of DNA-reactive mechanisms.
\nThe IWG found that glyphosate and glyphosate formulations induced DNA and chromosomal
\ndamage in mammals, and in human and animal cells in vitro. They referred to one study
\n(Bolognesi, 2009) reporting increases in blood markers of chromosomal damage
\n(micronuclei) in residents of several communities after spraying of glyphosate formulations,
\nto support this contention of genotoxicity.
\nHowever, the authors of the Bolognesi (2009) study concluded that overall, data suggesting
\nthat genotoxic damage (as evidenced by the micronuclei test) associated with glyphosate
\nspraying for control of illicit crops is slim, and any such effect appears to be transient.
\nEvidence indicates that the genotoxic risk potentially associated with exposure to glyphosate
\nin the areas where the herbicide is applied for coca and poppy eradication is low. The
\nattribution of a genotoxic effect due to glyphosate exposure rather than a multitude of other
\ndemographic and environmental causes seems rather tenuous given the uncertainty of
\nactual exposure.
\n11
\nIn a recent communication, EFSA summarised their appraisal of the genotoxicity studies. In
\nvitro tests of mutagenicity gave consistently negative results. In vitro tests of mammalian
\nchromosome aberration (all of those which had been performed under GLP conditions) were
\nalso negative. Positive results were found in some published in vitro studies of chromosomal
\naberrations, but these were not confirmed by in vivo studies addressing the appropriate
\nendpoints, such as the micronucleus test.
\nAs regards in vivo tests, all studies conducted according to internationally validated
\nguidelines for good laboratory practice (GLP) and some non-GLP published studies gave
\nnegative results. Two non-GLP studies were positive in mice treated intraperitoneally, but at
\nlevels close to or above the LD503 (possibly suggestive that this is a secondary effect), and
\none study had major flaws. No genotoxic effects on germ cells have been detected in rats or
\nmice treated orally at dose levels up to 2,000 mg\/kg\/day (the maximum dose level
\nrecommended for such studies). EFSA concluded that, considering the weight of evidence,
\nglyphosate is unlikely to be genotoxic in vivo.
\nAs regards glyphosate-based commercial formulations, a number of formulations with
\nunknown composition have given positive results when tested in vitro and in vivo. However
\nsome of the test systems are not validated and\/or interpretation is difficult due to possible
\nconfounding, such as cytotoxicity, specific organ toxicity or unclear relevance to humans
\n(such as tests in fish, amphibians, or invertebrates). Some of the co-formulants (such as
\npolyethoxylated tallow amine (often abbreviated to POEA)) may be more systemically toxic
\nthan glyphosate. However EFSA concluded that the genotoxic potential of such complete
\nformulations should be further assessed.
\nKier (2015) reviewed genotoxicity biomonitoring studies of glyphosate-based formulations.
\nHe found that most of the human biomonitoring studies were not informative because there
\nwas either a very low frequency of exposure to glyphosate formulations or exposure to a
\nlarge number of pesticides in addition to glyphosate without analysis of specific pesticide
\neffects. One pesticide sprayer biomonitoring study indicated there was no statistically
\nsignificant relationship between frequency of exposure to glyphosate formulations reported
\nfor the last spraying season and oxidative DNA damage. There were three studies of human
\npopulations in regions of glyphosate formulation aerial spraying. One study found increases
\nfor the cytokinesis-block micronucleus endpoint but these increases did not show statistically
\nsignificant associations with self-reported spray exposure and were not consistent with
\napplication rates. A second study found increases for the blood cell comet endpoint at high
\nexposures causing toxicity. However, a follow-up to this study two years after spraying did not indicate chromosomal effects.
\nOxidative stress<\/strong>
\nThe IWG found that glyphosate, glyphosate formulations, and AMPA induced oxidative stress in rodents and in vitro.
\nOxidative stress was only found in one study in rats administered intraperitoneal glyphosate active ingredient (Astiz et al, 2009), and in numerous studies using intraperitoneal administration or in vitro methods with glyphosate-based formulations. However, these studies used doses that exceeded normal occupational exposures by orders of magnitude
\nand the intraperitoneal route of exposure is not appropriate for evaluating human exposure.
\nGlyphosate has low gastrointestinal absorption and poor dermal absorption. It therefore
\n3
\n[LD50 is the dose of the substance required (usually expressed in relation to body weight) that
\nis estimated to kill 50% of the test population].
\n12
\nseems unlikely that human exposure would produce the sort of tissue levels used in the
\noxidative stress tests. There was also some inconsistency in results.
\nMost effects were seen when whole glyphosate formulations were tested. EFSA considered
\nthat generally testing of formulations should not be used for the toxicological evaluation of
\nactive substances because co-formulants may extensively alter the outcome. Thus any
\neffects found cannot then be attributed to the glyphosate active ingredient present.
\nDiscussion<\/strong>
\nThe IARC WG (IWG) classified glyphosate as probably carcinogenic to humans (Group 2A)\u201d
\nas the overall evaluation.
\nAs set out in their evaluation section, this was based on:
\n\u00b7 limited evidence\u201d in humans for the carcinogenicity of glyphosate, and
\n\u00b7
\nsufficient evidence\u201d in experimental animals for carcinogenicity of glyphosate.
\nThe rationale identifies that the IWG also notes mechanistic and other relevant data in
\nsupport of the conclusion; in particular the IWG cites strong evidence\u201d that glyphosate can operate by two key characteristics of known human carcinogens, namely genotoxicity and oxidative stress.
\nThis discussion section of the report will consider each of these sources of evidence in turn as contributing factors to the IWG\u2019s overall evaluation.
\nHuman epidemiological evidence<\/strong>
\nThe key cited studies in support of the limited evidence\u201d in humans for carcinogenicity of glyphosate consisted of three case-control investigations. The odds ratios (OR) for cases of
\nNHL and glyphosate exposures are summarised in the following table.
\nOdds ratios (OR) for cases of NHL and glyphosate exposures
\nStudy area
\nOR1 and 95% CI2
\nStudy reference
\nMidwest, USA
\n2.1 (1.1\u20134.0) [logistic
\nregression]
\nDe Roos et al, 2003
\n1.6 (0.9\u20132.8) [hierarchical
\nregression]
\nCanada
\n1.26 (0.87\u20131.8)
\nMcDuffie et al, 2001
\n1.20 (0.83\u20131.74) [adjusted for
\nmedical variables]
\nSweden
\n2.02 (1.1\u20133.71) [univariate]
\nErikson et al, 2008
\n1.51 (0.77\u20132.94) [multivariate]
\n1. OR is the odds ratio of outcome of interest between the relevant case group and the reference or control
\ngroup.
\n2. The 95% CI are the confidence intervals round the OR representing the limits within which there is 95%
\nconfidence that the true value falls.
\n13
\nThe first important observation is that depending on the statistical tests used only two
\nstudies (Midwest USA and Sweden) show OR values indicating statistical significance at the
\n95% level. In the Midwest USA, however, this is only true using logistic regression, while in
\nthe Swedish study only the univariate analysis showed statistical significance.
\nSome case control studies assessed data using dose (exposure)\/response or
\nintensity\/response to determine whether or not there is a trend to a higher incidence of
\ntumours in persons categorised as having higher exposures to glyphosate. While these
\napproaches are desirable, the criteria of exposure seem low. For one case-control study, the
\ncriterion for high or lower glyphosate use was greater than or less than two days of
\nglyphosate use\/year (McDuffie et al, 2001), whereas in another the criterion was greater
\nthan or less than 10 days of glyphosate use\/year (Eriksson et al, 2008). While the
\ndistribution of use category was not given in either study, 2\u201310 days of use per year seems a
\nlow benchmark for exposure comparisons. The direct glyphosate exposure findings with
\nrespect to NHL was not significant in the McDuffie et al, 2001 study, but they reported a
\ndose response based on this dose comparison and quoted the OR for exposure >2 day\/year
\nas 2.12 (95% CI 1.20\u20133.73).
\nThe direct glyphosate exposure findings with respect to NHL were significant in the Swedish
\nstudy using univariate evaluation, and the effect of dose-response in the Swedish study
\nappears to only be statistically significant using this approach (considering the data
\npresented in the IARC Monograph in Table 2.2, p23) which reported a higher OR for heavy\u201d
\nusers (>10 days\/year) of 2.36 (95% CI 1.04\u20135.37). It is noteworthy that the paper reports the
\nhighest OR, 2.81 (95% CI 1.27\u20136.22), for the association between exposure to MCPA and
\nNHL. This may be the explanation for the difference between the results using univariate and
\nmultivariate evaluation. When considering the latency period, >10 years exposure to
\nglyphosate had an OR of 2.26 (95% CI 1.16\u20134.4) in comparison to \u2264 10 years with an OR of
\n1.11 (95% CI 0.24\u20135.08), but these findings may be confounded by exposure to MCPA or
\nother phenoxy herbicide exposures. There could be residual confounding from MCPA
\nexposure if the participants under-reported earlier MCPA exposure. The apparent increased
\nrisk with latency for glyphosate exposure could be because participants who had sprayed
\npesticides for longer were more likely to have used the phenoxy herbicides (including
\nMCPA) earlier in their working lives.
\nThe AHS cohort study (De Roos, et al, 2005) had a more detailed assessment at different
\nexposure intensities as they used cumulative lifetime days of use and an intensity measure
\n(years of use x days\/year x estimated exposure level). The data (presented in Table 2.1 of
\nthe IARC Monograph on p12) for this cohort study showed no statistically significant
\ndifference for the trend to increased exposure with exposure bands at 0\u201320, 21\u201356 and 57\u2013
\n2,678 cumulative days of exposure, despite the higher exposure levels in comparison to the case-control studies.
\nIt is important in these circumstances to consider the overall data set. Rather than only
\nhighlighting the three case-control studies which identified a marginally statistically
\nsignificant association between reported glyphosate use and NHL, the overall assessment needs to take into account other studies which did not demonstrate such an association.
\nAlso, it is particularly important to note the lack of significant finding in a large cohort study
\n(the AHS) where the potential for recall bias is greatly reduced and should therefore be given
\ngreater weight than the case control studies. Cohort studies are generally considered more
\nreliable than case-control studies, because the population is defined and the exposure
\nparameters and the potential confounding exposures and lifestyle factors are established
\nprior to the adverse outcome of interest so that the potential for recall bias is less likely.
\n14
\nGiven the lack of confirmation of the small number of positive findings from case-control
\nstudies in the more powerful cohort study, the epidemiological support for the conclusion limited evidence\u201d in humans is not convincing.
\nExperimental animal studies<\/strong>
\nThe key cited studies in support of the sufficient evidence\u201d in experimental animals for carcinogenicity of glyphosate consisted of three studies in mice. These comprised one oral study demonstrating a positive trend for increased incidence of renal tubule carcinoma, one oral study in mice demonstrating a positive trend for increased incidence of hemangiosarcoma; and a supporting skin study demonstrating tumour promotion using a
\nglyphosate formulation. In addition, one rat study demonstrated an increased incidence of
\npancreatic islet cell adenomas.
\nIn assessing these data, the IWG used different statistical tests to those in the original
\nanalysis (trend analysis rather than a pairwise comparison against controls). The original
\nstudies were designed with the intention to assess statistical significance by means of a
\npairwise comparison between the test and control groups, so use of the trend assessment
\nby IARC to assess these data requires justification. IARC\u2019s use of the trend assessment
\ngave a positive response, but in none of the studies are the positive effects statistically
\nsignificant using the original statistical approaches. Also, the IWG did not take into account
\nthe generally accepted assessment of the same data by international panels of experts,
\nwhich took into account additional historical incidence data for hepatocellular adenomas in
\nthe rats and the presence of a viral infection in the mouse study which could have influenced
\nsurvival rates and the incidence of lymphomas.
\nThe promotion study using a glyphosate-based formulation should not be used as support
\nfor the carcinogenicity of glyphosate per se, since the test substance contains other
\ncomponents which might influence the outcome.
\nThe IWG did not evaluate some other studies which have been used by other regulators.
\nThese did not support the view that exposure to glyphosate in long-term feeding studies was
\nassociated with an increase in tumours at any sites. While the IWG approach is consistent
\nwith the IARC pre-amble and policy on the selection of study data, in the current
\ncircumstances this attributes inappropriate weight to the three studies which IWG considered
\nand for which their analysis found an increase in tumours. Firstly because other studies
\nwhich other reputable bodies found to be negative were not considered, and secondly
\nbecause the reasons why the above findings were not relied upon by other assessments
\nwere not taken into account by the IWG. In particular a lack of consistency (dose-response) in multiple studies, slight increases in incidence at the maximum tested dose only, or incidences within the historical control range.
\nTaking into account that the positive findings cited by the IWG were not assessed as
\nevidence of a carcinogenic effect in the view of other reputable bodies, and that the total
\ndata set of long-term carcinogenicity bioassays were consistently negative, it is concluded
\nthat the overall weight of evidence does not indicate that glyphosate is carcinogenic.
\nMechanism of action<\/strong>
\nThe IWG cites what is described as strong evidence\u201d that glyphosate can operate by two
\nkey characteristics of known human carcinogens \u2013 genotoxicity and oxidative stress.
\nThe studies used in support of this conclusion were primarily in vitro mammalian cell studies.
\nIn such studies the mammalian cells are directly exposed to the test substance (glyphosate
\nor a glyphosate-based formulation) at high concentrations which would not be reasonably
\nachieved in an in vivo exposure whether in animals or humans. All studies done according to
\ninternationally validated guidelines gave negative results, while studies using unvalidated
\n15
\ntest method\/species, or with glyphosate-containing formulations or using high intraperitoneal
\ndoses are inappropriate for assessment of genotoxicity to humans.
\nOther supporting evidence for this conclusion included DNA damage and micronuclei in
\nvarious populations allegedly exposed to glyphosate from sprays. Attributing the effects
\nfound to the exposure to glyphosate is questionable when the exposure, if any, was to
\nglyphosate-based formulations and unidentified demographic, geographical or lifestyle
\nfactors that could be responsible for the DNA damage.
\nIn relation to oxidative stress this was only found in one study in rats administered
\nintraperitoneal glyphosate active ingredient (Astiz et al, 2009), and in numerous studies
\nusing intraperitoneal administration or in vitro methods with glyphosate-based formulations.
\nThe intraperitoneal route of administration is not considered relevant to human exposures.
\nGlyphosate has low gastrointestinal absorption and poor dermal absorption. There was also some inconsistency in results. So the evidence for glyphosate causing oxidative stress is considered weak.
\nConclusion<\/strong>
\nThe overall conclusion is that \u2013 based on a weight of evidence approach, taking into account the quality and reliability of the available data \u2013 glyphosate is unlikely to be genotoxic or carcinogenic to humans and does not require classification under HSNO as a carcinogen or mutagen.<\/em>
\n16
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\nAcknowledgement
\nDr Michael Beasley MBChB, DComH, MSc, DIH, FFOM (I) for valuable assistance
\nwith the preparation of this review.
\n19<\/p>\n","protected":false},"excerpt":{"rendered":"

Chandre Dharmawardana The New Zealand government, after an long review of the weedicide Glyphosate (Roundup), has now given it the ALL CLEAR signal, confirming that it is VERY SAFE for use. Here is the report: http:\/\/www.epa.govt.nz\/Publications\/EPA_glyphosate_review.pdf BACKGROUND TO THE STORY: Sometime ago there were sensational claims that Glyphosate,\u00a0 the popular weedicide,\u00a0 causes kidney diseases, Cancer […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[85],"tags":[],"class_list":["post-57762","post","type-post","status-publish","format-standard","hentry","category-chandre-dharmawardana"],"_links":{"self":[{"href":"https:\/\/www.lankaweb.com\/news\/items\/wp-json\/wp\/v2\/posts\/57762","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.lankaweb.com\/news\/items\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.lankaweb.com\/news\/items\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.lankaweb.com\/news\/items\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.lankaweb.com\/news\/items\/wp-json\/wp\/v2\/comments?post=57762"}],"version-history":[{"count":0,"href":"https:\/\/www.lankaweb.com\/news\/items\/wp-json\/wp\/v2\/posts\/57762\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.lankaweb.com\/news\/items\/wp-json\/wp\/v2\/media?parent=57762"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.lankaweb.com\/news\/items\/wp-json\/wp\/v2\/categories?post=57762"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.lankaweb.com\/news\/items\/wp-json\/wp\/v2\/tags?post=57762"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}