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Incidence of nephritis and kidney failure reports in the US CDC’s hospital discharge data from 1998 to 2010 normalized to counts per million population each year. This includes all reports of ICD-9 codes from 580 to 589. 

Incidence of nephritis and kidney failure reports in the US CDC’s hospital discharge data from 1998 to 2010 normalized to counts per million population each year. This includes all reports of ICD-9 codes from 580 to 589. 

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Glyphosate is the active ingredient in the pervasive herbicide, Roundup, and its usage, particularly in the United States, has increased dramatically in the last two decades, in step with the widespread adoption of Roundup®-Ready core crops. The World Health Organization recently labelled glyphosate as “probably carcinogenic.” In this paper, we rev...

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... 152]. Exposure to Roundup at low doses increased GGT expression in rat testis and Sertoli cells [94]. A comparison between goats fed GM Roundup-Ready solvent-extracted soybean vs goats fed a conventional soy equivalent revealed that the male kids born to the goats fed the GM soy had elevated expression of GGT in both liver and kidney ( P < 0.01) [153]. A study has shown that 70% of GM Roundup-ready soy samples had significant levels of glyphosate, whereas the conventional soy did not [154]. Exposure of Wistar rats to the herbicide Glyphosate- Biocarb over a period of 75 days resulted in liver damage, including elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), suggesting irreversible hepatocyte damage, as well as large deposition of reticulin fibres containing collagen type III [155], suggesting liver fibrosis [156], which is a major risk factor for hepatocarcinogenesis. Excessive retinoic acid signalling in the liver is expected due to the interference of glyphosate with liver CYP enzymes [11, 157, 158], because the CYP2C gene family is needed to metabolize retinoic acid in the liver [159]. The action of retinoic acid is likely mediated through sonic hedgehog signalling [160]. Studies on mice have revealed that hedgehog signalling induces fibrosis and hepatocellular carcinoma [161]. Studies on tadpoles have demonstrated that glyphosate produces teratogenic effects characteristic of excessive retinoic acid signalling, and these effects were reversed by a retinoic acid antagonist [162]. Pancreatic cancer is one of the cancers whose incidence is going up in step with the increase in glyphosate usage on corn and soy crops ( R = 0.918; P ≤ 4.6 × 10 –7 .) [1]. As of 2002, pancreatic adenocarcinoma was the fourth leading cause of cancer death in the USA, with an overall 5-year survival rate of less than 5% [163]. We have already noted that excess methylglyoxal exposure can lead to diabetes. Direct evidence of this was obtained when methylglyoxal injection into Sprague Dawley rats caused pancreatic β -cell dysfunction [164]. We earlier discussed the rôle of excess iron deposition in the destruction of pancreatic β cells [134]. Glyphosate’s metal chelation effects led to severe manganese deficiency in cows [83]. Rats fed a diet deficient in manganese showed significantly lower concentrations of manganese in liver, kidney, heart and pancreas compared to controls [165]. Pancreatic insulin content was reduced by 63%, and insulin output was correspondingly reduced, suggesting that manganese deficiency may play a direct rôle in insulin-deficient diabetes and islet cell stress. Acinar cell carcinoma is the second most common type of pancreatic cancer, characterized histologically by zymogen-like granules as well as fibrillary internal structures in the tumour cells [166]. A comparison between mice fed GM soy and wild soy demonstrated alterations in pancreatic acinar cells including smaller zymogen granules and less zymogen content in one month-old mice, along with reduced production of α amylase [167]. The authors did not consider possible effects of glyphosate contamination, even though another study has shown significant glyphosate residues in GM soy as compared to conventional soy treated with glyphosate [154]. Pancreatic atrophy of the acinar cells along with degranulation and intracellular fibrillation is a fundamental aspect of the childhood wasting disease kwashiorkor [168], which is linked to disrupted gut microbes [169], and may also be in part attributable to glyphosate poisoning. A two-year study of glyphosate toxicity to rats reported by the EPA in 1991 showed several signs of tumours, which were ultimately dismissed partly because of a lack of a dose–response relationship, and in part because it was argued that historical controls (but not the controls in the study) demonstrated tumours at comparable rates, but under very different and uncontrolled dietary and lifestyle practices [170]. The most frequently observed tumours were pancreatic islet cell adenomas in males, thyroid C-cell adenomas and/or carcinomas in males and females, and hepatocellular adenomas and carcinomas in males. Both low-dose and high-dose, but not mid-dose, males had a statistically significant increased incidence of pancreatic islet cell adenomas. Chronic kidney disease (CKD) and cancer are closely linked in reciprocal fashion: cancer or its treatment can cause CKD and patients with CKD have increased risk of cancer. Dialysis patients have an increased risk ranging from 10% to 80%; kidney transplant recipients have a 3- to 4-fold increased risk of cancer [6]. The number of patients with kidney failure treated by dialysis and transplantation increased dramatically in the USA from 209 000 in 1991 to 472 000 in 2004 [171]. There have been concurrent increases in earlier stages of chronic kidney disease such as albuminuria and impaired glomerular filtration [172]. Since 2004, this trend has worsened. Figure 2 shows the trend over time in the US Centers for Disease Control (CDC)’s hospital discharge data 4 for ICD-9 codes 580-589, including acute and chronic glomerulonephritis, nephritis and nephropathy, acute and chronic renal failure, renal sclerosis, and disorders resulting from impaired renal function. There has been an alarming rise in the frequency of these conditions, especially since 2006. Studies on rats show that CYP 2B1 plays a pivotal rôle as an important site for ROS production through cytotoxicity in the glomeruli [173]. The breakdown of the CYP haem protein through attack by H 2 O 2 leads to the release of catalytic iron, which, in turn, generates more potent tissue-damaging oxidants such as the hydroxyl radical. Glyphosate’s induction of excess H 2 O 2 as discussed earlier would cause an increase in the bioavailability of catalytic free iron to work synergistically with H 2 O 2 to cause toxicity. Methylglyoxal and other glycating agents may be a significant factor in the development of kidney disease. Twelve weeks of administration through drinking water of methylglyoxal to Dahl salt-sensitive rats led to an increase in systolic blood pressure and significantly increased urinary albumin excretion, glomerular sclerosis, tubular injury, myocardial collagen content and cardiac perivascular fibrosis [174]. Renal markers of AGE production, oxidative stress and inflammation were all elevated. Acquired cystic kidney disease (ACKD) can lead to renal tumours, and the tumours often accumulate calcium oxalate crystals [175]. These tumours are often associated with distinctive morphological features, where the tumour cells have ill-defined cell membranes, abundant granular eosinophilic cytoplasm, large nuclei and prominent nucleoli. In another study identifying intratumoral calcium oxalate crystal deposition in two cases of high-grade renal carcinomas, the authors suggested a relationship between tumour growth and oxalate crystal deposition [176]. This suggests a rôle for oxalic acid added to glyphosate-based formulations. An in vitro study on rat testis and Sertoli cells demonstrated that Roundup triggers calcium-mediated cell death associated with reductions in levels of the antioxidant glutathione, along with thiobarbituric acid reactive species (TBARS) and protein carbonyls indicative of protein oxidation and glycation damage [94]. Adminis- tration of L-buthionine(S,R)-sulfoximine (BSO), a specific inhibitor of glutathione synthesis, to rats caused reduced glutathione levels in the kidneys and a marked increase in pathologies linked to polycystic kidney disease [177]. As we showed previously, Monsanto’s own studies revealed increased risk of cataracts following exposure to Roundup. Early-onset cataracts are associated with insufficient antioxidative activity and, therefore, are a potential risk of cancer, as verified in a recent nationwide study based in Taiwan [178]. Methylglyoxal is implicated in cataract development [179, 180]. Methylglyoxal induces endoplasmic reticulum stress in human lens epithelial cells, and activates an unfolded protein response leading to overproduction of ROS. Overexpression of Keap1 protein causes proteasomal degradation of Nrf2, thus suppressing Nrf2-dependent stress protection. As a consequence, the cellular redox balance is altered toward lens oxidation and cataract formation [179]. There is a link between cholestasis and cataracts via poor absorption of nutrients that protect the lens from UV damage. Studies on short-term exposure of catfish to sublethal levels of Roundup revealed toxicity to the gills, liver and kidneys [181]. The observed elevated levels of unconjugated bilirubin and alanine aminotransferase (ALT) are indicative of cholestasis, likely in part a consequence of impaired CYP enzyme function. Cholestasis impairs the absorption of fat-soluble vitamins and previtamins such as the carotenoids [182]. Lutein and zeaxanthin are carotenoids that play an important rôle in the lens and macular region of the retina to protect from oxidative damage due to sunlight exposure [183, 184]. They are highly lipophilic and, therefore, like the fat-soluble vitamins, depend on adequate bile flow for gastrointestinal absorption. Cholestatic patients have greatly reduced serum levels of these nutrients [182]. Tryptophan is a product of the shikimate pathway that glyphosate suppresses. A tryptophan-free diet induces cataracts in young Wistar rats, along with a significant decrease in lens weight and water-soluble lens protein [185]. Kynurenine is a breakdown product of tryptophan, and it has been suggested that kynurenine and its glycoside derivatives in the ocular lens protect the retina from UV light by absorbing UV radiation [186]. Kynurenine is present in excessive concentrations in cataracts [186]. Melanoma is one of the types of cancer that have been linked to glyphosate exposure in agriculture. An age-adjusted analysis revealed an 80% increased risk of melanoma ...

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... The study by Samsel and Seneff (2015) reported that rats undergoing glyphosate treatment over 26 months developed several tumors in the glands and organs. In addition, it has been shown that glyphosate exposure can increase the incidence of cancer in the general (Williams, Kroesb, and Munro 2000;Lopez et al. 2012), breast cancer (Thongprakaisang 2013;Mesnage et al. 2017) and Non-Hodgkin's Lymphoma (Chang and Delzell 2016;Hardell and Erikson 1999). ...
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This study evaluated the sociodemographic characteristics and behavior of the oral mucosa epithelium exposured to the herbicide glyphosate of family farmers in Cerro Largo, RS, Brazil. 120 individuals were selected for social data collection through interviews. According to the results, most of the interviewees uses glyphosate between 5-10 years, being exposed between 30 minutes to one hour each application and applying the herbicide 1-2 times a year. After the interview, we selected the subjects to the Micronucleus (MN) test. For this test, oral smears were performed in three distinct regions (cheek, mouth floor and tongue edges) of 10 test subjects (exposed to glyphosate, non-smoker and non-alcoholic) and 10 control subjects. Results showed that glyphosate exposure increased the frequency of MN in the test group (p = 0.0002), as well as the frequency of other cellular alterations, such as brokenegg (p = 0.001), binucleation (p = 0.0001) and karyolysis (p = 0.0004). Based on these findings, the extent use of glyphosate may be causing damage to the oral mucosa epithelium and this might respond adaptively through cellular modifications.
... The International Agency of the World Health Organization recently classified glyphosate as "possibly carcinogenic to humans" [73]. Although some researchers believed that glyphosate was not linked to carcinogenicity, epidemiological evidence supports a strong temporal correlation between the use of glyphosate on crops and a multitude of cancers, including breast cancer, pancreatic cancer, kidney cancer, thyroid cancer, and liver cancer [74]. The International Agency for Research on Cancer (IARC) also concluded that there is sufficient evidence in experimental animals for the carcinogenicity of glyphosate, including the appearance of several commonly occurring tumors in several tissues in rodents [75]. ...
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... In animals and humans, similar to the case in microorganisms, glyphosate is metabolized not only to aminomethylphosphonic acid (AMPA) but also to other metabolites, such as glyoxylate. 13 Although Ford et al. 14 showed that glyphosate is metabolized in mouse liver to glyoxylate, they used high doses (200 mg/kg) that were intraperitoneally administered once a day for 7 days. Thus, the reactive metabolite may affect cysteines in proteins and suppress fatty acid oxidation only at an excessive exposure. ...
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... The World health Organization has recently classified this herbicide as; "probably carcinogenic"."Epidemiological evidence supports strong temporal correlations between glyphosate usage on crops and a multitude of cancer types that are reaching epidemic proportions, including breast cancer, pancreatic cancer, kidney cancer, thyroid cancer, liver cancer, bladder cancer and myeloid leukemia" [12] and non-Hodgkin lymphoma [13]. ...
... Planting is carried out to the edge of the settlement, sometimes separated by a street and in others there are no separations because the crop starts at the edge of the land of the families. Pesticide spraying of soybean crop that surrounds the community is made without notice and regardless of weather, especially wind direction on the day of spraying; to this must be added the absence of barriers and buffer zones that are legally required [12]. Adults surveyed also did not receive any training regarding the handling of pesticides, their characteristics and classification. ...
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... [266]. Its wide application in agriculture impacted the burst of publications about the cancer incidence cases [267]. However some controversies exist because herbicide is claimed to be harmless in the used concentrations [268,269]. ...
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Full-text available
Glyphosate is the active substance in the herbicide, whose trademark is Roundup. This herbicide is used worldwide in weed control. There are a number of studies showing that glyphosate can cause genotoxicity/carcinogenicity. In this research, the genotoxicity of glyphosate was studied by making use of the theory of electron transfer coefficient (ETC) employing quantum chemical modeling. Quantum chemical molecular parameters were determined; the highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), the electrostatic potential (Eδ), the positive partial molecular charge (δ +), the negative partial molecular charge (δ−), the energy gap (EBg), which were used to evaluate the ETC. The modeling was performed for the pure substance and for cross bands. Hyperchem software was used to calculate the ETC with the semi-empirical parametric method (SE-PM3). The software was calibrated with the algorithms of the quantum methods and their parameterization. The results showed that as a pure substance, glyphosate has the highest stability of all substances, so it can accumulate in biological systems. As cross bands, glyphosate initially oxidizes the nitrogen bases of DNA, followed by RNA. Quantum chemical modeling suggests that glyphosate is a carcinogen to biological systems, since it interacts with the nitrogenous bases of DNA, forming very stable molecules. © 2020 Facultad de Ciencias de la Educacion. All rights reserved.