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The Herbicide Glyphosate and Its Apparently Controversial Effect on Human Health: An Updated Clinical Perspective
Abstract
Background:
Glyphosate (G) is the most common weed-killer in the world. Every year tons and tons of G are applied on crop fields. G was first introduced in the mid 1970s and since then its usage has gradually increased to reach a peak since 2005. Now G usage is approximately 100 -fold what it was in 1970. Its impact on human health was considered benign at the beginning. But over the years evidence of a pervasive negative effect of this pesticide on humans has been mounting. Nonetheless, G usage is allowed by government health control agencies (both in the United States and Europe), that rely upon the evidence produced by the G producer. However, the IARC (International Agency for Research on Cancer) in 2015 has stated that G is probable carcinogenic (class 2A), the second highest class in terms of risk.
Objective:
In this review we explore the effect of G on human health, focusing in particular on more recent knowledge.
Results:
We have attempted to untangle the controversy about the dangers of the product for human beings in view of a very recent development, when the so -called Monsanto Papers, consisting of Emails and memos from Monsanto came to light, revealing a coordinated strategy to manipulate the debate about the safety of glyphosate to the company’s advantage.
Conclusions:
The story of G is a recurrent one (see the tobacco story), that seriously jeopardizes the credibility of scientific study in the modern era.
... In DCM patients, renal deterioration can progress independently of HF. In fact, the deterioration can be due to drugs and environmental toxicants [36,37] that are avidly reabsorbed in renal tubules. This process is strongly enhanced by hypoperfusion, so these chemicals reach very high concentrations in the tubules and interstitium [36][37][38]. ...
... In fact, the deterioration can be due to drugs and environmental toxicants [36,37] that are avidly reabsorbed in renal tubules. This process is strongly enhanced by hypoperfusion, so these chemicals reach very high concentrations in the tubules and interstitium [36][37][38]. Given the high oxidative stress exerted by these molecules on the renal tissue and the interstitium in particular, further renal damage might take place that can boost further renal dysfunction with an intrarenal mechanism (chronic interstitial nephritis) [39], especially if chronic diabetic nephropathy is present [40]. ...
... The reduction of weight in obese individuals is another natural, nonpharmacological strategy to address strain-dependent diastolic dysfunction since weight reduction reduces HR by reducing the sympathetic drive that is elevated in obese people and also reduces blood volume expansion [17]. Therefore, patients with cardiorenal syndrome, apart from restricting Na [51], that is the mainstay of treatment to avoid volume expansion [52], should have a reduced exposure to drugs and toxicants [37]. Therefore, chronic administration of drugs should, if possible, be kept to a minimum, and environmental chemicals [36] and toxicants in food [37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53] should be avoided. ...
The aim of this study was to clarify the relative contribution of elevated left ventricle (LV) filling pressure (FP) estimated by pulmonary venous (PV) and mitral flow, transesophageal Doppler recording (TEE), and other extracardiac factors like obesity and renal insufficiency (KI) to exercise capacity (ExC) evaluated by cardiopulmonary exercise testing (CPX) in patients with dilated cardiomyopathy (DCM). During the CPX test, 119 patients (pts) with DCM underwent both peak VO2 consumption and then TEE with color-guided pulsed-wave Doppler recording of PVF and transmitral flow. In 78 patients (65%), peak VO2 was normal or mildly reduced (>14 mL/kg/min) (group 1) while it was markedly reduced (≤14 mL/kg/min) in 41 (group 2). In univariate analysis, systolic fraction (S Fract), a predictor of elevated pre-a LV diastolic FP, appeared to be the best diastolic parameter predicting a significantly reduced peak VO2. Logistic regression analysis identified five parameters yielding a unique, statistically significant contribution in predicting reduced ExC: creatinine clearance < 52 mL/min (odds ratio (OR) = 7.4, p = 0.007); female gender (OR = 7.1, p = 0.004); BMI > 28 (OR = 5.8, p = 0.029), age > 62 years (OR = 5.5, p = 0.03), S Fract < 59% (OR = 4.9, p = 0.02). Conclusion: KI was the strongest predictor of reduced ExC. The other modifiable factors were obesity and severe LV diastolic dysfunction expressed by blunted systolic venous flow. Contrarily, LV ejection fraction was not predictive, confirming other previous studies. This has important clinical implications.
... Moreover, people are already heavily exposed to harmful chemical and physical agents with genotoxic and endocrine disrupting properties (cancer promoting agents) such as pesticides [6,7], heavy metals [7] and electromagnetic fields [7]. Owing to the devastating effect of these genotoxic agents, the incidence and prevalence of chronic diseases (cancer in particular) in the USA and globally over the last 20 years has skyrocketed [8]. ...
... Moreover, people are already heavily exposed to harmful chemical and physical agents with genotoxic and endocrine disrupting properties (cancer promoting agents) such as pesticides [6,7], heavy metals [7] and electromagnetic fields [7]. Owing to the devastating effect of these genotoxic agents, the incidence and prevalence of chronic diseases (cancer in particular) in the USA and globally over the last 20 years has skyrocketed [8]. ...
... Moreover, people are already heavily exposed to harmful chemical and physical agents with genotoxic and endocrine disrupting properties (cancer promoting agents) such as pesticides [6,7], heavy metals [7] and electromagnetic fields [7]. Owing to the devastating effect of these genotoxic agents, the incidence and prevalence of chronic diseases (cancer in particular) in the USA and globally over the last 20 years has skyrocketed [8]. ...
Background:
A more sensitive transthoracic color Doppler technology (convergent color Doppler), along with a heart rate (HR) reduction and new tomographic planes, can greatly improve coronary blood flow velocity (BFV) recordings in the left main (LMCA) and left anterior descending (LAD) coronary arteries, allowing the detection of even a slight acceleration of BFV due to mild coronary stenosis.
Methods:
A group of 26 patients underwent convergent color Doppler transthoracic echocardiography (CC-Doppler TTE) in the LMCA and in the LAD coronary arteries before and after HR lowering. A second group of 71 patients scheduled for intravascular ultrasound, expanded to 96 with 25 more patients with normal LAD (by angiography/low likelihood of disease), underwent BFV Doppler recordings by CC-Doppler TTE of the whole LAD (specifically the proximal, mid and distal segments) to detect a localized increase in BFV, after attaining maximal and reference BFV in each segment.
Results:
In the first group, HR reduction dramatically improved the detection of optimal flow in the LMCA and LAD, from 4 to 54% and from 6 to 94% of the segments, respectively (P < 0.001). In the second group intravascular ultrasonography (IVUS) showed mild stenoses in 60 patients. The maximum velocity was higher in the diseased segment than normal segments (49 ± 24 vs. 33 ± 11 cm/s; P < 0.001) and as the reference velocity was similar (32 ± 9 vs. 33 ± 11 cm/s; P = ns), the % increase was also higher (52 ± 52 vs. 0.7 ± 3%; P < 0.001). Using a >21% increase in velocity as a cutoff value, the sensitivity and specificity of CC-Doppler TTE in detecting at least one LAD plaque were 87% (52/60 patients [pts]) and 100% (36/36 pts), respectively.
Conclusion:
CC-Doppler TTE evaluation of LAD BFV is greatly improved after reducing HR, allowing accurate noninvasive assessment of mild LAD stenosis with no radiation exposure.
... Microcirculation dysfunction, as recently reviewed, can be due to several conditions that can exert oxidative stress on endothelium with the consequent reduced bioavailability of nitric oxide and reduced activity of coronary ions channels ending in reducing both vasodilation and CFR [31,32]. These factors are hypertension, diabetes mellitus, tobacco smoke, oxidized low density lipoproteins, pesticide, heavy metals, electromagnetic field, viruses, alcohol and ionizing radiation to name some [33]. Atherosclerosis with the associated paradoxical vasoconstriction, is in part the extreme consequence of the previously listed factors [34]. ...
... In our case, the patient underwent 11.5 mSv by CTA and an estimated 7 mSv from fluoroscopy, yielding a total burden of ∼ =20 mSv. Such radiation exposure significantly increases cancer risk [52] especially in consideration that ionizing radiation genotoxic effect adds up to other DNA oxidative damage exerted by other numerous genotoxic agent present in the modern environment like pesticide, electromagnetic field, heavy metals, industrial solvent (toluene, benzene etc.) to name some [33]. In addition, CTA requires the use of iodinated contrast medium, that is highly nephrotoxic. ...
We report the case of a 71-year-old patient with many risk factors for coronary atherosclerosis, who underwent computed coronary angiography (CTA), in accordance with the guidelines, for recent onset atypical chest pain. CTA revealed critical (>50% lumen diameter narrowing) stenosis of the proximal anterior descending coronary, and the patient was scheduled for invasive coronary angiography (ICA). Before ICA he underwent enhanced transthoracic echo-Doppler (E-Doppler TTE) for coronary flow detection by color-guided pulsed-wave Doppler recording of the left main (LMCA) and whole left anterior descending coronary artery (LAD,) along with coronary flow reserve (CFR) in the distal LAD calculated as the ratio, of peak flow velocity during i.v. adenosine (140 mcg/Kg/m) to resting flow velocity. E-Doppler TTE mapping revealed only mild stenosis (28% area narrowing) of the mid LAD and a CFR of 3.20, in perfect agreement with the color mapping showing no flow limiting stenosis in the LMCA and LAD. ICA revealed only a very mild stenosis in the mid LAD and mild atherosclerosis in the other coronaries (intimal irregularities). Thus, coronary stenosis was better predicted by E-Doppler TTE than by CTA. Coronary flow and reserve as assessed by E-Doppler TTE trumps coronary anatomy as assessed by CTA, without exposing the patient to harmful radiation and iodinated contrast medium.
... The major finding in our case is that a precise diagnosis with echocardiography allowed pericardiocentesis to be avoided. As a general and golden rule in medicine, the elimination of the cause(s) brings about the healing process [7]. Thus, it is necessary to make a considerable effort to find out all the causes of a malady [7]. ...
... As a general and golden rule in medicine, the elimination of the cause(s) brings about the healing process [7]. Thus, it is necessary to make a considerable effort to find out all the causes of a malady [7]. In particular, echocardiography was able to visualize the helix (fixation screw) minimally protruding into the fluid-filled pericardial space; that prompted us to retract it by simply unscrewing it (the helix is retractable), with minimal disturbance for the patient, minimal fluoroscopy time and most of all, minimal postponement of the pericardiocentesis. ...
We report the case of a 51-year-old patient who underwent the implantation of a bi-ventricular implantable cardioverter defibrillator (ICD) complicated by a sub-acute right ventricular minimal perforation with pericardial effusion and echocardiographic signs of tamponade. A new echocardiographic plane orientation allowed us to diagnose this condition in emergency and to make the right decision without delay, which consisting in unscrewing the active fixation screw under fluoroscopy guidance, while the pericardiocentesis was postponed. Thanks to the intervention focused on eliminating the cause of the postcardiac injury syndrome, the patient recovered rapidly and ultimately avoided the pericardiocentesis procedure.
... [4] Oxidative stress and oxidative phosphorylation interruption secondary to GBH, plays a role in coronary artery disease when exposure-related oxidative stress over time induce cardiac subintimal inflammation. [9] Animal models found glyphosate increased myocardial contraction, while the surfactant in GBH decreased cardiac output, left ventricular stroke index, and mean arterial pressure. [10,11] Heart transplant rejection can manifest as allograft failure with new heart failure, arrhythmias, or death. ...
Glyphosate is a common herbicide utilized worldwide with known exposure related toxicities. Numerous adverse effects related to glyphosate exposure have been documented, specifically in non-human models, however literature is lacking on cardiotoxic effects specific to heart transplant patients. Rejection is the most common post-transplant complication and the diagnosis of such is vital in order to guide immediate and appropriate treatment. In addition to the endomyocardial biopsy, noninvasive genetic testing can aid in rejection diagnosis and distinguish between cell-mediated and antibody-mediated rejection. We describe a case of glyphosate exposure in a post orthotopic heart transplant and the subsequent heart transplant rejection, patient’s clinical course, treatment, and follow up.
... Its utilization has significantly increased following the introduction of genetically modified herbicide-tolerant crops, which allowed for extended glyphosate application periods 1,2 . According to the US National Pesticide Information Center (NPIC) the typical half-life of glyphosate is relatively short (1.5 months) 3 but highly variable in different soils ranging from few days to several years [4][5][6][7] . Environmental persistence of glyphosate is reflected by its frequent detection in ground and surface waters as well as drinking water [8][9][10][11] . ...
We demonstrate for the first time that the broad-spectrum herbicide glyphosate is a stable transformation product during manganese-driven oxidation of diethylenetriamine penta(methylenephosphonate) (DTPMP), a complexing agent widely used in household and industry applications. Glyphosate formation was observed at circumneutral pH (i) in the presence of MnO2 (with and without dissolved O2) as well as (ii) in the presence of Mn²⁺ and O2. Maximum glyphosate yields varied with reaction conditions and ranged from 0.06 to 0.16 mol-%. Given the ubiquitous presence of manganese in the environment and wastewater treatment systems, Mn-driven transformation of DTPMP likely contributes to glyphosate formation under environmentally relevant conditions. Our results support recent reports of municipal wastewater as a previously neglected source of glyphosate in European surface waters with aminopolyphosphonates as suspected precursors. Therefore, the current approach to protecting water resources from glyphosate contamination needs to be revised, which has significant environmental, legal and economic implications.
... Glyphosate, diuron, isoproturon, 2,4-D, tebuthiuron, bentazone, atrazine, dinitramine, propham, paraquat, among others, are some of the well-known herbicides that can be harmful to human health. Glyphosate, the most widely used herbicide globally, is classified as a probable carcinogen by IARC (Caiati et al., 2020). p0120 Fungicides such as pentachlorobenzene and its derivatives (Wu et al., 2016), as well as insecticides like alpha and beta-hexachlorocyclohexane and chlordecone, are known to cause cancer and other adverse health effects (Multigner et al., 2010). ...
... The reason for this is also their ability to increase ROS and oxidative stress production, which cannot be properly counteracted by the intracellular antioxidant system [48]. For instance, studies have shown that glyphosate, an herbicide widely used to control the weeds that compete with crops, can determine an overaccumulation of ROS and a reduction of the NADH and NADPH pool of the cells, compounding its cytotoxic and genotoxic effects [49,50]. Different studies, in fact, demonstrated increased serum biomarkers of oxidative stress in the blood of agricultural workers exposed to pesticides for a long time, together with a remarkable decrease in antioxidant enzyme levels [51,52]. ...
We are surrounded by factors called free radicals (FR), which attach to the molecules our body is made of, first among them the endothelium. Even though FR are to a certain extent a normal factor, nowadays we face an escalating increase in these biologically aggressive molecules. The escalating formation of FR is linked to the increased usage of man-made chemicals for personal care (toothpaste, shampoo, bubble bath, etc.), domestic laundry and dish-washer detergents, and also an ever wider usage of drugs (both prescription and over the counter), especially if they are to be used long-term (years). In addition, tobacco smoking, processed foods, pesticides, various chronic infectious microbes, nutritional deficiencies, lack of sun exposure, and, finally, with a markedly increasing impact, electromagnetic pollution (a terribly destructive factor), can increase the risk of cancer, as well as endothelial dysfunction, owing to the increased production of FR that they cause. All these factors create endothelial damage, but the organism may be able to repair such damage thanks to the intervention of the immune system supported by antioxidants. However, one other factor can perpetuate the state of inflammation, namely obesity and metabolic syndrome with associated hyperinsulinemia. In this review, the role of FR, with a special emphasis on their origin, and of antioxidants, is explored from the perspective of their role in causing atherosclerosis, in particular at the coronary level.
... Thus, the divergent conclusions of the US EPA and EFSA compared to those of IARC generated a controversy that led to several studies trying to explain why for such a disagreement (Mesnage and Antoniou, 2017). However, the consensus among several independent authors was that the discrepancies among EFSA, US EPA, and the IARC statements resulted from methodological differences in evaluating the available evidence and the different designs of the institutions in preparing their risk assessments (Meftaul et al., 2020;Caiati et al., 2019;Bozzini, 2020). ...
Glyphosate is a broad-spectrum and one of the most widely used herbicides in the world, which has led to its high environmental dissemination. In 2015, the International Agency for Research on Cancer stated that glyphosate was a probable human carcinogen. Since then, several studies have provided new data about the environmental exposure of glyphosate and its consequences on human health. Thus, the carcinogenic effects of glyphosate are still under debate. This work aimed to review glyphosate occurrence and exposure since 2015 up to date, considering studies associated with either environmental or occupational exposure and the epidemiological assessment of cancer risk in humans. These articles showed that residues of the herbicide were detectable in all spheres of the earth and studies on the population showed an increase in the concentration of glyphosate in biofluids, both in the general population and in the occupationally exposed population. However, the epidemiological studies under review provided limited evidence for the carcinogenicity of glyphosate, which was consistent with the International Agency for Research on Cancer classification as a "probable carcinogen".
... Both lethal and sublethal effects have been reported for (honey) bees [27][28][29], earthworms [30][31][32] and birds [33]. In addition, numerous human health effects (cancer, reproductive and developmental toxicity, acute toxicity) of herbicides have been documented [33][34][35], some of which, such as glyphosate, are highly controversial [36,37]. ...
Background
Pesticide use has been associated with risks for human health and an overall decline in biodiversity. Although herbicides are the most commonly used pesticides worldwide, they have received less attention in this debate. We investigated the extent to which long-term trends in herbicide use in Austria influence potential toxic exposures to non-target organisms and potential risks to humans. We analyzed official sales data of 101 herbicide active ingredients (AIs) approved in Austria between 2010 and 2019 regarding their ecotoxicological properties based on lethal doses (LD 50 and LC 50 ) weighed by their persistence in the environment (DT 50 ) for honeybees ( Apis mellifera ), earthworms ( Eisenia fetida ), and birds ( Serinus serinus ). Human health risks were qualitatively assessed based on official hazard statements for the AIs used.
Results
In Austria, herbicide amounts sold decreased significantly by 24% from 1480 to 1123 tonnes between 2010 and 2019. This also led to a considerable decrease in the amounts of AIs classified by H-statements of the EU Pesticides Database: − 71% acute inhalation toxicity, − 58% reproductive toxicity,− 47% specific target organ toxicity. Yet, 36% of herbicides used were still classified as highly hazardous pesticides according to the Pesticide Action Network. Surprisingly, over the same period, toxic loads to honeybees increased by 487% (oral exposure), while lethal toxic loads to earthworms increased by 498%, and to birds by 580%. This can be attributed to a shift toward the use of more acutely toxic and especially more persistent AIs. The most problematic AI for honeybees, earthworms, birds and humans was the highly persistent diquat. The further ranking of the most toxic herbicides varied considerably depending on the organism. It is important to note that this toxic load assessment, like official environmental risk assessments, evaluates the potential risk but not the actual fatalities or real-world exposure.
Conclusions
Our results show a trade-off between herbicide amounts and toxicological hazards to humans and other non-target organisms. These interdependencies need to be considered when implementing pesticide reduction targets to protect public health and biodiversity, such as the EU´s “farm-to-fork” strategy, which aims to reduce the amounts and risks of synthetic pesticides.
... Although the use of glyphosate is permitted by government regulatory agencies in the United States and Europe, over the years, there has been increasing evidence of a harmful effect of this herbicide on humans (Caiati et al., 2020). Glyphosate is moderately persistent in the surface and groundwater, which increases the diversity of possible animal and human exposure routes. ...
Glyphosate is the most widely used herbicide in the world. Although some studies have shown cardiac electrophysiological changes associated to glyphosate, the histopathological changes that this herbicide may cause in the cardiovascular system are not yet established. The aim of this study was to evaluate the cardiovascular effects of subchronic oral and inhalation exposure to the glyphosate herbicide in rats. Eighty albino Wistar rats were distributed into eight groups (five males and five females/group): inhalation control: nebulization with sodium chloride solution (NaCl); oral control: nebulized feed with NaCl; low inhalation concentration: nebulization with 3.71 × 10 ⁻³ grams of active ingredient per hectare (g.a.i./ha) of glyphosate; low oral concentration: nebulized feed with 3.71 × 10 ⁻³ g.a.i./ha of glyphosate; medium inhalation concentration: nebulization with 6.19 × 10 ⁻³ g.a.i./ha of glyphosate; medium oral concentration: nebulized feed with 6.19 × 10 ⁻³ g.a.i./ha of glyphosate; high inhalation concentration: nebulization with 9.28 × 10 ⁻³ g.a.i./ha of glyphosate; and high oral concentration: nebulized feed with 9.28 × 10 ⁻³ g.a.i./ha of glyphosate. After 75 days of exposure, the animals were euthanized, and aortas and hearts were collected for histopathological analysis. Fatty streaks were observed in most animals exposed to glyphosate and were more prevalent in male rats, regardless of the route of exposure ( p < 0.05). There were no differences in the measurements of the thickness of the right and left ventricle or in the collagen density of both ventricles in any of the groups evaluated ( p > 0.05). Our study suggests that glyphosate has atherogenic potential, regardless of the concentration and route of exposure.
... The residues of herbicides have been detected from air, water, soil, groundwater and food samples (Agostini et al. 2020). The toxic effects of glyphosate-based herbicides are recently being debated on large scale (Agostini et al. 2020;Caiati et al. 2020;Peillex and Pelletier 2020). Nonetheless, the studies have reported that herbicide residues are toxic for human cells (Peillex and Pelletier 2020). ...
Tillage is among the most important soil management practices, which exert strong impacts on weed flora composition in different cropping systems. The large-scale adoption of tillage and cropping systems warrants thorough investigation regarding their impacts on weed flora composition. Therefore, this study was aimed to assess weed flora composition of various barley-based cropping systems (BBCSs) under different tillage practices (TPs). Barley was sown in fallow-barley (F-B), maize-barley (M-B), cotton-barley (C-B), mungbean-barley (Mu-B) and sorghum-barley (S-B) cropping systems with zero tillage (ZT), conventional tillage (CT), minimum tillage (MT), strip tillage (ST) and CT with bed sowing (CTBS). Significant differences (p < 0.05) were recorded among study years and interactions among BBCSs and TPs. The C-B system with ST during 1st year recorded the highest density (35 m− 2) of broadleaved weeds, whereas the highest density (37.76 m− 2) of broadleaved weeds was noted for the same cropping system with MT. All TPs, except BS resulted in increased density of broadleaved weeds in 2nd year compared with 1st year of the study, whereas BS reduced broadleaved weeds’ density during 2nd year. Nonetheless, M-B cropping system with ST and S-B cropping system with CTBS recorded the lowest density of broadleaved weeds during 1st and 2nd year, respectively. Similarly, C-B cropping system with ZT (39.33 m− 2) and MT (24.00 m− 2) recorded the lowest density of grassy weeds during 1st and 2nd year respectively. Nonetheless, S-B system with CTBS and S-B and Mu-B systems with ST recorded no grassy weeds during 1st and 2nd year, respectively. The S-B and M-B cropping systems suppressed various broadleaved and grassy weed species due to their allelopathic potential. In conclusion, different BBCSs had varying weed flora composition under different TPs. Adapting ST and CTBS can lower weed infestation. Similarly, inclusion of sorghum in rotation could be a viable option for effective weed management of barley-based cropping systems. Moreover, long-term experiments are needed to infer the weed seed bank in different TPs and BBCSs.
... Weed management generally seeks to lessen the negative effect of weeds. However, some weed management methods predispose human health and the environment to hazard (Caiati et al., 2020). The use of plant extracts for weed suppression is also gaining attention for their environmental friendliness compared to herbicides. ...
The suitability of cassava effluent (CE) for weed management required investigation due to the comparative advantage of biological weed control over other methods. Screen-house experiment comprising four levels of CE concentration (60, 120, 180, and 240 μg CN /kg soil) in factorial combination with four levels of application frequency (one, two, three, and four times) and a control treatment where no CE was applied, were laid out in a Completely Randomized Design and replicated three times. Data on weed weight, density, and flora composition were collected. The data were subjected to analysis of variance (ANOVA), and Duncan multiple range test (DMRT) was used to separate the treatment means at P < 0.05. The result showed that 240 μg CN /kg soil, applied four times, performed best in reducing weed density. The CE concentration and frequency of application had selective control on weed species. The density of Mitracarpus hirtus (L.) decreased, whereas Panicum maximum (L.) and Cyperus rotundus (L.) were tolerant. Therefore, the sole use of CE for non-selective control in the weed population of high heterogenicity is not advisable.
Diethylenetriamine penta(methylenephosphonate) (DTPMP) and related aminopolyphosphonates (APPs) are widely used as chelating agents in household and industrial applications. Recent studies have linked APP emissions to elevated levels of the herbicide glyphosate in European surface waters. However, the transformation processes and products of APPs in the environment are largely unknown. We show that glyphosate is formed from DTPMP by reaction with manganese at near neutral pH in pure water and in wastewater. Dissolved Mn²⁺ and O2 or suspended MnO2 lead to the formation of glyphosate, which remains stable after complete DTPMP conversion. Glyphosate yields vary with the reaction conditions and reach up to 0.42 mol%. The ubiquitous presence of manganese in natural waters and wastewater systems underscores the potential importance of Mn-driven DTPMP transformation as a previously overlooked source of glyphosate in aquatic systems. These findings challenge the current paradigm of herbicide application as the sole source of glyphosate contamination and necessitate a reevaluation of water resource protection strategies.
Science and health journalism are tasked with informing the general public, as concisely and accurately as possible, about topics relevant to society, such as the health and environmental impact of smoking, the existence and dangers of climate change, the benefits of mask-wearing, the use of oral contraception, or the value of immunisation. At the same time, science and health, just like many other topics, have been politicised since the earliest recorded times, a phenomenon that often impacted their ability to positively shape society and continues to do so. In this chapter, we attempt to define politicisation, analyse some of the factors that favour its emergence and circulation in society, and present several examples of topics with scientific, medical, and public health relevance that became politicised globally, often with detrimental effects on individual and collective wellbeing. As we explore strategies to prevent or limit the political polarisation of science- and health-related topics, we emphasise the importance of identifying conspiratorial discourse and misinformation, particularly on social media, and the need to empower the consumption of information related to the multiple facets of health and media literacy.
Amaranthus türleri farklı habitatlara uyum ve rekabet yetenekleri nedeniyle dünya genelinde pek çok tarımsal ürünün verimini etkileyen en önemli yabancı otlar arasında yer almaktadır. Güçlü rekabet yeteneklerinin yanında herbisitlere dayanıklı biyotiplerinin varlığı da dikkate alındığında: Amaranthus türleri için alternatif yabancı ot kontrol stratejilerinin belirlenmesi önemlidir. Bu çerçevede ele alınan bu çalışma ile Amaranthus türlerinin biyolojik mücadelesinde kullanılabilecek veriler elde etmek, yabancı otlara yönelik alternatif mücadele çalışmalarını desteklemek ve biyolojik mücadele çalışmalarına bir kaynak sağlamak amaçlanmıştır. Bu amaçlar için Türkiye’nin Güneydoğu Anadolu Bölgesinde yer alan dört il genelinde 119 lokasyonda bir sürvey çalışmasıyla Amaranthus türleri ile beslenen böcek türleri tespit edilmiş ve bu türlerin ilgili bitkilerin mücadelesinde biyolojik mücadele ajanı olarak kullanım olanakları saha ve ön laboratuvar çalışmalarıyla araştırılmıştır. Örnekleme alanlarında (20m × 20m = 400 m2) karşılaşılan her bir Amaranthus türünde en az 10 adet bitkinin tüm bitki aksamları (kök, gövde, yaprak, çiçek, tohum) incelenmiştir. İncelemeler sırasında örneklenen bitkilerin zarar durumları ve böcek türlerinin biyolojik dönemlerine (ergin, larva ve pupa) ait veriler toplanmıştır. Bu bağlamda Amaranthus türleri üzerinde tespit edilen böceklere ait larva ve pupalar ile bu böcek türlerinin beslenme belirtilerin olduğu genç bitkiler laboratuvar ortamında takip edilmiştir. Elde edilen veriler değerlendirildiğinde; çalışma alanında Amaranthus retroflexus L., A. palmeri S. Watson ve A. albus L. olmak üzere üç farklı Amaranthus türü belirlenmiştir. Ayrıca, A. retroflexus ile A. palmeri türleri ile beslenen ve biyolojik dönemlerini bu bitkiler üzerinde geçiren iki Coleoptera: Curculionidae türü; Hypolixus pica (F.) ve Lixus subtilis Boheman, 1835 tanımlanmıştır. Laboratuvar koşullarında yapılan ön etkinlik çalışmaları sonucunda ise her iki böcek türünün de A. retroflexus ile A. palmeri türlerini baskı altına alabildiği belirlenmiştir. Ancak, ilgili böcek türlerinin etkinlik düzeyi biyolojik kontrol ajanlarının popülasyon yoğunluğuyla doğru orantılı olduğu için daha ayrıntılı bilgiler için detaylı saha ve laboratuvar çalışmalarının yapılması önerilmektedir.
In this study, the bio-zeolite (BZ) was successfully fabricated by solvothermal method from the rice husk. The fabricated BZ was thoroughly characterized by SEM, XRD, XRF, BET, and FT-IR. The BZ characteristics were demonstrated with a homogenous, porous, and crystal structure, a uniform round edge shape, a SiO2/Al2O3 ratio of about 2.65, a specific surface area of 3.31 m2 g− 1, and specific linkages of Si–O–Al, Si–O–Si, and Si–OH. Subsequently, the BZ particles were modified by the adsorption of a cationic surfactant CTAB. Then CTAB@BZ was applied as an effective adsorbent to remove the herbicide glyphosate (GP) from aqueous solutions. The GP removal variables were optimized at 10 mM CTAB, pH 5, free ionic strength, 1 mg mL− 1 BZ dosage, and 60 min contact time. The GP removal efficiency was more significantly enhanced by greater than 90 % with the surface modification. The GP adsorption isotherm was accorded to the pseudo-second-order model with multiple�adsorbed layer formation. The GP adsorption mechanisms were the main surface adsorption due to the major CTAB-GP electrostatic attractions.
Clethodim is a widely used and approved class II herbicide, with little information about its impact on the reproductive system. Herein, we investigated the male reproductive toxicity of clethodim using a mouse model. GrassOut Max (26% clethodim-equivalent) or 50 mg kg-1 body weight analytical grade clethodim (≥90%) were given orally to male mice for 10 d in varying doses. All parameters were assessed at 35 d from the first day of treatment. Significant decrease in testicular weight, decreased germ cell population, elevated DNA damage in testicular cells and lower serum testosterone level was observed post clethodim-equivalent exposure. Epididymal spermatozoa were characterized with significant decrease in motility, elevated DNA damage, abnormal morphology, chromatin immaturity and, decreased acetylated-lysine of sperm proteins. In the testicular cells of clethodim-equivalent treated mice, the expression of Erβ and Gper was significantly higher. Proteomic analysis revealed lower metabolic activity, poor sperm-oocyte binding potential and defective mitochondrial electron transport in spermatozoa of clethodim-equivalent treated mice. Further, fertilizing ability of spermatozoa was compromised and resulted in defective preimplantation embryo development. Together, our data suggest that clethodim exposure risks male reproductive function and early embryogenesis in Swiss albino mice via endocrine disrupting function.
Glyphosate is a universal herbicide with genital toxicity, but the effect of glyphosate on oocytes has not been reported. This study aimed to evaluate the effect of glyphosate (0, 10, 20, 50 and 100 mM) on bovine oocyte in vitro maturation. We showed that 50 mM glyphosate adversely affects the development of bovine oocytes. Exposure of oocytes to 50 mM glyphosate caused an abnormal reduction in oxidative (redox) levels compared with that in the control group, with a significantly higher reactive oxide species level (P < 0.05) and significantly lower glutathione (GSH) expression (P < 0.05). Additionally, the mRNA levels of antioxidant genes (SOD1, SOD2, SIRT2, SIRT3) and the mitochondrial membrane potential (MMP) were significantly reduced (P < 0.05). Furthermore, treatment with 50 mM glyphosate-induced apoptosis, and the mRNA levels of the apoptotic genes Caspase-3 and Caspase-4 were significantly higher than those in the control group (P < 0.05); however, the mRNA level of BAX was significantly higher than that in the control group (P < 0.01). Additionally, the mRNA levels of the anti-apoptotic genes Survivin and BCL-XL were significantly lower than those in the control group (P < 0.05), and oocyte quality was adversely affected. Together, our results confirmed that glyphosate impairs the quality of oocytes by promoting abnormal oocyte redox levels and apoptosis.
Background
We report the case of a 93-year-old patient with normal left ventricular function and severe mitral annulus calcification, with mild mitral steno-insufficiency.
Case Presentation
She had developed creeping drugs-induced renal toxicity that is generally totally overlooked, due mainly to statins, a proton pump inhibitor, and aspirin. The Na and fluid retention, along with hypertension that ensued, although not severe, caused acute heart failure (sub-pulmonary edema) by worsening the mitral insufficiency. This occurred due to a less efficient calcific mitral annulus contraction during systole and an increasing mitral transvalvular gradient, as the transvalvular mitral gradient has an exponential relation to flow. After the suspension of the nephrotoxic drugs and starting intravenous furosemide, she rapidly improved. At 6 months follow-up, she is stable, in an NYHA 1-2 functional class, despite the only partial recovery of the renal function.
Pesticide impact on food, environment and human health in Argentina. Bibliographic review and overcoming proposals.
Impacto de los plaguicidas en los alimentos, el ambiente y la salud en Argentina
Revisión bibliográfica y propuestas superadoras.
Keywords: Pesticides. Food safety. Environmental Pollution. Dietary Risk Assessment. Environmental Risk Assessment. Pesticide Toxicology. Carcinogenicity of pesticides. Pesticide residues. Health effects. Contamination on Natural Biota. Groundwater. Surface Water. Rainfall water. Soil. Biodiversity. Agribiodiversity. Agroecology. Protection zone. Buffer zone.
Palabras clave: Plaguicidas. Seguridad Alimentaria. Contaminación Ambiental. Evaluación de Riesgo Dietario. Evaluación de Riesgo Ambiental. Toxicología. Carcinogenicidad. Residuos de plaguicidas. Efectos en Salud Humana. Efectos en: Biota Natural; Agua subterránea; Agua Superficial; Agua de Lluvia; Suelo. Biodiversidad. Agrobiodiversidad. Agroecología. Zona de resguardo. Zona buffer.
Pesticides are unique environmental contaminants that are specifically introduced into the environment to control pests, often by killing them. Although pesticide application serves many important purposes, including protection against crop loss and against vector-borne diseases, there are significant concerns over the potential toxic effects of pesticides to non-target organisms, including humans. In many cases, the molecular target of a pesticide is shared by non-target species, leading to the potential for untoward effects. Here, we review the history of pesticide usage and the neurotoxicity of selected classes of pesticides, including insecticides, herbicides, and fungicides, to humans and experimental animals. Specific emphasis is given to linkages between exposure to pesticides and risk of neurological disease and dysfunction in humans coupled with mechanistic findings in humans and animal models. Finally, we discuss emerging techniques and strategies to improve translation from animal models to humans.
Glyphosate is the active ingredient in glyphosate-based herbicides (GBHs). Other chemicals in GBHs are presumed as inert by regulatory authorities and are largely ignored in pesticide safety evaluations. We identified the surfactants in a cross-section of GBH formulations and compared their acute toxic effects. The first generation of polyethoxylated amine (POEA) surfactants (POE-tallowamine) in Roundup are markedly more toxic than glyphosate and heightened concerns of risks to human health, especially among heavily-exposed applicators. Beginning in the mid-1990s, first-generation POEAs were progressively replaced by other POEA surfactants, ethoxylated etheramines, which exhibited lower non-target toxic effects. Lingering concern over surfactant toxicity was mitigated at least in part within the European Union by the introduction of propoxylated quaternary ammonium surfactants. This class of POEA surfactants are ∼100 times less toxic to aquatic ecosystems and human cells than previous GBH-POEA surfactants. As GBH composition is legally classified as confidential commercial information, confusion concerning the identity and concentrations of co-formulants is common and descriptions of test substances in published studies are often erroneous or incomplete. In order to resolve this confusion, laws requiring disclosure of the chemical composition of pesticide products could be enacted. Research to understand health implications from ingesting these substances is required.
Background
Despite the growing and widespread use of glyphosate, a broad-spectrum herbicide and desiccant, very few studies have evaluated the extent and amount of human exposure.
Objective
We review documented levels of human exposure among workers in occupational settings and the general population.
Methods
We conducted a review of scientific publications on glyphosate levels in humans; 19 studies were identified, of which five investigated occupational exposure to glyphosate, 11 documented the exposure in general populations, and three reported on both.
Results
Eight studies reported urinary levels in 423 occupationally and para-occupationally exposed subjects; 14 studies reported glyphosate levels in various biofluids on 3298 subjects from the general population. Average urinary levels in occupationally exposed subjects varied from 0.26 to 73.5 μg/L; environmental exposure urinary levels ranged from 0.16 to 7.6 μg/L. Only two studies measured temporal trends in exposure, both of which show increasing proportions of individuals with detectable levels of glyphosate in their urine over time.
Conclusions
The current review highlights the paucity of data on glyphosate levels among individuals exposed occupationally, para-occupationally, or environmentally to the herbicide. As such, it is challenging to fully understand the extent of exposure overall and in vulnerable populations such as children. We recommend further work to evaluate exposure across populations and geographic regions, apportion the exposure sources (e.g., occupational, household use, food residues), and understand temporal trends.
This article endeavours to explore the glyphosate saga through the prism of a socially acceptable risk approach to the governance of public health and environmental risks in the European Union. After a brief overview on the nature and rationale of socially acceptable risk approaches, the article analyses the controversial case of glyphosate’s renewal of approval, casting light on the position of the agencies and institutions involved throughout the risk assessment and risk management phases. Against this overall backdrop, the article deconstructs the European Commission’s artificial legal narrative on ‘sound’ science and glyphosate and contends that the Commission had scientific and legal grounds, as well as compelling political reasons, to accept the requests put forward by the ‘Ban Glyphosate’ European Citizens’ Initiative and the European Parliament. The Commission relied on a narrow evidence-based approach, disregarding the widespread public perception that the uncertain risks posed by glyphosate are socially unacceptable, and ignoring the argument that the existing risk management measures are insufficient to achieve the intended EU level of public health and environmental protection. In so doing, the Commission has ultimately lost a crucial opportunity to re-legitimise and re-democratise EU risk regulation.
Glyphosate is an important broad-spectrum herbicide used in agriculture and residential areas for weed and vegetation control, respectively. In our study, we analyzed the in vitro clastogenic and/or aneugenic effects of glyphosate by chromosomal aberrations and micronuclei assays. Human lymphocytes were exposed to five glyphosate concentrations: 0.500, 0.100, 0.050, 0.025, and 0.0125 μg/mL, where 0.500 μg/mL represents the established acceptable daily intake value, and the other concentrations were tested in order to establish the genotoxicity threshold for this compound. We observed that chromosomal aberration (CA) and micronuclei (MNi) frequencies significantly increased at all tested concentrations, with exception of 0.0125 μg/mL. Vice versa, no effect has been observed on the frequencies of nuclear buds and nucleoplasmic bridges, with the only exception of 0.500 μg/mL of glyphosate that was found to increase in a significant manner the frequency of nucleoplasmic bridges. Finally, the cytokinesis-block proliferation index and the mitotic index were not significantly reduced, indicating that glyphosate does not produce effects on the proliferation/mitotic index at the tested concentrations.
This paper reviews the court-released discovery documents obtained from litigation against Monsanto over its herbicide Roundup and through Freedom of Information Act requests (requests to regulatory agencies and public universities in the United States). We sought evidence of corporate malfeasance and undisclosed conflicts of interest with respect to issues of scientific integrity. The findings include evidence of ghostwriting, interference in journal publication, and undue influence of a federal regulatory agency.
Background
Glyphosate-based herbicides (GBHs) are broad-spectrum herbicides that act on the shikimate pathway in bacteria, fungi, and plants. The possible effects of GBHs on human health are the subject of an intense public debate for both its potential carcinogenic and non-carcinogenic effects, including its effects on microbiome. The present pilot study examines whether exposure to GBHs at doses of glyphosate considered to be “safe” (the US Acceptable Daily Intake - ADI - of 1.75 mg/kg bw/day), starting from in utero, may modify the composition of gut microbiome in Sprague Dawley (SD) rats.
Methods
Glyphosate alone and Roundup, a commercial brand of GBHs, were administered in drinking water at doses comparable to the US glyphosate ADI (1.75 mg/kg bw/day) to F0 dams starting from the gestational day (GD) 6 up to postnatal day (PND) 125. Animal feces were collected at multiple time points from both F0 dams and F1 pups. The gut microbiota of 433 fecal samples were profiled at V3-V4 region of 16S ribosomal RNA gene and further taxonomically assigned and assessed for diversity analysis. We tested the effect of exposure on overall microbiome diversity using PERMANOVA and on individual taxa by LEfSe analysis.
Results
Microbiome profiling revealed that low-dose exposure to Roundup and glyphosate resulted in significant and distinctive changes in overall bacterial composition in F1 pups only. Specifically, at PND31, corresponding to pre-pubertal age in humans, relative abundance for Bacteriodetes (Prevotella) was increased while the Firmicutes (Lactobacillus) was reduced in both Roundup and glyphosate exposed F1 pups compared to controls.
Conclusions
This study provides initial evidence that exposures to commonly used GBHs, at doses considered safe, are capable of modifying the gut microbiota in early development, particularly before the onset of puberty. These findings warrant future studies on potential health effects of GBHs in early development such as childhood.
Background:
Glyphosate, formulated as Roundup, is the world's most widely used herbicide. Glyphosate is used extensively on genetically modified (GM) food crops designed to tolerate the herbicide, and global use is increasing rapidly. Two recent reviews of glyphosate's health hazards report conflicting results. An independent review by the International Agency for Research on Cancer (IARC) found that glyphosate is a "probable human carcinogen". A review by the European Food Safety Agency (EFSA) found no evidence of carcinogenic hazard. These differing findings have produced regulatory uncertainty.
Regulatory actions:
Reflecting this regulatory uncertainty, the European Commission on November 27 2017, extended authorization for glyphosate for another 5 years, while the European Parliament opposed this decision and issued a call that pesticide approvals be based on peer-reviewed studies by independent scientists rather than on the current system that relies on proprietary industry studies.
Ramazzini institute response:
The Ramazzini Institute has initiated a pilot study of glyphosate's health hazards that will be followed by an integrated experimental research project. This evaluation will be independent of industry support and entirely sponsored by worldwide crowdfunding. The aim of the Ramazzini Institute project is to explore comprehensively the effects of exposures to glyphosate-based herbicides at current real-world levels on several toxicological endpoints, including carcinogenicity, long-term toxicity, neurotoxicity, endocrine disrupting effects, prenatal developmental toxicity, the microbiome and multi-generational effects.
Glyphosate is a synthesis product and chemical substance that entered in the global market during the 70s. In the beginning, the molecule was used as an active principle in a wide range of herbicides, with great success. This was mainly due to its systemic and non-selective action against vegetable organisms and also to the spread of Genetically Modified Organism (GMO) crops, which over the years were specifically created with a resistance to glyphosate. To date, the product is, for these reasons, the most sprayed and most used herbicide in the world. Because of its widespread diffusion into the environment, it was not long before glyphosate found itself at the center of an important scientific debate about its adverse effects on health and environment. In fact, in 2015 the IARC (International Agency for Research on Cancer, Lyon, France), an organization referred to as the specialized cancer agency of the World Health Organization (WHO, Geneva, Switzerland), classified the substance as "likely carcinogenic" to humans. This triggered an immediate and negative reaction from the producer, who accused the Agency and claimed that they had failed to carry out their studies properly and that these conclusions were largely contradictory to published research. Additionally, in 2015, just a few months after the IARC monography published on glyphosate, the EFSA (European Food Safety Authority, Parma, Italy), another WHO related organization, declared that it was "unlikely" that the molecule could be carcinogenic to humans or that it could cause any type of risk to human health. The conflict between the two organizations of the World Health Organization triggered many doubts, and for this reason, a series of independent studies were launched to better understand what glyphosate's danger to humans and the environment really was. The results have brought to light how massive use of the herbicide has created over time a real global contamination that has not only affected the soil, surface and groundwater as well as the atmosphere, but even food and commonly used objects, such as diapers, medical gauze, and absorbent for female intimate hygiene. How human health is compromised as a result of glyphosate exposure is a topic that is still very debatable and still unclear and unambiguous. This paper is a review of the results of the main independent recent scientific studies.
The present paper scrutinises the European authorities’ assessment of the carcinogenic hazard posed by glyphosate based on Regulation (EC) 1272/2008. We use the authorities’ own criteria as a benchmark to analyse their weight of evidence (WoE) approach. Therefore, our analysis goes beyond the comparison of the assessments made by the European Food Safety Authority and the International Agency for Research on Cancer published by others. We show that not classifying glyphosate as a carcinogen by the European authorities, including the European Chemicals Agency, appears to be not consistent with, and in some instances, a direct violation of the applicable guidance and guideline documents. In particular, we criticise an arbitrary attenuation by the authorities of the power of statistical analyses; their disregard of existing dose–response relationships; their unjustified claim that the doses used in the mouse carcinogenicity studies were too high and their contention that the carcinogenic effects were not reproducible by focusing on quantitative and neglecting qualitative reproducibility. Further aspects incorrectly used were historical control data, multisite responses and progression of lesions to malignancy. Contrary to the authorities’ evaluations, proper application of statistical methods and WoE criteria inevitably leads to the conclusion that glyphosate is ‘probably carcinogenic’ (corresponding to category 1B in the European Union).
Glyphosate (N-phosphonomethyl-glycine, GLP) is the most popular herbicide used worldwide. This study aimed to investigate the effects of glyphosate on rats' liver function and induction of pathological changes in ion levels and oxidative stress in hepatic tissue. Sprague-Dawley rats were treated orally with 0, 5, 50, and 500 mg/kg body weight of the GLP. After 5 weeks of treatment, blood and liver samples were analyzed for biochemical and histomorphological parameters. The various mineral elements content in the organs of the rats were also measured. Significant decreases were shown in the weights of body, liver, kidney and spleen between the control and treatment groups. Changes also happened in the histomorphology of the liver and kidney tissue of GLP-treated rats. The GLP resulted in an elevated level of glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT) and IL-1β in the serum. Besides, decreased total superoxide dismutase (T-SOD) activity and increased malondialdehyde (MDA) contents in the serum, liver, and kidney indicated the presence of oxidative stress. Moreover, increase of hydrogen peroxide (H2O2) level and catalase (CAT) activity in the serum and liver and decrease of glutathione (GSH) and lutathione peroxidase (GSH-Px) activity in the kidney tissue further confirmed the occurrence of oxidative stress. The results of RT-PCR showed that the mRNA expressions of IL-1α, IL-1β, IL-6, MAPK3, NF-κB, SIRT1, TNF-α, Keap1, GPX2, and Caspase-3 were significantly increased in the GLP-treated groups compared to the control group. Furthermore, PPARα, DGAT, SREBP1c, and SCD1 mRNA expressions were also remarkably increased in the GLP-treated groups compared to the control group. In addition, aluminum (Al), iron (Fe), copper (Cu), zinc (Zn), and magnesium (Mg) levels were showed a significant difference reduction or increase in rat liver, kidney, spleen, lung, heart, muscle, brain, and fat tissues. These results suggested that glyphosate caused obvious damage to rats' liver and caused various mineral elements content imbalances in various organs of rats. Ion imbalance could weaken antioxidant capacity and involve in the mechanism of liver oxidative damage caused by GLP.
Approval for glyphosate-based herbicides in the European Union (EU) is under intense debate due to concern about their effects on the environment and human health. The occurrence of glyphosate residues in European water bodies is rather well documented whereas only few, fragmented and outdated information is available for European soils. We provide the first large-scale assessment of distribution (occurrence and concentrations) of glyphosate and its main metabolite aminomethylphosphonic acid (AMPA) in EU agricultural topsoils, and estimate their potential spreading by wind and water erosion. Glyphosate and/or AMPA were present in 45% of the topsoils collected, originating from eleven countries and six crop systems, with a maximum concentration of 2mgkg(-1). Several glyphosate and AMPA hotspots were identified across the EU. Soil loss rates (obtained from recently derived European maps) were used to estimate the potential export of glyphosate and AMPA by wind and water erosion. The estimated exports, result of a conceptually simple model, clearly indicate that particulate transport can contribute to human and environmental exposure to herbicide residues. Residue threshold values in soils are urgently needed to define potential risks for soil health and off site effects related to export by wind and water erosion.
Freshwater ecosystems face very strong anthropogenic pressures, among which overexploitation, habitat degradation, flow modification, species invasion, and water pollution lead to growing threats on biodiversity. Urbanization through wastewater treatment, industry through the release of inorganic and organic chemicals, and agriculture through the use of pesticides and herbicides are the main factors involved in water pollution. In France, more precisely in the Pyrénées-Orientales department, the poor quality of the watercourses is attributable overall to the use of glyphosate-based herbicides in agricultural activities. Because these chemicals can impact individuals, populations, and biodiversity, we investigated, under experimental conditions, the physiological response of animals facing abiotic contaminants. We selected as a model, juveniles of the freshwater turtle Trachemys scripta elegans. We measured the gene expression and activity of the catalase and superoxide dismutase enzymes as well as the levels of lipid peroxidation, which are all oxidative stress biomarkers, in turtles challenged with high concentrations of glyphosate-based herbicides, on the one hand, and with degraded waters collected from a local watercourse, on the other. We also measured the acetylcholinesterase activity across the same animals. We showed through variations in gene expression and enzyme activity that a glyphosate commercial formulation induced a stress in turtles. A similar outcome was obtained when turtles faced degraded waters. The results indicated that the poor quality of regional waters could be a real threat for animal health. Because turtles are globally less sensitive to contaminants than amphibians, which are lacking in the degraded waters of the Pyrénées-Orientales department, they could constitute an excellent model to follow the evolution of water quality through the study of oxidative stress biomarkers. Environ Toxicol Chem 2017;9999:1–8.
Usage of the herbicide glyphosate on core crops in the USA has increased exponentially over the past two decades, in step with the exponential increase in autoimmune diseases including autism, multiple sclerosis, inflammatory bowel disease, type 1 diabetes, coeliac disease, neuromyelitis optica and many others. In this paper we explain how glyphosate, acting as a non-coding amino acid analogue of glycine, could erroneously be integrated with or incorporated into protein synthesis in place of glycine, producing a defective product that resists proteolysis. Whether produced by a microbe or present in a food source, such a peptide could lead to autoimmune disease through molecular mimicry. We discuss similarities in other naturally produced disease-causing amino acid analogues, such as the herbicide glufosinate and the insecticide L-canavanine, and provide multiple examples of glycine-containing short peptides linked to autoimmune disease, particularly with respect to multiple sclerosis. Most disturbing is the presence of glyphosate in many popular vaccines including the measles, mumps and rubella (MMR) vaccine, which we have verified here for the first time. Contamination may come through bovine protein, bovine calf serum, bovine casein, egg protein and/or gelatin. Gelatin sourced from the skin and bones of pigs and cattle given glyphosate-contaminated feed contains the herbicide. Collagen, the principal component of gelatin, contains very high levels of glycine, as do the digestive enzymes: pepsin, trypsin and lipase. The live measles virus could produce glyphosate-containing haemagglutinin, which might induce an autoimmune attack on myelin basic protein, commonly observed in autism. Regulatory agencies urgently need to reconsider the risks associated with the indiscriminate use of glyphosate to control weeds.
Use of glyphosate-based herbicides (GBHs) increased ∼100-fold from 1974 to 2014. Additional increases are expected due to widespread emergence of glyphosate-resistant weeds, increased application of GBHs, and preharvest uses of GBHs as desiccants. Current safety assessments rely heavily on studies conducted over 30 years ago. We have considered information on GBH use, exposures, mechanisms of action, toxicity and epidemiology. Human exposures to glyphosate are rising, and a number of in vitro and in vivo studies challenge the basis for the current safety assessment of glyphosate and GBHs. We conclude that current safety standards for GBHs are outdated and may fail to protect public health or the environment. To improve safety standards, the following are urgently needed: (1) human biomonitoring for glyphosate and its metabolites; (2) prioritisation of glyphosate and GBHs for hazard assessments, including toxicological studies that use state-of-the-art approaches; (3) epidemiological studies, especially of occupationally exposed agricultural workers, pregnant women and their children and (4) evaluations of GBHs in commercially used formulations, recognising that herbicide mixtures likely have effects that are not predicted by studying glyphosate alone.
The recent classification of glyphosate as a probable human carcinogen by the International Agency for Research on Cancer (IARC) was arrived at without a detailed assessment of exposure. Glyphosate is widely used as an herbicide, which might result in exposures of the general public and applicators. Exposures were estimated from information in the open literature and unpublished reports provided by Monsanto Company. Based on the maximum measured concentration in air, an exposure dose of 1.04 × 10 (-) (6 )mg/kg body mass (b.m.)/d was estimated. Assuming consumption of surface water without treatment, the 90th centile measured concentration would result in a consumed dose of 2.25 × 10 (-) (5 )mg/kg b.m./d. Estimates by the Food and Agriculture Organization of the United Nations (FAO) of consumed doses in food provided a median exposure of 0.005 mg/kg b.m./d (range 0.002-0.013). Based on tolerance levels, the conservative estimate by the US Environmental Protection Agency (US EPA) for exposure of the general population via food and water was 0.088 mg/kg b.m./d (range 0.058-0.23). For applicators, 90th centiles for systemic exposures based on biomonitoring and dosimetry (normalized for penetration through the skin) were 0.0014 and 0.021 mg/kg b.m./d, respectively. All of these exposures are less than the reference dose and the acceptable daily intakes proposed by several regulatory agencies, thus supporting a conclusion that even for these highly exposed populations the exposures were within regulatory limits.
Glyphosate has been rigorously and extensively tested for carcinogenicity by administration to mice (five studies) and to rats (nine studies). Most authorities have concluded that the evidence does not indicate a cancer risk to humans. The International Agency for Research on Cancer (IARC), however, evaluated some of the available data and concluded that glyphosate probably is carcinogenic to humans. The expert panel convened by Intertek assessed the findings used by IARC, as well as the full body of evidence and found the following: (1) the renal neoplastic effects in males of one mouse study are not associated with glyphosate exposure, because they lack statistical significance, strength, consistency, specificity, lack a dose-response pattern, plausibility, and coherence; (2) the strength of association of liver hemangiosarcomas in a different mouse study is absent, lacking consistency, and a dose-response effect and having in high dose males only a significant incidence increase which is within the historical control range; (3) pancreatic islet-cell adenomas (non-significant incidence increase), in two studies of male SD rats did not progress to carcinomas and lacked a dose-response pattern (the highest incidence is in the low dose followed by the high dose); (4) in one of two studies, a non-significant positive trend in the incidence of hepatocellular adenomas in male rats did not lead to progression to carcinomas; (5) in one of two studies, the non-significant positive trend in the incidence of thyroid C-cell adenomas in female rats was not present and there was no progression of adenomas to carcinomas at the end of the study. Application of criteria for causality considerations to the above mentioned tumor types and given the overall weight-of-evidence (WoE), the expert panel concluded that glyphosate is not a carcinogen in laboratory animals.
We conducted a systematic review of the epidemiologic literature for glyphosate focusing on non-Hodgkin?s lymphoma (NHL) and multiple myeloma (MM) ? two cancers that were the focus of a recent review by an International Agency for Research on Cancer Working Group. Our approach was consistent with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews. We evaluated each relevant study according to a priori criteria for study quality: adequacy of study size, likelihood of confounding, potential for other biases and adequacy of the statistical analyses. Our evaluation included seven unique studies for NHL and four for MM, all but one of which were case control studies for each cancer. For NHL, the case-control studies were all limited by the potential for recall bias and the lack of adequate multivariate adjustment for multiple pesticide and other farming exposures. Only the Agricultural Health (cohort) Study met our a priori quality standards and this study found no evidence of an association between glyphosate and NHL. For MM, the case control studies shared the same limitations as noted for the NHL case-control studies and, in aggregate, the data were too sparse to enable an informed causal judgment. Overall, our review did not find support in the epidemiologic literature for a causal association between glyphosate and NHL or MM.
The aim of this review is to summarize the incidence, prevalence, trend in mortality, and general
prognosis of coronary heart disease (CHD) and a related condition, acute coronary syndrome (ACS). Although
CHD mortality has gradually declined over the last decades in western countries, this condition still causes about
one-third of all deaths in people older than 35 years. This evidence, along with the fact that mortality from CHD
is expected to continue increasing in developing countries, illustrates the need for implementing effective primary
prevention approaches worldwide and identifying risk groups and areas for possible improvement.
p>Likewise the 1991 Gulf War, known as a “mother of all battles”, oxidative stress (OS) can be considered as a “mother” of many human diseases life threatening. OS is a condition in which oxidation exceeds the anti-oxidant reactions, causing an imbalance between oxidative and anti-oxidant systems, with prevalence of reactive oxygen species ROS [1-5]. These include: peroxide, superoxide, hydroxyl radical, singlet oxygen and others. Under normal conditions ROS are maintained at physiological levels by several endogenous antioxidant systems, as superoxide dismutase, catalase, glutathione peroxidases, lacto-peptidases, glutathione reductase and others [6]. However, if active ROS are excessively generated, the balance between the formation and the removal of these species is lost. Generating oxidative damage (disruption between antioxidant defenses and ROS production) [7]. ROS can be generated from both endogenous and exogenous sources. Endogenous ROS are produced in normal metabolic reactions. Exogenous ROS derive by exposure to cigarette smoke, environmental pollutants, consumption of alcohol in excess, exposure to ionizing radiations, viral and bacterial infections, and others [8]. Individual, hereditary factors, and lifestyle are the main determinants of OS.</p
Background:
Although animal studies have shown that exposure to glyphosate (a commonly used herbicide) does not result in glyphosate bioaccumulation in tissues, to our knowledge there are no published data on whether it is detectable in human milk and therefore consumed by breastfed infants.
Objective:
We sought to determine whether glyphosate and its metabolite aminomethylphosphonic acid (AMPA) could be detected in milk and urine produced by lactating women and, if so, to quantify typical consumption by breastfed infants.
Design:
We collected milk (n= 41) and urine (n= 40) samples from healthy lactating women living in and around Moscow, Idaho and Pullman, Washington. Milk and urine samples were analyzed for glyphosate and AMPA with the use of highly sensitive liquid chromatography-tandem mass spectrometry methods validated for and optimized to each sample matrix.
Results:
Our milk assay, which was sensitive down to 1 μg/L for both analytes, detected neither glyphosate nor AMPA in any milk sample. Mean ± SD glyphosate and AMPA concentrations in urine were 0.28 ± 0.38 and 0.30 ± 0.33 μg/L, respectively. Because of the complex nature of milk matrixes, these samples required more dilution before analysis than did urine, thus decreasing the sensitivity of the assay in milk compared with urine. No difference was found in urine glyphosate and AMPA concentrations between subjects consuming organic compared with conventionally grown foods or between women living on or near a farm/ranch and those living in an urban or suburban nonfarming area.
Conclusions:
Our data provide evidence that glyphosate and AMPA are not detectable in milk produced by women living in this region of the US Pacific Northwest. By extension, our results therefore suggest that dietary glyphosate exposure is not a health concern for breastfed infants. This study was registered atclinicaltrials.govasNCT02670278.
This systematic review and meta-analysis rigorously examines the relationship between glyphosate exposure and risk of lymphohematopoietic cancer (LHC) including NHL, Hodgkin lymphoma (HL), multiple myeloma (MM), and leukemia. Meta-relative risks (meta-RRs) were positive and marginally statistically significant for the association between any versus no use of glyphosate and risk of NHL (meta-RR = 1.3, 95% confidence interval (CI) = 1.0-1.6, based on six studies) and MM (meta-RR = 1.4, 95% CI = 1.0-1.9; four studies). Associations were statistically null for HL (meta-RR = 1.1, 95% CI = 0.7-1.6; two studies), leukemia (meta-RR = 1.0, 95% CI = 0.6-1.5; three studies), and NHL subtypes except B-cell lymphoma (two studies each). Bias and confounding may account for observed associations. Meta-analysis is constrained by few studies and a crude exposure metric, while the overall body of literature is methodologically limited and findings are not strong or consistent. Thus, a causal relationship has not been established between glyphosate exposure and risk of any type of LHC.
The broad-spectrum herbicide glyphosate (common trade name "Roundup") was first sold to farmers in 1974. Since the late 1970s, the volume of glyphosate-based herbicides (GBHs) applied has increased approximately 100-fold. Further increases in the volume applied are likely due to more and higher rates of application in response to the widespread emergence of glyphosate-resistant weeds and new, pre-harvest, dessicant use patterns. GBHs were developed to replace or reduce reliance on herbicides causing well-documented problems associated with drift and crop damage, slipping efficacy, and human health risks. Initial industry toxicity testing suggested that GBHs posed relatively low risks to non-target species, including mammals, leading regulatory authorities worldwide to set high acceptable exposure limits. To accommodate changes in GBH use patterns associated with genetically engineered, herbicide-tolerant crops, regulators have dramatically increased tolerance levels in maize, oilseed (soybeans and canola), and alfalfa crops and related livestock feeds. Animal and epidemiology studies published in the last decade, however, point to the need for a fresh look at glyphosate toxicity. Furthermore, the World Health Organization's International Agency for Research on Cancer recently concluded that glyphosate is "probably carcinogenic to humans." In response to changing GBH use patterns and advances in scientific understanding of their potential hazards, we have produced a Statement of Concern drawing on emerging science relevant to the safety of GBHs. Our Statement of Concern considers current published literature describing GBH uses, mechanisms of action, toxicity in laboratory animals, and epidemiological studies. It also examines the derivation of current human safety standards. We conclude that: (1) GBHs are the most heavily applied herbicide in the world and usage continues to rise; (2) Worldwide, GBHs often contaminate drinking water sources, precipitation, and air, especially in agricultural regions; (3) The half-life of glyphosate in water and soil is longer than previously recognized; (4) Glyphosate and its metabolites are widely present in the global soybean supply; (5) Human exposures to GBHs are rising; (6) Glyphosate is now authoritatively classified as a probable human carcinogen; (7) Regulatory estimates of tolerable daily intakes for glyphosate in the United States and European Union are based on outdated science. We offer a series of recommendations related to the need for new investments in epidemiological studies, biomonitoring, and toxicology studies that draw on the principles of endocrinology to determine whether the effects of GBHs are due to endocrine disrupting activities. We suggest that common commercial formulations of GBHs should be prioritized for inclusion in government-led toxicology testing programs such as the U.S. National Toxicology Program, as well as for biomonitoring as conducted by the U.S. Centers for Disease Control and Prevention.
The causes of autism spectrum disorder (ASD) are not well understood. Only a minority of cases are explainable by specific abnormalities in DNA sequence, whereas the majority are widely assumed to be linked to epigenetic effects, and/or likely impacted by environmental factors. Here, we postulate autism causation via environmental and/or dietary sourced toxin acting intermittently in utero on human fetuses to disrupt neurodevelopment in a non-dose dependent manner. Our theory is informed by a mini-review and correlation of selected studies from the research literature related to autism, including radiologic, anatomic, metabolic, neurodevelopmental, pharmacologic and MRI studies. In reviewing and analyzing evidence, we focus on data supporting interaction of the theorized harmful glycine mimetic at one or more of the following calcium inflow regulatory factors for neurons: the N-methyl D-aspartate (NMDA) receptor, the glycine receptor (GlyR) and/or the glycine transporter protein 1 (GlyT1). We postulate this harmful glycine mimetic to act by exerting a direct molecular disruption to calcium regulatory factors for neurons. This disruption appears to occur in a time sensitive, rather than a strictly dose-dependent manner, leading to haphazard disorganizations of the normally carefully choreographed steps of early neuronal migration. Within this analysis, we find support for the contention that a strong candidate for the putative harmful glycine mimetic is glyphosate, the active ingredient in the pervasive herbicide Roundup®. In addition to glyphosate's molecular similarity to glycine, glyphosate is known to have a propensity to avidly bind minerals such as manganese and magnesium, which minerals are implicated in the normal functioning of several neuronal calcium inflow regulatory factors. Our theory highlights areas deserving of further study.
Hard cover, 492 pages Publisher: InTech This book is divided into two sections namely: synthesis and properties of herbicides and herbicidal control of weeds. Chapters 1 to 11 deal with the study of different synthetic pathways of certain herbicides and the physical and chemical properties of other synthesized herbicides. The other 14 chapters (12-25) discussed the different methods by which each herbicide controls specific weed population. The overall purpose of the book, is to show properties and characterization of herbicides, the physical and chemical properties of selected types of herbicides, and the influence of certain herbicides on soil physical and chemical properties on microflora. In addition, an evaluation of the degree of contamination of either soils and/or crops by herbicides is discussed alongside an investigation into the performance and photochemistry of herbicides and the fate of excess herbicides in soils and field crops.
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 review the research
literature, with the goal of evaluating the carcinogenic potential of glyphosate. Glyphosate has a
large number of tumorigenic effects on biological systems, including direct damage to DNA in
sensitive cells, disruption of glycine homeostasis, succinate dehydrogenase inhibition, chelation
of manganese, modification to more carcinogenic molecules such as N-nitrosoglyphosate and
glyoxylate, disruption of fructose metabolism, etc. Epidemiological evidence supports strong
temporal correlations between glyphosate usage on crops and a multitude of cancers that are
reaching epidemic proportions, including breast cancer, pancreatic cancer, kidney cancer,
thyroid cancer, liver cancer, bladder cancer and myeloid leukaemia. Here, we support these
correlations through an examination of Monsanto’s early studies on glyphosate, and explain how
the biological effects of glyphosate could induce each of these cancers. We believe that the
available evidence warrants a reconsideration of the risk/benefit trade-off with respect to
glyphosate usage to control weeds, and we advocate much stricter regulation of glyphosate.
A huge increase in the incidence and prevalence of chronic diseases has been reported in the United
States (US) over the last 20 years. Similar increases have been seen globally. The herbicide
glyphosate was introduced in 1974 and its use is accelerating with the advent of herbicide-tolerant
genetically engineered (GE) crops. Evidence is mounting that glyphosate interferes with many
metabolic processes in plants and animals and glyphosate residues have been detected in both.
Glyphosate disrupts the endocrine system and the balance of gut bacteria, it damages DNA and is a
driver of mutations that lead to cancer.
In the present study, US government databases were searched for GE crop data, glyphosate
application data and disease epidemiological data. Correlation analyses were then performed on a
total of 22 diseases in these time-series data sets. The Pearson correlation coefficients are highly
-5
significant (< 10 ) between glyphosate applications and hypertension (R = 0.923), stroke (R = 0.925),
diabetes prevalence (R = 0.971), diabetes incidence (R = 0.935), obesity (R = 0.962), lipoprotein
metabolism disorder (R = 0.973), Alzheimer’s (R = 0.917), senile dementia (R = 0.994), Parkinson's (R
= 0.875), multiple sclerosis (R = 0.828), autism (R = 0.989), inflammatory bowel disease (R = 0.938),
intestinal infections (R = 0.974), end stage renal disease (R = 0.975), acute kidney failure (R = 0.978),
cancers of the thyroid (R = 0.988), liver (R = 0.960), bladder (R = 0.981), pancreas (R = 0.918), kidney
(R = 0.973) and myeloid leukaemia (R = 0.878).
-4
The Pearson correlation coefficients are highly significant (< 10 ) between the percentage of GE corn
and soy planted in the US and hypertension (R = 0.961), stroke (R = 0.983), diabetes prevalence (R =
0.983), diabetes incidence (R = 0.955), obesity (R = 0.962), lipoprotein metabolism disorder (R =
0.955), Alzheimer’s (R = 0.937), Parkinson's (R = 0.952), multiple sclerosis (R = 0.876), hepatitis C (R
= 0.946), end stage renal disease (R = 0.958), acute kidney failure (R = 0.967), cancers of the thyroid
(R = 0.938), liver (R = 0.911), bladder (R = 0.945), pancreas (R = 0.841), kidney (R = 0.940) and
myeloid leukaemia (R = 0.889). The significance and strength of the correlations show that the effects
of glyphosate and GE crops on human health should be further investigated.
It is widely accepted that in chemical carcinogenesis different modes-of-action exist, e.g. genotoxic (GTX) versus non-genotoxic (NGTX) carcinogenesis. In this context, it has been suggested that oxidative stress response pathways are typical for NGTX carcinogenesis. To evaluate this, we examined oxidative stress-related changes in gene expression, cell cycle distribution and (oxidative-) DNA damage in human hepatoma cells (HepG2) exposed to GTX-, NGTX- and non-carcinogens, at multiple time points (4-8-24-48-72h). Two GTX (Azathriopine, AZA/Furan), two NGTX (Tetradecanoyl-phorbol-acetate, TPA/Tetrachloroethylene, TCE) carcinogens as well as two non-carcinogens (Diazinon, DZN/D-mannitol, Dman) were selected, while per class one compound was deemed to induce oxidative stress and the other not. Oxidative stressors AZA, TPA and DZN induced a 10-fold higher number of gene expression changes over time compared to Furan, TCE or Dman treatment. Genes commonly expressed between AZA, TPA and DZN, were specifically involved in oxidative stress, DNA damage and immune responses. However, differences in gene expression between GTX and NGTX carcinogens did not correlate to oxidative stress or DNA damage, but could instead be assigned to compound-specific characteristics. This conclusion was underlined by results from functional readouts on ROS formation and (oxidative) DNA damage. Therefore, oxidative stress may represent the underlying cause for increased risk of liver toxicity and even carcinogenesis: however, it does not discriminate between GTX and NGTX carcinogens.
Despite a vast literature, atherosclerosis and the associated ischemia/reperfusion injuries remain today in many ways a mystery. Why do atheromatous plaques make and store a supply of cholesterol and sulfate within the major arteries supplying the heart? Why are treatment programs aimed to suppress certain myocardial infarction risk factors, such as elevated serum homocysteine and inflammation, generally counterproductive?
Our methods are based on an extensive search of the literature in atherosclerotic cardiovascular disease as well as in the area of the unique properties of water, the role of biosulfates in the vascular wall, and the role of electromagnetic fields in vascular flow. Our investigation reveals a novel pathology linked to atherosclerosis that better explains the observed facts than the currently held popular view.
We propose a novel theory that atherosclerosis can best be explained as being due to cholesterol sulfate deficiency. Furthermore, atheromatous plaques replenish the supply of cholesterol and sulfate to the microvasculature, by exploiting the inflammatory agent superoxide to derive sulfate from homocysteine and other sulfur sources. We argue that the sulfate anions attached to the glycosaminoglycans in the glycocalyx are essential in maintaining the structured water that is crucial for vascular endothelial health and erythrocyte mobility through capillaries. Sulfate depletion leads to cholesterol accumulation in atheromas, because its transport through water-based media depends on sulfurylation. We show that streaming potential induces nitric oxide (NO) release, and NO derivatives break down the extracellular matrix, redistributing sulfate to the microvasculature. We argue that low (less negative) zeta potential due to insufficient sulfate anions leads to hypertension and thrombosis, because these responses can increase streaming potential and induce nitric-oxide mediated vascular relaxation, promoting oxygen delivery. Our hypothesis is a parsimonious explanation of multiple features of atherosclerotic cardiovascular disease.
If our interpretation is correct, then it would have a significant impact on how atherosclerosis is treated. We recommend a high intake of sulfur-containing foods as well as an avoidance of exposure to toxicants that may impair sulfate synthesis.
Manganese (Mn) is an often overlooked but important nutrient, required in small amounts for multiple essential functions in the body. A recent study on cows fed genetically modified Roundup®‐Ready feed revealed a severe depletion of serum Mn. Glyphosate, the active ingredient in Roundup®, has also been shown to severely deplete Mn levels in plants. Here, we investigate the impact of Mn on physiology, and its association with gut dysbiosis as well as neuropathologies such as autism, Alzheimer’s disease (AD), depression, anxiety syndrome, Parkinson’s disease (PD), and prion diseases. Glutamate overexpression in the brain in association with autism, AD, and other neurological diseases can be explained by Mn deficiency. Mn superoxide dismutase protects mitochondria from oxidative damage, and mitochondrial dysfunction is a key feature of autism and Alzheimer’s. Chondroitin sulfate synthesis depends on Mn, and its deficiency leads to osteoporosis and osteomalacia. Lactobacillus, depleted in autism, depend critically on Mn for antioxidant protection. Lactobacillus probiotics can treat anxiety, which is a comorbidity of autism and chronic fatigue syndrome. Reduced gut Lactobacillus leads to overgrowth of the pathogen, Salmonella, which is resistant to glyphosate toxicity, and Mn plays a role here as well. Sperm motility depends on Mn, and this may partially explain increased rates of infertility and birth defects. We further reason that, under conditions of adequate Mn in the diet, glyphosate, through its disruption of bile acid homeostasis, ironically promotes toxic accumulation of Mn in the brainstem, leading to conditions such as PD and prion diseases.
Glyphosate, an herbicidal derivative of the amino acid glycine, was introduced to agriculture in the 1970s. Glyphosate targets and blocks a plant metabolic pathway not found in animals, the shikimate pathway, required for the synthesis of aromatic amino acids in plants. After almost forty years of commercial use, and multiple regulatory approvals including toxicology evaluations, literature reviews, and numerous human health risk assessments, the clear and consistent conclusions are that glyphosate is of low toxicological concern, and no concerns exist with respect to glyphosate use and cancer in humans. This manuscript discusses the basis for these conclusions. Most toxicological studies informing regulatory evaluations are of commercial interest and are proprietary in nature. Given the widespread attention to this molecule, the authors gained access to carcinogenicity data submitted to regulatory agencies and present overviews of each study, followed by a weight of evidence evaluation of tumor incidence data. Fourteen carcinogenicity studies (nine rat and five mouse) are evaluated for their individual reliability, and select neoplasms are identified for further evaluation across the data base. The original tumor incidence data from study reports are presented in the online data supplement. There was no evidence of a carcinogenic effect related to glyphosate treatment. The lack of a plausible mechanism, along with published epidemiology studies, which fail to demonstrate clear, statistically significant, unbiased and non-confounded associations between glyphosate and cancer of any single etiology, and a compelling weight of evidence, support the conclusion that glyphosate does not present concern with respect to carcinogenic potential in humans.
Human and environmental genotoxicity biomonitoring studies involving exposure to glyphosate-based formulations (GBFs) were reviewed to complement an earlier review of experimental genotoxicity studies of glyphosate and GBFs. The environmental and most of the human biomonitoring studies were not informative because there was either a very low frequency of GBF exposure or exposure to a large number of pesticides without analysis of specific pesticide effects. One pesticide sprayer biomonitoring study indicated there was not a statistically significant relationship between frequency of GBF exposure reported for the last spraying season and oxidative DNA damage. There were three studies of human populations in regions of GBF aerial spraying. One study found increases for the cytokinesis-block micronucleus endpoint but these increases did not show statistically significant associations with self-reported spray exposure and were not consistent with application rates. A second study found increases for the blood cell comet endpoint at high exposures causing toxicity. However, a follow-up to this study 2 years after spraying did not indicate chromosomal effects. The results of the biomonitoring studies do not contradict an earlier conclusion derived from experimental genotoxicity studies that typical GBFs do not appear to present significant genotoxic risk under normal conditions of human or environmental exposures.
Glyphosate is the most widely used broad-spectrum systemic herbicide in the world. Recent evaluations of the carcinogenic potential of glyphosate-based herbicides (GBHs) by various regional, national, and international agencies have engendered controversy. We investigated whether there was an association between high cumulative exposures to GBHs and increased risk of non-Hodgkin lymphoma (NHL) in humans. We conducted a new meta-analysis that includes the most recent update of the Agricultural Health Study (AHS) cohort published in 2018 along with five case-control studies. Using the highest exposure groups when available in each study, we report the overall meta-relative risk (meta-RR) of NHL in GBH-exposed individuals was increased by 41% (meta-RR = 1.41, 95% confidence interval, CI: 1.13-1.75). For comparison, we also performed a secondary meta-analysis using high-exposure groups with the earlier AHS (2005), and we calculated a meta-RR for NHL of 1.45 (95% CI: 1.11-1.91), which was higher than the meta-RRs reported previously. Multiple sensitivity tests conducted to assess the validity of our findings did not reveal meaningful differences from our primary estimated meta-RR. To contextualize our findings of an increased NHL risk in individuals with high GBH exposure, we reviewed publicly available animal and mechanistic studies related to lymphoma. We documented further support from studies of malignant lymphoma incidence in mice treated with pure glyphosate, as well as potential links between glyphosate / GBH exposure and immunosuppression, endocrine disruption, and genetic alterations that are commonly associated with NHL or lymphomagenesis. Overall, in accordance with findings from experimental animal and mechanistic studies, our current meta-analysis of human epidemiological studies suggests a compelling link between exposures to GBHs and increased risk for NHL.
Since its initial sales in the 1970s, the herbicide glyphosate attained widespread use in modern agriculture, becoming the most commercially successful and widely used herbicide of all time as of 2016. Despite a primary mechanism that targets a pathway absent from animal cells and regulatory studies showing safety margins orders of magnitude better than many other, more directly toxic herbicides, the safety status of glyphosate, has recently been brought into question by a slow accumulation of studies evincing more insidious health risks, especially when considered in combination with the surfactants it is usually applied with. Current, official views of respected international regulatory and health bodies remain divided on glyphosate's status as a human carcinogen, but the 2015 IARC decision to reclassify the compound as Category 2a (probably carcinogenic to humans) marked a sea change in the scientific community's consensus view. The goal of this review is to consider the state of science regarding glyphosate's potential as a human carcinogen and genotoxin, with particular focus on studies suggesting mechanisms which would go largely undetected in traditional toxicology studies, such as microbiome disruption and endocrine mimicry at very low concentrations.
Objective:
Examination of de-classified Monsanto documents from litigation in order to expose the impact of the company's efforts to influence the reporting of scientific studies related to the safety of the herbicide, glyphosate.
Methods:
A set of 141 recently de-classified documents, made public during the course of pending toxic tort litigation, In Re Roundup Products Liability Litigation were examined.
Results:
The documents reveal Monsanto-sponsored ghostwriting of articles published in toxicology journals and the lay media, interference in the peer review process, behind-the-scenes influence on retraction and the creation of a so-called academic website as a front for the defense of Monsanto products.
Conclusion:
The use of third-party academics in the corporate defense of glyhphosate reveals that this practice extends beyond the corruption of medicine and persists in spite of efforts to enforce transparency in industry manipulation.
Background:
Up to now, experimental studies on rodents have failed to provide definitive confirmation of the carcinogenicity of extremely low frequency electromagnetic fields (ELFEMF). Two recent studies performed in our laboratory on Sprague-Dawley rats reported a statistically significant increase in malignant tumors of different sites (mammary gland, C-cells carcinoma, hemolymphoreticular neoplasia, and malignant heart Schwannoma) when ELFEMF exposure was associated with exposure to formaldehyde (50 mg/l) or acute low dose of γ-radiation (0.1 Gy) (Soffritti et al., 2016a) (Soffritti et al., 2016b). The same doses of known carcinogenic agents (50 mg/l formaldehyde, or acute 0.1 Gy γ-radiation), when administered alone, previously failed to induce any statistically significant increase in the incidence of total and specific malignant tumors in rats of the same colony.
Objectives:
A lifespan whole-body exposure study was conducted to evaluate the possible carcinogenic effects of ELFEMF exposure administered alone to Sprague-Dawley rats, as part of the integrated project of the Ramazzini Institute (RI) for studying the effects on health of ELFEMF alone or in combination with other known carcinogens.
Methods:
Male and female Sprague-Dawley rats were exposed 19 h/day to continuous sinusoidal-50 Hz magnetic fields (S-50 Hz MF) at flux densities of 0 (control group), 2, 20, 100 or 1000µT, and to intermittent (30 min on/30 min off) S-50 Hz MF at 1000 µT, from prenatal life until natural death.
Results:
Survival and body weight trends in all groups of rats exposed to ELFEMF were comparable to those found in sex-matched controls. The incidence and number of malignant and benign tumors was similar in all groups. Magnetic field exposure did not significantly increase the incidence of neoplasias in any organ, including those sites that have been identified as possible targets in epidemiological studies (leukemia, breast cancer, and brain cancer).
Conclusions:
Life-span exposures to continuous and intermittent sinusoidal-50 Hz ELFEMFs, when administered alone, did not represent a significant risk factor for neoplastic development in our experimental rat model. In light of our previous results on the carcinogenic effects of ELFEMF in combination with formaldehyde and γ-radiation, further experiments are necessary to elucidate the possible role of ELFEMF as cancer enhancer in presence of other chemical and physical carcinogens.
The paper offers an attempt to determine whether emissions from the unconventional gas industry are associated with hospitalisations in the Darling Downs, Queensland, Australia. Hospitalisation data were obtained from the Darling Downs Hospital and Health Services (DDHHS) and Coal Seam Gas (CSG) emissions data from the National Pollutants Inventory (NPI). Hospital admissions for circulatory and respiratory conditions, controlled for population, increased significantly from 2007 to 2014 (p < 0.001). Acute circulatory admissions increased 133% (2198–5141) and acute respiratory admissions increased 142% (1257–3051). CSG emissions increased substantially over the same period: nitrogen oxides (489% to 10,048 tonnes), carbon monoxide (800% to 6800 tonnes), PM10 (6000% to 1926 tonnes), volatile organic compounds (337% to 670 tonnes) and formaldehyde (12 kg to over 160 tonnes). Increased cardiopulmonary hospitalisations are coincident with the rise in pollutants known to cause such symptoms. Apparently, controls to limit exposure are ineffectual. The burden of air pollution from the gas industry on the wellbeing of the Darling Downs population is a significant public health concern.
Background:
Glyphosate is the most commonly used herbicide worldwide, with both residential and agricultural uses. In 2015, the International Agency for Research on Cancer classified glyphosate as "probably carcinogenic to humans," noting strong mechanistic evidence and positive associations for non-Hodgkin lymphoma (NHL) in some epidemiologic studies. A previous evaluation in the Agricultural Health Study (AHS) with follow-up through 2001 found no statistically significant associations with glyphosate use and cancer at any site.
Methods:
The AHS is a prospective cohort of licensed pesticide applicators from North Carolina and Iowa. Here, we updated the previous evaluation of glyphosate with cancer incidence from registry linkages through 2012 (North Carolina)/2013 (Iowa). Lifetime days and intensity-weighted lifetime days of glyphosate use were based on self-reported information from enrollment (1993-1997) and follow-up questionnaires (1999-2005). We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) using Poisson regression, controlling for potential confounders, including use of other pesticides. All statistical tests were two-sided.
Results:
Among 54 251 applicators, 44 932 (82.8%) used glyphosate, including 5779 incident cancer cases (79.3% of all cases). In unlagged analyses, glyphosate was not statistically significantly associated with cancer at any site. However, among applicators in the highest exposure quartile, there was an increased risk of acute myeloid leukemia (AML) compared with never users (RR = 2.44, 95% CI = 0.94 to 6.32, Ptrend = .11), though this association was not statistically significant. Results for AML were similar with a five-year (RRQuartile 4 = 2.32, 95% CI = 0.98 to 5.51, Ptrend = .07) and 20-year exposure lag (RRTertile 3 = 2.04, 95% CI = 1.05 to 3.97, Ptrend = .04).
Conclusions:
In this large, prospective cohort study, no association was apparent between glyphosate and any solid tumors or lymphoid malignancies overall, including NHL and its subtypes. There was some evidence of increased risk of AML among the highest exposed group that requires confirmation.
Glyphosate is a very important herbicide that is widely used in the agriculture, and thus the exposure of humans to this substance and its metabolites has been noted. The purpose of this study was to assess DNA damage (determination of single and double strand-breaks by the comet assay) as well as to evaluate DNA methylation (global DNA methylation and methylation of p16 (CDKN2A) and p53 (TP53) promoter regions) in human peripheral blood mononuclear cells (PBMCs) exposed to glyphosate. PBMCs were incubated with the compound studied at concentrations ranging from 0.1 to 10?mM for 24?h. The study has shown that glyphosate induced DNA lesions, which were effectively repaired. However, PBMCs were unable to repair completely DNA damage induced by glyphosate. We also observed a decreased global DNA methylation level at 0.25?mM of glyphosate. Glyphosate at 0.25?mM and 0.5?mM increased p53 promoter methylation, while it did not induce statistically significant changes in methylation of p16 promoter. To sum up, we have shown for the first time that glyphosate (at high concentrations) may induce DNA damage in leucocytes such as PBMCs and cause DNA methylation in human cells in the concentrations range from 0.5 to 10?mM.
Background: Glyphosate is a widely used herbicide in the world. Coronary artery disease (CAD) has been recognized as widespread causes of death and disability. In our study, we aimed to investigate the difference in results of health examination among people whether exposed to glyphosate or not.
Methods: We recruited workers from glyphosate production line as the exposed group and workers without doing pesticide production as the non-exposed group. All the participants have taken health examination as well as finished personal health questionnaires. A total of 42 patients with CAD were found among the return patients. Individual and fix-point samplings were performed to monitor the level of glyphosate in workplace air around the production line. Glyphosate and AMPA in the plasma were measured by gas chromatography combined with GC/MS method. The association between measured variables and the incidence of CAD was evaluated in unconditional logistic regression models.
Results: The highest levels of permissible concentration-time weighted average (PC-TWA) (0.01–94.59 mg/m 3 ) and permissible concentration-short term exposure limit (PC-STEL) (0.01–20 mg/m3) were separately presented in the jobs like packing and drying. The average concentration of glyphosate and its metabolin aminomethylphonic acid (AMPA) 85481 in blood plasma was 9.13 and 4.20 ng/mL, respectively. Forty-two percent of glyphosate workers admitted wearing gauze mask or spectacles seldom worn when they worked. The incidence rates of hypertension, CAD, abnormal rate of ECG, total liver function index [including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein (TP)] and summary of renal function index were found significantly higher in the exposed group than non-exposed group (P Conclusions: Our results suggested that glyphosate might be a potential hazard factor to CAD.
The International Agency for Research on Cancer (IARC) published a monograph in 2015 concluding that glyphosate is “probably carcinogenic to humans” (Group 2A) based on limited evidence in humans and sufficient evidence in experimental animals. It was also concluded that there was strong evidence of genotoxicity and oxidative stress. Four Expert Panels have been convened for the purpose of conducting a detailed critique of the evidence in light of IARC’s assessment and to review all relevant information pertaining to glyphosate exposure, animal carcinogenicity, genotoxicity, and epidemiologic studies. Two of the Panels (animal bioassay and genetic toxicology) also provided a critique of the IARC position with respect to conclusions made in these areas. The incidences of neoplasms in the animal bioassays were found not to be associated with glyphosate exposure on the basis that they lacked statistical strength, were inconsistent across studies, lacked dose-response relationships, were not associated with preneoplasia, and/or were not plausible from a mechanistic perspective. The overall weight of evidence from the genetic toxicology data supports a conclusion that glyphosate (including GBFs and AMPA) does not pose a genotoxic hazard and therefore, should not be considered support for the classification of glyphosate as a genotoxic carcinogen. The assessment of the epidemiological data found that the data do not support a causal relationship between glyphosate exposure and non-Hodgkin’s lymphoma while the data were judged to be too sparse to assess a potential relationship between glyphosate exposure and multiple myeloma. As a result, following the review of the totality of the evidence, the Panels concluded that the data do not support IARC’s conclusion that glyphosate is a “probable human carcinogen” and, consistent with previous regulatory assessments, further concluded that glyphosate is unlikely to pose a carcinogenic risk to humans.
In 2015, the International Agency for Research on Cancer (IARC) published a monograph concluding there was strong evidence for genotoxicity of glyphosate and glyphosate formulations and moderate evidence for genotoxicity of the metabolite aminomethylphosphonic acid (AMPA). These conclusions contradicted earlier extensive reviews supporting the lack of genotoxicity of glyphosate and glyphosate formulations. The IARC Monograph concluded there was strong evidence of induction of oxidative stress by glyphosate, glyphosate formulations, and AMPA. The Expert Panel reviewed the genotoxicity and oxidative stress data considered in the IARC Monograph, together with other available data not considered by IARC. The Expert Panel defined and used a weight of evidence (WoE) approach that included ranking of studies and endpoints by the strength of their linkage to events associated with carcinogenic mechanisms. Importantly, the Expert Panel concluded that there was sufficient information available from a very large number of regulatory genotoxicity studies that should have been considered by IARC. The WoE approach, the inclusion of all relevant regulatory studies, and some differences in interpretation of individual studies led to significantly different conclusions by the Expert Panel compared with the IARC Monograph. The Expert Panel concluded that glyphosate, glyphosate formulations, and AMPA do not pose a genotoxic hazard and the data do not support the IARC Monograph genotoxicity evaluation. With respect to carcinogenicity classification and mechanism, the Expert Panel concluded that evidence relating to an oxidative stress mechanism of carcinogenicity was largely unconvincing and that the data profiles were not consistent with the characteristics of genotoxic carcinogens.
The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authority of the rapporteur Member State, the United Kingdom, for the pesticide active substance geraniol are reported. The context of the peer review was that required by Commission Regulation (EU) No 188/2011. The conclusions were reached on the basis of the evaluation of the representative uses of geraniol as a fungicide on table and wine grapes. The reliable endpoints concluded as being appropriate for use in regulatory risk assessment, derived from the available studies and literature in the dossier peer reviewed, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are identified.
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Samples of honey (sixty nine), pancake and corn syrup (twenty six), soy sauce (twenty eight), soy milk (eleven), and tofu (twenty) purchased in the Philadelphia, US metropolitan area were analyzed for glyphosate residue using ELISA. The limit of quantification (LOQ) and range of the method were determined for honey, pancake syrup, and corn syrup to be 15 to 800 ppb; soy sauce, soy milk, and tofu 75 to 4,000 ppb. Glyphosate residues above the limit of quantification were not found in pancake and corn syrup, soy milk, and tofu. Of the sixty-nine honey samples analyzed, forty-one samples, or fifty-nine percent (59%), had glyphosate concentrations above the method LOQ (15 ppb), with a concentration range between 17 and 163 ppb and a mean of 64 ppb. Eleven of the tested honey samples were organic; five of the organic honey samples, or forty-five percent (45%), contained glyphosate concentrations above the method LOQ, with a range of 26 to 93 ppb and a mean of 50 ppb. Of the fifty-eight non-organic honey samples, thirty-six samples, or sixty-two percent (62%), contained glyphosate concentrations above the method LOQ, with a range of 17 to 163 ppb and a mean of 66 ppb. In addition to comparison of production method (organic vs. conventional), the honey results were evaluated according to pollen source and by country of origin, grouped by GMO usage (prohibited, limited, or permitted). Glyphosate concentrations above the method LOQ (75 ppb) were also found in ten of the twenty-eight soy sauce samples evaluated (36%), with a concentration range between 88 and 564 ppb and a mean of 242 ppb; all organic soy sauce samples tested were below the method LOQ.
