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Abstract

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.

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... Although the human health impacts stemming from exposure to pesticides are not fully known or understood, an increasing number of studies describe adverse effects following acute occupational exposures [9], heightened risk of cancer [15][16][17][18], and residential proximity to farms heavily reliant on pesticides [19,20]. ...
... However, current regulatory systems have often failed to detect and/or mitigate some of the health effects triggered by pesticides. Examples include damage to the neurological system and brain from chlorpyrifos and other organophosphates [19,21], the impact of exposures to glyphosate-based herbicides on non-Hodgkin lymphoma [15,22,23], and adverse reproductive impacts of multiple pesticides [24,25]. These failures to detect and prevent adverse health outcomes arise from systemic shortcomings in how regulators, industry and public health professionals assess pesticide risks and strive to mitigate them. ...
... Some surfactants also markedly enhance toxicity to non-target organisms [40] and human-health risks [41]. Applicator exposure episodes leading to glyphosate doses high enough to trigger ocular damage [42], skin irritation [43], non-Hodgkin lymphoma [15], and gastrointestinal disorders [44,45] were not due to glyphosate alone, but to the glyphosate plus surfactants in formulated commercial products (e.g. MON 0818 for Roundup MON 2139) [41,46,47]. ...
Article
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Background Flaws in the science supporting pesticide risk assessment and regulation stand in the way of progress in mitigating the human health impacts of pesticides. Critical problems include the scope of regulatory testing protocols, the near-total focus on pure active ingredients rather than formulated products, lack of publicly accessible information on co-formulants, excessive reliance on industry-supported studies coupled with reticence to incorporate published results in the risk assessment process, and failure to take advantage of new scientific opportunities and advances, e.g. biomonitoring and “omics” technologies. Recommended Actions Problems in pesticide risk assessment are identified and linked to study design, data, and methodological shortcomings. Steps and strategies are presented that have potential to deepen scientific knowledge of pesticide toxicity, exposures, and risks. We propose four solutions: (1) End near-sole reliance in regulatory decision-making on industry-supported studies by supporting and relying more heavily on independent science, especially for core toxicology studies. The cost of conducting core toxicology studies at labs not affiliated with or funded directly by pesticide registrants should be covered via fees paid by manufacturers to public agencies. (2) Regulators should place more weight on mechanistic data and low-dose studies within the range of contemporary exposures. (3) Regulators, public health agencies, and funders should increase the share of exposure-assessment resources that produce direct measures of concentrations in bodily fluids and tissues. Human biomonitoring is vital in order to quickly identify rising exposures among vulnerable populations including applicators, pregnant women, and children. (4) Scientific tools across disciplines can accelerate progress in risk assessments if integrated more effectively. New genetic and metabolomic markers of adverse health impacts and heritable epigenetic impacts are emerging and should be included more routinely in risk assessment to effectively prevent disease. Conclusions Preventing adverse public health outcomes triggered or made worse by exposure to pesticides will require changes in policy and risk assessment procedures, more science free of industry influence, and innovative strategies that blend traditional methods with new tools and mechanistic insights.
... In ecological epidemiological studies the increased use of glyphosate has been followed by an increase in a wide variety of human diseases, including various forms of cancer, sometimes at a lag of several years (Swanson at al. 2014;Uyemura et al., 2017;Zhang et al., 2019). It should be emphasized that this does not imply a causal relationship (Mesnage and Antoniou, 2017). ...
... As dissipation and degradation are much slower than anticipated originally, glyphosate residues have accumulated in soil and water bodies, and consequently have increased in plant and animal products (Battaglin, 2014;Carles, 2019;Silva et al., 2018). Tolerance levels were set originally based on acute oral toxicities and have been raised as the measured residues in food and feed products rose over time (Benbrook, 2016;Myers et al., 2016;Zhang et al., 2019). Although the toxicity to mammals was initially considered to be low (Greim et al., 2015;O World Health Organiz, 2009), there is increasing emphasis on potential chronic effects of glyphosate as it accumulates in the environment and the food chain (Jarrell et al., 2020;Greim et al., 2015;Mesnage et al., 2015a;Mesnage et al., 2015b;Myers et al., 2016;Zhang et al., 2019). ...
... Tolerance levels were set originally based on acute oral toxicities and have been raised as the measured residues in food and feed products rose over time (Benbrook, 2016;Myers et al., 2016;Zhang et al., 2019). Although the toxicity to mammals was initially considered to be low (Greim et al., 2015;O World Health Organiz, 2009), there is increasing emphasis on potential chronic effects of glyphosate as it accumulates in the environment and the food chain (Jarrell et al., 2020;Greim et al., 2015;Mesnage et al., 2015a;Mesnage et al., 2015b;Myers et al., 2016;Zhang et al., 2019). ...
Article
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The herbicide glyphosate interferes with the shikimate pathway in plants and in major groups of microorganisms impeding the production of aromatic amino acids. Glyphosate application on plants results in a slow death, accelerated by reduced resistance to root pathogens. Extensive glyphosate use has resulted in increasing residues in soil and waterways. Although direct glyphosate effects on animals are limited, major concerns have arisen about indirect harmful side effects. In this paper, we focus on indirect effects of sublethal concentrations of glyphosate on plant, animal and human health due to shifts in microbial community compositions in successive habitats. Research results of glyphosate effects on microbial communities in soil, rhizosphere and animal guts have been contradictory due to the different integration levels studied. Most glyphosate studies have tested short-term treatment effects on microbial biomass or general community composition at higher taxonomic levels in soil, rhizosphere or animal intestinal tracts, and found little effect. More detailed studies showed reductions in specific genera or species as well as biological processes after glyphosate application. Plant growth promoting rhizobacteria and beneficial intestinal bacteria often are negatively affected, while pathogenic bacteria and fungi are enhanced. Such shifts in microbial community composition have been implicated in enhanced susceptibility of plants to Fusarium and Rhizoctonia, of birds and mammals to toxic Clostridium and Salmonella species, and of bees to Serratia and Deformed Wing Virus. In animals and humans, glyphosate exposure and concentrations in urine have been associated with intestinal diseases and neurological as well as endocrine problems, but cause-effect relationships need to be determined in more detail. Nevertheless, outbreaks of several animal and plant diseases have been related to glyphosate accumulation in the environment. Long-term glyphosate effects have been underreported, and new standards will be needed for residues in plant and animal products and the environment.
... Glyphosate-based formulations are among the most widely used herbicides in agriculture worldwide [2, 33,34]. Exposure to pesticides and herbicides have already been associated with autism [32,[34][35][36], but a causal association and the mechanisms linking these two factors remain to be established. ...
... In vitro studies have already suggested that GBHs are frequently more toxic than isolated glyphosate itself [61]. However, agricultural practices are based on glyphosate-based formulations, with RUp being the most frequently used worldwide [36,61]. For this reason, the results we describe cannot be attributed solely to glyphosate, but could be associated with other components of the formulation or even to the interaction between different ingredients in the formulation. ...
Article
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RoundUp® (RUp) is a comercial formulation containing glyphosate (N-(phosphono-methyl) glycine), and is the world’s leading wide-spectrum herbicide used in agriculture. Supporters of the broad use of glyphosate-based herbicides (GBH) claim they are innocuous to humans, since the active compound acts on the inhibition of enzymes which are absent in human cells. However, the neurotoxic effects of GBH have already been shown in many animal models. Further, these formulations were shown to disrupt the microbiome of different species. Here, we investigated the effects of a lifelong exposure to low doses of the GBH-RUp on the gut environment, including morphological and microbiome changes. We also aimed to determine whether exposure to GBH-RUp could harm the developing brain and lead to behavioral changes in adult mice. To this end, animals were exposed to GBH-RUp in drinking water from pregnancy to adulthood. GBH-RUp-exposed mice had no changes in cognitive function, but developed impaired social behavior and increased repetitive behavior. GBH-Rup-exposed mice also showed an activation of phagocytic cells (Iba-1–positive) in the cortical brain tissue. GBH-RUp exposure caused increased mucus production and the infiltration of plama cells (CD138-positive), with a reduction in phagocytic cells. Long-term exposure to GBH-RUp also induced changes in intestinal integrity, as demonstrated by the altered expression of tight junction effector proteins (ZO-1 and ZO-2) and a change in the distribution of syndecan-1 proteoglycan. The herbicide also led to changes in the gut microbiome composition, which is also crucial for the establishment of the intestinal barrier. Altogether, our findings suggest that long-term GBH-RUp exposure leads to morphological and functional changes in the gut, which correlate with behavioral changes that are similar to those observed in patients with neurodevelopmental disorders.
... Crop rotation with different planting dates and crop diversification, combined with limited soil disturbance, can disrupt weed-crop associations in addition to reducing yield loss and rebuilding soil fertility [165][166][167]. Glyphosate is the most used chemical weed control agent [168], but is debated because of its effects on soil biodiversity and soil microbial respiration [169] and human health [168]. [169]. ...
... Crop rotation with different planting dates and crop diversification, combined with limited soil disturbance, can disrupt weed-crop associations in addition to reducing yield loss and rebuilding soil fertility [165][166][167]. Glyphosate is the most used chemical weed control agent [168], but is debated because of its effects on soil biodiversity and soil microbial respiration [169] and human health [168]. [169]. ...
Article
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Coherent improvements in crop varieties and crop husbandry and soil management practices are needed to increase global crop production in a sustainable manner. However, these practices are often discussed separately, and as a result there is little overview. Here, we present a database and synthesis of 154 meta-analysis studies related to ten main crop husbandry and soil management practices, including crop type and rotations, tillage, drainage, nutrient management, irrigation and fertigation, weed management, pest management, crop residue management, mechanization and technology, and landscape management. Most meta-analysis studies were related to tillage (55), followed by crop type and rotations (32), nutrient management (25), crop residue management (19), and irrigation and fertigation (18). Few studies were related to landscape management (6) and mechanization and technology (2). In terms of outcome, studies focused on crop yield and quality (81), soil quality (73), and environmental impacts (56), and little on economic effects (7) or resource use efficiency (24). Reported effects of alternative practices, relative to conventional practice, were positive in general. Effect sizes were relatively large for environmental effects (nutrient leaching, greenhouse gas emissions), and small for soil quality (except for soil life) and crop yield. Together, meta-analysis studies indicate that there is large scope for increasing cropland productivity and minimizing environmental impacts. A roadmap is provided for integration and optimization of all ten practices, and recommendations are formulated to address the gaps in meta-analysis studies.
... Regarding recent studies, a meta-analysis published in 2019 showed an increased risk of NHL in individuals heavily exposed to GBHs [68], while a review of epidemiological studies published in 2020 reveals an absence of association between glyphosate exposure and the occurrence of NHL [69]. ...
... Since glyphosate is mainly applied in agricultural fields, and due to the increasing consumption of glyphosate in recent decades, the concerns about the impact that glyphosate and its metabolites may have on the environment have grown [68]. ...
Article
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Glyphosate is a systemic, broad-spectrum and post-emergent herbicide. The use of glyphosate has grown in the last decades, and it is currently the most used herbicide worldwide. The rise of glyphosate consumption over the years also brought an increased concern about its possible toxicity and consequences for human health. However, a scientific community consensus does not exist at the present time, and glyphosate’s safety and health consequences are controversial. Since glyphosate is mainly applied in fields and can persist several months in the soil, concerns have been raised about the impact that its presence in food can cause in humans. Therefore, this work aims to review the glyphosate use, toxicity and occurrence in diverse food samples, which, in certain cases, occurs at violative levels. The incidence of glyphosate at levels above those legally allowed and the suspected toxic effects of this compound raise awareness regarding public health.
... DES controversy lasted for nearly seven decades before its severe adverse effects were finally determined. Roundup [13][14]. The inability to determine latent product/drug harmful effects is not exceptional but FDA-approved drugs that have been removed for subsequently discovered side effects [12]. ...
... That is the most probable reason that lead was able to hurt mankind for thousands of years. This flawed approach has dominated all medicine systems for the entire human history, but has been refuted by our model based on post-1980 research discoveries [2][3], discoveries of organ's functional reserves [15][16][17], and cellular damage mechanisms [5,13]. ...
Article
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Several mRNA vaccines are used on the population in the U.S. I started predicting the dangers of mRNA vaccines before March 2021 and update my findings periodically. My prior model study enabled me to identify many flaws in clinical trials, side-effect evaluation methods and mechanism studies, and I also considered consistent failure in predicting drug side effects in the past and systematic failure of FDA in keeping out dangerous drugs from market. I found that the risks of vaccination cannot be determined by experiments alone and must be determined by using a combination of methods. By studying mRNA expression dynamics and kinetics, I predict that vaccination with mRNA vaccines may increase cancer risks, multiple organ failure risks, earlier death risks, genome alteration speeds by one or more mechanisms, alter the normal selection process for viral evolution resulting in more virulent viruses, and aggravate chronic diseases or cause healed diseases to relapse. Two root problems are practical inability to control expression sites and severe adverse reactions from repeated vaccination. Based on mRNA bio-distribution, the mRNA mainly strikes the liver and other vital organs, and poses grave dangers to persons whose vascular functional reserves are relatively small, or whose vascular systems are temporarily burdened by other causes such as viral infections or life activities. If an mRNA vaccine is administered on a pregnant woman by second or booster shots, spike protein synthesis in fetus brain disrupts the highly regulated protein synthesis processes, resulting in potential brain damages. In less than a year, most of my early predicted damages are being materialized or are on the track to hit the population. In this update, I present a benefits-and-risks map to show how the number of deaths caused by mRNA vaccines is grossly underestimated and why claimed benefits like 95% effectiveness rate and 90% death rate reduction are meaningless and misleading.
... In 2015 the International Agency for Research on Cancer (IARC) classified glyphosate as a probable human carcinogen. 15 This classification was supported by a meta-analysis that suggested an elevated risk of non-Hodgkin's lymphoma associated with glyphosate exposure, 16 although another large cohort study did not find a relationship between glyphosate and cancer risk. 17 Epidemiological studies have also found associations with other health problems, including shortened gestational length, 14 birth defects, 18 endocrine disruption, 12 and thyroid dysfunction. ...
... Another recent avenue of research is the development of "epigenetic clocks" that purport to measure biological age using DNA methylation at a selection of CpG sites. 52,53,54 Epigenetic age acceleration (biological age greater than chronological age) or a faster molecular pace of aging 55 have been associated with a host of adverse outcomes, including all-cause mortality, 56,57,58 risk for breast cancer, 59 B-cell lymphoma, 60 which have been associated with glyphosate 16 and AMPA 32 in epidemiological studies. Epigenetic age acceleration has also been associated with other environmental exposures, 61,62,63,64 but to our knowledge, the association between epigenetic age acceleration and glyphosate and AMPA measurements has not been previously explored. ...
Article
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Background: Glyphosate is the most commonly used herbicide in the world and is purported to have a variety of health effects, including endocrine disruption and an elevated risk of several types of cancer. Blood DNA methylation has been shown to be associated with many other environmental exposures, but to our knowledge, no studies to date have examined the association between blood DNA methylation and glyphosate exposure. Objective: We conducted an epigenome-wide association study to identify DNA methylation loci associated with urinary glyphosate and its metabolite aminomethylphosphonic acid (AMPA) levels. Secondary goals were to determine the association of epigenetic age acceleration with glyphosate and AMPA and develop blood DNA methylation indices to predict urinary glyphosate and AMPA levels. Methods: For 392 postmenopausal women, white blood cell DNA methylation was measured using the Illumina Infinium MethylationEPIC BeadChip array. Glyphosate and AMPA were measured in two urine samples per participant using liquid chromatography-tandem mass spectrometry. Methylation differences at the probe and regional level associated with glyphosate and AMPA levels were assessed using a resampling-based approach. Probes and regions that had an false discovery rate q<0.1 in ≥90% of 1,000 subsamples of the study population were considered differentially methylated. Differentially methylated sites from the probe-specific analysis were combined into a methylation index. Epigenetic age acceleration from three epigenetic clocks and an epigenetic measure of pace of aging were examined for associations with glyphosate and AMPA. Results: We identified 24 CpG sites whose methylation level was associated with urinary glyphosate concentration and two associated with AMPA. Four regions, within the promoters of the MSH4, KCNA6, ABAT, and NDUFAF2/ERCC8 genes, were associated with glyphosate levels, along with an association between ESR1 promoter hypomethylation and AMPA. The methylation index accurately predicted glyphosate levels in an internal validation cohort. AMPA, but not glyphosate, was associated with greater epigenetic age acceleration. Discussion: Glyphosate and AMPA exposure were associated with DNA methylation differences that could promote the development of cancer and other diseases. Further studies are warranted to replicate our results, determine the functional impact of glyphosate- and AMPA-associated differential DNA methylation, and further explore whether DNA methylation could serve as a biomarker of glyphosate exposure. https://doi.org/10.1289/EHP10174.
... A meta-analysis reported that the overall risk of NHL in individuals exposed to glyphosate-based herbicides was increased by 41 per cent. Animal studies also showed an association between pure glyphosate and malignant lymphoma (Zhang et al. 2019). Another systematic review showed that herbicide exposure and agricultural exposure to pesticides was associated with an increased risk of thyroid cancer (Han, Kim, and Song 2019). ...
Technical Report
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Workers around the world are facing a global health crisis due to occupational exposure to toxic chemicals. Many of these workers lose their life following such exposures, succumbing to fatal diseases, cancers and poisonings, or from fatal injuries following fires or explosions. We must also consider the additional burden that workers and their families face from non-fatal injuries resulting in disability, debilitating chronic diseases, and other health sequela, that unfortunately in many cases remain invisible. All of these deaths, injuries and illnesses are entirely preventable. The International Labour Organization (ILO) has long recognized that the protection of workers from hazardous chemicals is essential to ensuring healthy populations as well as sustainable environments. Nevertheless, workers continue to be disproportionally exposed to chemicals across almost all workplace sectors. Production of chemicals as well as the industries using them are expanding, which means a high potential for increased occupational exposure. Moreover, with new chemicals introduced every year, mechanisms for regulating exposure such as the implementation of occupational exposure limits, struggle to keep up. There is therefore an urgent need to take action and implement a range of effective measures to prevent harm to workers, their families, and wider communities. This global review was undertaken in order to provide a sound evidence base towards policy efforts. As such, it represents a much needed analysis of recent trends and priorities when it comes to protecting the health and safety of workers from occupational chemical exposures.
... Important human health concerns have been raised regarding glyphosate exposure. The International Agency for Research on Cancer (IARC), a specialized agency of the World Health Organization (WHO), linked non-Hodgkin lymphoma (NHL) to glyphosate exposure and classified glyphosate as a "probable carcinogenic (Group 2 A)" (IARC 2015); this association has been further confirmed (Leon et al. 2019;Zhang et al. 2019;Inserm 2021), whereas the evaluation conducted by the European Food Safety Authority (EFSA) concluded that glyphosate is "unlikely to pose a carcinogenic hazard to humans and the evidence does not support classification with regard to its carcinogenic potential" (EFSA 2015). Evaluation by the EFSA mostly relied on studies conducted by agrochemical industries (Portier et al. 2016;Benbrook 2019;Foucart 2021a, b). ...
Article
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France is the first pesticide-consuming country in Europe. Glyphosate is the most used pesticide worldwide and glyphosate is detected in the general population of industrialized countries, with higher levels found in farmers and children. Little data was available concerning exposure in France. Our objective was to determine glyphosate levels in the French general population and to search for an association with seasons, biological features, lifestyle status, dietary habits, and occupational exposure. This study includes 6848 participants recruited between 2018 and 2020. Associated data include age, gender, location, employment status, and dietary information. Glyphosate was quantified by a single laboratory in first-void urine samples using ELISA. Our results support a general contamination of the French population, with glyphosate quantifiable in 99.8% of urine samples with a mean of 1.19 ng/ml + / − 0.84 after adjustment to body mass index (BMI). We confirm higher glyphosate levels in men and children. Our results support glyphosate contamination through food and water intake, as lower glyphosate levels are associated with dominant organic food intake and filtered water. Higher occupational exposure is confirmed in farmers and farmers working in wine-growing environment. Thus, our present results show a general contamination of the French population with glyphosate, and further contribute to the description of a widespread contamination in industrialized countries.
... This fact is very relevant as this agrochemical is classified as a "probable carcinogen" to humans by the International Agency for Research on Cancer . Additionally, recent meta-analysis evidence suggests a compelling link between exposures to glyphosate-based herbicides and an increased risk of non-Hodgkin lymphoma (Zhang et al. 2019). ...
Article
The American continent is the largest producer of genetically modified crops worldwide, characterized by the massive use of pesticides and agrochemicals, of which numerous scientific studies and reports show risks to human health. The child-youth population living in these regions constitutes an age group with its own characteristics that make it more vulnerable to possible exposure to pesticide use. The use of satellite information on cloud platforms can facilitate the measurement and creation of exploratory indicators over large study areas to assess the degree of exposure in educational establishments. The objective of this research is to create and evaluate exploratory indicators of the proximity of intensive crops to educational establishments in central Argentina, using satellite spatial–temporal analysis methodologies. The study was conducted in the province of Córdoba (Argentina). A total of 2263 public and private sector educational institutions were selected, both urban and rural. Perimeter rings were created in each establishment, at different distances up to 2000 m from the periphery. Satellite data of active summer crops in the period 2016–2019 were calculated using the Google Earth Engine. Proximity indicators and crop coverage areas were created. Ninety-two per cent of the educational establishments analyzed have at least one crop field nearby within a radius of 2000 m. More than half of these have fields that are 500 m or less away. The peripheral occupation of crops in more than half of the educational establishments varies between 25 and 100% (in the entire ring). The establishments in dispersed rural areas would be the most exposed, with an average proximity to the first field of less than 180 m. Kindergartens and primary schools are closer and have a higher percentage of peripheral crops than the secondary and special education schools. Our research reveals a worrying panorama that combines the proximity of educational establishments to fields cultivated with GM crops; research that shows a higher degree of exposure to agricultural pesticide pollution and adverse health effects for this age group, and local regulations that allow their application close to educational establishments and cities where they carry out their main activities.
... 7 While its carcinogenicity continues to be debated, a recent meta-analysis identified a 41% increase in non-Hodgkin lymphoma among exposed workers. 8 Widespread use of glyphosate has been documented in Mexico, especially among rural communities with heavy agricultural activity. A total of 192 children included in a previous cross-sectional study, 73% of whom reported residues of glyphosate (urine first-morning spot), living near the largest lake in Mexico, Lake Chapala. ...
Article
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Background Glyphosate is one of the most commonly used pesticides in agricultural activities worldwide. For the last 20 years, its use has increased rapidly becoming a public health concern. The IARC classified glyphosate as probably carcinogenic; however, the reported evidence is not enough to establish a statement. Objective This work aimed to measure glyphosate levels in the urine of children from a single rural community in an endemic region of chronic kidney disease and malnutrition. Methods A cross-sectional study was carried out in a rural community in western Mexico. The study included 95 children between the ages of 6 and 16. A urine sample (first-morning spot) was obtained from children and processed to measure glyphosate levels using high-performance liquid chromatography coupled with tandem mass spectrometry. Results All samples tested positive for glyphosate levels. Urine glyphosate levels were related to the season and the age of the children. Conclusion Glyphosate is present in children of all ages in the community even if they were not in direct contact with it. No toxicity cases were reported, nor were there other health problems related to glyphosate. However, more long-term studies should be done that provide a statement regarding the harmful effects that glyphosate has on public health.
... While the use of pesticides has made higher agricultural production possible, this increase in use, on the other hand, has led to greater levels of contamination of the environment and to agrigultural farm workers. High exposure levels have been associated to adverse health effects, such as reproductive effects [4], Parkinson's disease [5], cardiovascular diseases [6], dyslipidemias [7], as well as the development of some types of cancers, such as non-Hodgkin's lymphoma [8,9], cutaneous melanoma [10], prostate [11] and colorectal cancers [12]. Many studies have demonstrated the genotoxic effects due to pesticide exposure, detected by chromosomal aberrations [13], sister chromatid exchange [14], comet assay [15,16], micronuclei in lymphocytes [16,17] and buccal cells [15], as well as the effect on telomere length [18]. ...
Article
Brazil is one of the largest consumers of pesticides in the world. This high consumption has resulted in higher potential health risk to agricultural farm workers due to occupational exposure. Hence, the aim of this study is to evaluate genomic instability, using Buccal Micronucleus Cytome (BMCyt) and telomere length (TL) measurement as biomarkers of occupational exposure to pesticides in rural workers living in the State of São Paulo, Brazil. Genomic instability was evaluated in 81 pesticide-exposed farm workers (69 males and 12 females) with a mean age of 49.16 ± 10.06 years and a mean time job of 30.00 ± 14.00 years,81 non-exposed individuals (62 males and 15 females) with a mean age of 47.87 ± 10.66 years. BMCyt results showed significantly higher levels of cell damage (micronuclei and binucleated cells) and cell death (karyorrhectic and condensed chromatin cells) in subjects exposed to pesticide when compared to those non-exposed (p < 0.05). Although our results did not show significant differences in TL among exposed and non-exposed groups, effects in TL due to pesticide exposure was found in a multivariable linear regression model when we stratified the groups by age (≤ 49 years and ≥ 50 years old; β = 11.21, p = 0.006). In addition, TL reduction on was identified in relationto an increase in cigarette pack consumption (β = -0.633, p = 0.045). Furthermore, exposure to specific pesticides presented different effects in TL. Cypermethrin exposure resulted in a reduction in TL (β = -18.039, p = 0.018), while abamectin exposure led to an increase in TL (β = 23.990, p = 0.007). Thus, our findings substantiate genomic instability due to pesticides exposure.
... ➢ Occupational factors: benzene, dyes, herbicides, pesticides [21][22][23][24]; ...
Article
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Non-Hodgkin’s malignant lymphomas are a heterogeneous group of hematological malignancies, characterized by a variety of clinical, morphological, histopathological, immuno-histochemical, molecular and evolutionary features. They represent a form of cancer that develops from the lymphatic tissue, as a result of the malignant transformation of B (85%) or T (15%) lymphocytes. Lymphomagenesis is described as a multi-stage process involving the mutation and proliferation of cell clones. Oxidative stress is defined as an imbalance of cellular redox status caused by the production of reactive oxygen species (ROS) and/ or by decreasing antioxidant systems that allows their accumulation in the cell. Small quantities of ROS are involved in physiological mechanisms such as cell growth and differentiation, cell signaling, antimicrobial defense, phagocytosis. Normally, cells are capable of defending themselves against ROS damage through various scavenger systems. On the other hand, excessive ROS contribute to various diseases such as carcinogenesis, ischemia, atherosclerosis, neurodegenerative diseases. Oxidative stress exerts noxious effects on the cell structures by inducing structural changes in membranes, lipids, proteins or DNA. The present review summarizes the latest findings in understanding the ROS-linked signaling pathways in the initiation of lymphomagenesis, disease progression, metastasis, as well as in the pharmacodynamics of specific treatments for this malignancy.
... While the use of pesticides has made higher agricultural production possible, this increase in use, on the other hand, has led to greater levels of contamination of the environment and to agrigultural farm workers. High exposure levels have been associated to adverse health effects, such as reproductive effects [4], Parkinson's disease [5], cardiovascular diseases [6], dyslipidemias [7], as well as the development of some types of cancers, such as non-Hodgkin's lymphoma [8,9], cutaneous melanoma [10], prostate [11] and colorectal cancers [12]. Many studies have demonstrated the genotoxic effects due to pesticide exposure, detected by chromosomal aberrations [13], sister chromatid exchange [14], comet assay [15,16], micronuclei in lymphocytes [16,17] and buccal cells [15], as well as the effect on telomere length [18]. ...
Article
Construction environment is composed of various substances classified as carcinogens. Thus, workers exposed in this environment can be susceptible to genomic instability that can be evaluated by absolute telomere length (TL). In this work, we evaluated TL in construction workers compared to a non-exposed group performed by qPCR assay. The TL was evaluated in 59 men exposed to the construction environment (10 years of exposure) and 49 men non-exposed. Our data showed that individuals exposed to the construction environment exhibited a significantly lower TL in relation to non-exposed group (p = 0.009). Also, on the multiple linear regression model, we observed that TL was significantly influenced by the construction environment exposure (p ≤ 0.001). Additionally, the arsenic exposure is associated to a shortening telomere (p ≤ 0.001), and the lead exposure caused an increase in TL (p ≤ 0.001). Thus, our findings suggest a modulation in TL by construction environment exposure, mainly by arsenic and lead exposure.
... (Guyton et al., 2015). Indeed, the exposure to this compound seems associated with the genesis of certain cancers, in particular non-Hodgkin's lymphomas (Leon et al., 2019;Zhang et al., 2019), and the chronic exposure to herbicides, including glyphosate, has been suggested to be the cause of unexplained chronic kidney disease in rice farm workers in Sri Lanka (Jayasumana et al., 2014) and sugarcane in El Salvador (Peraza et al., 2012), leading to the deaths of large numbers of people. Moreover, glyphosate seems to have cytotoxic and genotoxic effects on humans, causes inflammation, and affects lymphocyte functions and the interactions between microorganisms and the immune system (Peillex & Pelletier, 2020). ...
Article
A LC‐MS/MS method for the hair testing of glyphosate and aminomethylphosphonic acid (AMPA), its main biodegradation product has been developed. After decontamination, 50 mg of hair were grinded and sonicated in water for 2h. The method was fully validated in the 5‐500 pg/mg range for glyphosate and 10‐500 pg/mg for AMPA, and LOD were 2 and 5 pg/mg, respectively. Matrix effect for glyphosate and AMPA was compensated by isotope‐labelled internal standard. Four farmers who regularly used glyphosate, one farmer’s spouse who did not use glyphosate but her husband used it and 14 hair samples from non‐occupationally exposed subjects were tested. Glyphosate was found in the head hair of 3 farmers, with concentration in the 14‐188pg/mg range. The fourth was found negative, but with hair colored in red. Glyphosate was detected in 10/14 hair samples from non‐occupationally exposed subjects, at concentrations of 11.5 pg/mg or lower and only in one segment (0‐3 cm) of the farmer’s spouse (6 pg/mg). AMPA was detected in 5 subjects, above LOQ only in 2 of the 3 occupationally exposed subjects with positive glyphosate. Further studies should be conducted to validate this potential new biomarker which could be useful for assessing long‐term exposure to glyphosate.
... Concern over the carcinogenic effect of glyphosate has been largely stoked by legal cases in the United States over claims of non-Hodgkin Lymphoma caused by the herbicide. A study by Zhang et al. (2019) observed via a meta-analysis that the meta-relative risk of non-Hodgkin Lymphoma increased by 41% due to glyphosate-based herbicides. Additionally, in 2015, glyphosate was classified as probably carcinogenic to humans (Group 2A) by the International Agency for Research on Cancer (IARC) in addition to finding sufficient evidence of carcinogenicity in experimental animals (https://publications.iarc.fr/549). ...
... Total annual pesticide sales in Europe during the period 2011 to 2016 rose by approximately 14% from 386,400 to 439,400 tonnes of active ingredients (Peña et al., 2020). In the United States, the use of the broad spectrum herbicide glyphosate has risen by approximately 19,700% from 635 tonnes in 1974 to 125, 000 tonnes in 2014 (Zhang et al., 2019). While increased pesticide application has been beneficial in preventing hazardous diseases in crops, improving yields, and maintaining the economic viability of agriculture (Maggi et al., 2020), it has also increased the risk of subsequent human exposure, resulting in human health issues, such as neurological, respiratory and carcinogenic effects (Van Maele-Fabry et al., 2017;Ye et al., 2017;Pouchieu et al., 2018). ...
... Zhang et al., 39 in his meta-analysis, did not verify the relationship between glyphosate and ASD, but reported evidence from studies on humans, animals, and mechanics of a convincing link between exposure to glyphosate-based herbicides (GBHs) and increased meta-relative risk (meta-RR) of non-Hodgkin lymphoma (NHL) increased by 41% (meta-RR=1.41, 95%CI 1.13-1.75). ...
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Objective: The aim of this study was to evaluate the influence of early exposure to agricultural pesticides and their relationship with autism spectrum disorder. Data source: This systematic review was registered at PROSPERO as CRD42020204842. The subject was systematically analyzed on PubMed, Scopus, and Web of Science databases until April 2021. Only studies with humans with early exposure to agricultural pesticides and diagnosis of autism were included. Exclusion criteria were studies on pesticides for domestic or veterinary use and late exposure. There were no language and time restriction. The quality analysis of the studies used the Newcastle-Ottawa Scale. Data synthesis: Six case-control studies were included; three of them measured the route of exposure by maternal biomarkers and the others by the residence address. The studies had scores between moderate and high in the quality assessment tool. It was found high rates of association between early exposure to agricultural pesticides and autism and detection limit above the quantification for a sample of polychlorinated biphenyls, hexachlorobenzene, and dichlorodiphenyldichloroethylene. Conclusions: There is evidence concerning the exposure to agricultural pesticides in early life and the development of the autism spectrum disorder; however, more studies are required to better understand their possible association.
... This article focuses on the human health risks of EOs used as bioherbicides in an agronomic and horticultural context. Among all herbicides of which hazards have been studied, a huge need for less harmful herbicides exists since glyphosate has been banned in many countries [11][12][13][14]. After presenting some generalities about pesticides, risks and EOs, this paper provides a critical analysis of the risks to human health associated with the use of EO-based bioherbicides. ...
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In recent years, the development of new bio-based products for biocontrol has been gaining importance as it contributes to reducing the use of synthetic herbicides in agriculture. Conventional herbicides (i.e., the ones with synthetic molecules) can lead to adverse effects such as human diseases (cancers, neurodegenerative diseases, reproductive perturbations, etc.) but also to disturbing the environment because of their drift in the air, transport throughout aquatic systems and persistence across different environments. The use of natural molecules seems to be a very good alternative for maintaining productive agriculture but without the negative side effects of synthetic herb-icides. In this context, essential oils and their components are increasingly studied in order to produce several categories of biopesticides thanks to their well-known biocidal activities. However, these molecules can also be potentially hazardous to humans and the environment. This article reviews the state of the literature and regulations with regard to the potential risks related to the use of essential oils as bioherbicides in agricultural and horticultural applications.
... In its evaluation of the chemical, IARC has classified glyphosate as a group 2A carcinogen and acknowledges that, "a positive association has been observed for non-Hodgkin lymphoma" (IARC 2017). Zhang et al. (2019) conducted a meta-analysis of six studies and included data from the Agricultural Health Study. A meta-OR of 1.41 was identified for associations with glyphosate use and NHL . ...
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The incidence rate of non-Hodgkin lymphoma (NHL) is currently increasing within Canada as well as worldwide. Environmental pollutants are ubiquitous in the environment and can potentially increase an individual’s risk of developing NHL. The goal of this literature review was to identify environmental pollutants associated with diagnosis of NHL and summarize their current levels in human populations. Sixteen environmental pollutants were identified as having associations with NHL diagnosis, including dichlorodiphenyltrichloroethane (DDT), pentachlorophenol (PCP), polychlorinated biphenyls (PCBs), carbon tetrachloride, and various pesticides. PCB levels in human breast milk were highest in developed countries, while DDT levels were highest in malaria-endemic countries. 2,4-Dichlorophenoxyacetic acid and glyphosate levels were highest in individuals who were occupationally exposed to these chemicals. Humans are mainly exposed to the identified pollutants through food. PCBs were found within animal products such as milk and cheese, and a variety of pesticides were found in various fruits and vegetables. Individuals who followed vegan and vegetarian diets had lower levels of non-pesticide pollutants in their body due to limited consumption of animal products but had higher pesticide levels due to increased consumption of fruits and vegetables. However, organic diets proved to mitigate this issue. Further research needs to be conducted on a wider variety of pollutants to gain a comprehensive understanding of the effects of these pollutants in association with NHL.
... The prospects of WBE to estimate human exposure to pesticides is of particular interest. Exposure to pesticides has been linked to pose risks for human health and associated to for example cancer and Parkinson's disease (Allen and Levy, 2013;Weichenthal et al., 2012;Zhang et al., 2019). WBE can provide information about the exposure of the general population to pesticides via combined exposure routes including diet, household use and environmental exposure, and evade in this way time consuming and costly human biomonitoring sampling campaigns. ...
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Wastewater-based epidemiology (WBE) relies on the assessment and interpretation of levels of biomarkers in wastewater originating from a well-defined community. It has provided unique information on spatial and temporal trends of licit and illicit drug consumption, and has also the potential to give complementary information on human exposure to chemicals. Here, we focus on the accurate quantification of pesticide biomarkers (i.e., predominantly urinary metabolites) in influent wastewater at the ng L⁻¹ level to be used for WBE. In the present study, an advanced analytical methodology has been developed based on ultra-high-pressure liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS), for the simultaneous determination of 11 specific human biomarkers of triazines, urea herbicides, pyrethroids and organophosphates in urban wastewater. The sample treatment consisted of solid-phase extraction using Oasis HLB cartridges. Direct injection of the samples was also tested for all compounds, as a simple and rapid way to determine these compounds without sample manipulation (i.e. minimizing potential analytical errors). However, if extraction recoveries are satisfactory, SPE is the preferred approach that allow reaching lower concertation levels. Six isotopically labelled internal standards were evaluated and used to correct for matrix effects. Due to the difficulties associated with this type of analysis, special emphasis has been placed on the analytical challenges encountered. The satisfactory validated methodology was applied to urban wastewater samples collected from different locations across Europe revealing the presence of 2,6-EA, 3,4-DCA, 3-PBA and 4-HSA i.e, metabolites of metolachlor-s, urea herbicides, pyrethroids and chlorpropham, respectively. Preliminary data reported in this paper illustrate the applicability of this analytical approach for assessing human exposure to pesticides through WBE.
... Due to a low number of dogs (< 5%) living near landfills, coal plants, high-voltage transmission lines, or nuclear power plants, we were unable to statistically evaluate whether these pollutant sources were individually associated with lymphoma risk. Prior research has indicated exposure to various environmental pollutants may increase risk of NHL in people [7,[29][30][31][32]. The lack of statistically significant associations between individual manufacturing sites and chemical suppliers in this population may be due to limitations in sample size or distinct etiologies for different lymphoma subtypes, as hypothesized in human populations [33]. ...
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Plain English Summary Lymphoma is a common cancer affecting dogs, particularly Golden Retrievers. By identifying risk factors for lymphoma, work can be done to reduce harmful exposures or increase monitoring among dogs at a higher risk of disease. Using a subset of dogs from the Golden Retriever Lifetime Study, we sought to investigate whether dogs with lymphoma were more likely to live near certain environmental pollutant sources than dogs without lymphoma. Forty-nine Golden Retrievers with non-cutaneous lymphoma and 98 Golden Retrievers without a history of cancer were selected from the Golden Retriever Lifetime Study Cohort. We evaluated how close each dog lived to nine environmental pollutant sources: chemical plants, municipal dumps, manufacturing plants, incineration plants, railroad embankment tracks, landfills, coal plants, high-voltage transmission lines, and nuclear power plants. Additionally, we evaluated individual exposure to secondhand smoke, and average annual ozone and particulate matter exposure (as surrogate measures for air pollution) for each dog’s county of residence. None of the exposures examined were associated with an increased lymphoma risk in this population. More research is needed, including direct biomonitoring, to determine whether specific environmental exposures are associated with lymphoma in the Golden Retriever breed.
... According to the acute toxicity classification used in the United States, glyphosate is classified in category IV as a practically non-toxic substance [3] , but European Chemicals Agency classifies glyphosate as an eye irritant [4] as it may cause serious eye damage [2] . When it comes to chronic toxicity, studies have shown that exposure to glyphosate may be associated with QT interval prolongation and the occurrence of arrhythmias in humans [5] , oxidative-stress related organ damage [6] , hepatotoxic effects [7] , nephrotoxicity [8] , morphological changes in human erythrocytes [9] , increased risk of non-Hodgkin lymphoma [10] , compromised functioning of acetylcholinesterase with consequent deregulation in the transmission of nerve impulses [11] , DNA damage in human leukocytes [12] , teratogenic effects [13] , and endocrine disruption [6] , but there is no scientific consensus on whether the glyphosate should be considered as a hazardous substance or not. ...
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Glyphosate is a non-selective herbicide that targets the enzyme 5-enolpyruvyl-3-shikimate phosphate synthase. It has been used to effectively control perennial weed since 1974. There is some scientific evidence that supports concerns about glyphosate´s safety and potential health consequences for human health, such as eye irritation, cardiotoxicity, hepatotoxicity, nephrotoxicity, carcinogenicity, neurotoxicity, teratogenicity, mutagenicity and endocrine disruption, although there is no scientific consensus on this issue. Here, author summarized available up-to-date scientific evidence and explores the possible link between glyphosate maternal exposure and autism. Available up-to-date scientific evidence suggests that there may be a link between maternal glyphosate exposure and the increased risk for the development of autism in offspring, with possible pathophysiological mechanisms being increased levels of soluble epoxide hydrolase and Clostridium bacteria colonization of the intestinal tract, but more research is mandatory in order to establish the exact clinical relevance of here presented available scientific data.
... Aunado a una menor calidad nutricional de las tortillas industrializadas en relación con las artesanales, las primeras pueden contener secuencias recombinantes derivadas del uso de grano genéticamente modificado, el cual a su vez puede presentar residuos de herbicidas como glifosato, herbicida que ha sido recientemente reclasificado como un potencial carcinógeno en humanos (Guyton et al., 2015;IARC, 2017). La presencia de estas secuencias o moléculas puede tener consecuencias negativas para la salud, ya que el consumo de alimentos transgénicos ha sido relacionado con alteraciones endocrinas, cáncer, neurotoxicidad, toxicidad reproductiva y del desarrollo (Guyton, 2015;López-Revilla y Martínez, 2013;Zhang et al., 2019). En México, estos fenómenos podrían incrementarse por el consumo cotidiano durante el ciclo de vida de los individuos, debido a que se consumen alrededor de 12.3 millones de toneladas de maíz en forma de tortilla; de éstas, 64 % se elaboran a través del método tradicional de maíz-masa-tortilla y 36 % a través de la industria harinera (Sierra-Macías et al. 2010). ...
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La tortilla de maíz es un alimento básico de la dieta de los mexicanos y fuente importante de calorías y nutrientes, con un consumo diario per cápita elevado, por lo que la presencia de secuencias recombinantes derivadas de maíces genéticamente modificados puede ser problemático al representar una amenaza a la diversidad genética de este cultivo, la salud humana y la soberanía alimentaria. El objetivo de este estudio fue evaluar la presencia de las secuencias recombinantes promotor 35S (P35S CaMV) y terminador NOS (t-NOS) en muestras de masa para tortillas producidas durante 2018 en poblados urbanos y rurales de los municipios de Uruapan y Paracho en Michoacán, México. La hipótesis fue que tortillas producidas en poblados urbanos contendrían una mayor frecuencia de secuencias recombinantes que las producidas en poblados rurales, pues se asume un mayor uso de harina industrializada, donde previamente se ha documentado presencia de transgenes. Se obtuvieron muestras de masa de 92 tortillerías y se realizaron encuestas para conocer la procedencia del grano y posible uso de harina industrial en la elaboración de tortillas. Las muestras se agruparon en una zona urbana con siete sub-zonas y cuatro zonas rurales. Se analizaron 63 muestras de ADN a partir de masa para determinar la presencia de secuencias recombinantes mediante RT-PCR. Los resultados de las encuestas indicaron que el grano usado provino mayoritariamente (52 %) de Sinaloa (noroeste de México), mientras que la mayoría de productores (86.6 %) usan harina industrializada. Se detectaron transgenes en 20 de 63 muestras (32 %), con t-NOS como la secuencia más frecuente. El mayor porcentaje de muestras positivas se presentó en la zona urbana de Uruapan (80 %) y sólo hubo 5 % de positivos en zonas rurales. Esta diferencia podría deberse a un mayor uso de grano externo o harina industrializada en las zonas urbanas, mientras que en zonas rurales se utiliza grano de maíces nativos locales.
... According to Van Bruggen et al. [125] and El-Nahhal et al. [122], chemical crop protection products are carcinogenic. Many researchers have observed that increased exposure to herbicides increases the risk of non-Hodgkin lymphoma [138], multiple myeloma, breast cancer, colorectal cancer and skin cancer [139]. Exposure to herbicides also increases the risk of kidney disease, Alzheimer's disease, Parkinson's disease, ADHD and autism [125,140,141]. ...
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Meeting the nutritional needs of a dynamically developing global society is a major challenge. Despite the modernisation of agriculture, huge losses in the quality and quantity of crops occur each year, mainly due to weed species, which are the most important biotic limitation to agricultural production. Globally, approximately 1800 weed species cause a 31.5% reduction in plant production, which translates to USD 32 billion per year in economic losses. However, when the same herbicides are frequently applied, plants develop segetal immune mechanisms. There are currently around 380 herbicide-resistant weed biotypes worldwide. Due to the negative influence of herbicides on ecosystems and the legal regulations that limit the use of chemical crop protection products, it is necessary to develop a new method of weed control. Bioherbicides, based on living organisms or their secondary metabolites, seem to be an ideal solution. The biocontrol market is worth around EUR 550 million in Europe and EUR 1.6 billion worldwide, with an estimated 15% growth expected by 2025. Despite numerous studies that have demonstrated the effectiveness of microbial bioherbicides, only 25 mould-based bioherbicides are currently available to growers. Due to the high specificity and selectivity of biological crop protection products, as well as their low production costs and non-toxicity to the environment and human health, they would appear to be a safe alternative to chemical pesticides.
... A variety of infection agents, chemical agents, and deficiencies in the immune system are among the causes of NHL [162]. Zhang et al. [163] discovered that being exposed to GBH raises the risk of NHL among workers that are highly exposed to glyphosate. In 2020, NHL accounted for approximately 77,000 new cases and caused almost 20,000 deaths in the United States alone [164]. ...
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The use of synthetic molecules to achieve specific goals is steadily increasing in the environment, and these molecules adversely impact human health and ecosystem services. Considering the adverse effects, a better understanding of how these molecules behave in the environment and their associated risks is necessary to keep their use acceptably limited. To meet the demands of farmers and combat weed problems, woodlands and farmlands are sprayed with agrochemicals, primarily glyphosate-based herbicides. Farmers increasingly embrace these herbicides containing glyphosate. Glyphosate and aminomethylphosphonic acid (AMPA), a key metabolite of glyphosate, have been reported as toxicological concerns when they become more prevalent in the food chain. The chemical glyphosate has been linked to various health issues in humans and other living organisms, including endocrine disruption, reproductive issues, tumours, non-Hodgkin lymphomas, and liver, heart, and blood problems. Therefore, the current review aims to compile data on glyphosate-based herbicide use in the environment, potential risks to human and ecological health, and various maximum residual limits for crops as suggested by international organizations. As a result, regulatory agencies can advise glyphosate users on safe usage practices and synthesize herbicides more efficiently. Keywords: glyphosate-based herbicide; AMPA; toxicological effect; ecological risk; regulations
Article
Glyphosate, commonly known by its original trade name Roundup™, is the world's most widely used herbicide. Glyphosate and its metabolites have a profound negative environmental impact and long-term toxicity risk, including carcinogenicity, genotoxicity, and endocrine disruption, even at concentration levels too low to have a herbicidal effect. Therefore, the detection of these pollutants at low concentrations is an important task. To increase the sensitivity of the sensor, nanostructures were used. To analyze the presence of glyphosate and its metabolites in rye juice, two groups of samples were selected. In the first case, glyphosate at different concentrations was added to the water for irrigation on the first day, and then the rye samples were watered with pure water for 7 days. In the second case, the samples were watered with pure water for all 8 days, and glyphosate was artificially added just before the measurement. The obtained samples were studied by the Different Pulse Voltammetry (DPV) employing nanostructured working electrodes. To analyze changes in the DNA sequence, a Polymerase chain reaction (PCR) product obtained from samples of the first group was electrochemically studied. To confirm the results obtained, an electrophoresis method was also applied. The results indicate that the DPV signal obtained from samples with artificially added glyphosate has significant differences compared to the signal obtained from the juice of plants absorbing glyphosate in a natural way during growth. However, in both cases, the CuO nanostructure based sensor detects the presence of glyphosate or its metabolites compared to the control sample. The experiment also found significant changes in the DNA caused by exposure with glyphosate during the growth process of rye sprouts. A nanostructured electrochemical sensor was used for the detection of glyphosate residuals and genetic changes caused by glyphosate in untreated rye juice.
Article
Natural dyes from invasive plant species may serve as reliable, nontoxic, replicable alternatives to synthetic dyes. Novel approaches to invasive species control aids in restoration, incentivizes commercial uses, and results in large-scale removal with improved biodiversity. The purpose of the study was to test the dye effectiveness of three invasive plant species on organic cotton and wool for outdoor apparel in colorfastness to wet and dry crocking, perspiration, laundering, and antimicrobial action against Escherichia coli, Staphylococcus aureus, and Aspergillus Niger. Invasive plant roots used to dye were: Japanese barberry (Berberis thunbergii), wineberry (Rubus phoenicolasius), and oriental bittersweet (Celastrus orbiculatus). Mordants [Red oak acorn (Quercus rubra), acetate, and alum] expedited dyeing and fixation. Color intensity was measured using L*, a*, b*, and ∆E* values. Wool morphology produced better coloration. Barberry showed the most promising antimicrobial properties on cotton even though there was dye migration during wet crocking, perspiration, and laundering. The resulting earth tones and fabric weight are ideal for outdoor furniture or winter apparel.
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RESUMO Objetivo: O artigo objetiva examinar a controvérsia científica em relação ao agrotóxico glifosato, o qual, durante muitos anos, foi considerado seguro para a saúde humana e sustentável ambientalmente, mas que, na atualidade, está sendo questionado pelo sistema da ciência e pelo sistema do direito em relação aos riscos e ao dano futuro. Metodologia: A metodologia utilizada é a sistêmico-construtivista, a partir das contribuições de Niklas Luhmann, que possibilita examinar como cada sistema percebe o agrotóxico glifosato. No que tange às técnicas de procedimento, utiliza-se a revisão sistemática da literatura, pesquisa bibliográfica, documental e jurisprudencial. Resultados: Conclui-se que o sistema da ciência, ao comprovar correlação entre o glifosato e os danos à saúde humana, levou a sociedade a movimentos que vão desde a proibição do agrotóxico em alguns países até indenizações bilionárias às vítimas impetradas pelo sistema jurídico. Entretanto, o caminho é longo para que o agrotóxico mais consumido no mundo seja efetivamente banido. Contribuições: Ao examinar dados do sistema da ciência (pesquisas científicas), do sistema político (agências nacionais e internacionais de regulação) e do sistema do direito (ações e decisões na esfera judicial), o estudo oferece uma reflexão sobre o processo de autoconfrontação da sociedade com os riscos que ela própria criou ao lançar produtos, como o glifosato, sem pesquisas suficientes para indicar sua utilização segura. Palavras-chave: Agrotóxicos. Dano Futuro. Glifosato. Modernização Reflexiva. Risco à saúde
Thesis
H. pylori colonise l’estomac de près de la moitié de la population mondiale et y induit une inflammation chronique nommée gastrite, le plus souvent asymptomatique mais pouvant évoluer vers des pathologies gastroduodénales plus sévères dont le lymphome gastrique du MALT (mucosa-associated lymphoid tissue) ou LGM. Bien que n’apparaissant que chez un nombre restreint de sujets infectés, il est maintenant bien démontré que le développement du LGM est directement lié à l’infection par H. pylori. Dans cette pathologie, la stimulation antigénique chronique exercée par H. pylori sur la muqueuse gastrique entraîne un recrutement de lymphocytes et entretient une prolifération monoclonale de lymphocytes B s’organisant en follicules lymphoïdes normalement absents de la muqueuse gastrique. Le LGM s’inscrit donc dans un continuum de la réaction inflammatoire à H. pylori. Cependant, les mécanismes physiopathologiques conduisant à ce lymphome ne sont pas clairement élucidés. Les facteurs de virulence bactériens semblant jouer un rôle minime, l’étude des facteurs de l’hôte et notamment l’étude du microenvironnement inflammatoire paraît être une piste intéressante afin de mieux comprendre la physiopathologie de ce lymphome.Dans une première partie, nous nous sommes intéressés aux mécanismes moléculaires pouvant être impliqués via l’étude de la dérégulation des microARNs (miARNs). Nos résultats ont montré la surexpression de 4 miARNs (miR-155, miR-150, miR-196 et miR-138) et la sous-expression de 2 miARNs (miR-7 et miR-153) au niveau gastrique chez des patients atteints par ce lymphome, résultats globalement différents de ceux préalablement obtenus par l’équipe en modèle murin d3Tx. A l’exception du miR-138, les miARNs dérégulés agiraient en synergie, via des cibles validées, dans une voie de signalisation commune anti-apoptotique induisant une prolifération lymphocytaire B nécessaire au processus de lymphomagenèse.Certaines cytokines, dont la cytokine APRIL, joueraient également un rôle majeur dans la physiopathologie du LGM. L’équipe a ainsi développé un modèle prometteur de LGM basé sur l’utilisation de souris transgéniques pour la forme humaine de cette cytokine (Tg-hAPRIL). Dans une deuxième partie, nous nous sommes donc intéressés à l’étude de la polarisation de la réponse inflammatoire dans ce nouveau modèle et à sa comparaison avec celle observée chez l’homme. Nos résultats ont montré la présence d’une réponse inflammatoire gastrique équilibrée Th1, Th2 et T régulatrice au stade lymphome, aussi bien en modèle murin Tg-hAPRIL que chez l’homme. Après avoir confirmé la surexpression gastrique de la cytokine APRIL chez des patients atteints du LGM, nous avons mis en évidence, d’une part que les cellules cibles de la cytokine APRIL étaient majoritairement des lymphocytes B présents au sein des infiltrats lymphoïdes, appuyant ainsi l’hypothèse selon laquelle la cytokine APRIL participerait à la prolifération lymphocytaire B non contrôlée et, d’autre part que les cellules productrices de cette cytokine étaient de rares polynucléaires éosinophiles présents dans le microenvironnement tumoral, suggérant un rôle pro-tumoral de ce type cellulaire dans la lymphomagenèse gastrique.Pour conclure, l’ensemble de nos résultats met en évidence le rôle clé du microenvironnement inflammatoire gastrique dans le développement du LGM.
Thesis
Myanmar is the world's second-largest producer of opium poppy, the raw material from which heroin and opium are produced. 85% of this opium poppy is cultivated in rural areas of Shan State, where about 1 in 10 households in the villages are directly involved in opium poppy cultivation for the drug industry (MIMU, 2017). The economy of opium poppy permeates social and family dynamics; nonetheless, there is no research emphasizing gender practices in opium poppy cultivation for drug productions in Myanmar. Through the lens of intersectionality, I intend to uncover the gendered organization of opium poppy cultivation in Hopong, south Shan State, and register the experiences of peasant farmers with the gender approach of the Alternative Development (AD) project in the area. Being the first time an academic paper analyzes intersectionality in a drug economy in Southeast Asia, the research builds on a qualitative case study design, where interviews, participant observation, transient walks, surveys, and focus groups with opium poppy peasant farmers, gender specialists, and opinion pieces on the topic have been analyzed. By employing the concepts of intersectionality, agency, and subjectivity, this study concludes that the crop is fundamentally gendered, thus gender practices intersect in various ways with opium poppy cultivation. Meanwhile, a proper understanding of context is required for appropriate and meaningful interpretation of AD interventions in Hopong. In this sense, AD projects may not succeed unless intersectional and conflict-sensitive approaches are included in logical frameworks and intersections go beyond a blanketed 'women and youth' approach.
Article
Background: There is an absence of clinically relevant epidemiological data in regional Australia pertaining to haematological malignancies. Aim: To determine the incidence and geographical variation of haematological malignancies in North Queensland using a clinically appropriate disease classification. Methods: Retrospective, observational study of individual patient data records of all adults diagnosed with a haematological malignancy between 2005-2014 and residing within The Townsville Hospital Haematology catchment region. We report descriptive summaries, incidence rates and incidence-rate ratios of haematologic malignancies by geographic regions. Results: 1581 haematological malignancies (69% lymphoid, 31% myeloid) were diagnosed over the 10-year study period. Descriptive data is presented for 58 major subtypes as per the WHO diagnostic classification of tumours of haematopoietic and lymphoid tissues. The overall median age at diagnosis was 66 years with a male predominance (60%). We demonstrate a temporal increase in the incidence of haematologic malignancies over the study period. We observed geographical variations in the age-standardised incidence rates per 100,000 ranging from 0.5 to 233.5. Our data suggests an increased incidence rate ratio for haematological malignancies in some postcodes within the Mackay area compared to other regions. Conclusion: This study successfully reports on the incidence of haematological malignancies in regional Queensland using a clinically meaningful diagnostic classification system and identifies potential geographic hotspots. We advocate for such contemporary, comprehensive, and clinically meaningful epidemiological data reporting of blood cancer diagnoses in wider Australia. Such an approach will have significant implications toward developing appropriate data-driven management strategies and public health responses for haematological malignancies. This article is protected by copyright. All rights reserved.
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The current generation of carcinogenicity tests is often insufficient to predict cancer outcomes from pesticide exposures. In order to facilitate health risk assessment, The International Agency for Research on Cancer identified 10 key characteristics which are commonly exhibited by human carcinogens. The ToxTracker panel of six validated GFP-based mouse embryonic stem reporter cell lines is designed to measure a number of these carcinogenic properties namely DNA damage, oxidative stress and the unfolded protein response. Here we present an evaluation of the carcinogenic potential of the herbicides glyphosate, 2,4-D and dicamba either alone or in combination, using the ToxTracker assay system. The pesticide 2,4-D was found to be a strong inducer of oxidative stress and an unfolded protein response. Dicamba induced a mild oxidative stress response, whilst glyphosate did not elicit a positive outcome in any of the assays. The results from a mixture of the three herbicides was primarily an oxidative stress response, which was most likely due to 2,4-D with dicamba or glyphosate only playing a minor role. These findings provide initial information regarding the risk assessment of carcinogenic effects arising from exposure to a mixture of these herbicides.
Article
Glyphosate, a broad-spectrum herbicide, is globally used in crop production and persists in bread and flour. Tolerance limits for glyphosate in cereal products have been established internationally. In Lebanon, there are scarce published data on the level of glyphosate food products and consumer exposure levels remains unknown. All bread and flour products available (n = 164 samples) characterized by their distinct processing methods have been collected from Mount Lebanon and Beirut governorates. Glyphosate concentrations were assessed, using ELISA and compared across samples by brand, flour types and country of origin. The exposure level of the Lebanese population to glyphosate was also assessed through estimated daily intake calculations. Out of the assessed bread products and of flour products tested 80% and 100% were contaminated with glyphosate. All the values were below the international limits (30 mg/kg for bread and 0.5 mg/kg for flour). The glyphosate median residue level was significantly higher in unconventional bread (52.9 ppb), as compared to bran (28.5 ppb) and whole grain (25.7 ppb) and white bread (14.9 ppb) (p = 0.004). Highest percentage positive samples were found for unconventional bread types and lowest for brown bread type (100 and 69.2%, respectively). The findings also showed that glyphosate occurrence and level was statistically identical in all the flour samples including different types and country of origin (p = 0.75, 0.146, respectively). Lebanese population daily exposures to glyphosate through consumption of bread and flour products were estimated to be 0.0702 μg/kg BW/day and 0.1318 μg/kg BW/day, respectively. Daily bread exposure was only 0.000117% of the Acceptable Daily Intake (ADI) of 1 mg/kg/day as listed by Codex, and 0.00039% of the ADI of 0.5 mg/kg/day as listed by the German Federal Institute for Risk Assessment. Dietary exposure to glyphosate through flour and flour-based bread products seems to be low in Lebanon. Future extensive studies need to evaluate exposure to glyphosate from other staple foods and through other routes of exposure beyond diet.
Article
Brazil annually produces around 43 million tons of fruits and vegetables. Therefore, large amounts of pesticides are needed to grow these foods. The use of unauthorized or indiscriminate pesticides can lead to the adherence of residues of these compounds to the product in a concentration above the maximum residue limit (MRL). Pesticide residues (PRs) monitoring is a continuous challenge due to several factors influencing the detection of these compounds in the food matrix. Currently, several adaptations to conventional techniques have been developed to minimize these problems. This systematic review presents the main information obtained from 52 research articles, taken from five databases, on changes and advances in Brazil in sample preparation methods for determining PRs in fruits and vegetables in the last nine years. We cover the preexisting ones and some others that might be suitable alternatives approaches. In addition, we present a brief discussion on the monitoring of PRs in different Brazilian regions, and we found that residues belonging to the organophosphate and pyrethroid classes were detected more frequently. Approximately 67% of the residues detected are of irregular use in 28 types of fruits and vegetables commonly consumed and exported by Brazil.
Chapter
With rising environmental pollution and overuse of chemicals, the effect of emerging contaminants on human health is one of the major concerns. Human beings are exposed to various toxic chemicals like pesticides, perfluorinated chemicals, microplastics, 1,4 dioxins, and trihalomethane in occupational and environmental settings. According to the Fourth Report on Human Exposure to Environmental Chemicals, 2019, published by Centers for Disease Control and Prevention, detectable levels of 50 pesticides have been found in the body fluids of a representative sample of the United States population. These pesticides not only cause detrimental effects on human physiology but also induce long-term transgenerational effects. A large number of pesticides like permethrin, methoxychlor, and Dichlorodiphenyltrichloroethane have been reported to promote epigenetic alterations in rodent models. All such epigenetic and possible aneugenic change can serve as driving forces for evolution. Herein, we focus on the short-term effect of pesticides on human physiology, long-term epigenetic effects, and their evolutionary consequences.
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The undersigned, Jianqing Wu, submits this petition pursuant to 21 C.F.R. § 10.30 and 21 U.S.C. § 355, 21 U.S. § 564(g)(2), 21 U.S. § 379dd of the Federal Food, Drug, and Cosmetic Act and 42 U.S. § 262(a)(2) of the Public Health Service Act or any other statutory provision for which authority has been delegated to the Commissioner of Food and Drugs) to request the Commissioner of Food and Drugs to suspend all outstanding mRNA vaccine use authorizations, re-evaluate their effectiveness and safety, and revoke their use authorizations as soon as possible, and make a plan to systematically overhaul its approval framework. (This is first of a series of Citizen Petition and will be updated periodically to include new observation, new discoveries and new analysis).
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The controversy over glyphosate-based herbicides (GBHs), where there is extreme divergences in health and environmental assessments, is rooted in several methodological and normative factors. Foremost among them are the differences found in testing pure glyphosate compared to the testing of glyphosate formulations. The adjuvant chemicals found in formulations can be more toxic than the so-called “active ingredient.” Other factors can also account for why scientists reach different conclusions on the toxicological effects of GBH including the preconceptions and methodological choices they bring into the study. Lack of consensus on the science can be problematic for policymakers. The paper argues that the toxicological science behind the GBH assessments is embedded in a normative substratum, which must be considered in policy decisions.
Article
Objective To evaluate a potential association between blood and urine concentration of glyphosate and its metabolite, aminomethylphosphonic acid (AMPA), with severity of acute glyphosate (herbicide) poisoning. Methods In our retrospective study of acute glyphosate poisoning, we examined records from the French National Database of Poisonings, dated between January 1, 2004, and December 31, 2016. We compared the severity of poisoning among case individuals using the Fisher exact test and Wilcoxon test. Also, we calculated ROC curves to determine the cutoff for blood and urine concentration. Results A total of 17 plasma glyphosate, 11 urine glyphosate, 13 plasma AMPA, and 10 urine AMPA specimens were included in our study, with collection dates ranging from January 1, 2004, through December 31, 2016. Conclusion The optimal cutoff we discovered for blood concentration of AMPA was 0.88 mg/L; for glyphosate, it was 600 mg/L. The cutoff plasma concentration of AMPA has never been described in the literature, to our knowledge.
Article
Glyphosate (N-(phosphonomethyl)glycine) is broad-spectrum herbicide that is extensively used worldwide, but its effects on the soil microbiome are inconsistent. To provide a sound scientific basis for herbicide re-review and registration decisions, we conducted a four-year (2013–2016) study in which we consecutively applied glyphosate to a wheat (Triticum aestivum L.)–field pea (Pisum sativum L.)–canola (Brassica napus L.)–wheat crop rotation at five sites in the Canadian prairies. The glyphosate rates were 0, 1, 2, 4 and 8 kg ae ha⁻¹, applied pre-seeding and post-harvest every year. The wheat rhizosphere was sampled in the final year of the study and analysed for microbial biomass C (MBC), the composition and diversity of the microbiome, and activities of β-glucosidase, N-acetyl-β-glucosiminidase, acid phosphomonoesterase and arylsulphatase. Glyphosate did not affect MBC, the composition and diversity of prokaryotes and fungi, and the activities of three of the four enzymes measured in the wheat rhizosphere. The one effect of glyphosate was a wave-like response of N-acetyl-β-glucosaminidase activity with increasing application rates. The experimental sites had much greater effects, driven by soil pH and organic C, on the soil microbiome composition and enzyme activities than glyphosate. Soil pH was positively correlated with the relative abundance of Acidobacteriota but negatively correlated with that of Actinobacteriota and Basidiomycota. Soil organic C was positively correlated with the relative abundances of Proteobacteriota and Verrucomicrobiota, but negatively correlated with the relative abundance of Crenachaeota. The activity of acid phosphomonoesterase declined with increasing relative abundance of Acidobacteriota, but increased with that of Actinobacteriota and Basidiomycota. The activity of N-acetyl-β-glucosaminidase also increased with increasing relative abundance of Actinobacteriota but decreased with that of Mortierellomycota. β-glucosidase activity also decreased with increasing relative abundance of Mortierellomycota. The core fungal species observed in at least 90% of the samples were Humicola nigrescens, Gibberella tricincta and Giberella fujikuroi. Therefore, this multi-site study on the Canadian prairies revealed no significant effects of 4-year applications of glyphosate applied at different rates on most soil microbial properties despite differences in the properties among sites. However, it is important to keep evaluating glyphosate effects on the soil microbiome and its functioning because it is the most widely used herbicide worldwide.
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Drug industry, controlling medical publishers and large media promote flawed medicine for their revenues by systematically laundering medical knowledge in decades. They maintain and promote flawed research models and suppress disruptive discoveries, thereby precluding reform of medicine. In this study, I will deeply explore how the wrong life model, population-based research model, misused clinical trials, flawed statistical models, the symptom-based research methods, binary disease classification, failure to address the massive vital organ capacities, failure to correct biased caused by expected delay in realizing side effects, and failure to address the interference effects of non-controllable factors affect the conclusions of “effectiveness and safety” for mRNA vaccines. I will directly analyze three studies that have been relied upon by FDA in approving mNRA use authorizations: one BNT162b2 effectiveness study published in NEJM, one booster shot study published in NEJM and a Seven Integrated Health Care Organizations study published by CDC. I will expose fatal flaws in the frequency risk concept, effectiveness rate, and hazard reduction ratios, and show why 3% death rate, 95% effectiveness rate and 90% mortality reduction are all meaningless and misleading, and should never have been used as treatment guidance. I will also examine common biases that can be easily practiced by sponsors’ researchers to alter conclusions in favor of approval. By relying on laundered medical “knowledge”, FDA has consistently failed to predict latent drug side effects for any drugs and vaccines in its history. FDA approved disastrous DES in 1941, Swine Flu vaccine in 1976, and mRNA vaccines in 2020. The vaccines are used to deliver short-term benefits on a small percent of persons at the costs of damaging health, causing deaths that would be avoided, and shortening lifespans for all people in the population. I thus urge FDA to reevaluate all mRNA vaccines and revoke their use authorizations.
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Assessment of occupational pesticide exposure in epidemiological studies of chronic diseases is challenging. Biomonitoring of current pesticide levels might not correlate with past exposure relevant to disease aetiology, and indirect methods often rely on workers’ imperfect recall of exposures, or job titles. We investigated how the applied exposure assessment method influenced risk estimates for some chronic diseases. In three meta-analyses the influence of exposure assessment method type on the summary risk ratio (sRR) of prostate cancer (PC) (25 articles), non-Hodgkin’s lymphoma (NHL) (29 articles) and Parkinson’s disease (PD) (32 articles) was investigated. Exposure assessment method types analysed were: group-level assessments (eg, job titles), self-reported exposures, expert-level assessments (eg, job-exposure matrices) and biomonitoring (eg, blood, urine). Additionally, sRRs were estimated by study design, publication year period and geographic location where the study was conducted. Exposure assessment method types were not associated with statistically significant different sRRs across any of the health outcomes. Heterogeneity in results varied from high in cancer studies to moderate and low in PD studies. Overall, case–control designs showed significantly higher sRR estimates than prospective cohort designs. Later NHL publications showed significantly higher sRR estimates than earlier. For PC, studies from North America showed significantly higher sRR estimates than studies from Europe. We conclude that exposure assessment method applied in studies of occupational exposure to pesticides appears not to have a significant effect on risk estimates for PC, NHL and PD. In systematic reviews of chronic health effects of occupational exposure to pesticides, epidemiological study design, publication year and geographic location, should primarily be considered.
Chapter
The usage of pesticides in agricultural practices contributes to an improvement in food production through monitoring insects, weeds, and crop diseases, with the aim of ensuring food sustainability to meet the needs of increasing population. However, the widespread application of these substances has numerous harmful consequences on the soil and on both environmental and human health. Moreover, in developed nations, the nonrational usage of chemicals, as well as banned forms, presents a major danger and increases contaminated agricultural lands at alarming rates, as well as polluting surface and groundwater. Glyphosate [N-(phosphonomethyl) glycine] is a broad-spectrum systemic herbicide that blocks the enzyme required by plants to produce amino acids and proteins. At present, in all fields (environment, agriculture, toxicology), it has become important to talk about paraquat (1,1′-dimethyl-4,4′-bipyridium) when it comes to glyphosate. Similarly, in recent years, these two herbicides have been the focus of many toxicities and biodegradation studies. Bioremediation by microbial biotechnology is also one of the most recommended solutions to alleviate the impact of these contaminants and is known to be an environmentally safe soil and water remediation technology. The principle of bioremediation is the modification and removal of pesticides in the form of nontoxic compounds used as nutrients for plants. Several approaches are commonly used, such as biostimulation and bioaugmentation. The discovery of potent microbial strains and the screening of degradation genes are currently a challenge for scientific researchers. In this context, this chapter highlights and summarizes contaminants, their environmental implications, and the biotechnological use of bacteria that may be used for bioremediation in order to remediate polluted areas.
Article
Pollination, the transfer of pollen grains from the anther to the stigma, is a pre-requisite for fruit and seed set. Bees and other pollinators are involved in pollinating about 75% of our crop plants. Following the practice of monoculture cropping system in Western countries, managed pollinators, particularly honeybee colonies, are being used to sustain pollination and crop yield. During the last 3 to 4 decades, managed bees, as well as other wild pollinators, are declining markedly due to human-induced habitat degradation, particularly extensive application of pesticides and herbicides and the spread of pathogens. Concerted attempts are being made in developed countries, including vaccination of bees against diseases and the development of pollinator drones to sustain pollinators and crop productivity. However, in India, the plight of pollinators of crop species has been ignored. We hardly know anything about the pollination efficacy of our crops, such as legumes, oil, fruit, and vegetable crops, which are pollinator-dependent and add the nutritional value to our diet. Intensive studies on pollinators and pollination of our pollinator-dependent crops are urgently needed.
Article
South American agriculture focuses on extensive cereal and oilseed production destined mainly for the international market, followed by the horticultural production that takes place near urban centres. Extensive agriculture involves the use of fertilizers and pesticides for pest control. Among the latter, glyphosate-based herbicides (GBHs) are the most commercialized. In recent years, the increasing appearance of glyphosate (GP)-resistant weeds has led to the repeated application of higher doses of these products. Residual levels of the herbicides and their metabolites have therefore been reported in the environment, as well as toxic effects in animals and humans. The natural ability of bacteria and fungi to transform organic compounds in the environment has shown great potential to bioremediate GP in the soil. Some fungal species isolated from pesticide-contaminated sites are especially promising for this purpose, thanks to their enzymatic activity and their fast growth under optimal conditions. The present article offers an overview of the situation in Argentina regarding the use of GP. It also summarizes the data available which show a growing need to develop GP bioremediation strategies in the soil, based on the isolation of GP-degrading microorganisms adapted to water shortage conditions, such as fungi.
Article
Glyphosate is the active ingredient in Roundup™, the most widely used herbicide in the world. Glyphosate targets an essential enzyme in plants that is not found in animals. However, both glyphosate and Roundup™ are rated as Group 2 A, probably human carcinogens, and also have documented effects on reproduction, acting as endocrine disruptive chemicals. We have reviewed reports of the effects of glyphosate and Roundup™ on the mammalian nervous system function. As with several other herbicides, Roundup™ exposure has been associated with an increased risk of Parkinson's Disease and death of neurons in the substantia nigra. There is also some evidence implicating Roundup™ in elevated risk of autism. Other studies have shown the effects of Roundup™ on synaptic transmission in animal and cellular studies. The major mechanism of action appears to be oxidative stress, accompanied by mitochondrial dysfunction. In addition, some gut bacteria utilize the enzyme used by plants, and glyphosate and Roundup™ use has been shown to alter the gut microbiome. There is a large and growing body of evidence that the gut microbiome alters susceptibility to great number of human diseases, including nervous system function. The weight of the evidence indicates that in addition to cancer and reproductive effects, glyphosate and Roundup™ have significant adverse effects on the brain and behavior and increase the risk of at least some serious neurological diseases.
Article
This study reports the kinetics and isotherms of the adsorption of five herbicides, MCPA, mecoprop-P, 2,4-D, fluroxypyr and triclopyr, from aqueous solutions onto a range of raw and pyrolysed waste materials originating from an industrial setting. The raw waste materials investigated demonstrated little capability for any herbicide adsorption. Granulated activated carbon (GAC) was capable of the best removal of the herbicides, with >95% removal observed. A first order kinetic model fitted the data best for GAC adsorption of 2,4-D, while a pseudo-first order model fitted the data best for GAC adsorption of fluroxypyr and triclopyr, indicating that adsorption was via physisorption. A pseudo-second order kinetic model fitted the GAC adsorption of MCPA and mecoprop-P, which is indicative of chemisorption. The adsorption of the herbicides in all cases was best described by the Freundlich model, indicating that adsorption occurred onto heterogeneous surfaces.
Article
Glyphosate is the most widely used herbicide in the world and, in view of its toxicity, there is a quest for easy-to-use, but reliable methods to detect it in water. To address this issue, we realized a simple, rapid, and highly sensitive immunosensor based on gold coated magnetic nanoparticles ([email protected]) to detect glyphosate in tap water. Not only the gold shell provided a sensitive optical transduction of the biological signal – through the shift of the local surface plasmon resonance (LSPR) entailed by the nanoparticle aggregation –, but it also allowed us to use an effective photochemical immobilization technique to tether oriented antibodies straight on the nanoparticles surface. While such a feature led to aggregates in which the nanoparticles were at close proximity each other, the magnetic properties of the core offered us an efficient tool to steer the nanoparticles by a rotating magnetic field. As a result, the nanoparticle aggregation in presence of the target could take place at higher rate (enhanced diffusion) with significant improvement in sensitivity. As a matter of fact, the combination of plasmonic and magnetic properties within the same nanoparticles allowed us to realize a colorimetric biosensor with a limit of detection (LOD) of 20 ng∙L⁻¹.
Chapter
Since the 1970s, laboratory methods have been developed in molecular biology that allow for the manipulation of the DNA sequences of genes or the genome of an organism. Expression of proteins in bacteria, genetic modifications of mice and other animals or plants, and the CRISPR/cas9 gene editing technology are described. Finally the possibility of, and ethical issues around, gene editing in humans are discussed.
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Background The US EPA considers glyphosate as “not likely to be carcinogenic to humans.” The International Agency for Research on Cancer (IARC) has classified glyphosate as “probably carcinogenic to humans (Group 2A).” EPA asserts that there is no convincing evidence that “glyphosate induces mutations in vivo via the oral route.” IARC concludes there is “strong evidence” that exposure to glyphosate is genotoxic through at least two mechanisms known to be associated with human carcinogens (DNA damage, oxidative stress). Why and how did EPA and IARC reach such different conclusions? Results A total of 52 genotoxicity assays done by registrants were cited by the EPA in its 2016 evaluation of technical glyphosate, and another 52 assays appeared in the public literature. Of these, one regulatory assay (2%) and 35 published assays (67%) reported positive evidence of a genotoxic response. In the case of formulated, glyphosate-based herbicides (GBHs), 43 regulatory assays were cited by EPA, plus 65 assays published in peer-reviewed journals. Of these, none of the regulatory, and 49 published assays (75%) reported evidence of a genotoxic response following exposure to a GBH. IARC considered a total of 118 genotoxicity assays in six core tables on glyphosate technical, GBHs, and aminomethylphosphonic acid (AMPA), glyphosate’s primary metabolite. EPA’s analysis encompassed 51 of these 118 assays (43%). In addition, IARC analyzed another 81 assays exploring other possible genotoxic mechanisms (mostly related to sex hormones and oxidative stress), of which 62 (77%) reported positive results. IARC placed considerable weight on three positive GBH studies in exposed human populations, whereas EPA placed little or no weight on them. Conclusions EPA and IARC reached diametrically opposed conclusions on glyphosate genotoxicity for three primary reasons: (1) in the core tables compiled by EPA and IARC, the EPA relied mostly on registrant-commissioned, unpublished regulatory studies, 99% of which were negative, while IARC relied mostly on peer-reviewed studies of which 70% were positive (83 of 118); (2) EPA’s evaluation was largely based on data from studies on technical glyphosate, whereas IARC’s review placed heavy weight on the results of formulated GBH and AMPA assays; (3) EPA’s evaluation was focused on typical, general population dietary exposures assuming legal, food-crop uses, and did not take into account, nor address generally higher occupational exposures and risks. IARC’s assessment encompassed data from typical dietary, occupational, and elevated exposure scenarios. More research is needed on real-world exposures to the chemicals within formulated GBHs and the biological fate and consequences of such exposures.
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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.
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In this 28 day-study, we evaluated the effects of herbicide glyphosate administered by gavage to Wistar rats at daily doses equivalent to 0.1 of the acceptable operator exposure level (AOEL), 0.5 of the consumer acceptable daily intake (ADI), 1.75 (corresponding to the chronic population-adjusted dose, cPAD), and 10 mg kg-1 body weight (bw) (corresponding to 100 times the AOEL). At the end of each treatment, the body and liver weights were measured and compared with their baseline values. DNA damage in leukocytes and liver tissue was estimated with the alkaline comet assay. Oxidative stress was evaluated using a battery of endpoints to establish lipid peroxidation via thiobarbituric reactive substances (TBARS) level, level of reactive oxygen species (ROS), glutathione (GSH) level, and the activity of glutathione peroxidase (GSH-Px). Total cholinesterase activity and the activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were also measured. The exposed animals gained less weight than control. Treatment resulted in significantly higher primary DNA damage in the liver cells and leukocytes. Glyphosate exposure significantly lowered TBARS in the liver of the AOEL, ADI, and cPAD groups, and in plasma in the AOEL and cPAD group. AChE was inhibited with all treatments, but the AOEL and ADI groups significantly differed from control. Total ChE and plasma/liver ROS/GSH levels did not significantly differ from control, except for the 35 % decrease in ChE in the AOEL and ADI groups and a significant drop in liver GSH in the cPAD and 100xAOEL groups. AOEL and ADI blood GSH-Px activity dropped significantly, but in the liver it significantly increased in the ADI, cPAD, and 100xAOEL groups vs. control. All these findings show that even exposure to low glyphosate levels can have serious adverse effects and points to a need to change the approach to risk assessment of low-level chronic/sub-chronic glyphosate exposure, where oxidative stress is not necessarily related to the genetic damage and AChE inhibition.
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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.
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This article presents the first detailed overview of the mechanisms that may underlie the relation of obesity with B-cell non-Hodgkin lymphomas (NHLs) and multiple myeloma (MM). Epidemiologic studies, including meta-analyses of prospective cohorts, have reported that the risks of NHL and MM are significantly increased in obese, relative to normal weight, women and men. Accumulating experimental and clinical evidence suggests that inflammatory cytokines, hyperinsulinemia, and sex hormones could play a role in the association of obesity with B-cell NHL and MM carcinogenesis. There is, however, a paucity of data published from appropriate large prospective cohort studies, and studies concurrently measuring these correlated factors, to formally determine the likely biologic factors driving the relationship of obesity with NHL and MM. Additional strengths and weaknesses of the current literature, as well as study design issues that need to be considered in conducting these studies, such as the exclusion of type 2 diabetics or postmenopausal women using hormone therapy, are discussed.
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Smith et al. (Env. Health Perspect. 124: 713, 2016) identified 10 key characteristics (KCs), one or more of which are commonly exhibited by established human carcinogens. The KCs reflect the properties of a cancer-causing agent, such as 'is genotoxic,' 'is immunosuppressive' or 'modulates receptor-mediated effects,' and are distinct from the hallmarks of cancer, which are the properties of tumors. To assess feasibility and limitations of applying the KCs to diverse agents, methods and results of mechanistic data evaluations were compiled from eight recent IARC Monograph meetings. A systematic search, screening and evaluation procedure identified a broad literature encompassing multiple KCs for most (12/16) IARC Group 1 or 2A carcinogens identified in these meetings. Five carcinogens are genotoxic and induce oxidative stress, of which pentachlorophenol, hydrazine and malathion also showed additional KCs. Four others, including welding fumes, are immunosuppressive. The overall evaluation was upgraded to Group 2A based on mechanistic data for only two agents, tetrabromobisphenol A and tetrachloroazobenzene. Both carcinogens modulate receptor-mediated effects in combination with other KCs. Fewer studies were identified for Group 2B or 3 agents, with the vast majority (17/18) showing only one or no KCs. Thus, an objective approach to identify and evaluate mechanistic studies pertinent to cancer revealed strong evidence for multiple KCs for most Group 1 or 2A carcinogens but also identified opportunities for improvement. Further development and mapping of toxicological and biomarker endpoints and pathways relevant to the KCs can advance the systematic search and evaluation of mechanistic data in carcinogen hazard identification.
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Glyphosate is an herbicide widely used in the world, being applied in several crops, among them soybeans. Recently, glyphosate and its metabolite aminomethylphosphonic acid (AMPA) have been identified as possible contributors to the emergence of various diseases such as autism, Parkinson’s and Alzheimer’s diseases, as well as cancer. The child population consuming cereal-based foods is the most exposed to the effects of pesticides because of their developmental phase and they have a higher food intake per kilogram of body weight than adults. The presence of glyphosate and AMPA residues in soy-based infant formulas was evaluated during the years 2012-2017, totalizing 105 analyzes carried out on 10 commercial brands from different batches. Glyphosate and AMPA were determined by liquid chromatography with fluorescence detection after derivatization reaction. The method was validated and showed accuracy and precision with a limit of quantification (LOQ) of 0.02 mg kg⁻¹. Among those samples that contained levels above the LOQ, the variation of glyphosate residues was from 0.03 mg kg⁻¹ to 1.08 mg kg⁻¹ and for AMPA residues was from 0.02 mg kg⁻¹ to 0.17 mg kg⁻¹. This is the first scientific communication about glyphosate and AMPA contamination in soy-based infant formula in Brazil, The study was conducted under good laboratory practice (GLP) and supported by good scientific practice.
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A study was realized to ascertain whether eight selected pesticides would induce double strand breaks (DSB) in lymphocyte cultures and whether this damage would induce greater levels of proteins Rad51 participating in homologous recombination or of p-Ku80 participating in nonhomologous end joining. Only five pesticides were found to induce DSB of which only glyphosate and paraoxon induced a significant increase of p-Ku80 protein, indicating that nonhomologous end joining recombinational DNA repair system would be activated. The type of gamma-H2AX foci observed was comparable to that induced by etoposide at similar concentrations. These results are of importance since these effects occurred at low concentrations in the micromolar range, in acute treatments to the cells. Effects over longer exposures in actual environmental settings are expected to produce cumulative damage if repeated events of recombination take place over time.
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The broadband herbicide glyphosate (N-[phosphonomethyl]-glycine) and its main metabolite aminomethylphosphonic acid (AMPA) were analyzed by GC-MS-MS in 24 h-urine samples cryo-archived by the German Environmental Specimen Bank (ESB). Samples collected in 2001, 2003, 2005, 2007, 2009, 2011, 2012, 2013, 2014, and 2015 were chosen for this retrospective analysis. All urine samples had been provided by 20 to 29 years old individuals living in Greifswald, a city in north-eastern Germany. Out of the 399 analyzed urine samples, 127 (=31.8 %) contained glyphosate concentrations at or above the limit of quantification (LOQ) of 0.1μg/L. For AMPA this was the case for 160 (=40.1 %) samples. The fraction of glyphosate levels at or above LOQ peaked in 2012 (57.5 %) and 2013 (56.4 %) after having discontinuously increased from 10.0% in 2001. Quantification rates were lower again in 2014 and 2015 with 32.5 % and 40.0 %, respectively. The overall trend for quantifiable AMPA levels was similar. Glyphosate and AMPA concentrations in urine were statistically significantly correlated (spearman rank correlations coefficient=0.506, p≤0.001). Urinary glyphosate and AMPA levels tended to be higher in males. The possible reduction in exposure since 2013 indicated by ESB data may be due to changes in glyphosate application in agricultural practice. The ESB will continue monitoring internal exposures to glyphosate and AMPA for following up the time trend, elucidating inter-individual differences, and contributing to the ongoing debate on the further regulation of glyphosate-based pesticides
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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.
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Background: Accurate pesticide use data are essential when studying the environmental and public health impacts of pesticide use. Since the mid-1990s, significant changes have occurred in when and how glyphosate herbicides are applied, and there has been a dramatic increase in the total volume applied. Methods: Data on glyphosate applications were collected from multiple sources and integrated into a dataset spanning agricultural, non-agricultural, and total glyphosate use from 1974-2014 in the United States, and from 1994-2014 globally. Results: Since 1974 in the U.S., over 1.6 billion kilograms of glyphosate active ingredient have been applied, or 19 % of estimated global use of glyphosate (8.6 billion kilograms). Globally, glyphosate use has risen almost 15-fold since so-called "Roundup Ready," genetically engineered glyphosate-tolerant crops were introduced in 1996. Two-thirds of the total volume of glyphosate applied in the U.S. from 1974 to 2014 has been sprayed in just the last 10 years. The corresponding share globally is 72 %. In 2014, farmers sprayed enough glyphosate to apply ~1.0 kg/ha (0.8 pound/acre) on every hectare of U.S.-cultivated cropland and nearly 0.53 kg/ha (0.47 pounds/acre) on all cropland worldwide. Conclusions: Genetically engineered herbicide-tolerant crops now account for about 56 % of global glyphosate use. In the U.S., no pesticide has come remotely close to such intensive and widespread use. This is likely the case globally, but published global pesticide use data are sparse. Glyphosate will likely remain the most widely applied pesticide worldwide for years to come, and interest will grow in quantifying ecological and human health impacts. Accurate, accessible time-series data on glyphosate use will accelerate research progress.
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Systematic reviews should build on a protocol that describes the rationale, hypothesis, and planned methods of the review; few reviews report whether a protocol exists. Detailed, well-described protocols can facilitate the understanding and appraisal of the review methods, as well as the detection of modifications to methods and selective reporting in completed reviews. We describe the development of a reporting guideline, the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 (PRISMA-P 2015). PRISMA-P consists of a 17-item checklist intended to facilitate the preparation and reporting of a robust protocol for the systematic review. Funders and those commissioning reviews might consider mandating the use of the checklist to facilitate the submission of relevant protocol information in funding applications. Similarly, peer reviewers and editors can use the guidance to gauge the completeness and transparency of a systematic review protocol submitted for publication in a journal or other medium.
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Multiple myeloma (MM) has been linked to certain agricultural exposures, including pesticides. This analysis aimed to investigate the association between lifetime use of multiple pesticides and MM risk using two exposure metrics: number of pesticides used and days per year of pesticide use. A frequency-matched, population-based case-control study was conducted among men in six Canadian provinces between 1991 and 1994. Data from 342 MM cases and 1357 controls were analyzed using logistic regression to calculate odds ratios (OR) and 95% confidence intervals. Pesticides were grouped by type, chemical class, and carcinogenic potential, using a composite carcinogenic probability score. Selected individual pesticides were also examined. Regression models were adjusted for age, province of residence, use of proxy respondents, smoking, and selected medical history variables. The overall pattern of results was complex. Positive trends in risk were observed for fungicides (ptrend =0.04) and pesticides classified as probably carcinogenic or higher (ptrend =0.03). Excess risks of MM were observed among men who reported using at least one carbamate pesticide (OR=1.94, 1.16-3.25), one phenoxy herbicide (OR=1.56, 1.09-2.25), and ≥3 organochlorines (OR=2.21, 1.05-4.66). Significantly higher odds of MM were seen for exposure to carbaryl (OR=2.71, 1.47-5.00) and captan (OR=2.96, 1.40-6.24). Use of mecoprop for >2 days per year was also significantly associated with MM (OR=2.15, 1.03-4.48). Focusing on multiple pesticide exposures is important because this more accurately reflects how exposures occur in occupational settings. Significant associations observed for certain chemical classes and individual pesticides suggest that these may be MM risk factors. © 2013 Wiley Periodicals, Inc.
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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.