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Exposure to Glyphosate-Based Herbicides and Risk for Non-Hodgkin Lymphoma: A Meta-Analysis and Supporting Evidence
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.
... The US Environmental Protection Agency (EPA) [2] and the European Food Safety Authority (EFSA) [3] are among several regulatory authorities that have concluded that dietary exposure to active substance glyphosate is unlikely to pose cancer risk. But substantial data show that applicators of formulated glyphosate-based herbicides (GBHs) are often exposed dermally to much higher levels of GLY [4][5][6] and that repeated dermal exposure episodes over many years heightens cancer risk [7,8]. ...
... A team of scientists convened by the EPA's Office of Research and Development were split between a "possible" and "probable" GLY/GBH cancer classification based on existing data and then-applicable EPA cancer risk assessment guidelines [9]. Scientists not affiliated with GBH registrants have identified evidence linking GBH exposures to cancer outcomes [7,10,11]. Papers published since the completion of the EPA and IARC reviews have enhanced the weight-of-evidence supporting a linkage between GBH exposures and some hematopoietic cancers [8,10,12,13], especially among individuals handling and applying GBHs many times a year over several years [7]. ...
... Scientists not affiliated with GBH registrants have identified evidence linking GBH exposures to cancer outcomes [7,10,11]. Papers published since the completion of the EPA and IARC reviews have enhanced the weight-of-evidence supporting a linkage between GBH exposures and some hematopoietic cancers [8,10,12,13], especially among individuals handling and applying GBHs many times a year over several years [7]. ...
Despite episodic and variable patterns of exposure, the levels of glyphosate (GLY) detected in the urine of herbicide applicators and the general public are relatively stable across space (urban vs. rural) and time (weed spray season, not spray season). Substantial GLY metabolism data show that within minutes of entering the bloodstream, GLY moves into bone marrow, and then laterally through bone tissue and back into general circulation. As GLY moves through bone it comes into contact with calcium and a portion is immobilized via chelation. A novel two-part hypothesis is explored: first, the likely reason for the lack of variability in GLY levels in urine is that GLY stored in bone is excreted gradually over days to weeks, and augments the generally stable and modest levels of dietary exposure to GLY; and second, the prolonged systemic movement of GLY into bone marrow and bone extends contact between GLY and hematopoietic stem cells (HSC), increasing the risk of GLY-induced breaks and rearrangements in the DNA in HSCs. Studies confirm that GLY and glyphosate-based herbicides (GBHs) can trigger oxidative stress and impair DNA-repair mechanisms. Animal bioassays and epidemiology studies link GLY/GBH exposures to heightened risk of blood cancers, and possibly other pathologies. The hypothesis proposed here provides a plausible pathophysiologic basis for these observations relative, in particular, to blood cancers.
... There has been conflicting literature regarding the potential impact of glyphosate and AMPA on human health. A meta-analysis of human epidemiological studies by Zhang et al. (2019) [15] found that the highest cumulative exposure to glyphosate-based herbicides increased non-Hodgkin lymphoma risk by a statistically significant 41%, whereas another meta-analysis by Boffetta et al. [16] found no such relationship, claiming that the studies which have reported positive associations suffered from bias. A review by Mink et al. [17] did not find a consistent association between glyphosate and cancer risk. ...
... There has been conflicting literature regarding the potential impact of glyphosate and AMPA on human health. A meta-analysis of human epidemiological studies by Zhang et al. (2019) [15] found that the highest cumulative exposure to glyphosate-based herbicides increased non-Hodgkin lymphoma risk by a statistically significant 41%, whereas another meta-analysis by Boffetta et al. [16] found no such relationship, claiming that the studies which have reported positive associations suffered from bias. A review by Mink et al. [17] did not find a consistent association between glyphosate and cancer risk. ...
... Other reviews, which have examined the effects of glyphosate, GBHs, and AMPA on outcomes including non-Hodgkin's lymphoma (NHL) [15,18], epigenetic changes [82,83], endocrine disruption [84][85][86], reproductive system alterations [87], and fertility [88,89], have depicted potential detrimental effects glyphosate and GBHs could have on biological processes. In 2018, a review conducted by the International Agency for Research on Cancer (IARC) [18] concluded that glyphosate is a "probable human carcinogen", largely based on four studies showing higher frequencies of NHL in occupationally exposed workers [90][91][92][93]. ...
The potential connection between exposure to glyphosate and glyphosate-based herbicides (GBHs) and breast cancer risk is a topic of research that is rapidly gaining the public’s attention due to the conflicting reports surrounding glyphosate’s potential carcinogenicity. In this review, we synthesize the current published biomedical literature works that have explored associations of glyphosate, its metabolite, aminomethylphosphonic acid (AMPA), and GBHs with breast cancer risk in humans and human cell-based models. Using PubMed as our search engine, we identified a total of 14 articles that were included in this review. In the four human studies, urinary glyphosate and/or AMPA were associated with breast cancer risk, endocrine disruption, oxidative stress biomarkers, and changes in DNA methylation patterns. Among most of the 10 human cell-based studies, glyphosate exhibited endocrine disruption, induced altered gene expression, increased DNA damage, and altered cell viability, while GBHs were more cytotoxic than glyphosate alone. In summary, numerous studies have shown glyphosate, AMPA, and GBHs to have potential carcinogenic, cytotoxic, or endocrine-disruptive properties. However, more human studies need to be conducted in order for more definitive and supported conclusions to be made on their potential effects on breast cancer risk.
... 7 In 2015 for example, glyphosate was classified as a "probable human carcinogen" by the International Agency for Research on Cancer (IARC), a specialist agency of the World Health Organization (WHO). 8,9 Strong evidence from the literatures [10][11][12] indicates that sorption is a crucial process influencing herbicide fate in soils. The most critical input parameter in pesticide fate models is the molecule's affinity for soil. ...
... After collecting the supernatant and filtering it through a 0.45-um micron filter, the amount of glyphosate was determined using HPLC. Equation (9) was utilized to compute the equilibrium adsorption capacity, or q e (mg kg −1 ). ...
Background
The decline in wheat output in Ethiopia is widely attributed to pests, which has led to a rise in the usage of pesticides to boost productivity. The degree of pesticides sorption and degradation which influence the likelihood of environmental contamination from pesticides seeping into water bodies from soil has not yet been published for Ethiopian soils. The study aimed at to quantify the levels of pesticide residues, assess glyphosate’s adsorption capabilities and degradation rate in the soils.
Materials and methods
QuEChERS method of extraction was employed to determine the concentration of the respective pesticides. The adsorption capacities of glyphosate in agricultural soils of Cheha and Dinsho districts were measured using batch adsorption techniques.
Results
Six pesticide residues were found in 12 soil samples at varied quantities. Glyphosate (24.00-219.31 µg kg⁻¹), s-metolachlor (23.67-220.67 µg kg⁻¹), chlorpyrifos (27.74 202.67 µg kg⁻¹), pyroxulam (14.67-50.65 µg kg⁻¹), florasulam (78.00-250.67 µg kg⁻¹), malathion (15.00-49.67 µg kg⁻¹). The experimental results showed that glyphosate was slightly sorbed at SD10 soil (18.91 μg⁻¹⁻ⁿ mLⁿ g⁻¹) in comparison to SC1 soil (114.66 μg⁻¹⁻ⁿ mLⁿ g⁻¹). Organic matter and clay content proving to be the principal factors influencing the process. According to adsorption experimental data, chemisorption is the major process in glyphosate adsorption, with the pseudo-second order kinetic model providing the best fit (R² = .99). The soils in the study area exhibit notable variations in glyphosate rate of degradation (0.0076-0.0221 week⁻¹). The findings show that the main soil variables affecting the half-life (glyphosate degradation) were clay concentrations (R² = .48; P = .013), pH (R² = .55; P = .0055), Organic matter (R² = .74; P = .00027), Feox (R² = .50; P = .0105), and Alox (R² = .73; P = .00046).
Conclusion
The weak glyphosate adsorption capabilities of soils can be a good indicator that the pesticide residues in the soil are poised to endanger soil organisms and contaminate nearby water bodies through runoff and leaching.
... 6,12 The International Agency for Research on Cancer classifies glyphosate as a probable (Group 2A) human carcinogen, based on epidemiological associations of chronic, occupational exposure with an increased risk of non-Hodgkin's lymphoma (NHL). 13 Recent studies have also identified a consistent link between glyphosate exposure and an elevated risk of follicular lymphoma. 14,15 However, results remain inconclusive, as meta-analyses of existing reports show mixed findings, with some studies suggesting no significant association, 16 although this study has been criticized for potential methodological limitations. ...
... 14,15 However, results remain inconclusive, as meta-analyses of existing reports show mixed findings, with some studies suggesting no significant association, 16 although this study has been criticized for potential methodological limitations. 13,17 Further research is needed to clarify the relationship between glyphosate and lymphoid malignancies. Data on glyphosate and HCC risk has been limited to date, but accumulating evidence from animal studies shows that glyphosate generates reactive oxygen species and causes chronic inflammation and transcriptomic changes in the liver. ...
Glyphosate [N‐(phosphonomethyl) glycine], a systemic herbicide, is used globally (825 million kg/year) in 750+ formulations. The International Agency for Research on Cancer classified glyphosate is a probable human carcinogen (Group 2A), but epidemiological studies have been lacking for its association with liver cancer and chronic liver disease. We analyzed urine specimens from 591 patients with newly diagnosed liver cancer, chronic liver disease (CLD), and healthy individuals from five different medical centers between 2011 to 2016 in Thailand. Gas chromatography electrospray ionization mass spectrometry (GC‐ESI/MS) was used to quantify glyphosate and its metabolites, aminomethylphosphonic acid (AMPA) and phosphoric acid (PPA) to study their levels in urine of hepatocellular carcinoma (HCC) and CLD patients in comparison to matched healthy individuals. Significantly higher levels of glyphosate were found in CLD patients compared to HCC cases and hospital controls, while significantly elevated levels of both AMPA and PPA were observed in HCC and CLD patients compared to hospital controls. Glyphosate and its metabolites were also detected at low to moderately high levels in convenience samples of food products and drinking water. These results raise concerns about the potential role of glyphosate in chronic liver disease and liver cancer risk.
... There is cumulative toxicity in animals due to the daily pesticide load coming from feed, with documented synergic interaction in sub-threshold doses of different pesticides being present together 11 . These studies, and the evidence that glyphosate is an endocrine disruptor 4,12 , show that little is known on the long-term impact of multiple pesticides co-exposure at reproductive level and during humans' development. The highest consensus level is on evidence of Non-Hodgkin's lymphoma in humans 4,12,13 . ...
... These studies, and the evidence that glyphosate is an endocrine disruptor 4,12 , show that little is known on the long-term impact of multiple pesticides co-exposure at reproductive level and during humans' development. The highest consensus level is on evidence of Non-Hodgkin's lymphoma in humans 4,12,13 . ...
Introduction
An increasing number of rural communities express perception of health damage from glyphosate and other agrochemicals. We measure the presence of glyphosate in the human body, in order to create, together with the local community, a systemic model that highlights modifiable causal socio-environmental conditions.
Materials and methods
Participatory Action Research. Measurement of environmental factors and self-reported oncological disease were obtained in a three-stage probabilistic sampling (blocks, houses, family) of people living in French city - 9 de Julio-Buenos Aires. Glyphosate in urine was analyzed by liquid chromatography coupled to tandem mass spectrometry. The exposure pathway was obtained by interviewing positive cases. A conceptual systemic model was designed.
Results
of the total 46 blocks of French, 23 were included with systematic sampling and from the 76 houses selected (50%) one person was included in the study. Oncological disease was reported in 21.8% of the households. 13% of the population (95% CI 6.5-23) presented quantifiable glyphosate in urine in June 2023. Occupational exposure was ruled out in all cases. The main self-reported sources were: unloading agrochemicals in the nearby warehouse, the grain storage complex, pesticide drift and self-propelled sprayers that pass by on the street, variables belonging to economic and cultural conditions. A network of actors emerged who, gathered on a website, propose actions to the mayor’s office.
Discussion
This study has high external validity for public health decision makers regarding the determinants. It is necessary to notify the Argentine Integrated Health System, both suspected exposure and possibly related health events, and to design how to refer human samples to highly complex laboratories to measure pesticides.
Conclusion
the presence of glyphosate in urine was due to environmental exposure; It expresses a path of passive, involuntary and chronic absorption of environmental pollutants and is due to French’s agricultural activity with dominance of market forces in the system, poorly antagonized by care forces.
... Likewise, multiple epidemiological studies have also shown that chronic exposure to GBH can be harmful to human's health. [45][46][47]. Glyphosate and exposure to GBH have been linked to neurobehavioral ...
... Nonetheless, mounting evidence suggests that glyphosate may cause adverse health effects in humans via other mechanisms, thus requiring thorough investigation [5]. Likewise, multiple epidemiological studies have also shown that chronic exposure to GBH can be harmful to human's health [45][46][47]. Glyphosate and exposure to GBH have been linked to neurobe-havioral changes that stem from the impairment of neuronal developmental processes in mice [8]. In this study, we completed the serum metabolome profile of rats after their exposure to chronic GBH. ...
Glyphosate-based herbicides (GBHs) have gained extensive popularity in recent decades. For many years, glyphosate has been regarded as harmless or minimally toxic to mammals due to the absence of its primary target, the shikimic acid pathway in humans. Nonetheless, mounting evidence suggests that glyphosate may cause adverse health effects in humans via other mechanisms. In this study, we described the metabolomic changes in the serum of experimental rats exposed to chronic GBH using the highly sensitive LC-MS/MS technique. We investigated the possible relationship between chronic exposure to GBH and neurological disorders. Our findings suggest that chronic exposure to GBH can alter spatial learning memory and the expression of some important metabolites that are linked to neurophysiological disorders in young rats, with the female rats showing higher susceptibility compared to the males. This indicates that female rats are more likely to show early symptoms of the disorder on exposure to chronic GBH compared to male rats. We observed that four important metabolites (paraxanthine, epinephrine, L-(+)-arginine, and D-arginine) showed significant changes and involvement in neurological changes as suggested by ingenuity pathway analysis. In conclusion, our results indicate that chronic exposure to GBH can increase the risk of developing neurological disorders.
... Occupational exposure to glyphosate has been found to be associated with oxidative stress [39,40]. A meta-analysis of human biomonitoring data has been conducted, and the results indicate a significantly increased risk of developing non-Hodgkin lymphoma in cases of higher GBH exposure [41]. There is a paucity of data on childhood exposure to glyphosate, particularly for babies and young children [42]. ...
... Since the release of that report, public concern about the safety of glyphosate has grown, despite the US Environmental Protection Agency (USEPA 2016) deeming the herbicide safe to use when used in accordance with the instructions. Some subsequent epidemiological studies have found that frequent use and exposure to glyphosate are linked to an increased risk of non-Hodgkin's lymphoma (Myers et al. 2016;Zhang et al. 2019) or a subtype of non-Hodgkin's lymphoma, diffuse large B-cell lymphoma . However, the EPA (2020) has reviewed and criticised these studies and reiterated its own view that glyphosate should be categorised as "not likely to be carcinogenic to humans". ...
... Again more preferences toward conservation agriculture (CA) and glyphosate resistant transgenic crops such as maize which solely depends on herbicides to eradicate weeds also responsible for glyphosate residue build up. There is an argument on negative impact of glyphosate on human and animal health, but recent research findings from the University of Washington glyphosate increases risk of some cancers by 40% (Zhang et al., 2019). This aspect presence of glyphosate in ground water in those developed countries may pose serious health hazard, which should be taken care properly. ...
Herbicides become integral components in modern agriculture as it offers
low cost solution to manage weed flora both crop and non-crop field.
Currently, promotion of conservation agriculture (CA)-based crop cultivation practices solely depends on herbicides to counter weeds. Herbicides
were dominant agricultural chemicals used for crop protection purpose and
also used in higher quantities compared to others pesticides. There were large volume of
research articles on persistence of herbicides (specifically on herbicide residues) in soil had been done published
so far across the globe. But information on herbicide residues in ground water is scanty and
majority of the studies were reported from USA, Canada, and European
countries. Major citations on the presence of herbicide residues dominated
by triazine (atrazine, simezine, and metribuzin), chlor acetanilides (alachlor,
metalochlor, and acetachlor), phenoxy alkalonic acid (2,4-D), and organo phosphate (glyphosate) group of herbicides and along with their degraded
products. Spatial and temporal variation of herbicide residue content in
ground water were well documented by many researchers. It was observed
that herbicide residues present in ground water in ranged below or more than
maximum acceptable concentration (MAC) set by European Union (0.1 µg
L−1) despite the fact that those countries often used higher volume of herbicides for crop protection. The presence of herbicide residues more than MAC level in drinking
water may cause health hazard also reported from many countries like Peru,
Argentina, and Sri Lanka, etc. There is necessity of strong regulatory body for
monitoring of herbicide residues in ground water in each and every country.
Thus, future research should be focused to minimize herbicide residue load
in soil, water, and ecosystem. In this chapter, we have highlighted on the
presence of herbicide residues in ground water reported from across the
world, factors involved and way out pathways. Among the different methods
of remediation of herbicide residue in ground water, preventive measures
such as selection of appropriate herbicide, proper mixing & application
procedure, prevention of runoff, and irrigation management are of sustainable approach. Phytoremediation is of widely used method amid different
ground water remediation techniques. Bacterial (Comamonadaceae and
Sphingomonadales) and algal (Scenedesmus species) degradation were also
found effective for treatment of herbicidal ground water contamination.
Apart from this, a new nano-remediation technique was found effective for
remediation of atrazine and bromacil in ground wate
... For example, the herbicide glyphosate, commonly used in agriculture, has been classified by the IARC as a probable carcinogen to humans (Group 2A) [36]. Glyphosate exposure has been linked to an increased risk of non-Hodgkin lymphoma in some studies [37]. Additionally, organophosphate pesticides, widely used in insect control, have been Life 2025, 15, 160 10 of 14 associated with various cancer types. ...
The available literature reports inconclusive findings regarding the frequency of organic food consumption and cancer incidence. This systematic review evaluated the effect of the frequency of organic food consumption on overall and site-specific cancer risk. Four electronic databases (PubMed, Scopus, Web of Science Core Collection, and Embase), the gray literature, and the reference lists of the included reports were searched for eligible studies. Study screening, data abstraction, and risk of bias assessment were performed by two independent examiners. Hazard ratios (HRs) and 95% confidence intervals using a random effects model were utilized to synthesize the available data from the included studies. There was no difference between the two interventions regarding overall cancer (HR = 0.93, 95% CI: 0.78–1.12), breast cancer (HR = 1.01, 95% CI: 0.81–1.26), colorectal cancer (HR = 1.01, 95% CI: 0.93–1.10), and non-Hodgkin lymphoma risks (HR = 0.70, 95% CI: 0.17–2.94). The findings suggest that the overall and site-specific cancer risk are not associated with the frequency of consumption of organic foods. Further research is necessary to provide more evidence for the role of organic food consumption on the incidence of cancer using homogeneous methodologies to define the frequency of organic food consumption.
... In this regard, several studies have associated occupational pesticide exposure in farmers with various types of cancer, such as breast cancer (11), acute myeloid leukemia (12) and non-Hodgkin lymphoma (13). Additionally, there are articles demonstrating an increased cancer risk in towns or regions where large quantities of pesticides are used (14, 15). ...
The use of pesticides has enabled the development of contemporary industrial agriculture and significantly increased crop yields. However, they are also considered a source of environmental pollution and a potential hazard to human health. Despite national agencies and the scientific community analyzing pesticide safety, immunotoxicity assays are often not required, poorly designed, or underestimated. Epidemiological evidence indicates that pesticide exposure increases the risk of developing cancer. Therefore, pesticides may not only act as carcinogens per se but also as immunosuppressive agents that create a permissive context for tumor development. Given recent evidence demonstrating the critical role of the immune response in cancer progression, we will highlight the necessity of assessing the potential impacts of pesticides on the immune response, particularly on tumor immunosurveillance. In this Perspective article, we will focus on the need to critically review fundamental aspects of toxicological studies conducted on pesticides to provide a clearer understanding of the risks associated with exposure to these compounds to human health.
... A study using data from North America, the European Union, and Australia found that 2,4-D exposure was linked to specific subtypes of non-Hodgkin lymphoma (NHL), with those exposed for over six years at an increased risk for T-cell lymphoma [40]. Glyphosate has consistently been associated with various cancers, particularly non-Hodgkin lymphoma (NHL) [41,42]. Paraquat is known to cause tissue irritation and is classified as a carcinogenic substance due to its ability to induce the proliferation of cancer cells [19,43]. ...
Introduction
Cancer is a leading cause of disease burden worldwide. Although much of the existing literature, primarily from Western countries, suggests an association between pesticide exposure and cancer risk, these findings may not be directly applicable to the Thai population. This is due to differences in social, economic, and public health contexts, as well as variations in health status, pesticide use patterns, and self-protection behaviors. This study aimed to investigate the relationship between pesticide exposure and cancer risk among Thai farmers. The findings are expected to contribute valuable insights for public health prevention and control programs, as well as enhance the existing body of literature.
Methods
In this cross-sectional study, data were collected from 10,646 farmers aged 20 years and older through in-person interviews using a structured questionnaire. The association between pesticide exposure and cancer was analyzed using logistic regression, adjusting for potential confounding factors.
Results
The study identified a significant association between the historical use of pesticides, including insecticides, herbicides, and fungicides, and cancer risk. Among 39 individual pesticides examined, sixteen were found to have a significant odds ratio. The study’s results aligned with existing literature regarding the potential effects of glyphosate, paraquat, 2,4-D, folidol, chlorpyrifos, EPN, mevinphos, dichlorvos, endosulfan, dieldrin, mancozeb, maneb, and copper sulfate. Additionally, this study newly identified a significant association with propineb (OR = 2.41, 95% CI: 1.39–4.17), carbendazim (OR = 1.77, 95% CI: 1.11–2.81), and benomyl (OR = 4.04, 95% CI: 1.69–9.63).
Conclusion
The study found cancer prevalence among farmers in Nakhon Sawan, Thailand, to be associated with historical pesticide use. These findings aligned with existing literature, underscoring the potential effects of long-term pesticide exposure on cancer risk. This issue warrants increased public attention and stricter regulation of pesticide use. An effective exposure prevention program should be urgently implemented, particularly for Thai farmers.
... умирающему от неходжкинской лимфомы садовнику Джонсону, так как компания не указала в описании препарата, что глифосат в составе Roundup и Ranger Pro может стать причиной развития рака [62]. Менее чем через год были опубликованы данные о том, что существует связь между использованием глифосатсодержащих гербицидов и повышением риска заболевания неходжкинской лимфомой [63]. Отсутствие единого мнения о потенциальной опасности гербицидов на основе глифосата свидетельствует о необходимости дальнейшего тщательного исследования этого гербицида и его метаболитов, а также развития методов контроля их содержания в продуктах питания и объектах окружающей среды. ...
В обзоре представлена систематизированная информация по истории химического метода контроля сорной растительности с конца XIX в. до настоящего времени. Рассмотрены как неорганические гербициды (минеральные соли и кислоты), так и наиболее известные классы синтетических органических гербицидов: 2,4-дихлорфеноксиуксусная кислота (2,4-Д) и ее аналоги, замещенные мочевины, триазины, дипиридилы, амиды, карбаматы, сульфонилмочевины, имидазолиноны, арилоксифеноксипропионаты, циклогександионы и др. Подробно изложена история применения глифосата и современная оценка этого гербицида. Приведены данные об основных существующих биогербицидах и гербицидах на основе природных фитотоксинов.
The review presents systematized information on the history of the chemical method of weed control from the end of the XIX century to the present time. Both inorganic herbicides (mineral salts and acids) and the most well-known classes of synthetic organic herbicides are considered: 2,4-dichlorophenoxyacetic acid (2,4-d) and its analogues, substituted urea, triazines, dipyridiles, amides, carbamates, sulfonylureas, imidazolinones, aryloxyphenoxypropionates, cyclohexanediones etc. The history of glyphosate use and the current assessment of this herbicide are described in details. data on the main developed biogerbicides and herbicides based on natural phytotoxins are presented.
... The presence of these molecules in products of animal origin is a major concern for human health due to their easy transfer from agricultural products to animal tissues, along with their stability [2]. To monitor the presence of polar pesticides in food and ensure compliance with the EU maximum residue levels (MRLs), the European Commission promulgated a Regulation in 2022 providing for a multi-year control of pesticide residues in matrices of animal and plant origin, including ammonium glyphosate and glufosinate, and their metabolites, in bovine, pig and poultry fat, chicken eggs, bovine liver, and cow's milk [3,4,5]. ...
The detection and quantification of polar pesticides in liquid chromatography coupled with mass spectrometry present significant analytical challenges. This study compares the performance of three LC columns (Hypercarb™, Raptor Polar X™, and Anionic Polar Pesticide™) in separating and quantifying eleven polar pesticides in chicken eggs using a score-based methodology. Analytes include glyphosate, its metabolites, and other high-polarity pesticides like Ethephon, Glufosinate, and Fosetyl aluminum, included in the EU's official control plan. Polar pesticides, characterized by high polarity and hydrophilicity, lead to analytical issues such as poor retention and unconventional peak shapes with traditional reversed-phase methods. Their weak interaction with hydrophobic stationary phases complicates separation, necessitating specific stationary phases to enhance retention and selectivity. This study evaluates these columns' efficacy in complex matrices like chicken eggs and other food samples. Chromatographic separation was performed using a UPLC system coupled with a Q-TOF mass spectrometer; extraction and purification involved freeze-out, centrifugation, and filtration steps. The study highlights the critical role of column selection in achieving accurate and reliable separation and quantification of highly polar analytes in matrices of animal origin, offering in the meantime an easy-to-apply methodology of selection for the right determination of the best chromatographic column for different purposes.
... Members of civil society can also sue a regulatory agency for not implementing a protective law (Center for Food Safety, 2022) or product manufacturers when experts have assembled sufficient evidence, meeting a legal burden of proof, that a chemical causes serious harm. For example, repeated lawsuits against manufacturers of herbicides containing glyphosate have been successful because of strong evidence these products increase the risk of Non-Hodgkin's Lymphoma (Zhang et al., 2019), even though the EPA maintains that glyphosate does not cause cancer (Benbrook, 2019). ...
... Estos estudios y la evidencia de que el GLY es un disruptor endocrino 3,13,4 muestran que se sabe muy poco de la coexposición de múltiples plaguicidas sobre el impacto a largo plazo a nivel reproductivo y durante el desarrollo de humanos. El mayor nivel de consenso evidencia asociación entre GLY y linfoma no Hodgking en los seres humano 4,14,15 . ...
Introducción: cada vez más comunidades rurales expresan preocupación por posible daño a la salud por los agroquímicos. A partir de conocer la presencia en el cuerpo humano de glifosato es posible confeccionar, junto a los actores locales, un modelo sistémico que evidencie los condicionantes socioambientales de la salud. Materiales y métodos: Investigación-Acción Participativa. Muestreo probabilístico trietápico (manzanas, casas, familia) de French (Partido de 9 de Julio; Provincia Buenos Aires) para la medición de factores ambientales y autoinforme de enfermedad oncológica. Análisis de glifosato en orina por cromatografía líquida acoplada a espectrometría de masa en tándem. Entrevistas en profundidad a casos positivos para determinar la vía de exposición. Confección de un modelo conceptual para el análisis de la complejidad sistémica. Resultados: del total de las 46 manzanas de French, 23 manzanas fueron incluidas con muestreo sistemático y en 76 casas (50%) una persona fue seleccionada al azar. En el 21,8% de los hogares refirieron antecedentes de enfermedad oncológica. El 13% de la población (IC 95%: 6,5-23) presentó glifosato cuantificable en orina en junio de 2023. La exposición laboral se descartó en todos los casos, siendo las principales fuentes autorreferidas: “la descarga de agroquímicos en el galpón cercano”, “la cerealera”, “la deriva” y “los camiones mosquito que pasan por la calle”, variables pertenecientes a condicionantes económicos y culturales. Emergió una red de actores, a la espera de la problematización sociopolítica de los resultados mediada por el Honorable Concejo Deliberante (HCD) y las Organizaciones no Gubernamentales (ONG), que equilibren el sistema con fuerzas de cuidado. Discusión: estudio de alta validez externa. Se requiere informatizar sistemas de vigilancia comunitarios tanto para la sospecha de exposición como de posibles enfermedades relacionadas con agroquímicos; crear circuitos de derivación de muestras a laboratorios de alta complejidad y diseñar estrategias múltiples sobre los condicionantes para cuidar de posibles daños por exposición crónica. Conclusión: la presencia de glifosato en la orina se debió a exposición ambiental; expresa una vía de absorción pasiva, involuntaria y crónica de contaminantes ambientales que resulta de la actividad agropecuaria de French que no es antagonizada por fuerzas de cuidado.
... Glyphosate, marketed as Roundup R , is a common herbicide with an average of 280 million pounds applied to 298 crop acres yearly (23). Some studies have shown a correlation between exposure to glyphosate and an increased risk of lymphoma (24)(25)(26). The International Agency for Research on Cancer even classified glyphosate as a probable carcinogen in humans in 2015 (27). ...
Pesticides are an essential feature of modern-day agriculture that adds to the list of factors that increase cancer risk. Our study aims to comprehensively evaluate this relationship through a population-based approach that considers confounding variables such as county-specific rates of smoking, socioeconomic vulnerability, and agricultural land. We achieved our goal with the implementation of latent-class pesticide use patterns, which were further modeled among covariates to evaluate their associations with cancer risk. Our findings demonstrated an association between pesticide use and increased incidence of leukemia; non-Hodgkin's lymphoma; bladder, colon, lung, and pancreatic cancer; and all cancers combined that are comparable to smoking for some cancer types. Through our comprehensive analysis and unique approach, our study emphasizes the importance of a holistic assessment of the risks of pesticide use for communities, which may be used to impact future policies regarding pesticides.
... Furthermore, in some scenarios, we might expect male-plant reproductive allocation to be higher than in female plants, for example in wind-pollinated plants with a large production of nitrogen-rich pollen (Delph et al., 1993;Harris & Pannell, 2008). In fact, there is evidence of cases in which male plants show higher concentration of secondary metabolites associated with defense against herbivores (Bañuelos et al., 2004;Hjaltén, 1992;Yang et al., 2020;Zhang et al., 2019); including our study system B. cordata (Moreira et al., 2019). Finally, even if we did not find sex-bias in leaf water content and thickness, we found a strong seasonal pattern observed in these metrics that raises the question of whether other variables that show sex-dependence (like the secondary compounds F I G U R E 4 Interpolation and extrapolation curves of richness and arthropod diversity on male and female trees of B. cordata across three times. ...
Intraspecific variation in plants is expected to have profound impacts on the arthropod communities associated with them. Because sexual dimorphism in plants is expected to provide consistent variation among individuals of the same species, researchers have often studied the effect it has on associated arthropods. Nevertheless, most studies have focused on the effect of sexual dimorphism in a single or a few herbivores, thus overlooking the potential effects on the whole arthropod community. Our main objective was to evaluate effects of Buddleja cordata's plant‐sex on its associated arthropod community. We surveyed 13 pairs of male and female plants every 2 months during a year (June 2010 to April 2011). Every sampling date, we measured plant traits (water content and leaf thickness), herbivory, and the arthropod community. We did not find differences in herbivory between plant sex or through time. However, we found differences in water content through time, with leaf water‐content matching the environmental seasonality. For arthropod richness, we found 68 morphospecies associated with female and 72 with male plants, from which 53 were shared by both sexes. We did not observe differences in morphospecies richness; however, we found sex‐associated differences in the diversity of all species and differences on the diversity of the most abundant species with an interesting temporal component. During peak flowering season, male plants showed higher values on both parameters, but during the peak fructification season female plants showed the higher values on both diversity parameters. Our research exemplifies the interaction between plant‐phenology and plant‐sex as drivers of arthropod communities' diversity, even when plant sexual‐dimorphism is inconspicuous, and highlighting the importance of accounting for seasonal variation. We stress the need of conducting more studies that test this time‐dependent framework in other dioecious systems, as it has the potential to reconcile previous contrasting observations reported in the literature.
... Breast milk has been found to have DDT and DDE traces in the human species, putting nursing newborns at risk of exposure. According to a meta-analysis, glyphosate-based herbicides are associated with an increased incidence of non-Hodgkin's lymphoma (NHL) (Zhang et al., 2019c). Studies have shown that glyphosate promotes NHL in mice and is carcinogenic to rodents. ...
Endocrine disrupting chemicals or carcinogens have been known for decades for their endocrine signal disruption. Endocrine disrupting chemicals are a serious concern and they have been included in the top priority toxicants and persistent organic pollutants. Therefore, researchers have been working for a long time to understand their mechanisms of interaction in different human organs. Several reports are available about the carcinogen potential of these chemicals. The presented review is an endeavor to understand the hazard identification associated with endocrine disrupting carcinogens in relation to the human body. The paper discusses the major endocrine disrupting carcinogens and their potency for carcinogenesis. It discusses human exposure, route of entry, carcinogenicity and mechanisms. In addition, the paper discusses the research gaps and bottlenecks associated with the research. Moreover, it discusses the limitations associated with the analytical techniques for detection of endocrine disrupting carcinogens.
... According to the same authors, the work demonstrated that glyphosate is "less toxic than other pesticides", this condition does not weaken the "potential adverse health effects for humans", as it is also related to endocrine changes. Other studies corroborate the previously cited evidence on levels of human exposure to glyphosate, including the general population and occupationally exposed workers, such as the systematic literature review carried out by Gillezeau et al. [112] and the meta-analysis conducted by Zhang et al. [113], who evaluated the potential association between high and cumulative exposure to glyphosate and the risk of developing non-Hodgkin lymphoma in humans. This study indicates that there is an evident correlation between exposure to glyphosate and the increasing threat of non-Hodgkin's lymphoma. ...
Glyphosate is a broad-spectrum pesticide that has become the most widely used herbicide globally. However, concerns have risen regarding its potential health impacts due to food contamination. Studies have detected glyphosate in human blood and urine samples, indicating human exposure and its persistence in the organism. A growing body of literature has reported the health risks concerning glyphosate exposure, suggesting that the daily intake of contaminated food and water poses a public health concern. Furthermore, countries with high glyphosate usage and lenient regulations regarding food and water contamination may face more severe consequences. In this context, in this review, we examined the literature regarding food contamination by glyphosate, discussed its detection methods, and highlighted its risks to human health.
... Despite its productivity benefits, glyphosate's health impacts are strongly debated, with classifications ranging from "probably carcinogenic" (IARC, 2015) to "not carcinogenic" (ECHA, 2017). Meta-analysis indicates a correlation between long-term exposure to glyphosate-based herbicides and an increased prevalence of Non-Hodgkin lymphoma (NHL) (Zhang et al., 2019). However, establishing a causal relationship is challenging without direct experimentation (Álvarez et al., 2023). ...
Rwanda has been a notable player in sustainable development in the last decades, particularly in light of its agricultural practices. This paper offers a multifaceted viewpoint on the challenges faced by Rwanda's specialty coffee sector. Our holistic approach to studying the situation and possibilities included fieldwork, site visits, informal interviews with various stakeholders, from farmers to governmental officials, and an extensive literature study to support our findings. We highlight the challenges of optimizing the domestic supply chain and the effects of such developments on rural livelihoods. Poverty and lacking resources require a nuanced view toward sustainability, as ecological and economic sustainability do not align. The paper presents how certification programs can function as indicators of sustainability and stresses the need for policy evaluations. We also discuss the unique challenges faced by smallholder farmers in Rwanda and how corporate interests may interfere with long‐term sustainable development. As Rwanda continues to develop, this paper argues that the resilience and ingenuity of its people are crucial in the ongoing development of sustainable agricultural systems.
... Les herbicides à base de glyphosate, pesticides les plus vendus au Canada, sont utilisés sur plusieurs cultures, comme le soya et le maïs, pour la dessiccation des grains ou l'élimination des mauvaises herbes. Plusieurs études et une métanalyse ont montré les effets néfastes de ces herbicides sur la santé 3,4 . Par exemple, après sa revue de la littérature scientifique indépendante, le Centre International de Recherche sur le Cancer de l'Organisation mondiale de la Santé a conclu que le glyphosate et les herbicides à base de glyphosate (qui contiennent aussi d'autres produits chimiques) sont génotoxiques et probablement cancérigènes pour les êtres humains, et ont également une association positive avec les lymphomes non Hodgkiniens 5 . ...
... In spite of this, they found that the highest exposure quartile had an increased risk of acute myeloid leukemia (AML), but this result was not statistically significant [37]. A 2019 meta-analysis of this AHS data and five new case-control studies reported a 41% increased meta-relative risk of NHL for the highest GBH exposure groups [81]. However, a recent review of epidemiological studies published in 2020 criticized the weaknesses of this finding, stating that study discrepancies between exposure groups, the lack of direct comparison between each exposure group, and other epidemiological limitations skew the validity of this data [82]. ...
In recent years, organic agriculture has gained more popularity, yet its approach to food production and its potential impact on consumers’ health and various environmental aspects remain to be fully discovered. The goal of organic farming practices is to maintain soil health, sustain ecological systems, maintain fairness in its relationship with the environment and protect the environment in its entirety. Various health benefits have been associated with higher consumption of organic foods. This review identified some of these health benefits, including a reduction in obesity and body mass index (BMI), improvements in blood nutrient composition as well as reductions in maternal obesity and pregnancy-associated preeclampsia risks. Furthermore, organic food consumption can reduce the development of non-Hodgkin lymphoma (NHL) and colorectal cancers. Upon reviewing the existing literature regarding the nutritional value of organic foods, it was found that organic food contained higher levels of iron, magnesium and vitamin C. However, the evidence available to draw definitive causations remains limited due to study biases, short study durations and confounding variables; thus, it cannot be concluded that the organic diet provides any related health benefits. In this review, we provided essential insights and statistical analysis from the evidence available and consider study limitations to evaluate the potential of organic food consumption in positively impacting human health.
Pediatricians and pediatric trainees in North America are increasingly involved in caring for children and adolescents in or from low- and middle-income countries (LMICs). In many LMICs, toxic environmental exposures—notably outdoor and household air pollution, water pollution, lead, hazardous waste disposal, pesticides, and other manufactured chemicals—are highly prevalent and account for twice as great a proportion of disease and deaths among young children as in North America. Climate change will likely worsen these exposures.
It is important that pediatricians and other pediatric health professionals from high-income countries who plan to work in LMICs be aware of the disproportionately severe impacts of environmental hazards, become knowledgeable about the major toxic threats to children’s health in the countries and communities where they will be working, and consider environmental factors in their differential diagnoses. Likewise, pediatricians in high-income countries who care for children and adolescents who have emigrated from LMICs need to be aware that these children may be at elevated risk of diseases caused by past exposures to toxic environmental hazards in their countries of origin as well as ongoing exposures in products such as traditional foods, medications, and cosmetics imported from their original home countries.
Because diseases of toxic environmental origin seldom have unique physical signatures, the environmental screening history, supplemented by laboratory testing, is the principal diagnostic tool. The goal of this technical report is to enhance pediatricians’ ability to recognize, diagnose, and manage disease caused by hazardous environmental exposures, especially toxic chemical exposures, in all countries and especially in LMICs.
The advent of herbicide-tolerant genetically modified (GM) crops spurred rapid and widespread use of the herbicide glyphosate throughout US agriculture. In the two decades following GM-seeds’ introduction, the volume of glyphosate applied in the United States increased by more than 750%. Despite this breadth and scale, science and policy remain unresolved regarding the effects of glyphosate on human health. We identify the causal effect of glyphosate exposure on perinatal health by combining 1) county-level variation in glyphosate use driven by 2) the timing of the GM technology and 3) differential geographic suitability for GM crops. Our results suggest the introduction of GM seeds and glyphosate significantly reduced average birthweight and gestational length. While we find effects throughout the birthweight distribution, low expected-weight births experienced the largest reductions: Glyphosate’s birthweight effect for births in the lowest decile is 12 times larger than that in the highest decile. Together, these estimates suggest that glyphosate exposure caused previously undocumented and unequal health costs for rural US communities over the last 20 years.
Glyphosate, an herbicide largely used in various contexts, can have adverse effects on human health. Although it is currently the most applied pesticide worldwide, few studies evaluated the extent of human exposure via biomonitoring. To expand such information, biological monitoring of exposure to glyphosate was conducted.
The study has a before-and-after design to demonstrate the immediate impact of short-term interventions. Accordingly, the urine concentrations of glyphosate and its main biodegradation product (amino-methylphosphonic acid- AMPA) were measured before and the day after the single herbicide application in 17 male winegrowers. Urine samples were analyzed by high performance liquid chromatography coupled with a triple quadrupole mass spectrometer equipped with an electrospray ionization source.
Glyphosate and AMPA were not detectable in pre-application urine samples (limit of quantification for glyphosate (LOQG) was 0.1 μg/L; limit of quantification for AMPA (LOQAMPA) was 0.5 μg/L). After application, glyphosate urinary levels were above LOQG in all workers. The median, min, and max values were 2.30, 0.51, and 47.2 μg/L, respectively. The same values were found for 50 %, 5 % and 95 % percentiles. After assigning numerical values, such as one half the LOQ, to each of the non-detects, the “z” of Wilcoxon matched-pairs signed-ranks test was −3.62 (p = 0.0003), suggesting the pre-application values being significantly lower than the post-application urinary glyphosate concentration. A similar analysis was not feasible with AMPA urinary levels, which were detectable only in 3 workers, after application. 12 (71 %) workers were significantly exposed to glyphosate, but adherence to the adoption of personal protective equipment was good: 14 (82 %) workers used gloves, 13 (76 %) used overalls and 13 (76 %) facial masks.
Our data show that glyphosate can be absorbed by the workers after a single application and confirms the usefulness of biomonitoring in exposed workers. Further studies are needed in larger working populations and with multiple glyphosate applications, as well as to evaluate the correlations of glyphosate urine levels with exposure questionnaire data, in order to assess the actual relevance of risk and protection factors.
Several studies, have reported that glyphosate-based herbicides persist in the soil and are transported into other environmental matrices. This study evaluated the ability of Aspergillus oryzae AM2 and Mucor circinelloides 166 to remove glyphosate and aminomethylphosphonic acid from agricultural soil under field conditions. The strains are native to Argentinean agricultural soils, and they were assessed separately and in combination in 2 m × 1 m subplots. A completely randomized block design was used (5 treatments with 6 replicates each). The soil was sprayed with a commercial glyphosate-based herbicide formulation (3 kg ha-1) and inoculated with spores and/or conidial suspensions. Glyphosate and aminomethylphosphonic acid were measured at the beginning of the assay and at the end (150 days) by ultra-high performance liquid chromatography. In all the treatments, residual glyphosate levels were significantly lower at the end than at the start. The most significant removal percentages (p < 0.001) were 97%, obtained with A. oryzae AM2 (106 conidia/mL-1), and 93%, obtained with the combination of M. circinelloides 166 (106 spores mL-1) and A. oryzae AM2 (103 conidia mL-1). Aminomethylphosphonic acid decreased significantly (by 32%) in the uninoculated control. The same two treatments that were the most effective at removing glyphosate were the only ones in which the decrease in aminomethylphosphonic acid was higher than in the control (over 70%). This is the first study to demonstrate that these fungal strains can remove glyphosate and aminomethylphosphonic acid under field conditions. Thus, they could be good candidates for the remediation of herbicide-polluted sites.
Polar pesticides such as anionic or ionisable compounds have always provided a challenge for analytical chemists. Methods of analysis have been developed using a range of techniques including normal phase...
According to the World Health Organization, cancer is a leading cause of death globally. The disease’s prevalence is rapidly increasing in association with factors including the increased use of pesticides and herbicides, such as glyphosate, which is one of the most widely used herbicide ingredients. Although chemotherapy is currently the most common option for treatment, its high cost and rates of side effects make it less accessible to economically disadvantaged patients. Natural antioxidants and phytochemicals are being tested as anti-cancer agents due to their antiproliferative, antioxidative, and pro-apoptotic properties. Simarouba amara is one such plant and contains several alkaloid derivatives known to inhibit cancerous growth. Thus, we aimed to investigate the potential role of S. amara extract as a therapeutic agent against glyphosate-induced toxicity and tumor-like morphologies in regenerating and homeostatic planaria (Dugesia dorotocephala). We hypothesized that S. amara would reduce and prevent tumor-like lesions and toxicity in planarians exposed to glyphosate. We conducted several assays to determine the efficacy of Simarouba extract in reducing tumor-like lesions and morphological changes, increasing survival rate, mitigating blastema reduction, and maintaining locomotive velocity in glyphosate-exposed planarians. In three sets of trials, planarians treated with S. amara extract after glyphosate-induced toxicity showed higher negative phototaxicity compared to those treated with spring water after glyphosate exposure. S. amara also significantly increased the survival rate, subdued tumor-like lesions, and mitigated blastema reduction in glyphosate-exposed planarians compared to those treated with spring water. The results show that S. amara extract possesses therapeutic effects against weedicide-induced toxicity.
Our understanding of risk factors for the development of chronic lymphocytic leukemia (CLL) is still incomplete and includes genetic and environmental factors. CLL is one of the most familial of all cancers, yet common high-penetrance risk alleles have not been identified. Genome-wide association studies have identified many common variants with low relative risks, whereas exome-wide rare variant analysis has implicated ATM in CLL causation. Environmental factors have also been challenging to identify given the limited understanding of the relevant time period of exposure relative to diagnosis, and the inability to quantify past exposures. Agent Orange and glyphosate herbicides have perhaps the most data to support their role. CLL is preceded by a precursor condition called monoclonal B-cell lymphocytosis (MBL), which could therefore be considered a risk factor, but which itself is likely caused by the same risk factors that ultimately give rise to CLL. Although virtually all people with CLL have a preceding MBL phase, most people with MBL will not develop CLL.
Pesticides are chemical constituents used to prevent or control pests, including insects, rodents, fungi, weeds, and other unwanted organisms. Despite their advantages in crop production and disease management, the use of pesticides poses significant hazards to the environment and public health. Pesticide elements have now perpetually entered our atmosphere and subsequently contaminated water, food, and soil, leading to health threats ranging from acute to chronic toxicities. Pesticides can cause acute toxicity if a high dose is inhaled, ingested, or comes into contact with the skin or eyes, while prolonged or recurrent exposure to pesticides leads to chronic toxicity. Pesticides produce different types of toxicity, for instance, neurotoxicity, mutagenicity, carcinogenicity, teratogenicity, and endocrine disruption. The toxicity of a pesticide formulation may depend on the specific active ingredient and the presence of synergistic or inert compounds that can enhance or modify its toxicity. Safety concerns are the need of the hour to control contemporary pesticide-induced health hazards. The effectiveness and implementation of the current legislature in providing ample protection for human health and the environment are key concerns. This review explored a comprehensive summary of pesticides regarding their updated impacts on human health and advanced safety concerns with legislation. Implementing regulations, proper training, and education can help mitigate the negative impacts of pesticide use and promote safer and more sustainable agricultural practices.
Agriculture is considered as the backbone of all the developing countries not only for their livelihood but also as economic support. However, since the inception of agricultural practices, there is a continuous warfare between human and various detrimental candidates such as plant pathogens, weeds, phytophagous pests, etc. To combat these, synthetic chemicals such as pesticides, fertilizer and other related chemicals are used to enhance agricultural yield. However, non-judicious, inadvertent and indiscriminate use of these organic micropollutants (OMPs) caused detrimental effects on the environment and human health.
Organic micropollutants (OMPs) enter into the biotic-abiotic system through variable modes like irrigation water, animal excreta as manure/compost, sewerage wastewater, pesticide, fertilizer, etc. from where they reach the food system via various entry points like agricultural soil, groundwater, contaminated crops and fruits and finally via bioaccumulation to the food chain. Traces of OMPs are still being reported even from some of the discontinued pesticides such as DDT, heptachlor and atrazine in drinkable water. OMPs are stated to be more toxic as compared to their parent compounds and thus considered as potential threat to human health by triggering neurological dysfunctions, endocrine disruption and metabolism malfunctioning. OMPs are perils to biological elements of the ecosystem by damaging soil quality and alter soil biogeochemical processes and its micro-floral-faunal diversity by inducing genetic alterations. In addition to economical diversion for pesticides and synthetic agrochemical production, the deleterious effects of OMPs and their management will further raise a financial burden both for developed and developing countries. Hence, cost-effective, extensive screening methodologies, analytical techniques and scientific evidence-based robust technologies need to be developed for the identification, quantification and remediation of OMPs from soil, water and agricultural yield to discharge effective and healthy agroeconomic practices.
The consumption of ultra-processed food products (UPFP) is linked to the development of some kinds of cancers, which can also be caused by pesticides. However, there is not enough scientific evidence that UFPF may contain residues of pesticides. Some studies report that industrial processing drastically reduces pesticides. Nevertheless, other studies also report that the amount of pesticides increases. This research aimed to measure the concentration of pesticides. Samples of UPFP from plant origin such as soft drinks, nectars, soy drinks, corn chips, savory crackers, stuffed cookies, corn breakfast cereals, and loaf breads were analyzed. Samples of UPFP from animal origin such as pork sausage, hot dog sausage, mortadella, beef hamburger, chicken nuggets, yogurt, chocolate milk, and curd cheese were also analyzed. Pesticides were detected in 16 samples of the 27 products based on corn, wheat, soy, and sugarcane analyzed. Also, pesticides were detected in 14 samples of the 24 products based on meat and milk analyzed. Ten pesticides were detected: aminomethylphosphonic acid (AMPA), bifenthrin, lambda-cyhalothrin, cypermethrin, chlorpyrifos, fipronil sulfone, fluazuron, glyphosate, glufosinate, and methyl pirimiphos. Pirimiphos-methyl was found in all products of savory crackers, stuffed cookies, and loaf breads. Considering that residues of pesticides were found in 12 categories of products made in different industries involving different industrial processes, our study confirms that UPFP contains residues of pesticides.
Here, four MOFs, namely Sc-TBAPy, Al-TBAPy, Y-TBAPy, and Fe-TBAPy (TBAPy: 1,3,6,8-tetrakis(p-benzoic acid)pyrene), were characterized and evaluated for their ability to remediate glyphosate (GP) from water. Among these materials, Sc-TBAPy demonstrates superior performance in both the adsorption and degradation of GP. Upon light irradiation for 5 min, Sc-TBAPy completely degrades 100% of GP in a 1.5 mM aqueous solution. Femtosecond transient absorption spectroscopy reveals that Sc-TBAPy exhibits enhanced charge transfer character compared to the other MOFs, as well as suppressed formation of emissive excimers that could impede photocatalysis. This finding was further supported by hydrogen evolution half-reaction (HER) experiments, which demonstrated Sc-TBAPy’s superior catalytic activity for water splitting. In addition to its faster adsorption and more efficient photodegradation of GP, Sc-TBAPy also followed a selective pathway towards the oxidation of GP, avoiding the formation of toxic aminomethylphosphonic acid observed with the other M³⁺-TBAPy MOFs. To investigate the selectivity observed with Sc-TBAPy, electron spin resonance, depleted oxygen conditions, and solvent exchange with D2O were employed to elucidate the role of different reactive oxygen species on GP photodegradation. The findings indicate that singlet oxygen (¹O2) plays a critical role in the selective photodegradation pathway achieved by Sc-TBAPy.
With a growing global population, agricultural scientists are focusing on crop production management and the creation of new strategies for a higher agricultural output. However, the growth of undesirable plants besides the primary crop poses a significant challenge in agriculture, necessitating the massive application of herbicides to eradicate this problem. Several synthetic herbicides are widely utilized, with glyphosate emerging as a potential molecule for solving this emerging issue; however, it has several environmental and health consequences. Several weed species have evolved resistance to this herbicide, therefore lowering agricultural yield. The persistence of glyphosate residue in the environment, such as in water and soil systems, is due to the misuse of glyphosate in agricultural regions, which causes its percolation into groundwater via the vertical soil profile. As a result, it endangers many nontarget organisms existing in the natural environment, which comprises both soil and water. The current Review aims to provide a systemic analysis of glyphosate, its various effects on the environment, its subsequent impact on human health and animals, which will lead us toward a better understanding of the issues about herbicide usage and aid in managing it wisely, as in the near the future glyphosate market is aiming for a positive forecast until 2035.
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.
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.
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.
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.
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.
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.
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.
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.
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
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.
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.
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.
Systematic reviews and meta-analyses have become increasingly important in health care. Clinicians read them to keep up to date with their field [1],[2], and they are often used as a starting point for developing clinical practice guidelines. Granting agencies may require a systematic review to ensure there is justification for further research [3], and some health care journals are moving in this direction [4]. As with all research, the value of a systematic review depends on what was done, what was found, and the clarity of reporting. As with other publications, the reporting quality of systematic reviews varies, limiting readers' ability to assess the strengths and weaknesses of those reviews.
Several early studies evaluated the quality of review reports. In 1987, Mulrow examined 50 review articles published in four leading medical journals in 1985 and 1986 and found that none met all eight explicit scientific criteria, such as a quality assessment of included studies [5]. In 1987, Sacks and colleagues [6] evaluated the adequacy of reporting of 83 meta-analyses on 23 characteristics in six domains. Reporting was generally poor; between one and 14 characteristics were adequately reported (mean = 7.7; standard deviation = 2.7). A 1996 update of this study found little improvement [7].
In 1996, to address the suboptimal reporting of meta-analyses, an international group developed a guidance called the QUOROM Statement (QUality Of Reporting Of Meta-analyses), which focused on the reporting of meta-analyses of randomized controlled trials [8]. In this article, we summarize a revision of these guidelines, renamed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses), which have been updated to address several conceptual and practical advances in the science of systematic reviews (Box 1).
Box 1: Conceptual Issues in the Evolution from QUOROM to PRISMA
Completing a Systematic Review Is an Iterative Process
The conduct of a systematic review depends heavily on the scope and quality of included studies: thus systematic reviewers may need to modify their original review protocol during its conduct. Any systematic review reporting guideline should recommend that such changes can be reported and explained without suggesting that they are inappropriate. The PRISMA Statement (Items 5, 11, 16, and 23) acknowledges this iterative process. Aside from Cochrane reviews, all of which should have a protocol, only about 10% of systematic reviewers report working from a protocol [22]. Without a protocol that is publicly accessible, it is difficult to judge between appropriate and inappropriate modifications.
Animals assemble and maintain a diverse but host-specific gut microbial community. In addition to characteristic microbial compositions along the longitudinal axis of the intestines, discrete bacterial communities form in microhabitats, such as the gut lumen, colonic mucus layers and colonic crypts. In this Review, we examine how the spatial distribution of symbiotic bacteria among physical niches in the gut affects the development and maintenance of a resilient microbial ecosystem. We consider novel hypotheses for how nutrient selection, immune activation and other mechanisms control the biogeography of bacteria in the gut, and we discuss the relevance of this spatial heterogeneity to health and disease.
The effect of Roundup® on adrenal gland steroidogenesis and signaling pathway associated with steroid production was investigated. Doses of 10, 50, 100 and 250 mg/kg bw/d Roundup® were administered for two weeks to adult male rats. The 10 mg/kg bw/d dose which reduced circulatory corticosterone levels, but did not change food consumption and body weight, was selected for further study. The expression of cholesterol receptor (low density lipoprotein receptor), de novo cholesterol synthesis enzyme (3-hydroxy-3-methylglutaryl-coenzyme A synthase), hormone-sensitive lipase, steroidogenic acute regulatory protein (StAR) mRNA and phosphorylated form was decreased. Adrenocorticotropic hormone receptor (ACTH), melanocortin-2 receptor, expression was not changed but circulatory ACTH levels and adrenal cortex protein kinase A (PKA) activity were reduced. Surprisingly, exogenous ACTH treatment rescued steroidogenesis in Roundup®-treated animals. Apoptosis was evident at 250 mg/kg bw/d, but not at 10 mg/kg bw/d dose. These results suggest that Roundup® may be inhibitory to hypothalamic–pituitary axis leading to reduction in cyclic adenosine monophosphate (cAMP)/PKA pathway, StAR phosphorylation and corticosterone synthesis in the adrenal tissue.
Background:
Incidence rates of lymphoma are usually higher in men than in women, and oestrogens may protect against lymphoma.
Methods:
We evaluated occupational exposure to endocrine disrupting chemicals (EDCs) among 2457 controls and 2178 incident lymphoma cases and subtypes from the European Epilymph study.
Results:
Over 30 years of exposure to EDCs compared to no exposure was associated with a 24% increased risk of mature B-cell neoplasms (P-trend=0.02). Associations were observed among men, but not women.
Conclusions:
Prolonged occupational exposure to endocrine disruptors seems to be moderately associated with some lymphoma subtypes.
Pesticides can affect the health of living organisms through different mechanisms such as membrane denaturation. The evaluation of the deleterious effects of chemical agents on biological membranes can be performed through the analysis of the stability of erythrocytes against a concentration gradient of certain chemical agent in physiologic saline solution. This work analyzed the effect of the herbicide Roundup® on the membrane of human erythrocytes in blood samples collected with EDTA or heparin as anticoagulant agent. The results were analyzed through spectrophotometry at 540 nm and light microscopy. There was an agreement between spectrophometric and morphologic analyses. At the concentration limit recommended for agricultural purposes, Roundup® promoted 100% of hemolysis. The D50Roundup® values obtained for human blood samples collected with EDTA were not significantly different from those obtained for samples collected with heparin. However, the lysis curves presented lower absorbance values at 540 nm in the presence of blood collected with EDTA in relation to that collected with heparin, probably due to hemoglobin precipitation with EDTA. This work also analyzed the effects of three different Roundup® doses (0.148, 0.754 and 1.28 mg/kg) on the micronuclei frequency in bone marrow cells of Swiss mice in relation to a positive control of cyclophosphamide (250 mg/kg). The two highest Roundup® doses showed the same genotoxicity level as the positive control.
This paper describes results from a systematic review and a series of meta-analyses of nearly three decades worth of epidemiologic research on the relationship between non-Hodgkin lymphoma (NHL) and occupational exposure to agricultural pesticide active ingredients and chemical groups. Estimates of associations of NHL with 21 pesticide chemical groups and 80 active ingredients were extracted from 44 papers, all of which reported results from analyses of studies conducted in high-income countries. Random effects meta-analyses showed that phenoxy herbicides, carbamate insecticides, organophosphorus insecticides and the active ingredient lindane, an organochlorine insecticide, were positively associated with NHL. In a handful of papers, associations between pesticides and NHL subtypes were reported; B cell lymphoma was positively associated with phenoxy herbicides and the organophosphorus herbicide glyphosate. Diffuse large B-cell lymphoma was positively associated with phenoxy herbicide exposure. Despite compelling evidence that NHL is associated with certain chemicals, this review indicates the need for investigations of a larger variety of pesticides in more geographic areas, especially in low- and middle-income countries, which, despite producing a large portion of the world's agriculture, were missing in the literature that were reviewed.
We demonstrated that glyphosate possesses tumor promoting potential in mouse skin carcinogenesis and SOD 1, calcyclin (S100A6), and calgranulin B (S100A9) have been associated with this potential, although the mechanism is unclear. We aimed to clarify whether imbalance in between [Ca(2+)] i levels and oxidative stress is associated with glyphosate-induced proliferation in human keratinocytes HaCaT cells. The [Ca(2+)] i levels, ROS generation, and expressions of G1/S cyclins, IP3R1, S100A6, S100A9, and SOD 1, and apoptosis-related proteins were investigated upon glyphosate exposure in HaCaT cells. Glyphosate (0.1 mM) significantly induced proliferation, decreases [Ca(2+)] i , and increases ROS generation in HaCaT cells, whereas antioxidant N-acetyl-L-cysteine (NAC) pretreatment reverts these effects which directly indicated that glyphosate induced cell proliferation by lowering [Ca(2+)] i levels via ROS generation. Glyphosate also enhanced the expression of G1/S cyclins associated with a sharp decrease in G0/G1 and a corresponding increase in S-phases. Additionally, glyphosate also triggers S100A6/S100A9 expression and decreases IP3R1 and SOD 1 expressions in HaCaT cells. Notably, Ca(2+) suppression also prevented apoptotic related events including Bax/Bcl-2 ratio and caspases activation. This study highlights that glyphosate promotes proliferation in HaCaT cells probably by disrupting the balance in between [Ca(2+)] i levels and oxidative stress which in turn facilitated the downregulation of mitochondrial apoptotic signaling pathways.
Our aim was to evaluate whether postnatal exposure to a glyphosate-based herbicide (GBH) modifies mammary gland development in pre- and post-pubertal male rats. From postnatal day 1 (PND1) to PND7, male rats were injected subcutaneously every 48 h with either saline solution (vehicle) or 2 mg GBH/kg·bw. On PND21 and PND60, mammary gland and blood samples were collected. Estradiol (E2) and testosterone (T) serum levels, mammary gland histology, collagen fiber organization, mast cell infiltration, proliferation index, and estrogen (ESR1) and androgen receptor (AR) expression levels were evaluated. At PND21, GBH-exposed male rats exhibited greater development of the mammary gland with increased stromal collagen organization and terminal end buds (TEBs) compared to control rats. At PND60, the number of TEBs remained high and was accompanied by an increase in mast cell infiltration, proliferation and ESR1 expression in GBH-exposed male rats. In contrast, no effects were observed in E2 and T serum levels and AR expression in both days studied. Our results showed that a postnatal subacute treatment with GBH induces endocrine-disrupting effects in the male mammary gland in vivo, altering its normal development.
Research on disease causation often attempts to isolate the effects of individual factors, including individual genes or environmental factors. This reductionist approach has generated many discoveries, but misses important interactive and cumulative effects that may help explain the broad range of variability in disease occurrence observed across studies and individuals. A disease rarely results from a single factor, and instead results from a broader combination of factors, characterized here as intrinsic (I) and extrinsic (E) factors. Intrinsic vulnerability or resilience emanates from a variety of both fixed and shifting biological factors including genetic traits, while extrinsic factors comprise all biologically-relevant external stressors encountered across the lifespan. The I × E concept incorporates the multi-factorial and dynamic nature of health and disease and provides a unified, conceptual basis for integrating results from multiple areas of research, including genomics, G × E, developmental origins of health and disease, and the exposome. We describe the utility of the I × E concept to better understand and characterize the cumulative impact of multiple extrinsic and intrinsic factors on individual and population health. New research methods increasingly facilitate the measurement of multifactorial and interactive effects in epidemiological and toxicological studies. Tiered or indicator-based approaches can guide the selection of potentially relevant I and E factors for study and quantification, and exposomics methods may eventually produce results that can be used to generate a response function over the life course. Quantitative data on I × E interactive effects should generate a better understanding of the variability in human response to environmental factors. The proposed I × E concept highlights the role for broader study design in order to identify extrinsic and intrinsic factors amenable to interventions at the individual and population levels in order to enhance resilience, reduce vulnerability and improve health.
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.
The herbicide Roundup is sprayed onto genetically modified crops and applied as a desiccant to most small non–genetically modified grains. Use of this herbicide has increased since 1994 when genetically modified crops were introduced in the United States. Glyphosate, the primary ingredient in the herbicide, is found in these crops at harvest.¹ Environmental exposure through dietary intake of these crops has potential adverse health effects and can be assessed by measuring urinary excretion.²- 4 We measured excretion levels of glyphosate and its metabolite aminomethylphosphonic acid (AMPA) in participants from the Rancho Bernardo Study (RBS) of Healthy Aging.
Glyphosate is currently considered the most important herbicide of the world due to its broad-spectrum activity, effectiveness, and loss of global patent protection. Its ubiquitous presence in the environment due to anthropogenic activities and recalcitrance has the potential to affect animal behavior and interfere with ecological processes. Despite its important role in the protection of crops, it is important to establish strategies to reduce potential human exposure or decrease its presence in the environment. To date, only one microbial enzyme known as C-P lyase is acknowledged to drive complete glyphosate mineralization. AMPA, the common metabolite product of glyphosate biodegradation, still possesses the unique C-P bond of phosphonates and retains it toxic profile and recalcitrance. Thus, it is important to consider glyphosate and AMPA biodegradation altogether. Nevertheless, the potential to develop a bioremediation process is mainly limited by the genetic regulatory system that governs the expression of the C-P lyase, as it strongly depends on low environmental levels of phosphate. Thus, the complete mineralization of this herbicide by the sole use of microorganisms would remain insufficient until (1) more research on additional genetic control mechanisms of C-P lyase expression are explored, (2) alternative enzymes are studied in detailed, or (3) more complex and elaborated processes are considered. This work explores the available information on glyphosate biodegradation over the course of 40 years of study, the different pathways involving the C-P lyase, the genetic and physiological regulatory system that governs these processes, and the factors limiting the development of glyphosate bioremediation technologies.
Occupational exposures to chemicals have been implicated in the origin of cancers of the skin, lung, and urinary bladder. To evaluate the cancer experience of chemists in general, study was made of the causes of death among 3,637 members of the American Chemical Society who died between 1948 and 1967. A significantly higher proportion of deaths from cancer was found among male chemists in the two age categories, 20–64 years and over 64 years, as compared with professional men in general (P<0.001) and the elderly white male population (P <0.05) in the United States. Nearly half the excess cancer deaths were attributed to malignant lymphoma and carcinoma of the pancreas. Despite methodologic imperfections, these findings and other fragmentary data suggest that chemical agents may induce cancers of the pancreas and lymphoid tissue in man.
The US Environmental Protection Agency's voluntary National Radon Proficiency Programmes: Radon Measurement, and Reduction Proficiency are described, including their history and development, current status and future directions. The Radon Measurement Proficiency (RMP) and Radon Contractor Proficiency (RCP) programmes are fundamental to the Agency's programme to reduce the health risk associated with exposure to elevated radon levels in indoor air. Originally developed to provide technical assistance to States, the proficiency programmes now offer US consumers assurance of the quality of their radon measurements and reduction jobs. In other words, the proficiency programmes provide a means to consumers for deciding from which organisations or individuals to purchase radon services. This is especially important in the United States where most radon services are acquired through private enterprises rather than through the public sector. The Agency encourages the public to purchase radon measurement and reduction services only from organisations or individuals that have met the requirements of EPA's proficiency programmes. An increasing number of States require an EPA proficiency listing for their radon registration, licensing, and certification programmes. EPA estimates that about 85% of US companies offering radon services are participating in its proficiency programmes. Consequently, the Agency believes that the development and growth of quality radon services has kept pace with consumer demand. The United States markeplace for residential radon measurement and mitigation services has been dynamic since its inception in the mid-1980s. The fluidity of the market is likely to continue, with some significant changes appearing imminent. The US Congress is now considering legislation that would require participation in the Agency's radon proficiency programmes. In addition, this legislation contains provisions that would encourage consumer testing. Increased testing, coupled with a mandatory national proficiency programme, is likely to result in an increase in the quality of radon services available to the US public.
Lactose intolerance is characterized by low or inexistent levels of lactase, and the main treatment consists of dietary changes, especially replacing cow's milk by soy milk. Soy contains phytoestrogens, substances with known estrogenic activity, besides, glyphosate-based herbicides are extensively used in soy crops, being frequently a residue in soy beans, bringing to a concern regarding the consumption of soy-based products, especially for children in breastfeeding period with lactose intolerance. This study evaluated the pubertal toxicity of a soy milk rich feeding (supplemented or not with glyphosate, doses of 50 and 100 mg/kg) during prepubertal period in male rats. Endocrine disruption was observed through decrease in testosterone levels, decrease in Sertoli cell number and increase in the percentage of degenerated Sertoli and Leydig cells in animals receiving soy milk supplemented with glyphosate (both doses) and in animals treated only with soy milk. Animals treated with soy milk with glyphosate (both doses) showed decrease spermatids number and increase of epididymal tail mass compared to control, and decrease in the diameter of seminiferous tubules compared to soy milk control group. Animals receiving soy milk supplemented with 100 mg/kg glyphosate showed decrease in round spermatids and increase in abnormal sperm morphology, compared to control.
Glyphosate (GLY) is a common herbicide used worldwide but its effect on ovarian function in mammals is unknown. The aim of this study was to determine the potential endocrine disruptor effects of GLY on ovarian function evaluating cell proliferation, steroidogenesis and gene expression using bovine granulosa cells (GC) and theca cells as in vitro models. GC proliferation was impaired (P < 0.05) after exposure to GLY at 0.5, 1.7 and 5 μg ml−1. GC progesterone production was not affected (P ≥ 0.05) at all doses tested while estradiol production was inhibited (P < 0.05) by GLY at 5 μg ml−1. At the same concentration GLY showed no effect (P ≥ 0.05) on theca cell proliferation and steroidogenesis. At higher concentrations (0.01 and 0.3 mg ml−1), GLY had no significant effect (P ≥ 0.05) on GC proliferation and steroidogenesis. These studies, for the first time, suggest that GLY may affect the reproductive system in cattle via direct action on ovarian function; however, further studies will be required to understand better the mechanism of action and to determine the in vivo reproductive effects of GLY. Copyright
Glyphosate is one of the most used herbicides in agricultural lands worldwide. Wind-eroded sediment and dust, as an environmental transport pathway of glyphosate and of its main metabolite aminomethylphosphonic acid (AMPA), can result in environmental- and human exposure far beyond the agricultural areas where it has been applied. Therefore, special attention is required to the airborne transport of glyphosate and AMPA. In this study, we investigated the behavior of glyphosate and AMPA in wind-eroded sediment by measuring their content in different size fractions (median diameters between 715 and 8 μm) of a loess soil, during a period of 28 days after glyphosate application. Granulometrical extraction was done using a wind tunnel and a Soil Fine Particle Extractor. Extractions were conducted on days 0, 3, 7, 14, 21 and 28 after glyphosate application. Results indicated that glyphosate and AMPA contents were significantly higher in the finest particle fractions (median diameters between 8 and 18 μm), and lowered significantly with the increase in particle size. However, their content remained constant when aggregates were present in the sample. Glyphosate and AMPA contents correlated positively with clay, organic matter, and silt content. The dissipation of glyphosate over time was very low, which was most probably due to the low soil moisture content of the sediment. Consequently, the formation of AMPA was also very low. The low dissipation of glyphosate in our study indicates that the risk of glyphosate transport in dry sediment to off-target areas by wind can be very high. The highest glyphosate and AMPA contents were found in the smallest soil fractions (PM10 and less), which are easily inhaled and, therefore, contribute to human exposure.
Objectives Multiple myeloma (MM) has been linked to certain agricultural exposures, including pesticides, however the effects of exposure to multiple pesticides have not been explored. This analysis investigated the association between self-reported use of multiple pesticides and MM risk. Commonly used pesticide combinations and interactive effects were also assessed.
Methods A frequency matched population-based case-control study was conducted among men in 6 Canadian provinces between 1991 and 1994. Data from 342 MM cases and 1506 controls were analysed using logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). Pesticides were grouped by type, chemical class and carcinogenicity. Carcinogenic probability values were created using evaluations from the International Agency for Research on Cancer and U. S. Environmental Protection Agency. Regression models were adjusted for age, province of residence, use of proxy respondents, smoking, and selected medical history variables. Trends were examined using ordinal variables. Commonly used pesticide combinations were assessed for interaction on the additive scale using the interaction contrast ratio (ICR).
Results Multiple pesticide use was not associated with monotonically increasing odds of MM, although positive trends were observed for “probably” carcinogenic pesticides (ptrend = 0.01), insecticides (ptrend = 0.07), and fungicides (ptrend = 0.05). Higher odds of MM were observed among men who reported using at least one carbamate pesticide (OR = 1.99, 95% CI: 1.19–3.33), one phenoxyherbicide (OR = 1.60, 95% CI: 1.11–2.30), 3 or more “probably” carcinogenic pesticides (OR = 2.14, 95% CI: 1.01–4.52), and 3 or more organochlorines (OR = 2.26, 95% CI: 1.07–4.78). Investigating commonly used pesticide combinations, revealed increased odds among men who used both chlordane and mecoprop (OR = 2.18, 95% CI: 1.12–4.27; ICR = 0.63).
Conclusions Focusing on multiple pesticides is important because this more accurately reflects how exposures occur in occupational settings. Although the overall pattern of results was complex, excess risks observed for certain pesticide types and chemical classes suggest these may be MM risk factors.
A revision of the nearly 8 year old WHO classification of the lymphoid neoplasms and the accompanying monograph is being published. It reflects a consensus among hematopathologists, geneticists and clinicians regarding both updates to current entities as well as the addition of a limited number of new provisional entities. The revision clarifies the diagnosis and management of lesions at the very early stages of lymphomagenesis, refines the diagnostic criteria for some entities, details the expanding genetic/molecular landscape of numerous lymphoid neoplasms and their clinical correlates, and refers to investigations leading to more targeted therapeutic strategies. The major changes are reviewed with an emphasis on the most important advances in our understanding that impact our diagnostic approach, clinical expectations and therapeutic strategies for the lymphoid neoplasms.
The literature of regression analysis with missing values of the independent variables is reviewed. Six classes of procedures are distinguished: complete case analysis, available case methods, least squares on imputed data, maximum likelihood, Bayesian methods, and multiple imputation. Methods are compared and illustrated when missing data are confined to one independent variable, and extensions to more general patterns are indicated. Attention is paid to the performance of methods when the missing data are not missing completely at random. Least squares methods that fill in missing X's using only data on the X's are contrasted with likelihood-based methods that use data on the X's and Y. The latter approach is preferred and provides methods for elaboration of the basic normal linear regression model. It is suggested that more widely distributed software is needed that advances beyond complete-case analysis, available-case analysis, and naive imputation methods. Bayesian simulation methods and multiple imputation are reviewed; these provide fruitful avenues for future research.
Microbiota and host form a complex 'super-organism' in which symbiotic relationships confer benefits to the host in many key aspects of life. However, defects in the regulatory circuits of the host that control bacterial sensing and homeostasis, or alterations of the microbiome, through environmental changes (infection, diet or lifestyle), may disturb this symbiotic relationship and promote disease. Increasing evidence indicates a key role for the bacterial microbiota in carcinogenesis. In this Opinion article, we discuss links between the bacterial microbiota and cancer, with a particular focus on immune responses, dysbiosis, genotoxicity, metabolism and strategies to target the microbiome for cancer prevention.
A published method for analyzing multiple 2×2 contingency tables arising in retrospective studies of disease is extended in application and form. Extensions of application include comparisons of age-adjusted death rates, life-table analyses, comparisons of two sets of quantal dosage-response data, and miscellaneous laboratory applications as appropriate. Extensions in form involve considering multiple contingency tables with arbitrarily many rows and/or columns, where rows and columns are orderable, and may even be on a continuous scale. The assignment of some score for each row or column is essential to use of the method. With scores assigned, a deviation of the sum of cross products from expectation, and its variance conditioned on all marginal totals, are computed for each table and a chi square is determined corresponding to the grand total of the deviations. For various specific instances and for various scoring procedures, the procedure extends or is equivalent to the asymptotic form of many known non-parametric techniques.
Field studies on the uptake and persistence of glyphosate (N-(phosphonomethyl)glycine) on wild blueberry (Vacciniummyrtilloides Michx.) and red raspberry (Rubusstrigosus Michx.) under boreal forest (Matheson, Ont.) conditions were undertaken. Uptake studies indicated that less than 10% of glyphosate penetrated the fruit in the first 9 h postapplication. Results of the persistence studies showed a gradual decline in residue levels with time. Times to 50% dissipation for glyphosate residue as determined by curvilinear regression analyses were <20 days (95% confidence limit of 8–26 days) and <13 days (95% confidence limit of 6–14 days) for blueberry and raspberry fruit, respectively. Initial residue levels dissipated to approximately 4 and 6% after 61 and 33 days for the blueberry and raspberry, respectively. Results also showed that at no time during the study period did glyphosate levels in either substrate dissipate to below the maximum permissible residue level (0.01 ppm) as established by Health and Welfare Canada.