No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
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.
... A growing body of evidence points to GBH exposure-driven adverse impacts on human reproduction [22][23][24][25][26][27][28][29] and upon the incidence of certain cancers, especially non-Hodgkin lymphoma [30][31][32][33][34][35][36][37][38][39][40][41][42][43]. The first evidence of adverse reproductive impacts emerged before the introduction of Roundup Ready seeds. ...
... Several published reviews address differences in the OPP/EPA and IARC assessments of glyphosate/GBH carcinogenicity [32,[54][55][56]. Other reviews and meta-analyses focus on published epidemiology studies exploring whether dermal exposures to GBHs alter the risk of NHL [31,34,37]. ...
... Most published studies done by scientists not affiliated with or funded by registrants of GHB herbicides conclude that there is limited-to-ample epidemiological data establishing an association between GBH use and NHL. For example, a team of scientists including three individuals that served on the December 2016 Scientific Advisory Panel assessing GBH oncogenicity concludes their meta-analysis by saying: "The overall evidence from human, animal, and mechanistic studies presented here supports a compelling link between exposures to GBHs and increased risk of NHL" [31]. ...
Controversy over the oncogenicity of glyphosate-based herbicides (GBHs) persists seven years after a 2015 IARC Monograph classified glyphosate/GBHs as "probably carcinogenic" to humans. Most regulatory authorities have concluded that technical glyphosate poses little or no oncogenic risk via dietary exposure. The US EPA classified glyphosate as "not likely" to pose cancer risk in 1991, a decision reaffirmed in reports issued in 2017 and 2020. A Federal Circuit Court of Appeals in the US vacated EPA's assessment of glyphosate human-health risks in 2022 and required EPA to revisit old and take into account new data in its forthcoming, possibly final glyphosate/GBH reregistration decision. Divergent assessments of GBH genotoxicity are the primary reason for differing conclusions regarding GBH oncogenic potential. We assessed whether assays published since completion of the EPA and IARC reviews shed new light on glyphosate/GBH genotoxicity. We found 94 such assays, 33 testing technical glyphosate (73% positive) and 61 on GBHs (95% positive). Seven of 7 in vivo human studies report positive results. In light of genotoxicity results published since 2015, the conclusion that GBHs pose no risk of cancer via a genotoxic mechanism is untenable.
... [12,14,28,29,30,31] Usually, this development is skewed towards a particular subtype of lymphoma. [31,32,33,34,35,36,37,38,39,40] Our understanding of the shared underlying mechanisms among such heterogeneous conditions is extremely limited. However, similarities too striking to be the result of mere coincidence have been observed among seemingly unconnected lymphoma-predisposing conditions. ...
... [268] An association between herbicides and lymphoma has not been consistently shown across studies, though some evidence exists supporting an increased relative risk of lymphoma for the highest exposure quartile among pesticide users exposed to glyphosate, one of the most heavily used herbicides worldwide. [34,269] Additionally, a recent meta-analysis showed a significantly increased relative risk of lymphoma after glyphosate exposure. [34] Other risk factors associated with lymphoma include smoking status, residential or occupational exposure to petroleum, exposure to benzene and occupational exposure to metals, occupational exposure to chlorinated solvents, and employment as hairdresser. ...
... [34,269] Additionally, a recent meta-analysis showed a significantly increased relative risk of lymphoma after glyphosate exposure. [34] Other risk factors associated with lymphoma include smoking status, residential or occupational exposure to petroleum, exposure to benzene and occupational exposure to metals, occupational exposure to chlorinated solvents, and employment as hairdresser. [270,271,272,273,274,275] Smoking status was particularly associated with T-NHL subtypes and HL was associated with smoking status as well. ...
... However, several studies and reviews have found contrasting evidence regarding the potential impacts of glyphosate herbicides on wildlife, and ecosystem functionality (e.g., Santillo et al., 1989;Mackinnon and Freedman, 1993;Cole et al., 1997;Cole et al., 1998, Santillo et al., 1998, Howe et al., 2004Relyea, 2005;Relyea and Jones, 2009;Thompson et al., 2014;Abraham et al., 2018;Motta et al., 2018). Additionally, conclusions about potential impacts on human health and safety are highly contentious amongst the academic community (e.g., De Roos et al., 2005;Zhang et al., 2019) 2017). Neither ecological, nor risk assessment studies have been conducted through an Indigenous Knowledge lens to our knowledge. ...
... The toxicity and risk to human health posed by glyphosate and its formulations is an obvious concern to the general public including Indigenous communities, and a highly contentious issue amongst academics, and international regulators. Human health risk assessments have been conducted on glyphosate and/or its formulations by both academic researchers (De Roos et al., 2005;Zhang et al., 2019) Several reviews have been conducted analyzing how regulatory bodies could come to such drastically different conclusions around the same substance. These differences in rulings between regulatory agencies have largely been attributed to methodological differences in the evaluation of available evidence, as well as reliance on different data sets between regulatory bodies (Tarazona et al., 2017;Benbrook, 2019). ...
... and various regulatory agencies (European Food Safety Authority, 2015; Pest Management Regulatory Agency, 2015; United States Environmental Protection Agency, 2016; International Agency for Research on Cancer,2017), with discrepancies in results. These studies range in their conclusions from linking glyphosate with cancers such as non-Hodgkin's lymphoma(Zhang et al., 2019), to claiming no ill effects(De Roos et al., 2005;Greim et al., 2015).Health Canada's Pest Management Regulatory Agency (PMRA) launched a routine re-evaluation of glyphosate in 2009 (Pest Management Regulatory Agency, 2010). A report outlining the PMRA's decision was released in 2015 based on available information provided by the manufacturer of the pesticide, published scientific literature, environmental monitoring information (e.g. ...
Introduction
For decades, herbicide application in commercial forestry has been a serious concern for First Nations across northern Ontario. To date, the vast majority of studies concerning the impacts of glyphosate-based herbicides have been conducted through a Western scientific lens. Indigenous knowledge systems provide holistic frameworks which acknowledge the interconnectedness of the environment and provide a holistic view of relationships between flora, fauna, environment, and humans. This socio-ecological perspective is key to understanding the wide-ranging impacts of commercial forestry on the wellbeing of Indigenous Peoples.
Methods
Through a knowledge sharing workshop, “Connecting Guardians in a Changing World”, we interviewed community members from First Nations across the Robinson-Huron Treaty Area and asked them to share their knowledge and concerns regarding herbicide use in commercial forestry. Based on the topics discussed in the workshop, we conducted a literature review to further investigate documented Western scientific evidence on workshop participants’ concerns. We then wove the responses of participants and Western Science to identify key concerns of participants regarding the use of glyphosate-based herbicides, identify gaps in current knowledge, and to direct future research.
Results
We identified three main research gaps regarding glyphosate-based herbicide impacts used in forestry: 1) research regarding the direct effects of glyphosate-based herbicide toxicity to most of the fauna and flora of the Great Lakes region of northeastern Ontario as well as its environmental persistence, 2) research regarding the indirect effects of glyphosate-based herbicides to the ecosystem and resulting impacts of trophic cascades, and 3) research regarding the impacts of glyphosate-based herbicides to Indigenous culture and community wellbeing.
Discussion
By weaving knowledge systems in this way, we can conduct research through an inclusive system which prioritizes the inclusion of multiple ways of knowing, addressing environmental concerns in holistic and inclusive ways which emphasize the interconnectedness of the environment, including humans therein.
... The association between a large number of work classes and chemical compounds associated with the development of NHL and its subtypes has not been evaluated in any review. Reviews typically evaluate the association between the increased risk of overall NHL or some specific subtype with only one group of chemical agents or work class [21,22,46,47]. In our review, the following occupations: painter, driver, construction worker, hairdresser, chemical industry employee, solvent-exposed employees, agricultural mechanics and laborers, husbandry workers, and fishing laborers were the most The association between a large number of work classes and chemical compounds associated with the development of NHL and its subtypes has not been evaluated in any review. ...
... In our review, the following occupations: painter, driver, construction worker, hairdresser, chemical industry employee, solvent-exposed employees, agricultural mechanics and laborers, husbandry workers, and fishing laborers were the most The association between a large number of work classes and chemical compounds associated with the development of NHL and its subtypes has not been evaluated in any review. Reviews typically evaluate the association between the increased risk of overall NHL or some specific subtype with only one group of chemical agents or work class [21,22,46,47]. In our review, the following occupations: painter, driver, construction worker, hairdresser, chemical industry employee, solvent-exposed employees, agricultural mechanics and laborers, husbandry workers, and fishing laborers were the most investigated work classes used in the studies included in the review. ...
... A positive association between occupational exposure to some pesticides and the development of NHL was verified in the review study by Schinasi and Leon [94], in which they provided consistent evidence of this relationship. Exposure to glyphosate-based herbicides, 2,4-D and diazinon were also associated with increased risk of NHL in humans [22,46,47]. ...
Non-Hodgkin lymphoma (NHL) is a heterogeneous group with different types of diseases. It remains unclear as to what has led to an increase in incidences of NHL, however, chemical substance exposure is known to be one of the risk factors for the disease. Therefore, we performed a systematic review and meta-analysis including case-control, cohort, and cross-sectional observational epidemiological studies to verify the association between occupational exposure to carcinogens and NHL risk. Articles between the years 2000 and 2020 were collected. Two different reviewers performed a blind selection of the studies using the Rayyan QCRI web app. Post-completion, the selected articles were extracted and analyzed via the RedCap platform. Our review resulted in 2719 articles, of which 51 were included in the meta-analysis, resulting in an overall OR of 1.27 (95% CI 1.04–1.55). Furthermore, it was observed that the main occupation associated with the increased risk of NHL was that in which workers are exposed to pesticides. We therefore conclude that the evidence synthesis of the epidemiological literature supports an increased risk for NHL, regardless of subtype, considering occupational exposure to certain chemical compounds, mainly pesticides, benzene, and trichlorethylene, and certain classes of work, primarily in the field of agriculture.
... A growing body of evidence points to GBH exposure-driven adverse impacts on human reproduction [22][23][24][25][26][27][28][29] and upon the incidence of certain cancers, especially non-Hodgkin lymphoma [30][31][32][33][34][35][36][37][38][39][40][41][42][43]. The first evidence of adverse reproductive impacts emerged before the introduction of Roundup Ready seeds. ...
... Several published reviews address differences in the OPP/EPA and IARC assessments of glyphosate/GBH carcinogenicity [32,[54][55][56]. Other reviews and meta-analyses focus on published epidemiology studies exploring whether dermal exposures to GBHs alter the risk of NHL [31,34,37]. ...
... Most published studies done by scientists not affiliated with or funded by registrants of GHB herbicides conclude that there is limited-to-ample epidemiological data establishing an association between GBH use and NHL. For example, a team of scientists including three individuals that served on the December 2016 Scientific Advisory Panel assessing GBH oncogenicity concludes their meta-analysis by saying: "The overall evidence from human, animal, and mechanistic studies presented here supports a compelling link between exposures to GBHs and increased risk of NHL" [31]. ...
Controversy over the oncogenicity of glyphosate-based herbicides (GBHs) persists seven years after a 2015 IARC Monograph classified glyphosate/GBHs as “probably carcinogenic” to humans. Most regulatory authorities have concluded that technical glyphosate poses little or no oncogenic risk via dietary exposure. The US EPA classified glyphosate as “not likely” to pose cancer risk in 1991, a decision reaffirmed in reports issued in 2017 and 2020. A Federal Circuit Court of Appeals in the US vacated EPA’s assessment of glyphosate human-health risks in 2022 and required EPA to revisit old and take into account new data in its forthcoming, possibly final glyphosate/GBH reregistration decision. Divergent assessments of GBH genotoxicity are the primary reason for differing conclusions regarding GBH oncogenic potential. We assessed whether assays published since completion of the EPA and IARC reviews shed new light on glyphosate/GBH genotoxicity. We found 94 such assays, 33 testing technical glyphosate (73% positive) and 61 on GBHs (95% positive). Seven of 7 in vivo human studies report positive results. In light of genotoxicity results published since 2015, the conclusion that GBHs pose no risk of cancer via a genotoxic mechanism is untenable.
... Another meta-analysis carried out by Zhang et al., (2019), concluded that human exposure to glyphosate is associated with the risk of non-Hodgkin lymphoma (RR: 1.41; 95% CI: 1.13-1.75) and that there is a greater risk of Non-Hodgkin Lymphoma in groups that have greater exposure to the herbicide (RR: 1.45; 95% CI: 1.11-1.91), ...
... In addition, this meta-analysis was P á g i n a 3003 based on risk estimates from the included studies at the highest reported exposure level obtained from analyzes with the longest latency period. Kabat, Price & Tarone (2021) reviewed the work of Zhang et al., (2019) performing a sensitivity analysis to determine how the definition of exposure and the choice of latency period affect the summary estimate discussed previously, so in their own meta-analysis they included the more up-to-date results from casecontrol studies, noting that at higher exposure levels there is evidence of an association between glyphosate and non-Hodgkin lymphoma and this association was stronger when estimates from one study analysis were included cohort with a latency of 20 years (RR: 1.41; 95%CI: 1.13-1.76) and a latency of 15 years (RR: 1.25; 95%CI: 1.01-1.25); ...
El glifosato es un herbicida de amplio espectro no selectivo y sistémico, cualquier planta puede absorberlo a través de sus tejidos. Su función consiste en destruir las plantas consideradas “malas yerbas” por los agricultores, es decir aquellas que “roban” espacio, luz, agua y nutrientes a la siembra. Otro de los usos del glifosato ha sido la aspersión aérea del químico para combatir cultivos de coca, amapola y marihuana, en países como Colombia, lo cual ha terminado por afectar la biodiversidad de áreas selváticas, al impactar más allá de las especies y los cultivos que son objetivo En el año 2015, la International Agency for Research on Cancer, concluyó que el glifosato es una sustancia probablemente cancerígena, a pesar de que algunas agencias, como la Autoridad Europea de Seguridad Alimentaria (EFSA), han dicho que no implica un riesgo y otras han minimizado los peligros, siempre y cuando se use “apropiadamente”, como la Agencia de Protección Ambiental de Estados Unidos (US EPA). En el presente artículo se revisan estas posturas a la luz de estudios científicos que han evaluado el impacto del uso del glifosato sobre la salud humana, especialmente como agente potencialmente cancerígeno.
... Human GLY exposure may occur through food stuffs (Bai and Ogbourne 2016;Chen et al. 2013;Kolakowski et al. 2020;Zoller et al. 2018) and drinking water (Guo et al. 2016;Pérez 2011). Although several studies have suggested that GLY and GBH have risks for human health (Garry et al. 2002;Parvez et al. 2018;Savitz et al. 1997;Zhang et al. 2019), little is known about GLY-induced reproductive and multigenerational ovarian toxicity. Human urinary GLY detection supports exposure independent of occupational status (Bøhn et al. 2014;Connolly et al. 2018;Curwin et al. 2007;Gillezeau et al. 2019), and a link between urinary GLY level and shortened gestational length in women has been reported (Lesseur et al. 2022;Parvez et al. 2018). ...
... Human GLY exposure may occur through food stuffs (Bai and Ogbourne 2016;Chen et al. 2013;Kolakowski et al. 2020;Zoller et al. 2018) and drinking water (Guo et al. 2016;Pérez 2011). Although several studies have suggested that GLY and GBH have risks for human health (Garry et al. 2002;Parvez et al. 2018;Savitz et al. 1997;Zhang et al. 2019), little is known about GLY-induced reproductive and multigenerational ovarian toxicity. This study investigated the effects of pre-conceptional maternal exposure to GLY on F1 offspring reproductive health. ...
Glyphosate (GLY) is an herbicide used for rural and urban weed control. Urinary GLY in women is associated with shortened gestational length yet effects of GLY on offspring due to maternal exposure are unclear. This study tested the hypothesis that maternal chronic pre-conceptional GLY exposure would cause phenotypic and molecular changes in F1 offspring. Female C57BL/6 mice (7 wk old; n = 40) received saline vehicle control (CT; n = 20) or GLY (2 mg/Kg; n = 20) daily per os for ten weeks. At dosing completion, females were housed with unexposed males and divided into Cohort 1 who were euthanized at gestation day (GD) 14 (n = 10 per treatment), and Cohort 2 who completed gestation (n = 10 per treatment). F1 female ovarian and liver samples underwent LC-MS/MS and bioinformatic analysis. Maternal exposure did not affect litter (P > 0.05) sex ratio, or embryonic or neonatal gross phenotypes. In Cohort 2 offspring, no treatment effect on (P > 0.05) offspring anogenital distance, puberty onset or ovarian follicular composition was noted. Body weight was increased (P < 0.05) in male GLY-exposed compared to CT dam offspring. F1 females from GLY-exposed dams, had altered (P < 0.05) abundance of 54 ovarian and 110 hepatic proteins. Pathways altered in the ovary (FDR ≤ 0.07) included thermogenesis and PI3K-AKT signaling and in liver (FDR ≤ 0.08) included metabolic, glutathione metabolism, oxidative phosphorylation, non-alcoholic fatty liver disease, and thermogenesis. Thus, pre-conceptional GLY exposure affected offspring phenotypic and molecular profiles potentially impacting reproductive health.
... Our results are important given the various health effects attributed to exposure to glyphosate and AMPA. In 2015, the International Agency for Research on Cancer (IARC) classified glyphosate as probably carcinogenic compound (Guyton et al., 2015) and a meta-analysis of Zhang et al. (2019) (Zhang et al., 2019) confirmed an increased risk of non-Hodgkin lymphoma at higher exposure to glyphosate-based formulations. However, the carcinogenicity of glyphosate remains under discussion (Meftaul et al., 2020). ...
... Our results are important given the various health effects attributed to exposure to glyphosate and AMPA. In 2015, the International Agency for Research on Cancer (IARC) classified glyphosate as probably carcinogenic compound (Guyton et al., 2015) and a meta-analysis of Zhang et al. (2019) (Zhang et al., 2019) confirmed an increased risk of non-Hodgkin lymphoma at higher exposure to glyphosate-based formulations. However, the carcinogenicity of glyphosate remains under discussion (Meftaul et al., 2020). ...
... Recent epidemiologic studies have expanded knowledge of the human carcinogenicity of glyphosate and GBHs. A recent meta-analysis reports that GBHs are associated with a 41% increased relative risk of non-Hodgkin lymphoma among highly exposed individuals (Zhang et al. 2019). Skidmore et al. showed a significant temporal and geographical relationship between expansion of soy cultivation in the Brazilian Amazon and Cerrado regions and deaths from acute lymphoblastic leukemia in children, one of the most common pediatric blood-borne cancer (Skidmore et al. 2023). ...
Background
Glyphosate-based herbicides (GBHs) are the world’s most widely used weed control agents. There has been intense and increasing public health concern about glyphosate and GBHs since the International Agency for Research on Cancer classified glyphosate as a probable human carcinogen in 2015.
Aims
To further study the health effects of glyphosate and GBHs, the Ramazzini Institute, in collaboration with an international network of institutes and universities, has launched the Global Glyphosate Study (GGS), the most comprehensive toxicological study ever performed on these compounds. The GGS is an integrated study designed to test a wide range of toxicological outcomes including carcinogenicity, neurotoxicity, multi-generational effects, organ toxicity, endocrine disruption and prenatal developmental toxicity. The present study reports the first definitive results on leukemia incidence and mortality from the carcinogenicity arm of the GGS.
Method
Glyphosate and two GBHs, Roundup Bioflow (MON 52276) used in the European Union (EU) and RangerPro (EPA 524-517) used in the U.S., were administered long-term to Sprague-Dawley (SD) rats beginning in prenatal life until 104 weeks of age via drinking water at doses of 0.5, 5, and 50 mg/kg body weight/day. This dose range encompasses both the EU Acceptable Daily Intake (ADI) and the EU No Observed Adverse Effect Level (NOAEL) for glyphosate. Each experimental group was composed of 51 males and 51 females, the total number animals were 1020 (510 males and 510 females).
Results
In the animals exposed to glyphosate, a significantly increased trend in incidence of lymphoblastic leukemia was observed in males. In the Roundup Bioflow-treated animals, significantly increased trends were observed in incidence of lymphoblastic leukemia (males and females), monocytic leukemia (males), total myeloid leukemia (males), and all leukemias combined (males and females). In the RangerPro-treated animals, significantly increased trends were observed in incidence of lymphoblastic leukemia (males and females), monocytic leukemia (males) and all leukemias combined (males). 43% of leukemias deaths in the glyphosate and GBHs treated groups occurred before the first year of age (52 weeks).
Conclusions
Glyphosate and GBHs at exposure levels corresponding to the EU ADI and the EU NOAEL caused significant, dose-related increased trends in incidence of leukemia, a very rare malignancy, in SD rats. Notably, about half of the leukemia deaths seen in the glyphosate and GBH groups occurred at less than one year of age, comparable to less than 35-40 years of age in humans.
... 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 andPannell 2008). In fact, there is evidence of cases in which male plants show higher concentration of secondary metabolites associated with defense against herbivores (Hjaltén 1992, Bañuelos et al. 2004, Zhang et al. 2019, Yang et al. 2020; including our study systemB. cordata (Moreira et al. 2019). ...
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 two months during a year (June 2010-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.
... Next to the wide productivity gains from the use of glyphosate, its health impacts are a subject of debate, ranging from being classified as 'probably carcinogenic' (IARC, 2015) to 'not carcinogenic' (ECHA, 2017) . Metaanalysis suggests a higher prevalence of Non-Hodgkin lymphoma (NHL) in those exposed long-term to glyphosate-based herbicides (Zhang et al., 2019), but determining a causal relationship in humans is difficult without experimentation (Álvarez et al., 2023). ...
Rwanda has been a notable player in sustainable development in the last decades, particularly in its agricultural practices. Based on extensive literature study and recent fieldwork, this paper offers a multifaceted exploration of Rwanda's specialty coffee sector. It highlights 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 towards 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 developments of sustainable agricultural systems.
... The masculinization of agriculture oppressing women farmers and creation of monocultures incentivized by biotechnology industries in India with devastating effects for soils (Shiva, 1999), corporations and shareholder policy (Korten, 1998), and consequences of such corporate culture in Brazil's mining disaster (Garcia et al., 2017) exemplify ethical egoism. The consequences of egoism featuring profit gains rather than soil security and human health are exemplified by the recent glyphosate 2 controversy with contrasting claims in regard to human toxicity (carcinogenic risk) by multibillion dollar industry conglomerates, environmental advocates (Benbrook, 2019), and empirical studies (Zhang et al., 2019). Specifically, enculturated egoism and socially sanctioned egoism may pose greater threats to emerging trends, such as Digital Agriculture (Shepherd et al., 2018) and Digital Soil Mapping/Pedometrics (McBratney et al., 2018). ...
Although land ethics and ethics focused on agriculture have been formalized, an explicit general soil ethics is lacking. The human approach to nature has been one of ethical relativism. Human-centric ethics that justify in one way or another the primacy of human desires, needs, values, and benefits have caused soil degradation and some serious destruction of the soil environment and planet Earth. This chapter provides an overview of normative ethical strands applied to soils/nature/environment that include (1) natural ethics (Natural Law ethics) grounded either in (a) entelechy, vital natural principle or (b) religious moralities (ethics of Divine Commands); (2) virtue ethics associated with valuation of soils/nature/Earth; (3) deontological ethics that is duty, obligation, or rule ethics subdivided into (a) act deontological ethics, (b) rule deontological ethics, and (c) Kantian ethics; (4) consequentialist ethics focused on the consequences (such as soil carbon sequestration; well-being and flourishing of people) with (a) ethical egoism, (b) act utilitarianism, and (c) rule utilitarianism; (5) intuitionist theory that combines duty and consequential ethics; and (6) relational ethics with (a) stewardship ethics and (b) ethics of care. A novel integrative soil ethics—Pluralistic Integral Soil Ethics (PISE)—is presented. PISE synthesizes multiple ethical pillars into a coherent soil ethics that informs the use, management, preservation, conservation, security, health, quality, and sacredness of soils. This integrative soil ethics features three pillars. The first pillar is focused on soil and environmental valuation and people’s moral standards toward soil. This pillar explores the meaning of virtue, which is the quality of being morally good (“minimizing harm”) in regard to soil and environment. The second pillar is focused on soil and environmental literacy (i.e., observable data, facts, knowledge, maps, and models of soils) and assessment of the consequences of soil use and management through understanding of cause-effect relations. The third pillar is focused on soil and environmental competency and awareness. This pillar represents ethics of care that stresses the empathic subjective and intersubjective intimate relations with soil/nature. Soil care is associated with people’s closeness to personalize soils and making them one’s own through sensing, feeling, and experiences of soil and nature. PISE is an integrative ethics that reframes “soil care” as a noun into an active process, that is, “to take care of soils,” which is deliberately intentional to minimize soil degradation and honor soils in terms of their beauty and naturalness.
... Some pesticides are more toxic than others and have been linked to higher rates of cancer. For example, the herbicide glyphosate has been linked to an increased risk of non-Hodgkin lymphoma [247]. Overall, addressing the disparities associated with pesticide exposure and pesticide-induced cancers will require a multi-faceted approach that includes regulatory changes, increased access to protective equipment, education and training for workers, and increased public awareness about the risks associated with pesticides. ...
Pesticides are widely used in agriculture to control weeds, insects, fungi, rodents, and other pests, but their use can have negative effects on both the environment and human health. This article discusses the various ways in which individuals can be exposed to pesticides and the potential health effects of such exposure. Growing evidence suggests that exposure to pesticides can increase the risk of developing cancer, with any class of pesticides being a risk factor. Specific chemicals in many classes of pesticides have been linked to various types of cancer. This article discusses the link between pesticide exposure and various types of cancer, including lung, breast, genitourinary, leukemia, brain, and myeloma. Efforts should be made to limit exposure to reduce cancer incidence, particularly with regard to certain pesticides such as organochlorines, triazines, organophosphates, chlorophenoxy, pyrethroids, and carbamates. While some pesticides are not considered carcinogenic due to a lack of evidence, in vitro and in vivo studies have shown characteristics of carcinogens for some pesticides. Further studies are required to evaluate the carcinogenicity of pesticides and reduce disparities in cancer risks.KeywordsPesticideCancerCarcinogenEpidemiologyHealth Disparities
... Our study supports that the method currently in use to estimate glyphosate intake is not accurate, our results do not validate the issue of an acceptable daily intake (ADI), which is an estimation of the exposure to glyphosate with no impact on human health. The assessment of the impact of both chronic and acute glyphosate exposure on human health has been established by many toxicological scientific studies (Alarcon et al. 2019;Dallegrave et al. 2007;de Araujo et al. 2016;Garry et al. 2002;Gunarathna et al. 2018;Gunatilake et al. 2019;IARC 2015;Ingaramo et al. 2020;Inserm 2021;Jarrell et al. 2020;Jayasumana et al. 2014;Leon et al. 2019;Manservisi et al. 2019;Nevison 2014;Ongono et al. 2020;Savitz et al. 1997;von Ehrenstein et al. 2019;Zhang et al. 2019), which are not taken into consideration by the ADI estimate (Benbrook 2019;Foucard 2021;Portier et al. 2016). ...
The acceptable daily intake (ADI) is an estimate of the amount of a substance in food or beverages that can be consumed daily over a lifetime without presenting an appreciable risk to health. To assess the risk of ingesting glyphosate, regulatory agencies compare glyphosate daily intake to ADI. Based on published data on urine glyphosate levels measured according to known quantities of ingested glyphosate, our objectives were to test the robustness of the mathematical model currently used to calculate glyphosate daily intake, and to propose alternative models based on urinary excretion kinetics. Our results support that the quantity of ingested glyphosate is systematically underestimated by the model currently used by regulatory agencies, whereas the other models evaluated showed better estimations, with differences according to gender. Our results also show a great variability between individuals, leading to some uncertainties notably with regards to the ADI, and further support that glyphosate excretion varies significantly among individuals who follow a similar dosing regimen. In conclusion, our study highlights the lack of reliability of assessment processes carried out by regulatory agencies for glyphosate in particular, and pesticides in general, and questions the relevance of such processes supposed to safeguard human health and the environment.
... Otros factores en contra de la fumigación incluyen el riesgo para la salud y alimentación humana para las comunidades. Dado que se fumiga desde lo alto, el viento provoca que la sustancia agroquímica afecte no solo la coca sino también otros cultivos de alimentación básica como maíz y yuca (Camacho y Mejía 2017;Andreotti et al. 2018;Zhang et al. 2019). Así lo comunicaba un miembro de la comunidad del Valle del Río Cimitarra entrevistado (Christian Aid, 2018): ...
For years Colombia has been the world's largest coca producer. Its public management of crops for illicit use has swung between eradication, substitution, and, recently legalization. Forced eradication has been shown to be ineffective, and legalization is an incipient option, so the Peace Agreement puts forward substitution as the path to follow. Yet, what kind of substitution does it suggest? This article analyzes voluntary substitution projects in Peasant Reserve Zones. While some projects have evolved locally due in part to strong peasant associations, they have not gained traction nationally. In general, the difficulties inherent in any business play a role, but there are also structural limitations such as continued fumigations, obligations of prior eradication, the costs of production and transportation due to the lack of infrastructure and public services, and the issue of land rights, which limits peasants' access to the formal funding established by the Peace Agreement.
... Some particularly thorough reviews discuss health risks [29][30][31][32] and ecotoxicology [33], while more focused reviews elaborate on the effects on water fleas [34], on bees [35] and honeybees [36,37], on fish [38], on amphibians [39], in South American agriculture [40], as studied in Brazil [41], in aquatic systems [42,43], and to offspring of exposed mothers [44]. Other reviews focus on particular outcomes of toxicity, including cancer and genotoxicity [45][46][47], pregnancy outcomes [48][49][50], mammalian nervous systems [51], and autism spectrum disorders [52][53][54][55]. ...
Use of glyphosate and glyphosate-based herbicides is ubiquitous in US agriculture and widespread around the world. Despite marketing efforts to the contrary, numerous studies demonstrate glyphosate toxicity to non-target organisms including animals, primarily focusing on mortality, carcinogenicity, renal toxicity, reproductive, and neurological toxicity, and the biochemical mechanisms underlying these physiological outcomes. Glyphosate toxicity also impacts animal behavior, both in model systems and in agricultural and environmentally relevant contexts. In this review, we examine the effects of glyphosate and glyphosate-based herbicides on animal behaviors, particularly activity, foraging and feeding, anti-predator behavior, reproductive behaviors, learning and memory, and social behaviors. Glyphosate can be detected both in food and in the environment, and avoided through activity and feeding strategies. However, exposure also reduces activity, depresses foraging and feeding, increases susceptibility to predation, interferes with courtship, mating, fertility and maternal behaviors, decreases learning and memory capabilities, and disrupts social behaviors. Changes in animal behavior as a result of glyphosate toxicity are important because of their sometimes severe effects on individual fitness, as well as ecosystem health. Implications for human behavior are also considered.
... Larsen et al., 2020;Wan, 2015). In addition to acute poisoning (Mew et al., 2017), recurring exposures to low-doses of pesticides have been associated with negative health outcomes such as non-Hodgkin lymphoma (Zhang et al., 2019), Parkinson's disease (Tangamornsuksan et al., 2019), neuropsychological effects (Muñoz-Quezada et al., 2016), Type 2 diabetes (Evangelou et al., 2016), and Alzheimer's diseases (Yan et al., 2016). Prenatal and young children are particularly sensitive to pesticide pollution and are at a higher risk of early death and developing disease across their lifespan (Suk et al., 2016;Vrijheid et al., 2016). ...
Human populations and ecosystems are extensively exposed to pesticides. Most nations lack the capacity to control pesticide contamination and have limited availability of pesticide use information. Ecuador is a country with intense pesticide use with high exposure risks to humans and the environment, although relative or combined risks are not well understood. Here, we analyzed the distribution of application rates in Ecuador and identified regions of concern because of high potential exposure. We used a geospatial analysis to identify grid cells (∼8 km × 8 km) where the highest pesticide application rates and density of human populations overlap. Furthermore, we identified other regions of concern based on the number of amphibian species as an indicator of ecosystem integrity and the location of natural protected areas. We found that 28% of Ecuador's population dwelled in areas with high pesticide application rate. We identified an area of ∼512 km² in the Amazon region where high application rates, large human settlements, and a high number of amphibian species overlapped. Additionally, we distinguished clusters of pesticide application rates and human populations that intersected with natural protected areas. Ecuador exemplifies how pesticides are disproportionately applied in areas with the potential to affect human health and ecosystems' integrity. Global estimates of population dwelling, pesticide application rates, and environmental factors are key in prioritizing locations to conduct further exposure assessments. The modular and scalable nature of the geospatial tools we developed can be expanded and adapted to other regions of the world where data on pesticide use are limited.
... Arthropod pests are responsible for major yield losses worldwide: from 2001 to 2003, yield losses due to pest damage reached 28% in wheat and cotton, 26% in soybean, 37% in rice, 31% in maize, and 40% in potato [3]. Arthropod pest control heavily relies on synthetic chemical insecticides worldwide, which have major negative impacts on the environment and on human health; they are detrimental to non-target organisms and induce pest resistances, further increasing farmers' dependency on chemical insecticides [4][5][6]. ...
... There is now widespread awareness of the direct toxic effects of biocides on insect, animal, and human health (Ouidir et al., 2019;Attina et al., 2016;Sánchez-Bayo and Wyckhuys, 2019;Potter, 2015;Zhang et al., 2019;von Ehrenstein et al., 2019;De Long and Holloway, 2017;Weidenmüller et al., 2022;Potts et al., 2016;Lind et al., 2019;Kuehn, 2010;Defois et al., 2018;Rohr, 2021;Tanner et al., 2011;Douwes et al., 2018). What is less well appreciated is the impact of these compounds on microbial life (Clair et al., 2012;Kurenbach et al., 2017;Jørgensen et al., 2018), particularly soil microbes (Jacobsen and Hjelmso, 2014;Lo, 2010), and the resultant deleterious impact on plant, animal, and human health (Samaddar et al., 2021). ...
Humans have lived from equator to poles for millennia but are now increasingly intruding into the wild spaces of other species and steadily extruding ourselves from our own wild spaces, with a profound impact on: our relationship with the natural world; survival of other species; pollution; climate change; etc. We have yet to grasp how these changes directly impact our own health. The primary focus of this paper is on the beneficial influence of proximity to the natural environment. We summarize the evidence for associations between exposure to green space and blue space and improvements in health. In contrast, grey space - the urban landscape - largely presents hazards as well as reducing exposure to green and blue space and isolating us from the natural environment. We discuss various hypotheses that might explain why green, blue, and grey space affect health and focus particularly on the importance of the biodiversity hypothesis and the role of microbiota. We discuss possible mechanisms and exposure routes - air, soil, and water. We highlight the problem of exposure assessment, noting that many of our current tools are not fit for the purpose of understanding exposure to green and blue space, aerosols, soils, and water. We briefly discuss possible differences between indigenous perspectives on the nature of our relationship with the environment and the more dominant international-science view. Finally, we present research gaps and discuss future directions, particularly focusing on the ways in which we might - even in the absence of a full understanding of the mechanisms by which blue, green, and grey space affect our health - begin to implement policies to restore some balance to our environment of with the aim of reducing the large global burden of ill health.
... There is a wide range of human disorders and diseases related to the formulations of glyphosate-based herbicides. Some researchers include the following in the main anomalies found: metabolic alterations, damage to DNA, kidney damage, attention deficit disorder with hyperactivity (ADDH), Alzheimer, Parkinson, autism, leaky gut syndrome, non-Hodgkin lymphoma and anencephaly (Zhang et al., 2019). In Mexico, Rendón-von Osten and Dzul-Caamal (2017) reported traces of glyphosate in the urine of agricultural workers and groundwater, as well as in samples of bottled water. ...
The use of agrochemical products for the control of pests has been widely extended on a global scale in commercial agriculture, despite its impacts on human health and on biodiversity. Glyphosate is the most commonly used herbicide, with adverse effects on human health and the environment that have led to controversy in the technical-scientific arena. The aim of this essay was to identify the main researches/studies related to the herbicide glyphosate and record its impact on the biota, the environment and public health. In order to do this, a bibliographic search was carried out, limited to scientific articles in Scopus between 1980 and May, 2022. The search criteria were: glyphosate, Roundup®, toxicity, environmental impact, human health, water pollution, underground and surface water and nonpoint sources. A total of 1607 articles was found, with an increase of 178 % in scientific production in the last 10 years. The countries with the highest number of publications related to the topic of glyphosate were developed nations with intensive agriculture. Mexico is in sixteenth place, with 29 (1.8 %) scientific articles for the period studied, out of which only 17 % are studies in bodies of water. Based on the literature consulted and the co-occurrence map, the elements that are related to the impact on the bodies of water by glyphosate are the type of agriculture, location of the fields, rainfalls and the characteristics of the catchment area.
... This hazard classification was based on "limited" evidence of cancer in humans, mainly by the evidence derived from case-control studies of occupational exposure in Canada (McDuffie et al., 2001a), the United States (De Roos et al., 2003), and Sweden (Eriksson et al., 2008) that showed high risks for non-Hodgkin lymphoma (NHL). This conclusion was supported by three meta-analyses that assessed the same association between GBH exposure and NHL by different methodologies (Chang and Delzell, 2016;Schinasi and Leon, 2014;Zhang et al., 2019). Since then, glyphosate usage has been limited or forbidden in several countries. ...
Glyphosate is a broad-spectrum and one of the most widely used herbicides in the world, which has led to its high environmental dissemination. In 2015, the International Agency for Research on Cancer stated that glyphosate was a probable human carcinogen. Since then, several studies have provided new data about the environmental exposure of glyphosate and its consequences on human health. Thus, the carcinogenic effects of glyphosate are still under debate. This work aimed to review glyphosate occurrence and exposure since 2015 up to date, considering studies associated with either environmental or occupational exposure and the epidemiological assessment of cancer risk in humans. These articles showed that residues of the herbicide were detectable in all spheres of the earth and studies on the population showed an increase in the concentration of glyphosate in biofluids, both in the general population and in the occupationally exposed population. However, the epidemiological studies under review provided limited evidence for the carcinogenicity of glyphosate, which was consistent with the International Agency for Research on Cancer classification as a "probable carcinogen".
... As mammals do not have the shikimate pathway, it was initially thought that glyphosate could not negatively impact human health. However, multiple studies have linked glyphosate exposure with various diseases, including cancers (Zhang et al., 2019). These findings have increased focus on understanding the potential mechanism through which glyphosate exposure can cause toxic effects in humans. ...
The widespread use of glyphosate, a broad-spectrum herbicide, has resulted in significant human exposure, and recent studies have challenged the notion that glyphosate is safe for humans. Although the link between disease states and glyphosate exposure is increasingly appreciated, the mechanistic links between glyphosate and its toxic effects on human health are poorly understood. Recent studies have suggested that glyphosate may cause toxicity through modulation of the gut microbiome, but evidence for glyphosate-induced gut dysbiosis and its effect on host physiology at doses approximating the U.S. Acceptable Daily Intake (ADI = 1.75mg/kg body weight) is limited. Here, utilizing shotgun metagenomic sequencing of fecal samples from C57BL/6J mice, we show that glyphosate exposure at doses approximating the U.S. ADI significantly impacts gut microbiota composition. These gut microbial alterations were associated with effects on gut homeostasis characterized by increased proinflammatory CD4+IL17A+ T cells and Lipocalin-2, a known marker of intestinal inflammation. DATA AVAILABILITY: The shotgun metagenomic sequences are deposited in NCBI under BioProject PRJNA880821. All other data needed to evaluate the conclusions in the manuscript are present in the manuscript and/or the Supplementary Materials.
... Glyphosate (N-(phosphonomethyl) glycine) is the active ingredient in various herbicides, of which the most widely used is Roundup®. The use of Roundup has been linked to the development of non-Hodgkin lymphoma among agricultural workers 4,5 . In addition, some toxicity tests performed in laboratory animals and cell model systems suggest that glyphosate can be carcinogenic 6,7 . ...
The understanding of the possible human health effects of the new combinations of herbicides used in agricultural systems is challenging. We plan to evaluate the effects of glyphosate alone and a mixture of dicamba, glyphosate and 2,4-D. Wistar rats (ten males and ten females per group) will be exposed to a mixture of 0.3 mg/kg bw/day dicamba plus 0.5 mg/kg bw/day glyphosate plus 0.02 mg/kg bw/ day 2,4-D in drinking water, equivalent to their European Union acceptable daily intake (ADI) doses, from gestational day 6 till 3 months post-weaning. Glyphosate alone at its ADI and no-observed adverse effect level (NOAEL: 50 mg/ kg bw/day) will be also tested. This multisystem study aims to evaluate the impact of these herbicides on the antioxidant machinery, oxidative stress, DNA damage, and tissue histology in various organs (bone marrow, liver, kidneys, brain, gastrointestinal tract). Hormone levels, behavioral changes, and changes in the gut microbiota will also be studied. Mechanisms underlying these changes will be evaluated using gene expression markers, including transcriptomics in the bone marrow. The discovery of new mechanisms of toxicity from exposure to these common herbicides will inform epidemiology studies to test whether exposure to environmental levels in ‘real-life’ scenarios could point to the development of chronic disease.
... Agricultural intensification intends to satisfy the food demand of the growing human population. However, this process implies the use of synthetic pesticides (herbicides, fungicides and insecticides) and inorganic fertilizers, which also negatively impact on the ecosystems (i.e., loss of biodiversity, soil and water pollution) and human health (Lichtenberg et al. 2017;Zhang et al. 2019). As an alternative to this model of food production, ecological intensification consists of agricultural practices based on ecological processes that include the reduction in the use of pesticides and the enhancement of above and belowground biodiversity and its associated ecosystem services (pollination, pest control, nutrient cycling, among others), which agriculture depends on (Garibaldi et al. 2017). ...
Conventional agriculture has negative impacts on the ecosystems while ecological intensification can ameliorate these effects by enhancing ecological processes. Arbuscular mycorrhizal fungi (AMF) are plant root symbionts that improve access to soil nutrients affecting plant growth and biotic interactions. Agricultural managements differentially affect AMF communities, but how these changes feedback on aboveground plant interactions remains poorly studied. Lettuce (Lactuca sativa) is a common crop severely attacked by Liriomyza huidobrensis (Diptera: Agromizydae), a polyphagous leafminer that has developed resistance to various pesticides, for which managing plant defenses and tolerance represents a feasible option to regulate populations. The aim of this study was to investigate if AMF communities from ecological and conventional management produce differential effects on mycorrhizal interaction, tissue phosphorus content and growth of lettuce plants and on L. huidobrensis oviposition preference. In greenhouse, we compared the effects of soils from farms with conventional and ecological managements from central Argentina on lettuce plants, and exposed them to L. huidobrensis mated females. Mycorrhizal colonization was higher with AMF from ecological than conventional treatments, although plant biomass was lower in treatments with AMF than with sterile soils (Strl), or with soil microorganisms without AMF (MO), in both managements. Phosphorus content was significantly higher in plants with MO and AMF in comparison to Strl, with no difference between managements. Plants grown with AMF from ecological management soils were less attacked by leafminers. Also, the insect preferred to oviposit on plants with higher aerial biomass, and this preference increased in plants with lower P content.
... According to Meftaul et al. (2020), the advance of the use of Roundup® (whose formulation still includes the surfactant polyethoxylated tallow amine -POEA, often attributed as the main toxic agent present in the product) in the last 45 years has led to the emergence of several species resistant to the herbicide and has caused at least 20 countries to ban or restrict its use. These actions are also because important epidemiological studies have shown that glyphosate-based formulations, despite their supposed safety, are capable of triggering pathological processes in humans, such as neurotoxicity (Martinez and Al-Ahmad, 2019), genotoxicity (Tarboush et al., 2022), non-Hodgkin lymphoma (Zhang et al., 2019) and other endocrine disorders (Maddalon et al., 2021;Mesnage et al., 2015). ...
The vertiginous growth of consumers' preference for making purchases over the internet has been accompanied by the possibility of obtaining almost any type of product, with little perception of the inherent risks of this practice. In Brazil, although legislation has determined for more than a decade which concentrations and presentations of pesticides can be marketed, the lack of information and knowledge still prevails among the general public. The present study aimed to analyze information provided on glyphosate-based products marketed on Brazilian websites to determine possible factors that influence consumers' decision-making process. For this purpose, a form was prepared to collect information concerning positive and negative aspects of the products, mentions of risks, prices and quality assessments. Our results showed the presence of very few guidelines regarding human health risks (n = 3) or accident risks (n = 1) arising from the misuse of chemical agents on the websites but at the same time a greater concern to show the efficacy (n = 19), mode (n = 26) and dose of application (n = 23). Such findings allow us to affirm that there is still a great void of knowledge concerning risks of these chemical agents, which has been perpetrated by the apparent negligence of companies in providing such information and of the public authorities in supervising this activity. It is important that inspection measures are taken with regard to the quality and safety of the information disclosed in these media, improving consumers' perception of the risks of the practice both for their personal health and for the environment.
... Exposure misclassification on this scale and the concurrent inability to control confounding call into question the validity of results for every specific pesticide in this study. [11,16,25,39,59,72] The different authors used different conventions in their analyses. These meta-analyses are not primary data, but efforts to take a weighted average of the primary data to increase statistical precision and learn something about between study variability. ...
I reviewed the epidemiologic literature for glyphosate and non-Hodgkin's lymphoma (NHL) in the context of the frequency of exposure in each epidemiologic study, systemic dose from biomonitoring studies of applicators, and aspects of study quality. Nine studies were identified, 7 case control and 2 cohort, by a literature search and a review of reference lists from published studies and recent regulatory evaluations. All but one study involved exposure scenarios that were so infrequent that they are not credible for cancer causation. Most studies failed to address potential confounding from other pesticides. Only one study - the US Agricultural Health Study (AHS) - included individuals with relatively frequent exposure to glyphosate and involved comprehensive statistical analyses to address potential confounding by personal factors and other pesticide exposures. The AHS did not find an association between glyphosate and NHL, even among the most frequently exposed participants (≥ 109 days of use) (RR = 0.80, 95% CI 0.60, 1.06). These findings are consistent with observations that glyphosate systemic doses from agricultural applications are many orders of magnitude less than daily lifetime doses considered by regulatory agencies to impart no excess risk of deleterious health effects, even for sensitive subpopulations.
... Some pesticides are known to pose a risk to human health due to their endocrine disruptive properties (Tabb and Blumberg, 2006). Although there is no consistent epidemiologic evidence supportive of a positive association between pesticide exposure in occupational settings and cancer in general (Burns and Juberg, 2021), two recent meta-analyses show an association between occupational exposure to organophosphate pesticides, particularly Diazinon (Hu et al., 2017), and glyphosate-based herbicides with non-Hodgkin lymphomas (Zhang et al., 2020). However, epidemiologic evidence on pesticide exposure and childhood lymphoma remains scarce due to the rarity of childhood lymphoma. ...
Childhood cancer incidence is known to vary by age, sex, and race/ethnicity, but evidence is limited regarding external risk factors. We aim to identify harmful combinations of air pollutants and other environmental and social risk factors in association with the incidence of childhood cancer based on 2003-2017 data from the Georgia Cancer Registry. We calculated the standardized incidence ratios (SIR) of Central Nervous System (CNS) tumors, leukemia and lymphomas based on age, gender and ethnic composition in each of the 159 counties in Georgia, USA. County-level information on air pollution, socioeconomic status (SES), tobacco smoking, alcohol drinking and obesity were derived from US EPA and other public data sources. We applied two unsupervised learning tools (self-organizing map [SOM] and exposure-continuum mapping [ECM]) to identify pertinent types of multi-exposure combinations. Spatial Bayesian Poisson models (Leroux-CAR) were fit with indicators for each multi-exposure category as exposure and SIR of childhood cancers as outcomes. We identified consistent associations of environmental (pesticide exposure) and social/behavioral stressors (low socioeconomic status, alcohol) with spatial clustering of pediatric cancer class II (lymphomas and reticuloendothelial neoplasms), but not for other cancer classes. More research is needed to identify the causal risk factors for these associations.
... These authors concluded their study by stating that future human studies should attempt to further analyze the relationship between sex hormones and glyphosate exposure. Another recent meta-analysis revealed a significant link in human populations between high exposure to glyphosate/GBHs and the risk of non-Hodgkin lymphoma (NHL) (Zhang et., 2019). The linkage observed between glyphosate/GBHs and the risk of NHL supports our findings because previous studies reported disruption of sex hormones may contribute to lymphomagenesis/NHL (Hosgood et al., 2018). ...
Glyphosate-based herbicides (GBHs) are one of the most commonly used herbicides worldwide. Numerous in vitro and in vivo model system studies have demonstrated endocrine-disrupting chemical (EDC) properties associated with glyphosate/GBH exposure. The present hypothesis-testing study evaluated the potential inverse dose-dependent relationship between increasing urinary glyphosate and decreasing concentrations of blood sex hormones. Demographic and newly available lab test data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) were analyzed with survey regression modeling (adjusted for age, gender, race, and country of birth) in Statistical Analysis System (SAS) software. A total of 225, 615, 858 weighted-persons (sample n = 2130 persons) were examined for concentrations of urinary glyphosate and the serum sex hormones (including: total testosterone, total estradiol, and sex hormone binding globulin (SHBG)) among males and females, 6 years-old or older. This study revealed about 82% of the population of the United States examined had detectable urinary concentrations of glyphosate. A significant inverse correlation between concentrations of glyphosate and total estradiol and a trend towards an inverse correlation between concentrations of glyphosate and total testosterone were observed. Concentrations of SHBG and glyphosate did not correlate. Ratios of total testosterone:SHBG and total estradiol:SHBG (estimating the fraction of active sex hormones in the blood) were significantly inversely correlated with urinary concentrations of glyphosate. This epidemiological study associates widespread and ongoing glyphosate/GBH exposures with human endocrine-disruptions. Future studies should examine these phenomena in other databases and other endocrine-related disorders.
... Glyphosate, which has been advertised as 'safe' has been thoroughly investigated by toxicologists, especially ecotoxicologists, but the results are often unclear or contradictory; for instance, with respect to genotoxicity (for a recent review see Ojelade et al. [65]). However, statistics suggest that glyphosate-based herbicides can increase the risk of non-Hodgkin lymphoma (NHL) in humans by 40% [66]. ...
Cancer is one of the longest-known human diseases, yet only in recent times have we begun to perceive that the percentage of neoplasms caused by environmental factors, lifestyle and chemicals, is likely underestimated. The first medical reports associating cancer with pollutants like tars appeared by the early 20th century, but despite initial evidence relating oncogenesis and chromosomal alterations, only after the structure of DNA had been elucidated in the 1950s have genetic disorders been fully perceived as cause. This led to a growing interest in genotoxic and mutagenic pollutants. Even though we are now familiar with a range of environmental carcinogens spanning between aromatic hydrocarbons and asbestos to radionuclides and forms of carbon nanomaterials, establishing causal networks between pollutants and cancer remains cumbersome. In most part, this is due to the complexity of toxicant matrices, unknown modes-of-action of chemicals or their mixtures, the widening array of novel pollutants plus difficulties in subtracting background effects from true aetiology of disease. Recent advances in analytical chemistry, high-throughput toxicology, next-generation sequencing, computational biology and databases that allocate whole normal and cancer genomes, all indicate that we are on the verge of a new age of research into mechanistic ‘oncotoxicology’, but how can it impact risk assessment and prevention?
Brazil, a global frontrunner in pesticide consumption and sales, particularly glyphosate, appears to be at odds with other countries that increasingly ban these products in their territories. This study gathers the values of Acceptable Daily Intake and Maximum Residue Limits (MRL) in the European Union for dozens of substances and subsequently contrasts them with the corresponding benchmarks upheld in Brazil concerning its predominant crops. Furthermore, this study delves into the toxicity levels and the potential health ramifications of glyphosate on humans through the ingestion of food containing its residues. The findings from this research underscore a notable surge in glyphosate and pesticide sales and usage within Brazil over the past decade. In stark contrast to its European counterparts, Brazil not only sanctioned the sale and application of 474 new pesticides in 2019, but extended the authorization for glyphosate sales while downgrading its toxicity classification. Finally, this review not only uncovers disparities among research outcomes but also addresses the complexities of replacing glyphosate and introduces environmentally friendlier alternatives that have been subject to evaluation in the existing literature.
The article is available here
https://authors.elsevier.com/c/1hoyJ15DSlRh9F
Abstract
Glyphosate is the most widely used herbicide in the world. There is still no complete clarity about the degree of its genotoxicity and mutagenicity. In addition, its effect on bacterial biofilms, the main life form of soil microbial communities, has not been adequately studied. Toxicity and mutagenicity, as well as changes in the bacterial biofilm biomass, physiological activity, and the number of living cells in its composition in the presence of glyphosate were assessed using the Escherichia coli model. To assess damage to cellular components under the action of this pesticide, luminescent whole-cell bacterial lux-biosensors were used. Changes in the level of mutagenesis were studied by the method of rifampicin mutants. High integral toxicity of glyphosate, the average level of increased oxidative stress and protein damage were shown with the help of bacterial biosensors. All the studied concentrations of the pesticide completely or partially suppress the matrix and structure of the E. coli CDC F-50 biofilm formation, as well as the bacterial cells metabolic activity in the biofilm. At the concentrations of 6.7 and 0.67 g/L, glyphosate suppresses mutagenesis, probably due to general suppression of metabolism, and at the concentration of 0.0067 g/L, it enhances mutagenesis by six times compared with the spontaneous level. Suppression of bacterial biofilms formation, toxic effects on microorganisms, and mutagenesis enhancement by glyphosate can lead to negative consequences for natural microbiomes.
Cadmium (Cd) exposure to the animals including humans is reported as nephrotoxic compounds i.e., disturbing redox status (increase oxidative stress), mitochondrial dysfunction, renal cell death and altered transporters in the renal system. Hsp27 (a small heat shock protein) has been shown as one of the modulators in the renal dysfunction and increased against the Cd induced toxicity. However, no studies are reported on the genetic modulation of stress protein against the Cd-induced nephrotoxicity. The current study aimed to examine the protective role of hsp27 overexpression against the Cd-induced nephrotoxicity using Drosophila melanogaster as an animal model. D. melanogaster renal system includes nephrocytes and Malpighian tubules (MTs) that show the functional similarity with mammalian kidney nephron. Overexpression of the hsp27 was found to reduce the Cd induced oxidative stress, rescue cell death in MTs of Cd exposed D. melanogaster larvae. The rescued GSH level, NADPH level and glucose 6 phosphate dehydrogenase (G6PD) activity were also observed in the MTs of the Cd exposed organism. Function (efflux activity and fluid secretion rate) of the MTs was restored in Cd exposed hsp27 overexpressed larvae. Further, results were confirmed by restored brush border microvilli density and reduced uric acid level. Tissue specific knockdown of hsp27 developed Cd like phenotypes in MTs and the phenotypes enhanced in Cd exposed condition. The present study clearly shows the role of hsp27 overexpression in restoration of the MTs function and protection against the Cd induced renal toxicity.
Animals are increasingly exposed to potential stressors related to environmental change, and multiple stressors may alter the dynamics by which animals acquire resources and invest those resources into important life-history traits. Stress may lead to the prioritization of current reproduction to maximize lifetime reproduction (i.e., terminal investment [TI]) or, in contrast, prioritize somatic investment over current reproduction to facilitate future reproductive opportunities (i.e., reproductive restraint [RR]). Tests of the TI and RR hypotheses typically use immune challenges as stressors, and have not been explicitly tested in the context of environmental change even though warming influences resource allocation patterns across taxa. Further, the multiple-stressor framework has been a useful construct to clarify the costs of complex environmental shifts to animals, but it has not been leveraged to understand such effects on investment strategy. Thus, we tested the TI and RR hypotheses by manipulating widespread features of environmental change-glyphosate-based herbicide (GBH; Roundup®) exposure and a simulated heat wave-in the variable field cricket (Gryllus lineaticeps). A simulated heat wave affected the life-history tradeoff between investment into reproduction and soma. Specifically, heat wave prioritized investment into ovary mass over non-reproductive tissue, even after accounting for food consumption, in support of the TI hypothesis. In contrast, GBH exposure did not affect any measured trait, and crickets did not discriminate between tap water and GBH solution during drinking. Therefore, some-but not all-aspects of environmental change may alter resource investment strategies in animals. We encourage continued integration of the multiple-stressor framework and life-history theory to better understand how animals respond to their rapidly changing environments.
En este trabajo de tesis me propongo, mediante un enfoque transdisciplinario e interseccional, realizar un análisis filosófico del cancercapitalismo, entendiendo al mismo como un proceso (relación o estructura) cuyos momentos (cáncer y capitalismo) operan en diferentes escalas o planos ontológicos con autonomía relativa y con leyes propias, pero con una lógica subyacente similar que los vincula conceptualmente en tanto formas de acumulación.
Presentación: https://www.youtube.com/watch?v=0nrAEqQ76Uc&t=4s&ab_channel=MatiasBlaustein
Glyphosate was classified as a probable human carcinogen by the International Agency for Research on Cancer (IARC) partially due to strong mechanistic evidence in 2015. Since then, numerous studies of glyphosate and its formulations (GBF) have emerged. These studies can be evaluated for cancer hazard identification with the newly described ten key characteristics (KC) of carcinogens approach. Our objective was to assess all in vivo, ex vivo, and in vitro mechanistic studies of human and experimental animals (mammals) that compared exposure to glyphosate/GBF with low/no exposure counterparts for evidence of the ten KCs. A protocol with our methods adhering to PRISMA guidelines was registered a priori (INPLASY202180045). Two blinded reviewers screened all in vivo, ex vivo, and in vitro studies of glyphosate/GBF exposure in humans/mammals reporting any KC-related outcome available in PubMed before August 2021. Studies that met inclusion criteria underwent data extraction conducted in duplicate for each KC outcome reported along with key aspects of internal/external validity, results, and reference information. These data were used to construct a matrix that was subsequently analyzed in the program R to conduct strength of evidence and quality assessments. Of the 2537 articles screened, 175 articles met inclusion criteria, from which we extracted >50,000 data points related to KC outcomes. Data analysis revealed strong evidence for KC2, KC4, KC5, KC6, KC8, limited evidence for KC1 and KC3, and inadequate evidence for KC7, KC9, and KC10. Notably, our in-depth quality analyses of genotoxicity (KC2) and (KC8) endocrine disruption revealed strong and consistent positive findings. For KC2, we found: 1) studies conducted in humans provided stronger positive evidence than animal studies; 2) GBF elicited a stronger effect in both human and animal studies when compared to glyphosate alone; and 3) the highest quality studies in humans consistently revealed strong evidence of genotoxicity. Our analysis of KC8 indicated that glyphosate's ability to modulate hormone levels and estrogen receptor activity is sensitive to both exposure concentration and formulation. The modulations observed provide clear evidence that glyphosate interacts with receptors, alters receptor activation, and modulates the levels and effects of endogenous ligands (including hormones). Our findings strengthen the mechanistic evidence that glyphosate is a probable human carcinogen and provide biological plausibility for previously reported cancer associations in humans, such as non-Hodgkin lymphoma. We identified potential molecular interactions and subsequent key events that were used to generate a probable pathway to lymphomagenesis.
The herbicide Glyphosate (GLY), or N-(phosphonomethyl) glycine was synthesized in 1950 and applied to control weeds in agricultural production. For a long time, it was believed that it was an inert compound, but many studies have instead demonstrated over the years the dangers of GLY to the ecosystem and human health. Among the best-known effects, it is known that GLY interferes with the metabolic pathways of plants and the main groups of microorganisms, negatively influencing their growth. GLY interferes with the metabolic pathways of plants and major groups of microorganisms negatively affecting their growth. The extensive GLY application on fields results in a "slow death" of plants through the minor resistance to root pathogens and in increasing pollution of freshwaters and soils. Unfortunately, however, unlike the old beliefs, GLY can reach non-target destinations, in this regard, ecological studies and environmental epidemiology are of significant interest. In this review, we focus on the effects of acute and chronic exposure to GLY on the health of plants, animals, and humans from a One Health perspective. GLY has been linked to neurological and endocrine issues in both humans and animals, and behavioral modification on specific bioindicators, but the knowledge about the ratio cause-and-effect still needs to be better understood and elucidated. Environmental GLY residues analysis and policy acts will both require new criteria to protect environmental and human health.
Animal and epidemiologic studies suggest that there may be adverse health effects from exposure to glyphosate, the most highly used pesticide in the world, and its metabolite aminomethylphosphonic acid (AMPA). Meanwhile, consumption of organic foods (presumably grown free of chemical pesticides) has increased in recent years. However, there have been limited biomonitoring studies assessing the levels of human glyphosate and AMPA exposure in the United States. We examined urinary levels of glyphosate and AMPA in the context of organic eating behavior in a cohort of healthy postmenopausal women residing in Southern California and evaluated associations with demographics, dietary intake, and other lifestyle factors. 338 women provided two first-morning urine samples and at least one paired 24-h dietary recall reporting the previous day's dietary intake. Urinary glyphosate and AMPA were measured using LC-MS/MS. Participants reported on demographic and lifestyle factors via questionnaires. Potential associations were examined between these factors and urinary glyphosate and AMPA concentrations. Glyphosate was detected in 89.9% of urine samples and AMPA in 67.2%. 37.9% of study participants reported often or always eating organic food, 30.2% sometimes, and 32.0% seldom or never. Frequency of organic food consumption was associated with several demographic and lifestyle factors. Frequent organic eaters had significantly lower urinary glyphosate and AMPA levels, but not after adjustment for covariates. Grain consumption was significantly associated with higher urinary glyphosate levels, even among women who reported often or always eating organic grains. Soy protein and alcohol consumption as well as high frequency of eating fast food were associated with higher urinary AMPA levels. In conclusion, in the largest study to date examining paired dietary recall data and measurements of first-void urinary glyphosate and AMPA, the vast majority of subjects sampled had detectable levels, and significant dietary sources in the American diet were identified.
The present article critically and comprehensively reviews the most recent reports on smart sensors for determining glyphosate (GLP), an active agent of GLP-based herbicides (GBHs) traditionally used in agriculture over the past decades. Commercialized in 1974, GBHs have now reached 350 million hectares of crops in over 140 countries with an annual turnover of 11 billion USD worldwide. However, rolling exploitation of GLP and GBHs in the last decades has led to environmental pollution, animal intoxication, bacterial resistance, and sustained occupational exposure of the herbicide of farm and companies' workers. Intoxication with these herbicides dysregulates the microbiome-gut-brain axis, cholinergic neurotransmission, and endocrine system, causing paralytic ileus, hyperkalemia, oliguria, pulmonary edema, and cardiogenic shock. Precision agriculture, i.e., an (information technology)-enhanced approach to crop management, including a site-specific determination of agrochemicals, derives from the benefits of smart materials (SMs), data science, and nanosensors. Those typically feature fluorescent molecularly imprinted polymers or immunochemical aptamer artificial receptors integrated with electrochemical transducers. Fabricated as portable or wearable lab-on-chips, smartphones, and soft robotics and connected with SM-based devices that provide machine learning algorithms and online databases, they integrate, process, analyze, and interpret massive amounts of spatiotemporal data in a user-friendly and decision-making manner. Exploited for the ultrasensitive determination of toxins, including GLP, they will become practical tools in farmlands and point-of-care testing. Expectedly, smart sensors can be used for personalized diagnostics, real-time water, food, soil, and air quality monitoring, site-specific herbicide management, and crop control.
Clethodim is a widely used and approved class II herbicide, with little information about its impact on the reproductive system. Herein, we investigated the male reproductive toxicity of clethodim using a mouse model. GrassOut Max (26% clethodim-equivalent) or 50 mg kg-1 body weight analytical grade clethodim (≥90%) were given orally to male mice for 10 d in varying doses. All parameters were assessed at 35 d from the first day of treatment. Significant decrease in testicular weight, decreased germ cell population, elevated DNA damage in testicular cells and lower serum testosterone level was observed post clethodim-equivalent exposure. Epididymal spermatozoa were characterized with significant decrease in motility, elevated DNA damage, abnormal morphology, chromatin immaturity and, decreased acetylated-lysine of sperm proteins. In the testicular cells of clethodim-equivalent treated mice, the expression of Erβ and Gper was significantly higher. Proteomic analysis revealed lower metabolic activity, poor sperm-oocyte binding potential and defective mitochondrial electron transport in spermatozoa of clethodim-equivalent treated mice. Further, fertilizing ability of spermatozoa was compromised and resulted in defective preimplantation embryo development. Together, our data suggest that clethodim exposure risks male reproductive function and early embryogenesis in Swiss albino mice via endocrine disrupting function.
Wide-scale emergence of glyphosate-resistant weeds has led to an increase in the simultaneous application of herbicide mixtures exacerbated by the introduction of crops tolerant to glyphosate plus dicamba or glyphosate plus 2,4-D. This raises serious concerns regarding the environmental and health risks resulting from increased exposure to a mixture of herbicide active ingredients. We evaluated hepatotoxic effects following perinatal exposure to the endocrine disrupting herbicide glyphosate alone or in combination with 2,4-D and dicamba from gestational day-6 until adulthood in Wistar rats. Animals were administered with glyphosate at the European Union (EU) acceptable daily intake (ADI; 0.5 mg/kg bw/day) and no-observed-adverse-effect level (NOAEL; 50 mg/kg bw/day). A mixture of glyphosate with 2,4-D (0.3 mg/kg bw/day) and dicamba (0.02 mg/kg bw/day) with each at their EU ADI was evaluated. Redox status was determined by measuring levels of reduced glutathione, decomposition rate of Η2Ο2, glutathione reductase, glutathione peroxidase, total antioxidant capacity, thiobarbituric reactive substances, and protein carbonyls. Gene expression analysis of Nr1d1, Nr1d2, Clec2g, Ier3, and Gadd45g associated with oxidative damage to DNA, was also performed. Analysis of liver samples showed that exposure to the mixture of the three herbicides induced a marked increase in the concentration of glutathione and malondialdehyde indicative of a disturbance in redox balance. Nevertheless, the effect of increased lipid peroxidation was not discernible following a 3-month recuperation period where animals were withdrawn from pesticide exposure post-weaning. Interestingly, toxic effects caused by prenatal exposure to the glyphosate NOAEL were present after the same 3-month recovery period. No statistically significant changes in the expression of genes linked with genotoxicity were observed. Our findings reinforce the importance of assessing the combined effects of chemical pollutants at doses that are asserted by regulatory agencies to be safe individually.
Sustainable land management encompasses a range of activity that balance land use requirements with wider conservation and ecosystem impact considerations. Perennial invasive alien plants (IAPs), such as Japanese knotweed, cause severe ecological and socio-economic impacts, and methods to control their spread also come at a cost. Synthetic herbicides are generally viewed as less sustainable and more ecologically damaging than alternative approaches. Here we used a comparative Life Cycle Assessment to evaluate the sustainability of herbicide-based management approaches and physical alternatives, using a large-scale Japanese knotweed field study as a model IAP system. Glyphosate-based methods elicited the lowest environmental impacts and economic costs during production. Geomembrane covering and integrated physiochemical methods were the costliest and imposed the greatest impacts. We discuss the costs and benefits of chemical and physical approaches for the sustainable management of invaded land and question how sustainable environmental stewardship is defined for the control of IAPs.
Introduction
Pesticides pose a risk for cancer development and progression. People are continuously exposed to such substances by several routes, including daily intake of contaminated food and water, especially in countries that are highly pesticide consumers and have very permissive legislation about pesticide contamination as Brazil. This work investigated the relationship among pesticides, food contamination, and dietary cancer risk.
Methods
Analyzed two social reports from the Brazilian Government: the Program for Analysis of Residues of Pesticides in Food (PARA) and The National Program for Control of Waste and Contaminants (PNCRC).
Results and discussion
First, we characterized the main pesticide residues detected over the maximum limits allowed by legislation or those prohibited for use in food samples analyzed across the country. Based on this list, we estimated the dietary cancer risks for some of the selected pesticides. Finally, we searched for data about dietary cancer risks and carcinogenic mechanisms of each pesticide. We also provided a critical analysis concerning the pesticide scenario in Brazil, aiming to discuss the food contamination levels observed from a geographical, political, and public health perspective. Exposures to pesticides in Brazil violate a range of human rights when food and water for human consumption are contaminated.
In recent years, heavy metal contamination in agricultural soils in Jiangsu Province has attracted more and more attention. However, most studies have been characterized by their small scale, few samples, and short-term monitoring. The overall status and temporal accumulation characteristics of heavy metals have not been fully reflected. Therefore, this paper attempted to provide a comprehensive analysis of the current status of heavy metals and provide accurate information for soil pollution management in Jiangsu Province. This paper collected available data in the literature (1993–2021) on heavy metal-polluted agricultural soils in Jiangsu Province. Based on these available data, the weighted mean values of each heavy metal were obtained by meta-analysis. Then, the ecological risks in soils were evaluated and spatiotemporal variations in the accumulation of heavy metals were explored. In addition, suggestions for pollution prevention and control were made by predicting future heavy metal concentrations. The results showed that Cd and Hg were the major polluting elements in Jiangsu Province. The spatial enrichment of heavy metals followed the pattern of southern > northern > central. Heavy metal concentrations in Nanjing, Suzhou, and Xuzhou should be paid special attention. The ecological risk level of heavy metals in agricultural soils in Jiangsu Province was high, predominantly contributed by Hg and Cd. The accumulation of most heavy metals gradually decreased after 2010, while the opposite happened with Cd. Jiangsu Province should continue to take active pollution control measures in order to maintain the decreasing trend of heavy metal concentrations in farmland soils. This study could provide a scientific and theoretical basis for the development of pollution control and soil remediation measures.
Glyphosate-based herbicides (GBHs) are the most widely used agrochemicals worldwide, increasing the risk of their occurrence in the environment. This study aimed to explore effects and mechanisms of GBH exposure on placental development in vivo during pregnancy in mice. Pregnant mice received GBH by gavage at 0, 5, and 50 mg⋅kg-1⋅day-1 doses from gestational day (GD) 1 to GD 13 and were sacrificed on GD 13 or GD19. Our data indicated that GBH administration significantly increased the number of resorbed fetuses, reduced the weight of fetuses and placentas, and inhibited placental growth, as evident from decreased placental total area and spongiotrophoblast area on GD 19. GBH treatment also inhibited proliferation and induced apoptosis of placenta via upregulation of Bax, cleaved caspase-3 and -12 expression, and downregulation of B cell lymphoma (Bcl)-2 expression. Further study showed that GBH exposure significantly increased expression levels of glucose-regulated protein 78 (GRP78), protein kinase RNA-like endoplasmic reticulum kinase (PERK), and C/EBP homologous protein (CHOP) mRNAs and proteins and triggered oxidative stress in placenta on GD 13 and GD 19. In conclusion, our findings suggest that maternal exposure to GBH can impair placental development through the endoplasmic reticulum stress-mediated activation of GRP78/PERK/CHOP signaling pathway in mice.
Despite discourse advocating pesticide reduction, there has been an exponential increase in pesticide use worldwide in the agricultural sector over the last 30 years. Glyphosate-Based Herbicides (GBHs) are the most widely used pesticides on the planet as well as in Canada, where a total of almost 470 million kilograms of declared “active” ingredient glyphosate was sold between 2007 and 2018. GBHs accounted for 58% of pesticides used in the agriculture sector in Canada in 2017. While the independent scientific literature on the harmful health and environmental impacts of pesticides such as GBHs is overwhelming, Canada has only banned 32 “active” pesticide ingredients out of 531 banned in 168 countries, and reapproved GBHs in 2017 until 2032. This article, based on interdisciplinary and intersectoral research, will analyze how as a result of the scientific and regulatory captures of relevant Canadian agencies by the pesticide industry, the Canadian regulation and scientific assessment of pesticides are deficient and lagging behind other countries, using the GBH case as a basis for analysis. It will show how, by embracing industry narratives and biased evidence, by being receptive to industry demands, and by opaque decision making and lack of transparency, Health Canada’s Pest Management Regulatory Agency (PMRA) promotes commercial interests over the imperatives of public health and environmental protection.
Background:
Glyphosate is the most widely applied herbicide worldwide, and its use has been associated with increased risks of certain hematopoietic cancers in epidemiologic studies. Animal and in vitro experiments suggest that glyphosate may induce oxidative stress, a key characteristic of carcinogens; however, evidence in human populations remains scarce. We investigated associations between glyphosate exposure and urinary oxidative stress biomarkers in the Biomarkers of Exposure and Effect in Agriculture study, a molecular epidemiologic subcohort in the Agricultural Health Study.
Methods:
This analysis included 268 male farmers selected based on self-reported recent and lifetime occupational glyphosate use and 100 age- and geography-matched male non-farmers. Concentrations of glyphosate and oxidative stress biomarkers (8-hydroxy-2'-deoxyguanosine [8-OHdG], 8-iso-prostaglandin-F2α [8-isoprostane], and malondialdehyde [MDA]) were quantified in first-morning-void urine. We performed multivariable linear regression to evaluate associations of urinary glyphosate and self-reported glyphosate use with each oxidative stress biomarker.
Results:
Urinary glyphosate concentrations were positively associated with levels of 8-OHdG (highest vs. lowest glyphosate quartile; geometric mean ratio [GMR]=1.15, 95% confidence interval [CI]=1.03-1.28, Ptrend=.02) and MDA (GMR = 1.20, 95% CI = 1.03-1.40, Ptrend=.06) overall. Among farmers reporting recent glyphosate use (last 7 days), use in the previous day was also associated with significantly increased 8-OHdG and MDA levels. Compared with non-farmers, we observed elevated 8-isoprostane levels among farmers with recent, high past 12-month, or high lifetime glyphosate use.
Conclusions:
Our findings contribute to the weight of evidence supporting an association between glyphosate exposure and oxidative stress in humans and may inform evaluations of the carcinogenic potential of this herbicide.
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.
