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Comparative effects of the Roundup and glyphosate on mitochondrial oxidative phosphorylation
Abstract
The potential toxicity of the herbicide Roundup and its fundamental substance (glyphosate) was tested in bioenergetic functions of isolated rat liver mitochondria. Roundup stimulates succinate-supported respiration twice, with simultaneous collapse of transmembrane electrical potential, while glyphosate used in the same concentrations does not induce any significant effect. Additionally, Roundup depresses state 3 respiration by about 40%, at 15 mM, whereas uncoupled respiration in the presence of FCCP is depressed by about 50%. Depression of uncoupled respiratory activity is mediated through partial inhibition of mitochondrial complexes II and III, but not of complex IV. The phosphorylative system was affected by both a direct and an indirect effect on the F0F1 ATPase activity. The addition of uncoupled concentrations of Roundup to Ca2+-loaded mitochondria treated with Ruthenium Red resulted in non-specific membrane permeabilization, as evidenced by mitochondrial swelling in isosmotic sucrose medium. Therefore, the uncoupling of oxidative phosphorylation is also related to the non-specific membrane permeabilization induced by Roundup. Glyphosate alone does not show any relevant effect on the mitochondrial bioenergetics, in opposition to Roundup formulation products. The differences in the toxicity observed could be either attributed to some products of Roundup or to a synergic effect of glyphosate and formulation products. Bearing in mind that mitochondria is provided with a variety of bioenergetic functions mandatory for the regulation of intracellular aerobic energy production and electrolyte homeostasis, these results question the safety of Roundup on animal health.
... Olorunsogo et al. (1979) first reported that glyphosate caused an increased oxygenation rate of isolated mitochondria and caused oxidative stress. There is some evidence that mitochondrial damage is much more prominent with GBHs rather than in pure glyphosate (Peixoto, 2005), although glyphosate did the same, just at higher concentrations. Roundup™ treatment caused loss of mitochondrial membrane potential, swelling, and non-specific membrane permeabilization at a concentration (5 mM) at which glyphosate had no effect. ...
... They conclude that GCHs cause mitochondrial inhibition and hydrogen peroxide generation. Peixoto (2005) showed that Roundup™ interferes with mitochondrial bioenergetic reactions. Changes in mitochondrial respiration and membrane energization (Δψ) were monitored as an indicator of alteration in basic mitochondrial functions. ...
... Changes in mitochondrial respiration and membrane energization (Δψ) were monitored as an indicator of alteration in basic mitochondrial functions. Glyphosate stimulates oxidative stress in the liver and kidneys by disrupting mitochondrial metabolism in rats (Peixoto, 2005;Olorunsogo, 1990). de Liz Oliveira Cavalli et al. (2013) demonstrated oxidative stress in Sertoli cells exposed to Roundup™ by increased intracellular calcium, reduced glutathione, and increased levels of thiobarbituric acid. ...
Glyphosate is the active ingredient in Roundup™, the most widely used herbicide in the world. Glyphosate targets an essential enzyme in plants that is not found in animals. However, both glyphosate and Roundup™ are rated as Group 2 A, probably human carcinogens, and also have documented effects on reproduction, acting as endocrine disruptive chemicals. We have reviewed reports of the effects of glyphosate and Roundup™ on the mammalian nervous system function. As with several other herbicides, Roundup™ exposure has been associated with an increased risk of Parkinson's Disease and death of neurons in the substantia nigra. There is also some evidence implicating Roundup™ in elevated risk of autism. Other studies have shown the effects of Roundup™ on synaptic transmission in animal and cellular studies. The major mechanism of action appears to be oxidative stress, accompanied by mitochondrial dysfunction. In addition, some gut bacteria utilize the enzyme used by plants, and glyphosate and Roundup™ use has been shown to alter the gut microbiome. There is a large and growing body of evidence that the gut microbiome alters susceptibility to great number of human diseases, including nervous system function. The weight of the evidence indicates that in addition to cancer and reproductive effects, glyphosate and Roundup™ have significant adverse effects on the brain and behavior and increase the risk of at least some serious neurological diseases.
... The functional shift in mitochondria can lead to severe alterations of the general metabolism. In 2005 Peixoto showed that rat liver mitochondria were negatively affected by a glyphosate-based pesticide in combination with other compounds (Peixoto, 2005). ...
... Glyphosate up to 15 mM did not affect mitochondrial membrane potential, but Roundup at a concentration of 10 mM disrupted mitochondrial membrane potential in preparations from liver of Wistar rats (Peixoto, 2005). The mitochondrial mem-brane potential was lower in rat heart H9c2 cells exposed to a mixture of glyphosate and surfactant TN-20 (Kim et al., 2013). ...
... However, 0.5 mM of Roundup significantly depressed the respiratory chain and ADP/O ratio. Moreover, Roundup at concentrations up to 15 mM depressed operation of complex ІІІ and uncoupled respiration rates (Peixoto, 2005). ...
The effects of pesticides on the health of non-target living organisms in agricultural areas are critically important aspects for their safe use. Their release into the environment is an inevitable aspect for predicting and evaluation of the risk of their application. Roundup, a glyphosate-based herbicide, has been designed as an effective pesticide against weeds and now is the most widely used agrochemicals around the world due to its highly specific action of the biosynthesis of certain amino acids in plants. Despite it is claimed to be low toxic for not-target organisms, due to its broad application Roundup and products of its degradation were detected in organisms of diverse animals and humans. In this review, we describe animal and human studies of general adverse effects of Roundup and its principal substance glyphosate with focus on endocrine disruption, oxidative stress and behavioral disorders. At mechanistic level, we focus on the potential toxicity of the herbicide Roundup and glyphosate as effectors of bioenergetic functions of mitochondria. Their effects on mitochondrial membrane potential and oxidative phosphorylation are among described to date critical components responsible for its toxicity. Finally, we discuss general molecular mechanisms potentially involved in the interaction between glyphosate and mitochondria which to some extent are associated with generation of reactive oxygen species.
... Commercial glyphosate-based formulations most commonly range from concentrations of 1 %-41 % and generally comprise an aqueous mixture of the isopropylamine (IPA) salt of glyphosate, a surfactant, and various minor components. The mechanisms of toxicity of glyphosate formulations are complicated and unknown; both glyphosate and its surfactants can cause human poisoning, and IPA may be involved in the uncoupling of oxidative phosphorylation [56]. The clinical features of this herbicide poisoning are varied. ...
... Ingestion of >85 mL of a concentrated formulation may cause significant toxicity in adults, and the symptoms can include gastrointestinal corrosive effects on the mouth and throat, epigastric pain, dysphagia, renal and hepatic impairment, respiratory distress, impaired consciousness, shock, arrythmia, metabolic acidosis, and hyperkaliemia. Patients who orally ingest glyphosate should be treated with gastric lavage and catharsis in the early stages, as well as blood purification when necessary [56]. Gastrointestinal corrosion is common in patients who ingest glyphosate. ...
Background
Glyphosate is a widely used herbicide. Clinical presentations of glyphosate intoxication show variation, but hepatic portal venous gas(HPVG) caused by glyphosate poisoning is rarely reported. Herein, we report a rare case of ominous HPVG after ingesting glyphosate. HPVG, which used to be an ominous abdominal radiologic sign, is associated with numerous underlying abdominal pathologies, ranging from benign conditions that require no invasive treatment to potentially lethal diseases that necessitate prompt surgical intervention.
Case summary
A young woman who ingested 100 mL glyphosate 6-h prior was admitted to the emergency intensive care unit. Before admission to our hospital, the patient was administered gastric lavage treatment with 10000 mL of normal saline in the local hospital. After 14 h, her laboratory examinations showed systemic inflammatory response syndrome and multiple organ dysfunction syndrome, while the condition deteriorated. Computed tomography of the abdomen showed multilinear air densities in the portal vein, hepatic branches, and mesenteric vessels, intestinal obstruction, and intestinal necrosis. Septic shock and a severe abdominal infection were diagnosed. The patient was treated conservatively as they could not tolerate surgery and, after 20 h died of septic shock.
Conclusion
We reviewed 289 cases of "hepatic portal venous gas" in PUBMED and analyzed the etiology and treatment of HPVG accompanied by the underlying pathology. We concluded that HPVG is a radiological sign associated with various diseases, and the prognosis mainly depends on the underlying cause and clinical condition. As glyphosate may erode the digestive tract, attention should be paid to the volume, pressure, and speed of gastric lavage in treating glyphosate poisoning to avoid fatal complications such as HPVG. Abdominal symptoms need to be closely observed, and changes in the early onset of the condition in clinical practice need to be responded to promptly.
... Although glyphosate was originally thought to have no effect on humans, it is now rated by the International Agency for Research on Cancer (IARC) as a probable human carcinogen [21], and has effects on both female and male fertility [54],has neurological effects [1,36] and causes mitochondrial damage [46]. Animal and in vitro studies indicate that glyphosate exposure interferes with glucose uptake into adipocytes [13,47], is associated with liver fibrosis [40], increases apoptosis [11,20], induces oxidative stress [38,46], and alters the gut microbiome [24,33,39,48,51,59]. ...
... Although glyphosate was originally thought to have no effect on humans, it is now rated by the International Agency for Research on Cancer (IARC) as a probable human carcinogen [21], and has effects on both female and male fertility [54],has neurological effects [1,36] and causes mitochondrial damage [46]. Animal and in vitro studies indicate that glyphosate exposure interferes with glucose uptake into adipocytes [13,47], is associated with liver fibrosis [40], increases apoptosis [11,20], induces oxidative stress [38,46], and alters the gut microbiome [24,33,39,48,51,59]. These mechanisms are linked to the pathogenesis of MetS [9,35]. ...
Background
The prevalence of metabolic syndrome (MetS) in American adults increased from 37.6% in the 2011–12 period to 41.8% in 2017–2018. Environmental exposure, particularly to common compounds such as glyphosate, has drawn increasing attention as a potential risk factor.
Methods
We employed three cycles of data (2013–2018) from the National Health and Nutrition Examination Survey (NHANES) in a cross-sectional study to examine potential associations between urine glyphosate measurements and MetS incidence. We first created a MetS score using exploratory factor analysis (EFA) of the International Diabetes Federation (IDF) criteria for MetS, with data drawn from the 2013–2018 NHANES cycles, and validated this score independently on an additional associated metric, the albumin-to-creatinine (ACR) ratio. The score was validated via a machine learning approach in predicting the ACR score via binary classification and then used in multivariable regression to test the association between quartile-categorized glyphosate exposure and the MetS score.
Results
In adjusted multivariable regressions, regressions between quartile-categorized glyphosate exposure and MetS score showed a significant inverted U-shaped or saturating dose‒response profile, often with the largest effect for exposures in quartile 3. Exploration of potential effect modification by sex, race, and age category revealed significant differences by race and age, with older people (aged > 65 years) and non-Hispanic African American participants showing larger effect sizes for all exposure quartiles.
Conclusions
We found that urinary glyphosate concentration is significantly associated with a statistical score designed to predict MetS status and that dose–response coefficient is nonlinear, with advanced age and non-Hispanic African American, Mexican American and other Hispanic participants exhibiting greater effect sizes.
... An active ingredient in Roundup is organophosphate glyphosate, N-(phosphonomethyl)glycine, in the form of its isopropylamine salt, with additional formulations containing so-called "inert" ingredients in different proportions, that are believed to be more toxic than glyphosate (Phyu et al., 2004). The mechanism of glyphosate toxicity in non-target organisms is mostly unknown, but it may cause uncoupling of oxidative phosphorylation (Peixoto, 2005). Atrazine, a triazine herbicide, that consists of a triazine ring, along with five nitrogen and one chlorine atoms, is used in the form of emulsifiable concentrate, soluble powder and granules. ...
... The molecular mechanisms of oxidative stress induction by glyphosate-based Roundup and Atrazine are well characterized. Uncoupling of mitochondrial oxidative phosphorylation may be a major effect of herbicide intoxication (Pathak et al., 2011;Peixoto, 2005). The impaired mitochondrial function caused by glyphosatebased herbicides can be related to increased ROS generation (Bailey et al., 2018;Gomes and Juneau, 2016). ...
The use of glyphosate-based Roundup and triazine herbicide Atrazine has increased markedly in last decades. Thus, it is important to evaluate toxic effects of these herbicides to non-targeted organisms such as zooplankton to understand their safety toward aquatic ecosystems. In the current study, we performed Daphnia toxicity tests based on lethality to identify LC50 that provides acute aquatic toxicity classification criteria. LC50 for Roundup exposure for 24 hours was found to be 0.022 mg/L and 48 hours - 0.0008 mg/L. Atrazine showed LC50 at concentrations of 40 mg/L and 7 mg/L for 24 and 48 hours, respectively. We demonstrated that exposure to ecologically relevant concentrations of Roundup or Atrazine decreases lipid peroxidation and protein thiol levels, however caused increase in carbonyl protein and low-molecular-weight thiols content. Moreover, the herbicide treatments caused increase of superoxide dismutase activity. Our data suggest that at very low concentrations Roundup and Atrazine disturb free radical processes in D. magna.
... Every aspect of commercial food production involves the usage of chemical products that are toxic to the mitochondria [145,149,150]. Many of the chemicals used in commercial agriculture [151][152][153][154] through the various channels of processing, perseveration and presentation, degrade thiamine and other nutrients when consumed [155]. The combination of high sugar, high toxic load and low thiamine and nutritional value in general, are likely at the root of much of the metabolic dysfunction affecting western populations. ...
... Rounding out the modern threats to thiamine status in developed countries, pervasive exposures to environmental chemicals and industrial pollutants, damage mitochondrial functioning, even at low, and what are considered, non-toxic exposures [152,[177][178][179][180] accelerating the need for thiamine and other mitochondrial nutrients. ...
Thiamine or vitamin B1 is an essential, water-soluble vitamin required for mitochondrial energetics-the production of adenosine triphosphate (ATP). It is a critical and rate-limiting cofactor to multiple enzymes involved in this process, including those at the entry points and at critical junctures for the glucose, fatty acid, and amino acid pathways. It has a very short half-life, limited storage capacity, and is susceptible to degradation and depletion by a number of products that epitomize modern life, including environmental and pharmaceutical chemicals. The RDA for thiamine is 1.1-1.2 mg for adult females and males, respectively. With an average diet, even a poor one, it is not difficult to meet that daily requirement, and yet, measurable thiamine deficiency has been observed across multiple patient populations with incidence rates ranging from 20% to over 90% depending upon the study. This suggests that the RDA requirement may be insufficient to meet the demands of modern living. Inasmuch as thiamine deficiency syndromes pose great risk of chronic morbidity, and if left untreated, mortality, a more comprehensive understanding thiamine chemistry, relative to energy production, modern living, and disease, may prove useful.
... On the other hand, energy efficiency can be affected not only by the deficiency of these proteins but also by other factors related to the interaction network described in Table 6, in line with previous reports in honeybees treated with GLY associated with a mitochondrial protein deficiency (Cullen et al. 2023). Similarly, another report revealed that Roundup, a commercial GLY product, induces the uncoupling of oxidative phosphorylation in rat liver cells (Peixoto 2005). Thus, a reduction in protein levels or a failure of mitochondrial function can cause imbalances in metabolic processes related to energy deficiency. ...
Uncontrolled use of pesticides has caused a dramatic reduction in the number of pollinators, including bees. Studies on the effects of pesticides on bees have reported effects on both metabolic and neurological levels under chronic exposure. In this study, variations in the differential expression of head and thorax–abdomen proteins in Africanized A. mellifera bees treated acutely with sublethal doses of glyphosate and imidacloprid were studied using a proteomic approach. A total of 92 proteins were detected, 49 of which were differentially expressed compared to those in the control group (47 downregulated and 2 upregulated). Protein interaction networks with differential protein expression ratios suggested that acute exposure of A. mellifera to sublethal doses of glyphosate could cause head damage, which is mainly associated with behavior and metabolism. Simultaneously, imidacloprid can cause damage associated with metabolism as well as, neuronal damage, cellular stress, and impairment of the detoxification system. Regarding the thorax–abdomen fractions, glyphosate could lead to cytoskeleton reorganization and a reduction in defense mechanisms, whereas imidacloprid could affect the coordination and impairment of the oxidative stress response.
... While glyphosate was originally thought to have no effect on humans, it is now rated by the International Agency for Research on Cancer (IARC) as a probable human carcinogen (Guyton et al, 2015), it has actions on both female and male fertility (Serra et al., 2021), has neurological effects (Madani and Carpenter 2022) and causes mitochondrial damage (Peixoto 2005). Animal and in vitro studies indicate that glyphosate exposure interferes with glucose uptake into adipocytes (Prasad et Given the limitations in the available studies and the problems associated with the use of the thresholdbased de nitions from a research standpoint, our study aims are two-fold: (1) to create and validate a score that captures the continuous nature of risk factors that make up MetS, and (2), to employ this score in linear regression analyses that explore associations between urine glyphosate concentrations and MetS. ...
Background: Prevalence of the Metabolic Syndrome (MetS) in American adults has risen from 37.6% in the 2011-12 period to 41.8% in 2017-2018. Environmental exposure, particularly to common compounds such as glyphosate, has drawn increasing attention as a potential risk factor.
Methods: We employ three cycles of data (2013-2018) from the National Health and Nutrition Examination Survey (NHANES) in a cross-sectional study to examine potential associations between urine glyphosate measurements and the MetS. We first created a MetS score using Exploratory Factor Analysis of 6 International Diabetes Federation (IDF) criteria for MetS, with data drawn from the 2013-2018 NHANES cycles, and validated this score independently on an additional associated metric, Albumin to Creatinine Ratio. The score was validated via a machine-learning approach in predicting ACR score via binary classification, then used in multivariable regression to test association between quartile-categorized glyphosate exposure and the MetS score.
Results: In adjusted multivariable regressions, quartile regressions between glyphosate exposure and MetS score show a significant inverted U-shaped or saturating dose-response profile, often with largest effect for exposures in quartile 3. Exploration of potential effect modification by sex, race, and age category shows significant differences by race and age, with older people (ages > 65 years) and non-Hispanic African American participants showing larger effect sizes for all exposure quartiles.
Conclusions: We find that urinary glyphosate is significantly associated with a statistical score designed to capture the MetS, and that dose-response is nonlinear, with advanced age and non-Hispanic African American and Mexican American and other Hispanic participants showing higher effect sizes.
... The assessment of the impacts of GBH is performed without due consideration of the possible effects of the coformulants (water and undisclosed "other ingredients"), which represent 5%-15% of concentrated products by weight (Mesnage et al., 2019). When considering different kinds of organisms, some studies have reported that glyphosate alone has less or no relevant ecotoxicological effect compared to GBH (e.g., on mitochondrial bioenergetics, as shown in Peixoto [2005]; on human cells, as shown in Nagy et al. [2019]; on cellular and physiological processes in the digestive tract of bumblebees, as shown in Cullen et al. [2023]). The higher toxicity of GBH was attributed to coformulants or to a synergic effect of glyphosate and formulation products. ...
Glyphosate is the most widely applied herbicide worldwide, contaminating water, soils, and living organisms. Earthworms are emblematic soil organisms used as indicators of soil quality, but knowledge about the impacts of glyphosate and glyphosate-based herbicides (GBH) on these key soil organisms is scattered. Here, we examine this knowledge in detail to answer four questions: (1) Which endpoint is the most sensitive when assessing the effects of glyphosate or GBH in earthworms? (2) Which is most toxic to earthworms: glyphosate or GBH? (3) Are glyphosate and GBH harmful to earthworms when used at the recommended application dose? (4) What are the interactions between glyphosate or GBH and other chemicals in earthworms? The results indicate that a weak legislation led to improper assessment of the ecotoxicity of glyphosate during the last renewal in 2017. Our findings also highlighted that negative effects can occur in earthworms at the recommended application rate, although not after only a single application or when considering only the mortality of adult individuals. However, under more realistic conditions, that is, when assessing sensitive endpoints (e.g., reproduction, growth) and using species present in the field, after several applications per year, the negative effects of glyphosate or GBH on earthworms were observed at the subindividual, individual, population, and community levels, as well as on earthworm-mediated functions. Our recommendations are as follows: (i) competent agencies should collect more information on the toxicity of these compounds to earthworms before the next renewal deadline, with emphasis on the use of the updated legislation on the topic, and (ii) scientists should increase research on the effects of these herbicides on soil invertebrate species, with emphasis on earthworms, using guideline tests and obtain data from long-term field testing. Integr Environ Assess Manag 2024;20:1330–1336. © 2023 SETAC
Key Points
A weak legislation led to improper assessment of the ecotoxicity of glyphosate during the last renewal in 2017. Negative effects of glyphosate or glyphosate-based herbicides (GBH) on earthworms were observed at the subindividual, individual, population, and community levels, as well as on earthworm-mediated functions. We urgently recommend more research on glyphosate and GBH in the laboratory and in the field, using several applications at the recommended application dose, at time intervals that are normally used by farmers, and in research of more than one year.
... A study involving 56 male albno rats indicated that Roundup (a type of GBH) exposure was associated with decreased GSH concentration and increased lipid peroxidation (Owagboriaye et al. 2019). In addition, an in vitro study on isolated rat liver mitochondria revealed that Roundup inhibited ATPase activity and induced mitochondrial membrane permeabilization (Peixoto 2005). In conclusion, glyphosate is associated with alterations in glucose, lipids metabolism, inflammation, and increased oxidative stress, all of which result in IR and may be a potential mechanism for diabetes, but results from more basic research are required. ...
Glyphosate-based herbicides (GBHs) are used extensively around the world and have become the leading agrochemicals. However, study about the association between glyphosate exposure and the risk of diabetes mellitus (DM) is scarce. This study used 4 years of NHANES data (2013–2016) to further investigate the association. A total of 2535 participants were enrolled in this cross-sectional study. The baseline information and urinary glyphosate levels in diabetic and non-diabetic groups were compared. Using multivariable logistic regression mode, we explored the association between both the continuous and categorical forms of urinary glyphosate and DM risk. Further subgroup analyses based on categorical covariates were also conducted. Urinary glyphosate levels were 0.42 ng/ml in participants with diabetes and 0.34 ng/ml in participants without diabetes (P < 0.05). As a continuous variable, ln-transformed urinary glyphosate was significantly associated with an increased risk of DM in the most adjusted model (OR 1.28, 95% CI 1.03–1.57). However, the association was not significant in the most adjusted categorical model (P > 0.05).In further subgroup analyses, the associations remained significant in several subgroups. This study provides new evidence that glyphosate exposure was associated with a higher risk of diabetes in the American general adult population.
... The International Agency for Research on Cancer reports on glyphosate's ability to induce cancerogenesis in humans [18]. For years, numerous studies have been conducted to assess the effects of this herbicide on different animal populations [15][16][17][18][19][20][21][22]. The toxic effects of glyphosate were studied on different classes of vertebrates. ...
The presence of pesticides and their potential toxic effects on fish can pose a threat to aquatic ecosystems and human health. The present study aimed to evaluate the effect of commercial formulations of glyphosate (Roundup) on the survival rate, hematological parameters, and tissues (gills and liver) of juvenile grass carp (Ctenopharyngodon idella). For these purposes, we exposed the fish to 0, 50, 100, and 150 mL L −1 of Roundup for 96 hr. Results showed a significant correlation between the fish's mortality rate and pesticide concentrations (p<0:01); the LC 50 96 hr of Roundup was 75.838 mL L −1 in the present study. The concentrations above 50 mL L −1 induced significant tissue lesions seen as lamellar aneurism, leukocyte infiltration, distal hyperplasia, cloudy swelling, macrophage aggregates, and necrosis in the gills and liver. We also reported a significant correlation between the severity of tissue damage and Roundup concentration. The hematocrit, hemoglobin, white, and red blood cell count significantly reduced after 96 hr of exposure to 100 and 150 mL L −1. The opposite trend was reported for concentrations of glucose, albumin, cholesterol, total protein, and triglycerides. Finally, the fish exposed to 100 and 150 mL L −1 of Roundup displayed some clinical signs, such as increasing operculum movement, darkening the skin, and swimming near the surface during the movement test. Overall, our results showed that concentrations of Roundup higher than 50 mL L −1 can induce various toxic effects and significantly reduce the survival chance of juvenile grass carp. Roundup altered fish behavior, tissue functioning, and biochemical processes. In this study, we provided some basic knowledge about the effects of a glyphosate-based herbicide on aquatic organisms and possible environmental management.
... Glyphosate (glyphosate 41 percent SL) is the most frequently used non-selective broad spectrum organophospho-pure glyphosate to have a low acute toxicity (WHO 1994). Commercial glyphosate formulations, on the other hand, are said to be more acutely hazardous than pure glyphosate due to the addition of other chemicals (Amarante Junior et al. 2002;Peixoto 2005). In Roundup, a surfactant, polyethoxylated tallow amine (POEA), is administered to escalate its efficacy (Tsui and Chu 2004;Relyea 2005). ...
In the present study, a comprehensive research was executed to investigate the salient toxic effects of glyphosate herbicide in static water system by evaluating the haematobiochemical profiles of Labio rohita. A challenge study against Aeromonas hydrophila was conducted to determine disease susceptibility of the fish , treated to varying concentrations of commercial-grade glyphosate herbicide. A static range finding bioassay and definitive test revealed that the 96-h LC50 value of glyphosate was 10.16 mg l−1. The experimental fish were subjected to three sub-lethal concentrations of 2.06, 1.03 and 0.63 mg l−1 for 28 days and changes were documented bi-fortnightly to study haemato-biochemical alterations in the fish. Significantly (p < 0.05) low values in red blood corpuscles (RBC), haemoglobin (Hb), and hematocrit value (Hct) were documented. In contrast, a significant (p < 0.05) escalation in White Blood Corpuscles (WBC) was documented in comparison to the control. Biochemical and stress markers such as blood glucose, total protein, and alkaline phosphatase (ALP) were significantly (p < 0.05) low, whereas serum glutamate pyruvate transaminase (SGPT) and serum glutamate oxaloacetate transaminase (SGOT) escalated significantly (p < 0.05). Chronic exposure to glyphosate , on the other hand, had the least effect on the Na+ and K+ ions. Further, a challenge assay against A. hydrophila at three sub-lethal glyphosate concentrations demonstrated a synergistic impact that reduced the fish survivability. The findings conclude that persistent low glyphosate concentrations in
aquatic ecosystems show significant pathophysiological changes in L. rohita, with
increased vulnerability to infections. Altogether, our findings indicate the need to
further study the possible assessment for a sustainable bio-remediation technique,
mitigation of the detrimental effects of glyphosate exposure in fish, and recommendation of an acceptable residue concentration of the glyphosate in aquatic ecosystem.
... According to the U.S. EPA [60], approximately 50 % of inert adjuvants authorised for pesticide manufacture possess low or low/ moderate risk. Several reports confirmed that excipients present in products formulations can exert toxicity by themselves, separate from the pure compound [20,22,29,[61][62][63][64]. Our current observations suggest that the introduction of DNA single-strand breaks, cytotoxicity and apoptosis induced by Karate ® is most probably due to the existence of xenobiotic(s) involved in the adjuvant(s) of the LCT-based microformulation, enhancing the toxic profile of the pyrethroid commercial product. ...
Lambda-cyhalothrin (LCT) and its microformulation Karate® (25 % a.i.) were analysed for its genotoxicity and
cytotoxicity on Chinese hamster ovary (CHO-K1) cells. Cytokinesis-block micronucleus cytome (CBMN-cyt) and
alkaline single-cell gel electrophoresis (SCGE) bioassays were selected to test genotoxicity. Neutral red uptake
(NRU), succinic dehydrogenase activity (MTT) and apoptogenic induction were employed for estimating cyto-
toxicity. Both compounds were analysed within a concentration range of 0.1–100 µg/mL. Only LCT produced a
significant augment in the frequency of micronuclei (MNs) when the cultures were exposed to highest concen-
trations of 10 and 100 µg LCT/mL. A noticeable decrease in NDI was observed for cultures treated with LCT at 10
and 100 µg/mL. Karate® induced the inhibition of both the proportion of viable cells and succinic dehydrogenase
activity and triggered apoptosis 24 h of exposition. Whilst an increased GDI in CHO-K1 cells was observed in the
treatments with 1–100 µg Karate®/mL, the GDI was not modified in the treatments employing LCT at equivalent
doses. SCGE showed that Karate® was more prone to induce genotoxic effects than LCT. Only 50 µg/mL of
Karate® was able to increase apoptosis. Our results demonstrate the genomic instability and cytotoxic effects
induced by this pyrethroid insecticide, confirming that LCT exposure can result in a severe drawback for the
ecological equilibrium of the environment.
... A study involving 56 male albno rats indicated that Roundup (a type of GBH) exposure was associated with decreased GSH concentration and increased lipid peroxidation (Owagboriaye, Dedeke, et al., 2019). In addition, an in vitro study on isolated rat liver mitochondrial revealed that Roundup inhibited ATPase activity and induced mitochondrial membrane permeabilization (Peixoto, 2005). In conclusion, glyphosate is associated with alterations in glucose, lipids metabolism, in ammation, and increased oxidative stress, all of which result in IR and may be a potential mechanism for diabetes, but results from more basic research are required. ...
Background
Glyphosate-based herbicides (GBHs) are used extensively around the world and have become the leading agrochemicals. However, study about the association between glyphosate exposure and diabetes is scarce. This study used four years of NHANES data (2013–2016) to further investigate the association.
Methods
A total of 2,806 participants were enrolled in this cross-sectional study. The baseline information and urine glyphosate levels in diabetic and non-diabetic groups were compared. We also divided urine glyphosate levels into tertiles. Three models were developed using weighted logistic regression. Further subgroup analyses based on categorical variables were also conducted.
Results
Urine glyphosate levels were 0.35ng/ml in people with diabetes and 0.44ng/ml in participants without diabetes (P < 0.05). Regardless of adjustment, the highest glyphosate level in the tertile3 group was significantly linked with an elevated risk of diabetes (OR 1.595, 95% CI 1.016–2.504, P = 0.043) compared to the tertile1 group. Subgroup analyses suggested that the associations were constant in participants who were male, older age (60–100), had a college degree, income ratio = 5, BMI > 30, and smoking.
Conclusions
This study provides new evidence that glyphosate exposure was associated with a higher risk of diabetes in the American general adult population.
... The increase in starch granules could be caused by interruption of the respiratory chain in mitochondria due to oxidative stress and possibly also by the exposure to the cyanotoxins released by M. aeruginosa, triggering the accumulation in chloroplasts and the loss of thylakoids organization by alterations of mitochondrial activity (Peixoto, 2005). ...
Human activities significantly influence the health of aquatic ecosystems because many noxious chemical wastes are discharged into freshwater bodies. Intensive agriculture contributes to the deterioration by providing indirectly fertilizers, pesticides, and other agrochemicals that affect the aquatic biota. Glyphosate is one of the most used herbicides worldwide, and microalgae are particularly sensitive to its formulation, inducing displacement of some green microalgae from the phytoplankton that leads to alterations in the floristic composition, which fosters the abundance of cyanobacteria, some of which can be toxigenic. The combination of chemical stressors such as glyphosate and biological ones, like cyanotoxins and other secondary metabolites of cyanobacteria, could induce a combined effect potentially more noxious to microalgae, affecting not only their growth but also their physiology and morphology. In this study, we evaluated the combined effect of glyphosate (Faena®) and a toxigenic cyanobacterium on the morphology and ultrastructure of microalgae in an experimental phytoplankton community. For this purpose, Microcystis aeruginosa (a cosmopolitan cyanobacterium that forms harmful blooms) and the microalgae Ankistrodesmus falcatus, Chlorella vulgaris, Pseudokirchneriella subcapitata, and Scenedesmus incrassatulus were cultivated, individually and jointly, exposing them to sub-inhibitory concentrations of glyphosate (IC10, IC20, and IC40). Effects were evaluated through scanning electron (SEM) and transmission electron (TEM) microscopy. Exposure to Faena® produced alterations in the external morphology and ultrastructure of microalgae both individually and in combined cultures. SEM evidenced the loss of the typical shape and integrity of the cell wall and an increase in the biovolume. TEM revealed reduction and disorganization of the chloroplast, variation in starch and polyphosphate granules, formation of vesicles and vacuoles, cytoplasm degradation, and cell wall continuity loss. The presence of M. aeruginosa was, for microalgae, an additional stress factor adding to the chemical stress produced by Faena®, increasing the damage in their morphology and ultrastructure. These results alert to the effects that can be caused by glyphosate and the presence of toxigenic bacteria on the algal phytoplankton in contaminated and anthropic and eutrophic freshwater ecosystems.
... 28 Roundup has been shown experimentally to inhibit both succinate dehydrogenase and cytochrome C reductase, two enzymes that play a crucial role in mitochondrial oxidative phosphorylation. 29 Succinate dehydrogenase is the primary enzyme in Complex II, and cytochrome C reductase is crucial in Complex III. Succinate dehydrogenase is the only enzyme that is involved in both the citric acid cycle and oxidative phosphorylation. ...
... Glyphosate was known to affect essential eukaryotic mitochondria function since 1970s (Olorunsogo et. al. 1979, Peixoto 2005, Myers et al. 2016, van Bruggen et al. 2021, Strilbyska et al. 2022, Mesnage et al. 2022. How much this destruction of soil biota adds to soil CO2 or NOx emissions is unclear as this subject seems as yet uninvestigated. ...
Land’s basic metric is soil organic carbon (SOC) yet global estimates range 1,417–15,000 Gt C. Erosion of ancient topsoil and loss of soil taxa are most urgent of all context-triage concerns, and most ignored. Re-evaluation of topographical terrain on a non-flat Earth increases most soil dynamic inventories. Carbon credits of our neglected and disappearing SOC stocks are enumerated for mineral soils (~4,100 Gt C plus ca. 20–30% glomalin), Permafrost (>4,200 Gt C), peat (1,123 Gt C), plant roots (916 Gt C), litter (600 Gt C), microbes (200 Gt C), fungi (30 Gt C), biocrust (10–20 Gt C), earthworms (2.3–3.6 Gt C), termites (0.15 Gt C), nematodes (0.06 Gt C), ants (0.024 Gt C), and soil viruses (0.02–4.0 Gt C). Net contribution to atmospheric CO2 is more from biotic topsoil loss (>10 Gt C/yr) than fossil fuels (<10 Gt C/yr). Although higher CO2 results in a terrestrial greening effect with Net Primary Productivity (NPP) now ~220 Gt C/yr (cf. ~20 Gt C/yr Ocean NPP), this is arguably offset by topsoil erosion, desert expansion, plus fire at net ~16–20 Gt C/yr lost due, in part, to extravagant meat-eating with unsupportable, humus-depleting farm management. In particular, excess synthetic Nitrogen acidifies topsoil and destroys the natural SOC biota. Review shows critical topsoil loss up to 20,000 tonnes per second and, when soil microbes/invertebrates are properly considered, extinctions as high as 23 taxa per second. Sustainable Development Goals (SDGs) fail without solid soil foundation. Rather, heritage farm-data points to resolution in organic husbandry. Remedy via natural vermi-compost, 100% organic farming and practical Permaculture is under a simple premise that the Problem (i.e., SOC loss) is the Solution (viz., SOC restoration).
... 45 85 mg/L glifosat maruziyetinin sıçan karaciğer mitokondrisinde süksinata bağımlı solunum indeksinde azalmaya neden olduğu görülmüştür. 46 Glifosat maruziyeti sonrasında hepatositlerde solunum aktivitesinin azaldığı görülmüştür. 47 Subakut ve subkronik maruziyetin karaciğer üzerine etkisinin incelendiği bir çalışmada, sıçanlar 13 hafta boyunca 56 mg/kg ve 560 mg/kg GIBH'ye maruz bırakılmıştır. ...
... Thus, species that have a copy of the EPSPS gene may be impacted by the use of GBP. Nevertheless, even species that lack a copy of the EPSPS gene may be impacted by the herbicide through alternative non-target mechanisms43 , 44 . (ii) If the analysis of the EPSPS gene is not included in the design of the study, it is possible to get a good estimate by analyzing the 16S rRNA (bacteria) or ITS (fungi). ...
Glyphosate-based products (GBP) are the most common broad-spectrum herbicides worldwide. The target of glyphosate is the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) in the shikimate pathway, which is virtually universal in plants. The inhibition of the enzyme stops the production of three essential amino acids: phenylalanine, tyrosine, and tryptophan. EPSPS is also present in fungi and prokaryotes, such as archaea and bacteria; thus, the use of GBP may have an impact on the microbiome composition of soils, plants, herbivores, and secondary consumers. This article aims to present general guidelines to assess the effect of GBP on microbiomes from field experiments to bioinformatics analyses and provide a few testable hypotheses. Two field experiments are presented to test the GBP on non-target organisms. First, plant-associated microbes from 10 replicated control and GBP treatment plots simulating no-till cropping are sampled and analyzed. In the second experiment, samples from experimental plots fertilized by either poultry manure containing glyphosate residues or non-treated control manure were obtained. Bioinformatics analysis of EPSPS protein sequences is utilized to determine the potential sensitivity of microbes to glyphosate. The first step in estimating the effect of GBP on microbiomes is to determine their potential sensitivity to the target enzyme (EPSPS). Microbial sequences can be obtained either from public repositories or by means of PCR amplification. However, in the majority of field studies, microbiome composition has been determined based on universal DNA markers such as the 16S rRNA and the internal transcribed spacer (ITS). In these cases, sensitivity to glyphosate can only be estimated through a probabilistic analysis of EPSPS sequences using closely related species. The quantification of the potential sensitivity of organisms to glyphosate, based on the EPSPS enzyme, provides a robust approach for further experiments to study target and non-target resistant mechanisms.
... Furthermore, by investigating the interactive effects between the main ingredient and the surfactant, we also showed that glyphosate, when applied in combination with POEA (as is the case in many glyphosate-based herbicides), can further increase POEA-caused lethality. It is assumed that POEA acts synergistically with glyphosate at the mitochondrial level (Peixoto 2005). Frontera et al. (2011) indeed observed a larger decrease in oxygen consumption of Cherax quadricarinatus exposed to mixtures of POEA and glyphosate, which they attributed to enzyme inhibition, and which resulted in lowered protein levels and decreased somatic growth (Frontera et al. 2011). ...
Current international legislation regarding agrochemicals requires thorough toxicological testing mainly of the active ingredients. In a 96-h acute toxicity test we exposed Rana dalmatina and Bufo bufo tadpoles to either one of three concentrations of glyphosate, three concentrations of the surfactant (POEA), three concentrations of the two components together, or to non-contaminated water (control), and subsequently assessed mortality and body mass. To investigate whether simultaneous exposure to another stress factor influences effects of the contaminants, we performed tests both in the presence or absence of predator chemical cues. We found that the surfactant had significant harmful effects on tadpoles; survival was lowered by the highest concentration of the surfactant in case of R. dalmatina , while in B. bufo tadpoles it reduced survival already at medium concentrations. Body mass was significantly influenced by medium and high surfactant concentrations in both species. The presence of glyphosate did not have a significant effect by itself, but it slightly increased mortality in tadpoles exposed to medium concentrations of the surfactant in both species. The presence of chemical cues did not have an effect on the examined variables. Our study confirms that the toxicity of glyphosate-based herbicides is mainly due to the examined surfactant. Nonetheless, we found that glyphosate can enhance the harmful effect of the surfactant. These results stress that during the authorization process of new pesticide formulations, not only the active ingredients would need to be examined but the excipients should also be taken into account in an obligatory and systematic manner.
... For instance, Roundup ® caused the appearance of genotoxicity in the blood cells of alligator chicks, as well as in erythrocytes and liver cells of Corydoras paleatus fish (Poletta et al. 2009(Poletta et al. , 2011 in addition to other genotoxic effects Complimentary Contributor Copy reported in cell cultures such as mammalian bone marrow, hepatocytes, and lymphocytes (Kier and Kirkland 2013). In comparative studies between glyphosate alone and Roundup ® formulation, it was evidenced that this formulation is more toxic than glyphosate in several cell culture systems and in isolated mitochondria (Olorunsogo et al. 1979;Peixoto 2005;Benachour and Séralini 2009;. By using the alternative model Caenorhabditis elegans, it was possible to evidence abnormalities in the dopaminergic neurons, in addition to reduced fertility, inhibition of mitochondrial complex II and increase of hydrogen peroxide levels (McVey et al. 2016). ...
Glyphosate-based herbicides (GBHs) have been developed under the rationale of specifically targeting plants, since glyphosate mechanism is based on the inhibition of the shikimate pathway, present only in plants. However, this herbicide has been detected in aquatic ecosystems, wildlife and in humans and several studies have demonstrated its toxicity in different organisms. In order to better study the environmental impacts of this herbicide and its commercial formulations, animal models have been applied. Nematodes, aquatic organisms, insects and other organisms have provided important insights on the environmental impacts and important policies have been created for ecological and human health protection. This chapter reviews ecotoxicological and experimental studies on GBHs exposure and strategies that may reduce their environmental impact.
... Despite this, some proteins associated with ROS production and energy metabolism were also differentially affected by CF exposure. Glyphosate induced damage and dysfunction of the mitochondria has been widely reported in several animals (Peixoto, 2005;Lopes et al., 2018;A. G. Pereira et al., 2018;Neto da Silva et al., 2020) and combined with our findings here, highlight that the mitochondrion and its processes are particularly sensitive to glyphosate-exposure. ...
Glyphosate is one of the most widely used herbicides globally. It acts by inhibiting an enzyme in an aromatic amino synthesis pathway specific to plants and microbes, leading to the view that it poses no risk to other organisms. However, there is growing concern that glyphosate is associated with health effects in humans and an ever-increasing body of evidence that suggests potential deleterious effects on other animals including pollinating insects such as bees. Although pesticides have long been considered a factor in the decline of wild bee populations, most research on bees has focussed on demonstrating and understanding the effects of insecticides. To assess whether glyphosate poses a risk to bees, we characterised changes in survival, behaviour, sucrose solution consumption, the digestive tract proteome, and the microbiota in the bumblebee Bombus terrestris after chronic exposure to field relevant doses of technical grade glyphosate or the glyphosate-based formulation, RoundUp Optima+®. Regardless of source, there were changes in response to glyphosate exposure in important cellular and physiological processes in the digestive tract of B. terrestris, with proteins associated with oxidative stress regulation, metabolism, cellular adhesion, the extracellular matrix, and various signalling pathways altered. Interestingly, proteins associated with endocytosis, oxidative phosphorylation, the TCA cycle, and carbohydrate, lipid, and amino acid metabolism were differentially altered depending on whether the exposure source was glyphosate alone or RoundUp Optima+®. In addition, there were alterations to the digestive tract microbiota of bees depending on the glyphosate source No impacts on survival, behaviour, or food consumption were observed. Our research provides insights into the potential mode of action and consequences of glyphosate exposure at the molecular, cellular and organismal level in bumblebees and highlights issues with the current honeybee-centric risk assessments of pesticides and their formulations, where the impact of co-formulants on non-target organisms are generally overlooked.
... Edited by Roberto Romani * Pedro Brito pbrito@ufg.br 1 However, even animals not presenting the shikimate metabolic pathway, previous studies have demonstrated that GBH can induce cellular alterations in different animal models. GBH can cause epidermic metaplasia and gill malformation in anuran tadpoles (Rissoli et al. 2016;Howe et al. 2004) and can cause the loss of mitochondrial transmembrane potential and impair oxidative phosphorylation in rat cell cultures and rats in vivo (Gui et al. 2012;Peixoto 2005). Ultralow (0.1 ppb) chronic exposure of rats to GBH can alter hepatic metabolism, inducing non-alcoholic hepatic steatosis (Mesnage et al. 2015;2017). ...
Glyphosate-based herbicides (GBH) are the best-selling pesticides in Brazil, with hundreds of thousands of tons sold per year. There is no study investigating morphological alterations caused by GBH on the epithelium of the gut in bees. Here, we aimed to demonstrate effects of chronic ingestion of GBH in the midgut digestive cells of the Brazilian stingless bee Melipona quadrifasciata quadrifasciata Lepeletier 1836. We kept forager workers of M. quadrifasciata in laboratory conditions and fed on food contaminated with three different concentrations of GBH for 10 days, after which the midgut digestive cell structure and ultrastructure were analyzed. The presence of GBH in food did not affect food consumption, indicating that M. quadrifasciata bees do not reject food contaminated with GBH. As digestive cells of the midgut release apocrine secretion as a detoxication mechanism, we expected that the ingestion of food contaminated with GBH in the present study affect the height of midgut digestive cells. However, such reduction did not occur, probably because of the low-test concentrations. Although there were differences in digestive cell ultrastructure, ingestion of GBH impaired midgut digestive cell cohesion by disorganizing the smooth septate junctions between cells, which may probably be caused by the adjuvant “polyethoxylated tallow amine” present in the GBH. Previous studies demonstrated that GBH increase bees’ sensibility to intestine infections, based on the present results we hypothesized that the loss of cell cohesion in the midgut epithelium favors pathogenic microbial infections and harms food absorption, increasing bees’ mortality.
... Moreover, 341 adult zebrafish spermatozoa display decreased mitochondrial functionality after short-term 342 glyphosate exposure, though at concentrations exceeding those measured in the environment (5-343 10 mg/L; Lopes et al., 2014). Contrary to our findings, Peixoto et al. (2005) report that glyphosate 344 has no effect on mitochondria bioenergetics in isolated rat liver mitochondria. Together, these 345 results suggest glyphosate's mitochondrial effects are tissue and paradigm dependent, a finding 346 that would be masked by our whole animal in vivo approach. ...
Glyphosate-based herbicides (GBHs), the most recognized of which is Roundup ™ , are the most extensively used herbicides worldwide. GBHs were initially considered safe for animals since the primary target of the active ingredient, glyphosate, is only found in plants. Recent studies show that glyphosate can affect a range of animal physiologies; however, it remains poorly characterized as to whether animal GBH effects are mediated by glyphosate itself or are in response to toxic effects of the adjuvants and surfactants found in GBH formulations. Here we expose embryonic zebrafish to environmentally relevant doses of glyphosate or Roundup ™ and compare effects on two systems in the larvae: cellular bioenergetics, since glyphosate can affect mitochondrial function, and behaviour, as a systems-level readout of lasting developmental changes. We showed that exposure of embryonic zebrafish to low levels of glyphosate resulted in decreased mitochondrially-mediated basal respiration and hypoactive swimming behavior in larval stage, whereas exposure to Roundup ™ in this same treatment paradigm had the opposite effect, causing increased cellular respiration and increased locomotion. In addition, we also explored generational effects of F1 embryonic glyphosate or Roundup ™ exposure in the F2, and showed that offspring born to zebrafish exposed to low-level glyphosate or Roundup ™ during embryogenesis both exhibited reduced mitochondrially-mediated basal respiration and altered locomotion. Combined, these data show that embryonic exposure to glyphosate or the full formulation of GBHs caused differential effects on mitochondrial function and behaviours in vertebrates, with potential lasting effects on future generations. Figure 1.
Graphical abstract
Zebrafish (F1 generation) were exposed to glyphosate or Roundup ™ from zero to 48 hours, with behaviour and mitochondrial bioenergetics assessed at larval timepoints (2- and 5-dpf). Offspring of glyphosate and Roundup ™ exposed fish (F2 generation) behaviour and mitochondrial bioenergetics were assessed to the same paradigm as F1 fish at 5-dpf. Changes to core metabolic parameters and locomotion was observed in both F1 and F2 generations.
... The continuous blockage of complex III activity under high concentrations of glyphosate (≥ 75 µg l −1 ) may then result in lower oxidation of ubiquinol (UQH 2 ), with the consequent lower availability of ubiquinone (UQ) necessary for the activity of the dehydrogenases of complexes I and II, resulting in their decreased activities ( Fig. 4C and D). Different from our results, Peixoto (2005) did not observe any effect of glyphosate on the respiratory metabolism (at concentrations up to 845.354 mg l −1 ) or ETC enzyme activities (in concentrations up to 2.53 g l −1 ) of isolated rat liver mitochondria. In our study, however, the larvae and plants were exposed to glyphosate well before the evaluations, a methodology more similar to situations of environmental exposure to contaminants, for it considers alterations in the whole organism and associated effects on mitochondrial metabolism. ...
We evaluated the individual and combined effects of different environmentally representative concentrations of glyphosate (0, 25, 50, 75, and 100 µg l⁻¹) and aminomethylphosphonic acid (AMPA; 0, 12.5, 25, 37.5, and 50 µg l⁻¹) on the physiology of Aedes aegypti larvae, as well as the capacity of the aquatic macrophyte Salvinia molesta to attenuate those compounds’ toxicological effects. Larvae of Ae. aegypti (between the third and fourth larval stages) were exposed for 48 h to glyphosate and/or AMPA in the presence or absence of S. molesta. Glyphosate and AMPA induced sublethal responses in Ae. aegypti larvae during acute exposures. Plants removed up to 49% of the glyphosate and 25% of AMPA from the water, resulting in the exposure of larvae to lower concentration of those compounds in relation to media without plants. As a result, lesser effects of glyphosate and/or AMPA were observed on larval acetylcholinesterase, P450 reductase, superoxide dismutase, mitochondrial electron transport chain enzymes, respiration rates, and lipid peroxidation. In addition to evidence of deleterious effects by media contamination with glyphosate and AMPA on aquatic invertebrates, our results attest to the ability of S. molesta plants to mitigate the toxicological impacts of those contaminants.
Graphical abstract
... The active ingredients in Roundup are IPA-salt, polyethoxylated tallow amine (POEA) and other constituents [41]. These adjuvants can sometimes be even more toxic than glyphosate [42,43]. A thorough examination of surfactant co-formulants in glyphosate-based herbicides is urgently needed. ...
The use of synthetic molecules to achieve specific goals is steadily increasing in the environment, and these molecules adversely impact human health and ecosystem services. Considering the
adverse effects, a better understanding of how these molecules behave in the environment and their
associated risks is necessary to keep their use acceptably limited. To meet the demands of farmers
and combat weed problems, woodlands and farmlands are sprayed with agrochemicals, primarily
glyphosate-based herbicides. Farmers increasingly embrace these herbicides containing glyphosate.
Glyphosate and aminomethylphosphonic acid (AMPA), a key metabolite of glyphosate, have been
reported as toxicological concerns when they become more prevalent in the food chain. The chemical
glyphosate has been linked to various health issues in humans and other living organisms, including
endocrine disruption, reproductive issues, tumours, non-Hodgkin lymphomas, and liver, heart, and
blood problems. Therefore, the current review aims to compile data on glyphosate-based herbicide
use in the environment, potential risks to human and ecological health, and various maximum
residual limits for crops as suggested by international organizations. As a result, regulatory agencies
can advise glyphosate users on safe usage practices and synthesize herbicides more efficiently.
Keywords: glyphosate-based herbicide; AMPA; toxicological effect; ecological risk; regulations
... The animals exposed to the chemicals had lower oxygen consumption compared to the control. In addition, there is indication that POEA surfactant can act synergistically with glyphosate, depressing the activity of several mitochondrial complexes (Peixoto, 2005). ...
The use of agrochemicals has increased in recent years, following the growth of agricultural productions, to eliminate weeds that can compromise crop yields. The intensive use of these products combined with the lack of treatment of agricultural wastewater is causing contamination of the natural environment, especially the aquatic, by processes such as leaching and drifts. Glyphosate [N-(phosphonomethyl) glycine] is the most commonly used herbicide in agriculture worldwide. Studies have shown that this contaminant is toxic to a variety of fish species at the concentrations of environmental relevance. Pure glyphosate and its formulas can compromise biochemical, physiological, endocrine, and behavioral pathways. The behavior patterns of fish are a sensitive tool for risk assessment. Changes in behavior such as food search, escape from predators, and the courtship for reproduction can compromise the survival of species and even communities. In this sense, this review summarizes and discusses, for the first time, the toxic effects of glyphosate and its formulations on the behavior of fish in different life stages. Additionally, we associated the behavioral disturbances with other effects of glyphosate such as on energy imbalance, stress responses, AChE inhibition, and endocrine disruptors, evidence and described in the literature, were associated.
... Owing to excess exposure to free radicals at the level of intracellular organelles, these changes can be regarded as early manifestations of apoptosis and an adaptive process to adverse environments (Wakabayashi 2002). Peixoto (2005) observed that higher sub-lethal doses of GLP depressed mitochondrial respiratory function in rat liver cells. Additionally, light microscopy showed some hepatocytes in the GLP-treated liver with dark pyknotic nuclei, which is the most characteristic feature of apoptosis (Elmore 2007). ...
... In addition, the results of various studies support the greater toxicity of commercial glyphosate formulations compared to glyphosate administered alone [147,[204][205][206]. For this reason, the results analyzed herein cannot be attributed exclusively to glyphosate, as they could have been caused by other components of the formulation or even by possible synergy between these components and glyphosate [65,[207][208][209]. ...
Glyphosate, a non-selective systemic biocide with broad-spectrum activity, is the most widely used herbicide in the world. It can persist in the environment for days or months, and its intensive and large-scale use can constitute a major environmental and health problem. In this systematic review, we investigate the current state of our knowledge related to the effects of this pesticide on the nervous system of various animal species and humans. The information provided indicates that exposure to glyphosate or its commercial formulations induces several neurotoxic effects. It has been shown that exposure to this pesticide during the early stages of life can seriously affect normal cell development by deregulating some of the signaling pathways involved in this process, leading to alterations in differentiation, neuronal growth, and myelination. Glyphosate also seems to exert a significant toxic effect on neurotransmission and to induce oxidative stress, neuroinflammation and mitochondrial dysfunction, processes that lead to neuronal death due to autophagy, necrosis, or apoptosis, as well as the appearance of behavioral and motor disorders. The doses of glyphosate that produce these neurotoxic effects vary widely but are lower than the limits set by regulatory agencies. Although there are important discrepancies between the analyzed findings, it is unequivocal that exposure to glyphosate produces important alterations in the structure and function of the nervous system of humans, rodents, fish, and invertebrates.
... Thus, species that have a copy of the EPSPS gene may be impacted by the use of GBP. Nevertheless, even species that lack a copy of the EPSPS gene may be impacted by the herbicide through alternative non-target mechanisms43 , 44 . (ii) If the analysis of the EPSPS gene is not included in the design of the study, it is possible to get a good estimate by analyzing the 16S rRNA (bacteria) or ITS (fungi). ...
Glyphosate-based products (GBP) are the most common broad-spectrum herbicides worldwide. The target of glyphosate is the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) in the shikimate pathway, which is virtually universal in plants. The inhibition of the enzyme stops the production of three essential amino acids: phenylalanine, tyrosine, and tryptophan. EPSPS is also present in fungi and prokaryotes, such as archaea and bacteria; thus, the use of GBP may have an impact on the microbiome composition of soils, plants, herbivores, and secondary consumers. This article aims to present general guidelines to assess the effect of GBP on microbiomes from field experiments to bioinformatics analyses and provide a few testable hypotheses. Two field experiments are presented to test the GBP on non-target organisms. First, plant-associated microbes from 10 replicated control and GBP treatment plots simulating no-till cropping are sampled and analyzed. In the second experiment, samples from experimental plots fertilized by either poultry manure containing glyphosate residues or non-treated control manure were obtained. Bioinformatics analysis of EPSPS protein sequences is utilized to determine the potential sensitivity of microbes to glyphosate. The first step in estimating the effect of GBP on microbiomes is to determine their potential sensitivity to the target enzyme (EPSPS). Microbial sequences can be obtained either from public repositories or by means of PCR amplification. However, in the majority of field studies, microbiome composition has been determined based on universal DNA markers such as the 16S rRNA and the internal transcribed spacer (ITS). In these cases, sensitivity to glyphosate can only be estimated through a probabilistic analysis of EPSPS sequences using closely related species. The quantification of the potential sensitivity of organisms to glyphosate, based on the EPSPS enzyme, provides a robust approach for further experiments to study target and non-target resistant mechanisms.
... The syndrome bearing his name is caused by a sudden increase in intra-oesophageal pressure with negative intrathoracic pressure. This is commonly associated with retching and vomiting, but these symptoms may be absent in up to 45% of patients [3]. With a very low incidence of 3.1 per 1 000 000 people per year [4], early recognition and management are of utmost importance as the outcome is directly proportional to the time delay between onset of rupture and management [5]. ...
Glyphosate intoxication in a patient presenting with Boerhaave syndrome: A case report
... For instance, Roundup ® caused the appearance of genotoxicity in the blood cells of alligator chicks, as well as in erythrocytes and liver cells of Corydoras paleatus fish (Poletta et al. 2009(Poletta et al. , 2011 in addition to other genotoxic effects Complimentary Contributor Copy reported in cell cultures such as mammalian bone marrow, hepatocytes, and lymphocytes (Kier and Kirkland 2013). In comparative studies between glyphosate alone and Roundup ® formulation, it was evidenced that this formulation is more toxic than glyphosate in several cell culture systems and in isolated mitochondria (Olorunsogo et al. 1979;Peixoto 2005;Benachour and Séralini 2009;. By using the alternative model Caenorhabditis elegans, it was possible to evidence abnormalities in the dopaminergic neurons, in addition to reduced fertility, inhibition of mitochondrial complex II and increase of hydrogen peroxide levels (McVey et al. 2016). ...
Glyphosate [N-(phosphonomethyl)glycine] is one of the organophosphate herbicides which is most frequently used in agriculture, forestry, green public areas, and gardens for elimination of annual and perennial weeds. High efficiency in weed and pest control was achieved by using glyphosate, thus harvesting of clean and healthy final products was possible. However, extensive long-term application of glyphosate resulted in its accumulation in various environments. That accumulation poses a great concern for public health, suggesting the hazardous potential of this herbicide to various non-target organisms.
... non-essential amino acids, nucleotides, and fatty acid biosynthesis) (Chang et al., 2019;Windisch et al., 2011). Several authors have shown that GBHs were able to affect mitochondrial function in isolated mitochondria (Peixoto, 2005), cells (Luo et al., 2017), and fish (Davico et al., 2021;Lopes et al., 2014;Pereira et al., 2018). More specifically, inhibition of CCO activity and mitochondrial impairments in the brain of zebrafish were reported after chronic direct exposure to 65 μgL −1 of a GBH (Pereira et al., 2018). ...
In the past few decades, glyphosate became the most used herbicide substance worldwide. As a result, the substance is ubiquitous in surface waters. Concerns have been raised about its ecotoxicological impact, but little is known about its generational toxicity. In this study, we investigate the impact of an environmentally relevant concentration of glyphosate and its co-formulants on an F2 generation issued from exposed generations F0 and F1. Trans, inter and multigenerational toxicity of 1 μg L⁻¹ of the active substance was evaluated on early stages of development and juvenile rainbow trout (Oncorhynchus mykiss) using different molecular, biochemical, immuno-hematologic, and biometric parameters, behavior analysis, and a viral challenge. Reproductive parameters of generation F1 were not affected. However, developmental toxicity in generation F2 due to glyphosate alone or co-formulated was observed with head size changes (e.g. head surface up to +10%), and metabolic disruptions (e.g. 35% reduction in cytochrome-c-oxidase). Moreover, larvae exposed transgenerationally to Viaglif and intergenerationally to glyphosate and Roundup presented a reduced response to light, potentially indicating altered escape behavior. Overall methylation was, however, not altered and further experiments using gene-specific DNA metylation analyses are required. After several months, biochemical parameters measured in juvenile fish were no longer impacted, only intergenerational exposure to glyphosate drastically increased the susceptibility of rainbow trout to hematopoietic necrosis virus. This result might be due to a lower antibody response in exposed fish. In conclusion, our results show that generational exposure to glyphosate induces developmental toxicity and increases viral susceptibility. Co-formulants present in glyphosate-based herbicides can modulate the toxicity of the active substance. Further investigations are required to study the specific mechanisms of transmission but our results suggest that both non-genetic mechanisms and exposure during germinal stage could be involved.
Bees play a crucial role in pollination but are exposed to various pesticides during nectar and pollen collection, which can impact their health and pollination efficiency. This study aimed to investigate morphological and histochemical changes in the hypopharyngeal glands of Scaptotrigona postica after exposure to three chemical compounds: glyphosate, fipronil, and Tween. Nurse bees of S. postica were divided into four experimental groups and fed with sucrose syrup containing the compounds for 24 h. After the exposure period, the hypopharyngeal glands were analyzed for morphology using light microscopy and transmission electron microscopy. The hypopharyngeal glands of S. postica exhibited a tubuloacinar structure, with unicellular acini approximately 54 µm in diameter. Exposure to fipronil resulted in changes in the organization of the rough endoplasmic reticulum (RER) and increased area and sphericity of the acini compared to all other groups, as well as a higher presence of proteins in the cytoplasm compared to other pesticides, potentially due to increased food consumption. Bees exposed to glyphosate showed alterations in the mitochondria compared to all groups. The Tween group did not exhibit significant changes in cellular ultrastructure, only a smaller area and sphericity compared to the control group. The hypopharyngeal glands are highly sensitive to pesticides and are efficient bioindicators. Significant changes in these glands can compromise the maintenance of the colony.
The massive use of herbicides, particularly glyphosate‐based herbicides (GBHs), raises several worries, notably their neurotoxic effects. Several studies have explored the consequences of developmental exposure. Our work aims to determine the impact of maternal exposure to GBH on behavioral disorders and memory deficits, as well as the involvement of oxidative stress in the hippocampus and prefrontal cortex. In addition, our study explores the neuroprotective properties of melatonin in male and female offspring. Pregnant Wistar rats were injected with GBH 75 mg/kg during gestation and lactation. After weaning, the offspring were treated with melatonin (4 mg/kg) from postnatal days 30–58. Our results show that GBH increases anxiety‐like behavior levels in offspring, as well as depression‐like behavior. GBH also impairs working memory in progeny. While markers of oxidative stress show a disturbance in lipid peroxidation and catalase activity, with a more pronounced effect in females, on the other hand, melatonin considerably attenuated the neurotoxic impact observed in the offspring, with higher efficacy in females. The oxidative stress results confirm the antioxidant power of melatonin to counteract the damaging effects of exposure to environmental contaminants such as glyphosate‐based pesticides. It will then be interesting to further our work to fully understand the sex‐dependent effect of melatonin.
Glyphosate is one of the most commonly used herbicide globally. It is considered an endocrine-disrupting chemical (EDC) that can affect the production and function of various hormones including testosterone. Testosterone is an important sex hormone in men that governs sexual development, function, metabolism, and reproduction. Glyphosate has been associated with testosterone impairment in a number of experimental studies; however, the association between glyphosate exposure and testosterone among U.S. adult men in the general population is currently unknown. Data was leveraged from the National Health and Nutrition Examination Survey (NHANES), which is an annually conducted, population-based cross-sectional study. Urinary levels of glyphosate were quantified as measures of exposure. Total testosterone was quantified from the serum of adult men ages 18+, and a serum value of <300 ng/dL was used to define low testosterone. Chi-square, analysis of variance (ANOVA), and multivariable, weighted linear and logistic regression analyses were used to compare sociodemographic and biological characteristics between quartiles of glyphosate exposure, identify risk factors for glyphosate exposure and low testosterone, and to analyze the relationship between glyphosate and testosterone. A total of 441 adults were included in final analyses, representing 18,345,154 individuals after survey weighting. The geometric mean of glyphosate was 0.58 ng/mL (IQR: 0.26–0.66). Race/ethnicity was significantly associated with glyphosate exposure, where white men had higher mean glyphosate exposure compared to black men (β = 0.11, p = .04). Analysis of total glyphosate modeled as a continuous variable was not significantly associated with testosterone (β = 10.93, p = .75). Similarly, no significant associations were observed when categorizing urinary glyphosate into quartiles when evaluating continuous testosterone (β = 3.46 p = .85, β = −6.74 p = .78, β = 10.22 p = .75 for quartiles 2–4, respectively), and categorical testosterone (i.e. normal/low) (OR = 2.29 95% CI [0.61,8.58], OR = 0.88 95% CI [0.18,4.08], OR = 1.14 95% CI [0.39,3.30]) for quartiles 2–4, respectively. We present the first evaluation of population-based urinary glyphosate levels on testosterone among U.S. adult men. We observed no significant associations between glyphosate and testosterone levels. Future studies are warranted to corroborate these findings, and to test these associations in prospective studies and within populations exposed to high levels of glyphosate.
Mitochondria perform several biological functions in living organisms, such as ATP production; calcium, copper, and iron homeostasis; pyrimidine and steroid synthesis; thermogenesis; and calcium signaling. Xenobiotics have high affinity for compounds and present different potentials. When xenobiotics are present in the mitochondrial membrane, they lead to various disturbances and cause the organelle to collapse, altering the electron transport chain and resulting in loss of energy production and even cell death. Due to their structural and functional characteristics and because they can act as biosensors, mitochondria are important targets for assessing the toxicity of xenobiotics. Many methods, including colorimetry and fluorimetry, among others, can be used to clarify the mechanisms that induce mitochondrial damage and will be addressed throughout this chapter.
As an active ingredient in its derivative products, glyphosate has emerged as the most widespread herbicide in recent decades. Bovine serum albumin (BSA) as a carrier protein may be adversely affected by structural changes due to binding affinity with glyphosate, which may lead to dysfunctionality or metabolic disorders. This study aimed to investigate the interaction of glyphosate with BSA and its thermal fibrillation pathway employing techniques such as dynamic surface tension, fluorescence quenching, ThT binding, circular dichroism spectroscopy, and reactive oxygen species (ROS) measurement, as well as molecular dynamics (MD) studies. The adsorption dynamic analysis suggested hydrophobic moiety at higher concentrations of glyphosate upon interaction with BSA. MD results suggested a slight fluctuation due to glyphosate interaction with protein molecules. The carboxy group presented in glyphosate made a hydrogen bond with the hydroxyl group of TYR¹⁴⁷. The fluorescence quenching and diffusion studies approved BSA's increased unfolding and hydrophobicity resulting from glyphosate interaction, which would induce fibrillation/aggregation, according to our fibrillation kinetics data. The surface activity of glyphosate at higher concentrations and its approved involvement in structural changes of BSA through hydrogen bonding may raise concerns about its potential side effect on farm animals and the food cycle.
Glyphosate‐based herbicide Roundup, as the most employed herbicide used for multiple purposes in agriculture, adversely affects nontarget organisms. We tested the effects of Roundup applied at larval and adult stages. Roundup caused developmental delay and increased larvae mortality. Roundup treatment reduced hemolymph glucose and glycogen levels in adult flies of both sexes at the highest concentration tested. Sex‐dependent diverse effects were found in catalase and Cu,Zn superoxide dismutase (Cu,Zn‐SOD) activities. Decreased aconitase activity, contents of thiols, and lipid peroxides were found after larval Roundup exposure. Furthermore, chronic exposure to adult flies decreased appetite, body weight, and shortened lifespan. Thus, our results suggest that high concentrations of Roundup are deleterious to both larvae and adults, resulting in a shift of the metabolism and antioxidant defense system in Drosophila melanogaster. Roundup caused developmental delay and increased larvae mortality in Drosophila melanogaster. Roundup treatment during development reduced hemolymph glucose and glycogen levels in adult flies of both sexes at the highest concentration tested. Chronic exposure of adult flies decreased appetite, body weight, and shortened lifespan suggesting that high concentrations of Roundup are deleterious to both larvae and adults, resulting in a shift of the metabolism and antioxidant defense system in D. melanogaster.
Le glyphosate, substance active herbicide (SA) la plus utilisée dans le monde, est omniprésent dans les eaux de surface. L’évaluation de son écotoxicité et de celle des herbicides commerciaux à base de glyphosate (GBHs) est complexe et controversée. Le glyphosate et ses co-formulants peuvent être toxiques pour les poissons et leurs interactions ainsi que la transmission verticale de cette toxicité sont relativement peu étudiées. La toxicité directe et générationnelle d’une dose environnementale de glyphosate a été évaluée sur plusieurs générations de truites arc-en-ciel exposées chroniquement à la SA et à deux GBHs. L’état de santé des poissons a été déterminé via la mesure de paramètres biométriques, comportementaux et reproducteurs. L’immunité a été appréhendée lors d’infections virales expérimentales. Le métabolisme énergétique et le système antioxydant ont été suivis avec des marqueurs biochimiques. L’exposition directe aux contaminants n’a pas impacté la physiologie et la reproduction de la génération F0. Des perturbations du développement embryo-larvaire des descendances F1 et F2 ont été induites par les expositions directes, inter et transgénérationnelles ; avec un effet suggéré de la réexposition aux composés parentaux. Les modifications observées chez les stades précoces n’ont pas été détectées chez les truites juvéniles, bien que leur susceptibilité virale ait été affectée. La comparaison des effets du glyphosate et des GBHs semble montrer un rôle des co-formulants dans la modulation de la toxicité de la SA. Cependant, d’autres études sont nécessaires pour approfondir la compréhension liée aux mécanismes complexes de transmission de la toxicité du glyphosate.
Nowadays, glyphosate, and its commercial formulation (Roundup 41% SL, Bayer AG, Leverkusen, Germania), is the most widely used broad-spectrum herbicide in industrial agriculture for weed control. The massive use of this substance also affects aquatic ecosystems and water organisms around the world. The potential toxic effects of glyphosate on aquatic specimens should worry us. Indeed, animals such as grass carp are part of the human food chain, so exposure to glyphosate may cause environmental damage and harm human health. In this study, the effect of acute 96h exposure of the commercial formulation of glyphosate (Roundup) on blood biochemical indices of grass carp ( Ctenopharhyngoden idella ) was evaluated. Three different concentrations of glyphosate were chosen for exposure to three groups of 21 animals each. The lowest was 50mg.L ⁻¹ , the intermediate concentration was 100mg.L ⁻¹ , and the highest concentration was 150mg.L ⁻¹ . The toxicity of the pollutant was tested using lethal concentrations and determining the LC50 (lethal concentrations for 50% of fish). Histopathological damage to the gills and liver was also evaluated, as well as the survival rate of the fish. Results showed severe gill and liver damage, with necrosis, leukocyte infiltration, hyperplasia and hypertrophy, in the group exposed to the highest concentration of glyphosate (150 mg.L ⁻¹ ). Many biochemical changes were also observed, confirming the toxicity hypothesized at the start of the study.
The growing and widespread use of glyphosate-based herbicides (GBHs) has raised an intense public debate about the impact of environmental contamination on animal and human health, including male fertility. The aim of this study was to deepen the impact of glyphosate (Gly) and GBHs on mammalian sperm investigating the effect of in vitro exposure of stallion spermatozoa to Gly and to its commercial formulation Roundup® (R).
Spermatozoa were incubated at 37 °C with different Gly or R concentrations (from 0.5 to 720 μg/mL Gly or R at the same Gly-equivalent concentrations). After 1h of incubation motility, viability, acrosome integrity, mitochondrial activity and ROS production were assessed.
Gly, at all the concentrations tested, did not induce any detrimental impact on the sperm quality parameters evaluated. Conversely, R starting from 360 μg/mL (Gly-equivalent dose) significantly (P < 0.05) decreased total and progressive motility, viability, acrosome integrity, mitochondrial activity and the percentage of live spermatozoa with intact mitochondria not producing ROS.
Our results indicate that the commercial formulation R is more toxic than its active molecule Gly and that the negative impact on stallion sperm motility might be likely due to a detrimental effect mainly at membrane and mitochondrial level and, at least in part, to redox unbalance. Moreover, based on the data obtained, it can be hypothesized a species-specificity in sperm sensitivity to Gly and GBHs as horse spermatozoa were negatively influenced at higher concentrations of R compared to those reported in literature to be toxic for human and swine male germ cells.
This paper reports an investigation on the relationship between the proton electrochemical gradient (delta mu H+) and the cyclosporin A-sensitive permeability transition pore (PTP) in rat liver mitochondria. Using the SH group cross-linker phenylarsine oxide as the inducer, we show that both matrix pH and the membrane potential can modulate the process of PTP induction independently of Ca2+. We find that membrane depolarization induces the PTP per se when pHi is above 7.0, while at acidic matrix pH values PTP induction is effectively prevented. Since Ca2+ uptake leads to major modifications of the delta mu H+ (i.e. matrix alkalinization and membrane depolarization), we have explored the possibility that the Ca(2+)-induced changes of the delta mu H+ may contribute to PTP induction by Ca2+. Our data in mitochondria treated with Ca2+ plus N-ethylmaleimide and Ca2+ plus phosphate show that membrane depolarization is a powerful inducer of the PTP. Taken together, our observations indicate that the PTP can be controlled directly by the delta mu H+ both in the absence and presence of Ca2+, and suggest that a collapse of the membrane potential may be the cause rather than the consequence of PTP induction under many experimental conditions. Thus, many inducers may converge on dissipation of the membrane potential component of the delta mu H+ by a variety of mechanisms.
Increased risk for non-Hodgkin's lymphoma (NHL) following exposure to certain pesticides has previously been reported. To further elucidate the importance of phenoxyacetic acids and other pesticides in the etiology of NHL a pooled analysis was performed on two case-control studies, one on NHL and another on hairy cell leukemia (HCL), a rare subtype of NHL. The studies were population based with cases identified from cancer registry and controls from population registry. Data assessment was ascertained by questionnaires supplemented over the telephone by specially trained interviewers. The pooled analysis of NHL and HCL was based on 515 cases and 1141 controls. Increased risks in univariate analysis were found for subjects exposed to herbicides (OR 1.75, CI 95% 1.26-2.42), insecticides (OR 1.43, CI 95% 1.08-1.87), fungicides (OR 3.11, CI 95% 1.56-6.27) and impregnating agents (OR 1.48, CI 95% 1.11-1.96). Among herbicides, significant associations were found for glyphosate (OR 3.04, CI 95% 1.08-8.52) and 4-chloro-2-methyl phenoxyacetic acid (MCPA) (OR 2.62, CI 95% 1.40-4.88). For several categories of pesticides the highest risk was found for exposure during the latest decades before diagnosis. However, in multivariate analyses the only significantly increased risk was for a heterogeneous category of other herbicides than above.
An increased rate of non-Hodgkin's lymphoma (NHL) has been repeatedly observed among farmers, but identification of specific exposures that explain this observation has proven difficult.
During the 1980s, the National Cancer Institute conducted three case-control studies of NHL in the midwestern United States. These pooled data were used to examine pesticide exposures in farming as risk factors for NHL in men. The large sample size (n = 3417) allowed analysis of 47 pesticides simultaneously, controlling for potential confounding by other pesticides in the model, and adjusting the estimates based on a prespecified variance to make them more stable.
Reported use of several individual pesticides was associated with increased NHL incidence, including organophosphate insecticides coumaphos, diazinon, and fonofos, insecticides chlordane, dieldrin, and copper acetoarsenite, and herbicides atrazine, glyphosate, and sodium chlorate. A subanalysis of these "potentially carcinogenic" pesticides suggested a positive trend of risk with exposure to increasing numbers.
Consideration of multiple exposures is important in accurately estimating specific effects and in evaluating realistic exposure scenarios.
The effects of dicamba, a widely used broad-leaf herbicide, on rat liver mitochondrial bioenergetic activities were examined. The results obtained for state 4 respiration indicate not only an uncoupling effect, the result of an increase on the permeability of inner mitochondria membrane to protons, but also a strong inhibitory effect on the redox complexes. State 3 and respiration uncoupled by FCCP (carbonylcyanide p-trifluoromethoxyphenylhydrazone) were inhibited to approximately the same extent, i.e. by about 70%. Depression of respiratory activity is essentially mediated through partial inhibition of mitochondrial complexes II and III. ATPase activity was much less depressed by dicamba than ATP synthase activity. Therefore, a considerable part of the inhibition observed on ATP synthase is the result of an inhibition on the redox complexes. The loss of phosphorylation capacity, induced by dicamba, was in the last analysis not only the result of a direct effect of dicamba on the enzymatic complex (F(0)-F(1) ATPase) but also the result of a deleterious effect on the integrity of the mitochondrial membrane, which can promote an inhibition of the respiratory complexes and an increase of the proton permeability of the inner membrane.
Glyphosate [N-(phosphonomethyl)glycine]herbicide can be topically applied twice at rates as high as 0.84 kg a.e. (acid-equivalent) ha(-1) to glyphosate-resistant cotton (Gossypium hirsutum L.) cultivars until the fourth true leaf stage, with the requirement of at least 10 d and two nodes of growth between applications. But, such cultivars are not reproductively resistant to glyphosate applied topically or imprecisely directed after the four-leaf stage because glyphosate can curtail pollen development and ovule fertilization, which potentially reduces yield. Extending glyphosate resistance past the four-leaf stage would provide growers with additional weed management options. Our objective was to test under field conditions glyphosate resistance of cotton germplasm transformed with gene constructs previously shown to impart extended glyphosate resistance in the greenhouse. Four or six transgenic cotton lines containing one of several constructs conferring extended glyphosate resistance, plus the current glyphosate-resistant control ('Coker 312'-1445), were tested at nine U.S. locations in 2001. Within locations, treatment designs consisted of cross-classified arrangements of transgenic lines and glyphosate rates [0, 1.68, and 2.52 kg a.e. ha(-1)]. Treated plots received glyphosate over-the-top of cotton at four growth stages (3-, 6-, 10-, and 14-leaf crop stages). Compared with Coker 312-1445, extended glyphosate resistance was expressed as higher yields when glyphosate was applied topically at the four growth stages. Mature plant mapping confirmed extended glyphosate resistance of the new transgenic cotton through similar fruit distribution and weight with or without glyphosate treatment. The capability to apply glyphosate topically to cotton later in crop development will facilitate weed management and could reduce dependence on directed herbicides.
During the past years a comprehensive model for the regulation of mitochondrial oxidative phosphorylation has been developed. The model can account for the observed relationship among the cellular energy supply ([ATP][ADP][Pi]) the intramitochondrial reducing power ([NAD+][NADH]) and the cellular respiratory rate.
G rowers have overwhelmingly adopted glyphosate- resistant (Roundup Ready, Monsanto Co., Ches- Glyphosate (N-(phosphonomethyl)glycine) herbicide can be topi- terfield, MO) cotton cultivars since introduction in 1997. cally applied twice at rates as high as 0.84 kg a.e. (acid-equivalent) In 2002, about 72% of the U.S. hectarage was planted to ha 1 to glyphosate-resistant cotton (Gossypium hirsutum L.) cultivars until the fourth true leaf stage, with the requirement of at least 10 d cultivars containing the Monsanto glyphosate resistance and two nodes of growth between applications. But, such cultivars gene alone, or combined with Monsanto's Bollgard gene are not reproductively resistant to glyphosate applied topically or (derived from Bacillus thuringiensis var. kurstaki) con- imprecisely directed after the four-leaf stage because glyphosate can ferring protection from certain lepidopteran pest insects curtail pollen development and ovule fertilization, which potentially (Perlak et al., 1991; USDA-AMS, 2002). The popularity reduces yield. Extending glyphosate resistance past the four-leaf stage of glyphosate-resistant cotton cultivars reflects the broad- would provide growers with additional weed management options. spectrum weed control possible with glyphosate, plus Our objective was to test under field conditions glyphosate resistance capability to farm cotton on more hectares compared of cotton germplasm transformed with gene constructs previously with traditional weed management approaches (Cul- shown to impart extended glyphosate resistance in the greenhouse. pepper and York, 1998; York, 1997). Four or six transgenic cotton lines containing one of several constructs The limitation of the current cotton glyphosate resis- conferring extended glyphosate resistance, plus the current glypho-
Field studies were conducted in Alabama in 1998 and 1999 to evaluate fomesafen preemergence (PRE) in glyphosate-resistant cotton. Fomesafen (0.3 and 0.4 kg ai/ha), fluometuron (1.4 kg ai/ha), and pyrithiobac (0.05 kg ai/ha) were applied alone or in tank mixtures. Glyphosate (0.4 kg ae/ha) was applied postemergence over-the-top (POT) and postemergence directed (PD). Regardless of PRE treatment, POT followed by (fb) PD applications of glyphosate were necessary for greater than 82% sicklepod control at midseason. In the absence of glyphosate, fomesafen, and fomesafen-containing tank mixtures controlled common cocklebur and Ipomoea species 77 and 72%, respectively, 14 d after PD application. However, two applications of glyphosate were needed for .>94% season-long control of common cocklebur and Ipomoea species because of continued germination throughout the growing season. Postemergence applications of glyphosate added a 1,000 kg/ha seed cotton yield increase to all PRE treatments at both locations. Common cocklebur, Ipomoea species, and sicklepod control was not significantly increased by the addition of fomesafen PRE tank mixtures fb glyphosate postemergence as compared with glyphosate postemergence only.
This chapter describes the preparation and properties of succinie–cytochrome c reductase (complex II - III). Assays of enzymatic activity are carried out at 38° in a Beckman Model DU spectrophotometer, equipped with a photomultiplier. The final reaction mixture contains ten micromoles phosphate buffer (0.10 ml); one micromole NaN3 (0.01 ml); 0.2 micromole EDTA (0.02 ml); five mg BSA (0.05 ml); 10 micromoles potassium succinate, pH 7.0 (0.10 ml); and water to a volume of 0.9 ml. The enzyme preparation to be assayed is diluted to a concentration of 100-200 μg protein per milliliter in a solution of 0.88 M sucrose 0.005 M in succinatc. The enzyme-catalyzed reduction of cytochrome c by succinate proceeds at a linear rate under standard conditions over the first minute. Then specific activity is calculated. The resulting increase in absorbancy at 550 mμ is followed during this linear phase. In the method of preparation as described in the chapter, beef heart mitochondria are isolated in 0.25 M sucrose and are frozen at –40° for a period of 1-7 days. The yield and increase of activity during the purification of the succinic-cytochrome c reductase is also illustrated.
Acid dissociation constants have been measured for arsenic acid (H3AsO4), methylarsonic acid (CH3AsO3H2; MAA), dimethylarsinic acid [(CH3)2AsO2H; cacodylic acid], and N-(phosphonomethyl)glycine (HO2CCH2NHCH2PO3H2; glyphosate). A recently devised mathematical technique for pK and end point determinations which corrects for strong acid or base impurities was modified and used to analyze automatic titrator titration curves and correct pK values to zero ionic strength. Thermodynamic pK values = -log (aHaA/aAH) at 25°C are: H3AsO4, pK2 = 7.089 ± 0.01; MAA, pK1 = 4.114 ± 0.01, pK2 = 9.148 ± 0.01; cacodylic acid, pK1 = 6.288 ± 0.01; glyphosate, pK1 = 2.32 ± 0.03, pK2 = 5.86 ± 0.03, pK3 = 10.86 ± 0.03.
The penetration and effects of the sodium salt of glyphosate,N-(phosphonomethyl) glycine, in isolated potato tuber mitochondria were investigated. The penetration studyrequired the measurement of the volume of mitochondrial water space and this measurement was repeatedlycarried out using [14C]dextran giving a value of 3.53 μl mg−1 protein. After a 15 minute incubation periodwith medium containing 1 μM or 1 mM glyphosate, without respiratory substrate, almost no product was found in themembrane pellet, after disruption of the organelles in distilled water. In contrast, glyphosate was found in themitochondrial water in a range of concentrations close to the external medium concentration. These results show that, at leastthe diffusion equilibrium between the medium, the intermembrane space and the matrix area was readily reached forglyphosate. The greater part of the product penetrated during the first five minutes of the incubation period.The glyphosate content, in mitochondria operating at 25°, was not changed by adding either substrate. (state IV), orsubstrate + ADP (state III). The probability of an active glyphosate transport by the mitochondrial inner membrane wastherefore very unlikely. Glyphosate, at a concentration as high as 50 mM, was unable to change therespiratory activities of isolated potato tuber mitochondria(oxygen consumption rate with different substrates, ADP/O, respiratorycontrol values, etc.).
IntroductionAssay of Succinate Dehydrogenase and Succinoxidase in Animal TissuesApplication of Succinate Dehydrogenase Assays to Yeast, Bacteria, and Higher PlansNADH Dehydrogenase and NADH Oxidase AssaysAssay of Choline DehydrogenaseAssay of Mitochondrial α-Glycerophosphate Dehydrogenase
Public concern about the degradation of surface and groundwater quality has stimulated rigorous efforts to develop reliable biological methods for quantifying aquatic toxicity. Most methods have focused on the use of fish or aquatic invertebrates toassess risk to humans and other species posed by chemical pollutants in water. However, most of these tests are too expensive and timeconsuming to form the basis for affordable water quality surveillance programs on an extensive scale. For example, acute fish tests, which are the most commonly used, cost approximately $700 per assay and require 48 to 96 h to determine median lethal concentrations (LCbo) of test substances or water samples. Requirements for specialized laboratories, cultivation of test organisms, variations in response related to species difference, and cumbersome statistical procedures are among other important problems that diminish the utility of acute toxicity tests using fish. Only minor improvements in cost, time, and response factors are afforded by acute toxicity tests with aquatic invertebrates such as those based on mortality of the water flea (Daphnia magna). Consequently, there is a pressing need to develop rapid and inexpensive, yet reliable and sensitive tests to monitor microcontamlnant trends in water quality and to determine toxicity of complex effluents discharged into aquatic systems. Use of rapid in v~tro bloassays for monitoring water quality and determining toxicity of effluents or chemical substances is a recent development. Tests based on bacterial responses are at the forefront of this new category of bioassay. Dutka and Kwan (1981) compared four different microbial toxicity testing systems and found the Beckman Microtox TM bloassay, based on reducing light emission from Photobacterium phosphoreum due to the presence of toxins (Bullch 1979) to be fastest and most sensitive. However, this appraisal and subsequent studies have suggested that the utility of the 5-mln Microtox" test may be compromised by poor sensitivity and erratic reproducibility (Blondin et al. 1985) and by the occurrence of falsely negative results from environmental samples (Qureshl et al. 1982). Nevertheless, studies with bacterial test systems have established the feasibility of designing rapid and inexpensive in vitro bioassays that could be
The effects of exposure of human erythrocytes to different concentrations of Roundup Ultra 360 SL and its active compound glyphosate were studied. We studied hemolysis after 1, 5, and 24 h incubation; lipid peroxidation, hemoglobin oxidation, the level of reduced glutathione, and the activity of catalase after 1 h. Human erythrocytes were incubated with 100–1500 ppm (100 μg/ml erythrocytes at 5% hematocrite) Roundup Ultra 360 SL and glyphosate. We have found that after 1 h of incubation only Roundup Ultra 360 SL increased the level of methemoglobin, products of lipid peroxidation at 500 ppm and hemolysis at 1500 ppm [Curr. Top. Biophys. 26 (2002) 245], while its active compound glyphosate increased the level of methemoglobin and the level of lipid peroxidation at much higher dose—1000 ppm. At the same time hemolysis was observed to only at the highest dose of glyphosate (1500 ppm) and the longest time of incubation (24 h). Both Roundup Ultra 360 SL and glyphosate did not cause statistically significant changes in the level of GSH, but increased the activity of catalase. Roundup Ultra 360 SL provokes more changes in the function of erythrocytes than its active substance glyphosate, which is probably a result of the properties of additives. Taking into account the limited accumulation of Roundup Ultra 360 SL and glyphosate in the organism as well as the fact that the threshold doses which caused changes in erythrocytes for Roundup Ultra 360 SL were only 500 and 1000 ppm for glyphosate, one may conclude that this pesticide is safe towards human erythrocytes.
This chapter discusses the preparation and activity of native and chemically modified cytochromes c. Cytochrome c is extracted from ground and homogenized tissue with a dilute solution of aluminum sulfate at pH 4.5, the trivalent cations effectively displacing the protein even at low ionic strength. Aluminum ions are precipitated as the hydroxide at slightly alkaline pH, and each is replaced in solution by three monovalent ammonium ions. The cytochrome c is purified by (NH4)2SO4 fractionation and cation-exchange chromatography. This method of extraction is suited to vertebrate and invertebrate tissues, but for plant materials, protists, or fungi, special cytolysis procedures are often required before use of a similar scheme. Although both these aspects of cytochrome c function are interesting, it seems that the biologically significant evolutionary variations of cytochrome c structure predominantly affect the mechanics of protein–protein interaction with its physiological oxidants and reductants, rather than the mechanism of electron transfer.
The results presented reveal that glyphosate enhanced the rate of oxygen consumption by the mitochondria isolated from the livers of rats 5 hr after a single intraperitoneal dosing with glyphosate when the reaction medium was deficient in phosphate acceptor. The respiratory control ratios of these mitochondria were also reduced. At 60 mg/kg this parameter was reduced by at least 40 percent. The partial reactions of oxidative phosphorylation are presumed to be reflections at the reversibility and multistep nature of the coupling mechanisms. An important partial reaction of oxidative phosphorylation is adenosine triphosphatase (ATPase) activity which is characteristically stimulated by dinitrophnol and other uncoupling agents. Because of the enhancement effect of glyphosate on ADP-less respiration and its inhibitory effects on ADP-stimulated respiration in the mitochondria obtained from the livers of glyphosate-poisoned rats, the effect of the herbicide on ATPase activity was investigated. The results presented reveal that ATPase activity was enhanced in the livers of the animals treated with the herbicide. The activities of the dehydrogenases of the common two- or three- site substrates were also slightly enhanced in the hepatic mitochondria of the glyphosate-poisoned animals. These findings suggest that uncoupling of mitochondrial oxidative phosphorylation may be a major lesion in glyphosate intoxication.
The membrane potential of mitochondria was estimated from the accumulation of tetraphenyl phosphonium (TPP+), which was determined with the TPP+-selective electrode developed in the present study. The preparation and some operational parameters of the electrode were described. The kinetics for uptake by mitochondria of TPP+ and DDA+ (dibenzyldimethyl ammonium) were analyzed, and it was found that TPP+ permeated the mitochondrial membrane about 15 times faster than DDA+. The final amounts of accumulation of TPP+ and DDA+ by mitochondria were approximately equal. For the state-4 mitochondria, the membrane potential was about 180 mV (interior negative). Simultaneous measurements of TPP+-uptake and oxygen consumption showed that the transition between states 3 and 4 was detectable by use of the TPP+-electrode. After the TPP+-electrode showed that state-4 was reached, the extra-mitochondrial phosphorylation potential was measured. The difference in pH across the membrane was measured from the distribution of permeant anion, acetate, so as to calculate the proton electrochemical potential. The ratio of extra-mitochondrial phosphorylation potential to proton electro-chemical potential, n was close to 3. This value of n was also found to be 3 when ATP was hydrolyzed under the condition that the respiratory chain was arrested. The implication that n = 3 was discussed.
New spectrophotometric bioassay procedures have been developed for evaluating chemical toxicity, using electron transport particles isolated from bovine heart mitochondria, based on the ability of many toxic chemicals to interfere with the integrated function of electron transport enzymes. The sensitivity of the mitochondrial assay is compared to published sensitivities of other in vivo and in vitro toxicity testing methods. Regression analysis of logarithmically transformed toxicity values for 42 chemicals, including 8 pesticides, 5 drugs, 6 metals, 8 alcohols, 5 respiratory inhibitors, 4 phenols, and 2 phthalates, indicates excellent correlation between the sensitivity of the new assays and the sensitivity of mammalian cytotoxicity studies (r2 = 0.86). Data from aquatic exposure toxicity tests conducted in fish are also highly correlated with the mitochondrial assay results (r2 = 0.79). However, correlation of data from these methods with median lethal dose studies conducted in rats is not as good because of the inability of in vitro and aquatic exposure analyses to account for the gastrointestinal absorption, hepatic metabolism, and excretion processes which modify toxic responses following oral administration.
Three bioassays which use submitochondrial electron transport particles (ETP) to evaluate chemical toxicity have been developed. These tests were initially designed for use in water quality monitoring. However, they are also valuable for assessing the toxicity of new and existing chemicals. The current investigation studies the ability of these procedures to predict in vivo tissue concentrations associated with clinical illness in man. To examine this potential, data obtained using the mitochondrial tests were compared to chemical concentrations measured in human blood samples obtained during the acute stage of chemical-induced illness. Twenty-nine chemicals were used in the comparison including 6 metals, 8 pesticides, 5 drugs, 4 solvents and 3 alcohols. The results of this study support the hypothesis that the mitochondrial bioassays can successfully predict the in vivo toxicity of many diverse chemicals. Properly performed and evaluated, these short-term tests may be useful in identifying potential environmental pollutants, selecting compounds for market development and prioritizing substances for more extensive testing in animals.
Arrhenius plots of Ca++-stimulated ATP hydrolysis by sarcoplasmic reticulum (SR) show breaks (Tt) at 16.7°C and 11.5°C for rabbit and lobster preparations, respectively. The energies of activation (Eact) are about 10 and 19.5 Kcal/mole above and below Tt, respectively, and are similar for both lobster and rabbit SR. The antibiotic filipin increases Tt by about 7°C for both preparations, but the Eact above and below the new Tt values remain similar to those of the controls. Desintegrated membranes do not show breaks in Arrhenius plots and the Eact assume relatively high values. The Ca++ ionophore X-537A does not affect either the Tt values nor the Eact.
The effects of phenoxyacid herbicides 2,4-D (2,4-dichlorophenoxyacetic acid) and MCPA (4-chloro-2-methylphenoxyacetic acid), clofibrate, and glyphosate on hepatic and intestinal drug metabolizing enzyme activities were studied in rats intragastrically exposed for 2 weeks. The hepatic ethoxycoumarin O-deethylase activity increased about 2-fold with MCPA. Both 2,4-D and MCPA increased the hepatic epoxide hydrolase activity and decreased the hepatic glutathione S-transferase activity. MCPA also increased the intestinal activities of ethoxycoumarin O-deethylase and epoxide hydrolase. Glyphosate decreased the hepatic level of cytochrome P-450 and monooxygenase activities and the intestinal activity of aryl hydrocarbon hydroxylase. Clofibrate decreased the hepatic activities of UDPglucuronosyltransferase with p-nitrophenol or methylumbelliferone as the substrate. Also 2,4-D decreased the hepatic activity of UDPglucuronosyltransferase with p-nitrophenol as the substrate. MCPA decreased the intestinal activities of UDPglucuronosyltransferase with either p-nitrophenol or methylumbelliferone as the substrate. The results indicate that phenoxyacetic acids, especially MCPA, may have potent effects on the metabolism of xenobiotics. Glyphosate, not chemically related to phenoxyacids, seems to inhibit monooxygenases. Whether these changes are related to the toxicity of these xenobiotics remains to be clarified in further experiments.
In this work, the mitochondrial transmembrane electric potential (delta psi) of isolated mitochondria was used to evaluate the toxicity of some chemicals (endosulfan, 3,4-dichloroaniline, parathion, tributyltin and cadmium) and wastewater. Mitochondria were isolated from rat liver, and the delta psi measured in a suitable assay medium, using a sensitive tetraphenylphosphonium (TPP+) electrode. The test substance was pre-incubated in a rotenone-containing medium during 3 min with 1.0 mg of mitochondrial protein. Mitochondria were energised with succinate and after the establishment of a constant maximal potential ADP was added to induce the phosphorylative cycle. Chosen endpoints were the membrane potential from mitochondria oxidising succinate and the depolarisation induced by ADP. After the appropriate transformations the EC50 (effective concentration) was calculated for each toxicant. Even very low concentrations of a toxicant were able to affect the delta psi, thus showing its suitability as a biosensor in ecotoxicology and results were reproducible between tests. The utilisation of delta psi in screening tests of pure substances and wastewater seems to be very effective and can be carried out routinely.
Reviews on the safety of glyphosate and Roundup herbicide that have been conducted by several regulatory agencies and scientific institutions worldwide have concluded that there is no indication of any human health concern. Nevertheless, questions regarding their safety are periodically raised. This review was undertaken to produce a current and comprehensive safety evaluation and risk assessment for humans. It includes assessments of glyphosate, its major breakdown product [aminomethylphosphonic acid (AMPA)], its Roundup formulations, and the predominant surfactant [polyethoxylated tallow amine (POEA)] used in Roundup formulations worldwide. The studies evaluated in this review included those performed for regulatory purposes as well as published research reports. The oral absorption of glyphosate and AMPA is low, and both materials are eliminated essentially unmetabolized. Dermal penetration studies with Roundup showed very low absorption. Experimental evidence has shown that neither glyphosate nor AMPA bioaccumulates in any animal tissue. No significant toxicity occurred in acute, subchronic, and chronic studies. Direct ocular exposure to the concentrated Roundup formulation can result in transient irritation, while normal spray dilutions cause, at most, only minimal effects. The genotoxicity data for glyphosate and Roundup were assessed using a weight-of-evidence approach and standard evaluation criteria. There was no convincing evidence for direct DNA damage in vitro or in vivo, and it was concluded that Roundup and its components do not pose a risk for the production of heritable/somatic mutations in humans. Multiple lifetime feeding studies have failed to demonstrate any tumorigenic potential for glyphosate. Accordingly, it was concluded that glyphosate is noncarcinogenic. Glyphosate, AMPA, and POEA were not teratogenic or developmentally toxic. There were no effects on fertility or reproductive parameters in two multigeneration reproduction studies with glyphosate. Likewise there were no adverse effects in reproductive tissues from animals treated with glyphosate, AMPA, or POEA in chronic and/or subchronic studies. Results from standard studies with these materials also failed to show any effects indicative of endocrine modulation. Therefore, it is concluded that the use of Roundup herbicide does not result in adverse effects on development, reproduction, or endocrine systems in humans and other mammals. For purposes of risk assessment, no-observed-adverse-effect levels (NOAELs) were identified for all subchronic, chronic, developmental, and reproduction studies with glyphosate, AMPA, and POEA. Margins-of-exposure for chronic risk were calculated for each compound by dividing the lowest applicable NOAEL by worst-case estimates of chronic exposure. Acute risks were assessed by comparison of oral LD50 values to estimated maximum acute human exposure. It was concluded that, under present and expected conditions of use, Roundup herbicide does not pose a health risk to humans.
This 54-year-old man accidentally sprayed himself with the chemical agent glyphosate, a herbicide derived from the amino acid glycine. He developed disseminated skin lesions 6 hours after the accident. One month later, he developed a symmetrical parkinsonian syndrome. Two years after the initial exposure to glyphosate, magnetic resonance imaging revealed hyperintense signal in the globus pallidus and substantia nigra, bilaterally, on T2-weighted images. Levodopa/benserazide 500/125 mg daily provided satisfactory clinical outcome.
Experimental studies were performed on healthy, 80-100 g carp (Cyprinus carpio). Fish were exposed by emersion in Roundup (205 mg of glyphosate/l or 410 mg of glyphosate/l) in concentrations of 40- to 20-fold lower than those used in practice. Electron microscopy revealed that the herbicide caused appearance of myelin-like structures in carp hepatocytes, swelling of mitochondria and disappearance of internal membrane of mitochondria in carp at both exposure concentrations. It means that Roundup was harmful to carp when used in applied concentrations. Results of these studies enhance our knowledge of ultrastructural pathomorphology of fish organs following exposure to Roundup.
To assess human health risk from environmental chemicals, we have studied the effect on cell cycle regulation of the widely used glyphosate-containing pesticide Roundup. As a model system we have used sea urchin embryonic first divisions following fertilization, which are appropriate for the study of universal cell cycle regulation without interference with transcription. We show that 0.8% Roundup (containing 8 mM glyphosate) induces a delay in the kinetic of the first cell cleavage of sea urchin embryos. The delay is dependent on the concentration of Roundup. The delay in the cell cycle could be induced using increasing glyphosate concentrations (1-10 mM) in the presence of a subthreshold concentration of Roundup 0.2%, while glyphosate alone was ineffective, thus indicating synergy between glyphosate and Roundup formulation products. The effect of Roundup was not lethal and involved a delay in entry into M-phase of the cell cycle, as judged cytologically. Since CDK1/cyclin B regulates universally the M-phase of the cell cycle, we analyzed CDK1/cyclin B activation during the first division of early development. Roundup delayed the activation of CDK1/cyclin B in vivo. Roundup inhibited also the global protein synthetic rate without preventing the accumulation of cyclin B. In summary, Roundup affects cell cycle regulation by delaying activation of the CDK1/cyclin B complex, by synergic effect of glyphosate and formulation products. Considering the universality among species of the CDK1/cyclin B regulator, our results question the safety of glyphosate and Roundup on human health.
The parasitic plant Cuscuta campestris is dependent on its host for water, assimilates and amino acids. It can be controlled by the herbicide glyphosate, which inhibits 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), resulting in shikimate accumulation. In this study, C. campestris was parasitic on transgenic tobacco plants expressing green fluorescent protein (GFP) in the phloem. Changes in [14C]sucrose and GFP accumulation in the parasite were used as indicators of the herbicide's effect on translocation between the host and parasite. Host plants were treated with glyphosate 22 days after sowing. Shikimate accumulation in the parasite 1 day after glyphosate treatment (DAGT) confirmed EPSPS inhibition in C. campestris. No damage was visible in the host plants for the first 3 DAGT, while during that same time, a significant reduction in [14C]sucrose and GFP accumulation was observed in the parasite. Thus, we propose that the parallel reduction in GFP and sucrose accumulation in C. campestris is a result of a glyphosate effect on the parasite's ability to withdraw assimilates from the host.
Glyphosate-based herbicides are among the most widely used pesticides in the world. We compared the acute toxicity of the glyphosate end-use formulation Roundup Original to four North American amphibian species (Rana clamitans, R. pipiens, R. sylvatica, and Bufo americanus) and the toxicity of glyphosate technical, the polyethoxylated tallowamine surfactant (POEA) commonly used in glyphosate-based herbicides, and five newer glyphosate formulations to R. clamitans. For R. clamitans, acute toxicity values in order of decreasing toxicity were POEA > Roundup Original > Roundup Transorb > Glyfos AU; no significant acute toxicity was observed with glyphosate technical material or the glyphosate formulations Roundup Biactive, Touchdown, or Glyfos BIO. Comparisons between the four amphibian species showed that the toxicity of Roundup Original varied with species and developmental stage. Rana pipiens tadpoles chronically exposed to environmentally relevant concentrations of POEA or glyphosate formulations containing POEA showed decreased snout-vent length at metamorphosis and increased time to metamorphosis, tail damage, and gonadal abnormalities. These effects may be caused, in some part, by disruption of hormone signaling, because thyroid hormone receptor beta mRNA transcript levels were elevated by exposure to formulations containing glyphosate and POEA. Taken together, the data suggest that surfactant composition must be considered in the evaluation of toxicity of glyphosate-based herbicides.
Membrane biochemistry
- P Gazzotti
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- M Crompton
Gazzotti, P., Malmstron, K., Crompton, M., 1997. Membrane
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In: Special Review and Registration Division
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- Glyphosate
EPA, U.S., Glyphosate. In: Special Review and Registration
Division, O.O.P. Programs, Editor. 1993, Registration
Eligibility Decision (RED): Washington, D.C.
Membrane biochemistry
- Gazzotti