воскресенье, 17 ноября 2019 г.

Глифосат

Глифосат - гербицид широкого спектра, который также используют как дессикант для урожая.

Глифосат - самый используемый гербицид в мире. А устойчивость к глифосату - самый распространенный вид модификации гмо-растений, который подразумевает обязательный полив гербицидом растений и его повышенное накопление.Гербицид выпускается под марками Раундап, Торнадо и многими другими.


Соединение синтезировали в 1970 году. Принцип гербицидного действия глифосата основан на блокировке шикиматного пути, который есть у растений и бактерий, но отсутствует у животных. Собственно этот момент служил долгое время основанием для заявлений что глифосат якобы вообще на животных не действует. 

Однако при некотором количестве употребления глифосата внутрь крысы сразу погибали.  Также как показывают исследования организм может принять глифосат за какой-то из эндогенных гормонов, или молекулы глифосата могут ингибировать некоторые ферменты, что в дальнейшем увеличивает риск развития болезней. 

Первые исследования о возможном вреде пестицида появились еще в 80-х годах.
В 2000-х и 2010-х исследований с аналогичными результатами становится все больше. В том числе публикуют исследования находящие связь с некоторыми видами лимфомы. Однако утверждения про то, что глифосат безопасен продолжаются. Компания объясняет это тем, что все эти исследования неправильные, или там слишком большие дозы, или результаты "статистически незначимы". Указывает на правильные исследования, которые ничего опасного и связи с лимфомами не находят. Однако правильные исследования зачастую оплачены самой Монсанто. В настоящее время в США идут суды пользователей гербицида и компании Монсанто (сейчас Байер). Была опубликована переписка компании  Монсанто с рядом ученых и чиновников гос. организаций, которая недвусмысленно свидетельствует о коррупции и влиянии компании на результаты "независимых" исследований и заключения регулирующих органов. 

В любом случае в обществе к сожалению до сих пор достаточно распространено мнение, что этот гербицид очень безопасен, а значит лучше полить им  грядку или лужайку, чем полоть руками или ужасаться видом одуванчиков и будры плющевидной.




Выдержки из Pubmed:


2000
july
https://www.ncbi.nlm.nih.gov/pubmed/11460701
Szarek J1, Siwicki A, Andrzejewska A, Terech-Majewska E, Banaszkiewicz T. Effects of the herbicide Roundup on the ultrastructural pattern of hepatocytes in carp (Cyprinus carpio).
Токсическое действие Раундапа на гепатоциты карпа

2000
august
https://www.ncbi.nlm.nih.gov/pubmed/10964798
Walsh LP1, McCormick C, Martin C, Stocco DM. Roundup inhibits steroidogenesis by disrupting steroidogenic acute regulatory (StAR) protein expression.
Раундап влияет на экспрессию стероидогенного острого регуляторного белка (StAR).

2001
march
https://www.ncbi.nlm.nih.gov/pubmed/11237511
Daruich J1, Zirulnik F, Gimenez MS. Effect of the herbicide glyphosate on enzymatic activity in pregnant rats and their fetuses.
Контакт с агрохимикатами во время беременности вызывает аномалии в развитии.

2002
march
https://www.ncbi.nlm.nih.gov/pubmed/11896679
Marc J1, Mulner-Lorillon O, Boulben S, Hureau D, Durand G, Bellé R. Pesticide Roundup provokes cell division dysfunction at the level of CDK1/cyclin B activation
Глифосат вызывает дисфункцию на уровне CDK1/cyclin B активации


2004
november
https://www.ncbi.nlm.nih.gov/pubmed/15451553
Benedetti AL, Vituri Cde L, Trentin AG, Domingues MA, Alvarez-Silva M.The effects of sub-chronic exposure of Wistar rats to the herbicide Glyphosate-Biocarb.
Животные получали  4.87, 48.7, or 487 mg/kg глифосата-Биокарб раз в 2 дня, в течение 75 дней.  У всех групп наблюдались изменения в печени. 


2005
june
https://www.ncbi.nlm.nih.gov/pubmed/15929894
Richard S, Moslemi S, Sipahutar H, Benachour N, Seralini GE. Differential effects of glyphosate and roundup on human placental cells and aromatase.
Глифосат проявляет токсическое действие по отношению к человеческим плацентарным клетка в концентрациях более низких, чем обнаруживаются при сельскохозяйственном использовании.
.

2006
january
https://www.ncbi.nlm.nih.gov/pubmed/16373198
Siviková K, Dianovskỳ J. Cytogenetic effect of technical glyphosate on cultivated bovine peripheral lymphocytes.
Показан генотоксический эффект

2006
july
https://www.ncbi.nlm.nih.gov/pubmed/21783682
Gehin A, Guyon C, Nicod L.Glyphosate-induced antioxidant imbalance in HaCaT: The protective effect of Vitamins C and E.
Глифосат нарушал антиоксидантную систему защиты клеток. 

2006
october
https://www.ncbi.nlm.nih.gov/pubmed/16049272
Glusczak L, dos Santos Miron D, Crestani M, Braga da Fonseca M, de Araújo Pedron F, Duarte MF, Vieira VL. Effect of glyphosate herbicide on acetylcholinesterase activity and metabolic and hematological parameters in piava (Leporinus obtusidens).
Показано что глифосат снижал активность ацетилхолинэстеразы в мозге рыб. 
  Также рыбы накапливали больше гликогена и глюкозы в печены, но меньше в мышцах. Также ткани накапливали больше аммиака. 

2007
may
https://www.ncbi.nlm.nih.gov/pubmed/21783773
Soso AB, Barcellos LJ, Ranzani-Paiva MJ, Kreutz LC, Quevedo RM, Anziliero D, Lima M, Silva LB, Ritter F, Bedin AC, Finco JA. Chronic exposure to sub-lethal concentration of a glyphosate-based herbicide alters hormone profiles and affects reproduction of female Jundiá (Rhamdia quelen).
Результаты указывают на то, что присутствие глифосата в воде оказывают вредоносное действие на размножение Rhamdia quelen.

2007
july
https://www.ncbi.nlm.nih.gov/pubmed/17486286
Benachour N, Sipahutar H, Moslemi S, Gasnier C, Travert C, Séralini GE. Time- and dose-dependent effects of roundup on human embryonic and placental cells.
Полученные результаты предполагают что контакт с Раундапом может влияет на развитие эмбриона и репродуктивную систему человека.

2007
july
https://www.ncbi.nlm.nih.gov/pubmed/21783784
Hultberg M. Cysteine turnover in human cell lines is influenced by glyphosate.
При контакте человеческих клеток с глифосатом происходили серьезные изменения в концентрации цистеина.


2008
january
Cağlar S, Kolankaya D. The effect of sub-acute and sub-chronic exposure of rats to the glyphosate-based herbicide Roundup.
Показано негативное влияние на печень крыс


2008
april
https://www.ncbi.nlm.nih.gov/pubmed/17987383
Costa MJ, Monteiro DA, Oliveira-Neto AL, Rantin FT, Kalinin AL. Oxidative stress biomarkers and heart function in bullfrog tadpoles exposed to Roundup Original.
Показано вредное воздействие на головастиков лягушек-быка

2008
august
https://www.ncbi.nlm.nih.gov/pubmed/18638566
Cavalcante DG, Martinez CB, Sofia SH.Genotoxic effects of Roundup on the fish Prochilodus lineatus.
Показано генотоксическое действие на рыб. 


2009
january
https://www.ncbi.nlm.nih.gov/pubmed/19105591
Benachour N, Séralini GE. Glyphosate formulations induce apoptosis and necrosis in human umbilical, embryonic, and placental cells.
Показано токсическое действие на человеческие клетки

2009
august
https://www.ncbi.nlm.nih.gov/pubmed/19450865
Lushchak OV, Kubrak OI, Storey JM, Storey KB, Lushchak VI. Low toxic herbicide Roundup induces mild oxidative stress in goldfish tissues.
Оксидативный стресс у рыб

2009
august
https://www.ncbi.nlm.nih.gov/pubmed/19539684
Gasnier C, Dumont C, Benachour N, Clair E, Chagnon MC, Séralini GE. Glyphosate-based herbicides are toxic and endocrine disruptors in human cell lines.
Токсическое и эндокринное действие на человеческие клетки.

2010
january
https://www.ncbi.nlm.nih.gov/pubmed/19910015
Modesto KA, Martinez CB. Roundup causes oxidative stress in liver and inhibits acetylcholinesterase in muscle and brain of the fish Prochilodus lineatus.
Было показано, что раундап вызывет оксидативный стресс у рыб и ингибирует антихолинэстеразу.

2010
april
https://www.ncbi.nlm.nih.gov/pubmed/20012598
Romano RM, Romano MA, Bernardi MM, Furtado PV, Oliveira CA. Prepubertal exposure to commercial formulation of the herbicide glyphosate alters testosterone levels and testicular morphology.
У крыс глифосат уменьшал уровень тестостерона и изменял развитие семенников. 


2010
october
https://www.ncbi.nlm.nih.gov/pubmed/20695457
Paganelli A, Gnazzo V, Acosta H, López SL, Carrasco AE. Glyphosate-based herbicides produce teratogenic effects on vertebrates by impairing retinoic acid signaling.
Показан тератогенный эффект гербицидов на основе раундапа на позвоночных через влияние на передачу сигнала ретиноевой кислотой.  


2011
https://www.ncbi.nlm.nih.gov/pubmed/22702209
Ruamthum W, Visetson S, Milne JR, Bullangpoti V. Effect of glyphosate-based herbicide on acetylcholinesterase activity in tadpoles, Hoplobatrachus rugulosus.
Глифосат ингибировал ацетилхолинэсеразу у головастиков.


2011
january
https://www.ncbi.nlm.nih.gov/pubmed/20883798
Kreutz LC, Gil Barcellos LJ, de Faria Valle S, de Oliveira Silva T, Anziliero D, Davi dos Santos E, Pivato M, Zanatta R. Altered hematological and immunological parameters in silver catfish (Rhamdia quelen) following short term exposure to sublethal concentration of glyphosate.
Thus, in this study, silver catfish (Rhamdia quelen) were exposed to sublethal concentrations (10% of the LC(50-96 h)) of a glyphosate based herbicide and hematological and natural immune system parameters were evaluated. Silver catfish fingerlings exposed to glyphosate for 96 h had a significant reduction on blood erythrocytes, thrombocytes, lymphocytes and total leukocytes in contrast to a significant increase in the number of immature circulating cells. The effect of glyphosate on natural immune system was evaluated after 24h or 10 days exposure by measuring the phagocytic index of coelomic cells, and lysozyme, total peroxidase, bacteria agglutination, bactericidal activity and natural complement hemolytic activity in the serum of fingerlings. A significant reduction on phagocytic index, serum bacteria agglutination and total peroxidase was observed only after 24h exposure to glyphosate. In contrast, fingerlings exposed to glyphosate for 10 days had a significant lower serum bacteria agglutination and lysozyme activity. Glyphosate had no effect on serum bactericidal and complement natural hemolytic activity after 24h or 10 days exposure. Nonetheless, the information obtained in this study indicates that glyphosate contaminated water contributes to alter blood cells parameters and to reduce the activity of natural immune components important to mediate fish resistance to infecting microorganisms.

2011
january
https://www.ncbi.nlm.nih.gov/pubmed/21086158
Dutra BK, Fernandes FA, Failace DM, Oliveira GT. Effect of Roundup® (glyphosate formulation) in the energy metabolism and reproductive traits of Hyalella castroi (Crustacea, Amphipoda, Dogielinotidae).
Roundup(®) (glyphosate formulation) is a nonselective and posts emergent herbicide used for controlling aquatic weeds and different concentrations are used in cultures around the world. The objective of this investigation was to examine the effects of Roundup(®) (glyphosate formulation) on the biochemical composition, levels of lipoperoxidation, Na(+)/K(+)ATPase activity and reproductive traits in the Hyalella castroi. Amphipods were collected in summer 2009, in the southern Brazilian highlands. In the laboratory, the animals were kept in aquariums under controlled conditions for 7 days, and after this period they were exposed to 0.36, 0.52, 1.08 and 2.16 mg/l of glyphosate for 7 days. After the period of exposure, the animals were immediately frozen for determination of glycogen, proteins, lipids, triglycerides, cholesterol, levels of lipoperoxidation, and Na(+)/K(+)ATPase activity. During each day of the cultivation reproductive traits (number of reproductive pairs, ovigerous females and eggs in the marsupium) were observed. All concentrations of Roundup(®) induced significant decreases in all biochemical parameters and Na(+)/K(+)ATPase activity, and significant increase in lipoperoxidation levels. Showing this form a potentially toxic effect at very low concentrations, this pattern of results can lead to significant changes in trophic structure of limnic environments because these amphipods are important links in food chain in these habitats

2011
september
https://www.ncbi.nlm.nih.gov/pubmed/21555143
Griesinger LM, Evans SC, Rypstra AL.Effects of a glyphosate-based herbicide on mate location in a wolf spider that inhabits agroecosystems.
These data suggest that glyphosate-based herbicides are "info-disruptors" that alter the ability of males to detect and/or react fully to female signals.


2011
november
https://www.ncbi.nlm.nih.gov/pubmed/21465245
Glusczak L, Loro VL, Pretto A, Moraes BS, Raabe A, Duarte MF, da Fonseca MB, de Menezes CC, Valladão DM. Acute exposure to glyphosate herbicide affects oxidative parameters in piava (Leporinus obtusidens).
Teleostean fish (Leporinus obtusidens) were exposed to commercial glyphosate herbicide formulation at 0 (control), 3, 6, 10 or 20 mg L(-1) for 96 h. The effects of herbicide on plasmatic metabolic parameters, thiobarbituric acid reactive substances (TBARS), catalase activity, protein carbonyl, and mucus layer parameters were studied. Plasmatic glucose and lactate levels increased but protein levels showed reduction after herbicide exposure. TBARS levels in brain showed a reduction at all tested concentrations. However, liver demonstrated increased TBARS levels at all tested concentrations, whereas in white muscle TBARS production did not change after exposure to herbicide. Fish exposed to all concentrations of glyphosate showed increase in liver catalase activity and protein carbonyl. Herbicide exposure increased protein and carbohydrate levels of the mucus layer at all tested concentrations. The present results showed that, in 96 h, glyphosate changed toxicological parameters analyzed in piava.

2012
january
https://www.ncbi.nlm.nih.gov/pubmed/21643816
Hued AC, Oberhofer S, de los Ángeles Bistoni M. Exposure to a commercial glyphosate formulation (Roundup®) alters normal gill and liver histology and affects male sexual activity of Jenynsia multidentata (Anablepidae, Cyprinodontiformes).
sublethal concentration (0.5 mg/l) for 7 and 28 days. The estimated 96-h LC50 was 19.02 mg/l for both male and female fish. Gill and liver histological lesions were evaluated through histopathological indices allowing quantification of the histological damages in fish exposed to different concentrations of the herbicide. Roundup induced different histological alterations in a concentration-dependent manner. In subchronic-exposure tests, Roundup also altered normal histology of the studied organs and caused a significant decrease in the number of copulations and mating success in male fish exposed to the herbicide. It is expected that in natural environments contaminated with Roundup, both general health condition and reproductive success of J. multidenatata could be seriously affected.

2012
march
https://www.ncbi.nlm.nih.gov/pubmed/22200534
Clair E, Mesnage R, Travert C, Séralini GÉ. A glyphosate-based herbicide induces necrosis and apoptosis in mature rat testicular cells in vitro, and testosterone decrease at lower levels.
lyphosate, its active ingredient in plants and its main metabolite (AMPA) are among the first contaminants of surface waters. Roundup is being used increasingly in particular on genetically modified plants grown for food and feed that contain its residues. Here we tested glyphosate and its formulation on mature rat fresh testicular cells from 1 to 10000ppm, thus from the range in some human urine and in environment to agricultural levels. We show that from 1 to 48h of Roundup exposure Leydig cells are damaged. Within 24-48h this formulation is also toxic on the other cells, mainly by necrosis, by contrast to glyphosate alone which is essentially toxic on Sertoli cells. Later, it also induces apoptosis at higher doses in germ cells and in Sertoli/germ cells co-cultures. At lower non toxic concentrations of Roundup and glyphosate (1ppm), the main endocrine disruption is a testosterone decrease by 35%. The pesticide has thus an endocrine impact at very low environmental doses, but only a high contamination appears to provoke an acute rat testicular toxicity.''

2012
april
https://www.ncbi.nlm.nih.gov/pubmed/22369932
Heu C, Berquand A, Elie-Caille C, Nicod L. Glyphosate-induced stiffening of HaCaT keratinocytes, a Peak Force Tapping study on living cells.
Glyphosate is an extensively used herbicide that has been shown to increase the risk of cancer. Moreover there is increasing evidence suggesting that the mechanical phenotype plays an important role in malignant transformation....These experiments indicate glyphosate induces cell membrane stiffening, and the appearance of cytoskeleton structures at a subcellular level, for low cytotoxic concentrations whereas cells exposed to IC50 (inhibitory concentration 50%) treatment exhibit control-like mechanical behavior despite obvious membrane damages. Quercetin, a well-known antioxidant, reverses the glyphosate-induced mechanical phenotype.


2012
may
https://www.ncbi.nlm.nih.gov/pubmed/22331240
Koller VJ, Fürhacker M, Nersesyan A, Mišík M, Eisenbauer M, Knasmueller S. Cytotoxic and DNA-damaging properties of glyphosate and Roundup in human-derived buccal epithelial cells.
Aim of this investigation was to study the cytotoxic and genotoxic properties of G and R (UltraMax) in a buccal epithelial cell line (TR146), as workers are exposed via inhalation to the herbicide. R induced acute cytotoxic effects at concentrations > 40 mg/l after 20 min, which were due to membrane damage and impairment of mitochondrial functions. With G, increased release of extracellular lactate dehydrogenase indicative for membrane damage was observed at doses > 80 mg/l. Both G and R induced DNA migration in single-cell gel electrophoresis assays at doses > 20 mg/l. Furthermore, an increase of nuclear aberrations that reflect DNA damage was observed. The frequencies of micronuclei and nuclear buds were elevated after 20-min exposure to 10-20 mg/l, while nucleoplasmatic bridges were only enhanced by R at the highest dose (20 mg/l). R was under all conditions more active than its active principle (G). Comparisons with results of earlier studies with lymphocytes and cells from internal organs indicate that epithelial cells are more susceptible to the cytotoxic and DNA-damaging properties of the herbicide and its formulation. Since we found genotoxic effects after short exposure to concentrations that correspond to a 450-fold dilution of spraying used in agriculture, our findings indicate that inhalation may cause DNA damage in exposed individuals.

2012
may
https://www.ncbi.nlm.nih.gov/pubmed/22504123
Gui YX, Fan XN, Wang HM, Wang G, Chen SD. Glyphosate induced cell death through apoptotic and autophagic mechanisms.
Previous studies indicated that the exposure to glyphosate, a widely used herbicide, is possibly linked to Parkinsonism, however the underlying mechanism remains unclear. We investigated the neurotoxic effects of glyphosate in differentiated PC12 cells and discovered that it inhibited viability of differentiated PC12 cells in dose-and time-dependent manners. Furthermore, the results showed that glyphosate induced cell death via autophagy pathways in addition to activating apoptotic pathways. Interestingly, deactivation of Beclin-1 gene attenuated both apoptosis and autophagy in glyphosate treated differentiated PC12 cells, suggesting that Beclin-1 gene is involved in the crosstalk between the two mechanisms.

2012
september
https://www.ncbi.nlm.nih.gov/pubmed/22522424
Heu C, Elie-Caille C, Mougey V, Launay S, Nicod L. A step further toward glyphosate-induced epidermal cell death: involvement of mitochondrial and oxidative mechanisms.
We previously showed that glyphosate, an extensively used herbicide, provoked cytotoxic effects on cultured human keratinocytes, affecting their antioxidant capacities and impairing morphological and functional cell characteristics. The aim of the present study, carried out on the human epidermal cell line HaCaT, was to examine the part of apoptosis plays in the cytotoxic effects of glyphosate and the intracellular mechanisms involved in the apoptotic events. We have conducted different incubation periods to reveal the specific events in glyphosate-induced cell death. We observed an increase in the number of early apoptotic cells at a low cytotoxicity level (15%), and then, a decrease, in favor of late apoptotic and necrotic cell rates for more severe cytotoxicity conditions. At the same time, we showed that the glyphosate-induced mitochondrial membrane potential disruption could be a cause of apoptosis in keratinocyte cultures.

2012
september
https://www.ncbi.nlm.nih.gov/pubmed/22546541
Martini CN, Gabrielli M, Vila Mdel C. A commercial formulation of glyphosate inhibits proliferation and differentiation to adipocytes and induces apoptosis in 3T3-L1 fibroblasts.
 Therefore, it is important to investigate the putative toxic effects of these formulations which include not only glyphosate itself but also surfactants that may also be toxic... It was found that treatment of exponentially growing cells with GF for 48h inhibited proliferation in a dose-dependent manner. In addition, treatment with GF dilution 1:2000 during 24 or 48h inhibited proliferation and increased cell death, as evaluated by trypan blue-exclusion, in a time-dependent manner. We showed that treatment of 3T3-L1 fibroblasts with GF increased caspase-3 like activity and annexin-V positive cells as evaluated by flow cytometric analysis, which are both indicative of induction of apoptosis. It was also found that after the removal of GF, remaining cells were able to restore proliferation. On the other hand, GF treatment severely inhibited the differentiation of 3T3-L1 fibroblasts to adipocytes. According to our results, a glyphosate-based herbicide inhibits proliferation and differentiation in this mammalian cell line and induces apoptosis suggesting GF-mediated cellular damage.

2012
november
https://www.ncbi.nlm.nih.gov/pubmed/23044091
Larsen K, Najle R, Lifschitz A, Virkel G. Effects of sub-lethal exposure of rats to the herbicide glyphosate in drinking water: glutathione transferase enzyme activities, levels of reduced glutathione and lipid peroxidation in liver, kidneys and small intestine.
Wistar rats were exposed during 30 or 90 days to the highest level (0.7 mg/L) of GLP allowed in water for human consumption (US EPA, 2011) and a 10-fold higher concentration (7 mg/L). The low levels of exposure to the herbicide did not produce histomorphological changes. The production of TBARS was similar or tended to be lower compared to control animals not exposed to the herbicide. In rats exposed to GLP, increased levels of reduced glutathione (GSH) and enhanced glutathione peroxidase (GPx) activity may act as a protective mechanism against possible detrimental effects of the herbicide. Overall, this work showed certain biochemical modifications, even at 3-20-fold lower doses of GLP than the oral reference dose of 2mg/kg/day (US EPA, 1993). The toxicological significance of these findings remains to be clarified.

2013
https://www.ncbi.nlm.nih.gov/pubmed/24502134
Kwiatkowska M, Paweł J, Bukowska B. Glyphosate and its formulations--toxicity, occupational and environmental exposure
Initial reports about alleged biodegradability of glyphosate in the environment turned out to be wrong. It has been shown that glyphosate remains in the soil and can reach people by spreading along with groundwater. Recent publications have shown that glyphosate is detected at low concentrations in the human blood. Publications cited in this article, which indicate a possible induction of neoplastic changes by glyphosate formulation, have raised great concern and controversy in the scientific world. Presenting adverse effects of glyphosate and its formulations we focused on the role of glyphosate formulations in hormonal disorders by impeding the expression of steroidogenic acute regulatory protein and the inhibition of aromatase activity. The impact of glyphosate on oxygen reactive species formation, changes in redox system and the effect on necrosis and apoptosis in various types of cells was shown. We also revealed that glyphosate as a phosphonate herbicide does not inhibit directly the activity of acetylcholinesterase. Based on numerous studies it was noted that commercial formulations of glyphosate exhibit higher toxicity than that of the active substance itself.


2013
march
https://www.ncbi.nlm.nih.gov/pubmed/23273868
Vera-Candioti J, Soloneski S, Larramendy ML. Evaluation of the genotoxic and cytotoxic effects of glyphosate-based herbicides in the ten spotted live-bearer fish Cnesterodon decemmaculatus (Jenyns, 1842).
Furthermore, our results demonstrated that Panzer(®) and Credit(®) should be considered as glyphosate-based commercial formulations with genotoxic but not cytotoxic effect properties.

2013
march
https://www.ncbi.nlm.nih.gov/pubmed/23224423
Cuhra M, Traavik T, Bøhn T. Clone- and age-dependent toxicity of a glyphosate commercial formulation and its active ingredient in Daphnia magna.
Significant reduction of juvenile size was observed even in the lowest test concentrations of 0.05 mg a.i./l, for both glyphosate and Roundup. At 0.45 mg a.i./l, growth, fecundity and abortion rate was affected, but only in animals exposed to Roundup. At 1.35 and 4.05 mg a.i./l of both glyphosate and Roundup, significant negative effects were seen on most tested parameters, including mortality. D. magna was adversely affected by a near 100 % abortion rate of eggs and embryonic stages at 1.35 mg a.i./l of Roundup. The results indicate that aquatic invertebrate ecology can be adversely affected by relevant ambient concentrations of this major herbicide. We conclude that glyphosate and Roundup toxicity to aquatic invertebrates have been underestimated and that current European Commission and US EPA toxicity classification of these chemicals need to be revised.

2013
april
https://www.ncbi.nlm.nih.gov/pubmed/22821326
de Castilhos Ghisi N, Cestari MM.Genotoxic effects of the herbicide Roundup(®) in the fish Corydoras paleatus (Jenyns 1842) after short-term, environmentally low concentration exposure.
The objective of this study was to evaluate the genotoxic effect that the herbicide Roundup(®) (at a concentration of 6.67 μg/L, corresponding to 3.20 μg/L glyphosate) can have on the fish Corydoras paleatus. Treatment groups were exposed for 3, 6, and 9 days, and effects were analyzed using the piscine micronucleus test (PMT) and comet assay. A group subjected to filtered water only was used as a negative control. The PMT did not show differences between the control and exposed groups for any of the treatment times. In contrast, the comet assay showed a high rate of DNA damage in group exposed to Roundup(®) for all treatment times, both for blood and hepatic cells. We conclude that for the low concentration used in this research, the herbicide shows potential genotoxic effects.

2013
april
https://www.ncbi.nlm.nih.gov/pubmed/23224412
Shehata AA, Schrödl W, Aldin AA, Hafez HM, Krüger M.The effect of glyphosate on potential pathogens and beneficial members of poultry microbiota in vitro.
The presented results evidence that the highly pathogenic bacteria as Salmonella Entritidis, Salmonella Gallinarum, Salmonella Typhimurium, Clostridium perfringens and Clostridium botulinum are highly resistant to glyphosate. However, most of beneficial bacteria as Enterococcus faecalis, Enterococcus faecium, Bacillus badius, Bifidobacterium adolescentis and Lactobacillus spp. were found to be moderate to highly susceptible. Also Campylobacter spp. were found to be susceptible to glyphosate. A reduction of beneficial bacteria in the gastrointestinal tract microbiota by ingestion of glyphosate could disturb the normal gut bacterial community. Also, the toxicity of glyphosate to the most prevalent Enterococcus spp. could be a significant predisposing factor that is associated with the increase in C. botulinum-mediated diseases by suppressing the antagonistic effect of these bacteria on clostridia.

2013
april
https://www.ncbi.nlm.nih.gov/pubmed/23411353
Sandrini JZ, Rola RC, Lopes FM, Buffon HF, Freitas MM, Martins Cde M, da Rosa CE. Effects of glyphosate on cholinesterase activity of the mussel Perna perna and the fish Danio rerio and Jenynsia multidentata: in vitro studies.
Results demonstrated that cholinesterase from different fractions of all species tested was inhibited by glyphosate. The concentrations of glyphosate that inhibits 50% of cholinesterase activity (IC50) ranged from 0.62 mM for P. perna muscle to 8.43 mM for J. multidentata brain. According to this, cholinesterase from mussel seems to be more sensitive to glyphosate exposure than those from the fish D. rerio and J. multidentata.

2013
april
https://www.ncbi.nlm.nih.gov/pubmed/23396248
Krüger M, Shehata AA, Schrödl W, Rodloff A. Glyphosate suppresses the antagonistic effect of Enterococcus spp. on Clostridium botulinum.
During the last 10-15 years, an increase of Clostridium botulinum associated diseases in cattle has been observed in Germany. The reason for this development is currently unknown. The normal intestinal microflora is a critical factor in preventing intestinal colonisation by C. botulinum as shown in the mouse model of infant botulism. Numerous bacteria in the gastro-intestinal tract (GIT) produce bacteriocines directed against C. botulinum and other pathogens: Lactic acid producing bacteria (LAB) such as lactobacilli, lactococci and enterococci, generate bacteriocines that are effective against Clostridium spp. A reduction of LAB in the GIT microbiota by ingestion of strong biocides like glyphosate could be an explanation for the observed increase in levels of C. botulinum associated diseases. In the present paper, we report on the toxicity of glyphosate to the most prevalent Enterococcus spp. in the GIT. Ingestion of this herbicide could be a significant predisposing factor that is associated with the increase in C. botulinum mediated diseases in cattle.

2013
september
https://www.ncbi.nlm.nih.gov/pubmed/23756170
Thongprakaisang S, Thiantanawat A, Rangkadilok N, Suriyo T, Satayavivad J. Glyphosate induces human breast cancer cells growth via estrogen receptors.
Glyphosate exerted proliferative effects only in human hormone-dependent breast cancer, T47D cells, but not in hormone-independent breast cancer, MDA-MB231 cells, at 10⁻¹² to 10⁻⁶M in estrogen withdrawal condition. The proliferative concentrations of glyphosate that induced the activation of estrogen response element (ERE) transcription activity were 5-13 fold of control in T47D-KBluc cells and this activation was inhibited by an estrogen antagonist, ICI 182780, indicating that the estrogenic activity of glyphosate was mediated via ERs. Furthermore, glyphosate also altered both ERα and β expression. These results indicated that low and environmentally relevant concentrations of glyphosate possessed estrogenic activity. Glyphosate-based herbicides are widely used for soybean cultivation, and our results also found that there was an additive estrogenic effect between glyphosate and genistein, a phytoestrogen in soybeans. However, these additive effects of glyphosate contamination in soybeans need further animal study.

2013
december
https://www.ncbi.nlm.nih.gov/pubmed/24075644
Gholami-Seyedkolaei SJ, Mirvaghefi A, Farahmand H, Kosari AA. Effect of a glyphosate-based herbicide in Cyprinus carpio: assessment of acetylcholinesterase activity, hematological responses and serum biochemical parameters.
The LC₅₀-96 h of Roundup® to C. carpio was found to be 22.19 ppm. Common carp was subjected to Roundup® at 0 (control), 3.5, 7 and 14 ppm for 16 days, and the AChE activity is verified in tissues of gill, muscle, brain and liver. After 5 days, a significant decrease was observed in the AChE activity of muscle, brain and liver tissues. Besides, a time- and dose-dependent increase in mean cell hemoglobin (MCH) and mean cell volume (MCV) was observed. In contrast, a significant decrease was found in the quantities of hemoglobin (Hb), hematocrit (HCT) and, red (RBC) and white (WBC) blood cell count. Also, the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) in Roundup® treated groups were significantly higher than the controlled group at experimental periods. However, the level of alkaline phosphatase (ALP) had a significant reduction behavior during the sampling days.

2013
december
https://www.ncbi.nlm.nih.gov/pubmed/24678255
Samsel A, Seneff S. Glyphosate, pathways to modern diseases II: Celiac sprue and gluten intolerance.
 Here, we propose that glyphosate, the active ingredient in the herbicide, Roundup(®), is the most important causal factor in this epidemic. Fish exposed to glyphosate develop digestive problems that are reminiscent of celiac disease. Celiac disease is associated with imbalances in gut bacteria that can be fully explained by the known effects of glyphosate on gut bacteria. Characteristics of celiac disease point to impairment in many cytochrome P450 enzymes, which are involved with detoxifying environmental toxins, activating vitamin D3, catabolizing vitamin A, and maintaining bile acid production and sulfate supplies to the gut. Glyphosate is known to inhibit cytochrome P450 enzymes. Deficiencies in iron, cobalt, molybdenum, copper and other rare metals associated with celiac disease can be attributed to glyphosate's strong ability to chelate these elements. Deficiencies in tryptophan, tyrosine, methionine and selenomethionine associated with celiac disease match glyphosate's known depletion of these amino acids. Celiac disease patients have an increased risk to non-Hodgkin's lymphoma, which has also been implicated in glyphosate exposure. Reproductive issues associated with celiac disease, such as infertility, miscarriages, and birth defects, can also be explained by glyphosate. Glyphosate residues in wheat and other crops are likely increasing recently due to the growing practice of crop desiccation just prior to the harvest. We argue that the practice of "ripening" sugar cane with glyphosate may explain the recent surge in kidney failure among agricultural workers in Central America. We conclude with a plea to governments to reconsider policies regarding the safety of glyphosate residues in foods.


2014
january
https://www.ncbi.nlm.nih.gov/pubmed/24448465
Moreno NC, Sofia SH, Martinez CB. Genotoxic effects of the herbicide Roundup Transorb and its active ingredient glyphosate on the fish Prochilodus lineatus.
Erythrocytes and gill cells of fish exposed to glyphosate and to RT showed DNA damage scores significantly higher than control animals. These results revealed that both glyphosate itself and RT were genotoxic to gill cells and erythrocytes of P. lineatus, suggesting that their use should be carefully monitored considering their potential impact on tropical aquatic biota.

2014
february
https://www.ncbi.nlm.nih.gov/pubmed/24581382
Kwiatkowska M, Huras B, Bukowska B. The effect of metabolites and impurities of glyphosate on human erythrocytes (in vitro).
Some investigated metabolites and impurities caused a slight stronger damage to human erythrocytes than a glyphosate. The results clearly show that the changes induced in the erythrocytes can occur only as a result of poisoning with these compounds.

2014
april
https://www.ncbi.nlm.nih.gov/pubmed/24762670
Schinasi L, Leon ME. Non-Hodgkin lymphoma and occupational exposure to agricultural pesticide chemical groups and active ingredients: a systematic review and meta-analysis.
B cell lymphoma was positively associated with phenoxy herbicides and the organophosphorus herbicide glyphosate.

2014
june
https://www.ncbi.nlm.nih.gov/pubmed/24584268
Avigliano L, Fassiano AV, Medesani DA, Ríos de Molina MC, Rodríguez EM. Effects of glyphosate on growth rate, metabolic rate and energy reserves of early juvenile crayfish, Cherax quadricarinatus M.
Early juveniles of the crayfish Cherax quadricarinatus were exposed for 60 days to 10 and 40 mg/L of pure glyphosate (acid form) in freshwater. Mortality was 33 % at the highest concentration, while no differences in molting were noted among treatments. After the first month of exposure, weight gain was significantly (p < 0.05) reduced in the 40 mg/L group. At the end of the assay, lipid levels in muscle, as well as protein level in both hepatopancreas and muscle were significantly (p < 0.05) reduced. These results suggest long-term utilization of both lipid and protein as main energetic reserves, likely in response to the chronic stress associated with herbicide exposure. Besides, the lower pyruvate kinase activity in muscle suggests a possible metabolic depression in this tissue. The hemolymphatic ASAT:ALAT ratio showed higher levels than the control at the highest glyphosate concentration, indicating possible damage to several tissues.

2014
july
https://www.ncbi.nlm.nih.gov/pubmed/24930125
Cassault-Meyer E, Gress S, Séralini GÉ, Galeraud-Denis I. An acute exposure to glyphosate-based herbicide alters aromatase levels in testis and sperm nuclear quality.
Endocrine (aromatase, estrogen and androgen receptors, Gper1 in testicular and sperm mRNAs) and testicular functions (organ weights, sperm parameters and expression of the blood-testis barrier markers) were monitored at days 68, 87, and 122 after treatment, spermiogenesis and spermatogenesis. The major disruption is an increase of aromatase mRNA levels at least by 50% in treated rats at all times, as well as the aromatase protein. We have also shown a similar increase of Gper1 expression at day 122 and a light modification of BTB markers. A rise of abnormal sperm morphology and a decrease of the expression of protamine 1 and histone 1 testicular in epididymal sperm are observed despite a normal sperm concentration and motility.

2014
july
https://www.ncbi.nlm.nih.gov/pubmed/24985121
Larsen K, Najle R, Lifschitz A, Maté ML, Lanusse C, Virkel GL. Effects of Sublethal Exposure to a Glyphosate-Based Herbicide Formulation on Metabolic Activities of Different Xenobiotic-Metabolizing Enzymes in Rats.
The activities of different xenobiotic-metabolizing enzymes in liver subcellular fractions from Wistar rats exposed to a glyphosate (GLP)-based herbicide (Roundup full II) were evaluated in this work. Exposure to the herbicide triggered protective mechanisms against oxidative stress (increased glutathione peroxidase activity and total glutathione levels). Liver microsomes from both male and female rats exposed to the herbicide had lower (45%-54%, P < 0.01) hepatic cytochrome P450 (CYP) levels compared to their respective control animals. In female rats, the hepatic 7-ethoxycoumarin O-deethylase (a general CYP-dependent enzyme activity) was 57% higher (P < 0.05) in herbicide-exposed compared to control animals. Conversely, this enzyme activity was 58% lower (P < 0.05) in male rats receiving the herbicide. Lower (P < 0.05) 7-ethoxyresorufin O-deethlyase (EROD, CYP1A1/2 dependent) and oleandomycin triacetate (TAO) N-demethylase (CYP3A dependent) enzyme activities were observed in liver microsomes from exposed male rats. Conversely, in females receiving the herbicide, EROD increased (123%-168%, P < 0.05), whereas TAO N-demethylase did not change. A higher (158%-179%, P < 0.01) benzyloxyresorufin O-debenzylase (a CYP2B-dependent enzyme activity) activity was only observed in herbicide-exposed female rats. In herbicide-exposed rats, the hepatic S-oxidation of methimazole (flavin monooxygenase dependent) was 49% to 62% lower (P < 0.001), whereas the carbonyl reduction of menadione (a cytosolic carbonyl reductase-dependent activity) was higher (P < 0.05). Exposure to the herbicide had no effects on enzymatic activities dependent on carboxylesterases, glutathione transferases, and uridinediphospho-glucuronosyltransferases. This research demonstrated certain biochemical modifications after exposure to a GLP-based herbicide.

2014
july
https://www.ncbi.nlm.nih.gov/pubmed/25052523
Chłopecka M, Mendel M, Dziekan N, Karlik W.Glyphosate affects the spontaneous motoric activity of intestine at very low doses - in vitro study.
However, studies on glyphosate and its trade formulations reveal that it causes numerous morphological, physiological and biochemical disturbances in cells and organisms of animals, including mammals. Due to the fact that shortly after oral exposure glyphosate is detected in the highest amount in small intestine, the aim of this study was to evaluate the effect of this compound on the spontaneous motoric activity of intestine under in vitro conditions. The experiments were conducted on rat jejunum strips under isotonic conditions. The strips were incubated in buffered (pH 7.35) and non-buffered (pH 5.2) glyphosate solutions ranged from 0.003 to 1.7 g/L. The results indicate that glyphosate applied in buffered solution affects significantly the spontaneous motoric activity of rat isolated jejunum strips. The muscle response is biphasic (miorelaxation accompanied by contraction). The contraction is observed already at a dose of 0.003 g/L and the first significant biphasic reaction at a dose of 0.014 g/L. The incubation of jejunum strips with glyphosate in non-buffered solution (pH 5.2) results in a different reaction. The smooth muscle undergoes only persistent relaxation, which is stronger than the response to glyphosate solution in pH 7.35. Motility disturbances are also observed after glyphosate removal from the incubation solution. The gathered data suggests that glyphosate impairs gastrointestinal strips' motility at concentration that are noticed in human exposed to non-toxic doses of glyphosate.

2014
august
https://www.ncbi.nlm.nih.gov/pubmed/24831879
Avigliano L, Alvarez N, Loughlin CM, Rodríguez EM. Effects of glyphosate on egg incubation, larvae hatching, and ovarian rematuration in the estuarine crab Neohelice granulata.
Ovigerous females of the estuarine crab (Neohelice granulate) were exposed to both pure glyphosate (2.5 mg/L and 5 mg/L) and a glyphosate formulation (Roundup Ultramax, containing glyphosate at 2.5 mg/L acid equivalent). At the end of the egg incubation period, a significant reduction in the number of hatched larvae was seen as a result of Roundup exposure. Additionally, several larvae abnormalities were seen in both pure glyphosate (2.5 mg/L) and Roundup treatments, such as hydropsy and hypopigmented eyes, and atrophied eyes were observed in the Roundup treatment. To evaluate the effect of the herbicide on ovarian rematuration, females remained exposed for 32 d. Pure glyphosate at 2.5 mg/L stimulated ovarian maturation over control levels, mainly in terms of a higher gonadosomatic index and a higher percentage of vitellogenic oocytes. A plausible hypothesis to be tested in further experiments is that exposure to glyphosate disrupts the hormonal system controlling reproduction.

2014
august
https://www.ncbi.nlm.nih.gov/pubmed/24731878
Yusof S, Ismail A, Alias MS.Effect of glyphosate-based herbicide on early life stages of Java medaka (Oryzias javanicus): a potential tropical test fish.
Java medaka adults were cultured in the laboratory and the fertilized eggs of the F2 generation were exposed to different concentrations of glyphosate-based herbicide (100, 200, 300, 400 and 500 ppm) until they hatched. The survival and hatching rates of the embryos, changes in the heart rate and morphological impairments were recorded. Generally, survival and hatching percentage decreased as glyphosate concentration increased. Absence of pectoral fin(s) and cornea, permanently bent tail, irregular shaped abdomen, and cell disruption in the fin, head and abdomen are among the common teratogenic effects observed. Furthermore, risk factor also increased with the increased in glyphosate concentrations.

2014
august
https://www.ncbi.nlm.nih.gov/pubmed/24840881
Sinhorin VD, Sinhorin AP, Teixeira JM, Miléski KM, Hansen PC, Moreira PS, Kawashita NH Baviera AM, Loro VL. Effects of the acute exposition to glyphosate-based herbicide on oxidative stress parameters and antioxidant responses in a hybrid Amazon fish surubim (Pseudoplatystoma sp).
The fish were exposed to different herbicide concentrations for 96 h. The thiobarbituric acid-reactive substances (TBARS), protein carbonyls and antioxidant responses were verified. The 15 mg a.pL(-1) of herbicide resulted in the death of 50% of the fish after 96 h. An increase in liver and muscle TBARS levels was observed when fish were exposed to the herbicide. The protein carbonyl content was also increased in the liver (4.5mg a.pL(-1) concentration) and brain (2.25 mg a.pL(-1) concentration). The antioxidant activities decreased in the liver and brain after exposure to herbicide. Levels of ascorbic acid in the liver (2.25 mg a.pL(-1) and 4.5 mg a.pL(-1) concentrations) and brain (2.25 mg a.pL(-1) concentration) were increased post-treatment. Levels of total thiols were increased in the liver and brain (2.25 mg L(-1) and 7.5mg a.pL(-1), respectively). Glyphosate exposure, at the tested concentrations affects surubim health by promoting changes that can affect their survival in natural environment. Some parameters as TBARS and protein carbonyl could be early biomarkers for Roundup exposure in this fish species.

2014
september
https://www.ncbi.nlm.nih.gov/pubmed/24927388
Samanta P, Pal S, Mukherjee AK, Ghosh AR. Biochemical effects of glyphosate based herbicide, Excel Mera 71 on enzyme activities of acetylcholinesterase (AChE), lipid peroxidation (LPO), catalase (CAT), glutathione-S-transferase (GST) and protein content on teleostean fishes.
Effects of glyphosate based herbicide, Excel Mera 71 at a dose of 17.20mg/l on enzyme activities of acetylcholinesterase (AChE), lipid peroxidation (LPO), catalase (CAT), glutathione-S-transferase (GST) and protein content were measured in different tissues of two Indian air-breathing teleosts, Anabas testudineus (Bloch) and Heteropneustes fossilis (Bloch) during an exposure period of 30 days under laboratory condition. AChE activity was significantly increased in all the investigated tissues of both fish species and maximum elevation was observed in brain of H. fossilis, while spinal cord of A. testudineus showed minimum increment. Fishes showed significant increase LPO levels in all the tissues; highest was observed in gill of A. testudineus but lowest LPO level was observed in muscle of H. fossilis. CAT was also enhanced in both the fishes, while GST activity in liver diminished substantially and minimum was observed in liver of A. testudineus. Total protein content showed decreased value in all the tissues, maximum reduction was observed in liver and minimum in brain of A. testudineus and H. fossilis respectively. The results indicated that Excel Mera 71 caused serious alterations in the enzyme activities resulting into severe deterioration of fish health; so, AChE, LPO, CAT and GST can be used as suitable indicators of herbicidal toxicity.

2014
september
https://www.ncbi.nlm.nih.gov/pubmed/24912403
Lanctôt C, Navarro-Martín L, Robertson C, Park B, Jackman P, Pauli BD, Trudeau VL Effects of glyphosate-based herbicides on survival, development, growth and sex ratios of wood frog (Lithobates sylvaticus) tadpoles. II: agriculturally relevant exposures to Roundup WeatherMax® and Vision® under laboratory conditions.
We conclude that glyphosate-based herbicides have the potential to alter mRNA profiles during metamorphosis.

2014
october
https://www.ncbi.nlm.nih.gov/pubmed/25089920
Lopes FM, Varela Junior AS, Corcini CD, da Silva AC, Guazzelli VG, Tavares G, da Rosa CE. Effect of glyphosate on the sperm quality of zebrafish Danio rerio.
n this study, the effect of glyphosate on sperm quality of the fish Danio rerio was investigated after 24 and 96 h of exposure at concentrations of 5mg/L and 10mg/L. The spermatic cell concentration, sperm motility and motility period were measured employing conventional microscopy. The mitochondrial functionality, membrane integrity and DNA integrity were measured by fluorescence microscopy using specific probes. No significant differences in sperm concentration were observed; however, sperm motility and the motility period were reduced after exposure to both glyphosate concentrations during both exposure periods. The mitochondrial functionality and membrane and DNA integrity were also reduced at the highest concentration during both exposure periods. The results showed that glyphosate can induce harmful effects on reproductive parameters in D. rerio and that this change would reduce the fertility rate of these animals.

2014
october
https://www.ncbi.nlm.nih.gov/pubmed/25063858
Herbert LT, Vázquez DE, Arenas A, Farina WM. Effects of field-realistic doses of glyphosate on honeybee appetitive behaviour.
Apis mellifera is the main pollinator in agricultural environments and is a well-known model for behavioural research. Honeybees are also accurate biosensors of environmental pollutants and their appetitive behavioural response is a suitable tool with which to test sub-lethal effects of agrochemicals. We studied the effects of field-realistic doses of GLY on honeybees exposed chronically or acutely to the herbicide. We focused on sucrose sensitivity, elemental and non-elemental associative olfactory conditioning of the proboscis extension response (PER), and foraging-related behaviour. We found a reduced sensitivity to sucrose and learning performance for the groups chronically exposed to GLY concentrations within the range of recommended doses. When olfactory PER conditioning was performed with sucrose reward with the same GLY concentrations (acute exposure), elemental learning and short-term memory retention decreased significantly compared with controls. Non-elemental associative learning was also impaired by an acute exposure to GLY traces. Altogether, these results imply that GLY at concentrations found in agro-ecosystems as a result of standard spraying can reduce sensitivity to nectar reward and impair associative learning in honeybees. However, no effect on foraging-related behaviour was found. Therefore, we speculate that successful forager bees could become a source of constant inflow of nectar with GLY traces that could then be distributed among nestmates, stored in the hive and have long-term negative consequences on colony performance.

2014
november
Marques A, Guilherme S, Gaivão I, Santos MA, Pacheco M. Progression of DNA damage induced by a glyphosate-based herbicide in fish (Anguilla anguilla) upon exposure and post-exposure periods--insights into the mechanisms of genotoxicity and DNA repair.
Among the described effects to fish, genotoxicity has been pointed out as one of the most hazardous. However, the genotoxic mechanisms of Roundup® as well as the involvement of the oxidative DNA damage repair system are not entirely understood. Hence, this work aimed to improve the knowledge on the progression of DNA damage upon short-term exposure (3 days) and post-exposure (1-14 days) periods in association with DNA repair processes in Anguilla anguilla exposed to Roundup® (58 and 116 μg L⁻¹). DNA damage in hepatic cells was evaluated by the comet assay improved with the DNA-lesion specific endonucleases FPG and EndoIII. In order to evaluate the oxidative DNA damage repair ability, an in vitro base excision repair (BER) assay was performed, testing hepatic subcellular extracts. Besides the confirmation of the genotoxic potential of this herbicide, oxidative damage was implicit as an important mechanism of genetic damage, which showed to be transient, since DNA integrity returned to the control levels on the first day after cessation of exposure. An increased capacity to repair oxidative DNA damage emerging in the post-exposure period revealed to be a crucial pathway for the A. anguilla recovery; nevertheless, DNA repair machinery showed to be susceptible to inhibitory actions during the exposure period, disclosing another facet of the risk associated with the tested agrochemical.


2015
march
https://www.ncbi.nlm.nih.gov/pubmed/25883837
Samsel A, Seneff S. Glyphosate, pathways to modern diseases III: Manganese, neurological diseases, and associated pathologies.
Manganese (Mn) is an often overlooked but important nutrient, required in small amounts for multiple essential functions in the body. A recent study on cows fed genetically modified Roundup(®)-Ready feed revealed a severe depletion of serum Mn. Glyphosate, the active ingredient in Roundup(®), has also been shown to severely deplete Mn levels in plants. Here, we investigate the impact of Mn on physiology, and its association with gut dysbiosis as well as neuropathologies such as autism, Alzheimer's disease (AD), depression, anxiety syndrome, Parkinson's disease (PD), and prion diseases. Glutamate overexpression in the brain in association with autism, AD, and other neurological diseases can be explained by Mn deficiency. Mn superoxide dismutase protects mitochondria from oxidative damage, and mitochondrial dysfunction is a key feature of autism and Alzheimer's. Chondroitin sulfate synthesis depends on Mn, and its deficiency leads to osteoporosis and osteomalacia. Lactobacillus, depleted in autism, depend critically on Mn for antioxidant protection. Lactobacillus probiotics can treat anxiety, which is a comorbidity of autism and chronic fatigue syndrome. Reduced gut Lactobacillus leads to overgrowth of the pathogen, Salmonella, which is resistant to glyphosate toxicity, and Mn plays a role here as well. Sperm motility depends on Mn, and this may partially explain increased rates of infertility and birth defects. We further reason that, under conditions of adequate Mn in the diet, glyphosate, through its disruption of bile acid homeostasis, ironically promotes toxic accumulation of Mn in the brainstem, leading to conditions such as PD and prion diseases.

2015
april
https://www.ncbi.nlm.nih.gov/pubmed/25245870
Gress S, Lemoine S, Séralini GE, Puddu PE. Glyphosate-based herbicides potently affect cardiovascular system in mammals: review of the literature.
We observed in two mammalian species (rats and rabbits) direct cardiac electrophysiological changes, conduction blocks and arrhythmias among GBH-mediated effects.

2015
june
https://www.ncbi.nlm.nih.gov/pubmed/24728576
Helmer SH, Kerbaol A, Aras P, Jumarie C, Boily M. Effects of realistic doses of atrazine, metolachlor, and glyphosate on lipid peroxidation and diet-derived antioxidants in caged honey bees (Apis mellifera).
However, β-carotene, which was found to be the most abundant carotenoid, and at-ROH (derived from β-carotene) both decreased with increasing doses of atrazine and glyphosate.

2015
august
https://www.ncbi.nlm.nih.gov/pubmed/26302742
Mesnage R, Arno M, Costanzo M, Malatesta M, Séralini GE, Antoniou MN. Transcriptome profile analysis reflects rat liver and kidney damage following chronic ultra-low dose Roundup exposure.
Our results suggest that chronic exposure to a GBH in an established laboratory animal toxicity model system at an ultra-low, environmental dose can result in liver and kidney damage with potential significant health implications for animal and human populations.

2015
october
https://www.ncbi.nlm.nih.gov/pubmed/26282372
Mesnage R, Defarge N, Spiroux de Vendômois J, Séralini GE. Potential toxic effects of glyphosate and its commercial formulations below regulatory limits.
Glyphosate-based herbicides (GlyBH), including Roundup, are the most widely used pesticides worldwide. Their uses have increased exponentially since their introduction on the market. Residue levels in food or water, as well as human exposures, are escalating. We have reviewed the toxic effects of GlyBH measured below regulatory limits by evaluating the published literature and regulatory reports. We reveal a coherent body of evidence indicating that GlyBH could be toxic below the regulatory lowest observed adverse effect level for chronic toxic effects. It includes teratogenic, tumorigenic and hepatorenal effects. They could be explained by endocrine disruption and oxidative stress, causing metabolic alterations, depending on dose and exposure time. Some effects were detected in the range of the recommended acceptable daily intake. Toxic effects of commercial formulations can also be explained by GlyBH adjuvants, which have their own toxicity, but also enhance glyphosate toxicity. These challenge the assumption of safety of GlyBH at the levels at which they contaminate food and the environment, albeit these levels may fall below regulatory thresholds. Neurodevelopmental, reproductive, and transgenerational effects of GlyBH must be revisited, since a growing body of knowledge suggests the predominance of endocrine disrupting mechanisms caused by environmentally relevant levels of exposure.

2015
september
https://www.ncbi.nlm.nih.gov/pubmed/26333931
Balbuena MS, Tison L, Hahn ML, Greggers U, Menzel R, Farina WM. Effects of sublethal doses of glyphosate on honeybee navigation.
Here, we tested whether exposure to three sublethal concentrations of GLY (2.5, 5 and 10 mg l(-1): corresponding to 0.125, 0.250 and 0.500 μg per animal) affects the homeward flight path of honeybees in an open field. We performed an experiment in which forager honeybees were trained to an artificial feeder, and then captured, fed with sugar solution containing traces of GLY and released from a novel site either once or twice. Their homeward trajectories were tracked using harmonic radar technology. We found that honeybees that had been fed with solution containing 10 mg l(-1) GLY spent more time performing homeward flights than control bees or bees treated with lower concentrations. They also performed more indirect homing flights. Moreover, the proportion of direct homeward flights performed after a second release from the same site increased in control bees but not in treated bees. These results suggest that, in honeybees, exposure to levels of GLY commonly found in agricultural settings impairs the cognitive capacities needed to retrieve and integrate spatial information for a successful return to the hive. Therefore, honeybee navigation is affected by ingesting traces of the most widely used herbicide worldwide, with potential long-term negative consequences for colony foraging success.

2016
january
https://www.ncbi.nlm.nih.gov/pubmed/26381782
Dornelles MF, Oliveira GT. Toxicity of atrazine, glyphosate, and quinclorac in bullfrog tadpoles exposed to concentrations below legal limits.
This work sought to ascertain survival and possible changes in levels of glycogen, triglycerides, total lipids, cholesterol, protein, and lipid peroxidation in gills, liver, and muscle of bullfrog tadpoles (Lithobates catesbeianus) exposed to low concentrations of atrazine (2.5 μg L(-1)), glyphosate (18 μg L(-1)), and quinclorac (0.025 μg L(-1)) at laboratorial conditions. Tadpoles showed a reduction of glycogen and triglyceride in all organs and an increase in lipid peroxidation (LPO) compared with control animals. Total lipid in gills and muscle increased in exposure to atrazine, and gills alone in exposure to glyphosate, but decreased in gills, liver, and muscle after quinclorac. Cholesterol increased in gills and liver after atrazine, in gills and muscle after glyphosate, and decreased in liver after quinclorac

2016
january
https://www.ncbi.nlm.nih.gov/pubmed/26688330
Coullery RP, Ferrari ME, Rosso SB. Neuronal development and axon growth are altered by glyphosate through a WNT non-canonical signaling pathway.
Previous studies have demonstrated that glyphosate induces neurotoxicity in mammals. Therefore, its action mechanism on the nervous system needs to be determined. In this study, we report about impaired neuronal development caused by glyphosate exposure. Particularly, we observed that the initial axonal differentiation and growth of cultured neurons is affected by glyphosate since most treated cells remained undifferentiated after 1 day in culture. Although they polarized at 2 days in vitro, they elicited shorter and unbranched axons and they also developed less complex dendritic arbors compared to controls. To go further, we attempted to identify the cellular mechanism by which glyphosate affected neuronal morphology. Biochemical approaches revealed that glyphosate led to a decrease in Wnt5a level, a key factor for the initial neurite development and maturation, as well as inducing a down-regulation of CaMKII activity. This data suggests that the morphological defects would likely be a consequence of the decrease in both Wnt5a expression and CaMKII activity induced by glyphosate. Additionally, these changes might be reflected in a subsequent neuronal dysfunction. Therefore, our findings highlight the importance of establishing rigorous control on the use of glyphosate-based herbicides in order to protect mammals' health.

2016
february
https://www.ncbi.nlm.nih.gov/pubmed/26688238
Ghisi Nde C, de Oliveira EC, Prioli AJ. Does exposure to glyphosate lead to an increase in the micronuclei frequency? A systematic and meta-analytic review.
In conclusion, our results support the hypothesis that exposure to GLY and its formulations increases the frequency of MN formation.

2016
march
https://www.ncbi.nlm.nih.gov/pubmed/26632987
Gallegos CE, Bartos M, Bras C, Gumilar F, Antonelli MC, Minetti A. Exposure to a glyphosate-based herbicide during pregnancy and lactation induces neurobehavioral alterations in rat offspring.
To this end, pregnant Wistar rats were exposed through drinking water to 0.2% or 0.4% of a commercial formulation of glyphosate (corresponding to a concentration of 0.65 or 1.30g/L of glyphosate, respectively) during pregnancy and lactation and neurobehavioral alterations in offspring were analyzed. The postnatal day on which each pup acquired neonatal reflexes (righting, cliff aversion and negative geotaxis) and that on which eyes and auditory canals were fully opened were recorded for the assessment of sensorimotor development. Locomotor activity and anxiety levels were monitored via open field test and plus maze test, respectively, in 45- and 90-day-old offspring. Pups exposed to a glyphosate-based herbicide showed early onset of cliff aversion reflex and early auditory canal opening. A decrease in locomotor activity and in anxiety levels was also observed in the groups exposed to a glyphosate-containing herbicide. Findings from the present study reveal that early exposure to a glyphosate-based herbicide affects the central nervous system in rat offspring probably by altering mechanisms or neurotransmitter systems that regulate locomotor activity and anxiety.

2016
march
https://www.ncbi.nlm.nih.gov/pubmed/26773362
Roy NM, Carneiro B, Ochs J. Glyphosate induces neurotoxicity in zebrafish.
However, mounting evidence suggests that GBHs may not be as safe as once thought as initial studies in frogs suggest that GBHs may be teratogenic. Here we utilize the zebrafish vertebrate model system to study early effects of glyphosate exposure using technical grade glyphosate and the Roundup(®) Classic formulation. We find morphological abnormalities including cephalic and eye reductions and a loss of delineated brain ventricles. Concomitant with structural changes in the developing brain, using in situ hybridization analysis, we detect decreases in genes expressed in the eye, fore and midbrain regions of the brain including pax2, pax6, otx2 and ephA4. However, we do not detect changes in hindbrain expression domains of ephA4 nor exclusive hindbrain markers krox-20 and hoxb1a. Additionally, using a Retinoic Acid (RA) mediated reporter transgenic, we detect no alterations in the RA expression domains in the hindbrain and spinal cord, but do detect a loss of expression in the retina. We conclude that glyphosate and the Roundup(®) formulation is developmentally toxic to the forebrain and midbrain but does not affect the hindbrain after 24 h exposure.

2016
april
https://www.ncbi.nlm.nih.gov/pubmed/26508170
Murussi CR, Costa MD, Leitemperger JW, Guerra L, Rodrigues CC, Menezes CC, Severo ES, Flores-Lopes F, Salbego J, Loro VL. Exposure to different glyphosate formulations on the oxidative and histological status of Rhamdia quelen.
 Despite GLY being widely used in Brazil, there are few studies comparing the effects of commercial formulations in native freshwater fish species. Silver catfish (Rhamdia quelen) were exposed to three different commercial formulations of GLY 48% (Orium(®), Original(®) and Biocarb(®)) at 0.0, 2.5 and 5.0 mg/L for 96 h. The effects in thiobarbituric acid-reactive substances (TBARS), catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST) and histological alterations were analysed in the liver, whereas alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were studied in the plasma. In the liver, TBARS levels increased and CAT decreased in all treatments and herbicides tested in comparison with the control group. The SOD increased at 2.5 mg/L of Orium(®), Original(®) and 5.0 mg/L Orium(®) and Biocarb(®), whereas GST increased at 2.5 mg/L Orium(®) and decreased at 2.5 mg/L Biocarb(®) when compared to the control group. The main histopathological alterations in hepatic tissue were vacuolisation, leucocyte infiltration, degeneration of cytoplasm and melanomacrophage in all GLY treatments. The ALT decreased after exposure to 2.5 mg/L of Biocarb(®) and AST increased at 2.5 mg/L of Orium(®), Original(®) and 5.0 mg/L of Biocarb(®) in comparison with the control group. In summary, the oxidative damage generated by GLY may have caused the increased formation of free radicals that led to the histological alterations observed in hepatocytes.

2016
may
https://www.ncbi.nlm.nih.gov/pubmed/26856864
Pérez-Iglesias JM, Franco-Belussi L, Moreno L, Tripole S, de Oliveira C, Natale GS. Effects of glyphosate on hepatic tissue evaluating melanomacrophages and erythrocytes responses in neotropical anuran Leptodactylus latinasus.
Therefore, this study evaluated the effects of GLY on hepatic melanomacrophages as a response to environmental stressors. Three treatments were exposed to different concentrations of pure GLY (100, 1000, and 10,000 μg g(-1), respectively), and there was also a control group. After the experimental time, liver and blood were analyzed. Melanomacrophages (MMCs) were located between the hepatocyte cordons, close to sinusoids. GLY increased the melanin area in MMCs of Leptodactylus latinasus exposed since lowest concentration until highest concentration. GLY also changed the occurrence of hepatic catabolism pigments into melanomacrophages and erythrocyte nuclear abnormalities; therefore, it can interfere with the hepatic metabolism. In conclusion, GLY promotes alterations in the hepatic tissue and erythrocyte nuclear abnormalities.

2016
july
https://www.ncbi.nlm.nih.gov/pubmed/27258137
Larsen KE, Lifschitz AL, Lanusse CE, Virkel GL. The herbicide glyphosate is a weak inhibitor of acetylcholinesterase in rats.
In conclusion, GLP is a weak inhibitor of AChE in rats.

2016
august
https://www.ncbi.nlm.nih.gov/pubmed/27160633
Rissoli RZ, Abdalla FC, Costa MJ, Rantin FT, McKenzie DJ, Kalinin AL. Effects of glyphosate and the glyphosate based herbicides Roundup Original(®) and Roundup Transorb(®) on respiratory morphophysiology of bullfrog tadpoles.
Glyphosate-based herbicides are widely used in agriculture and are commonly found in water bodies. Roundup Original(®) (RO) contains an isopropylamine glyphosate (GLY) salt containing the surfactant POEA, while Roundup Transorb R(®) (RTR) contains a potassium salt of GLY with unknown surfactants. Both contain different compositions of so-called "inert" ingredients, more toxic than glyphosate. Amphibian tadpoles often experience variations in O2 availability in their aquatic habitats; an ability to tolerate hypoxia can condition their survival and fitness. We evaluated the impacts of sublethal concentrations of GLY (1 mg L(-1)), RO (1 mg L(-1) GLY a.e) and RTR (1 mg L(-1) GLY a.e) on metabolic rate (V·O2 - mLO2 Kg1 h(-1)) of bullfrog tadpoles during normoxia and graded hypoxia, and related this to morphology of their skin, their major site of gas exchange. In control (CT) V·O2 remained unaltered from normoxia until 40 mmHg, indicating a critical O2 tension between 40 and 20 mmHg. GLY significantly reduced V·O2, possibly due to epidermal hypertrophy, which increased O2 diffusion distance to O2 uptake. In contrast, RTR increased V·O2 during hypoxia, indicating an influence of "inert" compounds and surfactants. V·O2 of RO did not differ from CT, suggesting that any increase in V·O2 caused by exposure was antagonized by epidermal hypertrophy. Indeed, all herbicides caused marked alterations in skin morphology, with cell and epithelium wall presenting hyperplasia or hypertrophy and chromatid rupture. In summary, GLY, RO and RTR exert different effects in bullfrog tadpoles, in particular the surfactants and inert compounds appear to influence oxygen uptake.

2016
november
https://www.ncbi.nlm.nih.gov/pubmed/27486271
Ingaramo PI, Varayoud J, Milesi MM, Schimpf MG, Muñoz-de-Toro M, Luque EH. Effects of neonatal exposure to a glyphosate-based herbicide on female rat reproduction.
 Newborn female rats received vehicle or 2 mg/kg/day of a GBH on postnatal days (PND) 1, 3, 5 and 7. On PND90, the rats were mated to evaluate (i) the reproductive performance on gestational day (GD) 19 and (ii) the ovarian steroid levels, uterine morphology, endometrial cell proliferation, apoptosis and cell cycle regulators, and endocrine pathways that regulate uterine decidualization (steroid receptors/COUP-TFII/Bmp2/Hoxa10) at the implantation sites (IS) on GD9. The GBH-exposed group showed a significant increase in the number of resorption sites on GD19, associated with an altered decidualization response. In fact, on GD9, the GBH-treated rats showed morphological changes at the IS, associated with a decreased expression of estrogen and progesterone receptors, a downregulation of COUP-TFII (Nr2f2) and Bmp2 mRNA and an increased expression of HOXA10 and the proliferation marker Ki67(Mki67) at the IS. We concluded that alterations in endometrial decidualization might be the mechanism of GBH-induced post-implantation embryo loss.

2017
february
https://www.ncbi.nlm.nih.gov/pubmed/27287056
Guerrero Schimpf M, Milesi MM, Ingaramo PI, Luque EH, Varayoud J. Neonatal exposure to a glyphosate based herbicide alters the development of the rat uterus.
 Female Wistar pups received saline solution (control, C) or a commercial formulation of glyphosate (GBH, 2mg/kg) by sc injection every 48h from postnatal day (PND) 1 to PND7. Rats were sacrificed on PND8 (neonatal period) and PND21 (prepubertal period) to evaluate acute and short-term effects, respectively. The uterine morphology was evaluated in hematoxylin and eosin stained sections. The epithelial and stromal immunophenotypes were established by assessing the expression of luminal epithelial protein (cytokeratin 8; CK8), basal epithelial proteins (p63 and pan cytokeratin CK1, 5, 10 and 14); and vimentin by immunohistochemistry (IHC). To investigate changes on proteins that regulate uterine organogenetic differentiation we evaluated the expression of estrogen receptor alpha (ERα), progesterone receptor (PR), Hoxa10 and Wnt7a by IHC. The GBH-exposed uteri showed morphological changes, characterized by an increase in the incidence of luminal epithelial hyperplasia (LEH) and an increase in the stromal and myometrial thickness. The epithelial cells showed a positive immunostaining for CK8, while the stromal cells for vimentin. GBH treatment increased cell proliferation in the luminal and stromal compartment on PND8, without changes on PND21. GBH treatment also altered the expression of proteins involved in uterine organogenetic differentiation. PR and Hoxa10 were deregulated both immediately and two weeks after the exposure. ERα was induced in the stromal compartment on PND8, and was downregulated in the luminal epithelial cells of gyphosate-exposed animals on PND21. GBH treatment also increased the expression of Wnt7a in the stromal and glandular epithelial cells on PND21. Neonatal exposure to GBH disrupts the postnatal uterine development at the neonatal and prepubertal period. All these changes may alter the functional differentiation of the uterus, affecting the female fertility and/or promoting the development of neoplasias.

2017
february
https://www.ncbi.nlm.nih.gov/pubmed/27836263
Dos Santos AP, Rocha TL, Borges CL, Bailão AM, de Almeida Soares CM, de Sabóia-Morais SM. A glyphosate-based herbicide induces histomorphological and protein expression changes in the liver of the female guppy Poecilia reticulata.
Guppies were exposed to GBH for 24 h at 1.8 mg of glyphosate L-1, corresponding to 50% of the LC50, 96 h. The results indicate that the GBH at 1.8 mg of glyphosate L-1 induce the development of hepatic damage in P. reticulata, which is exposure-time dependent. The histopathological indexes demonstrate that GBH cause inflammatory, regressive, vascular and progressive disorders in the liver of guppies. Using 2D gel electrophoresis associated with mass spectrometry, 18 proteins that changed by GBH were identified and were related to the cellular structure, motility and transport, energy metabolism and apoptosis. The results show that the acute exposure to GBH causes hepatic histopathological damage related to protein expression profile changes in P. reticulata, indicating that a histopathological assessment associated with a proteomic analysis provides a valuable approach to assess the toxic effects of GBH in sentinel fish species.

2017
february
https://www.ncbi.nlm.nih.gov/pubmed/27916585
de Souza JS, Kizys MM, da Conceição RR, Glebocki G, Romano RM, Ortiga-Carvalho TM, Giannocco G, da Silva ID, Dias da Silva MR, Romano MA, Chiamolera MI. Perinatal exposure to glyphosate-based herbicide alters the thyrotrophic axis and causes thyroid hormone homeostasis imbalance in male rats.
The aim of the present study was to determine whether GBHs could also disrupt the hypothalamic-pituitary-thyroid (HPT) axis. Female pregnant Wistar rats were exposed to a solution containing GBH Roundup®Transorb (Monsanto). The animals were divided into three groups (control, 5mg/kg/day or 50mg/kg/day) and exposed from gestation day 18 (GD18) to post-natal day 5 (PND5). Male offspring were euthanized at PND 90, and blood and tissues samples from the hypothalamus, pituitary, liver and heart were collected for hormonal evaluation (TSH-Thyroid stimulating hormone, T3-triiodothyronine and T4-thyroxine), metabolomic and mRNA analyses of genes related to thyroid hormone metabolism and function. The hormonal profiles showed decreased concentrations of TSH in the exposed groups, with no variation in the levels of the thyroid hormones (THs) T3 and T4 between the groups. Hypothalamus gene expression analysis of the exposed groups revealed a reduction in the expression of genes encoding deiodinases 2 (Dio2) and 3 (Dio3) and TH transporters Slco1c1 (former Oatp1c1) and Slc16a2 (former Mct8). In the pituitary, Dio2, thyroid hormone receptor genes (Thra1 and Thrb1), and Slc16a2 showed higher expression levels in the exposed groups than in the control group. Interestingly, Tshb gene expression did not show any difference in expression profile between the control and exposed groups. Liver Thra1 and Thrb1 showed increased mRNA expression in both GBH-exposed groups, and in the heart, Dio2, Mb, Myh6 (former Mhca) and Slc2a4 (former Glut4) showed higher mRNA expression in the exposed groups. Additionally, correlation analysis between gene expression and metabolomic data showed similar alterations as detected in hypothyroid rats. Perinatal exposure to GBH in male rats modified the HPT set point, with lower levels of TSH likely reflecting post-translational events. Several genes regulated by TH or involved in TH metabolism and transport presented varying degrees of gene expression alteration that were probably programmed during intrauterine exposure to GBHs and reflects in peripheral metabolism. In conclusion, the role of GBH exposure in HPT axis disruption should be considered in populations exposed to this herbicide.

2017
march
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5370400/
Nicole E De Long. Alison C Holloway. Early-life chemical exposures and risk of metabolic syndrome//Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy (review)
Glyphosate has been shown to cause liver and kidney toxicities at low doses and to increase apoptosis and induce oxidative stress in preadipocytes

2017
april
https://www.ncbi.nlm.nih.gov/pubmed/27906609
Lopes FM, Caldas SS, Primel EG, da Rosa CE. Glyphosate Adversely Affects Danio rerio Males: Acetylcholinesterase Modulation and Oxidative Stress.
In the present study, reactive oxygen species (ROS) generation, antioxidant capacity against peroxyl radicals (ACAP), and lipid peroxidation (LPO), as well as the activity and expression of the acetylcholinesterase (AChE) enzyme, were evaluated in Danio rerio males exposed to 5 or 10 mg/L of glyphosate for 24 and 96 h. An increase in ACAP in gills after 24 h was observed in the animals exposed to 5 mg/L of glyphosate. A decrease in LPO was observed in brain tissue of animals exposed to 10 mg/L after 24 h, while an increase was observed in muscle after 96 h. No significant alterations were observed in ROS generation. AChE activity was not altered in muscles or brains of animals exposed to either glyphosate concentration for 24 or 96 h. However, gene expression of this enzyme in the brain was reduced after 24 h and was enhanced in both brain and muscle tissues after 96 h. Thus, contrary to previous findings that had attributed the imbalance in the oxidative state of animals exposed to glyphosate-based herbicides to surfactants and other inert compounds, the present study demonstrated that glyphosate per se promotes this same effect in zebrafish males. Although glyphosate concentrations did not alter AChE activity, this study demonstrated for the first time that this molecule affects ache expression in male zebrafish D. rerio.

2017
june
https://www.ncbi.nlm.nih.gov/pubmed/27917511
Perego MC, Schutz LF, Caloni F, Cortinovis C, Albonico M, Spicer LJ. Evidence for direct effects of glyphosate on ovarian function: glyphosate influences steroidogenesis and proliferation of bovine granulosa but not theca cells in vitro.
Глифосат может влиять на репродуктивную систему коров.


2017
june
https://www.ncbi.nlm.nih.gov/pubmed/28667585
Kašuba V, Milić M, Rozgaj R, Kopjar N, Mladinić M, Žunec S, Vrdoljak AL, Pavičić I, Čermak AMM, Pizent A, Lovaković BT, Želježić D. Effects of low doses of glyphosate on DNA damage, cell proliferation and oxidative stress in the HepG2 cell line.
We studied the toxic effects of glyphosate in vitro on HepG2 cells exposed for 4 and 24 h to low glyphosate concentrations likely to be encountered in occupational and residential exposures [the acceptable daily intake (ADI; 0.5 μg/mL), residential exposure level (REL; 2.91 μg/mL) and occupational exposure level (OEL; 3.5 μg/mL)]. The assessments were performed using biomarkers of oxidative stress, CCK-8 colorimetric assay for cell proliferation, alkaline comet assay and cytokinesis-block micronucleus (CBMN) cytome assay. The results obtained indicated effects on cell proliferation, both at 4 and 24 h. The levels of primary DNA damage after 4-h exposure were lower in treated vs. control samples, but were not significantly changed after 24 h. Using the CBMN assay, we found a significantly higher number of MN and nuclear buds at ADI and REL after 4 h and a lower number of MN after 24 h. The obtained results revealed significant oxidative damage. Four-hour exposure resulted in significant decrease at ADI [lipid peroxidation and glutathione peroxidase (GSH-Px)] and OEL [lipid peroxidation and level of total antioxidant capacity (TAC)], and 24-h exposure in significant decrease at OEL (TAC and GSH-Px). No significant effects were observed for the level of reactive oxygen species (ROS) and glutathione (GSH) for both treatment, and for 24 h for lipid peroxidation. Taken together, the elevated levels of cytogenetic damage found by the CBMN assay and the mechanisms of primary DNA damage should be further clarified, considering that the comet assay results indicate possible cross-linking or DNA adduct formation.

2017
august
https://www.ncbi.nlm.nih.gov/pubmed/28780397
Ingaramo PI, Varayoud J, Milesi MM, Guerrero Schimpf M, Alarcón R, Muñoz-de-Toro M, Luque EH. Neonatal exposure to a glyphosate-based herbicide alters uterine decidualization in rats.
Получение глифосата в новорожденном возрасте ухудшало в последствии состояние эндометрия у крыс.

2017
october
https://www.ncbi.nlm.nih.gov/pubmed/28846991
Cai W, Ji Y, Song X, Guo H, Han L, Zhang F, Liu X, Zhang H, Zhu B, Xu M. Effects of glyphosate exposure on sperm concentration in rodents: A systematic review and meta-analysis.(review)
Результаты мета-анализа поддерживают гипотезу что глифосат снижает качество спермы у грызунов.

2019
ноябрь
Glyphosate: Its Environmental Persistence and Impact on Crop Health and Nutrition
Ramdas Kanissery et al
https://www.mdpi.com/2223-7747/8/11/499/htm

2021
Juan P. Muñoz et al
Glyphosate and the key characteristics of an endocrine disruptor: A review
https://www.sciencedirect.com/science/article/abs/pii/S0045653520328149

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