Glyphosate – A potentially neurotoxic, genotoxic, and carcinogenic chemical which is ubiquitous in our food and environment

Abstract

Glyphosate (IUPAC name: N-(phosphonomethyl)glycine) is a non-selective broad-spectrum systemic herbicide and crop desiccant. It is primarily used to “kill weeds”, especially annual broadleaf weeds and grasses that compete with crops. Furthermore, it is utilized massively by the agricultural industry on many food crops which people consume on a daily basis (e.g., fruits, vegetables, grains, etc.).

Figure 1. Chemical structure of Glyphosate (chemical formula: C3H8NO5P).

Effects of glyphosate on the ovarian function of pregnant mice, the secretion of hormones and the sex ratio of their fetuses

Study Highlights

•Prenatal exposure to pure glyphosate affected sex ratios of litters.
•Glyphosate caused ovarian histopathological alterations in pregnant mice.
•Glyphosate disrupted the secretion of progesterone and estrogen in pregnant mice.
•Glyphosate disrupted expressions of steroidogenesis-related genes in pregnant mice.
•Glyphosate induced oxidative stress in ovary and serum of pregnant mice.

Visual summary


Abstract

Glyphosate is the active ingredient of the commercial formulation Roundup®, which is used worldwide. This study aimed to investigate the toxic effects of pure glyphosate or Roundup® on pregnant mice and their fetuses during pregnancy. From gestation days (GDs) 1–19, ICR mice were orally administered distilled water, 0.5% glyphosate solution or 0.5%-glyphosate Roundup® solution. The ovaries and serum were collected at GD19. The results showed decreases in body weight gain and, ovary and liver weight in glyphosate-treated mice. Additionally, histopathological alterations in the ovary including increased atretic follicles, interstitial fibrosis and decreased mature follicles were observed in the groups treated with glyphosate. The serum concentrations of both progesterone and estrogen were markedly altered after glyphosate exposure, and there were also changes in the expression of GnRH, LHR, FSHR, 3β-HSD and Cyp19a1 genes at the hypothalamic-pituitary-ovarian axis. Furthermore, oxidative stress was observed in the treated mice, increasing the activity of T-AOC, CAT and GSH-Px, as well as the MDA content in both the serum and ovary. With regard to litters, the sex ratio was significantly altered by pure glyphosate. These results show that glyphosate is able to cause several effects on pregnant mice, such as ovarian failure, interference with hormone secretion by affecting the steroidogenesis-related gene expression, and oxidative stress. The sex ratio of litters was also influenced by prenatal exposure to pure glyphosate.

URL:www.sciencedirect.com/science/article/pii/S0269749118330197

Glyphosate and Roundup® alter morphology and behavior in zebrafish

Study Highlights

•Glyphosate or Roundup® altered locomotion and aversive behavior in zebrafish larvae.
•Glyphosate or Roundup® reduced the locomotion in adult zebrafish.
•Glyphosate decreased ocular distance in zebrafish larvae.
•Roundup®-exposed adult zebrafish demonstrated impairment in memory.
•Glyphosate and Roundup® reduced agressive behavior in adult zebrafish.

Abstract

Glyphosate has become the most widely used herbicide in the world, due to the wide scale adoption of transgenic glyphosate resistant crops after its introduction in 1996. Glyphosate may be used alone, but it is commonly applied as an active ingredient of the herbicide Roundup®. This pesticide contains several adjuvants, which may promote an unknown toxicity. The indiscriminate application poses numerous problems, both for the health of the applicators and consumers, and for the environment, contaminating the soil, water and leading to the death of plants and animals. Zebrafish (Danio rerio) is quickly gaining popularity in behavioral research, because of physiological similarity to mammals, sensitivity to pharmacological factors, robust performance, low cost, short spawning intervals, external fertilization, transparency of embryos through larval stages, and rapid development. The aim of this study was evaluate the effects of glyphosate and Roundup® on behavioral and morphological parameters in zebrafish larvae and adults. Zebrafish larvae at 3 days post-fertilization and adults were exposed to glyphosate (0.01, 0.065, and 0.5 mg/L) or Roundup® (0.01, 0.065, and 0.5 mg/L) for 96 h. Immediately after the exposure, we performed the analysis of locomotor activity, aversive behavior, and morphology for the larvae and exploratory behavior, aggression and inhibitory avoidance memory for adult zebrafish. In zebrafish larvae, there were significant differences in the locomotor activity and aversive behavior after glyphosate or Roundup® exposure when compared to the control group. Our findings demonstrated that exposure to glyphosate at the concentration of 0.5 mg/L, Roundup® at 0.065 or 0.5 mg/L reduced the distance traveled, the mean speed and the line crossings in adult zebrafish. A decreased ocular distance was observed for larvae exposed at 0.5 mg/L of glyphosate. We verified that at 0.5 mg/L of Roundup®-treated adult zebrafish demonstrated a significant impairment in memory. Both glyphosate and Roundup® reduced aggressive behavior. Our data suggest that there are small differences between the effects induced by glyphosate and Roundup®, altering morphological and behavioral parameters in zebrafish, suggesting common mechanisms of toxicity and cellular response.

Glyphosate was first synthesized in 1950 as a potential pharmaceutical compound. It was discovered to be an herbicide by Monsanto chemist John E. Franz in 1970. Unfortunately glyphosate is found in almost all non-organic food crops (think about it when you buy ‘non-organic food’ in the supermarket next time) and the chemical is now ubiquitous in our environment (it has even been detected in the umbilical cord blood of newborns) because it has been used in agriculture for a long time and has spread throughout the environmental systems. The analogy of a drop of ink in a glass of water (cf. osmosis) is appropriate to communicate the concept of chemical dispersion throughout the environment. Its interactions and synergies with other chemical compounds are currently only poorly understood as the majority of studies focus on isolated compounds. However, since the industrial revolution our environment has been bombarded with countless synthetic chemicals an only time will tell what the cumulative effects on biology and life are. Currently nobody knows how all these chemical compounds interact. In other words, humanity is currently conducting a large scale biochemical experiment without any control group (and without ethical permission or consensus by the participants).
Analysis of concentrations of Glyphosate in pregnant versus nonpregnant women (i.e., in maternal and fetal cord blood)

Cattani, D., de Liz Oliveira Cavalli, V. L., Heinz Rieg, C. E., Domingues, J. T., Dal-Cim, T., Tasca, C. I., … Zamoner, A.. (2014). Mechanisms underlying the neurotoxicity induced by glyphosate-based herbicide in immature rat hippocampus: Involvement of glutamate excitotoxicity. Toxicology

Plain numerical DOI: 10.1016/j.tox.2014.03.001
DOI URL
directSciHub download

Roy, N. M., Carneiro, B., & Ochs, J.. (2016). Glyphosate induces neurotoxicity in zebrafish. Environmental Toxicology and Pharmacology, 42, 45–54.

Plain numerical DOI: 10.1016/j.etap.2016.01.003
DOI URL
directSciHub download


For further peer-reviewed scientific studies on the numerous reported neurotoxic effects of Glyphosate in the brain see bibliography below

In the USA there are currently ≈580 lawsuits pending against Monsanto (now BAYER). The lead case in The USA is 3:16-md-02741-VC. The first trial in the federal court is set for Feb. 25, 2019 in the U.S. District Court in San Francisco. In the UK Glyphosate is unfortunately still completely unregulated and readily available in regular supermarkets where it is advertised as an effective weed killer for gardeners (inter alia). Moreover, it is applied to almost all non-organic food crops (fruits, vegetables, grains, etc.) we all consume on a daily basis. It is impossible to “wash off” Glyphosate because it penetrates deep into the organism after it is topically applied. Moreover, the human body and brain has great difficulty to detox from Glyphosate and it accumulates in the human body and brain over time. The exact longitudinal effects of Glyphosate are hitherto unknown and therefore pose a significant risk to the environment and human health.

URL: usrtk.org/pesticides/mdl-monsanto-glyphosate-cancer-case-key-documents-analysis/

Investigative documentary: The world according to Monsanto



The Monsanto papers – The secret tactics Monsanto used to protect Glyphosate

Lecture on glyphosate by Dr. Seneff

Dr. Stephanie Seneff is a Senior Research Scientist at the MIT Computer Science and Artificial Intelligence Laboratory. She received the B.S. degree in Biophysics in 1968, the M.S. and E.E. degrees in Electrical Engineering in 1980, and the Ph.D degree in Electrical Engineering and Computer Science in 1985, all from MIT. For over three decades, her research interests have always been at the intersection of biology and computation – developing a computational model for the human auditory system, understanding human language so as to develop algorithms and systems for human computer interactions, as well as applying natural language processing (NLP) techniques to gene predictions. She has published over 170 refereed articles on these subjects, and has been invited to give keynote speeches at several international conferences. She has also supervised numerous Master’s and PhD theses at MIT.

In recent years, Dr. Seneff has focused her research interests back towards biology. She is concentrating mainly on the relationship between nutrition and health. Since 2011, she has published over 30 papers, together with colleagues, in various peer-reviewed medical and heath-related journals on topics such as modern day diseases (e.g., Alzheimer, autism, cardiovascular diseases), analysis and search of databases of drug side effects using NLP techniques, and the impact of nutritional deficiencies and environmental toxins on human health.

It is noteworthy how Wikipedia editors try to discredit her valid concerns by using cheap ad hominem arguments which do not address the crux of the problem. It is very difficult to add objective information to her Wikipedia entry (this known as “Wikipedia edit wars“).
But see: en.wikipedia.org/wiki/Stephanie_Seneff
Cf. www.globalresearch.ca/monsanto-accused-of-hiring-army-of-trolls-to-silence-online-dissent-court-papers/5588396

The Guardian stated the following:

“The internal correspondence noted by Johnson could support a jury finding that Monsanto has long been aware of the risk that its glyphosate-based herbicides are carcinogenic … but has continuously sought to influence the scientific literature to prevent its internal concerns from reaching the public sphere and to bolster its defenses in products liability actions,” Karnow wrote. “Thus there are triable issues of material fact.”
Monsanto “championed falsified data and attacked legitimate studies” that revealed dangers of its herbicides, and led a “prolonged campaign of misinformation” to convince government agencies, farmers and consumers that Roundup was safe, according to Johnson’s lawsuit.

URL: www.theguardian.com/business/2018/may/22/monsanto-trial-cancer-weedkiller-roundup-dewayne-johnson

“Biotech giant Monsanto is being accused of hiring, through third parties, an army of Internet trolls to counter negative comments, while citing positive “ghost-written” pseudo-scientific reports which downplay the potential risks of their products.”

On a larger scale, Monsanto allegedly

“quietly funnels money to ‘think tanks’ such as the ‘Genetic Literacy Project’ and the ‘American Council on Science and Health”– organizations intended to shame scientists and highlight information helpful to Monsanto and other chemical producers,” according to the plaintiffs.”

URL: www.globalresearch.ca/monsanto-accused-of-hiring-army-of-trolls-to-silence-online-dissent-court-papers/5588396

From a meta-analytic perspective the scientific evidence against the utilisation of Glyphosate is very strong. In addition, synergistic toxicity needs to be taken in account. Such synergies are unfortunately rarely addressed in the scientific literature (and even less frequently in public/political debates). We know that 1 + 1 is not always 2. Specifically, in the domain of chemistry and neurochemistry. Currently, nobody really knows how Glyphosate interacts with the numerous other chemical we unfortunately find in our environments. Even less is known about the longitudinal effects of such synergies. What we do know is that Monsanto has de facto been found guilty for crimes against nature and humanity in the past.
We should be specifically concerned about the potential genotoxic & mutagenic effects (i.e., damage to the human genome is irreversible). That is, the problem does not only concern this generation but the evolution of the species homō sapiēns as a whole (the Latin binomial ironically translates into “the wise/rational man”). Cross-generational responsibility is an important factor of governmental decision-making and it should be weighted accordingly.

As stated above, we are all exposed to Glyphosate on a daily basis (it is sprayed on almost all non-organic crops and it is widely distributed in our environment). Children are specifically susceptible to the detrimental effects because their blood-brain barrier (which filters exogenous substances) is less developed and because their bodies/brains are much smaller than those of adults.
A comparative historical perspective is very informative in this context. Remember that it took decades for the government to respond to the early warnings about tobacco, asbestos, and X-Rays.

The tobacco time line:
•The health effects of tobacco were first debated in 1856 in the medical journal The Lancet
•Dr. Isaac Adler suggested lung cancer was related to smoking in 1912
•A British medical journal published a study in 1950 finding that smokers were 50 times more likely to get lung cancer
•It wasn’t until 1997 that tobacco companies agreed to fund healthcare costs from smoking

cognitive-liberty.online/tabacco-timeline/

The X-Ray time line:
•Thomas Edison noted injuries from X-Rays in 1896
•Edison’s assistant died from X-Ray exposure in 1904
•Fluoroscopes were used in shoe stores to see through shoes to aid proper fitting in 1930
•The deaths of over 200 radiologists from radioactive cancer were published in 1934
•Radiation levels of fluoroscopes were questioned in 1949
•In 1990 the risk of cancer from radiation was found to be five times greater than previously thought

The Asbestos time line:
•A British factory inspector warned of asbestos harm in 1898
•Rat studies raised questions about harmful effects of asbestos dust in 1911
•U.S. insurers refused to cover asbestos worker’s claims in 1918
•From 1935 to 1949 lung cancer was reported in asbestos workers
•Asbestos was finally banned in the U.S. in 1989

Summa summarum, there is robust and substantial scientific evidence that Glyphosate is potentially neurotoxic, genotoxic, & cancerogenic. As can be seen from the timelines above (viz., tabacco, X-Rays, aspestos) it took many decades and untold casualties before those carcinogens were ever properly addressed. Glyphosate is a much bigger toxin than tobacco, X-Rays or asbestos due to the sheer numbers of people who are exposed to this chemical. As pointed out before, there is strong evidence that it has potentially highly detrimental irreversible effects on human genes and their expression. Genetic effects are by definition irreversible and molecular biology is in no position to correct such influences post festum any time soon (despite CRISPR/Cas9 and other gene editing technologies). The human “gene-pool” should be seen as a public good which needs to be protected. Otherwise future generation will pay a very high price for our irresponsible and irrational short-sighted and profit oriented behaviour (which dominates the current climate of profit-oriented neoliberalism). Further, Glyphosate  posses a very stable chemical structure and it lingers in the environment (and the human body/brain) for a very long time. The numbers of people now being affected is enormous (not just in the UK but worlwide). There isn’t enough time for us to wait for our government or industry to come to the realization that a serious problem exists. We know that they will be reluctant to make such an admission (for various reasons which go beyond the scope of this email). Reasonable precautions must be taken now! The evidence is before us. Research studies tell us there is a problem. We cannot afford to wait until industry and government are forced to admit that Glyphosate is dangerous. We did that with tobacco, X-Rays and asbestos.


References

Cattani, D., Cesconetto, P. A., Tavares, M. K., Parisotto, E. B., De Oliveira, P. A., Rieg, C. E. H., … Zamoner, A.. (2017). Developmental exposure to glyphosate-based herbicide and depressive-like behavior in adult offspring: Implication of glutamate excitotoxicity and oxidative stress. Toxicology

Plain numerical DOI: 10.1016/j.tox.2017.06.001
DOI URL
directSciHub download

Cattani, D., de Liz Oliveira Cavalli, V. L., Heinz Rieg, C. E., Domingues, J. T., Dal-Cim, T., Tasca, C. I., … Zamoner, A.. (2014). Mechanisms underlying the neurotoxicity induced by glyphosate-based herbicide in immature rat hippocampus: Involvement of glutamate excitotoxicity. Toxicology

Plain numerical DOI: 10.1016/j.tox.2014.03.001
DOI URL
directSciHub download

Cattani, D., Lúcia, V., Oliveira, D. L., Elise, C., Rieg, H., Domingues, J. T., … Zamoner, A.. (2014). Mechanisms underlying the neurotoxicity induced by glyphosate-based herbicide in immature rat hippocampus: Involvement of glutamate excitotoxicity. Toxicology

Plain numerical DOI: 10.1016/j.tox.2014.03.001
DOI URL
directSciHub download

Coullery, R. P., Ferrari, M. E., & Rosso, S. B.. (2016). Neuronal development and axon growth are altered by glyphosate through a WNT non-canonical signaling pathway. NeuroToxicology

Plain numerical DOI: 10.1016/j.neuro.2015.12.004
DOI URL
directSciHub download

Gallegos, C. E., Baier, C. J., Bartos, M., Bras, C., Domínguez, S., Mónaco, N., … Minetti, A.. (2018). Perinatal Glyphosate-Based Herbicide Exposure in Rats Alters Brain Antioxidant Status, Glutamate and Acetylcholine Metabolism and Affects Recognition Memory. Neurotoxicity Research

Plain numerical DOI: 10.1007/s12640-018-9894-2
DOI URL
directSciHub download

Ji, H., Xu, L., Wang, Z., Fan, X., & Wu, L.. (2018). Differential microRNA expression in the prefrontal cortex of mouse offspring induced by glyphosate exposure during pregnancy and lactation. Experimental and Therapeutic Medicine

Plain numerical DOI: 10.3892/etm.2017.5669
DOI URL
directSciHub download

Lajmanovich, R. C., Junges, C. M., Attademo, A. M., Peltzer, P. M., Cabagna-Zenklusen, M. C., & Basso, A.. (2013). Individual and mixture toxicity of commercial formulations containing glyphosate, metsulfuron-methyl, bispyribac-sodium, and picloram on rhinella arenarum tadpoles. Water, Air, and Soil Pollution

Plain numerical DOI: 10.1007/s11270-012-1404-1
DOI URL
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Landrigan, P. J., & Belpoggi, F.. (2018). The need for independent research on the health effects of glyphosate-based herbicides. Environmental Health: A Global Access Science Source

Plain numerical DOI: 10.1186/s12940-018-0392-z
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Martínez, M. A., Ares, I., Rodríguez, J. L., Martínez, M., Martínez-Larrañaga, M. R., & Anadón, A.. (2018). Neurotransmitter changes in rat brain regions following glyphosate exposure. Environmental Research

Plain numerical DOI: 10.1016/j.envres.2017.10.051
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Menéndez-Helman, R. J., Ferreyroa, G. V., Dos Santos Afonso, M., & Salibián, A.. (2012). Glyphosate as an acetylcholinesterase inhibitor in cnesterodon decemmaculatus. Bulletin of Environmental Contamination and Toxicology

Plain numerical DOI: 10.1007/s00128-011-0423-8
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Negga, R., Rudd, D. A., Davis, N. S., Justice, A. N., Hatfield, H. E., Valente, A. L., … Fitsanakis, V. A.. (2011). Exposure to Mn/Zn ethylene-bis-dithiocarbamate and glyphosate pesticides leads to neurodegeneration in Caenorhabditis elegans. NeuroToxicology

Plain numerical DOI: 10.1016/j.neuro.2011.02.002
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Negga, R., Stuart, J. A., Machen, M. L., Salva, J., Lizek, A. J., Richardson, S. J., … Fitsanakis, V. A.. (2012). Exposure to glyphosate-and/or Mn/Zn-ethylene-bis-dithiocarbamate-containing pesticides leads to degeneration of c-aminobutyric acid and dopamine neurons in caenorhabditis elegans. Neurotoxicity Research

Plain numerical DOI: 10.1007/s12640-011-9274-7
DOI URL
directSciHub download

Roy, N. M., Carneiro, B., & Ochs, J.. (2016). Glyphosate induces neurotoxicity in zebrafish. Environmental Toxicology and Pharmacology

Plain numerical DOI: 10.1016/j.etap.2016.01.003
DOI URL
directSciHub download

Yu, N., Tong, Y., Zhang, D., Zhao, S., Fan, X., Wu, L., & Ji, H.. (2018). Circular RNA expression profiles in hippocampus from mice with perinatal glyphosate exposure. Biochemical and Biophysical Research Communications

Plain numerical DOI: 10.1016/j.bbrc.2018.04.200
DOI URL
directSciHub download

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