The influence of glyphosate on the microbiota and production of botulinum neurotoxin during ruminal fermentation
Glyphosate triggered a shift in ruminal fluid microbiota populations production to favor botulinum neurotoxin, commonly considered one of the most poisonous proteins to ever be classified. This means that use of glyphosate could lead to ruminal disorders that affect the entire animal, which could be devastating for dairy and beef farming. Though the most toxic effects were only shown with glyphosate concentrations much higher than what is generally considered acceptable, there is still cause for concern. Especially because young animals may be susceptible to the effects of glyphosate at much lower concentrations than the adult animals that were used in this study.
Ackermann, W., Coenen, M., Schrödl, W., Shehata, A. A., & Krüger, M. (2015). The influence of glyphosate on the microbiota and production of botulinum neurotoxin during ruminal fermentation. Current microbiology, 70(3), 374-382. doi: 10.1007/s00284-014-0732-3
Glyphosate biomonitoring for farmers and their families: results from the Farm Family Exposure Study
Glyphosate, the active ingredient in Roundup, is one of the most commonly used herbicides in agriculture, particularly after the development of Gly-resistant crops. During this Family Farm Exposure Study, 48 farmers, their spouses, and their 79 children were tested for glyphosate residue in urine after exposure to glyphosate. Levels were compared on the day before exposure, the day of exposure, and three days after exposure to glyphosate. Among farmers, only 60% had detectible levels of glyphosate residue in urine on the day of use. The highest individual level was 14ppb or 0.0006mg/kg body weight, which is lower than the 2mg/kg/day EPA limit. Only 4% of spouses and 12% of children showed detectible levels of residue on the day of glyphosate application, all of whom either helped with application or were present when chemicals were mixed. Farmers that wore gloves during application were less likely to have urine residues.
Note: this study was funded and conducted by Roundup manufacturer, Monsanto Company.
Acquavella, J. F., Alexander, B. H., Mandel, J. S., Gustin, C., Baker, B., Chapman, P., & Bleeke, M. (2004). Glyphosate biomonitoring for farmers and their families: results from the Farm Family Exposure Study. Environmental Health Perspectives, 112(3), 321. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1241861/
Time-and dose-dependent effects of roundup on human embryonic and placental cells
This study expands on a previous study by the same authors (Differential Effects of Glyphosate and Roundup on Human Placental Cells and Aromatase, cited and summarized in this review) that showed the effect of Roundup on human JEG3 placental cells. This study expanded the time trials and did more extensive work on comparing the effects of Roundup versus glyphosate alone. This study also examined the effect on human embryonic cells. Again, glyphosate was shown to have a lesser enzyme inhibitory effect than Roundup formulations. Within 24 hours, 0.1% Roundup reduced estrogen production in embryonic cells by 19%. After 72 hours, the dose was toxic to cells.
Benachour, N., Sipahutar, H., Moslemi, S., Gasnier, C., Travert, C., & Séralini, G. E. (2007). Time-and dose-dependent effects of roundup on human embryonic and placental cells. Archives of Environmental Contamination and Toxicology, 53(1), 126-133. doi: 10.1007/s00244-006-0154-8
Urinary pesticide concentrations among children, mothers and fathers living in farm and non-farm households in Iowa
Pesticides have been classified by the National Resources Defense Council (NRDC) as one of the top five environmental threats to children’s health. In this study of Iowa farm and non-farm families (47 fathers, 48 mothers, 117 children) levels of atrazine, metolachlor, glyphosate, and chlorpyrifos metabolites in urine and household dust residue were tested. Farm families had higher levels of all pesticides, but they did not show higher levels of glyphosate. Glyphosate levels were the highest among non-farm children, probably due to the commercial use of glyphosate as an herbicide. There was a positive correlation between amounts of toxin in dust residue, and amount of metabolites in urine, but the results were inconclusive.
Curwin, B. D., Hein, M. J., Sanderson, W. T., Striley, C., Heederik, D., Kromhout, H., & Alavanja, M. C. (2007). Urinary pesticide concentrations among children, mothers and fathers living in farm and non-farm households in Iowa. Annals of Occupational Hygiene, 51(1), 53-65. doi: 10.1093/annhyg/mel062
The teratogenic potential of the herbicide glyphosate-Roundup® in Wistar rats
This study assessed the teratogenicity (potential to cause birth defects) of Roundup on Wistar rats. Maternal rats were exposed to 0, 500, 750, or 1000mg/Kg Roundup diluted in water from day 6 to 15 of their pregnancies. On day 21, offspring were delivered by cesarean section. Of the mothers exposed to 1000mg/Kg, 50% died during exposure period. No other deaths were observed during pregnancy. No significant weight differences were seen in either mothers or offspring. The most significant differences were in skeletal formation of offspring with 15.4%, 33.1%, 42.0, 57.3% of each respective concentration group showing malformations. Most common malformation was delayed ossification (hardening) of skull, sternebra, and limbs. Though the levels of Roundup used in this study are much higher than most humans would ever be exposed to, it does raise concern about the safety of herbicide use during pregnancy.
Dallegrave, E., Mantese, F. D., Coelho, R. S., Pereira, J. D., Dalsenter, P. R., & Langeloh, A. (2003). The teratogenic potential of the herbicide glyphosate-Roundup® in Wistar rats. Toxicology Letters, 142(1), 45-52. https://www.ncbi.nlm.nih.gov/pubmed/12765238
Exposure to a glyphosate-based herbicide during pregnancy and lactation induces neurobehavioral alterations in rat offspring
While glyphosate has been determined nontoxic for humans, there has been little research done on whether sub-lethal amounts of glyphosate (0.10 to 0.70mg/L) have any neurological effects. When pregnant rats were exposed to the pesticide Gilflogex (38g Gly/100cm3, 35.6%w/v Gly) in 0.65 and 1.30g/L concentrations locomotor activity, emotionality, and anxiety levels were affected in offspring. There were no statistically significant effects on maternal weight gain, litter size, or body weight of pups. Decreased locomotor activity in offspring could be an indication of decreased dopamine levels, which is correlated with locomotor disorders such as Parkinson’s. The changes in anxiety and emotionality levels could also indicate possible development of adult onset neurological disorders. Further studies must address whether glyphosate was the sole causal factor, or whether other neurotransmitter systems were somehow altered.
Gallegos, C. E., Bartos, M., Bras, C., Gumilar, F., Antonelli, M. C., & Minetti, A. (2016). Exposure to a glyphosate-based herbicide during pregnancy and lactation induces neurobehavioral alterations in rat offspring. Neurotoxicology, 53, 20-28. doi: 10.1016/j.neuro.2015.11.015
Glyphosate-based herbicides are toxic and endocrine disruptors in human cell lines
Roundup was demonstrated to be DNA damaging, as well as carcinogenic, mutagenic, and reprotoxic for human hepatic cells at concentrations well below the EPA authorized amount. Toxic effects were shown at as low as 5ppm Roundup, and endocrine disruption started at 0.5ppm which is 800 times lower than the federally acceptable level of 400ppm. Interestingly, glyphosate alone had almost no effect on human cell lines, but when combined with Roundup adjuvants, DNA damage and endocrine disruptions were observed. This could mean that glyphosate itself is still safe for human consumption but the formulation of Roundup needs to be re-evaluated.
Gasnier, C., Dumont, C., Benachour, N., Clair, E., Chagnon, M. C., & Séralini, G. E. (2009). Glyphosate-based herbicides are toxic and endocrine disruptors in human cell lines. Toxicology, 262(3), 184-191. doi:10.1016/j.tox.2009.06.006
Toxic effects of the herbicide Roundup in the guppy Poecilia vivipara acclimated to fresh water
Roundup is a broadly used agricultural herbicide. While it is considered nontoxic, there is increasing concern about its ecological effects particularly on aquatic ecosystems. Guppies exposed to Roundup in concentration of 130μgL-1 (lower than maximum acceptable amount of 700μgL-1 but still high enough to induce some effect) had no biochemical side effects on brain or muscle function. Decreased sperm quality was observed due largely to compromised membrane integrity. While there was no fish mortality observed, significantly decreased sperm quality and motility implies that reproduction would decrease or even stop depending on extent of exposure. In this study, fish were exposed to a median level of acceptable glyphosate contamination which means that sperm quality (and potentially other biochemical effects) could be more greatly affected.
Harayashiki, C. A. Y., Varela, A. S. Jr., Machado, A. A., Cabrera, Lda. C., Primel, E. G., Bianchini, A., & Corcini, C. D. (2013). Toxic effects of the herbicide Roundup in the guppy Poecilia vivipara acclimated to fresh water. Aquatic toxicology, 142, 176-184. doi: 10.1016/j.aquatox.2013.08.006
Toxic effects of the herbicide Roundup® Regular on Pacific Northwestern amphibians
Amphibians have often been shown to have higher levels of sensitivity to exposure to environmental toxins. After exposure of 6 amphibian species larvae to Roundup at environmentally acceptable conditions, all showed shorter time to death. Time to death decreased from 16 days to as low as 1 day with increased concentration of Roundup. While some species were more susceptible to the effects than others, all showed decreased life spans after larval exposure.
King, J. J., & Wagner, R. S. (2010). Toxic effects of the herbicide Roundup® Regular on Pacific Northwestern amphibians. Northwestern Naturalist, 91(3), 318-324. http://www.jstor.org/stable/40983228
Detection of glyphosate residues in animals and humans
Though glyphosate is one of the most broadly used herbicides, its effect on humans is almost unknown. While its short-term effects are considered safe, little work has been done on long term side effects in humans and other mammals. After testing for glyphosate residue in the urine of dairy cows, hares, rabbits, and humans, all who consumed normal diets throughout the study, accumulated and excreted glyphosate residues. The levels of glyphosate in humans who ate solely organic food diets was lower, and levels of residue were much higher in chronically ill individuals than in generally healthy ones. Additionally, residues were shown in liver, kidney, and intestine tissue.
Krüger, M., Schledorn, P., Schrödl, W., Hoppe, H. W., Lutz, W., & Shehata, A. A. (2014). Detection of glyphosate residues in animals and humans. Journal of Environmental & Analytical Toxicology, 4(2), 1. doi: 10.4172/2161-0525.1000210
Gestational and lactational exposure to atrazine via the drinking water causes specific behavioral deficits and selectively alters monoaminergic systems in C57BL/6 mouse dams, juvenile and adult offspring
Atrazine is one of the most commonly used pesticides in US agriculture, and is thus one of the most frequently detected in drinking water. In this study, after pregnant mice were exposed to atrazine in various levels through drinking water during gestation and lactation periods, neurological effects were observed in both mothers and offspring. Even the lowest concentration of atrazine exposure (3mg/L drinking water) showed decreased object recognition ability in both mothers and offspring. Interestingly, the effects were more profound in female offspring than they were in males. Atrazine was also shown to create hyperactivity in offspring that did not persist into adulthood.
Lin, Z., Dodd, C. A., Xiao, S., Krishna, S., Ye, X., & Filipov, N. M. (2014). Gestational and lactational exposure to atrazine via the drinking water causes specific behavioral deficits and selectively alters monoaminergic systems in C57BL/6 mouse dams, juvenile and adult offspring. Toxicological Sciences, 141(1), 90-102. doi: 10.1093/toxsci/kfu107
Low toxic herbicide Roundup induces mild oxidative stress in goldfish tissues
Though Roundup is environmentally safe in most conditions and concentrations, there is rising concern about its effect on aquatic environments when it has the ability to persist for a long time. While Roundup in water is still generally safe for human consumption, it may affect biochemical systems of aquatic organisms. This study examined antioxidant properties in goldfish in brain, liver, and kidney pathways. While levels of lipid peroxides (LOOH), common markers of oxidative cellular damage, were largely unaffected.
Lushchak, V., Kubrak, O. I., Storey, J. M., Storey, K. B., & Lushchak, V. I. (2009). Low toxic herbicide Roundup induces mild oxidative stress in goldfish tissues. Chemosphere, 76(7), 932-937. doi: 10.1016/j.chemosphere.2009.04.045
Effects of Roundup Transorb on fish: hematology, antioxidant defenses and acetylcholinesterase activity
Roundup Transorb (RDT) has been marketed as a faster, more effective way to get to the roots of invading plants. Unlike other Roundup formulations, it is marketed as being effective in 60 minutes or less due to its unique surfactant. It is also classified (Class III) as being harmful to the environment. Teleost fish, whose biochemical pathways are very similar to those of mammals, showed reduced brain and muscle acetylcholinesterase activity (key to neurotransmission). The fish also showed an increase in hematocrit due to increased release of white blood cells due immune system activation. Additionally, presence of oxidants in RDT interferes with antioxidation properties in the fish, leading many of them to develop buildup in hepatic tissue. While there was no mortality observed, and all other biochemical effects were observed at sub-lethal levels, there is still cause for concern.
Modesto, K. A., & Martinez, C. B. (2010). Effects of Roundup Transorb on fish: hematology, antioxidant defenses and acetylcholinesterase activity. Chemosphere, 81(6), 781-787. doi: 10.1016/j.chemosphere.2010.07.005
Major pesticides are more toxic to human cells than their declared active principles
While the active principles (AP) in pesticides are always tested for toxicity before being marketed, the formulations and adjuvants are rarely subjected to such analysis. In tests of 9 APs on human embryonic, placental, and hepatic cell the formulation was more toxic than the AP alone in all cases. In 8 cases, the formulations were more than a hundred times more toxic than the AP. Additionally, all cells were exposed to formulation in amounts well below agriculturally acceptable dilutions. Pesticides, insecticides, and herbicides were all tested for AP and formula toxicity. Fungicides proved to be the most toxic to human cells, followed by herbicides and insecticides.
Mesnage, R., Defarge, N., Spiroux de Vendômois, J., & Séralini, G. E. (2014). Major pesticides are more toxic to human cells than their declared active principles. BioMed research international, 2014. http://dx.doi.org/10.1155/2014/179691
The lethal impact of Roundup on aquatic and terrestrial amphibians
Amphibians are often exposed to Roundup runoff in soil or water in their natural environments. While Roundup has been shown to have little effect on adult amphibians, this study shows that there is a significant effect on larval amphibians when they are directly sprayed with Roundup mixtures. Tadpoles were places in various aquatic environments (sand, soil, no soil) and exposed to 25.2% Roundup formulations by direct spray method. After three weeks, 96-100% of tadpoles in water had died. Experiments were repeated with frogs on land, and within one day after exposure to Roundup direct spray, 68-86% died. Soil, sand, and dry environments did not have any effect on Roundup toxicity.
Relyea, R. A. (2005). The lethal impact of Roundup on aquatic and terrestrial amphibians. Ecological applications, 15(4), 1118-1124. doi: 10.1890/04-1291
Differential effects of glyphosate and roundup on human placental cells and aromatase
Though glyphosate has been shown to be relatively safe by multiple studies, the formulation Roundup has significantly more toxic effects than Gly alone. Roundup was shown in this study to reduce the viability of JEG3 human placental cells at concentrations 10 times lower than glyphosate alone. Roundup reduced aromatase (enzyme also known as estrogen synthase, essential in production of estrogen) activity at concentrations 100 times lower than glyphosate alone, proving its endocrine disruption abilities. It also interfered with mRNA levels, causing decrease in enzyme levels and activity. All of these effects were shown within 18 hours of exposure and at levels lower than are agriculturally acceptable (effects began at 0.1% roundup in water, agriculture ranges 1-2%).
Richard, S., Moslemi, S., Sipahutar, H., Benachour, N., & Seralini, G. E. (2005). Differential effects of glyphosate and roundup on human placental cells and aromatase. Environmental health perspectives, 716-720. https://www.ncbi.nlm.nih.gov/pubmed/15929894
Glyphosate impairs male offspring reproductive development by disrupting gonadotropin expression
Exposure to glyphosate during gestation can effect sexual behavior of male offspring, potentially due to the proven endocrine disrupting effects of glyphosate. In this study, the sexual behavior of 60-day old male rats who were exposed to glyphosate during their gestation was analyzed. Partner preferences, serum testosterone concentrations, sperm production, estradiol, FSH, LH, weight of testicles, and weight of seminal vesicles were all analyzed. Males who were exposed to glyphosate in utero spent significantly more time with female mice when they were exposed on PND60 (post natal day). There were no significant differences in time to ejaculation. Treated mice did show higher levels of testosterone, LH, and FSH. Weight of testicles and seminal vesicles was not different for treated versus untreated mice.
Romano, M. A., Romano, R. M., Santos, L. D., Wisniewski, P., Campos, D. A., de Souza, P. B., … & de Oliveira, C. A. (2012). Glyphosate impairs male offspring reproductive development by disrupting gonadotropin expression. Archives of toxicology, 86(4), 663-673. doi: 10.1007/s00204-011-0788-9
Roundup inhibits steroidogenesis by disrupting steroidogenic acute regulatory (StAR) protein expression
While Roundup has been shown to be reproductively disruptive to many species, the specific mechanism hasn’t been specifically shown. Mouse MA-10 Leydig testicular cells were used to show steroid biosynthesis and the effects of Roundup on specific pathways. Roundup reduced steroidogenesis (production of steroid hormones) by 65% while having little to no effect on other protein synthesis pathways within 24 hours. Steroidogenesis was decreased due to regulatory protein (StAR) transcription repression, meaning that Roundup more than likely affected the process at the DNA level. Though Roundup had an effect on steroid production, this study did not show significant effects of the active ingredient glyphosate alone.
Walsh, L. P., McCormick, C., Martin, C., & Stocco, D. M. (2000). Roundup inhibits steroidogenesis by disrupting steroidogenic acute regulatory (StAR) protein expression. Environmental Health Perspectives, 108(8), 769. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1638308/