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Bibliography Index

Cessna et al., 1994

Cessna, A. J., Darwent, A. L., Kirkland, K. J., Townley-Smith, L., Harker, K. N., & Lefkovitch, L. P.; “Residues of glyphosate and its metabolite AMPA in wheat seed and foliage following preharvest applications;” Canadian Journal of Plant Science, 1994, 74(3), 653-661; DOI: 10.4141/cjps94-117.

ABSTRACT:

In a 2-yr study at four locations in western Canada, residues of glyphosate and its major metabolite aminomethyl-phosphonic acid (AMPA) were measured in the seed and foliage of wheat (Triticum aestivum L.) following preharvest applications at rates of 0.45, 0.9 or 1.7 kg acid equivalent ha−1. Herbicide treatments were applied in early August to mid-September at seed moisture contents ranging from 52 to 12%. Glyphosate and AMPA residues in the seed increased as the rate of application increased, and decreased as the seed moisture content at the time of application decreased. However, when the maximum application rate of 1.7 kg ha−1 was sprayed at seed moisture contents of 40% or less, glyphosate residues in the seed were < 5 mg kg−1, the Maximum Residue Level recently established by Health Canada. Glyphosate and AMPA residues in the straw also increased with increasing application rate, but there was no consistent pattern in residues of either chemical with seed moisture content at the time of application. Physiological maturity of the crop, rainfall washoff, and application rate appeared to play important roles in determining the magnitude of glyphosate and AMPA residues in the seed and straw of wheat. Key words: Glyphosate, AMPA, residues, wheat, seed, preharvest application. FULL TEXT

Cessna et al., 2002

Cessna, A. J., Darwent, A. L., Townley-Smith, L., Harker, K. N., & Kirkland, K.; “Residues of glyphosate and its metabolite AMPA in field pea, barley and flax seed following preharvest applications;” Canadian Journal of Plant Science, 2002, 82(2), 485-489; DOI: 10.4141/p01-094.

ABSTRACT:

Maximum residue levels have been established by Health Canada for seed of several crops treated with preharvest applications of glyphosate, a common practice on the Canadian prairies. Residues of glyphosate and its major metabolite aminomethylphosphonic acid (AMPA) were determined at crop maturity in flax seed at one site in western Canada and in the seed and straw of field pea and barley at another site following preharvest applications of the herbicide. Glyphosate was applied at rates of 0.45, 0.9 and 1.7 kg ha-1 to each crop in early August to mid-September at four stages of crop development. In all crops, mean residues of glyphosate and AMPA increased with increasing application rate of glyphosate and decreased when the herbicide was applied at later stages of crop development. FULL TEXT

Aris and Leblanc, 2011

Aris, Aziz, & Leblanc, Samuel; “Maternal and fetal exposure to pesticides associated to genetically modified foods in Eastern Townships of Quebec, Canada.;” Reproductive Toxicology, 2011, 31, 528-533; DOI: 10.1016/j.reprotox.2011.02.004.

ABSTRACT:

Pesticides associated to genetically modified foods (PAGMF), are engineered to tolerate herbicides such as glyphosate (GLYP) and gluphosinate (GLUF) or insecticides such as the bacterial toxin bacillus thuringiensis (Bt). The aim of this study was to evaluate the correlation between maternal and fetal exposure, and to determine exposure levels of GLYP and its metabolite aminomethyl phosphoric acid (AMPA), GLUF and its metabolite 3-methylphosphinicopropionic acid (3-MPPA) and Cry1Ab protein (a Bt toxin) in Eastern Townships of Quebec, Canada. Blood of thirty pregnant women (PW) and thirty-nine nonpregnant women (NPW) were studied. Serum GLYP and GLUF were detected in NPW and not detected in PW. Serum 3-MPPA and CryAb1 toxin were detected in PW, their fetuses and NPW. This is the first study to reveal the presence of circulating PAGMF in women with and without pregnancy, paving the way for a new field in reproductive toxicology including nutrition and utero-placental toxicities. FULL TEXT

Nielsen et al., 2018

Nielsen, L. N., Roager, H. M., Casas, M. E., Frandsen, H. L., Gosewinkel, U., Bester, K., Licht, T. R., Hendriksen, N. B., & Bahl, M. I.; “Glyphosate has limited short-term effects on commensal bacterial community composition in the gut environment due to sufficient aromatic amino acid levels;” Environmental Pollution, 2018, 233, 364-376; DOI: 10.1016/j.envpol.2017.10.016.

ABSTRACT:

Recently, concerns have been raised that residues of glyphosate-based herbicides may interfere with the homeostasis of the intestinal bacterial community and thereby affect the health of humans or animals. The biochemical pathway for aromatic amino acid synthesis (Shikimate pathway), which is specifically inhibited by glyphosate, is shared by plants and numerous bacterial species. Several in vitro studies have shown that various groups of intestinal bacteria may be differently affected by glyphosate. Here, we present results from an animal exposure trial combining deep 16S rRNA gene sequencing of the bacterial community with liquid chromatography mass spectrometry (LC-MS) based metabolic profiling of aromatic amino acids and their downstream metabolites. We found that glyphosate as well as the commercial formulation Glyfonova((R))450 PLUS administered at up to fifty times the established European Acceptable Daily Intake (ADI = 0.5 mg/kg body weight) had very limited effects on bacterial community composition in Sprague Dawley rats during a two-week exposure trial. The effect of glyphosate on prototrophic bacterial growth was highly dependent on the availability of aromatic amino acids, suggesting that the observed limited effect on bacterial composition was due to the presence of sufficient amounts of aromatic amino acids in the intestinal environment. A strong correlation was observed between intestinal concentrations of glyphosate and intestinal pH, which may partly be explained by an observed reduction in acetic acid produced by the gut bacteria. We conclude that sufficient intestinal levels of aromatic amino acids provided by the diet alleviates the need for bacterial synthesis of aromatic amino acids and thus prevents an antimicrobial effect of glyphosate in vivo. It is however possible that the situation is different in cases of human malnutrition or in production animals. FULL TEXT

Larsen et al., 2012

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;” Environmental Toxicology and Pharmacology, 2012, 34(3), 811-818; DOI: 10.1016/j.etap.2012.09.005.

ABSTRACT:

Glyphosate (GLP), the active ingredient of many weed killing formulations, is a broad spectrum herbicide compound. 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. FULL TEXT

Chlopecka et al., 2017

Chlopecka, M., Mendel, M., Dziekan, N., & Karlik, W.; “The effect of glyphosate-based herbicide Roundup and its co-formulant, POEA, on the motoric activity of rat intestine – In vitro study;” Environmental Toxicology and Pharmacology, 2017, 49, 156-162; DOI: 10.1016/j.etap.2016.12.010.

ABSTRACT:

The study was aimed at evaluating the effect of Roundup, polyoxyethylene tallow amine (POEA) and mixture of glyphosate and POEA in different levels on the motoric activity of jejunum strips. The incubation in the Roundup solutions caused a significant, mostly miorelaxant, reversible reaction of smooth muscle; only in the highest tested dose which is equivalent to the agricultural concentration (1% corresponding to 1.7g glyphosate/L) there was an irreversible disturbance of the spontaneous contractility and reactivity. The incubation in POEA solutions in the range of low doses (0.256; 1.28; 6.4mg/L) resulted in a biphasic muscle reaction (relaxation and contraction); whereas in the range of high doses, i.e. 32; 160 and 800mg/L (agricultural spray concentrations) induced only a miorelaxant, irreversible response. The results indicate very high toxicity of POEA which exceeds the toxicity of the commercial formulations. Besides, it is postulated that glyphosate and POEA may display antagonistic interaction towards the motoric activity of gastrointestinal tract. FULL TEXT

Ford et al., 2017

Ford, B., Bateman, L. A., Gutierrez-Palominos, L., Park, R., & Nomura, D. K.; “Mapping Proteome-wide Targets of Glyphosate in Mice;” Cell Chemical Biology, 2017, 24(2), 133-140; DOI: 10.1016/j.chembiol.2016.12.013.

ABSTRACT:

Glyphosate, the active ingredient in the herbicide Roundup, is one of the most widely used pesticides in agriculture and home garden use. Whether glyphosate causes any mammalian toxicity remains highly controversial. While many studies have associated glyphosate with numerous adverse health effects, the mechanisms underlying glyphosate toxicity in mammals remain poorly understood. Here, we used activity-based protein profiling to map glyphosate targets in mice. We show that glyphosate at high doses can be metabolized in vivo to reactive metabolites such as glyoxylate and react with cysteines across many proteins in mouse liver. We show that glyoxylate inhibits liver fatty acid oxidation enzymes and glyphosate treatment in mice increases the levels of triglycerides and cholesteryl esters, likely resulting from diversion of fatty acids away from oxidation and toward other lipid pathways. Our study highlights the utility of using chemoproteomics to identify novel toxicological mechanisms of environmental chemicals such as glyphosate. FULL TEXT

Ren et al., 2019

Ren, X., Dai, P., Perveen, A., Tang, Q., Zhao, L., Jia, X., Li, Y., & Li, C.; “Effects of chronic glyphosate exposure to pregnant mice on hepatic lipid metabolism in offspring;” Environmental Pollution, 2019, 254(Pt A), 112906; DOI: 10.1016/j.envpol.2019.07.074.

ABSTRACT:

Glyphosate is the active ingredient in Roundup, one of the most popular herbicides in the world, and its toxicity has caused increasing concerns. The present study aims to investigate the toxic effects of prenatal exposure to pure glyphosate or Roundup on lipid metabolism in offspring. During gestational days (GDs), ICR mice (from Institute of Cancer Research) were given distilled water, 0.5% glyphosate solution (w/v, 0.5 g/100 ml) or 0.5%-glyphosate Roundup solution orally. The livers and serum samples of the offspring were collected on gestational day 19 (GD19), postnatal day 7 (PND7) and PND21. The results showed a significant decrease in the body weight and obvious hepatic steatosis with excessive lipid droplet formation in offspring. Moreover, the concentrations of lipids such as triglycerides (TGs), total cholesterol (T-CHO), and low-density lipoprotein cholesterols (LDL-C) increased to a significant extent in both the serum and livers. Furthermore, there were significant differences in the expression levels of the genes SREBP1C, SREBP2, Fasn, Hmgcr, Hmgcs and PPARa, which are related to lipid biosynthesis or catabolism in the liver. These results demonstrate that chronic prenatal exposure to glyphosate can result in lipid metabolism disruption in the offspring of mice, as glyphosate exerts a negative influence on the expression of lipogenesis genes. FULL TEXT

Stur et al., 2019

Stur, E., Aristizabal-Pachon, A. F., Peronni, K. C., Agostini, L. P., Waigel, S., Chariker, J., Miller, D. M., Thomas, S. D., Rezzoug, F., Detogni, R. S., Reis, R. S. D., Silva Junior, W. A., & Louro, I. D.; “Glyphosate-based herbicides at low doses affect canonical pathways in estrogen positive and negative breast cancer cell lines;” Plos One, 2019, 14(7), e0219610; DOI: 10.1371/journal.pone.0219610.

ABSTRACT:

Glyphosate is a broad-spectrum herbicide that is used worldwide. It represents a potential harm to surface water, and when commercially mixed with surfactants, its uptake is greatly magnified. The most well-known glyphosate-based product is Roundup. This herbicide is potentially an endocrine disruptor and many studies have shown the cytotoxicity potential of glyphosate-based herbicides. In breast cancer (BC) cell lines it has been demonstrated that glyphosate can induce cellular proliferation via estrogen receptors. Therefore, we aimed to identify gene expression changes in ER+ and ER- BC cell lines treated with Roundup and AMPA, to address changes in canonical pathways that would be related or not with the ER pathway, which we believe could interfere with cell proliferation. Using the Human Transcriptome Arrays 2.0, we identified gene expression changes in MCF-7 and MDA-MB-468 exposed to low concentrations and short exposure time to Roundup Original and AMPA. The results showed that at low concentration (0.05% Roundup) and short exposure (48h), both cell lines suffered deregulation of 11 canonical pathways, the most important being cell cycle and DNA damage repair pathways. Enrichment analysis showed similar results, except that MDA-MB-468 altered mainly metabolic processes. In contrast, 48h 10mM AMPA showed fewer differentially expressed genes, but also mainly related with metabolic processes. Our findings suggest that Roundup affects survival due to cell cycle deregulation and metabolism changes that may alter mitochondrial oxygen consumption, increase ROS levels, induce hypoxia, damage DNA repair, cause mutation accumulation and ultimately cell death. To our knowledge, this is the first study to analyze the effects of Roundup and AMPA on gene expression in triple negative BC cells. Therefore, we conclude that both compounds can cause cellular damage at low doses in a relatively short period of time in these two models, mainly affecting cell cycle and DNA repair. FULL TEXT

Wang et al., 2019

Wang, L., Deng, Q., Hu, H., Liu, M., Gong, Z., Zhang, S., Xu-Monette, Z. Y., Lu, Z., Young, K. H., Ma, X., & Li, Y.; “Glyphosate induces benign monoclonal gammopathy and promotes multiple myeloma progression in mice;” Journal of Hematology & Oncology, 2019, 12(1), 70; DOI: 10.1186/s13045-019-0767-9.

ABSTRACT:

BACKGROUND: Glyphosate is the most widely used herbicide in the USA and worldwide. There has been considerable debate about its carcinogenicity. Epidemiological studies suggest that multiple myeloma (MM) and non-Hodgkin lymphoma (NHL) have a positive and statistically significant association with glyphosate exposure. As a B cell genome mutator, activation-induced cytidine deaminase (AID) is a key pathogenic player in both MM and B cell NHL.

METHODS: Vk*MYC is a mouse line with sporadic MYC activation in germinal center B cells and considered as the best available MM animal model. We treated Vk*MYC mice and wild-type mice with drinking water containing 1000 mg/L of glyphosate and examined animals after 72 weeks.

RESULTS: Vk*MYC mice under glyphosate exposure developed progressive hematological abnormalities and plasma cell neoplasms such as splenomegaly, anemia, and high serum IgG. Moreover, glyphosate caused multiple organ dysfunction, including lytic bone lesions and renal damage in Vk*MYC mice. Glyphosate-treated wild-type mice developed benign monoclonal gammopathy with increased serum IgG, anemia, and plasma cell presence in the spleen and bone marrow. Finally, glyphosate upregulated AID in the spleen and bone marrow of both wild-type and Vk*MYC mice.

CONCLUSIONS: These data support glyphosate as an environmental risk factor for MM and potentially NHL and implicate a mechanism underlying the B cell-specificity of glyphosate-induced carcinogenesis observed epidemiologically. FULL TEXT

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