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Motta et al., 2018

Motta, Erick V S, Raymann, Kasie, & Moran, Nancy A, “Glyphosate perturbs the gut microbiota of honey bees,” Proceedings of the National Academy of Sciences of the United States of America, 2018, 115(41), 10305-10310. DOI: 10.1073/pnas.1803880115.

ABSTRACT:

Glyphosate, the primary herbicide used globally for weed control, targets the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) enzyme in the shikimate pathway found in plants and some microorganisms. Thus, glyphosate may affect bacterial symbionts of animals living near agricultural sites, including pollinators such as bees. The honey bee gut microbiota is dominated by eight bacterial species that promote weight gain and reduce pathogen susceptibility. The gene encoding EPSPS is present in almost all sequenced genomes of bee gut bacteria, indicating that they are potentially susceptible to glyphosate. We demonstrated that the relative and absolute abundances of dominant gut microbiota species are decreased in bees exposed to glyphosate at concentrations documented in the environment. Glyphosate exposure of young workers increased mortality of bees subsequently exposed to the opportunistic pathogen Serratia marcescens. Members of the bee gut microbiota varied in susceptibility to glyphosate, largely corresponding to whether they possessed an EPSPS of class I (sensitive to glyphosate) or class II (insensitive to glyphosate). This basis for differences in sensitivity was confirmed using in vitro experiments in which the EPSPS gene from bee gut bacteria was cloned into Escherichia coli. All strains of the core bee gut species, Snodgrassella alvi, encode a sensitive class I EPSPS, and reduction in S. alvi levels was a consistent experimental result. However, some S. alvi strains appear to possess an alternative mechanism of glyphosate resistance. Thus, exposure of bees to glyphosate can perturb their beneficial gut microbiota, potentially affecting bee health and their effectiveness as pollinators. FULL TEXT

Milic et al., 2018

Milic, Mirta, Zunec, Suzana, Micek, Vedran, Kasuba, Vilena, Mikolic, Anja, Lovakovic, Blanka Tariba, Semren, Tanja Zivkovic, Pavicic, Ivan, Cermak, Ana Marija Marjanovic, Pizent, Alica, Vrdoljak, Ana Lucic, Valencia-Quintana, Rafael, Sanchez-Alarcon, Juana, & Zeljezic, Davor, “Oxidative stress, cholinesterase activity, and DNA damage in the liver, whole blood, and plasma of Wistar rats following a 28-day exposure to glyphosate,” Archives of Industrial Hygiene and Toxicology, 2018, 69(2), 154-168. DOI: 10.2478/aiht-2018-69-3114.

ABSTRACT:

In this 28 day-study, we evaluated the effects of herbicide glyphosate administered by gavage to Wistar rats at daily doses equivalent to 0.1 of the acceptable operator exposure level (AOEL), 0.5 of the consumer acceptable daily intake (ADI), 1.75 (corresponding to the chronic population-adjusted dose, cPAD), and 10 mg kg-1 body weight (bw) (corresponding to 100 times the AOEL). At the end of each treatment, the body and liver weights were measured and compared with their baseline values. DNA damage in leukocytes and liver tissue was estimated with the alkaline comet assay. Oxidative stress was evaluated using a battery of endpoints to establish lipid peroxidation via thiobarbituric reactive substances (TBARS) level, level of reactive oxygen species (ROS), glutathione (GSH) level, and the activity of glutathione peroxidase (GSH-Px). Total cholinesterase activity and the activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were also measured. The exposed animals gained less weight than control. Treatment resulted in significantly higher primary DNA damage in the liver cells and leukocytes. Glyphosate exposure significantly lowered TBARS in the liver of the AOEL, ADI, and cPAD groups, and in plasma in the AOEL and cPAD group. AChE was inhibited with all treatments, but the AOEL and ADI groups significantly differed from control. Total ChE and plasma/liver ROS/GSH levels did not significantly differ from control, except for the 35 % decrease in ChE in the AOEL and ADI groups and a significant drop in liver GSH in the cPAD and 100xAOEL groups. AOEL and ADI blood GSH-Px activity dropped significantly, but in the liver it significantly increased in the ADI, cPAD, and 100xAOEL groups vs. control. All these findings show that even exposure to low glyphosate levels can have serious adverse effects and points to a need to change the approach to risk assessment of low-level chronic/sub-chronic glyphosate exposure, where oxidative stress is not necessarily related to the genetic damage and AChE inhibition. FULL TEXT

Milesi et al., 2018

Milesi, Maria M, Lorenz, Virginia, Pacini, Guillermina, Repetti, Maria R, Demonte, Luisina D, Varayoud, Jorgelina, & Luque, Enrique H, “Perinatal exposure to a glyphosate-based herbicide impairs female reproductive outcomes and induces second-generation adverse effects in Wistar rats,” Archives of Toxicology, 2018, 92(8), 2629-2643. DOI: 10.1007/s00204-018-2236-6.

ABSTRACT:

Glyphosate-based herbicides (GBHs) are the most globally used herbicides raising the risk of environmental exposition. Here, we investigated whether perinatal exposure to low doses of a GBH alters the female reproductive performance, and/or induced second-generation effects related to congenital anomalies or growth alterations. Pregnant rats (F0) received a GBH through food, in a dose of 2 mg (GBH-LD: GBH-low dose group) or 200 mg (GBH-HD: GBH-high dose group) of glyphosate/kg bw/day from gestational day (GD) 9 until weaning. Body weight gain and vaginal canal-opening of F1 females were recorded. Sexually mature F1 females were mated to evaluate their reproductive performance by assessing the pregnancy rate, and on GD19, the number of corpora lutea, the implantation sites (IS) and resorption sites. To analyze second-generation effects on F2 offspring, we analyzed the fetal morphology on GD19, and assessed the fetal length and weight, and the placental weight. GBH exposure neither altered the body weight gain of F1 females, nor vaginal opening onset. Although all GBH-exposed F1 rats became pregnant, a lower number of IS was detected. F2 offspring from both GBH groups showed delayed growth, evidenced by lower fetal weight and length, associated with a higher incidence of small for gestational age fetuses. In addition, higher placental weight and placental index were found in F2 offspring from GBH-HD dams. Surprisingly, structural congenital anomalies (conjoined fetuses and abnormally developed limbs) were detected in the F2 offspring from GBH-HD group. In conclusion, perinatal exposure to low doses of a GBH impaired female reproductive performance and induced fetal growth retardation and structural congenital anomalies in F2 offspring. FULL TEXT

Mesnage et al., 2017

Mesnage, Robin, & Antoniou, Michael N, “Ignoring Adjuvant Toxicity Falsifies the Safety Profile of Commercial Pesticides,” Frontiers in Public Health, 2017, 5, 361. DOI: 10.3389/fpubh.2017.00361.

ABSTRACT:

Commercial formulations of pesticides are invariably not single ingredients. Instead they are cocktails of chemicals, composed of a designated pesticidal “active principle” and “other ingredients,” with the latter collectively also known as “adjuvants.” These include surfactants, antifoaming agents, dyes, etc. Some adjuvants are added to influence the absorption and stability of the active principle and thus promote its pesticidal action. Currently, the health risk assessment of pesticides in the European Union and in the United States focuses almost exclusively on the stated active principle. Nonetheless, adjuvants can also be toxic in their own right with numerous negative health effects having been reported in humans and on the environment. Despite the known toxicity of adjuvants, they are regulated differently from active principles, with their toxic effects being generally ignored. Adjuvants are not subject to an acceptable daily intake, and they are not included in the health risk assessment of dietary exposures to pesticide residues. Here, we illustrate this gap in risk assessment by reference to glyphosate, the most used pesticide active ingredient. We also investigate the case of neonicotinoid insecticides, which are strongly suspected to be involved in bee and bumblebee colony collapse disorder. Authors of studies sometimes use the name of the active principle (for example glyphosate) when they are testing a commercial formulation containing multiple (active principle plus adjuvant) ingredients. This results in confusion in the scientific literature and within regulatory circles and leads to a misrepresentation of the safety profile of commercial pesticides. Urgent action is needed to lift the veil on the presence of adjuvants in food and human bodily fluids, as well as in the environment (such as in air, water, and soil) and to characterize their toxicological properties. This must be accompanied by regulatory precautionary measures to protect the environment and general human population from some toxic adjuvants that are currently missing from risk assessments. FULL TEXT

Martinez et al., 2018

Martinez, Daisy A, Loening, Ulrich E, & Graham, Margaret C, “Impacts of glyphosate-based herbicides on disease resistance and health of crops: a review,” Environmental Sciences Europe, 2018, 30(1), 2. DOI: 10.1186/s12302-018-0131-7.

ABSTRACT:

Based on experimental data from laboratory and field, numerous authors have raised concern that exposure to glyphosate-based herbicides (GBHs) may pre-dispose crops to damage by microbial pathogens. In this review, we distinguish and evaluate two principal pathways by which GBHs may affect the susceptibility of crops to disease: pathway 1-via disruptions to rhizosphere microbial ecology, and pathway 2-via restriction of nutrients to crops. We conclude that GBHs have the potential to undermine crop health in a number of ways, including: (i) impairment of the innate physiological defences of glyphosate-sensitive (GS) cultivars by interruption of the shikimic acid pathway; (ii) impairment of physiological disease defences has also been shown to occur in some glyphosate-resistant (GR) cultivars, despite their engineered resistance to glyphosate’s primary mode of action; (iii) interference with rhizosphere microbial ecology (in particular, GBHs have the potential to enhance the population and/or virulence of some phytopathogenic microbial species in the crop rhizosphere); and finally, (iv) the as yet incompletely elucidated reduction in the uptake and utilisation of nutrient metals by crops. Future progress will best be achieved when growers, regulators and industry collaborate to develop products, practices and policies that minimise the use of herbicides as far as possible and maximise their effectiveness when used, while facilitating optimised food production and security. FULL TEXT

Kniss, 2016

Kniss, A. R., “Long-term trends in the intensity and relative toxicity of herbicide use,” Nature Communications, 2017, 8, 14865. DOI: 10.1038/ncomms14865.

ABSTRACT:

Herbicide use is among the most criticized aspects of modern farming, especially as it relates to genetically engineered (GE) crops. Many previous analyses have used flawed metrics to evaluate herbicide intensity and toxicity trends. Here, I show that herbicide use intensity increased over the last 25 years in maize, cotton, rice and wheat. Although GE crops have been previously implicated in increasing herbicide use, herbicide increases were more rapid in non-GE crops. Even as herbicide use increased, chronic toxicity associated with herbicide use decreased in two out of six crops, while acute toxicity decreased in four out of six crops. In the final year for which data were available (2014 or 2015), glyphosate accounted for 26% of maize, 43% of soybean and 45% of cotton herbicide applications. However, due to relatively low chronic toxicity, glyphosate contributed only 0.1, 0.3 and 3.5% of the chronic toxicity hazard in those crops, respectively. FULL TEXT

Kwiatkowska et al., 2017

Kwiatkowska, Marta, Reszka, Edyta, Wozniak, Katarzyna, Jablonska, Ewa, Michalowicz, Jaromir, & Bukowska, Bozena, “DNA damage and methylation induced by glyphosate in human peripheral blood mononuclear cells (in vitro study),” Food and Chemical Toxicology, 2017, 105, 93-98. DOI: 10.1016/j.fct.2017.03.051.

ABSTRACT:

Glyphosate is a very important herbicide that is widely used in the agriculture, and thus the exposure of humans to this substance and its metabolites has been noted. The purpose of this study was to assess DNA damage (determination of single and double strand-breaks by the comet assay) as well as to evaluate DNA methylation (global DNA methylation and methylation of p16 (CDKN2A) and p53 (TP53) promoter regions) in human peripheral blood mononuclear cells (PBMCs) exposed to glyphosate. PBMCs were incubated with the compound studied at concentrations ranging from 0.1 to 10 mM for 24 h. The study has shown that glyphosate induced DNA lesions, which were effectively repaired. However, PBMCs were unable to repair completely DNA damage induced by glyphosate. We also observed a decrease in global DNA methylation level at 0.25 mM of glyphosate. Glyphosate at 0.25 mM and 0.5 mM increased p53 promoter methylation, while it did not induce statistically significant changes in methylation of p16 promoter. To sum up, we have shown for the first time that glyphosate (at high concentrations from 0.5 to 10 mM) may induce DNA damage in leucocytes such as PBMCs and cause DNA methylation in human cells. FULL TEXT

Koo et al., 2018

Koo, Dal-Hoe, Molin, William T, Saski, Christopher A, Jiang, Jiming, Putta, Karthik, Jugulam, Mithila, Friebe, Bernd, & Gill, Bikram S, “Extrachromosomal circular DNA-based amplification and transmission of herbicide resistance in crop weed Amaranthus palmeri,” Proceedings of the National Academy of Sciences of the United States of America, 2018, 115(13), 3332-3337. DOI: 10.1073/pnas.1719354115.

ABSTRACT:

Gene amplification has been observed in many bacteria and eukaryotes as a response to various selective pressures, such as antibiotics, cytotoxic drugs, pesticides, herbicides, and other stressful environmental conditions. An increase in gene copy number is often found as extrachromosomal elements that usually contain autonomously replicating extrachromosomal circular DNA molecules (eccDNAs). Amaranthus palmeri, a crop weed, can develop herbicide resistance to glyphosate [N-(phosphonomethyl) glycine] by amplification of the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene, the molecular target of glyphosate. However, biological questions regarding the source of the amplified EPSPS, the nature of the amplified DNA structures, and mechanisms responsible for maintaining this gene amplification in cells and their inheritance remain unknown. Here, we report that amplified EPSPS copies in glyphosate-resistant (GR) A. palmeri are present in the form of eccDNAs with various conformations. The eccDNAs are transmitted during cell division in mitosis and meiosis to the soma and germ cells and the progeny by an as yet unknown mechanism of tethering to mitotic and meiotic chromosomes. We propose that eccDNAs are one of the components of McClintock’s postulated innate systems [McClintock B (1978) Stadler Genetics Symposium] that can rapidly produce soma variation, amplify EPSPS genes in the sporophyte that are transmitted to germ cells, and modulate rapid glyphosate resistance through genome plasticity and adaptive evolution. FULL TEXT

Kongtip et al., 2017

Kongtip, Pornpimol, Nankongnab, Noppanun, Phupancharoensuk, Ratanavadee, Palarach, Chonlada, Sujirarat, Dusit, Sangprasert, Supha, Sermsuk, Malasod, Sawattrakool, Namthip, & Woskie, Susan Renee, “Glyphosate and Paraquat in Maternal and Fetal Serums in Thai Women,” Journal of Agromedicine, 2017, 22(3), 282-289. DOI: 10.1080/1059924x.2017.1319315.

ABSTRACT:

OBJECTIVES: This longitudinal study measured the glyphosate and paraquat concentrations found in maternal and umbilical cord serum in 82 pregnant women who gave birth in three provinces of Thailand.

METHODS: Through questionnaires and biological samples collected at childbirth, factors such as personal characteristics, family members occupation, agricultural activities, and herbicide use in agricultural work were evaluated as predictors of glyphosate and paraquat levels in the pregnant women. Statistical analysis used univariate and binary multiple logistic regression, where the outcome was the probability of exposure to paraquat or glyphosate above the limit of detection associated with occupation and household factors.

RESULTS: The glyphosate concentrations in the pregnant women’s serum at childbirth (median: 17.5, range: 0.2-189.1 ng/mL) were significantly higher (P < .007) than those in the umbilical cord serum (median: 0.2, range: 0.2-94.9 ng/mL). However, the paraquat concentrations in the serum of the pregnant women at childbirth (83% </=limit of detection [LOD], with maximum of 58.3 ng/mL) were similar to those in the umbilical cord serum (80% <LOD, with maximum of 47.6 ng/mL). Women with glyphosate levels >LOD in serum at childbirth were 11.9 times more likely to report work as an agriculturist (P < .001), 3.7 times more likely to live near agricultural areas (P = .006), and 5.9 times more likely to have a family member who worked in agriculture (P < .001). The only factors affecting paraquat exposures in pregnant women at childbirth were reporting the agricultural activity of digging in farm soil and working in the agricultural fields in the third trimester of pregnancy.

CONCLUSIONS: These results show that pregnant women who work in agriculture or live in families that work in agriculture have higher exposures to the herbicides glyphosate and paraquat. The potential for long-term health impacts of these prenatal exposures to children should be evaluated, and greater regulation of the sale and use of herbicides should be considered in Thailand. FULL TEXT

Henner and Backhaus, 2019

Hollert, Henner, & Backhaus, Thomas, “Some food for thought: a short comment on Charles Benbrook´s paper ‘How did the US EPA and IARC reach diametrically opposed conclusions on the genotoxicity of glyphosate-based herbicides?’ and its implications,” Environmental Sciences Europe, 2019, 31(1). DOI: 10.1186/s12302-019-0187-z.

ABSTRACT:

Not available.  FULL TEXT

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