Ward, E. M., “Glyphosate Use and Cancer Incidence in the Agricultural Health Study: An Epidemiologic Perspective,” Journal of the National Cancer Institute, 2018, 110(5), 446-447. DOI: 10.1093/jnci/djx247.
ABSTRACT:
Not Available. FULL TEXT
Valle, A. L., Mello, F. C. C., Alves-Balvedi, R. P., Rodrigues, L. P., & Goulart, L. R., “Glyphosate detection: methods, needs and challenges,” Environmental Chemistry Letters, 2018. DOI: 10.1007/s10311-018-0789-5.
ABSTRACT:
Glyphosate is considered toxicologically harmful and presents potential association with human carcinogenesis and other chronic diseases, including mental and reproductive behaviors. The challenges to analyse and demonstrate its toxicity are likely due to its metal-chelating properties, the interference of organic compounds in the environment, and similarity with its by-products. Whereas there is a link with serious health and environmental problems, there is an absence of public health policies, which is probably due to the difficulties in detecting glyphosate in the environment, further complicated by the undetectable hazard in occupational safety and health. The historical lenient use of glyphosate in transgenic-resistant crops, corroborated by the fact that it is not easily detected, creates the “Glyphosate paradox”, by which it is the most widely used herbicide and one of the most hardly determined. In this review, we revisited all available technologies for detection and quantification of glyphosate, including their drawbacks and advantages, and we further discuss the needs and challenges. Briefly, most of the technologies require high-end equipments and resources in low throughput, and none of them are adequate for real-time field tests, which may explain the lack of studies on occupational health associated with the chemical hazard. The real-time detection is an urgent and highly demanded need to improve public policies. FULL TEXT
Townsend, M., Peck, C., Meng, W., Heaton, M., Robison, R., & O’Neill, K., “Evaluation of various glyphosate concentrations on DNA damage in human Raji cells and its impact on cytotoxicity,” Regulatory Toxicology and Pharmacology, 2017, 85, 79-85. DOI: 10.1016/j.yrtph.2017.02.002.
ABSTRACT:
Glyphosate is a highly used active compound in agriculturally based pesticides. The literature regarding the toxicity of glyphosate to human cells has been highly inconsistent. We studied the resulting DNA damage and cytotoxicity of various glyphosate concentrations on human cells to evaluate DNA damaging potential. Utilizing human Raji cells, DNA damage was quantified using the comet assay, while cytotoxicity was further analyzed using MTT viability assays. Several glyphosate concentrations were assessed, ranging from 15 mM to 0.1 muM. We found that glyphosate treatment is lethal to Raji cells at concentrations above 10 mM, yet has no cytotoxic effects at concentrations at or below 100 muM. Treatment concentrations of 1 mM and 5 mM induce statistically significant DNA damage to Raji cells following 30-60 min of treatment, however, cells show a slow recovery from initial damage and cell viability is unaffected after 2 h. At these same concentrations, cells treated with additional compound did not recover and maintained high levels of DNA damage. While the cytotoxicity of glyphosate appears to be minimal for physiologically relevant concentrations, the compound has a definitive cytotoxic nature in human cells at high concentrations. Our data also suggests a mammalian metabolic pathway for the degradation of glyphosate may be present. FULL TEXT
Tarazona, J. V., Court-Marques, D., Tiramani, M., Reich, H., Pfeil, R., Istace, F., & Crivellente, F., “Glyphosate toxicity and carcinogenicity: a review of the scientific basis of the European Union assessment and its differences with IARC,” Archives of Toxicology, 2017, 91(8), 2723-2743. DOI: 10.1007/s00204-017-1962-5.
ABSTRACT:
Glyphosate is the most widely used herbicide worldwide. It is a broad spectrum herbicide and its agricultural uses increased considerably after the development of glyphosate-resistant genetically modified (GM) varieties. Since glyphosate was introduced in 1974, all regulatory assessments have established that glyphosate has low hazard potential to mammals, however, the International Agency for Research on Cancer (IARC) concluded in March 2015 that it is probably carcinogenic. The IARC conclusion was not confirmed by the EU assessment or the recent joint WHO/FAO evaluation, both using additional evidence. Glyphosate is not the first topic of disagreement between IARC and regulatory evaluations, but has received greater attention. This review presents the scientific basis of the glyphosate health assessment conducted within the European Union (EU) renewal process, and explains the differences in the carcinogenicity assessment with IARC. Use of different data sets, particularly on long-term toxicity/carcinogenicity in rodents, could partially explain the divergent views; but methodological differences in the evaluation of the available evidence have been identified. The EU assessment did not identify a carcinogenicity hazard, revised the toxicological profile proposing new toxicological reference values, and conducted a risk assessment for some representatives uses. Two complementary exposure assessments, human-biomonitoring and food-residues-monitoring, suggests that actual exposure levels are below these reference values and do not represent a public concern. FULL TEXT
Szepanowski, F., Szepanowski, L. P., Mausberg, A. K., Albrecht, P., Kleinschnitz, C., Kieseier, B. C., & Stettner, M., “Differential impact of pure glyphosate and glyphosate-based herbicide in a model of peripheral nervous system myelination,” Acta Neuropatholologica, 2018, 136(6), 979-982. DOI: 10.1007/s00401-018-1938-4.
ABSTRACT:
Not available. FULL TEXT
Santovito, A., Ruberto, S., Gendusa, C., & Cervella, P., “In vitro evaluation of genomic damage induced by glyphosate on human lymphocytes,” Environmental Science and Pollution Research International, 2018, 25(34), 34693-34700. DOI: 10.1007/s11356-018-3417-9.
ABSTRACT:
Glyphosate is an important broad-spectrum herbicide used in agriculture and residential areas for weed and vegetation control, respectively. In our study, we analyzed the in vitro clastogenic and/or aneugenic effects of glyphosate by chromosomal aberrations and micronuclei assays. Human lymphocytes were exposed to five glyphosate concentrations: 0.500, 0.100, 0.050, 0.025, and 0.0125 mug/mL, where 0.500 mug/mL represents the established acceptable daily intake value, and the other concentrations were tested in order to establish the genotoxicity threshold for this compound. We observed that chromosomal aberration (CA) and micronuclei (MNi) frequencies significantly increased at all tested concentrations, with exception of 0.0125 mug/mL. Vice versa, no effect has been observed on the frequencies of nuclear buds and nucleoplasmic bridges, with the only exception of 0.500 mug/mL of glyphosate that was found to increase in a significant manner the frequency of nucleoplasmic bridges. Finally, the cytokinesis-block proliferation index and the mitotic index were not significantly reduced, indicating that glyphosate does not produce effects on the proliferation/mitotic index at the tested concentrations. FULL TEXT
Rice, J.R., Dunlap, P., Ramaiahgari, S., Ferguson, S., Smith-Roe, S.L., & DeVito, M., “Poster: Effects of Glyphosate and its Formulations on Markers of Oxidative Stress and Cell Viability in HepaRG and HaCaT Cell Lines, 2018, Presented at the Society of Toxicology Conference.
ABSTRACT:
Glyphosate (GLY) is the active ingredient found in herbicide formulations worldwide. GLY is toxic to plants by disrupting the shikimate amino acid synthesis pathway. The present day intensive use of GLY began with the introduction of GLY-resistant crops in the late 1990s. Although GLY has a low toxicity profile for humans and mammals, conflicting reports exist as to whether it poses a cancer risk for humans. The USEPA and European regulatory agencies have described GLY as unlikely to pose a carcinogenic hazard to humans. However, the International Agency for Research on Cancer (IARC) has classified GLY as “probably carcinogenic to humans”.
IARC proposed that oxidative stress may be a mechanism by which GLY could potentially cause cancer. To address this hypothesis, we are testing GLY in human cell lines using several assays that detect reactive oxygen species (ROS) or their effects. Studies were designed to compare the point of departure for the effects of GLY on cell viability (CellTiter-Glo assay) to the point of departure for effects in oxidative damage assays. We also directly compared the effects of GLY versus GLY salts, as well as GLY and adjunct active ingredients versus formulations. We used a high content, 384-well plate approach to generate extensive dose-response curves for multiple comparisons.
Assays (CellTiter-Glo, ROS-Glo, and JC10) were performed after 1 or 24 h of exposure to test articles. GLY and GLY isopropylamine decreased cell viability and altered mitochondrial membrane potential (MMP) at ≥ 10 mM, but did not affect ROS production. The formulations were more potent than GLY alone. Cell viability and MMP were significantly altered at 1 h by the formulations. Based on GLY concentrations, these mixtures were over 1000x more potent than GLY alone. In contrast to the robust induction of ROS by positive controls at both time points, formulations had no effect on ROS at 1 h and showed a marginal increase in ROS at 24 h. These data suggest that GLY does not induce oxidative stress. In addition, the formulations marginally increased oxidative stress only after significant loss of cell viability. The results were very similar for both HepaRG and HaCaT cell lines, suggesting that xenobiotic metabolism has little impact on cell viability and oxidative stress induced by these chemicals. FULL TEXT
Nardi, Jessica, Moras, Patricia Bonamigo, Koeppe, Carina, Dallegrave, Eliane, Leal, Mirna Bainy, & Rossato-Grando, Luciana Grazziotin, “Prepubertal subchronic exposure to soy milk and glyphosate leads to endocrine disruption,” Food and Chemical Toxicology, 2017, 100, 247-252. DOI: 10.1016/j.fct.2016.12.030.
ABSTRACT:
Lactose intolerance is characterized by low or inexistent levels of lactase, and the main treatment consists of dietary changes, especially replacing dairy milk by soy milk. Soy contains phytoestrogens, substances with known estrogenic activity, besides, glyphosate-based herbicides are extensively used in soy crops, being frequently a residue in soy beans, bringing to a concern regarding the consumption of soy-based products, especially for children in breastfeeding period with lactose intolerance. This study evaluated the pubertal toxicity of a soy milk rich feeding (supplemented or not with glyphosate, doses of 50 and 100 mg/kg) during prepubertal period in male rats. Endocrine disruption was observed through decrease in testosterone levels, decrease in Sertoli cell number and increase in the percentage of degenerated Sertoli and Leydig cells in animals receiving soy milk supplemented with glyphosate (both doses) and in animals treated only with soy milk. Animals treated with soy milk with glyphosate (both doses) showed decrease spermatids number and increase of epididymal tail mass compared to control, and decrease in the diameter of seminiferous tubules compared to soy milk control group. Animals receiving soy milk supplemented with 100 mg/kg glyphosate showed decrease in round spermatids and increase in abnormal sperm morphology, compared to control. FULL TEXT
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, 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