Bibliography Tag: full text available

Bibliography Index

Zhang et al., 2019a

Zhang, Luoping, Rana, Iemaan, Shaffer, Rachel M., Taioli, Emanuela, & Sheppard, Lianne, “Exposure to Glyphosate-Based Herbicides and Risk for Non-Hodgkin Lymphoma: A Meta-Analysis and Supporting Evidence,” Mutation Research/Reviews in Mutation Research, In Press, 2019. DOI: 10.1016/j.mrrev.2019.02.001.

ABSTRACT:

Glyphosate is the most widely used broad-spectrum systemic herbicide in the world. Recent evaluations of the carcinogenic potential of glyphosate-based herbicides (GBHs) by various regional, national, and international agencies have engendered controversy. We investigated whether there was an association between high cumulative exposures to GBHs and increased risk of non-Hodgkin lymphoma (NHL) in humans. We conducted a new meta-analysis that included the most recent update of the Agricultural Health Study (AHS) cohort published in 2018 along with five case-control studies. Using the highest exposure groups when available in each study, we report the overall meta-relative risk (meta-RR) of NHL in GBH-exposed individuals was increased by 41% (meta-RR = 1.41, 95% CI, confidence interval: 1.13–1.75). For comparison, we also performed a secondary meta-analysis using high-exposure groups with the earlier AHS (2005), and we determined a meta-RR for NHL of 1.45 (95% CI: 1.11–1.91), which was higher than the meta-RRs reported previously. Multiple sensitivity tests conducted to assess the validity of our findings did not reveal meaningful differences from our primary estimated meta-RR. To contextualize our findings of an increased NHL risk in individuals with high GBH exposure, we reviewed available animal and mechanistic studies, which provided supporting evidence for the carcinogenic potential of GBH. We documented further support from studies of malignant lymphoma incidence in mice treated with pure glyphosate, as well as potential links between GBH exposure and immunosuppression, endocrine disruption, and genetic alterations that are commonly associated with NHL. Overall, in accordance with evidence from experimental animal and mechanistic studies, our current meta-analysis of human epidemiological studies suggests a compelling link between exposures to GBHs and increased risk for NHL. FULL TEXT

Wozniak et al., 2018

Wozniak, E., Sicinska, P., Michalowicz, J., Wozniak, K., Reszka, E., Huras, B., Zakrzewski, J., & Bukowska, B., “The mechanism of DNA damage induced by Roundup 360 PLUS, glyphosate and AMPA in human peripheral blood mononuclear cells – genotoxic risk assessement,” Food and Chemical Toxicology, 2018, 120, 510-522. DOI: 10.1016/j.fct.2018.07.035.

ABSTRACT:

Glyphosate is the most heavily applied among pesticides in the world, and thus human exposure to this substance continues to increase. WHO changed classification of glyphosate to probably cancerogenic to humans, thus there is urgent need to assess in detail genotoxic mechanism of its action. We have assessed the effect of glyphosate, its formulation (Roundup 360 PLUS) and its main metabolite (aminomethylphosphonic acid, AMPA) in the concentration range from 1 to 1000muM on DNA damage in human peripheral blood mononuclear cells (PBMCs). The cells were incubated for 24h. The compounds studied and formulation induced DNA single and double strand-breaks and caused purines and pyrimidines oxidation. None of compounds examined was capable of creating adducts with DNA, while those substances increased ROS (including (*)OH) level in PBMCs. Roundup 360 PLUS caused damage to DNA even at 5muM, while glyphosate and particularly AMPA induced DNA lesions from the concentration of 250muM and 500muM, respectively. DNA damage induced by glyphosate and its derivatives increased in order: AMPA, glyphosate, Roundup 360 PLUS. We may conclude that observed changes were not associated with direct interaction of xenobiotics studied with DNA, but the most probably they occurred through ROS-mediated effects. FULL TEXT

Ward, 2018

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 et al., 2018

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 et al., 2017

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 et al., 2017

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 et al., 2018

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 et al., 2018

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 et al., 2018

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 et al., 2017

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

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