De Almeida et al., 2018
De Almeida, L. K. S., Pletschke, B. I., & Frost, C. L., “Moderate levels of glyphosate and its formulations vary in their cytotoxicity and genotoxicity in a whole blood model and in human cell lines with different estrogen receptor status,” 3 Biotech, 2018, 8(10), 438. DOI: 10.1007/s13205-018-1464-z.
ABSTRACT:
In vitro studies were conducted to determine the short-term cytotoxic and genotoxic effects of pure glyphosate and two glyphosate formulations (Roundup® and Wipeout®) at concentrations relevant to human exposure using whole blood (cytotoxicity) and various cancer cell lines (cytotoxicity and genotoxicity). Pure glyphosate (pure glyph) and Roundup® (Ro) showed similar non-monotonic toxicological profiles at low dose exposure (from 10 microg/ml), whereas Wipeout® (Wo) demonstrated a monotonic reduction in cell viability from a threshold concentration of 50 microg/ml, when tested in whole blood. We evaluated whether using various cancer cells (the estrogen-E2-responsive HEC1A, MCF7 and the estrogen-insensitive MDA-MB-231) exposed to moderate doses (75-500 microg/ml) would indicate varied toxicity and results indicated significant effects in the HEC1A cancer cells. A non-monotonic reduction in cell viability was observed in HEC1A exposed to pure glyph (75-500 microg/ml) and proliferative effects were observed after exposure to Wo (75, 125 and 250 microg/ml). Genotoxicity assessment (test concentration 500 microg/ml) demonstrated DNA damage in the HEC1A and MDA-MB-231 cells. Adjuvants and/or glyphosate impurities were potential contributing factors of toxicity based on the differential toxicities displayed by Ro and Wo in human whole blood and the HEC1A cells. This study contributes to the existing knowledge about in vitro exposure to moderate concentrations of glyphosate or glyphosate formulations at cytotoxic and genotoxic levels. In addition, a suggestion on the relevance of the estrogen receptor status of the cell lines used is provided, leading to the need to further investigate a potential endocrine disruptive role. FULL TEXT
Davoren and Schiestl, 2018
Davoren, Michael J, & Schiestl, Robert H., “Glyphosate-based herbicides and cancer risk: a post-IARC decision review of potential mechanisms, policy and avenues of research,” Carcinogenesis, 2018, 39:10, 1207-1215. DOI:10.1093/carcin/bgy105.
ABSTRACT:
Since its initial sales in the 1970s, the herbicide glyphosate attained widespread use in modern agriculture, becoming the most commercially successful and widely used herbicide of all time as of 2016. Despite a primary mechanism that targets a pathway absent from animal cells and regulatory studies showing safety margins orders of magnitude better than many other, more directly toxic herbicides, the safety status of glyphosate has recently been brought into question by a slow accumulation of studies suggesting more subtle health risks, especially when considered in combination with the surfactants it is usually applied with. Current, official views of respected international regulatory and health bodies remain divided on glyphosate’s status as a human carcinogen, but the 2015 International Agency for Research on Cancer decision to reclassify the compound as Category 2A (probably carcinogenic to humans) marked a sea change in the scientific community’s consensus view. The goal of this review is to consider the state of science regarding glyphosate’s potential as a human carcinogen and genotoxin, with particular focus on studies suggesting mechanisms that would go largely undetected in traditional toxicology studies, such as microbiome disruption and endocrine mimicry at very low concentrations. FULL TEXT
Cook, 2019
Cook, Kara, “Glyphosate in Beer and Wine,” 2019, CALPIRG Education Fund Report.
SUMMARY:
To explore how much Roundup we’re drinking, U.S. PIRG tested beer and wine for glyphosate/Roundup. As we’ve confirmed in this study, Roundup is found in beer and wine. This aligns with past studies on the topic, which found that glyphosate is found in almost all adult beverages. For example, in 2016, beer testing in Germany also revealed residues of glyphosate in every single sample tested, even in independent beers. After that study was released, German brewers managed to severely limit the amount of glyphosate used in crops for brewing, and saw marked improvement in a 2017 follow-up study. A study from 2018 in Latvia came to similar conclusions as the original German study, finding glyphosate in all products tested. FULL TEXT
Connolly et al., 2019
Connolly, Alison, Coggins, Marie A, Galea, Karen S, Jones, Kate, Kenny, Laura, & McGowan, Padraic. “Evaluating Glyphosate Exposure Routes and Their Contribution to Total Body Burden: A Study Among Amenity Horticulturalists,” Annals of Work Exposures and Health, 2019, DOI: 10.1093/annweh/wxy104. .
ABSTRACT:
OBJECTIVE: To evaluate determinants of dermal and inadvertent ingestion exposure and assess their contribution to total body burden among amenity horticultural users using glyphosate-based pesticide products.
METHODS: A dermal and inadvertent ingestion exposure assessment was completed alongside a biomonitoring study among amenity horticultural workers. Linear mixed effect regression models were elaborated to evaluate determinants of exposure and their contribution to total body burden.
RESULTS: A total of 343 wipe and glove samples were collected from 20 workers across 29 work tasks. Geometric mean (GM) glyphosate concentrations of 0.01, 0.04 and 0.05 microg cm-2 were obtained on wipes from the workers’ perioral region and left and right hands, respectively. For disposable and reusable gloves, respectively, GM glyphosate concentrations of 0.43 and 7.99 microg cm-2 were detected. The combined hand and perioral region glyphosate concentrations explained 40% of the variance in the urinary (microg l-1) biomonitoring data.
CONCLUSION: To the author’s knowledge, this is the first study to have investigated both dermal and inadvertent exposure to glyphosate and their contribution to total body burden. Data show the dermal exposure is the prominent route of exposure in comparison to inadvertent ingestion but inadvertent ingestion may contribute to overall body burden. The study also identified potential exposure to non-pesticide users in the workplace and para-occupational exposures. FULL TEXT
Clausing et al., 2018
Clausing, P., Robinson, C., & Burtscher-Schaden, H., “Pesticides and public health: an analysis of the regulatory approach to assessing the carcinogenicity of glyphosate in the European Union,” Journal of Epidemiology and Community Health, 2018, 72(8), 668-672, DOI:10.1136/jech-2017-209776.
ABSTRACT:
The present paper scrutinises the European authorities’ assessment of the carcinogenic hazard posed by glyphosate based on Regulation (EC) 1272/2008. We use the authorities’ own criteria as a benchmark to analyse their weight of evidence (WoE) approach. Therefore, our analysis goes beyond the comparison of the assessments made by the European Food Safety Authority and the International Agency for Research on Cancer published by others. We show that not classifying glyphosate as a carcinogen by the European authorities, including the European Chemicals Agency, appears to be not consistent with, and in some instances, a direct violation of the applicable guidance and guideline documents. In particular, we criticise an arbitrary attenuation by the authorities of the power of statistical analyses; their disregard of existing dose-response relationships; their unjustified claim that the doses used in the mouse carcinogenicity studies were too high and their contention that the carcinogenic effects were not reproducible by focusing on quantitative and neglecting qualitative reproducibility. Further aspects incorrectly used were historical control data, multisite responses and progression of lesions to malignancy. Contrary to the authorities’ evaluations, proper application of statistical methods and WoE criteria inevitably leads to the conclusion that glyphosate is ‘probably carcinogenic’ (corresponding to category 1B in the European Union). FULL TEXT
Caballero et al., 2018
Caballero, M., Amiri, S., Denney, J. T., Monsivais, P., Hystad, P., & Amram, O., “Estimated Residential Exposure to Agricultural Chemicals and Premature Mortality by Parkinson’s Disease in Washington State,” International Journal of Environmental Research and Public Health, 2018, 15(12). DOI: 10.3390/ijerph15122885.
ABSTRACT:
The aim of this study was to examine the relationship between estimated residential exposure to agricultural chemical application and premature mortality from Parkinson’s disease (PD) in Washington State. Washington State mortality records for 2011(-)2015 were geocoded using residential addresses, and classified as having exposure to agricultural land-use within 1000 meters. Generalized linear models were used to explore the association between land-use associated with agricultural chemical application and premature mortality from PD. Individuals exposed to land-use associated with glyphosate had 33% higher odds of premature mortality than those that were not exposed (Odds Ratio (OR) = 1.33, 95% Confidence Intervals (CI) = 1.06(-)1.67). Exposure to cropland associated with all pesticide application (OR = 1.19, 95% CI = 0.98(-)1.44) or Paraquat application (OR = 1.22, 95% CI = 0.99(-)1.51) was not significantly associated with premature mortality from PD, but the effect size was in the hypothesized direction. No significant associations were observed between exposure to Atrazine (OR = 1.21, 95% CI = 0.84(-)1.74) or Diazinon (OR = 1.07, 95% CI = 0.85(-)1.34), and premature mortality from PD. The relationship between pesticide exposure and premature mortality aligns with previous biological, toxicological, and epidemiological findings. Glyphosate, the world’s most heavily applied herbicide, and an active ingredient in Roundup((R)) and Paraquat, a toxic herbicide, has shown to be associated with the odds of premature mortality from PD. FULL TEXT
Benbrook, 2019
Benbrook, Charles M., “How did the US EPA and IARC reach diametrically opposed conclusions on the genotoxicity of glyphosate-based herbicides?,” Environmental Sciences Europe, 2019, 31(1), DOI:10.1186/s12302-018-0184-7.
ABSTRACT:
BACKGROUND: The US EPA considers glyphosate as “not likely to be carcinogenic to humans.” The International Agency for Research on Cancer (IARC) has classified glyphosate as “probably carcinogenic to humans (Group 2A).” EPA asserts that there is no convincing evidence that “glyphosate induces mutations in vivo via the oral route.” IARC concludes there is “strong evidence” that exposure to glyphosate is genotoxic through at least two mechanisms known to be associated with human carcinogens (DNA damage, oxidative stress). Why and how did EPA and IARC reach such different conclusions?
RESULTS: A total of 52 genotoxicity assays done by registrants were cited by the EPA in its 2016 evaluation of technical glyphosate, and another 52 assays appeared in the public literature. Of these, one regulatory assay (2%) and 35 published assays (67%) reported positive evidence of a genotoxic response. In the case of formulated, glyphosatebased herbicides (GBHs), 43 regulatory assays were cited by EPA, plus 65 assays published in peer-reviewed journals. Of these, none of the regulatory, and 49 published assays (75%) reported evidence of a genotoxic response following exposure to a GBH. IARC considered a total of 118 genotoxicity assays in six core tables on glyphosate technical, GBHs, and aminomethylphosphonic acid (AMPA), glyphosate’s primary metabolite. EPA’s analysis encompassed 51 of these 118 assays (43%). In addition, IARC analyzed another 81 assays exploring other possible genotoxic mechanisms (mostly related to sex hormones and oxidative stress), of which 62 (77%) reported positive results. IARC placed considerable weight on three positive GBH studies in exposed human populations, whereas EPA placed little or no weight on them.
CONCLUSIONS: EPA and IARC reached diametrically opposed conclusions on glyphosate genotoxicity for three primary reasons: (1) in the core tables compiled by EPA and IARC, the EPA relied mostly on registrant-commissioned, unpublished regulatory studies, 99% of which were negative, while IARC relied mostly on peer-reviewed studies of which 70% were positive (83 of 118); (2) EPA’s evaluation was largely based on data from studies on technical glyphosate, whereas IARC’s review placed heavy weight on the results of formulated GBH and AMPA assays; (3) EPA’s evaluation was focused on typical, general population dietary exposures assuming legal, food-crop uses, and did not take into account, nor address generally higher occupational exposures and risks. IARC’s assessment encompassed data from typical dietary, occupational, and elevated exposure scenarios. More research is needed on real-world exposures to the chemicals within formulated GBHs and the biological fate and consequences of such exposures. FULL TEXT
Benbrook, 2018
Benbrook, Charles, “Why Regulators Lost Track and Control of Pesticide Risks: Lessons From the Case of Glyphosate-Based Herbicides and Genetically Engineered-Crop Technology,” Current Environmental Health Reports, 5:3, 387-395, 2018, DOI:10.1007/s40572-018-0207-y.
ABSTRACT:
PURPOSE OF REVIEW: The approval of genetically engineered (GE) crops in the late 1990s triggered dramatic changes in corn, soybean, and cotton pest management systems, as well as complex, novel regulatory challenges. Lessons learned are reviewed and solutions described.
RECENT FINDINGS: Government-imposed resistance management provisions can work and adapt to changing circumstances, but within the private sector, pressures to gain and hold market share have thus far trumped the widely recognized need for resistance management. Risks arising from the use of formulated pesticides often exceed by a wide margin those in regulatory risk assessments based on data derived from studies on nearly 100% pure active ingredients.
SUMMARY: Innovative policy changes are needed in four problem areas: excessive faith in the accuracy of pre-market risk assessments and regulatory thresholds; post-approval monitoring of actual impacts; risk arising from formulated pesticides, rather than just pure active ingredient; challenges inherent in assessing and mitigating the combined impacts of all GE traits and associated pesticides on agroecosystems, as opposed to each trait or pesticide alone; and, tools to deal with failing pest management systems. FULL TEXT
Bailey et al., 2018
Bailey, D. C., Todt, C. E., Burchfield, S. L., Pressley, A. S., Denney, R. D., Snapp, I. B., Negga, R., Traynor, W. L., & Fitsanakis, V. A., “Chronic exposure to a glyphosate-containing pesticide leads to mitochondrial dysfunction and increased reactive oxygen species production in Caenorhabditis elegans,” Environmental Toxicology and Pharmacology, 2048, 57, 46-52. DOI: 10.1016/j.etap.2017.11.005.
ABSTRACT:
Glyphosate-containing herbicides are among the most widely-used in the world. Although glyphosate itself is relatively non-toxic, growing evidence suggests that commercial herbicide formulations may lead to increased oxidative stress and mitochondrial inhibition. In order to assess these mechanisms in vivo, we chronically (24h) exposed Caenorhabditis elegans to various concentrations of the glyphosate-containing herbicide TouchDown (TD). Following TD exposure, we evaluated the function of specific mitochondrial electron transport chain complexes. Initial oxygen consumption studies demonstrated inhibition in mid- and high-TD concentration treatment groups compared to controls. Results from tetramethylrhodamine ethyl ester and ATP assays indicated reductions in the proton gradient and ATP levels, respectively. Additional studies were designed to determine whether TD exposure resulted in increased reactive oxygen species (ROS) production. Data from hydrogen peroxide, but not superoxide or hydroxyl radical, assays showed statistically significant increases in this specific ROS. Taken together, these data indicate that exposure of Caenorhabditis elegans to TD leads to mitochondrial inhibition and hydrogen peroxide production. FULL TEXT
Anifandis et al., 2017
Anifandis, G., Amiridis, G., Dafopoulos, K., Daponte, A., Dovolou, E., Gavriil, E., Gorgogietas, V., Kachpani, E., Mamuris, Z., Messini, C. I., Vassiou, K., & Psarra, A. G., “The In Vitro Impact of the Herbicide Roundup on Human Sperm Motility and Sperm Mitochondria,” Toxics, 2017, 6:1, DOI:10.3390/toxics6010002.
ABSTRACT:
Toxicants, such as herbicides, have been hypothesized to affect sperm parameters. The most common method of exposure to herbicides is through spraying or diet. The aim of the present study was to investigate the effect of direct exposure of sperm to 1 mg/L of the herbicide Roundup on sperm motility and mitochondrial integrity. Sperm samples from 66 healthy men who were seeking semen analysis were investigated after written informed consent was taken. Semen analysis was performed according to the World Health Organization guidelines (WHO, 2010). Mitochondrial integrity was assessed through mitochondrial staining using a mitochondria-specific dye, which is exclusively incorporated into functionally active mitochondria. A quantity of 1 mg/L of Roundup was found to exert a deleterious effect on sperm’s progressive motility, after 1 h of incubation (mean difference between treated and control samples = 11.2%) in comparison with the effect after three hours of incubation (mean difference = 6.33%, p < 0.05), while the relative incorporation of the mitochondrial dye in mitochondria of the mid-piece region of Roundup-treated spermatozoa was significantly reduced compared to relative controls at the first hour of incubation, indicating mitochondrial dysfunction by Roundup. Our results indicate that the direct exposure of semen samples to the active constituent of the herbicide Roundup at the relatively low concentration of 1 mg/L has adverse effects on sperm motility, and this may be related to the observed reduction in mitochondrial staining. FULL TEXT