Environmental Protection Agency, “Revised Glyphosate Issue Paper: Evaluation of Carcinogenic Potential,” Office of Pesticide Programs, December 12, 2017, Available at: https://cfpub.epa.gov/si/si_public_record_Report.cfm?Lab=OPP&dirEntryId=337935.
SUMMARY:
Not available. FULL TEXT
DeVito, Michael, “Update on NTP Studies of Glyphosate,” Presented at the National Toxicology Program (NTP) Board of Scientific Counselors Meeting, December 7-8, 2017.
SUMMARY:
Not available. FULL TEXT
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, 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
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
Donald T. Wigle , Tye E. Arbuckle , Michelle C. Turner , Annie Bérubé , Qiuying Yang , Shiliang Liu & Daniel Krewski, “Epidemiologic Evidence of Relationships Between Reproductive and Child Health Outcomes and Environmental Chemical Contaminants,” Journal of Toxicology and Environmental Health, Part B, 11, 2008, DOI: 10.1080/10937400801921320
ABSTRACT:
This review summarizes the level of epidemiologic evidence for relationships between prenatal and/or early life exposure to environmental chemical contaminants and fetal, child, and adult health. Discussion focuses on fetal loss, intrauterine growth restriction, preterm birth, birth defects, respiratory and other childhood diseases, neuropsychological deficits, premature or delayed sexual maturation, and certain adult cancers linked to fetal or childhood exposures. Environmental exposures considered here include chemical toxicants in air, water, soil/house dust and foods (including human breast milk), and consumer products. Reports reviewed here included original epidemiologic studies (with at least basic descriptions of methods and results), literature reviews, expert group reports, meta-analyses, and pooled analyses. Levels of evidence for causal relationships were categorized as sufficient, limited, or inadequate according to predefined criteria. There was sufficient epidemiological evidence for causal relationships between several adverse pregnancy or child health outcomes and prenatal or childhood exposure to environmental chemical contaminants. These included prenatal high-level methylmercury (CH3Hg) exposure (delayed developmental milestones and cognitive, motor, auditory, and visual deficits), high-level prenatal exposure to polychlorinated biphenyls (PCBs), polychlorinated dibenzofurans (PCDFs), and related toxicants (neonatal tooth abnormalities, cognitive and motor deficits), maternal active smoking (delayed conception, preterm birth, fetal growth deficit [FGD] and sudden infant death syndrome [SIDS]) and prenatal environmental tobacco smoke (ETS) exposure (preterm birth), low-level childhood lead exposure (cognitive deficits and renal tubular damage), high-level childhood CH3Hg exposure (visual deficits), high-level childhood exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (chloracne), childhood ETS exposure (SIDS, new-onset asthma, increased asthma severity, lung and middle ear infections, and adult breast and lung cancer), childhood exposure to biomass smoke (lung infections), and childhood exposure to outdoor air pollutants (increased asthma severity). Evidence for some proven relationships came from investigation of relatively small numbers of children with high-dose prenatal or early childhood exposures, e.g., CH3Hg poisoning episodes in Japan and Iraq. In contrast, consensus on a causal relationship between incident asthma and ETS exposure came only recently after many studies and prolonged debate. There were many relationships supported by limited epidemiologic evidence, ranging from several studies with fairly consistent findings and evidence of dose-response relationships to those where 20 or more studies provided inconsistent or otherwise less than convincing evidence of an association. The latter included childhood cancer and parental or childhood exposures to pesticides. In most cases, relationships supported by inadequate epidemiologic evidence reflect scarcity of evidence as opposed to strong evidence of no effect. This summary points to three main needs: (1) Where relationships between child health and environmental exposures are supported by sufficient evidence of causal relationships, there is a need for (a) policies and programs to minimize population exposures and (b) population-based biomonitoring to track exposure levels, i.e., through ongoing or periodic surveys with measurements of contaminant levels in blood, urine and other samples. (2) For relationships supported by limited evidence, there is a need for targeted research and policy options ranging from ongoing evaluation of evidence to proactive actions. (3) There is a great need for population-based, multidisciplinary and collaborative research on the many relationships supported by inadequate evidence, as these represent major knowledge gaps. Expert groups faced with evaluating epidemiologic evidence of potential causal relationships repeatedly encounter problems in summarizing the available data. A major driver for undertaking such summaries is the need to compensate for the limited sample sizes of individual epidemiologic studies. Sample size limitations are major obstacles to exploration of prenatal, paternal, and childhood exposures during specific time windows, exposure intensity, exposure–exposure or exposure–gene interactions, and relatively rare health outcomes such as childhood cancer. Such research needs call for investments in research infrastructure, including human resources and methods development (standardized protocols, biomarker research, validated exposure metrics, reference analytic laboratories). These are needed to generate research findings that can be compared and subjected to pooled analyses aimed at knowledge synthesis.
Cocco, Pierluigi, Satta, Giannina, Dubois, Stefania, Pili, Claudia, Pilleri, Michela, Zucca, Mariagrazia, ‘t Mannetje, Andrea Martine, Becker, Nikolaus, Benavente, Yolanda, de Sanjosé, Silvia, Foretova, Lenka, Staines, Anthony, Maynadié, Marc, Nieters, Alexandra, Brennan, Paul, Miligi, Lucia, Ennas, Maria Grazia, & Boffetta, Paolo, “Lymphoma risk and occupational exposure to pesticides: results of the EPILYMPH study,” Occupational and Environmental Medicine, 2013, 70(2), 91, DOI: 10.1136/oemed-2012-100845.
ABSTRACT:
OBJECTIVES: We investigated the role of occupational exposure to specific groups of agrochemicals in the aetiology of lymphoma overall, B cell lymphoma and its most prevalent subtypes.
METHODS: In 1998–2003, 2348 incident lymphoma cases and 2462 controls were recruited to the EPILYMPH case-control study in six European countries. A detailed occupational history was collected in cases and controls. Job modules were applied for farm work including specific questions on type of crop, farm size, pests being treated, type and schedule of pesticide use. In each study centre, industrial hygienists and occupational experts assessed exposure to specific groups of pesticides and individual compounds with the aid of agronomists. We calculated the OR and its 95% CI associated with lymphoma and the most prevalent lymphoma subtypes with unconditional logistic regression, adjusting for age, gender, education and centre.
RESULTS: Risk of lymphoma overall, and B cell lymphoma was not elevated, and risk of chronic lymphocytic leukaemia (CLL) was elevated amongst those ever exposed to inorganic (OR=1.6, 95% CI 1.0 to 2.5) and organic pesticides (OR=1.5, 95% CI 1.0 to 2.1). CLL risk was highest amongst those ever exposed to organophosphates (OR=2.7, 95% CI 1.2 to 6.0). Restricting the analysis to subjects most likely exposed, no association was observed between pesticide use and risk of B cell lymphoma.
CONCLUSIONS: Our results provide limited support to the hypothesis of an increase in risk of specific lymphoma subtypes associated with exposure to pesticides. FULL TEXT
Hohenadel, Karin, Harris, Shelley A, McLaughlin, John R, Spinelli, John J, Pahwa, Punam, Dosman, James A, Demers, Paul A, & Blair, Aaron., “Exposure to multiple pesticides and risk of non-Hodgkin lymphoma in men from six Canadian provinces,” International Journal of Environmental Research and Public Health, 2011, 8(6), 2320-2330. doi:10.3390/ijerph8062320.
ABSTRACT:
Non-Hodgkin lymphoma (NHL) has been linked to several agricultural exposures, including some commonly used pesticides. Although there is a significant body of literature examining the effects of exposure to individual pesticides on NHL, the impact of exposure to multiple pesticides or specific pesticide combinations has not been explored in depth. Data from a six-province Canadian case-control study conducted between 1991 and 1994 were analyzed to investigate the relationship between NHL, the total number of pesticides used and some common pesticide combinations. Cases (n=513) were identified through hospital records and provincial cancer registries and controls (n=1,506), frequency matched to cases by age and province of residence, were obtained through provincial health records, telephone listings, or voter lists. In multiple logistic regression analyses, risk of NHL increased with the number of pesticides used. Similar results were obtained in analyses restricted to herbicides, insecticides and several pesticide classes. Odds ratios increased further when only ‘potentially carcinogenic’ pesticides were considered (OR[one pesticide]=1.30, 95% CI=0.90-1.88; OR[two to four]=1.54, CI=1.11-2.12; OR[five or more]=1.94, CI=1.17-3.23). Elevated risks were also found among those reporting use of malathion in combination with several other pesticides. These analyses support and extend previous findings that the risk of NHL increases with the number of pesticides used and some pesticide combinations. FULL TEXT
Buddhini Samarasinghe, “The Hallmarks of Cancer, Parts 1-9,” Scientific American, September 1, 2013-October 8, 2014.
SUMMARY:
The Hallmarks of Cancer are the ten characteristics that differentiate a cancer cell from a normal cell. Over the course of a year, science translator Dr. Buddhini Samarasinghe tackled each of the the ten Hallmarks of Cancer in a guest blog series for Scientific American.
The blogs break down the basic biology of each Hallmark and what happens when the system breaks down. It is important to understand these Hallmarks as we investigate the influence of chemicals and how they may act individually and in groups to disrupt enough of these Hallmark mechanisms to cause cancer.
Why is this paper so important? Cancer, as we know by now, is an incredibly complicated disease. A single tumor sample could have over a hundred different mutations; nearly one in every two hundred genes in the human genome. If two breast cancer specimens are compared, the set of mutated genes are far from identical. Every tumor is unique. Weinberg and Hanahan simplified this dauntingly complex disease to six underlying principles. The hugely complicated beast that is cancer, so diverse that even the same organ can have many different tumor types, was reduced to just six common traits that every single cancer shares, to facilitate that transformation from a normal cell to a cancer cell. It answers the ‘how does cancer happen’ question very elegantly, and we gain insight into all the different things that go wrong in a cancer cell. FULL TEXT
Richmond, Martha E., “Glyphosate: A review of its global use, environmental impact, and potential health effects on humans and other species,” Journal of Environmental Studies and Sciences, Published online 09/28/2018, doi:10.1007/s13412-018-0517-2.
ABSTRACT:
Glyphosate, [N-(phosphonomethyl) glycine], was synthesized in 1950 and patented as a chemical chelator, capable of binding metals such as calcium, magnesium, and manganese. Glyphosate’s ability to bind to manganese was later found to inhibit an enzyme used by plants and bacteria for biosynthesis ofthree amino acids found in all proteins, and the commercial value ofthis property led to the development and marketing of glyphosate as a broad-spectrum herbicide. In 1974, the Monsanto Chemical Company introduced the herbicide as Roundup™, a formulation of glyphosate and adjuvants. Roundup™ was originally used for weed control in specific farming and landscaping operations and around power lines and train tracks. Following introduction of Roundup Ready™ seeds, in the 1990s, glyphosate use increased significantly. Although Monsanto’s patent on glyphosate expired in 2002, the widespread and growing use ofRoundup Ready™ seed globally and competitive glyphosate marketing by other chemical companies have led to glyphosate’s significant increase in the environment. Concerns about potential adverse effects have also grown. While, at present, many regulatory agencies have determined that there is little risk of adverse health effects to the general public or to farmworkers using proper handling techniques, the International Agency for Research on Cancer (IARC) assessing hazard data on glyphosate identified it in 2016 as a category 2A carcinogen (likely to cause human cancer). Response to this classification has been divided: The agribusiness industry has been forceful in its opposition, while other experts support IARC’s classification. The following article examines these issues. It also examines the basis for regulatory decisions, controversies involved, and questions of environmental justice that may or may not be addressed as glyphosate continues to be used. FULL TEXT