Bibliography Tag: glyphosate and cancer risks

Franke et al., 2021

Franke, Adrian A., Li, Xingnan, Shvetsov, Yurii B., & Lai, Jennifer F.; “Pilot study on the urinary excretion of the glyphosate metabolite aminomethylphosphonic acid and breast cancer risk: The Multiethnic Cohort study;” Environmental Pollution, 2021, 277, 116848; DOI: https://doi.org/10.1016/j.envpol.2021.116848.

ABSTRACT:

Breast cancer is the most commonly diagnosed female cancer and the second leading cause of death in women in the US, including Hawaii. Accumulating evidence suggests that aminomethylphosphonic acid (AMPA), the primary metabolite of the herbicide glyphosate—a probable human carcinogen, may itself be carcinogenic. However, the relationship between urinary AMPA excretion and breast cancer risk in women is unknown. In this pilot study, we investigated the association between pre-diagnostic urinary AMPA excretion and breast cancer risk in a case-control study of 250 predominantly postmenopausal women: 124 cases and 126 healthy controls (individually matched on age, race/ethnicity, urine type, date of urine collection, and fasting status) nested within the Hawaii biospecimen subcohort of the Multiethnic Cohort. AMPA was detected in 90% of cases and 84% of controls. The geometric mean of urinary AMPA excretion was nearly 38% higher among cases vs. controls (0.087 vs 0.063 ng AMPA/mg creatinine) after adjusting for race/ethnicity, age and BMI. A 4.5-fold higher risk of developing breast cancer in the highest vs. lowest quintile of AMPA excretion was observed (ORQ5 vs. Q1: 4.49; 95% CI: 1.46–13.77; ptrend = 0.029). To our knowledge, this is the first study to prospectively examine associations between urinary AMPA excretion and breast cancer risk. Our preliminary findings suggest that AMPA exposure may be associated with increased breast cancer risk; however, these results require confirmation in a larger population to increase study power and permit careful examinations of race/ethnicity differences.


Benbrook, 2020

Benbrook, Charles; “Shining a Light on Glyphosate-Based Herbicide Hazard, Exposures and Risk: Role of Non-Hodgkin Lymphoma Litigation in the USA;” European Journal of Risk Regulation, 2020, 11(3), 498-519; DOI: 10.1017/err.2020.16.

ABSTRACT:

Roundup, and other glyphosate-based herbicides, are the most heavily used pesticides in the history of the USA and globally. In March 2015, the International Agency for Research on Cancer (IARC) classified glyphosate as a “probable human carcinogen”. A portion of the 695,000 Americans then living in 2015 with non-Hodgkin lymphoma (NHL) became aware of IARC’s decision. Several thousand Roundup–NHL lawsuits had been filed by the end of 2017, rising to 18,400 by July 2019 and 42,000 by November 2019. Three cases have gone to trial, each won by the plaintiffs. The author has served as an expert witness for the plaintiffs in this litigation and has been compensated for his time spent. The impact of the litigation on the independent assessment of the science useful in determining whether glyphosate and glyphosate-based herbicide exposures are linked to NHL is reviewed, as is why the US Environmental Protection Agency (EPA) and IARC reached such different judgements regarding glyphosate human cancer hazard and risk. Two important “lessons learned” regarding the EPA versus IARC assessment of glyphosate cancer hazard and risk are highlighted. The first arises from differences in the magnitude of applicator risks from mostly dermal exposures to formulated glyphosate-based herbicides compared to just dietary exposures to technical glyphosate. The second relates to missed opportunities to markedly lower applicator exposures and risks with little or no impact on sales via reformulation, added warnings and worker safety provisions, company-driven stewardship programmes and greater determination by the EPA in the 1980s to compel Monsanto to add common-sense worker protection provisions onto Roundup labels (eg “wear gloves when applying this product”). Policy reforms designed to alleviate systemic problems with how pesticide hazards, exposures and risks are analysed, regulated and mitigated are described. FULL TEXT


Connolly et al., 2020

Connolly, A., Coggins, M. A., & Koch, H. M.; “Human Biomonitoring of Glyphosate Exposures: State-of-the-Art and Future Research Challenges;” Toxics, 2020, 8(3); DOI: 10.3390/toxics8030060. https://www.ncbi.nlm.nih.gov/pubmed/32824707.

ABSTRACT:

Glyphosate continues to attract controversial debate following the International Agency for Research on Cancer carcinogenicity classification in 2015. Despite its ubiquitous presence in our environment, there remains a dearth of data on human exposure to both glyphosate and its main biodegradation product aminomethylphosphonic (AMPA). Herein, we reviewed and compared results from 21 studies that use human biomonitoring (HBM) to measure urinary glyphosate and AMPA. Elucidation of the level and range of exposure was complicated by differences in sampling strategy, analytical methods, and data presentation. Exposure data is required to enable a more robust regulatory risk assessment, and these studies included higher occupational exposures, environmental exposures, and vulnerable groups such as children. There was also considerable uncertainty regarding the absorption and excretion pattern of glyphosate and AMPA in humans. This information is required to back-calculate exposure doses from urinary levels and thus, compared with health-based guidance values. Back-calculations based on animal-derived excretion rates suggested that there were no health concerns in relation to glyphosate exposure (when compared with EFSA acceptable daily intake (ADI)). However, recent human metabolism data has reported as low as a 1% urinary excretion rate of glyphosate. Human exposures extrapolated from urinary glyphosate concentrations found that upper-bound levels may be much closer to the ADI than previously reported. FULL TEXT


Meftaul et al.; 2020

Meftaul, I. M., Venkateswarlu, K., Dharmarajan, R., Annamalai, P., Asaduzzaman, M., Parven, A., & Megharaj, M.; “Controversies over human health and ecological impacts of glyphosate: Is it to be banned in modern agriculture?;” Environmental Pollution, 2020, 263(Pt A), 114372; DOI: 10.1016/j.envpol.2020.114372.

ABSTRACT:

Glyphosate, introduced by Monsanto Company under the commercial name Roundup in 1974, became the extensively used herbicide worldwide in the last few decades. Glyphosate has excellent properties of fast sorption in soil, biodegradation and less toxicity to nontarget organisms. However, glyphosate has been reported to increase the risk of cancer, endocrine-disruption, celiac disease, autism, effect on erythrocytes, leaky-gut syndrome, etc. The reclassification of glyphosate in 2015 as ‘probably carcinogenic’ under Group 2A by the International Agency for Research on Cancer has been broadly circulated by anti-chemical and environmental advocacy groups claiming for restricted use or ban of glyphosate. In contrast, some comprehensive epidemiological studies involving farmers with long-time exposure to glyphosate in USA and elsewhere coupled with available toxicological data showed no correlation with any kind of carcinogenic or genotoxic threat to humans. Moreover, several investigations confirmed that the surfactant, polyethoxylated tallow amine (POEA), contained in the formulations of glyphosate like Roundup, is responsible for the established adverse impacts on human and ecological health. Subsequent to the evolution of genetically modified glyphosate-resistant crops and the extensive use of glyphosate over the last 45 years, about 38 weed species developed resistance to this herbicide. Consequently, its use in the recent years has been either restricted or banned in 20 countries. This critical review on glyphosate provides an overview of its behaviour, fate, detrimental impacts on ecological and human health, and the development of resistance in weeds and pathogens. Thus, the ultimate objective is to help the authorities and agencies concerned in resolving the existing controversies and in providing the necessary regulations for safer use of the herbicide. In our opinion, glyphosate can be judiciously used in agriculture with the inclusion of safer surfactants in commercial formulations sine POEA, which is toxic by itself is likely to increase the toxicity of glyphosate. FULL TEXT


Williams et al., 2000

Williams, G. M., Kroes, R., & Munro, I. C.; “Safety evaluation and risk assessment of the herbicide Roundup and its active ingredient, glyphosate, for humans;” Regulatory Toxicology and Pharmacology, 2000, 31(2 Pt 1), 117-165; DOI: 10.1006/rtph.1999.1371.

ABSTRACT:

Reviews on the safety of glyphosate and Roundup herbicide that have been conducted by several regulatory agencies and scientific institutions worldwide have concluded that there is no indication of any human health concern. Nevertheless, questions regarding their safety are periodically raised. This review was undertaken to produce a current and comprehensive safety evaluation and risk assessment for humans. It includes assessments of glyphosate, its major breakdown product [aminomethylphosphonic acid (AMPA)], its Roundup formulations, and the predominant surfactant [polyethoxylated tallow amine (POEA)] used in Roundup formulations worldwide. The studies evaluated in this review included those performed for regulatory purposes as well as published research reports. The oral absorption of glyphosate and AMPA is low, and both materials are eliminated essentially unmetabolized. Dermal penetration studies with Roundup showed very low absorption. Experimental evidence has shown that neither glyphosate nor AMPA bioaccumulates in any animal tissue. No significant toxicity occurred in acute, subchronic, and chronic studies. Direct ocular exposure to the concentrated Roundup formulation can result in transient irritation, while normal spray dilutions cause, at most, only minimal effects. The genotoxicity data for glyphosate and Roundup were assessed using a weight-of-evidence approach and standard evaluation criteria. There was no convincing evidence for direct DNA damage in vitro or in vivo, and it was concluded that Roundup and its components do not pose a risk for the production of heritable/somatic mutations in humans. Multiple lifetime feeding studies have failed to demonstrate any tumorigenic potential for glyphosate. Accordingly, it was concluded that glyphosate is noncarcinogenic. Glyphosate, AMPA, and POEA were not teratogenic or developmentally toxic. There were no effects on fertility or reproductive parameters in two multigeneration reproduction studies with glyphosate. Likewise there were no adverse effects in reproductive tissues from animals treated with glyphosate, AMPA, or POEA in chronic and/or subchronic studies. Results from standard studies with these materials also failed to show any effects indicative of endocrine modulation. Therefore, it is concluded that the use of Roundup herbicide does not result in adverse effects on development, reproduction, or endocrine systems in humans and other mammals. For purposes of risk assessment, no-observed-adverse-effect levels (NOAELs) were identified for all subchronic, chronic, developmental, and reproduction studies with glyphosate, AMPA, and POEA. Margins-of-exposure for chronic risk were calculated for each compound by dividing the lowest applicable NOAEL by worst-case estimates of chronic exposure. Acute risks were assessed by comparison of oral LD50 values to estimated maximum acute human exposure. It was concluded that, under present and expected conditions of use, Roundup herbicide does not pose a health risk to humans.


Crump et al., 2020

Crump, K., Crouch, E., Zelterman, D., Crump, C., & Haseman, J.; “Accounting for Multiple Comparisons in Statistical Analysis of the Extensive Bioassay Data on Glyphosate;” Toxicology Science, 2020; DOI: 10.1093/toxsci/kfaa039.

ABSTRACT:

Glyphosate is a widely used herbicide worldwide. In 2015, the International Agency for Research on Cancer (IARC) reviewed glyphosate cancer bioassays and human studies and declared that the evidence for carcinogenicity of glyphosate is sufficient in experimental animals. We analyzed ten glyphosate rodent bioassays, including those in which IARC found evidence of carcinogenicity, using a multi-response permutation procedure that adjusts for the large number of tumors eligible for statistical testing and provides valid false-positive probabilities. The test statistics for these permutation tests are functions of p-values from a standard test for dose-response trend applied to each specific type of tumor. We evaluated three permutation tests, using as test statistics the smallest p-value from a standard statistical test for dose-response trend and the number of such tests for which the p-value is less than or equal to 0.05 or 0.01. The false-positive probabilities obtained from two implementations of these three permutation tests are: smallest p-value: 0.26, 0.17, p-values </= 0.05: 0.08, 0.12, p-values </= 0.01: 0.06, 0.08. In addition, we found more evidence for negative dose-response trends than positive. Thus, we found no strong evidence that glyphosate is an animal carcinogen. The main cause for the discrepancy between IARC’s finding and ours appears to be that IARC did not account for the large number of tumor responses analyzed and the increased likelihood that several of these would show statistical significance simply by chance. This work provides a more comprehensive analysis of the animal carcinogenicity data for this important herbicide than previously available. FULL TEXT


Vineis, 2019

Vineis, P.; “Public Health and Independent Risk Assessment;” American Journal of Public Health, 2019, 109(7), 978-980; DOI: 10.2105/AJPH.2019.305142.

FULL TEXT


Samet, 2019

Samet, J. M.; “Expert Review Under Attack: Glyphosate, Talc, and Cancer;” American Journal of Public Health, 2019, 109(7), 976-978; DOI: 10.2105/AJPH.2019.305131.

FULL TEXT


Schaden et al., 2020

Schaden, Helmut Burtscher, Clausing, Peter, & Van Scharen, Hans. “Factsheet: Dangerous Confidence in ‘Good Laboratory Practices,'” February 11, 2020, Corporate Europe Observatory and PAN Germany.

SUMMARY:

Our authorisation system for chemicals is based on the principle that manufacturers must prove, by means of scientifc studies, that their products do not pose unacceptable risks to public health and the environment. It is therefore also the responsibility of manufacturers to commission certifed contract laboratories to carry out the toxicological studies necessary for the approval procedure. As a guarantee against manipulation and falsifcation of these “regulatory” studies, regulatory authorities worldwide rely on the certifed standard of “Good Laboratory Practice” (GLP). This standard provides for strict documentation requirements and regular internal and external controls. However, the current fraud scandal involving a German contract laboratory certifed according to GLP, shows that this trust is unlikely to be justifed. According to reports, GLP studies have been manipulated and falsifed there since 2005.

  • Recent research now shows that LPT has also produced studies that were part of the study package for the EU-wide approval of glyphosate in December 2017: One in seven studies in this package, which was the basis to grant re-approval for glyphosate, came from LPT. These fndings are worrying in two ways: – On the one hand, there is the fundamental question of whether the risk assessments for medicines, pesticides and chemicals based on LPT studies can be trusted.
  •  Even more worrying is the general realisation that laboratories, despite the supposedly “tamper-proof” GLP standard, are apparently able to falsify studies over years and decades without being noticed by the control authorities.

The classifcation of glyphosate as “non-carcinogenic” and “not genotoxic“o is based, among other things, on the European authorities’ full confdence in the GLP system. In the EU assessment proces GLP studies were automatically classifed as reliable; This in stark contrast with the numerous “non-GLP studies” from university research, peer reviewed and published, most of which reported evidence of a genotoxic effect and an increased risk of lymphatic cancer in users of glyphosate, were disqualifed by the authorities as “unreliable“.

The LPT counterfeiting scandal reveals the failure of a regulatory system, that places the commissioning and preparation of studies in the hands of industry. At the same time, it confrms the urgency of a fundamental reform of this system for identifying the risks of chemicals, as called for by the European coalition “Citizens for Science in Pesticide Regulation” in October 2018. FULL TEXT


Perro, 2019

Perro, Michelle, “Childhood Leukemia, the Microbiome, and Glyphosate: A Doctor’s Perspective,” GMOScience.org, January 15, 2019.

SUMMARY:

  • Childhood leukemia is on the rise
  • Exposure to pesticides is known to increase the risk of childhood leukemia, as well as other types of cancer
  • New research links an impoverished gut microbiome (bacterial community) and chronic inflammation with increased risk of childhood leukemia
  • Diet-related ways are being sought to improve the microbiome and prevent the inflammation that triggers childhood leukemia
  • Glyphosate herbicides are used on around 90% of GM crops; glyphosate has been classified as a probable carcinogen by the World Health Organization’s cancer agency IARC
  • Exposure to glyphosate-based and other pesticides has been shown to disrupt the gut microbiome in laboratory animals
  • People who eat organic food have been found to have a 25% reduced risk of cancer
  • Clinical experience shows that switching to an organic and non-GMO diet improves people’s health
  • Controlled studies are needed to verify how switching to an organic and non-GMO diet affects the microbiome and certain disease conditions.

FULL TEXT