Stur et al., 2019
Stur, E., Aristizabal-Pachon, A. F., Peronni, K. C., Agostini, L. P., Waigel, S., Chariker, J., Miller, D. M., Thomas, S. D., Rezzoug, F., Detogni, R. S., Reis, R. S. D., Silva Junior, W. A., & Louro, I. D.; “Glyphosate-based herbicides at low doses affect canonical pathways in estrogen positive and negative breast cancer cell lines;” Plos One, 2019, 14(7), e0219610; DOI: 10.1371/journal.pone.0219610.
ABSTRACT:
Glyphosate is a broad-spectrum herbicide that is used worldwide. It represents a potential harm to surface water, and when commercially mixed with surfactants, its uptake is greatly magnified. The most well-known glyphosate-based product is Roundup. This herbicide is potentially an endocrine disruptor and many studies have shown the cytotoxicity potential of glyphosate-based herbicides. In breast cancer (BC) cell lines it has been demonstrated that glyphosate can induce cellular proliferation via estrogen receptors. Therefore, we aimed to identify gene expression changes in ER+ and ER- BC cell lines treated with Roundup and AMPA, to address changes in canonical pathways that would be related or not with the ER pathway, which we believe could interfere with cell proliferation. Using the Human Transcriptome Arrays 2.0, we identified gene expression changes in MCF-7 and MDA-MB-468 exposed to low concentrations and short exposure time to Roundup Original and AMPA. The results showed that at low concentration (0.05% Roundup) and short exposure (48h), both cell lines suffered deregulation of 11 canonical pathways, the most important being cell cycle and DNA damage repair pathways. Enrichment analysis showed similar results, except that MDA-MB-468 altered mainly metabolic processes. In contrast, 48h 10mM AMPA showed fewer differentially expressed genes, but also mainly related with metabolic processes. Our findings suggest that Roundup affects survival due to cell cycle deregulation and metabolism changes that may alter mitochondrial oxygen consumption, increase ROS levels, induce hypoxia, damage DNA repair, cause mutation accumulation and ultimately cell death. To our knowledge, this is the first study to analyze the effects of Roundup and AMPA on gene expression in triple negative BC cells. Therefore, we conclude that both compounds can cause cellular damage at low doses in a relatively short period of time in these two models, mainly affecting cell cycle and DNA repair. FULL TEXT
Teleken et al., 2019
Teleken, J. L., Gomes, E. C. Z., Marmentini, C., Moi, M. B., Ribeiro, R. A., Balbo, S. L., Amorim, E. M. P., & Bonfleur, M. L.; “Glyphosate-based herbicide exposure during pregnancy and lactation malprograms the male reproductive morphofunction in F1 offspring;” Journal of Developmental Origins of Health and Disease, 2019, 1-8; DOI: 10.1017/s2040174419000382.
ABSTRACT:
One of the most consumed pesticides in the world is glyphosate, the active ingredient in the herbicide ROUNDUP(R). Studies demonstrate that glyphosate can act as an endocrine disruptor and that exposure to this substance at critical periods in the developmental period may program the fetus to induce reproductive damage in adulthood. Our hypothesis is that maternal exposure to glyphosate during pregnancy and lactation in mice will affect the development of male reproductive organs, impairing male fertility during adult life. Female mice consumed 0.5% glyphosate-ROUNDUP(R) in their drinking water [glyphosate-based herbicide (GBH) group] or filtered water [control (CTRL) group] from the fourth day of pregnancy until the end of the lactation period. Male F1 offspring were designated, according to their mother’s treatment, as CTRL-F1 and GBH-F1. Female mice that drank glyphosate displayed reduced body weight (BW) gain during gestation, but no alterations in litter size. Although GBH male F1 offspring did not exhibit modifications in BW, they demonstrated delayed testicular descent. Furthermore, at PND150, GBH-F1 mice presented a lower number of spermatozoa in the cauda epididymis and reduced epithelial height of the seminiferous epithelium. Notably, intratesticular testosterone concentrations were enhanced in GBH-F1 mice; we show that it is an effect associated with increased plasma and pituitary concentrations of luteinizing hormone. Therefore, data indicate that maternal exposure to glyphosate-ROUNDUP(R) during pregnancy and lactation may lead to decreased spermatogenesis and disruptions in hypothalamus-pituitary-testicular axis regulation in F1 offspring.
Wang et al., 2019
Wang, L., Deng, Q., Hu, H., Liu, M., Gong, Z., Zhang, S., Xu-Monette, Z. Y., Lu, Z., Young, K. H., Ma, X., & Li, Y.; “Glyphosate induces benign monoclonal gammopathy and promotes multiple myeloma progression in mice;” Journal of Hematology & Oncology, 2019, 12(1), 70; DOI: 10.1186/s13045-019-0767-9.
ABSTRACT:
BACKGROUND: Glyphosate is the most widely used herbicide in the USA and worldwide. There has been considerable debate about its carcinogenicity. Epidemiological studies suggest that multiple myeloma (MM) and non-Hodgkin lymphoma (NHL) have a positive and statistically significant association with glyphosate exposure. As a B cell genome mutator, activation-induced cytidine deaminase (AID) is a key pathogenic player in both MM and B cell NHL.
METHODS: Vk*MYC is a mouse line with sporadic MYC activation in germinal center B cells and considered as the best available MM animal model. We treated Vk*MYC mice and wild-type mice with drinking water containing 1000 mg/L of glyphosate and examined animals after 72 weeks.
RESULTS: Vk*MYC mice under glyphosate exposure developed progressive hematological abnormalities and plasma cell neoplasms such as splenomegaly, anemia, and high serum IgG. Moreover, glyphosate caused multiple organ dysfunction, including lytic bone lesions and renal damage in Vk*MYC mice. Glyphosate-treated wild-type mice developed benign monoclonal gammopathy with increased serum IgG, anemia, and plasma cell presence in the spleen and bone marrow. Finally, glyphosate upregulated AID in the spleen and bone marrow of both wild-type and Vk*MYC mice.
CONCLUSIONS: These data support glyphosate as an environmental risk factor for MM and potentially NHL and implicate a mechanism underlying the B cell-specificity of glyphosate-induced carcinogenesis observed epidemiologically. FULL TEXT
Landrigan and Goldman, 2011
Landrigan, Philip J, & Goldman, Lynn R; “Children’s vulnerability to toxic chemicals: a challenge and opportunity to strengthen health and environmental policy;” Health Affairs, 2011, 30(5), 842-850; DOI: 10.1377/hlthaff.2011.0151.
ABSTRACT:
A key policy breakthrough occurred nearly twenty years ago with the discovery that children are far more sensitive than adults to toxic chemicals in the environment. This finding led to the recognition that chemical exposures early in life are significant and preventable causes of disease in children and adults. We review this knowledge and recommend a new policy to regulate industrial and consumer chemicals that will protect the health of children and all Americans, prevent disease, and reduce health care costs. The linchpins of a new US chemical policy will be: first, a legally mandated requirement to test the toxicity of chemicals already in commerce, prioritizing chemicals in the widest use, and incorporating new assessment technologies; second, a tiered approach to premarket evaluation of new chemicals; and third, epidemiologic monitoring and focused health studies of exposed populations. FULL TEXT
Picchi, 2019
Aimee Pichhi, “Cheerios, Nature Valley cereals contain Roundup ingredient, study finds,” CBS News, June 13, 2019.
SUMMARY:
CBS This Morning coverage of the EWG report on glyphosate residues in cereals. Full Video
Bakian et al., 2019
Bakian, Amanda V., & VanDerslice, James A.; “Pesticides and autism;” BMJ, 2019, 364, l1149; DOI: 10.1136/bmj.l1149.
ABSTRACT:
Editorial in response to von Ehrenstein et al., 2019.
Kubsad et al., 2019
Kubsad, D., Nilsson, E. E., King, S. E., Sadler-Riggleman, I., Beck, D., & Skinner, M. K.; “Assessment of Glyphosate Induced Epigenetic Transgenerational Inheritance of Pathologies and Sperm Epimutations: Generational Toxicology;” Scientific Reports, 2019, 9(1), 6372; DOI: 10.1038/s41598-019-42860-0.
ABSTRACT:
Ancestral environmental exposures to a variety of factors and toxicants have been shown to promote the epigenetic transgenerational inheritance of adult onset disease. One of the most widely used agricultural pesticides worldwide is the herbicide glyphosate (N-(phosphonomethyl)glycine), commonly known as Roundup. There are an increasing number of conflicting reports regarding the direct exposure toxicity (risk) of glyphosate, but no rigorous investigations on the generational actions. The current study using a transient exposure of gestating F0 generation female rats found negligible impacts of glyphosate on the directly exposed F0 generation, or F1 generation offspring pathology. In contrast, dramatic increases in pathologies in the F2 generation grand-offspring, and F3 transgenerational great-grand-offspring were observed. The transgenerational pathologies observed include prostate disease, obesity, kidney disease, ovarian disease, and parturition (birth) abnormalities. Epigenetic analysis of the F1, F2 and F3 generation sperm identified differential DNA methylation regions (DMRs). A number of DMR associated genes were identified and previously shown to be involved in pathologies. Therefore, we propose glyphosate can induce the transgenerational inheritance of disease and germline (e.g. sperm) epimutations. Observations suggest the generational toxicology of glyphosate needs to be considered in the disease etiology of future generations. FULL TEXT
Attina et al., 2016
Attina, T. M., Hauser, R., Sathyanarayana, S., Hunt, P. A., Bourguignon, J. P., Myers, J. P., DiGangi, J., Zoeller, R. T., & Trasande, L.; “Exposure to endocrine-disrupting chemicals in the USA: a population-based disease burden and cost analysis;” Lancet Diabetes and Endocrinol, 2016, 4(12), 996-1003; DOI: 10.1016/S2213-8587(16)30275-3.
ABSTRACT:
BACKGROUND: Endocrine-disrupting chemicals (EDCs) contribute to disease and dysfunction and incur high associated costs (>1% of the gross domestic product [GDP] in the European Union). Exposure to EDCs varies widely between the USA and Europe because of differences in regulations and, therefore, we aimed to quantify disease burdens and related economic costs to allow comparison.
METHODS: We used existing models for assessing epidemiological and toxicological studies to reach consensus on probabilities of causation for 15 exposure-response relations between substances and disorders. We used Monte Carlo methods to produce realistic probability ranges for costs across the exposure-response relation, taking into account uncertainties. Estimates were made based on population and costs in the USA in 2010. Costs for the European Union were converted to US$ (euro1=$1.33).
FINDINGS: The disease costs of EDCs were much higher in the USA than in Europe ($340 billion [2.33% of GDP] vs $217 billion [1.28%]). The difference was driven mainly by intelligence quotient (IQ) points loss and intellectual disability due to polybrominated diphenyl ethers (11 million IQ points lost and 43 000 cases costing $266 billion in the USA vs 873 000 IQ points lost and 3290 cases costing $12.6 billion in the European Union). Accounting for probability of causation, in the European Union, organophosphate pesticides were the largest contributor to costs associated with EDC exposure ($121 billion), whereas in the USA costs due to pesticides were much lower ($42 billion).
INTERPRETATION: EDC exposure in the USA contributes to disease and dysfunction, with annual costs taking up more than 2% of the GDP. Differences from the European Union suggest the need for improved screening for chemical disruption to endocrine systems and proactive prevention.
FUNDING: Endocrine Society, Ralph S French Charitable Foundation, and Broad Reach Foundation. FULL TEXT
Soffritti et al., 2002
Soffritti, Morando, Belpoggi, Fiorella, Minardi, Franco, & Maltoni, Cesare; “Ramazzini Foundation Cancer Program: History and Major Projects, Life-Span Carcinogenicity Bioassay Design, Chemicals Studied, and Results;” Annals of the New York Academy of Sciences, 2002, 982, 26-45.
ABSTRACT:
The Ramazzini Foundation research program was started over thirty years ago. The features of this program are: (1) systematic and integrated project design; (2) consistency over time; (3) homogeneity of approach: key members of the team remain unchanged; and (4) choice to work on new frontiers of scientific research. The program centers mainly on three projects: Project 1: experimental carcinogenicity bioassays; Project 2: experimental anticarcinogenesis assays to identify factors and active principles (compounds) capable of opposing the onset of tumors while being suitable for preventive/ chemopreventive intervention; Project 3: epidemiological studies, both descriptive and analytical, on tumor incidence and mortality in persons professionally and environmentally exposed to industrial carcinogenic risks. The project involving experimental carcinogenicity bioassays for the identification of exogenous carcinogens (environmental and industrial above all) began in 1966. This project has included 398 experimental bioassays on 200 compounds/ agents using some 148,000 animals monitored until their spontaneous death. Among the studies already concluded, 47 agents have shown “clear evidence” of carcinogenicity. The results have demonstrated for the first time that (1) vinyl chloride can cause liver angiosarcoma as well as other tumors; (2) benzene is carcinogenic in experimental animals for various tissues and organs; (3) formaldehyde may produce lymphomas and leukemias; and (4) methyl-tertbutyl ether (MTBE), the most common oxygenated additive used in gasolines, can cause lymphomas/leukemias. Many of the results achieved have led to the introduction of norms and measures of primary prevention. FULL TEXT
Ford and Schust, 2009
Ford, Holly B., & Schust, Danny J.; “Recurrent pregnancy loss: etiology, diagnosis, and therapy;” Reviews in Obstetrics & Gynecology, 2009, 2(2), 76-83.
ABSTRACT:
Spontaneous pregnancy loss is a surprisingly common occurrence, with approximately 15% of all clinically recognized pregnancies resulting in pregnancy failure. Recurrent pregnancy loss (RPL) has been inconsistently defined. When defined as 3 consecutive pregnancy losses prior to 20 weeks from the last menstrual period, it affects approximately 1% to 2% of women. This review highlights the current understanding of the various etiologies implicated in RPL, including factors known to be causative, as well as those implicated as possible causative agents. The appropriate diagnostic evaluation, therapy, and prognosis are also addressed. FULL TEXT