Avila-Vazquez et al., 2015

Medardo Avila-Vazquez, Agustina Etchegoyen, Eduardo Maturano and Luciana Ruderman, “Cancer and detrimental reproductive effects in an Argentine agricultural community environmentally exposed to glyphosate,” The Journal of Biological Physics and Chemistry, 2015, 15:3, DOI: 10.4024/09VA15A.jbpc.15.03

ABSTRACT:

Argentina utilizes about 200 000 tonnes of glyphosate for its agriculture each year. People living near the fields treated with glyphosate often mention an increase in cancer and reproductive alterations. In Monte Maiz, an agricultural settlement with approximate population 8000, we conducted an environmental test assessing water, soil and particulate material contamination as well as an epidemiological study to detect and locate cases of cancer, abortion and genetic abnormality. The site utilizes annually 650 tonnes of glyphosate applied over an area of 65 000 ha. The glyphosate is concentrated and prepared for dispersal in the settlement. We detected glyphosate in particulate material and grain husks and it was found to be present at an even higher concentration on the ground in the village than in the surrounding rural area. The rate of spontaneous abortion in Monte Maiz is three times higher than the national average and the rate of occurrence of genetic abnormality is about twice the national average. Cancer occurrence is between two and three times the reference values for the entire nation with regard to incidence, prevalence and mortality. Although it is of course impossible to establish direct causality, the indicators that emerge from the correlated variables strongly suggest a public health problem of significant proportions, requiring immediate attention.

McBirney et al., 2017

Margaux McBirney, Stephanie E. King, Michelle Pappalardo, Elizabeth Houser, Margaret Unkefer, Eric Nilsson, Ingrid Sadler-Riggleman, Daniel Beck, Paul Winchester, Michael K. Skinner, “Atrazine induced epigenetic transgenerational inheritance of disease, lean phenotype and sperm epimutation  pathology biomarkers,” PLOS One, 2017, 12:9, DOI: 10.1371/journal.pone.0184306

ABSTRACT:

Ancestral environmental exposures to a variety of environmental toxicants and other factors have been shown to promote the epigenetic transgenerational inheritance of adult onset disease. The current study examined the potential transgenerational actions of the herbicide atrazine. Atrazine is one of the most commonly used herbicides in the agricultural industry, in particular with corn and soy crops. Outbred gestating female rats were transiently exposed to a vehicle control or atrazine. The F1 generation offspring were bred to generate the F2 generation and then the F2 generation bred to generate the F3 generation. The F1, F2 and F3 generation control and atrazine lineage rats were aged and various pathologies investigated. The male sperm were collected to investigate DNA methylation differences between the control and atrazine lineage sperm. The F1 generation offspring (directly exposed as a fetus) did not develop disease, but weighed less compared to controls. The F2 generation (grand-offspring) was found to have increased frequency of testis disease and mammary tumors in males and females, early onset puberty in males, and decreased body weight in females compared to controls. The transgenerational F3 generation rats were found to have increased frequency of testis disease, early onset puberty in females, behavioral alterations (motor hyperactivity) and a lean phenotype in males and females. The frequency of multiple diseases was significantly higher in the transgenerational F3 generation atrazine lineage males and females. The transgenerational transmission of disease requires germline (egg or sperm) epigenetic alterations. The sperm differential DNA methylation regions (DMRs), termed epimutations, induced by atrazine were identified in the F1, F2 and F3 generations. Gene associations with the DMRs were identified. For the transgenerational F3 generation sperm, unique sets of DMRs (epimutations) were found to be associated with the lean phenotype or testis disease. These DMRs provide potential biomarkers for transgenerational disease. The etiology of disease appears to be in part due to environmentally induced epigenetic transgenerational inheritance, and epigenetic biomarkers may facilitate the diagnosis of the ancestral exposure and disease susceptibility. Observations indicate that although atrazine does not promote disease in the directly exposed F1 generation, it does have the capacity to promote the epigenetic transgenerational inheritance of disease.  FULL TEXT

Avila-Vazquez et al., 2018

Avila-Vazquez, M., Difilippo, F.S., Lean, B.M., Maturano, E. and Etchegoyen, A., “Environmental Exposure to Glyphosate and Reproductive Health Impacts in Agricultural Population of Argentina,” Journal of Environmental Protection, 2018, 9, DOI: 10.4236/jep.2018.93016.

ABSTRACT:

Argentina annually utilizes 240,000 tones of glyphosate in industrial agriculture and a change in the profile of morbidity is perceived for physicians of agricultural areas; now reproductive disorders seem to prevail. The objective of this study is to determine concurrence of glyphosate exposure and  reproductive disorders in a typical argentine agricultural town (Monte Maíz). An ecological study was developed with an environmental analysis of pollution sources including measurements of glyphosate and other pesticides and a cross-sectional study of spontaneous abortions and congenital abnormalities prevalence. Glyphosate was detected in soil and grain dust and was found to be at an even higher concentration in the village soil than in the rural area; 650 tonnes of glyphosate are used annually in the region and manipulated inner town contaminating the soil and dust in suspension of the town creating an burden of environmental exposure to glyphosate of 79 kg per person per year. We do not find other relevant sources of pollution. The spontaneous abortion and congenital abnormalities rates are three and two times higher than the national average reported by the national health (10% vs. 3% and 3% – 4.3% vs 1.4% respectively). Our study verified high environmental exposure to glyphosate in association with increased frequencies of reproductive disorders  (spontaneous abortion and congenital abnormalities) in argentine agricultural village, but is unable to make assertions cause-effect. Further studies are required with designs for such purposes. FULL TEXT

Lim et al., 2009

Soo Lim, Sun Young Ahn, In Chan Song, Myung Hee Chung, Hak Chul Jang, Kyong Soo Park, Ki-Up Lee, Youngmi Kim Pak , Hong Kyu Lee, “Chronic Exposure to the Herbicide, Atrazine, Causes Mitochondrial Dysfunction and Insulin Resistance,” PLOS One, 2009, 4:4, DOI: 10.1371/journal.pone.0005186

ABSTRACT:

There is an apparent overlap between areas in the USA where the herbicide, atrazine (ATZ), is heavily used and obesity-prevalence maps of people with a BMI over 30. Given that herbicides act on photosystem II of the thylakoid membrane of chloroplasts, which have a functional structure similar to mitochondria, we investigated whether chronic exposure to low concentrations of ATZ might cause obesity or insulin resistance by damaging mitochondrial function. Sprague-Dawley rats (n = 48) were treated for 5 months with low concentrations (30 or 300 µg kg⁻¹ day⁻¹) of ATZ provided in drinking water. One group of animals was fed a regular diet for the entire period, and another group of animals was fed a high-fat diet (40% fat) for 2 months after 3 months of regular diet. Various parameters of insulin resistance were measured. Morphology and functional activities of mitochondria were evaluated in tissues of ATZ-exposed animals and in isolated mitochondria. Chronic administration of ATZ decreased basal metabolic rate, and increased body weight, intra-abdominal fat and insulin resistance without changing food intake or physical activity level. A high-fat diet further exacerbated insulin resistance and obesity. Mitochondria in skeletal muscle and liver of ATZ-treated rats were swollen with disrupted cristae. ATZ blocked the activities of oxidative phosphorylation complexes I and III, resulting in decreased oxygen consumption. It also suppressed the insulin-mediated phosphorylation of Akt. These results suggest that long-term exposure to the herbicide ATZ might contribute to the development of insulin resistance and obesity, particularly where a high-fat diet is prevalent. FULL TEXT

Gillam, 2018

Carey Gillam, “Weedkiller found in granola and crackers, internal FDA emails show,” The Guardian, April 30, 2018.

SUMMARY:

A Freedom of Information Act request for internal FDA emails shows that recent testing for glyphosate residues in foods has revealed that “FDA has had trouble finding any food that does not carry traces of the pesticide.”  This is the first wide-scale quantification of herbicide residues in foods, and internal emails show that FDA scientists tested many common foods during informal testing to validate the process the agency would use to test official samples.  These samples are not “official” and would not be included in the upcoming residue report.  Some results have been above the legal threshold, such as a sample of corn where glyphosate was detected at 6.5 ppm, well over the legal limit of 5.0 ppm.  The FDA is also expanding residue testing for dicamba and 2.4-D as use of these herbicides is expected to rise in the near future with the introduction of new GE crops that are resistant to these active ingredients.  FULL TEXT

Di Renzo et al., 2015

Gian Carlo Di Renzo, Jeanne A. Conry, Jennifer Blake, Mark S. DeFrancesco, Nathaniel DeNicola, James N. Martin Jr., Kelly A. McCue, David Richmond, Abid Shah, Patrice Sutton, Tracey J. Woodruff, Sheryl Ziemin van der Poel, Linda C. Giudice, “International Federation of Gynecology and Obstetrics opinion on reproductive health impacts of exposure to toxic environmental chemicals,” International Journal of Gynecology and Obstetrics, 2015, 131, DOI: 10.1016/j.ijgo.2015.09.002

ABSTRACT:

Exposure to toxic environmental chemicals during pregnancy and breastfeeding is ubiquitous and is a threat to healthy human reproduction. There are tens of thousands of chemicals in global commerce, and even small exposures to toxic chemicals during pregnancy can trigger adverse health consequences. Exposure to toxic environmental chemicals and related health outcomes are inequitably distributed within and between countries; universally, the consequences of exposure are disproportionately borne by people with low incomes. Discrimination, other social factors, economic factors, and occupation impact risk of exposure and harm. Documented links between prenatal exposure to environmental chemicals and adverse health outcomes span the life course and include impacts on fertility and pregnancy, neurodevelopment, and cancer. The global health and economic burden related to toxic environmental chemicals is in excess of millions of deaths and billions of dollars every year. On the basis of accumulating robust evidence of exposures and adverse health impacts related to toxic environmental chemicals, the International Federation of Gynecology and Obstetrics (FIGO) joins other leading reproductive health professional societies in calling for timely action to prevent harm. FIGO recommends that reproductive and other health professionals advocate for policies to prevent exposure to toxic environmental chemicals, work to ensure a healthy food system for all, make environmental health part of health care, and champion environmental justice. FULL TEXT

Séralini et al., 2014

Gilles-Eric Séralini, Emilie Clair, Robin Mesnage, Steeve Gress, Nicolas Defarge, Manuela Malatesta, Didier Hennequin and Joël Spiroux de Vendômois, “Republished study: long-term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize,” Environmental Sciences Europe, Bridging Science and Regulation at the Regional and European Level, 2014, 26:14. DOI: 10.1186/s12302-014-0014-5

ABSTRACT

BACKGROUND: The health effects of a Roundup-tolerant NK603 genetically modified (GM) maize(from 11% in the diet), cultivated with or without Roundup application and Roundup alone (from 0.1 ppb of the full pesticide containing glyphosate and adjuvants) in drinking water, were evaluated for 2 years in rats. This study constitutes a follow-up investigation of a 90-day feeding study conducted by Monsanto in order to obtain commercial release of this GMO, employing the same rat strain and analyzing biochemical parameters on the same number of animals per group as our investigation. Our research represents the first chronic study on these substances, in which all observations including tumors are reported chronologically. Thus, it was not designed as a carcinogenicity study. We report the major findings with 34 organs observed and 56 parameters analyzed at 11 time points for most organs.

RESULTS: Biochemical analyses confirmed very significant chronic kidney deficiencies, for all treatments and both sexes; 76% of the altered parameters were kidney-related.In treated males, liver congestions and necrosis were 2.5 to 5.5 times higher.Marked and severe nephropathies were also generally 1.3 to 2.3 times greater. In females, all treatment groups showed a two- to threefold increase in mortality,and deaths were earlier. This difference was also evident in three male groups fed with GM maize. All results were hormone- and sex-dependent, and the pathological profiles were comparable. Females developed large mammary tumors more frequently and before controls; the pituitary was the second most disabled organ; the sex hormonal balance was modified by consumption of GM maize and Roundup treatments.Males presented up to four times more large palpable tumors starting 600 days earlier than in the control group, in which only one tumor was noted. These results may be explained by not only the non-linear endocrine-disrupting effects of Roundup but also by the over expression of the EPSPS transgene or other mutational effects in the GM maize and their metabolic consequences.

CONCLUSION: Our findings imply that long-term (2 year) feeding trials need to be conducted to thoroughly evaluate the safety of GM foods and pesticides in their full commercial formulations.  FULL TEXT

Lopes et al., 2014

Lopes FM, Varela Junior AS, Corcini CD, da Silva AC, Guazzelli VG, Tavares G, da Rosa CE, “Effect of glyphosate on the sperm quality of zebrafish Danio rerio,” Aquatic Toxicology, 2014, 155, DOI: 10.1016/j.aquatox.2014.07.006.

ABSTRACT

Glyphosate is a systemic, non-selective herbicide widely used in agriculture worldwide. It acts as an inhibitor of the enzyme 5-enolpyruvylshikimate-3-phosphate synthase by interrupting the synthesis of essential aromatic amino acids. This pathway is not present in animals, although some studies have shown that the herbicide glyphosate can affect fish reproduction. In this study, the effect of glyphosate on sperm quality of the fish Danio rerio was investigated after 24 and 96 h of exposure at concentrations of 5mg/L and 10mg/L. The spermatic cell concentration, sperm motility and motility period were measured employing conventional microscopy. The mitochondrial functionality, membrane integrity and DNA integrity were measured by fluorescence microscopy using specific probes. No significant differences in sperm concentration were observed; however, sperm motility and the motility period were reduced after exposure to both glyphosate concentrations during both exposure periods. The mitochondrial functionality and membrane and DNA integrity were also reduced at the highest concentration during both exposure periods. The results showed that glyphosate can induce harmful effects on reproductive parameters in D. rerio and that this change would reduce the fertility rate of these animals.

Armiliato et al., 2014

Armiliato N, Ammar D, Nezzi L, Straliotto M, Muller YM, Nazari EM, “Changes in ultrastructure and expression of steroidogenic factor-1 in ovaries of zebrafish Danio rerio exposed to glyphosate,” Journal of Toxicology and Environmental Health A, 2014, 77:7, DOI: 10.1080/15287394.2014.880393.

ABSTRACT

Glyphosate is a broad-spectrum organophosphate (OP) herbicide, highly soluble in water, and when applied in terrestrial systems it penetrates into soil, eventually reaching the aquatic community and affecting nontarget organisms. The aim of this study was to evaluate the toxicity of glyphosate on ovaries of zebrafish (Danio rerio). Ovaries (n = 18 per triplicate) were exposed to 65 μg/L of glyphosate [N-(phosphonomethyl) glycine] for 15 d. This concentration was determined according to Resolution 357/2005/CONAMA/Brazil, which establishes the permissible concentration of glyphosate in Brazilian inland waters. Nonexposed ovaries (n = 18 per triplicate) were used as control. Subsequently, morphology and expression of steroidogenic factor-1 (SF-1) of exposed and nonexposed ovaries was determined. No apparent changes were noted in general morphology of exposed and nonexposed ovaries. However, a significant increase in diameter of oocytes was observed after exposure to glyphosate. When ovarian ultrastructure was examined the presence of concentric membranes, appearing as myelin-like structures, associated with the external membranes of mitochondria and with yolk granules was found. After glyphosate exposure, immunohistochemistry and immunoblotting revealed greater expression of SF-1 in the oocytes, which suggests a relationship between oocyte growth and SF-1 expression. These subtle adverse effects of glyphosate on oocytes raised a potential concern for fish reproduction. These results contribute to understanding glyphosate-induced toxicity to nontarget organisms, showing subcellular and molecular impairments that may affect reproduction in +female fish.

Romano et al., 2011

Romano MA, Romano RM, Santos LD, Wisniewski P, Campos DA, de Souza PB, Viau P, Bernardi MM, Nunes MT, de Oliveira CA, “Glyphosate impairs male offspring reproductive development by disrupting gonadotropin expression.,” Archives in Toxicology, 2012, 86:4, DOI: 10.1007/s00204-011-0788-9.

ABSTRACT:

Sexual differentiation in the brain takes place from late gestation to the early postnatal days. This is dependent on the conversion of circulating testosterone into estradiol by the enzyme aromatase. The glyphosate was shown to alter aromatase activity and decrease serum testosterone concentrations. Thus, the aim of this study was to investigate the effect of gestational maternal glyphosate exposure (50 mg/kg, NOAEL for reproductive toxicity) on the reproductive development of male offspring. Sixty-day-old male rat offspring were evaluated for sexual behavior and partner preference; serum testosterone concentrations, estradiol, FSH and LH; the mRNA and protein content of LH and FSH; sperm production and the morphology of the seminiferous epithelium; and the weight of the testes, epididymis and seminal vesicles. The growth, the weight and age at puberty of the animals were also recorded to evaluate the effect of the treatment. The most important findings were increases in sexual partner preference scores and the latency time to the first mount; testosterone and estradiol serum concentrations; the mRNA expression and protein content in the pituitary gland and the serum concentration of LH; sperm production and reserves; and the height of the germinal epithelium of seminiferous tubules. We also observed an early onset of puberty but no effect on the body growth in these animals. These results suggest that maternal exposure to glyphosate disturbed the masculinization process and promoted behavioral changes and histological and endocrine problems in reproductive parameters. These changes associated with the hypersecretion of androgens increased gonadal activity and sperm production.