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Bibliography Index

Weichenthal et al., 2010

Scott Weichenthal, Connie Moase, and Peter Chan, “A Review of Pesticide Exposure and Cancer Incidence in the Agricultural Health Study Cohort,” Environmental Health Perspectives, 118, DOI: 10.1289/ehp.0901731

ABSTRACT:

OBJECTIVE: We reviewed epidemiologic evidence related to occupational pesticide exposures and cancer incidence in the Agricultural Health Study (AHS) cohort.

DATA SOURCES: Studies were identified from the AHS publication list available at http://aghealth.nci.nih.gov as well as through a Medline/PubMed database search in March 2009. We also examined citation lists. Findings related to lifetime-days and/or intensity-weighted lifetime-days of pesticide use are the primary focus of this review, because these measures allow for the evaluation of potential exposure–response relationships.

DATA SYNTHESIS: We reviewed 28 studies; most of the 32 pesticides examined were not strongly associated with cancer incidence in pesticide applicators. Increased rate ratios (or odds ratios) and positive exposure–response patterns were reported for 12 pesticides currently registered in Canada and/or the United States (alachlor, aldicarb, carbaryl, chlorpyrifos, diazinon, dicamba, S-ethyl-N,N-dipropylthiocarbamate, imazethapyr, metolachlor, pendimethalin, permethrin, trifluralin). However, estimates of association for specific cancers were often imprecise because of small numbers of exposed cases, and clear monotonic exposure–response patterns were not always apparent. Exposure misclassification is also a concern in the AHS and may limit the analysis of exposure–response patterns. Epidemiologic evidence outside the AHS remains limited with respect to most of the observed associations, but animal toxicity data support the biological plausibility of relationships observed for alachlor, carbaryl, metolachlor, pendimethalin, permethrin, and trifluralin.

CONCLUSIONS: Continued follow-up is needed to clarify associations reported to date. In particular, further evaluation of registered pesticides is warranted.

FULL TEXT

Mesnage et al., 2016

Robin Mesnage, Sarah Z. Agapito-Tenfen, Vinicius Vilperte, George Renney, Malcolm Ward, Gilles-Eric Séralini, Rubens O. Nodari & Michael N. Antoniou, “An integrated multi-omics analysis of the NK603 Roundup-tolerant GM maize reveals metabolism  disturbances caused by the transformation process,” Nature: Scientific Reports, 2016, 6:37855, DOI: 10.1038/srep37855

ABSTRACT:

Glyphosate tolerant genetically modified (GM) maize NK603 was assessed as ‘substantially equivalent’ to its isogenic counterpart by a nutrient composition analysis in order to be granted market approval. We have applied contemporary in depth molecular profiling methods of NK603 maize kernels (sprayed or unsprayed with Roundup) and the isogenic corn to reassess its substantial equivalence status. Proteome profiles of the maize kernels revealed alterations in the levels of enzymes of glycolysis and TCA cycle pathways, which were reflective of an imbalance in energy metabolism. Changes in proteins and metabolites of glutathione metabolism were indicative of increased oxidative stress. The most pronounced metabolome differences between NK603 and its isogenic counterpart consisted of an increase in polyamines including N-acetyl-cadaverine (2.9-fold), N-acetylputrescine (1.8-fold), putrescine (2.7-fold) and cadaverine (28-fold), which depending on context can be either protective or a cause of toxicity. Our molecular profiling results show that NK603 and its isogenic control are not substantially equivalent. FULL TEXT

Paz-y-Miño et al., 2007

César Paz-y-Miño, María Eugenia Sánchez,  Melissa Arévalo,  María José Muñoz, Tania Witte, Gabriela Oleas De-la-Carrera,  Paola E. LeoneI, “Evaluation of DNA damage in an Ecuadorian population exposed to glyphosate,” Genetics and Molecular Biology, 2007, 30:2, DOI: 10.1590/S1415-47572007000300026

ABSTRACT:

We analyzed the consequences of aerial spraying with glyphosate added to a surfactant solution in the northern part of Ecuador. A total of 24 exposed and 21 unexposed control individuals were investigated using the comet assay. The results showed a higher degree of DNA damage in the exposed group (comet length = 35.5 µm) compared to the control group (comet length = 25.94 µm). These results suggest that in the formulation used during aerial spraying glyphosate had a genotoxic effect on the exposed individuals. FULL TEXT

 

Alvarez-Moya et al., 2014

Carlos Alvarez-Moya, Mónica Reynoso Silva, Carlos Valdez Ramírez, David Gómez Gallardo, Rafael León Sánchez, Alejandro Canales Aguirre, Alfredo Feria Velasco, “Comparison of the in vivo and in vitro genotoxicity of glyphosate isopropylamine salt in three different organisms,” Genetics and Molecular Biology, 2014, 37:1, DOI: 10.1590/S1415-47572014000100016

ABSTRACT:

There is considerable controversy with regard to the genotoxicity of glyphosate, with some reports stating that this compound is non-toxic for fish, birds and mammals. In this work, we used the comet assay to examine the genotoxicity of glyphosate isopropylamine (0.7, 7, 70 and 700 µM) in human lymphocytes, erythrocytes of Oreochromis niloticus and staminal nuclei of Tradescantia (4430) in vitro and in vivo. Cells, nuclei and fish that had and had not been exposed to 5 mM N-nitrosodiethylamine (NDEA) were used as positive and negative controls, respectively. Significant (p < 0.01) genetic damage was observed in vivo and in vitro in all cell types and organisms tested. Human lymphocytes and Tradescantia hairs showed lower genetic damage in vivo compared to in vitro, possibly because of efficient metabolization of the herbicide. In O. niloticus erythrocytes, significant (p < 0.001) genotoxicity was observed at > 7 µM, whereas in vitro, glyphosphate was genotoxic in human lymphocytes and Tradescantia hairs at > 0.7 µM. These results indicate that glyphosate is genotoxic in the cells and organisms studied at concentrations of 0.7-7 µM. FULL TEXT

 

Avila-Vazquez et al., 2017

Medardo Avila-Vazquez, Eduardo Maturano, Agustina Etchegoyen, Flavia Silvina Difilippo, Bryan Maclean, “Association between Cancer and Environmental Exposure to Glyphosate,” International Journal of Clinical Medicine, 2017, 8:2, DOI: 10.4236/ijcm.2017.82007

ABSTRACT:

BACKGROUND: Argentina, Brazil, Paraguay and Uruguay farm transgenic seeds glyphosate resistant. Argentina annually utilizes 240,000 tonnes of glyphosate in agriculture. A change in the profile of morbidity and mortality is perceived in agricultural areas; cancer seems to prevail. Monte Maíz is a typical argentine agricultural town with 8000 inhabitants; the Mayor and residents of Monte Maiz requested an environmental health study due to perceived increase in cancer frequencies.

METHODS: An exploratory ecological study was developed to assess the urban environmental contamination and the frequencies and distribution of cancer through an environmental analysis of pollution sources including measurements of pesticides in water, soil and grain dust, and a cross-sectional study of cancer patients that explore associations with different variables.

RESULTS: 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 are used annually in the region and manipulated inner town. We do not find other relevant sources of pollution. Cancer incidence, prevalence, and mortality are between two and three times higher than the reference values (Globocan 2012, WHO) for the entire nation (706/100,000 persons vs. 217/100,000; 2123/100,000 persons vs. 883.82/100,000 and 383/100,000 persons vs. 115.13/100,000, respectively).

CONCLUSION: This study detects high glyphosate pollution in association with increased frequencies of cancer in a typical argentine agricultural village, and by design, cannot make claims of causality. Other study designs are required, but if we corroborate the concrescence of high exposure to glyphosate and cancer. FULL TEXT

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

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