Shaw, 2017

William Shaw, PhD, “Elevated Urinary Glyphosate and Clostridia Metabolites With Altered Dopamine Metabolism in Triplets With Autistic Spectrum Disorder or Suspected Seizure Disorder: A Case Study,” Integrative Medicine, 2017, 16:1.

CONTEXT: Autism is a neurodevelopmental disorder for which a number of genetic, environmental, and nutritional causes have been proposed. Glyphosate is used widely as a crop desiccant and as an herbicide in fields of genetically modified foods that are glyphosate resistant. Several researchers have proposed that it may be a cause of autism, based on epidemiological data that correlates increased usage of glyphosate with an increased autism rate.

OBJECTIVE:  The current study was intended to determine if excessive glyphosate was present in the triplets and their parents and to evaluate biochemical findings for the family to determine the potential effects of its presence.

DESIGN: The author performed a case study with the cooperation of the parents and the attending physician.

SETTING: The study took place at The Great Plains Laboratory, Inc (Lenexa, KS, USA).

PARTICIPANTS: Participants were triplets, 2 male children and 1 female, and their parents. The 2 male children had autism, whereas the female had a possible seizure disorder. All 3 had elevated urinary glyphosate, and all of the triplets and their mother had elevated values of succinic acid or tiglylglycine, which are indicators of mitochondrial dysfunction.

INTERVENTION:
The participants received a diet of organic food only.

OUTCOME MEASURES:
The study performed organic acids, glyphosate, toxic chemicals and tiglylglycine, and creatinine testing of the participants’ urine.

RESULTS:
The 2 male triplets with autism had abnormalities on at least 1 organic acids test, including elevated phenolic compounds such as 4-cresol, 3-[3-hydroxyphenyl]-3-hydroxypropionic acid and 4-hydroxyphenylacetic acid, which have been previously associated with Clostridia bacteria and autism. The female, who was suspected of having a seizure disorder but not autism, did not have elevated phenolic compounds but did have a significantly elevated value of the metabolite tiglylglycine, a marker for mitochondrial dysfunction and/or mutations. One male triplet was retested postintervention and was found to have a markedly lower amount of glyphosate in his urine.

CONCLUSIONS:
The pattern of metabolites in the urine samples of the males with autism are consistent with a recent theory of autism that connects widespread glyphosate use with alteration of animal and human gastrointestinal flora. That theory is that the normally beneficial bacteria species that are sensitive to glyphosate are diminished and harmful bacteria species, such as Clostridia, that are insensitive to glyphosate, are increased following exposure to glyphosate. Excessive dopamine, caused by inhibition of dopamine-beta-hydroxylase by Clostridia metabolites, in turn, produces oxidative species that damage neuronal Krebs cycle enzymes, neuronal mitochondria, and neuronal structural elements such as the neurofibrils.  FULL TEXT

Kriebel et al., 2016

David Kriebel, ScD, Polly J. Hoppin, ScD, Molly M. Jacobs, MPH, Richard W. Clapp, DSc, “Environmental and Economic Strategies for Primary Prevention of Cancer in Early Life,” Pediatrics, 2016, 138:s1, DOI: 10.1542/peds.2015-4268

ABSTRACT:

This article summarizes the evidence for environmental toxic exposures contributing to cancers in early life, focusing on the most common cancer sites in this age group. It provides examples of widespread avoidable exposures to human carcinogens through air, water, and food and then describes recent examples of successful initiatives to reduce exposure to chemicals linked to these cancer sites, through government policy, industry initiatives, and consumer activism. State government initiatives to reduce toxic chemical exposures have made important gains; the Toxics Use Reduction Act of Massachusetts is now 25 years old and has been a major success story. There are a growing number of corporate initiatives to eliminate toxics, especially carcinogens, from the products they manufacture and sell. Another important opportunity for cancer prevention is provided by online databases that list chemicals, their toxicity, and lower-toxicity alternatives; these can be used by businesses, health care institutions, consumers, and workers to reduce exposures to chemicals of concern. The article concludes by inviting pediatricians and public health professionals to include elimination of carcinogen exposures in their work to promote primary prevention of cancer in early life. FULL TEXT

Lerro et al., 2017

Catherine C. Lerro, Laura E. Beane Freeman, Lützen Portengen, Daehee Kang, Kyoungho Lee, Aaron Blair, Charles F. Lynch, Berit Bakke, Anneclaire J. De Roos, and Roel C.H. Vermeulen, “A longitudinal study of atrazine and 2,4-D exposure and oxidative stress markers among Iowa corn farmers,” Environmental and Molecular Mutagenesis, 2017, 58, DOI: 10.1002/em.22069

ABSTRACT:

Reactive oxygen species, potentially formed through environmental exposures, can overwhelm an organism’s antioxidant capabilities resulting in oxidative stress. Long-term oxidative stress is linked with chronic diseases. Pesticide exposures have been shown to cause oxidative stress in vivo. We utilized a longitudinal study of corn farmers and non-farming controls in Iowa to examine the impact of exposure to the widely used herbicides atrazine and 2,4-dichlorophenoxyacetic acid (2,4-D) on markers of oxidative stress. 225 urine samples were collected during five agricultural time periods (pre-planting, planting, growing, harvest, off-season) for 30 farmers who applied pesticides occupationally and 10 controls who did not; all were non-smoking men ages 40–60. Atrazine mercapturate (atrazine metabolite), 2,4-D, and oxidative stress markers (malondialdehyde [MDA], 8-hydroxy-2′-deoxyguanosine [8-OHdG], and 8-isoprostaglandin-F_2α [8-isoPGF]) were measured in urine. We calculated β estimates and 95% confidence intervals (95%CI) for each pesticide-oxidative stress marker combination using multivariate linear mixed-effect models for repeated measures. Farmers had higher urinary atrazine mercapturate and 2,4-D levels compared to controls. In regression models, after natural log transformation, 2,4-D was associated with elevated levels of 8-OHdG (β=0.066, 95%CI=0.008–0.124) and 8-isoPGF (β=0.088, 95%CI=0.004–0.172). 2,4-D may be associated with oxidative stress because of modest increases in 8-OHdG, a marker of oxidative DNA damage, and 8-isoPGF, a product of lipoprotein peroxidation, with recent 2,4-D exposure. Future studies should investigate the role of 2,4-D-induced oxidative stress in the pathogenesis of human diseases.  FULL TEXT

Winston et al., 2016

Jennifer J. Winston, Michael Emch, Robert E. Meyer, Peter Langlois, Peter Weyer, Bridget Mosley, Andrew F. Olshan, Lawrence E. Band, Thomas J. Luben and the National Birth Defects Prevention Study, “Hypospadias and maternal exposure to atrazine via drinking water in the National Birth Defects Prevention study,” Environmental Health, 15:76, DOI: 10.1186/s12940-016-0161-9

ABSTRACT:

BACKGROUND: Hypospadias is a relatively common birth defect affecting the male urinary tract. It has been suggested that exposure to endocrine disrupting chemicals might increase the risk of hypospadias by interrupting normal urethral development.

METHODS: Using data from the National Birth Defects Prevention Study, a population-based case-control study, we considered the role of maternal exposure to atrazine, a widely used herbicide and potential endocrine disruptor, via drinking water in the etiology of 2nd and 3rd degree hypospadias. We used data on 343 hypospadias cases and 1,422 male controls in North Carolina, Arkansas, Iowa, and Texas from 1998–2005. Using catchment level stream and groundwater contaminant models from the US Geological Survey, we estimated atrazine concentrations in public water supplies and in private wells. We assigned case and control mothers to public water supplies based on geocoded maternal address during the critical window of exposure for hypospadias (i.e., gestational weeks 6–16). Using maternal questionnaire data about water consumption and drinking water, we estimated a surrogate for total maternal consumption of atrazine via drinking water. We then included additional maternal covariates, including age, race/ethnicity, parity, and plurality, in logistic regression analyses to consider an association between atrazine and hypospadias.

RESULTS: When controlling for maternal characteristics, any association between hypospadias and daily maternal atrazine exposure during the critical window of genitourinary development was found to be weak or null (odds ratio for atrazine in drinking water = 1. 00, 95 % CI = 0.97 to 1.03 per 0.04 μg/day increase; odds ratio for maternal consumption = 1.02, 95 % CI = 0.99 to 1.05; per 0.05 μg/day increase).

CONCLUSIONS: While the association that we observed was weak, our results suggest that additional research into a possible association between atrazine and hypospadias occurrence, using a more sensitive exposure metric, would be useful.  FULL TEXT

Lebov et al., 2016

Jill F. Lebov, MSPH, PhD, Lawrence S. Engel, PhD, David Richardson, PhD, Susan L. Hogan, PhD, Jane A. Hoppin, ScD, and Dale P. Sandler, PhD, “Pesticide use and risk of end-stage renal disease among licensed pesticide applicators in the Agricultural Health Study,” Occupational and Environmental Medicine, 2016, 7, DOI: 10.1136/oemed-2014-102615

ABSTRACT:

OBJECTIVES: Experimental studies suggest a relationship between pesticide exposure and renal impairment, but epidemiological evidence is limited. We evaluated the association between exposure to 41 specific pesticides and end-stage renal disease (ESRD) incidence in the Agricultural Health Study (AHS), a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina.

METHODS: Via linkage to the United States Renal Data System, we identified 320 ESRD cases diagnosed between enrollment (1993-1997) and December 2011 among 55,580 male licensed pesticide applicators. Participants provided pesticide use information via self-administered questionnaires. Lifetime pesticide use was defined as the product of duration and frequency of use and then modified by an intensity factor to account for differences in pesticide application practices. Cox proportional hazards models, adjusted for age and state, were used to estimate associations between ESRD and: 1) ordinal categories of intensity-weighted lifetime use of 41 pesticides, 2) poisoning and high-level pesticide exposures, and 3) pesticide exposure resulting in a medical visit or hospitalization.

RESULTS: Positive exposure-response trends were observed for the herbicides alachlor, atrazine, metolachlor, paraquat, and pendimethalin, and the insecticide chlordane. More than one medical visit due to pesticide use (HR = 2.13; 95% CI: 1.17, 3.89) and hospitalization due to pesticide use (HR = 3.05; 95% CI: 1.67, 5.58) were significantly associated with ESRD.

CONCLUSIONS: Our findings support an association between ESRD and chronic exposure to specific pesticides and suggest pesticide exposures resulting in medical visits may increase the risk of ESRD. FULL TEXT

Agopian et al., 2013a

A.J. Agopian, PhD, Yi Cai, MS, Peter H. Langlois, PhD, Mark A. Canfield, PhD, and Philip J. Lupo, PhD, “Maternal Residential Atrazine Exposure and Risk for Choanal Atresia and Stenosis in Offspring,” Journal of Pediatrics 2013, 162:3, DOI: 10.1016/j.jpeds.2012.08.012

ABSTRACT:

OBJECTIVE: To assess the relationship between estimated residential maternal exposure to atrazine during pregnancy and the risk for choanal atresia or stenosis in offspring.

STUDY DESIGN: Data for 280 nonsyndromic cases and randomly selected, population-based controls delivered between 1999 and 2008 were obtained from the Texas Birth Defects Registry. County-level estimates of atrazine levels obtained from the US Geological Survey were assigned to cases and controls based on maternal county of residence at delivery. Unconditional logistic regression was used to assess the relationship between maternal residential atrazine exposure and the risk for choanal atresia or stenosis in offspring.

RESULTS: Compared with offspring of mothers with low levels of estimated residential atrazine exposure, those with high levels had nearly a 2-fold increase in risk for choanal atresia or stenosis (aOR, 1.79; 95% CI, 1.17-2.74). A significant linear trend was also observed with increasing levels of atrazine exposure (adjusted P = .002).

CONCLUSION: A link between maternal exposure to endocrine disruptors, such as atrazine, and the risk of choanal atresia is plausible based on previous findings. Our results lend further support to this hypothesis.  FULL TEXT

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:

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