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Bibliography Index

Bradman et al., 2013

Bradman, Asa; Kogut, Katherine; Eisen, Ellen A; Jewell, Nicholas P; Quiros-Alcala, Lesliam; Castorina, Rosemary; Chevrier, Jonathan; Holland, Nina T;  Barr, Dana Boyd; Kavanagh-Baird, Geri; Eskenazi, Brenda, “Variability of organophosphorous pesticide metabolite levels in spot and 24-hr urine samples collected from young children during 1 week,” Environmental Health Perspectives, 2013, 121:118-124. DOI:10.1289/ehp.1104808.

ABSTRACT:

BACKGROUND: Dialkyl phosphate (DAP) metabolites in spot urine samples are frequently used to characterize children’s exposures to organophosphorous (OP) pesticides. However, variable exposure and short biological half-lives of OP pesticides could result in highly variable measurements, leading to exposure misclassification.

OBJECTIVE: We examined within- and between-child variability in DAP metabolites in urine samples collected during 1 week.

METHODS: We collected spot urine samples over 7 consecutive days from 25 children (3-6 years of age). On two of the days, we collected 24-hr voids. We assessed the reproducibility of urinary DAP metabolite concentrations and evaluated the sensitivity and specificity of spot urine samples as predictors of high (top 20%) or elevated (top 40%) weekly average DAP metabolite concentrations.

RESULTS: Within-child variance exceeded between-child variance by a factor of two to eight, depending on metabolite grouping. Although total DAP concentrations in single spot urine samples were moderately to strongly associated with concentrations in same-day 24-hr samples (r approximately 0.6-0.8, p < 0.01), concentrations in spot samples collected > 1 day apart and in 24-hr samples collected 3 days apart were weakly correlated (r approximately -0.21 to 0.38). Single spot samples predicted high (top 20%) and elevated (top 40%) full-week average total DAP excretion with only moderate sensitivity ( approximately 0.52 and approximately 0.67, respectively) but relatively high specificity ( approximately 0.88 and approximately 0.78, respectively).

CONCLUSIONS: The high variability we observed in children’s DAP metabolite concentrations suggests that single-day urine samples provide only a brief snapshot of exposure. Sensitivity analyses suggest that classification of cumulative OP exposure based on spot samples is prone to type 2 classification errors.  FULL TEXT

Bradman et al., 2003

Bradman A, Barr DB, Claus Henn BG, Drumheller T, Curry C, Eskenazi B, “Measurement of pesticides and other toxicants in amniotic fluid as a potential biomarker of prenatal exposure: a validation study,” Environmental Health Perspectives, 2003, 111:1779-1782. DOI:10.1289/ehp.6259.

ABSTRACT:

Prenatal pesticide exposures may adversely affect children’s health. However, exposure and health research is hampered by the lack of reliable fetal exposure data. No studies have been published that report measurements of commonly used nonpersistent pesticides in human amniotic fluid, although recent studies of pesticides in urine from pregnant women and in meconium indicate that fetuses are exposed to these chemicals. Amniotic fluid collected during amniocentesis is the only medium available to characterize direct fetal exposures early in pregnancy (approximately 18 weeks of gestation). As a first step in validating this exposure biomarker, we collected 100 amniotic fluid samples slated for disposal and evaluated analytical methods to measure organophosphate and carbamate pesticides and metabolites, synthetic pyrethroid metabolites, herbicides, and chlorinated phenolic compounds. The following six phenols were detected (detection frequency): 1- and 2-naphthol (70%), 2,5-dichlorophenol (55%), carbofuranphenol (5%), ortho-phenylphenol (30%), and pentachlorophenol (15%), with geometric mean concentrations of 0.72, 0.39, 0.12, 0.13, and 0.23 microg/L, respectively, for positive values. The organophosphate metabolites diethylphosphate and dimethylphosphate were detected in two (10%) samples, and dimethylthiophosphate was detected in one (5%) sample, with geometric mean concentrations of 0.31, 0.32, and 0.43 microg/L, respectively, for positive values. These levels are low compared with levels reported in urine, blood, and meconium in other studies, but indicate direct exposures to the young fetus, possibly during critical periods of development. Results of this pilot study suggest that amniotic fluid offers a unique opportunity to investigate fetal exposures and health risks.  FULL TEXT

Samarasinghe, 2013-2014

Buddhini Samarasinghe, “The Hallmarks of Cancer, Parts 1-9,” Scientific American, September 1, 2013-October 8, 2014.

SUMMARY:

The Hallmarks of Cancer are the ten characteristics that differentiate a cancer cell from a normal cell. Over the course of a year, science translator Dr. Buddhini Samarasinghe tackled each of the the ten Hallmarks of Cancer in a guest blog series for Scientific American.

The blogs break down the basic biology of each Hallmark and what happens when the system breaks down. It is important to understand these Hallmarks as we investigate the influence of chemicals and how they may act individually and in groups to disrupt enough of these Hallmark mechanisms to cause cancer.

Why is this paper so important? Cancer, as we know by now, is an incredibly complicated disease. A single tumor sample could have over a hundred different mutations; nearly one in every two hundred genes in the human genome. If two breast cancer specimens are compared, the set of mutated genes are far from identical. Every tumor is unique. Weinberg and Hanahan simplified this dauntingly complex disease to six underlying principles. The hugely complicated beast that is cancer, so diverse that even the same organ can have many different tumor types, was reduced to just six common traits that every single cancer shares, to facilitate that transformation from a normal cell to a cancer cell. It answers the ‘how does cancer happen’ question very elegantly, and we gain insight into all the different things that go wrong in a cancer cell.  FULL TEXT

Pallett, 2018

Pallett K, “Engineered Crop Tolerance to Glyphosate and its Impact on the Use of the Herbicide,” Outlooks on Pest Management, December 2018. doi:10.1564/v29_dec_11.

ABSTRACT:

The agricultural importance and particularly the consequences of the use of glyphosate in crops engineered to be tolerant to this non-selective herbicide is discussed in some of the other articles in this special issue of Outlooks on Pest Management. However, a specific article reviewing the science and magnitude of what can be considered as a major scientific development in plant science is justified and is the most important aspect of the success of this herbicide (Duke & Powles, 2008). FULL TEXT

Richmond, 2018

Richmond, Martha E., “Glyphosate: A review of its global use, environmental impact, and potential health effects on humans and other species,” Journal of Environmental Studies and Sciences, Published online 09/28/2018, doi:10.1007/s13412-018-0517-2.

ABSTRACT:

Glyphosate, [N-(phosphonomethyl) glycine], was synthesized in 1950 and patented as a chemical chelator, capable of binding metals such as calcium, magnesium, and manganese. Glyphosate’s ability to bind to manganese was later found to inhibit an enzyme used by plants and bacteria for biosynthesis ofthree amino acids found in all proteins, and the commercial value ofthis property led to the development and marketing of glyphosate as a broad-spectrum herbicide. In 1974, the Monsanto Chemical Company introduced the herbicide as Roundup™, a formulation of glyphosate and adjuvants. Roundup™ was originally used for weed control in specific farming and landscaping operations and around power lines and train tracks. Following introduction of Roundup Ready™ seeds, in the 1990s, glyphosate use increased significantly. Although Monsanto’s patent on glyphosate expired in 2002, the widespread and growing use ofRoundup Ready™ seed globally and competitive glyphosate marketing by other chemical companies have led to glyphosate’s significant increase in the environment. Concerns about potential adverse effects have also grown. While, at present, many regulatory agencies have determined that there is little risk of adverse health effects to the general public or to farmworkers using proper handling techniques, the International Agency for Research on Cancer (IARC) assessing hazard data on glyphosate identified it in 2016 as a category 2A carcinogen (likely to cause human cancer). Response to this classification has been divided: The agribusiness industry has been forceful in its opposition, while other experts support IARC’s classification. The following article examines these issues. It also examines the basis for regulatory decisions, controversies involved, and questions of environmental justice that may or may not be addressed as glyphosate continues to be used. FULL TEXT

Panzacchi et al., 2018

Panzacchi, S., Mandrioli, D., Manservisi, F., Bua, L., Falcioni, L., Spinaci, M., Galeati, G., Dinelli, G., Miglio, R., Mantovani, A., Lorenzetti, S., Hu, J., Chen, J., Perry, M. J., Landrigan, P. J., & Belpoggi, F. “The Ramazzini Institute 13-week study on glyphosate-based herbicides at human-equivalent dose in Sprague Dawley rats: study design and first in-life endpoints evaluation,” Environmental Health, 17(1), 52, 2018.  doi:10.1186/s12940-018-0393-y.

ABSTRACT:

BACKGROUND: Glyphosate-based herbicides (GBHs) are the most widely used pesticides worldwide, and glyphosate is the active ingredient of such herbicides, including the formulation known as Roundup. The massive and increasing use of GBHs results in not only the global burden of occupational exposures, but also increased exposure to the general population. The current pilot study represents the first phase of a long-term investigation of GBHs that we are conducting over the next 5 years. In this paper, we present the study design, the first evaluation of in vivo parameters and the determination of glyphosate and its major metabolite aminomethylphosphonic acid (AMPA) in urine.

METHODS: We exposed Sprague-Dawley (SD) rats orally via drinking water to a dose of glyphosate equivalent to the United States Acceptable Daily Intake (US ADI) of 1.75 mg/kg bw/day, defined as the chronic Reference Dose (cRfD) determined by the US EPA, starting from prenatal life, i.e. gestational day (GD) 6 of their mothers. One cohort was continuously dosed until sexual maturity (6-week cohort) and another cohort was continuously dosed until adulthood (13-week cohort). Here we present data on general toxicity and urinary concentrations of glyphosate and its major metabolite AMPA.

RESULTS: Survival, body weight, food and water consumption of the animals were not affected by the treatment with either glyphosate or Roundup. The concentration of both glyphosate and AMPA detected in the urine of SD rats treated with glyphosate were comparable to that observed in animals treated with Roundup, with an increase in relation to the duration of treatment. The majority of glyphosate was excreted unchanged. Urinary levels of the parent compound, glyphosate, were around 100-fold higher than the level of its metabolite, AMPA.

CONCLUSIONS: Glyphosate concentrations in urine showed that most part of the administered dose was excreted as unchanged parent compound upon glyphosate and Roundup exposure, with an increasing pattern of glyphosate excreted in urine in relation to the duration of treatment. The adjuvants and the other substances present in Roundup did not seem to exert a major effect on the absorption and excretion of glyphosate. Our results demonstrate that urinary glyphosate is a more relevant marker of exposure than AMPA in the rodent model. FULL TEXT

Mao et al., 2018

Mao, Q., Manservisi, F., Panzacchi, S., Mandrioli, D., Menghetti, I., Vornoli, A., Bua, L., Falcioni, L., Lesseur, C., Chen, J., Belpoggi, F., & Hu, J., “The Ramazzini Institute 13-week pilot study on glyphosate and Roundup administered at human-equivalent dose to Sprague Dawley rats: effects on the microbiome,” Environmental Health, 17(1), 50, 2018. doi:10.1186/s12940-018-0394-x.

ABSTRACT:

BACKGROUND: Glyphosate-based herbicides (GBHs) are broad-spectrum herbicides that act on the shikimate pathway in bacteria, fungi, and plants. The possible effects of GBHs on human health are the subject of an intense public debate for both its potential carcinogenic and non-carcinogenic effects, including its effects on microbiome. The present pilot study examines whether exposure to GBHs at doses of glyphosate considered to be “safe” (the US Acceptable Daily Intake – ADI – of 1.75 mg/kg bw/day), starting from in utero, may modify the composition of gut microbiome in Sprague Dawley (SD) rats.

METHODS: Glyphosate alone and Roundup, a commercial brand of GBHs, were administered in drinking water at doses comparable to the US glyphosate ADI (1.75 mg/kg bw/day) to F0 dams starting from the gestational day (GD) 6 up to postnatal day (PND) 125. Animal feces were collected at multiple time points from both F0 dams and F1 pups. The gut microbiota of 433 fecal samples were profiled at V3-V4 region of 16S ribosomal RNA gene and further taxonomically assigned and assessed for diversity analysis. We tested the effect of exposure on overall microbiome diversity using PERMANOVA and on individual taxa by LEfSe analysis.

RESULTS: Microbiome profiling revealed that low-dose exposure to Roundup and glyphosate resulted in significant and distinctive changes in overall bacterial composition in F1 pups only. Specifically, at PND31, corresponding to pre-pubertal age in humans, relative abundance for Bacteriodetes (Prevotella) was increased while the Firmicutes (Lactobacillus) was reduced in both Roundup and glyphosate exposed F1 pups compared to controls.

CONCLUSIONS: This study provides initial evidence that exposures to commonly used GBHs, at doses considered safe, are capable of modifying the gut microbiota in early development, particularly before the onset of puberty. These findings warrant future studies on potential health effects of GBHs in early development such as childhood. FULL TEXT

Landrigan and Belpoggi, 2018

Landrigan, P. J., and Belpoggi, F.,”The need for independent research on the health effects of glyphosate-based herbicides,” Environmental Health, 17(1), 51, 2018, doi:10.1186/s12940-018-0392-z.

ABSTRACT:

BACKGROUND: Glyphosate, formulated as Roundup, is the world’s most widely used herbicide. Glyphosate is used extensively on genetically modified (GM) food crops designed to tolerate the herbicide, and global use is increasing rapidly. Two recent reviews of glyphosate’s health hazards report conflicting results. An independent review by the International Agency for Research on Cancer (IARC) found that glyphosate is a “probable human carcinogen”. A review by the European Food Safety Agency (EFSA) found no evidence of carcinogenic hazard. These differing findings have produced regulatory uncertainty.

REGULATORY ACTIONS: Reflecting this regulatory uncertainty, the European Commission on November 27 2017, extended authorization for glyphosate for another 5 years, while the European Parliament opposed this decision and issued a call that pesticide approvals be based on peer-reviewed studies by independent scientists rather than on the current system that relies on proprietary industry studies.

RAMAZZINI INSTITUTE RESPONSE: The Ramazzini Institute has initiated a pilot study of glyphosate’s health hazards that will be followed by an integrated experimental research project. This evaluation will be independent of industry support and entirely sponsored by worldwide crowdfunding. The aim of the Ramazzini Institute project is to explore comprehensively the effects of exposures to glyphosate-based herbicides at current real-world levels on several toxicological endpoints, including carcinogenicity, long-term toxicity, neurotoxicity, endocrine disrupting effects, prenatal developmental toxicity, the microbiome and multi-generational effects. FULL TEXT

Harari et al., 2010

Harari, Raul, Julvez, Jordi, Murata, Katsuyuki, Barr, Dana, Bellinger, David C., Debes, Frodi, & Grandjean, Philippe, “Neurobehavioral deficits and increased blood pressure in school-age children prenatally exposed to pesticides,” Environmental Health Perspectives, 118, 890-896, 2010, doi:10.1289/ehp.0901582.

ABSTRACT:

BACKGROUND: The long-term neurotoxicity risks caused by prenatal exposures to pesticides are unclear, but a previous pilot study of Ecuadorian school children suggested that blood pressure and visuospatial processing may be vulnerable.

OBJECTIVES: In northern Ecuador, where floriculture is intensive and relies on female employment, we carried out an intensive cross-sectional study to assess children’s neurobehavioral functions at 6-8 years of age.

METHODS: We examined all 87 children attending two grades in the local public school with an expanded battery of neurobehavioral tests. Information on pesticide exposure during the index pregnancy was obtained from maternal interview. The children’s current pesticide exposure was assessed from the urinary excretion of organophosphate metabolites and erythrocyte acetylcholine esterase activity.

RESULTS: Of 84 eligible participants, 35 were exposed to pesticides during pregnancy via maternal occupational exposure, and 23 had indirect exposure from paternal work. Twenty-two children had detectable current exposure irrespective of their prenatal exposure status. Only children with pre-natal exposure from maternal greenhouse work showed consistent deficits after covariate adjustment, which included stunting and socioeconomic variables. Exposure-related deficits were the strongest for motor speed (Finger Tapping Task), motor coordination (Santa Ana Form Board), visuospatial performance (Stanford-Binet Copying Test), and visual memory (Stanford-Binet Copying Recall Test). These associations corresponded to a developmental delay of 1.5-2 years. Prenatal pesticide exposure was also significantly associated with an average increase of 3.6 mmHg in systolic blood pressure and a slight decrease in body mass index of 1.1 kg/m2. Inclusion of the pilot data strengthened these results.

CONCLUSIONS: These findings support the notion that prenatal exposure to pesticides-at levels not producing adverse health outcomes in the mother-can cause lasting adverse effects on brain development in children. Pesticide exposure therefore may contribute to a “silent pandemic” of developmental neurotoxicity. FULL TEXT

Gullickson, 2018

Gil Gullickson, “Minnesota Dicamba Temperature, Cutoff Dates Credited for Less Off-Target Movement,”  Successful Farming, Published Online September 27, 2018.

SUMMARY:

Looks at upcoming re-registration decision on dicamba by EPA.  Reports that “in 2017, inquiries regarding off-target dicamba in the Roundup Ready 2 Xtend system tallied 99 inquires per 1 million acres. This year, it’s down to 13 per 1 million acres, and most revolved around weed-control issues, says Brett Begemann, Bayer Crop Science chief operating officer. Xtend soybean acreage is up, though, having doubled from last year’s 25 million acres to this year’s nearly 50 million acres.” Fact that 100,000 farmers and applicators attended dicamba training made a big difference. On Minnesota restrictions: “Compared with states that did not have cutoff dates, Minnesota had limited complaints of off-site dicamba movement in 2018, says Gunsolus. In 2017, there were over 250 reports of dicamba damage, he says. In 2018, MDA has so far fielded 52 reports of dicamba damage covering 1,850 acres, says Joshua Stamper, director of the pesticide and fertilizer management division for the MDA.” FULL TEXT

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