Wijkstrom et al., 2018
Wijkstrom, Julia; Jayasumana, Channa; Dassanayake, Rajeewa; Priyawardane, Nalin; Godakanda, Nimali; Siribaddana, Sisira; Ring, Anneli; Hultenby, Kjell
Soderberg, Magnus; Elinder, Carl-Gustaf; Wernerson, Annika, “Morphological and clinical findings in Sri Lankan patients with chronic kidney disease of unknown cause (CKDu): Similarities and differences with Mesoamerican Nephropathy, PLoS One, 2018, 13:3, DOI:10.1371/journal.pone.0193056.
ABSTRACT:
In Sri Lanka, an endemic of chronic kidney disease of unknown origin (CKDu) is affecting rural communities. The endemic has similarities with Mesoamerican Nephropathy (MeN) in Central America, however it has not yet been clarified if the endemics are related diagnostic entities. We designed this study of kidney biopsies from patients with CKDu in Sri Lanka to compare with MeN morphology. Eleven patients with CKDu were recruited at the General Hospital, Polonnaruwa, using similar inclusion and exclusion criteria as our previous MeN studies. Inclusion criteria were 20-65 years of age and plasma creatinine 100-220 mumol/L. Exclusion criteria were diabetes mellitus, uncontrolled hypertension and albuminuria >1g/24h. Kidney biopsies, blood and urine samples were collected, and participants answered a questionnaire. Included participants were between 27-61 years of age and had a mean eGFR of 38+/-14 ml/min/1.73m2. Main findings in the biopsies were chronic glomerular and tubulointerstitial damage with glomerulosclerosis (8-75%), glomerular hypertrophy and mild to moderate tubulointerstitial changes. The morphology was more heterogeneous and interstitial inflammation and vascular changes were more common compared to our previous studies of MeN. In two patients the biopsies showed morphological signs of acute pyelonephritis but urine cultures were negative. Electrolyte disturbances with low levels of serum sodium, potassium, and/or magnesium were common. In the urine, only four patients displayed albuminuria, but many patients exhibited elevated alpha-1-microglobulin and magnesium levels. This is the first study reporting detailed biochemical and clinical data together with renal morphology, including electron microscopy, from Sri Lankan patients with CKDu. Our data show that there are many similarities in the biochemical and morphological profile of the CKDu endemics in Central America and Sri Lanka, supporting a common etiology. However, there are differences, such as a more mixed morphology, more interstitial inflammation and vascular changes in Sri Lankan patients. FULL TEXT
Connolly et al., 2018
Connolly A, Jones K, Basinas I, Galea KS, Kenny L, McGowan P, Coggins MA, “Exploring the half-life of glyphosate in human urine samples,” International Journal of Hygeine and Environmental Health, 2018 (EPub), doi:10.1016/j.ijheh.2018.09.004.
ABSTRACT:
BACKGROUND: The International Agency for Research on Cancer (IARC) has recently classified glyphosate as a Group 2A ‘probably carcinogenic to humans’. Due to this carcinogenic classification and resulting international debate, there is an increased demand for studies evaluating human health effects from glyphosate exposures. There is currently limited information on human exposures to glyphosate and a paucity of data regarding glyphosate’s biological half-life in humans.
OBJECTIVE: This study aims to estimate the human half-life of glyphosate from human urine samples collected from amenity horticulture workers using glyphosate based pesticide products.
METHODS: Full void urine spot samples were collected over a period of approximately 24 h for eight work tasks involving seven workers. The elimination time and estimation of the half-life of glyphosate using three different measurement metrics: the unadjusted glyphosate concentrations, creatinine corrected concentrations and by using Urinary Excretion Rates (UER) (μgL−1, μmol/mol creatinine and UER μgL−1) was calculated by summary and linear interpolation using regression analysis.
RESULTS: This study estimates the human biological half-life of glyphosate as approximately 5 ½, 10 and 7 ¼ hours for unadjusted samples, creatinine corrected concentrations and by using UER (μgL−1, μmol/mol creatinine, UER μgL−1), respectively. The approximated glyphosate half-life calculations seem to have less variability when using the UER compared to the other measuring metrics.
CONCLUSION: This study provides new information on the elimination rate of glyphosate and an approximate biological half-life range for humans. This information can help optimise the design of sampling strategies, as well as assisting in the interpretation of results for human biomonitoring studies involving this active ingredient. The data could also contribute to the development or refinement of Physiologically Based PharmacoKinetic (PBPK) models for glyphosate. FULL TEXT
Jayasumana, 2015b
Jayasumana C, Paranagama P, Agampodi S, Wijewardane C, Gunatilake S, Siribaddana S, “Drinking well water and occupational exposure to Herbicides is associated with chronic kidney disease in Padavi-Sripura, Sri Lanka,” 2015, Environmental Health, 14:6, DOI:10.1186/1476-069X-14-6.
ABSTRACT:
BACKGROUND: The chronic kidney disease of unknown etiology (CKDu) among paddy farmers in was first reported in 1994 and has now become most important public health issue in dry zone of Sri Lanka. The objective was to identify risk factors associated with the epidemic in an area with high prevalence.
METHODS: A case control study was carried out in Padavi-Sripura hospital in Trincomalee district. CKDu patients were defined using health ministry criteria. All confirmed cases (N = 125) fulfilling the entry criteria were recruited to the study. Control selection (N = 180) was done from people visiting the hospital for CKDu screening. Socio-demographic and data related to usage of applying pesticides and fertilizers were studied. Drinking water was also analyzed using ICP-MS and ELISA to determine the levels of metals and glyphosate.
RESULTS: Majority of patients were farmers (N = 107, 85.6%) and were educated up to ‘Ordinary Level’ (N = 92, 73.6%). We specifically analyzed for the effect modification of, farming by sex, which showed a significantly higher risk for male farmers with OR 4.69 (95% CI 1.06-20.69) in comparison to their female counterparts. In the multivariable analysis the highest risk for CKDu was observed among participants who drank well water (OR 2.52, 95% CI 1.12-5.70) and had history of drinking water from an abandoned well (OR 5.43, 95% CI 2.88-10.26) and spray glyphosate (OR 5.12, 95% CI 2.33-11.26) as a pesticide. Water analysis showed significantly higher amount of hardness, electrical conductivity and glyphosate levels in abandoned wells. In addition Ca, Mg, Ba, Sr, Fe, Ti, V and Sr were high in abandoned wells. Surface water from reservoirs in the endemic area also showed contamination with glyphosate but at a much lower level. Glyphosate was not seen in water samples in the Colombo district.
CONCLUSION: The current study strongly favors the hypothesis that CKDu epidemic among farmers in dry zone of Sri Lanka is associated with, history of drinking water from a well that was abandoned. In addition, it is associated with spraying glyphosate and other pesticides in paddy fields. Farmers do not use personnel protective equipments and wears scanty clothing due to heat when spraying pesticides. FULL TEXT
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